Synergistic induction of mitotic pyroptosis and tumor remission by inhibiting proteasome and WEE family kinases.

Mitotic catastrophe (MC), which occurs under dysregulated mitosis, represents a fascinating tactic to specifically eradicate tumor cells. Whether pyroptosis can be a death form of MC remains unknown. Proteasome-mediated protein degradation is crucial for M-phase. Bortezomib (BTZ), which inhibits the 20S catalytic particle of proteasome, is approved to treat multiple myeloma and mantle cell lymphoma, but not solid tumors due to primary resistance. To date, whether and how proteasome inhibitor affected the fates of cells in M-phase remains unexplored. Here, we show that BTZ treatment, or silencing of PSMC5, a subunit of 19S regulatory particle of proteasome, causes G2- and M-phase arrest, multi-polar spindle formation, and consequent caspase-3/GSDME-mediated pyroptosis in M-phase (designated as mitotic pyroptosis). Further investigations reveal that inhibitor of WEE1/PKMYT1 (PD0166285), but not inhibitor of ATR, CHK1 or CHK2, abrogates the BTZ-induced G2-phase arrest, thus exacerbates the BTZ-induced mitotic arrest and pyroptosis. Combined BTZ and PD0166285 treatment (named BP-Combo) selectively kills various types of solid tumor cells, and significantly lessens the IC50 of both BTZ and PD0166285 compared to BTZ or PD0166285 monotreatment. Studies using various mouse models show that BP-Combo has much stronger inhibition on tumor growth and metastasis than BTZ or PD0166285 monotreatment, and no obvious toxicity is observed in BP-Combo-treated mice. These findings disclose the effect of proteasome inhibitors in inducing pyroptosis in M-phase, characterize pyroptosis as a new death form of mitotic catastrophe, and identify dual inhibition of proteasome and WEE family kinases as a promising anti-cancer strategy to selectively kill solid tumor cells.

Research on the prognostic value of adjusting intraperitoneal three-dimensional quality evaluation mode in laparoscopic cholecystectomy patients.

BACKGROUND: Benign gallbladder diseases have become a high-prevalence condition not only in China but also worldwide. The main types of benign gallbladder diseases include gallbladder polyps, acute and chronic cholecystitis, and gallstones, with gallstones being the most common, accounting for over 70% of cases. Although the mortality rate of benign gallbladder diseases is low, they carry obvious potential risks. Studies have shown that an increased incidence of benign gallbladder diseases can increase the risk of cardiovascular diseases and gallbladder cancer, resulting in a substantial disease burden on patients and their families. AIM: To assess the medical utility of the Configuration-Procedure-Consequence (CPC) three-dimensional quality evaluation model in modulating the prognosis of laparoscopic cholecystectomy patients. METHODS: A total of 98 patients who underwent laparoscopic cholecystectomy in our hospital from February 2020 to January 2022 were selected as the subjects. According to the random number table method, they were divided into a study group and a control group, with 49 patients in each group. The control group received routine perioperative care, while the study group had the addition of the CPC three-dimensional quality evaluation. The postoperative recovery-related indicators (time to first flatus, time to oral intake, time to ambulation, hospital stay), stress indicators (cortisol and adrenaline levels), distinctions in anxiety and depression status, and the incidence of perioperative complications were compared. RESULTS: The time to first flatus, time to oral intake, time to ambulation, and hospital stay of the study group patients were obviously lower than those of the control group patients, with statistical significance (P < 0.05). On the 1st day after admission, there were no obvious distinctions in cortisol and adrenaline levels in blood samples, as well as in the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) scores between the study group and the control group (P > 0.05). However, on the 3rd day after surgery, the cortisol and adrenaline levels, as well as SAS and SDS scores of the study group patients, were obviously lower than those of the control group patients (P < 0.05). The study group had 2 cases of incisional infection and 1 case of pulmonary infection, with a total incidence of complications of 6.12% (3/49), which was obviously lower than the 20.41% (10/49) in the control group (P < 0.05). CONCLUSION: Implementing the CPC three-dimensional quality evaluation model for patients undergoing laparoscopic cholecystectomy can help accelerate their perioperative recovery process, alleviate perioperative stress symptoms, mitigate anxiety, depression, and other adverse emotions, and to some extent, reduce the incidence of perioperative complications.

