ObjectiveTo investigate the effect of solute carrier family 7 member 5 (SLC7A5) inhibitor JPH203 on renal fibrosis induced by unilateral ureteral obstruction in mice. MethodsSixteen SPF male C57BL/6 mice were randomly divided into the control group and the experimental group, with 8 mice in each group. The mouse model of renal fibrosis was established by unilateral ureteral obstruction. From the third day after surgery, the mice in the control group were intraperitoneally injected with phosphate-buffered saline (PBS) for 11 consecutive days, and the injection dose was 200 μL/d. Mice in the experimental group received intraperitoneal injection of JPH203 (50 mg/kg) every day for 11 days. On day 14, the mice were euthanized, then the kidney tissues were obtained. Hematoxylin and eosin (HE) staining was used to assess renal tissue damage, Masson staining was used to evaluate collagen fiber deposition in the extracellular matrix, and immunohistochemistry was used to detect the levels of fibroblast activation markers α-smooth muscle actin (α-SMA) and collagen type Ⅰ (COL-Ⅰ) in kidney tissues. Western blotting was further performed to measure the expression levels of SLC7A5 and transforming growth factor-β1 (TGF-β1), as well as the phosphorylation levels of mammalian target of rapamycin complex 1 (mTORC1) signaling pathway-related molecules. Real-time quantitative PCR was used to verify changes in the mRNA levels of SLC7A5, α-SMA, and COL-Ⅰ in kidney tissues. ResultsCompared with the control group, the experimental group showed reduced destruction of renal tissue structure and a significantly lower pathological injury score (P<0.05). Additionally, collagen deposition in the extracellular matrix was decreased, and the percentage of collagen fiber area was significantly reduced (P<0.001) in the experimental group. The levels of fibroblast activation markers α-SMA and COL-Ⅰ were significantly lower in the experimental group (both P<0.001). The expression levels of SLC7A5 and TGF-β1 were also significantly decreased (P<0.001), and the phosphorylation levels of mTORC1 signaling pathway-related proteins 4E-BP1 and mTORC1 were significantly reduced (P<0.001). Real-time quantitative PCR confirmed that the mRNA levels of SLC7A5, α- SMA, and COL-Ⅰ in kidney tissues were significantly lower in the experimental group (P<0.001). ConclusionJPH203 may inhibit the progression of renal fibrosis in mice by suppressing SLC7A5 expression, regulating the mTORC1 signaling pathway, and altering fibroblast activation status.

