Three-dimensional rattan-derived electrodes with directional channels and large mass loadings for high-performance aqueous zinc-ion batteries.

Aqueous zinc-ion batteries (AZIBs) have emerged as prospective candidates for wide-scale energy storage, benefiting from their exceptional reliability and budget-friendliness. To tackle the challenge of limited energy density of AZIBs, it is pivotal to explore cathodes with substantial mass loadings. In this study, rattan is converted into a three-dimensional (3D) current collector with directional channels, high compressive strength, good electrolyte affinity, and superior electrochemical stability through a process involving ultraviolet light irradiation-assisted delignification followed by high-temperature carbonization. Using this current collector and a straightforward slurry pasting method, a 3D MnO2 cathode featuring substantial loading amount of 10 mg cm-2 for active material can be constructed. This cathode's rich channel structure allows the carbon nanotube/MnO2 composite material to establish full contact with the electrolyte, significantly facilitating interfacial charge transfer. The optimized cathode achieves an outstanding areal capacity of 3.65 mAh cm-2 at 0.1 A/g and sustains 1.52 mAh cm-2 at 1 A/g. Besides, the capacity retention remains at 60.2 % after 1000 cycles, even under such large mass loading. Notably, the fabrication procedure of the 3D cathode is simple, and the associated costs are relatively low compared to other 3D cathodes for AZIBs. These findings present an effective strategy for developing cost-effective and high-performance electrodes with large areal capacities, advancing energy storage technologies.

Improved high-current-density hydrogen evolution reaction kinetics on single-atom Co embedded in an order pore-structured nitrogen assembly carbon support.

Single-atom catalysis is a subcategory of heterogeneous catalysis with well-defined active sites. Numerous endeavors have been devoted to developing single-atom catalysts for industrially applicable catalysis, including the hydrogen evolution reaction (HER). High-current-density electrolyzers have been pursued for single-atom catalysts to increase active-site density and enhance mass transfer. Here, we reasoned that a single-atom metal embedded in nitrogen assembly carbon (NAC) catalysts with high single-atom density, large surface area, and ordered mesoporosity, could fulfil an industrially applicable HER. Among several different single-atom catalysts, the HER overpotential with the best performing Co-NAC reached a current density of 200 mA cm-2 at 310 mV, which is relevant to industrially applicable current density. Density functional theory (DFT) calculations suggested feasible hydrogen binding on single-atom Co resulted in the promising HER activity over Co-NAC. The best-performing Co-NAC showed robust performance under alkaline conditions at a current density of 50 mA cm-2 for 20 h in an H-cell and at a current density of 150 mA cm-2 for 100 h in a flow cell.

Three-dimensional gel network structure of agarose interlayer dispersed Pd nanoparticles in copper foam electrode for electrocatalytic degradation of doxycycline hydrochloride.

In this study, we successfully prepared palladium/agarose/copper foam (Pd/AG/CF) composite electrodes by utilizing the three-dimensional network structure agarose (AG), a green material derived from biomass, and homogeneously immobilizing palladium (Pd) atoms on a copper foam (CF) substrate through a facile route. The electrode showed excellent performance in the electrocatalytic degradation of doxycycline (DOX), with a high DOX degradation rate of 92.19 % in 60 min. In-depth studies revealed that palladium can form metal-metal interactions with the CF substrates, which enhances the electron transfer on the catalyst surface. In addition, the introduction of agarose effectively prevented the agglomeration of palladium nanoparticles. In addition, the hydroxyl functional groups in the molecular structure of agarose facilitate interactions between water molecules and the electrode interface through the formation of hydrogen bonds, thereby further enhancing the efficiency of the electrocatalytic reaction. In addition to good stability and reusability. Microbial toxicity test results show that the degraded wastewater has minimal impact on the environment. Also, possible degradation pathways of DOX were explored in this study. Finally, a novel continuous flow reactor was designed, featuring a unique design that ensures full contact between wastewater and the composite electrodes, thereby achieving continuous and efficient treatment of antibiotic wastewater.

Integration of clinical and blood parameters in risk prognostication for patients receiving immunochemotherapy for extensive stage small cell lung cancer: real-world data from two centers.

