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Abstract Background The molecular genetic diagnosis of congenital adrenal hyperplasia (CAH) is very challenging due to the high homology between the CYP21A2 gene and its pseudogene CYP21A1P. Methodology This study aims to assess the clinical efficacy of targeted long-read sequencing (T-LRS) by comparing it with a control method based on the combined assay (NGS, Multiplex ligation-dependent probe amplification and Sanger sequencing) and to introduce T-LRS as a first-tier diagnostic test for suspected CAH patients to improve the precise diagnosis of CAH. Results A large cohort of 562 participants including 322 probands and 240 family members was enrolled for the perspective (96 probands) and prospective study (226 probands). The comparison analysis of T-LRS and control method have been performed. In the perspective study, 96 probands were identified using both the control method and T-LRS. Concordant results were detected in 85.42% (82/96) of probands. T-LRS performed more precise diagnosis in 14.58% (14/96) of probands. Among these, a novel 4141 kb deletion involving CYP21A2 and TNXB was established. A new diagnosis was improved by T-LRS. The duplications were also precisely identified to clarify the misdiagnosis by MLPA. In the prospective study, Variants were identified not only in CYP21A2 but also in HSD3B2 and CYP11B1 in 226 probands. Expand to 322 probands, the actual frequency of duplication haplotype (1.55%) could be calculated due to the accurate genotyping. Moreover, 75.47% of alleles with SNVs/indels, 22.20% of alleles with deletion chimeras. Conclusion T-LRS has higher resolution and reduced cost than control method with accurate diagnosis. The clinical utility of L-LRS could help to provide precision therapy to CAH patients, advance the life-long management of this complex disease and promote our understanding of CAH.

Background: In endoscopic nasobiliary drainage (ENBD), it is complicated to reposition the catheter from the mouth to nostril. We developed a new technique using an 1-mL syringe tube combined with guide-wire when repositioning an ENBD tube from mouth to nose. The aim of this study was to verify its utility. Methods: A single-center, prospective, randomized, controlled study was conducted between January 2021 and December 2022. Compared to traditional guide-wire technique, the new technique added a 1-mL syringe tube readily available in clinical work. The primary outcome was the ENBD repositioning time.The secondary outcomes included number of ENBD repositioning operations and technical success rate. Results: A total of 253 patients who underwent ENBD during the study period. Among them, 241 patients were enrolled in this study. The procedure time was significantly shorter in the new technique group than in the conventional group (60.7 vs. 98.7, p

The high porosity and tunable chemical functionality of metal-organic frameworks (MOFs) make it a promising catalyst design platform. High-throughput screening of catalytic performance is feasible since the large MOF structure database is available. In this study, we report a machine learning model for high-throughput screening of MOF catalysts for the CO2 cycloaddition reaction. The descriptors for model training were judiciously chosen according to the reaction mechanism, which leads to high accuracy up to 97% for the 75% quantile of the training set as the classification criterion. The feature contribution was further evaluated with SHAP and PDP analysis to provide a certain physical understanding. 12,415 hypothetical MOF structures and 100 reported MOFs were evaluated under 100 °C and 1 bar within one day using the model, and 239 potentially efficient catalysts were discovered. Among them, MOF-76(Y) achieved the top performance experimentally among reported MOFs, in good agreement with the prediction.

Fluoropolymers play a crucial role as binders in polymer-bonded explosive (PBX) formulations. However, there is a lack of clear understanding of the effects of increased fluoropolymer crystallinity on the shock response of PBXs in the service environment. This study investigated the shock Hugoniots of two widely applied fluoropolymer binders: (1) F2314 from China—a copolymer with a molar ratio of vinylidene fluoride (VDF) to chlorotrifluoroethylene (CTFE) of 1:4 and (2) F2313 from the United States, also known as Kel F-800, with a VDF to CTFE molar ratio of 1:3. The Hugoniot curves of both fluoropolymers were calculated based on equilibrium molecular dynamics (MD) and a mixing rule. Furthermore, the corresponding P–V curves were obtained through fitting using the Tait equation of state (EOS). Their calculated parameters, including zero-pressure bulk modulus (κo) and sound velocity (co), agreed well with experimental data. The results reveal that the Hugoniots of amorphous F2314 and F2313 exhibited negligible differences. However, increasing crystallinity significantly impacted the Hugoniot curves of both fluoropolymers, especially for F2314 with high crystallinity. The obtained macroscopic characteristic parameters, namely κo and co, exhibited an exponential dependence on crystallinity. Physically, this phenomenon can be attributed to a reduction in the compressible free volume of the fluoropolymers due to a more orderly chain arrangement. Additionally, under the same compression ratio, the shock temperature of the fluoropolymers increased with the crystallinity, posing potential safety risks to explosives. These findings establish a correlation between the crystallinity of fluoropolymers and the shock properties of PBXs, providing a theoretical reference for the formulation design of fluoropolymer-based PBXs.

Abstract Enhancing the sensitivity of radiotherapy (RT) towards renal cell carcinoma (RCC) remains a challenge because RCC is a radioresistant tumor. In this work, we design and report asymmetrically Polyethylene Glycol (PEG)ylated and amphipathic heptamethine indocyanine dyes for efficient radiosensitization of RCC treatment. They were synthesized by modifying different lengths of PEG chains as hydrophilic moieties on one N-alkyl chain of a mitochondria-targeting heptamethine indocyanine dye (IR-808), and a radiosensitizer 2-nitroimidazole (NM) as a hydrophobic moiety on another N-alkyl chain. The PEG modification significantly improved water solubility, decreased the intermolecular π–π large aggregates, thereby enhanced renal excretion. The asymmetrical and amphipathic modification enhanced the preferential accumulation in renal tumors through self-assembly into small-size nanoparticles in aqueous environment. Radiosensitization was further improved by preferential accumulation in renal tumor cells and their mitochondria as mitochondria play a crucial role in rapid cancer cell growth, metastasis, and RT resistance. Additionally, the modification also increased the abilities of fluorescence emission and photostability, which is meaningful for imaging-guided precise RCC RT. Therefore, our findings may present a theranostic radiosensitizer for renal tumor-targeted imaging and radiosensitization. Graphical Abstract

Abstract Ferroptosis has been shown to play a crucial role in preventing cancer development, but the underlying mechanisms of dysregulated genes and genetic alternations driving cancer development by regulating ferroptosis remain unclear. Here, we showed that the synergistic role of ELF3 overexpression and PTEN deficiency in driving lung cancer development was highly dependent on the regulation of ferroptosis. Human ELF3 (hELF3) overexpression in murine lung epithelial cells only caused hyperplasia with increased proliferation and ferroptosis. hELF3 overexpression and Pten genetic disruption significantly induced lung tumor development with increased proliferation and inhibited ferroptosis. Mechanistically, we found it was due to the induction of SCL7A11, a typical ferroptosis inhibitor, and ELF3 directly and positively regulated SCL7A11 in the PTEN-deficient background. Erastin-mediated inhibition of SCL7A11 induced ferroptosis in cells with ELF3 overexpression and PTEN deficiency and thus inhibited cell colony formation and tumor development. Clinically, human lung tumors showed a negative correlation between ELF3 and PTEN expression and a positive correlation between ELF3 and SCL7A11 in a subset of human lung tumors with PTEN-low expression. ELF3 and SCL7A11 expression levels were negatively associated with lung cancer patients’ survival rates. In summary, ferroptosis induction can effectively attenuate lung tumor development induced by ELF3 overexpression and PTEN downregulation or loss-of-function mutations.