Roux-en-Y Gastric Bypass Surgery for the Prevention of Long-term Renal Function Damage in Type 2 Diabetes: A Clinical Study.

Objective: Type 2 diabetes mellitus (T2DM) is strongly associated with obesity, a significant risk factor for the occurrence and progression of chronic kidney disease. In recent years, weight loss surgery has become an important treatment option for diabetes. This study examined whether Roux-en-Y gastric bypass surgery, a new metabolic bariatric surgery approach, can effectively reduce the risk of long-term renal impairment in individuals with type 2 diabetes. Methods: In a cohort study, 60 individuals suffering from both obesity and type 2 diabetes were stratified and randomly divided into 2 groups based on gender and weight. The control group (30 cases) received internal medicine treatment; the observation group (30 cases) received Roux-en-Y gastric bypass surgery. The study compared the changes in glycated hemoglobin, fasting blood glucose, fasting insulin, fasting C-peptide, postprandial 2-hour blood glucose, postprandial 2-hour insulin, postprandial 2-hour C-peptide, weight, waist circumference, and BMI before and at 6, 12, and 18 months after treatment. Kidney function-related indicators such as urinary protein excretion, microalbuminuria, and creatinine clearance were also compared. Results: There were no significant differences in the above indicators between the 2 groups before treatment (P > .05). After 6, 12, and 18 months of treatment, the levels of glycated hemoglobin, fasting blood glucose, fasting insulin, fasting C-peptide, postprandial 2-hour blood glucose, postprandial 2-hour insulin, postprandial 2-hour C-peptide, weight, waist circumference, and BMI were significantly decreased compared to before treatment (P < .05). Urinary protein excretion and microalbuminuria decreased, while creatinine clearance increased after 6, 12, and 18 months of surgery (P < .05). The differences in indicators between the 2 groups at each point after surgery were statistically significant (P < .05). Conclusion: Roux-en-Y gastric bypass surgery was more effective than medical treatment in treating type 2 diabetes and mitigating long-term kidney function damage. These findings confirm the clinical utility of Roux-en-Y gastric bypass surgery in these conditions, indicating its potential for generalization and reference.

Plasma ctDNA enhances the tissue-based detection of oncodriver mutations in colorectal cancer.

PURPOSE: The advent of circulating tumor DNA (ctDNA) technology has provided a convenient and noninvasive means to continuously monitor cancer genomic data, facilitating personalized cancer treatment. This study aimed to evaluate the supplementary benefits of plasma ctDNA alongside traditional tissue-based next-generation sequencing (NGS) in identifying targetable mutations and tumor mutational burden (TMB) in colorectal cancers (CRC). METHODS: Our study involved 76 CRC patients, collecting both tissue and plasma samples for NGS. We assessed the concordance of gene mutational status between ctDNA and tissue, focusing on actionable genes such as KRAS, NRAS, PIK3CA, BRAF, and ERBB2. Logistic regression analysis was used to explore variables associated with discordance and positive mutation rates. RESULTS: In total, 26 cancer-related genes were identified. The most common variants in tumor tissues and plasma samples were in APC (57.9% vs 19.7%), TP53 (55.3% vs 22.4%) and KRAS (47.4% vs 43.4%). Tissue and ctDNA showed an overall concordance of 73.53% in detecting actionable gene mutations. Notably, plasma ctDNA improved detection for certain genes and gene pools. Variables significantly associated with discordance included gender and peritoneal metastases. TMB analysis revealed a higher detection rate in tissues compared to plasma, but combining both increased detection. CONCLUSIONS: Our study highlights the importance of analyzing both tissue and plasma for detecting actionable mutations in CRC, with plasma ctDNA offering added value. Discordance is associated with gender and peritoneal metastases, and TMB analysis can benefit from a combination of tissue and plasma data. This approach provides valuable insights for personalized CRC treatment.

