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.

Dissecting the Distinct Tumor Microenvironments of HRD and HRP Ovarian Cancer: Implications for Targeted Therapies to Overcome PARPi Resistance in HRD Tumors and Refractoriness in HRP Tumors.

High-grade serous tubo-ovarian cancer (HGSTOC) is an aggressive gynecological malignancy including homologous recombination deficient (HRD) and homologous recombination proficient (HRP) groups. Despite the therapeutic potential of poly (ADP-ribose) polymerase inhibitors (PARPis) and anti-PDCD1 antibodies, acquired resistance in HRD and suboptimal response in HRP patients necessitate more precise treatment. Herein, single-cell RNA and single-cell T-cell receptor sequencing on 5 HRD and 3 HRP tumors are performed to decipher the heterogeneous tumor immune microenvironment (TIME), along with multiplex immunohistochemistry staining and animal experiments for validation. HRD tumors are enriched with immunogenic epithelial cells, FGFR1+PDGFRß+ myCAFs, M1 macrophages, tumor reactive CD8+/CD4+ Tregs, whereas HRP tumors are enriched with HDAC1-expressing epithelial cells, indolent CAFs, M2 macrophages, and bystander CD4+/CD8+ T cells. Significantly, customized therapies are proposed. For HRD patients, targeting FGFR1+PDGFRß+ myCAFs via tyrosine kinase inhibitors, targeting Tregs via anti-CCR8 antibodies/TNFRSF4 stimulation, and targeting CXCL13+ exhausted T cells by blocking PDCD1/CTLA-4/LAG-3/TIGIT are proposed. For HRP patients, targeting indolent CAFs, targeting M2 macrophages via CSF-1/CSF-1R inhibitors, targeting bystander T cells via tumor vaccines, and targeting epithelial cells via HDAC inhibitors. The study provides comprehensive insights into HRD and HRP TIME and tailored therapeutic approaches, addressing the challenges of PARPi-resistant HRD and refractory HRP tumors.

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.

Correlates of symptom burden in renal dialysis patients: a systematic review and meta-analysis.

BACKGROUND: Patients receiving renal dialysis often experience a wide range of symptoms. These symptoms contribute to a significant symptom burden that significantly affects patients' quality of life and serves as a significant predictor of healthcare resource utilization and patient prognosis. It is necessary to synthesize existing evidence to draw reliable conclusions to deepen the understanding of symptom burden. OBJECTIVE: A systematic review and meta-analysis were conducted to identify the relevant factors of symptom burden in patients receiving renal dialysis. METHODS: The systematic review and meta-analysis was conducted by searching nine databases for studies reporting the correlates between symptom burden and demographic variables, disease factors, and psychosocial factors from inception to 24 June 2024. After two researchers independently conducted literature search, data extraction, and quality evaluation, meta-analysis was conducted using R Language and Stata 15.1 Software. This study has been registered in the PROSPERO. RESULTS: Sixty-two studies were included in this review. Results showed that the symptom burden of renal dialysis patients was positively correlated with age, gender, working status, medical cost, dialysis age, quality of sleep, nutritional status, comorbidities, depression, anxiety, disease uncertain, avoidance coping and resignation coping, and negatively correlated with marital status, income, serum sodium, quality of life, social support, subjective well-being, and self-management ability. CONCLUSIONS: Our findings reveal that many factors, including demographic, disease-related, and psychosocial variables, affect symptom burden. The results can supply information for health promotion and relief symptom burden for patients receiving renal dialysis.Registered number: CRD42024507577.

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; ••: ••-••.

Electron Tandem Transport Channel in a Cu3P/Sv-ZnIn2S4 p-n Heterojunction for Photothermal-Photocatalytic Benzyl Alcohol Oxidation and H2 Production.

