Photocatalytic Antimicrobials: Principles, Design Strategies, and Applications.

Nowadays, the increasing emergence of antibiotic-resistant pathogenic microorganisms requires the search for alternative methods that do not cause drug resistance. Phototherapy strategies (PTs) based on the photoresponsive materials have become a new trend in the inactivation of pathogenic microorganisms due to their spatiotemporal controllability and negligible side effects. Among those phototherapy strategies, photocatalytic antimicrobial therapy (PCAT) has emerged as an effective and promising antimicrobial strategy in recent years. In the process of photocatalytic treatment, photocatalytic materials are excited by different wavelengths of lights to produce reactive oxygen species (ROS) or other toxic species for the killing of various pathogenic microbes, such as bacteria, viruses, fungi, parasites, and algae. Therefore, this review timely summarizes the latest progress in the PCAT field, with emphasis on the development of various photocatalytic antimicrobials (PCAMs), the underlying antimicrobial mechanisms, the design strategies, and the multiple practical antimicrobial applications in local infections therapy, personal protective equipment, water purification, antimicrobial coatings, wound dressings, food safety, antibacterial textiles, and air purification. Meanwhile, we also present the challenges and perspectives of widespread practical implementation of PCAT as antimicrobial therapeutics. We hope that as a result of this review, PCAT will flourish and become an effective weapon against pathogenic microorganisms and antibiotic resistance.

[Effect of 28-day administration of Psoraleae Fructus water extract on early liver injury in rats].

This study aims to investigate the hepatotoxicity of Psoraleae Fructus water extract and the underlying mechanism in rats. Forty-eight rats were randomly assigned into four groups: a blank group and low-(BZGL, 6.25 g·kg~(-1)), medium-(BGZM, 12.5 g·kg~(-1)), and high-dose(BGZH, 25 g·kg~(-1)) Psoraleae Fructus water extract groups. The rats were treated for 28 days, and toxicity and mortality were observed daily. After 28 days, the rats were sacrificed, and the body weight, liver index, and liver-to-brain ratio were calculated. The morphological changes in the liver tissue were observed, and the serum levels of related biochemical indicators were measured. The results showed that compared with the blank group, Psoraleae Fructus water extracts of different doses decreased the body weight, increased the liver index and liver-to-brain ratio, and caused liver hypertrophy and pathological changes. Pathological examination revealed that the rats in Psoraleae Fructus water extract groups had bile duct hyperplasia, inflammatory cell infiltration, and liver cell fibrosis. Compared with the blank group, BGZL elevated the levels of alanine transaminase(ALT), α-glutathione S-transferase(α-GST), and total bile acid(TBA)(P<0.05), and BGZM and BGZH elevated the levels of ALT, TBA, α-GST, γ-glutamyl transferase(γ-GT), purine nucleoside phosphorylase(PNP), ornithine carbamoyltransferase(OCT), and arginase(ArgI)(P<0.05). Compared with the blank group, Psoraleae Fructus water extracts of different doses down-regulated the mRNA and protein levels of bile salt export pump(BSEP) and farnesoid X receptor(FXR) and up-regulated the mRNA and protein levels of tumor necrosis factor-α(TNF-α), nuclear factor kappaB(NF-κB), and cholesterol 7 alpha-hydroxylase(CYP7A1)(P<0.05). The results suggested that Psoraleae Fructus water extract caused toxicity in rats, showing a dose-toxicity relationship. Psoraleae Fructus water extract may cause liver damage, which may be due to its effect on liver bile acid secretion and induction of inflammation.

Engineering Single-Atom Active Sites on Covalent Organic Frameworks for Boosting CO2 Photoreduction.

