Novel muscle-derived extracellular matrix hydrogel promotes angiogenesis and neurogenesis in volumetric muscle loss.

Volumetric muscle loss (VML) represents a clinical challenge due to the limited regenerative capacity of skeletal muscle. Most often, it results in scar tissue formation and loss of function, which cannot be prevented by current therapies. Decellularized extracellular matrix (DEM) has emerged as a native biomaterial for the enhancement of tissue repair. Here, we report the generation and characterization of hydrogels derived from DEM prepared from WT or thrombospondin (TSP)-2 null muscle tissue. TSP2-null hydrogels, when compared to WT, displayed altered architecture, protein composition, and biomechanical properties and allowed enhanced invasion of C2C12 myocytes and chord formation by endothelial cells. They also displayed enhanced cell invasion, innervation, and angiogenesis following subcutaneous implantation. To evaluate their regenerative capacity, WT or TSP2 null hydrogels were used to treat VML injury to tibialis anterior muscles and the latter induced greater recruitment of repair cells, innervation, and blood vessel formation and reduced inflammation. Taken together, these observations indicate that TSP2-null hydrogels enhance angiogenesis and promote muscle repair in a VML model.

Rapid UV Photo-Cross-Linking of α-Lactalbumin Hydrogel Biomaterial To Enable Wound Healing.

Although both the function and biocompatibility of protein-based biomaterials are better than those of synthetic materials, their usage as medical material is currently limited by their high costs, low yield, and low batch-to-batch reproducibility. In this article, we show how α-lactalbumin (α-LA), rich in tryptophan, was used to produce a novel type of naturally occurring, protein-based biomaterial suitable for wound dressing. To create a photo-cross-linkable polymer, α-LA was methacrylated at a 100-g batch scale with >95% conversion and 90% yield. α-LAMA was further processed using photo-cross-linking-based advanced processing techniques such as microfluidics and 3D printing to create injectable hydrogels, monodispersed microspheres, and patterned scaffolds. The obtained α-LAMA hydrogels show promising biocompatibility and degradability during in vivo testing. Additionally, the α-LAMA hydrogel can accelerate post-traumatic wound healing and promote new tissue regeneration. In conclusion, cheap and safe α-LAMA-based biomaterials could be produced, and they have a beneficial effect on wound healing. As a result, there may arise a potential partnership between the dairy industry and the development of pharmaceuticals.

Selection of indicators reporting response rate in pharmaceutical trials for systemic lupus erythematosus: preference and relative sensitivity.

OBJECTIVE: SLE is a common multisystem autoimmune disease with chronic inflammation. Many efficacy evaluation indicators of randomised clinical trials (RCTs) for SLE have been proposed but the comparability remains unknown. We aim to explore the preference and comparability of indicators reporting response rate and provide basis for primary outcome selection when evaluating the efficacy of SLE pharmaceutical treatment. METHODS: We systematically searched three databases and three registries to identify pharmacological intervention-controlled SLE RCTs. Relative discriminations between indicators were assessed by the Bayesian hierarchical linear mixed model. RESULTS: 33 RCTs met our inclusion criteria and we compared eight of the most commonly used indicators reporting response rate. SLE Disease Activity Index 4 (SLEDAI-4) and SLE Responder Index 4 were considered the best recommended indicators reporting response rate to discriminate the pharmacological efficacy. Indicator preference was altered by disease severity, classification of drugs and outcome of trials, but SLEDAI-4 had robust efficacy in discriminating ability for most interventions. Of note, BILAG Index-based Combined Lupus Assessment showed efficacy in trials covering all-severity patients, as well as non-biologics RCTs. The British Isles Lupus Assessment Group response and Physician's Global Assessment response were more cautious in evaluating disease changes. Serious adverse event was often applied to evaluate the safety and tolerability of treatments rather than efficacy. CONCLUSIONS: The impressionable efficacy discrimination ability of indicators highlights the importance of flexibility and comprehensiveness when choosing primary outcome(s). As for trials that are only evaluated by SLEDAI-4, attention should be paid to outcome interpretation to avoid the exaggeration of treatment efficacy. Further subgroup analyses are limited by the number of included RCTs. PROSPERO REGISTRATION NUMBER: CRD42022334517.

