Effectiveness, safety, and biomarker analysis of lenvatinib plus toripalimab as chemo-free therapy in advanced intrahepatic cholangiocarcinoma: a real-world study.

BACKGROUND: Treatment options for advanced intrahepatic cholangiocarcinoma (ICC) are currently limited. Chemo-containing regimens are the mainstay treatments but associated with notable toxicity, poor tolerance, and reduced compliance, necessitating exploration of alternative therapies. Lenvatinib plus PD-1 inhibitors has shown substantial clinical activity in preliminary studies. This study aimed to assess the effectiveness and safety of lenvatinib plus toripalimab (a novel PD-1 antibody) as chemo-free therapy in advanced ICC. METHODS: This retrospective study included consecutive advanced ICC patients receiving lenvatinib plus toripalimab between February 2019 and December 2023. The main outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors and exploratory analyses for genetic alternations were also conducted. RESULTS: A total of 78 patients were included, with a median follow-up of 25.9 months. Median OS and PFS were 11.3 (95% CI: 9.5-13.1) and 5.4 (95% CI: 3.8-7.0) months, respectively. ORR was 19.2% and DCR was 75.6%. The incidence of grade 3 or 4 adverse events (AEs) was 50.0%, with no grade 5 AEs reported. Patients with normal baseline CA19-9 levels exhibited a higher ORR (p = 0.011), longer PFS (11.5 versus 4.6 months; HR 0.47; p=0.005), and OS (21.0 versus 9.7 months; HR 0.43; p=0.003). The presence of IDH1 mutations correlated with increased ORR (60.0% versus 8.9%, p=0.016). CONCLUSION: Lenvatinib plus toripalimab represents an effective and well-tolerated chemo-free therapeutic option for advanced ICC. Baseline CA19-9 levels and IDH1 mutations may serve as predictive treatment-related biomarkers.

Insulin Resistance Surrogates May Predict HTN-HUA in Young, Non-Obese Individuals.

Objective: To compare the associations of three surrogate markers of insulin resistance (IR) [glucose and triglycerides (TyG index), TyG index with BMI (TyG-BMI), and the ratio of triglycerides divided by HDL-C (TG/HDL-C)] with hypertensive patients (HTN) plus hyperuricemia (HUA) (HTN-HUA) in young, non-obese individuals. Methods: Data from a cross-sectional epidemiological study of an annual health check-up population aged younger than 66 years were used to calculate the three IR surrogate indexes. The association with HTN-HUA and insulin resistance surrogates was examined with multinomial logistic regression and a receiver operating characteristic (ROC) curve. Results: A total of 6952 participants were included, including 671 (9.65%) participants with HTN alone, 272 (3.91%) participants with HUA alone, and 62 (0.90%) participants with HTN and HUA. Binary multiple-logistic regression results showed that TG/HDL-C was significantly correlated with HTN, HUA, and HTN-HUA. Compared with the lowest quartile, the odds ratios (95% CI) of the highest quartile of TG/HDL-C for HTN-HUA were 3.462 (1.138~10.530). TG/HDL-C and TyG-BMI had moderate discriminative abilities for HTN-HUA, and the area under the curve was 0.748 (0.682~0.815), 0.746 (0.694~0.798). Conclusion: Our study suggests that TG/HDL-C had a significant correlation with HTN-HUA and that TG/HDL-C had moderate discriminative abilities for HTN-HUA.

Long-term impacts of socioeconomic status and childhood trauma on depression in older adults: social work strategies.

This study explores the impact of life course socioeconomic status (SES) and childhood trauma on depressive symptoms in Chinese middle-aged and older adults, while also examining the role of chronic diseases and implications for social work practice. Using data from 9,942 participants, structural equation was established to investigate these relationships. Results reveals that low childhood SES positively affects depressive symptoms through low SES in mid-to-late life (std. ß = 0.168, p < .001), and domestic child abuse negatively impacts depressive symptoms through low SES in mid-to-late life (std. ß=-0.020, p < .001). Additionally, experiencing peer bullying is directly associated with depressive symptoms (std. ß = 0.145, p < .001). Exposure to domestic violence is directly related to depressive symptoms (std. ß = 0.078, p < .001) and indirectly leads to more severe depressive symptoms through chronic disease (std. ß = 0.023, p < .001). Social workers in healthcare settings can utilize these findings to better understand risk factors for depression and provide trauma-informed care and economic assistance across the life course. Additional training for social workers on the lasting impacts of childhood adversity is warranted. By intervening at both individual and policy levels, social work practitioners can help break cycles of poverty and poor health stemming from childhood.

