Geobacter (40.30%) worked for power generation, while Xanthobacter (11.11%), Bradyrhizobium (9.04%), and Achromobacter (7.30%) functioned in SDZ removal. Actinobacteria mainly clustered in the cathode, in which Microbacterium (9.85%) was responsible for SDZ removal. Bacteroidetes, associated with the degradation of SDZ, showed no significant difference between the anode and cathode. Cathodic and part of anodic bacteria could remove SDZ efficiently in MFCs through synergistic interactions and produce metabolites for exoelectrogenic bacteria. The potential hosts of antibiotic resistance genes (ARGs) presented mainly at the anode, while cathodic bacteria might be responsible for ARGs reduction. This work elucidated the role of microorganisms and their synergistic interaction in MFCs and provided a reference to generate power and remove antibiotics using MFCs.Microbial fuel cells (MFCs) could achieve the removal of antibiotics and generate power in the meantime, a process in which the bacterial community structure played a key role. Previous work has mainly focused on microbes in the anode, while their role in the cathode was seldomly mentioned. Thus, this study explored the bacterial community of both electrodes in MFCs under sulfadiazine (SDZ) pressure. The results showed that the addition of SDZ had a limited effect on the electrochemical performance, and the maximum output voltage was kept at 0.55 V. As the most abundant phylum, Proteobacteria played an important role in both the anode and cathode. Among them,  The misuse and overuse of antibiotics has not only caused environmental pollution, but it has also stimulated the selection of antibiotic resistance genes (ARGs) . Hence, 2, nitrate and nitrite as electron acceptors [2 in the air as an electron acceptor without the cathode chamber, so they could increase the mass transfer effective and reduced cost, and O2 diffusion from air to the cathode would help the removal of nitrogen without aeration. Therefore, air-cathode MFCs also showed excellent performance in removing antibiotics [A microbial fuel cell (MFC) is regarded as a promising alternative treatment to realize waste resource utilization as well as the removal of antibiotics ,3. It incceptors . Antibiocceptors ,5,6, andibiotics ,7,8.2 in the cathode side to the anode chamber to increase the power generation of MFCs [Bacterial community structure played a key role during the power output and contaminant removal in MFCs. Therefore, it is necessary to understand the microbial status in the MFCs to clarify the relationship between power generation and pollutant removal. Previous research revealed that the dominant phylum in MFCs were Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria. The bacteria affiliated with these phyla were classified into two groups (degradation related and exoelectrogenic) . The mec of MFCs . Therefo of MFCs ,17. Yuan of MFCs . The disThis work investigated the efficacy of air-cathode MFCs in wastewater treatment, with SDZ as the representative antibiotic. SDZ is reported to be one of the most common sulfonamides and is used frequently in veterinary medicine . The eleAnalytical reagent sulfadiazine was purchased from Biotopped Science & Technology Co., Ltd. . A graphite fiber brush and carbon cloth were acquired from Cetech CO., Ltd. . The catalyst (20% Pt/C) was obtained from Johnson Matthey Co., Ltd. . The concentration of stock solution for sulfadiazine was 5 g/L and preserved in a 4 °C refrigerator for further use. Other chemicals were purchased from Sinopharm chemical regent Co., Ltd. .The MFC reactors were constructed with a fiber brush anode and carbon cloth cathode . They we4+-N), and total dissolved nitrogen (TDN) were analyzed according to the standard method (See v/v = 25/75), the flow rate was 1 mL/min, and the injection volume was 20 μL.Because there were many suspended solids in the MFCs effluent, it was easy to cause deviation due to uneven sampling. The samples were filtrated by a 0.45-μm filter  and detected. The concentrations of chemical oxygen demand (COD), ammonium-nitrogen  via online monitoring and recording every 30 min. The power density was normalized by the projected surface area of one side of the cathode. A standard three-electrode system was employed for electrochemical tests. The anode was the working electrode, while the cathode was the counter electrode, and Ag/AgCl was used as the reference electrode. Cyclic voltammetry (CV) was carried out on the electrochemical workstation  by sweeping the cell potential from −0.8 V to +0.6 V at a rate of 5 mV/s. Electrochemical impedance spectroscopy (EIS) measurements were conducted at the open circuit voltage (OCV) of the MFCs with the amplitude set to 5 mV and using a frequency range of 100 kHz–0.1 Hz, with the anode chamber filled with a fresh anolyte .intI1, intI2, sul1, sul2, sul3, and sulA were tested, and the primers were set in The samples were collected from the MFCs anode and cathode biofilms in triplicate. The shape of the carbon brush and carbon cloth were different, and for the convenience of the comparison, weight was used for quantification (1/4 of carbon brush and 1/6 of carbon cloth was used for DNA extraction). DNA extraction and real-time quantitative PCR (qPCR) were performed according to methods used in a previous study . DNA samHigh throughput sequencing was performed at Beijing Allwegene Technology Co. Ltd., Beijing, China. See p < 0.05 was considered statistically significant. The changes of the bacterial community at the phylum-level made use of Circos-0.67–7 software , and the networks were performed using Networkx software  (p < 0.05), according to the relative contents of each genu after classification.The basic statistical calculations and analysis were performed using SPSS 23.0  and Origin 9.1 . 4+-N, and TDN was 86.55%, 45.15%, and 45.64% in the MFCs, respectively, and it was 83.46%, 9.56%, and 11.27% in the open circuit treatment, respectively  [The maximum output voltage was 0.55 V c, and thAg/AgCl) . It was Ag/AgCl) . In addiThe goods coverage of all tested samples was 99%, which indicated that the sizes of all libraries were enough to cover the bacterial communities. As shown in Firmicutes, Ignavibacteriae, Chloroflexi, Lentisphaerae, and Euryarchaeota were mainly enriched in the anode, while Actinobacteria mainly clustered in the cathode; Proteobacteria and Bacteroidetes existed both in the anode and cathode . Among tGeobacter , Bradyrhizobium , and Mesorhizobium  affiliated with Alphaproteobacteria were enriched in the cathode  but was scarcely reported in MFCs. They accumulated in the cathodic community in this experiment, possibly due to the fact that Xanthobacter thrives in micro-oxygen environments [Bradyrhizobium could degrade antibiotics via co-metabolism with acetate [Mesorhizobium is an aerobic bacterium using oxygen as the terminal electron acceptor to respire. The possible role of Mesorhizobium was to remove acetate and SDZ degradation products because it could metabolize amino salts, nitrates, and various amino acids using various carbohydrates and organic acid as the carbon source [Azospirillum  affiliated with Alphaproteobacteria was enriched in the anode, which have been reported to be resistant to antibiotics using a wide range of carbon sources [Bradyrhizobium, Mesorhizobium, and Azospirillum could produce extracellular polysaccharides, which supported their metabolism [Achromobacter  and Castellaniella  affiliated with Betaproteobacteria were enriched in the cathode  affiliated with Betaproteobacteria was enriched in the anode as denitrification organisms, which could denitrify under anaerobic conditions and could use the electrode as the electron acceptor [Hydrogenophaga, an autotrophic H2-oxidizing bacteria, could utilize hydrogen as the energy source [Comamonas as facultative anaerobic microorganisms have been isolated from MFCs, which contributed to the power generation with acetate as the electron donor [Hydrogenophaga  and Comamonas ). Pseudomonas , which belong to Gammaproteobacteria, were enriched in the anode  and Dokdonella  affiliated with Gammaproteobacteria were enriched in both the anode and cathode. Stenotrophomonas is able to degrade many xenobiotic aromatic compounds [Dokdonella is usually found in the aerobic biological systems to remove nitrogen and degrade aromatic hydrocarbons simultaneously [Proteobacteria was most abundant in the anode (70.7%) and cathode (62.6%). The difference was further explicated at the class-level a. The moeobacter b. Geobacbacteria ,27. Geobhe anode ,27; ther cathode b. Xanthoronments , as wellronments . Similar acetate . Mesorhin source . Azospir sources . It was tabolism ,31. Achr cathode b. Achromonamides , and Casnditions , so theyacceptor . They coy source . Comamonon donor . They behe anode b. As ele of MFCs , so theyompounds . Dokdoneaneously , so theyp < 0.01)  and Pseudoclavibacter , which belong to Actinobacteria, clustered in the cathode , Mycobacterium (1.03% vs. 0.43%), and Gordonia  affiliated with Actinobacteria existed both in the anode and the cathode  into phthalate, CO2, and other chemicals by decarboxylation, dioxygenation, hydrolysis, and ring-cleavage reactions [Gordonia is an aerobic bacterial genus, but it was found in the anode in previous studies [Actinobacteria were widely used in water treatment field, as they can use glucose, starch, and cellulose as carbon sources . The abu < 0.01) a, due to cathode c. Microb for SDZ ; therefoc sulfur ; therefo cathode c. Rhodocnditions . They conditions . Mycobaceactions . Gordoni studies ,47, whicProteiniphilum  and Petrimonas  affiliated with Bacteroidetes mainly accumulated in the anode  and the cathode (1.17%) (Bacteroidetes were enriched both in the anode (10.28%) and cathode (14.86%) without a significant difference between each other. he anode c, possibtabolism ,49, whic (1.17%) c. ConsidGeobacter; it was responsible for power generation. Alphaproteobacteria, Betaproteobacteria, and Gammaproteobacteria colonized both the anode and cathode and were associated with the degradation of SDZ; Actinobacteria mainly clustered in the cathode, which were responsible for the removal of SDZ; Bacteroidetes showed no significant difference between the anode and cathode, and they were associated with the degradation of SDZ. The nature (aerobic/anaerobic) and function of bacterial genera decided their distribution in the anode and cathode.Generally, Proteobacteria