Global epidemiology of atopic dermatitis: a comprehensive systematic analysis and modelling study.

BACKGROUND: Atopic dermatitis (AD) is the leading cause of the global burden from skin disease; no study has provided global and country-specific epidemiological estimates of AD. OBJECTIVES: To quantify global, regional and country-specific estimates of the epidemiology of AD. METHODS: A comprehensive search for epidemiological studies in AD was conducted in four electronic databases (PubMed, Embase, Web of Science and China National Knowledge Infrastructure). A Bayesian hierarchical linear mixed model was constructed to calculate epidemiological estimates of AD considering the heterogeneity of regions, countries, type of diagnoses and age strata. RESULTS: In total, 344 studies met the inclusion criteria. Incidence varied substantially with the location and age of the surveyed participants. The global prevalence of AD and the population affected by AD were estimated to be 2.6% [95% uncertainty interval (UI) 1.9-3.5] and 204.05 million people, respectively. Around 101.27 million adults and 102.78 million children worldwide have AD, corresponding to prevalence rates of 2.0% (95% UI 1.4-2.6) and 4.0% (95% UI 2.8-5.3), respectively. Females were more likely to suffer from AD than males: the global prevalence of AD in females was 2.8% (95% UI 2.0-3.7%) and affected 108.29 million people, while in males the corresponding estimates were 2.4% (95% UI 1.7-3.3%) and 95.76 million people. CONCLUSIONS: Epidemiological AD data are lacking in 41.5% of countries worldwide. The epidemiology of AD varies substantially with age and sex and is distributed unequally across geographical regions.

Rolipram suppresses migration and invasion of human choriocarcinoma cells by inhibiting phosphodiesterase 4-mediated epithelial-mesenchymal transition.

Rolipram is a selective phosphodiesterase-4 (PDE4) inhibitor. The effect of rolipram on the metastasis of choriocarcinoma is barely known. Here, we evaluated the role of rolipram in the migration and invasion of human choriocarcinoma cells in vitro. Human choriocarcinoma cells lines JEG3 and JAR were used in this study. The expression profile of PDE4 subfamily members in choriocarcinoma cells was evaluated using real-time PCR. The migration and invasion properties of choriocarcinoma cells before and after inhibition of PDE4 by rolipram or RNAi-directed knockdown were evaluated in vitro. Expression levels of MMP9, TIMP1, E-cadherin, vimentin, TGFß1, SMAD1, and SMAD4 of choriocarcinoma cells were compared before and after rolipram treatment, RNAi-directed knockdown of PDE4D, and overexpression of PDE4D. We found PDE4D was the most commonly expressed isoform of PDE4 both in JEG3 and JAR cells. Rolipram and knockdown of PDE4D were efficient to inhibit the migration and invasion of choriocarcinoma cells in vitro, accompanied by decreased expression of MMP9 and TIMP1. Furthermore, rolipram and knockdown of PDE4D promoted the expression of E-cadherin but reduced the expression of vimentin in choriocarcinoma cells, and overexpression of PDE4D decreased the expression of E-cadherin but promoted the expression of vimentin. Rolipram suppressed migration and invasion of human choriocarcinoma cells in vitro, possibly by inhibiting epithelial-mesenchymal transition through PDE4 inhibition.

Global, regional, and national incidence and prevalence of systemic sclerosis.

