Antitumorigenic potential of Lactobacillus-derived extracellular vesicles: p53 succinylation and glycolytic reprogramming in intestinal epithelial cells via SIRT5 modulation.

OBJECTIVE: Colorectal cancer progression involves complex cellular mechanisms. This study examines the effects of Lactobacillus plantarum-derived extracellular vesicles (LEVs) on the SIRT5/p53 axis, focusing on glycolytic metabolic reprogramming and abnormal proliferation in intestinal epithelial cells. METHODS: LEVs were isolated from Lactobacillus plantarum and incubated with Caco-2 cells. Differential gene expression was analyzed through RNA sequencing and compared with TCGA-COAD data. Key target genes and pathways were identified using PPI network and pathway enrichment analysis. Various assays, including RT-qPCR, EdU staining, colony formation, flow cytometry, and Western blotting, were used to assess gene expression, cell proliferation, and metabolic changes. Co-immunoprecipitation confirmed the interaction between SIRT5 and p53, and animal models were employed to validate in vivo effects. RESULTS: Bioinformatics analysis indicated the SIRT5/p53 axis as a critical pathway in LEVs' modulation of colorectal cancer. LEVs were found to inhibit colorectal cancer cell proliferation and glycolytic metabolism by downregulating SIRT5, influencing p53 desuccinylation. In vivo, LEVs regulated this axis, reducing tumor formation in mice. Clinical sample analysis showed that SIRT5 and p53 succinylation levels correlated with patient prognosis. CONCLUSION: Lactobacillus-derived extracellular vesicles play a pivotal role in suppressing colonic tumor formation by modulating the SIRT5/p53 axis. This results in decreased glycolytic metabolic reprogramming and reduced proliferation in intestinal epithelial cells.

Robot-assisted radical nephroureterectomy using the KangDuo Surgical Robot-01 Sys-tem versus the da Vinci System: a multicenter prospective randomized controlled trial.

INTRODUCTION: We aim to compare the safety and effectiveness of the KangDuo (KD)-Surgical Robot-01 (KD-SR-01) system and the da Vinci (DV) system for robot-assisted radical nephroureterectomy (RARNU). MATERIALS AND METHODS: This multicenter prospective randomized controlled trial was conducted between March 2022 and September 2023. Group 1 included 29 patients undergoing KD-RARNU. Group 2 included 29 patients undergoing DV-RARNU. Patient demographic and clinical characteristics, perioperative data, and follow-up outcomes were collected prospectively and compared between the two groups. RESULTS: There were no significant differences in patient baseline demographic and preoperative characteristics between the two groups. The success rates in both groups were 100% without conversion to open or laparoscopic surgery or positive surgical margins. No significant difference was observed in docking time [242 (120-951) s vs 253 (62-498) s, P = 0.780], console time [137 (55-290) min vs 105 (62-220) min, P = 0.114], operative time [207 (121-460) min vs 185 (96-305) min, P = 0.091], EBL [50 (10-600) mL vs 50 (10-700) mL, P = 0.507], National Aeronautics and Space Administration Task Load Index scores, and postoperative serum creatinine levels between the two groups. None of the patients showed evidence of distant metastasis, local recurrence, or equipment-related adverse events during the four-week follow-up. One (3.4%) patient in Group 2 experienced postoperative enterovaginal and enterovesical fistulas (Clavien-Dindo grade III). CONCLUSIONS: The KD-SR-01 system is safe and effective for RARNU compared to the DV Si or Xi system. Further randomized controlled studies with larger sample sizes and longer durations are required.

Novel therapeutic targets: bifidobacterium-mediated urea cycle regulation in colorectal cancer.

