Delay in fracture healing or non-union can be devastating complication. Recent studies have reported that teriparatide (TP) demonstrated effectively on callus formation and mechanical strength and zoledronate (ZA) increased the callus size and resistance at the fracture site in rat fracture model. In this study, the effects of combination therapy with low dose TP and ZA on fracture healing was evaluated.From 1 week post-operation, TP (5 times a week administration) and ZA (0.1 mg/kg single administration) were administered by dividing the rats into the following five groups: TP 1 μg group {T(1): TP 1 μg/kg}, ZA group (ZA:0.1 mg/kg), TP1 μg+ZA group {T(1)+ZA: TP 1 μg/kg+ZA}, TP 10 μg+ZA group {T(10)+ZA: TP 10 μg/kg + ZA}, and control group . Rt femurs were excised 7 weeks after the surgery; bone fusions were evaluated with soft X-ray images on a 4-point scale. And the histopathological examination was performed in demineralized and non-demineralized specimens. Furthermore, the Radiographic Union Scale was conducted in all specimens.2 and 17.75 mm2 in the T(1)+ZA and T(10)+ZA groups, respectively, while 10.65 mm2 (p < 0.05) in the C group. Furthermore, the callus area in the T(10)+ZA group was also observed to have significantly increased to 78.78%, compared with 54.63% and 44.11% in the C and T(1)+ZA groups, respectively (p < 0.01). Histopathologically, cartilage tissue and immature callus formation were observed at the bone junction in the C group; however, the osseous bridge formation of mature callus was observed in the ZA, T(1)+ZA, and T(10)+ZA groups.About the bone fusions rates, C, T(1), ZA, T(1)+ZA, and T(10)+ZA groups demonstrated 20.0%, 55.6%, 70.0%, 70.0%, and 80.0%, respectively, and with 4-point scale, each group was 0.50, 1.56, 2.00, 2.60, and 2.80 points, respectively. The callus volume was significantly increased to 16.66 mmIt is suggested that administration of low dose TP and ZA in combination may lead to the treatment of delayed union of fracture. We hope the combination treatment may become one of new therapeutic strategy. Although improvements in surgical methods for fractures of the femoral shaft have resulted in delayed fracture healing and nonunion in up to 5–10% of patients, subsequent treatment upon the occurrence of nonunion is challenging. Achieving early bone union and returning patients to society under such unfavorable conditions are important issues to address [Teriparatide (TP), which was used in the present study, affects osseous tissue, and its effect varies according to the administration method. While a catabolic effect on the bone is observed during continuous administration, an anabolic effect occurs when it is intermittently administered. Since 2010, TP has been widely used as a therapeutic drug for osteoporosis in Japan; however, it is expected to be clinically applied in the future as a therapeutic agent that promotes fracture healing because of its intense osteogenesis-promoting effect. Coppola et al. reported that TP administration was really effective for the management of non-unions in four cases; however, the efficacy of the TP in delayed or non-unions was not clear . HoweverIn contrast, bisphosphonate (BP) has a bone resorption inhibitory action and has been demonstrated to effectively improve bone mineral density (BMD), normalize elevated levels of serum bone metabolism markers, and lower the risk of bone fractures , 7. FurtAlthough there are not many studies on the effect of combined TP and ZA therapy on the process of bone fracture healing, the effectiveness of this treatment has been reported; it increases bone mass:volume ratio of the callus as well as bone mass and width , 12. TheA total of 50 male Sprague–Dawley rats  were divided into five groups. From 1 week post-operation, TP  (5 times a week administration) and ZA (Novartis Pharma KK Tokyo Japan) (0.1 mg/kg single administration) were administered by dividing the rats into the following 5 groups: TP 1 μg group {T(1): TP 1 μg/kg}, ZA group (ZA:0.1 mg/kg), TP1 μg+ZA group {T(1)+ZA:TP 1 μg/kg+ZA}, TP10 μg+ZA group {T(10)+ZA: TP 10 μg/kg+ZA}, and control group .Approval was obtained from the Oita University animal research committee prior to animal experimentation . The Sprague–Dawley rats were anesthetized by an intraperitoneal injection containing 0.3–0.4 ml of 0.15 mg/kg medetomidine + 2 mg/kg midazolam + 2.5 mg/kg butorphanol. The right hind limb was prepared for the operation under standard sterile conditions. With the rat in the lateral position, the right femur was located using the posterolateral approach. The periosteum of the femur was circumferentially incised and elevated and stripped. Then, the femur at osteotomy site was exposed. A transverse osteotomy was performed at the mid-shaft of the femoral bone, the fracture fragments were contacted and stabilized, and the intramedullary was then fixed using a stainless steel wire . The wire was cut on the surface of the intercondylar groove to avoid knee joint motion restriction. The material was applied and wrapped circumferentially around the fracture site. The fascial and skin incisions were closed with a 3–0 nylon suture.Immediately following surgery and on subsequent days, the rodents received analgesics (buprenorphine subcutaneously and paracetamol). The rodents were housed in separate cages and fed food and water ad libitum, and their conditions were monitored daily. The rats were humanly euthanized 6 weeks after the operation, and the operated right femoral bones were explanted and separated from the stainless steel wire before analysis. We used the left femoral bones, which had not been operated upon, as controls in the biomechanical analysis.The explanted femoral bones obtained at the 7-week time point were photographed using a Softex X-ray apparatus  employing HS Fuji Softex film  at 45 cm with 30 kV and 15 mA for 20 s. The fusion was quantified using anteroposterior (A-P) and lateral radiographs. Three blinded independent observers scored the bone formation in each rat using a 4-point scale. Fracture union was judged by visual assessment of the mineralized callus bridging the fracture line in the A-P radiographs  and lateral radiographs . The bone fusion was considered to be more than 2 points with soft X-ray images on a 4-point scale. Furthermore, the Radiographic Union Scale for Tibial fractures in Tibial Fracture (RUST) was conducted in all specimens . The RUSn = 4 per groups).Ten specimens of one group were divided into two kinds of staining. For the HE staining, 4 of 10 specimens were performed, and for the non-demineralized and toluidine blue staining, 6 of 10 specimens were performed in a random manner. After extraction, the femoral bones were dissected, and the specimens were fixed in 70% ethanol. The specimens were then decalcified using a standard 10% decalcifying solution of HCl  , washed with running tap water, and transferred to 75% ethanol. Serial sagittal sections (5 μm) were carefully cut from the paraffin blocks using a microtome  at the level of the femoral fracture. The sections were stained with hematoxylin and eosin (HE) and evaluated qualitatively under a light microscope (n = 6 per groups). After staining with toluidine blue, bone morphometry was performed to up to 0.43 mm proximal and distal to the bone fracture area . Measurement items included callus volume (CV), callus area (CA), and cartilage tissue area (Ca.A).Furthermore, non-demineralized specimens were obtained from glycolmenthacrylate resin-embedded slices, and the calcification state and cells in the fracture area were observed . Statistical significance was set at < 0.05.In the C and T1) group, the fracture line could be clearly identified, and immature callus formation was observed. In particular, callus continuity was not achieved in the C group. Conversely, in the ZA, T(1)+ZA, and T(10)+ZA groups, the fracture line was unclear, the callus was thick, and continuity was confirmed   group scoring 6.67 ± 2.24 points, the ZA group scoring 7.90 ± 3.10 points, the T(1)+ZA group scoring 9.20 ± 3.65 points, and the T(10)+ZA group scoring 10.2 ± 2.57 points, indicating significantly more progress in bone union in the T(1)+ZA and T(10)+ZA groups than in the C group (In the C and T(1) group, verifying the fracture site by HE staining identified the fracture and confirmed extensive chondrogenesis. Furthermore, while several specimens demonstrated thin immature callus formation, callus continuity could not be confirmed in many specimens. Although a few chondrocytes were identified in the T(1)+ZA group, they were enlarged. Compared to the C group, the fracture line was unclear. Furthermore, in the T(10)+ZA group, chondrocytes could not be identified, but mature callus and advanced bone union were confirmed Fig. .Fig. 3Bo2 in the C group, 8.01 ± 1.46 mm2 in the T(1) group, and 12.79 ± 1.28 mm2 in the ZA group, but was significantly higher at 16.66 ± 2.35 mm2 in the T(1)+ZA group and 17.75 ± 2.85 mm2 in the T(10)+ZA group (P < 0.01). Similarly, CA was 54.63% ± 5.31% in the C group, 44.11% ± 4.13% in the T(1) group, 62.84 ± 5.89% in the ZA group, and 62.57% ± 2.75% in the T(1)+ZA group, but was significantly higher at 78.78% ± 0.85% in the T(10)+ZA group (P < 0.001). However, Ca.A was 0.74 ± 0.51 mm2 in the C group, 0.06 ± 0.11 mm2 in the T(1) group, 0.01 ± 0.02 mm2 in the T(1)+ZA group, but it could not be confirmed in the ZA and T(10)+ZA group (P < 0.05)  groups, whereas osseous bridge formation of the mature callus was observed in the ZA, T(1)+ZA, and T(10)+ZA groups. Furthermore, bone union was seen resulting from endochondral ossification in the ZA, T(1)+ZA, and T(10)+ZA groups, and mature bone tissue was identified in the T(10)+ZA group -β and platelet-derived growth factor were induced from platelets. Furthermore, interleukin (IL)-2 and IL-6 were derived from inflammatory cells, and TGF-β promoted mesenchymal cell differentiation. Within 24 h after fracture, mesenchymal stem cells secreted bone morphogenetic proteins. In the fracture gap, mesenchymal stem cell differentiation began on day 3 after fracture and cartilage and soft callus began forming. On day 5, at the same site, type II collagen mRNA expression was observed, which peaked on day 9. From around day 14, the soft callus began calcifying, appearing like a primary or secondary spongy bone surrounding the growth plate cartilage. This implies that endochondral ossification occurs after cartilage formation at the site of bone fracture and that membranous ossification occurs near the bone fracture site. The bone that has just been ossified is often fibrous bone, which is remodeled and converted into lamellated bone. It can be said that bone fracture healing is achieved through the combination of all these histological changes [In this study, the periosteum of the femur was circumferentially incised and elevated and stripped, then, the femur at osteotomy site was exposed. A transverse osteotomy was performed at the mid-shaft of the femoral bone; the fracture fragments were contacted and stabilized. We had performed several times of experiments of femoral fracture model, and the average rate of bone union was almost 10–20% of the cases in stripping of periosteum. Cartilage formation is taking place in the cambium layer of the periosteum, and chondrocyte precursor cells also reside in this location. Accordingly, bone union must rely on endochondral ossification. To date, studies have illustrated that TP promotes endochondral ossification from cartilage formation occurring in the fracture gap and promotes membranous ossification near the fracture site. Furthermore, TP promotes callus remodeling and reduces the bridging callus, simultaneously increases the degree of calcification, improves the dynamic quality of callus, and promotes a normal bone fracture healing process.Nakazawa et al. injected 10 μg/kg of PTH in a rat closed femoral fracture model and analyzed the promotion of bone fracture healing at the molecular level . CompareRegarding the effect of BP on endochondral ossification, it has been suggested that the size and strength of the callus can be controlled by regulating bone remodeling during the healing process. Consequently, the timing and regimen of BP therapy can have a significant impact on the formation and strength of the callus. In our preliminary experiment, we established that 1 week after fracture is the optimal timing of a single intraperitoneal injection of ZA for the rate of bone union, bone formation, and strength testing . FurtherHistopathological findings of the species revealed that ZA treatment not only increases callus formation but also improves trabecular microarchitecture. ZA given systemically as a single dose at the optimal time could reduce catabolic osteoclastic resorption caused by TP. However, there were no evidence of ZA-induced suppression of anabolic bone formation caused by TP. The fusion rates in rat femurs administered both ZA and TP were higher than those of rats administered ZA only 6 weeks after surgery.The present study demonstrated that the synergistic effect of low-dose TP and ZA promoted callus formation, increased callus mass, and helped to promote bone union in a rat refractory fracture model. The synergistic effect of the combination of TP with the anabolic effect and ZA with the anti-catabolic effect was also demonstrated. Because ZA promotes the apoptosis of osteoclasts, remodeling is delayed, which, in turn, can impede the change from fibrous bone to lamellated bone. Hence, detailed investigations of the bone structure through long-term observations are required in the future.The present experiment shows that administration of low-dose TP and ZA in combination is able to enhance callus formation, increase callus volume, and help to promote bone union in a rat refractory fracture model. We hope the combination treatment may become one of new therapeutic strategy in delay in fracture healing or non-union of patients.