played an important role both in the anode and cathode, without a significant difference as the predominant phylum: Deltaproteobacteria mainly accumulated in the anode, represented by the genus of Geobacter, Pseudomonas, Azospira, and Comamonas) and degradation-related bacteria . Based on the variation of bacterial communities in the biofilms, the ecological model of SDZ biodegradation in air-cathode MFCs was proposed  or Gordonia to low molecular organics. Nitrification bacteria used the O2 from cathode. The oxygen-utilizing of cathodic bacteria can create anoxic zones, offering a favorable zone for denitrifying bacteria and exoelectrogenic bacteria. Almost all cathodic bacteria and part of anodic bacteria were involved in nitrification and denitrification. The microorganisms in air-cathode MFCs can be functionally categorized into the following two groups: exoelectrogenic bacteria (proposed a. Substr2 to form dihydroxyl SDZ (I-①). As mentioned in Mycobacterium might work in the process by deoxygenation. Moreover, Microbacterium was able to degrade SDZ into 2-aminopyrimidine, which was initiated by NADH-dependent ipso-hydroxylation [p-anilinesulfonic acid was further hydrolyzed to generate aniline and sulfate (I-③), or N atoms were bio-consumed to form benzenesulfinic acid (II-②), then leading to the formation of benzene and sulfate. During this process, Pseudoclavibacter was responsible for biodesulfurization. The benzene and catechol can be decomposed into acetate and pyruvate by Proteiniphilun, Petrimonas, Rhodococcus, and Castellaniella . 2-amino-4,6-dihydro-pyrimidine contains more electron-donating functional groups, which render the molecules more prone to electrophilic attack by oxygenases of aerobic bacteria (mainly cathodic bacteria); then, it was decomposed into N2, formic acid, and acetate by nitrifiers/denitrifiers  [Geobacter for power generation. The degradation of SDZ was the result of the synergistic reaction of anodic and cathode bacteria in air-cathode MFCs. O2 was harmful to power generation in MFCs, but it was conducive to remove contaminants. Therefore, the role of O2 in air-cathode MFCs should be reconsidered.Based on published literature, the possible degradation pathway of SDZ is shown in xylation , corresp⑦, II-⑥) . FinallyAll the reactions in air-cathode MFCs can be summarized as follows: (1) Exoelectrogenic bacteria were responsible for power generation in the anode of air-cathode MFCs; (2) The electrons provided by exoelectrogenic bacteria could increase the metabolic reaction of degradation-related bacteria located in the anode and cathode; (3) Degradation-related bacteria might contribute to the power generation by producing metabolites, which could be used as electron donors by the electroactive bacteria. These functional bacteria could effectively remove pollutants and generate power via complex synergistic interactions.intI1, intI2, sul1, and sul2 were detected in the anode and cathode. This is consistent with previous work that showed that sul3 and sulA were not detected in any samples [intI1 and intI2, are natural mobile genetic elements that can capture, integrate, and express resistance gene cassettes with the help of integrase genes. Integrase genes, being important players in ARG transfer, were the driving force for bacterial evolution. Integrons have been reported to be involved in the occurrence of new resistant and pathogenic species [sul2 belong to the latter [intI1, intI2, sul1, and sul2 in the anode was higher than that of the cathode  and function of bacteria decided their distribution in the anode and cathode. The electrons provided by exoelectrogenic bacteria could increase the metabolic reaction of degradation-related bacteria, and degradation-related bacteria might contribute to the power generation by producing secondary metabolites. They could remove SDZ and generate power through synergistic interactions. The potential hosts of ARGs mainly presented in anodic bacteria, while cathodic bacteria possibly played a role in ARG reduction. Regardless, the spread risk of antibiotic resistance should be seriously concerned for both electrodes.


To study the dynamic changes of local metrics in patients with toothache  in the resting state, in order to further understand the changes of central neural mechanism in patients with dental pain and its effect on cognition and emotion.Thirty patients with TA and thirty matched healthy (HC) control volunteers were recruited, and resting-state functional magnetic resonance (rs-MRI) scans were performed on all subjects, and data were analyzed to compare group differences in three dynamic local indices: dynamic regional homogeneity (dReHO), dynamic low-frequency fluctuation amplitude (dALFF) and dynamic fractional low-frequency fluctuation amplitude (dfALFF). In addition, the association between dynamic local metrics in different brain regions of TA patients and scores on the Visual Analog Scale (VAS) and the Hospital Anxiety and Depression Scale (HADS) was investigated by Pearson correlation analysis.p < 0.01, cluster level P < 0.05). Pearson correlation analysis showed that dReHo values of left precuneus and left angular gyrus were positively correlated with VAS scores in TA group. dReHo value of right posterior central gyrus was positively correlated with HADS score (P < 0.05).In this study, we found that The local metrics of TA patients changed with time Compared with the HC group, TA patients showed increased dReHo values in the left superior temporal gyrus, middle frontal gyrus, precentral gyrus, precuneus, angular gyrus, right superior frontal gyrus, middle temporal gyrus, postcentral gyrus and middle frontal gyrus, increased dALFF values in the right superior frontal gyrus, and increased dfALFF values in the right middle temporal gyrus, middle frontal gyrus and right superior occipital gyrus (There are differences in the patterns of neural activity changes in resting-state brain areas of TA patients, and the brain areas that undergo abnormal changes are mainly pain processing brain areas, emotion processing brain areas and pain cognitive modulation brain areas, which help to reveal their underlying neuropathological mechanisms. In the hope of further understanding its effects on cognition and emotion. Toothache (TA) is a common pain in the maxillofacial area, which can be divided into odontogenic and non-odontogenic toothache. Odontogenic toothache mainly due to various irritations of the tooth itself or its surrounding soft tissues, such as pulpitis, periodontitis, pericoronitis, periapical inflammation, and cavities. Previous studies have shown that odontogenic toothache is mainly mediated by Toll-like receptors (TLR). Microbial infection or tissue damage releases endogenous ligands, which activates TLR and leads to the up-regulation of NF-κB, which causes a series of downstream reactions and affects peripheral nerve endings, leading to the generation of pain . Some nors-MRI is a tool to study spontaneous functional alterations in the human brain by measuring changes in blood oxygen level-dependent (BOLD) signals; it is a non-invasive and reproducible tool for studying functional alterations in the brain that is widely used in clinical research –14. StudThis study was based on a sliding window , 28 to sBased on the Declaration of Helsinki, This study was approved by the Institutional Review Board of the First Affiliated Hospital of Nanchang University. Written informed consent was obtained from each subject before the study.Thirty TA patients were recruited from the Department of Dentistry, The First Affiliated Hospital of Nanchang University, Diagnosis by an experienced dentist. thirty volunteers matched for gender, age, and education level of TA patients were also recruited, all of whom were right-handed.The inclusion criteria for the TA group were as follows: 1) Pain in the pulp and/or periodontal tissues caused by dental or non-dental diseases; 2) Acute or chronic TA; 3) No other diseases causing painful symptoms ; 4) Toothache with no obvious etiology that could not be attributed to other diseases; 5) Conventional MRI of the head was normal; 6) All subjects had no contraindications to MRI examination ; 7) Absence of psychiatric and neurological disorders , cardiovascular disease, cerebral infarction, diabetes, hypertension, et al.The exclusion criteria for the TA group were as follows: 1) Presence of non-toothache; 2) First-degree relatives with hereditary non-toothache syndrome; 3) Conventional MRI scan with functional and structural lesions in the brain; 4) History of head and facial trauma and surgery; 5) Contraindications for MRI, such as metal implants or claustrophobia; 6) Psychiatric and neurological disorders, cardiovascular diseases, cerebral infarction, diabetes, hypertension, et al.; 7) Incomplete data from MRI scans or clinical assessment.Inclusion criteria for 30 healthy controls: 1) No symptoms of odontogenic and non-odontogenic toothache; 2) Conventional MRI of the head was normal; 3) Absence of psychiatric and neurological disorders, cardiovascular disease, cerebral infarction, diabetes, hypertension, et al.; 4) Denied a history of drug or alcohol abuse; 5) No other diseases causing painful symptoms.Prior to the MRI scan, the investigators collected clinical information from the subjects, including gender, age, duration of toothache, duration, pain location, past history, and HADS score. The pain level was assessed using a VAS. A 10-cm ruler was used to score the subject's pain from 0 to 10, and a scale of 0–10 was marked on the ruler for the patient to mark the level of pain on the ruler. The higher the score, the greater the intensity of the pain. A score of “0” indicates no pain and “10” indicates severe and intolerable pain. The cognitive function of patients were assessed by MoCA .TE = 2.26 ms, TR = 1,900 ms, flip angle = 9°, acquisition matrix = 256 × 256, field of view = 250 × 250 mm, thickness = 1.0 mm, gap = 0.5 mm, voxel 1.0 × 1.0 × 1.0 mm. rs-fRMI functional image scan parameters TE = 30 ms, TR = 2,000 ms, flip angle = 90°, acquisition matrix = 64 × 64, field of view = 220 × 220 mm, thickness = 4.0 mm, gap = 1.2 mm, voxel 3.0 × 3.0 × 4.0 mm.All participants used a 3.0T magnetic resonance system  scanner with 8-channel phased-array magnetic head coils to collect MRI data in the First Affiliated Hospital of Nanchang University. The subjects were informed of the precautions to