Symmetrical structure design of PLGA Biodegradable sinus stents and structure optimization based on surrogate models.

This study aims to enhance the degradation uniformity of PLGA sinus stents to minimize fracture risk caused by stress corrosion. Symmetric stent structures were introduced and compared to sinusoidal structure in terms of stress and degradation uniformity during implantation and degradation processes. Three surrogate models were employed to optimize the honeycomb-like structure. Results showed honeycomb-like structures exhibited the superior stress distribution and highest degradation uniformity. The kriging model achieved the smallest error and degradation uniformity of 83.24%. In conclusion, enhancing the symmetry of stent structures improves degradation uniformity, and the kriging model has potential for the optimization of stent structures.

QL1604 plus paclitaxel-cisplatin/carboplatin in patients with recurrent or metastatic cervical cancer: an open-label, single-arm, phase II trial.

OBJECTIVE: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. METHODS: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. RESULTS: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46). The median duration of response was 9.6 months (95% confidence interval [CI]=5.5-not estimable). The median progression-free survival was 8.1 months (95% CI=5.7-14.0). Forty-five (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). CONCLUSION: QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can't tolerate bevacizumab, which needs to be further verified in phase III confirmatory study. Trial RegistrationClinicalTrials.gov Identifier: NCT04864782.

Comparison of microbial communities in unleached and leached ionic rare earth mines.

The leaching of ionic rare earth elements has caused serious environmental pollution and ecological damage. Microorganisms play a crucial role in soil ecosystems and are one of the most important components of these systems. However, there are fewer studies related to the changes that occur in microbial community structure and diversity before and after leaching in ionic rare earth mines. In this study, Illumina high-throughput sequencing was used to examine the diversity and composition of soil microorganisms on the summit, hillside, and foot valley surfaces of unleached and leached mines after in situ leaching. The results showed that microbial diversity and abundance in the surface soil of the unleached mine were higher than those in the leached mine, and leaching had a significant impact on the microbial community of mining soil. pH was the main factor affecting the microbial community. Proteobacteria, Actinobacteriota, and Chloroflexi were phyla that showed high abundance in the soil. Network analysis showed that microbial interactions can improve microbial adaptation and stability in harsh environments. PICRUSt2 predictions indicate functional changes and linkages in soil microbial communities.

Prevention strategies for the recurrence of venous leg ulcers: A scoping review.

Venous leg ulcer (VLU) is the most severe manifestations of chronic venous disease, which has characterized by slow healing and high recurrence rates. This typically recalcitrant and recurring condition significantly impairs quality of life, prevention of VLU recurrence is essential for helping to reduce the huge burden of patients and health resources, the purpose of this scoping review is to analyse and determine the intervention measures for preventing recurrence of the current reported, to better inform healthcare professionals and patients. The PubMed, Embase, Web of Science, Cochrane Library databases, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wan Fang Data and Chongqing VIP Information (CQVIP) were accessed up to June 17, 2023. This scoping review followed the five-steps framework described by Arksey and O'Malley and the PRISMA extension was used to report the review. Eleven articles were included with a total of 1503 patients, and adopted the four effective measures: compression therapy, physical activity, health education, and self-care. To conclude, the use of high pressure compression treatment for life, supplementary exercise therapy, and strengthen health education to promote self-care are recommended strategies of VLU prevention and recurrence. In addition, the importance of multi-disciplinary teams to participate in the care of VLU in crucial.

Iruplinalkib (WX-0593) Versus Crizotinib in ALK TKI-Naive Locally Advanced or Metastatic ALK-Positive NSCLC: Interim Analysis of a Randomized, Open-Label, Phase 3 Study (INSPIRE).

