Insight into the generation of toxic by-products during UV/H2O2 degradation of carbamazepine: Mechanisms, N-transformation and toxicity.

Carbamazepine (CBZ) is a widely used anticonvulsant drug that has been detected in aquatic environments. This study investigated the toxicity of its by-products (CBZ-BPs), which may surpass CBZ. Unlike the previous studies, this study offered a more systematic approach to identifying toxic BPs and inferring degradation pathways. Furthermore, quadrupole time-of-flight (QTOF) and density functional theory (DFT) calculations were employed to analyze CBZ-BP structures and degradation pathways. Evaluation of total organic carbon (TOC) and total nitrogen (TN) mineralization rates, revealed carbon (C) greater susceptibility to mineralization compared with nitrogen (N). Furthermore, three rules were established for CBZ decarbonization and N removal during degradation, observing the transformation of aromatic compounds into aliphatic hydrocarbons and stable N-containing organic matter over time. Five potentially highly toxic BPs were screened from 14 identified BPs, with toxicity predictions guiding the selection of commercial standards for quantification and true toxicity testing. Additionally, BP207 emerged as the most toxic, supported by the predictive toxicity accumulation model (PTAM). Notably, highly toxic BPs feature an acridine structure, indicating its significant contribution to toxicity. These findings offered valuable insights into the degradation mechanisms of emerging contaminants and the biosafety of aquatic environments during deep oxidation.

Nanopatterning of beaded poly(lactic acid) nanofibers for highly electroactive, breathable, UV-shielding and antibacterial protective membranes.

Despite great potential in fabrication of biodegradable protective membranes by electrospinning of poly(lactic acid) (PLA) nanofibers, it is still thwarted by smooth surfaces and poor electroactivity that challenge the promotion of electret properties and long-term air filtration performance. Here, a microwave-assisted synthetic method was used to customize dielectric TiO2 nanocrystals of ultrasmall and uniform dimensions (∼30 nm), which were homogeneously embedded at beaded PLA nanofibers (PLA@TiO2, diameter of around 280 nm) by the combined "electrospinning-electrospray" approach. With small amounts of TiO2 (2, 4 and 6 wt%), the nanopatterned PLA@TiO2 nanofibrous membranes (NFMs) were characterized by largely increased dielectric constants (nearly 1.9), surface potential (up to 1.63 kV) and triboelectric properties (output voltage of 12.2 V). Arising from the improved electroactivity and self-charging mechanisms, the nanopatterned PLA@TiO2 NFMs exhibited remarkable PM0.3 filtration properties (97.9 %, 254.6 Pa) even at the highest airflow rate of 85 L/min, surpassing those of pure PLA membranes (86.2 %, 483.7 Pa). This was moreover accompanied by inhibition rates of 100 % against both E. coli and S. aureus, as well as excellent UV-blocking properties (UPF as high as 3.8, TUVA of 50.9 % and TUVB of 20.1 %). The breathable and electroactive nanopatterned PLA NFMs permit promising applications in multifunctional protective membranes toward excellent UV shielding and high-efficiency removal of both PMs and pathogens.

Nanopatterned Electroactive Polylactic Acid Nanofibrous MOFilters for Efficient PM0.3 Filtration and Bacterial Inhibition.

Biodegradable polylactic acid (PLA) nanofibrous membranes (NFMs) hold great potential to address the increasing airborne particulate matter (PM) and dramatic accumulation of plastic/microplastic pollution. However, the field of PLA NFM-based filters is still in its infancy, frequently dwarfed by the bottlenecks regarding relatively low surface activity, poor electroactivity, and insufficient PM capturing mechanisms. This effort discloses a microwave-assisted approach to minute-level synthesis of dielectric ZIF-8 nanocrystals with high specific surface area (over 1012 m2/g) and ultrasmall size (∼240 nm), which were intimately anchored onto PLA nanofibers (PLA@ZIF-8) by a combined "electrospinning-electrospray" strategy. This endowed the PLA@ZIF-8 NFMs with largely increased electroactivity in terms of elevated dielectric coefficient (an increase of 202%), surface potential (up to 5.8 kV), and triboelectric properties (output voltage of 30.8 V at 10 N, 0.5 Hz). Given the profound control over morphology and electroactivity, the PLA@ZIF-8 NFMs exhibited efficient filtration of PM0.3 (97.1%, 85 L/min) with a decreased air resistance (592.5 Pa), surpassing that of the pure PLA counterpart (88.4%, 650.9 Pa). This was essentially ascribed to realization of multiple filtration mechanisms for PLA@ZIF-8 NFMs, including enhanced physical interception, polar interactions, and electrostatic adsorption, and the unique self-charging function triggered by airflow vibrations. Moreover, perfect antibacterial performance was achieved for PLA@ZIF-8, showing ultrahigh inhibition rates of 99.9 and 100% against E. coli and S. aureus, respectively. The proposed hierarchical structuring strategy, offering the multifunction integration unattainable with conventional methods, may facilitate the development of biodegradable long-term air filters.