BACKGROUND: Immune checkpoint inhibitors (ICIs) had modest advances in the treatment of extensive-stage small cell lung cancer (ES-SCLC) in clinical trials, but there is a lack of biomarkers for prognosis in clinical practice. METHODS: We retrospectively collected data from ES-SCLC patients who received ICIs combined chemotherapy from two centers in China, integrated clinical and blood parameters, and constructed risk prognostication for immunochemotherapy. The population was divided into high- and low-risk groups, and the performance of the model was assessed separately in the training and validation cohorts. RESULTS: Two hundred and twenty and 43 patients were included in the training and validation groups, respectively. The important predictors were screened including body mass index, liver metastases, coefficient variation of red blood cell distribution width, lactate dehydrogenase, albumin, and C-reactive protein. Predicting 1-year overall survival (OS), the AUC values under ROC for the model under training, internal validation, and external validation were 0.760, 0.732, and 0.722, respectively, and the calibration curve and clinical decision curve performed well. Applied the model to divide patients into low-risk and high-risk groups, and the median OS was 23.7 months and 9.1 months, and the median progression-free survival was 8.2 months and 4.8 months, respectively; furthermore, this ability to discriminate survival was also observed in the validation cohort. CONCLUSIONS: We constructed a novel prognostic model for ES-SCLC to predict survival employing baseline tumor burden, nutritional and inflammatory parameters, it is easily measured to screen high-risk patient populations.

Macrophage targeted graphene oxide nanosystem synergize antibiotic killing and host immune defense for Tuberculosis Therapy.

Tuberculosis (TB), a deadly disease caused by Mycobacterium tuberculosis (Mtb) infection, remains one of the top killers among infectious diseases worldwide. How to increase targeting effects of current anti-TB chemotherapeutics and enhance anti-TB immunological responses remains a big challenge in TB and drug-resistant TB treatment. Here, mannose functionalized and polyetherimide protected graphene oxide system (GO-PEI-MAN) was designed for macrophage-targeted antibiotic (rifampicin) and autophagy inducer (carbamazepine) delivery to achieve more effective Mtb killings by combining targeted drug killing and host immunological clearance. GO-PEI-MAN system demonstrated selective uptake by in vitro macrophages and ex vivo macrophages from macaques. The endocytosed GO-PEI-MAN system would be transported into lysosomes, where the drug loaded Rif@Car@GO-PEI-MAN system would undergo accelerated drug release in acidic lysosomal conditions. Rif@Car@GO-PEI-MAN could significantly promote autophagy and apoptosis in Mtb infected macrophages, as well as induce anti-bacterial M1 polarization of Mtb infected macrophages to increase anti-bacterial IFN-γ and nitric oxide production. Collectively, Rif@Car@GO-PEI-MAN demonstrated effectively enhanced intracellular Mtb killing effects than rifampicin, carbamazepine or GO-PEI-MAN alone in Mtb infected macrophages, and could significantly reduce mycobacterial burdens in the lung of infected mice with alleviated pathology and inflammation without systemic toxicity. This macrophage targeted nanosystem synergizing increased drug killing efficiency and enhanced host immunological defense may be served as more effective therapeutics against TB and drug-resistant TB.

Comparative investigation of exosome extraction from rat bone marrow mesenchymal stem cells using three different methodologies.

Exosomes have been identified as crucial mediators in numerous physiological and pathological processes, emerging as a focal point of scientific inquiry. This study aims to compare three methods for isolating exosomes from rat bone marrow mesenchymal stem cells: ultracentrifugation (UC), ultrafast separation system (EXODUS), and commercial precipitation kit (EXO-kit). First, the investigation compared exosomal morphology, particle size distribution, and expression of marker proteins. Subsequently, the RNA content, protein concentration, and purity of exosomes were evaluated. Finally, the impact of these exosomes on cellular metabolic viability and migration capacity was assessed. Results indicated that exosomes exhibited spherical or elliptical membrane structures, and most of the exosomes extracted by the three methods were in the range of 30to 200 nm. UC-extracted exosomes demonstrated the least impurities and clearest background, followed by EXODUS-extracted exosomes, and lastly EXO-kit-extracted exosomes. The EXO-kit-extracted exosomes yielded the highest RNA and protein content, whereas those isolated through UC exhibited superior purity. Furthermore, exosomes extracted from EXODUS and EXO-kit methods effectively enhanced the metabolic viability and migratory ability of osteoblast precursor cells compared to UC-extracted exosomes. In conclusion, each of the three methodologies presents advantages and limitations. Therefore, the selection of an appropriate exosome extraction technique should be based on specific experimental objectives and requirements.

