Hypericum perforatum L. attenuates depression by regulating Akkermansia muciniphila, tryptophan metabolism and NFκB-NLRP2-Caspase1-IL1ß pathway.

BACKGROUND: Gut microbiota dysbiosis significantly contributes to progression of depression. Hypericum perforatum L. (HPL) is traditionally used in Europe for treating depression. However, its mechanism remains largely underexplored. PURPOSE: This study aims to investigate the pivotal gut microbiota species and microbial signaling metabolites associated with the antidepressant effects of HPL. METHODS: Fecal microbiota transplantation was used to assess whether HPL mitigates depression through alterations in gut microbiota. Microbiota and metabolic profiling of control, chronic restraint stress (CRS)-induced depression, and HPL-treated CRS mice were examined using 16S rRNA gene sequencing and metabolomics analysis. The influence of gut microbiota on HPL's antidepressant effects was assessed by metabolite and bacterial intervention experiments. RESULTS: HPL significantly alleviated depression symptoms in a manner dependent on gut microbiota and restored gut microbial composition by enriching Akkermansia muciniphila (AKK). Metabolomic analysis indicated that HPL regulated tryptophan metabolism, reducing kynurenine (KYN) levels derived from microbiota and increasing 5-hydroxytryptophan (5-HTP) levels. Notably, supplementation with KYN activated the NFκB-NLRP2-Caspase1-IL1ß pathway and increased proinflammatory IL1ß in the hippocampus of mice with depression. Interestingly, mono-colonization with AKK notably increased 5-hydroxytryptamine (5-HT) and decreased KYN levels, ameliorating depression symptoms through modulation of the NFκB-NLRP2-Caspase1-IL1ß pathway. CONCLUSIONS: The promising therapeutic role of HPL in treating depression is primarily attributed to its regulation of the NFκB-NLRP2-Caspase1-IL1ß pathway, specifically by targeting AKK and tryptophan metabolites.

miR-455/GREM1 axis promotes colorectal cancer progression and liver metastasis by affecting PI3K/AKT pathway and inducing M2 macrophage polarization.

BACKGROUND: Colorectal cancer is among the most common malignant tumors affecting the gastrointestinal tract. Liver metastases, a complication present in approximately 50% of colorectal cancer patients, are a considerable concern. Recently, studies have revealed the crucial role of miR-455 in tumor pathogenesis. However, the effect of miR-455 on the progression of liver metastases in colorectal cancer remains controversial. As an antagonist of bone morphogenetic protein(BMP), Gremlin 1 (GREM1) may impact organogenesis, body patterning, and tissue differentiation. Nevertheless, the role of miR-455 in regulating GREM1 in colorectal cancer liver metastases and how miR-455/GREM1 axis influences tumour immune microenvironment is unclear. METHODS: Bioinformatics analysis shows that miR-455/GREM1 axis plays crucial role in liver metastasis of intestinal cancer and predicts its possible mechanism. To investigate the impact of miR-455/GREM1 axis on the proliferation, invasion, and migration of colorectal cancer cells, colony formation assay, wound healing and transwell assay were examined in vitro. The Dual-Luciferase reporter gene assay and RNA pull-down assay confirmed a possible regulatory effect between miR-455 and GREM1. In vivo, colorectal cancer liver metastasis(CRLM) model mice was established to inquiry the effect of miR-455/GREM1 axis on tumor growth and macrophage polarization. The marker of macrophage polarization was tested using immunofluorescence(IF) and quantitative real-time polymerase chain reaction(qRT-PCR). By enzyme-linked immunosorbent assay (ELISA), cytokines were detected in culture medium supernatants. RESULTS: We found that miR-455 and BMP6 expression was increased and GREM1 expression was decreased in liver metastase compared with primary tumor. miR-455/GREM1 axis promotes colorectal cancer cells proliferation, migration, invasion via affected PI3K/AKT pathway. Moreover, downregulating GREM1 augmented BMP6 expression in MC38 cell lines, inducing M2 polarization of macrophages, and promoting liver metastasis growth in CRLM model mice. CONCLUSION: These data suggest that miR-455/GREM1 axis promotes colorectal cancer progression and liver metastasis by affecting PI3K/AKT pathway and inducing M2 macrophage polarization. These results offer valuable insights and direction for future research and treatment of CRLM.

Identification of diabetic retinopathy classification using machine learning algorithms on clinical data and optical coherence tomography angiography.

