Bacterial exonuclease III expands its enzymatic activities on single-stranded DNA.

Bacterial exonuclease III (ExoIII), widely acknowledged for specifically targeting double-stranded DNA (dsDNA), has been documented as a DNA repair-associated nuclease with apurinic/apyrimidinic (AP)-endonuclease and 3'→5' exonuclease activities. Due to these enzymatic properties, ExoIII has been broadly applied in molecular biosensors. Here, we demonstrate that ExoIII (Escherichia coli) possesses highly active enzymatic activities on ssDNA. By using a range of ssDNA fluorescence-quenching reporters and fluorophore-labeled probes coupled with mass spectrometry analysis, we found ExoIII cleaved the ssDNA at 5'-bond of phosphodiester from 3' to 5' end by both exonuclease and endonuclease activities. Additional point mutation analysis identified the critical residues for the ssDNase action of ExoIII and suggested the activity shared the same active center with the dsDNA-targeted activities of ExoIII. Notably, ExoIII could also digest the dsDNA structures containing 3'-end ssDNA. Considering most ExoIII-assisted molecular biosensors require the involvement of single-stranded DNA (ssDNA) or nucleic acid aptamer containing ssDNA, the activity will lead to low efficiency or false positive outcome. Our study revealed the multi-enzymatic activity and the underlying molecular mechanism of ExoIII on ssDNA, illuminating novel insights for understanding its biological roles in DNA repair and the rational design of ExoIII-ssDNA involved diagnostics.

A new classification for emergency critically ill patients and analysis of their adverse events during intrahospital transport: A cluster analysis.

BACKGROUND: Critical patients may experience various adverse events during transportation within hospitals. Therefore, quickly evaluating and classifying patients before transporting them from the emergency department and focusing on managing high-risk patients are critical. At present, no unified classification method exists; all the current approaches are subjective. AIMS: To ensure transportation safety, we conducted a cluster analysis of critically ill patients transferred from the emergency department to the intensive care unit. STUDY DESIGN: Single-centre cohort study. This study was conducted at a comprehensive first-class teaching hospital in Beijing. Convenience sampling and continuous enrolment were employed. We collected data from 1 January 2019, to 31 December 2021. All patients were transferred from the emergency department to the intensive care unit, and cluster analysis was conducted using five variables. RESULTS: A total of 584 patients were grouped into three clusters. Cluster 1 (high systolic blood pressure group) included 208 (35.6%) patients. Cluster 2 (high heart rate and low blood oxygen group) included 55 (9.4%) patients. Cluster 3 (normal group) included the remaining 321 (55%) patients. The oxygen saturation levels of all the patients were lower after transport, and the proportion of adverse events (61.8%) was the highest in Cluster 2 (p < .05). CONCLUSIONS: This study utilized data on five important vital signs from a cluster analysis to explore possible patient classifications and provide a reference for ensuring transportation safety. RELEVANCE TO CLINICAL PRACTICE: Before transferring patients, we should classify them and implement targeted care. Changes in blood oxygen levels in all patients should be considered, with a focus on the occurrence of adverse events during transportation among patients with high heart rates and low blood oxygen levels.

Optimizing anterior urethral stricture assessment: leveraging AI-assisted three-dimensional sonourethrography in clinical practice.

PURPOSE: This investigation sought to validate the clinical precision and practical applicability of AI-enhanced three-dimensional sonographic imaging for the identification of anterior urethral stricture. METHODS: The study enrolled 63 male patients with diagnosed anterior urethral strictures alongside 10 healthy volunteers to serve as controls. The imaging protocol utilized a high-frequency 3D ultrasound system combined with a linear stepper motor, which enabled precise and rapid image acquisition. For image analysis, an advanced AI-based segmentation process using a modified U-net algorithm was implemented to perform real-time, high-resolution segmentation and three-dimensional reconstruction of the urethra. A comparative analysis was performed against the surgically measured stricture lengths. Spearman's correlation analysis was executed to assess the findings. RESULTS: The AI model completed the entire processing sequence, encompassing recognition, segmentation, and reconstruction, within approximately 5 min. The mean intraoperative length of urethral stricture was determined to be 14.4 ± 8.4 mm. Notably, the mean lengths of the urethral strictures reconstructed by manual and AI models were 13.1 ± 7.5 mm and 13.4 ± 7.2 mm, respectively. Interestingly, no statistically significant disparity in urethral stricture length between manually reconstructed and AI-reconstructed images was observed. Spearman's correlation analysis underscored a more robust association of AI-reconstructed images with intraoperative urethral stricture length than manually reconstructed 3D images (0.870 vs. 0.820). Furthermore, AI-reconstructed images provided detailed views of the corpus spongiosum fibrosis from multiple perspectives. CONCLUSIONS: The research heralds the inception of an innovative, efficient AI-driven sonographic approach for three-dimensional visualization of urethral strictures, substantiating its viability and superiority in clinical application.

