Predictive effect of estimated glomerular filtrate rate by creatinine or cystatin C on mortality in patients with coronary artery disease.

BACKGROUND: Renal dysfunction leads to poor prognosis of patients with coronary artery disease (CAD). Current studies have reported the prognosis or mortality of various diseases using different estimated glomerular filtrate rate (eGFR) formulas, while the performance of these equations is unclear in CAD patients. We aim to evaluate the predict effect of creatinine-based eGFR (eGFRcr), cystatin C-based eGFR (eGFRcys), and both creatinine and cystatin C-based eGFR (eGFRcr-cys) in CAD patients. METHODS: A total of 23,178 patients with CAD were included from CIN-II cohort study. The association of eGFRcr, eGFRcys and eGFRcr-cys with cardiovascular and all-cause mortality was detected by Cox regression analysis. The predictive effect of eGFRcr, eGFRcys and eGFRcr-cys on mortality was assessed. RESULTS: During a median follow up of 4.3 years, totally 2051 patients (8.8%) experience all-cause mortality, of which 1427 patients (6.2%) died of cardiovascular disease. For the detection of cardiovascular mortality among CAD patients, eGFRcr-cys had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.730, which was significantly better than eGFRcr (AUC = 0.707, p < 0.001) and eGFRcys (AUC = 0.719, p < 0.001). Similar results were observed in all-cause mortality. Restricted cubic spline showed a U-shaped association between eGFRcr and all outcomes in patients with both reduced and supranormal eGFR levels, while a L-shaped association in eGFRcys and eGFRcr-cys. CONCLUSIONS: Estimated GFR based on both creatinine and cystatin C has highest predictive effect for cardiovascular and all-cause mortality among CAD patients. Meanwhile, supranormal eGFRcr may indicate a higher risk of mortality.

Impact of stapler versus manual closure techniques on pharyngocutaneous fistula development post-total laryngectomy: A systematic review and meta-analysis.

Pharyngocutaneous fistula (PCF) is a major complication after total laryngectomy, with significant morbidity and mortality. Whether mechanical stapler closure of the pharynx reduces fistula rates compared to hand-sewn techniques remains unclear. We conducted an updated systematic review and meta-analysis to clarify this question. Five databases were systematically searched from inception through November 2023 for studies comparing stapler versus suture closure for fistula outcomes after laryngectomy. Odds ratios (OR) were pooled using random-effects models and fixed-effects models. Subgroup and sensitivity analyses were performed. Risk of bias was appraised using NHLBI tools. Nine studies with 803 patients were included. Mechanical closure significantly reduced fistula incidence versus suture closure (OR = 0.57, 95% CI 0.34-0.95, p = 0.03). Subgroup analysis found that stapling's protective effect varied by patient age, country/region, linear stapler size and female percentage. Stapling reduced fistula odds by 80% in the Turkey subgroup (OR = 0.20, 95% CI 0.09-0.50) but showed no benefit in other regions. Patients <60 years showed an 84% fistula reduction with stapling (OR = 0.17, 95% CI 0.06-0.45), whereas older subgroups did not. Linear stapler size of 60 mm significantly reduced fistula occurrence while 75 mm did not. There was no evidence that low female percentage mitigated stapling benefits. Mechanical stapler closure after total laryngectomy meaningfully reduces the likelihood of postoperative PCF formation compared to hand-sewn closure, especially for patients younger than 60 years old. The absolute risk reduction supports its utility to prevent this complication.

Iron-modified biochar effectively mitigates arsenic-cadmium pollution in paddy fields: A meta-analysis.