BACKGROUND: To apply machine learning (ML) algorithms to perform multiclass diabetic retinopathy (DR) classification using both clinical data and optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional observational study, clinical data and OCTA parameters from 203 diabetic patients (203 eye) were used to establish the ML models, and those from 169 diabetic patients (169 eye) were used for independent external validation. The random forest, gradient boosting machine (GBM), deep learning and logistic regression algorithms were used to identify the presence of DR, referable DR (RDR) and vision-threatening DR (VTDR). Four different variable patterns based on clinical data and OCTA variables were examined. The algorithms' performance were evaluated using receiver operating characteristic curves and the area under the curve (AUC) was used to assess predictive accuracy. RESULTS: The random forest algorithm on OCTA+clinical data-based variables and OCTA+non-laboratory factor-based variables provided the higher AUC values for DR, RDR and VTDR. The GBM algorithm produced similar results, albeit with slightly lower AUC values. Leading predictors of DR status included vessel density, retinal thickness and GCC thickness, as well as the body mass index, waist-to-hip ratio and glucose-lowering treatment. CONCLUSIONS: ML-based multiclass DR classification using OCTA and clinical data can provide reliable assistance for screening, referral, and management DR populations.

MAL2 reprograms lipid metabolism in intrahepatic cholangiocarcinoma via EGFR/SREBP-1 pathway based on single-cell RNA sequencing.

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive cancer characterized by a poor prognosis and resistance to chemotherapy. In this study, utilizing scRNA-seq, we discovered that the tetra-transmembrane protein mal, T cell differentiation protein 2 (MAL2), exhibited specific enrichment in ICC cancer cells and was strongly associated with a poor prognosis. The inhibition of MAL2 effectively suppressed cell proliferation, invasion, and migration. Transcriptomics and metabolomics analyses suggested that MAL2 promoted lipid accumulation in ICC by stabilizing EGFR membrane localization and activated the PI3K/AKT/SREBP-1 axis. Molecular docking and Co-IP proved that MAL2 interacted directly with EGFR. Based on constructed ICC organoids, the downregulation of MAL2 enhanced apoptosis and sensitized ICC cells to cisplatin. Lastly, we conducted a virtual screen to identify sarizotan, a small molecule inhibitor of MAL2, and successfully validated its ability to inhibit MAL2 function. Our findings highlight the tumorigenic role of MAL2 and its involvement in cisplatin sensitivity, suggesting the potential for novel combination therapeutic strategies in ICC.

Preliminary Purification and Partial Characterization of a Functional Bacteriocin of Lacticaseibacillus paracasei Zhang and Mining for its Gene Cluster.

Bacteriocins produced by lactic acid bacteria (LAB) have good potential for use as food biopreservatives. Lacticaseibacillus paracasei Zhang (L. paracasei Zhang) is both a food use and a probiotic bacterium. This study aimed to purify and preliminary characterize the active antibacterial metabolite of L. paracasei Zhang. The cell-free supernatant of L. paracasei Zhang was collected and purified by ultrafiltration and gel filtration chromatography. The 1-3 kDa active fraction could inhibit the growth of Staphylococcus aureus but not Escherichia coli. Further antibacterial activity assays revealed its capacity to suppress various foodborne and human opportunistic pathogens (including Staphylococcus aureus, Pseudomonas fluorescens, Pseudomonas aeruginosa, Listeria monocytogenes, and Bacillus cereus), but not fungi. The antibacterial activity showed good tolerance to heat (40 to 100 °C), acid-base (pH 2-3 and pH 6-10), and digestions by a number of industrial and animal/human enzymes (such as trypsin, pepsin, α-amylase, and protease K, except papain); these desired properties make it a suitable biopreservative to be used in harsh and complex industrial production processes. The high papain sensitivity suggested a proteinaceous/peptide nature of the bioactivity. Moreover, our genomic data mining for bacteriocin through BAGEL4 revealed an area of interest encoding a complete set of putative genes required for bacteriocin production. In conclusion, our study showed that L. paracasei Zhang can produce extracellular functional antibacterial metabolite, likely a class II bacteriocin. Our preliminary extraction and characterization of the active metabolite demonstrated that it has good potential to be used as a biopreservative or an agent for suppressing gastrointestinal infections.

Sulfur doping-induced morphological and electronic structure modification of polyoxometalate FeWO4 for enhanced removal of organic pollutants from water.