INTRODUCTION: Iruplinalkib (WX-0593) is a new-generation, potent ALK tyrosine kinase inhibitor (TKI) that has been found to have systemic and central nervous system (CNS) efficacy in ALK-positive NSCLC. We compared the efficacy and safety of iruplinalkib with crizotinib in patients with ALK TKI-naive, locally advanced or metastatic ALK-positive NSCLC. METHODS: In this open-label, randomized, multicenter, phase 3 study, patients with ALK-positive NSCLC were randomly assigned to receive iruplinalkib 180 mg once daily (7-d run-in at 60 mg once daily) or crizotinib 250 mg twice daily. The primary end point was progression-free survival (PFS) assessed by Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included PFS by investigator, objective response rate (ORR), time to response, duration of response, intracranial ORR and time to CNS progression by IRC and investigator, overall survival, and safety. An interim analysis was planned after approximately 70% (134 events) of all 192 expected PFS events assessed by IRC were observed. Efficacy was analyzed in the intention-to-treat population. Safety was assessed in the safety population, which included all randomized patients who received at least one dose of the study drugs. This study is registered with Center for Drug Evaluation of China National Medical Products Administration (CTR20191231) and Clinicaltrials.gov (NCT04632758). RESULTS: From September 4, 2019, to December 2, 2020, a total of 292 patients were randomized and treated; 143 with iruplinalkib and 149 with crizotinib. At this interim analysis (145 events), the median follow-up time was 26.7 months (range: 3.7-37.7) in the iruplinalkib group and 25.9 months (range: 0.5-35.9) in the crizotinib group. The PFS assessed by IRC was significantly longer among patients in the iruplinalkib group (median PFS, 27.7 mo [95% confidence interval (CI): 26.3-not estimable] versus 14.6 mo [95% CI: 11.1-16.5] in the crizotinib group; hazard ratio, 0.34 [98.02% CI: 0.23-0.52], p < 0.0001). The ORR assessed by IRC was 93.0% (95% CI: 87.5-96.6) in the iruplinalkib group and 89.3% (95% CI: 83.1-93.7) in the crizotinib group. The intracranial ORR was 90.9% (10 of 11, 95% CI: 58.7-99.8) in the iruplinalkib group and 60.0% (nine of 15, 95% CI: 32.3-83.7) in the crizotinib group for patients with measurable baseline CNS metastases. Incidence of grade 3 or 4 treatment-related adverse events was 51.7% in the iruplinalkib group and 49.7% in the crizotinib group. CONCLUSIONS: Iruplinalkib was found to have significantly improved PFS and improved intracranial antitumor activity versus crizotinib. Iruplinalkib may be a new treatment option for patients with advanced ALK-positive and ALK TKI-naive NSCLC. FUNDING: This study was funded by Qilu Pharmaceutical Co., Ltd., Jinan, People's Republic of China, and partly supported by the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

Effects of feeding different levels of dietary corn silage on growth performance, rumen fermentation and bacterial community of post-weaning dairy calves.

OBJECTIVE: The objective of this study was to evaluate the growth performance, rumen fermentation parameters and bacterial community of post-weaning dairy calves in response to five diets varying in corn silage (CS) inclusion. METHODS: A total of forty Holstein weaned bull calves (80±3 days of age;128.2±5.03 kg at study initiation) were randomized into five groups (8 calves/group) with each receiving one of five dietary treatments offered as total mixed ration in a 123-d feeding study. Dietary treatments were control diet (CON; 0% CS dry matter [DM]); Treatment 1 (T1; 27.2% CS DM); Treatment 2 (T2; 46.5% CS DM); Treatment 3 (T3; 54.8% CS DM); and Treatment 4 (T4; 67.2% CS DM) with all diets balanced for similar protein and energy concentration. RESULTS: Results showed that calves offered CS had greater average daily gain, body length and chest depth growth, meanwhile altered rumen fermentation indicated by decreased rumen acetate concentrations. Principal coordinate analysis showed the rumen bacterial community structure was affected by varying CS inclusion diets. Bacteroidetes and Firmicutes were the predominant bacterial phyla in the calf rumens across all treatments. At the genus level, the abundance of Bacteroidales_RF16_group was increased, whereas Unclassified_ Lachnospiraceae was decreased for calves fed CS. Furthermore, Spearman's correlation test between the rumen bacteria and rumen fermentation parameters indicated that Bacteroidales_RF16_group and Unclassified Lachnospiraceae were positively correlated with propionate and acetate, respectively. CONCLUSION: The results of the current study suggested that diet CS inclusion was beneficial for post-weaning dairy calf growth, with 27.2% to 46.5% CS of diet DM recommended to achieve improved growth performance. Bacteroidales_RF16_group and Unclassified Lachnospiraceae play an important role in the rumen fermentation pattern for post-weaning calves fed CS.