Solar carbon dioxide (CO2) conversion is an emerging solution to meet the challenges of sustainable energy systems and environmental/climate concerns. However, the construction of isolated active sites not only influences catalytic activity but also limits the understanding of the structure-catalyst relationship of CO2 reduction. Herein, we develop a universal synthetic protocol to fabricate different single-atom metal sites (e.g., Fe, Co, Ni, Zn, Cu, Mn, and Ru) anchored on the triazine-based covalent organic framework (SAS/Tr-COF) backbone with the bridging structure of metal-nitrogen-chlorine for high-performance catalytic CO2 reduction. Remarkably, the as-synthesized Fe SAS/Tr-COF as a representative catalyst achieved an impressive CO generation rate as high as 980.3 µmol g-1 h-1 and a selectivity of 96.4%, over approximately 26 times higher than that of the pristine Tr-COF under visible light irradiation. From X-ray absorption fine structure analysis and density functional theory calculations, the superior photocatalytic performance is attributed to the synergic effect of atomically dispersed metal sites and Tr-COF host, decreasing the reaction energy barriers for the formation of *COOH intermediates and promoting CO2 adsorption and activation as well as CO desorption. This work not only affords rational design of state-of-the-art catalysts at the molecular level but also provides in-depth insights for efficient CO2 conversion.

Incorporating Boron into Niobic Acid Nanosheets Enables Generation of Multiple Reactive Oxygen Species for Superior Antibacterial Action.

Photocatalytic therapy is an alternative antibacterial pathway but most photocatalysts are limited by light absorption, charge transfer and insufficient production of reactive oxygen species (ROS). Herein, the authors utilize boron doped niobic acid nanosheets (B-HNbO3 NSs) as a superior photocatalytic antibacterial platform. The experimental results and density functional theory (DFT) confirm that superior photocatalytic therapy activity is mainly due to boron doping, which not only promotes the generation and separation of electrons and holes, but also enhances the adsorption of water and oxygen molecules on B-HNbO3 NSs. Consequently, multiple ROS including hydroxyl radicals (•OH), superoxide radicals (•O2- ), and singlet oxygen (1 O2 ) are generated under light irradiation, resulting in outstanding bacterial killing ability of B-HNbO3 NSs. Besides, oxygen is produced during the therapy process, thus alleviating the inflammatory response caused by hypoxia. Furthermore, molecular dynamics (MD) simulations verify that the nanosheet structure makes it possess strong electrostatic attraction for bacterial cell membranes, leading to physical insertion and damage to bacterial cells. Therefore, bactericidal rates for four types of bacteria are all more than 99%, proving its excellent and broad-spectrum antibacterial capacity. Moreover, B-HNbO3 NSs could be applied to treat biofilm-coated medical devices in vivo, suggesting its possibility in practical application.

Paenibacillus hamazuiensis sp. nov., a bacterium isolated from Hamazui hot spring in Yunnan province, south-west China.

A bacterial strain, Gram-positive, aerobic, rod-shaped, motile, designated YIM B00624T which was isolated from a Hamazui hot spring in Tengchong, Yunnan province, south-west China. The strain grew well on International Streptomyces Project (ISP) 2 medium and colonies were creamy yellow, flat and circular. The results of 16S rRNA gene sequence similarity analysis showed that strain YIM B00624T was closely related to the type strain of Paenibacillus filicis S4T (95.9%). The main menaquinone of strain YIM B00624T was menaquinone-7 (MK-7) and major fatty acids were anteiso-C15:0, anteiso-C17:0 and C16:0. The isolate contained meso-diaminopimelic acid as the diagnostic diamino acid and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine and four unidentified glycolipids. The DNA G+C content of strain YIM B00624T was 53.4 mol%. Based on physiological, phenotypic and chemotaxonomic data, strain YIM B00624T belongs to a novel species of the genus Paenibacillus, for which the name Paenibacillus hamazuiensis sp. nov. is proposed. The type strain is YIM B00624T (= CGMCC 1.19245T = KCTC 43365T).

Dyadobacter diqingensis sp. nov., isolated from Baima snow mountain of Diqing Tibetan Autonomous Prefecture in Yunnan province, south-west China.

A Gram-negative, aerobic, nonmotile, rod-shaped and yellow-pigment-producing bacteria was isolated from Baima snow mountain of Diqing Tibetan Autonomous Prefecture in Yunnan province, south-west China and characterized using a polyphasic approach. The results of 16S rRNA gene sequence similarity analysis showed that strain YIM B04101T was closely related to the type strain of Dyadobacter koreensis DSM 19938T (97.81%) and Dyadobacter frigoris AR-3-8T (97.95%). The predominant respiratory quinone was menaquinone-7 (MK-7). The major polar lipid was phosphatidylethanolamine. The major fatty acids were summed feature 3 (C16:1ω7c/C16:1ω6c), C18:1ω9c and C16:0. The DNA G + C content was 43.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain YIM B04101T belonged to a cluster comprising species of the genus Dyadobacter. However, it differed from its closest relative, Dyadobacter koreensis KCTC 12537T and Dyadobacter frigoris AR-3-8T, in many physiological properties. Based on these phenotypic characteristics and phylogenetic distinctiveness, strain YIM B04101T is considered to be a novel species of the genus Dyadobacter, for which the name Dyadobacter diqingensis sp. nov. is proposed. The type strain is YIM B04101T (= CGMCC 1.19249T = CCTCC AB 2021270).

