Solvent engineering for scalable fabrication of perovskite/silicon tandem solar cells in air.

Perovskite/silicon tandem solar cells hold great promise for realizing high power conversion efficiency at low cost. However, achieving scalable fabrication of wide-bandgap perovskite (~1.68 eV) in air, without the protective environment of an inert atmosphere, remains challenging due to moisture-induced degradation of perovskite films. Herein, this study reveals that the extent of moisture interference is significantly influenced by the properties of solvent. We further demonstrate that n-Butanol (nBA), with its low polarity and moderate volatilization rate, not only mitigates the detrimental effects of moisture in air during scalable fabrication but also enhances the uniformity of perovskite films. This approach enables us to achieve an impressive efficiency of 29.4% (certified 28.7%) for double-sided textured perovskite/silicon tandem cells featuring large-size pyramids (2-3 µm) and 26.3% over an aperture area of 16 cm2. This advance provides a route for large-scale production of perovskite/silicon tandem solar cells, marking a significant stride toward their commercial viability.

Immune checkpoint inhibitors in colorectal cancer: limitation and challenges.

Colorectal cancer exhibits a notable prevalence and propensity for metastasis, but the current therapeutic interventions for metastatic colorectal cancer have yielded suboptimal results. ICIs can decrease tumor development by preventing the tumor's immune evasion, presenting cancer patients with a new treatment alternative. The increased use of immune checkpoint inhibitors (ICIs) in CRC has brought several issues. In particular, ICIs have demonstrated significant clinical effectiveness in patients with MSI-H CRC, whereas their efficacy is limited in MSS. Acquired resistance can still occur in patients with a positive response to ICIs. This paper describes the efficacy of ICIs currently in the clinical treatment of CRC, discusses the mechanisms by which acquired resistance occurs, primarily related to loss and impaired presentation of tumor antigens, reduced response of IFN-λ and cytokine or metabolic dysregulation, and summarizes the incidence of adverse effects. We posit that the future of ICIs hinges upon the advancement of precise prediction biomarkers and the implementation of combination therapies. This study aims to elucidate the constraints associated with ICIs in CRC and foster targeted problem-solving approaches, thereby enhancing the potential benefits for more patients.

Liensinine sensitizes colorectal cancer cells to oxaliplatin by targeting HIF-1α to inhibit autophagy.

BACKGROUND: Oxaliplatin is the most common chemotherapeutic agent for patients with colorectal cancer. However, its anti-cancer efficacy is restricted by drug resistance occurring through several mechanisms, including autophagy. Liensinine exerts a considerable anti-tumor effect and can regulate autophagy. Inhibition of autophagy is a strategy to reverse resistance to oxaliplatin. The aim of this study was to check if liensinine can enhance the therapeutic efficacy of oxaliplatin in colorectal cancer and if so, elucidate its mechanism. METHODS: Two colorectal cancer cell lines, HCT116 and LoVo, and one normal intestinal epithelial cell, NCM-460 were used for in vitro experiments. Cell Counting Kit-8 (CCK-8), colony formation, and flow cytometry assays were used to evaluate the cytotoxicity of liensinine and oxaliplatin. Network pharmacology analysis and Human XL Oncology Array were used to screen targets of liensinine. Transfections and autophagy regulators were used to confirm these targets. The relationship between the target and clinical effect of oxaliplatin was analyzed. Patient-derived xenograft (PDX) models were used to validate the effects of liensinine and oxaliplatin. RESULTS: CCK-8 and colony formation assays both showed that the combination treatment of liensinine and oxaliplatin exerted synergistic effects. Results of the network pharmacology analysis and Human XL Oncology Array suggested that liensinine can inhibit autophagy by targeting HIF-1α/eNOS. HIF-1α was identified as the key factor modulated by liensinine in autophagy and induces resistance to oxaliplatin. HIF-1α levels in tumor cells and prognosis for FOLFOX were negatively correlated in clinical data. The results from three PDX models with different HIF-1α levels showed their association with intrinsic and acquired resistance to oxaliplatin in these models, which could be reversed by liensinine. CONCLUSIONS: Research on the relationship between HIF-1α levels and the clinical effect of oxaliplatin is lacking, and whether liensinine regulates HIF-1α is unknown. Our findings suggest that liensinine overcomes the resistance of colorectal cancer cells to oxaliplatin by suppressing HIF-1α levels to inhibit autophagy. Our findings can contribute to improving prognosis following colorectal cancer therapy.

