Bithiophene-Functionalized Infrared Two-Photon Absorption Metal Complexes as Single-Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100% survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.

Fabrication of amino- and hydroxyl dual-functionalized magnetic microporous organic network for extraction of zearalenone from traditional Chinese medicine prior to the HPLC determination.

Efficient enrichment of trace zearalenone (ZEN) from the complex traditional Chinese medicine (TCM) samples is quite difficult, but of great significance for TCM quality control. Herein, we reported a novel magnetic solid phase extraction (MSPE) strategy for ZEN enrichment using the amino- and hydroxyl dual-functionalized magnetic microporous organic network (Fe3O4@MON-NH2-OH) as an advanced adsorbent combined with the high-performance liquid chromatography (HPLC) determination. Efficient extraction of ZEN was achieved via the possible hydrogen bonding, hydrophobic, and π-π interactions between Fe3O4@MON-NH2-OH and ZEN. The adsorption capacity of Fe3O4@MON-NH2-OH for ZEN was 215.0 mg g-1 at the room temperature, which was much higher than most of the reported adsorbents. Under the optimal condition, the developed Fe3O4@MON-NH2-OH-MSPE-HPLC method exhibited wide linear range (5-2500 µg L-1), low limits of detection (1.4-35 µg L-1), less adsorbent consumption (5 mg), and large enhancement factor (95) for ZEN. The proposed method was successfully applied to detect trace ZEN from 10 kinds of real TCM samples. Conclusively, this work demonstrates the Fe3O4@MON-NH2-OH can effectively extract trace ZEN from the complex TCM matrices, which may open up a new way for the application of MONs in the enrichment and extraction of trace contaminants or active constituents from the complex TCM samples.

Evidence and causes of recent decreases in nitrogen deposition in temperate forests in Northeast China.

High reactive nitrogen (N) emissions due to anthropogenic activities in China have led to an increase in N deposition and ecosystem degradation. The Chinese government has strictly regulated reactive N emissions since 2010, however, determining whether N deposition has reduced requires long-term monitoring. Here, we report the patterns of N deposition at a rural forest site (Qingyuan) in northeastern China over the last decade. We collected 456 daily precipitation samples from 2014 to 2022 and analysed the temporal dynamics of N deposition. NH4+-N, NO3--N, and total inorganic N (TIN) deposition ranged from 10.5 ± 3.5 (mean ± SD), 6.1 ± 1.6, and 16.6 ± 4.7 kg N ha-1 year-1, respectively. Over the measurement period, TIN deposition at Qingyuan decreased by 55 %, whereas that in comparable sites in East Asia declined by 14-34 %. We used a random forest model to determine factors influencing the deposition of NH4+-N, NO3--N, and TIN during the study period. NH4+-N deposition decreased by 60 % because of decreased agricultural NH3 emissions. Furthermore, NO3--N deposition decreased by 42 %, due to reduced NOx emissions from agricultural soil and fossil fuel combustion. The steep decline in N deposition in northeastern China was attributed to reduced coal consumption, improved emission controls on automobiles, and shifts in agricultural practices. Long-term monitoring is needed to assess regional air quality and the impact of N emission control regulations.

Differential Impact of 0.01% and 0.05% Atropine Eyedrops on Ocular Surface in Young Adults.

Purpose: To evaluate the effect of low-concentration (0.01% and 0.05%) atropine eyedrops on ocular surface characteristics in young adults. Methods: Twenty-six myopic students aged 18 to 30 years were randomly assigned to receive either 0.01% or 0.05% atropine once nightly for 14 days, followed by cessation, with a ≥14-day interval between each administration. Assessments were conducted one, two, seven, and 14 days after using atropine with corresponding timepoints after atropine cessation. Tear meniscus height and first and average noninvasive keratograph tear film breakup time (NIKBUT-first, NIKBUT-average) were measured using Keratograph 5M, whereas the objective scatter index (OSI) was measured by OQAS II devices; the ocular surface disease index (OSDI) score was also obtained. Results: The mean OSI peaked after two days of administration of 0.05% atropine (ß = 0.51, P = 0.001), accompanied by significant decreases in NIKBUT-first (ß = -7.73, P < 0.001) and NIKBUT-average (ß = -8.10, P < 0.001); the OSDI peaked after 14 days (ß = 15.41, P < 0.001). The above parameters returned to baseline one week after atropine discontinuation (all P > 0.05). NIKBUT-first and NIKBUT-average reached their lowest points after 14 days of 0.01% atropine administration (NIKBUT-first: ß = -4.46, P = 0.005; NIKBUT-average: ß = -4.42, P = 0.001), but those significant changes were diminished once atropine treatment stopped. Conclusions: Young adult myopes experienced a significant but temporary impact on the ocular surface with 0.05% atropine administration, whereas 0.01% atropine had a minimal effect. Translational Relevance: The investigation of the ocular surface effects of different concentrations of atropine may inform evidence-based clinical decisions regarding myopia control in young adults.