Cancer stem cells (CSCs) represent a distinct subpopulation of cells characterized by self-renewal capacity, differentiation potential, and critical roles in driving tumor progression, therapeutic resistance, recurrence, and maintenance of the tumor microenvironment. Targeting CSCs has emerged as a pivotal direction in cancer research, offering novel strategies to overcome drug resistance and prevent metastasis and relapse. Lysosomes, traditionally recognized as central organelles for intracellular degradation and recycling, are indispensable for cellular homeostasis. Dysregulation of lysosomal function is intimately linked to various diseases, including cancer. In tumors, aberrant lysosomal activity can promote malignant progression through mechanisms such as altering metabolic pathways, enhancing lysosomal exocytosis, modulating drug resistance, and interfering with autophagy-lysosomal pathways. Recent studies have underscored the involvement of lysosomes in regulating CSC properties. This review synthesizes findings on lysosomal regulation of CSCs through the following aspects. (1) Lysosomes exert complex and critical bidirectional control over CSC stemness maintenance through three degradation pathways that are dependent on their degradative function. (i) The lysophagy pathway. This pathway exhibits dual roles. Activation can sustain CSC functions; for instance, in glioblastoma, hypoxia upregulates Gal-8 via the STAT3/HIF1α signaling axis to induce autophagy, supporting stem cell survival. In head and neck squamous cell carcinoma, degradation of GSK3β activates the Wnt pathway, enhancing stemness. Conversely, this pathway can suppress stemness by degrading stemness-related proteins such as BMI-1 and OCT4A, thereby impairing CSC self-renewal capacity. (ii) Mitophagy pathway. In non-small cell lung cancer stem cells, mitophagy-related mechanisms, such as the accumulation of mitochondrial DNA (mtDNA) activating the TLR9-Notch1-AMPK signaling axis, have been shown to promote CSC proliferation. (iii) Autophagosome-dependent lysosomal degradation pathway. This pathway directly regulates stemness-related proteins in a bidirectional manner. Enhanced degradative function can promote CSC properties, exemplified by the degradation of NUMB to activate Notch signaling. Conversely, attenuated degradative function can also enhance stemness by stabilizing oncoproteins (e.g., protecting Frizzled-1 from degradation to sustain Wnt signaling) or preventing the degradation of tumor suppressors (e.g., inhibiting Notch degradation). (2) Constituent proteins of lysosomes, including membrane proteins and luminal acid hydrolases, participate in regulating CSC stemness. Regarding membrane proteins, LAMP2A facilitates chaperone-mediated autophagy to maintain stemness in glioblastoma and ovarian cancer. V-ATPase, by maintaining an acidic luminal environment, promotes proliferation and drug resistance in glioma stem cells. Among hydrolases, cathepsins B and L are highly expressed in pancreatic and ovarian cancers and correlate with poor prognosis. Furthermore, targeting lysosomes to induce lysosomal membrane permeabilization (LMP) triggers lysosome-mediated cell death, presenting a potential therapeutic strategy for eradicating CSCs.(3) The acidic luminal environment, single-membrane structure, and the presence of transmembrane transporters (e.g., ABCA3) enable lysosomes to passively trap or actively uptake and sequester chemotherapeutic drugs. Subsequent drug extrusion via exocytosis confers drug resistance. In CSCs, this lysosome-mediated drug sequestration, often cooperating with autophagy, establishes multimodal drug resistance. Therefore, targeting lysosomal function represents a potential strategy to overcome therapy resistance. The central role of lysosomes in regulating CSC stemness and resistance positions them as highly promising therapeutic targets. Strategies aimed at disrupting lysosomal function to selectively eliminate CSCs include: inhibiting the lysosome-autophagy system using agents like IITZ or lovastatin; inducing lysosomal membrane permeabilization (LMP) with compounds such as hexamethylene amiloride to compromise membrane stability; and disrupting the acidic luminal environment using drugs like siramesine or the K/H transport compound 2. In conclusion, lysosomes critically regulate CSC stemness maintenance and drug resistance through degradative pathways, membrane protein functions, luminal hydrolase activities, and drug sequestration mechanisms. This redefines the lysosome from a traditional “waste disposal unit” to a “signal integration center” in CSCs. The duality and context-dependency of lysosomal function in CSCs offer novel insights into the heterogeneity observed across different tumors. Targeting lysosomal vulnerabilities—such as inducing LMP, disrupting acidity, or blocking autophagic flux—provides a strategy to bypass canonical CSC resistance mechanisms and directly trigger cell death. This establishes the lysosome as a key target to overcome CSC-mediated therapy resistance, paving the way for developing diverse candidate drugs and innovative combination therapies in oncology.

