Dear Editor,Sarcoptes scabiei var. homini, and mainly occurs in immunocompromised populations or people with poor sanitary conditions.Crusted or Norwegian scabies is an uncommon but highly contagious form of scabies, which is caused by the mite A 62-year-old man who complained of scaled plaques on the glans and buttocks for 2-years was referred to our clinic. Two years ago, the patient noticed some red papules on his glans and buttocks with an itching sensation, and the lesions gradually fused as plaques with white scales. He had been multiply diagnosed with psoriasis vulgaris and prescribed topical steroid treatment such as triamcinolone for a long time without significant improvement. The patient has a medical history of type 1 diabetes mellitus for more than 15-years but has never been well controlled.Treponema pallidum particle agglutination and HIV were both negative. A biopsy from his glans lesions revealed numerous mites and eggs transects in the stratum corneum (Physical examination revealed erythematous plaques covered with thick white scales on the glans and gluteal region , and sma corneum . A diagn corneum .Figure 1Previous studies have shown that several pre-existing conditions may predispose these crusted scabies, such as AIDS, T-cell lymphoma, Down syndrome and immunosuppression in transplant recipients.Crusted scabies is characterized by massive colonization of mites in the epidermis, which lead to keratinocytic hyperplasia, crusted or superimposed eruptions. Psoriasis is one of the important differential diagnosis. Interestingly, it was reported that patients with scabies have a higher risk of subsequent psoriasis.Inappropriate treatment can lead to the worsening of lesions. Using topical corticosteroids can decrease pro-inflammatory cytokines and phagocyte activity, which can thus alter the natural course of scabies, which lead to reduced immune responses and an itching sensation and then promote a crusted scabies appearance.None declared.Yuanyuan Wang: Approval of the final version of the manuscript; elaboration and writing of the manuscript; effective participation in research orientation; critical review of the literature.Yeqiang Liu: Approval of the final version of the manuscript; effective participation in research orientation; intellectual participation in pathology research of the case; critical review of the manuscript.Fu-Quan Long: Fu-Quan Long: Approval of the final version of the manuscript; conception and planning of the study; critical review of the literature and manuscript; elaboration and writing of the manuscript, and in charge of the whole manuscript.None declared.


Recent advances in studies of ionic liquids (IL) and ionic liquid–solvent mixtures are reviewed. Selected experimental, simulation, and theoretical results for electrochemical, thermodynamical, and structural properties of IL and IL-solvent mixtures are described. Special attention is paid to phenomena that are not predicted by the classical theories of the electrical double layer or disagree strongly with these theories. We focus on structural properties, especially on distribution of ions near electrodes, on electrical double layer capacitance, on effects of confinement, including decay length of a dissjoining pressure between confinig plates, and on demixing phase transition. In particular, effects of the demixing phase transition on electrochemical properties of ionic liquid–solvent mixtures for different degrees of confinement are presented. Ionic liquids (ILs) and IL–solvent mixtures (ILS) have turn into the research focus in electrochemistry due to their intriguing properties, such as exceptional electrochemical and thermal stability and low vapor pressure that make them attractive materials for several applications ,2. NamelFor various industrial applications of fluids and fluid mixtures, confinement effects play a very important role . ILs undMost of the studies of IL-solvent mixtures confined by micro and mesopores have been focused on thermodynamic states far from phase transitions. Nevertheless, fluids under confinement show an interesting physics close to state transformations. Typical examples are the wetting transition and the capillary condensation ,30,31 whIL-solvent mixtures can undergo a demixing phase transition, in analogy to charge-neutral liquids, and in recent experiments, phase diagrams for various ILs and various solvents have been determined. In particular, organic IL with a polar solvent like water can phase-separate at room temperature, and the critical point of this phase separation is of the order of 400 K. The studies of the phase separation in IL-solvent mixtures concerned mainly the bulk systems. The investigation of the effect of proximity to the demixing phase transition on electrochemical properties of confined IL-solvent mixtures has started only very recently ,36,37.In this review, we describe the classical theories of electrical double layers briefly and define the fundamental quantities in Electrical double layer (EDL) results from the formation of a ‘cloud’ rich in ions with a charge of a sign opposite to the surface charge (known as counterions) and poor in ions of the same sign (known as coions). The EDL width is determined by the interplay between the ions’ thermal motion, which tends to homogenize their distribution, and the Coulombic attraction of the counterions to the surface and repulsion of the coions from it ,39.Helmholtz proposed the first model for describing EDLs in 1853. In his model, the surface charge was neutralized by counterions which were assumed to be adsorbed at the electrode surface . This moT temperature. The Debye screening length characterizes the thickness of the EDL, while the Bjerrum length is the distance between the ions at which the Coulomb potential equals the thermal energy In the early 20th century, the achievements of Gouy, Chapman, Debye, Hückel, and Langmuir developed the classical theory of electrolytes and the so-called Poisson-Boltzmann (PB) model gathered such achievements ,42. In tU −, [NO3]− and [BF4]− as alternative anions. The resulting ILs were easy to manipulate and awaken scientific attention due to their particular properties. The third generation of ILs exhibits tunable chemical and physical properties depending upon the desired applications −), and such a difference has been attributed to the electron delocalization and the hydrogen bonding absence. In the case of thermal stability, Ngo et al. [− > [Tf2N]− ∼ [BF4]− > halides. Concerning the cation size, there is no significant effect when increasing the size from 1-butyl to 1-octyl ([BMIM]+ to [OMIM]+). Regarding the viscosity, Xu et al. ,3635,36]capillary ionization that is analogous to the capillary condensation can occur. At the capillary ionization transition, the IL-rich phase condenses in the pore for the chemical potential of ions corresponding to the stability of the IL-poor phase in bulk. The studies of the effect of the capillary ionization on electrochemical properties of IL-solvent mixtures confined in mesopores, however, started only very recently capillaryT for tentials c, and thprofiles  one can profiles b, the chQ (see Equation (Q are both continuous functions of voltage. At Equation ) and theEquation ), respecCapillary ionization transition is accompanied by an abrupt increase of the charge accumulated in the pore. This fact has important consequences for the capacitance c and theU  structural properties and patterns formed by ions near electrodes, (ii) effects of confinement, in particular the dependence of the disjoining pressure between confining plates on the concentration of ions in IL-solvent mixtures (iii) electrical double-layer capacitance, stored energy and charge, especially near the demixing phase transition in IL-solvent mixtures and (iv) capillary ionization transition in porous electrodes and its effect on capacitance, energy and charge. On the one hand, there is a need for a theoretical explanation of experimental results that contradict classical theories, and on the other hand, there are theoretical predictions that need to be verified by simulations and experiments. The first case concerns, in particular, the structure and mechanical properties of confined IL-solvent mixtures. The second case concerns the theoretical predictions of the effects of phase transitions on electrochemical properties of IL-solvent mixtures near a single electrode and in slit-shaped pores. These predictions have been confirmed in simulation studies of a coarse-grained model of IL-solvent mixture , but sti


In today's society, the prevention and treatment of diabetes mellitus and its subsequent complications have brought trouble to human beings. Complications caused by diabetes bring not only physical and mental pain to patients but also a heavy economic burden to families. And once diabetic complications occur, they are often irreversible and very difficult. At present, some studies suggest that nanotechnology can treat some diabetic complications. This paper reviews the application of nanotechnology in the repair of diabetic segmental bone injury, the healing of diabetic skin ulcers, the therapeutic effect, and improvement strategies and deficiencies of nanotechnology in diabetic complications. Diabetes is a common disease in life. Its long-term hyperglycemia will cause damage to the various tissues and organs of the body and may lead to complications. These complications will have a significant impact on patients, with diabetic complications involving acute metabolic disorders such as DKA and hyperosmolar hyperglycemia syndrome; there are some common chronic complications of diabetes such as diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, peripheral neuropathy, diabetic foot, segmental bone injury, and other complications . DiabetiNanotechnology, as a newly developed discipline, has been innovative and applied in the fields of materials science, environmental science, biological science, medicine, chemistry, and so on. In recent years, more and more research has applied nanotechnology to the study of diabetic complications, mainly including treatment and strategy. This paper is going to review this part.Nanotechnology is a new and important technology in the 21st century. It is a kind of science and technology that uses single atom and molecule to make materials. It studies the properties and applications of materials with structure size ranging from 0.1 to 100 nm. Through the arrangement and combination of various particles, a new arrangement of matter is created. With the rapid development of nanotechnology, it has been widely used in medicine, materials science, electronic industry, energy industry, and other disciplines and fields . NanomatNanoemulsion is a nonequilibrium system with an average particle size of 1-100 nm in the proper proportion of oil phase, water phase, and surfactant. It has low viscosity, high efficiency, high permeability, low preparation difficulty, and high safety. It can improve the bioavailability. Because of its special particle size, it also has slow release and targeting effects .At the same time, according to the characteristics of the drug