OBJECTIVES: To estimate the global and country-specific unbiased epidemiological data of SSc. METHODS: Epidemiological studies were systematically searched in four databases. A Bayesian hierarchical linear mixed model was constructed to estimate epidemiological data. RESULTS: 82 studies were included and epidemiological data on SSc were missing for 83.9% of countries worldwide. The global SSc incidence and newly diagnosed population were estimated to be 8.64 per 100,000 person-years (1.78-23.57) and 0.67 million (0.14-1.84) people annually, respectively. Regarding prevalence, the global SSc prevalence and affected population were 18.87 per 100,000 persons (1.55-25.28) and 1.47 million (0.12-1.97) people, respectively. Relatively higher incidence and prevalence were observed in females, adults, and high-income level countries. CONCLUSIONS: We provide a comprehensive synthesis of SSc epidemiology and fill data gaps in most countries. Especially in low- and middle-income countries, epidemiological studies of SSc are insufficient. Further large-scale and standardized reported epidemiological investigations of SSc are imperative.

MRI-based radiomics nomogram in patients with high-risk placenta accreta spectrum: can it aid in the prenatal diagnosis of intraoperative blood loss?

PURPOSE: To develop and validate the nomogram by combining MRI-derived radiomics and clinical features for preoperatively predicting massive intraoperative blood loss (IBL) in high-risk placenta accreta spectrum (PAS) patients. METHODS: A total of 152 high-risk PAS patients from Hospital A were enrolled and constituted the training cohort, and 64 patients from Hospital B constituted the validation cohort. Clinical features were analyzed retrospectively. Placental regions of interest were manually positioned on sagittal T2-weighted HASTE images for each patient to extract quantitative radiomics features. Clinical model, radiomics model, and nomogram were built to predict the risk of massive IBL. The diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUC) and the DeLong test. Decision curve analysis (DCA) was performed to determine the performance of the best predictive model. RESULTS: The nomogram (AUC = 0.866 and 0.876, respectively) and radiomics model (AUC = 0.821 and 0.855, respectively) outperformed the clinical model (AUC = 0.685 and 0.619, respectively) both in the training and validation cohorts (Delong test, P < 0.05). Furthermore, the nomogram performed best with an accuracy of 0.844, sensitivity of 0.882, and specificity of 0.830 for differentiating massive IBL in the validation cohort. DCA confirmed the clinical utility of the nomogram. CONCLUSION: The nomogram can be used to noninvasively predict massive IBL patients and guide obstetricians to make reasonable preoperative treatment plans.

Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study.

OBJECTIVES: To quantify global, regional and country-specific estimates of epidemiology of systemic lupus erythematosus (SLE). METHODS: Four databases were systematically searched, and a Bayesian hierarchical linear mixed model was constructed to estimate the global, regional, and country-specific incidence and prevalence of SLE. RESULTS: 112 studies met the inclusion criteria. The global SLE incidence and newly diagnosed population were estimated to be 5.14 (1.4 to 15.13) per 100 000 person-years and 0.40 million people annually, respectively. In women, the values were 8.82 (2.4 to 25.99) per 100 000 person-years and 0.34 million people annually, while in men, the estimates were 1.53 (0.41 to 4.46) per 100 000 person-years and 0.06 million people annually, respectively. Poland, the USA and Barbados had the highest estimates of SLE incidence. Regarding prevalence, the global SLE prevalence and affected population were estimated to be 43.7 (15.87 to 108.92) per 100 000 persons and 3.41 million people, respectively. In women, the values were 78.73 (28.61 to 196.33) per 100 000 persons and 3.04 million people, while in men the estimates were 9.26 (3.36 to 22.97) per 100 000 persons and 0.36 million people, respectively. The United Arab Emirates, Barbados and Brazil had the highest SLE prevalence. In addition to regional and sex differences, age and prevalence estimation method (period or point prevalence) differences could also lead to variations in epidemiological SLE findings. CONCLUSIONS: Epidemiological data on SLE are lacking for 79.8% of countries worldwide. The epidemiology of SLE varies substantially between different sex and age groups and is distributed unequally among geographical regions; specifically, SLE occurs more frequently in high-income countries.

Integrated transcriptome and trajectory analysis of cutaneous T-cell lymphoma identifies putative precancer populations.