The physicochemical properties as well as electromagnetic parameters and microwave absorption performance were characterized by XRD, SEM, TEM, RS, TGA, and VNA, respectively. The results indicate a nuclear-shell morphology of this hybrid for amorphous carbon coated on the surface of Zn0.5Co0.5Fe2O4 and Mn0.5Ni0.5Fe2O4 mixed polycrystalline ferrites. In addition, the MWCNTs synchronously enwind in the nuclear-shell NPs to form a special cross-linking structure. The outstanding low frequency microwave absorption property is attributed to the synergistic effect of dielectric and magnetic loss, better impedance matching condition, and excellent attenuation characteristics of the as-prepared paramagnetic quaternary hybrid. Maximum RL of −35.14 dB at 0.56 GHz with an effective absorption bandwidth in the range of 0.27–1.01 GHz can be obtained with thickness of 5 mm. This hybrid exhibits superior low frequency microwave absorption properties compared with other ferrite-carbon nanocomposites. This investigation provides a new route to prepare suitable candidates for the absorption of electromagnetic waves in a low frequency band on account of its good performance and simple preparation process.In this study, the quaternary hybrid of (Zn M.M. Ismail et al. [2O4/PANI-PTSA composite by sol-gel method; the as-prepared composite presented a wider absorption range and maximum RL was −28.4 dB at 8.1 GHz. Q. Chen et al. [2@Mn0.6Zn0.4Fe2O4 composite by using chemical co-precipitation technology; the optimal RL value of the composite with thickness of 2 mm was able to reach up to −44.24 dB at 11.57 GHz as well as bandwidth of RL < −10 dB from 9.04 to 16.16 GHz. S. Acharya et al. [The rapid development of detection and communication technologies in the military and commercial fields has resulted in more attention being paid to electromagnetic interference (EMI), electromagnetic pollution, and radar stealth. The creation of microwave absorption materials (MAMs) with good performance is an effective approach to address these problems ,2,3,4. Il et al.  synthesin et al.  fabricat3O4 NPs with multi-walled carbon nanotubes (MWCNTs) to enhance the electromagnetic absorption of ferrites for excellent dielectric loss, special one-dimensional nanostructure, low density and resistivity, and good thermal stability of MWCNTs. Moreover, the electromagnetic wave absorption of the composite in a low frequency band can also be heightened with the doping of MWCNTs [In spite of this, present investigations on MAMs are mainly focused in the frequency range of 2–18 GHz. The electromagnetic absorption of these composites is very limited in the low frequency range of 0.1–2 GHz. However, the electromagnetic radiation generated from electronic devices used daily is in a low frequency range, and the detection frequency of many radars e.g. meter-wave radar, phased array radar, spaceborne radar, etc. has been extended to the low frequency region. Hence, this poses a significant challenge in the design of MAMs with outstanding electromagnetic wave absorption capacity in the low frequency band ,26. In rf MWCNTs . 0.5Co0.5Fe2O4/Mn0.5Ni0.5Fe2O4)@C-MWCNTs (denoted as (ZCFO/MNFO)@C-MWCNTs henceforth) hybrid was synthesized via a two-step solvothermal method. The phase analysis, micro- and crystal structures, elemental distribution, Raman spectrum, thermogravimetry properties, electromagnetic parameters, and electromagnetic absorption performance of the as-prepared hybrid were characterized by X-Ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), Raman spectroscopy (RS), thermogravimetric analysis (TGA), and vector network analyzer (VNA) respectively. The intrinsic mechanisms of microwave absorption were also discussed. The results show that the quaternary hybrid can have excellent electromagnetic wave absorbing performance in a low frequency range, and such a hybrid can be used as a promising electromagnetic wave absorber in this band. Therefore, in the present work, the (Zn2), cobalt chloride hexahydrate (CoCl2·6H2O), ferric chloride hexahydrate (FeCl3·6H2O), polyethylene glycol-6000, and sodium acetate trihydrate (NaAc) were purchased from Kelong Chemical Reagent Co. Ltd, Chengdu, China. The nickel chloride hexahydrate (NiCl2·6H2O) was purchased from Basf Biotechnology Co. Ltd, Hefei, China. The ethylene glycol and manganese chloride tetrahydrate (MnCl2·4H2O) were purchased from Sinopharm Chemical Reagent Co. Ltd, Shanghai, China. The multi-walled carbon nanotubes were purchased from Xianfeng Nano Technology Co. Ltd, Shuzhou, China. Zinc chloride (ZnCl0.5Co0.5Fe2O4 nanoparticles (denoted as ZCFO NPs henceforth) were prepared via the solvothermal synthesis method [The Zns method . In deta0.5Co0.5Fe2O4/Mn0.5Ni0.5Fe2O4)@C-MWCNTs hybrid was obtained via the solvothermal method once again, i.e. 1.2375 g manganese chloride tetrahydrate, 1.485 g nickel chloride hexahydrate, and 6.75 g ferric chloride hexahydrate were in order dissolved in 200 mL ethylene glycol. Subsequently, 18 g sodium acetate trihydrate, 5 g polyethylene glycol 6000, and 2.6292 g ZCFO NPs obtained from the previous process and 0.8025 g MWCNTs were added into the above solution with ultrasonic dispersion and persistent stirring for 30 min. Then, the mixed solution was sealed in a Teflon-lined stainless-steel autoclave and the reaction temperature was maintained at 200 °C for 12 h. Finally, the as-prepared product was separated with a magnet and washed with ethanol, after which it was dried at 50 °C for 6 h. MWCNTs content in the as-prepared nanocomposite was ~12 wt%, which was decided as an optimal proportion according to our previous investigations and can be calculated by the mole ratio of reactants [0.5Co0.5Fe2O4/Mn0.5Ni0.5Fe2O4 hybrid (denoted as ZCFO/MNFO henceforth) was done following the same process, without the addition of MWCNTs.The . The superficial micro-morphology of hybrids was characterized by a Scanning Electron Microscope . The transmission morphology, Selected Area Electron Diffraction (SAED), and elemental distribution were characterized by a Transmission Electron Microscope . Raman spectra was measured with a Raman spectroscopy (In Via Reflex) by using a laser wavelength of 532 nm. Data of Thermogravimetric Analysis (TGA) was collected in air at a heating rate of 10 °C/min. The samples used for microwave absorption measurements were prepared by blending the products with paraffin in a mass percentage of 40 wt%; then the prepared samples were pressed into a toroidal shape with Φout = 7.00 mm, Φin = 3.04 mm, and different thicknesses of 2–5 mm. The S-parameters of S11 and S21 can be tested with coaxial transmission and reflection method by using the TD3618C Vector Network Analyzer . Thus, complex permittivity and permeability can be calculated on the basis of Nicolson and Ross’s theory [The crystal structures of hybrids were analyzed by an X-ray diffraction system with Cu-s theory .θ = 18.29°, 30.08°, 35.44°, 37.06°, 43.06°, 53.45°, 56.97°, 62.59°, 70.95°, and 74.01° are in good agreement with the (111), (220), (311), (222), (400), (422), (511), (440), (620), and (533) planes (JCPDS card no.22-1012). No other impurity peak was observed, confirming the spinel structure of ZCFO ferrite [θ = 44.51° and 51.85°, assigned to the (111) and (200) planes of less Ni elementary substance (JCPDS card no.04-0850) reduced by ethylene glycol during the secondary hydrothermal reaction. Moreover, it shows that there exists a weak diffraction peak at 2θ = 26.38° corresponding to the (002) plane of MWCNTs (JCPDS card no.41-1487) in the quaternary (ZCFO/MNFO)@C-MWCNTs hybrid, indicating that the MWCNTs is composited well with ferrites. The intensity of this diffraction peak is much weaker than those of ferrites, as the wall thickness of MWCNTs used here is thin enough [The phase composition of the as-prepared hybrids has been confirmed by XRD; the patterns are illustrated in  ferrite . In addin enough .−1) and G band (~1577 cm−1), and the intensity ratio of ID/IG is 1.21. In general, the D band corresponds to disordered structures and G band relates to the vibration of sp2-bonded carbon atoms. The intensity of D and G band is weakened after the MWCNTs are composited with ferrites; these two bands are located at ~1340 cm−1 and ~1581 cm−1, respectively. The intensity ratio of ID/IG in the quaternary hybrid is 1.58, which is higher than that of raw MWCNTs, indicating a decrease of in-plane sp2 domains’ size and the increase of unrepaired defects with an enhanced degree of disorder [−1, 602 cm−1 and 677 cm−1 correspond to the T2g, A1g and Eg modes of ferrites [2g mode represents the characteristic of the octahedral sites, whereas the A1g mode is due to the symmetric stretching of oxygen atoms at the tetrahedral site [Raman spectroscopy is an important technology used to characterize the disorder in sp2 carbon materials. disorder . These ddisorder ,39. Moreferrites ,40. Usuaral site . Figure ε = ε′ − jε′′) and permeability (μ = μ′ − jμ′′) of the hybrids are calculated and shown in ε′ is enhanced slightly in the whole range to coat MNFO on the surface of the ZCFO micro-grains. However, the ε′ of the quaternary hybrid was observably strengthened in the low frequency domain due to the addition of MWCNTs; it decreases from 35.36 to 1.22 in the range of 0.1~3 GHz owing to the glorious dielectric properties of MWCNTs [ε′′ of ZCFO increases first and then decreases with the enhancement of frequency in ε′′ of ZCFO/MNFO is reinforced to 1.40 at 1.22 GHz, whereas, this tendency can be further enhanced by the doping of MWCNTs; the imaginary part of permittivity in the quaternary hybrid achieves 4.89 at 0.23 GHz and be comparatively higher in the measurement range, particularly in the low frequency domain. To the best of our knowledge, the permittivity of hybrid in gigahertz band strongly depends on interfacial polarization and dipole polarization. The formation of a NPs@C core-shell structure due to the addition of MWCNTs and the convolving of MWCNTs among particles will immensely increase multiple interfacial polarization; moreover, the defects in imperfect carbon structure and ferrites, and the oxygen-containing groups on MWCNTs will also enhance dipole polarization of the as-prepared quaternary hybrid. Thus, the ε′ and ε′′ would be enlarged due to the enhancement of dielectric polarization behavior; nevertheless, the generation of displacement current significantly lags behind the build-up potential as the frequency increases, leading to the reduction of both real and imaginary part of permittivity [ε′ of MAMs represents the storage capacity of microwave energy during the transmission process of electromagnetic wave, while the ε′′ shows the microwave energy loss ability [ε′′ in the quaternary hybrid may be helpful for dielectric absorption of the electromagnetic wave. μ′ of ZCFO and ZCFO/MNFO increase with the enhancement of frequency, and their μ′′ increase first and then decrease. Whereas, there is a surprise phenomenon that both the μ′ and μ′′ would be enhanced to a large extent with the cladding of carbon and doping of MWCNTs; the μ′ increases from 1.86 to 17.6, while the μ′′ decreases from 39.79 to 13.07. This is attributed to that fact that the adhered carbon and MWCNTs can interconnect