Emerging insights into traditional Chinese medicine associated with neurodegenerative diseases: A bibliometric analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Research suggests that traditional Chinese medicine (TCM) holds promise in offering innovative approaches to tackle neurodegenerative disorders. In our endeavor, we conducted a comprehensive bibliometric analysis to delve into the landscape of TCM research within the realm of neurodegenerative diseases, aiming to uncover the present scenario, breadth, and trends in this field. This analysis presents potentially valuable insights for the clinical application of traditional Chinese medicine and provides compelling evidence supporting its efficacy in the treatment of neurodegenerative conditions. AIM OF THE STUDY: The incidence of neurodegenerative diseases is on the rise, yet effective treatments are still lacking. Research indicates that TCM could offer novel perspectives for addressing neurodegenerative conditions. Nonetheless, the literature on this topic is intricate and multifaceted, with existing reviews offering only limited coverage. To gain a thorough understanding of TCM research in neurodegenerative diseases, we undertook a bibliometric analysis to explore the current status, scope, and trends in this area. MATERIALS AND METHODS: A literature search was carried out on April 1, 2024, utilizing the Web of Science Core Collection (WoSCC). Visualization and quantitative analyses were then performed with the assistance of CiteSpace, VOSviewer, and R software. RESULTS: A total of 6856 articles were retrieved in the search. Research on TCM for neurodegenerative diseases commenced in 1989 and has exhibited a notable overall growth since then. Main research contributors include East Asian countries like China, as well as the United States. Through our analysis, we identified 15 highly productive authors, 10 top-tier journals, 13 citation clusters, 11 influential articles, and observed a progression in keyword evolution across 4 distinct categories. In 2020, there was a significant upsurge in the knowledge base, collaboration efforts, and publication output within the field. This field is interdisciplinary: network pharmacology emerges as the cutting-edge paradigm in TCM research, while Alzheimer's disease remains a prominent focus among neurodegenerative conditions due to its evolving etiology. A burst detection analysis unveils that in 2024, the focal points of research convergence between TCM and neurodegenerative diseases lie in two key biological processes or mechanisms: autophagy and microbiota. CONCLUSIONS: For the first time, this study quantitatively and visually captures the evolution of TCM in addressing neurodegenerative diseases, showcasing a notable acceleration in recent years. Our findings underscore the pivotal role of interdisciplinary collaboration and the necessity for increased global partnerships. Network pharmacology, leveraging the advancements of the big data era, embraces a holistic and systematic approach as a novel paradigm in exploring traditional Chinese medicine and unraveling their fundamental mechanisms. Three ethnomedical plants-Tianma, Renshen, and Wuweizi-demonstrate the promise of their bioactive compounds in treating neurodegenerative disorders, bolstered by their extensive historical usage for such ailments. Moreover, our intricate analysis of the evolutionary trajectories of key themes such as targets and biomarkers substantially enriches our comprehension of the underlying mechanisms involved.

Insights into the Pathogenesis and Treatment of Chemotherapy-Induced Neuropathy: A Focus on Oxidative Stress and Neuroinflammation.

Cancer is a high-morbidity disease prevalent worldwide. Chemotherapy is the primarily used regimen for cancer treatment; however, it also brings severe side effects. Chemotherapy-induced Peripheral Neuropathy (CIPN) and Chemotherapy-induced Cognitive Impairment (CICI) are two main complications occurring in chemotherapy. They are both associated with nervous system injury and are therefore collectively referred to as Chemotherapy-induced Neuropathy (CIN). CIPN induces neuralgia and numbness in limbs, while CICI causes amnesia and cognitive dysfunction. Currently, there are no effective therapeutics to prevent or cure CIN, so research into new drugs to alleviate CIN becomes urgent. Oxidative stress and neuroinflammation are the common pathogenic mechanisms of CIPN and CICI. Excessive Reactive Oxygen Species (ROS) and pro-inflammatory cytokines cause peripheral nervous system damage and hence CIPN. Peripheral ROS and cytokines also change the permeability of the blood-brain barrier, thereby increasing oxidative stress and neuroinflammation in the central nervous system, ultimately leading to CICI. Several antidepressants have been used to treat CIN and exhibited good clinical effects. Their potential pharmacological mechanism has been reported to ameliorate oxidative stress and neuroinflammation, guiding a new feasible way for effective therapeutic development against CIN. This mini-review has summarized the latest advances in the research on CIN with respect to clinical status, pathogenesis, and treatment. It has also discussed the potential of repurposing antidepressants for CIN treatment and prospected the strategy of developing therapeutics by targeting oxidative stress and neuroinflammation against CIN.

piR112710 attenuates diabetic cardiomyopathy through inhibiting Txnip/NLRP3-mediated pyroptosis in db/db mice.