The development of photocatalytic systems with an electron tandem transport channel represents a promising avenue for improving the utilization of photogenerated electrons and holes despite encountering significant challenges. In this study, ZnIn2S4 (Sv-ZIS) with sulfur vacancies was fabricated using a solvothermal technique to create defect energy levels. Subsequently, Cu3P nanoparticles were coupled onto the surface of Sv-ZIS, forming a Cu3P/Sv-ZIS p-n heterojunction with an electron tandem transport channel. Experimental findings demonstrated that this tandem transport channel enhanced the carrier lifetime and separation efficiency. In addition, mechanistic investigations unveiled the formation of a robust built-in electric field (BEF) at the interface between Cu3P and Sv-ZIS, providing a driving force for electron migration. The combined consequences of the transport channel, the strong BEF, and photothermal effect led to a surface carrier separation efficiency of 65.85%. Consequently, Cu3P/Sv-ZIS achieved simultaneous H2 yield and benzaldehyde production rates of 18,101.4 and 15,012.6 µmol·g-1·h-1, which were 2.31 and 2.62 times higher than those of ZnIn2S4, respectively. This work exemplifies the design of the p-n heterojunction for the efficient utilization of photogenerated electrons and holes.

The role of Foxo3a in neuron-mediated cognitive impairment.

Cognitive impairment (COI) is a prevalent complication across a spectrum of brain disorders, underpinned by intricate mechanisms yet to be fully elucidated. Neurons, the principal cell population of the nervous system, orchestrate cognitive processes and govern cognitive balance. Extensive inquiry has spotlighted the involvement of Foxo3a in COI. The regulatory cascade of Foxo3a transactivation implicates multiple downstream signaling pathways encompassing mitochondrial function, oxidative stress, autophagy, and apoptosis, collectively affecting neuronal activity. Notably, the expression and activity profile of neuronal Foxo3a are subject to modulation via various modalities, including methylation of promoter, phosphorylation and acetylation of protein. Furthermore, upstream pathways such as PI3K/AKT, the SIRT family, and diverse micro-RNAs intricately interface with Foxo3a, engendering alterations in neuronal function. Through several downstream routes, Foxo3a regulates neuronal dynamics, thereby modulating the onset or amelioration of COI in Alzheimer's disease, stroke, ischemic brain injury, Parkinson's disease, and traumatic brain injury. Foxo3a is a potential therapeutic cognitive target, and clinical drugs or multiple small molecules have been preliminarily shown to have cognitive-enhancing effects that indirectly affect Foxo3a. Particularly noteworthy are multiple randomized, controlled, placebo clinical trials illustrating the significant cognitive enhancement achievable through autophagy modulation. Here, we discussed the role of Foxo3a in neuron-mediated COI and common cognitively impaired diseases.

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.

Effects of (pre)frailty and cognitive reserve on mild cognitive impairment among community-dwelling older adults.

OBJECTIVE: We aimed to identify the effect of lifespan cognitive reserve and (pre)frailty on mild cognitive impairment (MCI) among older adults. MATERIALS AND METHODS: A total of 4420 older adults aged above 60 with intact cognition recruited in 2011/2012 were followed up in 2015 from the China Health and Retirement Longitudinal Study (CHARLS). The assessment of MCI was based on executive function, episodic memory, and visual-spatial ability. (Pre)frailty was assessed by the validated version of the Fried physical frailty phenotype scale. The lifespan cognitive reserve consisted of the highest educational level, occupational complexity, and participation in leisure activities. Modified Poisson regression models were used to identify the risk of MCI in relation to (pre)frailty and lifespan cognitive reserve index. We examined the interactions of (pre)frailty and lifespan cognitive reserve index on both additive and multiplicative scales. RESULTS: Baseline (pre)frailty significantly increased the risk of MCI after 3-4 years of follow-up, and high cognitive reserve protected individuals from the risk of MCI. There was an additive interaction between (pre)frailty and the low lifespan cognitive reserve (the relative excess interaction risk=1.08, 95 % CI= 0.25-1,91), but no multiplicative interaction (RR=0.95, 95 % CI= 0.67-1.37). The risk of MCI was larger among older adults with comorbid (pre)frailty and low cognitive reserve than those with each condition alone. CONCLUSION: Cognitive reserve attenuates the risk of MCI associated with (pre)frailty. This finding implicates the urgency for identifying and managing MCI among frail older adults who accumulate low cognitive reserve in the life course.

Does Social Support Moderate the Relationship Between Frailty and Functional Ability Trajectory Among Community-Dwelling Older Adults?