Abstract Background Parkinson’s disease (PD) is a progressive neurodegenerative disease associated with functional and structural alterations beyond the nigrostriatal dopamine projection. However, the structural-functional (SC-FC) coupling changes in combination with subcortical regions at the network level are rarely investigated in PD. Methods SC-FC coupling networks were systematically constructed using the structural connectivity obtained by diffusion tensor imaging and the functional connectivity obtained by resting-state functional magnetic resonance imaging in 53 PD and 72 age- and sex-matched healthy controls (HCs). Then, we explored how SC-FC coupling varied within and between several well-defined functional domains. Results Results showed that the SC-FC coupling in patients with PD was globally reduced in comparison with HCs. Specifically, regional SC-FC decoupled in the inferior parietal lobule, occipitotemporal cortex, motor cortex, and higher-order association cortex in patients with PD. Moreover, PD showed intranetwork SC-FC decoupling in the visual network (VIS), limbic and higher-order association networks. Furthermore, internetwork decoupling mainly linked to the VIS, the somatomotor network (SOM), the dorsal attention network, and the default mode network, was observed, increased internetwork coupling was found between the subcortical network and the SOM in PD (all p

Abstract Background Several therapeutic drugs have been authorized for the treatment of patients with Coronavirus disease 2019 (COVID-19). However, further research on the mechanisms of action, efficacy, and target populations of these novel therapeutic drugs are necessary. This study included mild, moderate, severe, and critical COVID-19 patients to evaluate azvudine’s effectiveness across different severity levels. Methods We conducted a retrospective cohort study of patients with COVID-19 admitted to our hospital from December 1, 2022, to March 31, 2023. Patients were divided into retrospective cohorts receiving azvudine antiviral therapy and standard treatment, and were followed-up for up to 28 days. Results Prior to data processing, azvudine treatment was associated with reduced mortality rates at 7 days (1.09/1000 persons vs. 5.06/1000 persons, P

Abstract Artemisia argyi Lévl. et Vant. (A. argyi) leaf possesses various health promoting functions contributed by its main bioactive flavonoids. In this study, the anti-aging effect and mechanism of Artemisia argyi leaf extract (AALE) were identified using Caenorhabditis elegans (C. elegans) as a model. The results showed that the AALE promoted the lifespan and stress resistance of C. elegans. It was found that the AALE boosted the expression of oxidative stress-related proteins by regulating the insulin/ IGF-1 signaling (IIS) pathway, which then activated the transcription factors DAF-16/FOXO. The results of RNA-sequence analysis indicated that the changes of genes in nematodes treated with AALE were associated with the responses against oxidative stress, cell maturation, and immune reaction, and stress. The positive results suggest that Artemisia argyi leaf could have the robust benefits for improving healthy aging as well as preventing aging-related diseases in the human body.

Double-layered thermal barrier coatings (DL-TBCs) have been developed to meet multiple service requirements, such as low thermal conductivity, high thermal stability, and high fracture toughness. Conventional DL-TBCs are often designed on the basis of equal total thickness to have long lifespans, which may weaken the thermal insulation. The reason is that the single-scale designed structure often has opposite effects on the thermal and mechanical properties. To enhance both the thermal insulation and lifespan, this work designed durable DL-TBCs at multiple scales under equivalent thermal insulation. The macroscopic thickness ratio of the top layer to the bottom layer was tailored to optimize the total and single thicknesses, and the microscopic pore size in the top layer was tailored to resist sintering. Six groups of samples with different thickness ratios were prepared. The thermal cycling test revealed that the lifespan of DL-TBCs first increases but then decreases with increasing thickness ratio. The optimized thickness ratio is 2:3 for DL-TBCs, which have the largest lifespan among the six groups. The cross-sectional morphologies revealed that the failure mode changed from the spallation of the top layer to the delamination of the total double layers. The long lifespan of the optimized DL-TBCs stems from the cotailored thickness ratio and porous structure in the top layer to lower the total cracking driving force.

A MoS2 concentration gradient coating of an osteoarticular-like structure with efficient strain transfer efficiency was prepared on titanium alloy via multiple plasma electrolytic oxidation. This structure facilitates efficient strain transfer by dissipating compressive and shear strains via dislocation annihilation and MoS2 interlayer sliding, thereby preserving a strain gradient. Leveraging this mechanism, the coefficient of friction was reduced by 50.2% compared to graphene coatings, while the frictional stabilization time was extended by 160% about Single MoS2/TiO2. This study elucidates the dislocation behavior and the mechanisms of strain transfer during friction within this structure.

Abstract Background As core members of hospice care team, the hospice nurses’ ability to care for patients not only directly affects the standard of patient care, but also significantly impacts patient quality of life. It can be seen that it is very meaningful for patients to improve the caring behavior of hospice nurses. Therefore, it is necessary to deeply explore the influencing factors of nurses’ caring behavior and further clarify the mechanism between them. Methods The STROBE guideline was performed to report this study. We conducted a cross-sectional survey from December 2023 to February 2024. In this study, 392 hospice nurses were recruited from tertiary public hospitals in East China by convenient sampling method. Participants were investigated using the Practice Environment Scale, Professional Identity Scale, and Caring Behaviors Inventory. Structural equation modelling was utilized to verify the research hypotheses. Results The results revealed that there were significant and positive correlations between work environment, professional identity and caring behavior. Furthermore, professional identity partially mediated the relationship between work environment and caring behavior. Conclusion Work environment is critical to improving hospice nurses’ caring behavior. Professional identity plays an intermediary role impacting how work environment promotes caring behavior among Chinese hospice nurses. Nursing managers should have a correct understanding of the relationship between them. Targeted measures and coping strategies need to be actively taken to create a better working environment for hospice nurses. This would enhance professional identity, and thereby promote caring behavior.