Wolframite (FeWO4), a typical polyoxometalate, serves as an auspicious candidate for heterogeneous catalysts, courtesy of its high chemical stability and electronic properties. However, the electron-deficient surface-active Fe species in FeWO4 are insufficient to cleave H2O2 via Fe redox-mediated Fenton-like catalytic reaction. Herein, we doped Sulfur (S) atom into FeWO4 catalysts to refine the electronic structure of FeWO4 for H2O2 activation and sulfamethoxazole (SMX) degradation. Furthermore, spin-state reconstruction on S-doped FeWO4 was found to effectively refine the electronic structure of Fe in the d orbital, thereby enhancing H2O2 activation. S doping also accelerated electron transfer during the conversion of sulfur species, promoting the cycling of Fe(III) to Fe(II). Consequently, S-doped FeWO4 bolstered the Fenton-like reaction by nearly two orders of magnitude compared to FeWO4. Significantly, the developed S-doped FeWO4 exhibited a remarkable removal efficiency of approximately 100% for SMX within 40 min in real water samples. This underscores its extensive pH adaptability, robust catalytic stability, and leaching resistance. The matrix effects of water constituents on the performance of S-doped FeWO4 were also investigated, and the results showed that a certain amount of Cl-, SO42-, NO3-, HCO3- and PO43- exhibited negligible effects on the degradation of SMX. Theoretical calculations corroborate that the distinctive spin-state reconstruction of Fe center in S-doped FeWO4 is advantageous for H2O2 decomposition. This discovery offers novel mechanistic insight into the enhanced catalytic activity of S doping in Fenton-like reactions and paves the way for expanding the application of FeWO4 in wastewater treatment.

New insights into mechanisms and interventions of locoregional therapies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is responsible for a significant number of cancer-related deaths worldwide and its incidence is increasing. Locoregional treatments, which are precision procedures guided by imaging to specifically target liver tumors, play a critical role in the management of a substantial portion of HCC cases. These therapies have become an essential element of the HCC treatment landscape, with transarterial chemoembolization (TACE) being the treatment of choice for patients with intermediate to advanced stages of the disease. Other locoregional therapies, like radiofrequency ablation, are highly effective for small, early-stage HCC. Nevertheless, the advent of targeted immunotherapy has challenged these established treatments. Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have shown remarkable efficacy in clinical settings. However, their specific uses and the development of resistance in subsequent treatments have led clinicians to reevaluate the future direction of HCC therapy. This review concentrates on the distinct features of both systemic and novel locoregional therapies. We investigate their effects on the tumor microenvironment at the molecular level and discuss how targeted immunotherapy can be effectively integrated with locoregional therapies. We also examine research findings from retrospective studies and randomized controlled trials on various combined treatment regimens, assessing their validity to determine the future evolution of locoregional therapies within the framework of personalized, comprehensive treatment.

Functional dissection of parabrachial substrates in processing nociceptive information.

Painful stimuli elicit first-line reflexive defensive reactions and, in many cases, also evoke second-line recuperative behaviors, the latter of which reflects the sensing of tissue damage and the alleviation of suffering. The lateral parabrachial nucleus (lPBN), composed of external- (elPBN), dorsal- (dlPBN), and central/superior-subnuclei (jointly referred to as slPBN), receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption. However, the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear. In this study, we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor ( NK1R) (lPBN NK1R) are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle, while elPBN neurons are dispensable for driving such reactions. Notably, lPBN NK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats. Lastly, both lPBN NK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions. Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.

T-DNA insertion in Arabidopsis caused coexisting chromosomal inversion and duplication at megabase level.

Agrobacteria-mediated transformation is widely used in plant genetic engineering to introduce exogenous genes and create mutant lines through random T-DNA insertion and gene disruption. When T-DNA fragments are inserted into the plant genome, it could cause chromosomal abnormalities. In this study, we investigated the genetic basis of pleiotropic phenotypes observed in the T-DNA insertion mutant lnc161. We discovered that there are four T-DNA insertions present in the lnc161 genome, which disrupted the genes LNC161 (AT3G05035), AT3G57400, AT5G05630, and AT5G16450, respectively. However, none of these insertions were the causative mutation that leads to the lnc161 phenotypes. Strikingly, through genetic analyses and high throughput sequencing, we found an inversion of about 19.8 Mb sequences between LNC161 and AT3G57400. Moreover, the sequences between AT5G05630 and AT5G16450 (about 3.7 Mb) were translocated from chromosome 5 to chromosome 3, adjacent to the inversion sequences, and were duplicated. This duplication led to an up-regulation of genes expression in this region, potentially resulting in pleiotropic morphological traits in lnc161. Overall, this study provides a case showing complex chromosomal re-arrangement induced by T-DNA insertion.

