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Background Despite considerable efforts, ischemic stroke (IS) remains a challenging clinical problem. Therefore, the discovery of effective therapeutic and targeted drugs based on the underlying molecular mechanism is crucial for effective IS treatment. Methods A cDNA-encoding peptide was cloned from RNA extracted from Rana limnocharis skin, and the mature amino acid sequence was predicted and synthesized. Hemolysis and acute toxicity of the peptide were tested. Furthermore, its neuroprotective properties were evaluated using a middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats and an oxygen–glucose deprivation/reperfusion (OGD/R) model in neuron-like PC12 cells. The underlying molecular mechanisms were explored using microRNA (miRNA) sequencing, quantitative real-time polymerase chain reaction, dual-luciferase reporter gene assay, and western blotting. Results A new peptide (NP1) with an amino acid sequence of ‘FLPAAICLVIKTC’ was identified. NP1 showed no obvious toxicities in vivo and in vitro and was able to cross the blood–brain barrier. Intraperitoneal administration of NP1 (10 nmol/kg) effectively reduced the volume of cerebral infarction and relieved neurological dysfunction in MCAO/R model rats. Moreover, NP1 significantly alleviated the decrease in viability and increase in apoptosis of neuron-like PC12 cells induced by OGD/R. NP1 effectively suppressed inflammation by reducing interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in vitro and in vivo. Furthermore, NP1 up-regulated the expression of miR-6328, which, in turn, down-regulated kappa B kinase β (IKKβ). IKKβ reduced the phosphorylation of nuclear factor-kappa B p65 (NF-κB p65) and inhibitor of NF-κB (I-κB), thereby inhibiting activation of the NF-κB pathway. Conclusions The newly discovered non-toxic peptide NP1 (‘FLPAAICLVIKTC’) exerted neuroprotective effects on cerebral ischemia–reperfusion injury by reducing inflammation via the miR-6328/IKKβ/NF-κB axis. Our findings not only provide an exogenous peptide drug candidate and endogenous small nucleic acid drug candidate but also a new drug target for the treatment of IS. This study highlights the importance of peptides in the development of new drugs, elucidation of pathological mechanisms, and discovery of new drug targets.

Cities are usually the final destination for consumable goods and services produced along supply chains and the most appropriate scale to implement policy. Consumption-based policies could complement current carbon emissions mitigation actions, but such studies at the city level are relatively rare. We used a demand-driven input-output model to explore a historical time series (1987–2012) of consumption-based emissions in Tianjin for the first time, a typical industrial city which has the largest carbon footprint in China. The results reveal the differences between consumption- and production-based emissions, and Tianjin has transformed from a producer city into a typical consumer city since 2000s, mainly due to infrastructure construction. There is more capital investment in industrial infrastructures than in real estate in Tianjin, causing the largest carbon footprint. The trade deficit and different carbon intensity have substantial influences on consumption-based emissions. Finally, population, income, and urbanization could enable a more accurate interpretation of urban carbon footprint growth. Demand-driven policy implications for addressing these emissions in booming industrial cities are discussed and provide a new perspective on carbon emissions mitigation. Our results offer valuable lessons on industrial cities’ strategies and initiatives for climate change mitigation worldwide, particularly in developing countries.

Background Bacterial vaginosis (BV) is one of the most common vaginal infectious diseases in female reproductive period. Although the existing view is that probiotic treatment may be one of the feasible methods for the treatment of BV, different intervention methods lead to different treatment results. Therefore, up-to-date and comprehensive evidence in this regard is essential for the development of intervention strategies. Objective This meta-analysis aims to systematically evaluate the role of probiotics in the treatment of BV in adult women. Methods We searched the databases of Embase, Cochrane Library, PubMed, Web of Science and ClinicalTrials.gov for Randomized Controlled Trials published until November 7, 2021. Meta-analysis was performed by Revman5.3 software to systematically evaluate the clinical efficacy of probiotics adjunctive therapy in the treatment of BV. The literatures were screened and evaluated according to the inclusion and exclusion criteria. Chi-square test was used to test the heterogeneity between trials. Random or Fixed effect models were used to analyze the cure rate of BV. Results Fourteen randomized controlled trials compared the efficacy of probiotics with antibiotic therapy (probiotics + antibiotics group) versus antibiotics alone or plus placebo (antibiotics (+ placebo) group) for BV [Risk Ratios (RR) = 1.23, 95% CI (1.05, 1.43), P = 0.009]. Three compared the efficacy of probiotics regimen (probiotics group) and antibiotics (antibiotics group) in the treatment of BV [RR = 1.12, 95% CI (0.60, 2.07), P = 0.72]. Another Three compared the efficacy of probiotics regimen (probiotics group) with placebo (placebo group) [RR = 15.20, 95% CI (3.87, 59.64), P < 0.0001]. Conclusion Our meta-analysis suggests probiotics may play a positive role in the treatment of BV, but more strong evidence is needed. Plain Language Summary Our meta-analysis found that probiotics may play an active role in adjuvant treatment of bacterial vaginosis by conventional antibiotic therapy. It was emphasized that oral administration of L. rhamnose was more effective than vaginal application of L. rhamnose in the treatment of bacterial vaginosis. The therapeutic effect of probiotics varies with the administration route and dosage of probiotics.