Daphnetin, a coumarin derivative isolated from Daphne odorifera, has anti-tumor effects. The MAPK, STAT3, and NF-κB signaling pathways are closely related to the pathogenesis of lung cancer. To investigate the effect of daphnetin on anti-lung adenocarcinoma A549 cells and its mechanism. The anti-tumor effects of daphnetin on the proliferation, clone formation, migration, and invasion of A549 lung adenocarcinoma cells were investigated. The results showed that daphnetin inhibited the proliferation, colony formation, migration, and invasion of A549 cells through the MAPK/STAT3/NF-KB pathway, and mainly inhibited the clonal formation and migration of A549 cells through the JNK pathway. These results provide a new research direction and theoretical basis for the use of daphnetin in the inhibition of lung adenocarcinoma.

Abstract Objective Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by hormonal imbalances and insulin resistance (IR). Among the metabolic abnormalities associated with PCOS, obesity is often present concurrently. Nevertheless, the correlation between obesity, sex hormone levels, and blood lipid profiles in PCOS patients with IR remains uncertain. Methods This is a cross-sectional study including a total of 206 Chinese women diagnosed with PCOS, enrolled between March 2016 and December 2021. The participants’ anthropometric measurements, such as weight, height, waist circumference, and hip circumference, were recorded. Additionally, fasting blood samples were collected to measure various parameters, including fasting glucose, insulin levels, lipid profiles, and sex hormone levels. Results Our findings highlight that obesity exhibited a significant correlation with lower levels of sex hormone binding globulin (SHBG) and elevated levels of free androgen index (FAI), fasting insulin, and HOMA-IR in PCOS patients diagnosed with IR. However, no significant association between obesity and blood lipid profiles was observed within this particular group of women. Conclusion This study suggests that among PCOS patients with IR, lower levels of SHBG and higher levels of FAI are associated with obesity. These findings indicate that SHBG and FAI may have the potential to serve as a biomarker for the initial identification and prognosis of IR in PCOS patients. Trial registration Retrospectively registered on 25/04/2020 at ClinicalTrials.gov Identifer: NCT04264832.

To simultaneously detect 13 illegally added chemical drugs, a high performance liquid chromatography (HPLC) analytical method applicable to health food products for improving sexual function and prostate function was established. The samples were processed by vortex shaking for 1 min, followed by methanol extraction for 10 min under the ultrasonic condition. Then, the sample was separated on an Agilent 5 HC-C18 (2) column (250 mm×4.6 mm, 5 µm) with a gradient separation using methanol-phosphate-triethylamine buffer as the mobile phase. The detection wavelengths were of 218 nm and 245 nm, the column temperature was 30 ℃, and the sample size was 10 µL. Results showed that the correlation coefficients (r) in the linear range were all greater than 0.999, the detection limits were 0.76～4.61 mg/kg, the average recoveries were 92.4%~100.7%, and the relative standard deviations were 0.44%~1.06%. The method was applied to the rapid screening of 65 batches of health foods for improving sexual and prostate function, and results indicated that paroxetine hydrochloride was detected in 2 batches of samples (15.26 mg/tablet, 6.34 mg/pellet, respectively) and yohimbine hydrochloride was detected in 1 batch of samples (10.12 mg/pellet). In summary, the method is easy to conduct and characterized with high sensitivity and reliability, which is suitable for daily supervision and inspection of illegal added drugs in health foods for improving sexual and prostate function.

Abstract The harmonic problems caused by non‐linear factors of the grid connected inverter (GCI) system are more complicated, including both non‐characteristic harmonics emitted by the dead‐time and the changes in harmonic impedance characteristics. Harmonics interact with the changing impedance, and even cause harmonic amplification and resonance. The harmonic deterioration of the multiple GCIs system is serious. To analyse the mechanism and way of harmonic deterioration in grid‐connected system caused by nonlinear factors, the active impedance models of single inverter and multiple GCIs system including dead‐time effect and digital control delay are established first. In view of this, the influence mechanism of non‐linear factors on system stability is explored. The improved modal analysis method is used to traverse the network series parallel resonance caused by nonlinear factors. The results show that both the dead‐time effect and digital control delay reduce phase margin of the system, resulting in the resonant frequency shift and the resonant peak increase. When the harmonic excitation source interacts with the complex network under the influence of nonlinear factors, it will lead to further deterioration of harmonics. Finally, based on the MATLAB and RT‐LAB hardware‐in‐the‐loop simulation platforms, a multiple GCIs system model is built to verify the correctness of the established active impedance model and harmonic deterioration analysis.

AIM: To investigate the causal effect of inflammatory bowel disease (IBD) on ocular inflammation using Mendelian randomization (MR) analysis. METHODS: Genetic instruments associated with inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn's disease (CD) were derived from the largest genome-wide association studies (GWAS) published to date. The FinnGen research project was utilized to identify genetic risk variants associated with conjunctivitis, keratitis, iridocyclitis, chorioretinitis, episcleritis, and optic neuritis. All participants were of European ancestry. Three methods which included inverse variance weighting (IVW), weighted median (WM), and MR-Egger regression were performed to estimate the causal association in this study. IVW took the inverse variance of each study as the weight to calculate the weighted average of effect sizes, to summarize the effect sizes of multiple independent studies, which could provide the most precise estimated results. IVW was used as the primary outcome, while WM and MR-Egger were used to improve the estimation of IVW. RESULTS: A nominal causal effect of genetically predicted IBD on risk of non-infectious conjunctivitis, keratitis, iridocyclitis, and optic neuritis, but not on chorioretinitis or episcleritis. After Bonferroni correction, the results showed that genetically predicted UC was significantly associated with an increased risk of iridocyclitis (IVW: OR, 1.17; 95%CI, 1.10-1.24, P=2.54×10-7). CD was significantly associated with conjunctivitis (IVW: OR, 1.05; 95%CI, 1.03-1.08, P=3.20×10-5), keratitis (IVW: OR, 1.06; 95%CI, 1.02-1.09; P=1.13×10-3), and iridocyclitis (IVW: OR, 1.09; 95%CI, 1.04-1.14; P=1.43×10-4). CONCLUSION: IBD causally poses a risk of inflammation of conjunctiva, cornea, Iris-ciliary body complex, and optic neuritis. CD is more closely associated with the eye inflammation than UC. These impliy that the relationship of IBD and different parts of the eye structure are different, and provide novel evidence linking based on the association of the gut-eye axis.