PIWI-interacting RNAs (piRNAs) are involved in the regulation of hypertrophic cardiomyopathy, heart failure and myocardial methylation. However, their functions and the underlying molecular mechanisms in diabetic cardiomyopathy (DCM) have yet to be fully elucidated. In the present study, a pyroptosis-associated piRNA (piR112710) was identified that ameliorates cardiac remodeling through targeting the activation of inflammasomes and mitochondrial dysfunction that are mediated via the thioredoxin-interacting protein (Txnip)/NLRP3 signaling axis. Subsequently, the cardioprotective effects of piR112710 on both the myocardium from db/db mice and cardiomyocytes from neonatal mice that were incubated with a high concentration of glucose combined with palmitate were examined. piR112710 was found to significantly improve cardiac dysfunction in db/db mice, characterized by improved echocardiography, lower levels of fibrosis, attenuated expression levels of inflammatory factors and pyroptosis-associated proteins (namely, Txnip, ASC, NLRP3, caspase-1 and GSDMD-N), and enhanced myocardial mitochondrial respiratory functions. In cultured neonatal mice cardiomyocytes, piR112710 deficiency and high glucose along with palmitate treatment led to significantly upregulated expression levels of pyroptosis associated proteins and collagens, oxidative stress, mitochondrial dysfunction and increased levels of inflammatory factors. Supplementation with piR112710, however, led to a reversal of the aforementioned changes induced by high glucose and palmitate. Mechanistically, the cardioprotective effect of piR112710 appears to be dependent upon effective elimination of reactive oxygen species and inactivation of the Txnip/NLRP3 signaling axis. Taken together, the findings of the present study have revealed that the piRNA-mediated inhibitory mechanism involving the Txnip/NLRP3 axis may participate in the regulation of pyroptosis, which protects against DCM both in vivo and in vitro. piR112710 may therefore be a potential therapeutic target for the reduction of myocardial injury caused by cardiomyocyte pyroptosis in DCM.

Platelet and Erythrocyte Membranes Coassembled Biomimetic Nanoparticles for Heart Failure Treatment.

Cardiac fibrosis is a prevalent pathological process observed in the progression of numerous cardiovascular diseases and is associated with an increased risk of sudden cardiac death. Although the BRD4 inhibitor JQ1 has powerful antifibrosis properties, its clinical application is extremely limited due to its side effects. There remains an unmet need for effective, safe, and low-cost treatments. Here, we present a multifunctional biomimetic nanoparticle drug delivery system (PM&EM nanoparticles) assembled by platelet membranes and erythrocyte membranes for targeted JQ1 delivery in treating cardiac fibrosis. The platelet membrane endows PM&EM nanoparticles with the ability to target cardiac myofibroblasts and collagen, while the participation of the erythrocyte membrane enhances the long-term circulation ability of the formulated nanoparticles. In addition, PM&EM nanoparticles can deliver sufficient JQ1 with controllable release, achieving excellent antifibrosis effects. Based on these advantages, it is demonstrated in both pressures overloaded induced mouse cardiac fibrosis model and MI-induced mouse cardiac fibrosis that injection of the fusion membrane biomimetic nanodrug carrier system effectively reduced fibroblast activation, collagen secretion, and improved cardiac fibrosis. Moreover, it significantly mitigated the toxic and side effects of long-term JQ1 treatment on the liver, kidney, and intestinal tract. Mechanically, bioinformatics prediction and experimental validation revealed that PM&EM/JQ1 NPs reduced liver and kidney damage via alleviated oxidative stress and mitigated cardiac fibrosis via the activation of oxidative phosphorylation activation. These results highlight the potential value of integrating native platelet and erythrocyte membranes as a multifunctional biomimetic drug delivery system for treating cardiac fibrosis and preventing drug side effects.

Causal Associations of Cognitive Reserve and Hierarchical Aging-Related Outcomes: A Two-Sample Mendelian Randomization Study.

