Quaternary ammonium grafted chitosan hydrogel with enhanced antibacterial performance as tannin acid and deferoxamine carrier to promote diabetic wound healing.

The delay of diabetic wound healing puts a huge burden on the society. The key factors hindering wound healing include bacterial infection, unresolved inflammation and poorly generated blood vessels. In this paper, glycidyl trimethyl ammonium chloride (GTA) was grafted to chitosan (CS) to obtain quaternary ammonium grafted chitosan (QCS) with enhanced antibacterial performance, and then cross-linked by dialdehyde terminated poly(ethylene oxide) (PEO DA) to construct QCS/PEO DA hydrogel with tissue adhesion, biodegradation and self-healing properties. The QCS/PEO DA hydrogel is loaded with tannin acid (TA) and deferoxamine (DFO) to enhance antioxidant property and angiogenesis. At the same time, the TA and DFO loaded TA@DFO/hydrogel preserved the biocompatibility and biodegradability of chitosan. Moreover, the multifunctional hydrogel behaved excellent hemostatic properties in mice model and significantly promoted the healing efficacy of diabetic wounds. Overall, the TA@DFO/hydrogel is promising anti-infection dressing material for diabetic wound healing.

Antisense Oligonucleotide Therapy for Calmodulinopathy.

BACKGROUND: Calmodulinopathies are rare inherited arrhythmia syndromes caused by dominant heterozygous variants in CALM1, CALM2, or CALM3, which each encode the identical CaM (calmodulin) protein. We hypothesized that antisense oligonucleotide (ASO)-mediated depletion of an affected calmodulin gene would ameliorate disease manifestations, whereas the other 2 calmodulin genes would preserve CaM level and function. METHODS: We tested this hypothesis using human induced pluripotent stem cell-derived cardiomyocyte and mouse models of CALM1 pathogenic variants. RESULTS: Human CALM1F142L/+ induced pluripotent stem cell-derived cardiomyocytes exhibited prolonged action potentials, modeling congenital long QT syndrome. CALM1 knockout or CALM1-depleting ASOs did not alter CaM protein level and normalized repolarization duration of CALM1F142L/+ induced pluripotent stem cell-derived cardiomyocytes. Similarly, an ASO targeting murine Calm1 depleted Calm1 transcript without affecting CaM protein level. This ASO alleviated drug-induced bidirectional ventricular tachycardia in CalmN98S/+ mice without a deleterious effect on cardiac electrical or contractile function. CONCLUSIONS: These results provide proof of concept that ASOs targeting individual calmodulin genes are potentially effective and safe therapies for calmodulinopathies.

Changes in gender disparities of depressive symptoms among middle-aged and older adults in China: an age-period-cohort analysis.

PURPOSE: Depression is one of the most common mental disorders and substantially decreases socioemotional well-being and health-related quality of life. Analyzing temporal patterns in depressive symptoms can reveal emerging risks that require attention and have implications for mental health promotion. The present study disentangled age, period, and cohort (APC) effects on trends in depressive symptoms and their gender disparities among China's nationally representative samples of middle-aged and older adults. METHODS: Using four-wave data (2011, 2013, 2015, and 2018) from the China Health and Retirement Longitudinal Study (N = 65455), APC effects were quantified based on the hierarchical APC model. The 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10) was used to measure depressive symptoms. RESULTS: Depressive symptoms increased during late life and stabilized after reaching an advanced age. After further adjusting for individual characteristics, depressive symptoms exhibited a negative trend with advancing age. The mean levels of depressive symptoms remained stable during the study period. Depressive symptoms varied significantly across cohorts, with those born in 1949-1951 having the most severe depressive symptoms. Significant life-course and cohort variations existed in the gender gaps in depressive symptoms. Although women had higher mean scores on the CES-D-10 scale throughout the life course, the gender gaps in depressive symptoms gradually narrowed with age, as depressive symptoms decreased more rapidly among women. A widening trend in gender gaps in depressive symptoms was found among those born after the mid-1950s, mainly driven by a notable decline in depressive symptoms among men CONCLUSIONS: The convergence of living conditions between genders in late life, as a result of traditional Chinese culture, may have narrowed the gender gap in depressive symptoms. However, given the widening gender disparities in depressive symptoms among younger cohorts, more attention should be paid to women's mental health in the context of China's rapid socioeconomic development.

