Integrated physiological, transcriptomic and metabolomic analyses reveal the mechanism of peanut kernel weight reduction under waterlogging stress.

Waterlogging stress (WS) hinders kernel development and directly reduces peanut yield; however, the mechanism of kernel filling in response to WS remains unknown. The waterlogging-sensitive variety Huayu 39 was subjected to WS for 3 days at 7 days after the gynophores touched the ground (DAG). We found that WS affected kernel filling at 14, 21, and 28 DAG. WS decreased the average filling rate and kernel dry weight, while transcriptome sequencing and widely targeted metabolomic analysis revealed that WS inhibited the gene expression in starch and sucrose metabolism, which reduced sucrose input and transformation ability. Additionally, genes related to ethylene and melatonin synthesis and the accumulation of tryptophan and methionine were upregulated in response to WS. WS upregulated the expression of the gene encoding tryptophan decarboxylase (AhTDC), and overexpression of AhTDC in Arabidopsis significantly reduced the seed length, width, and weight. Therefore, WS reduced the kernel-filling rate, leading to a reduction in the 100-kernel weight. This survey informs the development of measures that alleviate the negative impact of WS on peanut yield and quality and provides a basis for exploring high-yield and high-quality cultivation, molecular-assisted breeding, and waterlogging prevention in peanut farming.

An E7-retinoblastoma protein pathway mechanism may account for the higher carcinogenic ability of HPV16 over HPV58 in cervical cancer.

Background: Among human papillomavirus (HPV) type, HPV16 displays the strongest carcinogenic capacity for cervical cancer, but the mechanism underlying this phenomenon remains unclear. We investigated the effect and the underlying mechanism of HPV16 on higher carcinogenic capacity than HPV58. Methods: We collected 4,030 cervical exfoliated cell samples for genotyping HPV using HybriBio's proprietary flow-through hybridization technique, liquid-based cytology (LBC), colposcopy, and biopsies if indicated. Four plasmids containing E6 and E7 of HPV16 and 58 were constructed and transfected into 293T and U2OS cells. We detected the cell phenotype using Cell Counting Kit 8 (CCK8) assay, Transwell assay, flow cytometry, and apoptosis assay; the expression of retinoblastoma protein (Rb) and phosphorylated Rb (pRb) was determined via Western blot; and the cell activity was determined via a zebrafish model treated with or without roscovitine. Results: The positive rates of HPV16 and 58 were, respectively, 18.9% and 19.7% in the ≤ low-grade squamous intraepithelial lesion (LSIL) group, 49.5% and 19.6% (P<0.001) in the high-grade squamous intraepithelial lesion (HSIL) group, 65.3% and 9.0% (P<0.001) in the cancer group. In vitro, both 293T and U2OS cells with overexpressed HPV16 E6 and E7 displayed significantly higher cell proliferation, faster cell invasion, decreased cell apoptosis, and accelerated cell cycle from G1 phase to S phase compared to those with overexpressed HPV58 E6 and E7 (all P values <0.05). Rb loss of function was observed in cells with HPV16 E7 overexpression, while a greater level of phosphorylated Rb was observed in cells with HPV58 E7 overexpression. Roscovitine restored Rb expression and decreased the cell activity in zebrafish. Conclusions: HPV16 possesses a stronger carcinogenic ability than does HPV 58, and the mechanism underlying this effect may be the impairment of the E7-Rb pathway.

Phenology response of subtropical Chinese fir (Cunninghamia lanceolata) to soil warming, precipitation exclusion and their interaction.