A first-in-human, open-label, dose-escalation and dose-expansion phase I study to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of QL1604, a humanized anti-PD-1 mAb, in patients with advanced or metastatic solid tumors.

Background: QL1604 is a humanized immunoglobulin G4 monoclonal antibody against programmed cell death protein 1. This first-in-human, open-label phase I study aimed to investigate the safety and tolerability and to identify the recommended doses of QL1604 for future studies. Pharmacokinetics/pharmacodynamics (PK/PD) and preliminary antitumor activity were also assessed. Methods: Patients with advanced or metastatic solid tumors who failed or had no standard therapies available were recruited. In the dose-escalation phase, patients were treated with QL1604 at 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg intravenously once every 2 weeks (Q2W) in an accelerated titration with a traditional 3 + 3 design, followed by a dose-expansion phase at 3 mg/kg Q2W, 3 mg/kg once every 3 weeks (Q3W), 10 mg/kg Q2W and a fixed dose of 200 mg Q3W. Dose-limiting toxicities (DLTs) were assessed during the first 28 days after the first dose of study drug. Adverse events (AEs) were graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, and antitumor activity of QL1604 was evaluated by investigators on the basis of Response Evaluation Criteria in Solid Tumors version 1.1. Results: A total of 35 patients with advanced or metastatic solid tumors were enrolled. DLTs were reported in one patient at the dose level of 3 mg/kg Q2W (grade 3 immune-mediated myositis and myasthenia gravis), and maximum tolerated dose was not reached. The most frequent treatment-related AEs (≥10%) were fatigue (37.1%), anemia (22.9%), increased blood thyroid-stimulating hormone (17.1%), increased aspartate aminotransferase (AST) (17.1%), increased alanine aminotransferase (ALT) (14.3%), decreased white blood cell (WBC) count (11.4%), rash (14.3%), and pruritus (14.3%). AEs leading to discontinuation of QL1604 occurred in three of the 35 patients (8.6%). Partial responses (PRs) occurred in seven patients, resulting in an objective response rate of 20.0% (7/35). Single dose of QL1604 exhibited a dose-dependent increase in the exposure ranging from 0.3 mg/kg to 10 mg/kg. Mean receptor occupancy (RO) for QL1604 at the dose of 3 mg/kg (Q2W and Q3W) and 200 mg (Q3W) was greater than 80% during cycle 1 after one infusion. Conclusion: QL1604 monotherapy exhibited favorable safety, PK, and signal of antitumor activity in patients with advanced or metastatic solid tumors, and the results supported further clinical studies of QL1604. On the basis of the safety, PK, and RO data, the recommended dosage for further clinical trials is 3 mg/kg or a fixed dose of 200 mg given every 3 weeks. Clinical Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT05649761?term=QL1604&draw=2&rank=1, identifier NCT05649761.

Drug-drug conjugates self-assembled nanomedicines triggered photo-/immuno- therapy for synergistic cancer treatments.