Comparison of Hypervirulent and Non-Hypervirulent Carbapenem-Resistant Acinetobacter baumannii Isolated from Bloodstream Infections: Mortality, Potential Virulence Factors, and Combination Therapy In Vitro.

Hypervirulent carbapenem-resistant Acinetobacter baumannii (hv-CRAB) has emerged in bloodstream infections (BSI). Cases of BSI caused by hv-CRAB (hv-CRAB-BSI) had posed a significant threat to hospitalized patients. In this study, 31 CRAB strains isolated from Chinese BSI patients were analyzed, of which 24 were identified as hv-CRAB-BSI and 7 as non-hv-CRAB-BSI, using the Galleria mellonella infection model. Patients with hv-CRAB-BSI had higher rates of septic shock (79.2% vs. 14.3%, p = 0.004) and mortality (66.7% vs. 14.3%, p = 0.028). All strains were resistant to most antibiotics but sensitive to colistin. Hv-CRAB-BSI showed lower resistance to minocycline than non-hv-CRAB-BSI (54.2% vs. 100%, p = 0.03). Whole-genome sequencing revealed that the detection rates of immune modulation genes ptk and epsA in hv-CRAB-BSI were significantly higher than in non-hv-CRAB-BSI (91.7% vs. 28.6%, p = 0.002). Additionally, all ST457 hv-CRAB-BSI lacked abaR, and all ST1486 non-hv-CRAB-BSI lacked adeG. The checkerboard dilution method assessed the efficacies of various antibiotic combinations, revealing that although synergism was rarely observed, the combination of colistin and minocycline showed the best efficacy for treating CRAB-BSI, regardless of whether the infections were hv-CRAB-BSI or non-hv-CRAB-BSI. These findings highlight the importance of analyzing molecular characteristics and exploring effective treatment strategies for hv-CRAB-BSI.

Selenium-enriched yeast regulates aquaporins to alleviate atrazine-induced hepatic ionic homeostasis disturbance in Japanese quails.

Atrazine (ATR), a commonly used herbicide, carries a risk to the health of humans and animals due to its persistence in the environment and accumulation in the body. The main metabolic processes of ATR was occurred in the liver. Therefore, the accumulation of ATR in the body can cause serious hepatic injury. This research aimed to clarify the toxicological effect of ATR and explore the potential protective benefits of selenium-enriched yeast (Yeast-Se) in alleviating liver toxicity induced by ATR. Quails were treated with ATR and Yeast-Se for 28 days. The results indicated that ATR inhibited quail growth and development and caused liver dysfunction. Pathological analysis showed that ATR led to central vein congestion and gallbladder epithelial cells shedding and necrosis. In addition, ATR significantly changed hepatic ion content (Na+, K+, Cl-, Ca2+, Mg2+) and decreased Na+-K+-ATPase and Ca2+/Mg2+-ATPase activities. Notably, supplementary Yeast-Se protects against ATR-induced liver ionic disorder by reversing ATPase activity and increasing ATPase subunits expression. In addition, supplementary Yeast-Se significantly up-regulated the expression of aquaporins (AQPs). In summary, these results indicated that Yeast-Se may regulates AQPs to alleviate ATR-induced ionic homeostasis disturbance in liver.

Environmental micro-molar H2O2 reduces the efficiency of glyphosate biodegradation in soil.