BACKGROUND AND PURPOSE: Colorectal cancer (CRC) is a widespread malignancy with a complex and not entirely elucidated pathogenesis. This study aims to explore the role of Bifidobacterium in the urea cycle (UC) and its influence on the progression of CRC, a topic not extensively studied previously. EXPERIMENTAL APPROACH: Utilizing both bioinformatics and experimental methodologies, this research involved analyzing bacterial abundance in CRC patients in comparison to healthy individuals. The study particularly focused on the abundance of BA. Additionally, transcriptomic data analysis and cellular experiments were conducted to investigate the impact of Bifidobacterium on ammonia metabolism and mitochondrial function, specifically examining its regulation of the key UC gene, ALB. KEY RESULTS: The analysis revealed a significant decrease in Bifidobacterium abundance in CRC patients. Furthermore, Bifidobacterium was found to suppress ammonia metabolism and induce mitochondrial dysfunction through the regulation of the ALB gene, which is essential in the context of UC. These impacts contributed to the suppression of CRC cell proliferation, a finding corroborated by animal experimental results. CONCLUSIONS AND IMPLICATIONS: This study elucidates the molecular mechanism by which Bifidobacterium impacts CRC progression, highlighting its role in regulating key metabolic pathways. These findings provide potential targets for novel therapeutic strategies in CRC treatment, emphasizing the importance of microbiota in cancer progression.

A retrospective study of the efficacy of sulbactam in the treatment of patients with extensively drug-resistant Acinetobacter baumannii infections.

PURPOSE: Sulbactam (SBT) is one of the most significant treatments for patients with extensively drug-resistant Acinetobacter baumannii (XDR-AB). However, the efficacy and safety of SBT and its high dose regimen has not been well documented. This retrospective study aimed to assess the efficacy and safety of SBT-based treatment, particularly at high-dose (≥ 6 g/day), for XDR-AB infection. METHOD: A total of 52 XDR-AB infected patients treated with intravenous SBT at Peking Union Medical College Hospital were included. The primary outcome was 28-day all-cause mortality, while the secondary outcome was 14-day clinical response and the time of response. The formulation of SBT in our study is 0.5 g per vial. RESULTS: Among the patients, the 28-day all-cause mortality rate was 36.5% (19/52), and the favorable 14-day clinical response rate was 59.6% (31/52). The 28-day mortality was independently associated coinfection with gram-positive bacteria (GPB) and a shorter duration of therapy. Patients with intracranial infection might have a longer survival time. A favorable 14-day clinical response was associated with the dose of SBT, and a longer treatment duration. However, the higher creatinine clearance (CrCl) associated with a worse clincal response. In addition, a higher SBT dosage was significantly correlated with a shorter time to clinical response. No adverse effects related were reported. CONCLUSION: The single-agent formulation of SBT emerges as a promising alternative for the treatment of XDR-AB infection, such as intracranial infection, particularly at high doses (≥ 6 g/day). Besides, longer duration of treatment correlates with higher survival rate and better favorable clinical response. Higher CrCl negatively correlates with favorable clinical response.

Renal function after ureteral reconstruction surgery in patients with solitary kidney.

Background: Ureteral strictures (US) could lead to impaired kidney function, which was alleviated by ureteral reconstruction surgery. However, solitary kidney (SK) patients with US were more complicated to treat. This study aimed to evaluate the impact of reconstruction surgery on renal function based on estimated glomerular filtration rate (eGFR) in patients with SK. Methods: We retrospectively enrolled patients who underwent reconstruction surgery between April 2014 to March 2022. eGFR was measured pre- and postoperatively. The 'static renal function' was defined as a change in eGFR of 20% or less at the last follow-up, and the 'worsening renal function group' was defined as a decrease of greater than 20%. Results: A total of 61 SK patients were involved. The success rate of ureteral reconstruction surgery was 90.16% (55/61). The median follow-up time was 20.8 months (range, 3.7-109.2 months). The median eGFR was 65.5 (range, 15.1-99.9) and 65.3 (range, 3.8-123.4) mL/min/1.73 m2 at the baseline and the last follow-up. No statistically significant difference in eGFR was observed between the preoperative baseline and last follow-up visits (P=0.58). However, in patients with baseline renal dysfunction [chronic kidney disease (CKD) stage 3-5], the eGFR significantly improved at the last follow-up compared to the baseline (P=0.02). Three patients developed a 'worsening renal function' (4.92%). Besides, the systolic blood pressures (SBP) at follow-up significantly reduced compared to the preoperative baseline (P=0.002). Conclusions: Ureteral reconstruction surgery is an effective treatment to preserve renal function, which also achieves a high success rate and is associated with the reduction of SBP for SK patients with US.