Sonochemical Synthesis of Natural Polyphenolic Nanoparticles for Modulating Oxidative Stress.

Natural polyphenolic compounds play a vital role in nature and are widely utilized as building blocks in the fabrication of emerging functional nanomaterials. Although diverse fabrication methodologies are developed in recent years, the challenges of purification, uncontrollable reaction processes and additional additives persist. Herein, a modular and facile methodology is reported toward the fabrication of natural polyphenolic nanoparticles. By utilizing low frequency ultrasound (40 kHz), the assembly of various natural polyphenolic building blocks is successfully induced, allowing for precise control over the particle formation process. The resulting natural polyphenolic nanoparticles possessed excellent in vitro antioxidative abilities and in vivo therapeutic effects in typical oxidative stress models including wound healing and acute kidney injury. This study opens new avenues for the fabrication of functional materials from naturally occurring building blocks, offering promising prospects for future advancements in this field.

Pericyte signaling via soluble guanylate cyclase shapes the vascular niche and microenvironment of tumors.

Pericytes and endothelial cells (ECs) constitute the fundamental components of blood vessels. While the role of ECs in tumor angiogenesis and the tumor microenvironment is well appreciated, pericyte function in tumors remains underexplored. In this study, we used pericyte-specific deletion of the nitric oxide (NO) receptor, soluble guanylate cyclase (sGC), to investigate via single-cell RNA sequencing how pericytes influence the vascular niche and the tumor microenvironment. Our findings demonstrate that pericyte sGC deletion disrupts EC-pericyte interactions, impairing Notch-mediated intercellular communication and triggering extensive transcriptomic reprogramming in both pericytes and ECs. These changes further extended their influence to neighboring cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) through paracrine signaling, collectively suppressing tumor growth. Inhibition of pericyte sGC has minimal impact on quiescent vessels but significantly increases the vulnerability of angiogenic tumor vessels to conventional anti-angiogenic therapy. In conclusion, our findings elucidate the role of pericytes in shaping the tumor vascular niche and tumor microenvironment and support pericyte sGC targeting as a promising strategy for improving anti-angiogenic therapy for cancer treatment.

Identification of prognostic models for glycosylation-related subtypes and tumor microenvironment infiltration characteristics in clear cell renal cell cancer.

Background: One of the most fatal forms of cancer of the urinary system, renal cell carcinoma (RCC), significantly negatively impacts human health. Recent research reveals that abnormal glycosylation contributes to the growth and spread of tumors. However, there is no information on the function of genes related to glycosylation in RCC. Methods: In this study, we created a technique that can be used to guide the choice of immunotherapy and chemotherapy regimens for RCC patients while predicting their survival prognosis. The Cancer Genome Atlas (TCGA) provided us with patient information, while the GeneCards database allowed us to collect genes involved in glycosylation. GSE29609 was used as external validation to assess the accuracy of prognostic models. The "ConsensusClusterPlus" program created molecular subtypes based on genes relevant to glycosylation discovered using differential expression analysis and univariate Cox analysis. We examined immune cell infiltration as measured by estimate, CIBERSORT, TIMER, and ssGSEA algorithms, Tumor Immune Dysfunction and Exclusion (TIDE) and exclusion of tumour stemness indices (TSIs) based on glycosylation-related molecular subtypes and risk profiles. Stratification, somatic mutation, nomogram creation, and chemotherapy response prediction were carried out based on risk factors. Results: We built and verified 16 gene signatures associated with the prognosis of ccRCC patients, which are independent prognostic variables, and identified glycosylation-related genes by bioinformatics research. Cluster 2 is associated with lower human leukocyte antigen expression, worse overall survival, higher immunological checkpoints, and higher immune escape scores. In addition, cluster 2 had significantly better angiogenic activity, mesenchymal EMT, and stem ability scores. Higher immune checkpoint genes and human leukocyte antigens are associated with lower overall survival and a higher risk score. Higher estimated and immune scores, lesser tumor purity, lower mesenchymal EMT, and higher stem scores were all characteristics of the high-risk group. High amounts of tumor-infiltrating lymphocytes, a high mutation load, and a high copy number alteration frequency were present in the high-risk group.Discussion.According to our research, the 16-gene prognostic signature may be helpful in predicting prognosis and developing individualized treatments for patients with renal clear cell carcinoma, which may result in new personalized management options for these patients.