Background Amphibian derived pro-healing peptides as molecular probes might provide a promising strategy for development of drug candidates and elucidation of cellular and molecular mechanisms of skin wound healing. A novel skin amphibian peptide, OA-RD17, was tested for modulation of cellular and molecular mechanisms associated with skin wound healing. Methods Cell scratch, cell proliferation, trans-well, and colony formation assays were used to explore the pro-healing ability of peptide OA-RD17 and microRNA-632 (miR-632). Then, the therapeutic effects of OA-RD17 and miR-632 were assessed in mice, diabetic patient ex vivo skin wounds and SD rats. Moreover, hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and immunofluorescence staining were performed to detect skin wound tissue regeneration, inflammatory factors expression, and macrophage polarization. Finally, RNA sequencing, molecular docking, co-localization, dual luciferase reporter, real-time quantitative reverse transcription PCR (RT-qPCR), and Western blotting were used to explore the mechanism of OA-RD17 and miR-632 on facilitating skin wound healing. Results The non-toxic peptide (OA-RD17) promoted macrophage proliferation and migration by activating MAPK and suppressed inflammation by inhibiting NF-κB. In keratinocytes, OA-RD17 inhibited excessive inflammation, and activated MAPK via the Toll-like receptor 4 (TLR4) to promote proliferation and migration, as well as up-regulate the expression of miR-632, which targeted GSK3β to activate Wnt/β-catenin to boost proliferation and migration in a positive feedback manner. Notably, OA-RD17 promoted transition from the inflammatory to proliferative stage, accelerated epidermal and granulation regeneration, and exhibited therapeutic effects on mouse and diabetic patient ex vivo skin wounds. MiR-632 activated Wnt/β-catenin to promote full-thickness skin wound healing in rats. Conclusions OA-RD17 exhibited promising therapeutic effects on mice (full-thickness, deep second-degree burns), and ex vivo skin wounds in diabetic patients by regulating macrophages proliferation, migration, and polarization (MAPK, NF-κB), and keratinocytes proliferation and migration (TLR4/MAPK/miR-632/Wnt/β-catenin molecular axis). Moreover, miR-632 also activated Wnt/β-catenin to promote full-thickness skin wound healing in rats. Notably, our results indicate that OA-RD17 and miR-632 are promising pro-healing drug candidates. Graphical Abstract

Background The kidney is particularly vulnerable to toxins due to its abundant blood supply, active tubular reabsorption, and medullary interstitial concentration. Currently, calcium phosphate-induced and calcium oxalate-induced nephropathies are the most common crystalline nephropathies. Hyperoxaluria may lead to kidney stones and progressive kidney disease due to calcium oxalate deposition leading to oxalate nephropathy. Hyperoxaluria can be primary or secondary. Primary hyperoxaluria is an autosomal recessive disease that usually develops in childhood, whereas secondary hyperoxaluria is observed following excessive oxalate intake or reduced excretion, with no difference in age of onset. Oxalate nephropathy may be overlooked, and the diagnosis is often delayed or missed owning to the physician’s inadequate awareness of its etiology and pathogenesis. Herein, we discuss the pathogenesis of hyperoxaluria with two case reports, and our report may be helpful to make appropriate treatment plans in clinical settings in the future. Case presentation We report two cases of acute kidney injury, which were considered to be due to oxalate nephropathy in the setting of purslane ( portulaca oleracea ) ingestion. The two patients were elderly and presented with oliguria, nausea, vomiting, and clinical manifestations of acute kidney injury requiring renal replacement therapy. One patient underwent an ultrasound-guided renal biopsy, which showed acute tubulointerstitial injury and partial tubular oxalate deposition. Both patients underwent hemodialysis and were discharged following improvement in creatinine levels. Conclusions Our report illustrates two cases of acute oxalate nephropathy in the setting of high dietary consumption of purslane. If a renal biopsy shows calcium oxalate crystals and acute tubular injury, oxalate nephropathy should be considered and the secondary causes of hyperoxaluria should be eliminated.

Background Gut microbes were closely related to women’s health. Previous studies reported that the gut microbes of premenopausal women were different from those of postmenopausal women. However, little was known about the relationship between gut microbiota dysbiosis and menopausal syndrome (MPS). The aim of this study was to explore the relationship between MPS and gut microbes. Methods Patients with MPS (P group, n  = 77) and healthy women (H group, n  = 24) at menopause were recruited in this study. The stool specimen and clinical parameters (demographic data, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), et al) of participants’ were collected. We evaluated the differences in gut microbes by 16S ribosomal RNA gene sequencing. We used LEfSe to identify gut microbes with varying abundances in different groups. The Spearman correlation coefficients of clinical parameters and gut microbes were calculated. PICRUSt was used to predict the potential KEGG Ortholog functional profiles of microbial communities. Results The abundance of 14 species differed substantially between the MPS and menopausal healthy women (LDA significance threshold > 2.0) according to LEfSe analysis. Using Spearman’s correlation analysis, it was discovered that E2 had a positive correlation with  Aggregatibacter segnis, Bifidobacterium animalis, Acinetobacter guillouiae ( p < 0.05, these three species were enriched in menopausal healthy women), while FSH and LH had a negative correlation with them ( p < 0.05). KEGG level3 metabolic pathways relevant to cardiovascular disease and carbohydrate metabolism were enriched in the MPS ( p < 0.05), according to functional prediction by PICRUST and analyzed by Dunn test. Conclusion There was gut microbiota dysbiosis in MPS, which is reflected in the deficiency of the abundance of Aggregatibacter segnis , Bifidobacterium animalis and Acinetobacter guillouiae related to the level of sex hormones. In MPS individuals, species with altered abundances and unique functional pathways were found.

