Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior.

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response. Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region-specific, particularly involving the corticolimbic system, including the ventral tegmental area, nucleus accumbens, prefrontal cortex, amygdala, and hippocampus. Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology. In this review, we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression. We focused on associated molecular pathways and neural circuits, with special attention to the brain-derived neurotrophic factor-tropomyosin receptor kinase B signaling pathway and the ventral tegmental area-nucleus accumbens dopamine circuit. We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature, severity, and duration of stress, especially in the above-mentioned brain regions of the corticolimbic system. Therefore, BDNF might be a biological indicator regulating stress-related processes in various brain regions.

Activation of the NLRP3-CASP-1 inflammasome is restrained by controlling autophagy during Glaesserella parasuis infection.

Infection with Glaesserella parasuis, the primary pathogen behind Glässer's disease, is often associated with diverse clinical symptoms, including serofibrinous polyserositis, arthritis, and meningitis. Autophagy plays a dual role in bacterial infections, exerting either antagonistic or synergistic effects depending on the nature of the pathogen. Our previous studies have demonstrated that autophagy serves as a defense mechanism, combating inflammation and invasion caused by infection of highly virulent G. parasuis. However, the precise mechanisms remain to be elucidated. Pathogens exhibit distinct interactions with inflammasomes and autophagy processes. Herein, we explored the effect of autophagy on inflammasomes during G. parasuis infection. We found that G. parasuis infection triggers NLRP3-dependent pro-CASP-1-IL-18/IL-1ß processing and maturation pathway, resulting in increased release of IL-1ß and IL-18. Inhibition of autophagy enhances NLRP3 inflammasome activity, whereas stimulation of autophagy restricts it during G. parasuis infection. Furthermore, assembled NLRP3 inflammasomes undergo ubiquitination and recruit the autophagic adaptor, p62, facilitating their sequestration into autophagosomes during G. parasuis infection. These results suggest that the induction of autophagy mitigates inflammation by eliminating overactive NLRP3 inflammasomes during G. parasuis infection. Our research uncovers a mechanism whereby G. parasuis infection initiates inflammatory responses by promoting the assembly of the NLRP3 inflammasomes and activating NLRP3-CASP-1, both of which processes are downregulated by autophagy. This suggests that pharmacological manipulation of autophagy could be a promising approach to modulate G. parasuis-induced inflammatory responses.

Circular RNA circNIPBL regulates TP53-H179R mutations in NNK-induced bronchial epithelial carcinogenesis.

Exposure to environmental carcinogens is a significant contributor to cancer development, with genetic and epigenetic alterations playing pivotal roles in the carcinogenic process. However, the interplay between epigenetic regulation and genetic changes in carcinogenesis has yet to receive comprehensive attention. This study investigates the impact of continuous exposure to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on bronchial epithelial cells, leading to malignant transformation. Our findings reveal the down-regulation of the tumor suppressor-like circular RNA circNIPBL during oncogenic processes concomitant with the accumulation of the TP53-H179R, a single nucleotide variant. Diminished circNIPBL expression enhances the proliferative, distant metastatic, and tumor-forming capabilities of NNK-induced cancerous cells and lung cancer cell lines (A549, H1299), while also promoting the accumulation of TP53-H179R during NNK-induced carcinogenesis. Mechanistic investigations demonstrate that circNIPBL interacts with HSP90α to regulate the translocation of AHR into the nucleus, which may be a potential regulatory mechanism for NNK-induced carcinogenesis and TP53-H179R accumulation. This study introduces a novel perspective on the interplay between genetic alterations and epigenetic regulation in chemical carcinogenesis, which provides novel insight into the etiology of cancer.

Age Estimation by Machine Learning and CT-Multiplanar Reformation of Cranial Sutures in Northern Chinese Han Adults.