Glyphosate is one of the most widely used pesticides globally. The environmental micro-molar hydrogen peroxide (H2O2)-driven Fenton reaction has been reported to degrade herbicides in natural water. However, the impact of micro-molar H2O2 (50 µM) on the degradation of glyphosate in soil and glyphosate-degrading bacteria remains unclear. In this study, degradation of glyphosate in the sterilized and unsterilized soil system and MSM medium under micro-molar H2O2 was investigated; bacterial diversity, enzyme activity and gene abundance in the soil following micro-molar H2O2 addition were also investigated. The results indicated that the addition of micro-molar H2O2 facilitated the degradation of glyphosate in a sterilized environment, resulting in a 76.30% decrease in glyphosate within 30 days. The degradation of glyphosate increased by 52.32% compared to the control treatment. However, in an unsterilized environment, the addition of micro-molar H2O2 leads to a reduction in the biodegradation efficiency of glyphosate. Bacteria, enzymes and specific genes were found to be affected to varying degrees. Firstly, micro-molar H2O2 affects the relative abundance of functional bacteria related to glyphosate degradation, such as Afipia, Microcoleus and Pseudomonas. Secondly, micro-molar H2O2 resulted in a decrease in soil phosphatase activity. Thirdly, the expression of resistance genes was affected, particularly the glyphosate resistance gene aroA. The findings presented a novel research perspective on the degradation of soil glyphosate by micro-molar H2O2.

Molecular Epidemiology and Horizontal Transfer Mechanism of optrA-Carrying Linezolid-Resistant Enterococcus faecalis.

The aim of this work was to provide a theoretical and scientific basis for the treatment, prevention, and control of clinical drug-resistant bacterial infections by studying the molecular epidemiology and horizontal transfer mechanism of optrA-carrying linezolid-resistant Enterococcus faecalis strains (LREfs) that were clinically isolated in a tertiary hospital in Kunming, China. Non-repetitive LREfs retained in a tertiary A hospital in Kunming, China. The strains were identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The transferability and horizontal transfer mechanism of optrA gene were analyzed using polymerase chain reaction (PCR), whole-genome sequencing (WGS), and conjugation experiments. A total of 39 LREfs strains were collected, and all of them were multi-drug resistant. There were 30 LREfs strains (76.9%) carrying the optrA gene, The cfr, poxtA genes and mutations in the 23S rRNA gene were not detected. The conjugation experiments showed that only three of 10 randomly selected optrA-carrying LREfs were successfully conjugated with JH2-2. Further analysis of one successfully conjugated strain revealed that the optrA gene, located in the donor bacterium, formed the IS1216E-erm(A)-optrA-fexA-IS1216E transferable fragment under the mediation of the mobile genetic element (MGE) IS1216E, which was then transferred to the recipient bacterium via horizontal plasmid transfer. Carrying the optrA gene is the primary resistance mechanism of LREfs strains. The optrA gene could carry the erm(A) and fexA genes to co-transfer among E. faecalis. MGEs such as insertion sequence IS1216E play an important role in the horizontal transfer of the optrA gene.

Early-stage postoperative depression and anxiety following orthognathic surgery: a cross-sectional study.

BACKGROUND: The objective of this study was to observe the incidence and potential risk factors of postoperative depression and anxiety in patients during the early period after undergoing orthognathic surgery. METHODS: From March 7 to September 7, 2023, patients ≥ 18 years of age who were scheduled for elective orthognathic surgery under general anesthesia in Peking University School and Hospital of Stomatology were included in this study. We prospectively evaluated their degrees of pre- and postoperative depression and anxiety using the Patient Health Questionnaire-9 and the State Trait Anxiety Inventory. Associations between the perioperative factors and occurrences of postoperative anxiety and depression were evaluated using a multivariate logistic regression model. RESULTS: A total of 371 patients were included in the analysis. Within five days after surgery, we observed the occurrence of depression in 32% (116) of the patients and anxiety in 72.8% (270) of them. Their preoperative depression score on the Pain Catastrophizing Scale and intraoperative urine output were significantly associated with a higher risk of postoperative depression. The presence of preoperative anxiety, postoperative moderate-to-severe pain, postoperative nausea and vomiting and postoperative insomnia were significantly associated with a higher risk of postoperative anxiety. Furthermore, a monthly income ≥ ¥10000 was found to be significantly associated with a lower risk of postoperative anxiety. CONCLUSIONS: Postoperative depression and anxiety are common among patients who undergo orthognathic surgery. Moreover, preoperative psychological status and incidence of postoperative adverse events were associated with an increased risk of depression and anxiety after surgery. The results of the present study suggest that careful psychological assessment and appropriate management are necessary to improve patients' recovery following orthognathic surgery.