Impact of ambient air pollution on colorectal cancer risk and survival: insights from a prospective cohort and epigenetic Mendelian randomization study.

BACKGROUND: This study investigates the associations between air pollution and colorectal cancer (CRC) risk and survival from an epigenomic perspective. METHODS: Using a newly developed Air Pollutants Exposure Score (APES), we utilized a prospective cohort study (UK Biobank) to investigate the associations of individual and combined air pollution exposures with CRC incidence and survival, followed by an up-to-date systematic review with meta-analysis to verify the associations. In epigenetic two-sample Mendelian randomization analyses, we examine the associations between genetically predicted DNA methylation related to air pollution and CRC risk. Further genetic colocalization and gene-environment interaction analyses provided different insights to disentangle pathogenic effects of air pollution via epigenetic modification. FINDINGS: During a median 12.97-year follow-up, 5767 incident CRC cases among 428,632 participants free of baseline CRC and 533 deaths in 2401 patients with CRC were documented in the UK Biobank. A higher APES score was associated with an increased CRC risk (HR, 1.03, 95% CI = 1.01-1.06; P = 0.016) and poorer survival (HR, 1.13, 95% CI = 1.03-1.23; P = 0.010), particularly among participants with insufficient physical activity and ever smokers (Pinteraction > 0.05). A subsequent meta-analysis of seven observational studies, including UK Biobank data, corroborated the association between PM2.5 exposure (per 10 µg/m3 increment) and elevated CRC risk (RR,1.42, 95% CI = 1.12-1.79; P = 0.004; I2 = 90.8%). Genetically predicted methylation at PM2.5-related CpG site cg13835894 near TMBIM1/PNKD and cg16235962 near CXCR5, and NO2-related cg16947394 near TMEM110 were associated with an increased CRC risk. Gene-environment interaction analysis confirmed the epigenetic modification of aforementioned CpG sites with CRC risk and survival. INTERPRETATION: Our study suggests the association between air pollution and CRC incidence and survival, underscoring the possible modifying roles of epigenomic factors. Methylation may partly mediate pathogenic effects of air pollution on CRC, with annotation to epigenetic alterations in protein-coding genes TMBIM1/PNKD, CXCR5 and TMEM110. FUNDING: Xue Li is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001), the National Nature Science Foundation of China (No. 82204019) and Healthy Zhejiang One Million People Cohort (K-20230085). ET is supported by a Cancer Research UK Career Development Fellowship (C31250/A22804). MGD is supported by the MRC Human Genetics Unit Centre Grant (U127527198).

Analysis of Factors Influencing Prognosis and Assessment of 60 Cases of Decompensated Cirrhotic Patients with Portal Hypertension.

Objective: To investigate the risk factors for the development of portal hypertension in patients with decompensated cirrhosis and analyze their prognosis. Methods: Patients with decompensated cirrhosis who were admitted to our hospital and Qu fu People's Hospital from June 2022 to June 2023 were included in this study. Among them, there were 45 male and 15 female patients, with a median age of 56 (range: 35-77) years. A comparative analysis was performed between Group A (hepatic venous pressure gradient, HVPG <16 mmHg) and Group B (HVPG ≥16 mmHg) patients, along with various clinical outcomes. Multivariate analysis was conducted to explore the risk factors influencing the occurrence of portal hypertension and adverse prognosis in patients with cirrhosis. Results: In Group A patients with portal hypertension, we observed lower levels of aspartate aminotransferase, laminin, serum hyaluronic acid, type III procollagen N-terminal peptide, total bile acids, and cholylglycine acid compared to Group B. On the other hand, levels of alanine aminotransferase, white blood cells, and serum albumin were higher in Group A than in Group B. These differences between the groups were statistically significant (P < 0.05). Multivariate analysis of the aforementioned risk factors indicated that low white blood cell count, high cholylglycine acid levels, and high serum hyaluronic acid levels were identified as independent risk factors for the occurrence of difficult-to-control complications in decompensated portal hypertension among patients with liver cirrhosis (P < 0.05). Conclusion: Liver cirrhosis patients with portal hypertension and multiple risk factors like low white blood cell count and high liver transaminase levels should be cautious regarding the progression of portal hypertension when combined with splenomegaly, liver fibrosis, and bile stasis, as it often indicates a poor prognosis.