YouTube as a source of information for cryptococcal infection: A cross-sectional study.

Objective: Immunocompromised individuals, particularly HIV patients, worldwide are at risk from cryptococcal infection. There are a number of videos of cryptococcal infection and more and more individuals may search these videos, but the quality of videos on YouTube is unclear. This study set out to assess the content and quality of YouTube videos regarding cryptococcal infection. Methods: The keywords "Cryptococcus," "Cryptococcosis" and "Cryptococcal infection" were searched on YouTube. The videos were evaluated and graded by two impartial raters. A 14-point content score was used to categorize videos as bad, good or exceptional. The reliability and quality were evaluated utilizing the DISCERN instrument and a 5-point global quality score. Videos were then divided into groups based on uploading sources and content types. Results: A total of 46 videos were located, and the ratings provided by the two raters were identical. Our scoring algorithm determined that 54.3% (n = 25), 32.6% (n = 15) and 13.0% (n = 6) of the videos were poor, decent and exceptional, respectively. Regarding quality, no difference was identified between the various video categories. The global quality scale, number of views, days posted, content score and DISCERN showed a significant positive relationship. Conclusions: Professional individuals or healthcare organizations should be encouraged to submit high-quality videos for the expanding internet population, as only a small proportion of available videos had exceptional quality.

Derivation and validation of a nomogram incorporating modifiable lifestyle factors to predict development of colorectal adenomas after negative index colonoscopy.

This retrospective cohort study aimed to identify baseline patient characteristics involving modifiable lifestyle factors that are associated with the development of colorectal adenomas, and establish and validate a nomogram for risk predictions among high-risk populations with negative index colonoscopy. A total of 83,076 participants who underwent an index colonoscopy at the Tianjin Union Medical Center between 2004 and 2019 were collected. According to meticulous inclusion and exclusion criteria, 249 subjects were enrolled and categorized into the primary and validation cohorts. Based on the primary cohort, we utilized the LASSO-Cox regression and the univariate/multivariate Cox proportional hazards (Cox-PH) regression parallelly to select variables, and incorporated selected variables into two nomogram models established using the multivariate Cox-PH regression. Comparison of the Akaike information criterion and the area under the receiver operating characteristic curve of the two models demonstrated that the nomogram model constituted by four covariates retained by the LASSO-Cox regression, including baseline age, body mass index, physical activity and family history of colorectal cancer (CRC) in first-degree relatives, performed better at predicting adenoma-free survival probabilities. Further validation including the concordance index, calibration plots, decision curve analysis and Kaplan-Meier survival curves also revealed good predictive accuracy, discriminating ability, clinical utility and risk stratification capacity of the nomogram model. Our nomogram will assist high-risk individuals with negative index colonoscopy to prevent colorectal adenoma occurrence and CRC morbidity with improved cost-effectiveness.

SF3B3-regulated mTOR alternative splicing promotes colorectal cancer progression and metastasis.

BACKGROUND: Aberrant alternative splicing (AS) is a pervasive event during colorectal cancer (CRC) development. SF3B3 is a splicing factor component of U2 small nuclear ribonucleoproteins which are crucial for early stages of spliceosome assembly. The role of SF3B3 in CRC remains unknown. METHODS: SF3B3 expression in human CRCs was analyzed using publicly available CRC datasets, immunohistochemistry, qRT-PCR, and western blot. RNA-seq, RNA immunoprecipitation, and lipidomics were performed in SF3B3 knockdown or overexpressing CRC cell lines. CRC cell xenografts, patient-derived xenografts, patient-derived organoids, and orthotopic metastasis mouse models were utilized to determine the in vivo role of SF3B3 in CRC progression and metastasis. RESULTS: SF3B3 was upregulated in CRC samples and associated with poor survival. Inhibition of SF3B3 by RNA silencing suppressed the proliferation and metastasis of CRC cells in vitro and in vivo, characterized by mitochondria injury, increased reactive oxygen species (ROS), and apoptosis. Mechanistically, silencing of SF3B3 increased mTOR exon-skipped splicing, leading to the suppression of lipogenesis via mTOR-SREBF1-FASN signaling. The combination of SF3B3 shRNAs and mTOR inhibitors showed synergistic antitumor activity in patient-derived CRC organoids and xenografts. Importantly, we identified SF3B3 as a critical regulator of mTOR splicing and autophagy in multiple cancers. CONCLUSIONS: Our findings revealed that SF3B3 promoted CRC progression and metastasis by regulating mTOR alternative splicing and SREBF1-FASN-mediated lipogenesis, providing strong evidence to support SF3B3 as a druggable target for CRC therapy.