Generation of cytotoxic aptamers specifically targeting fibroblast-like synoviocytes by CSCT-SELEX for treatment of rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease characterised by aggressive fibroblast-like synoviocytes (FLSs). Very few RA patients-derived FLSs (RA-FLSs)-specific surface signatures have been identified, and there is currently no approved targeted therapy for RA-FLSs. This study aimed to screen therapeutic aptamers with cell-targeting and cytotoxic properties against RA-FLSs and to uncover the molecular targets and mechanism of action of the screened aptamers. METHODS: We developed a cell-specific and cytotoxic systematic evolution of ligands by exponential enrichment (CSCT-SELEX) method to screen the therapeutic aptamers without prior knowledge of the surface signatures of RA-FLSs. The molecular targets and mechanisms of action of the screened aptamers were determined by pull-down assays and RNA sequencing. The therapeutic efficacy of the screened aptamers was examined in arthritic mouse models. RESULTS: We obtained an aptamer SAPT8 that selectively recognised and killed RA-FLSs. The molecular target of SAPT8 was nucleolin (NCL), a shuttling protein overexpressed on the surface and involved in the tumor-like transformation of RA-FLSs. Mechanistically, SAPT8 interacted with the surface NCL and was internalised to achieve lysosomal degradation of NCL, leading to the upregulation of proapoptotic p53 and downregulation of antiapoptotic B-cell lymphoma 2 (Bcl-2) in RA-FLSs. When administrated systemically to arthritic mice, SAPT8 accumulated in the inflamed FLSs of joints. SAPT8 monotherapy or its combination with tumour necrosis factor (TNF)-targeted biologics was shown to relieve arthritis in mouse models. CONCLUSIONS: CSCT-SELEX could be a promising strategy for developing cell-targeting and cytotoxic aptamers. SAPT8 aptamer selectively ablates RA-FLSs via modulating NCL-p53/Bcl-2 signalling, representing a potential alternative or complementary therapy for RA.

An in-depth review of the dermal toxicity of T-2 toxin: Clinical symptoms, injury mechanisms, and treatment approach.

T-2 toxin, a notable mycotoxin derived from the Fusarium genus, possesses significant heat and ultraviolet radiation resilience, making its elimination from food or feed sources a challenging task. T-2 toxin can be rapidly absorbed from inhalation dust particles, ingest food and skin contact. T-2 toxin has skin toxicity, which can cause varying degrees of structural and functional damage to the skin tissue depending on the type of animal, age, and dose of toxin. Skin contact is not a prerequisite for T-2 toxin to exert skin toxicity, T-2 toxin can also cause skin damage when ingested through the digestive tract. The core dermal toxic molecular mechanism of T-2 toxin is oxidative damage and inflammatory reaction. Some physical methods and chemical methods were used to remove T-2 toxin from the surface of the skin, to have a certain mitigating effect on dermal toxicity caused by T-2 toxin. Grasping T-2 toxin's skin toxicity mechanism is vital for creating effective prevention and treatments. This paper summarizes the comprehensive date from in vitro and in vivo studies, highlighting the molecular mechanism of skin damage by T-2 toxin and current treatment strategies, to provide reference for further research on the skin toxicity of T-2 toxin.

Classification of soybean seeds based on RGB reconstruction of hyperspectral images.