OBJECTIVES: To establish age estimation models of northern Chinese Han adults using cranial suture images obtained by CT and multiplanar reformation (MPR), and to explore the applicability of cranial suture closure rule in age estimation of northern Chinese Han population. METHODS: The head CT samples of 132 northern Chinese Han adults aged 29-80 years were retrospectively collected. Volume reconstruction (VR) and MPR were performed on the skull, and 160 cranial suture tomography images were generated for each sample. Then the MPR images of cranial sutures were scored according to the closure grading criteria, and the mean closure grades of sagittal suture, coronal sutures (both left and right) and lambdoid sutures (both left and right) were calculated respectively. Finally taking the above grades as independent variables, the linear regression model and four machine learning models for age estimation (gradient boosting regression, support vector regression, decision tree regression and Bayesian ridge regression) were established for northern Chinese Han adults age estimation. The accuracy of each model was evaluated. RESULTS: Each cranial suture closure grade was positively correlated with age and the correlation of sagittal suture was the highest. All four machine learning models had higher age estimation accuracy than linear regression model. The support vector regression model had the highest accuracy among the machine learning models with a mean absolute error of 9.542 years. CONCLUSIONS: The combination of skull CT-MPR and machine learning model can be used for age estimation in northern Chinese Han adults, but it is still necessary to combine with other adult age estimation indicators in forensic practice.

Gene identification, expression analysis, and molecular docking of SAT and OASTL in the metabolic pathway of selenium in Cardamine hupingshanensis.

KEY MESSAGE: Identification of selenium stress-responsive expression and molecular docking of serine acetyltransferase (SAT) and O-acetyl serine (thiol) lyase (OASTL) in Cardamine hupingshanensis. A complex coupled with serine acetyltransferase (SAT) and O-acetyl serine (thiol) lyase (OASTL) is the key enzyme that catalyzes selenocysteine (Sec) synthesis in plants. The functions of SAT and OASTL genes were identified in some plants, but it is still unclear whether SAT and OASTL are involved in the selenium metabolic pathway in Cardamine hupingshanensis. In this study, genome-wide identification and comparative analysis of ChSATs and ChOASTLs were performed. The eight ChSAT genes were divided into three branches, and the thirteen ChOASTL genes were divided into four branches by phylogenetic analysis and sequence alignment, indicating the evolutionary conservation of the gene structure and its association with other plant species. qRT-PCR analysis showed that the ChSAT and ChOASTL genes were differentially expressed in different tissues under various selenium levels, suggesting their important roles in Sec synthesis. The ChSAT1;2 and ChOASTLA1;2 were silenced by the VIGS system to investigate their involvement in selenium metabolites in C. hupingshanensis. The findings contribute to understanding the gene functions of ChSATs and ChOASTLs in the selenium stress and provide a reference for further exploration of the selenium metabolic pathway in plants.

Tricarboxylic Acid Cycle Regulation of Metabolic Program, Redox System, and Epigenetic Remodeling for Bone Health and Disease.

Imbalanced osteogenic cell-mediated bone gain and osteoclastic remodeling accelerates the development of osteoporosis, which is the leading risk factor of disability in the elderly. Harmonizing the metabolic actions of bone-making cells and bone resorbing cells to the mineralized matrix network is required to maintain bone mass homeostasis. The tricarboxylic acid (TCA) cycle in mitochondria is a crucial process for cellular energy production and redox homeostasis. The canonical actions of TCA cycle enzymes and intermediates are indispensable in oxidative phosphorylation and adenosine triphosphate (ATP) biosynthesis for osteogenic differentiation and osteoclast formation. Knockout mouse models identify these enzymes' roles in bone mass and microarchitecture. In the noncanonical processes, the metabolites as a co-factor or a substrate involve epigenetic modification, including histone acetyltransferases, DNA demethylases, RNA m6A demethylases, and histone demethylases, which affect genomic stability or chromatin accessibility for cell metabolism and bone formation and resorption. The genetic manipulation of these epigenetic regulators or TCA cycle intermediate supplementation compromises age, estrogen deficiency, or inflammation-induced bone mass loss and microstructure deterioration. This review sheds light on the metabolic functions of the TCA cycle in terms of bone integrity and highlights the crosstalk of the TCA cycle and redox and epigenetic pathways in skeletal tissue metabolism and the intermediates as treatment options for delaying osteoporosis.