and the different emulsion, it has different ways of administration: transdermal administration, oral administration, mucosal administration, injection administration, etc. .The nanomaterials are hydrogel, a three-dimensional network system with a particle size less than 200 nm . With thIn recent years, nanotechnology has played an important role in the diagnosis and treatment of diabetes , 39. It In recent years, with the continuous improvement of people's living standards and quality, people's dietary structure and daily habits have undergone great changes, which also makes the incidence of diabetes increased. In recent years, the number of diabetic patients in the world has increased year by year and the global prevalence rate of diabetes 9.3% in 2019 . DiabeteDiabetic nephropathy (DN) is one of the main causes of nephropathy. At present, there is no effective means to prevent the occurrence and development of DN, and the prevention and treatment of DN have not achieved satisfactory results. In recent years, nanotechnology has been added to the treatment of DN, which can improve the efficacy of drugs and the prognosis of patients with diabetes, thus effectively reducing the pain and economic pressure of patients. The pathogenesis of DN is complex, including the mutation of genetic factors; the imbalance of glucose metabolism leads to the activation of multiple endocrine pathways; there is a production of a large number of endothelial nitric oxide synthase and advanced glycation end products (ages); the inhibition of the formation of nitric oxide is also an inducing condition of the disease, including insulin inhibition, inflammatory reactions, and renal hemodynamic changes. These conditions jointly promote the occurrence and development of the DN Exhibition , 44. Stuβ1 and fibronectin) and inflammatory cytokines including MCP-1 and TNF-α and significantly reduced the activation of NF-κB expression and PKC activity. According to the existing research results, we can conclude that CT-PLGA-NPs can reduce diabetic nephropathy through antifibrosis and anti-inflammatory effects.Poly(lactic-co-glycolic acid) (PLGA) is a kind of synthetic polymer material. Yang  developeAhangarpour et al.  evaluateThe nanoliposomes containing Eprosartan mesylate were prepared by Ahad et al. , in STZ-Diabetic retinopathy (DR), with an increasing number of diabetic patients, has become the first cause of blindness in 16-64 years of age . The pre2) nanoparticles. It can effectively inhibit angiogenesis in vitro and has no toxic effect on the retina. Intravitreal injection of particles also inhibited neovascularization. This study shows that TiO2 nanoparticles can be used in the treatment of retinopathy mouse models at the concentration level [Nanotechnology is widely used in the treatment of DR and has entered a new stage and has been applied in clinical practice. Some researchers have developed silicate (SI) nanoparticles and tested their antiangiogenesis effects on retinal neovascularization. Histological analysis showed that silicon nanoparticles had no toxic effect on retinal tissue and could inhibit the formation of retinal neovascularization. Therefore, silicon nanoparticles can effectively treat retinal neovascularization induced by vascular endothelial growth factor , 51. Kimon level , 53. A son level , 54.Diabetic cardiomyopathy (DCM) is a myocardial disease that occurs in patients with diabetes and cannot be explained by other cardiac diseases. Some studies have shown that oxidative stress injury to myocardial cells caused by diabetes mellitus is an important factor leading to a series of complications such as DCM, which will eventually lead to myocardial contractile and diastolic dysfunction . MyocardIn the nanotechnology applied in DCM, PSS-loaded nanoparticles were prepared using poly(lactic-co-glycolic acid) (PLGA) as a drug carrier and modified double emulsion solvent evaporation method. Yu et al. studied the effect of PSS-NP on vascular endothelial function in DCM rats. The results showed that PSS-NP could significantly improve ventricular wall motion and cardiac systolic and diastolic functions in DCM rats. It can regulate the ultrastructure of myocardial microvascular endothelial cells in DCM rat heart, thus slowing the further development of vascular endothelial dysfunction. The concentration of nitric oxide synthase (eNOS) and vascular endothelial growth factor A (VEGFA) in serum was significantly increased, further alleviating vascular endothelial injury in DCM rats .Studies have explored the therapeutic effect of acidic fibroblast growth factor-l (FGFl) nanoliposomes combined with ultrasound targeted microbubble blasting (UTMD) for DCM. This study evaluated the therapeutic effect of FGFl nanoliposomes combined with UTMD by detecting cardiac function indexes. The results showed that the left ventricular systolic pressure (LVESP), left ventricular end diastolic pressure (LVEDP), and maximum rate of left ventricular development pressure (LV ± DP/dtmax) in the FGFl-combined treatment group were significantly better than those in other treatment groups and DCM groups. The results suggest that FGFl can improve myocardial systolic and diastolic function in DCM rats. Collagen volume fraction (CVF) and apoptotic index of cardiomyocytes in each group were measured. The CVF and apoptosis index of cardiomyocytes in the FGFl-combined treatment group were found to be significantly lower than those in other treatment groups and DCM groups. It is suggested that DCM combined with fluorescence light microscopy (FLM) can improve cardiac function in rats. However, the MVD of rats in the FGFl-combined treatment group was significantly higher than that in the DCM group and other treatment groups, suggesting that FGFl-combined treatment can improve the myocardial microvascular lesions of DCM rats, which may increase myocardial blood flow and reduce oxidative stress injury in DCM rats. Therefore, FGFl nanoliposomes combined with UTMD can improve myocardial pathological and functional changes induced by diabetes .It is not difficult to see that nanotechnology has performed well in animal experiments for the treatment of DCM. However, it is worth considering whether it can have good clinical effects as animal experiments and whether the biocompatibility, biodegradability, and drug release timing of the nanodrugs mentioned above are good.Diabetic peripheral neuropathy (DNP) causes a high incidence rate of diabetic complications, which is a chronic disease and a key cause of foot ulceration and amputation. According to the relevant data statistics , 60, forSatellite glial cells (SGCs) encapsulate the neuronal bodies in the dorsal root ganglion (DRG). Purinergic 2 (P2) Y12 receptor was expressed on SGC in DRG. The activation of SGC plays an important role in the pathogenesis of DNP. Curcumin has anti-inflammatory and antioxidant properties. Due to poor metabolic stability and low bioavailability of curcumin in vivo, encapsulated curcumin nanoparticles were used to improve its targeting and bioavailability. Some scholars have studied the two of them. Curcumin coated with nanoparticles can reduce the upregulation of P2Y12 receptor on SGC in DRG and reduce the mechanical and thermal hyperalgesia of DM rats .At the same time, the effect of nanocurcumin on the severity of sensorimotor polyneuropathy (DSPN) in patients with type 2 diabetes mellitus (T2DM) has been studied. The results show that short-term nanocurcumin supplementation can improve and reduce the severity of DSPN in T2DM patients. In addition, serum FBS and HbA1c levels have decreased significantly. This observation provides a window of opportunity to improve DSPN by controlling hyperglycemia in T2DM patients .Nano-mir-146a-5p improved the velocity of nerve conduction and alleviated morphological injury and demyelination of the sciatic nerve in DPN rats. Nano-mir-146a-5p inhibited the expression of inflammatory cytokines, caspase-3, and cleaved caspase-3 in the sciatic nerve. In addition, mir-146a-5p nanoparticles can promote the expression of myelin basic protein. These results indicate that mir-146a-5p has a protective effect on the peripheral nerve in the DPN rat model, which may occur by regulating inflammatory reactions and apoptosis .Diabetic foot refers to foot ulcer, infection, and deep tissue destruction associated with abnormal distal nerves of lower limbs and different degrees of peripheral vascular disease. It is often a combination of multiple risk factors that eventually lead to diabetic foot. Diabetic foot ulcer (DFUs) is one of the major and serious complications of diabetic patients, which can lead to lower limb amputation or even death, causing physiological pain to patients and also economic burden. The principle of diabetic foot treatment is to create a clean and suitable microenvironment for the local wound of the foot and to promote its repair as soon as possible. Wound healing is a very complex process, which needs to be carried out in order. Therefore, the ideal wound dressing should be nonallergic and nontoxic, can keep the wound environment moist, allows gas exchange, protects the wound from microbial damage, and absorbs wound exudate .Nanotechnology has been widely used in the research of wound dressing for diabetes, such as chitosan, gold, silver, and curcumin. Among these nanomaterials, there is increasing research on structural similarity, biocompatibility, and biodegradability between biopolymers and typical skin. Metal nanoparticles, such as silver and gold, are also good choices for wound dressings due to their antibacterial activity and low toxicity .PLGA has many advantages, such as good biocompatibility, biodegradability, and mechanical strength. Due to its correlation with growth factors, PLGA has become one of the most studied polymers in diabetic wounds. In one study, PLGA microspheres loaded with recombinant human EGF nanoparticles (NPS) were prepared to improve the biological half-life of PLGA microspheres loaded with recombinant human EGF (rhEGF) and to keep growth factors in contact with wound surface. RhEGF was embedded in the wound surface of diabetic rats and released for 24 hours. Proliferation of fibroblasts was the fastest, and the cure rate was the fastest in rhEGF NP group . In addiα-lipoic acid (ALA) extracted from green tea can reduce the expression of RAGE in fibroblasts (Hs68) and promote wound healing in diabetic mice. In addition, the level of VEGF in the treatment group was higher compared with the control group, suggesting that angiogenesis was improved [The mixture of antioxidant EGCG, gold nanoparticles (AuNP), and active oxygen scavenger improved , 68.Curcumin is a natural product that has been widely used in recent years. It has been reported to have a variety of properties, including anti-inflammatory, antioxidant, anticancer, and antibacterial activity. Recent studies have also shown antidiabetes and promoting wound healing . CurcumiGao et al.  successfHan and others  tested tIn the field of wound dressing, the application of nanotechnology is also very gratifying. It not only uses a lot of new synthetic molecular materials but also combines