ferrite NPs in the conductive network, strengthening the coupling effect between different components. As per the theoretical calculation of Kazantseva et al. [δ is the scale of conductive media, R the radius of ferrite NPs, and Λ can be expressed as:ω is angular frequency. Hence, the permeability of the hybrid can be varied with different frequencies for the change of R and Λ. This may be the reason why both μ′ and μ′′ increased with the cladding of carbon and doping of MWCNTs [The complex permittivity @C-MWCNTs in μ′′ of the quaternary hybrid for the reason mentioned above [ed above . RL), which is calculated according to the transmission line theory, as follows [inZ in Equation (3) is input impedance: rε is the permittivity, rμ the permeability, Z0 the impedance of air, d the thickness of sample, c the velocity of light in vacuum, and f the frequency. RL curves of the ZCFO, ZCFO/MNFO, and (ZCFO/MNFO)@C-MWCNTs hybrids at different thickness. As seen in RL value is −4.54 dB at 3 GHz; this maximum value is enlarged to −7.11 dB when thickness is 3 mm. Nevertheless, there appears an inconspicuous RL peak of −7.33 dB at 2.84 GHz at 4 mm, and when the thickness is further increased to 5 mm, the maximum peak shift to 2.16 GHz with intensity of −8.29 dB. RL of the ZCFO/MNFO hybrid; it can be noted that the absorption peaks present in the thickness of 3 mm, 4 mm, and 5 mm, and the absorption intensity, are enhanced to −7.79 dB, −9.25 dB, and −9.34 dB, respectively. This is ascribed to the increased interfacial polarization between ZCFO and MNFO. However, this situation will be improved prodigiously as the MWCNTs have been doped in the ferrites to form the quaternary hybrid. It is interesting to note that the maximum RL of 2 mm is −15.95 dB at 2.14 GHz with the −10 dB absorption bandwidth between the frequency range of 1.46–2.88 GHz (1.42 GHz), which is attributed to the preferable synergistic effect of dielectric properties of MWCNTs and magnetic properties of ferrites, as well as the enhanced multi-interface polarization and conduction loss of micro-current in MWCNTs [RL are −19.57 dB at 0.99 GHz (bandwidth below −10 dB is 0.65–1.46 GHz), −23.72 dB at 0.74 GHz (bandwidth below −10 dB is 0.48–1.09 GHz), and −35.14 dB at 0.56 GHz (bandwidth below −10 dB is 0.27–1.01 GHz), respectively. In general, more than 90% electromagnetic wave energy is dissipated during its transmission in hybrid as the RL is below −10 dB, according to the theory of transmission line; here, the maximum absorption peak < −30 dB means that the abrasive electromagnetic wave energy is greater than 99.9% [RL absorption peak moves to the lower frequency region with the addition of thickness in the absorber; this is due to the quarter wavelength resonance effect [Usually, the electromagnetic absorption of hybrid can be characterized by the parameter of electromagnetic wave reflection loss RLn MWCNTs .These faan 99.9% . MoreoveinZ/Z0| is close to one [inZ/Z0| of the ZCFO, ZCFO/MNFO and (ZCFO/MNFO)@C-MWCNTs hybrids at thickness of 5 mm. It suggests that the optimal impedance matching frequency of these three hybrids are 2.61 GHz, 2.13 GHz, and 0.58 GHz, respectively, which is why the frequency of strong absorption peak in the quaternary hybrid is obviously lower than that of the other two, and more electromagnetic wave is transmitted into the hybrid to be dissipated under suitable matching conditions. In addition, the magnetic loss of the ferrite component is always generated from natural resonance loss, eddy current loss, domain wall resonance loss, and hysteresis loss. However, the domain wall resonance loss generally occurs in MHz range and hysteresis loss is weak in the weak field condition [C0 is calculated as follows [C0 will maintain a constant as the frequency changes, if the magnetic loss originates from the eddy current loss. C0 values are almost constant within the frequency range of 2.0–3.0 GHz for ZCFO and ZCFO/MNFO, indicating that the magnetic loss in this range is mainly due to the eddy current loss, while the natural resonance loss mainly exists in the range of 0.1–2.0 GHz. However, this frequency range of the eddy current loss enlarges to 1.5–3.0 GHz for the (ZCFO/MNFO)@C-MWCNTs quaternary hybrid, and the value of C0 changes dramatically within 0.1–1.5 GHz, manifesting a strong natural resonance loss to enhance the magnetic absorption of the microwave.The impedance matching condition is very important in determining the incidence and reflection of microwave on the surface of the absorber. The more microwaves enter the absorber to be dissipated when the value of |e to one . Figure ondition . Thus, tondition :(6)μ″≈2πα also gives an important meaning to the electromagnetic absorption ability of hybrids; this attenuation property of the absorber can be deduced as [α of a single ZCFO is limited and there is a maximum value of 80.14 at 2.78 GHz. This situation can be improved in the ZCFO/MNFO hybrid—the α increases first and then decreases in the measurement frequency range; the maximum value is enhanced to 90.78 at 2.26 GHz due to the accessorial interface polarization loss between the ZCFO and MNFO ferrites. However, the attenuation constant in the quaternary hybrid is enhanced to a large extent—it also increases initially and decreases afterwards, while the maximum value of α is 235.19 at 1.35 GHz, which is ascribed to the high values of ε′′ and μ′′, indicating the excellent microwave absorption properties of this hybrid. Furthermore, the plots of ε′ and ε′′ in the ZCFO, ZCFO/MNFO and (ZCFO/MNFO)@C-MWCNTs hybrids have been displayed in The attenuation constant duced as ,60:(8)α=0.5Co0.5Fe2O4@Mn0.5Ni0.5Fe2O4)@C-MWCNTs hybrid with preeminent electromagnetic wave absorption properties in low frequency band was fabricated via a two-step solvothermal synthesis method. The significant electromagnetic absorption properties of the as-prepared paramagnetic quaternary hybrid are attributed to the synergistic effect of dielectric loss , magnetic loss , preferable impedance matching condition, and outstanding attenuation characteristics. Hence, the maximum RL of −35.14 dB at 0.56 GHz with an effective absorption bandwidth (RL < −10 dB) in the frequency range of 0.27–1.01 GHz (0.74 GHz) can be obtained when the thickness of the absorber is 5 mm. Most important of all, the processing method used here is very simple, and it provides a new route to prepare suitable candidates for the absorption of microwave in low frequency band. In summary, the (Zn


Evidence concerning the relationship between objectively-measured attributes of the built environment with cardio-metabolic risk in populations from lower- and middle-income countries is lacking. In this paper, we describe the association between the objectively-measured built environment with body mass index, blood pressure and physical activity in adult South Africans.This cross-sectional study included 341 adults aged ≥35 years drawn from the Cape Town arm of the Prospective Urban Rural Epidemiology (PURE) cohort study. All Cape Town PURE participants were invited to take part in the study. Actigraph GT3X accelerometer and Geographic Information Systems were used to measure physical activity and built environment attributes .In age and sex adjusted models (reference 500 m), access to community centers (1000 m) was positively related to body mass index [beta 4.70 (95%CI: 2.06 to 7.34)] and diastolic blood pressure [4.97 (0.00 to 9.95)]. Distance from a community center (1600 m) was positively related to diastolic blood pressure [6.58 (1.57 to 11.58)] and inversely with moderate-to-vigorous physical activity [− 69.30 (− 134.92 to − 3.70)]. Distance to a shopping center (1600 m) was positively related to body mass index [4.78 (1.11 to 8.45)] and shopping center (1000 m) was positively related to systolic blood pressure respectively [76.99 (0.03 to 83.95)].Distance to community and shopping centers were significantly associated with BMI, systolic, diastolic blood pressure and moderate-to-vigorous physical activity. Future research should include multiple aspects of built environment variables in order to provide for a broader understanding of their effect on cardiovascular risk profile of African populations. Non-communicable diseases, such as cardiovascular disease (CVD), are the leading cause of death in high income and many low- and middle income countries (LMICs) , includiRapid epidemiological shifts in population health and disease burden have been linked to changes in the built environment that may promote or adversely affect active transport, such as walking to and from places, because this has been associated with reduced risk of obesity, and non-communicable diseases (NCDs) –8. A recBuilt environments that support utilitarian walking, with destinations in close proximity, have been linked to lower body mass index (BMI) , blood pGiven that cardiovascular disease in South Africa and Africa at large is increasing , developParticipants in the current study were drawn from the Langa Township site of the Prospective Urban Rural Epidemiology (PURE) cohort study in Cape Town, South Africa. The cohort, established in 2009, included 2064 Black South African men and women aged 35–70 years. In this study, all PURE participants were invited to take part in the study. Included participants had to: (1) be aged 35–70 years, (2) be living within identified household, and (3) have no disability that precluded walking.N = 459) with valid anthropometric measurements were used for geocoding. We merged each participant’s accelerometer data with the corresponding GIS data according to their ID numbers, so that each Geographic Information System (GIS) point had a corresponding accelerometer count. However, only a representative sample of 341 individuals, both men and women, with valid data on GIS and accelerometer measurements were included in the analysis. We excluded 118 (25.70%) individuals without valid GIS and accelerometer data.This was a cross-sectional survey nested within PURE follow-up evaluation conducted in 2013. Addressee’s of all the Langa PURE cohort participants  where trained research assistants carried out all physical measurements and introduced accelerometers. A dedicated research assistant instructed and demonstrated how to wear the monitor above the right hip during all waking hours for seven consecutive days, except during water activities and showering. All protocol and standard guidelines were followed during the initializing period of the accelerometers . Socio-d2).Height to the nearest 0.1 cm was measured using a portable stadiometer with participant standing in bare feet and upright. Weight to the nearest kilogram, was measured using a portable bathroom weighing scale , with participants lightly dressed. BMI was calculated as weight (kg) divided by height (mhave you been diagnosed with hypertension?”Trained staff measured blood pressure (BP) using an Omron 711  automated device with the appropriate cuff size for the measured mid-upper-arm circumference and taken after the subject had been seated at rest for at least 10 min. Blood pressure measurements were taken on the left arm of each participant in a sitting position. Two readings were made 3–4 min apart and the averaged reading used