PURPOSE: Two-sample Mendelian randomization methods were used to explore the causal effects of cognitive reserve proxies, such as educational attainment, occupational attainment, and physical activity (PA), on biological (leukocyte telomere length), phenotypic (sarcopenia-related features), and functional (frailty index and cognitive performance) aging levels. RESULTS: Educational attainment had a potential protective effect on the telomere length (ß = 0.10, 95% CI: 0.08-0.11), sarcopenia-related features (ß = 0.04-0.24, 95% CI: 0.02-0.27), frailty risk (ß = -0.31, 95% CI: -0.33 to -0.28), cognitive performance (ß = 0.77, 95% CI: 0.75-0.80). Occupational attainment was causally related with sarcopenia-related features (ß = 0.07-0.10, 95% CI: 0.05-0.14), and cognitive performance (ß = 0.30, 95% CI: 0.24-0.36). Device-measured PA was potentially associated with one sarcopenia-related feature (ß = 0.14, 95% CI: 0.03-0.25). CONCLUSIONS: Our findings support the potential causality of educational attainment on biological, phenotypic, and functional aging outcomes, of occupational attainment on phenotypic and functional aging-related outcomes, and of PA on phenotypic aging-related outcomes.

Development and Validation of Prediction Models for Incident Reversible Cognitive Frailty Based on Social-Ecological Predictors Using Generalized Linear Mixed Model and Machine Learning Algorithms: A Prospective Cohort Study.

This study aimed to develop and validate prediction models for incident reversible cognitive frailty (RCF) based on social-ecological predictors. Older adults aged ≥60 years from China Health and Retirement Longitudinal Study (CHARLS) 2011-2013 survey were included as training set (n = 1230). The generalized linear mixed model (GLMM), eXtreme Gradient Boosting, support vector machine, random forest, and Binary Mixed Model forest were used to develop prediction models. All models were evaluated internally with 5-fold cross-validation and evaluated externally via CHARLS 2013-2015 survey (n = 1631). Only GLMM showed good discrimination (AUC = 0.765, 95% CI = 0.736, 0.795) in training set, and all models showed fair discrimination (AUC = 0.578-0.667, 95% CI = 0.545, 0.725) in internal and external validation. All models showed acceptable calibration, overall prediction performance, and clinical usefulness in training and validation sets. Older adults were divided into three groups using risk score based on GLMM, which could assist healthcare providers to predict incident RCF, facilitating early identification of high-risk population.

Impacts of subjective cognitive decline and mild cognitive impairment on the effectiveness of an exercise intervention among community-dwelling (Pre)frail older adults.

BACKGROUND: Subjective cognitive decline (SCD) is prevalent in community-dwelling (pre)frail older adults. This study aimed to investigate whether baseline subjective cognitive decline (SCD) and mild cognitive impairment (MCI) impacted the effectiveness of an exercise intervention among (pre)frail older adults. METHODS: This is a post hoc analysis of a stepped-wedge cluster randomized trial among (pre)frail older adults across six communities. The intervention effectiveness was examined among (pre)frail older people among subgroups with normal cognition (n = 44), SCD (n = 58), or MCI (n = 30). RESULTS: The normal cognition group had both immediate and persistent treatment responses to most outcomes. The SCD group showed positive responses to frailty (0-, 12-, 24 week), ambulation and dynamic balance (0-week), and depressive symptoms (12-week). The MCI group exhibited immediate improvement in frailty, cognition, depressive symptoms, social support and QoL, which persisted only in frailty status, social support and mental QoL at follow-ups. The MCI group showed superior immediate responses to cognitive function and depressive symptoms compared to another two subgroups. No differences were found between the normal cognition and SCD groups except for cognitive status (12-week). CONCLUSIONS: (Pre)frail people with SCD or MCI had fewer improved outcomes compared to those with normal cognition regardless of immediate or persistent improvements. The incorporation of cognitive strategies with exercise interventions are recommended among (pre)frail older adults with SCD or MCI.

Single-Image SVBRDF Estimation Using Auxiliary Renderings as Intermediate Targets.