Plant phenology plays an important role in nutrient cycling and carbon balance in forest ecosystems, but its response to the interaction of global warming and precipitation reduction remains unclear. In this study, an experiment with factorial soil warming (ambient, ambient +5 °C) and precipitation exclusion (ambient, ambient -50 %) was conducted in a subtropical Chinese fir (Cunninghamia lanceolata) plantation. We investigated the effects of soil warming, precipitation exclusion, and their interactions on Chinese fir phenology involving the timing of tree height and fine root growth. In the meantime, the impact of tree height growth and related climatic factors on fine root production was also assessed. The results showed that: (1) more variable phenology responses were observed in fine root growth than in tree height growth to the climatic treatments; the duration of fine root growth and tree height growth was significantly reduced by the precipitation exclusion and warming treatment, respectively; phenology differences of fine roots and tree heights exerted by the solo warming and precipitation exclusion treatment were further enlarged by the combined treatment; and despite the greater inter-annual phenology stability of tree height growth than fine roots, both of them showed insignificant response to all the climate treatments; (2) asynchrony of phenology between tree height and fine root growth was significantly extended by solo warming and precipitation exclusion treatments, and further extended by the combined treatment; (3) fine root production was significantly and positively correlated with atmospheric, and soil temperature, and tree height growth as well, which was altered by warming and precipitation exclusion treatments. Our results demonstrated that climatic changes significantly and differently enlarge phenology differences for both above and below ground plant components, extend the phenology asynchrony between above and below ground, and also reveal the sensitive and variable nature of root phenology. Overall, these phenology responses to climatic change may contribute to weaken the close link between fine root production and tree height growth, which may result in mismatch between nutrient demand and supply timing in Chinese fir plantation.

A chest CT-based nomogram for predicting survival in acute myeloid leukemia.

BACKGROUND: The identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML). METHODS: 952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements. RESULTS: Three CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P < 0.01). A CT-MSF nomogram showed a performance with AUCs of 0.717, 0.794, 0.796 and 0.792 for predicting the 1-, 2-, 3-, and 5-year overall survival (OS) probabilities in the validation cohort, which were significantly higher than the ELN risk model. Moreover, a new MSN stratification system (MSF nomogram plus ELN risk model) could stratify patients into new high, intermediate and low risk group. Patients with high MSN risk may benefit from intensive treatment (P = 0.0011). CONCLUSIONS: In summary, the chest CT-MSF nomogram, integrating myosarcopenia, spleen_CTV, and SF_CTV features, could be used to predict prognosis of AML.

Tumor phylogeography reveals block-shaped spatial heterogeneity and the mode of evolution in Hepatocellular Carcinoma.

Solid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at the macroscopic (i.e., whole tumor) level is under-explored. Using a phylogeographic approach, we sequence genomes and transcriptomes from 235 spatially informed sectors across 13 hepatocellular carcinomas (HCC), generating one of the largest datasets for studying sITH. We find that tumor heterogeneity in HCC segregates into spatially variegated blocks with large genotypic and phenotypic differences. By dissecting the transcriptomic heterogeneity, we discover that 30% of patients had a "spatially competing distribution" (SCD), where different spatial blocks have distinct transcriptomic subtypes co-existing within a tumor, capturing the critical transition period in disease progression. Interestingly, the tumor regions with more advanced transcriptomic subtypes (e.g., higher cell cycle) often take clonal dominance with a wider geographic range, rejecting neutral evolution for SCD patients. Extending the statistical tests for detecting natural selection to many non-SCD patients reveal varying levels of selective signal across different tumors, implying that many evolutionary forces including natural selection and geographic isolation can influence the overall pattern of sITH. Taken together, tumor phylogeography unravels a dynamic landscape of sITH, pinpointing important evolutionary and clinical consequences of spatial heterogeneity in cancer.

The Association Between Tinnitus Sensation-Level Loudness and Sleep Quality in Patients With Subjective Consecutive Tinnitus: A Mediation Analysis.

PURPOSE: So far, there have been no in-depth analyses of the connection between tinnitus sensation-level loudness and sleep quality. Accordingly, the present study was formulated as a mediation analysis focused on exploring this relationship. METHOD: Overall, 1,255 adults with consecutive subjective tinnitus who had sought outpatient treatment were enrolled in the present study. RESULTS: Direct effects of tinnitus sensation-level loudness on sleep quality were not statistically significant (95% confidence intervals [CI] include zero), as measured by the point estimate, -0.016. However, the 95% CI for indirect effects did not include zero when assessing the Self-Rating Anxiety Scale (SAS) scores, the Self-Rating Depression Scale (SDS) scores, the visual analogue scale (VAS) scores, and self-reported tinnitus annoyance. CONCLUSIONS: These results suggest that tinnitus sensation-level loudness does not directly have an effect on sleep quality. However, it indirectly impacts sleep quality, mediated by SAS scores, SDS scores, the impact of tinnitus on life measured using the VAS, and self-reported tinnitus annoyance. As such, alleviating anxiety and depression in patients with tinnitus may result in reductions in their insomnia even if there is no reduction in tinnitus loudness. Importantly, otolaryngologists and other clinicians treating tinnitus should refer patients with tinnitus suffering from insomnia with comorbid depression or anxiety for appropriate psychological and/or psychiatric treatment.