for the definition of hypertension (systolic blood pressure-SBP ≥ 140 mmHg and/or diastolic blood pressure-DBP ≥ 90 mmHg). In the current study, systolic and diastolic blood were treated as continuous variables. Additionally, self-reported hypertension was defined as previously diagnosed hypertension by a physician based on a positive answer to the question “Objective measurement of physical activity (PA) was done using the ActiGraph GT3X . The technical specifications and performance characteristics of the Actigraph accelerometer have been described elsewhere . ActigraBuilt environment attributes were assessed using Global Information System (GIS) -derived variables. The location of each participant’s residence was geocoded using ArcGIS 9.3 (ESRI Inc). Three road distance buffers  were generated around each participant’s household . Neighbop < 0.05. All data were analysed using SPSS® version 22 for Windows (IBM Corp: Armonk New York).The descriptive data are presented as means ± standard deviation or count and percentages. The Chi squared test and t-test were used to compare socio-demographic characteristics selected CVD risk factors and built environment attributes by gender. In age and sex adjusted models, linear regression analyses using 500 m as reference buffer were executed to assess the association between built environment attributes and selected CVD risk factors including BP, BMI and PA. Statistical tests were considered significant at t (339) = − 1.64, p = 0.101, d = 0.22. Furthermore, 41.9% of the participants were unmarried, 61.9% had completed secondary school, 61.9% were unemployed, 93.5% earned between ZAR2000–5000 per month and 92.7% did not own a car. These characteristics were similar between men and women . Additionally, 28.2% of the participants smoked while 35.2% were current drinkers, with significant gender differences in both smoking and drinking status (both p ≤ 0.005), Table The socio-demographic characteristics of the participants are displayed in Table t (339) = − 7.69, p = < 0.001, d = 0.09, Table t (339) = − 2.29, p = 0.047, d = 0.29.The mean BMI was higher in women (33.0 ± 6.8) than in men (26.3 ± 6.5), t (102) = − 0.615, p = 0.540, d = 0.12. The mean MVPA was similar in males (3.9 ± 3.1) and females (3.4 ± 3.5), t (102) = 0.66, p = 0.509, d = 0.13. Total MVPA was also similar in females (314.9 ± 120.3) and males (309.3 ± 115.8), t (102) = − 0.61, p = 0.543, d = 0.12.The mean counts per minute spent in objectively measured MPA was 314.0 ± 116.9 for female and (300.0 ± 118.8) for male, p > 0.05), Table The GIS buffer from participants’ home was predominantly 500 m (61.0% of participants) for the community center, 500 m (42.8%) for the shopping center and 500 m (49.6%) for the taxi station. Likewise, no gender differences were noted across BE attributes (2 higher BMI and 4.51 (− 0.68 to 8.36) mmHg higher DBP, while residing 1600 m away was associated with 2.40 (0.14 to 4.57) kg/m2 higher BMI. Residing 1000 m away from the taxi rank was associated with 5.22 (1.52 to 8.88) mmHg lower DBP, Table In univariate linear regression models Table , distancIn multivariate regression models, adjusted for sex and age, the distance to a community center (1000) remained associated with BMI 4.70 (2.06 to 7.34), DBP 4.97 (− 0.00 to 9.95) mmHg and MVPA -69.30 (− 134.92 to − 3.70). The distance to shopping center (1600 m) was positively associated with BMI [beta 4.78 (1.11 to 8.45)] and 1000 m was associated with SBP [76.99 (0.03 to 83.95)]  remained associated with BMI, DBP and MVPA. The distance to shopping center (1600 m and 1000 m) were positively associated with BMI and SBP, respectively Table . In a fuThis study supports the growing evidence that a walkable neighborhood environment is associated with fewer CVD risk factors , 33, 34.A number of potential advantages have been suggested that explain the beneficial effects of living near community services, including increased physical activity, and lowering obesity and hypertension . HoweverAnother potential mechanism for the relationship between proximity to a community center, and health outcomes may be found in a study from the Netherlands, where high quality, open public space was associated with a lower systolic blood pressure . AnotherIn this study setting, the shopping center was located near to the rail station, meaning that poor residents staying far away will usually need to take public transport to access the shopping center, thus resulting in less frequent walking trips. In addition, a proportion of our participants, who were employed, had to cover long distance to and from jobs. As a consequence, they may have had less time to shop and prepare healthy food for their households or may have had to depend on street food and ‘spaza’ shops for meals clustered near rail or bus stations, which were less unhealthy . All theThe present study has some limitations. Its cross-sectional design did not allow defining causality association among characteristics. The study area, the Langa Township, has limited variability in land use, and consequently only variables available in the GIS database could be examined. For example, there was no GIS data available on local corner shops (spaza) considered to be selling unhealthy food. Therefore, more GIS data are required to better study BE association in South Africa. In addition, available variables were not categorized into contrasting socioeconomic levels (low/high) and built environments (low/high). Hence, these results are not necessarily being applicable to other neighborhoods in Cape Town. The study’s sample size may have been too small especially for accelerometer to observe clear differences and trends. Another concern is that although the accelerometers provide objective measures that remove self-report biases, they do not capture all forms of PA accurately . Moreover, participants were also asked to remove the monitors during activities involving water, which exclude swimming for instance from the PA data. Furthermore, the study didn’t measure muscle mass which has the potential to influence the BMI. The study also had strengths. This is the first study to provide evidence on the direct association between objectively measured built environment and physical activity with BMI, SBP, DBP, in an Africa context.The current study has provided for the first time, evidence to support an association between access to community resources and amenities, proximity to community and shopping centers, as well as transit stops, and objectively measured physical activity, along with CVD risk factors, BMI, SBP and DBP among South African adults. The current study indicates that public health approach such as increasing proximity and access of community services in neighborhoods would potentially assist in reducing population’s cardio-metabolic disease risk, by creating opportunities for physical activity and healthy food choices. However, similar studies should be replicated in other African countries before any firm conclusions can be ascertained.


Hediste diversicolor) cultured under integrated multi-trophic aquaculture (IMTA) conditions display an improved fatty acids (FA) profile than conspecifics from the wild, thus being more suitable for maturation diets of marine fish and shrimp. Nonetheless, their use may represent a potential pathway for pathogens. The objective of the present study was to determine if high-pressure processing (HPP), as an approach to safeguard microbiological safety, could promote significant shifts on the FA profiles of different sized ragworms. An analysis of similarities (ANOSIM) revealed the existence of significant differences in the FA profile and lipid quality indexes (atherogenicity (AI), thrombogenicity (TI) and polyene (PI)) of control and HPP treated ragworms of all tested sizes . Saturated (SFA) and monounsaturated FA (MUFA) increased after HPP, while polyunsaturated FA  and highly unsaturated FA  decreased. The amount of docosahexaenoic acid (DHA) in polychaetes exposed to HPP decreased an average of 25%, when compared with the levels recorded in control groups. The values of PI significantly decreased after HPP, while those of AI and TI displayed a significant increase. Despite the shifts in the FA profile of ragworms exposed to HPP, these still display a superior profile to that of wild specimens, namely the presence of DHA. Therefore, HPP can be considered as a suitable approach to safeguard the biosecurity of cultured polychaetes, without compromising their nutritional value, and support the principles of circular economy through the use of IMTA.Ragworms ( Therefore, the present study aims to determine the effects of high-pressure processing (HPP) on H. diversicolor FA profile and experimentally verify if this technology can be used for whole ragworms preservation without compromising their nutritional value.The inclusion of the polychaete c matter ,6,7,8. Pc matter ,9,10. Inc matter ,12. Whenbricius)  and Soles, 1758) . In broos, 1758) ,15,16. Ts, 1758) . Specifiychaetes . In moreychaetes . Arachidychaetes . Eicosapcid AA - :4n-6 andcid AA - :4n-6 andd shrimp . If one d shrimp ,23,24, tHigh-pressure processing is a non-thermal preservation technology that has rapidly become highly relevant in food industry, as it represents a physical additive-free food preservation technology . The mosAs the inactivation of microorganisms through HPP has already been thoroughly demonstrated, including for the most common pathogens affecting aquaculture see , this asThe following null hypothesis was tested: 0: There are no significant differences in the FA profile and lipid quality indexes of fresh whole depurated small, medium and large-sized H. diversicolor and conspecifics exposed to HPP.HH. diversicolor in the control group and those exposed to HPP.H. diversicolor size classes . In control samples of H. diversicolor, EPA was the dominant FA in all size classes contributing to 25%, 24% and 22% of the total FA content presented by S, M and L, respectively. The average content of this FA was 7.53 ± 0.11 µg mg−1 DW, 6.32 ± 0.02 µg mg−1 DW and 6.68 ± 0.17 µg mg−1 DW for S, M and L, respectively. Palmitic acid (16:0) was the most dominant SFA, with 4.09 ± 0.06 µg mg−1 DW, 3.46 ± 0.18 µg mg−1 DW and 4.57 ± 0.11 µg mg−1 DW for S, M and L, respectively. Concerning MUFA, the most representative fatty acid was 20:1n-9, with 2.20 ± 0.03 µg mg−1 DW, 1.91 ± 0.07 µg mg−1 DW and 2.06 ± 0.02 µg mg−1 DW being recorded for S, M and L, respectively. In H. diversicolor exposed to HPP, EPA was also the most representative FA with 6.77 ± 0.11 µg mg−1 DW, 5.07 ± 0.05 µg mg−1 DW and 5.33 ± 0.17 µg mg−1 DW to S, M and L, respectively. Palmitic acid content was 4.58 ± 0.06 µg mg−1 DW, 4.77 ± 0.07 µg mg−1 DW and 6.57 ± 0.18 µg mg−1 DW in S, M and L, respectively. The class MUFA was characterized by the fatty acids 18:1n-5  and the 20:1n-9 groups .Both in control and HPP samples, a total of 23 fatty acids were recorded for the different p = 0.003). Considering size class  the ANOSIM analysis also showed significant differences  between the size group with a strong difference within each group. In fact, in HPP treated H. diversicolor SFA increased from 7.01; 5.89, and 7.58 µg mg−1 DW to 7.81; 