The incidence of cutaneous T-cell lymphoma (CTCL) increases with age, and blood involvement portends a worse prognosis. To advance our understanding of the development of CTCL and identify potential therapeutic targets, we performed integrative analyses of paired single-cell RNA and T-cell receptor (TCR) sequencing of peripheral blood CD4+ T cells from patients with CTCL to reveal disease-unifying features. The malignant CD4+ T cells of CTCL showed highly diverse transcriptomic profiles across patients, with most displaying a mature Th2 differentiation and T-cell exhaustion phenotype. TCR-CDR3 peptide prediction analysis suggested limited diversity between CTCL samples, consistent with a role for a common antigenic stimulus. Potential of heat diffusion for affinity-based trajectory embedding transition analysis identified putative precancerous circulating populations characterized by an intermediate stage of gene expression and mutation level between the normal CD4+ T cells and malignant CTCL cells. We further revealed the therapeutic potential of targeting CD82 and JAK that endow the malignant CTCL cells with survival and proliferation advantages.

Dysregulation of TSP2-Rac1-WAVE2 axis in diabetic cells leads to cytoskeletal disorganization, increased cell stiffness, and dysfunction.

Fibroblasts are a major cell population that perform critical functions in the wound healing process. In response to injury, they proliferate and migrate into the wound space, engaging in extracellular matrix (ECM) production, remodeling, and contraction. However, there is limited knowledge of how fibroblast functions are altered in diabetes. To address this gap, several state-of-the-art microscopy techniques were employed to investigate morphology, migration, ECM production, 2D traction, 3D contraction, and cell stiffness. Analysis of cell-derived matrix (CDM) revealed that diabetic fibroblasts produce thickened and less porous ECM that hindered migration of normal fibroblasts. In addition, diabetic fibroblasts were found to lose spindle-like shape, migrate slower, generate less traction force, exert limited 3D contractility, and have increased cell stiffness. These changes were due, in part, to a decreased level of active Rac1 and a lack of co-localization between F-actin and Waskott-Aldrich syndrome protein family verprolin homologous protein 2 (WAVE2). Interestingly, deletion of thrombospondin-2 (TSP2) in diabetic fibroblasts rescued these phenotypes and restored normal levels of active Rac1 and WAVE2-F-actin co-localization. These results provide a comprehensive view of the extent of diabetic fibroblast dysfunction, highlighting the regulatory role of the TSP2-Rac1-WAVE2-actin axis, and describing a new function of TSP2 in regulating cytoskeleton organization.

ACh signaling modulates activity of the GABAergic signaling network in the basolateral amygdala and behavior in stress-relevant paradigms.

The balance between excitatory and inhibitory (E/I) signaling is important for maintaining homeostatic function in the brain. Indeed, dysregulation of inhibitory GABA interneurons in the amygdala has been implicated in human mood disorders. We hypothesized that acetylcholine (ACh) signaling in the basolateral amygdala (BLA) might alter E/I balance resulting in changes in stress-sensitive behaviors. We therefore measured ACh release as well as activity of calmodulin-dependent protein kinase II (CAMKII)-, parvalbumin (PV)-, somatostatin (SOM)- and vasoactive intestinal protein (VIP)-expressing neurons in the BLA of awake, behaving male mice. ACh levels and activity of both excitatory and inhibitory BLA neurons increased when animals were actively coping, and decreased during passive coping, in the light-dark box, tail suspension and social defeat. Changes in neuronal activity preceded behavioral state transitions, suggesting that BLA activity may drive the shift in coping strategy. In contrast to exposure to escapable stressors, prolonging ACh signaling with a cholinesterase antagonist changed the balance of activity among BLA cell types, significantly increasing activity of VIP neurons and decreasing activity of SOM cells, with little effect on CaMKII or PV neurons. Knockdown of α7 or ß2-containing nAChR subtypes in PV and SOM, but not CaMKII or VIP, BLA neurons altered behavioral responses to stressors, suggesting that ACh signaling through nAChRs on GABA neuron subtypes contributes to stress-induced changes in behavior. These studies show that ACh modulates the GABAergic signaling network in the BLA, shifting the balance between SOM, PV, VIP and CaMKII neurons, which are normally activated coordinately during active coping in response to stress. Thus, prolonging ACh signaling, as occurs in response to chronic stress, may contribute to maladaptive behaviors by shifting the balance of inhibitory signaling in the BLA.