Bifurcated Polymorphic Transition and Thermochromic Fluorescence of a Molecular Crystal Involving Three-Dimensional Supramolecular Gear Rotation.

The ability of molecules to move and rearrange in the solid state accounts for the polymorphic transition and stimuli-responsive properties of molecular crystals. However, how the crystal structure determines the molecular motion ability remains poorly understood. Here, we report that a three-dimensional (3D) supramolecular gear network in the green-emissive polymorph 1G of a dialkylamino-substituted anthracene-pentiptycene π-system (1) enables an unusual bifurcated polymorphic transition into a yellow-emissive polymorph (1Y) and a new green-emissive polymorph (1G*) via 3D correlated supramolecular rotation. The 90° forward correlated rotation causes the molecular conformation between the octyl and the anthracene units to change from syn to anti, the ladder-like supramolecular columns to constrict, and the gear network to disengage. This cooperative molecular motion is marked by the gradual formation of an intermediate state (1I) across the entire crystal from 170 to 230 °C, which then undergoes bifurcated (forward or backward rotation) and irreversible transitions to form polymorphs 1Y and 1G* at 230-235 °C. Notably, 1G* is similar to 1G but lacks gear engagement, preventing its transformation into 1Y. Nevertheless, 1G can be restored by grinding 1Y or 1G* or fuming with dichloromethane (DCM) vapor. This work illustrates the correlation between the crystal structure and solid-state molecular motion behavior and demonstrates how a 3D molecular gear system efficiently transmits thermal energy to drive the polymorphic transition and induce fluorochromism through significant conformational and packing changes.

Solution-Processed Metal Oxide Thin-Film Transistor at Low Temperature via A Combination Strategy of H2 O2 -Inducement Technique and Infrared Irradiation Annealing.

Solution processing has emerged as a promising technique for the fabrication of oxide thin-film transistors (TFTs), offering advantages such as low cost, high throughput, and exceptional compositional control. However, achieving reasonable electrical properties typically demands high annealing temperatures in the fabrication process. In addressing this challenge, a novel combination strategy is proposed that involves integrating the H2 O2 inducement technique with infrared (IR) irradiation annealing. The study investigates the effects of precursors and IR irradiation annealing temperatures on the electrical properties of In2 O3 TFTs. It is found that H2 O2 can help accelerate the decomposition of organic residues, while IR irradiation annealing could enhance the film densification. By employing the proposed strategy, metal oxide TFTs consisting of a Zr-Al-O dielectric fabricated at 230 °C and an In2 O3 channel layer fabricated at 185 °C demonstrated high performance with field-effect mobility = 31.7 cm2  V-1 ·s-1 , threshold voltage = 1.3 V, subthreshold swing = 0.13 V per decade, and on-to-off current ratio = 1.1 × 105 . This work demonstrates the proposed combinational strategy is a general method to fabricate not only metal oxide semiconductors but also dielectrics.

Association Between Long-Term Exposure to Ambient Air Pollution and the Risk of Mild Cognitive Impairment in a Chinese Urban Area: A Case-Control Study.

Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina. Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study. Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk. Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants. Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.

Understanding phosphorus fractions and influential factors on urban road deposited sediments.

Phosphorus (P) is a primary pollutant that builds-up on urban road surfaces. Understanding the fraction and load characteristics of P, as well as their relationship with urban factors, is helpful for assessing the ecological risk of urban receiving water bodies. This study presents the characteristics of build-up loads of P fractions in road-deposited sediments (RDS) in Guangzhou, China, analyzes their correlation with three urban factors (road, traffic, and land-use area), and then estimates the exceedance probability of P in stormwater runoff over the past 10 years. The results showed that detrital apatite phosphorus (De-P) performed the highest build-up load on urban road surfaces, followed by apatite phosphorus (Ca-P), iron-bound phosphorus (Fe-P), exchangeable phosphorus (Ex-P), aluminum-bound phosphorus (Al-P), organophosphorus (POP), dissolved inorganic phosphorus (DIP), occluded phosphorus (Oc-P), and dissolved organic phosphorus (DOP). Depression depth, road materials, and land-use fractions affected the P fractions. The P in the RDS may have originated from three distinct sources: road background, domestic waste, and untreated wastewater discharge. In the most recent 10 years, the event mean concentrations of total P in the RDS have had a 30 % probability of exceeding 0.4 mg L-1, which indicates a serious threat of P to receiving water bodies. The outcomes of this study are expected to provide valuable guidance for elucidating the principal categories of urban non-point source P pollution and enhancing the ecological health of urban water environments.