Production of Jet Fuel Range Aromatics by Alkylation of Benzene with Olefins over Bifunctional Ga/ZSM-5 Catalyst.

Aromatic components of C8-C15 are playing indispensable roles in multi-functional properties of jet fuel. Here, we reported the controllable alkylation of benzene with mixed olefins of ethylene and propylene toward C8-C15 aromatic hydrocarbons for jet fuels over the bifunctional Ga/ZSM-5 catalyst. The resultant 2Ga/ZSM-5 exhibited a superior selectivity of 86.4% (yield of 55.5%) to C8-C15 range aromatics, at benzene conversion of 40.3%, ethylene and propylene conversion of 99.5% and 99.2%, respectively. The incorporation of Ga species could effectively weaken the strong acid sites of ZSM-5 and endow 2Ga/ZSM-5 catalyst with appropriate acidity, therefore facilitating the benzene alkylation process and suppressing the undesired hydrogen transfer or aromatization side reactions as well, thus improving the yield of desired C8-C15aromatics for jet fuels. This work provided insight into the development of promising bifunctional catalyst for the oriented transformation of biomass-derived chemicals to aviation fuels.

The low-entropy hydration shell mediated ice-binding mechanism of antifreeze proteins.

Antifreeze proteins (AFPs) can inhibit ice crystal growth. The ice-binding mechanism of AFPs remains unclear, yet the hydration shells of AFPs are thought to play an important role in modulating the binding of AFPs and ice. Here, we performed all-atom molecular dynamics simulations of an AFP from Choristoneura fumiferana (CfAFP) at four different temperatures, with a focus on analysis at 240 and 300 K, to investigate the dynamic and thermodynamic characteristics of hydration shells around ice-binding surfaces (IBS) and non-ice-binding surfaces (NIBS). Our results revealed that the dynamics of CfAFP hydration shells were highly heterogeneous, with its IBS favoring a less dense and more tetrahedral solvation shell, and NIBS hydration shells having opposite features to those of the IBS. The IBS of nine typical hyperactive AFPs were found to be in pure low-entropy hydration shell region, indicating that low-entropy hydration shell region of IBS and the tetrahedral arrangements of water molecules around them mediate the ice-binding mechanism of AFPs. It is because the entropy increase of the low-entropy hydration shell around IBS, while the higher entropy water molecules at NIBS most likely prevent ice crystal growth. These findings provide new mechanistic insights into the ice-binding of AFPs.

Ursolic acid, an inhibitor of TMEM16A, co-loaded with cisplatin in hydrogel drug delivery system for multi-targeted therapy of lung cancer.

The efficacy of single chemotherapy drugs in cancer treatment is often limited. Combining administration targeting multiple targets has emerged as an effective strategy to improve cancer treatment. Ursolic acid, a triterpenoid compound in various natural foods, was identified as a novel inhibitor of lung cancer specific target TMEM16A. The IC50 of ursolic acid on the whole-cell current of TMEM16A was 13.85 ± 1.64 µM. Molecular dynamics simulations and site-directed mutagenesis experiments indicated the binding sites of ursolic acid on TMEM16A as L381, R535, E623, and C625. Ursolic acid significantly inhibited the proliferation and migration of LA795 cells, while promoting cancer cell apoptosis. Mechanistic studies revealed that ursolic acid inhibited lung cancer through the MAPK and EMT pathways, and induced DNA and membrane damage. Next, a degradable and self-repairing hydrogel drug-loading system was designed to enhance the targeting effect of the ursolic acid and cisplatin drug combination. In vivo experiments showed that the hydrogel-loaded ursolic acid and cisplatin enhanced the antitumor activity and reduced the toxicity. This study presents a novel approach of multi-target combination therapy using ursolic acid and cisplatin, combined with the targeted delivery capability of the hydrogel system, which significantly improves the therapeutic efficacy in lung cancer.

A novel "turn-on" NIR fluorescent probe based on benzothianone for the detection of palladium species and its application in cell and zebrafish.