Although immunotherapies have made progress in cancer treatment, their clinical response rates vary widely and are typically low due to sparse immune cell infiltration (immune "cold") and suppressive tumor immune microenvironment (TIME). A simple yet effective approach that integrates a variety of immune-stimulating and TIME-modulating functions could potentially address this clinical challenge. Herein, we conjugate two small molecules, including a photosensitizer (pyropheophorbide-a, PA) and a Toll-like receptor 7/8 agonist (resiquimod, R848), into prodrug (PA-R848) that self-assembles into PA-R848 esterase responsive nanoparticles (PARE NPs) with 100% drug composition and synergistic photo-/immune- therapeutic effects. In PARE NPs, PA exhibits strong phototherapeutic effects which ablate the primary tumor directly and elicits immunogenic cell death (ICD) to promote the immune response. R848 effectively polarizes the M2-type tumor-associated macrophage (TAM) to M1-type TAM, consequently reversing the "cold" and suppressive TIME when working together with phototherapy. The PARE NPs can efficiently pare down the tumor development by two synergisms, including i) synergistic immunotherapy between ICD and TAM polarization; ii) and the antitumor effects between phototherapy and immunotherapy. On a head-neck squamous cell carcinoma mouse model, PARE NPs combined with PD-1 antibody eliminate primary tumors, and significantly inhibit the progress of distant tumors thanks to the robust antitumor immunity enhanced by the PARE NPs.

Nomogram to predict feeding intolerance in critically ill children.

Feed intolerance (FI) is significantly associated with poor prognosis in critically ill patients. This study aimed to understand the characteristics of children with FI and identify the factors predicting FI in critically ill children. This retrospective cohort study was conducted between January 2017 and June 2022 in the Pediatric Intensive Care Unit of a specialized children's hospital. Eighteen factors, including age, body mass index for age z-score (BAZ) < -2, paediatric index of mortality (PIM)3 score, Glasgow coma scale score, mechanical ventilation (MV), enteral nutrition delay, vasoactive drugs, sedatives, sepsis, heart disease, neurological disease, hypokalemia, arterial PH < 7.35, arterial partial pressure of oxygen (PaO2), blood glucose, hemoglobin, total protein, and albumin, were retrieved to predict FI. The outcome was FI during PICU stay. During the study period, a total of 854 children were included, of which 215 children developed FI. Six predictors of FI were selected: PIM3 score, MV, sepsis, hypokalemia, albumin, and PaO2. Multivariate logistic regression analysis showed that higher PIM3 score, MV, sepsis, hypokalemia, and lower PaO2 were independent risk factors for FI, whereas higher albumin was an independent protective factor for FI. The C-index of the predictive nomogram of 0.943 was confirmed at internal validation to be 0.940, indicating a good predictive value of the model. Decision curve analysis shows good clinical applicability of the nomogram in predicting FI.    Conclusion: The nomogram was verified to have a good prediction performance based on discrimination, calibration, and clinical decision analysis. What is Known: • Research has demonstrated that gastrointestinal (GI) dysfunction is not only a fundamental element of Multiple Organ Dysfunction Syndrome (MODS), but also the initiator of MODS. • Previous study has demonstrated a significant association between FI and poor prognosis in critically ill patients. What is New: • We excluded patients with primary gastrointestinal tract disease from our study, and we observed an incidence of FI of 25.2% in the Pediatric Intensive Care Unit (PICU). • Our study revealed that PIM3 score, MV, sepsis, hypokalemia, albumin, and PaO2 are significant predictors of FI.

Methylotrophic methanogens and bacteria synergistically demethylate dimethylarsenate in paddy soil and alleviate rice straighthead disease.