The escalating problem of compound arsenic (As) and cadmium (Cd) contamination in agricultural soils necessitates the urgency for effective remediation strategies. This is compounded by the opposing geochemical behaviors of As and Cd in soil, and the efficacy of biochar treatment remains unclear. This pioneering study integrated 3780 observation pairs referred from 92 peer-reviewed articles to investigate the impact of iron-modified biochar on As and Cd responses across diverse soil environments. Regarding the treatments, 1) biochar significantly decreased the exchangeable and acid-soluble fraction of As (AsF1, 20.9%) and Cd (CdF1, 24.0%) in paddy fields; 2) iron-modified biochar significantly decreased AsF1 (32.0%) and CdF1 (27.4%); 3) iron-modified biochar in paddy fields contributed to the morphological changes in As and Cd, mainly characterized by a decrease in AsF1 (36.5%) and CdF1 (36.3%) and an increase in the reducible fraction of As (19.7%) and Cd (39.2%); and 4) iron-modified biochar in paddy fields increased As (43.1%) and Cd (53.7%) concentrations in the iron plaque on root surfaces. We conclude that iron-modified biochar treatment of paddy fields is promising in remediating As and Cd contamination by promoting the formation of iron plaque.

Efficacy and Mechanism of Hypofractionation Radiotherapy Combined with PD-1 Inhibitors in a Model of Head and Neck Melanoma.

Head and neck mucosal melanoma is one of the most common types of melanoma in China, but the prognosis is worse than other types, and there is no effective treatment plan to improve patient survival. This study analyzes the efficacy of hypofractionation radiotherapy combined with PD-1 inhibitor in the treatment of head and neck mucosal melanoma, as well as its impact on the tumor immune microenvironment. NPSG mice were used to construct a humanized bilateral lesion tumor model of the humanized immune system. The models were divided into an RT (8 Gy)+anti PD-1 group, an RT (2 GyX4)+anti PD-1 group, an Anti PD-1 group, an RT (8 Gy) group, and a blank group. Differences in efficacy and immune cells in blood, lymph nodes, and tumor tissues were compared between different treatment groups. The treatment effect of RT (8 Gy)+anti PD-1 was better than the other groups with a tumor growth inhibition value (TGI) over 60%. Significant recruitment and activation of CD8+T cells were found in the blood, lymph nodes, and tumor tissues and significantly inhibited the level of PD-1+CD8+T cells in the group of RT (8 Gy)+anti PD-1. This study confirmed the efficacy of hypofractionation radiotherapy combined with PD-1 inhibitors, which can inhibit tumor growth and produce distant effects. The appearance of a distant effect is related to the enhancement in the number and activity of CD8+T cells in the local tumor and peripheral blood and lymph nodes. This study confirms the therapeutic and immune regulatory effect of hypofractionation radiotherapy combined with PD-1 inhibitors.

Identification and validation of a T cell marker gene-based signature to predict prognosis and immunotherapy response in gastric cancer.

Although the role of T cells in tumor immunity and modulation of the tumor microenvironment (TME) has been extensively studied, their precise involvement in gastric adenocarcinoma remains inadequately explored. In this work, we analyzed the single-cell RNA sequencing data set in GSE183904 and identified 322 T cell marker genes using the "FindAllMarkers" method of the R package "Seurat". STAD patients in the TCGA database were divided into high-risk and low-risk categories based on risk scores. The five-gene prediction signature based on T cell marker genes can predict the prognosis of gastric cancer patients with high accuracy. In the training cohort, the areas under the receiver operating characteristic (ROC) curve were 0.667, 0.73, and 0.818 at 1, 3, and 5 years. External validation of the predictive signature was also performed using multiple clinical subgroups and GEO cohorts. To help with practical application, a diagnostic model was created that shows values of 0.732, 0.752, and 0.816 for the relevant areas under the ROC curve at 1, 3, and 5 years. The T cell marker genes identified in this study may serve as potential therapeutic targets, and the developed predictive signatures and nomograms may aid in the clinical management of gastric cancer.

Washing antimony and arsenic from agricultural soil with eco-friendly organic acids and the relevant bioavailability assessment.