Full-chain analysis on emerging contaminants in soil: Source, migration and remediation.

Emerging contaminants (ECs) are gaining attention due to their prevalence and potential negative impacts on the environment and human health. This paper provides a comprehensive review of the status and trends of soil pollution caused by ECs, focusing on their sources, migration pathways, and environmental implications. Significant ECs, including plastics, synthetic polymers, pharmaceuticals, personal care products, plasticizers, and flame retardants, are identified due to their widespread use and toxicity. Their presence in soil is attributed to agricultural activities, urban waste, and wastewater irrigation. The review explores both horizontal and vertical migration pathways, with factors such as soil type, organic matter content, and moisture levels influencing their distribution. Understanding the behavior of ECs in soil is critical to mitigating their long-term risks and developing effective soil remediation strategies. The paper also examines the advantages and disadvantages of in situ and ex situ treatment approaches for ECs, highlighting optimal physical, chemical, and biological treatment conditions. These findings provide a fundamental basis for addressing the challenges and governance of soil pollution induced by ECs.

Alantolactone attenuates high-fat diet-induced inflammation and oxidative stress in non-alcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a chronic disease with an increasing incidence, which can further develop into liver fibrosis and hepatocellular carcinoma at the end stage. Alantolactone (Ala), a sesquiterpene lactone isolated from Asteraceae, has shown anti-inflammatory effects in different models. However, the therapeutic effect of Ala on NAFLD is not clear. METHODS: C57BL/6 mice were fed a high-fat diet (HFD) to induce NAFLD. After 16 weeks, Ala was administered by gavage to observe its effect on NAFLD. RNA sequencing of liver tissues was performed to investigate the mechanism. In vitro, mouse cell line AML-12 was pretreated with Ala to resist palmitic acid (PA)-induced inflammation, oxidative stress and fibrosis. RESULTS: Ala significantly inhibited inflammation, fibrosis and oxidative stress in HFD-induced mice, as well as PA-induced AML-12 cells. Mechanistic studies showed that the effect of Ala was related to the induction of Nrf2 and the inhibition of NF-κB. Taken together, these findings suggested that Ala exerted a liver protective effect on NAFLD by blocking inflammation and oxidative stress. CONCLUSIONS: The study found that Ala exerted a liver protective effect on NAFLD by blocking inflammation and oxidative stress, suggesting that Ala is an effective therapy for NAFLD.

Effects of short-term supplementation with DHA-enriched phosphatidylcholine and phosphatidylserine on lipid profiles in the brain and liver of n-3 PUFA-deficient mice in early life after weaning.

BACKGROUND: Lack of n-3 polyunsaturated fatty acids during the period of maternity drastically lowers the docosahexaenoic acid (DHA) level in the brain of offspring and studies have demonstrated that different molecular forms of DHA are beneficial to brain development. The aim of this study was to investigate the effect of short-term supplementation with DHA-enriched phosphatidylserine (PS) and phosphatidylcholine (PC) on DHA levels in the liver and brain of congenital n-3-deficient mice. RESULTS: Dietary supplementation with DHA significantly changed the fatty acid composition of various phospholipid molecules in the cerebral cortex and liver while DHA-enriched phospholipid was more effective than DHA triglyceride (TG) in increasing brain and liver DHA. Both DHA-PS and DHA-PC could effectively increase the DHA levels, but DHA in the PS form was superior to PC in the contribution of DHA content in the brain ether-linked PC (ePC) and liver lyso-phosphatidylcholine molecular species. DHA-PC showed more significant effects on the increase of DHA in liver TG, PC, ePC, phosphatidylethanolamine (PE) and PE plasmalogen (pPE) molecular species and decreasing the arachidonic acid level in liver PC plasmalogen, ePC, PE and pPE molecular species compared with DHA-PS. CONCLUSION: The effect of dietary interventions with different molecular forms of DHA for brain and liver lipid profiles is different, which may provide theoretical guidance for dietary supplementation of DHA for people. © 2024 Society of Chemical Industry.