Microorganisms play a key role in arsenic (As) biogeochemistry, transforming As species between inorganic and organic forms and different oxidation states. Microbial As methylation is enhanced in anoxic paddy soil, producing primarily dimethylarsenic (DMAs), which can cause rice straighthead disease and large yield losses. DMAs can also be demethylated in paddy soil, but the microorganisms driving this process remain unclear. In this study, we showed that the enrichment culture of methylotrophic methanogens from paddy soil demethylated pentavalent DMAs(V) efficiently. DMAs(V) was reduced to DMAs(III) before demethylation. 16S rRNA gene diversity and metagenomic analysis showed that Methanomassiliicoccus dominated in the enrichment culture, with Methanosarcina and Methanoculleus also being present. We isolated Methanomassiliicoccus luminyensis CZDD1 and Methanosarcina mazei CZ1 from the enrichment culture; the former could partially demethylate trivalent DMAs(III) but not DMAs(V) and the latter could demethylate neither. Addition of strain CZDD1 to the enrichment culture greatly accelerated DMAs(V) demethylation. Demethylation of DMAs(V) in the enrichment culture was suppressed by ampicillin, suggesting the involvement of bacteria. We isolated three anaerobic bacterial strains including Clostridium from the enrichment culture, which could produce hydrogen and reduce DMAs(V) to DMAs(III). Furthermore, augmentation of the Methanomassiliicoccus-Clostridium coculture to a paddy soil decreased DMAs accumulation by rice and alleviated straighthead disease. The results reveal a synergistic relationship whereby anaerobic bacteria reduce DMAs(V) to DMAs(III) for demethylation by Methanomassiliicoccus and also produce hydrogen to promote the growth of Methanomassiliicoccus; enhancing their populations in paddy soil can help alleviate rice straighthead disease.

Standardized nursing mode effectively controls pain caused by radiotherapy and chemotherapy in patients with advanced cancer.

OBJECTIVE: To explore the application value of a standardized nursing model in pain management of advanced cancer patients undergoing radiotherapy and chemotherapy. METHODS: The clinical data of 166 patients with advanced cancer who suffered pain after receiving radiotherapy and chemotherapy in the Oncology Department of Guang'an People's Hospital from June 2020 to June 2021 were retrospectively analyzed. Among them, 83 patients who received routine care were grouped as a control group, while the other 83 patients who received standardized cancer pain nursing based on routine nursing were set as the experimental group. The location, duration, and degree of pain (numeric rating scales, NRS) and quality of life (European Quality of Life Scale, QLQ-C30) of patients were evaluated. RESULTS: Before treatment and nursing intervention, there were no significant differences in the location, duration, or degree of pain as well as in patients' quality of life between the two groups (all P>0.05). During and after radiotherapy, the pain was mainly concentrated in the skin of the radiation field, and the duration of pain increased with the number of rounds of radiotherapy. After nursing, patients in the experimental group showed lower NRS scores than those in the control group (P<0.05); the scores of physical function, role function, emotional function, cognitive function, social function and general health status of the experimental group were higher than those of the control group (all P<0.05); and the scores of fatigue, nausea and vomiting, pain, insomnia, loss of appetite and constipation in the experimental group were lower than those in the control group (all P<0.05). CONCLUSION: A standardized cancer pain nursing model can effectively alleviate the radio-chemotherapy induced pain of cancer patients and effectively improve their quality of life.

Longitudinal Changes in Milk Microorganisms in the First Two Months of Lactation of Primiparous and Multiparous Cows.

The present experiment was carried out to analyze the longitudinal changes in milk microorganisms. For this purpose, milk samples were collected from 12 healthy cows (n = 96; six primiparous cows and six multiparous cows) at eight different time points. The characteristics and variations in microbial composition were analyzed by 16S rRNA gene high-throughput sequencing. In the primiparous group, higher and more stable alpha diversity was observed in transitional and mature milk compared with the colostrum, with no significant difference in alpha diversity at each time point in the multiparous group. Proteobacteria, Firmicutes, Bacteroidota, and Actinobacteriota were the most dominant phyla, and Pseudomonas, UCG-005, Acinetobacter, Vibrio, Lactobacillus, Bacteroides, Serratia, Staphylococcus, and Glutamicibacter were the most dominant genera in both primiparous and multiparous cow milk. Some typically gut-associated microbes, such as Bacteroides, UCG-005, and Rikenellaceae_RC9_gut_group, etc., were enriched in the two groups. Biomarker taxa with the day in time (DIM) were identified by a random forest algorithm, with Staphylococcus showing the highest degree of interpretation, and the difference in milk microbiota between the two groups was mainly reflected in 0 d-15 d. Additionally, network analysis suggested that there were bacteria associated with the total protein content in milk. Collectively, our results disclosed the longitudinal changes in the milk microbiota of primiparous and multiparous cows, providing further evidence in dairy microbiology.