be taken and their cooperation was obtained before the scans. During the scans, the subjects were placed supine on the examination bed, head first, The head was immobilized with foam and the subjects were given noise-canceling headphones to reduce head movements and noise effects. During the examination, all subjects were awake and had their eyes closed. Prior to the resting-state functional MRI scans, all subjects underwent routine T1-weighted and T2-weighted image acquisition to exclude many structural brain lesions that could affect brain function and microstructure. Resting-state functional MRI scans included 176 T1 structural images and 240 rs-fRMI functional images.T1 structural images were scanned with At the end of the scan, the image quality should be checked, and if the image does not meet the requirements, the results of this scan should be discarded, or the scan should be repeated with the subject's permission.http://www.MRIcro.com) to analyze the acquired information and exclude incomplete data. Preprocessing of resting-state functional MR images and structural images was performed in the SPM12 (http://www.fil.ion.ucl.ac.uk/spm) and DPABI packages (http://rfmri.org/DPABI)(http://rfmri.org/DPABI) running on Matlab R2018b. The preprocessing steps were as follows: The DICOM format was converted to NIFTI by removing the first 10 time points for each participant to eliminate the effects of magnetic saturation and MRI scanner noise; then time-layer correction and head motion correction for the remaining 230 volumes  toolkit based on DPABI . For dynt-tests and chi-square analyses were performed using statistical software . Age was compared between patients with TA and HCs using a two-sample t-test. Sex differences were determined using chi-square tests.To detect group differences in demographic variables between TAs and HCs, two-sample t-tests in the SPM12 software .Statistical comparisons of dReHO, dAFLL, and dfALFF in the HC and TA groups were performed using two-sample two-sided To further test the reliability of our results for the three dynamic local metrics, we reanalyzed the rs-fMRI data using two additional window lengths (20 and 40 TRs).P < 0.05).Dpabi Viewer software was used to obtain the locations of the brain regions for statistical analysis. The dReHO, dAFLL, and dfALFF values of the abnormal brain regions in the patient group were extracted, and Pearson linear analyses of dReHO, dAFLL, and dfALFF values with VAS and HADS scores were performed using SPSS Statistics , with ages of 26.06 ± 4.85 and 28.20 ± 3.95, respectively .Pearson correlation analysis showed that the dReHo values of the left angular  and leftPain is a common, unpleasant, subjective experience, and is one of the main reasons for visiting a healthcare facility, with approximately 40% of people suffering from different types of pain . Pain prReHo primarily measures the temporal synchrony of regional neural activity between spatially adjacent regions , and dReALFF reflects the power of the brain in the frequency range of 0.01–0.08 Hz, and its measurement of signal intensity in low-frequency oscillations of local spontaneous neural activity can reflect the intensity of spontaneous local fluctuations in the brain . DALFF rThe ratio of the amplitude in the low-frequency range of the fALFF to the total amplitude in the full frequency range reveals the relative effect of a specific low frequency over the entire frequency range . dfALFF Correlation analysis showed that dReHO values of left angular gyrus and left precuneus were positively correlated with VAS scores in TA group. Angular gyrus is a common center connecting multiple networks of “pain matrix,” and precuneus is the central node of DMN. We hypothesized that pain would cause changes in “pain matrix” and DMN, and the more severe the pain, the more obvious the activation., The dReHo values of the right postcentral gyrus was positively correlated with the HADS score. The postcentral gyrus is the primary sensory cortex, part of the “pain matrix,” and is involved in the processing of pain. There is a correlation between pain and anxiety and depression, and the stronger the activation of the postcentral gyrus, the more pronounced the degree of anxiety and depression.In conclusion, patients with TA have abnormal alterations in pain-processing brain regions, emotion-processing brain regions, and pain-cognitive modulation brain regions, and these brain regions and correlate with VAS and HADS scores, suggesting that TA causes abnormal cognitive and emotional alterations, which helps to reveal the underlying neuropathological mechanisms.Although this study revealed dynamic local metric changes in patients with TA, it had some limitations. First, only 30 TA patients were included in this study, which is a small sample size, and this study was a single-center study. We will expand the sample size in subsequent studies. Second, this study was not conducted longitudinally, but mainly as a cross-sectional study. In the future, we will conduct a longitudinal study to observe the treatment methods of TA and the changes in brain function at each treatment stage and compare the treatment effects of each treatment method and each stage. Third, the inclusion criteria for TA patients were not strict, did not further distinguish between acute and chronic TA, and did not clearly distinguish between odontogenic and non-odontogenic pain, In the future, TA will be further refined and classified. Finally, the remaining temporomandibular joint (TMJ)-related problems and toothache caused by bruxism were not included in this study and will be added in later studies to make the study more enriched and reliable. Despite the above and limitations of our study, the pathogenesis of TA can still be considered to be related to abnormalities in specific areas of the brain, which can help to find an objective and reliable neurobiological imaging marker of TA as well as to further understand the effects and modulation of pain on consciousness and cognition.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Medicinal Morality Council of Nanchang University's First Affiliated Hospital. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.YH guided and designed the MRI experiment, besides, they reviewed and revised the manuscript. XT and BL analyzed the resting-state fMRI data. MW and GX analyzed and discussed the ideas of the manuscript. MW organized the results and wrote the manuscript. TW and XZ helped with statistics and graphing. YZ and XL collected resting fMRI data and applied for the ethics. All authors contributed to the article and approved the submitted version.


B, were more than 3. Similarly, the value of an interfacial parameter, K, was less than 1.21  as per the Nicolais–Narkis model, which indicated better interfacial interaction. For composite films, the modified Halpin–Tsai model was revised again by introducing the orientation factor, α, which was 0.333 for the randomly oriented continuous nanofiber-reinforced composites, and the exponential shape factor, ξ = (2In this study, a simple approach was described to investigate the theoretical models for electrospun polymer nanofiber-reinforced nanocomposites. For predicting the tensile strength of the electrospun nylon 6 nanofiber-reinforced polyurethane acrylate composites, conventional Pukanszky, Nicolais–Narkis, Halpin–Tsai, and Neilson models were used, while for Young’s modulus, Halpin–Tsai, modified Halpin–Tsai, and Hui–Shia models were used. As per the Pukanszky model, composite films showed better interaction since the values of the interaction parameter,  Polymer nanocomposites reveal significant high-performance properties using small fractions of nanofillers in the polymer matrices. The excellent properties of nanocomposites have attracted extensive attention in distinct technologies such as automobiles, energy, sensors, fuel cells, agriculture, and biotechnology ,2,3,4,5.During the last few decades, the electrospinning technique experienced substantial progress and attracted researchers from various fields, such as biomedical, sensors, energy, and environmental applications ,10,11. MDue to their higher molecular orientation and higher crystallinity, ultrafine-diameter nanofibers show improved mechanical performance, including tensile strength, Young’s modulus, and toughness compared to microfibers ,18. ManyRecently, many electrospun nanofibers have been successfully employed to reinforce the polymer matrix. Many processes have been reported for the fabrication of nanofiber-reinforced composites, including solution impregnation, layer-by-layer coating, dip-coating, melt mixing with short electrospun nanofibers, in situ fabrication, casting, draining, and subsequent stacking by hot-press ,22,23,24Polymer nanocomposites do not follow the rule of mixture for estimating mechanical properties, as conventional composites do. However, the mechanical characteristics of the composites cannot be estimated correctly due to the small fractions, novel size, and properties of the nanomaterials. Distinct models were suggested to predict the mechanical characteristics of nanofiller-reinforced polymer composites and short fiber-reinforced composites. However, not a single study  has been published on the estimation of mechanical properties of nanofiber-reinforced composites. It is crucial to investigate the mechanical properties with modeling and simulation studies of the nanofiber-reinforced polymer nanocomposites. They became significant motifs because of the need for the advancement of these materials for in high-performance engineering applications. Gao et al. presented a numeric model to evaluate the elastic characteristics of the high-aspect-ratio short aramid fiber-reinforced composites . Sun et cE) of the nylon 6 nanofiber-reinforced polyurethane acrylate nanocomposites (N6/PUA) were evaluated from experimental and theoretical views. The Pukanszky, Nicolais–Narkis, Halpin–Tsai, and Neilson models for the ultimate yield strength, and the Halpin–Tsai, modified Halpin–Tsai, and Hui−Shia model were used, assuming randomly oriented continuous nanofibers. Moreover, the assumptions of these models showed good agreement with the experimental results.In this study, the ultimate tensile strength and Young’s modulus /formic acid  polymer solution was used as a precursor solution to electrospun nanofibers using electrospinning units . Difunctional polyurethane