Soyabean is an incredibly significant component of Chinese agricultural product, and categorizing soyabean seeds allows for a better understanding of the features, attributes, and applications of many species of soyabean. This enables farmers to choose appropriate seeds for sowing in order to increase production and quality. As a result, this thesis provides a method for classifying soybean seeds that uses hyperspectral RGB picture reconstruction. Firstly, hyperspectral images of seven varieties of soybean, H1, H2, H3, H4, H5, H6 and H7, were collected by hyperspectral imager, and by using the principle of the three base colours, the R, G and B bands which have more characteristic information are selected to reconstruct the images with different texture and colour characteristics to generate a new dataset for seed segmentation, and finally, a comparison is made with the classification effect of the seven models. The experimental results in ResNet34 show that the classification accuracy of the dataset before and after RGB reconstruction increases from 88.87% to 91.75%, demonstrating that RGB image reconstruction can strengthen image features; ResNet18, ResNet34, ResNet50, ResNet101, CBAM-ResNet34, SENet-ResNet34, and SENet-ResNet34-DCN models have classification accuracies of 72.25%, 91.75%, 89%, 88.48%, 92.28%, 92.80%, and 94.24%, respectively.SENet-ResNet34-DCN achieves the greatest classification accuracy results, with a model loss of roughly 0.3. The proposed SENet-ResNet34-DCN model is the most effective at classifying soybean seeds. By classifying and optimally selecting seed varieties, agricultural production can become more scientific, efficient, and sustainable, resulting in higher returns for farmers and contributing to global food security and sustainable development.

The shared molecular mechanism of spinal cord injury and sarcopenia: a comprehensive genomics analysis.

Introduction: The occurrence of Spinal cord injury (SCI) brings economic burden and social burden to individuals, families and society, and the complications after SCI greatly affect the rehabilitation and treatment of patients in the later stage.This study focused on the potential biomarkers that co-exist in SCI and sarcopenia, with the expectation to diagnose and prognose patients in the acute phase and rehabilitation phase using comprehensive data analysis. Methods: The datasets used in this study were downloaded from Gene Expression Omnibus (GEO) database. Firstly, the datasets were analyzed with the "DEseq2" and "Limma" R package to identify differentially expressed genes (DEGs), which were then visualized using volcano plots. The SCI and sarcopenia DEGs that overlapped were used to construct a protein-protein interaction (PPI) network. Three algorithms were used to obtain a list of the top 10 hub genes. Next, validation of the hub genes was performed using three datasets. According to the results, the top hub genes were DCN, FSTL1, and COL12A1, which subsequently underwent were Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. We also assessed immune cell infiltration with the CIBERSORT algorithm to explore the immune cell landscape. The correlations between the hub genes and age and body mass index were investigated. To illustrate the biological mechanisms of the hub genes more clearly, a single-cell RNA-seq dataset was assessed to determine gene expression when muscle injury occurred. According to our analysis and the role in muscle, we chose the fibro/adipogenic progenitors (FAPs) cluster in the next step of the analysis. In the sub cluster analysis, we use the "Monocle" package to perform the trajectory analysis in different injury time points and different cell states. Results: A total of 144 overlapped genes were obtained from two datasets. Following PPI network analysis and validation, we finally identified three hub-genes (DCN, FSTL1, and COL12A1), which were significantly altered in sarcopenic SCI patients both before and after rehabilitation training. The three hub genes were also significantly expressed in the FAPs clusters. Furthermore, following injury, the expression of the hub genes changed with the time points, changing in FAPs cluster. Discussion: Our study provides comprehensive insights into how muscle changes after SCI are associated with sarcopenia by moving from RNA-seq to RNA-SEQ, including Immune infiltration landscape, pesudotime change and so on. The three hub genes identified in this study could be used to distinguish the sarcopenia state at the genomic level. Additionally, they may also play a prognostic role in evaluating the efficiency of rehabilitation training.

Effect of body contour changes on the setup and dosimetric accuracy of radiotherapy after cervical cancer surgery.