Discovery of novel peptide-dehydroepiandrosterone hybrids inducing endoplasmic reticulum stress with effective in vitro and in vivo anti-melanoma activities.

Steroid hybrids have emerged as a type of advantageous compound as they could offer improved pharmacological and pharmaceutical properties. Here, we report a series of novel peptide-dehydroepiandrosterone hybrids, which would effectively induce endoplasmic reticulum stress (ERS) and lead to apoptosis with outstanding in vitro and in vivo anti-melanoma effects. The lead compound IId among various steroids conjugated with peptides and pyridines showed effective in vivo activity in B16 xenograft mice: in medium- and high-dose treatment groups (60 and 80 mg/kg), compound IId would significantly inhibit the growth of tumours by 98%-99% compared to the control group, with the highest survival rate as well. Further mechanism studies showed that compound IId would damage the endoplasmic reticulum and upregulate the ERS markers C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78), which could further regulate caspase and Bcl-2 family proteins and lead to cell apoptosis. The compound IId was also proven to be effective in inhibiting B16 cell migration and invasion.

Integrating Shared Socioeconomic Pathway-informed adaptation into temperature-related mortality projections under climate change.

The extent to which populations will successfully adapt to continued warming temperatures will be a crucial factor in determining future health burdens. Previous health impact assessments of future temperature-related mortality burdens mostly disregard adaptation or make simplistic assumptions. We apply a novel evidence-based approach to model adaptation that takes into account the fact that adaptation potential is likely to vary at different temperatures. Temporal changes in age-specific mortality risk associated with low and high temperatures were characterised for Scotland between 1974 and 2018 using temperature-specific RR ratios to reflect past changes in adaptive capacity. Three scenarios of future adaption were constructed consistent with the SSPs. These adaptation projections were combined with climate and population projections to estimate the mortality burdens attributable to high (above the 90th percentile of the historical temperature distribution) and low (below the 10th percentile) temperatures up to 2080 under five RCP-SSP scenarios. A decomposition analysis was conducted to attribute the change in the mortality burden into adaptation, climate and population. In 1980-2000, the heat burden (21 deaths/year) was smaller than the colder burden (312 deaths/year). In the 2060-2080 period, the heat burden was projected to be the highest under RCP8.5-SSP5 (1285 deaths/year), and the cold burden was the highest under RCP4.5-SSP4 (320 deaths/year). The net burden was lowest under RCP2.6-SSP1 and highest under RCP8.5-SSP5. Improvements in adaptation was the largest factor reducing the cold burden under RCP2.6-SSP1 whilst temperature increase was the biggest factor contributing to the high heat burdens under RCP8.5-SSP5. Ambient heat will become a more important health determinant than cold in Scotland under all climate change and socio-economic scenarios. Adaptive capacity will not fully counter projected increases in heat deaths, underscoring the need for more ambitious climate mitigation measures for Scotland and elsewhere.

Pathogenesis-Guided Rational Engineering of Nanotherapies for the Targeted Treatment of Abdominal Aortic Aneurysm by Inhibiting Neutrophilic Inflammation.