Magnesium oxide nanoparticles reduce clubroot by regulating plant defense response and rhizosphere microbial community of tumorous stem mustard (Brassica juncea var. tumida).

Clubroot, caused by Plasmodiophora brassicae, is a major disease that significantly impairs the yield of cruciferous crops and causes significant economic losses across the globe. The prevention of clubroot, especially in tumorous stem mustard (without resistant varieties), are is limited and primarily relies on fungicides. Engineered nanoparticles have opened up new avenues for the management of plant diseases, but there is no report on their application in the prevention of clubroot. The results showed that the control efficacy of 500 mg/L MgO NPs against clubroot was 54.92%. However, when the concentration was increased to 1,500 and 2,500 mg/L, there was no significant change in the control effect. Compared with CK, the average fresh and dry weight of the aerial part of plants treated with MgO NPs increased by 392.83 and 240.81%, respectively. Compared with the F1000 treatment, increases were observed in the content of soil available phosphorus (+16.72%), potassium (+9.82%), exchangeable magnesium (+24.20%), and water-soluble magnesium (+20.64%) in the 1,500 mg/L MgO NPs treatment. The enzyme-linked immune sorbent assay (ELISA) results showed that the application of MgO NPs significantly increased soil peroxidase (POD, +52.69%), alkaline protease (AP, +41.21%), alkaline phosphatase (ALP, +79.26%), urease (+52.69%), and sucrase (+56.88%) activities; And also increased plant L-phenylalanine ammonla-lyase (PAL, +70.49%), polyphenol oxidase (PPO, +36.77%), POD (+38.30%), guaiacol peroxidase (POX, +55.46%) activities and salicylic acid (SA, +59.86%) content. However, soil and plant catalase (CAT, -27.22 and - 19.89%, respectively), and plant super oxidase dismutase (SOD, -36.33%) activities were significantly decreased after the application of MgO NPs. The metagenomic sequencing analysis showed that the MgO NPs treatments significantly improved the α-diversity of the rhizosphere soil microbial community. The relative abundance of beneficial bacteria genera in the rhizosphere soil, including Pseudomonas, Sphingopyxis, Acidovorax, Variovorax, and Bosea, was significantly increased. Soil metabolic functions, such as oxidative phosphorylation (ko00190), carbon fixation pathways in prokaryotes (ko00720), indole alkaloid biosynthesis (ko00901), and biosynthesis of various antibiotics (ko00998) were significantly enriched. These results suggested that MgO NPs might control clubroot by promoting the transformation and utilization of soil nutrients, stimulating plant defense responses, and enriching soil beneficial bacteria.

Red blood cell folate and benign prostatic hyperplasia: results from the NHANES 2001-2008.

BACKGROUND: Benign prostatic hyperplasia (BPH) affects 30% of men worldwide, folate is essential for life. However, few studies have investigated the relationship between folate levels and BPH. The present study aims to explore the relationship between red blood cell (RBC) folate, a better indicator of long-term folate intake, and BPH in United States (US) men. METHODS: We used statistics from four cycles of the "National Health and Nutrition Examination Survey" (NHANES2001-2008), RBC folate data come from laboratory data and BPH date come from questionnaire data. A multivariate conditional logistic regression model and subgroup analysis were using to assess the association between RBC folate and BPH. RESULTS: 647 males from four survey cycles in the NHANES2001-2008, of which, 574 men (88.7%) had BPH. After adjusting for potential confounders, a considerable correlation was observed between RBC folate and BPH; With the first quintiles of RBC folate as the reference, multivariable-adjusted odds ratios (ORs) and confidence intervals (95% CIs) of the second, third, fourth, and the highest quintiles were 1.19 (0.58 ∼ 2.44), 1.39 (0.65 ∼ 2.97), 2.27 (0.96 ∼ 5.39), 2.26 (1.35 ∼ 3.76) and 5.37 (1.85 ∼ 15.59), respectively. CONCLUSIONS: Individuals with high levels of RBC folate were associated with an increased risk of self-reported benign prostatic hyperplasia of US men.