Prevalence and Risk Factors for COPD in an Urbanizing Rural Area in Western China: A Cross-Sectional Study.

Purpose: To investigate the prevalence and risk factors for chronic obstructive pulmonary disease (COPD) in a rural area in western China with severe air pollution. Patients and Methods: 10% of local residents aged 40 years and above were included using a convenience sampling method. This was a cross-sectional study. A self-designed questionnaire was used to collect participants' demographic data. The screening program was comprised of two steps: First, a portable electronic spirometer was used for COPD screening. Those participants with FEV1/FVC ratio <0.7 were then referred to a confirmatory pulmonary function (PF) test. COPD was confirmed according to the 2020 Global Initiative for Chronic Obstructive Lung Disease criteria. Results: A total of 4577 participants aged 40 years old or above were included in the final analysis. Examination with a mobile spirometer identified 1159 individuals for confirmatory testing; after that, of the 1159 individuals, 889 were diagnosed with COPD by the confirmatory PF test. The prevalence of COPD among the target group was 19.4%. Older age, male sex (odds ratio [OR] = 1.537, 95% confidence interval [CI] 1.246-1.894), smoking history (OR = 1.338, 95% CI 1.069-1.675), family history of respiratory disease (OR = 1.625, 95% CI 1.350-1.957), education level (OR = 0.735, 95% CI 0.617-0.876), overweight (OR = 0.614, 95% CI 0.517-0.730) and obesity (OR = 0.572, 95% CI 0.449-0.721) were identified as independent factors associated with COPD. The screening program helped earlier detection of COPD in 719 participants. Conclusion: COPD was highly prevalent in the rural area studied. Rural residents who were older, current or ever-smokers, male and those who had a lower education level were more vulnerable to developing COPD. The COPD screening program may be helpful for earlier disease detection in rural health-care settings.

Ginsenoside Re attenuates myocardial ischemia/reperfusion induced ferroptosis via miR-144-3p/SLC7A11.

BACKGROUND: Ginsenoside Re is an active component in ginseng that confers protection against myocardial ischemia/reperfusion (I/R) injury. Ferroptosis is a type of regulated cell death found in various diseases. PURPOSE: Our study aims to investigate the role of ferroptosis and the protective mechanism of Ginsenoside Re in myocardial ischemia/reperfusion. METHODS: In the present study, we treated rats for five days with Ginsenoside Re, then established the myocardial ischemia/reperfusion injury rat model to detect molecular implications in myocardial ischemia/reperfusion regulation and to determine the underlying mechanism. RESULTS: This study identifies the mechanism behind ginsenoside Re's effect on myocardial ischemia/reperfusion injury and its regulation of ferroptosis through miR-144-3p. Ginsenoside Re significantly reduced cardiac damage caused by ferroptosis during myocardial ischemia/reperfusion injury and glutathione decline. To determine how Ginsenoside Re regulated ferroptosis, we isolated exosomes from VEGFR2+ endothelial progenitor cells after ischemia/reperfusion injury and performed miRNA profiling to screen the miRNAs aberrantly expressed in the process of myocardial ischemia/reperfusion injury and ginsenoside Re treatment. We identified that miR-144-3p was upregulated in myocardial ischemia/reperfusion injury by luciferase report and qRT-PCR. We further confirmed that the solute carrier family 7 member 11 (SLC7A11) was the target gene of miR-144-3p by database analysis and western blot. In comparison with ferropstatin-1, a ferroptosis inhibitor, in vivo studies confirmed that ferropstatin-1 also diminished myocardial ischemia/reperfusion injury induced cardiac function damage. CONCLUSION: We demonstrated that ginsenoside Re attenuates myocardial ischemia/reperfusion induced ferroptosis via miR-144-3p/SLC7A11.

Boosting ROS-Mediated Lysosomal Membrane Permeabilization for Cancer Ferroptosis Therapy.

