Multicomponent Polymerizations of Elemental Sulfur, CH2Cl2, and Aromatic Amines toward Chemically Recyclable Functional Aromatic Polythioureas.

The exploration of new polymer materials required the development of efficient, economic, robust, and scalable synthetic routes, taking energy consumption, environmental benefit, and sustainability into overall consideration. Herein, through retro-polymerization analysis of functional aromatic polythioureas, a multicomponent reaction of elemental sulfur, CH2Cl2, and aromatic amines was designed with the assistance of fluoride, and efficient, economic, and robust multicomponent polymerizations (MCPs) of these three abundantly available cheap monomers, elemental sulfur, CH2Cl2, and aromatic diamines, were developed to realize scalable conversion directly from sulfur to a series of functional aromatic polythioureas with high molecular weights (Mn up to 50,800 g/mol) in excellent yields (up to 98%). The synergistic cooperation of the strong and selective coordination of thiourea with gold ions and the redox property of aromatic polythiourea enable in situ reduction of Au3+ to elemental gold under a normal bench condition. Furthermore, the functional aromatic polythiourea could be chemically recycled through aminolysis with NH3·H2O to afford a diamine monomer in 83% isolated yield. The development of elemental sulfur-based MCP has brought the opportunity to access cost-effective and sustainable sulfur-containing functional polymer materials, which is anticipated to provide a solution for the utilization of sulfur waste and making profitable polymer materials.

Unveiling the Impact of Epstein-Barr Virus on the Risk of Prostate Cancer: A Mendelian Randomization Study.

Given the consistent detection of Epstein-Barr virus (EBV) in prostate tissues and the clinical evidence suggesting its involvement in prostate cancer (PCa), the potential association between EBV infection and PCa warrants further investigation. This study aimed to assess the causal relationship between EBV infection and PCa using Mendelian randomization (MR). We utilized data from a publicly available genome-wide association study (GWAS) on PCa, alongside data on five serum anti-EBV virus-related antibodies. Our findings indicate a potential causal link between serum EBV EA-D antibody levels and an increased risk of PCa. These results highlight the need for additional research to elucidate the mechanisms by which EBV may contribute to the progression of PCa, potentially offering new insights into its pathogenesis and therapeutic targets.

Effect of intraoperative anastomotic reinforcement suture on the prevention of anastomotic leakage of double-stapling anastomosis for laparoscopic rectal cancer: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The use of sutures to strengthen the anastomosis after rectal cancer surgery to reduce the possibility of anastomotic leakage has been debated. The aim of this systematic review and meta-analysis was to investigate the influence of intraoperative anastomotic reinforcing sutures on anastomotic leakage of double-stapling anastomosis for laparoscopic rectal cancer surgery. METHODS: A systematic search of PubMed, Embase, Web of Science, and Cochrane databases was performed to identify literature examining anastomotic leak as the primary outcome to compare studies of laparoscopic surgery for rectal cancer using the double-stapling anastomosis technique with or without intraoperative anastomotic reinforcement with sutures. RESULTS: A total of 1122 rectal cancer patients from 5 nonrandomized studies were included in the research. In the combined trial, intraoperative anastomotic reinforcement sutures significantly reduced the incidence of anastomotic leakage in patients who underwent laparoscopic rectal cancer surgery (OR, 0.32; 95% CI, 0.19-0.55; p < 0.0001). With or without intraoperative anastomotic reinforcing sutures, the incidence of postoperative reoperation for anastomotic leak did not differ substantially (OR, 0.32; 95% CI, 0.08-1.21, p = 0.09). Moreover, the surgery was prolonged due to anastomotic reinforcement with sutures (OR, 6.64; 95% CI, - 6.18 to 19.47, p = 0.31). CONCLUSIONS: Intraoperative anastomotic reinforcement with sutures may be associated with a lower incidence of anastomotic leakage. The amount of research evidence is limited because most of the studies analyzed did not include patients with factors such as neoadjuvant therapy or prophylactic stomas. Therefore, additional multicenter randomized controlled studies with larger size samples are needed to support the validity of the approach.