acrylate oligomer  and isobornyl acrylate monomer diluent (Miramer M1140) were supplied by Miwon Specialty Chemicals Co. Ltd., Jeonbuk-do, Korea. Irgacure 184D  was used as a photocatalyst.2, Arc system). The detailed procedures of the electrospinning of nylon 6, fabrication of N6/PUA nanocomposites, and characterizations were reported in our earlier research [The UV-curable polyurethane acrylate (PUA) matrix system was formulated with 50% difunctional polyurethane acrylate oligomer, 45% isobornyl acrylate monomer (as a diluent), and 5% of Irgacure 184D. Nylon 6 nanofiber-reinforced polyurethane acrylate nanocomposite films were fabricated by over-coating the nanofibers on the PUA matrix system, which consisted of casting, electrospinning, and UV curing. The formulated UV-curable PUA matrix system was cast on the glass substrate, and nylon 6 nanofibers were electrospun on the PUA-coated glass substrate for different deposition times  without any break. Afterward, the nanocomposite was cured in a conveyor-belt-type UV-curing machine LZ-U101  fixed with a gallium lamp , parameter B can be calculated with Equation (2):The Pukanszky model  explainecσ) and tensile yield stress of a polymer matrix (mσ) deviates as a two-thirds power law function, with K as an interfacial parameter for filler matrix adhesion. Equation (3) is stated as follows:For the Nicolais–Narkis model, the ratio of the tensile yield stress of the composite (fϕ), filler properties, structure, and interfacial interaction. If the adhesion between the filler and matrix polymer is not established, then the filler cannot bear the applied load, and the whole load is transferred to the matrix phase. In this equation, the parameter K counts for the adhesion between the reinforcement (filler) and matrix. The lower the K value, the stronger the adhesion. For an extreme case of weak adhesion, the theoretical value of K is 1.21 [The mechanical characteristics of the nanocomposites rely on the volume fraction  and (5), as follows:icient K , as statφ as a filler packing factor. According to the Neilson model, the tensile strength is given as the following Equations (8) and (9):Similarly, the Neilson model is termed the modified Halpin–Tsai model, as Neilson revised the original equation by introducing maxφ is the maximum packing fraction constant, and it is 0.82 for randomly oriented fibers.cE of several nanocomposites, where the reinforcement is in the form of nanofibers, nanotubes, nanorods, and nanoparticles with capricious aspect ratios [fE, cE, and mE are the Young’s modulus of the fiber, composite, and matrix, respectively. fϕ is the nanofiber volume fraction, and η is the shape factor relating to the reinforcement geometry. τ is the aspect ratio lThe Halpin–Tsai Model anticipates the t ratios ,33,34,35α, accounted for the randomly oriented fiber. Likewise, in this case, the orientation factor, α, accounted for the randomly oriented fibers. If the length of the fiber is larger than the thickness of the samples, the fibers are assumed to be randomly oriented, and the value of the parameter is considered to be 0.333 (α = 1/3). If the length of the fiber is much smaller than the thickness of the specimen in randomly oriented fiber composites, then α = 1/6 is used [The Halpin–Tsai model (Equations (10) and (11)) correlates the modulus of the unidirectional fiber composites to the fiber volume fraction. This model cannot authentically predict the modulus of nanofiber-reinforced polymer nanocomposites, since it does not deliberate definite features of the nanofibers such as their high surface area, very high aspect ratio of nanofibers, dispersion of the nanofibers, and exceptional Young’s modulus of the nanofibers. However, nanofiber-reinforced polymer nanocomposites have a random alignment of the nanofibers in the matrix. Much research explored anticipating the modulus of randomly aligned fiber-reinforced composites by modifying the Halpin–Tsai model ,36,37. I is used ,36,38,39τ, to the ξ = –(20) are stated as follows:α’ is the converse of the aspect ratio , and g is assumed to be a geometric parameter of composites, which is expressed in Equations (18) and (19). Equation (18) refers to the incorporation of fiber-shaped fillers, while Equation (19) is applicable to the incorporation of flake- or plate-like nanofillers. Additionally, for a flawless interface, g would be stated in Equation (20).The Hui–Shia model equation broadens the estimation of  fillers . The HuicE, tensile strengths, and % elongation were collected according to the average six sample estimates for an individual case. The mechanical characteristics of N6/PUA nanocomposites are noted in cE of the nanocomposites were enhanced with the introduction of nylon 6 nanofibers. There were no significant variations observed in % strains compared to the reference samples for each composite.The discrepancy is much more familiar in modeling nanocomposite properties by the conventional rule of mixture or micromechanics models. In this section, we implemented the different models, and compared model predictions with the same set of available experimental data compiled in the previous study . The matB was determined by befitting experimental values with the mathematical values, and derived from the minimum sum of squares of variance more than from experimental values of composite strength. Pukanszky’s model underestimated the experimental data with the tensile strength of nanofiber-reinforced nanocomposites, when constant B = 0. It means that the nanofiber-reinforced nanocomposites dominated with better interfacial adhesion amongst the polymer nanofibers and matrices, and thus amelioration in tensile properties was depicted with the embodiment of reinforcement of the nanofibers. For the curve fitting, the constant B values were calculated by employing Equation (2), constant B values were 6.82, 5.75, 5.05, 4.27, and 4.04 for the N-15, N-30, N-60, N-2 h, and N-4 h N6/PUA nanocomposites, respectively, which indicated that nanofiber-reinforced nanocomposites at a nanofiber content from 0.004 to 0.066 vol%, revealed better interfacial bonding, resulting in more effective filler–matrix load transfer.The theoretical values of tensile strength were estimated with the Pukanszky model using Equations (1) and (2), and compared to the experimental values of nylon 6 nanofiber-reinforced PUA polymer nanocomposites. The constant K were considered as 1, −1, −2, and −5 for the Nicolais–Narkis model. Using values of K, the tensile strength was estimated for the composites using Equation (1). As shown in K values were approximately −5 for the N6/PUA matrix composites.The theoretical predictions of tensile strength were compared employing the Nicolais–Narkis model Equation (3) and compared to the experimental values, as depicted in φ, the values were quite similar to the Halpin–Tsai equation  and (5). However, the experimental and Halpin–Tsai model values showed higher bound values than the experimental values for the high-volume fraction of the nanofibers in composites. After modification of the Halpin–Tsai equation by Neilson with the introduction of factor equation b.cE of the N6/PUA nanocomposites with the different volume fractions are plotted in cE of not merely unidirectional aligned fiber-reinforced composites, but also of several nanocomposites where the reinforcement phase has functionality relating to the aspect ratio in regards to CNF, CNTs, and cellulose nanofibers. As shown in cE as the volume fraction of nanofibers is enhanced. The experimental data of relative strength and the predictions of the model did not properly follow the experimental data at numerous nanofibers concentrations because of the absence of some parameters, such as an alignment of the nanofibers, shape factor, and aggregation in the composites.The deviations of ξ and orientation factor α were introduced, and modified the model as shown in Equations (12) and (13). In this research, ξ values were assumed and the graph was plotted for nanofiber-reinforced composites, as shown in cE of nanofiber-reinforced nanocomposites, and it was clearly found that the calculations were above the experimental data as volume fractions of the nanofibers increased in the composites. There was no significant difference observed for ξ > 200. Furthermore, the ξ  had the form of ξ =  and (13) with the following exponential shape factor:After periodically modifying the coefficients of aggregation ξ. In this study, the shape factor ξ was picked to conceal the randomly aligned nanofibers with different volume fractions, and it underrated the value of cE of the nanofibers loading to a little below 0.008% volume fraction. Moreover, the mechanical characteristics of the composites at marginally higher wt% of nanofibers were a little overestimated using this modified model by reasonably extrapolating results.However, model Equations (12) and (13), associated with Equation (21), are termed the modified Halpin–Tsai equation for nanofiber-reinforced composites. cE of the nanofiber-reinforced composites, α’, an inverse of the aspect ratio was correlated with the perfect interface geometric parameter g [α’ = 0.001). Therefore, for calculating the geometric parameter g, Equation (19) was used, and it perfectly matched with the values from Equation (20). It is well known that the orientation of the dispersed phase has a substantial effect on the composite cE. It was evidenced from their geometry that disk- or plate-like fillers can contribute equal reinforcement in two directions if proportionately oriented, while fibers contribute primary reinforcement in one direction. In this case, the nanofibers were randomly oriented, and if the longitudinal modulus and transverse modulus were known, the effective modulus of the composite in all orthogonal directions [cE,E11, and E22 are effective, longitudinal, and transverse Young’s moduli of the composite, respectively. x is the constant to govern the stress transfer amongst the fibers and matrix systems in the composites, which is based on the curve fitting with experimental data (0 < x < 1). As shown in x was calculated to be about 0.9, but it could only provide a rough estimation for cE of randomly oriented nanofiber-reinforced composites. The percentage errors of cE prediction for nanofiber-reinforced composites became much less than the experimental result data, and theoretical predictions appeared to overestimate experimental result data