The plastid-localized lipoamide dehydrogenase 1 is crucial for redox homeostasis, tolerance to arsenic stress and fatty acid biosynthesis in rice.

Soil contamination with arsenic (As) can cause phytotoxicity and reduce crop yield. The mechanisms of As toxicity and tolerance are not fully understood. In this study, we used a forward genetics approach to isolate a rice mutant, ahs1, that exhibits hypersensitivity to both arsenate and arsenite. Through genomic resequencing and complementation tests, we identified OsLPD1 as the causal gene, which encodes a putative lipoamide dehydrogenase. OsLPD1 was expressed in the outer cell layer of roots, root meristem cells, and in the mesophyll and vascular tissues of leaves. Subcellular localization and immunoblot analysis demonstrated that OsLPD1 is localized in the stroma of plastids. In vitro assays showed that OsLPD1 exhibited lipoamide dehydrogenase (LPD) activity, which was strongly inhibited by arsenite, but not by arsenate. The ahs1 and OsLPD1 knockout mutants exhibited significantly reduced NADH/NAD+ and GSH/GSSG ratios, along with increased levels of reactive oxygen species and greater oxidative stress in the roots compared with wild-type (WT) plants under As treatment. Additionally, loss-of-function of OsLPD1 also resulted in decreased fatty acid concentrations in rice grain. Taken together, our finding reveals that OsLPD1 plays an important role for maintaining redox homeostasis, conferring tolerance to arsenic stress, and regulating fatty acid biosynthesis in rice.

Clinical outcomes following discontinuation of metformin in patients with type 2 diabetes and advanced chronic kidney disease in Hong Kong: a territory-wide, retrospective cohort and target trial emulation study.

Background: Current labelling advises discontinuation of metformin when estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 due to increased risk of lactic acidosis. However, in real-world practice, the risk-benefit ratios remain uncertain. We examined the risk associations of discontinued-metformin use with cardiorenal and clinical outcomes in patients with type 2 diabetes (T2D) and advanced chronic kidney disease. Methods: In this territory-wide, retrospective cohort and target trial emulation study, we included Chinese patients attending the Hong Kong Hospital Authority (HA) and enrolled in the Risk-Assessment-and-Management-Programme-for-Diabetes-Mellitus (RAMP-DM) from 2002 to 2019. Patients were stratified by discontinuation of metformin within six months after reaching eGFR < 30 ml/min/1.73 m2 from January 1, 2002 to December 31, 2018, and followed up until December 31 2019. We excluded patients who had observational time <6 months from eGFR < 30 ml/min/1.73 m2, and had their eGFR measured during a hospitalisation episode due to acute kidney injury, or missing diagnosis date of diabetes. We compared the risk associations of metformin discontinuation with clinical outcomes. The primary outcomes were major adverse cardiovascular events (MACE), end-stage kidney disease (ESKD), cancer, and all-cause mortality. A Cox-model with time-dependent exposure and covariates was used to estimate the hazard ratio (HR) of outcomes in a propensity-score overlap-weighted cohort. The risk of occurrence of lactic acidosis (serum lactate > 5.0 mmol/L with a concomitant blood pH < 7.35 or ICD-9 codes of 276.2) in discontinued-metformin versus continued-metformin users was assessed in a separate register-based cohort. Findings: A total of 33,586 metformin users with new-onset eGFR < 30 ml/min/1.73 m2 were included in the study, 7500 (22.3%) of whom discontinued metformin within 6 months whereas 26,086 (77.7%) continued use of metformin. During a median follow-up of 3.8 (IQR: 2.2-6.1) years, 16.4% (5505/33,586), 30.1% (10,113/33,586), and 7.1% (2171/30,682) had incident MACE, ESKD, and cancer respectively, and 44.4% (14,917/33,586) died. Compared to continued-metformin use, discontinuation was associated with higher risk of MACE (weighted and adjusted HR = 1.40, 95% CI: 1.29-1.52), ESKD (HR = 1.52, 1.42-1.62), and death (HR = 1.22, 1.18-1.27). No association was observed for cancer (HR = 0.93, 0.85-1.01). Discontinued-metformin users had higher change in HbA1c change at 6-month of follow-up versus continued-metformin users (weighted mean HbA1c level change: 0.5% [0.4-0.6%] versus 0.2% [0.1-0.2]). In the separate register-based cohort (n = 3235), null association was observed between metformin use and risk of lactic acidosis (weighted HR = 0.94 [0.53-1.64]). Interpretation: Our results suggest that discontinuation of metformin in patients with T2D and chronic kidney disease may be associated with increased risk of cardiovascular-renal events. Use of metformin below eGFR of 30 ml/min/1.73 m2 may be associated with cardiovascular, renal, and mortality benefits that need to be weighed against the risk of lactic acidosis, but further research is needed to validate these findings. Funding: CUHK Impact Research Fellowship Scheme.