GATA6 Suppresses Lung Adenocarcinoma Progression by Activating CFTR to Modulate Arachidonic Acid Metabolism.

BACKGROUND: CFTR, which belongs to the ATP-binding cassette transporter family and whose members are always involved in cancer progression, is implicated in lung adenocarcinoma (LUAD) progression, but the underlying mechanism remains undefined. Therefore, this study intended to investigate how CFTR works exactly on LUAD progression. METHODS: Bioinformatics methods were utilized to analyze GATA6 and CFTR expression in LUAD and targeting relationship, followed by a pathway enrichment analysis of CFTR. GATA6 and CFTR expression levels were assessed by qRT-PCR. Cell viability and proliferation were detected through MTT and colony formation assays. An arachidonic acid (AA) assay kit was utilized to measure AA content. mRNA and protein expression levels of genes (cPLA2, COX-2, and CYP1A1) related to the AA metabolism pathway were detected by qRT-PCR and western blot, respectively. Moreover, the Dual-luciferase reporter gene assay and ChIP were used to verify the binding of GATA6 and CFTR promoters. RESULTS: GATA6 and CFTR were lowly expressed in LUAD, and CFTR was enriched in the AA metabolism pathway. GATA6 activated CFTR transcription. Cellular and rescue experiments revealed that low or high CFTR expression could foster or hamper LUAD cell viability and proliferation, and concomitant treatment of indomethacin, an AA metabolism pathway inhibitor, mitigated stimulation on LUAD progression by low CFTR expression. Silencing of GATA6 reversed the suppressive impact of CFTR overexpression on LUAD progression via modulation of the AA metabolism pathway. CONCLUSION: The activation of CFTR by GATA6 hampered LUAD progression by modulating the AA metabolism pathway, suggesting that GATA6/CFTR axis might be a therapeutic target for LUAD patients.

Oxygen glucose deprivation-pretreated astrocyte-derived exosomes attenuates intracerebral hemorrhage (ICH)-induced BBB disruption through miR-27a-3p /ARHGAP25/Wnt/ß-catenin axis.

BACKGROUND: Blood brain barrier (BBB) breakdown is one of the key mechanisms of secondary brain injury following intracerebral hemorrhage (ICH). Astrocytes interact with endothelial and regulate BBB integrity via paracrine signaling factors. More and more studies reveal astrocyte-derived extracellular vesicles (ADEVs) as an important way of intercellular communication. However, the role of ADEV in BBB integrity after ICH remains unclear. METHODS: ADEVs were obtained from astrocytes with or without oxygen and glucose deprivation (OGD) pre-stimulation and the role of ADEVs in ICH was investigated using ICH mice model and ICH cell model. The potential regulatory effect of ADEVs on endothelial barrier integrity was identified by TEER, western blot and immunofluorescence in vitro. In vivo, functional evaluation, Evans-blue leakage and tight junction proteins (TJPs) expression were analyzed. MiRNA sequencing revealed that microRNA-27a-3p (miR-27a-3p) was differentially expressed miRNA in the EVs from OGD-pretreated astrocytes compared with normal control. The regulatory mechanism of miR-27a-3p was assessed using Luciferase assay, RT-PCR, western blot and immunofluorescence. RESULTS: OGD-activated astrocytes reduced hemin-induced endothelial hyper-permeability through secreting EVs. OGD-activated ADEVs alleviated BBB dysfunction after ICH in vivo and in vitro. MicroRNA microarray analysis indicated that miR-27a-3p is a major component that was highly expressed miRNA in OGD pretreated-ADEVs. OGD-ADEVs mitigated BBB injury through transferring miR-27a-3p into bEnd.3 cells and regulating ARHGAP25/Wnt/ß-catenin pathway. CONCLUSION: Taken together, these findings firstly revealed that miR-27a-3p, as one of the main components of OGD-pretreated ADEVs, attenuated BBB destruction and improved neurological deficits following ICH by regulating endothelial ARHGAP25/Wnt/ß-catenin axis. OGD-ADEVs might be a novel strategy for the treatment of ICH. this study implicates that EVs from OGD pre-stimulated astrocytes.