them with natural products. However, the permeability, air permeability, and clinical effect compared to other dressings still need to be compared.Segmental bone defect is very likely to occur after a comminuted fracture caused by trauma. When a bone defect reaches a certain degree, no bone healing can be produced. However, due to the toxicity of hyperglycemia and microvascular complications, bone formation decreases, bone resorption increases, bone turnover is accelerated, and bone mineral loss leads to osteoporosis. Diabetic patients are therefore more likely to have comminuted fracture and segmental bone defect. Its surgical repair needs more filling materials, and postoperative healing is more difficult, which has been a difficult problem for clinicians.The traditional repair method of segmental bone defect is to fill the defect area with autograft or allogeneic bone transplantation and bone replacement materials. Among all bone transplantation materials, the source of autogenous bone is very limited, the duration of surgery is long, and the number of patient suffering is high; the use of allogeneic bone is easy to produce a rejection reaction and increases the chance of incision infection, and the implanted bone is easy to be absorbed, which leads to failure of operation. Many bone substitute materials (such as hydroxyapatite) have some physical and chemical properties which affect the combination of bone tissue and are not ideal. NHAC is a kind of nanosized bone frame biomaterial based on the bionic principle. Its composition and structure are similar to that of autogenous bone. NHAC is also an ideal repair material for diabetic comminuted fracture and segmental bone defect. It can also solve the shortage of the source of bone extraction, avoid the pain of autogenous bone extraction, shorten the operation time, and mix with autogenous bone particles. It also promotes the healing of fractures .Some scholars have found that the addition of adiponectin nanomicrospheres can promote the adhesion and proliferation of osteoblasts on the surface of titanium implants under type 2 diabetes mellitus, improve the alkaline phosphatase (ALP) activity of osteoblasts, induce more collagen secretion and extracellular matrix mineralization, and promote the expression of osteogenic related genes and their corresponding proteins .Diabetic patients are accompanied by hyperglycemia and insulin resistance, which may lead to the formation of atherosclerosis, causing the progression of diabetic vascular diseases. Patients with type 2 diabetes are particularly at risk of vascular injury. In many patients with diabetes, their cholesterol and triglycerides reach dangerously high levels and accumulate in the lumens of their vascular system .As we all know, oxidative stress is the main cause of cardiovascular disease . The risOxidative stress caused by diabetes can lead to decreased fertility in diabetic men . The lowAs a new technology, nanotechnology is the most promising scientific field of this century. With the development of nanotechnology, more and more new nanomaterials will be developed and applied in medical treatment, which will promote the development of modern medicine, bring forward new ideas, and make new contributions to the prevention and treatment of diseases.Under the condition of modern medical treatment, the incidence rate of diabetes is still rising. The complications of diabetes are more and more harmful to patients. Effective treatment measures are of great importance. With the development of nanotechnology, many materials have been considered for biomedical applications and disease treatment. It is still a difficult problem to find a suitable carrier and method. It is worth noting that many traditional Chinese medicine ingredients can also be incorporated into the use of nanotechnology, which can make great progress in the follow-up research.Nanotechnology plays an important role in the field of nanomedicine, especially in the drug delivery system. In many nanotechnology drug delivery ways, the most convenient way is oral administration, but the physiological obstacles in the body, such as the pH change in the digestive tract environment and the enzyme degradation process in the body, limit the more play of this way. Compared with traditional drug delivery, these nanostructures have several advantages. In addition to overcoming the pharmacokinetic and pharmacodynamic limitations of many potential therapeutic molecules, they may also be used for advanced drug delivery purposes, such as targeted drug delivery, controlled release, and enhanced permeability and retention (EPR) effects .The challenges of nanotechnology in medical application are mainly manifested in an unstable preparation process and lack of biosafety evaluation system . Due to Although nanotechnology has been initially applied in various disease trials, a series of problems such as biodegradability, biocompatibility, drug release time, stability and integrity of biomacromolecules, and targeting of nanoparticles still need to be further improved and improved. Moreover, it is necessary to use nanotechnology in clinical treatment. Further molecular studies are needed to check its safety, in order to better serve the clinical disease treatment.


With the development of the times, cardiovascular diseases have become the biggest cause of death in the global aging society, causing a serious social burden. Atherosclerosis is a chronic inflammatory disease, which can occur in large and medium-sized blood vessels in the whole body. It takes atherosclerotic plaque as the typical pathological change and endothelial injury as the core pathophysiological mechanism. It is the pathological basis of coronary heart disease, peripheral artery disease, cerebrovascular disease, and other diseases. Recent studies have shown that chronic stress plays an important role in the occurrence and development of atherosclerosis, endothelial injury, lipid metabolism, and chronic inflammation. This process involves a large number of molecular targets. It is usually the cause of atherosclerotic cardiovascular and cerebrovascular diseases. If chronic stress factors exist for a long time, patients have genetic susceptibility, and the combination of environmental factors triggers the pathogenesis, which may eventually lead to complete blockage of the blood vessels, unstable rupture of plaques, and serious adverse cardiovascular events. This paper reviews the role of chronic stress in the occurrence and development of atherosclerosis, focusing on the pathophysiological mechanism. With the development of economy, the total prevalence of cardiovascular disease in the world is increasing year by year. At present, the total number of cardiovascular diseases exceeds 587 million. In 2019 alone, 18.6 million people died and 34.4 million were disabled, with an upward trend year by year [β-adrenal receptor on the surface of macrophages, stimulates macrophages to produce more cytokine catecholamine, induces the expression of related inflammatory cytokines, and promotes the progress of inflammation [Chronic stress refers to the nonspecific pathophysiological response caused by the change of the body's steady state under the long-term stimulation of various adverse factors in vivo and abroad. Generally speaking, it is the emotional experience of people under the pressure that they are difficult to adapt , 8. The ammation –16. Chroammation , 18. ChrThe purpose of this paper is to comprehensively review the effects of chronic stress on the occurrence and development of atherosclerosis, pay special attention to the pathophysiological mechanism of chronic stress in the occurrence and development of atherosclerosis, and especially explore how chronic stress accelerates the progress of atherosclerosis from the aspects of chronic inflammation, hemodynamics, lipid metabolism, adipose tissue interaction, and the progress of atherosclerotic plaque, so as to provide some ideas for clinical intervention and basic research .It has been elucidated that atherosclerosis is essentially a chronic inflammatory disease. Inflammation plays a role in all stages of atherosclerosis, including accumulation of foam cells, formation of fatty streaks and fibrous plaques, rupture of acute plaques, and formation of thrombus –23, evenκB pathway activates proinflammatory cytokines such as MCP-1 and IL-1αand IL-6 and, at the same time, leads to the increase of intimal macrophage/monocyte ratio [κB pathway also downregulates HMGB1 protein-mediated PPARγ/LXRα. The expression of ABCA1 pathway reduces the antiatherosclerotic effect of ATP binding cassette transporter 1 (ABCA-1) [Clinical and animal experiments have shown that for inflammatory factors, long-term chronic stress can increase the concentration of blood cortisol through HPA axis on the one hand and change the steady-state balance of autonomic nervous system and increase the content of catecholamine by stimulating sympathetic adrenal system and reducing the vagus nerve tension on the other hand. Both cause the decrease of anti-inflammatory ability; the continuous progress of inflammation; the increase of the concentration of inflammatory cytokines, serum IL-6, and TNF; the increase of the expression of IL-6 and TNF in the liver and spleen; and the increase of CRP can also cause the change of inflammatory cytokines –26. In ate ratio , 34, so te ratio . Interes(ABCA-1) . TherefoDyslipidemia is the first recognized independent risk factor for intima and media thickening of atherosclerosis . Higher Hyperlipidemia and chronic stress interact to form a vicious circle, which together leads to the progress of atherosclerosis. Some researchers stimulated mice with chronic mild unpredictable stress (CMS), which also proved that CMS can increase the plasma concentration of corticosterone and lipids, increase the atherosclerosis index, and lead to the impairment of thoracic aortic function . In addiNormal endothelium maintains vascular tension and structure by regulating the balance between vasodilators (such as NO and prostacyclin) and vasoconstrictors (such as endothelin-1 and norepinephrine) .The resuThe response of vascular endothelium to chronic stress is the adaptation to its harmful effects. This adaptation is NO dependent , 60. In Salvia miltiorrhiza can restore endothelial function to a certain extent by increasing the amount of NO and the level of eNOS [However, long-term chronic stress may lead to endothelial dysfunction, vascular remodeling, and systolic hypertension through vascular oxidative stress. The decrease of endothelium-dependent relaxation was observed in this process, which may be related to the decrease of endothelial NO synthase activity and the decrease of NO bioavailability , 68. In  of eNOS . Similar of eNOS . Studies of eNOS . On the  of eNOS –77. TherObesity is associated with chronic stress and atherosclerosis. Chronic stress can cause excessive fat accumulation to a certain extent . StudiesAt present, chronic stress is more closely related to abdominal obesity. One view is that excessive glucocorticoid secretion caused by chronic stress will affect fat distribution and promote