Comparison Between Hemodialysis and Peritoneal Dialysis in the Risks for Disease Activity in LN-ESRD Patients: A Systematic Review and Meta-analysis.

Context: End-stage renal disease (ESRD) is the advanced stage of a progressive loss of kidney function. About 10% of all patients with lupus nephritis (LN) eventually progress to ESRD, which may necessitate renal replacement therapy (RRT), such as hemodialysis (HD), peritoneal dialysis (PD), and/or kidney transplant. Research hasn't confirmed which dialysis options, prior to kidney transplantation, are beneficial to patients' prognoses. Objective: The study intended to compare the risks-related to disease activity, exercise, all-cause infection, all-cause cardiovascular events, and mortality-of the use of HD and PD for LN-ESRD adults, as the initial alternative treatment before renal transplantation. Design: The research team performed a narrative review and analyzed the data obtained about clinical outcomes for HD and peritoneal dialysis. For the review, the research team searched the PubMed, EMBASE, and SCOPUS databases. The search used the keywords: end-stage renal disease, renal replacement therapy, hemodialysis and peritoneal dialysis. Setting: The study made in Affiliated Hospital of Hebei University, China. Participants: The studies included 15 636 patients who had been diagnosed with LN-ESRD prior to renal transplantation. Outcome Measures: For the data analysis, the research team divided the data into two groups, one of which included the data on the clinical outcomes for HD patientsand one of which included the data on the clinical outcomes for PD patients. The study evaluated four types of risks: lupus-flare risks, all-cause infection risks, all-cause cardiovascular events risk, and risk of mortality. Results: The 16 studies found in the review reported one or more outcomes of interest for the two dialysis modalities, HD and PD. The analysis of the data from the 16 studies showed that HD was associated with a higher risk than PD: (1) of lupus flares, with RR = 1.23 (confidence interval: 0.82, 1.85), but the difference didn't reach statistical significance (P = .31); (2) of all-cause infection risk, with RR = 1.02 (confidence interval: 0.66, 1.59), but the difference didn't reach statistical significance (P = .92); (3) of all-cause cardiovascular events, with RR = 1.44 (confidence interval: 1.02, 2.04), and the difference reached statistical significance (P = .04); and (4) of mortality risk, with RR = 1.29 (confidence interval: 0.95, 1.75), but the difference didn't reach statistical significance (P = .10). Conclusions: The current study may have reference significance for clinical treatment of ESRD. Except for all-cause cardiovascular events in which PD was superior to HD, offering better outcomes, both treatment modalities provide more or less similar clinical outcomes as effective initial choices for RRT in LN-ESRD patients prior to renal transplant. The current research team, however, encourages further research on the question, addressing better the possible sources of biases encountered in the current study.

Organic Photo-antimicrobials: Principles, Molecule Design, and Applications.

The emergence of multi-drug-resistant pathogens threatens the healthcare systems world-wide. Recent advances in phototherapy (PT) approaches mediated by photo-antimicrobials (PAMs) provide new opportunities for the current serious antibiotic resistance. During the PT treatment, reactive oxygen species or heat produced by PAMs would react with the cell membrane, consequently leaking cytoplasm components and effectively eradicating different pathogens like bacteria, fungi, viruses, and even parasites. This Perspective will concentrate on the development of different organic photo-antimicrobials (OPAMs) and their application as practical therapeutic agents into therapy for local infections, wound dressings, and removal of biofilms from medical devices. We also discuss how to design highly efficient OPAMs by modifying the chemical structure or conjugating with a targeting component. Moreover, this Perspective provides a discussion of the general challenges and direction for OPAMs and what further needs to be done. It is hoped that through this overview, OPAMs can prosper and will be more widely used for microbial infections in the future, especially at a time when the global COVID-19 epidemic is getting more serious.