Application of the Six-Minute Walk Test in Assessment of the Cardiopulmonary Function of Children With Idiopathic Scoliosis.

STUDY DESIGN: A retrospective observational study. OBJECTIVE: To assess whether the six-minute walk test (6MWT) can predict cardiopulmonary function in children with idiopathic scoliosis (IS) as an alternative to the cardiopulmonary exercise test (CPET). SUMMARY OF BACKGROUND DATA: Cardiopulmonary functional impairment in the setting of IS is a common health problem. A simple and convenient assessment method is needed. MATERIALS AND METHODS: We recruited 65 children (eight male, 57 female) aged 10.70 to 14.84 years old with IS. Radiographic characteristics of the cohort were measured, including Risser's sign and Cobb angle. We measured cardiopulmonary exercise tolerance using both the 6MWT and CPET and their corresponding indicators, including six-minute walking distance (6MWD) and peak oxygen uptake (peak VO 2 ), respectively. Pearson correlation analysis was used to determine the relationship between 6MWT indicators and IS parameters. Linear regression models were used to explore the relationship between 6MWT and CPET response indicators. RESULTS: Over a third of the cohort (35.4%) had a Risser's sign grade of 0, with 21.5% in grade 2 and 3, respectively. The cohort's mean Cobb angle was 26.02°. 6MWD was significantly positively correlated with Risser's sign ( R =0.258; P =0.038) and change in respiratory rate positively correlated with vertebral rotation ( R =0.264; P =0.034). 6MWD positively correlated with peak VO 2 , peak VO 2 /heart rate (HR), and metabolic equivalents, and negatively correlated with the ventilation equivalent of the carbon dioxide slope (VE/VCO 2 slope) ( P <0.05). These four CPET indicators were found to be predicted from 6MWD in the linear regression model ( P <0.05). CONCLUSIONS: CPET response indicators, especially peak VO 2 , can be predicted using 6MWD, among other factors. The 6MWT can therefore be used to rapidly and efficiently predict the cardiorespiratory tolerance of children with IS. LEVEL OF EVIDENCE: 3.

Meta-analysis of clinical adverse events after CABG vs. PCI in patients with chronic kidney disease and coronary artery disease.

AIM: To investigate the efficacy and postoperative clinical adverse events of coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) for chronic kidney disease (CKD) study participants combined with coronary artery disease (CAD). METHODS: All randomized controlled trials (RCTs) that focus on the therapeutic effect evaluation of CABG and PCI and their effect on postoperative clinical adverse events as well as main adverse cardiovascular and cerebrovascular events (MACCEs) in CKD study participants with CAD were screened from the following databases, including CNKI, CBM, Wan Fang, VIP, Embase, PubMed, as well as Cochrane library clinical controlled trials. The study was conducted under the PRISMA 2020 criteria. Data were extracted, and quality control was evaluated from the modified Jadad rating scale. Meta-analysis was then undertaken through STATA 16.0 software. RESULTS: A total of 5 RCTs were obtained, including 1198 patients. Study participants were subdivided into two groups, including the PCI group (n = 604) and the CABG group (n = 594). Meta-analysis of clinical adverse events results showed that the long-term survival results of CAD patients with CKD who underwent PCI were worsened compared to CABG, such as long-term MACCEs (RR = 1.59, 95%CI: 1.04-2.43) and the long-term repeated revascularization (RR = 2.48, 95%CI: 1.76-3.49). Also, cardiac death (RR = 1.68, 95%CI:1.04-2.71), as well as cerebrovascular accident (RR = 1.74, 95%CI:1.04-2.90) in CABG group was significantly lower than that in PCI group. CONCLUSION: This meta-analysis showed that CABG provided a better therapeutic effect than PCI in CKD patients with CAD when considering long-term prognosis. However, more prospective RCTs are needed to define the proper revascularization strategy for CAD patients with CKD.

