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Background In this study, the association between human papillomavirus (HPV) infection and related cervical intraepithelial neoplasia (CIN) or cervical cancer and vaginal microbiome was evaluated in Chinese cohorts. Methods The vaginal bacterial composition of five groups, HPV-infected women without CINs (HPV, n  = 78), women with low-grade squamous intraepithelial lesions (LSIL, n  = 51), women with high-grade squamous intraepithelial lesions (HSIL, n  = 23), women with invasive cervical cancer (Cancer, n  = 9) and healthy women without HPV infection (Normal, n  = 68), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3 – 4) using Illumina MiSeq. Results HPV infection increased vaginal bacterial richness and diversity regardless of the status of CINs. The vaginal bacterial richness and diversity were further augmented in women with cervical cancer. Lactobacillus was the most abundant genus in all groups. HPV infection had a negative influence on the abundances of Lactobacillus , Gardnerella and Atopobium . Accordingly, HPV infection increased the relative abundance of Prevotella , Bacillus , Anaerococcus , Sneathia , Megasphaera , Streptococcus and Anaerococcus . The increased proportions of Bacillus , Anaerococcus and the reduced abundance of Gradnerella vaginalis were probably related with the progression of CINs severity. HPV infection without CINs or cancerous lesions was strongly associated with Megasphaera . The most abundant bacterium in the LSIL group was Prevotella amnii . However, Prevotella timonensis , Shuttleworthia and Streptococcaceae at the family level were three taxa related to HSIL. Furthermore, more taxa were associated with the Cancer group including Bacillus , Sneathia , Acidovorax , Oceanobacillus profundus , Fusobacterium , Veillonellaceae at the family level, Anaerococcus and Porphyromonas uenonis . Samples in the Normal group were mostly assigned to CST III. HPV infection converted the vaginal bacterial community structure from CST III to CST IV. Furthermore, the proportions of CST IV were gradually augmented with the progression of the severity of CINs. Conclusions This work interpreted the differential vaginal bacteria under HPV infection and various precancerous or cancerous lesions in a Chinese cohort. We distinguished the specific microbes and the vaginal bacterial structure that were related with the progression of CINs severity in Chinese women.

In catalytic asymmetric reactions, the formation of chiral molecules generally relies on a direct chirality transfer (point or axial chirality) from a chiral catalyst to products in the stereo-determining step. Herein, we disclose a transient-axial-chirality transfer strategy to achieve asymmetric reaction. This method relies on transferring point chirality from the catalyst to a dirhodium carbene intermediate with axial chirality, namely a transient-axial-chirality since this species is an intermediate of the reaction. The transient chirality is then transferred to the final product by C(sp 2 )-H functionalization reaction with exceptionally high enantioselectivity. We also generalize this strategy for the asymmetric cascade reaction involving dual carbene/alkyne metathesis (CAM), a transition-metal-catalyzed method to access chiral 9-aryl fluorene frameworks in high yields with up to 99% ee . Detailed DFT calculations shed light on the mode of the transient-axial-chirality transfer and the detailed mechanism of the CAM reaction. The formation of chiral molecules generally relies on direct chirality transfer from catalyst to products. Here, the authors report a strategy based on point chirality transfer from the catalyst to a dirhodium carbene intermediate with axial chirality, which is then transferred to products via C(sp 2 )-H functionalization.

Ferroptosis is a non-traditional form of regulated cell death, characterized by iron overload and lipid peroxidation. Exploration of ferroptosis in chronic kidney disease (CKD) has been extremely limited to date. In this study, we established a rat model of CKD by 5/6 nephrectomy, treated CKD rats with the ferroptosis inducer, cisplatin (CDDP), and the ferroptosis inhibitor, deferoxamine mesylate (DFO), and observed the resulting pathologic changes (injury markers and fibrosis) and ferroptotic biochemical indices. Kidney iron deposition, lipid peroxidation, mitochondrial defects, ferroptosis marker induction, and TUNEL staining positivity were detected in CKD group rats. Further, treatment with CDDP or DFO influenced renal injury and fibrosis by affecting ferroptosis, rather than apoptosis, and ferroptosis occurs in the remnant kidney due to disordered iron metabolism. In conclusion, our study shows for the first time that 5/6 nephrectomy induces ferroptosis in the remnant kidney and clarifies the underlying pathogenesis. Moreover, we demonstrate that ferroptosis is involved in CKD progression and represents a therapeutic target in chronic kidney injury and renal fibrosis.