Abstract Lung Cancer remains the leading cause of cancer deaths in the USA and worldwide. Non-small cell lung cancer (NSCLC) harbors high transcriptomic intratumor heterogeneity (RNA-ITH) that limits the reproducibility of expression-based prognostic models. In this study, we used multiregional RNA-seq data (880 tumor samples from 350 individuals) from both public (TRACERx) and internal (MDAMPLC) cohorts to investigate the effect of RNA-ITH on prognosis in localized NSCLC at the gene, signature, and tumor microenvironment levels. At the gene level, the maximal expression of hazardous genes (expression negatively associated with survival) but the minimal expression of protective genes (expression positively associated with survival) across different regions within a tumor were more prognostic than the average expression. Following that, we examined whether multiregional expression profiling can improve the performance of prognostic signatures. We investigated 11 gene signatures collected from previous publications and one signature developed in this study. For all of them, the prognostic prediction accuracy can be significantly improved by converting the regional expression of signature genes into sample-specific expression with a simple function—taking the maximal expression of hazardous genes and the minimal expression of protective genes. In the tumor microenvironment, we found a similar rule also seems applicable to immune ITH. We calculated the infiltration levels of major immune cell types in each region of a sample based on expression deconvolution. Prognostic analysis indicated that the region with the lowest infiltration level of protective or highest infiltration level of hazardous immune cells determined the prognosis of NSCLC patients. Our study highlighted the impact of RNA-ITH on the prognostication of NSCLC, which should be taken into consideration to optimize the design and application of expression-based prognostic biomarkers and models. Multiregional assays have the great potential to significantly improve their applications to prognostic stratification.

Abstract. Tuberculosis (TB) is a prominent infectious disease globally that imposes a substantial health burden. Genital TB (GTB), an extrapulmonary manifestation, leads to complications such as tubal adhesions, blockage, and diminished ovarian function, culminating in infertility, and is recognized as a prevalent cause of infertility in nations with high-burden TB. In regions with low TB rates, infertility and active TB during pregnancy have been reported to be most common among female immigrants from countries with high-burden TB. In the context of TB, pregnant women often exhibit exacerbated symptoms after in vitro fertilization-embryo transfer (IVF-ET), heightening the risk of dissemination. Miliary pulmonary TB and tuberculous meningitis pose a serious threat to maternal and fetal health. This article integrates recent epidemiological data and clinical research findings, delineating the impact of TB on infertility and assisted reproduction and particularly focusing on the diagnosis and treatment of GTB, underscored by the imperative of TB screening before IVF-ET. Our objective is to increase awareness among respiratory and reproductive health professionals, promoting multidisciplinary management to enhance clinical vigilance. This approach seeks to provide patients with judicious reproductive plans and scientifically rigorous pregnancy management, thereby mitigating adverse pregnancy outcomes related to TB activity.

Abstract Protein aggregation plays key roles in age-related degenerative diseases, but how different proteins coalesce to form inclusions that vary in composition, morphology, molecular dynamics and confer physiological consequences is poorly understood. Here we employ a general reporter based on mutant Hsp104 to identify proteins forming aggregates in human cells under common proteotoxic stress. We identify over 300 proteins that form different inclusions containing subsets of aggregating proteins. In particular, TDP43, implicated in Amyotrophic Lateral Sclerosis (ALS), partitions dynamically between two distinct types of aggregates: stress granule and a previously unknown non-dynamic (solid-like) inclusion at the ER exit sites (ERES). TDP43-ERES co-aggregation is induced by diverse proteotoxic stresses and observed in the motor neurons of ALS patients. Such aggregation causes retention of secretory cargos at ERES and therefore delays ER-to-Golgi transport, providing a link between TDP43 aggregation and compromised cellular function in ALS patients.

Objective: To investigate the protective effect of fermented Lycium barbarum polysaccharides (FLBP) on the intestine in an aging mouse model. Methods: The aging model was established by continuous subcutaneous injection of 1 000 mg/(kg mb · d) D-galactose in the back of the neck, followed by gavage of low (150 mg/(kg mb · d)) and high (300 mg/(kg mb · d)) doses of FLBP. After 10 weeks, body mass, organ indexes, serum inflammatory markers and anti-inflammatory indicators including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 levels, intestinal permeability, intestinal barrier damage biomarkers such as lipopolysaccharide (LPS) and lipopolysaccharide binding protein (LBP) contents, the histological structure of the colon, colonic mucin 2 (Muc2) expression, intestinal flora composition and fecal short-chain fatty acid contents were detected and analyzed. Results: High-dose FLBP antagonized D-galactose-induced growth retardation and thymus atrophy, decreased the serum levels of TNF-α, IL-1β and IL-6 and significantly increased serum IL-10 levels in the aging mice (P < 0.05). Furthermore, FLBP significantly ameliorated colonic barrier damage in mice, as evidenced by a significant decrease in intestinal permeability, LPS and LBP contents (P < 0.05), alterations in colonic tissue structure, and a significant increase in MUC2 secretion (P < 0.05). Meanwhile, FLBP regulated the gut microbiota composition by changing the α- and β-diversity, increasing the relative abundance of the beneficial bacteria norank_f_Muribaculaceae and Lactobacillus, and decreasing the relative abundance of the harmful bacteria Atopostipes and Jeotgalicoccus, and increasing the fecal contents of acetic acid, propionic acid, valeric acid and isobutyric acid significantly (P < 0.05). Conclusion: High-dose FLBP reduced circulating pro-inflammatory cytokine levels and enhanced anti-inflammatory function in aging mice, which might be related to improving colonic barrier function, regulating the intestinal flora composition, and increasing the levels of beneficial SCFAs in the intestinal tract of mice. This study provides a theoretical reference for the application of FLBP as a functional food ingredient for intestinal health.

Abstract Background Spiroplasma eriocheiris has been proved to be a pathogen causing tremor disease of Eriocheir sinensis, it is also infectious to other aquatic crustaceans, resulting in a serious threat on the sustainable development of the aquaculture industry. S. eriocheiris is a helical-shaped microbe without a cell wall, and its motility is related to the cytoskeleton protein MreB which belongs to the actin superfamily and has five MreB homologs. Results In this study, we purified MreB3, MreB4 and MreB5, and successfully prepared monoclonal antibodies. After S. eriocheiris treated with actin stabilizator Phalloidin and inhibitors A22, we found that Phalloidin and A22 affect the S. eriocheiris morphology by altering MreB expression. We confirmed that the ability of S. eriocheiris to invade E. sinensis was increased after treatment with Phalloidin, including that the morphology of E. sinensis blood lymphocytes was deteriorated, blood lymphocytes viability was decreased, peroxidase activity and cell necrosis were increased. On the contrary, the pathogenicity of S. eriocheiris decreased after treatment with A22. Conclusions Our findings suggest that the MreB protein in S. eriocheiris plays a crucial role in its morphology and pathogenicity, providing new insights into potential strategies for the prevention and control of S. eriocheiris infections.