Ultrasensitive and specific photoelectrochemical sensor for hydrogen peroxide detection based on pillar[5]arene-functionalized Au nanoparticles and MWNTs hybrid BiOBr heterojunction.

A photoelectrochemical sensor for target detection of hydrogen peroxide was designed based on a new heterojunction nanocomposite which was sulfhydryl-borate ester-modified A1/B1-type pillar[5]arene (BP5)-functionalized Au NPs and multi-walled carbon nanotubes hybridized with bismuth bromide oxide (Au@BP5/MWNTs-BiOBr). The specific sensor was based on the direct induction of oxidation by hydrogen peroxide of the borate ester group of pillar[5]arene. Additionally, the local surface plasmon resonance (LSPR) of Au NPs enhanced visible light capture, the host-guest complexation of BP5 with H2O2 enhanced photocurrent response, the layer-by-layer stacked nanoflower structure of BiOBr provided large specific surface area with more active sites, and the conductivity of MWNTs enhanced the charge separation efficiency and significantly improves the stability of PEC. Their synthesis effect significantly increased the photocurrent signal and further enhanced the detection result. Under the optimal conditions, the linear concentration range of H2O2 detected by the Au@BP5/MWNTs-BiOBr sensor was from 1 to 60 pmol/L. The limit of detection (LOD) and the limit of quantification (LOQ) of the method were 0.333 pmol/L and 1 pmol/L, respectively, and the sensitivity was 6.471 pmol/L. Importantly, the PEC sensor has good stability, reproducibility, and interference resistance and can be used for the detection of hydrogen peroxide in real cells.

Mitigation of inflammatory bowel disease-related osteoporosis by oxyberberine: Insights into the RANKL/NF-κB signaling pathway.

Inflammatory bowel disease is linked to a higher occurrence of bone loss. Oxyberberine can effectively improve experimental inflammatory bowel disease. However, no study has shown the effect of oxyberberine on inflammatory bowel disease induced bone loss. The present study was performed to investigate the role of oxyberberine in inflammatory bowel disease induced osteoporosis in chronic inflammatory bowel disease mice model. The inflammatory bowel disease mice were orally given two doses of oxyberberine daily. Blood, colon, and bone specimens were collected for biomarker assessments and histological examinations. Bone biomechanical properties and key proteins and genes involved in the receptor activator of nuclear factor kappa-B ligand/nuclear factor kappa-B signaling pathway were evaluated. Additionally, the binding characteristics of oxyberberine and receptor activator of nuclear factor kappa-B ligand were evaluated by in silico simulation. Results indicated that oxyberberine treatment significantly attenuated the macroscopic damage, colonic shortening, and histological injury from the colon. Furthermore, oxyberberine decreased serum inflammatory cytokine levels. The intervention with oxyberberine significantly mitigated the deterioration of bone mass, biomechanical properties, and microstructural parameters. Moreover, the upregulated osteoclast formation factors in model mice were significantly abolished by oxyberberine. In silico simulation results also showed that oxyberberine was firmly bound with target protein. Hence, our findings indicated that oxyberberine had the potential to mitigate inflammatory bowel disease induced inflammation in bone, inhibit osteoclast formation through regulating the receptor activator of nuclear factor kappa-B ligand/nuclear factor kappa-B signaling pathway, and might be a valuable approach in preventing bone loss associated with inflammatory bowel disease.