BACKGROUND: Functional ability is the important prerequisite to live independently and achieve aging in place, which depends on the complex interaction of intrinsic and extrinsic factors. Identifying the trends and influencing factors of functional ability would contribute to the accurate assessment and intervention of geriatric health. This study aimed to disentangle the moderating effect of 3 types of social support, namely objective support, subjective support, and support utilization, on the relationship between frailty and functional ability trajectories. METHODS: This was a secondary analysis using data from a prospective 3-wave study with a sample of 777 Chinese community-dwelling older adults. Social support was assessed using the Social Support Rating scale. Frailty was assessed using the FRAIL scale. Functional ability was measured by the Lawton Instrumental Activities of Daily Living scale. Latent growth curve models were implemented to test their relationships. RESULTS: Objective support but not subjective support or support utilization moderated on the relationship between frailty and functional ability slope. Functional ability decline over time was buffered by objective support among robust individuals but exacerbated among (pre)frail individuals. CONCLUSIONS: The moderating effect of social support on the relationship between frailty and functional ability trajectory varies by support types, which reminded that social support may be a promising intervention target to maintain functional independence for frail individuals, opening up a new perspective on social support in the field of disability prevention. Effective interventions should particularly address objective support in conjunction with empowering the frail older population to optimize the trajectory of functional ability.

Carbene-Catalyzed [4+2] Cycloaddition of Cyclobutenones and Isatins for Quick Access to Chiral Chlorine-Containing Spirocyclic δ-Lactones.

Here we report a carbene-catalyzed enantio- and diastereoselective [4+2] cycloaddition reaction of cyclobutenones with isatins for the quick and efficient synthesis of spirocyclic δ-lactones bearing a chiral chlorine. A broad range of substrates with various substitution patterns proceed smoothly in this reaction, with the spirooxindole δ-lactone products afforded in generally good to excellent yields and optical purities under mild reaction conditions.

Joint trajectories of loneliness, social isolation and sarcopenia and associations with adverse outcomes: A prospective cohort study.

This study aimed to examine joint trajectories of loneliness, social isolation and sarcopenia and their associations with adverse outcomes. A total of 4701 participants aged ≥60 years who had a baseline and at least one follow-up assessment of loneliness, social isolation and sarcopenia across 2011, 2013 and 2015 waves in China Health and Retirement Longitudinal Study. Adverse outcomes were obtained in 2018 wave. Joint trajectories were fit using the parallel process latent class growth analysis, and their associations with adverse outcomes were evaluated using modified Poisson regression. Joint trajectory patterns for social relationship and sarcopenia did not vary by the assessment for sarcopenia, but did vary by the assessment for social relationship. Older adults exhibit distinct joint trajectories and those with persistent combination of loneliness or social isolation and sarcopenia experience greatest risk of adverse outcomes. These findings implicate integration of health care and social care for community-dwelling older adults.

Phosphotungstic Acid Clusters Decorated Znln2S4 Nanoflowers as Molecular-Scale S-Scheme Heterojunctions for Simultaneous H2 Evolution and Benzyl Alcohol Upgrading.

Simultaneous utilization of photogenerated electrons and holes to achieve overall redox reactions is attractive but still far from practical application. The emerging step (S)-scheme mechanism has proven to be an ideal approach to inhibit charge recombination and supply photoinduced charges with highest redox potentials. Herein, a hierarchical phosphotungstic acid (H3PW12O40, HPW)@Znln2S4 (ZISW) heterojunction was prepared through one-pot hydrothermal method for simultaneous hydrogen (H2) evolution and benzyl alcohol upgrading. The fabricated HPW-based heterojunctions indicated much enhanced visible-light absorption, promoted photogenerated charge transfer and inhibited charge recombination, owing to hierarchical architecture based on visible-light responsive Znln2S4 microspheres, and S-scheme charge transfer pathway. The S-scheme mechanism was further verified by free-radical trapping electron spin resonance (ESR) spectra. Moreover, the wettability of composite heterojunction was improved by the modification of hydrophilic HPW, contributing to gaining active hydrogen (H+) from water sustainably. The optimal ZISW-30 heterojunction photocatalyst indicated an enhanced hydrogen evolution rate of 27.59 mmol g-1 h-1 in benzyl alcohol (10 vol. %) solution under full-spectrum irradiation, along with highest benzaldehyde production rate is 8.32 mmol g-1 h-1. This work provides a promising guideline for incorporating HPW into S-scheme heterojunctions to achieve efficient overall redox reactions.