Recently, single-image SVBRDF capture is formulated as a regression problem, which uses a network to infer four SVBRDF maps from a flash-lit image. However, the accuracy is still not satisfactory since previous approaches usually adopt endto-end inference strategies. To mitigate the challenge, we propose "auxiliary renderings" as the intermediate regression targets, through which we divide the original end-to-end regression task into several easier sub-tasks, thus achieving better inference accuracy. Our contributions are threefold. First, we design three (or two pairs of) auxiliary renderings and summarize the motivations behind the designs. By our design, the auxiliary images are bumpiness-flattened or highlight-removed, containing disentangled visual cues about the final SVBRDF maps and can be easily transformed to the final maps. Second, to help estimate the auxiliary targets from the input image, we propose two mask images including a bumpiness mask and a highlight mask. Our method thus first infers mask images, then with the help of the mask images infers auxiliary renderings, and finally transforms the auxiliary images to SVBRDF maps. Third, we propose backbone UNets to infer mask images, and gated deformable UNets for estimating auxiliary targets. Thanks to the well designed networks and intermediate images, our method outputs better SVBRDF maps than previous approaches, validated by the extensive comparisonal and ablation experiments.

Effectiveness of interventions for informal caregivers of community-dwelling frail older adults: A systematic review and meta-analysis.

AIM: Systematic reviews on interventions for informal caregivers of community-dwelling frail older adults were published over a decade ago and they mistook frailty for other severe age-related conditions like disability and dementia. Therefore, this study aimed to systematically synthesize these interventions supporting these caregivers identified by an acknowledged frailty assessment instrument and to examine their effectiveness on caregiver-related outcomes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Fourteen electronic databases, grey literature and reference lists were systematically searched for randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) from inception to November 3, 2023. METHODS: Methodology quality and risk of bias were assessed. Data were meta-analysed using the Comprehensive Meta-Analysis, version 3.0. Studies and outcomes unsuitable for meta-analysis were summarized by narrative syntheses. RESULTS: Four studies consisting of three RCTs and one NRCT were included involving 350 participants. Interventions for caregivers of frail older adults included multicomponent interventions (n = 3) and education intervention (n = 1). Interventions had a moderate effect on reducing depression and showed nonsignificant effects on caregiver burden, caregiving time or quality of life (QoL). The PEDro scores for RCTs ranged from 6 to 8, indicating good methodologic quality, but were all judged as high risk of bias. The NRCT reported all methodologic aspects and was at low risk of bias. CONCLUSIONS: Few studies focus on interventions targeting caregivers of frail older adults, and their effectiveness may vary by outcomes. This review suggested the potential benefits of these interventions in reducing caregivers' depression. IMPACT: The differential effectiveness by outcomes and high risk of bias of studies implicate that more rigorous studies are warranted.

Joint trajectories of pain, depression and frailty and associations with adverse outcomes among community-dwelling older adults: A longitudinal study.

This study aimed to examine joint trajectories of pain, depression and frailty and their associations with adverse outcomes. Four waves of national data from the China Health and Retirement Longitudinal Study (CHARLS 2011-2018) were used, involving 4217 participants aged ≥60 years. Joint trajectories were fit using parallel-process latent class growth analysis, and their associations with adverse outcomes were evaluated using modified Poisson regression. Four joint trajectories were identified. Compared with most favorable group, other three joint trajectory groups had higher risk of functional disability and hospitalization. Slowly progressive pain, depression and frailty and persistent combination of pain, depression and frailty were also associated with cognitive decline, while slowly reduced pain and depression but persistent frailty was associated with all-cause mortality. The findings highlight unique characteristics and health impacts of concurrent changes in pain, depression and frailty over time, implicating the integrated physical and psychological care for older adults.

Development and validation of a risk scoring tool for predicting incident reversible cognitive frailty among community-dwelling older adults: A prospective cohort study.

AIM: Reversible cognitive frailty (RCF) is an ideal target to prevent asymptomatic cognitive impairment and dependency. This study aimed to develop and validate prediction models for incident RCF. METHODS: A total of 1230 older adults aged ≥60 years from China Health and Retirement Longitudinal Study 2011-2013 survey were included as the training set. The modified Poisson regression and three machine learning algorithms including eXtreme Gradient Boosting, support vector machine and random forest were used to develop prediction models. All models were evaluated internally with fivefold cross-validation, and evaluated externally using a temporal validation method through the China Health and Retirement Longitudinal Study 2013-2015 survey. RESULTS: The incidence of RCF was 27.4% in the training set and 27.5% in the external validation set. A total of 13 important predictors were selected to develop the model, including age, education, contact with their children, medical insurance, vision impairment, heart diseases, medication types, self-rated health, pain locations, loneliness, self-medication, night-time sleep and having running water. All models showed acceptable or approximately acceptable discrimination (AUC 0.683-0.809) for the training set, but fair discrimination (AUC 0.568-0.666) for the internal and external validation. For calibration, only modified Poisson regression and eXtreme Gradient Boosting were acceptable in the training set. All models had acceptable overall prediction performance and clinical usefulness. Older adults were divided into three groups by the risk scoring tool constructed based on modified Poisson regression: low risk (≤24), median risk (24-29) and high risk (>29). CONCLUSIONS: This risk tool could assist healthcare providers to predict incident RCF among older adults in the next 2 years, facilitating early identification of a high-risk population of RCF. Geriatr Gerontol Int 2024; ••: ••-••.