Does the active hydrogen atom in the hydantoin anion affect the physical properties, CO2 capture and conversion of ionic liquids?

Compared to the effect of the active hydrogen atom in the cation in protic ionic liquids (ILs) on their properties and applications, there are very few reports on the role of the active hydrogen atom in the anion. In order to better understand the role of the active hydrogen atom in the anion, the physical properties, CO2 capture and conversion of three hydantoin-based anion-functionalized ILs ([P4442][Hy], [P4442]2[Hy], and [HDBU][Hy]) have been investigated via experiments, spectroscopy, and DFT calculations in this work. The results show that the active hydrogen atom in the anion can form anionic hydrogen bonding networks, which significantly increase the melting point and viscosity and decrease the basicity of the IL, thereby weakening its ability to capture and convert CO2. Interestingly, [P4442][Hy] undergoes a solid/liquid two-phase transition during CO2 absorption/desorption due to the formation of quasi-intramolecular hydrogen bonding between the active hydrogen atom and the O- atom of the absorbed CO2, suggesting that the presence of the active hydrogen atom gives [P4442][Hy] the potential to be an excellent molecular switch. As there is no active hydrogen atom in the anion of [P4442]2[Hy], it shows excellent CO2 capture and conversion performance through the double-site interaction. [HDBU][Hy] shows the weakest catalytic CO2 conversion due to the presence of active hydrogen atoms on both its anion and cation. Therefore, the active hydrogen atom in the anion may play a more important role in the properties and potential applications of ILs than the active hydrogen atom in the cation.

The lack of PPARα exacerbated the progression of non-alcoholic steatohepatitis in mice with spleen deficiency syndrome by triggering an inflammatory response.

Background: In addition to abnormal liver inflammation, the main symptoms of non-alcoholic steatohepatitis (NASH) are often accompanied by gastrointestinal digestive dysfunction, consistent with the concept of spleen deficiency (SD) in traditional Chinese medicine. As an important metabolic sensor, whether peroxisome proliferator-activated receptor alpha (PPARα) participates in regulating the occurrence and development of NASH with SD (NASH-SD) remains to be explored. Methods: Clinical liver samples were collected for RNA-seq analysis. C57BL/6J mice induced by folium sennae (SE) were used as an SD model. qPCR analysis was conducted to evaluate the inflammation and metabolic levels of mice. PPARα knockout mice (PPARαko) were subjected to SE and methionine-choline-deficient (MCD) diet to establish the NASH-SD model. The phenotype of NASH and the inflammatory indicators were measured using histopathologic analysis and qPCR as well. Results: The abnormal expression of PPARα signaling, coupled with metabolism and inflammation, was found in the results of RNA-seq analysis from clinical samples. SD mice showed a more severe inflammatory response in the liver evidenced by the increases in macrophage biomarkers, inflammatory factors, and fibrotic indicators in the liver. qPCR results also showed differences in PPARα between SD mice and control mice. In PPARαko mice, further evidence was found that the lack of PPARα exacerbated the inflammatory response phenotype as well as the lipid metabolism disorder in NASH-SD mice. Conclusion: The abnormal NR signaling accelerated the vicious cycle between lipotoxicity and inflammatory response in NAFLD with SD. Our results provide new evidence for nuclear receptors as potential therapeutic targets for NAFLD with spleen deficiency.

Trends in all-cause and cause-specific mortality in older adults with and without diabetes: A territory-wide analysis in one million older adults in Hong Kong.