[Effect of low-dose dopamine adjuvant therapy on inflammatory factors and prognosis in preterm infants with necrotizing enterocolitis].

OBJECTIVE: To study the effect of low-dose dopamine adjuvant therapy on inflammatory factors and prognosis in preterm infants with necrotizing enterocolitis (NEC). METHODS: A total of 100 preterm infants with NEC from June 2017 to June 2019 were enrolled and divided into a dopamine treatment group and a conventional treatment group using a random number table, with 50 infants in each group. The infants in the conventional treatment group were given symptomatic treatment, and those in the dopamine treatment group were given low-dose dopamine adjuvant therapy in addition to the conventional treatment. ELISA was used to measure the levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8). The two groups were compared in terms of time to relief of clinical symptoms, fasting time, treatment outcome, prognosis, and adverse reactions. RESULTS: Both groups had significant reductions in the levels of CRP, TNF-α, and IL-8 after treatment, and the dopamine treatment group had significantly lower levels of these markers than the conventional treatment group after treatment (P<0.05). Compared with the conventional treatment group, the dopamine treatment group had significantly shorter time to defecation improvement, time to relief of abdominal distension and diarrhea, and fasting time (P<0.05), a significantly higher response rate (P<0.05), and a significantly lower surgery rate (P<0.05). There were no significant differences in the mortality rate and incidence of adverse events between the two groups (P>0.05). CONCLUSIONS: Low-dose dopamine adjuvant therapy can effectively improve the levels of inflammatory factors and clinical symptoms in preterm infants with NEC and has good safety, and therefore, it holds promise for clinical application.

Urinary neutrophil gelatinase-associated lipocalin as a biomarker to monitor renal function in patients with obstructive ureteral calculi.

PURPOSE: Our study aimed to investigate the clinical significance of urinary neutrophil gelatinase-associated lipocalin (NGAL) as an effective real-time monitoring biomarker of renal function in patients with obstructive ureteral calculi presenting renal colic. METHODS: A cohort of 89 first-visit patients with renal colic caused by unilateral ureteral calculi were retrospectively reviewed. 46 of which received double-J ureteral stent placement (group 1) and the remaining 43 treated conservatively with analgesics and hydration (group 2) when diagnosed. Urinary NGAL (uNGAL) values in the baseline, 2 h and 1 day after treatments were recorded. The variation of this parameter over time and the association with patients' characteristics were analyzed. RESULTS: uNGAL levels decreased as time went by for patients receiving double-J ureteral stent placement (47.23 ± 28.32 ng/mL for baseline, 40.73 ± 21.86 ng/mL for 2 h and 34.67 ± 18.00 ng/mL for 1 day after operation; p = 0.0363). Nevertheless, for those treating conservatively, the levels emerged a mild increase (50.63 ± 32.30 ng/mL, 56.00 ± 32.01 ng/mL and 60.63 ± 34.08 ng/mL, correspondingly; p = 0.3708). By analyzing the association between uNGAL variation and patients' characteristics of group 1, operation duration showed the best correlation coefficient (Pearson r = 0.6106, r2 = 0.3728, p < 0.0001). CONCLUSIONS: uNGAL can be used as a biomarker to monitor the renal function effectively when serum creatinine (sCr) was within normal limits. And double-J ureteral stent can be considered as a protective factor to renal function in patients with obstructive ureteral calculi presenting renal colic.

Integrative transcriptome analysis identifies genes and pathways associated with enzalutamide resistance of prostate cancer.