Joint trajectories of physical frailty and social frailty and associations with adverse outcomes: A prospective cohort study.

BACKGROUND: We examined joint trajectories of physical frailty and social frailty as well as their associations with adverse outcomes. METHODS: We conducted a prospective cohort study by using five waves of national data from China Health and Retirement Longitudinal Study (CHARLS 2011-2020), involving 4531 participants aged ≥60 years. We identified 4-year trajectories at three examinations from 2011 to 2015 using parallel process latent class growth analysis. Adverse outcomes were obtained from 2015 to 2020 across two subsequent waves. We calculated hazard ratios (HR) using Cox proportional hazard models. We also conducted analyses by gender. RESULTS: Three joint trajectories were identified, including persistent absence of physical and social frailty (58.5 %), no physical frailty but social frailty (28.1 %), and persistent combination of physical and social frailty (13.4 %). Compared with persistent absence of physical and social frailty, no physical frailty but social frailty and persistent combination of physical and social frailty were associated with higher risk of instrumental activities of daily living (IADL) disability (HR = 1.182-2.020, 95 % CI: 1.014-2.416) and all-cause mortality (HR = 1.440-2.486, 95 % CI: 1.211-3.009). The persistent combination of physical and social frailty was also associated with ADL disability (HR = 2.412, 95 % CI: 1.999-2.911) and falls (HR = 1.410, 95 % CI: 1.196-1.662). Gender differences were observed in relationships between joint trajectories and adverse outcomes. CONCLUSION: Community-dwelling older adults exhibit distinct joint trajectories and those with persistent combination of physical and social frailty experience greatest risk of incident adverse outcomes. Clinical and public health measures targeting physical or social frailty should account for both and be gender-specific.

Effects of cognitive reserve on cognitive frailty among older adults: A population-based prospective cohort study.

AIM: We investigated the effect of lifespan cognitive reserve and its components on cognitive frailty among older adults. METHODS: A total of 4922 participants aged ≥65 years were recruited in 2008 and were followed up in 2011 from the Chinese Longitudinal Healthy Longevity Survey. Cognitive frailty was determined through the simultaneous presence of physical frailty (pre-frailty or frailty) and mild cognitive impairment, excluding concurrent dementia. The assessment of physical frailty and mild cognitive impairment was based on the Fatigue, Resistence, Ambulation, Illness, Loss of weight (FRAIL) (Fatigue, Resistence, Ambulation, Illness, Loss) and Mini-Mental State Examination scale, respectively. The lifespan cognitive reserve consisted of education attainment, occupational complexity and later-life leisure activities. We used logistic regression models to estimate the risk of cognitive frailty associated with the lifespan cognitive reserve and its components. RESULTS: A higher level of lifespan cognitive reserve, higher educational attainment or leisure activities engagement, but not occupational complexity, were associated with lower risk of incident cognitive frailty. Furthermore, cognitive, social and physical activities were associated with lower risk of incident cognitive frailty. CONCLUSION: Cognitive reserve, particularly educational attainment and leisure activities, can protect from cognitive frailty. This implicates that individuals should accumulate cognitive reserve in their lifespan, and older adults should actively participate in leisure activities to prevent cognitive frailty. Geriatr Gerontol Int 2024; 24: 398-403.

Engineering Atomic Ag1-N6 Sites with Enhanced Performance of Eradication Drug-Resistant Bacteria over Visible-Light-Driven Antibacterial Membrane.