7.85, and 10.32 µg mg−1 DW for S, M and L, respectively. Regarding HUFA, there was a decrease in FA content from 11.47; 10.35, and 10.37 µg mg−1 DW to 10.25; 7.97, and 8.44 µg mg−1 DW for S, M and L, respectively, with shifts in EPA content being mostly responsible for this decrease.The ANOSIM analysis performed on the FA content of polychaete samples from the control group and those exposed to HPP revealed the existence of significant differences  in ragworms with the same size exposed to HPP, when contrasted to control organisms. While AI significantly increased in specimens exposed to HPP, TI and PI significantly decreased.p = 0.003) between the FA content of polychaetes in control versus HPP treatment, as well as between indexes   see .Acinetobacter, Aeromonas, Escherichia coli, Enterobacter, Klebsiella, Photobacterium, Pseudomonas aeruginosa, Salmonella and Vibrio anguillarum), some of which infect fish, decreased to undetectable levels when treated at 300 MPa during 15 min  treated at 310 MPa during 6 min [Oncorhynchus mykiss) and fresh catfish fillets (Silurus glanis) treated at 400, or 600 MPa during 1 and 5 min [Crassostrea gigas) treated at 293 MPa during 2 min [Oncorhynchus kisutch) treated at 135, 170 and 200 MPa during 30 s [Oncorhynchus mykiss) and Mahi Mahi (Coryphaena hippurus) treated at 150, 300, 450, and 600 MPa during 15 min [Salmo salar) treated at 150 MPa and 300 MPa during 15 min [High-pressure processing has been used with success as a food preservation process since the 1990’s . This fo min see . Microornd 5 min ; oystersng 2 min ; coho saing 30 s ; rainbowH. diversicolor, the present study shows that HPP treatment at 300 MPa during 15 min had a significant effect. Even though these results differ from a study where Atlantic salmon  was exposed to the same HPP treatment [Oncorhynchus mykiss); mahi mahi (C. hippurus) [S. salar) [Concerning the effects of HPP on the FA content of reatment , this mareatment . However. salar) ; and Ron. salar) . SFA are. salar) ,37,38. A. salar) ,39. Thes. salar) . The pot. salar) .H. diversicolor. While lipid quality indexes varied significantly in polychaetes of all sizes after exposure to HPP, the nutritional quality of these organisms remained high and certainly of interest for farmers relying on these organisms to trigger maturation in marine fish and shrimp. These results are in agreement with previous findings. It has been previously shown [O. kisutch) display no significant differences. Another study [Scomber scombrus) exposed to 150, 300, 450 MPa with a holding time of 0, 2.5 and 5 min. According to other study [M. merluccius) and sardinella (Sardinella aurita) [In the present study it was expected that the loss of HUFA would be reflected in quality indices. Our results demonstrated that HPP treatment induced a reduction of HUFA, including AA, EPA and DHA in ly shown  that at er study  revealeder study , the dec aurita) .H. diversicolor has a high potential for bioremediation of IMTA systems, as this species is capable of retaining highly valued FA, such as HUFAS  [According to other studies,  and AA) ,10. The H. diversicolor was sampled (five replicates per tank) using a hand corer . In the laboratory, all sampled specimens were sorted into three pre-established size classes  < 30 mm; medium, TL between 30 and 50 mm; and large, TL > 50 mm) and left to depurate for 24 h in aerated containers with pre-combusted sand (at 450 °C for 5 h) and artificial seawater  and freshwater purified by a reverse osmosis unit and matching the salinity of 21 at the IMTA facility). In order to test the effect of HPP in H. diversicolor, six samples of each polychaete size class were weighted to obtain a similar biomass (5 g), with half of those samples (three per size class) being used as a control group (fresh specimens) and the other half being stored in heat sealed hermetic plastic bags and exposed to HPP.Ragworms were cultured under the IMTA set-up described by Marques et al. . At the H. diversicolor samples were exposed to 300 MPa (3000 bar) during 15 min. Other study [High-pressure processing treatment was performing using a hydrostatic press  in a pressure vessel of 35 mm diameter and 100 mm height, at room temperature (21 °C) using as pressurizing fluid a mixture of water and propylene glycol. Hermetic plastic bags with er study  reportedH. diversicolor biomass) and dissolved in 1 mL of the internal standard solution of a fatty acid 21:0 in n-hexane (0.021 g L−1). Afterwards, 0.2 mL of methalonic KOH solution (2 mol L−1) was added, the tube was sealed and mixed vigorously in a vortex shaker for 2 min. Following this procedure, 2 mL of a saturated NaCl solution was added, and centrifugation of the mixture took place for 5 min at 3000 rpm to separate the organic phase. Then 1 mL of organic phase was transferred into a vial and the excess of solvent was evaporated with a stream of nitrogen gas. The dried sample obtained was dissolved in n-hexane (1 mL) and analysed using a GC-FID. The detector and injector were kept at 250 °C, with hydrogen as carrier gas. Fatty acid methyl ester (FAME) were separated in a fused-silica capillary column, DB-FFAP column (30 m × 320 µm × 0.25 µm)  with the following temperature programme: 75 °C , 20 °C min−1 to 155 °C (4 min), 2 °C min−1 to 180 °C (16.5 min), 4 °C min−1 to 250 °C (44 min). The identification of the fatty acids was done by matching the peaks with previously inject internal standards. The FA content (µg mg−1DW) in the analysed samples was calculated considering the relation between mass the area of fatty acids and the internal standard (21:0). In the present study PUFA are defined as all FA with 2 or 3 double bonds and highly unsaturated fatty acids (HUFA) (FA with ≥ 4 double bonds) are considered separately and not within PUFA.The separation of fatty acids methyl esters (FAMEs) was performed using a 7890B gas chromatograph system  with a flame ionization detector (GC-FID) following the methodology described by Aued-Pimentel et al. . The maiLipid quality indexes, namely the atherogenicity index (AI) and thrombogenicity index (TI) were determined according to Ulbricht and Southgate , while tAI and TI can be used to assess the nutritional quality of polychaetes, being calculated through Equations (1) and (2):Concerning PI, this index can be used as a measure of PUFA damage, being a good proxy for lipid oxidation, and can be calculated according to Equation (3):H. diversicolor  in the different treatments (control and HPP), with R values close to one indicating maximum differences between groups and values near zero indicating a complete group overlay. An identical analysis was used to identify if there were any significant differences in lipid quality indexes. To evaluate the percentage that each FA contributed to the dissimilarities recorded between treatments a SIMPER (similarity percentage) analysis was also performed, with those contributing with 50% of cumulative dissimilarities being highlighted. PRIMER v6 with the PERMANOVA+ add-on software  was used to perform all statistical analysis referred above, which are described in detail in [p < 0.05), with STATISTICA v8 software  being used to perform these analyses.A resemblance matrix using the content of each FA on each polychaete sample was prepared using the Bray-Curtis similarity coefficient, after performing a log (x + 1) transformation to emphasize compositional similarity rather than on quantitative differences . A two-wetail in . The exiFrom a biosecurity perspective, HPP can be considered as a suitable approach to treat ragworms and safeguard that these do not act as a pathway for pathogens when fed to valuable fish and shrimp broodstock. When such ragworms are produced under an IMTA framework and display a higher percentage of valuable HUFAs than conspecifics from the wild, there is still a positive trade-off between using this premium polychaetes and sacrificing part of their HUFA content  due to HPP to secure microbiological safety. Overall, the basis for a circular economy is supported using the present approach and contributes to SDG 14 targets concerning aquaculture, as it integrates environmental sustainability, safety and economic growth.


The present case underscores the importance of considering the association of severe thrombocytopenia or immune thrombocytopenia with cytomegalovirus (CMV) infection because CMV‐induced thrombocytopenia occasionally requires antiviral therapy. The present case underscores the importance of considering the association of severe thrombocytopenia or immune thrombocytopenia with cytomegalovirus (CMV) infection because CMV‐induced thrombocytopenia occasionally requires antiviral therapy. However, CMV infection occasionally induces severe thrombocytopenia.It is difficult to distinguish CMV‐induced thrombocytopenia from CMV‐related secondary ITP. However, early detection of CMV infection is paramount because CMV‐induced thrombocytopenia occasionally requires antiviral therapy.22 saturation of 100% on room air. He had neither hepatomegaly nor splenomegaly. A laboratory examination showed a white blood cell count of 23 600/µL with 11.0% atypical lymphocytes, CD4‐positive cell count of 1044/µL, a hemoglobin level of 11.9 g/dL, and platelet count of 4000/µL. Immature platelet fraction was normal (2.9%). CD4/CD8 ratio was also normal (0.82). The size of platelet was normal. The aspartate aminotransferase and alanine aminotransferase levels were 59 IU/L and 55 IU/L, respectively. Immunoglobulin G (IgG), IgA, and IgM were 773, 21, and 50 mg/dL, respectively. A coagulation test was normal. His chest/abdominal CT findings were normal.A 38‐day‐old boy was admitted to our hospital because of the presence of petechiae from trunk to legs and oral wet purpura. His mother was a 35‐year‐old woman  with no remarkable medical history. Her pregnancy course was uncomplicated, and her platelet count was also normal during pregnancy. There were no hemorrhagic episodes during the perinatal period of the boy, and he was born at full term via aspiration delivery. His weight at birth was 3304 g. The baby was breast‐fed and had no remarkable family history. He underwent a medical check‐up on the 31st day after birth, which revealed no particular problems. At admission, he was afebrile with blood pressure of 98/60 mm Hg, pulse of 142/min, respiratory rate of 36/min, and OPlatelet transfusion was performed after admission because ITP was not suspected due to his age. However, his platelet count was only 12 000/µL after platelet transfusion  is the most common cause of severe thrombocytopenia in newborns.In the retrospective analysis, there were no significant differences between CMV‐induced thrombocytopenia and CMV‐related secondary ITP in terms of age, sex, and platelet count at diagnosis.In conclusion, CMV should be evaluated in suspected cases of refractory thrombocytopenia because CMV infection occasionally induces severe and refractory thrombocytopenia, requiring antiviral therapy.The authors have no conflicts of interests to declare.SU, TM, NN, NS, ST, SM, YT, and MK: participated in patient's evaluation and treatment. SU, TM, IM, NN, MK, and KI: reviewed and revised the manuscript. All authors read and approved the final manuscript.