Antimony (Sb) and arsenic (As) contamination in agricultural soil poses human health risks through agricultural products. Soil washing with degradable low molecular weight organic acids (LMWOAs) is an eco-friendly strategy to remediate agricultural soils. In this study, three eco-friendly LMWOAs, oxalic acid (OA), tartaric acid (TA), and citric acid (CA), were used to treat Sb and As co-contaminated agricultural soil from Xikuangshan mine area. The OA, TA, and CA washed out 18.4, 16.8, and 26.6% of Sb and 15.3, 19.9, and 23.8% of As from the agricultural soil, with CA being the most efficient reagent for the soil washing. These organic acids also led to pH decline and macronutrients losses. Fraction analysis using a sequential extraction procedure showed that the three organic acids targeted and decreased the specifically sorbed (F2) (by 19.3-37.6% and 2.41-23.5%), amorphous iron oxide associated (F3) (by 49.1-61.2% and 51.2-70.2%), and crystallized iron oxide associated (F4) (by 12.3-26.0% and 26.1-29.1%) Sb and As. The leachability of Sb and As, as well as their concentrations and bioconcentration factor (BCF) in vegetables reduced due to the soil washing. It demonstrated that the bioavailability of both the elements was decreased by the organic acids washing. The concentrations of Sb and As in typical vegetable species cultivated in CA washed soil were less than the threshold value for consumption safety, while those in OA and TA washed soils were still higher than the value, suggesting that only CA is a potential washing reagent in soil washing for Sb- and As-contaminated agricultural soil.

Erratum: Author correction to 'Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties: Preparation, characterization and application in vaginal drug delivery system' [Acta Pharm Sin B 7 (2017) 593-602].

[This corrects the article DOI: 10.1016/j.apsb.2017.03.002.].

Addressing implicit bias in adversarial imitation learning with mutual information.

Adversarial imitation learning (AIL) is a powerful method for automated decision systems due to training a policy efficiently by mimicking expert demonstrations. However, implicit bias is present in the reward function of these algorithms, which leads to sample inefficiency. To solve this issue, an algorithm, referred to as Mutual Information Generative Adversarial Imitation Learning (MI-GAIL), is proposed to correct the biases. In this study, we propose two guidelines for designing an unbiased reward function. Based on these guidelines, we shape the reward function from the discriminator by adding auxiliary information from a potential-based reward function. The primary insight is that the potential-based reward function provides more accurate rewards for actions identified in the two guidelines. We compare our algorithm with SOTA imitation learning algorithms on a family of continuous control tasks. Experiments results show that MI-GAIL is able to address the issue of bias in AIL reward functions and further improve sample efficiency and training stability.

Correction: Ci et al. Enhanced Delivery of Imatinib into Vaginal Mucosa via a New Positively Charged Nanocrystal-Loaded in Situ Hydrogel Formulation for Treatment of Cervical Cancer. Pharmaceutics 2019, 11, 15.

In the original publication [...].

Preparation and Characterization of Biomass Tannin-Based Flexible Foam Insoles for Athletes.

The exploitation of bio-based foams implies an increase in the use of renewable biological resources to reduce the rapid consumption of petroleum-derived resources. Both tannins and furfuryl alcohol are derived from forestry resources and are, therefore, considered attractive precursors for the preparation of tannin-furanic foams. In addition, toughening modification of tannin-furanic foams using polyvinyl alcohol (PVOH) results in a more flexible network-like structure, which imparts excellent flexibility to the foams, whose relative properties are even close to those of polyurethane foams, which are the most used for fabrication of insoles for athletes. In addition, the addition of PVOH does not affect the thermal insulation properties of the foams by testing the thermal conductivity, resilience, and elongation at break, while reducing the brittleness of the samples and improving the mechanical properties. Also, the observation of the morphology of the foam shows that the compatibility between PVOH and tannin-furanic resin is good, and the cured foam does not show fragmentation and collapse, while the bubble pore structure is uniform. The developed flexible foam derived from biomass resources endows the foam with good thermal insulation properties and high mechanical properties, and the samples exhibit suitable physical parameters to be used as flexible insoles for athletes.

Genetic Screens for Floral Mutants in Arabidopsis thaliana: Enhancers and Suppressors.

The flower is a hallmark feature that has contributed to the evolutionary success of land plants. Diverse mutagenic agents have been employed as a tool to genetically perturb flower development and identify genes involved in floral patterning and morphogenesis. Since the initial studies to identify genes governing processes such as floral organ specification, mutagenesis in sensitized backgrounds has been used to isolate enhancers and suppressors to further probe the molecular basis of floral development. Here, we first describe two commonly employed methods for mutagenesis (using ethyl methanesulfonate (EMS) or T-DNAs as mutagens), and then describe three methods for identifying a mutation that leads to phenotypic alterations: traditional map-based cloning, modified high-efficiency thermal asymmetric interlaced PCR (mhiTAIL-PCR), and deep sequencing in the plant model Arabidopsis thaliana.