The Current Position of Postoperative Radiotherapy for Salivary Gland Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Because of the rarity, heterogeneous histology, and diverse anatomical sites of salivary gland cancer (SGC), there are a limited number of clinical studies on its management. This study reports the cumulative evidence of postoperative radiotherapy (PORT) for SGC of the head and neck. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases between 7th and 10th November 2023. RESULTS: A total of 2962 patients from 26 studies between 2007 and 2023 were included in this meta-analysis. The median RT dose was 64 Gy (range: 56-66 Gy). The median proportions of high-grade, pathological tumor stage 3 or 4 and pathological lymph node involvement were 42% (0-100%), 40% (0-77%), and 31% (0-75%). The pooled locoregional control rates at 3, 5, and 10 years were 92% (95% confidence interval [CI], 89-94%), 89% (95% CI, 86-93%), and 84% (95% CI, 73-92%), respectively. The pooled disease-free survival (DFS) rates at 3, 5, and 10 years were 77% (95% CI, 70-83%), 67% (95% CI, 60-74%), and 61% (95% CI, 55-67%), respectively. The pooled overall survival rates at 3, 5, and 10 years were 84% (95% CI, 79-88%), 75% (95% CI, 72-79%), and 68% (95% CI, 62-74%), respectively. Severe late toxicity ≥ grade 3 occurred in 7% (95% CI, 3-14%). CONCLUSION: PORT showed favorable long-term efficacy and safety in SGC, especially for patients with high-grade histology. Considering that DFS continued to decrease, further clinical trials exploring treatment intensification are warranted.

TracrRNA reprogramming enables direct PAM-independent detection of RNA with diverse DNA-targeting Cas12 nucleases.

Many CRISPR-Cas immune systems generate guide (g)RNAs using trans-activating CRISPR RNAs (tracrRNAs). Recent work revealed that Cas9 tracrRNAs could be reprogrammed to convert any RNA-of-interest into a gRNA, linking the RNA's presence to Cas9-mediated cleavage of double-stranded (ds)DNA. Here, we reprogram tracrRNAs from diverse Cas12 nucleases, linking the presence of an RNA-of-interest to dsDNA cleavage and subsequent collateral single-stranded DNA cleavage-all without the RNA necessarily encoding a protospacer-adjacent motif (PAM). After elucidating nuclease-specific design rules, we demonstrate PAM-independent RNA detection with Cas12b, Cas12e, and Cas12f nucleases. Furthermore, rationally truncating the dsDNA target boosts collateral cleavage activity, while the absence of a gRNA reduces background collateral activity and enhances sensitivity. Finally, we apply this platform to detect 16 S rRNA sequences from five different bacterial pathogens using a universal reprogrammed tracrRNA. These findings extend tracrRNA reprogramming to diverse dsDNA-targeting Cas12 nucleases, expanding the flexibility and versatility of CRISPR-based RNA detection.

A review of factors affecting the soil microbial community structure in wetlands.

Microbial community in wetland soils is crucial for maintaining the stability of the wetland ecosystem. Nevertheless, the soil microbial community is sensitive to the environmental stress in wetlands. This leads to the possibility that the microbial community structure may be influenced by environmental factors. To gain an in-depth understanding in the response of microbial community structure in wetland soils under different environmental factors, this review comprehensively explores the factors of natural conditions (e.g., different types of wetland, soil physical and chemical properties, climate conditions), biological factors (e.g., plants, soil animals), and human activities (e.g., land use, soil pollution, grazing). Those factors can affect microbial community structure and activities in wetland soils through different ways such as (i) affecting the wetland soil environment in which soil microorganisms survived in, (ii) influencing the available nutrients (e.g., carbon, nitrogen) required for microbial activity, and (iii) the direct effects on soil microorganisms (toxicity or promotion of resistant species). This review can provide references for the conservation of microbial diversity in wetland soils, the maintenance of wetland ecosystem balance, and the wetland ecological restoration.