A three-factor-three-level Box-Behnken design (BBD) consisting of 30 experimental runs is employed with three independent variables: initial AMO concentration, catalyst dosage, and pH. The experimental results are analyzed in terms of AMO degradation and mineralization, the latter of which is measured using dissolved organic carbon (DOC). The results show that the photocatalytic degradation of AMO follows pseudo-first-order kinetics. AMO degradation efficiency and the pseudo-first-order rate constants decrease with increasing initial AMO concentration and pH and increase with increasing catalyst dosage. Though AMO degradation is almost fully complete under the experimental conditions, DOC removal is much lower; the highest DOC removal rate is 35.82% after 180 min. Using these experimental results, second-order polynomial response surface models for AMO and DOC removal are constructed. In the AMO removal model, the first-order terms are the most significant contributors to the prediction, followed by the quadratic and interaction terms. Initial AMO concentration and pH have a significant negative impact on the photocatalytic degradation of AMO, while catalyst dosage has a significant positive impact. In contrast, in the DOC removal model, the quadratic terms make the most significant contribution to the prediction and the first-order terms the least. The optimal conditions for the photocatalytic degradation of AMO are found to be an initial AMO concentration of 1.0 μM, a catalyst dosage of 0.104 g/L, and a pH of 4, under which almost complete removal of AMO is achieved (99.99%).This study investigates the photocatalytic degradation of amoxicillin (AMO) by simulated solar irradiation using WO It is also the most commonly prescribed antibiotic in South Korea, with approximately 97 tons of AMO produced annually2. AMO is on the World Health Organization’s List of Essential Medicines, a list of the most important medications needed in a basic health system3. After ingestion, it is excreted in urine and feces and enters aqueous environments through the water cycle 4. AMO has been detected in various sources, including wastewater treatment plants  and raw sewage (280 ng/L) in Australia6; wastewater treatment plants (1.80–622 ng/L) in Italy9; urban effluent  in Spain10; surface water in Australia (200 ng/L)6, the UK (39–245 ng/L)11, and South Korea (0.02–1.07 µg/L)12; and hospital effluent in Australia (900 ng/L)6, Spain10, and Germany (28.0–82.7 µg/L)13. The presence of high levels of AMO has potential risks for ecosystems and human health. For example, toxic effects of AMO on aquatic organisms have been reported in a number of studies, including the blue-green alga Synechococcus leopoliensis7 and the cyanobacterium Microcystis aeruginosa14. AMO has also been reported to cause the premature hatching, malformation, and changes in enzyme activity in both embryonic and adult zebrafish (Danio rerio)15 and to induce oxidative stress in the brain, gills, liver, and kidneys of common carp (Cyprinus carpio)16.Amoxicillin (AMO), a moderate-spectrum bacteriolytic β-lactam antibiotic, was one of the most frequently used antimicrobial agents in 71 countries between 2000 and 2010cle Fig. 4. AMO hain-situ production of highly reactive hydroxyl radicals (•OH) with the help of one or more primary oxidants , energy sources , and/or catalysts 19. Refractory pollutants in water react with •OH, leading to their decomposition or mineralization into CO2, H2O, and inorganic ions19. Previous studies of AOPs, some of which are summarized in Table 20, Fenton21 and photo-Fenton22, UV or solar photolysis with catalysts such as TiO2 and ZnO27). In particular, heterogeneous photocatalysis has shown considerable potential as a versatile, low-cost, environmentally friendly, and sustainable AOP treatment technology for the removal of emerging contaminants, including AMO.With the increased use of AMO worldwide, AMO levels in water and wastewater are expected to rise, so the effective removal of AMO using wastewater treatment processes has become more important. However, conventional treatment processes, which mostly rely on biological treatment, are not effective in eliminating AMO. Therefore, it is necessary to develop new alternatives to remove this pollutant from wastewater. In recent years, various wastewater treatment methods have been proposed for AMO degradation; a subset of these, advanced oxidation processes (AOPs), has been found to be highly efficient in removing AMO from wastewater. AOPs rely on the 2, ZnO, WO3, Fe2O3, CdO, CdS, GaS, GaP, SnO2, ZnS, and SrTiO3) with a light source  to generate highly reactive transitory species  of the catalyst are transferred to the conduction band (CB), generating an electron-hole pair. This leads to the formation of •OH via oxidation, with H2O or OH− molecules reacting with VB holes 2 and CB electrons 2 and UV/ZnO)30. However, the use of UV light in the treatment of large volumes of industrial effluent is not feasible or economical. Hence, researchers have focused on using simulated sunlight and developing solar/visible photocatalysts, which exhibit high activity levels under solar and visible light radiation. Because solar energy is a cheap, abundant, non-polluting, renewable, and readily available energy source in most parts of the world32, solar photocatalysis has become a target green technology for the treatment of water and wastewater.Heterogeneous photocatalysis involves the irradiation of a semiconductor catalyst  has been reported to date. WO3, which has a narrow band gap energy (2.4–2.8 eV), is a visible light responsive catalyst with stable physicochemical properties38. WO3 is physiochemically stable and is mechanically robust in aqueous solutions, while the production of high-purity WO3 is relatively facile and cost-effective, making it a suitable choice for the photocatalytic degradation of organic pollutants under solar irradiation41. Therefore, the objective of this study is to employ WO3-assisted photocatalysis in a simulated solar irradiation system to facilitate AMO degradation.Though a few studies have focused on the degradation of AMO via solar photocatalysis using TiO3-assisted photocatalytic degradation of AMO under simulated solar irradiation are presented in Fig. 42. The VB holes of WO3 have a high oxidation power (EVB = + 3.1–3.2 VNHE), where EVB is the valance band edge at the normal hydrogen electrode (NHE), which facilitates the oxidation of water •OH, as presented in Eqs  via disproportionation with protons , the pH at the zero point charge (pHZPC) for the photocatalyst, and the pH of the medium itself. In general, a suitable ECB  for the CB = −0.28 VNHE, and a neutral or basic pH (≥7.0) supports the formation of •OH and H2O247. Because WO3 has a lower ECB (+0.3–0.5 VNHE), it cannot provide sufficient potential for the reduction of O245. Consequently, •OH is primarily generated via oxidative paths, after which, due to its strong oxidizing ability, it breaks AMO down into smaller intermediates or inorganics such as CO2 and H2O.The proposed reaction mechanisms for the WOd in Eqs  and , a technique commonly used in process analysis and modeling.48. The main objective of RSM is to determine the optimal operating conditions for a given system or to determine a region that satisfies operating specifications. Hence, RSM allows the optimal conditions for various reactions to be identified to reduce time, labor, and material costs. RSM also quantifies the relationships between controllable input parameters and obtained response surfaces. An adequate number of experiments is required to develop a mathematical model for predicting degradation efficiency and to determine the direct and interactive effects of the operating conditions. Central composite design (CCD) and Box–Behnken design (BBD) are the two most common experimental design methods for RSM50. The BBD is more convenient and less expensive than the CCD for the same number of factors. Therefore, we utilize RSM-BBD to optimize the operating conditions and increase the efficiency of AMO degradation.RSM is a collection of mathematical and statistical techniques that are useful for developing, improving, and optimizing various processes. It can be used to evaluate the relative significance of several factors even in the presence of complex interactions3 as a catalyst, (ii) examine the effects of different operating conditions  on the photocatalytic degradation of AMO, and (iii) optimize the operating conditions based on RSM-BBD.In summary, this study aims to (i) assess the AMO degradation and mineralization efficiency of simulated solar irradiation using WO16H19N3O5S, MW: 365.40 g/mol) and tungsten (VI) oxide  were purchased from Sigma-Aldrich, US. The properties of AMO are provided in Table −1) and diluted as required.Amoxicillin  for liquid chromatography coupled with mass spectrometry (LC–MS/MS) analysis. All samples were filtered through 0.20-μm PTFE syringe filters to remove WO3 and were stored in amber glass vials at 4 °C until analysis. The working solutions were continuously stirred during the experiment.The photocatalytic solar irradiation set-up consisted of a light source and a photocatalytic reactor Fig. . The ligCPH analyzer . The standard solution for DOC calibration was prepared using potassium hydrogen phthalate in the range of 1–20 mgC/L.The residual AMO concentration was analyzed using Shimadzu LC-MS 8045. Sample separation was performed using an HSS C18 column  with a gradient elution program using a mobile phase consisting of a mixture of water containing 0.1% formic acid and acetonitrile. Table degradation) and change in the pseudo-first-order rate constant (∆k) of AMO under different experimental conditions were calculated using Eqs kC0 (µМ) is the initial AMO concentration, C (µМ) is the AMO concentration at time t, k (min−1) is the pseudo-first-order rate constant, t (min) is the reaction time, AMO removali and AMO removalj are the degradation efficiency (%) under the experimental conditions i and j, respectively, and ki and kj are the pseudo-first-order rate constants (min−1) under the experimental conditions i and j, respectively. Mineralization based on DOC was determined after 180 min.Degradation kineticsIn this study, RSM based on BBD was employed to optimize the photocatalytic degradation of AMO. The RSM process can be divided into five stages Fig. : (1) selY is the predicted response, Xi and Xj are the independent variables, 48:The experimental data were analyzed using Minitab statistical software  and fitted to a second-order (quadratic) polynomial model as follows:Y is the predicted response, b0 is the model constant, b1, b2, and b3 are the linear coefficients, b12, b13, and b23 are the interaction coefficients, and b11, b22, and b33 are the quadratic coefficients.In this study, we have three independent variables , and the mathematical relationship model is written exclusively asp-values were used to determine the order of the model 51. A multiple regression analysis was performed to fit the response function to the experimental data. The significance of each coefficient was determined from the t-values and associated p-values. Coefficients with t-values greater than 95% or p-values smaller than 0.05 were considered statistically significant.To evaluate the full quadratic approximation of the BBD response surface model, an analysis of variance (ANOVA) for the experimental response was conducted. The F-values and associated 0) against time (t) at different concentrations, as expressed by Eq. (k) was determined from the slope of the linear regression line of ln (C0/C) versus time. The pseudo-first-order rate constants and the linear regression coefficient (R2) for the photodegradation kinetics of AMO are given in Fig. The photodegradation kinetics of AMO followed a pseudo-first-order kinetic model by plotting ln(C/Cd by Eq. . The pse2 ≥ 0.989). This indicates that the degradation of AMO in both simulated solar photolysis and WO3/simulated solar photocatalysis follows pseudo-first-order kinetics with high linear regression coefficients. It was also found that WO3 photocatalysis was much more efficient than direct photolysis in terms of AMO degradation as the pseudo-first-order rate constants for WO3 photocatalysis increased at least 22-fold compared to that for direct photolysis  on photocatalytic degradation, experiments with initial concentrations of 1.0 and 2.0 µМ were carried out. As shown in Figs 0 when the other two parameters  were unchanged. AMO degradation was found to follow a pseudo-first-order kinetic model in all cases. Pseudo-first-order rate constants (k) were calculated from the slope of degradation plots (R2 > 0.986), and it was found that they decreased as C0 increased. More specifically, as the C0 increased from 1.0 µМ to 2.0 µМ, the degradation efficiency and pseudo-first-order rate constants decreased, as calculated using Eqs : ∆degradation = −19.69% (from 90.49% at C0 = 1.0 µМ to 70.79% at C0 = 2.0 µМ) and ∆k = 2.0-fold decrease (from 0.0138 min−1 at C0 = 1.0 µМ to 0.0070 min−1 at C0 = 2.0 µМ).Case 1 : ∆degradation = −6.05% (from 99.51% at C0 = 1.0 µМ to 93.46% at C0 = 2.0 µМ) and ∆k = 2.1-fold decrease (from 0.0315 min−1 at C0 = 1.0 µМ to 0.0150 min−1 at C0 = 2.0 µМ).Case 2 : ∆degradation = −7.65% (from 97.69% at C0 = 