[The application of transcervical non-inflatable endoscopic posterior inferior sternocleidomastoid approach in thyroid surgery].

Objective:To investigate the clinical efficacy and safety of transcervical non-inflatable endoscopic thyroidectomy through the posterior inferior sternocleidomastoid approach. Methods:From December 2022 to May 2023, the clinical data of 35 patients with papillary thyroid carcinoma treated by transcervical non-inflatable endoscopic surgery via posterior inferior sternocleidomastoid approach were retrospectively analyzed. There were 14 males and 21 females, with an average age of 44.7 years. The operation time, bleeding volume, postoperative recovery, complications and follow-up were recorded. Results:All 35 patients successfully completed the surgery, with an average operation time of 4 hours and 7 minutes, an average bleeding volume of 14 ml, and an average postoperative hospital stay of 3.5 days. There were no serious complications and no obvious neck discomfort during postoperative follow-up. Conclusion:Transcervical non-inflatable endoscopic thyroidectomy via posterior inferior sternocleidomastoid approach is safe and effective, with fast postoperative recovery,high appearance satisfaction and good neck comfort.

Induction chemotherapy-based organ-preservation protocol improve the function preservation compared with immediate total laryngectomy for locally advanced hypopharyngeal cancer-Results of a matched-pair analysis.

BACKGROUND: We performed a paired analysis to compare the therapeutic effect between the induction chemotherapy-based organ-preservation approach and immediate total laryngectomy in hypopharyngeal squamous cell carcinoma patients requiring total laryngectomy. METHODS: 351 patients who were treated with organ-preservation approach were compared with 110 patients who were treated with total laryngectomy. The main measures and outcomes were progression-free survival (PFS), overall survival (OS), and larynx function preservation survival (LFPS). RESULTS: No statistical difference was observed for 3-, 5-, and 10-year PFS and OS in two groups. In the organ-preservation group, the 3-, 5-, and 10-year LFPS was 30.7%, 23.3%, and 16.6%, respectively. The LFPS of Stage III > Stage IV, N0 > N1 > N2 > N3, T2 > T3 > T4, CR > PR > SD > PD patients (all p values <0.05). CONCLUSIONS: Survival outcomes did not significantly differ between the two groups. The organ-preservation approach allowed more than 70% of the survivors to retain their larynx function.

Incidental thyroid carcinomas: experiences related to the surgery of head and neck cancers.

Background: Incidental thyroid carcinomas (ITCs) in patients undergoing head and neck surgery are rare, but there are no standard guidelines for the treatment of this situation. This retrospective study sought to detail our experiences in the treatment of ITCs related to the surgery of head and neck cancers. Methods: We conducted a retrospective analysis of the data about the ITCs in the patients with head and neck cancer, who underwent surgical treatments at Beijing Tongren Hospital in the past 5 years. The number and size of the thyroid nodules, postoperative pathology, follow-up results, and other information were recorded in detail. All the patients underwent surgical treatment and were followed-up for >1 year. Results: A total of 11 patients (10 male and 1 female) with ITC were included in this study. The patients had an average age of 58 years. Most of the patients (72.7%, 8/11) had laryngeal squamous cell cancer, and 7 were diagnosed with thyroid nodules on ultrasound. The surgical procedures for laryngeal and hypopharyngeal cancers included partial laryngectomy, total laryngectomy, and hypopharyngectomy. All the patients underwent thyroid stimulating hormone (TSH) suppression therapy. No recurrence or mortality events from thyroid carcinoma were observed. Conclusions: More attention needs to be paid to ITCs in head and neck surgery patients. Additionally, more research and the long-time follow-up of ITC patients are needed to extend understandings. For patients with head and neck cancers, if the suspicious thyroid nodules are found pre-operatively by ultrasound, fine-needle aspiration (FNA) is recommended. If FNA cannot be performed, the guidelines for thyroid nodules should be followed. In patients with postoperative ITC, TSH suppression therapy and follow-up is indicated.