Abdominal aortic aneurysm (AAA) remains a fatal disease in the elderly. Currently, no drugs can be clinically used for AAA therapy. Considering the pivotal role of neutrophils in the pathogenesis of AAA, herein we propose the targeted therapy of AAA by site-specifically regulating neutrophilic inflammation. Based on a luminol-conjugated α-cyclodextrin material (LaCD), intrinsically anti-inflammatory nanoparticles (NPs) were engineered by simple nanoprecipitation, which were examined as a nanotherapy (defined as LaCD NP). After efficient accumulation in the aneurysmal aorta and localization in pathologically relevant inflammatory cells in rats with CaCl2-induced AAA, LaCD NP significantly alleviated AAA progression, as implicated by the decreased aortic expansion, suppressed elastin degradation, inhibited calcification, and improved structural integrity of the abdominal aorta. By functionalizing LaCD NP with alendronate, a calcification-targeting moiety, the in vivo aneurysmal targeting capability of LaCD NP was considerably enhanced, thereby affording significantly potentiated therapeutic outcomes in AAA rats. Mechanistically, LaCD NP can effectively inhibit neutrophil-mediated inflammatory responses in the aneurysmal aorta. Particularly, LaCD NP potently attenuated the formation of neutrophil extracellular traps (NETs), thereby suppressing NETs-mediated pro-inflammatory events and NETosis-associated negative effects responsible for AAA progression. Consequently, we demonstrated the effectiveness and underlying mechanisms of anti-NETosis nanotherapies for the targeted treatment of AAA. Our findings provide promising insights into discovering precision therapies for AAA and other inflammatory vascular diseases.

Andrographolide sensitizes KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the EGFR/AKT and PDGFRß/AKT signaling pathways.

BACKGROUND: Cetuximab, an inhibitor targeting EGFR, is widely applied in clinical management of colorectal cancer (CRC). Nevertheless, drug resistance induced by KRAS-mutations limits cetuximab's anti-cancer effectiveness. Furthermore, the persistent activation of EGFR-independent AKT is another significant factor in cetuximab resistance. Nevertheless, the mechanism that EGFR-independent AKT drives cetuximab resistance remains unclear. Thus, highlighting the need to optimize therapies to overcome cetuximab resistance and also to explore the underlying mechanism. PURPOSE: This work aimed to investigate whether and how andrographolide enhance the therapeutic efficacy of cetuximab in KRAS-mutant CRC cells by modulating AKT. METHODS: The viabilities of CRC cell lines were analyzed by CCK-8. The intracellular proteins phosphorylation levels were investigated by Human Phospho-kinase Antibody Array analysis. Knockdown and transfection of PDGFRß were used to evaluate the role of andrographolide on PDGFRß. The western blotting was used to investigate Wnt/ß-catenin pathways, PI3K/AKT, and EMT in KRAS-mutant CRC cells. The animal models including subcutaneous tumor and lung metastasis were performed to assess tumor response to therapy in vivo. RESULTS: Andrographolide was demonstrated to decrease the expression of PI3K and AKT through targeting PDGFRß and EGFR, and it enhanced cetuximab effect on KRAS-mutant CRC cells by this mechanism. Meanwhile, andrographolide helped cetuximab to inhibit Wnt/ß-catenin, CRC cell migration and reduced Vimentin expression, while increasing that of E-cadherin. Lastly, co-treatment with cetuximab and andrographolide reduced the growth of KRAS-mutant tumors and pulmonary metastases in vivo. CONCLUSIONS: Our findings suggest that andrographolide can overcome the KRAS-mutant CRC cells' resistance to cetuximab through inhibiting the EGFR/PI3K/AKT and PDGFRß /AKT signaling pathways. This research provided a possible theory that andrographolide sensitizes KRAS-mutant tumor to EGFR TKI.

Higher air pollution exposure in early life is associated with worse health among older adults: A 72-year follow-up study from Scotland.

Air pollution increases the risk of mortality and morbidity. However, limited evidence exists on the very long-term associations between early life air pollution exposure and health, as well as on potential pathways. This study explored the relationship between fine particle (PM2.5) exposure at age 3 and limiting long-term illness (LLTI) at ages 55, 65 and 75 using data from the Scottish Longitudinal Study Birth Cohort 1936, a representative administrative cohort study. We found that early life PM2.5 exposure was associated with higher odds of LLTI in mid-to-late adulthood (OR = 1.10, 95% CI: 1.06, 1.14 per 10 µg m-3 increment) among the 2085 participants, with stronger associations among those growing up in disadvantaged families. Path analyses suggested that 15-21% of the association between early life PM2.5 concentrations and LLTI at age 65 (n = 1406) was mediated through childhood cognitive ability, educational qualifications, and adult social position. Future research should capitalise on linked administrative and health data, and explore causal mechanisms between environment and specific health conditions across the life course.

Highly Efficient Monolithic Perovskite/Perovskite/Silicon Triple-Junction Solar Cells.