The development of an efficient palladium probe holds significant application value, considering the detrimental impact of palladium contaminants on human health. Thus, it is critical to create a sensitive detection method. To this end, a fluorescent probe TM-TPA-Pd based on benzothianone structure was designed, using allyl carbonate as the Pd0 recognition unit. TM-TPA-Pd exhibited high sensitivity (1.4 eq), selectivity, near-infrared (NIR) fluorescence (798 nm), and low detection limit (0.46 µM) for Pd0 with a rapid "turn-on" fluorescence signal (5 min). Furthermore, TM-TPA-Pd has extremely low cytotoxicity and has been successfully applied to detecting cells and zebrafish, which has great potential for palladium detection in biological systems.

A Multi-State Model Study of the Disability-Free Life Expectancy Among Older Adults with Chronic Multimorbidity Based on CHARLS - China, 2011-2020.

What is already known about this topic?: Chronic disease multimorbidity is prevalent among older Chinese people, seriously affecting their well-being and quality of life. What is added by this report?: This study estimated the impact of multimorbidity on the risk of health state transitions and health expectancy among older adults in China. It used population-representative, long-term longitudinal data and multi-state Markov modeling along with microsimulation methods. What are the implications for public health practice?: The study results suggest that the Chinese government should strengthen the prevention and management of multimorbidity and accelerate the transition from chronic disease management to multimorbidity management.

Study on the recovery of bladder function in patients with cervical cancer after operation by portable ultrasound combined.

BACKGROUND: Postoperative urination dysfunction is a common complication after surgery in patients with cervical cancer. Portable bladder ultrasound are commonly utilized in clinical practice for measuring residual urine volume. This study aimed to the effect of bladder function training combined with portable ultrasound monitoring on bladder function recovery in patients with cervical cancer after training. METHODS: A total of 40 postoperative patients with cervical cancer were randomly divided into a control group (A) and an experimental group (B) of 20 cases each. Group A was given routine postoperative care, while group B was given bladder function training. Urgent urine bladder volume were taken twice daily after removal of the urinary catheter and monitored for five consecutive days. The difference of urgent urine bladder volume and bladder filling rate were compared by t-test and chi-square test respectively. The 36-item Short Form Health Survey (SF-36) was used to evaluate the quality of life of patients before and after intervention, and compared by Mann-Whitney U test. RESULTS: There was no significant difference in preoperative urgent urine volume between the two groups. After catheter removal, the bladder volume of patients in the B increased, while the bladder volume of patients in the A increased less and fluctuated greatly. The bladder filling rate in the A was significantly lower than that in the B (5/15 vs 17/18, p < 0.05). After intervention, the quality of life of the experimental group was better than that of the control group, including scores of general health, mental health, vitality, and physical role (p < 0.05). CONCLUSION: Postoperative cervical cancer patients trained to hold urine by portable ultrasound monitoring are able to recover bladder function.

Alleviating effect of chlorogenic acid on oxidative damage caused by hydrogen peroxide in bovine intestinal epithelial cells.

Chlorogenic acid (CGA) is a polyphenol substance contained in many plants, which has good antioxidant activity. This experiment aimed to explore the protective effects of CGA on hydrogen peroxide(H2O2)-induced inflammatory response, apoptosis, and antioxidant capacity of bovine intestinal epithelial cells (BIECs-21) under oxidative stress and its mechanism. The results showed that compared with cells treated with H2O2 alone, CGA pretreatment could improve the viability of BIECs-21. Importantly, Chlorogenic acid pretreatment significantly reduced the formation of malondialdehyde (MDA), lowered reactive oxygen species (ROS) levels, and enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) (P<0.05). In addition, CGA can also improve the intestinal barrier by increasing the abundance of tight junction proteins claudin-1 and occuludin. Meanwhile, CGA can reduce the gene expression levels of pro-inflammatory factors Interleukin-6 (IL-6) and Interleukin-8 (IL-8), increase the expression of anti-inflammatory factor Interleukin-10 (IL-10), promote the expression of the nuclear factor-related factor 2 (Nrf2) signaling pathway, enhance cell antioxidant capacity, and inhibit Nuclear Factor Kappa B (NF-κB) the activation of the signaling pathway reducing the inflammatory response, thereby alleviating inflammation and oxidative stress damage.