Topological Transformation of Hydrogen-Terminated Germanium to Germanium Nanosheets for Fast Lithium Storage.

Germanium has been recognized as a promising anode material for lithium-ion batteries (LIBs) due to its high theoretical capacity and excellent lithium-ion diffusivity. Nonetheless, it is challenging to enhance both the high-rate performance and long-term cycling stability simultaneously. This study introduces a novel heterostructure composed of germanium nanosheets integrated with graphene (Ge NSs@Gr). These nanosheets undergo an in situ phase transformation from a hydrogen-terminated multilayer germanium compound termed germanane (GeH) derived via topochemical deintercalation from CaGe2. This approach mitigates oxidation and prevents restacking by functionalizing the exfoliated germanane with octadecenoic organic molecules. The resultant germanium nanosheets retain their structural integrity from CaGe2 and present an exposed, active (111) surface that features an open crystal lattice, facilitating swift lithium-ion migration conducive to lithium storage. The composite material delivers a substantial reversible capacity of 1220 mA h g-1 at a current density of 0.2 C and maintains a capacity of 456 mA h g-1 even at an ultrahigh current density of 10 C over extended cycling. Impressively, a capacity of 316 mA h g-1 remains after 5000 cycles. The exceptional high-rate performance and durable cycling stability underscore the Ge NSs@Gr anode's potential as a highly viable option for LIBs.

Chitosan-based high-performance flexible supercapacitor via "in-situ co-doping/self-regulation-activation" strategy.

The construction of N, P co-doped hierarchically porous carbons (NPHPC) by a facile and green approach is crucial for high-performance energy storage but still an enormous challenge. Herein, an environment-friendly "in-situ co-doping, self-regulation-activation" strategy is presented to one-pot synthesize NPHPC using a phytic acid-induced polyethyleneimine/chitosan gel (PEI-PA-CS) as single precursor. NPHPC displayed a specific surface area of up to 1494 m2 g-1, high specific capacitance of 449 F g-1 at 1 A g-1, outstanding rate capability and cycling durability in a wide temperature range (-20 to 60 °C). NPHPC and PEI-PA-CS electrolyte assembled symmetric quasi-solid-state flexible supercapacitor presents superb energy outputs of 27.06 Wh kg-1 at power density of 225 W kg-1. For capacitive deionization (CDI), NPHPC also exhibit an excellent salt adsorption capacity of 16.54 mg g-1 in 500 mg L-1 NaCl solution at a voltage of 1.4 V, and regeneration performance. This study provides a valuable reference for the rational design and synthesis of novel biomass-derived energy-storage materials by integrating phytic acid induced heteroatom doping and pore engineering.

Association of life's essential 8 with risk of recurrent cardiovascular events among patients with coronary heart disease.