Purpose: The body contour of patients with cervical cancer is prone to change between radiotherapy sessions. This study aimed to investigate the effect of body contour changes on the setup and dosimetric accuracy of radiotherapy. Methods: 15 patients with cervical cancer after surgery were randomly selected for retrospective analysis. The body contours on the once-per-week cone-beam computed tomography (CBCT) were registered to the planning CT (pCT) for subsequent evaluation. A body contour conformity index (CIbody) was defined to quantify the variation of body changes. The body volume measured by CBCT was collected, and its relative difference in reference with the first CBCT was calculated and denoted by ΔVn. The relative setup errors, denoted by ΔSELR, ΔSEAP, ΔSESI, and ΔSEvec for left-right, anterior-posterior, superior-inferior, and vectorial shifts, respectively, were defined as the difference in measured setup errors between the reference and following CBCTs. The planned dose was calculated on the basis of virtual CT generated from CBCT and pCT by altering the CT body contour to fit the body on CBCT without deformable registration. The correlations between body contour changes and relative setup errors as well as dosimetric parameters were evaluated using Spearman's correlation coefficient rs . Results: CIbody was found to be negatively correlated with the superior-inferior and vectorial relative setup errors ΔSESI (rs = -0.448, p = 0.001) and ΔSEvec (rs = -0.387, p = 0.002), and no significant correlation was found between relative setup errors and ΔVn. Moreover, ΔVn was negatively correlated with ΔD2 (rs = -0.829, p < 0.001), ΔD98 (rs = -0.797, p < 0.001), and ΔTVPIV (rs = -0.819, p < 0.001). ΔD2, ΔD98, and ΔTVPIV were negatively correlated with ΔVn (p < 0.005). No correlation was found for other examined dosimetric parameters. Conclusion: The body contour change of patients could be associated with the setup variability. The effect of body contour changes on dose distribution is minimal. The extent of body change could be used as a metric for radiation therapists to estimate the setup errors.

A Self-Healing and Sweat-Chargeable Hydrogel Electrolyte for All-in-One Flexible Supercapacitors.

Flexible solid-state supercapacitors (SCs) with hydrogel as an electrolyte and separator combine the advantages of wearability and energy storage and exhibit a broad application prospect in wearable energy textiles. However, irreversible electrolyte damage and unstable electrode-electrolyte interfaces during mechanical deformations remain bottlenecks in realizing truly wearable applications. Herein, poly(acrylic acid) (PAA)-Fe hydrogels were prepared through a simple thermal polymerization strategy. The dynamic reversible metal coordination bonds between Fe3+ and carboxylic acids confers the hydrogels with excellent self-healing properties. As expected, the prepared hydrogels exhibited superior mechanical strength (tensile stress of 45.80 kPa), ionic conductivity (0.076 S cm-1), and self-healing properties. Subsequently, the SCs were constructed using composite hydrogel electrodes (MnO2@CC embedded in the PAA-Fe hydrogels) as symmetrical electrodes (marked as MSCs). The reversible metal coordination bonds between composite hydrogel electrodes formed an ultrastable electrode/electrolyte interface in the all-in-one MSCs, thus revealing excellent mechanical durability. The all-in-one MSCs delivered a remarkable specific capacitance (30.98 F g-1 at 0.2 A g-1), excellent cyclic stability (87.24% after 5000 cycles), outstanding mechanical deformation stability, and impressive electrochemical output stability after self-healing (capacitance retention of 85.34% after five cycles of cutting/self-healing). It is noteworthy that the all-in-one MSCs employed NaCl as an electrolyte, which can be obtained from human sweat. As a proof of the self-charged concept, the all-in-one MSCs can be reused in sweat, whose capacitance was maintained at 90.05% of the initial state after three repetitions. This work is expected to shine light into the design of all-in-one and fabric-based SCs and the development of wearable energy textiles.

Banxia Xiexin Tang attenuates high glucose-induced hepatocyte injury by activating SOD2 to scavenge ROS via PGC-1α/IGFBP1.

This study aimed to explore the protective mechanism of Banxia Xiexin Tang (BXXXT) on liver cell damage caused by high glucose (H-G) and to clarify its molecular regulatory pathways. First, the main components in BXXXT-containing serum were analyzed by high-performance liquid chromatography (HPLC) to provide basic data for subsequent experiments. Subsequently, the effect of BXXXT on high glucose (H-G)-induced hepatocyte activity was evaluated through screening of the optimal concentration of drug-containing serum. Experimental results showed that BXXXT significantly reduced the loss of cell activity caused by high glucose. Further research focuses on the regulatory effect of BXXXT on high glucose-induced hepatocyte apoptosis, especially its effect on the PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α) pathway. Experimental results showed that BXXXT reduced high-glucose-induced hepatocyte apoptosis and exerted its protective effect by upregulating the activity of the PGC-1α pathway. BXXXT significantly increased the expression level of IGFBP1 (insulin-like growth factor-binding proteins) in hepatocytes under a high-glucose environment. It cleared mitochondrial ROS (reactive oxygen species) by enhancing SOD2 (superoxide dismutase) enzyme activity and maintained the survival of hepatocytes under a high-glucose environment. Finally, the regulation of PGC-1α by BXXXT is indeed involved in the regulation of IGFBP1 expression in hepatocytes and its downstream SOD2 effector signaling. Taken together, this study provides an in-depth explanation of the protective mechanism of BXXXT on hepatocytes in a high-glucose environment, focusing on regulating the expression of the PGC-1α pathway and IGFBP1, and reducing cell damage by scavenging ROS. This provides an experimental basis for further exploring the potential of BXXXT in the treatment of diabetes-related liver injury. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04060-0.