Effect of spectacle lenses with aspherical lenslets on choroidal thickness in myopic children: a 3-year follow-up study.

BACKGROUND: To investigate the impact of wearing spectacle lenses with highly aspherical lenslets (HAL) for 3 years and the impact of switching from single-vision lenses (SVL) to HAL on choroidal thickness (ChT). METHODS: Fifty-one participants who had already worn HAL for 2 years continued wearing them for an additional year (HAL group). Further, 50 and 41 participants who had worn spectacle lenses with slightly aspherical lenslets (SAL) and SVL for 2 years, respectively, switched to wearing HAL for another year (SAL-HAL and SVL-HAL groups). Additionally, 48 new participants aged 10-15 years were enrolled to wear SVL at the third year (new-SVL group). ChT was measured every 6 months throughout the study. RESULTS: Significant differences were observed in the changes in ChT among the four groups at the third year (all P < 0.05 except for the outer nasal region: P = 0.09), with the new-SVL group showing larger reductions compared with the other three groups. However, none of the three HAL-wearing groups showed significant changes in ChT at the third year (all P > 0.05). When comparing the changes in ChT for 3 years among the HAL, SAL-HAL, and SVL-HAL groups, significant differences were found before switching to HAL, but these differences were abolished after all participants switched to HAL. CONCLUSIONS: Compared to those in the SVL group, choroid thinning was significantly inhibited in all the HAL groups. Wearing HAL for 3 years no longer had a choroidal thickening effect but could still inhibit choroidal thinning compared to wearing SVL. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry (ChiCTR1800017683), http://www.chictr.org.cn/showproj.aspx?proj=29789 .

Impact of COVID-19 pandemic on depression incidence and healthcare service use among patients with depression: an interrupted time-series analysis from a 9-year population-based study.

BACKGROUND: Most studies on the impact of the COVID-19 pandemic on depression burden focused on the earlier pandemic phase specific to lockdowns, but the longer-term impact of the pandemic is less well-studied. In this population-based cohort study, we examined the short-term and long-term impacts of COVID-19 on depression incidence and healthcare service use among patients with depression. METHODS: Using the territory-wide electronic medical records in Hong Kong, we identified all patients aged ≥ 10 years with new diagnoses of depression from 2014 to 2022. We performed an interrupted time-series (ITS) analysis to examine changes in incidence of medically attended depression before and during the pandemic. We then divided all patients into nine cohorts based on year of depression incidence and studied their initial and ongoing service use patterns until the end of 2022. We applied generalized linear modeling to compare the rates of healthcare service use in the year of diagnosis between patients newly diagnosed before and during the pandemic. A separate ITS analysis explored the pandemic impact on the ongoing service use among prevalent patients with depression. RESULTS: We found an immediate increase in depression incidence (RR = 1.21, 95% CI: 1.10-1.33, p < 0.001) in the population after the pandemic began with non-significant slope change, suggesting a sustained effect until the end of 2022. Subgroup analysis showed that the increases in incidence were significant among adults and the older population, but not adolescents. Depression patients newly diagnosed during the pandemic used 11% fewer resources than the pre-pandemic patients in the first diagnosis year. Pre-existing depression patients also had an immediate decrease of 16% in overall all-cause service use since the pandemic, with a positive slope change indicating a gradual rebound over a 3-year period. CONCLUSIONS: During the pandemic, service provision for depression was suboptimal in the face of increased demand generated by the increasing depression incidence during the COVID-19 pandemic. Our findings indicate the need to improve mental health resource planning preparedness for future public health crises.

Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

Exploration of factors affecting hemodynamic stability following pheochromocytoma resection - cohort study.