Due to the deficient catalase, abundant reduced iron and low acidic environment in lysosomes, inducing lysosomal membrane permeabilization (LMP) through Fenton reaction-based reactive oxygen species (ROS) generation recently attracts increasing attention in cancer therapy. However, the lysosomal membranes are protected by highly glycosylated membrane proteins and several endolysosomal damage-response mechanisms can rapidly repair the injured lysosomes. To produce sufficient ROS and cause complete lysosomal membranes rupture, a lysosome-targeted ROS inducer, N-(3-Aminopropyl) morpholine grafted cross-linked lipoic acid vesicles with vitamin C-loading (VC@N3AM cLAVs), is developed. VC@N3AM cLAVs efficiently accumulate in lysosomes and convert into two redox couples LA/DHLA (dihydrolipoic acid, reduced form of LA) and VC/DHA (dehydroascorbic acid, oxidized form of VC) by the lysosomal glutathione, which can not only produce a large amount of H2 O2 by pro-oxidant action but also accelerate iron transformation through the cyclic redox reactions between each other and cause the efficient conversion of the generated H2 O2 into highly toxic •OH. Both in vitro and in vivo experiments demonstrate that VC@N3AM cLAVs can effectively enhance ROS production and boost LMP, finally initiation irreversible death of tumor cells via ferroptosis pathway, thus representing a potential anticancer drug for cancer therapy.

Prevalence of possible sarcopenia in community-dwelling older Chinese adults: a cross-sectional study.

OBJECTIVES: To determine the prevalence of possible sarcopenia and its association with other conditions in older adults in Bengbu, China. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional study of 1082 community-dwelling Chinese people aged at least 60 years from March to June 2022. METHODS: Handgrip strength and information regarding associated conditions were collected. Possible sarcopenia was estimated based on handgrip strength with cut-off values (<28 kg in men; <18 kg in women) recommended by the Asia Working Group for Sarcopenia in 2019. Mann-Whitney U tests, χ2 tests and binary logistic regression analyses were used to explore relationships between possible sarcopenia and associated conditions. RESULTS: Possible sarcopenia was more prevalent in men (52.79%, n=246, age 79.43±7.33 years among men with possible sarcopenia) than in women (44.48%, n=274, age 78.90±7.71 years among women with possible sarcopenia). In men, possible sarcopenia positively correlated with high age (OR 2.658, 95% CI 1.758 to 4.019), physical inactivity (OR 2.779, 95% CI 1.646 to 4.691) and diabetes (OR 4.269, 95% CI 2.397 to 7.602), and negatively with hypertension (OR 0.586, 95% CI 0.384 to 0.893). The risk of possible sarcopenia in men decreased by 12.6% for every 1 kg/m2 increase of body mass index (OR 0.874, 95% CI 0.817 to 0.935). In women, possible sarcopenia positively correlated with high age (OR 3.821, 95% CI 2.677 to 5.455), physical inactivity (OR 2.185, 95% CI 1.488 to 3.210) and arthritis (OR 2.076, 95% CI 1.411 to 3.056). CONCLUSION: Possible sarcopenia is prevalent in older adults and the factors affecting possible sarcopenia are different in men and women. Health education about these target factors can be considered as a potential measure to prevent possible sarcopenia.

RNA polymerase III directly participates in DNA homologous recombination.

A recent study showed that RNA transcription is directly involved in DNA homologous recombination (HR). The first step in HR is end resection, which degrades a few kilobases or more from the 5'-end strand at DNA breaks, but the 3'-end strand remains strictly intact. Such protection of the 3'-end strand is achieved by the transient formation of an RNA-DNA hybrid structure. The RNA strand in the hybrid is newly synthesized by RNA polymerase III. The revelation of the existence of an RNA-DNA hybrid intermediate should further help resolve several long-standing questions of HR. In this article, we also put forward our views on some controversial issues related to RNA-DNA hybrids, RNA polymerases, and the protection of 3'-end strands.