Abstract Background SARC-F questionnaire is a simple and convenient tool for sarcopenia screening, and SARC-CalF is a modified version of it. The developments of their Chinese versions are warranted for the clinical use for Chinese population. This study aimed to culturally adapt the SARC-F questionnaire into Chinese using standardized methods, validate the reliability and diagnostic accuracy of the Chinese version SARC-F and SARC-CalF against five sarcopenia diagnosis criteria, and determine optimal cut-off values for clinical practice in Chinese population. Methods The translation and cross-cultural adaptation of SARC-F into Chinese were conducted following the methodological report from European Union Geriatric Medicine Society Sarcopenia Special Interest Group. The Chinese version of SARC-F was validated through a diagnostic test, using diagnostic criteria of sarcopenia recommended by the revised 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) consensus, Asian Working Group for Sarcopenia (AWGS2019) consensus, the International Working Group on Sarcopenia (IWGS), the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium and the Sarcopenia Definition and Outcomes Consortium (SDOC). Additional analysis was done against the criteria of severe sarcopenia according to the revised EWGSOP2 and AWGS2019. Results The Chinese version of SARC-F was well translated and demonstrated good reliability and acceptability. The diagnostic test included 1859 community-dwelling older individuals from two medical centers. Against five different definitions of sarcopenia, the Chinese version of SARC-F showed reasonable diagnostic accuracy for sarcopenia screening (AUC 0.614–0.821), and was demonstrated low sensitivity (13.7–37.9%) but high specificity (94.8–97.7%) with a cut-off value of ≥ 4. SARC-CalF significantly enhanced the diagnostic accuracy of SARC-F when using definitions of EWGSOP2, AWGS2019 and IWGS (all P ≤ 0.001). A score of ≥ 2 for SARC-F and ≥ 7 for SARC-CalF were established as optimal cut-off points for identifying older individuals as at risk of sarcopenia in Chinese population. Conclusions The Chinese version SARC-F is of reasonable reliability and validity for sarcopenia screening. Despite its low sensitivity, it proves to be a useful tool to identify severe cases in community taking advantage of its simplicity. SARC-CalF appears to be a more suitable screening tool for clinical use in detecting sarcopenia.

Abstract Objective The objective of this study was to investigate the activity and connectivity of cerebral and cerebellar cortices underlying the sensory trick (ST) effects in patients with cervical dystonia (CD), using electroencephalography (EEG). Methods We recruited 15 CD patients who exhibited clinically effective ST and 15 healthy controls (HCs) who mimicked the ST maneuver. EEG signals and multiple‐channel electromyography (EMG) were recorded simultaneously during resting and acting stages. EEG source analysis and functional connectivity were performed. To account for the effects of sensory processing, we calculated relative power changes as the difference in power spectral density between resting and the maneuver execution. Results ST induced a decrease in low gamma (30–50 Hz) spectral power in the primary sensory and cerebellar cortices, which remained lower than in HCs during the maintenance period. Compared with HCs, patients exhibited consistently strengthened connectivity within the sensorimotor network during the maintenance period, particularly in the primary sensory‐sensorimotor cerebellum connection. Interpretation The application of ST resulted in altered cortical excitability and functional connectivity regulated by gamma oscillation in CD patients, suggesting that this effect cannot be solely attributed to motor components. The cerebellum may play important roles in mediating the ST effects.

Abstract Background Aside from the canonical role of PDL1 as a tumour surface-expressed immune checkpoint molecule, tumour-intrinsic PDL1 signals regulate non-canonical immunopathological pathways mediating treatment resistance whose significance, mechanisms, and therapeutic targeting remain incompletely understood. Recent reports implicate tumour-intrinsic PDL1 signals in the DNA damage response (DDR), including promoting homologous recombination DNA damage repair and mRNA stability of DDR proteins, but many mechanistic details remain undefined. Methods We genetically depleted PDL1 from transplantable mouse and human cancer cell lines to understand consequences of tumour-intrinsic PDL1 signals in the DNA damage response. We complemented this work with studies of primary human tumours and inducible mouse tumours. We developed novel approaches to show tumour-intrinsic PDL1 signals in specific subcellular locations. We pharmacologically depleted tumour PDL1 in vivo in mouse models with repurposed FDA-approved drugs for proof-of-concept clinical translation studies. Results We show that tumour-intrinsic PDL1 promotes the checkpoint kinase-2 (Chk2)-mediated DNA damage response. Intracellular but not surface-expressed PDL1 controlled Chk2 protein content post-translationally and independently of PD1 by antagonising PIRH2 E3 ligase-mediated Chk2 polyubiquitination and protein degradation. Genetic tumour PDL1 depletion specifically reduced tumour Chk2 content but not ATM, ATR, or Chk1 DDR proteins, enhanced Chk1 inhibitor (Chk1i) synthetic lethality in vitro in diverse human and murine tumour models, and improved Chk1i efficacy in vivo. Pharmacologic tumour PDL1 depletion with cefepime or ceftazidime replicated genetic tumour PDL1 depletion by reducing tumour Chk2, inducing Chk1i synthetic lethality in a tumour PDL1-dependent manner, and reducing in vivo tumour growth when combined with Chk1i. Conclusions Our data challenge the prevailing surface PDL1 paradigm, elucidate important and previously unappreciated roles for tumour-intrinsic PDL1 in regulating the ATM/Chk2 DNA damage response axis and E3 ligase-mediated protein degradation, suggest tumour PDL1 as a biomarker for Chk1i efficacy, and support the rapid clinical potential of pharmacologic tumour PDL1 depletion to treat selected cancers.