Exposure to environmental doses of DEHP causes phenotypes of polycystic ovary syndrome.

Globally, approximately 6-20% of women who are of reproductive age suffer from polycystic ovary syndrome (PCOS), with environmental factors believed to be significant contributors. Di-2-ethylhexyl phthalate (DEHP) is known to be an endocrine disruptor, and is also suspected of being associated with the occurrence of PCOS, but in vivo studies to verify this association are lacking. In this study, female SD rats were exposed to DEHP at levels of 0.1, 1.0, and 10mg/kg/d, which are comparable to daily human exposure, to explore its potential role in the development of PCOS. The findings indicated that DEHP exposure reduced ovarian and uterine coefficients, decreased accumulation of primordial follicles, increased the prevalence of atretic and cystic follicles and fibrosis in ovarian tissues, altered serum hormone levels, elevated blood glucose levels and insulin resistance, disrupted the endocrine system and resulted in significant oxidative damage in the ovarian tissues. These results imply that DEHP exposure may cause lesions resembling PCOS to develop. By analyzing the differential expression of the proteome, and using GO and KEGG enrichment analyses, we found they were mainly enriched in the metabolic pathway and in the PPAR signaling pathway. We confirmed that activation of the PPARγ signaling pathway caused by DEHP exposure, is related to the emergence of PCOS-like lesions. This research provides direct in vivo experimental evidence for the association between DEHP exposure and PCOS.

SET8 inhibition preserves PTEN to attenuate kidney cell apoptosis in cisplatin nephrotoxicity.

The aberrant expression of SET8, a histone methyltransferase that mediates H4 lysine 20 mono-methylation (H4K20me1), is implicated in the pathogenesis of various tumors, however, its role in acute kidney injury (AKI) is unknown. Here we showed that SET8 and H4K20me1 were upregulated in the murine kidney with AKI induced by cisplatin, along with increased renal tubular cell injury and apoptosis and decreased expression of E-cadherin and Phosphatase and Tensin Homolog (PTEN). Suppression of SET8 by UNC0379 improved renal function, attenuated tubule damage, and restored expression of PTEN, but not E-cadherin. UNC0379 was also effective in lessening cisplatin-induced DNA damage response (DDR) as indicated by reduced expression of γ-H2AX, p53, p21, and alleviating cisplatin-impaired autophagy as shown by retained expression of Atg5, Beclin-1, and CHMP2A and enhanced levels of LC3-II in the kidney. Consistently, inhibition of SET8 with either UNC0379 or siRNA mitigated apoptosis and DDR, and restored autophagy, along with PTEN preservation in cultured renal proximal tubular epithelial cell (TKPTs) exposed to cisplatin. Further studies showed that inhibition of PTEN with Bpv or siRNA potentiated cisplatin-induced apoptosis, DDR, and hindered autophagy, and conversely, alleviated by overexpression of PTEN in TKPTs. Finally, blocking PTEN largely abolished the inhibitory effect of UNC0379 on apoptosis. Taken together, these results suggest that SET8 inhibition protects against cisplatin-induced AKI and renal cell apoptosis through a mechanism associated with the preservation of PTEN, which in turn inhibits DDR and restores autophagy.

Structure of POU2AF1 recombinant protein and it affects the progression and treatment of liver cancer based on WGCNA and molecular docking analysis.