Enhanced Selective Degradation of Pharmaceutical and Personal Care Products by ß-Cyclodextrin-Decorated ZIF-67 Nanocomposites in Reclaimed Water.

A peroxymonosulfate oxidation system was developed via modification of ß-cyclodextrin (ß-CD) on the surface of Fe2+-doped ZIF-67 (CD/Fe@ZIF-67) as an activator. The 99.7% carbamazepine, 91.3% bisphenol A (BPA), and 95.4% diclofenac (DCF) degradation efficiency were achieved within 10 min, 60, and 1 min, respectively. The hydrophobicity of these three pollutants is positively correlated with their adsorption kinetic constants by CD/Fe@ZIF-67 due to the introduction of ß-CD. Scavenger experiments and electron spin resonance spectra confirmed that carbamazepine was preferentially oxidized by SO4•- [λ(SO4•-)(70.5%) > λ(•OH)(28.2%) > λ(O2•-)(1.3%)], where SO4•- and O2•- played dominant roles in the degradation of BPA [λ(SO4•-)(71.7%) > λ(O2•-)(22.8%) > λ(•OH)(5.5%)], and O2•- was responsible for DCF removal [λ(O2•-) = 93.2%]. Additionally, the particulate catalyst was immobilized in the shell side of a ceramic membrane in a membrane reactor for catalyst recovery. This reactor achieved nearly 100% removal efficiency under optimal conditions: 0.036 wt % catalyst loading, 0.5 mM peroxymonosulfate concentration, 1 L inflow, 10 mg/L initial carbamazepine concentration, and 0.012 L/min hydraulic retention time. In summary, this study elucidates the active role of ß-CD in a polymetallic/peroxymonosulfate system and provides valuable insights into the development of effective oxidation methods for pharmaceutical and personal care products in wastewater.

Electrochemical water splitting enhancement by introducing mesoporous NiCoFe-trimetallic phosphide nanosheets as catalysts for the oxygen evolution reaction.

Transition metal-based catalysts are widely used in electrocatalysis, especially in the field of water splitting, due to their excellent electrochemical performance, which focuses on improving the efficiency of the complex oxygen evolution reaction (OER) that occurs at the anode. Transition metal-based catalysts will undergo electrochemical surface reconstruction and form (oxy)hydroxide-based hybrids, which consider the actual active sites for OER. So many efforts have been made to know the origin of the effect of electrochemical surface reconstruction on the performance of the OER. Herein, NiCoFe-phosphide catalyst nanosheets were constructed by a simple one-step hydrothermal reaction by adding oleylamine and ethanol to water solvent during the preparation of the catalyst precursor and high-temperature gas-phase phosphating and significantly showed high effectiveness catalytic activity and conductivity in comparison to normal and traditional preparation methods. Electrochemical analysis, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and high-resolution transmission electron microscopy (HRTEM) demonstrate that the surface was constructed during the electrochemical reaction and formed an amorphous layer of MOx(OH)y active sites, which increased the electrochemical surface area and promoted charge transfer. As well, the synthesized NiCoFePx-PNSs catalyst nanosheets exhibit excellent catalytic activity with a low overpotential equal to 259 mV to achieve the OER at a current density of 10 mA cm-2 and a low Tafel slope of 50.47 mV dec-1 which is better than for most reported transition metal-based electrocatalysts. This work provides a new design for a transition metal-based catalyst for OER as well as further insights into the effect of electrochemical surface reconstruction on intrinsic activity and OER performance.

Two-dimensional molybdenum boride coordinating with ruthenium nanoparticles to boost hydrogen generation from hydrolytic dehydrogenation of ammonia borane.