BACKGROUND: Enzalutamide, a novel androgen receptor (AR) signaling inhibitor, has been widely used to increase survival in patients with castration-resistant prostate cancer. However, resistance to enzalutamide invariably develops. METHODS: To understand the underlying mechanisms of resistance to enzalutamide, we performed integrative analysis on multiple transcriptome datasets to identify those genes constantly up- or down-regulated in response to enzalutamide treatment. RESULTS: There were 703 and 581 differentially expressed genes derived from enzalutamide-sensitive and -resistant cell lines, respectively. Functional enrichment analysis on these genes demonstrated that biological processes of cell proliferation and ubiquitin mediated proteolysis pathway are specifically disturbed in sensitive cell lines but not resistant ones. Such divergence explained why enzalutamide ineffective for resistant prostate cancer. CONCLUSIONS: Taken together, the present study revealed a set of critical genes, which can provide etiologic clues as to enzalutamide-resistant prostate cancer and guide novel therapeutic approaches.

Efficient green phosphor realized by Ce3+→Tb3+ energy transfer in Li3Sc2(PO4)3 for ultraviolet white light-emitting diodes.

A series of Ce3+/Tb3+ doped Li3Sc2(PO4)3 phosphors has been obtained using high temperature solid state reactions. Density functional theory (DFT) calculations using the CASTEP module have given an insight into the bandgap and electronic structures of the hosts. The phase formation and the crystal structure of the prepared samples were verified using X-ray diffraction and Rietveld structure refinement analysis. Samples singly doped with Ce3+ ions had an intense emission centered at 350 nm under UV light irradiation, while samples singly doped with Tb3+ ions exhibited a typical green emission under 230 nm irradiation. Efficient Ce3+→Tb3+ energy transfer can cause the Li3Sc2(PO4)3:Ce3+,Tb3+ samples to have an intense green emission at very low Tb3+ concentrations under 285 nm excitation, making Li3Sc2(PO4)3:Ce3+,Tb3+ an efficient UV-excited green phosphor. The mechanism and critical distance for Ce3+→Tb3+ energy transfer in the phosphor were determined by detailed luminescence decay curve analysis utilizing the I-H model. Moreover, a WLED device was fabricated using our prepared green phosphor.

Comprehensive miRNA Analysis of Human Umbilical Cord-Derived Mesenchymal Stromal Cells and Extracellular Vesicles.

BACKGROUND/AIMS: Mesenchymal stromal cells (MSCs) participate in the tissue-specific repair of many different organs, especially the kidney. Their effects are primarily mediated by the paracrine release of factors including extracellular vesicles (EVs), which are composed of micro-vesicles and exosomes. The corresponding microRNAs (miRNAs) of EVs are considered important for their biological functions. METHODS: MSCs were cultured from the human umbilical cord, and EVs were isolated from the medium. The expression levels of miRNAs in MSCs and EVs were determined by microarray analysis, and gene ontology (GO) was used to analyze the functions of their target genes. RESULTS: MSCs and EVs had similar miRNA expression profiles, with the exception of a small number of selectively enriched miRNAs. GO analysis indicated that, unlike MSCs, the target genes of EV-enriched miRNAs were associated with calcium channel regulation and cell junction activities, which may indicate that MSC and EVs have different regulatory properties. Angiogenesis, oxidative stress, and inflammatory signaling pathways related to the repair of renal injury were also analyzed, and EV-enriched miRNAs targeted genes associated with oxidative stress, T cell activation, and Toll-like receptor signaling. The miRNAs enriched in both MSCs and EVs targeted different genes in signaling pathways regulating angiogenesis and chemokine release. CONCLUSION: MSCs and their EVs shared similar miRNA component, and some selectively enriched miRNAs observed in MSCs and EVs may affect different target genes through some specific signaling pathways.

The risk factors of Urethrocutaneous fistula after hypospadias surgery in the youth population.