Functional Genetic Variants in TGFß1 and TGFßR1 in miRNA-Binding Sites Predict Outcomes in Patients with HPV-positive Oropharyngeal Squamous Cell Carcinoma.

PURPOSE: TGFß1 and TGFß receptor 1 (TGFßR1) participate in regulation of the host's immune system and inflammatory responses and may serve as prognostic biomarkers for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). EXPERIMENTAL DESIGN: This study included 1,013 patients with incident OPSCC, of whom 489 had tumor HPV16 status determined. All patients were genotyped for two functional polymorphisms: TGFß1 rs1800470 and TGFßR1 rs334348. Univariate and multivariate Cox regression models were performed to evaluate associations between the polymorphisms and overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). RESULTS: Patients with TGFß1 rs1800470 CT or CC genotype had 70%-80% reduced risks of OS, DSS, and DFS compared with patients with TT genotype, and patients with TGFßR1 rs334348 GA or GG genotype had 30%-40% reduced risk of OS, DSS, and DFS compared with patients with AA genotype. Furthermore, among patients with HPV-positive (HPV+) OPSCC, the same patterns were observed but the risk reductions were greater: up to 80%-90% for TGFß1 rs1800470 CT or CC genotype and 70%-85% for TGFßR1 rs334348 GA or GG genotype. The risk reductions were still greater (up to 17 to 25 times reduced) for patients with both TGFß1 rs1800470 CT or CC genotype and TGFßR1 rs334348 GA or GG genotype compared with patients with both TGFß1 rs1800470 TT genotype and TGFßR1 rs334348 AA genotype among patients with HPV+ OPSCC. CONCLUSIONS: Our findings indicate that TGFß1 rs1800470 and TGFßR1 rs334348 may individually or jointly modify risks of death and recurrence in patients with OPSCC, particularly those with HPV+ OPSCC undergoing definitive radiotherapy, and may serve as prognostic biomarkers, which could lead to better personalized treatment and improved prognosis.

Acid-Mediated Formation of Soybean Isolate Protein Emulsion Gels with Soybean Oil as an Active Component.

In this study, the effect of soybean oil concentration on the rheology, water-holding capacity, and thermal stability of acid-mediated soy protein isolate (SPI) emulsion gels was investigated. The microstructure was analyzed and interpreted by CLSM and SEM observations. The results showed that the addition of soybean oil improved the elastic properties of the acid-mediated SPI emulsion gels. The storage modulus increased from 330 Pa (2% soybean oil concentration) to 545 Pa (8% soybean oil concentration) with a significant increase (p < 0.05). The increase in soybean oil concentration resulted in more SPI-coated oil droplets acting as active particles, enhancing the gel network. The acid-mediated SPI emulsion gels became more disordered as the soybean oil concentration increased, with the fractal dimension increasing from 2.92 (2%) to 2.95 (8%). The rheological properties, thermal analysis, and microstructure of 6% SPI gel and acid-mediated SPI emulsion gels with 2% to 8% soybean oil concentration were compared. The acid-mediated SPI emulsion gels with soybean oil as the active filler showed improved gel properties, greater thermal stability, and a homogeneous network structure compared to the acid-mediated SPI emulsion gels.

Four thermostatic steps: A novel CRISPR-Cas12-based system for the rapid at-home detection of respiratory pathogens.