Characterizing the Efficacy and Safety of Chemotherapy Plus Everolimus in HER2-Negative Metastatic Breast Cancer Harboring Altered PI3K/AKT/mTOR.

BACKGROUND: The clinical outcomes of chemotherapy (CT) for the treatment of metastatic triple-negative (TN) and hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) have proven to be disappointing. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway, a tumor-promoting signaling cascade frequently mutated in breast cancer (BC), has been implicated in chemoresistance. In this study, our objective is to investigate the efficacy and safety of combining everolimus with chemotherapy in mBC patients exhibiting mutations in the PI3K/AKT/mTOR pathway. METHODS: We conducted a retrospective analysis to characterize the efficacy, safety, and their association with clinical and molecular characteristics of metastatic lesions in 14 patients with HER2- mBC. These patients harbored at least one altered member of the PI3K/AKT/mTOR signaling pathway and were treated with a combination of a chemotherapy agent and the mTOR inhibitor everolimus (CT+EVE). RESULTS: The majority of patients belonged to the triple-negative (TN) subtype (9/14, 64.3%), having already undergone 2 lines of chemotherapy (CT) in the metastatic setting (11, 78.6%). These patients carried altered phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and were administered a vinorelbine-containing regimen (10, 71.4%). The objective response rate (ORR) was 42.9%, with a disease control rate of 92.9%. The median progression-free survival (PFS) and overall survival (OS) were 5.9 (95% confidence interval (CI): 4.9-13.6) months and 14.3 (95% CI: 8.5-not reached (NR)) months, respectively. Patients with fewer prior treatment lines tended to exhibit longer PFS. OS, PFS, and ORR were comparable between hormone receptor-positive (HR+) and triple-negative breast cancer (TNBC) patients, but numerical improvements were noted in patients with a single PI3K pathway alteration compared to those with more than one alteration. Genomic alterations that surfaced upon progression on CT+EVE included cyclin dependent kinase 4 (CDK4) and epidermal growth factor receptor (EGFR) amplification, as well as neurofibromin 1 (NF1) mutation, suggesting potential mechanisms of acquired resistance. An analysis of adverse events indicated manageable toxicities. CONCLUSIONS: The findings of this study suggest both activity and safety for the combination of chemotherapy and the mTOR inhibitor everolimus (CT+EVE) in patients with HER2- mBC who have alterations in the PI3K pathway, particularly those who have received fewer prior chemotherapy. However, it is crucial to note that large-scale, randomized control studies are warranted to more comprehensively characterize the efficacy and safety of this combination therapy.

Adenine base editor-based correction of the cardiac pathogenic Lmna c.1621C > T mutation in murine hearts.

Base editors are emerging as powerful tools to correct single-nucleotide variants and treat genetic diseases. In particular, the adenine base editors (ABEs) exhibit robust and accurate adenine-to-guanidine editing capacity and have entered the clinical stage for cardiovascular therapy. Despite the tremendous progress using ABEs to treat heart diseases, a standard technical route toward successful ABE-based therapy remains to be fully established. In this study, we harnessed adeno-associated virus (AAV) and a mouse model carrying the cardiomyopathy-causing Lmna c.1621C > T mutation to demonstrate key steps and concerns in designing a cardiac ABE experiment in vivo. We found DeepABE as a reliable deep-learning-based model to predict ABE editing outcomes in the heart. Screening of sgRNAs for a Cas9 mutant with relieved protospacer adjacent motif (PAM) allowed the reduction of bystander editing. The ABE editing efficiency can be significantly enhanced by modifying the TadA and Cas9 variants, which are core components of ABEs. The ABE systems can be delivered into the heart via either dual AAV or all-in-one AAV vectors. Together, this study showcased crucial technical considerations in designing an ABE system for the heart and pointed out major challenges in further improvement of this new technology for gene therapy.