Conformal Macroporous Inverse Opal Oxynitride-Based Photoanode for Robust Photoelectrochemical Water Splitting.

Direct photoelectrochemical (PEC) water splitting is of prime importance in sustainable energy conversion systems; however, it is a big challenge to simultaneously control light harvesting and charge transport for the improvement of PEC performance. Herein, we report a three-dimensional ordered macroporous (3DOM) CsTaWO6-xNx inverse opal array as a promising candidate for the first time. To address the critical challenge, an ultrathin carbon-nitride-based layer-intercalated 3DOM CsTaWO6-xNx architecture as a conformal heterojunction photoanode was assembled. This state-of-the-art conformal heterojunction photoanode with carrier-separation efficiency up to 88% achieves a high current density of 4.59 mA cm-2 at 1.6 V versus a reversible hydrogen electrode (vs RHE) under simulated AM 1.5G illumination, which is approximately 3.4 and 17 times larger than that of pristine CsTaWO6-xNx inverse opals and powers photoelectrodes in alkaline media, corresponding to an incident photon-to-current efficiency of 32% at 400 nm and outstanding stability for PEC water splitting. Density functional theory calculations propose that the intimate interface of a conformal photoanode optimizes the charge separation and transfer, thus enhancing the intrinsic water oxidation performance. This work enables us to elucidate the pivotal importance of 3DOM architectures and conformal heterostructures and the promising contributions to excellent PEC water-splitting applications.

Engineering Single-Atomic Ni-N4-O Sites on Semiconductor Photoanodes for High-Performance Photoelectrochemical Water Splitting.

Direct photoelectrochemical (PEC) water splitting is a promising solution for solar energy conversion; however, there is a pressing bottleneck to address the intrinsic charge transport for the enhancement of PEC performance. Herein, a versatile coupling strategy was developed to engineer atomically dispersed Ni-N4 sites coordinated with an axial direction oxygen atom (Ni-N4-O) incorporated between oxygen evolution cocatalyst (OEC) and semiconductor photoanode, boosting the photogenerated electron-hole separation and thus improving PEC activity. This state-of-the-art OEC/Ni-N4-O/BiVO4 photoanode exhibits a record high photocurrent density of 6.0 mA cm-2 at 1.23 V versus reversible hydrogen electrode (vs RHE), over approximately 3.97 times larger than that of BiVO4, achieving outstanding long-term photostability. From X-ray absorption fine structure analysis and density functional theory calculations, the enhanced PEC performance is attributed to the construction of single-atomic Ni-N4-O moiety in OEC/BiVO4, facilitating the holes transfer, decreasing the free energy barriers, and accelerating the reaction kinetics. This work enables us to develop an effective pathway to design and fabricate efficient and stable photoanodes for feasible PEC water splitting application.

Engineering Lattice Oxygen Activation of Iridium Clusters Stabilized on Amorphous Bimetal Borides Array for Oxygen Evolution Reaction.

Developing robust oxygen evolution reaction (OER) catalysts requires significant advances in material design and in-depth understanding for water electrolysis. Herein, we report iridium clusters stabilized surface reconstructed oxyhydroxides on amorphous metal borides array, achieving an ultralow overpotential of 178 mV at 10 mA cm-2 for OER in alkaline medium. The coupling of iridium clusters induced the formation of high valence cobalt species and Ir-O-Co bridge between iridium and oxyhydroxides at the atomic scale, engineering lattice oxygen activation and non-concerted proton-electron transfer to trigger multiple active sites for intrinsic pH-dependent OER activity. The lattice oxygen oxidation mechanism (LOM) was confirmed by in situ 18 O isotope labeling mass spectrometry and chemical recognition of negative peroxo-like species. Theoretical simulations reveal that the OER performance on this catalyst is intrinsically dominated by LOM pathway, facilitating the reaction kinetics. This work not only paves an avenue for the rational design of electrocatalysts, but also serves the fundamental insights into the lattice oxygen participation for promising OER application.

Liver metabolic perturbations of heat-stressed lactating dairy cows.