BACKGROUND: The current research aims to evaluate the risk factors of urethrocutaneous fistula after hypospadias surgery among the youth in China. METHODS: One hundred twenty hypospadias patients were enrolled in our study. All of them were defined as Tanner 4 or 5. The information collected from the participants include age, urethral operation history, urinary comorbidities before operation, urine test before operation, body temperature before and after operation, type of surgical repair, chordee degree, urethral defect length and whether received vesicostomy after surgery or not. Independent t test, chi-square test and multivariate logistic regression were performed to evaluate the risk factor of urethrocutaneous fistula. RESULTS: Among the enrolled patients, 39 patients (32.5%) developed urethrocutaneous fistula after hypospadias repair. Our result showed significant association between the group with urethrocutaneous fistula and the group without urethrocutaneous fistula with respect to age, pyuria before operation, urethral defect length and the urethral operation history. The following logistic regression showed that urethral defect length and the urethral operation history were the risk factors of urethrocutaneous fistula. CONCLUSIONS: Urethral defect length and urethral operation history should be taken into consideration before undergoing hypospadias surgery since our study discovered that the risk of developing urethrocutaneous fistula after hypospadias repair is associated with urethral defect length and urethral operation history. Age, surgical procedure, type of surgical repair, chordee degree and other factors were not obviously related to the development of urethrocutaneous fistula.

Genetic variants in 5p13.2 and 7q21.1 are associated with treatment for benign prostatic hyperplasia with the α-adrenergic receptor antagonist.

BACKGROUND: The etiology of benign prostatic hyperplasia (BPH) has not been well established. The preferred medical treatment for many men with symptomatic benign prostatic hyperplasia is either an α-adrenergic receptor antagonist (α-blocker), or a 5α-reductase inhibitor. Single nucleotide polymorphism (SNP) is a powerful tool for successful implementation of individualized treatment. METHODS: Eighteen SNPs associated with drug efficacy in a Chinese population were genotyped in 790 BPH cases (330 aggressive and 460 non-aggressive BPH cases) and 1008 controls. All BPH patients were treated with α-adrenergic blockers for at least 9 months. We tested the associations between tagging single nucleotide polymorphism and BPH risk/aggressiveness, clinical characteristics at baseline, including the International Prostate Symptom Score (IPSS) and total prostate volume, and changes in clinical characteristics after treatment. RESULTS: There were nine SNPs associated with BPH risk, clinical progression and therapeutic effect. (1) There were nine tSNPs been chosen in CYP3A4, CYP3A5 and RANBP3L genes. (2) The SNP, rs16902947 in RANBP3L at 5p13.2 (p = .01), was significantly associated with BPH. (3) We found two SNPs, rs16902947 in RANBP3L at 5p13.2 (p = .0388) and rs4646437 in CYP3A4 at 7q21.1 (p = .0325), associated with drug effect. (4) Allele "G" for rs16902947 was found to be risk alleles for BPH risk (OR= 2.357, 95%CI 1.01-1.48). The "A" allele of rs4646437 was associated with lower IPSS at baseline (ß= -0.4232, p= .03255). CONCLUSIONS: rs16902947, rs16902947 and rs4646437 single nucleotide polymorphisms are significantly associated with the clinical characteristics of benign prostatic hyperplasia and the efficacy of benign prostatic hyperplasia treatment.

Prostate cancer detection with real-time elastography using a bi-plane transducer: comparison with step section radical prostatectomy pathology.

PURPOSE: To evaluate elastography using a bi-plane transducer for localizing prostate cancer (PCa) in patients scheduled for radical prostatectomy (RP), in comparison with step section pathological analysis. METHODS: Fifty-six consecutive PCa patients underwent real-time elastography examination with a bi-plane transducer before RP. Transverse elastographic images were obtained from the apex to the base by slightly compressing and releasing the prostate tissue using the probe. The diagnostic performance of elastography was evaluated in correlation with step section RP histopathology. RESULTS: In 56 PCa patients, gray-scale ultrasonography detected at least one lesion in 36 patients, whereas elastography detected at least one lesion in 53 patients (P = 0.001). The overall sensitivity, specificity and accuracy of elastography in depicting tumor lesions were 67.6, 89.5 and 82.7 %, respectively. The detection rate of a PCa lesion with elastography was best in the left posterior region, followed by the right posterior region. Elastography was more sensitive in detecting PCa lesions with higher Gleason scores, diameter >5 mm and extracapsular extension. CONCLUSIONS: The additional use of elastography with the bi-plane transducer can improve PCa detection rate by providing more information about tissue stiffness within the prostate gland.

