Jiehua Ma

Aims: Senile vaginitis is a common clinical condition with limited treatment options. Estrogen deficiency leads to atrophy of the vaginal walls and thinning of the mucosa. It is noteworthy that although vaginal atrophy is an almost universal consequence of menopause, many postmenopausal women do not develop genitourinary symptoms. These observations collectively indicate that estrogen-independent pathogenic mechanisms are involved. In our preliminary study, through metabolomic screening, we identified three functionally relevant metabolites, namely guggulsterone (GS), umbelliprenin, and inosinic acid. This study seeks to elucidate the pathogenic mechanism of GS in senile vaginitis and to unveil novel therapeutic avenues for this condition. Results: Cellular and animal experiments confirm that GS elevates intracellular ferrous iron (Fe ²⁺ ), malondialdehyde, and reactive oxygen species levels in vaginal epithelial cells, thereby inducing ferroptosis and upregulating the expression of inflammatory factors in vaginal tissues. Consequently, these processes compromise vaginal mucosal integrity, thereby exacerbating epithelial atrophy and the progression of inflammation. Treatment with the ferroptosis inhibitor ferrostatin-1 partially reversed the accumulation of Fe ²⁺ , lipid peroxides, and cellular oxidative stress. By utilizing a combination of lipidomic mass spectrometry, molecular docking, and surface plasmon resonance, it was collectively demonstrated that GS directly binds to heme oxygenase 1 (HMOX1). Utilizing VK2/E6E7 cell models with lentivirus-mediated HMOX1 knockdown and overexpression, this study demonstrates that GS might contribute to ferroptosis in vaginal epithelial cells by upregulating HMOX1 expression. Notably, treatment with MG132 potentiated the GS-induced upregulation of HMOX1, whereas the autophagy-lysosome inhibitor bafilomycin A1 had no significant effect. These findings suggest that GS may upregulate HMOX1 levels by inhibiting its degradation through the proteasome pathway. Innovation and Conclusion: Collectively, these findings establish GS as a critical regulator of vaginal epithelial cell ferroptosis through HMOX1 targeting, revealing new therapeutic avenues for senile vaginitis. Antioxid. Redox Signal. 45, 618–635.

Macrophages use pattern recognition receptors (PRRs) to recognize, capture, and phagocytize pathogens. Recreating artificial systems to mimic such receptors for manipulating macrophage predation is both scientifically exciting and technologically relevant to anti-infection. Nevertheless, fabricating synthetic PRR-mimicking receptors with a predictable and stable structure remains a challenge. Herein, we use circular aptamers as building blocks to create artificial DNA receptors (ADRs) that mimic the function of PRRs. After modification of ADRs on macrophages, they can stably recognize specific pathogens and promote the phagocytosis of macrophages, akin to natural PRRs. As dynamic structures, these ADRs can be flexibly activated or inactivated by external DNA molecules, akin to protein receptors responding to small-molecule ligands. Owing to the programmability of the DNA reaction, Boolean logic operations can be introduced to logically manipulate the predation behavior of macrophages, exhibiting the characteristics of artificial receptors. Furthermore, ADRs can be integrated with other functional DNA motifs, e.g., CpG DNA, to enhance the activation and antibacterial capacity of macrophages with higher efficiency. Overall, we believe that this artificial receptor not only broadens the application of DNA nanotechnology in cell biology but also contributes to ongoing efforts to remodel the innate immune system for fighting infection in consideration of the growing emergence of multidrug-resistant bacteria.

Aerobic vaginitis (AV) is a long-standing inflammatory disease that affects female patients. The use of antibiotics is a common means for AV treatment, but it will indiscriminately kill both pathogenic bacteria and beneficial strains, which easily causes vaginal dysbacteriosis and infection recurrence. Herein, we describe a bioinspired strategy for fabricating gelated cell sheet–supported lactobacillus biofilms (GCS-LBs) for AV treatment. Compared with common planktonic probiotic formulations, probiotic biofilms forming on a robust GCS exhibit enhanced stress tolerance and better colonization capacity in the mouse vagina. Moreover, DNA nanodevices are decorated on the GCS and dynamically report the microenvironment change of biofilms for timely evaluating bacterium activity, both in vitro and in vivo. Consequently, GCS-LBs are used for treating AV in an Escherichia coli –infected mouse model, which shows enhanced therapeutic efficacy compared with conventional antibiotic or lactobacillus monotherapy. Overall, the GCS-LB shows promise as a potent multifunctional tool to combat bacterial infection.