Abstract Background Fertilization practices control bacterial wilt-causing Ralstonia solanacearum by shaping the soil microbiome. This microbiome is the start of food webs, in which nematodes act as major microbiome predators. However, the multitrophic links between nematodes and the performance of R. solanacearum and plant health, and how these links are affected by fertilization practices, remain unknown. Results Here, we performed a field experiment under no-, chemical-, and bio-organic-fertilization regimes to investigate the potential role of nematodes in suppressing tomato bacterial wilt. We found that bio-organic fertilizers changed nematode community composition and increased abundances of bacterivorous nematodes (e.g., Protorhabditis spp.). We also observed that pathogen-antagonistic bacteria, such as Bacillus spp., positively correlated with abundances of bacterivorous nematodes. In subsequent laboratory and greenhouse experiments, we demonstrated that bacterivorous nematodes preferentially preyed on non-pathogen-antagonistic bacteria over Bacillus. These changes increased the performance of pathogen-antagonistic bacteria that subsequently suppressed R. solanacearum. Conclusions Overall, bacterivorous nematodes can reduce the abundance of plant pathogens, which might provide a novel protection strategy to promote plant health. Video Abstract

Abstract The spatial arrangement of immune cells within the tumor microenvironment (TME) and their interactions play critical roles in the initiation and development of cancer. Several advanced technologies such as imaging mass cytometry (IMC) providing the immunological landscape of the TME with single-cell resolution. In this study, we develop a new method to quantify the spatial proximity between different cell types based on single-cell spatial data. Using this method on IMC data from 416 lung adenocarcinoma patients, we show that the proximity between different cell types is more correlated with patient prognosis compared to the traditional features such immune cell density and fractions. Consistent with previous reports, our results validate that proximity of T helper (Th) and B cells to cancer cells is associated with survival benefits. More importantly, we discover that the proximity of M2 macrophages to multiple immune cells is associated with poor prognosis. When Th/B cells are stratified into M2-distal and M2-proximal, the abundance of the former but not the latter category of Th/B cells is correlated with enhanced patient survival. Additionally, the abundance of M2-distal and M2-proximal cytotoxic T cells (Tc) is respectively associated with good and poor prognosis. Our results indicate that the prognostic effect of Th, Tc, and B cells in the tumor microenvironment is modulated by the nearby M2 macrophages. The proposed new method proposed can be readily applied to all single-cell spatial data for revealing functional impact of immune cell interactions.

Abstract Background This study aimed to identify the roles of L-tryptophan (Trp) and its rate-limiting enzymes on the receptivity of bovine endometrial epithelial cells. Real-time PCR was conducted to analyze the differential expression of genes between different groups of bovine endometrial epithelial cells. Western blot was performed to detect Cyclooxygenase-2 (COX2) expression after treatment with Trp or kynurenine (the main metabolites of Trp). The kynurenine assay was used to examine if Trp or prostaglandin E2 (PGE2) can increase the production of kynurenine in the bovine endometrial epithelial cells. Results Trp significantly stimulates insulin growth factor binding protein 1 (IGFBP1) expression, a common endometrial marker of conceptus elongation and uterus receptivity for ruminants. When bovine endometrial epithelial cells are treated with Trp, tryptophan hydroxylase-1 remains unchanged, but tryptophan 2,3-dioxygenase 2 (TDO2) is significantly increased, suggesting tryptophan is mainly metabolized through the kynurenine pathway. Kynurenine significantly stimulates IGFBP1 expression. Furthermore, Trp and kynurenine significantly increase the expression of aryl hydrocarbon receptor (AHR). CH223191, an AHR inhibitor, abrogates the induction of Trp and kynurenine on IGFBP1. PGE2 significantly induces the expression of TDO2, AHR, and IGFBP1. Conclusions The regulation between Trp / kynurenine and PGE2 may be crucial for the receptivity of the bovine uterus.

Abstract Background This retrospective study aimed to analyze the evolution of primary indications and surgical techniques for corneal transplantation in Southern China from 2012 to 2021. Methods The medical charts of all patients who underwent keratoplasty between January 2012 and December 2021 at Zhongshan Ophthalmic Centre, Sun Yat-Sen University, Guangzhou, Southern China were reviewed. We collected and analyzed the primary indications for corneal transplantation and the surgical methods used in each keratoplasty. Results The total number of corneal transplantations was 7,286 during this decade, increasing from 210 cases in 2012 to 1054 cases in 2021. The primary indications for keratoplasty included acquired nontraumatic corneal diseases (56.2%), congenital corneal abnormalities (16.4%), acquired traumatic corneal diseases (14.0%), and regraft (13.4%). Infectious keratitis was the leading indication among all keratoplasties (18.5%), followed by regraft (13.4%). Over the decade, the proportion of infectious keratitis gradually decreased (P = 0.013), while the proportion of regraft increased (P = 0.019). The predominant surgical technique was penetrating keratoplasty (PKP), accounting for 56.7%. However, the number of deep anterior lamellar keratoplasty (DALK) and endothelial keratoplasty (EK) significantly increased from 2012 to 2021 (P = 0.007 and P = 0.002). Conclusions The annual number of corneal transplants significantly increased from 2012 to 2021. In the past decade, infectious keratitis and regraft have become the leading primary indications for corneal transplantation. Although the use of customized lamellar techniques has dramatically increased, PKP remains the predominant surgical technique for keratoplasty.

Abstract In a multicenter case–control investigation, we assessed the efficacy of the Electrooculogram Signal Analysis (EOG-SA) method, which integrates attention-related visual evocation, electrooculography, and nonlinear analysis, for distinguishing between intellectual and developmental disabilities (IDD) and typical development (TD) in children. Analyzing 127 participants (63 IDD, 64 TD), we applied nonlinear dynamics for feature extraction. Results indicated EOG-SA’s capability to distinguish IDD, with higher template thresholds and Correlation Dimension values correlating with clinical severity. The template threshold proved a robust indicator, with higher values denoting severe IDD. Discriminative metrics showed areas under the curve of 0.91 (template threshold) and 0.85/0.91 (D2), with sensitivities and specificities of 77.6%/95.9% and 93.5%/71.0%, respectively. EOG-SA emerges as a promising tool, offering interpretable neural biomarkers for early and nuanced diagnosis of IDD.

Abstract We aimed to explore the mineralization characteristics of soil organic carbon(SOC) under different plant species in semi-arid grassland and provide basic soil carbon cycling data. Leymus chinensis, Stipa krylovii Roshev, Artemisia frigida, and Agrophorn cristam (L.) Gaertn were selected as the plant species. Incubation experiment were conducted on SOC mineralization in soil aggregates with particle sizes of > 2, 1–2, 0.25–1, and 2 mm was the highest, exceeding that of A. cristam (L.) Gaertn by approximately 136.14%. S. krylovii Roshev (70.73%), L. chinensis (58.05%), and A. frigida (33.73%) exhibited pronounced promotion effects on mineralization. The potential SOC mineralization of S. krylovii Roshev was the greatest among all species at the same soil particle size. The potential SOC mineralization was highest at a particle size of > 2 mm for all plant types. All plant types increased the SOC mineralization rate and cumulative mineralization in soils with large particle sizes, the mineralization reaction occurred more strongly. Organic carbon cumulative SOC mineralization rapidly increased in all tests during the first 20 days and gradually slowed thereafter.