Biodegradable Electroactive Nanofibrous Air Filters for Long-Term Respiratory Healthcare and Self-Powered Monitoring.

The concept of triboelectric nanogenerator (TENG)-based fibrous air filters, in which the electroactive fibers are ready to enhance the electrostatic adsorption by sustainable energy harvesting, is appealing for long-term respiratory protection and in vivo real-time monitoring. This effort discloses a self-reinforcing electroactivity strategy to confer extreme alignment and refinement of the electrospun poly(lactic acid) (PLA) nanofibers, significantly facilitating formation of electroactive phases (i.e., ß-phase and highly aligned chains and dipoles) and promotion of polarization and electret properties. It endowed the PLA nanofibrous membranes (NFMs) with largely increased surface potential and filtration performance, as exemplified by efficient removal of PM0.3 and PM2.5 (90.68 and 99.82%, respectively) even at the highest airflow capacity of 85 L/min. With high electroactivity and a well-controlled morphology, the PLA NFMs exhibited superior TENG properties triggered by regular respiratory vibrations, enabling 9.21-fold increase of surface potential (-1.43 kV) and nearly 68% increase of PM0.3 capturing (94.3%) compared to those of conventional PLA membranes. The remarkable TENG mechanisms were examined to elaborately monitor the personal respiration characteristics, particularly those triggered large and rapid variations of output voltages like coughing and tachypnea. Featuring desirable biocompatibility and degradability, the self-powered PLA NFMs permit promising applications in the fabrication of ecofriendly air filters toward high-performance purification and intelligent monitoring.

One-stage versus two-stage management for acute cholecystitis associated with common bile duct stones: a retrospective cohort study.

BACKGROUND: Both one-stage [laparoscopic cholecystectomy (LC) plus laparoscopic common bile duct exploration (LCBDE)] and two-stage [endoscopic retrograde cholangiopancreatography (ERCP) followed by sequential LC] approaches are effective treatment for concomitant common bile duct (CBD) stones and gallstone. Although many studies compared one-stage with two-stage surgical approach for cholecysto-choledocholithiasis, there are very few studies compared the two management strategies for acute cholecystitis (AC) associated with CBD stones. METHODS: Between January 2014 and December 2019, patients with concomitant AC and CBD stones proposed to early surgery were retrospectively studied. The patients were scheduled to undergo either the one-stage [LCBDE and LC (LCBDE+LC) were undertaken at the same operation] or two-stage [preoperative ERCP for CBD stone clearance was followed by LC 1-3 days later (pre-ERCP+LC)] procedure. The success rate of complete stone clearance, procedure-related complication, hospital stay, hospitalization charges and later biliary complications were compared between the two groups. RESULTS: Sixty patients were included in the study, 28 in the one-stage group and 32 in the two-stage group. There was no significant difference in the success rate of complete stone clearance (96.4% vs. 93.8%, P = 1.000), complication rate (10.7% vs. 9.4%, P = 1.000), incidence of pancreatitis (0 vs. 6.3%, P = 0.494) or length of hospital stay (12 ± 5 vs. 11 ± 4 days, P = 0.393) between the two groups. CONCLUSION: For patients with concomitant AC and choledocholithiasis proposed to early surgery, both the one-stage (LCBDE+LC) and two-stage (pre-ERCP+LC) approaches were acceptable and broadly comparable in achieving clearance of CBD stones.

Laparoscopic versus open pancreaticoduodenectomy for pancreatic and periampullary tumor: A meta-analysis of randomized controlled trials and non-randomized comparative studies.