Sexually transmitted infections (STIs) are associated with vaginal dysbiosis, and co-infections are common but understudied. In this study, 6217 reproductive-age women are recruited from 38 study centres across China at baseline and 2738 participants are followed up at 6 months. We profile the vaginal microbiota by 16S rRNA gene sequencing in conjunction with measurement of nine common STIs. The primary outcome of this study is STI status, and secondary outcome is the risk of cervical lesions. Mycoplasmas hominis (MH) far exceeds other STIs in the association with vaginal microbiota, whereases previously reported associations between Human papillomavirus (HPV) and vaginal dysbiosis might be confounded by the co-infected MH in this study. Both MH infection and increased bacterial diversity are independently associated with increased risk of cervical lesion in HPV-negative women (Shannon, OR (odds ratio) = 1.71, 95% CI (confidence interval) = 1.23-2.36; MH, OR = 2.42 95% CI = 1.36-4.30). These associations are also identified in longitudinal analyses (Shannon, HR (hazard ratio) = 1.72, 95% CI = 1.04-2.86; MH, HR = 2.37, 95% CI = 0.98-5.72). Our findings highlight the importance of considering MH status when studying vaginal microbiota in cervical lesions, and suggest the need for further investigation of microbiota-associated mechanisms in HPV-negative cervical lesions. (ClinicalTrials.gov. NCT04694495). Here, in a study of over 6,000 women across China, the authors show that Mycoplasma hominis infection strongly influences vaginal microbiota and is linked to higher risk of cervical lesions, highlighting its importance in women’s reproductive health.

For vaginal microbiota studies, diverse 16S rRNA gene regions were applied for amplification and sequencing, which affect the comparability between different studies as well as the species-level resolution of taxonomic classification. We conducted comprehensive evaluation on the methods which influence the accuracy for the taxonomic classification and established an optimal pipeline to achieve high species-level resolution for vaginal microbiota with short amplicons, which will facilitate future studies.

Introduction: Tremendous evidence indicates that N6-methyladenosine (m6A) epigenetic modification and m6A-related enzymes constitute a complex network, which jointly regulates prevailing pathological processes and various signaling pathways in humankind. Currently, the role of the m6A-mediated molecular regulatory network in hepatocellular carcinoma (HCC) remains elusive. Methods: We recruited expression and pathological files of 368 HCC patients from The Cancer Genome Atlas cohort. Four public datasets serve as external authentication sets for nearest template prediction (NTP) validation. The correlation between 35 regulators and their prognostic value was compared. Gene set variation analysis (GSVA) was used to explore the latent mechanism. Four independent algorithms (ssGSEA, xCell, MCP-counter, and TIMER) were used to calculate the ratio of tumor cells and non-tumor cells to evaluate the tumor immune microenvironment. The m6Ascore model was established by principal component analysis (PCA). Prediction of immunotherapy and potential drugs was performed using TIDE and SubMap. Results: A total of 35 m6A regulators were widely associated, most of which were risk factors for HCC patients. The m6A phenotypic-cluster revealed differences in regulator transcriptional level, gene mutation frequency, functional pathways, and immune cell infiltration abundance under distinct m6A patterns. As expected, the m6A gene cluster confirmed the aforementioned results. The m6Ascore model further found that patients in the high-m6Ascore group were associated with lower tumor purity, higher enrichment of immune and stromal cells, upregulation of metabolic pathways, lower expression of m6A regulators, and favorable outcomes. Low-m6Ascore patients were associated with adverse outcomes. Notably, low-m6Ascore patients might be more sensitive to anti-PD-L1 therapy. Conclusion: This study found that a classification model based on the m6A manner could predict HCC prognosis and response to immunotherapy for HCC patients, which might improve prognosis and contribute to clinical individualized decision-making.

Pancreatic cancer (PC) is a malignant tumour of the human digestive system that has a poor prognosis. Exosomes contain proteins and nucleic acids, and constitute a class of extracellular vesicles defined as membrane-bound nanovesicles of endocytic origin, with a diameter of 40-150 nm. Exosomes are potential diagnostic markers of PC; however, their roles in cancer initiation and progression remain unclear. Previous studies have focused on the molecular mechanisms and functions of exosomes that allow them to accelerate PC cell proliferation, migration and invasion. The present review discusses the interactions between exosomes and the pathophysiology of PC. The potential clinical applications of exosomes are also discussed.