OBJECTIVE: The objective of the present study was to elucidate the mechanism underlying liver metabolic perturbations in dairy cows exposed to heat stress (HS). METHODS: Liquid chromatography massabl spectrometry was used to analyze metabolic differences in livers of 20 dairy cows, with and without exposure to HS. RESULTS: The results revealed 33 potential metabolite candidate biomarkers for the detection of HS in dairy cows. Fifteen of these metabolites (glucose, lactate, pyruvate, acetoacetate, ß-hydroxybutyrate, fumaric acid, citric acid, choline, glycine, proline, isoleucine, leucine, urea, creatinine, and orotic acid) were previously found to be potential biomarkers of HS in plasma or milk, discriminating dairy cows with and without HS. CONCLUSION: All the potential diagnostic biomarkers were involved in glycolysis, amino acid, ketone, tricarboxylic acid, or nucleotide metabolism, indicating that HS mainly affected energy and nucleotide metabolism in lactating dairy cows.

Perceived built environment as a mediator linking objective built environment and leisure-time physical activity in Chinese cities.

Numerous studies have suggested that the perceived built environment is shaped by the objective built environment and influences human physical activity. However, the empirical examination of this pathway remains scant. Addressing this gap, our study investigates whether the built environment affects leisure-time physical activity through its impact on the perceived built environment, utilizing data collected from 760 residents in Fuzhou, China. Structural Equation Modeling results reveal a modest correlation between objective and perceived built environment elements, with the objective built environment being a stronger predictor of leisure-time physical activity. Notably, perceived recreational facilities significantly mediate the relationship between objective recreational facilities and leisure-time physical activity, accounting for 15% of the variance in physical activity due to objective recreational facilities. This mediation effect is consistent across subpopulations, irrespective of residential self-selection biases. These results highlight the imperative for urban planning and policy to extend beyond mere spatial allocation of amenities to enhancing both the actual and perceived accessibility of these facilities, thus underlining the study's profound implications for public health and urban development strategies.

Acute renal failure caused by Sjögren's syndrome and rheumatoid arthritis overlap syndrome.

Introduction: Sjögren's syndrome (SS) and rheumatoid arthritis (RA) are two chronic autoimmune diseases. To date, there have been few reports on the overlap between SS and RA in China, especially regarding correlated acute renal failure cases. Methods: To provide a reference for our clinical peers, this article presents the case report of an elderly female patient who was diagnosed with acute renal failure caused by SS and RA overlap syndrome. Results: We also provide a relevant analysis of SS and RA overlap syndrome treatment. Conclusions: We also provide a relevant analysis of SS and RA overlap syndrome treatment.

Efficacy of tacrolimus monotherapy in primary membranous nephropathy.

Objective: The aim of this study was to observe the remission of primary membranous nephropathy (PMN) and evaluate the efficacy of tacrolimus (TAC) monotherapy for PMN in comparison with TAC combined with a low-dose glucocorticoid (GC) protocol (TAC + GC). Methods: This was tested in a prospective monocentric observational trial of 70 patients with PMN, of whom 34 received TAC (0.05-0.075 mg/kg/day) or 36 received TAC (0.05-0.075 mg/kg/day) and GC (0.3-0.5 mg/kg/day of prednisone). Results: At 3, 6, 9, and 12 months of treatment, the effective rates in the TAC group and the TAC + GC group were similar (P > 0.05). The urinary protein quantification was reduced in patients under both therapeutic protocols, and the differences in the proteinuria quantification at 3, 6, 9, and 12 months of treatment were not statistically significant between the two groups (P > 0.05). The overall incidence of adverse reactions in the TAC group was lower than that in the TAC + GC group (23.5% < 36.1%), and the difference was statistically significant (P < 0.05). Conclusion: TAC monotherapy for PMN could effectively reduce urinary protein quantification and increase serum albumin levels. Compared with TAC + GC, TAC monotherapy for PMN had no difference in efficacy and fewer incidences of adverse reactions.

Oleanolic Acid Promotes the Formation of Probiotic Escherichia coli Nissle 1917 (EcN) Biofilm by Inhibiting Bacterial Motility.