Microglia Modulate Neurodevelopment in Autism Spectrum Disorder and Schizophrenia.

Neurodevelopmental disorders (NDDs) include various neurological disorders with high genetic heterogeneity, characterized by delayed or impaired cognition, communication, adaptive behavior, and psychomotor skills. These disorders result in significant morbidity for children, thus burdening families and healthcare/educational systems. However, there is a lack of early diagnosis and effective therapies. Therefore, a more connected approach is required to explore these disorders. Microglia, the primary phagocytic cells within the central nervous system, are crucial in regulating neuronal viability, influencing synaptic dynamics, and determining neurodevelopmental outcomes. Although the neurobiological basis of autism spectrum disorder (ASD) and schizophrenia (SZ) has attracted attention in recent decades, the role of microglia in ASD and SZ remains unclear and requires further discussion. In this review, the important and frequently multifaceted roles that microglia play during neurodevelopment are meticulously emphasized and potential microglial mechanisms that might be involved in conditions such as ASD and SZ are postulated. It is of utmost importance to acquire a comprehensive understanding of the complexities of the interplay between microglia and neurons to design effective, targeted therapeutic strategies to mitigate the effects of NDDs.

Distribution of and Temporal Variation in Volatiles in Tea (Camellia sinensis) Flowers during the Opening Stages.

Tea (Camellia sinensis) flowers emit a large amount of volatiles that attract pollinators. However, few studies have characterized temporal and spatial variation in tea floral volatiles. To investigate the distribution of volatiles within tea flowers and their variation among opening stages, volatile components from different parts of tea flowers and different opening stages were collected by headspace solid-phase microextraction and analyzed by gas chromatography-mass spectrometry. A total of 51 volatile compounds of eight chemical classes were identified in the tea flowers. Volatile compounds were most abundant in tea flowers of the Shuchazao cultivar. Acetophenone, 1-phenylethanol, 2-phenylethanol, and benzyl alcohol were the most abundant volatiles. Terpenes were common in the sepals, and benzoids were common in the stamens. The fatty acid derivatives were mainly distributed in the pistils and receptacles and were less abundant in the petals, sepals, and stamens. During the opening phase of tea flowers, the volatile content increased 12-fold, which mainly stemmed from the increase in benzoids. These results enhance our understanding of the formation of volatiles in tea flowers.

Engineering large and geometrically controlled vascularized nerve tissue in collagen hydrogels to restore large-sized volumetric muscle loss.

Developing scalable vascularized and innervated tissue is a critical challenge for the successful clinical application of tissue-engineered constructs. Collagen hydrogels are extensively utilized in cell-mediated vascular network formation because of their naturally excellent biological properties. However, the substantial increase in hydrogel contraction induced by populated cells limits their long-term use. Previous studies attempted to mitigate this issue by concentrating collagen pre-polymer solutions or synthesizing covalently crosslinked collagen hydrogels. However, these methods only partially reduce hydrogel contraction while hindering blood vessel formation within the hydrogels. To address this challenge, we introduced additional support in the form of a supportive spacer to counteract the contraction forces of populated cells and prevent hydrogel contraction. This approach was found to promote cell spreading, resist hydrogel contraction, control hydrogel/tissue geometry, and even facilitate the engineering of functional blood vessels and host nerve growth in just one week. Subsequently, implanting these engineered tissues into muscle defect sites resulted in timely anastomosis with the host vasculature, leading to enhanced myogenesis, increased muscle innervation, and the restoration of injured muscle functionality. Overall, this innovative strategy expands the applicability of collagen hydrogels in fabricating large vascularized nerve tissue constructs for repairing volumetric muscle loss (∼63 %) and restoring muscle function.