AIMS: Direct comparisons of population-level trends in all-cause and cause-specific mortalities among older adults with and without diabetes are lacking. METHODS: We performed a territory-wide analysis of 1,142,000 unique older adults aged ≥ 65 years (31.7 % with diabetes) with at least one attendance in the Hong Kong Hospital Authority in 2014-2018. We used Joinpoint regression to describe trends of age- and sex-standardised all-cause and cause-specific mortalities (cardiovascular disease [CVD], cancer, and non-CVD and non-cancer) in older adults with and without diabetes. RESULTS: All-cause mortality decreased in older adults with (average annual percent change [AAPC] = -1.6, 95 % confidence interval [-2.7, -0.4]) and without (AAPC = -3.1 [-4.2, -2.1]) diabetes. Largest declines were seen for CVD-cause mortalities for people with and without diabetes (AAPC = -5.5 [-6.8, -4.1] vs AAPC = -5.8 [-8.6, -2.9], respectively). Cancer-cause mortalities were similar in both groups with no change. Men with diabetes showed less favourable improvements. An increasing mortality trend was seen only in the 65-69 age-group regardless of diabetes status. CONCLUSIONS: Mortality continued to decline in older adults with and without diabetes, mainly driven by a decline in CVD deaths, with no narrowing of the mortality gap. Our findings call for continued actions to address excess mortalities especially in older men with diabetes and younger older adults.

The Dual Angiogenesis Effects via Nrf2/HO-1 Signaling Pathway of Melatonin Nanocomposite Scaffold on Promoting Diabetic Bone Defect Repair.

Purpose: Given the escalating prevalence of diabetes, the demand for specific bone graft materials is increasing, owing to the greater tendency towards bone defects and more difficult defect repair resulting from diabetic bone disease (DBD). Melatonin (MT), which is known for its potent antioxidant properties, has been shown to stimulate both osteogenesis and angiogenesis. Methods: MT was formulated into MT@PLGA nanoparticles (NPs), mixed with sodium alginate (SA) hydrogel, and contained within a 3D printing polycaprolactone/ß-Tricalcium phosphate (PCL/ß-TCP) scaffold. The osteogenic capacity of the MT nanocomposite scaffold under diabetic conditions was demonstrated via in vitro and in vivo studies and the underlying mechanisms were investigated. Results: Physicochemical characterization experiments confirmed the successful fabrication of the MT nanocomposite scaffold, which can achieve long-lasting sustained release of MT. The in vitro and in vivo studies demonstrated that the MT nanocomposite scaffold exhibited enhanced osteogenic capacity, which was elucidated by the dual angiogenesis effects activated through the NF-E2-related factor 2/Heme oxygenase 1 (Nrf2/HO-1) signaling pathway, including the enhancement of antioxidant enzyme activity to reduce the oxidative stress damage of vascular endothelial cells (VECs) and directly stimulating vascular endothelial growth factor (VEGF) production, which reversed the angiogenesis-osteogenesis uncoupling and promoted osteogenesis under diabetic conditions. Conclusion: This study demonstrated the research prospective and clinical implications of the MT nanocomposite scaffold as a novel bone graft for treating bone defect and enhancing bone fusion in diabetic individuals.

EP300 regulates the SLC16A1-AS1-AS1/TCF3 axis to promote lung cancer malignancies through the Wnt signaling pathway.

Objective: To investigate the regulatory mechanism of EP300 in the interaction between SLC16A1-AS1 and TCF3 to activate the Wnt pathway, thereby promoting malignant progression in lung cancer. Methods: In lung cancer cell lines, SLC16A1-AS1 was knocked down, and the impact of this knockdown on the malignant progression of lung cancer cells was assessed through clonogenic assays, Transwell assays, and apoptosis experiments. The regulatory relationship between EP300 and SLC16A1-AS1 was investigated through bioinformatic analysis and ChIP experiments. The expression of SLC16A1-AS1 and TCF3 in 56 paired lung cancer tissues was examined using RT-qPCR, and their correlation was analyzed. The interaction between TCF3 and SLC16A1-AS1 was explored through bioinformatic analysis and CoIP experiments. Activation of the Wnt/ß-catenin pathway was assessed by detecting the accumulation of ß-catenin in the nucleus through Western blotting. The role of EP300 in regulating the effect of SLC16A1-AS1/TCF3-mediated Wnt/ß-catenin signaling on lung cancer malignant progression was validated through in vitro and in vivo experiments. Results: SLC16A1-AS1 is highly expressed in lung cancer and regulates its malignant progression. EP300 mediates histone modifications on the SLC16A1-AS1 promoter, thus controlling its expression. SLC16A1-AS1 exhibits specific interactions with TCF3, and the SLC16A1-AS1/TCF3 complex activates the Wnt/ß-catenin pathway. EP300 plays a critical role in regulating the impact of SLC16A1-AS1/TCF3-mediated Wnt/ß-catenin signaling on lung cancer malignant progression. Conclusion: EP300 regulates the SLC16A1-AS1/TCF3-mediated Wnt/ß-catenin signaling pathway, influencing the malignant progression of lung cancer.