Energy evolution mechanism of structural surfaces in sandstones with different dips based on the energy principle.

A uniaxial compression test was conducted on sandstone specimens at various inclination angles to determine the energy evolution characteristics during deformation and damage. Based on the principle of minimum energy dissipation, an intrinsic model incorporating the damage threshold was developed to investigate the mechanical properties of sandstone at different inclination angles, and the energy damage evolution during deformation and damage. This study indicated that when the inclination angle of the structural surface remained below 40°, sandstone exhibited varying mechanical properties based on different inclination angles. The peak strain was positively correlated with the inclination angle, whereas the compressive strength and modulus of elasticity showed negative correlations. From an energy perspective, the deformation and damage of sandstone under external loading entail processes of energy input, accumulation, and dissipation. Moreover, higher inclination angles of the structural surface resulted in a smaller absorbed peak strain and a reduced proportion of dissipated energy relative to the energy input, thereby affecting the evolution of energy damage throughout the process. As the inclination angle of the structural surface increased, the absorbed total strain at the peak value decreased, whereas the proportion of the dissipated energy increased. Additionally, the damage threshold and critical value of the rock specimens increased with the inclination angle. The critical value, a composite index comprising the peak strain, compressive strength, and elastic modulus, also increased accordingly. These findings can offer a novel perspective for analyzing geological disasters triggered by fissure zones within underground rock formations.

PVA/PAA/DMTD electrospun nanofibrous membrane for the selective adsorption of Pb(II) ions in liquid foods.

Lead (Pb(II)) contamination is common in liquid foods and can result from Pb(II) being present in the raw materials or during handling processes. However, due to the complexity of food matrices, there is limited data available concerning Pb(II) ion removal from food sources. This study focused on fabricating a PVA/PAA/DMTD electrospun nanofibrous membrane (ENFM) to efficiently and selectively remove Pb(II) ions from liquid foods. The PVA/PAA/DMTD ENFM had a maximum adsorption capacity of 138.3 mg/g for Pb(II) ions and demonstrated high selectivity toward the removal of Pb(II) ions. Negative values of the Gibbs free energy (ΔG°) showed that the spontaneous nature of the adsorption process was feasible at different temperatures. Moreover, it successfully removed Pb(II) ions from selected samples of commercially available drinks. Therefore, this adsorbent exhibits significant potential for removing Pb(II) ions from liquid food products, thereby reducing daily dietary exposure to Pb(II).

[Microbial electrochemical snorkels: principle, structure, and applications in environmental amelioration].

Microbial electrochemical technology (MET) represents a novel approach demonstrating promising application prospects in emerging strategic industries such as environment protection, energy saving, and sustainable energy production. Among different METs, microbial electrochemical snorkels (MES) are praised for the simple design, high flexibility, and low costs. Several pilot MESs have been employed to mitigate environmental issues in European and American countries. Despite the rapid development, only one review article on MES has been published so far. Here we review the latest achievements in this field and introduce the principles, structures, functions, and applications of MESs. Moreover, we summarize the key challenges and the future research areas in this field, aiming to give insights into the research on MESs and other METs and improve the applications of such technologies.

Development and validation of a clinical diagnostic model for surgical site infection after surgery in patients with gastric cancer.