HOTAIR/miR-1277-5p/ZEB1 axis mediates hypoxia-induced oxaliplatin resistance via regulating epithelial-mesenchymal transition in colorectal cancer.

The hypoxic microenvironment contributes to the chemoresistance of many malignant tumors including colorectal cancer (CRC). Accumulating studies have indicated that long non-coding RNAs (lncRNAs) play important roles in chemotherapy resistance. In this study, we aimed to determine the effect of lncRNAs in hypoxia-mediated resistance in CRC and its potential mechanism. Here, we discovered that hypoxia-induced oxaliplatin resistance and HOX transcript antisense RNA (HOTAIR) expression was increased in hypoxia-treated CRC cell lines and CRC tumors. Knockdown of HOTAIR by siRNA reduced the viability and proliferation of CRC cells treated with oxaliplatin and reversed hypoxia-induced resistance. Mechanically, we found that HOTAIR modulates zinc finger E-box binding homeobox 1 (ZEB1) expression by negative regulations of miR-1277-5p. When miR-1277-5p was silenced, knockdown of HOTAIR was unable to reduce the oxaliplatin resistance in CRC cells. In mouse models of CRC, HOTAIR knockdown markedly inhibited the tumor growth when treated with oxaliplatin. Thus, HOTAIR/miR-1277-5p/ZEB1 axis appears a promising therapeutic target for improving the oxaliplatin efficacy in CRC.

Social Media Disorder, Mental Health, and Validation of the Chinese Version of 27-Item Social Media Disorder Scale in Chinese College Students.

Objective: With the widespread use of social media, excessive use of social media may lead to problematic behaviors such as social media disorder, which has a negative impact on teenagers' mental health. Thus, it is an urgent need to provide a measurement tool to assess social media addiction in different cultures. The aim of this study was to assess the psychometric properties of the Chinese version of 27-item Social Media Disorder (SMD) Scale (developed using the diagnostic criteria of DSM-V Internet Gaming Disorder) in college students, and to verify its impact on mental health. Methods: Two online surveys were conducted among a total of 1,539 Chinese college students, including 1,316 subjects in sample 1 and 223 subjects in sample 2. The discrimination, criterion validity, construct validity and reliability of the Chinese version of SMD-27 scale were examined. Results: The Chinese version of SMD-27 scale showed excellent psychometric properties. The item-total correlation coefficients of the scale ranged from 0.31 to 0.56, and the item-dimension correlations of the scale ranged from 0.459 to 0.834. Findings from confirmatory factor analysis indicated a great fit of the model of the Chinese version of SMD-27, with CFI = 0.956, TLI = 0.951, RMSEA = 0.036 in sample one and CFI = 0.970, TLI = 0.967, RMSEA = 0.040 in sample two, thus confirming the second-order factor structure of the scale. The SMD-27 scale showed good internal consistency between two different samples with their respective Cronbach's alpha of 0.87 and 0.92, and good test-retest reliability over a period of 1 month. In addition, multiple regression results generally supported the impact of social media addiction on mental health. Conclusion: This study provides evidence that the Chinese version of SMD-27 scale is applicable to Chinese college populations, and it is a promising tool for the study of social media addiction in China.

Early childhood development and parental training interventions in rural China: a systematic review and meta-analysis.