Objective To understand mosquito density, species composition, and seasonal variations around the Beijing Capital International Airport(BCIA)and provide scientific evidence for mosquito-borne disease prevention and control. Methods Meteorological data were collected from 2016 to 2022, and mosquito density was monitored at seven surveillance sites around the BCIA from May to October each year using CO2-baited mosquito traps to analyze the relationship between mosquito density and meteorological factors. Results In total,68 518 female mosquitoes were captured, with a mosquito density of 10.20 per light · hour. The dominant species was Culex pipiens pallens(73.90%), followed by Aedes albopictus(9.71%)and Ae. vexans(9.29%);the mosquito density was highest in 2016(14.8 per light·hour)and lowest in 2022(4.46 per light·hour). Significant statistical differences were observed in mosquito density among different species(F=18.118, P<0.05). The density of Cx. pipiens pallens and other mosquito species showed a mutually exclusive trend; the peak of mosquito density varied based on years and habitats, with significant statistical differences in mosquito density among different habitats(F=8.504, P<0.05). The highest mosquito density was observed near the Wenyu River(21.50 per light·hour), whereas the lowest was recorded at the BCIA construction site(2.44 per light· hour). The monthly average temperature(r=0.595), monthly average highest temperature(r=0.575), and monthly average lowest temperature(r=0.624)showed moderate positive correlations, whereas the monthly average air pressure(r=-0.484)showed a moderate negative correlation. The monthly average minimum temperature was included in the regression model(F=25.575, P<0.000), and the equation Y=1.029X4-8.181 was used. The monthly average air pressure 2 months prior(b=-2.418, β=-1.619, P<0.05)and the monthly average relative humidity(b=-0.739, β=-1.201, P<0.05)significantly negatively predicted the mosquito density. Notably, the regression equation used was y=2526.170+(-2.418)X9+(-0.739)X13. The exposure-response analysis revealed that the density of mosquitoes was not linearly related to the average monthly air pressure, rainfall, and duration of sunshine. Conclusions The dominant mosquito species around the BCIA was Cx. pipiens pallens, Ae. albopictus, and Ae. vexans. During the control of Cx. pipiens pallens, the impact on other mosquito species must also be considered. Environmental management, breeding sites, and scientific use of pesticides should be prioritized based on the activity periods of mosquitoes. Further studies on mosquitoes and meteorological factors should be conducted to provide references and novel avenues for mosquito control.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is higher among individuals with inflammatory bowel disease (IBD) than in the general population. Emerging evidence indicates that the development of MASLD in patients with IBD may occur independently of traditional metabolic risk factors, suggesting a unique pathophysiological mechanism distinct from conventional MASLD pathways. Bile acids (BAs), which act as critical signaling molecules in enterohepatic circulation, play an essential role in maintaining gastrointestinal homeostasis through bidirectional gut–liver axis communication. These molecules are increasingly recognized as pivotal regulators in the progression of both MASLD and IBD. While previous studies have characterized the dynamics of BA in blood or fecal samples under both conditions, a comprehensive understanding of their metabolic profiles and the associated interactions within the gut–liver axis is still lacking. This review synthesizes current evidence from studies employing BA metabolomics to investigate IBD and MASLD. By focusing on BA signatures, we summarize conserved alterations between these two conditions and their potential mechanisms of disease progression. Our review advances understanding of BA-mediated pathways in IBD and MASLD, providing a foundation for assessing their roles in contributing to the pathogenesis of MASLD in patients with IBD.

There is a substantial unmet need for treatments in the field of pediatric rare diseases, and investigator initiated trial(IIT) provide a critical pathway for testing and developing new drugs or treatment strategies. However, healthcare institutions, when conducting such research, must address compliance risks related to project approval, contract management, data protection, and conflict of interest management. This study aims to analyze the particularities and challenges of IIT in pediatric rare diseases, review relevant regulations and regulatory requirements, and provide healthcare institutions with a reference framework for compliance risk management to maximize the benefits of IIT. Based on literature review, analysis of laws and regulations, practical work experience, and frameworks from other institutions, we summarize the unique aspects of pediatric rare disease IIT in terms of participant characteristics, innovative technologies, and organizational structures.On this basis, targeted compliance management recommendations are proposed, which include establishing a risk rating and full-cycle risk monitoring mechanism, a consent and ethical review mechanism tailored to pediatric participants, a robust contract management mechanism, a comprehensive data security management mechanism, and a multidisciplinary team and multi-channel compensation mechanism. The study concludes that healthcare institutions, funders, and other collaborating entities should implement compliance management in line with the characteristics of IIT to ensure the safety and effectiveness of research and facilitate innovation and development in the treatment of pediatric rare diseases.