[Network Meta-analysis of Chinese patent medicines combined with antibiotics in treatment of pelvic inflammatory diseases].

To evaluate the efficacy and safety of different Chinese patent medicines in the treatment of pelvic inflammatory disease(PID) using network Meta-analysis. The databases of CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science were searched, and from the time of database construction to July 16, 2023, the randomized controlled trial(RCT) of Chinese patent medicines combined with antibiotics in the treatment of PID included in these databases was collected. The quality of the included literature was evaluated using the Cochrane risk of bias tool, and data was analyzed using RevMan 5.4 and Stata 16 software. Forty-six RCTs were finally included, including Kangfu Xiaoyan Suppositories, Fuke Qianjin Tablets/Capsules, Kangfuyan Capsules, Fuyanxiao Capsules, Huahong Tablets/Capsules, Fuyanshu Capsules, Fuyue Tablets, Jingangteng Capsules, and Fuyan Kangfu Capsules. Network Meta-analysis showed that,(1) in terms of clinical effective rate, the optimal intervention was Kangfu Xiaoyan Suppositories combined with antibiotics.(2) In terms of lowering hypersensitive C-reactive protein(hs-CRP), the optimal intervention was Huahong Tablets/Capsules combined with antibiotics.(3) In terms of lowering tumor necrosis factor-α(TNF-α), the optimal intervention was Fuyue Tablets combined with antibiotics.(4) In terms of lowering recurrence rate, the optimal intervention was Fuyanshu Capsules combined with antibiotics.(5) In terms of safety, the intervention with the least adverse reactions was Kangfuyan Capsules combined with antibiotics. The results show that Chinese patent medicines combined with antibiotics in the treatment of PID can improve the comprehensive efficacy, reduce the patient's hs-CRP and TNF-α, and have a low recurrence rate, as well as safe and reliable efficacy. In clinical treatment, Kangfu Xiaoyan Suppositories or Kangfuyan Capsules combined with antibiotics can be preferred. Due to the limitations of the sample size and the quality of the literature, more large-sample and high-quality studies are needed to validate the conclusions.

Oxygen vacancy-rich nickel oxide nanoplatforms for enhanced photothermal and chemodynamic therapy combat methicillin-resistant Staphylococcus aureus.

Bacterial infections pose a global concern due to high fatality rates, particularly with the rise of drug-resistant bacteria and biofilm formation. There is an urgent need for innovative strategies to combat this issue. A study on chemodynamic therapy (CDT) using nanozymes in conjunction with photothermal therapy (PTT) has displayed potential in addressing drug-resistant bacterial infections. However, the effectiveness of this combined approach is limited by inadequate light absorption. This work suggests the NiOx nanoparticles enriched with oxygen vacancies enhance CDT and PTT to overcome this challenge. The presence of oxygen vacancies in NiOx can reduce the energy gap between its valence band and conduction band, facilitating oxygen adsorption. NiOx has exhibited notable antibacterial properties and complete eradication of biofilms in both laboratory and animal trials. In animal abscess models, NiOx demonstrated antibacterial and anti-inflammatory effects in the initial stages, while also promoting wound healing and tissue regeneration by influencing immune factors and encouraging collagen deposition and neovascularization. With positive biosafety and biocompatibility profiles, the oxygen vacancy-enhanced CDT and PTT therapy proposed in this article hold promise for effective sterilization, deep biofilm removal, and treatment of infections caused by drug-resistant bacteria. STATEMENT OF SIGNIFICANCE: This study constructs oxygen vacancies NiOx nanoparticles (NiOx NPs) to improve the efficacy of photothermal therapy and chemodynamic therapy. The presence of oxygen vacancies in NiOx NPs helps bridge the energy gap between its valence band and conduction band, facilitating oxygen adsorption and improving catalytic efficiency. In both in vivo and in vitro antibacterial experiments, NiOx NPs demonstrate effective antibacterial and anti-inflammatory properties. Furthermore, it aids in wound healing and tissue regeneration by modulating immune factors, collagen deposition, and angiogenesis. This approach presents a promising collaborative strategy for utilizing nickel-based defective nanomaterials in combating deep drug-resistant bacterial infections.