INTRODUCTION: Inadequate care during early childhood can lead to long-term deficits in skills. Parenting programmes that encourage investment in young children are a promising tool for improving early development outcomes and long-term opportunities in low-income and middle-income regions, such as rural China. METHODS: We conducted a systematic review and a meta-analysis to investigate the prevalence of early developmental delays and stimulating parenting practices as well as the effect of parental training programmes on child development outcomes in rural China. We obtained data in English from EconPapers, PubMed, PsycARTICLES, Cochrane Library, Web of Science and Scopus (Elsevier) and in Chinese from China National Knowledge Infrastructure, Wanfang Data and VIP Information. We conducted frequentist meta-analyses of aggregate data and estimated random-effects meta-regressions. Certainty of evidence was rated according to the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: We identified 19 observational studies on the prevalence of developmental delays and stimulating parenting practices for children under 5 years of age (n=19 762) and ten studies on the impact of parental training programmes on early child development (n=13 766). Children's risk of cognitive, language and social-emotional delays in the rural study sites (covering 14 provinces mostly in Central and Western China) was 45%, 46%, and 36%, respectively. Parental training programmes had a positive impact on child cognition, language and social-emotional development. CONCLUSION: There is evidence to suggest that early developmental delay and the absence of stimulating parenting practices (ie, reading, storytelling and singing with children) may be prevalent across rural, low-income and middle-income regions in Central and Western China. Results support the effectiveness of parental training programmes to improve early development by encouraging parental engagement. TRIAL REGISTRATION NUMBER: This study was registered with PROSPERO (CRD42020218852).

Synthesis of 5-(1-Alkoxyalkylidene)tetronates by Direct Condensation Reactions of Tetronates with Thionolactones and Thionoesters.

We report a two-step approach to bicyclic and monocyclic 5-(1-alkoxyalkylidene)tetronates starting from lactones/esters. The method features the use of thionolactones and thionoesters as activated forms of lactones/esters that allows the direct condensation with tetronates via one-pot enolate formation, nucleophilic addition, S-methylation, and DBU-promoted elimination. The value of the method was demonstrated by the stereoselective syntheses of two natural products: 5,6-Z-fadyenolide (Z/E ratio = 6:1) and 9,10-methylenedioxy-5,6-Z-fadyenolide (Z/E ratio = 9:1).

XPD inhibits cell growth and invasion and enhances chemosensitivity in esophageal squamous cell carcinoma by regulating the PI3K/AKT signaling pathway.

Esophageal squamous cell carcinoma (ESCC) is a lethal disease due to its high aggressiveness. The aim of the present study was to investigate the role of xeroderma pigmentosum complementation group D (XPD) in the growth and invasion of ESCC and to elucidate the potential underlying molecular mechanisms. Western blot analysis and RT­qPCR were used to detect the expression level of XPD in ESCC tissue samples and adjacent normal esophageal tissue samples. The pEGFP­N2/XPD plasmid was transfected into human ESCC cell lines (EC9706 and EC109). The proliferation, apoptosis, migration and invasion of EC9706 or EC109 cells were assessed following transfection with the XPD overexpression plasmid. The chemosensitivity of EC9706 or EC109 cells to cisplatin or fluorouracil was evaluated by CCK­8 assay. The expression levels of phosphoinositide 3­kinase (PI3K)/AKT, nuclear factor (NF)­κB, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and mitogen­activated protein kinase (MAPK) signaling pathway­related genes were detected by RT­qPCR and western blot analysis. The results demonstrated that the expression level of XPD was markedly lower in ESCC tissue samples than in adjacent normal esophageal tissue samples. The pEGFP­N2/XPD plasmid was successfully transfected into EC9706 or EC109 cells, inducing XPD overexpression. A High XPD expression markedly suppressed cell proliferation, migration and invasion, and increased the apoptotic rate of EC9706 and EC109 cells. Furthermore, the overexpression of XPD significantly increased the chemosensitivity of EC9706 and EC109 cells to cisplatin or fluorouracil. Following XPD overexpression, the expression levels of PI3K, p­AKT, c­Myc, Cyclin D1, Bcl­2, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)­9 were markedly downregulated, while the expression level of p21 was markedly upregulated. On the whole, the findings of the present study demonstrate that XPD inhibits the growth and invasion of EC9706 and EC109 cells, whilst also enhancing the chemosensitivity of EC9706 and EC109 cells to cisplatin or fluorouracil by regulating the PI3K/AKT signaling pathway. XPD may thus be an underlying target for ESCC treatment and drug resistance.