Abstract Background Soil nutrient status and soil-borne diseases are pivotal factors impacting modern intensive agricultural production. The interplay among plants, soil microbiome, and nutrient regimes in agroecosystems is essential for developing effective disease management. However, the influence of nutrient availability on soil-borne disease suppression and associated plant-microbe interactions remains to be fully explored. T his study aims to elucidate the mechanistic understanding of nutrient impacts on disease suppression, using phosphorous as a target nutrient. Results A 6-year field trial involving monocropping of tomatoes with varied fertilizer manipulations demonstrated that phosphorus availability is a key factor driving the control of bacterial wilt disease caused by Ralstonia solanacearum. Subsequent greenhouse experiments were then conducted to delve into the underlying mechanisms of this phenomenon by varying phosphorus availability for tomatoes challenged with the pathogen. Results showed that the alleviation of phosphorus stress promoted the disease-suppressive capacity of the rhizosphere microbiome, but not that of the bulk soil microbiome. This appears to be an extension of the plant trade-off between investment in disease defense mechanisms versus phosphorus acquisition. Adequate phosphorus levels were associated with elevated secretion of root metabolites such as L-tryptophan, methoxyindoleacetic acid, O-phosphorylethanolamine, or mangiferin, increasing the relative density of microbial biocontrol populations such as Chryseobacterium in the rhizosphere. On the other hand, phosphorus deficiency triggered an alternate defense strategy, via root metabolites like blumenol A or quercetin to form symbiosis with arbuscular mycorrhizal fungi, which facilitated phosphorus acquisition as well. Conclusion Overall, our study shows how phosphorus availability can influence the disease suppression capability of the soil microbiome through plant-microbial interactions. These findings highlight the importance of optimizing nutrient regimes to enhance disease suppression, facilitating targeted crop management and boosting agricultural productivity. Video Abstract

The exploration of the first member of Permian Maokou Formation (Maokou 1) in the Weiyuan area of southern Sichuan Basin has been limited. Previous analyses of cast thin sections and argon ion electron microscopy based on earlier drilling data suggested that talc pores were the primary reservoir spaces, with talc formation significantly contributing to the reservoir. However, the latest drilling data shows substantial differences in the types of reservoir spaces and the genesis of the Maokou 1 marlstone reservoirs compared to earlier understanding. It is necessary to further clarify the main controlling factors for the development of these reservoirs in the Maokou 1 member. Through core observation, thin section identification, physical property analysis, nitrogen adsorption, argon ion polishing scanning electron microscopy, and quantitative pore characterization, the primary reservoir spaces and types of the Maokou 1 marlstone were analyzed from both qualitative and quantitative perspectives. The main controlling factors for the development of these reservoirs were identified by combining total organic carbon (TOC) content determination, rare earth element analysis, and whole rock X-ray diffraction. High-quality reservoirs in the Maokou 1 member of the Weiyuan area are developed in marlstone, characterized by low porosity and permeability fractures and pore-type reservoirs, predominantly Type Ⅲ with some Type Ⅱ reservoirs. The main reservoir spaces include corroded pores, organic matter pores, and talc pores and fractures, with pore development closely related to TOC content. Talc formation, dolomitization, and silicification did not significantly contribute to secondary reservoir spaces, and their contribution to porosity is minimal. The development of marlstone reservoirs is jointly controlled by early dissolution, sedimentary facies, and organic matter abundance. Early dissolution is the key to the formation of corroded pores and fractures, while high primary productivity and high organic matter settling rate of the inner gentle slope shallow water environment provided the material basis for the formation of organic matter pores. This understanding provides theoretical support for the exploration of similar oil and gas reservoirs in the basin.

Background: A Delphi consensus was conducted to formulate an expert opinion on the definition of in-vitro fertilization (IVF) success, to provide a reference basis for clinical practice. Methods: Chinese experts in assisted reproductive technology (ART) were surveyed using the Delphi method. Based on the literature related to IVF success, eight experts developed a framework of statements and items. A questionnaire was then distributed to 23 experts to canvas their opinions on these statements. If consensus was not achieved, the statement was revised and revoted upon until a consensus was reached. Results: Consensus was reached for 19 statements related to the definition of IVF success, the most relevant of which are summarized as follows: (1) Goal of IVF treatment ([Formula: see text] statement): to attain a healthy live birth in the shortest possible time and with the lowest possible risks; (2) Definition of IVF success ([Formula: see text] statements): effectiveness, safety, and efficiency of IVF treatment should be included in the definition of success, with the cumulative live birth rate per ovarian stimulation cycle within 2 years being a performance indicator (PI) of success, and IVF success should be measured from a patient-centered perspective, including the patient’s burden and satisfaction. (3) Assurance of IVF success ([Formula: see text] statements): to provide evidence-based treatment and avoid the introduction of IVF add-ons into routine clinical practice without any clear evidence of benefit, optimize treatment quality by establishing and monitoring key PIs, and improving quality control systems. (4) Hurdles of IVF success ([Formula: see text] statements): cycle cancellation before oocyte pickup and treatment discontinuation after failed cycles are hurdles of success to IVF. Conclusions: Based on the Delphi method, the expert opinion on the definition of IVF success has been formed, which could complement guidelines and may help improve treatment outcomes.

Abstract Benzene and SO2, coexisting as hazardous air pollutants in some cases, such as in coke oven emissions, have led to detrimental health and environmental effects. Physisorbents offer promise in capturing benzene and SO2, while their performance compromises at low concentration. Particularly, the simultaneous capture of trace benzene and SO2 under humid conditions is attractive but challenging. Here, we address this issue by constructing a robust pyrazolate metal-organic framework (MOF) sorbent featuring rich accessible Ni(II) sites with low affinity to water and good stability. This material achieves a high benzene uptake of 5.08 mmol g–1 at 10 Pa, surpassing previous benchmarks. More importantly, it exhibits an adsorption capacity of ~0.51 mmol g–1 for 10 ppm benzene and ~1.21 mmol g–1 for 250 ppm SO2 under 30% relative humidity. This work demonstrates that a pioneering MOF enables simultaneous capture of trace benzene and SO2, highlighting the potential of physisorbents for industrial effluent remediation, even in the presence of moisture.