Metabolomics reveals ascorbic acid inhibits ferroptosis in hepatocytes and boosts the effectiveness of anti-PD1 immunotherapy in hepatocellular carcinoma.

BACKGROUND: Immunotherapy combined with molecular targeted therapy is increasingly popular in patients with advanced hepatocellular carcinoma (HCC). However, immune-related adverse events(irAEs) brought on by immunotherapy increase the likelihood of side effects, thus it is important to look into ways to address this issue. METHODS: Different metabolite patterns were established by analyzing metabolomics data in liver tissue samples from 10 patients(divided into severe and mild liver injury) before and after immuno-targeted therapy. After establishing a subcutaneous tumor model of HCC, the mice were divided into PBS group, ascorbic acid(AA) group, and anti-PD1 + tyrosine kinase inhibitor (TKI) group, anti-PD1 + TKI + AA group. Liver tissue were stained with hematoxylin-eosin staining(HE) and the content of aspartate transaminase (AST) and alanine transaminase(ALT) in blood were determined. The mechanism was confirmed by western blotting, mass cytometry, and other techniques. RESULTS: Through metabolomics analysis, AA was significantly reduced in the sample of patients with severe liver injury caused by immuno-targeted therapy compared to patients with mild liver injury. The addition of AA in vivo experiments demonstrated a reduction in liver injury in mice. In the liver tissues of the anti-PD1 + TKI + AA group, the protein expressions of SLC7A11,GPX4 and the level of glutathione(GSH) were found to be higher compared to the anti-PD1 + TKI group. Mass cytometry analysis revealed a significant increase in the CD11b+CD44+ PD-L1+ cell population in the AA group when compared to the PBS group. CONCLUSIONS: AA could reduce liver injury by preventing hepatocyte SLC7A11/GPX4 ferroptosis and improve the immunotherapy effect of anti-PD1 by boosting CD11b+CD44+PD-L1+cell population in HCC.

Both viable Bifidobacterium longum subsp. infantis B8762 and heat-killed cells alleviate the intestinal inflammation of DSS-induced IBD rats.

In view of the safety concerns of probiotics, more and more attention is paid to the beneficial effects of dead probiotics cells. Herein, we investigated and compared the alleviation effects of viable Bifidobacterium longum subsp. infantis B8762 (B. infantis B8762) and its heat-killed cells on dextran sodium sulfate (DSS)-induced inflammatory bowel disease (IBD) rats. Four groups of rats (n = 12 per group) were included: normal control, DSS-induced colitis rats without bacterial administration (DSS), DSS-induced colitis rats with viable B. infantis B8762 administration (VB8762), and DSS-induced colitis rats with dead B. infantis B8762 administration (DB8762). Our results showed that both VB8762 and DB8762 administration exerted significant protective effects on DSS-induced IBD rats, as evidenced by a reduction in mortality, disease activity index score, body weight loss, as well as decreased histology score, which were companied by a significant decrease in serum pro-inflammatory factors compared with DSS group, and a stronger effect on modulating the fecal microbiota alpha-diversity and beta-diversity compared with DSS group. Additionally, the fecal metabolome results showed that both VB8762 and DB8762 interventions indeed altered the fecal metabolome profile and related metabolic pathways of DSS-induced IBD rats. Therefore, given the alleviation effects on colitis, the DB8762 can be confirmed to be a postbiotic. Overall, our findings suggested that VB8762 and DB8762 had similar ability to alleviate IBD although with some differences. Due to the minimal safety concern of postbiotics, we propose that the postbiotic DB8762 could be a promising alternative to probiotics to be applied in the prevention and treatment of IBDs.IMPORTANCEInflammatory bowel disease (IBD) has emerged as a global disease because of the worldwide spread of western diets and lifestyles during industrialization. Up to now, many probiotic strains are used as a modulator of gut microbiota or an enhancer of gut barrier to alleviate or cure IBD. However, there are still many issues of using probiotics, which were needed to be concerned about, for instance, safety issues in certain groups like neonates and vulnerable populations, and the functional differences between viable and dead microorganisms. Therefore, it is of interest to investigate the beneficial effects of dead probiotics cells. The present study proved that both viable Bifidobacterium longum subsp. infantis B8762 and heat-killed cells could alleviate dextran sodium sulfate-induced colitis in rats. The findings help to support that some heat-killed probiotics cells can also exert relevant biological functions and can be used as a postbiotic.