Structural and theoretical basis for drug development targeting TMEM16A: Inhibition mechanism of tracheloside analogs.

Ion channels play a crucial role in the electrophysiological activities of organisms. The calcium-activated chloride channel TMEM16A is involved in various physiological processes. Therefore, inhibitors of TMEM16A are used to treat diseases caused by TMEM16A dysfunction. However, the unclear inhibition mechanism hinders the progress of drug development. Based on our previous study, we found that the molecular structures of TMEM16A inhibitors tracheloside, matairesinoside and arctigenin are similar. In this study, we conducted a structure-based virtual screening of tracheloside analogs from the PubChem database. The six tracheloside analogs with the highest affinity to TMEM16A were selected, and their inhibitory effects were detected by fluorescence and electrophysiological experiments. Subsequently, the interaction between the tracheloside analogs and TMEM16A was investigated through molecular docking and site-directed mutagenesis. Based on the above results, the mechanism of inhibition of TMEM16A gated conformation by tracheloside analogs was proposed. These findings provide a structural and theoretical basis for drug development targeting TMEM16A.

Comparative transcriptome analysis reveals the different responding mechanisms of ovary and hepatopancreas following polyI:C challenge in Macrobrachium nipponense.

The ovary in mammals has developed specialized mechanisms for protection against pathogen infections; however, the understanding of the innate immune system in the ovary of crustaceans is still limited. To elucidate the ovary's defense mechanisms in response to viral challenges, we subjected oriental river prawns (Macrobrachium nipponense) to poly I:C, a double-stranded RNA analog that emulates viral dsRNA, and analyzed the ovary's transcriptome profiles. Concurrently, RNA-seq analysis was performed on the hepatopancreas, a well-recognized immune-related tissue, following poly I:C challenge to investigate the distinct response mechanisms of the ovary and hepatopancreas and to gain a comprehensive understanding of the immune responses in both tissues. The results indicate that 1368 genes are differentially expressed in the ovary, with 903 genes upregulated and 465 genes downregulated. Subsequent analysis reveals that these differentially expressed genes (DEGs) include numerous genes associated with innate immunity, such as members of the C-type lectin, fibrinogen-related protein (Frep), Toll-like receptor, and NOD-like receptor (NLR) gene families, as well as acid phosphatase, scavenger receptor, crustin, Down syndrome cell adhesion molecule (Dscam), hemocyanin, and lipopolysaccharide and beta-1,3-glucan binding protein (LGBP). Furthermore, the DEGs include several genes related to ovary development, such as sox8, vitellogenin, progranulin, cyclin-dependent kinase, ecdysone receptor, frizzled, and members of the Fox gene family. In the hepatopancreas, a total of 729 DEGs were identified. Comparison of the DEGs in both tissues indicates that only 91 genes are common to both groups, highlighting significant tissue-specific responses to poly I:C stimulation. This study aims to enhance our understanding of the immune protective mechanisms employed by the ovary in response to pathogen exposure and establishes a foundation for investigating ovarian reproductive immunity in crustaceans.

Lower serum LDL-C levels are associated with poor prognosis in severe fever with thrombocytopenia syndrome: a single-center retrospective cohort study.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease triggered by a novel bunyavirus (SFTSV). Characterized by fever, thrombocytopenia, leukocytopenia, and multiple organ dysfunction manifestations, its primary mode of transmission is through tick bites. Despite the critical role of lipid metabolism in viral infections, the role of lipids in SFTS remains unclear. Methods: This retrospective study analyzed 602 patients with SFTS treated at the Shandong Public Health Clinical Center from January 2021 to December 2023. Based on the endpoint events, patients were classified into survival (S) and death (D) groups. The S group was further classified into non-critical (non-C) and critical (C) groups based on symptoms. All patients were followed up for at least 28 days after admission. Propensity score matching, multivariable logistic regression, survival analysis, time trend analysis, and mediation analysis were conducted to assess the association between LDL-C levels and prognosis in SFTS. Results: The serum LDL-C levels on admission were significantly lower in the D and C groups than in the S and non-C groups. The logistic regression models indicated a potential association between LDL-C levels and a poor prognosis in SFTS. The restricted cubic spline showed a unidirectional trend between LDL-C levels and mortality, with a cutoff value of 1.59 mmol/L. The survival analysis revealed higher and earlier mortality in the low-LDL-C group than in the high-LDL-C group. The trends over 28 days post-admission showed that the serum LDL-C levels gradually increased in SFTS, with a favorable prognosis. Finally, the mediation analysis indicated that low LDL-C levels are associated with mortality through poor hepatic, cardiac, and coagulation functions. Conclusion: Low LDL-C levels are potentially associated with a poor prognosis in SFTS.