the selective accumulation of visceral fat , accompaThe latest research shows that chronic stress can not only cause the progression of atherosclerotic plaque but also accelerate the change of plaque instability. On the one hand, after 12 weeks of mild chronic stress exposure, the area of main atherosclerotic plaque in the ApoE-/-mice doubled compared with the unexposed mice . On the β-blockers, and antiplatelet drugs) are essential in the treatment of these diseases and control the presence of corresponding chronic stress factors. In future studies, we will pay more attention to the influence mechanism of chronic stress on atherosclerosis, and it is a novel insight to develop targeted drugs for the prevention and treatment of atherosclerosis against chronic stress in the future.With the change of life rhythm, the impact of chronic stress on human health has attracted more and more attention. We reviewed the effects of chronic stress on the occurrence and development of atherosclerosis, focusing on the pathophysiological mechanisms, including chronic inflammation, hemodynamic changes, lipid metabolism changes, adipose tissue interaction, plaque progression, and so on. The related changes will eventually lead to abnormal vascular structure and atherosclerotic cardiovascular disease. But due to a perfect self-regulation mechanism in the body, acute internal environment disorder has a relatively weak impact on program genes. However, under the condition of chronic stress, abnormal gene expression can be induced continuously. Since chronic stressors cannot be removed, gene-induced changes in abnormal cell function are irreversible. At present, it has been confirmed that atherosclerosis is a pathological state in which the apoptosis of endothelial cells is excessive and apoptosis of smooth muscle cells is insufficient. The abnormal expression of these cells is closely related to the disturbance of internal environment and endocrine function under chronic stress. The anti-inflammatory effect of statins is based on lipid regulation to reduce the decline of inflammatory factors caused by chronic stress in the body. Chronic diseases such as diabetes and hypertension can be used as chronic stressors to increase the corresponding inflammatory factors and promote the formation of atherosclerosis. Drugs (including betas, angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists,


Resting-state functional magnetic resonance imaging (rs-fMRI), which measures the spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signal, is increasingly utilized for the investigation of the brain’s physiological and pathological functional activity. Rodents, as a typical animal model in neuroscience, play an important role in the studies that examine the neuronal processes that underpin the spontaneous fluctuations in the BOLD signal and the functional connectivity that results. Translating this knowledge from rodents to humans requires a basic knowledge of the similarities and differences across species in terms of both the BOLD signal fluctuations and the resulting functional connectivity. This review begins by examining similarities and differences in anatomical features, acquisition parameters, and preprocessing techniques, as factors that contribute to functional connectivity. Homologous functional networks are compared across species, and aspects of the BOLD fluctuations such as the topography of the global signal and the relationship between structural and functional connectivity are examined. Time-varying features of functional connectivity, obtained by sliding windowed approaches, quasi-periodic patterns, and coactivation patterns, are compared across species. Applications demonstrating the use of rs-fMRI as a translational tool for cross-species analysis are discussed, with an emphasis on neurological and psychiatric disorders. Finally, open questions are presented to encapsulate the future direction of the field. Resting-state functional magnetic resonance imaging (rs-fMRI), which detects the spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signal, is a powerful, non-invasive tool for the investigation of the brain’s intrinsic functional organization at the macroscale level. Functional connectivity of the brain can be calculated by finding the Pearson correlation between the BOLD signals of different brain areas. This results in spatial maps reflective of the brain’s intrinsic functional organization . DiffereMuch of the same general neural architecture is present in both humans and rodents, which accounts for the preponderance of rodent work in neuroscience. At the same time, differences in brain size, relative volumes of brain areas, and the presence or absence of cortical folding present obvious differences across species. In this manuscript, we aim to provide a comprehensive overview of features extracted from rs-fMRI studies in humans and rodents (rats and mice), with the goal of identifying similarities and differences that are important for the translation of knowledge gained in rodents to studies in humans. Resting-state networks are the most commonly reported features for both humans and animals, but we intend to go beyond basic functional connectivity analysis to report commonalities in network dynamics, community structure, and application to disease characterization. Before delving into the main aim, however, we will first touch upon the image acquisition parameters as well as the relative influences of the well-known fMRI signal confounds, such as motion and physiological noise, in both species. We hope that this manuscript will highlight areas for further investigation into important species-specific features and identify commonalities across species that increase confidence in investigations of animal models of brain disorders.The power of rs-fMRI lies in its ability to acquire information about activity non-invasively throughout the whole brain, making it suitable for use in healthy human subjects. This non-invasive characterization of brain function can be matched with invasive or time-consuming manipulations in rodents to provide insight into the neurophysiological processes that give rise to the BOLD fluctuations and create a better framework for the interpretation of rs-fMRI studies in humans. As a result, rodent studies have been invaluable for understanding the neural basis of rs-fMRI. Non-invasive techniques such as electroencephalography (EEG), electrocorticography (ECoG), or magnetoencephalography (MEG) that are suitable for human studies can measure extracranial electrical or magnetic fields resulting from neural activity but have limitations in terms of sensitivity, localization, and resolution. In rodents, however, the BOLD signal can be directly compared to valuable invasive methods that are not feasible in humans, including concurrent microelectrode recordings  or intraTools for genetic manipulation are available and particularly well-developed in rodents, making analysis possible to understand the genetic underpinnings of the structural and functional architecture of the brain. Two of the most prominent tools involving genetic manipulation, optogenetics and chemogenetics, use light and pharmacological agents respectively, to manipulate the activity of neurons. The combination of either of these techniques with fMRI allows for the stimulation or suppression of a specific cell type or pathway while simultaneously imaging the whole-brain functional response to the manipulation. For example, optogenetic-fMRI (ofMRI) has been used to examine the BOLD response to the activation of specific cellular populations , and optRodent models could open the possibility of probing alterations that are observed in patient populations. For neurological disorders in particular, due to the origins of the BOLD signal, it is often difficult to tell if a change in functional connectivity arises from an alteration in the structural connections between areas, an alteration in the activity of the areas, or an alteration in the vasculature that affects neurovascular coupling. If, however, an animal model of the disorder presents the same alteration in functional connectivity, its underlying causes can be investigated using a variety of imaging, recording, and histological techniques. The mouse model, in particular, due to its universally available transgenic animals, has served as a major tool for exploring pathogenic mechanisms of a variety of brain diseases . A diagrOne of the important motivations of rodent fMRI involvement could be taking advantage of minimum motion level procedures and fine controlling physiological conditions with ventilation in anesthesia and muscle relaxation in conventional experimental rodents. BOLD fMRI quality has been typically related to head motion levels that may introduce uncertainty in both image artifacts and brain state in physiological state variation. For instance, rat fMRI in ventilation may have minimized head motion, roughly multiple folders or even one order smaller than human data in translation and rotation of all three directions, especially respiration-related direction, demonstrated in 3 volume of the mouse brain  is the most widely used acquisition technique for both human and rodent studies. Echo times must be shorter in rodents due to the shorter T2* at high magnetic field strength. The small size of the rodent brain combined with the high field and proximity of susceptibility gradients can also cause substantial distortion and signal dropout. On the positive side, stronger gradients can be used to provide the necessary high spatial resolution. Rodent data is frequently non-isotropic, with an in-plane resolution of 0.2–0.5 mm and 0.4–1.0 mm slice thickness  while is3 voxels  comparedman data . Repetitman data  and rodeman data . Researcman data . These pA critical difference between typical rs-fMRI studies in humans and rodents is that anesthesia is typically used in rodents to prevent motion and minimize stress. For task-related fMRI, this has limited rodent studies to simple sensory stimuli, since studies of emotion, behavior, and/or task are not possible in animal models under anesthesia. This is less of an issue for rs-fMRI, where no stimulus is required. Notably, the anesthesia condition may be considered as a simplified but unique brain state for investigating brain intrinsic network activity with minimum peripheral inputs and outputs in addition to the benefits of fine physiological control on experimental rodents. However, anesthetics alter cerebral blood flow and blood volume, which impact the BOLD signal, along with the neural activity. For example, medetomidine is a noradrenergic antagonist that can produce undesired effects on whole-brain fMRI BOLD signals . DiffereSpecifically, for rs-fMRI, networks are more highly localized under light isoflurane anesthesia and become less spatially specific under deep isoflurane anesthesia , and much of the specificity under deep isoflurane anesthesia was recovered after global signal regression . While tIn addition, rs-fMRI in awake rodents has been explored with a measure of reduced stress levels, despite the challenges involved, with a