Effect of two different doses of nalbuphine for postoperative analgesia in children with cleft palate: a randomized controlled trial.

BACKGROUND: Cleft palate repair surgery may result in severe pain in the immediate postoperative period. The aim of this study is to compare the effects of different doses of nalbuphine for postoperative analgesia in children with cleft palate. METHODS: From November 2019 to June 2021, 90 children (45 males and 45 females, age 9-20 months old, ASA class I-II) were selected for palatoplasty. They were randomly divided into three groups: the control group (Group C), the N1 group (postoperative analgesia with 0.05 mg/kg/h nalbuphine) and the N2 group (postoperative analgesia with 0.075 mg/kg/h nalbuphine). Each group had 30 cases. Nalbuphine was not continuously infused in Group C but was continuously infused in Groups N1 and N2 at rates of 0.05 mg/kg/h and 0.075 mg/kg/h, respectively, for 24 h for postoperative analgesia. The FLACC analgesia score and Ramsay Sedation score were recorded at 10 min (T1), 30 min (T2), 2 h (T3), 12 h (T4) and 24 h (T5) after the operation. Adverse reactions such as nausea, vomiting and respiratory depression were observed and recorded. RESULTS: Compared with those in Group C, the FLACC scores in the N1 and N2 groups decreased significantly at T1-T5 (p < 0.05); the Ramsay Sedation score in the N1 group was significantly higher at T3 and T4 (p < 0.05), and that in the N2 group was significantly higher at T1-T5 (p < 0.05). Compared with that in the N1 group, the FLACC score in the N2 group was not significantly different, and the Ramsay Sedation score increased significantly at T5 (p < 0.05). CONCLUSION: Using 0.05 mg/kg/h Nalbuphine continuously for 24 h for postoperative analgesia in children with cleft palate has a better effect and fewer adverse reactions. TRIAL REGISTRATION: This study was registered at ChiCTR1900027385 (11/11/2019).

Preliminary study of the effect of gut microbiota on the development of prostatitis.

BACKGROUND: Dysbacteriosis of intestinal tract may cause systemic inflammation, making distant anatomical locations more susceptible to illness. Recent research has demonstrated that the microbiome can affect both prostatitis and the inflammation of the prostate that is linked to prostate cancer. It is still unclear, though, whether this relationship indicates causation. We conducted a Mendelian randomization investigation on two samples to fully uncover gut microbiota's potential genetic causal role in prostatitis. METHOD: Prostatitis (1859 prostatitis cases and 72,799 controls) was utilized as the outcome, while SNPs highly linked with 196 microbial taxa (18 340 people) were chosen as instrumental factors. Random effects, inverse variance weighting, weighted medians, and MR-Egger were used to analyze causal effects. The Cochran's Q test, funnel plot, leave-one-out analysis, and MR-Egger intercept test were all used in the sensitivity analysis. RESULTS: A causal effect in lowering the incidence of prostatitis is anticipated for five gut microorganisms (Methanobacteria, Methanobacteriaceae, Erysipelatoclostridium, Parasutterella, and Slackia; P < 0.05). Four gut bacteria, including Faecalibacterium, LachnospiraceaeUCG004, Sutterella, and Gastranaerophilales, are predicted to play a causal role in increasing the risk of prostatitis (P < 0.05). There were no discernible estimates of pleiotropy or heterogeneity. CONCLUSION: Our investigation established the genetic links between nine gut microorganisms and prostatitis, which may offer fresh perspectives and a theoretical framework for the future prevention and management of prostatitis.

Silane Effects on Adhesion Enhancement of 2K Polyurethane Adhesives.