Background: Surgical site infection (SSI) is a common and serious complication following gastric cancer surgery, often linked to patient age, surgery duration, and the surgical approach taken. Accurate prediction and personalized mitigation of SSI risk are crucial for improving surgical outcomes. While prior studies have focused on SSI rates after open and laparoscopic gastric cancer surgeries, it is important to also consider robot-assisted procedures. This study aims to develop a predictive model for SSI after radical gastric cancer surgery, validate it through external testing, and provide a reliable tool for clinical use. Methods: Data from 763 postoperative gastric cancer patients were analyzed, with 601 in the training set from Gansu Provincial People's Hospital and 162 in the validation set from The First Hospital of Lanzhou University. All available variables were considered as potential predictors, and factors influencing SSI post-surgery were identified using logistic regression. A nomogram model was then created for precise SSI risk prediction. Results: Among the 763 gastric cancer patients, 10.9% experienced postoperative SSI. Significant differences were noted in the American Society of Anesthesiologists (ASA) physical status classification system classification, preoperative albumin levels, surgical approach, and reconstruction techniques between groups. Age, surgery duration, surgical approach, total gastrectomy, and tumor diameter were identified as significant predictors of SSI. The nomogram model showed high predictive accuracy, with concordance index (C-index) values of 0.834 in the training set and 0.798 in the validation set. Calibration plots and decision curve analysis (DCA) further validated the model's performance. Conclusions: This study identified five key predictors of postoperative SSI in gastric cancer and developed a nomogram model to enhance SSI prediction. These findings have important implications for preventing SSI in gastric cancer surgeries.

Preoperative neutrophil-to-lymphocyte ratio predicts symptomatic anastomotic leakage in elderly colon cancer patients: Multicenter propensity score-matched analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a composite inflammatory biomarker, is associated with the prognosis in patients with colorectal tumors. However, whether the NLR can be used as a predictor of symptomatic postoperative anastomotic leakage (AL) in elderly patients with colon cancer is unclear. AIM: To assess the role of the NLR in predicting the occurrence of symptomatic AL after surgery in elderly patients with colon cancer. METHODS: Data from elderly colon cancer patients who underwent elective radical colectomy with anastomosis at three centers between 2018 and 2022 were retrospectively analyzed. Receiver operating characteristic curve analysis was performed to determine the best predictive cutoff value for the NLR. Twenty-two covariates were matched using a 1:1 propensity score matching method, and univariate and multivariate logistic regression analyses were used to determine risk factors for the development of postoperative AL. RESULTS: Of the 577 patients included, 36 (6.2%) had symptomatic AL. The optimal cutoff value of the NLR for predicting AL was 2.66. After propensity score matching, the incidence of AL was significantly greater in the ≥ 2.66 NLR subgroup than in the < 2.66 NLR subgroup (11.5% vs 2.5%; P = 0.012). Univariate logistic regression analysis revealed statistically significant correlations between blood transfusion intraoperatively and within 2 d postoperatively, preoperative albumin concentration, preoperative prognostic nutritional index, and preoperative NLR and AL occurrence (P < 0.05); multivariate logistic regression analysis revealed that an NLR ≥ 2.66 [odds ratio (OR) = 5.51; 95% confidence interval (CI): 1.50-20.26; P = 0.010] and blood transfusion intraoperatively and within 2 d postoperatively (OR = 2.52; 95%CI: 0.88-7.25; P = 0.049) were risk factors for the occurrence of symptomatic AL. CONCLUSION: A preoperative NLR ≥ 2.66 and blood transfusion intraoperatively and within 2 d postoperatively are associated with a higher incidence of postoperative symptomatic AL in elderly patients with colon cancer. The preoperative NLR has predictive value for postoperative symptomatic AL after elective surgery in elderly patients with colon cancer.

CRISPR genome-wide screening identifies PAK1 as a critical driver of ARSI cross-resistance in prostate cancer progression.

Next-generation androgen receptor signaling inhibitors (ARSIs), such as enzalutamide (Enza) and darolutamide (Daro), are initially effective for the treatment of advanced prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). However, patients often relapse and develop cross-resistance, which consequently makes drug resistance an inevitable cause of CRPC-related mortality. By conducting a comprehensive analysis of GEO datasets, CRISPR genome-wide screening results, ATAC-seq data, and RNA-seq data, we systemically identified PAK1 as a significant contributor to ARSI cross-resistance due to the activation of the PAK1/RELA/hnRNPA1/AR-V7 axis. Inhibition of PAK1 followed by suppression of NF-κB pathways and AR-V7 expression effectively overcomes ARSI cross-resistance. Our findings indicate that PAK1 represents a promising therapeutic target gene for the treatment of ARSI cross-resistant PCa patients in the clinic. STATEMENT OF SIGNIFICANCE: PAK1 drives ARSI cross-resistance in prostate cancer progression.