Wide-bandgap metal halide perovskites have demonstrated promise in multijunction photovoltaic (PV) cells. However, photoinduced phase segregation and the resultant low open-circuit voltage (Voc) have greatly limited the PV performance of perovskite-based multijunction devices. Here, a alloying strategy is reported to achieve uniform distribution of triple cations and halides in wide-bandgap perovskites by doping Rb+ and Cl- with small ionic radii, which effectively suppresses halide phase segregation while promoting the homogenization of surface potential. Based on this strategy, a Voc of 1.33 V is obtained from single-junction perovskite solar cells, and a VOC approaching 3.0 V and a power conversion efficiency of 25.0% (obtained from reverse scan direction, certified efficiency: 24.19%) on an 1.04 cm2 photoactive area can be achieved in a perovskite/perovskite/c-Si triple-junction tandem cell, where the certification efficiency is by far the greatest performance of perovskite-based triple-junction tandem solar cells. This work overcomes the performance deadlock of perovskite-based triple-junction tandem cells by setting a materials-by-design paradigm.

Does cycle commuting reduce the risk of mental ill-health? An instrumental variable analysis using distance to nearest cycle path.

BACKGROUND: Previous studies have linked cycling with improved mental wellbeing but these studies tend to use cross-sectional survey data that have small sample sizes and self-reported health measures, and are potentially susceptible to omitted-variable bias and reverse causation. We use an instrumental variable approach and an objective measure of mental ill-health taken from linked administrative data to ask: 'Does cycle commuting reduce the risk of mental ill-health?' METHODS: Our study links data on commuting in Edinburgh and Glasgow from the Scottish population census with mental health prescriptions from the National Health Service Prescribing Information System records. We use road distance from home to nearest cycle path as an instrumental variable for cycle commuting. RESULTS: In total, 378 253 people aged 16-74 years living and working in the City of Edinburgh and Glasgow City council areas at the 2011 census were included in our study; 1.85% of commuters in Glasgow and 4.8% of commuters in Edinburgh cycled to work. Amongst cyclists, 9% had a prescription for mental health compared with 14% amongst non-cyclists. Using a bivariate probit model, we estimate a mean average reduction in prescriptions for antidepressants and/or anxiolytics in the 5 years following the census of -15.1% (95% CI: -15.3% to -15.0%) amongst cycle commuters compared with those who use any other mode to commute. CONCLUSIONS: This work suggests that cycle commuting is causally related to reduced mental ill-health and provides further evidence in support of the promotion of active travel to encourage commuters travelling shorter distances to shift to cycle commutes.

A longitudinal analysis of the impact of the local tobacco retail availability and neighbourhood deprivation on male smoking behaviours in Shanghai, China.

Some evidence from Western high-income countries suggests local tobacco retail availability and neighbourhood deprivation may influence smoking behaviours. However, this assertion has not been considered in China, where 44% of males continue to smoke. Data were analysed from Chinese males (n = 2054) who participated in Waves 3-5 (2009-2015) of the International Tobacco Control (ITC) China Survey by linking information on tobacco retail availability (estimated through population weighted Kernel Density of tobacco retailers in 2019) and neighbourhood deprivation (calculated as a composite score derived from the 2010 Chinese census) across Shanghai. Generalised Estimating Equation models were fitted to examine the impacts of local tobacco availability and neighbourhood deprivation on smoking behaviours (current smoking versus current non-smoking, quitting versus current smoking, longer durations of smoking abstinence versus current smoking) using the longitudinal data. Examining the impacts separately, participants living in neighbourhoods with greater availability and higher levels of deprivation were less likely to maintain longer durations of smoking abstinence in both unadjusted and adjusted models. Neighbourhood deprivation, but not availability, was found to be associated with higher odds of being a current smoker. Examining the impacts jointly, neighbourhood deprivation was still positively associated with current smoking and negatively associated with longer durations of smoking abstinence, but the negative association between availability and longer durations of smoking abstinence disappeared. The findings offer some evidence that greater tobacco retail availability and deprivation are obstacles on prolonged smoking cessation among males in Shanghai, China. Policymakers should consider small-area level place-based restrictions in China, such as reducing the availability of tobacco, as part of a comprehensive tobacco control strategy aimed at addressing the high prevalence of smoking.

Reducing Perovskite/C60 Interface Losses via Sequential Interface Engineering for Efficient Perovskite/Silicon Tandem Solar Cell.