Hepatocellular carcinoma, also referred to as HCC, is the most frequent form of primary liver cancer. It is anticipated that the discovery of the molecular pathways related with HCC would open up new possibilities for the treatment of HCC.WGCNA (Weighted gene co-expression network analysis) and molecular docking analysis were used to study the structural characteristics of POU2AF1 recombinant protein and its interaction with related proteins. Normal samples were placed in one group, and tumor samples were placed in another group inside the GEO database. We continued our investigation of the DEGs by performing an enrichment analysis using GO and KEGG. The GSCA platform is utilized in the process of doing an analysis of the connection between gene expression and medication sensitivity. In the end, the core target and the active molecule were both given the green light for a molecular docking investigation. POU2AF1 is being considered as a possible therapeutic target for HCC, and the results of our work have presented novel concepts for the treatment of HCC.

α7-nAChR/P300/NLRP3-regulated pyroptosis mediated poor articular cartilage quality induced by prenatal nicotine exposure in female offspring rats.

Nicotine is developmentally toxic. Prenatal nicotine exposure (PNE) affects the development of multiple fetal organs and causes susceptibility to a variety of diseases in offspring. In this study, we aimed to investigate the effect of PNE on cartilage development and osteoarthritis susceptibility in female offspring rats. Wistar rats were orally gavaged with nicotine on days 9-20 of pregnancy. The articular cartilage was obtained at gestational day (GD) 20 and postnatal week (PW) 24, respectively. Further, the effect of nicotine on chondrogenic differentiation was explored by the chondrogenic differentiation model in human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs). The PNE group showed significantly shallower Safranin O staining and lower Collagen 2a1 content of articular cartilage in female offspring rats. Further, we found that PNE activated pyroptosis in the articular cartilage at GD20 and PW24. In vitro experiments revealed that nicotine inhibited chondrogenic differentiation and activated pyroptosis. After interfering with nod-like receptors3 (NLRP3) expression by SiRNA, it was found that pyroptosis mediated the chondrogenic differentiation inhibition of WJ-MSCs induced by nicotine. In addition, we found that α7-nAChR antagonist α-BTX reversed nicotine-induced NLRP3 and P300 high expression. And, P300 SiRNA reversed the increase of NLRP3 mRNA expression and histone acetylation level in its promoter region induced by nicotine. In conclusion, PNE caused chondrodysplasia and poor articular cartilage quality in female offspring rats. PNE increased the histone acetylation level of NLRP3 promoter region by α7-nAChR/P300, which resulting in the high expression of NLRP3. Further, NLRP3 mediated the inhibition of chondrogenic differentiation by activating pyroptosis.

Polysulfone membranes decorated with Fe-Mn binary oxide nanoparticles and polydopamine for enhanced arsenate/arsenite adsorptive removal.

Arsenic contamination of water is a global environmental concern, and membrane technology combined with nanotechnology contributes to more efficient removal of arsenic. In this study, Fe-Mn oxide (FM), Polydopamine (PDA), and PDA-modified FM (PFM) were incorporated into polysulfone (PSF) to prepare adsorption membranes (PFMP) for arsenic removal. The prepared nanoparticles and membranes were characterized using TEM, SEM, FTIR, TGA, contact angle, and pure water flux. The introduction of particles enhanced the hydrophilicity of the membranes and significantly enhanced the pure water flux of the membranes. Adsorption experiments indicated that the PFMP membrane exhibited the best arsenic removal performance, with maximum adsorption capacities for As(III) and As(V) were 11.57 mg/g and 12.39 mg/g, respectively. The Langmuir model fitted the adsorption isotherms well, and the kinetics followed the pseudo-second-order model. The filtration experiment revealed that the PFMP membrane was capable of reducing As(III) solution (915 L/m2) and As(V) solution (1075 L/m2) from a concentration of 100 µg/L to the safe limit of As (＜10 µg/L). The As-loaded membrane was regenerated using NaOH solution (pH = 11), and the filtration experiment was repeated. FTIR and XPS demonstrated that the mechanism of the reaction between the membrane and arsenic was ligand exchange, where the arsenic ions were bonded to the oxygen ions to form Mn-O-As and Fe-O-As.