Digital health literacy and associated factors among internet users from China: a cross-sectional study.

BACKGROUND: As the internet develops and 5G technology becomes increasingly prominent, the internet has become a major source of health-related information. Increasingly, people use the internet to find health-related information, and digital health literacy is now a set of essential capabilities to improve their health in the digital era. However, little is known about the factors that influencing digital health literacy. This study aimed to assess digital health literacy scores and identify its influencing factors among internet users in China. Additionally, this study explored the participant's actual skills using an additional set of performance-based items from the Digital Health Literacy Instrument (DHLI). METHODS: An online cross-sectional study was conducted in August 2022. Participants aged ≥18 years were recruited to complete the survey. Data were collected using the Chinese revised version of the DHLI, the self-reported internet use questionnaire, and the sociodemographic questionnaire. We conducted multivariate linear regression analyses to explore the relationships among the sociodemographic variables, behavior of internet use, and the digital health literacy scores. RESULTS: In total, 702 participants completed the survey. The mean DHLI score was 2.69 ± 0.61. Multivariate linear regression analyses showed that the age groups 35-49 (ß = - 0.08, P = 0.033), 50-64 (ß = - 0.161, P < 0.001), and ≥ 65 (ß = - 0.138, P < 0.001) were negatively associated with DHL scores. However, education level, including bachelor's or associate degree (ß = 0.255, P = 0.002) and master's degree and above (ß = 0.256, P < 0.001), frequency of health-related Internet usage (ß = 0.192, P < 0.001), the number of digital devices used (ß = 0.129, P = 0.001), and OHISB (ß = 0.103, P = 0.006) showed a positive relationship with DHL scores. CONCLUSIONS: The study findings demonstrate that age, educational levels, number of technological devices used, and greater use of the web for health information were independently associated with DHL scores. Healthcare providers should consider providing training programs tailored to specific sociodemographic factors to improve the ability that find and use accurate information online to meet digital health services, which contributes to enhance their self-management and reduce health disparities.

Tailoring Charge Separation in ZnIn2S4@CdS Hollow Nanocages for Simultaneous Alcohol Oxidation and CO2 Reduction under Visible Light.

Artificial photosynthesis provides a sustainable strategy for producing usable fuels and fine chemicals and attracts broad research interest. However, conventional approaches suffer from low reactivity or low selectivity. Herein, we demonstrate that photocatalytic reduction of CO2 coupled with selective oxidation of aromatic alcohol into corresponding syngas and aromatic aldehydes can be processed efficiently and fantastically over the designed S-scheme ZnIn2S4@CdS core-shell hollow nanocage under visible light. In the ZnIn2S4@CdS heterostructure, the photoexcited electrons and holes with weak redox capacities are eliminated, while the photoexcited electrons and holes with powder redox capacities are separated spatially and preserved on the desired active sites. Therefore, even if there are no cocatalysts and no vacancies, ZnIn2S4@CdS exhibits high reactivity. For instance, the CO production of ZnIn2S4@CdS is about 3.2 and 3.4 times higher than that of pure CdS and ZnIn2S4, respectively. More importantly, ZnIn2S4@CdS exhibits general applicability and high photocatalytic stability. Trapping agent experiments, 13CO2 isotopic tracing, in situ characterizations, and theoretical calculations reveal the photocatalytic mechanism. This study provides a new strategy to design efficient and selective photocatalysts for dual-function redox reactions by tailoring the active sites and regulating vector separation of photoexcited charge carriers.