Purpose: Surgery is the only way to cure pheochromocytoma; however, postoperative hemodynamic instability is one of the main causes of serious complications and even death. This study's findings provide some guidance for improved clinical management. Patients and methods: This study was to investigate the factors leading to postoperative hemodynamic instability in the postoperative pathology indicated pheochromocytoma from May 2016 to May 2022. They were divided into two groups according to whether vasoactive drugs were used for a median number of days or more postoperatively. The factors affecting the postoperative hemodynamics in the perioperative period (preoperative, intraoperative, and postoperative) were then evaluated. Results: The median number of days requiring vasoactive drug support postoperatively was three in 234 patients, while 118 (50.4%) patients required vasoactive drug support for three days or more postoperatively. The results of the multivariate analysis indicated more preoperative colloid use (odds ratio [OR]=1.834, confidence interval [CI]:1.265-2.659, P=0.001), intraoperative use of vasoactive drug (OR=4.174, CI:1.882-9.258, P<0.001), and more postoperative crystalloid solution input per unit of body weight per day (ml/kg/d) (OR=1.087, CI:1.062-1.112, P<0.001) were risk factors for predicting postoperative hemodynamic instability. The optimal cutoff point of postoperative crystalloid use were 42.37 ml/kg/d. Conclusion: Hemodynamic instability is a key issue for consideration in the perioperative period of pheochromocytoma. The amount of preoperative colloid use, the need for intraoperative vasoactive drugs, and postoperative crystalloid solution are risk factors for predicting postoperative hemodynamic instability (registration number: ChiCT2300071166).

Genome Analysis of Multiple Polysaccharide-Degrading Bacterium Microbulbifer thermotolerans HB226069: Determination of Alginate Lyase Activity.

Polysaccharide-degrading bacteria are key participants in the global carbon cycle and algal biomass recycling. Herein, a polysaccharide lyase-producing strain HB226069 was isolated from Sargassum sp. from Qingge Port, Hainan, China. Results of the phylogenetic of the 16S rRNA gene and genotypic analysis indicated that the isolate should be classified as Microbulbifer thermotolerans. The whole genome is a 4,021,337 bp circular chromosome with a G+C content of 56.5%. Analysis of the predicted genes indicated that strain HB226069 encoded 161 carbohydrate-active enzymes (CAZymes), and abundant putative enzymes involved in polysaccharide degradation were predicted, including alginate lyase, fucosidase, agarase, xylanase, cellulase, pectate lyase, amylase, and chitinase. Three of the putative polysaccharide lyases from PL7 and PL17 families were involved in alginate degradation. The alginate lyases of strain HB226069 showed the maximum activity of 117.4 U/mL at 50 °C, pH 7.0, and 0.05 M FeCl3, while exhibiting the best stability at 30 °C and pH 7.0. The Thin Layer Chromatography (TLC) and Electrospray Ionization Mass Spectrometry (ESI-MS) analyses indicated that the alginate oligosaccharides (AOSs) degraded by the partially purified alginate lyases contained oligosaccharides of DP2-DP5 and monosaccharide while reacting for 36 h. The complete genome of M. thermotolerans HB226069 enriches our understanding of the mechanism of polysaccharide lyase production and supports its potential application in polysaccharide degradation.

Identifying an immunogenic cell death-related gene signature contributes to predicting prognosis, immunotherapy efficacy, and tumor microenvironment of lung adenocarcinoma.

BACKGROUND: Immunogenic cell death (ICD) is a regulated form of cell death that triggers an adaptive immune response. The objective of this study was to investigate the correlation between ICD-related genes (ICDGs) and the prognosis and the immune microenvironment of patients with lung adenocarcinoma (LUAD). METHODS: ICD-associated molecular subtypes were identified through consensus clustering. Subsequently, a prognostic risk model comprising 5 ICDGs was constructed using Lasso-Cox regression in the TCGA training cohort and further tested in the GEO cohort. Enriched pathways among the subtypes were analyzed using GO, KEGG, and GSVA. Furthermore, the immune microenvironment was assessed using ESTIMATE, CIBERSORT, and ssGSEA analyses. RESULTS: Consensus clustering divided LUAD patients into three ICDG subtypes with significant differences in prognosis and the immune microenvironment. A prognostic risk model was constructed based on 5 ICDGs and it was used to classify the patients into two risk groups; the high-risk group had poorer prognosis and an immunosuppressive microenvironment characterized by low immune score, low immune status, high abundance of immunosuppressive cells, and high expression of tumor purity. Cox regression, ROC curve analysis, and a nomogram indicated that the risk model was an independent prognostic factor. The five hub genes were verified by TCGA database, cell sublocalization immunofluorescence analysis, IHC images and qRT-PCR, which were consistent with bioinformatics analysis. CONCLUSIONS: The molecular subtypes and a risk model based on ICDGs proposed in our study are both promising prognostic classifications in LUAD, which may provide novel insights for developing accurate targeted cancer therapies.