The coordination between carrier and active metal is critical to the catalytic efficiency of ammonia borane (AB) hydrolysis reaction. In the present study, we report a new type of catalytic support based on molybdenum boride (MBene) MoAl1-xB and demonstrate that the effective combination of MoAl1-xB with Ru nanoparticles can realize the significantly enhanced performance for hydrogen generation. Owing to the efficient activation and dissociation of reactants, the optimal Ru/MoAl1-xB catalyst achieves the large turnover frequency of 494 molH2 molRu-1 min-1, high hydrogen generation rate of 119817 mL min-1 gRu-1 and favorable apparent activation energy of 39.2 kJ mol-1 for the catalytic hydrolysis of AB under alkaline-free condition. The isotopic test suggests the cleavage of OH bond in H2O is the rate-determining step for hydrolysis reaction, while the fracture of B-H bond in AB is also well revealed by attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy. Significantly, the flexible on-demand hydrogen generation is achieved by using chemical switches for on-off AB hydrolysis. This study provides a new support platform based on two-dimensional MBene to exploit efficient catalysts to boost AB dehydrogenation.

Low energy-consumption oriented membrane fouling control strategy in anaerobic fluidized membrane bioreactor.

Anaerobic fluidized membrane bioreactors (AFMBR) has attracted growing interest as an emerging wastewater treatment technology towards energy recovery from wastewater. AFMBR combines the advantages of anaerobic digestion and membrane bioreactors and shows great potential in overcoming limiting factors such as membrane fouling and low efficiency in treating low-strength wastewater such as domestic sewage. In AFMBR, the fluidized media performs significant role in reducing the membrane fouling, as well as improving the anaerobic microbial activity of AFMBRs. Despite extensive research aimed at mitigating membrane fouling in AFMBR, there has yet to emerge a comprehensive review focusing on strategies for controlling membrane fouling with an emphasis on low energy consumption. Thus, this work overviews the recent progress of AFMBR by summarizing the factors of membrane fouling and energy consumption in AFMBR, and provides targeted in-depth analysis of energy consumption related to membrane fouling control. Additionally, future development directions for AFMBR are also outlooked, and further promotion of AFMBR engineering application is expected. By shedding light on the relationship between energy consumption and membrane fouling control, this review offers a useful information for developing new AFMBR processes with an improved efficiency, low membrane fouling and low energy consumption, and encourages more research efforts and technological advancements in the domain of AFMBR.

Activating peroxymonosulfate with Fe-doped biochar for efficient removal of tetracycline: Dual action of reactive oxygen species and electron transfer.

If pharmaceutical wastewater is not managed effectively, the presence of residual antibiotics will result in significant environmental contamination. In addition, inadequate utilization of agricultural waste represents a squandering of resources. The objective of this research was to assess the efficacy of iron-doped biochar (Fe-BC) derived from peanut shells in degrading high concentrations of Tetracycline (TC) wastewater through activated peroxymonosulfate. Fe-BC demonstrated significant efficacy, achieving a removal efficiency of 87.5% for TC within 60 min without the need to adjust the initial pH (20 mg/L TC, 2 mM PMS, 0.5 g/L catalyst). The degradation mechanism of TC in this system involved a dual action, namely Reactive Oxygen Species (ROS) and electron transfer. The primary active sites were the Fe species, which facilitated the generation of SO4•-, •OH, O2•-, and 1O2. The presence of Fe species and the C=C structure in the Fe-BC catalyst support the electron transfer. Degradation pathways were elucidated through the identification of intermediate products and calculation of the Fukui index. The Toxicity Estimator Software Tool (T.E.S.T.) suggested that the intermediates exhibited lower levels of toxicity. Furthermore, the system exhibited exceptional capabilities in real water and circulation experiments, offering significant economic advantages. This investigation provides an efficient strategy for resource recycling and the treatment of high-concentration antibiotic wastewater.

Real-world safety profile of tetracyclines in children younger than 8 years old: an analysis of FAERS database and review of case report.