Objective: This meta-analysis compares the perioperative outcomes of laparoscopic pancreaticoduodenectomy (LPD) to those of open pancreaticoduodenectomy (OPD) for pancreatic and periampullary tumors. Background: LPD has been increasingly applied in the treatment of pancreatic and periampullary tumors. However, the perioperative outcomes of LPD versus OPD are still controversial. Methods: PubMed, Web of Science, EMBASE, and the Cochrane Library were searched to identify randomized controlled trials (RCTs) and non-randomized comparative trials (NRCTs) comparing LPD versus OPD for pancreatic and periampullary tumors. The main outcomes were mortality, morbidity, serious complications, and hospital stay. The secondary outcomes were operative time, blood loss, transfusion, postoperative pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH), bile leak (BL), delayed gastric emptying (DGE), lymph nodes harvested, R0 resection, reoperation, and readmission. RCTs were evaluated by the Cochrane risk-of-bias tool. NRCTs were assessed using a modified tool from the Methodological Index for Non-randomized Studies. Data were pooled as odds ratio (OR) or mean difference (MD). This study was registered at PROSPERO (CRD42022338832). Results: Four RCTs and 35 NRCTs concerning a total of 40,230 patients (4,262 LPD and 35,968 OPD) were included. Meta-analyses showed no significant differences in mortality (OR 0.91, p = 0.35), serious complications (OR 0.97, p = 0.74), POPF (OR 0.93, p = 0.29), PPH (OR 1.10, p = 0.42), BL (OR 1.28, p = 0.22), harvested lymph nodes (MD 0.66, p = 0.09), reoperation (OR 1.10, p = 0.41), and readmission (OR 0.95, p = 0.46) between LPD and OPD. Operative time was significantly longer for LPD (MD 85.59 min, p < 0.00001), whereas overall morbidity (OR 0.80, p < 0.00001), hospital stay (MD -2.32 days, p < 0.00001), blood loss (MD -173.84 ml, p < 0.00001), transfusion (OR 0.62, p = 0.0002), and DGE (OR 0.78, p = 0.002) were reduced for LPD. The R0 rate was higher for LPD (OR 1.25, p = 0.001). Conclusions: LPD is associated with non-inferior short-term surgical outcomes and oncologic adequacy compared to OPD when performed by experienced surgeons at large centers. LPD may result in reduced overall morbidity, blood loss, transfusion, and DGE, but longer operative time. Further RCTs should address the potential advantages of LPD over OPD. Systematic review registration: PROSPERO, identifier CRD42022338832.

Utility of Tokyo Guidelines 2018 in early laparoscopic cholecystectomy for mild and moderate acute calculus cholecystitis: A retrospective cohort study.

Background: Tokyo Guidelines 2018 (TG18) proposed laparoscopic cholecystectomy (LC) for acute calculus cholecystitis (ACC) irrespective of the duration of symptoms. This retrospective study assessed the impact of utility of TG18 in early LC for ACC. Methods: From 2018 to 2020, 66 patients with mild (grade I) and moderate (grade II) ACC who underwent early surgery were studied. Subgroup analyses were based on timing of surgery and operation time. Results: A total of 32 and 34 patients were operated within and beyond 7 days since ACC onset. More patients with grade II ACC were in the beyond 7 days group (P < 0.05). More patients with enlarged gallbladder were in the within 7 days group (P < 0.05). The duration of symptoms to admission, symptoms to LC, and operation time were longer in the beyond 7 days group (P < 0.05). There were no significant differences regarding intraoperative blood loss, conversion to bail-out procedures, complication rate, hospital stay, and cost between the two groups (P > 0.05). Longer operation time was significantly associated with duration of symptoms to admission, symptoms to LC, and conversion to laparoscopic subtotal cholecystectomy (LSC) (P < 0.05). Conclusion: In a subset of carefully selected patients, applying TG18 in early LC for mild and moderate ACC results in acceptable clinical outcomes. Standardized safe steps and conversion to LSC in difficult cases are important.

NOP14 regulates the growth, migration, and invasion of colorectal cancer cells by modulating the NRIP1/GSK-3ß/ß-catenin signaling pathway.