number of groups successfully conducting rs-fMRI studies in unanesthetized rats or mice . ParticuMotion varies greatly in rodent rs-fMRI depending on whether awake or anesthetized animals are used. In anesthetized and ventilated rodents, motion is minimal compared to humans as demonstrated in Respiratory and cardiac rates are much faster for rodents than for humans. Rates vary across individuals and strains but are on the order of 85 breaths per minute/300 beats per minute for rats  and 160 Functional connectivity refers to coherent changes in the BOLD fluctuations from different areas of the brain, often captured as correlation values. Regions that then show a high statistical association are referred to as a resting-state network (RSN). In humans, there are a variety of nomenclatures that are used to describe RSNs. A broadly used set of RSNs defined on human cortical regions was determined by While the RSNs described in As shown in The olfactory network in humans was not discerned as a separate network in the whole brain RSN analysis as was revealed in rodents, although a recent study was able to detect the human olfactory network using functional connectome analysis . The olfThe limbic network, acting as one of the most complicated systems in the brain, is involved in various brain functions, including homeostasis, memory, emotions, olfaction, and many more . Note thThe default network or default mode network (DMN) is a network suppressed during tasks and activated during resting-state, such as during mind-wandering; it has also been found to be active during remembering, imaging the future, and making social inferences . A key fThe frontoparietal network in humans is also known as the central executive network, which supports the executive function and goal-oriented, cognitively demanding tasks . Though The salience/ventral attention network encompasses the salience network and ventral attention network, two of which are found to be highly associated  and are Apart from the above increasingly discovered homologous networks, the existence of homologous RSNs involved in other higher cognitive functions in rodents is still left as an open question. In particular, the dorsal attention network and the ventral attention network  have not yet been discovered in rodents . These tCross-species studies may also demonstrate that there are inconsistent neurological patterns between species that may require different processing methods. For example, rats and mice exhibit cortical differences in rs-fMRI data where unilateral cortical networks exist for mice versus bilateral networks in rats . AdditioThe global signal is obtained by averaging the BOLD timecourses over the entire brain. Fluctuations in the global signal have been linked to physiological fluctuations, mainly respiratory effects, head motion, scanner-related effects, and vascular effects . Along wA number of properties of functional connectivity are common across species. In general, there is a substantial overlap of structural and functional connectivity in both rodents and humans. In the rat, a meta-analysis of tracing data combined with rs-fMRI found a Spearman rank-order correlation of 0.48 between the structural and functional connectivity matrices . In the Functional connectivity gradients, typically obtained using dimensionality reduction on voxel-wise functional connectivity matrices, identify spatial axes along which voxels exhibit similar functional connectivity profiles . FunctioFunctional connectivity can also be described in terms of a graph, where nodes represent different parcels of the brain and edges represent the correlation between them. Graphical analytical tools can then be utilized to describe the community structure of functionally connected regions. For node determination, many brain atlases have been developed for brain network analysis. In mice studies, the anatomical atlas provided by Australian Mouse Brain Mapping Consortium and the Allen Mouse Brain Atlas has been widely used ,2020. FoTo determine the brain organization, clustering or graph theory-based community detection methods are often used . In partC. elegans)  . For exaelegans) . In humaelegans) . The exiIn the last decade, researchers have increasingly turned to a time-varying assessment of functional connectivity, which provides information about the evolving state of the brain, rather than the time-averaged picture obtained when functional connectivity is calculated over the course of the whole scan . These dSliding window correlation is one of the most basic approaches of time-varying analysis and involves calculating the correlation between pairs of brain areas  for a time window from a scan, rather than for the entire scan . The winEarly studies in rodents examined sliding window correlation between a few pairs of areas and were instrumental in showing that apparent dynamics could arise from the properties of the BOLD signal itself . NeverthIn humans, sliding window correlation is typically applied to parcellated brain signals, with the resulting matrices of functional connectivity over the course of the scan then clustered to identify common brain states . This apIn humans, there is evidence that the relative occurrence of brain states based on sliding window correlation reflects the relative arousal of the subject . It is nQuasi-periodic patterns (QPPs) are spatiotemporal patterns of activity that occur repeatedly throughout the scan. A pattern-finding algorithm has been developed  and popuMultimodal studies in rodents have been key to developing a better understanding of the neurophysiology underlying QPPs. Early work showed that they are present in CBV-weighted data, as well as BOLD . Using sQuasi-periodic patterns are similar across species in that they appear to involve analogous areas. In humans, activity propagates from the somatomotor network to the default mode network . In ratsIn humans, QPPs involve the whole brain, including subcortical areas and the cerebellum , and regThe timing of the QPPs varies across species. In humans, it is approximately 20 s in length, while in rodents, the length of the QPP varies depending on the anesthetic used ∼5–10 s; . The varCoactivation patterns (CAPs) analysis is another method used to capture dynamically evolving brain activity. It was illustrated in sliding window correlation, quasi-periodic patterns, and coactivation patterns. Please see a full description of the technicalities and parameters used for these three methods in Like other dynamic approaches that are purely based on fMRI measurement, it is hard to interpret whether the distinct spatial patterns revealed by CAPs are attributed to fluctuations in neural activities or physiological noise, with fMRI being an indirect measurement of neural activities. Applying the CAPs method to animal models, like rodents, can play an important role in investigating the neural correlates of such temporal fluctuations because of the availability of more direct and invasive measurements of neural activity. in vivo study from 2016, Cognitive neuroscience has made extensive use of fMRI to study the mechanisms underlying cognitive processes like memory, learning, and attention. In rodents, the main barrier to similar studies is the common use of anesthesia, which makes it impossible to perform similar behavioral studies in the scanner. However, using rs-fMRI, researchers are able to examine functional connectivity before and after a variety of behavioral training. In this case, changes that occur during the training itself are not observed and anesthesia can be used during the scans. In an The use of rodent models allows the direct investigation of the relationship between BOLD and neural activity using simultaneous non-invasive  and invasive  recordings   , these stection) .The use of animal models to study human neurological disorders is advantageous for many reasons, some of the most notable being the many possibilities afforded by genetic manipulation , the greAlzheimer’s disease (AD) is a neurodegenerative disease that accounts for the majority of dementia cases . A fullyMany studies in humans have shown alterations in functional connectivity and network dysfunction in brains that have been affected by AD. Abnormal DMN connectivity, especially decreased DMN connectivity, has been shown to occur in prodromal and later stages of AD , with reGABRG2 genetic variant, which is known to cause early-onset absence epilepsy and febrile seizures. The variable findings point to the importance of understanding the diversity in etiologies that lead to different pathological processes in epilepsy.Epilepsy is a brain disorder characterized by the excessive firing of neurons causing recurrent seizures and is a condition of altered neural network organization . A recenTo focus on a relatively less heterogeneous group, we turn to studies of temporal lobe epilepsy (TLE). It is the subtype of epilepsy that has been studied most extensively in relation to disruptions in resting-state brain connectivity, the DMN in particular . As in ITaken together, studies have shown the utility of rs-fMRI in understanding the disruptions in networks in epilepsy and possible correlations with neurocognitive functioning. Varying results among studies is a reflection of the heterogeneity of the disorder, encompassing diverse etiologies and pathologies under the same diagnosis. Given the variability in connectivity changes both at the group and individual levels, longitudinal studies tracking change over time as well as those comparing pre- and post- treatment would be crucial to support using functional connectivity measures as a biomarker in epilepsy.Studies of brain functional connectivity in ADHD have commonly involved the DMN, frontoparietal, and corticostriatal networks. A systematic review by A systematic review of rs-fMRI studies in ASD revealed both hypoconnectivity and hyperconnectivity in and between different regions and networks . A findiCntnap2 was found to have decreased connectivity between the cingulate cortex and the retrosplenial cortex, which represent the anterior component of the mouse DMN and a posterior hub, respectively  of anesthesia. Both the type of anesthetic and the delivery protocol also vary across studies. The move to unanesthetized animals would mitigate this aspect of site-to-site variability, but imaging awake rodents remain challenging and less robust .In humans, most studies use one of a handful of atlases to parcellate the brain. Standard atlases remain to be adopted in rodents, although some excellent candidates are emerging . The abiAlthough neuroimaging studies from rats and mice are often lumped together in the single category of “rodents,” there are substantial differences across the species that have barely been explored. Even more, there are differences between strains for each species . While sIt is well known that animal models often do not capture key aspects of human cognition and disorders such as neurodevelopmental disorders ; multiplWhat causes the widespread coordination that we observe as functional connectivity? This is the fundamental question for rs-fMRI researchers, and animal studies