1.0 µМ to 90.04% at C0 = 2.0 µМ) and ∆k = 1.6-fold decrease (from 0.0210 min−1 at C0 = 1.0 µМ to 0.0129 min−1 at C0 = 2.0 µМ).Case 3  were calculated from the slopes of the resulting linear plots (R2 > 0.988). Figure k are outlined below:The effect of catalyst dosage on the photocatalytic degradation of AMO was also investigated Figs  and S4, 0 = 1.0 µМ): ∆degradation = 7.20% (from 90.49% at WO3 = 0.1 g/L to 97.69% at WO3 = 0.5 g/L) and ∆k = 1.5-fold increase (from 0.0138 min−1 at WO3 = 0.1 g/L to 0.0210 min−1 at WO3 = 0.5 g/L).Case 1 : ∆degradation = 19.09% (from 71.36% at WO3 = 0.1 g/L to 90.45% at WO3 = 0.5 g/L) and ∆k = 1.9-fold increase (from 0.0072 min−1 at WO3 = 0.1 g/L to 0.0135 min−1 at WO3 = 0.5 g/L).Case 2 : ∆degradation = 19.25% (from 70.79% at WO3 = 0.1 g/L to 90.04% at WO3 = 0.5 g/L) and ∆k = 1.8-fold increase (from 0.0070 min−1 at WO3 = 0.1 g/L to 0.0129 min−1 at WO3 = 0.5 g/L).Case 3 : ∆degradation = 4.87% (from 99.51% at pH 4 to 94.64% at pH 8) and ∆k = 1.8-fold decrease (from 0.0315 min−1 at pH 4 to 0.0171 min−1 at pH 8).Case 1 : ∆degradation = 20.73% (from 92.09% at pH 4 to 71.36% at pH 8) and ∆k = 2.1-fold decrease (from 0.0149 min−1 at pH 4 to 0.0072 min−1 at pH 8).Case 2 : ∆degradation = 15.08% (from 93.46% at pH 4 to 78.38% at pH 8) and ∆k = 1.7-fold decrease (from 0.0150 min−1 at pH 4 to 0.0088 min−1 at pH 8).Case 3 (C3 and AMO. The pH at the point of zero charge (pHZPC) for WO3 is 1.954. Therefore, the WO3 surface is negatively charged above a pH of 1.9. On the other hand, ionic AMO species are positively charged at acidic pH and negatively charged at alkaline pH57. At an acidic pH, AMO and WO3 have opposing charges, thus the electrostatic attraction between the AMO molecules and the catalyst surface increases the absorption rate of AMO onto the WO3 surface, leading to an increase in degradation efficiency and the rate constants. At an alkaline pH, both AMO and WO3 are negatively charged, leading to repulsive forces between the AMO molecules and the WO3 surface. Thus, adsorption onto the surface of WO3 is limited, meaning lower degradation efficiency and rate constants. Therefore, when the pH increased from 4 to 8, the repulsive forces hindered the absorption of AMO onto the WO3 surface. As a result, the AMO degradation efficiency and pseudo-first-order rate constants decreased.This can be explained by changes to the surface charges of WO0 of 1.5 µМ, a WO3 dosage of 0.1 g/L, and a pH of 4. Although AMO removal was high under the same conditions (95.61%), DOC removal was quite low, with a ~40% lower removal rate. This was due to the formation of intermediates that could not be completely mineralized under these experimental conditions. Other studies have reported similar discrepancies between AMO and DOC removal using different AOPs  removal rate of only 18.2% after 20 min. Using Fenton’s reagent treatment, Ay et al.21 reported complete AMO degradation and a TOC removal rate of 37% after 15 min. Therefore, the degradation of AMO does not necessarily lead to the complete mineralization of the products and transformed intermediates of AMO. It should be kept in mind that intermediate products can be toxic in aquatic environments59, thus the optimization of the process parameters should also target complete mineralization as an end goal.To assess the photocatalytic degradation of AMO in terms of mineralization, DOC was measured. Of the 30 experimental runs using three-factor-three-level BBD, the highest DOC removal rate was 35.82% at a C1 , Y2 , Y3 , and Y4  – were expressed as second-order polynomial equations. The complete Box-Behnken design matrix, with the three independent variables  and the predicted and experimental values of the four responses , is presented in Table A three-factor-three-level Box-Behnken design (BBD) consisting of 30 experimental runs was adopted to optimize the experimental data. Three operational parameters – initial AMO concentration , catalyst dosage , and pH (C) – were chosen as independent variables for BBD Table . Because1, Y2, Y3, and Y4 models, respectively) greater than the tabular F-value for α = 0.05  tabular = 3.1860). The p-values of the four models were very low , which confirms that the models were statistically significant at a 5% level. The F-value is a statistically valid measure of how well the factors describe the variation in the data in that the mean and estimated factor effects are real. The p-value is relatively low (p < 0.05), demonstrating the significance of the model. Thus, with their large F-values and small p-values, the four models explain the measured data well, with the corresponding coefficients demonstrating high significance.The quality of the model fit was evaluated using analysis of variance (ANOVA); the results are presented in Table 1 and Y4 was statistically significant (p < 0.05), meaning there was a greater than 5% chance of prediction failure compared to experimental data for AMO removal after 30 min and DOC removal after 180 min. In contrast, the LOF for the models Y2 and Y3 was statistically insignificant , meaning Y2 and Y3 can be successfully used for prediction and optimization. Furthermore, to determine whether the models fit the experimental data well and whether the independent variables had a significant effect on the responses, coefficients of determination (R2) were used. R2 represents the proportion of the variation in the response that is explained by a model and is a statistical measure used for the goodness-of-fit for a model61. R2 always falls between 0 and 1. The closer R2 is to 1, the more closely the model fits the experimental data and the better it can predict the response62. In the present study, R2 was found to be 0.8874, 0.9274, 0.9558, and 0.9049 for the Y1, Y2, Y3, and Y4 models, respectively, indicating that the quadratic polynomial models were a good fit for the experimental results.To evaluate whether the models could successfully be used for prediction, the lack of fit (LOF) was assessed. The LOF for the models Y2 also explain the goodness-of-fit for a model. Adjusted R2 is used to compare the goodness-of-fit for a regression model that contains a differing number of intendant variables. A high value for adjusted R2 indicates high significance, and the smaller the gap between R2 and adjusted R2, the stronger the goodness-of-fit for a model61. Predicted R2 is used to determine how well a regression model is able to make a response prediction. In the present study, adjusted R2 was 0.8368, 0.8948, 0.9359, and 0.8621 for the Y1, Y2, Y3, and Y4 models, representing high significance. Likewise, the small gap between R2 and predicted R2 shown in Table Adjusted and predicted R2 results together confirmed that all of four models were statistically significant and could be used to predict the degradation of AMO using photocatalysis.In addition, the diagnostic plots presented in Fig. 63TPCi, TPCij, and TPCii are the total percentage contribution of the first-order, interaction, and quadratic terms, respectively, and SSi, SSij, and SSii are the computed sum of squares for the first-order, interaction, and quadratic terms, respectively.The quantitative effects of the independent variables in each of the four models were evaluated using the ANOVA results and percentage contributions (PCs) for each individual factor Table . The PCsi) of 90.18% for Y1, 87.98% for Y2, and 81.35% for Y3. The second highest contribution was exhibited by the interaction terms, with a total percentage contribution (TPCij) of 5.52% for Y1, 6.43% for Y2, and 13.31% for Y3. As the reaction time increased from 30 min to 180 min, the contributions of the first-order terms decreased by 8.83%, while those of the quadratic and interaction terms increased by 1.04% and 7.79%, respectively, indicating that the combined effects of the variables on AMO removal increased with increased reaction time, though they were still much less influential than the effects of the variables individually.Figure 1 model , the three first-order terms  and one interaction term (AC) were found to be statistically significant (p < 0.05). In particular, pH (C) exhibited the highest level of significance, with a contribution of 54.05%. The TPCi for the first-order terms was 90.18%, with the lowest contribution shown by the quadratics terms.In the Y2 model , three first-order terms  and two interaction terms (AB and BC) were statistically significant (p < 0.05). The first-order terms had the highest level of significance (with a contribution of 87.98%), followed by the interaction terms and the quadratics terms , all of the terms  were statistically significant for AMO removal (p < 0.05). Based on the results of the three time-specific models , it was found that the first-order terms made the greatest contribution to AMO degradation over the entire reaction time. For the three first-order terms, in the early stages of the reaction process , AMO removal was significantly affected by initial pH, with a contribution of 54.05%, while the roles of other two factors became more important as the reaction time increased.In the Y4), all of the terms except C (p = 0.400) and AB (p = 0.087) were statistically significant. In contrast to Y1–Y3, the first-order terms accounted for only 18.65% of the TPC, while the interaction and quadratic terms exhibited a combined contribution of 93.29% , followed by B2 and C2. In addition, BC accounted for 22.00% of the TPCij of 26.85%.In the 180-min DOC removal model  was selected and analyzed to determine the optimal conditions based on RSM and BBD for AMO degradation efficiency in the proposed photocatalysis process.Over the 30 experimental runs, the highest AMO degradation was 99.64% with C0 versus catalyst dosage  response surface plots and two-dimensional (2D) contour plots for AMO degradation efficiency (%) are presented in Fig. age Fig. , C0 vers pH Fig. , and cat pH Fig. .Figure 90 increased from 1.0 μM to 2.0 μM, while AMO removal only dropped by 6.38% at a dosage of 0.5 g/L. The negative coefficient (−6.21) for A in the response function (Eq. 3.3) also confirmed the antagonistic effect of initial AMO concentration on AMO removal. As mentioned in the previous section, one reason for this inverse relationship between initial AMO concentration and AMO degradation efficiency might be the reduction in the number of available active sites on the photocatalyst surface and the deactivation of the catalyst due to the accumulation of products and reactants on its surface. Conversely, when the catalyst dosage increased, AMO removal increased when the initial AMO concentration was constant. Specifically, at an initial AMO concentration of 1.0 μM, AMO removal increased by 5.84% when catalyst dosage increased from 0.1 g/L to 0.5 g/L. Similarly, at an initial AMO concentration of 2.0 μM, the AMO removal increased by 17.89% for the same increase in catalytic dosage. The positive coefficient (5.93) for B in Eq. (3.3) also confirmed that catalytic dosage had no antagonistic effect on the response. A possible explanation for this may be that there was an increase in the number of available active sites on the photocatalyst, resulting in an increased in •OH generation, and thus greater AMO degradation.Figure 3 = 0.3 g/L). It can be observed that both initial AMO concentration and pH had a negative effect on AMO removal. At pH 4, AMO removal decreased by 7.29%, compared to a decrease of 17.51% at pH 8, when the initial AMO concentration increased from 1.0 μM to 2.0 μM. Similarly, when pH increased from 4 to 8, AMO removal decreased by 5.94% at an initial AMO concentration of 1.0 μM and by 16.15% at an initial AMO concentration of 2.0 μM. The inverse relationship between these two factors and AMO degradation efficiency was also illustrated by the negative coefficients for A (−6.21) and C (−5.53) in Eq. (3.3).Figure The interaction effects of catalyst dosage and pH on AMO degradation efficiency are presented in Fig. One of the main objectives of this study was to find the optimal conditions for the target parameters in order to maximize AMO degradation. Thus, the desired goal was defined as a maximum AMO degradation of 100%. Using Minitab software, the optimal conditions for maximum AMO degradation were found to be an initial AMO concentration of 1.0 μM, a catalyst dosage of 0.104 g/L, and a pH of 4. Under these conditions, AMO and DOC removal after 180 min were predicted to be 99.99% and 24.75%, respectively.3-assisted photocatalytic degradation of AMO with three influencing factors  was investigated using simulated solar irradiation. Based on AMO and DOC removals, the following conclusions were drawn:3 dosage. Compared to almost compete AMO degradations, much lower mineralization  was found, presumably due to the intermediate products formed via AMO oxidation.The photocatalytic degradation of AMO followed pseudo-first-order kinetics. The pseudo-first-order rate constants and degradation efficiencies decreased with increasing initial AMO concentration and pHs, while showed increasing with more WOThe second-order polynomial regression models revealed good fit to the experimental data. The total percentage contributions showed that the highest contributions to AMO removals were by the first-order terms, however, in the regression models of DOC removals, contributions by the quadratic terms were significantly increased.3 dosage of 0.104 g/L, and pH of 4 were found to be optimum conditions for complete removal of AMO.Initial AMO concentration of 1.0 μM, WOIn this study, the WOSupplementary Information