BACKGROUND: The study aims to obtain the real-world safety profile of tetracyclines in children younger than 8 years old and provide reference for clinical drug applications. RESEARCH DESIGN AND METHODS: We made a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database through OpenVigil 2 and conducted a review of case reports regarding adverse drug reactions (ADRs) of tetracyclines in children younger than 8-year-old. RESULTS: FAERS analysis identified 32 ADRs of tetracyclines in children younger than 8-year-old. Respiratory, thoracic, and mediastinal disorders contained the most frequent ADRs among all system organ classes (SOCs). The top three positive signals with the highest proportional reporting ratio (PRR) were laryngeal injury, Horner's syndrome and methaemoglobinaemia. Sixteen published tetracyclines-associated cases in children younger than 8-year-old were identified in the literature, concentrating in three SOCs. Gastrointestinal disorders were the most commonly reported cases (n = 12). CONCLUSIONS: Several ADRs were newly reported only in children younger than 8-year-old in our research, including Horner's syndrome and methemoglobinemia. We recommended that the clinical practitioners should pay attention to the ADRs both in instruction and beyond the label. Take close care of children and timely intervene when the treatment is inevitable.

Risk Factors of New Symptomatic Fractures After Vertebroplasty: A Retrospective Cohort Study of 268 Patients with Painful Osteoporotic Vertebral Compression Fracture.

OBJECTIVE: To evaluate the risk factors of new osteoporotic vertebral compression fractures (OVCFs) after percutaneous vertebroplasty (PVP). METHODS: From January 2016 to November 2019, patients suffering from OVCFs were retrospectively reviewed. The independent influence factors for new OVCFs after PVP were assessed, from following variables: age, sex, body mass index, bone mineral density (BMD), history of alcoholism, smoking, hypertension, diabetes, glucocorticoid use, and prior vertebral fractures, the number of initial fractures, mean cement volume, method of puncture, D-type of cement leakage, and regular antiosteoporosis treatment. RESULTS: A total of 268 patients with 347 levels met the inclusion criteria and were finally included in this study. Forty-nine levels of new OVCFs among 33 patients (12.31%) were observed during the follow-up period. It indicated that female (adjusted odds ratio [OR]: 6.812, 95% confidence interval {CI}: [1.096, 42.337], P = 0.040), lower BMD (adjusted OR: 0.477, 95% CI: [0.300, 0.759], P = 0.002), prior vertebral fractures (adjusted OR: 16.145, 95% CI: [5.319, 49.005], P = 0.000), and regular antiosteoporosis treatment (adjusted OR: 0.258, 95% CI: [0.086, 0.774], P = 0.016) were independent influence factors for new OVCF. The cut-off value of BMD to reach new OVCF was -3.350, with a sensitivity of 0.660 and a specificity of 0.848. CONCLUSION: Female, lower BMD (T-score of lumbar), prior vertebral fractures, and regular antiosteoporosis treatment were independent influencing factors. BMD (T-score of lumbar) lower than -3.350 would increase risk for new OVCF, and none osteoporotic treatment has detrimental effect on new onset fractures following PVP.

Robot-Assisted Radical Nephroureterectomy Using the KangDuo-Surgical Robot-01 System: A Prospective, Single-Center, Single-Arm Clinical Study.

Purpose: To investigate the feasibility, safety, and efficacy of the KangDuo-Surgical Robot-01 (KD-SR-01) system for robot-assisted radical nephroureterectomy (RARNU). Materials and Methods: This prospective, single-center, single-arm clinical study of patients with upper tract urothelial carcinoma (UTUC) was conducted from August 2022 to July 2023 using the KD-SR-01 system. The perioperative and follow-up data were prospectively recorded. The National Aeronautics and Space Administration task load index was calculated to present ergonomics. The technique was described in detail. Results: A total of 13 patients underwent RARNU. None of the cases conversed to laparoscopic procedure or open procedure. The median docking time and console time were 524 seconds (range 139-963 seconds) and 102.2 minutes (range 55.3-249.3 minutes), respectively. The median estimated blood loss was 40 mL (range 10-100 mL). None of the patients required intraoperative blood transfusion. The median postoperative hospital stay was 4 days (range 2-7 days). Intraoperative or postoperative complications (Clavien-Dindo grade I) occurred in nine patients. The surgeon task load index global score achieved 1.05 ± 1.86. Three patients received the single-docking technique, demonstrating similar perioperative results compared with patients with redocking. The study is registered at www.chictr.org.cn (ChiCTR2200056672). Conclusions: The KD-SR-01 system was feasible, safe, and effective for RARNU.