Objective To explore the efficacy and mechanism of the aqueous extract of Sauropus spatulifolius in treating constipation based on network pharmacology analysis and experiments.Meth-ods Network pharmacology analysis was conducted using an online platform to investigate the molec-ular mechanism of Sauropus spatulifolius in treating constipation.Loperamide-induced mouse consti-pation models and intestinal epithelial cell(IEC)injury models were constructed.Therapeutic effects were evaluated using indicators such as the time to the first black stool,fecal water content,and gas-trointestinal transit rate.Annexin V-FITC staining was used to assess apoptosis,JC-1 staining was used to detect mitochondrial membrane potential,chemiluminescence was used to measure adenosine triphosphate(ATP)levels,and western blotting was used to detect the expression of relevant proteins.Results Network pharmacology analysis revealed that 29 active components in Sauropus spatulifolius targeted 19 genes associated with constipation,with AKT1 identified as one of the key genes.Exper-imental results demonstrated that the aqueous extract of Sauropus spatulifolius effectively alleviated loperamide-induced constipation symptoms in mice,including weight loss,reduced intestinal motili-ty,prolonged defecation time,and decreased fecal water content.Additionally,the aqueous extract of Sauropus spatulifolius inhibited IEC-6 cell apoptosis,restored mitochondrial membrane potential,and maintained intracellular ATP levels.The therapeutic mechanism involved downregulating the ex-pression of Bel-2-associated X protein(Bax),cytochrome C,Cleaved-Caspase3,and aquaporin 3(AQP3),as well as enhancing protein kinase B(Akt)phosphorylation.Conclusion The aque-ous extract of Sauropus spatulifolius effectively ameliorates constipation symptoms in mouse models,and its mechanism may be related to improving intestinal cell energy metabolism,inhibiting IEC ap-optosis,and reducing AQP3 expression,suggesting that Sauropus spatulifolius could serve as a po-tential drug for the clinical treatment of constipation.

RNA methylation is a key process in the epigenetic regulation of post-transcriptional gene expression.5-Methylcytosine(m⁵C)is a type of RNA methylation,commonly existing in eukaryotic mRNA and non-coding RNAs.It mainly regulates transfer RNA stability,ribosomal RNA assembly,and mRNA translation,stability,and translation.RNA methylation is dynamically reversible and regulated by methyltransferase,demethylase,and methylation recognition protein.It has been confirmed that aberrant m⁵C RNA methylation is involved in the pathogenesis of non-neoplastic kidney diseases.This article summarizes the current progress of m⁵C RNA methylation associated with non-neoplastic acute and chronic kidney diseases,aiming to provide potential targets for the diagnosis and treatment of such diseases.
Humans ; Methylation ; 5-Methylcytosine/metabolism* ; Kidney Diseases/metabolism* ; Epigenesis, Genetic ; RNA Methylation

Depressive disorder is a kind of mental disorder characterized by persistent and significant depressed mood, with complex etiology and high recurrence rate. At present, more precise and effective diagnostic and therapeutic approaches are still required. Increasing evidence suggests that hypoxia inducible factor-1 (HIF-1) and related pathways are involved in regulating the development and recovery of depression. HIF-1 enhances neuroplasticity, mitigates neuroinflammatory responses, alleviates oxidative stress, and modulates brain energy metabolism by influencing specific molecules associated with depression. This paper reviews pertinent domestic and international studies, examine the potential mechanisms of HIF-1 in the pathogenesis and progression of depression, and explore antidepressant treatment strategies targeting the HIF-1 signaling pathway. This article provides novel insights into elucidating the pathogenesis of depression and developing innovative therapeutic approaches.

Objective To compare the quality of liquids dispensed by intelligent dispensing robot and traditional manual in PIVAS,to ensure the safety of clinical infusion.Methods Using omeprazole and ambroxol as the main drugs and 5％glucose injection and 0.9％sodium chloride solution as the solvent,a number of quality indexes including drug residues and the number of insoluble particles were evaluated in the two modes of manual and robotic dispensing,respectively.Results Under the robot dispensing mode and manual dispensing mode,the residual amount of drugs was less than 5％,the insoluble particles were far less than the limit,the pH value was in line with the human infusion range,and the endotoxin and aseptic culture were negative results,with no statistical significance(P＞0.05).Conclusions The quality of liquid dispensed under the robotic dispensing mode is guaranteed,and there is no significant difference in the quality of liquid dispensed with the traditional manual dispensing mode,which provides a reliable guarantee for the large-scale application of robotic dispensing in intravenous admixture service.