New insights into the interplay between autophagy, gut microbiota and insulin resistance in metabolic syndrome.

Metabolic syndrome (MetS) is a widespread and multifactorial disorder, and the study of its pathogenesis and treatment remains challenging. Autophagy, an intracellular degradation system that maintains cellular renewal and homeostasis, is essential for maintaining antimicrobial defense, preserving epithelial barrier integrity, promoting mucosal immune response, maintaining intestinal homeostasis, and regulating gut microbiota and microbial metabolites. Dysfunctional autophagy is implicated in the pathological mechanisms of MetS, involving insulin resistance (IR), chronic inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, with IR being a predominant feature. The study of autophagy represents a valuable field of research with significant clinical implications for identifying autophagy-related signals, pathways, mechanisms, and treatment options for MetS. Given the multifactorial etiology and various potential risk factors, it is imperative to explore the interplay between autophagy and gut microbiota in MetS more thoroughly. This will facilitate the elucidation of new mechanisms underlying the crosstalk among autophagy, gut microbiota, and MetS, thereby providing new insights into the diagnosis and treatment of MetS.

SLC4A4 is a novel driver of enzalutamide resistance in prostate cancer.

The androgen receptor signaling inhibitor (ARSI) enzalutamide (Enz) has shown critical efficacy in the treatment of advanced prostate cancer (PCa). However, the development of drug resistance is a significant factor contributing to mortality in PCa patients. We aimed to explore the key mechanisms of Enz-resistance. Through analysis of GEO databases, we identified SLC4A4 as a novel driver in Enz resistance. Long-term Enz treatment leads to the up-regulation of SLC4A4, which in turn mediates P53 lactylation via the NF-κB/STAT3/SLC4A4 axis, ultimately leading to the development of Enz resistance and progression of PCa. SLC4A4 knockdown overcomes Enz resistance both in vitro and in vivo. Hence, our results suggest that targeting SLC4A4 could be a promising therapeutic strategy for Enz resistance. STATEMENT OF SIGNIFICANCE: SLC4A4 is a novel driver of enzalutamide resistance.

Identification of sanguinarine as a novel antagonist for perfluorooctanoate/perfluorooctane sulfonate-induced senescence of hepatocytes: An integrated computational and experimental analysis.

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS), two prominent per- and polyfluoroalkyl substances (PFASs), are potentially harmful to many human organs. However, there only exist limited methods to mitigate their health hazards. The aim of this study is to combine a bioinformatics analysis with in vitro experiments to discover small molecules that can alleviate liver damage caused by PFOA/PFOS. We identified 192 and 82 key genes related to hepatocytes exposed to PFOA and PFOS, respectively. The functional enrichment analysis of key genes suggested cellular senescence may be important in PFOA/PFOS-induced hepatotoxicity. The in vitro models revealed that PFOA/PFOS led to hepatocyte senescence by increasing the activity of SA-ß-gal, inducing mitochondrial dysfunction, impacting cell cycle arrest, and elevating the expressions of p21, p53, IL-1ß, and SASP-related cytokines. The drug-target gene set enrichment analysis method was employed to compare the transcriptome data from the Gene Expression Omnibus database (GEO), Comparative Toxicogenomics Database (CTD), and the high-throughput experiment- and reference-guided database (HERB), and 21 traditional Chinese medicines (TCMs) were identified that may alleviate PFOA/PFOS-induced liver aging. The experimental results of co-exposure to PFOA/PFOS and TCMs showed that sanguinarine has particular promise in alleviating cellular senescence caused by PFOA/PFOS. Further investigations revealed that the mTOR-p53 signaling pathway was involved in PFOA/PFOS-mediated hepatic senescence and can be blocked using sanguinarine.