Development and validation of a novel nomogram for predicting overall survival patients with neuroblastoma.

PURPOSE: The aim of this study was to develop a nomogram specially for predicting overall survival (OS) for Chinese patients with neuroblastoma (NB). METHODS: Patients with pathologically confirmed NB who were newly diagnosed and received treatments at our hospital from October 2013 to October 2021 were retrospectively reviewed. The nomogram for OS were built based on Cox regression analysis. The validation of the prognostic model was evaluated by concordance index (C-index), calibration curves, and decision curve analyses (DCAs). RESULTS: A total of 254 patients with NB were included in this study. They were randomly divided into a training cohort (n = 178) and a validation cohort (n = 76) at a ratio of 7:3. Multivariate analyses revealed that prognostic variables significantly related to the OS were age at diagnosis, bone metastasis, hepatic metastasis, INSS stage, MYCN status and DNA ploidy. The nomogram was constructed based on above 6 factors. The C-index values of the nomogram for predicting 3-year and 5-year OS were 0.926 and 0.964, respectively. The calibration curves of the nomogram showed good consistency between nomogram prediction and actual survival. The DCAs showed great clinical usefulness of the nomograms. Furthermore, patients with low-risk identified by our nomogram had much higher OS than those with high-risk (p < 0.001). CONCLUSION: The nomogram we constructed exhibited good predictive performance and could be used to assist clinicians in their decision-making process.

Targeted Integration of siRNA against Porcine Cytomegalovirus (PCMV) Enhances the Resistance of Porcine Cells to PCMV.

In the world's first pig-to-human cardiac cytomegalovirus (PCMV), xenotransplant and elevated levels of porcine key factors contributing to patient mortality were considered. This has renewed attention on PCMV, a virus widely prevalent in pigs. Currently, there are no effective drugs or vaccines targeting PCMV, and its high detection difficulty poses challenges for prevention and control research. In this study, antiviral small hairpin RNA (shRNA) was selected and inserted into the Rosa26 and miR-17-92 loci of pigs via a CRISPR/Cas9-mediated knock-in strategy. Further in vitro viral challenge experiments demonstrated that these genetically edited pig cells could effectively limit PCMV replication. Through this process, we constructed a PCMV-infected cell model, validated partial viral interference sites, enhanced gene knock-in efficiency, performed gene editing at two different gene loci, and ultimately demonstrated that RNA interference (RNAi) technology combined with CRISPR/Cas9 has the potential to generate pig cells with enhanced antiviral infection capabilities. This opens up possibilities for the future production of pig populations with antiviral functionalities.

Insight into key interactions between diverse factors and membrane fouling mitigation in anaerobic membrane bioreactor.

Anaerobic membrane bioreactors (AnMBRs) have garnered considerable attention as a low-energy and low-carbon footprint treatment technology. With an increasing number of scholars focusing on AnMBR research, its outstanding performance in the field of water treatment has gradually become evident. However, the primary obstacle to the widespread application of AnMBR technology lies in membrane fouling, which leads to reduced membrane flux and increased energy demand. To ensure the efficient and long-term operation of AnMBRs, effective control of membrane fouling is imperative. Nevertheless, the interactions between various fouling factors are complex, making it challenging to predict the changes in membrane fouling. Therefore, a comprehensive analysis of the fouling factors in AnMBRs is necessary to establish a theoretical basis for subsequent membrane fouling control in AnMBR applications. This review aims to provide a thorough analysis of membrane fouling issues in AnMBR applications, particularly focusing on fouling factors and fouling control. By delving into the mechanisms behind membrane fouling in AnMBRs, this review offers valuable insights into mitigating membrane fouling, thus enhancing the lifespan of membrane components in AnMBRs and identifying potential directions for future AnMBR research.