With excellent properties such as great flexibility, outstanding chemical resistance, and superb mechanical strength, two-part polyurethane (2K PU) adhesives have been widely applied in many applications, including those in transportation and construction. Despite the extensive use, their adhesion to nonpolar polymer substrates still needs to be improved and has been widely studied. The incorporation of silane molecules and the use of plasma treatment on substrate surfaces are two popular methods to increase the adhesion of 2K PU adhesives, but their detailed adhesion enhancement mechanisms are still largely unknown. In this research, sum frequency generation (SFG) vibrational spectroscopy was used to probe the influence of added or coated silanes on the interfacial structure at the buried polypropylene (PP)/2K PU adhesive interface in situ. How plasma treatment on PP could improve adhesion was also investigated. To achieve maximum adhesion, two methods to involve silanes were studied. In the first method, silanes were directly mixed with the 2K PU adhesive before use. In the second method, silane molecules were spin-coated onto the PP substrate before the PU adhesive applied. It was found that the first method could not improve the 2K PU adhesion to PP, while the second method could substantially enhance such adhesion. SFG studies demonstrated that with the second method silane molecules chemically reacted at the interface to connect PP and 2K PU adhesive to improve the adhesion. With the first method, silane molecules could not effectively diffuse to the interface to enhance adhesion. In this research, plasma treatment was also found to be a useful method to improve the adhesion of the 2K PU adhesive to nonpolar polymer materials.

Curative effect of immediate reconstruction after neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis.

Background: The safety of mastectomy (MT) with immediate reconstruction (IR) in breast cancer patients who have completed neoadjuvant chemotherapy (NAC) is not apparent. This meta-analysis aims to systematically evaluate the differences in surgical complications and postoperative survival rates between MT with IR (MT+IR) and MT alone in post-NAC breast cancer patients. Methods: The PubMed, Embase, Cochrane Library, WanFang Data, and CNKI databases were systematically searched, and cohort studies of post-NAC breast cancer patients with MT+IR or MT surgery were collected from databases inception to May 25, 2023. Two researchers independently executed literature screening, data extraction, and bias risk assessment, and meta-analysis was performed using Revman 5.3 software. Results: A total of 12 studies involving 7378 cases who have accepted NAC were collected for this study. The results showed that compared with the MT group, the relative risk of surgical complications in the MT+IR group was increased by 44%, with no statistical significant [RR=1.44, 95% CI (0.99, 2.09), P=0.06]. While among study subgroups with a median follow-up of less than one year, more surgical complications occurred in the MT+IR group by 23% [RR=1.23, 95% CI (1.00, 1.52), P=0.05]. There was no significant differences in overall survival, disease-free survival, local relapse-free survival, and distant metastasis-free survival between the two groups. Conclusions: Compared with the MT, MT+IR does not affect the postoperative survival rate in post-NAC breast cancer patients, accompanied by a mild increase in short-term surgical complications, but no significant difference in long-term complications. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023421150.

Risk factors and predictors of urogenous sepsis after percutaneous nephrolithotomy for idiopathic calcium oxalate nephrolithiasis.

Background: The aim of this study was to use bioinformatics approaches to screen and identify the key genes of idiopathic calcium oxalate nephrolithiasis, and explore its potential molecular mechanism. Methods: The GSE73680 kidney stone data set was downloaded from the Gene Expression Omnibus (GEO). R software (The R Foundation for Statistical Computing) was used to screen differentially expressed genes. GeneMANIA and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) databases were used to analyze related genes interacting with crucial genes, and a protein-protein interaction (PPI) network was constructed. The differential genes were then subjected to the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. The clinical data of 156 patients who received percutaneous nephrolithotomy (PCNL) therapy at our facility between January 2013 and December 2017 were retrospectively analyzed. The various parameters associated with postoperative urogenous sepsis were identified using multivariable logistic regression analysis. Results: The study discovered one differentially expressed gene was nucleotide-binding oligomerization domain-containing protein 2 (NOD2). GO and KEGG analysis showed that NOD2 might affect the occurrence of idiopathic calcium oxalate kidney stones by affecting inflammation, receptor expression, immune environment, necrosis, apoptosis, and other pathways. The clinical parameter of patients who participated in the study, including preoperative urinary white blood cell (WBC) count, preoperative urinary nitrite, stone diameter, operation time, WBC count, and WBC D values, were statistically different between the systemic inflammatory response syndrome (SIRS) group and the urosepsis group. According to multivariate logistic regression analysis, the preoperative urine nitrite, calculus diameter, blood WBC, and NOD2 expression 3 hours after surgery were all independently associated with the urosepsis development. Conclusions: Preoperative urinary nitrite positive status, postoperative WBC count ≥2.98×109/L 3 hours after operation, stone diameter >6 cm, and low expression of NOD2 in renal papillary tissue are more likely to cause the urinary source of idiopathic calcium oxalate nephrolithiasis after PCNL urogenous sepsis. These parameters also offer a viable treatment paradigm for the perioperative management of PCNL in treating idiopathic calcium oxalate kidney stones.