Aluminum-Induced Alterations to the Cell Wall and Antioxidant Enzymes Involved in the Regulation of the Aluminum Tolerance of Chinese Fir (Cunninghamia lanceolata).

Chinese fir (Cunninghamia lanceolata), which is an important coniferous tree species in China, is mainly planted in acidic soils with toxic aluminum (Al) levels. However, the consequences of Al toxicity and its resistance mechanism in Chinese fir remain largely uncharacterized. In this study, the Al-induced modification and possible role of cell wall in regulating Al tolerance in Chinese fir were investigated by using seedlings with contrasting Al tolerance, namely, Al-sensitive (YX02) and Al-resistant (YX01) genotypes. The results in present work showed that Al treatment resulted in a dose- and time-dependent inhibition of root growth and oxidative damage in both genotypes, but more in YX02 than in YX01. The severe oxidative damage observed in YX02 under Al stress was found to correlate with lower antioxidant enzyme activities as compared with YX01. The greater root growth inhibition observed in YX02 compared with YX01 was associated with a higher accumulation of Al in pectin and hemicllulose 1 (HC1) fraction because of the higher pectin and HC1 contents and the lower degree of pectin demethylation due to enhanced pectin methylesterase activity in YX02, which ultimately enhanced cell wall binding capacity for Al in YX02. Taken together, our results suggested that enhancement of antioxidant enzyme activities and cell wall modification-induced Al exclusion are the two mechanisms responsible for the Al tolerance of Chinese fir.

Radiative coupling of two quantum emitters in arbitrary metallic nanostructures.

We propose a general formalism beyond Weisskopf-Wigner approximation to efficiently calculate the coupling matrix element, evolution spectrum and population evolution of two quantum emitters in arbitrary metallic nanostructures. We demonstrate this formalism to investigate the radiative coupling and decay dynamics of two quantum emitters embedded in the two hot spots of three silver nano-spheroids. The vacuum Rabi oscillation in population evolution and the anti-crossing behavior in evolution spectrum show strong radiative coupling is realized in this metallic nanostructure despite its strong plasmon damping. Our formalism can serve as a flexible and efficient calculation tool to investigate the distant coherent interaction in a large variety of metallic nanostructures, and may be further developed to handle the cases for multiple quantum emitters and arbitrary dielectric-metallic hybrid nanostructures.

Clinical observation of sacubitril valsartan sodium in the treatment of resistant hypertension: A randomized clinical trial.

Objective: To investigate the effectiveness and safety of sacubitril valsartan sodium in the treatment of resistant hypertension (RH). Methods: This study is a single-center, prospective, randomized controlled study. According to the inclusion and exclusion criteria, patients with RH who met the criteria were screened, and all patients adjusted their drug treatment (valsartan 80 mg, amlodipine 5 mg, and hydrochlorothiazide 12.5 mg). After 4 weeks of drug elution, the random envelope method was used for random grouping. The treatment group took sacubitril valsartan sodium 200 mg, amlodipine 5 mg, hydrochlorothiazide 12.5 mg, and the control group took valsartan 80 mg, amlodipine 5 mg, and hydrochlorothiazide 12.5 mg for 8 weeks. The 24 h ambulatory blood pressure (BP) and the echocardiography index using the office sphygmomanometer were observed in the patients. Results: A total of 100 patients with RH were included in the two groups, with 50 cases in each group. There were no significant differences in sex, age, or comorbid diseases between the two groups. During the 8-week follow-up, the office BP of the research group were significantly decreased (24.78/17.86 mmHg) compared with those of the control group. In the research group the 24 h average BP, daytime average BP, and nighttime average BP were 144.84/79.82, 147.10/82.06, and 138.67/76.31 mmHg at baseline, and reduced to 128.96/73.32, 131.50/74.94, and 122.11/69.27 mmHg at week 8, which were significantly decreased (P < 0.05 or P < 0.01), and the left ventricular ejection fraction was significantly increased (P < 0.05), compared with the control group. Conclusion: Sacubitril valsartan sodium can effectively reduce BP and improve cardiac function in RH.