Fish reproduction requires suitable salinity and temperature, as well as sufficient energy. This study investigated temperature and salinity effects on ovarian development of Lateolabrax maculatus and energy metabolism differences between reproduction and growth. Two salinities (4‰ and 30‰) and temperatures (18 ± 1 °C and 30 ± 1 °C) formed four treatments: SWNT (30‰, 30 ± 1 °C), SWLT (30‰, 18 ± 1 °C), FWLT (4‰, 18 ± 1 °C), and FWNT (4‰, 30 ± 1 °C). GSI and sex hormones (FSH, LH, E2, and 17α,20β-DHP) were measured. Transcriptome analysis explored how temperature and salinity regulate ovarian development in L. maculatus, while integrated transcriptomic and targeted energy metabolomic analyses revealed energy metabolism differences between ovary and muscle during this process. The results showed that low salinity (4‰) and low temperature (18 ± 1 °C) synergistically promoted ovarian development in the FWLT group, as indicated by a significant increase in GSI and elevated levels of key sex hormones (FSH, LH, E2, and 17α,20β-DHP). Transcriptome analysis showed that low temperature activated pathways involved in steroidogenesis, oocyte maturation, and meiosis, and genes such as ADCY6, PRKACB, CPEB4, FZD7-A, and CCND2 were significantly upregulated. Salinity changes mainly affected amino acid metabolism, cholesterol metabolism, and the insulin signaling pathway. Genes such as PCSK9 and CKM may regulate ovarian development by regulating hormone synthesis and energy metabolism. Comprehensive transcriptome and metabolome analyses show that glycolysis is downregulated and oxidative phosphorylation is upregulated in the ovary, suggesting that ovarian oogenesis tends to be energized by aerobic metabolism. The TCA cycle may be used more for providing biosynthetic precursors and facilitating the transport of substrates between the mitochondrion and the cytoplasm rather than just as a source of ATP. Muscle tissue relies primarily on glycolysis for rapid energy production and may redistribute energy to the gonads, prioritizing the energy needs of the ovaries and contributing to the dynamic balance between reproduction and growth. This study provides insights into the molecular mechanisms of how environmental factors regulate fish reproduction, providing a theoretical basis and potential molecular targets for the regulation of reproduction and optimization of aquaculture environments.

Background We aimed to comprehensively evaluate the immunologic landscape at baseline and upon chemotherapy in cervical cancer. The information should aid ongoing clinical investigations of checkpoint blockade immunotherapies in this disease setting. Methods A series of 109 cervical carcinoma patients was retrospectively assayed before and after neoadjuvant chemotherapy. Tumour-infiltrating immune markers (CD3, CD4, CD8, CD20, CD56, CD68, PD-1, PD-L1) were assessed by immunohistochemistry. RNA sequencing analysis was performed on matched pre- and post-treatment fresh-frozen tissues. Results At diagnosis, diverse immune cell types including CD20+ B cells, CD3+ T cells, CD56+ natural killer (NK) cells, and CD68+ macrophages were detected in different proportions of cervical carcinoma. Unsupervised hierarchical clustering evidently showed that CD4+ and CD8+ T cell abundance correlated with PD-L1 expression. Based on the immune infiltration patterns, the patients could be stratified into four groups with prognostic relevance, namely, ‘immuno-active’, ‘immuno-medial’, ‘immuno-NK’, and ‘immuno-deficient’. Neoadjuvant chemotherapy was associated with increased CD4, CD8, CD20, and CD56 signals, most prominently in good responders. Transcriptomic data corroborated the improved anticancer immunity and identified immunosuppressive CD200 upregulation following chemotherapeutic intervention. Conclusions A subset of cervical cancer harbours active immune microenvironment, and chemotherapy treatment may further exert locoregional immunostimulation. Immune checkpoint inhibitors as combination or maintenance therapies warrant future exploration in clinic.

Cervical cancer is the third most common malignancy among Chinese women in both incidence and mortality. Its progression is closely linked to complex interactions among immune cells within the tumor microenvironment (TME). As key components of the immune landscape, different T cell subsets play diverse and dynamic roles in shaping tumor immunity. This review provides a comprehensive overview of the roles of various T cell subsets in the TME of cervical cancer, with a focus on their distribution, functional heterogeneity, dynamic balance, and variations across different pathological subtypes and disease stages. We also highlight the intricate crosstalk between T cells and other immune cells in the TME and discuss recent advances in T cell-related immunotherapies for cervical cancer, including immune checkpoint inhibitors and HPV-targeted vaccines. By elucidating the roles of distinct T cell subsets and relevant immunotherapeutic approaches within the TME, this review provides insights into potential therapeutic targets and approaches for improving cervical cancer treatment and patient outcome.

Background Triple-negative breast cancer (TNBC) is a highly aggressive malignant disease with a high rate of recurrence and metastasis, few effective treatment options and poor prognosis. Here, we designed and constructed a combined photothermal immunotherapy strategy based on cancer cell membrane-coated biomimetic black phosphorus quantum dots (BBPQDs) for tumor-targeted photothermal therapy and anti-PD-L1 mediated immunotherapy. Results BBPQDs have good photothermal conversion efficiency and can efficiently target tumor cells through homologous targeting and tumor homing. Under near infrared irradiation, we found that BBPQDs kill tumors directly through photothermal effects and induce dendritic cells maturation. In vivo studies have confirmed that the combined photothermal immunotherapy strategy displays a stronger antitumor activity than anti-PD-L1 monotherapy. In addition, BBPQDs-mediated photothermal therapy in combination with anti-PD-L1 treatment inhibit tumor recurrence and metastasis by reprograming the immunosuppressive tumor microenvironment into an immune-active microenvironment, and promoting the local and systemic antitumor immune response. We further found that the combined photothermal immunotherapy strategy can produce an immune memory effect against tumor rechallenge. Conclusions This study provides a novel therapeutic strategy for inhibiting the recurrence and metastasis of TNBC, with broad application prospects.