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide. Recently, nucleolar complex protein 14 (NOP14) has been discovered to play a critical role in cancer development and progression, but the mechanisms of action of NOP14 in colorectal cancer remain to be elucidated. In this study, we used collected colorectal cancer tissues and cultured colorectal cancer cell lines (SW480, HT29, HCT116, DLD1, Lovo), and measured the mRNA and protein expression levels of NOP14 in colorectal cancer cells using qPCR and western blotting. GFP-NOP14 was constructed and siRNA fragments against NOP14 were synthesized to investigate the importance of NOP14 for the development of colorectal cells. Transwell migration assays were used to measure cell invasion and migration, CCK-8 kits were used to measure cell activity, and flow cytometry was applied to the observation of apoptosis. We found that both the mRNA and protein levels of NOP14 were significantly upregulated in CRC tissues and cell lines. Overexpression of GFP-NOP14 markedly promoted the growth, migration, and invasion of the CRC cells HT19 and SW480, while genetic knockdown of NOP14 inhibited these behaviors. Overexpression of NOP14 promoted the expression of NRIP1 and phosphorylated inactivation of GSK-3ß, leading to the upregulation of ß-catenin. Genetic knockdown of NOP14 had the opposite effect on NRIP1/GSK-3/ß-catenin signals. NOP14 therefore appears to be overexpressed in clinical samples and cell lines of colorectal cancer, and promotes the proliferation, growth, and metastasis of colorectal cancer cells by modulating the NRIP1/GSK-3ß/ß-catenin signaling pathway.

Evaluation of hepatotoxicity induced by 2-ethylhexyldiphenyl phosphate based on transcriptomics and its potential metabolism pathway in human hepatocytes.

Increasing use of organophosphorus flame retardants (OPFRs) has aroused great concern to their uncertain environment risk, especially to human health risk. In our study, hepatotoxicity screening of six aryl-OPFRs, potential hepatotoxicity mechanism of 2-ethylhexyldiphenyl phosphate (EHDPP) using RNA-sequencing and its metabolites were investigated in human hepatocytes (L02). The toxicity results demonstrated that EHDPP should be prioritized for further research with the highest toxicity. Further RNA-seq results through GO and KEGG enrichment analysis indicated that exposure to 10 mg/L of EHDPP significantly affected energy homeostasis, endoplasmic reticulum (ER) stress, apoptosis, cell cycle, and inflammation response in cells. The top 12 hub genes were validated by RT-qPCR and conformed to be mainly related to glycolysis and ER stress, followed by cell cycle and inflammation response. Western blot, apoptosis detection, glycolysis stress test, and cell cycle analysis were further performed to verify the above main pathways. Additionally, it was found in the metabolism experiment that detoxification of EHDPP by phase I and phase II metabolism in cells wasn't significant until 48 h with a metabolic rate of 6.12%. EHDPP was stable and still dominated the induction of toxicity. Overall, this study provided valuable information regarding the toxicity and potential metabolism pathway of EHDPP.

Laparoscopic Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy for Type 2 Diabetes Mellitus in Nonseverely Obese Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Recently, randomized controlled trials (RCTs) have indicated that bariatric surgery in nonseverely obese patients with a body mass index (BMI) less than 35 kg/m2 might be even superior to medical therapy with regard to type 2 diabetes mellitus (T2DM) remission, but the efficacy of laparoscopic Roux-en-Y gastric bypass (LRYGB) compared with laparoscopic sleeve gastrectomy (LSG) in nonseverely obese patients has not been conclusively determined. The objective of this study is to compare LRYGB versus LSG for T2DM in nonseverely obese patients. METHODS: A meta-analysis identifying RCTs evaluating LRYGB versus LSG for T2DM in nonseverely obese patients was conducted. The primary outcome was T2DM remission. Additional analyses comprised percent excess weight loss (%EWL), BMI, waist circumference, hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), serum lipid level, medication use, quality of life, and adverse events. RESULTS: Four RCTs concerning total 296 patients were included. T2DM remission rate and %EWL were of no difference between the two bariatric procedures. LRYGB was associated with lower BMI, waist circumference, low-density lipoprotein, and higher high-density lipoprotein than LSG. However, HbA1c, FPG, total cholesterol, and triglyceride were not significantly different between the two surgical groups. The medication use and quality of life were improved in both two groups. The gastroesophageal reflux diseases of LRYGB group were less than that of LSG group. Dumping syndromes were noted more frequently in the LRYGB group. CONCLUSIONS: Both LRYGB and LSG have comparative effect on resolving T2DM in nonseverely obese patients at midterm follow-up. Further RCTs should address the potential risks and long-term effects of LRYGB and LSG in nonseverely obese patients.

Upregulation of WEE1 is a potential prognostic biomarker for patients with colorectal cancer.