Utilizing visible light for water disinfection is a more convenient, safe, and practical alternative to ultraviolet-light sterilization. Herein, we developed silver (Ag) single-atom anchored g-C3N4 (P-CN) nanosheets (Ag1/CN) and then utilized a spin-coating method to fabricate the Ag1/CN-based-membrane for effective antibacterial performance in natural water and domestic wastewater. The incorporated Ag single atom formed a Ag1-N6 motif, which increased the charge density around the N atoms, resulting in a built-in electric field ∼17.2 times stronger than that of pure P-CN and optimizing the dynamics of reactive oxygen species (ROS) production. Additionally, the Ag1-N6 motif inhibited the release of Ag ions, ensuring good biocompatibility. Based on the first-principles calculation, the adsorption energy of O2 on the Ag1/CN (-0.32 eV) was lower than that of P-CN (-0.07 eV), indicating that loaded Ag single atom can lower the energy barrier for O2 activation, generating extra *OH radicals that cooperated with *O2- to effectively neutralize bacteria. As a result, the Ag1/CN powder-catalyst with the concentration of 30 ppm demonstrated a 99.9% antibacterial efficiency against drug-resistant bacteria (Escherichia coli, Staphylococcus aureus, kanamycin-resistant Escherichia coli, and methicillin-resistant Staphylococcus aureus) under visible-light irradiation for 4 h. This efficacy was 24.8 times higher than that of the P-CN powder catalyst. Moreover, the Ag1/CN-based-membrane can maintain a 99.9% bactericidal efficiency for natural water and domestic wastewater treatment using a homemade flow device, demonstrating its potential for water disinfection. Notably, the visible-light-driven antibacterial efficiency of the Ag1/CN catalyst outperformed the majority of the reported g-C3N4-based catalysts/membranes.

Design and Synthesis of Pleuromutilin Derivatives as Antibacterial Agents Using Quantitative Structure-Activity Relationship Model.

The quantitative structure-activity relationship (QSAR) is one of the most popular methods for the virtual screening of new drug leads and optimization. Herein, we collected a dataset of 955 MIC values of pleuromutilin derivatives to construct a 2D-QSAR model with an accuracy of 80% and a 3D-QSAR model with a non-cross-validated correlation coefficient (r2) of 0.9836 and a cross-validated correlation coefficient (q2) of 0.7986. Based on the obtained QSAR models, we designed and synthesized pleuromutilin compounds 1 and 2 with thiol-functionalized side chains. Compound 1 displayed the highest antimicrobial activity against both Staphylococcus aureus ATCC 29213 (S. aureus) and Methicillin-resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentrations (MICs) < 0.0625 µg/mL. These experimental results confirmed that the 2D and 3D-QSAR models displayed a high accuracy of the prediction function for the discovery of lead compounds from pleuromutilin derivatives.

In situ synthesis of graphitic carbon nitride nanosheet/Ti3C2Tx MXene/TiO2 Z-scheme heterojunctions boosting charge transfer for full-spectrum driven photocatalytic sterilization.

The development of a full-spectrum responsive photocatalytic germicide with excellent charge separation efficiency to harvest high antimicrobial efficacy is a key goal yet a challenging conundrum. Herein, graphitic carbon nitride nanosheet (PCNS)/Ti3C2Tx MXene/TiO2 (PMT) Z-scheme heterojunctions with robust interface contact were crafted by in situ interfacial engineering. The strong internal electrical field (IEF) from PCNS to TiO2, evinced by the Kelvin Probe Force Microscopy (KPFM) characterization, can obtain high charge separation efficiency with 73.99%, compared to Schottky junction PCNS/Ti3C2Tx (PM, 32.88%) and PCNS (17.70%). The Ti3C2Tx component can not only serve as a transfer pathway to accelerate the recombination of photoexcited electrons of TiO2 and holes of PCNS under the Ultraviolet-visible (UV-vis) light irradiation, but also replenish the photogenic electron concentrations to semiconductors in the near-infrared (NIR) light illumination. Meanwhile, the increased temperature due to the localized surface plasmon resonance (LSPR) can further boost the electronic activity to the generation of reactive oxygen species (ROS). Taken together, the PMT performs a high disinfection efficiency up to 99.40% under full solar spectrum illumination, 3.88 and 9.75 times higher than PCNS and TiO2, respectively, surpassing many reported Z-scheme heterojunctions. This work offers guidance for the design of Z-scheme heterojunction with the implanting of plasmons to secure excellent full-spectrum responsive photocatalytic sterilization performance.