Rodent-Proof Wall: An Efficient Physical Method for Controlling Rodents and its Efficiency Statistics.

Rodent damage poses a significant threat to crops, human life, and health. Compared to chemical rodent control, such as placing poisonous baits, it is more economical and environmentally friendly to use physical methods, such as building a rodent-proof wall. This study introduces a method of physically controlling harmful rodents and four methods of calculating the effect of rodents control. To understand the controlling effect of the rodent-proof wall, an investigation was conducted on the Dongting Lake beach and corresponding farmland in the embankment in April and July 2012. Our findings illustrated that the density of the reed vole Microtus fortis in the farmland with rodent-proof walls was 0.52%, significantly lower than that in the farmland without rodent-proof walls (1.76%) after artificial trapping and drug extermination (χ2 = 3.900, P = 0.048). The density of M. fortis that had migrated into the farmland in dikes with a rodent-proof wall decreased by 98.53%, significantly higher than the decrease of density in dikes without a rodent-proof wall (86.61%) (χ2 = 11.060, P = 0.01). The results demonstrated the effectiveness of rodent-proof wall control. Therefore, building a rodent-proof wall should be advocated and vigorously promoted to prevent the migration of rodents into the Dongting Lake area and similar environments, as they cause harm.

Iodide-umpolung catalytic system for non-traditional amide coupling from nitroalkanes and amines.

An N-iodosuccinimide (NIS) catalyst was developed for use in the non-traditional synthesis of amide derivatives from nitroalkanes and amines. In contrast to traditional oxidative catalysis, this catalytic system involves reversing the polarities of two catalytic components (umpolung) by means of a hypervalent iodine reagent. A variety of functional groups were tolerated in the reaction, suggesting that they have the potential for use in other types of oxidative catalytic reactions.

Comparing Telerehabilitation and Home-based Exercise for Shoulder Disorders: A Systematic Review and Meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to quantitatively compare the effects of telerehabilitation and home-based exercise for shoulder disorders. DATA SOURCES: We conducted a search for eligible studies in PubMed, EMBASE, Web of Science, Cochrane Library, and MEDLINE databases following Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. STUDY SELECTION: Independent reviewers selected randomized controlled trials that compared the effects of telerehabilitation and home-based exercise in individuals with shoulder disorders. DATA EXTRACTION: Two reviewers independently conducted data extraction and assessed the risk of bias using the Cochrane Risk of Bias tool. DATA SYNTHESIS: A total of 7 studies with 508 participants were included. Compared with home-based exercise, telerehabilitation showed superior improvements in range of motion (flexion: standardized mean difference [SMD] 0.35, 95% confidence interval [CI] 0.14 to 0.56; abduction: SMD 0.37, 95% CI 0.16 to 0.58; external rotation: SMD 0.43, 95% CI 0.22 to 0.64; internal rotation: SMD 0.33, 95% CI 0.08 to 0.58), functional outcomes (Shoulder Pain and Disability Index: SMD -0.37, 95% CI -0.61 to -0.12; shortened Disabilities of the Arm, Shoulder and Hand questionnaire: mean difference [MD] -4.51, 95% CI -8.70 to -0.32), and quality of life (EuroQol Five Dimensions Questionnaire: MD 0.04, 95% CI 0.01 to 0.07). Telerehabilitation was not different from home-based exercise in terms of pain relief (SMD -0.19, 95% CI -0.60 to 0.23). Subgroup analysis demonstrated that telerehabilitation provided significant pain relief when sustained for over 12 weeks (SMD -0.46, 95% CI -0.81 to -0.11). CONCLUSIONS: Telerehabilitation is more effective than home-based exercise in improving range of motion, functional outcomes, and quality of life for patients with shoulder disorders. Telerehabilitation significantly outperforms home-based exercise in relieving pain when continued for over 12 weeks.

Integration of hepatitis B virus into patients' sperm genome and its clinical risks.