Dual oxidase Duox and Toll-like receptor 3 TLR3 in the Toll pathway suppress zoonotic pathogens through regulating the intestinal bacterial community homeostasis in Hermetia illucens L.

Black soldier fly (BSF; Hermetia illucens L.) larvae can convert fresh pig manure into protein and fat-rich biomass, which can then be used as aquafeed for select species. Currently, BSF is the only approved insect for such purposes in Canada, USA, and the European Union. Pig manure could serve as a feed substrate for BSF; however, it is contaminated with zoonotic pathogens (e.g., Staphylococcus aureus and Salmonella spp.). Fortunately, BSF larvae inhibit many of these zoonotic pathogens; however, the mechanisms employed are unclear. We employed RNAi, qRT-PCR, and Illumina MiSeq 16S rDNA high-throughput sequencing to examine the interaction between two immune genes (Duox in Duox-reactive oxygen species [ROS] immune system and TLR3 in the Toll signaling pathway) and select pathogens common in pig manure to decipher the mechanisms resulting in pathogen suppression. Results indicate Bsf Duox-TLR3 RNAi increased bacterial load but decreased relative abundance of Providencia and Dysgonomonas, which are thought to be commensals in the BSF larval gut. Bsf Duox-TLR3 RNAi also inactivated the NF-κB signaling pathway, downregulated the expression of antimicrobial peptides, and diminished inhibitory effects on zoonotic pathogen. The resulting dysbiosis stimulated an immune response by activating BsfDuox and promoting ROS, which regulated the composition and structure of the gut bacterial community. Thus, BsfDuox and BsfTLR3 are important factors in regulating these key gut microbes, while inhibiting target zoonotic pathogens.

The role of extracellular matrix in the pathophysiology of diabetic wounds.

Impaired healing leading to the formation of ulcerated wounds is a critical concern in patients with diabetes. Abnormalities in extracellular matrix (ECM) production and remodeling contribute to tissue dysfunction and delayed healing. Specifically, diabetes-induced changes in the expression and/or activity of structural proteins, ECM-modifying enzymes, proteoglycans, and matricellular proteins have been reported. In this review, we provide a summary of the key ECM molecules and associated changes in skin and diabetic wounds. Such information should allow for new insights in the understanding of impaired wound healing and lead to the development of ECM-based therapeutic strategies.

Small-world properties of the whole-brain functional networks in patients with obstructive sleep apnea-hypopnea syndrome.

OBJECTIVE: To explore the small-world properties of brain functional networks in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) to aid diagnosis. METHODS: A total of 29 OSAHS patients and 26 matched healthy volunteers were scanned with blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) separately, and the whole brain was divided into 90 districts via automated anatomical labeling. The matrix Z was then built through a Fisher Z transformation. Two-sample t tests were applied to evaluate the changes in small-world properties in OSAHS patients compared to the control group. The properties included Eglobal, Elocal, and small-world parameters Lp, Cp, γ, λ, and σ. RESULTS: Both groups satisfied the small-world properties (σ > 1) within the sparsity range of 0.1-0.2. However, compared with the control group, the OSAHS group performed significantly lower in Cp, Elocal, and Eglobal (p < 0.05) and higher in Lp (p < 0.05). The γ, σ, and λ values were not significantly different between the two groups. CONCLUSION: Both healthy and OSAHS patients exhibited small-world properties in functional networks, but a subset of these small-world properties in OSAHS patients performed differently. These changes will not only provide a new perspective for pathophysiological mechanisms of OSAHS but will also help in understanding the disease in terms of whole-brain functional networks.