The outbreak of coronavirus disease 2019 (COVID-19) in 2019 has severely damaged the world's economy and public health and made people pay more attention to respiratory infectious diseases. However, traditional quantitative real-time polymerase chain reaction (qRT-PCR) nucleic acid detection kits require RNA extraction, reverse transcription, and amplification, as well as the support of large-scale equipment to enrich and purify nucleic acids and precise temperature control. Therefore, novel, fast, convenient, sensitive and specific detection methods are urgently being developed and moving to proof of concept test. In this study, we developed a new nucleic acid detection system, referred to as 4 Thermostatic steps (4TS), which innovatively allows all the detection processes to be completed in a constant temperature device, which performs extraction, amplification, cutting of targets, and detection within 40 min. The assay can specifically and sensitively detect five respiratory pathogens, namely SARS-CoV-2, Mycoplasma felis (MF), Chlamydia felis (CF), Feline calicivirus (FCV), and Feline herpes virus (FHV). In addition, a cost-effective and practical small-scale reaction device was designed and developed to maintain stable reaction conditions. The results of the detection of the five viruses show that the sensitivity of the system is greater than 94%, and specificity is 100%. The 4TS system does not require complex equipment, which makes it convenient and fast to operate, and allows immediate testing for suspected infectious agents at home or in small clinics. Therefore, the assay system has diagnostic value and significant potential for further reducing the cost of early screening of infectious diseases and expanding its application. KEY POINTS: • The 4TS system enables the accurate and specific detection of nucleic acid of pathogens at 37 °C in four simple steps, and the whole process only takes 40 min. •A simple alkali solution can be used to extract nucleic acid. • A small portable device simple to operate is developed for home diagnosis and detection of respiratory pathogens.

High resveratrol-loaded microcapsules with trehalose and OSA starch as the wall materials: Fabrication, characterization, and evaluation.

To improve the solubility and stability of resveratrol (Res), Res nanocrystals (Res-ncs) as the capsule core were prepared by wet milling using hydroxypropyl methyl cellulose (HPMCE5), sodium dodecyl sulfate (SDS), and polyvinylpyrrolidone (PVPK30) as stabilizers, along with trehalose and octenyl succinic anhydride (OSA) modified starch were used as the wall material to produce Res microcapsules (Res-mcs) via spray drying. The fresh-prepared Res-ncs and rehydrated Res-mcs had mean particle sizes of 190.30 ± 3.43 and 204.70 ± 3.60 nm, zeta potentials of -13.90 ± 0.28 and - 11.20 ± 0.34 mV, and the loading capacities (LC) were as high as 73.03 % and 28.83 %. Particle morphology showed that Res-mcs had more regular and smooth spherical structures. FTIR indicated that Res may have hydrogen bonding with the walls. XRD and DSC exhibited that Res in nanocrystals and microcapsules existed mostly as amorphous structures. The solubility of Res-mcs and Res-ncs was increased, with excellent redispersibility and rapid dissolution of Res in vitro. The antioxidant properties of Res-mcs were protected and improved. With the walls acting as a physical barrier, Res-mcs have better photothermal stability than raw Res. Res-mcs have a relative bioavailability of 171.25 %, which is higher than that of raw Res.

Dietary cholesterol drives the development of nonalcoholic steatohepatitis by altering gut microbiota mediated bile acid metabolism in high-fat diet fed mice.

Nonalcoholic fatty liver disease (NAFLD) is the most widespread chronic liver disorder globally. Unraveling the pathogenesis of simple fatty liver to nonalcoholic steatohepatitis (NASH) has important clinical significance for improving the prognosis of NAFLD. Here, we explored the role of a high-fat diet alone or combined with high cholesterol in causing NASH progression. Our results demonstrated that high dietary cholesterol intakes accelerate the progression of spontaneous NAFLD and induces liver inflammation in mice. An elevation of hydrophobic unconjugated bile acids cholic acid (CA), deoxycholic acid (DCA), muricholic acid and chenodeoxycholic acid, was observed in high-fat and high-cholesterol diet fed mice. Full-length sequencing of the 16S rDNA gene of gut microbiota revealed a significant increase in the abundance of Bacteroides, Clostridium, and Lactobacillus that possess bile salt hydrolase activity. Furthermore, the relative abundance of these bacterial species was positively correlated with content of unconjugated bile acids in liver. Moreover, the expression of genes related to bile acid reabsorption (organic anion-transporting polypeptides, Na+-taurocholic acid cotransporting polypeptide, apical sodium dependent bile acid transporter and organic solute transporter ß) was found to be increased in mice with a high-cholesterol diet. Lastly, we observed that hydrophobic bile acids CA and DCA induce an inflammatory response in free fatty acids-induced steatotic HepG2 cells. In conclusion, high dietary cholesterol promotes the development of NASH by altering gut microbiota composition and abundance and thereby influencing with bile acid metabolism.