Probiotic biofilms have been beneficial in the fight against infections, restoring the equilibrium of the host's gut microbiota, and enhancing host health. They are considered a novel strategy for probiotic gut colonization. In this case, we evaluated the effects of various active substances from traditional Chinese medicine on Escherichia coli Nissle 1917 (EcN) to determine if they promote biofilm formation. It was shown that 8-64 µg/mL of oleanolic acid increased the development of EcN biofilm. Additionally, we observed that oleanolic acid can effectively suppress biofilm formation in pathogenic bacteria such as Salmonella and Staphylococcus aureus. Next, we assessed the amount of EcN extracellular polysaccharides, the number of live bacteria, their metabolic activity, the hydrophobicity of their surface, and the shape of their biofilms using laser confocal microscopy. Through transcriptome analysis, a total of 349 differentially expressed genes were identified, comprising 134 upregulated and 215 downregulated genes. GO functional enrichment analysis and KEGG pathway enrichment analysis revealed that oleanolic acid functions are through the regulation of bacterial motility, the iron absorption system, the two-component system, and adhesion pathways. These findings suggest that the main effects of oleanolic acid are to prevent bacterial motility, increase initial adhesion, and encourage the development of EcN biofilms. In addition, oleanolic acid interacts with iron absorption to cooperatively control the production of EcN biofilms within an optimal concentration range. Taking these results together, this study suggests that oleanolic acid may enhance probiotic biofilm formation in the intestines, presenting new avenues for probiotic product development.

Recombinant Keratin-Chitosan Cryogel Decorated with Gallic Acid-Reduced Silver Nanoparticles for Wound Healing.

Background: Wound healing is a complex physiological process that can be roughly divided into four stages: hemostasis, inflammation, proliferation, and remodeling. Conventional wound dressings often fail to meet the diverse needs of these healing stages due to their limited functionality. Cryogels, however, possess several attractive properties, such as large, interconnected pores, good mechanical strength, and ease of modification, making them suitable for developing advanced dressings with multiple functions. In this study, we developed a multifunctional cryogel dressing, with biocompatible polysaccharides as the main component, designed to provide a breathable, moist, and antibacterial microenvironment for chronic infected wounds, thereby promoting wound healing. Methods: Recombinant keratin 31 (RK31) was combined with chitosan (CS) to produce a CS/RK31 cryogel, referred to as CK. Gallic acid-reduced silver nanoparticles (GA/Ag NPs) were incorporated as the active antibacterial component to create the CS/K31@GA/Ag cryogel, known as CKGA. The cryogel was characterized using scanning electron microscopy (SEM) and a universal testing machine, and its biocompatibility was assessed in vitro. The dynamic hemostatic performance of the cryogel was evaluated with a rat tail amputation bleeding model. Additionally, the antibacterial effects of the cryogel against Staphylococcus aureus and Escherichia coli were tested using agar diffusion assays and turbidimetry. The antioxidant capacity of the CKGA cryogel was also measured in vitro. Finally, the cryogel's ability to promote wound healing was tested in an SD rat model of infected wounds. Results: Characterization results showed that the CKGA cryogel features an interpenetrating porous network structure and exhibits excellent mechanical properties, with a swelling rate of up to 1800%. Both in vitro and in vivo experiments confirmed that the cryogel has good biocompatibility, effectively absorbs exudates, and rapidly stops bleeding. The addition of GA/Ag NPs provided significant antibacterial effects, achieving an inhibition rate of over 99.9% against both S. aureus and E. coli. Furthermore, CKGA cryogels demonstrated a strong scavenging capacity for ROS in a dose-dependent manner. Studies using the SD rat infected wound model showed that the cryogel effectively inhibited bacterial proliferation on wound surfaces, reduced local tissue inflammation, and promoted the healing of infected wounds. Conclusion: The multifunctional cryogel, with its rapid hemostatic, antibacterial, and antioxidant properties, as well as its ability to promote cell proliferation, could be widely used as a wound dressing for the healing of bacterial infections.

Role and Therapeutic Potential for Targeting Fibroblast Growth Factor 10/FGFR1 in Relapsed Rheumatoid Arthritis.