Network Pharmacology Analysis and Machine-Learning Models Confirmed the Ability of YiShen HuoXue Decoction to Alleviate Renal Fibrosis by Inhibiting Pyroptosis.

Purpose: YiShen HuoXue decoction (YSHXD) is a formulation that has been used clinically for the treatment of renal fibrosis (RF) for many years. We aimed to clarify therapeutic effects of YSHXD against RF and potential pharmacological mechanisms. Materials and Methods: We used network pharmacology analysis and machine-learning to screen the core components and core targets of YSHXD against RF, followed by molecular docking and molecular dynamics simulations to confirm the reliability of the results. Finally, we validated the network pharmacology analysis experimentally in HK-2 cells and a rat model of RF established by unilateral ureteral ligation (UUO). Results: Quercetin, kaempferol, luteolin, beta-sitosterol, wogonin, stigmasterol, isorhamnetin, baicalein, and dihydrotanshinlactone progesterone were identified as the main active components of YSHXD in the treatment of unilateral ureteral ligation-induced RF, with IL-6, IL1ß, TNF, AR, and PTGS2 as core target proteins. Molecular docking and molecular dynamics simulations further confirmed the relationship between compounds and target proteins. The potential molecular mechanism of YSHXD predicted by network pharmacology analysis was confirmed in HK-2 cells and UUO rats. YSHXD downregulated NLRP3, ASC, NF-κBp65, Caspase-1, GSDMD, PTGS2, IL-1ß, IL-6, IL-18, TNF-α, α-SMA and upregulated HGF, effectively alleviating the RF process. Conclusion: YSHXD exerts important anti-inflammatory and anti-cellular inflammatory necrosis effects by inhibiting the NLRP3/caspase-1/GSDMD-mediated pyroptosis pathway, indicating that YSHXD represents a new strategy and complementary approach to RF therapy.

Antibiotic resistance profile of Helicobacter pylori to 14 antibiotics: a multicenter study in Fujian, China.

Background and aim: Efficacy of Helicobacter pylori (H. pylori) eradication is related to the local antimicrobial resistance epidemiology. We aimed to investigate the antibiotic resistance of H. pylori in Fujian, China. Methods: H. pylori-infected patients in four centers were enrolled in the study from Oct 2019 to Jan 2022. The bacteria were isolated, cultured and identified from the biopsy of patients' gastric mucosa samples. Antimicrobial susceptibility testing was performed by a modified broth microdilution method for H. pylori to seven guideline-recommended antibiotics and seven potential choices for H. pylori eradication. Results: A total of 205 H. pylori strains were isolated. The resistance rates of amoxicillin (AMX), amoxicillin and clavulanate potassium (AMC), cefixime (CFM), gentamicin (GEN), tetracycline (TET), doxycycline (DOX), azithromycin (AZM), clarithromycin (CLR), levofloxacin (LVFX), sparfloxacin (SPFX), metronidazole (MTZ), tinidazole (TID), rifampicin (RFP) and furazolidone (FZD) were 11.22%, 12.20%, 7.32%, 12.20%, 4.88%, 4.39%, 44.39%, 43.90%, 30.24%, 21.46%, 40.98%, 45.85%, 5.37% and 10.24%, respectively. The rates of pan-sensitivity, single, double, triple and multiple resistance for seven guideline-recommended antibiotics were 32.68%, 30.24%, 13.17%, 7.76%, and 14.15%, respectively. The main double-resistance patterns were CLR+MTZ (10/205, 5%) and CLR+LVFX (9/205, 4%). The main triple-resistance pattern was CLR+MTZ+ LVFX (15/205, 7%). Conclusions: In Fujian, the prevalence of H. pylori resistance to AZM, CLR, LVFX, SPFX, MTZ, and TID was high, whereas that to AMX, AMC, GEN, CFM, TET, DOX, RFP and FZD was relatively low. CFM and DOX are promising new choices for H. pylori eradication.