at higher volume fractions. The overestimated results could be based on the geometric constants engaged in the equation.Hui–Shia model Equations (14) and (15) demonstrated higher aspect ratio estimation with the presence of randomly oriented fillers in matrix systems, and an increasing degree of fiber aggregation with increasing fiber content. For predicting the ameter g ,40,41. Trections  could beFrom the above analysis, we can identify that in order to obtain more precise predictions of the tensile properties of nanofiber-reinforced polymer nanocomposites, nanofiber aspect ratio, distribution of nanofibers, and volume fraction of the nanofibers are fundamentally important. These models simultaneously review these parameters and ensure a simple approach to predict the mechanical characteristics of the nanofiber-reinforced polymer nanocomposites. However, it is a significant challenge to establish a more comprehensive model capable of considering the nanofiber geometry, agglomeration, critical nanofiber length, and so on, which is the subject of future research.fV). Additionally, theoretical values predicted using the modified Halpin–Tsai model showed close agreement with the available experimental values of Young’s modulus, due to the introduction of exponential shape factor ξ in the form of ξ = (2A comparative study among the experimental results and several theoretical models of filler reinforcement was implemented to predict the mechanical characteristics of electrospun nylon 6 nanofiber-reinforced PUA nanocomposites. Our findings suggested that the theoretical results predicted employing the Pukanszky model and Nicolais–Narkis model are in close agreement with the tensile strength experimental values of the nanofiber-reinforced nanocomposites. Meanwhile, the Neilson and Halpin–Tsai models of tensile strength showed higher bound values than the experimental values for the high-volume fraction of the nanofibers in composites (for 0.033 and 0.066


Serofast status after therapy in syphilis patients is a common phenomenon. A proportion of patients who have serofast status exhibit abnormal cerebrospinal fluid test results, which can be defined as asymptomatic neurosyphilis (ANS); however, it remains unclear whether ANS patients can achieve serological cure after anti-neurosyphilis treatment as quickly as other serofast patients. In this study, non-treponemal pallidum antibody serological responses were studied in ANS and serofast control patients, and the cumulative rates of serological cure in the ANS group were 9.6, 22.1, 25.9, and 30.2% in 3, 6, 9, and 12 month after treatment, which were statistically higher than those of the serofast control group. The change gap in serological cure rates was even more pronounced within 6 months after treatment, but the majority of ANS patients had no change in serofast status at 12 months after treatment. Our study indicates that anti-neurosyphilis therapy can partially change the serofast status. As serofast status cannot easily be changed even under neurosyphilis treatment in the majority of patients, the pathogenesis of this condition needs further research. Syphilis is an old disease that can cause serious health problems without treatment. Since the introduction of penicillin in 1943, there have been great improvements in syphilis treatment. Theoretically, syphilis is a sexually transmitted disease that can be cured. However, in actual clinical settings, judging whether syphilis has already been cured is not an easy task . The etiTreponema pallidum infecting the central nervous system, which can occur at any stage of syphilis. ANS is a type of neurosyphilis without any neurological symptoms, and its diagnosis relies on CSF test abnormalities, including positive venereal disease laboratory research tests (VDRL), abnormal white blood cell (WBC) counts, and elevated protein , whereas categorical variables are described by numbers and percentages. Associations between categorical variables were assessed using the chi-square test. Titers were obtained 3, 6, 9, and 12 months after enrollment, and Kaplan–Meier product-limit survival curves were used to examine the rates of serologic response to treatment. All hypothesis testing was two-sided, and P = 0.023). The serum RPR titer of the ANS group was higher than that of the serofast control group at the time of lumbar puncture .According to the recommended CSF assessment criteria for asymptomatic serofast patients, 445 HIV-negative serofast syphilis patients were enrolled in Beijing Ditan Hospital, Capital Medical University, between September 2015 and August 2018. All of the patients had received lumbar puncture for CSF testing, and the median time from first diagnosis of syphilis to lumbar puncture was 24  months. Through CSF examination, 136 participants (30.6%) exhibited an abnormal CSF test that could be diagnosed as ANS (ANS group), whereas 309 participants (69.4%) exhibited a normal CSF test result (serofast control group). The demographic and clinical characteristics of the two groups are listed in The patients in the ANS group were treated with aqueous crystalline penicillin G, 4 million units IV every 4 h for 14 days, followed by benzathine penicillin G, 2.4 million units IM weekly for 3 weeks. Re-treatment was not recommended in the serofast control group. All of the participants were followed every 3 months for serological tests.The proportion of evaluable participants who exhibited serological response varied by group and time after therapy. The rates of serological cure at 3, 6, 9, and 12 months are shown in Survival analyses using the log-rank test were conducted to determine the proportion of patients with unchanged serofast status. The time-dependent accumulated serological cure rates after treatment at 3, 6, 9, and 12 months are shown in Some researchers have suggested CSF FTA-ABS as an exclusion criterion for neurosyphilis diagnosis, but others disagree . We testThe rates of serological cure were 10.7, 25.3, 30.7, and 33.3% in the CSF FTA-ABS IgG(+) patients at 3, 6, 9, and 12 months, respectively. In contrast, the rates of serological cure were 8.2, 18, 21.3, and 26.2% at 3, 6, 9, and 12 months, respectively, in the CSF FTA-ABS IgG(-) patients. The difference in serological cure rates between the two groups was not significant .Despite the availability of effective treatments, 15–20% of persons with early syphilis are referred to as being serofast, and the incidence of serofast status in late syphilis is much higher . At presIn the present study, 136 serofast patients with abnormal CSF tests were treated according to the guideline for neurosyphilis therapy. As expected, a decline in RPR titer was observed as early as 3 months after treatment as compared with the control group. The rates of serologic cure gradually increased over time, from 9.6% in the third month to 22.1, 25.9, and 30.2% at 6, 9, and 12 months, respectively. A significant difference in serological cure rates as compared with the control group was observed. Our results demonstrate the benefit of serological cure in ANS patients after treatment and indicate the importance of screening for ANS in serofast patients. Treatment with a neurosyphilis-directed regimen could significantly improve the serological cure rate in this group of patients.Some research has suggested that CSF FTA-ABS might be better suited to exclude rather than confirm a diagnosis of neurosyphilis, but there are limitations to CSF treponemal testing, as the negative predictive value of any test is dependent on the prevalence of the condition in the population in which the test is undertaken . TherefoThe survival curve chart clearly shows that the increase in the serological cure rate of syphilis is more obvious after 3 months and 6 months of neurosyphilis treatment, and the gap in the syphilis serological cure rate trend between the ANS group and the serofast control group became steady after 6 months. Although the difference in serological cure rates between the ANS group and serofast control group with neurosyphilis treatment was statistically significant, nearly 70% of cases in the ANS group retained serofast status at 12 months after treatment. In our previous study, the neuron damage biomarker of symptomatic neurosyphilis was not present in the majority of patients with ANS  of patients in the 6 months after anti-neurosyphilis treatment in the ANS group. Good adherence to CSF testing during long-term follow-up is difficult in actual clinical settings. Although all ANS patients had undergone a full course of anti-neurosyphilis treatment, we could not determine the percentage of ANS patients in which the CSF returned to normal; Second, Although there was no statistical difference in the serological cure rate between the CSF FTA-ABS(+) and CSF FTA-ABS (-) groups, there was a difference in the serological cure rate between the two groups, which needs to be further studied with an enlarged sample size in the future. Third, there were some difference in baseline age and RPR titers between ANS and serofast control groups, which might reflected the facts in real world, we don’t think these difference will influence the results, Since the inclusion and exclusion criteria were the same, the indicator for evaluating the treatment effect was the change in RPR titer before and after treatment, rather than a direct comparison of RPR titers. Some studies suggest that the RRP titer declines more slowly in the elderly, but in this study, although there is a difference in age between the two groups, the older patients are in the ANS group, which may affect the serum cure rate of some ANS patients, but The statistical results of the comparison between the two groups were not affected.ANS is one of reasons for serofast status of syphilis patient, this study demonstrated that some ANS could achieve serological cure after anti-neurosyphilis treatment, However, a significant proportion of ANS remained serofast status after 1 year of treatment, and the reasons deserve further investigation.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by the Institutional Ethics Committee of Beijing Ditan Hospital, Capital Medical University. The patients/participants provided their written informed consent to participate in this study.JL and W-HL wrote the main manuscript text. T-WZ, CZ, and H-WY collected the clinical data. All authors contributed to the article and approved the submitted version.