The ion channels in sperm tail play an important role in triggering key physiological reactions, e.g., progressive motility, hyperactivation, required for successful fertilization. Among them, CatSper and KSper have been shown to be important ion channels for the transport of Ca ²⁺ and K ⁺ . Moreover, the voltage‐gated proton channel Hv1, the sperm‐specific sodium‐hydrogen exchanger (sNHE), the epithelial sodium channel (ENaC), members of the temperature‐sensitive TRP channel family, and the cystic fibrosis transmembrane regulator (CFTR) are also found in the flagellum. This review focuses on the latest advances in ion channels located at the flagellum, describes how they affect sperm physiological function, and summarizes some primary mutual regulation mechanism between ion channels, including PH, membrane potential, and cAMP. These ion channels may be promising targets for clinical application in infertility.

CRISPR/Cas-based systems are highly attractive for developing next-generation diagnostic technologies because of their intrinsic merits such as simplicity, sensitivity, and specificity. However, currently, nucleic acid amplification procedures are still needed to achieve attomolar sensitivity in most CRISPR/Cas-based assays, which causes high cost, operation difficulty, and low efficiency. Herein, we combine the CRISPR/Cas12a-based assay and a single-microbead detection platform for one-step and amplification-free detection of DNA at the single-molecule level. By modifying DNA reporters on a biomimetic membrane-coated microbead, the activated Cas12a by targets will cleave these reporters and lighten the bead within 10 min. The method allows the detection of the target down to three copies in a 5 μL sample. Furthermore, we successfully apply this method for the specific identification of viral infection, foodborne bacteria, and DNA mutation in real samples without extra nucleic acid amplification. We believe that this approach offers new insights for developing CRISPR/Cas-based DNA assays in biomedical applications.

Background Vaginal lubrication is a crucial physiological response that occurs at the beginning of sexual arousal. However, research on lubrication disorders (LD) is still in its infancy, and the role of long non-coding RNAs (lncRNAs) in LD remains unclear. This study aimed to explore the function of lncRNAs in the pathogenesis of vaginal LD. Methods The expression profiles of LD and normal control (NC) lncRNAs were examined using next-generation sequencing (NGS), and eight selected differentially expressed lncRNAs were verified by quantitative real-time PCR. We conducted GO annotation and KEGG pathway enrichment analyses to determine the principal functions of significantly deregulated genes. LncRNA-mRNA co-expression and protein-protein interaction (PPI) networks were constructed and the lncRNA transcription factors (TFs) were predicted. Results From the results, we identified 181,631 lncRNAs and 145,224 mRNAs in vaginal epithelial tissue. Subsequently, our preliminary judgment revealed a total of 499 up-regulated and 337 down-regulated lncRNAs in LD. The top three enriched GO items of the dysregulated lncRNAs included the following significant terms: “contractile fiber part,” “actin filament-based process,” and “contractile fiber”. The most enriched pathways were “cell-extracellular matrix interactions,” “muscle contraction,” “cell-cell communication,” and “cGMP-PKG signaling pathway”. Our results also showed that the lncRNA-mRNA co-expression network was a powerful platform for predicting lncRNA functions. We determined the three hub genes, ADCY5, CXCL12, and NMU, using PPI network construction and analysis. A total of 231 TFs were predicted with RHOXF1, SNAI2, ZNF354C and TBX15 were suspected to be involved in the mechanism of LD. Conclusion In this study, we constructed the lncRNA-mRNA co-expression network, predicted the lncRNA TFs, and comprehensively analyzed lncRNA expression profiles in LD, providing a basis for future studies on LD clinical biomarkers and therapeutic targets. Further research is also needed to fully determine lncRNA’s role in LD development.