To assess the association between low serum creatinine (SCr) value at admission and the risk of respiratory failure requiring mechanical ventilation in hospitalized patients. A retrospective cohort study was conducted at a tertiary referral hospital. All hospitalized adult patients from 2011 through 2013 who had an admission SCr value were included in this study. Patients who were mechanically ventilated at the time of admission were excluded. Admission creatinine was stratified into 7 groups: ≤0.4, 0.5–0.6, 0.7–0.8, 0.9–1.0, 1.1–1.2, 1.3–1.4, and ≥1.5 mg/dL. The primary outcome was the occurrence of respiratory failure requiring mechanical ventilation during hospitalization. Logistic regression analysis was used to assess the independent risk of respiratory failure based on various admission SCr, using SCr of 0.7–0.8 mg/dL as the reference group in the analysis of all patients and female subgroup and of 0.9–1.0 mg/dL in analysis of male subgroup. A total of 67,045 eligible patients, with the mean admission SCr of 1.0 ± 0.4 mg/dL, were studied. Of these patients, 799 (1.1%) had admission SCr of ≤0.4 mg/dL, and 2886 (4.3%) developed respiratory failure requiring mechanical ventilation during hospitalization. The U-curve relationship between admission SCr and respiratory failure during hospitalization was observed, with the nadir incidence of in-hospital respiratory failure in SCr of 0.7–0.8 mg/dL and increased in-hospital respiratory failure associated with both reduced and elevated admission SCr. After adjustment for confounders, very low admission SCr of ≤0.4 mg/dL was significantly associated with increased in-hospital respiratory failure , exceeding the risk related to markedly elevated admission SCr of ≥1.5 mg/dL . The association remained significant in the subgroup analysis of male and female patients. Low SCr value at admission is independently associated with increased in-hospital respiratory failure requiring mechanical ventilation in hospitalized patients. It is eliminated by kidneys, mostly via glomerular filtration and partly via secretion at proximal tubule2. Therefore, creatinine clearance could be used to estimate the glomerular filtration rate (eGFR) by measuring serum creatinine (SCr), urine creatinine, and volume4. Additionally, SCr can be a reflection of muscle mass and diet. Some patients might have decreased SCr independent of eGFR such as vegetarians, patients with muscle wasting or critically ill individuals7.Creatinine is a breakdown metabolite of creatine phosphate in muscle8. Failure of ventilation is one of the major causes of acute respiratory failure. Management of respiratory failure includes treating the primary cause of respiratory failure and ventilatory support. The respiratory support could include nasal cannula, noninvasive ventilation, invasive ventilation, and ECMO9. In severe respiratory failure, to improve gas exchange and decrease work of breathing, mechanical ventilation is often needed10. Malnutrition, premorbid frailty, and severity of illness  II score) are associated with a higher need of mechanical ventilation among respiratory failure patients. Even though low SCr is associated with poor nutritional status and decreased muscle mass, low SCr has not been reported in the literature to be a predictor of respiratory failure requiring mechanical ventilation.Respiratory failure is a serious condition caused by either lung pathology resulting in imbalances in oxygen or carbon dioxide exchanges. Ventilation of air in the lungs closely depends on strength and workload of respiratory musclesTherefore, our goal is to investigate the association between low SCr at admission and the risk of respiratory failure requiring mechanical ventilation.st, 2011 and December 31st, 2013, who had available SCr measurement at the time of admission. Patients who had end-stage renal disease or were on mechanical ventilation at hospital admission were excluded. ESRD was determined by International Classification of Diseases, 9th Revision, (ICD-9) diagnosis code of 458.21, 585.5, 585.6, 792.5, 996.56, 996.68, and 996.73 or by eGFR < 15 mL/min/1.73 m2. If a patient had recurring hospital admissions throughout the study period, we used only data on the first hospital admission. Mayo Clinic Institutional Review Board reviewed and approved this project (IRB number 15-000024) and waived informed consent due to the minimal risk nature of this study. The study was conducted in accordance with the relevant guidelines and regulations.We conducted this retrospective cohort study at a tertiary referral center care. We explored our hospital database to collect data on all patients aged ≥18 years and admitted to Mayo Clinic, Minnesota, between January 12) at admission. We grouped principal diagnoses based on ICD-9 code. We collected comorbid condition utilizing a previously validated information abstraction algorithm and calculated the Charlson Comorbidity Index (CCI)11 to evaluate comorbidity burden.We collected the needed data from our institutional electronic medical record system. This database comprises demographic characteristics, diagnosis and procedure codes, hospital admission information, flow sheet information of inpatients and outpatients, and results of laboratory test. We defined the admission SCr as the initial SCr level in 24 hours of hospital admission. We categorized admission SCr into 7 groups: ≤0.4, 0.5–0.6, 0.7–0.8, 0.9–1.0, 1.1–1.2, 1.3–1.4 and ≥1.5 mg/dL. We calculated body mass index (BMI) using  for continuous variables. The restricted cubic spline, with six knots were placed at 0.4, 0.6, 0.8, 1.0, 1.2 and 1.4 mg/dL of serum creatinine, was utilized to depict the potential non-linear association between SCr at the admission and risk of respiratory failure requiring mechanical ventilation. In the analysis of all patients, an admission SCr group of 0.7–0.8 mg/dL was used as the reference group for comparison. For the subgroup analyses, we use the same SCr range for female patients, whereas we selected an admission SCr group of 0.9–1.0 mg/dL in the analysis of male patients. These SCr limits were associated with the lowest unadjusted in-hospital mortality. We performed logistic regression analysis to assess the independent association of SCr levels with the development of RF requiring mechanical ventilation during hospitalization. We constructed a multivariable model to adjust for priori–defined covariates, including age, race, sex, BMI, principal diagnosis, CCI, diabetes mellitus, congestive heart failure, coronary artery disease, peripheral vascular disease, stroke, chronic obstructive pulmonary disease, hemiplegia/paraplegia, or cirrhosis. We performed subgroup analysis stratified by sex and tested interaction between sex and admission SCr on respiratory failure outcome. We performed linear regression analysis to assess the independent association between admission SCr levels and mechanical ventilation duration among patients with respiratory failure. As mechanical ventilation duration had a skewed distribution, hence, we summarized duration as median with interquartile range (IQR) and we log-transformed its value before entering into the model . We constructed restricted cubic spline using STATA version 14.1 .We summarize continuous variables as mean ± standard deviation (SD) and categorical variables as number (%).We compared baseline demographics and clinical characteristics between admission SCr groups utilizing the χdel Fig. . We repoThis work was performed at Mayo Clinic in Rochester, MN.2 and 1.0 ± 0.4 mg/dL, respectively. Very low admission SCr of ≤0.4 mg/dL was observed in 779 (1.2%) patients, whereas 6,174 (9.2%) had markedly elevated admission SCr of ≥1.5 mg/dL. Patients with low admission SCr tended to be younger, female, non-White, with lower BMI, and albumin while they had a higher prevalence of hemiplegia/paraplegia. The association of various admission SCr levels with CCI revealed a U-shaped distribution, with a nadir of CCI at an admission SCr of 0.7–0.8 mg/dL (P < 0.001).Among 76,696 hospitalized patients with available SCr at hospital admission through the study period, we excluded 2,702 ESRD patients and 6,949 patients who were on mechanical ventilation at hospital admission to include a total of 67,045 patients in the analysis. Table Among 67,045 patients, 2,886 (4.3%) developed respiratory failure requiring mechanical ventilation during hospitalization. We found a U-shaped distribution for in-hospital respiratory failure and admission SCr levels, with the lowest in-hospital respiratory failure found in patients with admission SCr of 0.7–0.8 mg/dL Fig. . When adAmong 34,722 male patients, the mean admission SCr level was 1.1 ± 0.4 mg/dL. Very low admission SCr of ≤0.4 noted in 139 (0.4%) and 1,737 (5.0%) developed respiratory failure requiring mechanical ventilation during hospitalization. The lowest incidence of in-hospital respiratory failure was in male patients with admission SCr of 0.9–1.0 mg/dL (4.1%). In adjusted analysis, low admission SCr of ≤0.4, 0.5–0.6 mg/dL, and elevated admission SCr of 1.3–1.4, and ≥1.5 mg/dL were significantly associated with higher risk of in-hospital respiratory failure compared with admission SCr of 0.9–1.0 mg/dL Table , Fig. 2.Among 32,323 female patients, the mean admission SCr was 0.8 ± 0.3 mg/dL. Very low admission SCr ≤0.4 was seen in 660 (2.0%) patients, and 1,149 (3.6%) developed respiratory failure requiring mechanical ventilation during hospitalization. The lowest incidence of in-hospital respiratory failure was found in female patients with admission SCr of 0.7–0.8 mg/dL (2.6%). In adjusted analysis, low admission SCr of ≤0.4, 0.5–0.6 mg/dL, and elevated admission SCr of 1.1–1.2, 1.3–1.4, and ≥1.5 mg/dL were significantly associated with increased risk of in-hospital respiratory failure compared with admission SCr of 0.7–0.8 mg/dL Table , Fig. 2.The median duration of mechanical ventilation was 46 (IQR 20-117) hours among patients with respiratory failure. A restricted cubic spline in Fig. Our findings revealed that either SCr ≤0.6 mg/dL or ≥1.1 mg/dL at admission was significantly associated with a higher risk of respiratory failure requiring mechanical ventilation. Low SCr at admission ≤0.6 mg/dL in both men and women was significantly associated with a higher risk of respiratory failure requiring mechanical ventilation. Furthermore, low SCr at admission ≤0.4 mg/dL was significantly associated with longer duration of mechanical ventilation compared to admission level of SCr 0.7–0.8 mg/dL.13, which are strong risk factors for mechanical ventilation and a predictor of difficult weaning for mechanical ventilation as a reserved function of respiratory muscle and diaphragm among these patients is lesser than normal patients14. Moreover, malnutrition also results in weaker cellular mediated immunity and impaired surfactant production16. Even though volume overload could dilute SCr and result in lower levels18, we used SCr at admission before fluid resuscitation occurred and also adjusted for congestive heart failure to reduce the likelihood that fluid overload confounded the association. While high SCr could be due to acute kidney injury originated from the severity of primary illness, sepsis, or other causes20, all these conditions increase the risk of respiratory failure requiring mechanical ventilation as well.To the best of our knowledge, we are the first group to report a lower SCr as an independent predictor for risk of respiratory failure requiring mechanical ventilation as well as an independent predictor for risk of prolonged duration of mechanical ventilation. We also depicted a U-curved association between SCr at admission and risk of respiratory failure requiring mechanical ventilation. Low SCr could reflect muscular wasting or sarcopenia and poor nutritional statusSeveral limitations of this study are worth mentioning. This is a retrospective observational study so most likely there would be some residual confounders. Also, this is a single-center study with mostly White patients which may impact the generalizability of our data. Furthermore, we used only SCr at admission as a laboratory value without considering other laboratory values such as electrolytes or albumin, which might be potential confounders as well. However, there are several strengths to our study. We enrolled a large cohort of 67,045 patients to be able to adjust for several confounders which were specified a priori. Also, we used restricted cubic spline to visualize a potential non-linear association between SCr and risk of respiratory failure requiring mechanical ventilation. Last but not least, we also explored for effect modification by sex on this association.In summary, low SCr level at admission is independently associated with increased in-hospital respiratory failure requiring mechanical ventilation. This association has been observed in patients of both sexes. Additionally, SCr ≤0.4 or ≥1.5 mg/dL were significantly associated with longer duration of mechanical ventilation compared to patients with SCr level at the admission of 0.7–0.8 mg/dL.Supplementary information