MEG-PPIS: a fast protein-protein interaction site prediction method based on multi-scale graph information and equivariant graph neural network.

MOTIVATION: Protein-protein interaction sites (PPIS) are crucial for deciphering protein action mechanisms and related medical research, which is the key issue in protein action research. Recent studies have shown that graph neural networks have achieved outstanding performance in predicting PPIS. However, these studies often neglect the modeling of information at different scales in the graph and the symmetry of protein molecules within three-dimensional space. RESULTS: In response to this gap, this paper proposes the MEG-PPIS approach, a PPIS prediction method based on multi-scale graph information and E(n) equivariant graph neural network (EGNN). There are two channels in MEG-PPIS: the original graph and the subgraph obtained by graph pooling. The model can iteratively update the features of the original graph and subgraph through the weight-sharing EGNN. Subsequently, the max-pooling operation aggregates the updated features of the original graph and subgraph. Ultimately, the model feeds node features into the prediction layer to obtain prediction results. Comparative assessments against other methods on benchmark datasets reveal that MEG-PPIS achieves optimal performance across all evaluation metrics and gets the fastest runtime. Furthermore, specific case studies demonstrate that our method can predict more true positive and true negative sites than the current best method, proving that our model achieves better performance in the PPIS prediction task. AVAILABILITY AND IMPLEMENTATION: The data and code are available at https://github.com/dhz234/MEG-PPIS.git.

Sb/As immobilization and soil function improvement under the combined remediation strategy of modified biochar and Sb-oxidizing bacteria at a smelting site.

Antimony (Sb) and arsenic (As) lead to soil pollution and structural degradation at Sb smelting sites. However, most sites focus solely on Sb/As immobilization, neglecting the restoration of soil functionality. Here, we investigated the effectiveness of Fe/H2O2 modified biochar (Fe@H2O2-BC) and Sb-oxidizing bacteria (Bacillus sp. S3) in immobilizing Sb/As and enhancing soil functional resilience at an Sb smelting site. Over a twelve-month period, the leaching toxicity of As and Sb was reduced to 0.05 and 0.005 mg L-1 (GB3838-2002) respectively, with 1% (w/w) Fe@H2O2-BC and 2% (v/v) Bacillus sp. S3 solution. Compared to CK, the combination of Fe@H2O2-BC and Bacillus sp. S3 significantly reduced the bioavailable As/Sb by 98.00%/93.52%, whilst increasing residual As and reducible Sb fractions by 210.31% and 96.51%, respectively. The combined application generally improved soil aggregate structure, pore characteristics, and water-holding capacity. Fe@H2O2-BC served as a pH buffer and long-term reservoir of organic carbon, changing the availability of carbon substrates to bacteria. The inoculation of Bacillus sp. S3 facilitated the transformation of Sb(III)/As(III) to Sb(V)/As(V) and differentiated the composition and functional roles of bacterial communities in soils. The combination increased the abundance of soil saprotrophs by 164.20%, whilst improving the relative abundance of N- and S-cycling bacteria according to FUNGuild and FAPROTAX analysis. These results revealed that the integrated application was instrumental in As/Sb detoxification/immobilization and soil function restoration, which demonstrating a promising microbially-driven ecological restoration strategy at Sb smelting sites.

Coupled hydraulics and carbon economy underlie age-related growth decline and revitalisation of sand-fixing shrubs after crown removal.

Crown removal revitalises sand-fixing shrubs that show declining vigour with age in drought-prone environments; however, the underlying mechanisms are poorly understood. Here, we addressed this knowledge gap by comparing the growth performance, xylem hydraulics and plant carbon economy across different plant ages (10, 21 and 33 years) and treatments (control and crown removal) using a representative sand-fixing shrub (Caragana microphylla Lam.) in northern China. We found that growth decline with plant age was accompanied by simultaneous decreases in soil moisture, plant hydraulic efficiency and photosynthetic capacity, suggesting that these interconnected changes in plant water relations and carbon economy were responsible for this decline. Following crown removal, quick resprouting, involving remobilisation of root nonstructural carbohydrate reserves, contributed to the reconstruction of an efficient hydraulic system and improved plant carbon status, but this became less effective in older shrubs. These age-dependent effects of carbon economy and hydraulics on plant growth vigour provide a mechanistic explanation for the age-related decline and revitalisation of sand-fixing shrubs. This understanding is crucial for the development of suitable management strategies for shrub plantations constructed with species having the resprouting ability and contributes to the sustainability of ecological restoration projects in water-limited sandy lands.