play a key role in elucidating the underlying mechanisms using multimodal, invasive measurement techniques as well as non-invasive fMRI. At the most basic level, it appears that the general mechanisms that relate neural activity to the changes in blood oxygenation measured with fMRI are similar across species, which increases confidence that work in animals can help to interpret work in humans. Recent advances in the evolutionary study have enabled quantifying the functional homology across animals and humans through a function-based method for cross-species alignment (lignment . Focusinlignment . HoweverHow do we obtain results that are most comparable across species? Certainly, robust protocols for imaging unanesthetized animals would be a large step toward improving comparability. In the meantime, obtaining data under multiple contrasting anesthetic conditions (nditions  can helpAnother important issue is that motion artifacts must be minimized in both species. The human fMRI studies are mostly relying on participants’ cooperation to avoid voluntary head motion along with immobilizing assistance. Rodent fMRI are mostly relying on anesthesia and ventilation, but head motion spikes were often observed in the awake state due to the animal struggling in the fixed position, which is even though reduced a lot over the training session. Notably, the subjects’ motion may be relevant to stress levels and brain physiological and functional state variations that would add complicated situations in functional brain activity. These unwanted physiological contributions can affect the images in each species in different ways, so careful cleanup is needed . With thRodent models have played and will continue to play an important role in understanding the functional architecture of the brain as measured with rs-fMRI. While differences in acquisition strategies, particularly the use of anesthesia, make comparisons between rodents and humans less than straight-forward, the observation of comparable networks across species increases confidence that multimodal studies in animal models can help to interpret rs-fMRI in humans. Research in rodent models has already established a firm neural basis for both time-averaged and time-varying characterizations of functional networks, and further investigation will provide more insight into the mechanisms that coordinate systems-level neural activity and hemodynamics. Resting-state fMRI is already being applied in animal models of human disorders and, in some but not all cases, has detected alterations consistent with those observed in the patient population. Further efforts to understand the correspondence of rs-fMRI across species and the development of improved animal models may eventually allow researchers to probe the mechanisms that underlie alterations in functional connectivity.NX, TL, NA, MN, and SK contributed to the overall organization of this review. NX, TL, NA, AL, XZ, MN, W-JP, and SK contributed to writing. NX, TL, NA, AL, XZ, BY, EM, VK, W-JP, and SK contributed to the edits. TL contributed to the 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.


In this short review (Perspective), we identify key features of the performance of biocatalysts developed by the immobilization of enzymes on the supports containing magnetic nanoparticles (NPs), analyzing the scientific literature for the last five years. A clear advantage of magnetic supports is their easy separation due to the magnetic attraction between magnetic NPs and an external magnetic field, facilitating the biocatalyst reuse. This allows for savings of materials and energy in the biocatalytic process. Commonly, magnetic NPs are isolated from enzymes either by polymers, silica, or some other protective layer. However, in those cases when iron oxide NPs are in close proximity to the enzyme, the biocatalyst may display a fascinating behavior, allowing for synergy of the performance due to the enzyme-like properties shown in iron oxides. Another important parameter which is discussed in this review is the magnetic support porosity, especially in hierarchical porous supports. In the case of comparatively large pores, which can freely accommodate enzyme molecules without jeopardizing their conformation, the enzyme surface ordering may create an optimal crowding on the support, enhancing the biocatalytic performance. Other factors such as surface-modifying agents or special enzyme reactor designs can be also influential in the performance of magnetic NP based immobilized enzymes. Magnetic nanoparticle (NP)-containing supports for catalytic and biocatalytic systems have received considerable attention as they allow for significant improvements in process intensification, as well as savings in both energy and materials due to magnetic recovery ,11,12,13Clearly, for all these systems, magnetic recovery is a straightforward advantage which is commonly discussed in literature due to the facilitated biocatalyst reuse. Two major design features of magnetic biocatalysts are reported. In one case, magnetic NPs are isolated from the biocatalytic species. In the other case, they are in the vicinity of enzyme molecules. The latter design feature could become a crucial factor if the bioactivity of immobilized enzymes is influenced by the presence of magnetic NPs, normally consisting of metal oxide or ferrite. In this case, however, attention needs to be paid to the pH of the reaction solution because metal oxide or ferrite NPs are digested by acids, so the biocatalyst will lose its magnetic character. Finally, we will discuss other important parameters which could significantly influence the biocatalytic performance, whether magnetic NPs are isolated from enzymes , or exposed to the reactants. One of the most influential parameters is hierarchical porosity, where pore sizes can vary from micropores to macropores, providing both efficient mass transfer in the biocatalytic reaction, and a proper positioning of enzymes inside the pore for maximized activity. The parameters, such as an addition of surface-modifying agents or utilizing special enzyme reactor designs, can be also crucial for the performance of magnetic NP-based immobilized enzymes.Due to the above advantages, studies of magnetic NP-based biocatalytic systems have enjoyed an intense growth in the last decade. From 2016 to date, 523 papers have been published which show the publication profile displayed in In this review, we will discuss magnetic NP-containing supports for immobilized enzymes from the viewpoint of magnetic separation, and an enhancement of the biocatalytic activity due to the presence of oxide or ferrite NPs, surface modifiers, etc., following these trends from 2016 through to July of 2021.The magnetic recovery of immobilized enzymes is normally realized by tethering enzymes to magnetic NPs via some linkers such as polymers, difunctional molecules, etc. ,35,36,37Finally, the formation of magnetic NPs in the presence of polymers is often preferred because it simplifies the biocatalyst preparation process ,45.2), alumina (Al2O3), and zirconia (ZrO2), or in the same supports but containing magnetite NPs in the support pores , revealed that biocatalysts based on magnetic supports are noticeably more active than those based on non-magnetic supports . Th. Th3O4-SAcross numerous studies, hierarchical porosity of biocatalyst supports has been shown to be crucial in influencing the biocatalyst performance ,64,65,66Magnetic microspheres with hierarchical porosity (PFMMs) were fabricated using a non-conventional precursor—a novel rigid-flexible dendrimer synthesized by interfacial polymerization of trimesoyl chloride (TMC) and 1,6-hexanediamine (HDA)  66]..66].Pseudomonas fluorescens lipase (PFL). The increased rigidity of this support compared to that of the support based on fully flexible dendrimers also allowed an improved reusability of the immobilized PFL.PFMMs possess pore sizes in the range of 5–75 nm and excellent loading capacity for covalent immobilization of 3O4 NPs using a solvothermal method, and employed for immobilization of chloroperoxidase or horseradish peroxidase . Po. Po63]. The surface modification depends on the method of the magnetic support preparation and on the components of the biocatalyst . There aA polyhistidine-tag (His-tag) has been utilized for modifying the surface of “sea-urchin” shaped NPs composed of the Ni silicate shell and the magnetite core . Such a Candida rugosa lipase (CRL) [The other objective of the surface modification deals with tuning the hydrophobicity–hydrophilicity balance for better compatibility of the enzyme, support, and the substrate ,83,85,86se (CRL) . Hexadecse (CRL) . This biFunctional ionic liquids have been reported as modifying agents for lipase immobilization on a magnetic support ,86. The In this short review, we analyzed the major advantages of magnetic supports for enzyme immobilization, and the influence of their structural features on the biocatalytic properties. The most straightforward advantage of magnetic biocatalysts is the easy separation due to magnetic forces between magnetic NPs and an external magnetic field, facilitating the biocatalyst reuse. It allows for savings of energy, materials, and time, facilitates reuse, and results in less expensive processes, paving the way for future industrial applications. Another remarkable benefit is realized when enzymes are attached in close proximity to iron oxide NPs, thus allowing for synergy between the enzyme and iron oxide NPs due to the inherent enzyme-like activity of the latter. We believe this enhancement is underutilized because, very frequently, iron oxide NPs are isolated from enzymes by silica or polymer shells with the assumption that magnetic NPs could be detrimental for biocatalyst performance. Indeed, this could be the case if the media is acidic  or if iron oxide promotes a side reaction. We believe that for all other cases, co-existence of immobilized enzymes and iron oxide NPs in proximity to each other is highly beneficial.The other major benefit of magnetic biocatalysts is the skillfully developed hierarchical porosity of the supports, allowing a controlled enzyme immobilization for the design of efficient biocatalysts. The advantages of hierarchical porosity include easy mass transport of reacting molecules in large pores, optimal self-assembly of enzyme molecules inside the medium size pores (resulting in an enhancement of the enzyme activity), and preservation of structural integrity of the biocatalyst due to small pores. Magnetic MOFs grant an additional advantage of pore ordering.Finally, surface modifying agents play an important role in the enhancement of the biocatalytic performance, for example, in the case of hydrophobic lipases, allowing one to adjust the support or lipase hydrophobicity, and to improve compatibility between the magnetic support, enzyme, and reacting molecules. We believe a combination of the advantages of magnetic nanoparticles (magnetic separation and enzyme-like properties) with well-designed porosity and targeted surface modification is a promising avenue for the successful development of efficient magnetic biocatalysts.