Trichobilharzia sp. “peregra” from the snail host Radix balthica in a subarctic lake under both natural and laboratory seasonal conditions. We demonstrated a circadian rhythm with the highest emergence during the morning hours, being seasonally independent of the photo- and thermo-period regimes of subarctic summer and autumn, as well as relatively high production of cercariae at low temperatures typical of northern environments. These patterns were consistent under both field and laboratory conditions. While light intensity triggered and prolonged cercarial emergence, the temperature had little effect on cercarial rhythms but regulated seasonal output rates. This suggests an adaptive strategy of bird schistosomes to compensate for the narrow transmission window. Our results fill a gap in our knowledge of the transmission dynamics and success of bird schistosomes under high latitude conditions that may serve as a basis for elucidating future potential risks and implementing control measures related to the spread of cercarial dermatitis due to global warming.The emergence of cercariae from infected mollusks is considered one of the most important adaptive strategies for maintaining the trematode life cycle. Short transmission opportunities of cercariae are often compensated by periodic daily rhythms in the cercarial release. However, there are virtually no data on the cercarial emergence of bird schistosomes from freshwater ecosystems in northern latitudes. We investigated the daily cercarial emergence rhythms of the bird schistosome  Schistosoma) in the tropics and subtropics [Trichobilharzia being the most common causative agents of this water-borne eruptive skin disease in temperate zones [Schistosomes are digenetic trematodes that cause human schistosomiasis  to cete zones . Schistote zones ,10,11,12te zones ,14,15,16te zones ,17.Trichobilharzia [Lymnaea stagnalis–Trichobilharzia szidati [The transmission opportunities of non-feeding and short-lived cercariae  are oftilharzia ,4,5, par szidati ,30,31,33 szidati  and wateIn addition to light exposure, the cercarial release from infected snails is strongly regulated by temperature, both with respect to emergence rhythms and increased cercarial output at elevated temperatures  were also assessed. Based on the literature records, the effect of light is expected to be reflected in diurnal emergence, with chronobiological circadian patterns peaking once in the morning hours after the onset of illumination, regardless of the season. Temperature changes are expected to regulate seasonal cercarial output rates toward higher emergence in the summer. In contrast, we expect an overall mild temperature effect on cercarial diel rhythms due to small daily fluctuations in water temperature within each season in the subarctic lacustrine environment.Radix balthica  (Gastropoda: Lymnaeidae) examined between 2016–2018, 99 snails (3.2%) were infected with Trichobilharzia sp. “peregra” , of which 65 snails released cercariae, although none in October 2016 and 2017 , indicating comparable snail sizes and thus a negligible effect of the snail size on the seasonal/annual variation in cercarial output rates.The daily output rates of cercariae in the field differed between years and seasons, with a higher emergence in August than in October, as well as in August 2018 compared to August 2016 and 2017 . CercariTrichobilharzia sp. “peregra” from their Radix balthica snail hosts under different seasonal light and temperature conditions in a subarctic lacustrine environment. Current knowledge on the cercarial emergence patterns and rates from molluscan hosts in the Arctic and subarctic is still scarce and almost exclusively includes marine trematodes  or 6 and 12 h diel intervals (August 2016 and 2018). Patterns in cercarial emergence are often trematode-specific [Trichobilharzia and snails from different latitudes in Europe and North America between 44°–56°N, where most research efforts have focused [Trichobilharzia species is probably independent of the snail host species and parasite geographical distribution, and thus of the wide range of seasonal temperature and light conditions under which they live.In accordance with our first expectation based on literature records on the cercarial emergence of bird schistosomes, the cercariae of specific ,65 and tspecific ,22,23. B focused ,29,30,31Trichobilharzia sp. “peregra” were consistent in both summer and autumn, indicating a stable seasonal pattern in the occurrence of emergence peaks, similarly to other trematodes and schistosomes [Trichobilharzia sp. “peregra” found in the autumn were likely due to the exceptionally warm summer in August 2018, which resulted in about 2 °C warmer water in the lake, accelerating trematode development and thus cercarial release in the autumn [In addition, cercarial rhythms of stosomes ,42,65. Ae autumn ,48,64,66e autumn ,49,52) aTrichobilharzia sp. “peregra” was also strongly light- and temperature-dependent, but with different effects on daily emergence rates and rhythms. First, the diurnal shedding was prolonged during polar days in summer with 20 h continuous daylight, consistent with the extensive evidence from marine trematodes in Arctic areas [Schistosoma spp. [Trichobilharzia sp. “peregra” in our study were only light-regulated such that the release of almost all cercariae was triggered at sunrise, followed by a steady decline during the day and inhibition at dark. This is confirmed by the highest shedding in the morning when light intensity was still low (range of 11–236 Lx during different seasons and years). Nonetheless, light intensity appeared to influence individual emergence patterns from snail hosts, depending on weather changes. While heterogeneous emergence in summer 2017 was likely determined by variable conditions, alternating rainy, cloudy and sunny days, more stable rhythms were observed during sunny weather in summer 2018. Prokofiev et al. [Trichobilharzia sp. “peregra”, with a large phenotype that may facilitate parasite transmission [Light and temperature are the most important and often interacting factors affecting the emergence of cercariae from snail hosts  and theic areas , but seeoma spp. ,22,43. Toma spp. . Second,oma spp. ,64. Birdoma spp. ,8,14,16 v et al.  suggestev et al. ,67,68. Asmission .Trichobilharzia sp. “peregra”. In freshwater ecosystems at northern latitudes, daily and seasonal variations in water temperature  are less pronounced  and thit study, ,48,64. Hal range ), our real range ,40,41,70al range . Such a al range ,60,61,62al range . For exaperature . This superature . In addiperature ,56, are perature ,72,73, wTrichobilharzia sp. “peregra”. In addition, multiple infections with trematodes in snail hosts usually lead to reduced cercarial production and eventually to the exclusion of the less competitive subordinate species [Diplostomum, Plagiorchis) or weak  competitive ability towards the generally subordinate Trichobilharzia [Trichobilharzia sp. “peregra” appeared to be unaffected, as the number of cercariae emerging from double-infected snails was in the range or even higher than that observed from single infections. Other factors such as multiple genotypes of conspecific trematodes, the condition of the snail host in relation to food availability, age and intensity of infection, or experimental conditions may also cause variation in the cercarial output [Trichobilharzia sp. “peregra” in the laboratory followed the same consistent pattern as in the field.Several factors other than light and temperature could have contributed to the variable output rates, either at the total  or individual emergence level. For example, the increased cercarial output could be due to larger snails providing more space for parasite multiplication and subsequent cercarial production ,74,75. A species ,77,78. Il output ,80,81. IAnas penelope, Anas platyrhynchos, Aythya fuligula, Bucephala clangula) are considered possible definitive hosts of Trichobilharzia sp. “peregra” [The cercariae emerge from the snails as a result of a stimuli-dependent process (temperature and/or light) that is also usually synchronized with the chronobiological behavior of the next host in the parasite’s life cycle when the chances of a mutual encounter are higher ,17,19. Tperegra” . The cerperegra” ,84, indiperegra” ,21,22,23In summary, our study highlights an important feature for the successful transmission of bird schistosomes in subarctic environments, namely well-established adaptations to adverse climatic conditions. This was evident in prolonged emergence during summer, relatively high output rates in cold waters, and some degree of polymorphism in cercarial emergence in response to local environmental conditions. These observations complement our previous findings on the functional and ecological roles of bird schistosomes and other trematode taxa ,56,57,58Radix balthica snails were collected by hand in the littoral zone (<1 m depth) of the subarctic freshwater Lake Takvatn in northern Norway . Takvatn is an oligotrophic dimictic lake at an altitude of 214 m above sea level, with a surface area of 15 km2 and a maximum depth of ca. 80 m. The lake is usually ice-free for 5–6 months from mid-June to late November. Radix balthica is the dominant molluscan species and first intermediate host for the majority of larval trematodes in Takvatn (19 of 24 species/lineages), of which Trichobilharzia franki haplotype “peregra” sensu Jouet et al. (2010)  is the ilharzia ,55,56,58Trichobilharzia sp. “peregra” prevalence in snail populations  until the start of the acclimatization process when snails were kept without food also during all field and laboratory experiments. None of the experimental snails harbored double infections prior to the start of experiments. Snails were dissected at the end or during experiments (due to spontaneous death) to confirm their infection status.Sampling and emergence experiments were conducted from 2016–2018 in August and October, representing two seasons (summer and autumn) with distinct water temperature and light conditions . In total 3058 snails were collected and individually screened for trematode patent infections , followed by snail dissections for prepatent infections  when no cercarial shedding was observed for two days in order to determine the overall and ulations . Snail p Takvatn ,55,56,57re found . Althoughe study . All expTrichobilharzia sp. “peregra” was monitored in two types of experiments: (i) in the field under natural photo- and thermo-periods, and (ii) in the laboratory under simulation of field conditions. Cercarial emergence of in situ for two days prior to the start of the experiments. (i) In the field experiments, experimental snails were placed into 40 mL transparent plastic beakers