[Chaihu Sanshen Capsules protect rats from myocardial ischemia reperfusion injury via PKCßâ ¡/NOX2/ROS signaling pathway].

This study aims to explore the pathogenesis of myocardial ischaemia reperfusion injury(MIRI) based on oxidative stress-mediated programmed cell death and the mechanism and targets of Chaihu Sanshen Capsules in treating MIRI via the protein kinase Cß(PKCßⅡ)/NADPH oxidase 2(NOX2)/reactive oxygen species(ROS) signaling pathway. The rat model of MIRI was established by the ligation of the left anterior descending branch. Rats were randomized into 6 groups: sham group, model group, clinically equivalent-, high-dose Chaihu Sanshen Capsules groups, N-acetylcysteine group, and CGP53353 group. After drug administration for 7 consecutive days, the area of myocardial infarction in each group was measured. The pathological morphology of the myocardial tissue was observed by hematoxylin-eosin(HE) staining. The apoptosis in the myocardial tissue was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL). Enzyme-linked immunosorbent assay(ELISA) was employed to measure the le-vels of indicators of myocardial injury and oxidative stress. The level of ROS was detected by flow cytometry. The protein and mRNA levels of the related proteins in the myocardial tissue were determined by Western blot and real-time quantitative PCR(RT-qPCR), respectively. Compared with the sham group, the model group showed obvious myocardial infarction, myocardial structural disorders, interstitial edema and hemorrhage, presence of a large number of vacuoles, elevated levels of myocardial injury markers, myocardial apoptosis, ROS, and malondialdehyde(MDA), lowered superoxide dismutase(SOD) level, and up-regulated protein and mRNA le-vels of PKCßⅡ, NOX2, cysteinyl aspartate specific proteinase-3(caspase-3), and acyl-CoA synthetase long-chain family member 4(ACSL4) in the myocardial tissue. Compared with the model group, Chaihu Sanshen Capsules reduced the area of myocardial infarction, alleviated the pathological changes in the myocardial tissue, lowered the levels of myocardial injury and oxidative stress indicators and apoptosis, and down-regulated the mRNA and protein levels of PKCßⅡ, NOX2, caspase-3, and ACSL4 in the myocardial tissue. Chaihu Sanshen Capsules can inhibit oxidative stress and programmed cell death(apoptosis, ferroptosis) by regulating the PKCßⅡ/NOX2/ROS signaling pathway, thus mitigating myocardial ischemia reperfusion injury.

Association between alcohol consumption and peripheral artery disease: Two de novo prospective cohorts and a systematic review with meta-analysis.

AIMS: The association between alcohol consumption and risk of peripheral artery disease (PAD) is inconclusive. We conducted this study to examine the association between alcohol consumption and PAD risk in two de novo cohort studies and a meta-analysis of observational studies. METHODS AND RESULTS: A systematic review was conducted to identify studies on alcohol consumption in relation to PAD risk. We further used data from two cohorts of 70,116 Swedish and 405,406 British adults and performed a meta-analysis of results from previously published studies and current cohort studies. There was a U-shaped association between alcohol consumption and incident PAD risk in the Swedish and British cohorts. The meta-analysis of results of these two cohorts and previously published studies found that compared with non- or never-drinkers, the relative risk of PAD was 0.83 (95% confidence interval [CI] 0.77-0.89), 0.81 (95% CI 0.74-0.90), and 0.94 (95% CI 0.83-1.07) for light, moderate, and high-to-heavy alcohol drinkers, respectively. The nonlinear meta-analysis revealed a possibly U-shaped association between alcohol consumption and PAD risk (P-nonlinearity <0.001). The risk of PAD was observed to be the lowest for 2 drinks/week and to be pronounced for ≥10 drinks/week. All these associations persisted in a sensitivity meta-analysis including cohort and other type of observational studies. CONCLUSION: Alcohol intake ≤ 2 drinks/week was associated with a reduced risk of PAD and the risk of PAD became pronounced with intake ≥10 drinkers/week.