Background In this study, the association between high-risk human papillomavirus (hrHPV) infection and the vaginal microbiome in pregnant women was evaluated in Chinese cohorts. Methods The vaginal bacterial composition of four groups, 38 hrHPV-infected pregnant women (PHR, n  = 38), pregnant women without HPV infection (PN, n  = 48), nonpregnant women with hrHPV infection (NPHR, n  = 19) and nonpregnant women without HPV infection (NPN, n  = 30), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3–4) using Illumina MiSeq. Results The results revealed that both pregnancy and HPV infection can increase vaginal bacterial microbial richness and diversity, with the bacterial composition being most influenced by pregnancy. Lactobacillus was the most dominant genus among all samples. NPN samples were dominated by CST (community state type) III, mainly composed of Lactobacillus iners . Both pregnancy and hrHPV infection were accompanied by an increased proportion of CST I (dominated by Lactobacillus crispatus ), as opposed to CST III. Bifidobacterium , Bacillus , Megasphaera , Sneathia , Prevotella , Gardnerella , Fastidiosipila and Dialister were found to be biomarkers for hrHPV-infected women, though different genera ( Bifidobacterium , Megasphaera , Bacillus , Acidovorax , Oceanobacillus and Lactococcus ) were associated with hrHPV-infected pregnant women. Conclusions This work uncovered a probable synergistic effect of hrHPV infection and pregnancy on the vaginal microbial composition. HPV infection in pregnant women was associated with a more complex and diverse microbial environment.

Background: Primordial germ cells (PGC) are the progenitor cells of sperm and eggs during the embryonic stage. The maternal gene vasa has been widely studied for its role in PGC origin, and other genes like dead end (dnd) have also been identified. Objectives: Spotted sea bass is an important economic marine fish, and the study of its germ cell characteristics provides important basic data for future population breeding and protection. Methods: In this study, we cloned the full-length sequences of Lmvasa (2384 bp, encoding 1905 aa) and Lmdnd (1523 bp, encoding 386 aa) using RACE. Temporal and spatial expression patterns of Lmvasa and Lmdnd in embryos and gonads were analyzed by PCR, immunohistochemistry, and in situ hybridization. We also used microinjections of chimeric RNA containing GFP and Lmvasa 3′ UTR to visualize PGCs. Results: Our results showed that Lmvasa and Lmdnd are expressed primarily in early embryonic development (pre-blastula stage) and were expressed only in the gonads. Immunohistochemistry revealed abundant expression of Lmvasa and Lmdnd proteins in spermatogonia, weak expression in spermatocytes, and no expression in spermatozoa. In ovaries, both genes were expressed throughout oogenesis. Furthermore, PGCs in spotted sea bass belonged to an early localization pattern. Microinjection experiments demonstrated that Lmvasa 3′ UTR effectively labeled PGCs in embryos of spotted sea bass, zebrafish, and medaka. Conclusions: These findings may contribute to understanding PGC development in spotted sea bass and other Percidae.

Renal interstitial fibrosis, a condition prevalent in aging humans and animals, is closely linked to the eventual development of renal failure. Establishing an animal model that exactly replicates the pathogenesis of renal interstitial fibrosis induced by natural aging in humans is crucial for advancing mechanistic studies and testing antifibrotic therapies. Implanted allogeneic or xenogeneic cells are cleared by the immune system when stem cell therapy is applied in nonimmunodeficient animal fibrosis models, affecting the effect of the intervention and making it difficult to demonstrate the survival, proliferation, differentiation, or secretion of the delivered autologous human-derived cells. This study effectively developed a model of spontaneous renal interstitial fibrosis linked to natural aging in 43-week-old NOD/SCID mice. Compared with those of 12- and 32-week-old mice, the kidneys of the model mice exhibited prominent fibrosis characteristics, accompanied by numerous fibrous septa and collagen deposition, increased COL1A1 expression, and decreased MMP9 expression. SA-β-gal activity and P21 gene expression levels increased, confirming renal cell senescence in the model mice. Additionally, an increase in α-SMA staining indicated an increase in epithelial–mesenchymal transition. More importantly, we observed TGF-β-SMAD3 pathway activation, mitochondrial dysfunction, decreased antioxidant capacity, oxidative stress, and an enhanced inflammatory response in the model group, consistent with renal interstitial fibrosis in elderly individuals. In this comprehensive investigation, we successfully developed a spontaneous mouse model of renal interstitial fibrosis and revealed the molecular pathways contributing to increased susceptibility to kidney injury and renal fibrosis in elderly individuals.