filled with filtered lake water  and attached to an experimental metal device designed to immerse the beakers in the water . At the (ii) The laboratory experiments were conducted after a three-day acclimatization period of snails in a climatic chamber; a temperature- and irradiance-controlled room allowing an automatic adjustment to specific values according to daily and seasonal temperature and light fluctuations in the field. The lake water was tempered to the selected temperature before the laboratory experiments.Temperature and light intensity parameters were measured every five minutes using data loggers (Onset HOBO UA-002-64 Pendant 64 K) during all field and laboratory experiments. In addition, weather condition was visually monitored in the field in terms of recording sunny, rainy and cloudy days. The meteorological conditions within daylight during the field experiments in August 2016 consisted of the first two days with alternating sunny and cloudy weather and the third being a sunny day. In August 2017, the first day was mostly cloudy, while it was sunny in the mornings with occasional overcast until noon, followed by cloudy and rainy afternoons with occasional sunshine during the remaining two days of experiments. In August 2018, all three days were sunny. In this year, an unusually warm summer was recorded throughout Europe with exceptionally high Arctic temperatures relative to the long-term average and the hottest summer ever recorded in Norway, with air temperatures even exceeding 30 °C, which is 10 to 15 °C above the normal range for July and August . TypicalIn situ emergence was therefore conducted in a side stream flowing into Lake Takvatn , enabling us to identify emergence peaks. However, a different number of intervals per day was used in the field and laboratory experiments Table A1In subsequent years 2017 and 2018, the experimental constructions were improved to be fully submerged directly in the lake (at a depth of 15 cm and a distance of 3 m from shore), using a transparent lid covering the beakers with experimental snails c,d. All Daily rhythms with emergence peaks were determined according to the protocol described in Vyhlídalová and Soldánová . BrieflyThe use of different diel intervals August 2016), high mortality rates of infected snails resulting in an incomparable number of replicates (August 2017), and the low numbers of emerged cercariae in general (October 2018) or during some intervals (August 2018) Table A116, high Trichobilharzia-infected snails collected at different years and seasons, and a selection of snails with similar sizes was impossible due to low number of available replicates or low shedding (p < 0.05.Daily output rates were tested in relation to snail size (shell length) because larger snails usually produce more cercariae ,74,75. Eshedding Table A1shedding Table A1


Fbln4SMKO mice (n = 10) at ages two and six months. The results of the simulations were used to quantify potential biofluidic biomarkers, complementing the geometrical biomarkers obtained directly from the images. Comparing the different geometrical and biofluidic biomarkers to the mouse lifespan, it was found that mean oscillatory shear index (OSImean) and minimum time-averaged wall shear stress (TAWSSmin) at six months showed the largest correlation with lifespan , with both correlations being positive . When change between two and six months was considered, the change in TAWSSmin showed a much stronger correlation than OSImean (r2 = 0.75 vs. 0.24), and the correlation was negative . The results highlight potential biomarkers of ATAA outcomes that can be obtained through noninvasive imaging and computational simulations.The prediction of risk to the patient in ascending thoracic aortic aneurysm (ATAA) is a significant challenge and the subject of much active research. In the present work, a combination of mouse model experiments and computer simulations was used to explore potential biomarkers that correlate with mouse lifespan, used as a surrogate for risk of a catastrophic event. Image-based, mouse-specific fluid-structure-interaction models were developed for  They affect approximately 15,000 people in the US per year and, in critical cases, they will grow in size and eventually rupture. When an ATAA ruptures, it can be fatal in up to 80% of the cases . The criNumerous biomarkers –8] have have8] hin vivo measurement of aortic wall mechanical properties  ha hain vivoperties .Fbln4SMKO mouse model , , p, pFbln4S2.2.1We used a combination of experimental and numerical techniques to capture changes in the geometry, mechanical properties, and fluid-solid dynamics during the development and formation of ATAA in mice. 2.2SMKOFbln4) were used in this study ..(4)σs⋅p is the spatially averaged pressure at each outlet, Q is the inflow rate at each outlet, dR is the distal resistance, pR is the proximal resistance, and C is the compliance of the downstream vasculature. The values for dR, pR, and C were based on literature , an, an45], mean   ar armax)  an an67] anhis area , 72] of ofin vivhis area , for exahis area  may provhis area , which i1776342_Sup_Info


Furthermore, we also focus on the contribution of the atrial natriuretic peptide, cyclooxygenase, renin–angiotensin–aldosterone system, and endothelin on hyperfiltration. Proposing potential treatments based on these mechanisms may offer new therapeutic opportunities to reduce the renal burden in this population.In the existing stages of diabetic kidney disease (DKD), the first stage of DKD is called the preclinical stage, characterized by glomerular hyperfiltration, an abnormally elevated glomerular filtration rate. Glomerular hyperfiltration is an independent risk factor for accelerated deterioration of renal function and progression of nephropathy, which is associated with a high risk for metabolic and cardiovascular disease. It is imperative to understand hyperfiltration and identify potential treatments to delay DKD progress. This paper summarizes the current mechanisms of hyperfiltration in early DKD. We pay close attention to the effect of glucose reabsorption mediated by sodium–glucose cotransporters and renal growth on hyperfiltration in DKD patients, as well as the mechanisms of nitric oxide and adenosine actions on renal afferent arterioles  Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease, and its diagnostic standards include a decline in renal function, diabetic retinopathy, urine albumin-to-creatinine ratio increases, and a reduction in the glomerular filtration rate (GFR) . Due to 51Cr-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) to measure GFR in the 1990s (99mTc-DTPA) clearance (Glomerular hyperfiltration is observed in type 1 diabetes mellitus (T1DM) and T2DM . At preshe 1990s , while ilearance . On the learance , 23. Notlearance . In T1DMlearance , 19, 24.learance . TherefoTo date, the most common hypothesis about the mechanisms of diabetic hyperfiltration is the tubular event , 25–34. Nearly 180 g of glucose is filtrated by the renal glomerulus every day, and little-to-no concentration of glucose is present in the urine, which is related to the reabsorption of the renal tubule. Glucose appears in urine when filtered glucose surpasses the maximum renal absorptive capacity. SGLTs are present in proximal tubules  where soThere are two dominating SGLTs in the proximal tubule that are responsible for glucose reabsorption, SGLT2 and SGLT1 . Evidenc+ levels and induced diabetic hyperfiltration and kidney injury , which, in turn, excites many carriers including the Naycosuria , 58. In ycosuria . Similarycosuria . This obycosuria . Hence, ycosuria .The contribution of a newly oral antidiabetic drug, SGLT2 inhibitors (SGLT2is), has been well established in T1DM and T2DM. It recovers the signal of TGF by increasing the concentration of sodium in macula densa, ameliorating glomerular hypertension and hyperfiltration to the same extent as the tubular hypothesis . ReducinWhile SGLT1, as a main protein carrier of intestinal glucose absorption, also has great therapeutic potential , a dual At the onset of diabetes, kidneys grow due to expanded nephron size; renal hypertrophy occurs mainly in the cortex of the diabetic kidney and is linked to subsequent proximal tubular hyperreabsorption , 55. UehBased on a renal tubule growth phenotype, researchers found an inverse relationship between dietary NaCl intake and GFR, which is called salt paradox . In otheTGF is a negative feedback system, which is modulated by sensing the concentration of sodium chloride in the macula densa , 77. TGFExcept for A1AR-mediated vasoconstriction in the low concentration range, the adenosine diphasic response has been shown in the isolation and perfusion of renal glomerular arterioles . AnotherIn addition, A2bAR has a pathogenic effect in early glomerular dysfunction in diabetic rats . An expeNO was thought to be a powerful vasodilator . The incRecent research has proposed a novel idea that increased production of NOS-dependent NO in the macula densa results from sensing elevated glucose concentration in the luminal of macula densa through SGLT1, thereby reducing TGF activity resulting in hyperfiltration –100. RaiMeanwhile, this pathway can also be activated after a high-protein meal . Accordi2 (PGE2), prostaglandin I2 (PGI2), prostaglandin F2 alpha (PGF2α), and thromboxane B2 (The COX-metabolite of arachidonic acid is prostaglandins (PGs); it plays a pivotal role in regulating the renal blood flow and GFR. Several observations in the diabetic mice model have verified that renal PGs are increased, including prostaglandin Eoxane B2 , 105. Inoxane B2 . Both meoxane B2 .2 and PGI2  receptor, strengthens the effect of ANP and mitigates the hyperfiltration and renal tubular injury in the animal models of early DKD . This maRegarding the intrarenal hemodynamic alterations, the role of RAAS cannot be ignored –121. AngFurthermore, angiotensin 1-7 (Ang1-7)-mediated production by angiotensin- converting enzyme2 is also associated with hyperfiltration . Ren et A receptor located on the vascular smooth muscle stimulates vascular constriction, whereas the release of NO and PG triggers vasodilation through the ETB receptor , is vital in maintaining the homeostasis of sodium and water, as well as controlling the glomerular vascular tone and hemodynamics . Like Anreceptor , 130. Unreceptor . Elevatereceptor . Recentlreceptor . Evidencreceptor , 130. Rereceptor , 131. Enreceptor –136. Desreceptor  and whetWith increasing attention to the DKD, there is growing evidence that hyperfiltration affects the progression of DKD. It occurs through a variety of mechanisms, including glucose reabsorption mediated by SGLTs, renal growth, the adenosine signal, and SGLT1-NOS1-pathway; all of these elevate GFR through weakened TGF signaling. While vasoactive mediators cause changes in GFR by altering the vascular resistance of the afferent and efferent arterioles, we attempt to propose underlying therapies to improve hyperfiltration. Clinical trials have demonstrated the renal protective effect of SGLT2is and RAAS inhibition. Upregulated A2aAR, PKC-β inhibitors, and endothelin-receptor antagonists provide new ideas for delaying the progression of DKD, but their limitations also need to be considered. Further studies of renal prognosis are needed to assess the long-term effectiveness and safety of these strategies.YY: conceptualization, software, writing—original draft. GX: idea, funds, and paper revision. All authors contributed to the article and approved the submitted version.This work was supported by the National Natural Science Foundation of China (No. 81970583 & 82060138), the Nature Science Foundation of Jiangxi Province (No. 20202BABL206025), and the Projects in the Second Affiliated Hospital of Nanchang University (No. 2019YNLZ12008).