The association between alcohol consumption and the risk of peripheral artery disease is conflicting between studies and thus remains undetermined. In the two de novo cohort analyses, we found a U-shaped association between alcohol consumption and peripheral artery disease risk in the Swedish and British populations. In the meta-analysis, light-to-moderate consumption of alcohol was associated with a reduced risk of peripheral artery disease. The dose-response meta-analysis showed that the risk of peripheral artery disease became pronounced for alcohol consumption ≥10 drinkers/week. This is an observational study that cannot infer causality between alcohol consumption and peripheral artery disease risk. We are not able to assess the specific associations to different types of alcoholic beverages.

Long-term prognosis of patients with gallbladder carcinoma after curative-intent resection based on changes in the ratio of carbohydrate antigen 19-9 to total bilirubin (CA19-9/TB): a multicenter retrospective cohort study.

BACKGROUND: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients. METHODS: Prospectively colleced data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analysed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2×103 U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS. RESULTS: The normal group (n=179 patients) and the normalization group (n=73 patients) had better OS and RFS than the non-normalization group (n=65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P<0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P=0.255; RFS, P=0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P=0.025; RFS, P=0.003). CONCLUSIONS: Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients.

DNA methylation remodeling and the functional implication during male gametogenesis in rice.

BACKGROUND: Epigenetic marks are reprogrammed during sexual reproduction. In flowering plants, DNA methylation is only partially remodeled in the gametes and the zygote. However, the timing and functional significance of the remodeling during plant gametogenesis remain obscure. RESULTS: Here we show that DNA methylation remodeling starts after male meiosis in rice, with non-CG methylation, particularly at CHG sites, being first enhanced in the microspore and subsequently decreased in sperm. Functional analysis of rice CHG methyltransferase genes CMT3a and CMT3b indicates that CMT3a functions as the major CHG methyltransferase in rice meiocyte, while CMT3b is responsible for the increase of CHG methylation in microspore. The function of the two histone demethylases JMJ706 and JMJ707 that remove H3K9me2 may contribute to the decreased CHG methylation in sperm. During male gametogenesis CMT3a mainly silences TE and TE-related genes while CMT3b is required for repression of genes encoding factors involved in transcriptional and translational activities. In addition, CMT3b functions to repress zygotic gene expression in egg and participates in establishing the zygotic epigenome upon fertilization. CONCLUSION: Collectively, the results indicate that DNA methylation is dynamically remodeled during male gametogenesis, distinguish the function of CMT3a and CMT3b in sex cells, and underpin the functional significance of DNA methylation remodeling during rice reproduction.

A comprehensive investigation of the interactions of human serum albumin with polymeric and hybrid nanoparticles.

Nanoparticles (NPs) engineered as drug delivery systems continue to make breakthroughs as they offer numerous advantages over free therapeutics. However, the poor understanding of the interplay between the NPs and biomolecules, especially blood proteins, obstructs NP translation to clinics. Nano-bio interactions determine the NPs' in vivo fate, efficacy and immunotoxicity, potentially altering protein function. To fulfill the growing need to investigate nano-bio interactions, this study provides a systematic understanding of two key aspects: (i) protein corona (PC) formation and (ii) NP-induced modifications on protein's structure and stability. A methodology was developed by combining orthogonal techniques to analyze both quantitative and qualitative aspects of nano-bio interactions, using human serum albumin (HSA) as a model protein. Protein quantification via liquid chromatography-mass spectrometry, and capillary zone electrophoresis (CZE) clarified adsorbed protein quantity and stability. CZE further unveiled qualitative insights into HSA forms (native, glycated HSA and cysteinylated), while synchrotron radiation circular dichroism enabled analyzing HSA's secondary structure and thermal stability. Comparative investigations of NP cores (organic vs. hybrid), and shells (with or without polyethylene glycol (PEG)) revealed pivotal factors influencing nano-bio interactions. Polymeric NPs based on poly(lactic-co-glycolic acid) (PLGA) and hybrid NPs based on metal-organic frameworks (nanoMOFs) presented distinct HSA adsorption profiles. PLGA NPs had protein-repelling properties while inducing structural modifications on HSA. In contrast, HSA exhibited a high affinity for nanoMOFs forming a PC altering thereby the protein structure. A shielding effect was gained through PEGylation for both types of NPs, avoiding the PC formation as well as the alteration of unbound HSA structure.