Wide-bandgap (WBG) perovskite solar cells hold tremendous potential for realizing efficient tandem solar cells. However, nonradiative recombination and carrier transport losses occurring at the perovskite/electron-selective contact (e.g. C60 ) interface present significant obstacles in approaching their theoretical efficiency limit. To address this, a sequential interface engineering (SIE) strategy that involves the deposition of ethylenediamine diiodide (EDAI2 ) followed by sequential deposition of 4-Fluoro-Phenethylammonium chloride (4F-PEACl) is implemented. The SIE technique synergistically narrows the conduction band offset and reduces recombination velocity at the perovskite/C60 interface. The best-performing WBG perovskite solar cell (1.67 eV) delivers a power conversion efficiency (PCE) of 21.8% and an impressive open-circuit voltage of 1.262 V. Moreover, through integration with double-textured silicon featuring submicrometer pyramid structures, a stabilized PCE of 29.6% is attained for a 1 cm2 monolithic perovskite/silicon tandem cell (certified PCE of 29.0%).

Factors influencing advanced colorectal neoplasm anatomic site distribution in China: An epidemiological study based on colorectal cancer screening data.

OBJECTIVE: Existing studies indicate that advanced colorectal neoplasms exhibit distinct clinical and biological traits based on anatomical sites. However, in China, especially for advanced colorectal neoplasms, there's limited information available on these traits. Our primary objective is to comprehensively study the characteristics of advanced colorectal neoplasm patients in different anatomical sites in China. METHODS: We selected information from the colorectal cancer screening database in Tianjin, China, since 2010 as the study subject. We chose valid information from 3113 patients with comprehensive data and diagnosed advanced colorectal neoplasms (ANs) from a pool of 19,308 individuals to be included in the study. We then conducted further analysis to examine the correlation between these epidemiological data and tumor location. RESULTS: Among the 3113 patients, neoplasms in the left side of the colon accounted for the largest proportion, while neoplasms in the right side of the colon had the smallest proportion, followed by rectal neoplasms. The highest proportion of advanced colorectal neoplasms was found among men. In the age group of 39-49 years old, the proportion of left late-stage advanced colon neoplasms was equal to that of right late-stage advanced colon neoplasms, while late-stage advanced rectal neoplasms increased with age. Smoking, drinking, and a history of colon cancer in first-degree relatives showed statistically significant associations with the location distribution of advanced colorectal neoplasms. A history of appendicitis, appendectomy, cholecystitis, or cholecystectomy did not significantly affect the location distribution of advanced colorectal neoplasms. However, among patients with such histories, there was a statistically significant relationship between advanced colon neoplasms on the right and those on the left and in the rectum. Similar results were observed for BMI. CONCLUSION: Our research findings demonstrate that advanced colorectal neoplasms display unique epidemiological characteristics depending on their anatomical locations, and these distinctions deviate from those observed in Western populations. These insights contribute to a more comprehensive understanding of the topic and offer valuable guidance for future research in China. We advocate for further investigations centered on the anatomical location of colorectal neoplasms to enhance the precision of colorectal cancer (CRC) screening and treatment.

The association between falls and depressive symptoms among older adults: evidence from the China Health and Retirement Longitudinal Study.

Background: Falls place a heavy burden on older adults and families, and there was little research on the relationship between falls and depressive symptoms among older adults in China. This study is designed to examine the association between falls and depressive symptoms in Chinese older adults. Methods: This study was based on 9,539 data sets from the China Health and Retirement Longitudinal Study (CHARLS) in 2018. The 10-item Center for Epidemiologic Studies-Depression Scale (CESD-10) was used to access depressive symptoms in older adults. A logistic regression model was used to calculate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for falls and depressive symptoms, adjusted for possible confounders. The Classification and regression tree (CART) demonstrates the prediction of the target variable values based on other variables. Results: In this study, 9,539 older people were selected: 60-69 years old accounted for 63.0%, 70-79 years old accounted for 29.7%, and 80 years old and above accounted for 7.3%. Male accounted for 49.7% and female for 50.3%. The rate of falls among older adults was 21.4%, and the rate of depressive symptoms was 33.9%. Adjusted ORs (OR = 1.37, 95% CI: 1.23, 1.53) showed a significant association between falls and depressive symptoms among older adults. Subgroup analysis revealed that this association was statistically significant across male (OR = 1.29, 95% CI: 1.23, 1.53) and female (OR = 1.42, 95% CI: 1.23, 1.64), 60-69 aged (OR = 1.38, 95% CI: 1.19, 1.60) and 70-79 aged (OR =1.42, 95% CI: 1.16, 1.74), rural (OR = 1.42, 95% CI: 1.25, 1.61), <15,000 CNY (OR = 1.35, 95% CI: 1.19, 1.54) and more than 25,000 CNY (OR = 1.42, 95% CI: 1.09, 1.85). Additionally, The CART model showed that the probability (73.0%) of falls was highest among older adults with depressive symptoms who self-rated poor health and female gender. Conclusions: This cross-sectional study demonstrated a significant association between falls and depressive symptoms in Chinese older adults. The findings provide some evidence and support for risk monitoring, screening for depressive symptoms, and early prevention in the high-risk older population.