Pan-cancer subclonal mutation analysis of 7,827 tumors predicts clinical outcome.

Intra-tumor heterogeneity is an important driver of tumor evolution and therapy response. Advances in precision cancer treatment will require understanding of mutation clonality and subclonal architecture. Currently the slow computational speed of subclonal reconstruction hinders large cohort studies. To overcome this bottleneck, we developed Clonal structure identification through Pairwise Penalization, or CliPP, which clusters subclonal mutations using a regularized likelihood model. CliPP reliably processed whole-genome and whole-exome sequencing data from over 12,000 tumor samples within 24 hours, thus enabling large-scale downstream association analyses between subclonal structures and clinical outcomes. Through a pan-cancer investigation of 7,827 tumors from 32 cancer types, we found that high subclonal mutational load (sML), a measure of latency time in tumor evolution, was significantly associated with better patient outcomes in 16 cancer types with low to moderate tumor mutation burden (TMB). In a cohort of prostate cancer patients participating in an immunotherapy clinical trial, high sML was indicative of favorable response to immune checkpoint blockade. This comprehensive study using CliPP underscores sML as a key feature of cancer. sML may be essential for linking mutation dynamics with immunotherapy response in the large population of non-high TMB cancers.

Atavistic strategy for the treatment of hyperuricemia via ionizable liposomal mRNA.

Hyperuricemia is associated with an increased risk of gout, hypertension, diabetes, and cardiovascular diseases. Most mammals maintain normal serum uric acid (SUA) via urate oxidase (Uox), an enzyme that metabolizes poorly-soluble UA to highly-soluble allantoin. In contrast, Uox became a pseudogene in humans and apes over the long course of evolution. Here we demonstrate an atavistic strategy for treating hyperuricemia based on endogenous expression of Uox in hepatocytes mediated by mRNA (mUox) loaded with an ionizable lipid nanoparticle termed iLAND. mUox@iLAND allows effective transfection and protein expression in vitro. A single dose of mUox@iLAND lowers SUA levels for several weeks in two female murine models, including a novel long-lasting model, which is also confirmed by metabolomics analysis. Together with the excellent safety profiles observed in vivo, the proposed mRNA agent demonstrates substantial potential for hyperuricemia therapy and the prevention of associated conditions.

Exploring the potential of cryptochlorogenic acid as a dietary adjuvant for multi-target combined lung cancer treatment.

BACKGROUND: Lung cancer is a highly malignant disease with limited treatment options and significant adverse effects. It is urgent to develop novel treatment strategies for lung cancer. In recent years, TMEM16A has been confirmed as a specific drug target for lung cancer. The development of TMEM16A-targeting drugs and combined administration for the treatment of lung cancer has become a research hotspot. METHODS: Fluorescence screening and electrophysiological experiments were conducted to confirm the inhibitory effect of CCA on TMEM16A. Molecular dynamics simulation and site-directed mutagenesis were employed to analyze the binding mode of CCA and TMEM16A. CCK-8, colony formation, wound healing, transwell, and annexin-V experiments were conducted to explore the regulatory effects and mechanisms of CCA on the proliferation, migration, and apoptosis of lung cancer cells. Tumor model mice and pharmacokinetic experiments were used to examine the efficacy and safety of CCA and cisplatin in vivo. RESULTS: This study firstly confirmed that CCA effectively inhibits TMEM16A to exert anticancer effects and analyzed the pharmacological mechanism. CCA bound to S517/N546/E623/E633/Q637 of TMEM16A through hydrogen bonding and electrostatic interactions. It inhibited the proliferation and migration, and induced apoptosis of lung cancer cells by targeting TMEM16A. In addition, the combined administration of CCA and cisplatin exhibited a synergistic effect, enhancing the efficacy of lung cancer treatment while reducing side effects. CONCLUSION: CCA is an effective novel inhibitor of TMEM16A, and it synergizes with cisplatin in anticancer treatment. These findings will provide new research ideas and lead compound for the combination therapy of lung cancer.