Organic wastes have the potential to be used as soil organic amendments after undergoing a process of stabilization such as composting or as a resource of renewable energy by anaerobic digestion (AD). Both composting and AD are well-known, eco-friendly approaches to eliminate and recycle massive amounts of wastes. Likewise, the application of compost amendments and digestate (the by-product resulting from AD) has been proposed as an effective way of improving soil fertility. The study of microbial communities involved in these waste treatment processes, as well as in organically amended soils, is key in promoting waste resource efficiency and deciphering the features that characterize microbial communities under improved soil fertility conditions. To move beyond the classical analyses of metataxonomic data, the application of co-occurrence network approaches has shown to be useful to gain insights into the interactions among the members of a microbial community, to identify its keystone members and modelling the environmental factors that drive microbial network patterns. Here, we provide an overview of essential concepts for the interpretation and construction of co-occurrence networks and review the features of microbial co-occurrence networks during the processes of composting and AD and following the application of the respective end products (compost and digestate) into soil. The activity of the ever-increasing human population generates millions of tons of solid organic wastes  . The inaBroadly, organic wastes can be classified into the following categories: (i) animal manures: solid, semisolid and liquid by-products generated by animals grown to produce meat, milk, eggs and other agricultural products; (ii) plant residues: crop wastes including stalks and stubble (stems), leaves, green manures and seed pods; (iii) waste from manufacturing processes: by-products coming from different industrial activities such as exhausted seeds, hoof and horn meal, animal feathers and fur, wastes from sugar extraction, distillery waste and biosolids from paper mills; and (iv) biosolids: treated wastewater residues from municipal wastewater treatment plants ,7. Some Composting involves the aerobic humification of biomass by microorganisms under controlled conditions . Under o4 and 30% CO2) and a by-product called digestate [2 and ammonia. At the final phase, called methanogenesis, hydrogen, acetate and CO2 are converted into CH4 [AD involves the anaerobic processing of raw wastes using a microbial consortium composed of hydrolytic, acidogenic and acetogenic bacteria as well as methanogenic archaea that work sequentially during the process, generating biogas , ITS , 18S rRNA, etc.) . The datIn a given microbial community, individual members interact with one another to form a complex network of positive, negative and neutral interactions . By inteSeveral tools, such as differential equation-based, Bayesian and relevance/co-expression network approaches, have been developed to conduct network analyses in genomic biology . Among tWhen a network is constructed, significant positive and negative interactions among all the nodes in the network are determined and graphically represented , and difThe most useful indices to characterize nodes are (i) connectivity, which is the number of links of a node to other nodes; (ii) path length, which is the shortest path between two nodes; (iii) the clustering coefficient, which describes how well a node is connected with its neighbors; and (iv) betweenness centrality, which indicates the number of the shortest paths that pass through the node among the shortest paths existing between every pair of nodes . BetweenA typical co-occurrence network analysis in a microbiome study usually comprises a graphical representation of the networks along with the calculation of the aforementioned network topological indices and the identification of keystone OTUs/ASVs for each of the networks being constructed. Furthermore, direct comparisons of networks and their topological features are made in order to gain insights into, for instance, the effect of a specific treatment on microbial network patterns. Factors driving differences between samples or experimental treatments can be elucidated by applying Mantel and partial Mantel tests correlating the network topology and the changes in physicochemical or environmental conditions .Exploring the interactions among microbial taxa coexisting in composting matrixes has not received enough attention yet . PuttingOn the contrary, the occurrence of negative relationships in a network may be attributed to parasitism, antagonism, predation or competition . Zhu et Bacillus and Ureibacillus from the phylum Firmicutes appeared as a keystone during the thermophilic phase of dairy manure composting [4+ concentration and pH. Actinobacteria from the genera Nonomuraea, Actinomadura, Mycobacterium and Sphaerisporangium were more characteristic of the composting maturation phase [3− concentration, all of them used as proxies of compost maturity [Rhizobiales and Pseudomonas, respectively, were also identified as keystone OTUs when maize straw was used as the raw material for co-composting with green soybean hulls  and seaobiales; ). Pseudoobiales; , which it growth ,77. All Chaetomium sp., Penicillium sp., Trichoderma sp., Trichosporon sp., Arthrographis sp. and Aspergillus sp. constitute the core fungal genera during composting. These fungi are in general efficient lignocellulose degraders and, like in the case of Aspergillus sp., some species can also promote compost maturation [The evaluation of fungal co-occurrence network patterns during composting remains underexplored compared with bacteria . Ascomycturation . The funturation ,72,81,82The comprehensive understanding of the microbial communities in terms of interactions between network patterns and operational parameters, biodiversity and system functions is crucial to decipher the factors governing the stability and performance of the AD bioreactors . PreviouVeillonellaceae family (glycerol degrading) and Candidatus Cloacimonetes (volatile fatty acids fermenters), was found in detriment of the syntrophic bacteria. Consequently, the methanogenesis failed 72 h after organic overloading, when the pH reached values lower than 6. Overall, the network analysis provided useful information about a succession of functionally redundant microorganisms, most likely because of niche specialization during organic overloading.Ecological network analysis has also been used to better understand how biogas-producing microbiomes are constructed based on specific operational conditions such as the organic loading rate (a measure of the quantity of influent substrate entering the digester per unit of time), the hydraulic retention time (the average length of time that a soluble compound remains in an AD bioreactor), temperature (the mesophilic vs. thermophilic conditions) and the nature of the feedstocks . For exaXu et al.  revealedMethanobrevibacter and Methanobacterium), as well as substrate-hydrolyzing and hydrogen-producing bacteria  at elevated temperatures (50 °C), resulting in an enhancement of CH4 production. The variations of microbial interactions in terms of network modularity and deterministic processes based on topological features corresponded well with the variations of CH4 productions, but not with the variation of temperatures. A common successional pattern of microbial interactions was observed at different temperatures, which showed that both the deterministic processes and the network modularity increased over time during the digestion process, improving the stability and efficiency of the AD-bioreactor.Temperature also plays a crucial role in the microbial interactions that affect the stability and performance of AD . Based oCandidatus Cloacomonas, Methanospirillum and Methanosphaera, while in the second one they belonged to the archaeal groups Methanobrevibacter and Candidatus Methanoplasma. This study also pointed out the presence of Parcubacteria uncultured bacteria, Candidatus Cloacomonas and Candidatus Methanoplasma as the keystone OTUs to maintain AD functioning, regardless of the type of manure.The nature of the feedstocks has also been pointed out to play a key role in determining not only the network topological properties in AD bioreactors, but also the taxonomic affiliation of the keystone OTUs . VendrusSustainable agriculture advocates for the use of environmentally-sound practices that enhance and/or maintain soil fertility . The addnirS containing denitrifiers networks gradually increased along with the compost rate. This is of particular importance for the productivity of plants given that nitrification and denitrification are among the most important soil N transformations.In this regard, the application of compost amendments into soil has been shown to increase network complexity for both bacteria and fungi when compared to inorganic fertilization and/or unamended treatments ,102,103.In addition, amending soil with compost was shown to enhance the synergistic interactions within bacterial and fungal co-occurrence networks . These lCeratobasidium and Typhula. Interestingly, Tang et al. [Nevertheless, research on the impact of digestate on soil microbial network patterns is still in its infancy. In a recent study from Tang et al. , they deg et al.  significCo-occurrence network analyses are starting to be applied with success to metataxonomic data in surveys studying the microbial communities driving processes such as compositing and anaerobic digestion and in organically amended soils. This approach represents a step forward in our understanding of the interactions among the members of a microbial community and the identification of its keystone members. Likewise, the existing works have shown that the study of network patterns is useful to decipher the environmental factors that control a specific process  by modulating the network properties of a microbial community. Most of the existing studies on networks consider only bacterial communities; thus, further studies also considering archaeal and fungal communities are needed. The application of microbial network approaches to metagenomic data can also provide a new perspective in the functional study of microbial communities. Co-occurrence networks thus have potential to become default analyses in microbial ecology studies.