BACKGROUND: Like the coronavirus disease 2019, the hepatitis B virus is also wreaking havoc worldwide, which has infected over 2 billion people globally. Using an experimental animal model, our previous research observed that the hepatitis B virus genes integrated into human spermatozoa can replicate and express after being transmitted to embryos. However, as of now, this phenomenon has not been confirmed in clinical data from patients. OBJECTIVES: To explore the integration of the hepatitis B virus into patients' sperm genome and its potential clinical risks. MATERIALS AND METHODS: Forty-eight patients with chronic hepatitis B virus infection were categorized into two groups: Test Group-1 comprised 23 patients without integration of hepatitis B virus DNA within the sperm genome. Test Group-2 comprised 25 patients with integration of hepatitis B virus DNA within the sperm genome. Forty-eight healthy male donors were included as control. The standard semen parameter analysis, real-time polymerase chain reaction, quantitative real-time polymerase chain reaction, sperm chromatin structure assay, fluorescence in situ hybridization, and immunofluorescence assays were utilized. RESULTS: The difference in the median copy number of hepatitis B virus DNA per mL of sera between Test Group-1 and Group-2 was not statistically significant. In Test Group-2, the integration rate of hepatitis B virus DNA was 0.109%, which showed a significant correlation with the median copy number of hepatitis B virus DNA in motile spermatozoa (1.18 × 103 /mL). Abnormal semen parameters were found in almost all these 25 patients. The integrated hepatitis B virus S, C, X, and P genes were detected to be introduced into sperm-derived embryos through fertilization and retained their function in replication, transcription, and translation. CONCLUSION: Our findings suggest that hepatitis B virus infection can lead to sperm quality deterioration and reduced fertilization capacity. Furthermore, viral integration causes instability in the sperm genome, increasing the potential risk of termination, miscarriage, and stillbirth. This study identified an unconventional mode of hepatitis B virus transmission through genes rather than virions. The presence of viral sequences in the embryonic genome poses a risk of liver inflammation and cancer.

piRNA loading triggers MIWI translocation from the intermitochondrial cement to chromatoid body during mouse spermatogenesis.

The intermitochondrial cement (IMC) and chromatoid body (CB) are posited as central sites for piRNA activity in mice, with MIWI initially assembling in the IMC for piRNA processing before translocating to the CB for functional deployment. The regulatory mechanism underpinning MIWI translocation, however, has remained elusive. We unveil that piRNA loading is the trigger for MIWI translocation from the IMC to CB. Mechanistically, piRNA loading facilitates MIWI release from the IMC by weakening its ties with the mitochondria-anchored TDRKH. This, in turn, enables arginine methylation of MIWI, augmenting its binding affinity for TDRD6 and ensuring its integration within the CB. Notably, loss of piRNA-loading ability causes MIWI entrapment in the IMC and its destabilization in male germ cells, leading to defective spermatogenesis and male infertility in mice. Collectively, our findings establish the critical role of piRNA loading in MIWI translocation during spermatogenesis, offering new insights into piRNA biology in mammals.

Relationship between fear of evaluation, ambivalence over emotional expression, and self-compassion among university students.

BACKGROUND: This study focuses on college students as research subjects, exploring the relationship between fear of evaluation, ambivalence over emotional expression, and self-care, as well as the moderating effect of self-care on the prediction of ambivalence over emotional expression by fear of evaluation. METHODS: This study selected physical education college students in Sichuan Province as the research participants. Convenience sampling was used to recruit participants through public recruitment information and questionnaire links on online platforms commonly used by college students. The questionnaire was distributed at two different time points to reduce the effect of common method bias. A total of 858 questionnaires were distributed, after excluding duplicate responses, a total of 743 valid questionnaires were obtained. RESULTS: The result as following: (1) College students exhibit a moderate to high level of negative fear of evaluation, ambivalence over emotional expression, and self-care, with female students having higher negative fear of evaluation; (2) There are significant correlations between fear of evaluation, ambivalence over emotional expression, and self-care; (3) Fear of evaluation and self-care can predict ambivalence over emotional expression, but self-care does not have a moderating effect on the prediction of ambivalence over emotional expression by fear of evaluation; (4) Self-care and negative self-care both have a moderating effect on the prediction of emotion rumination by positive fear of evaluation. CONCLUSIONS: In the past, rumination has often been considered a manifestation of excessive rumination and anxiety. However, this study found that self-compassion's modulation on fear of positive evaluation intensifies its impact on emotional rumination. Research suggests that moderate emotional rumination may not necessarily be a negative outcome and reflects a positive emotional adjustment process to some extent. Therefore, future studies can further explore the growth and decline of internal rumination processes in self-compassion or counseling, and potentially gain a better understanding of key elements of personal growth.