OBJECTIVE: Fibroblast-like synoviocytes (FLSs) contribute to inflammation and joint damage in rheumatoid arthritis (RA). However, the regulatory mechanisms of FLSs in relapse and remission of RA remain unknown. Identifying FLS heterogeneity and their underlying pathogenic roles may lead to discovering novel disease-modifying antirheumatic drugs. METHODS: Combining single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics, we sequenced six matched synovial tissue samples from three patients with relapse RA and three patients in remission. We analyzed the differences in the transcriptomes of the FLS subsets between the relapse and remitted phases. We validated several key signaling pathways using quantitative real-time PCR (qPCR) and multiplex immunohistochemistry (mIHC). We further targeted the critical signals in vitro and in vivo using the collagen-induced arthritis (CIA) model in rats. RESULTS: Lining and sublining FLS subsets were identified using scRNA-seq. Differential analyses indicated that the fibroblast growth factor (FGF) pathway was highly activated in the lining FLSs from patients with relapse RA for which mIHC confirmed the increased expression of FGF10. Although the type I interferon pathway was also activated in the lining FLSs, in vitro stimulation experiment suggested that it was independent of the FGF10 pathway. FGF10 knockdown by small interfering RNA in FLSs significantly reduced the expression of receptor activator of NF-κB ligand. Moreover, recombinant FGF10 protein enhanced bone erosion in the primary human-derived pannus cell culture, whereas the FGF receptor (FGFR) 1 inhibitor attenuated this process. Finally, administering an FGFR1 inhibitor displayed a therapeutic effect in a CIA rat model. CONCLUSION: The FGF pathway is a critical signaling pathway in relapse RA. Targeted tissue-specific inhibition of FGF10/FGFR1 may provide new opportunities to treat patients with relapse RA.

Depression in the next generation is related with maternal behaviors: A cross-comparison by alternating rat's mother care.

This study investigated the potential impacts of depressive rats' maternal behavior as an early life stress on the outcome of offspring as an adulthood. Offspring from the same mother were divided into two groups, half of them were fostered or remained by a depressive mother, and the other half remained or fostered by a control mother, respectively. The results showed that offspring fostered by depressive mothers presented significant depressive behaviors. Meanwhile, depressive mothers engaged in more grooming during the light cycle, but less off-the-pup behavior during the dark phase. In conclusion, offspring exposed to a postnatal depressive maternal environment developed a depressive-like behavior. Contrarily, postpartum maternal behaviors play an essential role, which might determine the outcome of the next generation. Furthermore, the appropriate timing of postpartum maternal caring sequences, which might eliminate prenatal stressful influences, was recognized and might be a promising approach for reducing children's predisposition to mental disorders in their life time.

Determinants of Sarcopenia in Elderly Patients with Chronic Kidney Disease.

INTRODUCTION: This study was conducted to determine the factors affecting the development of sarcopenias in elderly patients with chronic kidney disease (CKD), in order to provide future clinical reference and guidance in preventing the occurrence of sarcopenias in patients with CKD. METHODS: We included 116 CKD patients admitted to affiliated Hospital of Hebei University for retrospective analysis between September 2019 and March 2022. Fifty-one CKD patients with sarcopenias were selected as the observation group (OG) and 65 CKD patients without sarcopenias were considered as the control group (CG). Clinical baseline data such as age and sex were recorded, venous blood was collected for routine examination, and a multi-frequency body composition analyzer was applied to measure patients' body composition. Grip strength, middle arm circumstances (MAC) and triceps skin-fold thickness (TSF) were also measured. Then, patients' sleep quality, nutritional status and negative psychological status were assessed by using the Pittsburgh Sleep Quality Index (PSQI), Malnutrition inflammation score (MIS), and Self-rating Anxiety/Depression Scale (SAS/SDS), respectively. Differences in test results were compared inter-group, and the factors affecting the occurrence of sarcopenias in CKD patients were analyzed by multiple Logistic regression. RESULTS: OG patients were older than CG patients, with a higher number of female patients. Their BMI, bone mass, MAC, serum creatinine (Scr), uric acid (UA) and triglyceride (TG) were lower (P < .05). According to multiple Logistic regression analysis, age, as well as PSQI, MIS, SAS, and SDS scores were the risk factors for sarcopenias in CKD, while BMI, bone mass, MAC, Scr, UA and TG were protective factors (P < .05). CONCLUSION: Age, poor sleep quality, poor nutritional status and negative emotions are independent risk factors for sarcopenias in CKD patients, while BMI, bone mass, MAC, UA, TG, and Scr are independent protective factors.  DOI: 10.52547/ijkd.7537.