Much effort has been made to remediate the degraded mine lands that bring severe impacts to the natural environments. However, it remains unclear what drives the recovery of biodiversity and ecosystem functions, making the restoration of these fragile ecosystems a big challenge. The interactions among plant species, soil communities, and abiotic conditions, i.e., plant-soil feedbacks (PSFs), significantly influence vegetation development, plant community structure, and ultimately regulate the recovery of ecosystem multi-functionality. Here, we present a conceptual framework concerning PSFs patterns and potential mechanisms in degraded mine lands. Different from healthy ecosystems, mine lands are generally featured with harsh physical and chemical properties, which may have different PSFs and should be considered during the restoration. Usually, pioneer plants colonized in the mine lands can adapt to the stressful environment by forming tolerant functional traits and gathering specific soil microbial communities. Understanding the mechanisms of PSFs would enhance our ability to predict and alter both the composition of above- and below-ground communities, and improve the recovery of ecosystem functions in degraded mine lands. Finally, we put forward some challenges of the current PSFs study and discuss avenues for further research in the ecological restoration of degraded mine lands. In the terrestrial ecosystem, plants alter their surrounding biotic and abiotic soil conditions through root- and litter-induced effects, which in turn influence the growth, productivity, and generation of the coexistent and subsequent plants. This is called plant-soil feedbacks (PSFs) . IncreasDegraded mine lands are generally provided with a sparse density of vegetation, soil compaction and acidification, heavy metal toxicity, and nutrient deficiency , which mHere, we address plant-soil feedbacks based on soil properties, plant functional traits, and soil communities in contaminated mine tailings and discuss their consequences for the ecosystem functioning and potential remediation practices. We first describe the current situation and obstacles for ecological restoration of mine lands, then focus on how plant and soil communities interact under harsh conditions. We also review the litter- and rhizosphere-induced PSFs based on multiple plant functional traits and the interactions with associated microorganisms for the tolerant plants established in mine areas. Moreover, we discuss how the understanding of PSFs plays a pivotal role in accelerating the recovery of ecosystem functions including pollutant control, primary productivity, decomposition, nutrient availability, and cycling. In the end, we summarize the challenges and prospects of PSFs study in abandoned mining areas, emphasizing more efforts should be made to fulfill the imperative knowledge and practical gaps.via natural processes , N , and S (sulfate reduction)  . The rhiduction) . Howeverduction) , availabduction) , soil orduction) , redox sduction) , and espduction) . Technicduction) . Additioduction) .Plenty of studies have utilized plant-microbe association in mine lands bioremediation, but few of them have figured out how PSFs influence ecological succession, leading to incomplete and unsustainable remediation. As the intensive interactions and complexity of cooperation among plants and soil biotic and abiotic components , it is uPlant-soil feedbacks can be affected by soil physical, chemical, and biogeochemical properties. As shown in Due to the scattered or bare vegetation, the soils of the degraded mine lands are always compacted and suffer from either drought or excessive wetness . Both tovia AM nutrient uptake pathway  are more related to a microbial community dominated by bacteria compared with that by fungi , leadingvia improvement of nutrient acquisition (The interaction and symbiosis between plants and rhizospheric microbes sometimes are also considered as root biotic traits of plants , which auisition , enhanceuisition , and ameuisition . The laruisition . The AMFuisition . Some pruisition . Rhizobiuisition . Additiouisition . Howeveruisition .Together, though relevant researches are increasing, what we know about how plant functional traits and soil microbes facilitate plant growth in degraded mine lands is still far from enough. The integration of shoot and root functional traits and the associated soil communities can help understand the ecological strategy of tolerant plants in driving PSFs in mine lands and select ideal plant functional groups to trigger and accelerate the natural succession process. Digging into the functioning of soil communities on assisting plants performance in mine lands may disentangle the complexity of PSFs and improve the application of bioremediation in the future.To evaluate the consequences of the ecological restoration in degraded lands , increasOnonis tridentate L. can form patchy fertility islands beneath its canopy on bare gypsum substrates via the symbiosis with below-ground N-fixing rhizobia (Functional trait-based approaches play important roles in interpreting the variability of biodiversity and multifunctionality recovery . With a rhizobia . Hence, Soil communities also serve as an important factor driving plant diversity and ecosystem multifunctionality . EmpiricIn degraded mine land systems, the terminal objective is to restore a stable and sustainable ecosystem with abundant species and multifunctionality. Figuring out the possible patterns and underlying mechanisms of PSFs in mine lands is significant for understanding and predicting the process of succession under these barren toxic conditions. It is also critical for applying the PSFs mechanisms and functional trait-based approaches in nature-based solutions to accelerate the remediation. Although ecological researchers gradually focus on plant-soil systems of various environments, a large research gap remains in the restoration of these harsh environments. Here we put forward the perspectives and challenges of PSFs in degraded mine areas that require further research.Firstly, studies about PSFs in degraded mine lands are necessary. As primary succession sites, degraded mine lands possess few biotic lives and little abiotic material legacy. It is an ideal scene to study the impact of PSFs on the initial formation and interactions of above- and below-ground communities. However, the establishment and regeneration of plant communities and the gathering of multiple species in mine lands are difficult and always take a long time, making the field study difficult. Simultaneously, manipulative experiments in the laboratory are also necessary for precisely understanding the patterns and the influence factors of PSFs. But the problem is that it is hard to fully simulate the condition in the wild. For example, intermittent drought is common in most mine lands, but the lab-grown plant may wither if they are not watered continuously and then we will not even have the biomass for PSFs calculation. Thus, a big challenge for researchers is to think over and make the choice of proper cultivating conditions between better for plant growth and simulating the true field environment.Secondly, it is important to find out the key environmental factors and mechanisms that determine plant community succession in mine lands. Lots of abiotic stresses impede plant growth, but the critical abiotic factors that determine PSFs remain unknown. Moreover, the response of PSFs is usually context- and time-dependent. Identifying the most important factors that alter or hinder the primary succession can assist restoration efforts in degraded mine lands.Thirdly, the economic spectrum of tolerant plant functional traits is waiting to be figured out. For one thing, knowing the functional traits that plants are equipped to overcome harsh environments can help to understand the plant economics spectrum along with environmental stresses and provide insights into a trait-based selection of candidate plant species for the restoration of mining sites. For another, plant functional traits are also useful to indicate the relationships between plants and soil community and predict plant effects on succession processing and ecosystem functioning.Fourthly, it is necessary to combine the structure and functioning of the soil community with the performance of tolerant plants in mine lands to enhance phytoremediation. More emphasis is required on the development of trait-assisted and belowground-derived recovery approaches based on theoretical mechanisms of PSFs. We should surmount the obstacles along the way to revealing PSFs mechanisms and their application on the restoration. This may lead to an important complement to the theory of restoration ecology.S-CZ and Y-TT conceived the ideas. H-XZ and W-SL provided the figures. S-CZ wrote the first draft of the manuscript. W-SL, Y-TT, YC, and HH reversed the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.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.