Corn Oil-Water Separation: Interfacial Behavior of Extended Surfactant and Glutelin.

The purification and collection of various products from oil/water mixtures are routine procedures. However, the presence of emulsifiers that can displace other surface active components in the mixtures can significantly influence the efficiency of such procedures. Previously, we investigated interfacial mechanisms of zein protein-induced emulsification and the opposing surfactant-induced demulsification related to corn oil refinement. In this paper, we further investigated a different class of protein, glutelin, inside corn and proved that glutelin acts as an oil/water emulsifier in an acidic water environment. Furthermore, an extended surfactant's protein disordering and removal ability was tested and compared with a conventional surfactant. An extended surfactant contains a poly(propylene oxide) or poly(propylene oxide)-poly(ethylene oxide) chain inserted between the hydrophilic head and the hydrophobic tail. In this study, a nonlinear optical spectroscopic technique, sum frequency generation (SFG) vibration spectroscopy, was used to study the behavior of glutelin and extended as well as regular surfactants at the corn oil/water or aqueous solution interface. In most cases, the conventional surfactant shows better protein disordering or removal ability than the extended surfactant. However, with the addition of heat and salt to an extended surfactant solution, the experiment resulted in a substantial increase in the extended surfactant's protein disorder or removal ability.

Evidence for a causal effect of major depressive disorder, anxiety on prostatitis risk: A univariate and multivariate Mendelian randomization study.

BACKGROUND: Observational studies have shown an association between major depressive disorder (MDD), anxiety, and prostatitis. However, the causal relationship between MDD, anxiety, and prostatitis remains controversial. Therefore, we aimed to use two-sample Mendelian randomization (MR) to assess the causal effects of MDD and anxiety on prostatitis. METHODS: We conducted univariable and multivariable MR analyses using summary statistics from publicly available genome-wide association studies to estimate the causal relationships between MDD, anxiety, and prostatitis risk. In the main MR analysis, the inverse-variance weighted (IVW) method was used, while secondary methods included the weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual and outlier (MR-PRESSO) tests to detect and correct for the presence of pleiotropy. RESULTS: MDD had 97 independent instrumental variables (IVs) and anxiety had 15 IVs. Univariable MR analysis showed that genetically determined MDD had a detrimental causal effect on prostatitis (IVW: odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.12-1.92, p = 0.005), while no causal relationship was found between anxiety and prostatitis (IVW: OR = 0.25, 95% CI = 0.02-2.82, p = 0.26). More convincingly, after adjusting for confounding factors such as body mass index, alcohol consumption, and smoking, the genetic liability for MDD remained associated with prostatitis risk, with no strong evidence of anxiety affecting prostatitis incidence. CONCLUSION: This study supports the notion that MDD has a detrimental effect on prostatitis risk, and strategies focused on addressing MDD may be one of the cornerstones for treating prostatitis. The potential preventive value of treating MDD for prostatitis should be further investigated in future research.

Transformation and Detection of Soybean Hairy Roots.