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Result: A total of 24 studies and 2306 patients were included. The PSD-related lobar and deep brain regions included the insular cortex, frontal lobe, temporal gyrus, basal ganglia, postcentral, precentral, precuneus, corona radiate, etc. Among these brain regions, the insular cortex was most frequently reported (taking up 54.2%) in the included studies. Furthermore, the total incidence rate of PSD was around 40.4%, and the incidence of male was nearly 2.57 times as much as that of female . Conclusions: In lobar and deep brain regions, the insular cortex may be most relevant to PSD and aspiration, which may be a potentially promising target in the treatment of PSD.Objective: To investigate the relationship of lobar and deep brain regions with post-stroke dysphagia (PSD). Method: The databases of Medline, Embase, Web of Science, and Cochrane Library were searched from the establishment to May 2022. Studies that investigated the effects of lesions in lobar and deep brain regions on swallowing function after stroke were screened. The primary outcomes were PSD-related brain regions . The secondary outcomes were the incidence rate of PSD. The brain regions with the most overlap in the included studies were considered to be most relevant to PSD, and were presented as percentages. Data were compared utilizing the  Strokes are common diseases; in the aggregate, they are among the leading causes of mortality and long-term disability in developed countries, and their incidence is increasing as the population ages. There are an estimated 100 million individuals living with stroke sequelae worldwide, which has an enormous impact on patients’ quality of life and raises the financial burden of medical treatment ,3,4. EarThe medulla oblongata is usually considered to be the swallowing center, where the swallowing central pattern generator (swCPG) participates in the coordinated contraction of lingual, pharyngeal, and laryngeal muscles ,10. HoweNeuroimaging technologies, including functional magnetic resonance imaging (fMRI), make it possible to identify the relationship between brain regions and PSD ,19,20. MSeveral studies have reported that neuroanatomical location is linked to the incidence, severity, and characteristics of PSD ,17,24,25Medline, Embase, Web of Science, and the Cochrane Library were systematically searched from the establishment to May 2022. We manually searched the related studies with the MESH term “stroke” or “post-stroke” or “poststroke” or “hemiplegia” or “hemiparesis” or “paresis” or “paretic” or “hemipareticand” and “lesion” or “site” or “region” and “dysphagia” or “swallowing disorder” or “deglutition”. A hand search was additionally performed to screen the articles to further clarify potentially eligible studies in the pre-selected articles. The full search strategy and Mesh terms were detailed in the Inclusion criteria were: (1) detailed brain regions related to stroke were confirmed by MRI or CT; (2) age >18 years old; (3) swallowing function was evaluated by VFSS, FEES, or clinical evaluations; (4) studies published in English; (5) case-control studies; (6) prospective or retrospective cohort studies with consecutive enrollment; (7) randomized controlled trials; and (8) human as a study population. Excluded criteria were: (1) the detailed brain regions and swallowing function were not described; (2) studies were not published in English.Two well-trained evaluators (JQ and XC) independently extracted data from the abstract, original texts, additional appendices, and protocols. Disagreements were resolved by discussion with the third author (ZMW). The studied were screened for review as per the Population, Intervention, Comparison, Outcomes, and Study design (PICOS) criteria . Full teWe utilized relevant elements from the Cochrane Collaboration’s risk of bias checklist . Two autwww.nitrc.org/projects/bnv/ (accessed on 31 October 2017) and Mricon software (www. mccauslandcenter.sc.edu/MRIcro/mricron (accessed on 2 May 2016). Differences between groups were identified by the two-tailed independent-sample t-tests or χ2 analyses for continuous variables and frequency-based variables (as appropriate). All statistical analyses were performed using SPSS software .The brain regions with the most overlap in the included studies were considered to be most relevant to PSD. The cortical surface maps were generated by BrainNet viewer software  meet the inclusion criteria and are included in the final analysis. n = 1712) of the population were male. The median sample size was 95 (ranging from 20 to 342). Thirteen of the included studies were supratentorial strokes [Of 24 studies (2306 patients), the median age of participants was 68.60 (age range from 61.1 to 75.0 years), and 57.24% n = 17 of the p strokes ,33,34,35 strokes , and sev strokes ,40,41,42 strokes ,44, one  strokes , while tAs shown in The swallowing assessment tools included the Water Swallowing Test (WST) ,43, VideThe MRI was used for the diagnosis of stroke in the 24 articles, in which four articles reported using DWI scans ,34,35,43The PSD-related lobar and deep brain regions included insular cortex  ,37,39,41A total of twelve studies reported the effect of the insular cortex on PSD. These studies were conducted on an acute phase of stroke, investigated the potential lesion pattern related to PSD, and found that the right insular cortex is related to swallowing dysfunction and predictive for the development of dysphagia ,16,29. AThe aspiration-related brain regions included insular cortex (8.3%) ,42, pariThe incidence rates of PSD were 63.6%, 41.1%, 54.9%, 82.5%, 48%, 35%, 47.8%, and 50% in acute phase of stroke ,41,43,442 = 196.17, p < 0.001), while there was no statistical difference in incidence rate between ischemic and hemorrhagic stroke groups , as well as right and left hemispheric stroke groups   .brainsciThe present study found that the PSD-related lobar and deep brain regions included the insular cortex, frontal lobe, temporal gyrus, basal ganglia, postcentral, precentral, precuneus, corona radiate, etc., in which the insular cortex might be most relevant to PSD and aspiration after PSD and was reported in 54.2% of included studies. Furthermore, the total incidence rate of PSD was around 40.4%, and the incidence of male was nearly 2.57 times as much as that of female.The swallowing function is not only regulated by the medulla oblongata, but by the lobar and deep brain regions. Different lobar and deep brain regions participate in different aspects of swallowing function. For example, lobar regions like the parietal–temporal lobes are associated with oropharyngeal residue, while the somatosensory cortex governs and executes motions by controlling and providing feedback to the brainstem and is responsible for the laryngeal elevation and vestibular closure ,45. BesiThe present study found that the insular cortex may be most relevant to PSD. The insular cortex is involved in an overwhelming variety of functions, including decision-making, complex social functions, addiction, and sensory processing, to represent feelings ,48. It iThe aspiration is a common but serious sequela after PSD and is associated with abnormal swallow–breathing coordination . The insMeanwhile, the lobar and deep brain neural networks also play an important role in swallow–breathing coordination. On the one hand, the insular cortex participates in the coordination of swallowing function. The previous studies adopted fMRI to explore the features of the cerebral cortex for PSD patients and found that the insular cortex was activated obviously during the swallowing task . For heaOn the other hand, the insular cortex also participates in the coordination of respiratory function. Brain imaging studies have provided evidence that dyspnea is associated with activation of the insular cortex . MeanwhiAccording to the previous research, we proposed a new hypothesis for the mechanism of the insular cortex on aspiration after PSD. Firstly, the brainstem receives input signals from peripheral organs , in which the swCPG and rCPG located in the brainstem are reciprocal inhibition. Secondly, the thalamus receives input signals from the brainstem. Eventually, the insular cortex receives input signals from the thalamus. The stroke in the insular cortex may disturb the reciprocal inhibition relationship of swCPG and rCPG, which may lead to PSD and aspiration after PSD .Several suggestions can be recommended according to our results. Firstly, the insular cortex participates in the various aspects of swallowing and can be a potentially promising target for the treatment of aspiration. For example, noninvasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), is a practical technique which has proved effective, and is widely used to promote the recovery of PSD . HoweverThe present study has several limitations. First, the relationship between the brain stem and dysphagia is not investigated in the present study. Second, only studies that presented detailed stroke lesion sites were included, while those on the large areas of the brain regions were excluded, which might cause potential bias. Third, the studies included in the present research were limited to those in English, which may lead to bias. Fourth, the relationship between brain lesions and dysphagia after stroke was investigated based on qualitative analysis rather than quantitative analysis due to the limited data. Therefore, high-quality quantitative analysis studies are needed.The PSD-related lobar and deep brain regions included the insular cortex, frontal lobe, parietal lobe, basal ganglia, etc., in which insular cortex may be the area most relevant to PSD and aspiration after PSD.