Multiple free-radical-trapping and hydrogen-bonding-enhanced polyurethane foams with long-lasting flame retardancy, aging resistance, and toughness.

Flexible polyurethane foam (FPUF) is a ubiquitous material utilized in furniture cushions, mattresses, and various technical applications. Despite the widespread use, FPUF faces challenges in maintaining long-lasting flame retardancy and aging resistance, particularly in harsh environments, while retaining mechanical robustness. Here, we present a novel approach to address these issues by enhancing FPUF through multiple free-radical-trapping and hydrogen-bonding mechanisms. A hindered amine phosphorus-containing polyol (DTAP) was designed and chemically introduced into FPUF. The distinctive synergy between hindered amine and phosphorus-containing structures enables the formation of multiple hydrogen bonds with urethane, while also effectively capturing free radicals across a broad temperature spectrum. As a result, incorporating only 5.1 wt% of DTAP led to the material successfully passing vertical burning tests and witnessing notable enhancements in tensile strength, elongation at break, and tear strength. Even after enduring accelerated thermal aging for 168 hours, the foam maintained exceptional flame retardancy and mechanical properties. This study offers novel insights into material enhancement, simultaneously achieving outstanding long-lasting flame retardancy, toughness, and anti-aging performance.

Discovery of 4-(isopentyloxy)-3-nitrobenzamide derivatives as xanthine oxidase inhibitors through a non-anthraquinone exploration.

In our previous study, we reported a series of N-(9,10-anthraquinone-2-carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug-like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure-activity relationship (SAR) studies, we identified a series of 4-(isopentyloxy)-3-nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4-isopentyloxy-N-(1H-pyrazol-3-yl)-3-nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC50 value of 0.13 µM. Compound 6k showed favorable drug-like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24-fold improvement in IC50, along with a 1.6-fold enhancement in LE and a 3.7-fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug-like characteristics, thereby warranting further exploration.

Numerical simulation and experimental study of three-phase distribution characteristics of leaked light non-aqueous phase liquid from buried pipelines in soils containing groundwater and gas.

Leakage accidents of buried pipelines have become increasingly common due to the prolonged service of some pipelines which have been in use for more than 150 years. Therefore, there is an urgent need for accurate prediction of pollution scope to aid in the development of emergency remediation strategies. This study investigated the distribution of a light non-aqueous phase liquid in soils containing gas and water through numerical simulations and laboratory experiments. Firstly, a three-dimensional porous medium model was established using ANSYS FLUENT, and for the first time, the distribution of gas and groundwater in soil environments was simulated in the model. Subsequently, the distribution of the three phases of diesel, gas, and water in soil was studied with different leakage velocities and it was found that the leakage velocity played a significant role in the distribution. The areas of diesel in soils at 60 min were 0.112 m2, 0.194 m2, 0.217 m2, and 0.252 m2, with corresponding volumes of 0.028 m3, 0.070 m3, 0.086 m3, and 0.106 m3, respectively, for leakage velocities of 1.3 m/s, 3.4 m/s, 4.6 m/s, and 4.9 m/s. Calculation formulas for distribution areas and volumes were also developed to aid in future prevention and control strategies under different leakage velocities. The study also compared the distribution areas and volumes of diesel in soils with and without groundwater, and it was found that distribution scopes were larger in soils containing groundwater due to capillary force. In order to validate the accuracy of the numerical simulation, laboratory experiments were conducted to study the diffusion of oil, gas, and water under different leakage velocities. The results showed good agreement between the experiments and the simulations. The research findings are of great significance for preventing soil pollution and provide a theoretical basis for developing scientifically sound soil remediation strategies.

Single-cell transcriptomic profiling reveals decreased ER protein Reticulon3 drives the progression of renal fibrosis.

Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3's role in CKD's narrative and position it as a promising therapeutic contender.