Agrobacterium rhizogenes is a soil bacteria with extensive infectivity, which can infect almost all dicotyledonous plants and a few monocotyledonous plants to induce root nodules. This is caused by the root-inducing plasmid, which contains genes responsible for the autonomous growth of root nodules and crown gall base synthesis. Structurally, it is similar to the tumor-inducing plasmid in that it mainly contains the Vir region, the T-DNA region, and the functional region of crown gall base synthesis. Its T-DNA is integrated into the nuclear genome of the plant with the assistance of Vir genes, causing hairy root disease in the host plant and the formation of hairy roots. The roots produced by Agrobacterium rhizogenes-infested plants are characterized by a fast growth rate, high degree of differentiation, physiological, biochemical, and genetic stability, and ease of manipulation and control. In particular, the hairy root system is an efficient and rapid research tool for plants that have no affinity for transformation by Agrobacterium rhizogenes and low transformation efficiency. The establishment of germinating root culture system for the production of secondary metabolites in the original plants through the genetic transformation of natural plants mediated by root-inducing plasmid in Agrobacterium rhizogenes has become a new technology combining plant genetic engineering and cell engineering. It has been widely used in a variety of plants for different molecular purposes, such as pathological analysis, gene function verification, and secondary metabolite research. Chimeric plants obtained by induction of Agrobacterium rhizogenes that can be expressed instantaneously and contemporarily are more rapidly obtained, compared to tissue culture and stably inheritable transgenic strains. In general, transgenic plants can be obtained in approximately one month.

DeepTPpred: A Deep Learning Approach With Matrix Factorization for Predicting Therapeutic Peptides by Integrating Length Information.

The abuse of traditional antibiotics has led to increased resistance of bacteria and viruses. Efficient therapeutic peptide prediction is critical for peptide drug discovery. However, most of the existing methods only make effective predictions for one class of therapeutic peptides. It is worth noting that currently no predictive method considers sequence length information as a distinct feature of therapeutic peptides. In this article, a novel deep learning approach with matrix factorization for predicting therapeutic peptides (DeepTPpred) by integrating length information are proposed. The matrix factorization layer can learn the potential features of the encoded sequence through the mechanism of first compression and then restoration. And the length features of the sequence of therapeutic peptides are embedded with encoded amino acid sequences. To automatically learn therapeutic peptide predictions, these latent features are input into the neural networks with self-attention mechanism. On eight therapeutic peptide datasets, DeepTPpred achieved excellent prediction results. Based on these datasets, we first integrated eight datasets to obtain a full therapeutic peptide integration dataset. Then, we obtained two functional integration datasets based on the functional similarity of the peptides. Finally, we also conduct experiments on the latest versions of the ACP and CPP datasets. Overall, the experimental results show that our work is effective for the identification of therapeutic peptides.

Identification and validation of fatty acid metabolism-related lncRNA signatures as a novel prognostic model for clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a main subtype of renal cancer, and advanced ccRCC frequently has poor prognosis. Many studies have found that lipid metabolism influences tumor development and treatment. This study was to examine the prognostic and functional significance of genes associated with lipid metabolism in individuals with ccRCC. Using the database TCGA, differentially expressed genes (DEGs) associated with fatty acid metabolism (FAM) were identified. Prognostic risk score models for genes related to FAM were created using univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Our findings demonstrate that the prognosis of patients with ccRCC correlate highly with the profiles of FAM-related lncRNAs (AC009166.1, LINC00605, LINC01615, HOXA-AS2, AC103706.1, AC009686.2, AL590094.1, AC093278.2). The prognostic signature can serve as an independent predictive predictor for patients with ccRCC. The predictive signature's diagnostic effectiveness was superior to individual clinicopathological factors. Between the low- and high-risk groups, immunity research revealed a startling difference in terms of cells, function, and checkpoint scores. Chemotherapeutic medications such lapatinib, AZD8055, and WIKI4 had better outcomes for patients in the high-risk group. Overall, the predictive signature can help with clinical selection of immunotherapeutic regimens and chemotherapeutic drugs, improving prognosis prediction for ccRCC patients.