WEE1 is a serine/threonine protein kinase that inactivates cell division cycle 2 and is therefore a critical cell cycle regulator. Increased WEE1 expression has been observed in numerous types of human malignancies, including hepatocellular carcinoma and melanoma. WEE1 inhibition also results in evident anti-tumor effects in several human tumor cells including colon cancer cells, suggesting WEE1 as a potential therapeutic target for the treatment of cancer. However, the expression pattern of WEE1 in colorectal cancer (CRC) remains unclear. In the present study, WEE1 mRNA expression in 43 cases of CRC tissues matched with adjacent normal tissues was determined by reverse-transcription quantitative polymerase chain reaction. The results demonstrated that WEE1 mRNA expression was significantly increased in CRC tissues and that this upregulation correlated significantly with hepatic metastasis, distant metastasis and high tumor node metastasis (TNM) stage of CRC. Additionally, WEE1 protein in 102 CRC tissue samples was detected by immunohistochemistry, and positive staining of WEE1 was identified in more than half of patients with CRC. WEE1 staining scores were also observed to be associated with distant metastasis and high TNM stage of CRC. In addition, patients with CRC with high WEE1 staining score (2+ or 3+) exhibited either poorer overall survival or poorer disease-free survival compared with those with low WEE1 staining score (0 or 1+). The multivariable Cox model also identified a high WEE1 staining score as well as high TNM stage to be independent prognostic factors for CRC. In conclusion, WEE1 upregulation is associated with a high degree of malignancy and poor prognosis of CRC, suggesting WEE1 as a potential prognostic biomarker for CRC.

Mus81 knockdown improves chemosensitivity of hepatocellular carcinoma cells by inducing S-phase arrest and promoting apoptosis through CHK1 pathway.

As a critical endonuclease in DNA repair, Mus81 is traditionally regarded as a tumor suppressor, but recently correlated with the sensitivity of mitomycin C and 5-fluorouracil in colon cancer and breast cancer cells. However, its role in chemosensitivity of other human malignancies still remains unknown. This study therefore aims to investigate the effects of Mus81 knockdown on the chemosensitivity of hepatocellular carcinoma (HCC), a usually chemorefractory tumor, and explore the underlying mechanisms. Mus81 expression in HepG2 and Bel-7402 HCC cell lines was depleted by lentivirus-mediated short hairpin RNA and the elevated sensitivity of these Mus81-inhibited HCC cells to therapeutic agents, especially to epirubicin (EPI), was evidenced by MTT assay and an HCC chemotherapy mouse model. Flow cytometric analysis also showed that Mus81 knockdown lead to an obvious S-phase arrest and an elevated apoptosis in EPI-treated HepG2 and Bel-7402 cells, which could be rescued by CHK1 inhibition. The activation of CHK1/CDC25A/CDK2 pathway was also demonstrated in Mus81-inhibited HepG2 cells and xenograft mouse tumors under EPI treatment. Meanwhile, the apoptosis of HepG2 cells in response to EPI was remarkably promoted by Mus81 knockdown through activating p53/Bax/Caspase-3 pathway under the controlling of CHK1. In addition, CHK2 inhibition slightly raised CHK1 activity, thereby enhancing the S-phase arrest and apoptosis induced by EPI in Mus81-suppressed HCC cells. In conclusion, Mus81 knockdown improves the chemosensitivity of HCC cells by inducing S-phase arrest and promoting apoptosis through CHK1 pathway, suggesting Mus81 as a novel therapeutic target for HCC.

[Clinical significance of tumor budding detection in stage II colon cancer].

OBJECTIVE: To investigate the association of tumor budding with recurrence and survival of patients with stage II colon cancer, in order to identify patients with high-risk recurrence who may benefit from adjuvant therapy. METHODS: Clinical data of 112 stage II colon cancer patients in Guangzhou Red Cross Hospital between 1998 and 2007 were analyzed retrospectively. The degree of tumor budding was assessed by two observers and classified according to the number of tumor buds in the area with the greatest budding intensity on HE stain slides, as high-grade budding (≥10, n=30) and low-grade budding (≤9, n=82). Progression-free and cancer-specific survival were analyzed using the Kaplan-Meier method and Cox regression. RESULTS: All the patients were followed up and the median follow-up was 78 months. The 5-year progression-free survival rates for patients with high-grade and low-grade budding were 65.3% and 90.7% respectively (P=0.008). The 5-year cancer-specific survival rates were 72.1% and 93.8% respectively (P=0.001). Cox regression analysis demonstrated tumor budding was an independent predictor of disease progression (RR=4.572, 95%CI:2.218-11.746, P=0.002) and cancer-related death (RR=4.116, 95%CI:1.657-10.384, P=0.012). CONCLUSION: Tumor budding is a strong prognostic index for adverse outcome in stage II colon cancer patients,which may serve as a prognostic marker to identify patients with high risk of recurrence who may benefit from adjuvant therapy.