Pharmaceutical Integrated Experiment (PIE) is a systematic and comprehensive compulsory course for undergraduates majoring in pharmacy and pharmaceutical engineering. This course mainly focuses on integrating the theoretical knowledge of various disciplines into practice, enabling students to master the key processes of drug research and production. In view of the shortcomings of traditional PIE teaching in many domestic colleges and universities, we adopted teaching reform and exploration in 2021 and 2022. Specifically, based on our experience in development of novel SIRT5 inhibitors, we presented a project-based teaching model and selected "Design, Synthesis and Biological Evaluation of Potential SIRT5 Inhibitors" as a case to implement such teaching model. In our course, students worked in a small group to participate in seven interrelated course segments. Throughout the course, we paid attention to process assessment and students' multirole participation in course. We effectively combined the student's course grades and survey results to evaluate students' overall learning effect. Compared to traditional PIE course teaching, this project-based PIE course teaching model is more likely to stimulate students' enthusiasm for self-directed learning due to the more continuous and permeable experimental content, thereby effectively improving the teaching quality of PIE courses.

IntroductionThis study investigates how anxiety, depression, and sleep disorders impact heart rate variability (HRV) in the elderly, exploring the clinical implications of HRV changes.MethodsWe examined 355 patients (163 men, 192 women) at Xijing Hospital from July 2021 to December 2022 during health check-ups. Demographics were recorded, and emotional status was assessed using the Hamilton Anxiety Scale (HAMA) and the Hamilton Depression Scale (HAMD). The Pittsburgh Sleep Quality Scale (PSQI) evaluated sleep quality. Patients were categorized into groups A-G based on the presence of emotional states and sleep disorders. HRV indices—SDNN, SDANN, RMSSD, PNN50, LF/HF, LF, and HF—were analyzed using ANOVA and multivariate logistic regression.ResultsNo statistically significant differences were observed in demographic, clinical, and lifestyle factors across the eight groups. Variables assessed included age, sex, body mass index (BMI), fasting blood glucose, glycated hemoglobin (HbA1c), blood lipids, blood pressure, heart rate, and histories of smoking and alcohol consumption. Additionally, the presence of hypertension, diabetes, coronary heart disease, marital status, income, and education level were evaluated, with all showing equivalence (P > 0.05). Significant differences in HRV indices were observed across groups, particularly in group G (patients with anxiety, depression and sleep disorders), which showed decreased HRV parameters except LF/HF, and group H (control group), which showed increased parameters, also except LF/HF (P < 0.01). Anxiety was an independent risk factor for reduced SDNN, SDANN, and LF (P ≤ 0.01), and increased LF/HF ratio (P < 0.01). Depression was linked to decreased SDNN, RMSSD, PNN50, and HF (P < 0.05). Sleep disorders independently predicted reduced PNN50 and SDANN (P < 0.01).ConclusionHRV indices of individuals with varying emotional states and sleep disorders exhibited varying degrees of decrease. Anxiety, depression, and sleep disorders presented a superimposed effect on HRV. SDNN, SDANN, RMSSD, PNN50, HF and LF of HRV are of great reference value in the diagnosis of emotional and sleep disorders. For elderly patients experiencing cognitive impairment, HRV is anticipated to serve as a convenient and effective tool for assessing mood and sleep disorders.

Intestinal barrier damage causes an imbalance in the intestinal flora and microbial environment, promoting a variety of gastrointestinal diseases. This study aimed to explore the mechanism by which adipose-derived stem cells (ADSCs) repair intestinal barrier damage. The human colon adenocarcinoma cell line Caco-2 and rats were treated with lipopolysaccharide (LPS) to establish in vitro and in vivo models, respectively, of intestinal barrier damage. The expression of inflammatory cytokines (TNF-α, HMGB1, IL-1β and IL-6), antioxidant enzymes (iNOS, SOD and CAT), and oxidative products (MDA and 8-iso-PGF2α) was detected using ELISA kits and related reagent kits. Apoptosis-related proteins (Bcl-2, Bax, Caspase-3 and Caspase-9), tight junction proteins (ZO-1, Occludin, E-cadherin, and Claudin-1) and p38 MAPK pathway-associated protein were detected by Western blotting. In addition, cell viability and apoptosis was determined by a CCK-8 kit and flow cytometry, respectively. Cell permeability was assayed by the transepithelial electrical resistance value and FITC-dextran concentration. The homing effect of ADSCs was detected by fluorescence labeling, and intestinal barrier tissue was observed by HE staining. After ADSC treatment, the level of phosphorylated p38 MAPK protein decreased, the expression of inflammatory factors, oxidative stress and cell apoptosis decreased, the expression of tight junction proteins increased, and cell permeability decreased in Caco-2 cells stimulated with LPS. In rats, ADSCs are directionally recruited to damaged intestinal tissue. ADSCs significantly decreased the levels of D-lactate, diamine oxidase (DAO) and FITC-dextran induced by LPS. ADSCs promoted tight junction proteins and inhibited oxidative stress in intestinal tissue. These effects were reversed after the use of a p38 MAPK activator. ADSCs can be directionally recruited to intestinal tissue, upregulate tight junction proteins, and reduce apoptosis and oxidative stress by inhibiting the p38MAPK signaling pathway. This study provides novel insights into the treatment of intestinal injury.

IntroductionRiptortus pedestris is a destructive pest that threatens multiple leguminous crops in China. The intestinal microbiota plays a crucial role in the growth and reproduction of host insects. However, the composition and function of the gut microbiota at different developmental stages remain unclear.MethodsHere, metagenomic sequencing was performed to clarify the gut microbial diversity and function in 2nd-, 3rd-, 4th-, and 5th- instar nymphs (2 N–5 N) and female adults (FAs) of R. pedestris and the effects of vital gut bacteria on development was detected. The gut bacteria have the stage specificity, indicating their function in the development of R. pedestris.ResultsEnterococcus and Caballerronia were the predominant bacteria present during the development of the 2 N–FAs. In addition, the microbial abundances in the 3 N and 4 N guts were significantly greater than those in the others guts. Furthermore, 5 N harbored the abundant microbiota Burkholderia-Paraburkholderia-Caballeronia. The metabolic pathways were significantly enriched from 2 N to FAs. Carbohydrate metabolism, including glycoside hydrolases (GHs) and glycosyl transferases (GTs), occurs throughout the entire developmental stage. Many antibiotic resistance genes (ARGs) were detected from 2 N to FAs. The bacteria from Pseudomonadota and Bacillota presented a broad spectrum of antibiotic resistance. Excitingly, Burkholderia bacteria eliminated by antibiotic treatment were unable to molt normally, and their lifespan was shortened in nymphs, indicating that the gut microbiota had a significant effect on nymph development.ConclusionIn summary, our results, for the first time, systematically illustrate the abundance and function across the gut microbiota from the different developmental stages of R. pedestris and demonstrate that the genera Burkholderia are crucial during the development of R. pedestris. This study provides the basis for stinkbug management strategies that focus on the pivotal gut microbiota.