Novel 3D-printing bilayer GelMA-based hydrogel containing BP,ß-TCP and exosomes for cartilage-bone integrated repair.

The integrated repair of cartilage and bone involves the migration and differentiation of cells, which has always been a difficult problem to be solved. We utilize the natural biomaterial gelatin to construct gelatin methacryloyl (GelMA), a hydrogel scaffold with high cell affinity. GelMA is mixed with different components to print a bi-layer porous hydrogel scaffold with different modulus and composition in upper and lower layers through three-dimensional (3D) printing technology. The upper scaffold adds black phosphorus (BP) and human umbilical cord mesenchymal stem cells (hUMSCs) exosomes (exos) in GelMA, which has a relatively lower elastic modulus and is conducive to the differentiation of BMSCs into cartilage. In the lower scaffold, in addition to BP and hUMSCs exos,ß-tricalcium phosphate (ß-TCP), which has osteoconductive and osteoinductive effects, is added to GelMA. The addition ofß-TCP significantly enhances the elastic modulus of the hydrogel scaffold, which is conducive to the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).In vitroexperiments have confirmed that the bi-layer scaffolds can promote osteogenesis and chondrogenic differentiation respectively. And in the rabbit cartilage-bone injury model, MRI and micro-CT results show that the 3D printed bi-layer GelMA composite scaffold has a repair effect close to normal tissue.

Early life PM2.5 exposure, childhood cognitive ability and mortality between age 11 and 86: A record-linkage life-course study from Scotland.

BACKGROUND: Living in areas with high air pollution concentrations is associated with all-cause and cause-specific mortality. Exposure in sensitive developmental periods might be long-lasting but studies with very long follow-up are rare, and mediating pathways between early life exposure and life-course mortality are not fully understood. METHODS: Data were drawn from the Scottish Longitudinal Study Birth Cohort of 1936, a representative record-linkage study comprising 5% of the Scottish population born in 1936. Participants had valid age 11 cognitive ability test scores along with linked mortality data until age 86. Fine particle (PM2.5) concentrations estimated with the EMEP4UK atmospheric chemistry transport model were linked to participants' residential address derived from the National Identity Register in 1939 (age 3). Confounder-adjusted Cox regression estimated associations between PM2.5 and mortality; regression-based causal mediation analysis explored mediation through childhood cognitive ability. RESULTS: The final sample consisted of 2734 individuals with 1608 deaths registered during the 1,833,517 person-months at risk follow-up time. Higher early life PM2.5 exposure increased the risk of all-cause mortality (HR = 1.03, 95% CI: 1.01-1.04 per 10 µg m-3 increment), associations were stronger for mortality between age 65 and 86. PM2.5 increased the risk of cancer-related mortality (HR = 1.05, 95% CI: 1.02-1.08), especially for lung cancer among females (HR = 1.11, 95% CI: 1.02-1.21), but not for cardiovascular and respiratory diseases. Higher PM2.5 in early life (≥50 µg m-3) was associated with lower childhood cognitive ability, which, in turn, increased the risk of all-cause mortality and mediated 25% of the total associations. CONCLUSIONS: In our life-course study with 75-year of continuous mortality records, we found that exposure to air pollution in early life was associated with higher mortality in late adulthood, and that childhood cognitive ability partly mediated this relationship. Findings suggest that past air pollution concentrations will likely impact health and longevity for decades to come.