AIMS: To examine the association of Life's Essential 8 (LE8) with the risk of recurrent cardiovascular events among patients with CHD. METHODS: This prospective cohort study included 11,997 patients with CHD from the UK Biobank. The LE8 score was generated using five lifestyle factors (diet, body mass index, physical activity, smoking, and sleep) and three biological factors (blood lipids, blood glucose, and blood pressure). LE8 score ranged from 0 to 100 and was categorized into quartiles. Cox proportional hazards regression models were applied to estimate the hazard ratio (HR) and 95% CI (confidence interval). RESULTS: During a median follow up of 12.5 years, we documented 3366 recurrent cardiovascular events, 1068 myocardial infarction, 1829 heart failure events, 703 strokes, and 934 cardiovascular deaths. The multivariable-adjusted HR (95% CI) for the highest versus the lowest quartile of LE8 score was 0.57 (0.50, 0.65) for recurrent cardiovascular events, 0.66 (0.52, 0.83) for myocardial infarction, 0.54 (0.45, 0.67) for heart failure, 0.50 (0.36, 0.68) for stroke, and 0.46 (0.37, 0.56) for cardiovascular death. Furthermore, the population attributable fraction of the lowest to the highest quartile of LE8 score were ranged from 16.2% to 32.5% for the various cardiovascular outcomes. In addition, biomarkers including renal function and inflammation collectively explained 47.6%-87.7% of the associations between the lifestyle factors and recurrent cardiovascular events. CONCLUSIONS: Better cardiovascular health as measured by LE8 was associated with significantly lower risk of recurrent cardiovascular events among patients with CHD. Clinicians should prioritize educating patients with CHD on the importance of optimal cardiovascular health for secondary prevention. In addition, our findings indicated significant mediation effect of biomarkers involving of glycemic control, renal function, liver function, lipid profile, and systemic inflammation on the associations between overall lifestyle factors and recurrent cardiovascular events.

Microbiome and metabolome analyses reveal significant alterations of gut microbiota and bile acid metabolism in ETEC-challenged weaned piglets by dietary berberine supplementation.

This study mainly investigated the effects of berberine (BBR) on the bile acid metabolism in gut-liver axis and the microbial community in large intestine of weaned piglets challenged with enterotoxigenic Escherichia coli (ETEC) by microbiome and metabolome analyses. Sixty-four piglets were randomly assigned to four groups including Control group, BBR group, ETEC group, and BBR + ETEC group. Dietary BBR supplementation upregulated the colonic mRNA expression of Occludin, Claudin-5, trefoil factor 3 (TFF3), and interleukin (IL)-10, and downregulated colonic IL-1ß and IL-8 mRNA expression in piglets challenged with ETEC K88 (p < 0.05). The hepatic non-targeted metabolome results showed that dietary BBR supplementation enriched the metabolic pathways of primary bile acid biosynthesis, tricarboxylic acid cycle, and taurine metabolism. The hepatic targeted metabolome analyses showed that BBR treatment increased the hepatic concentrations of taurocholic acid (TCA) and taurochenodeoxycholic acid (TDCA), but decreased the hepatic cholic acid (CA) concentration (p < 0.05). Further intestinal targeted metabolome analyses indicated that the deoxycholic acid (DCA), hyocholic acid (HCA), 7-ketodeoxycholic acid (7-KDCA), and the unconjugated bile acid concentrations in ileal mucosa was decreased by dietary BBR treatment (p < 0.05). Additionally, BBR treatment significantly upregulated the hepatic holesterol 7 α-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) mRNA expression, and upregulated the ileal mRNA expression of farnesoid X receptor (FXR) and apical sodium-dependent bile acid transporter (ASBT) as well as the colonic mRNA expression of FXR, fibroblast growth factor19 (FGF19), takeda G protein-coupled receptor 5 (TGR5) and organic solute transporters beta (OST-ß) in piglets (p < 0.05). Moreover, the microbiome analysis showed that BBR significantly altered the composition and diversity of colonic and cecal microbiota community, with the abundances of Firmicutes (phylum), and Lactobacillus and Megasphaera (genus) significantly increased in the large intestine of piglets (p < 0.05). Spearman correlation analysis showed that the relative abundances of Megasphaera (genus) were positively correlated with Claudin-5, Occludin, TFF3, and hepatic TCDCA concentration, but negatively correlated with hepatic CA and glycocholic acid (GCA) concentration (p < 0.05). Moreover, the relative abundances of Firmicute (phylum) and Lactobacillus (genus) were positively correlated with hepatic TCDCA concentration (p < 0.05). Collectively, dietary BBR supplementation could regulate the gut microbiota and bile acid metabolism through modulation of gut-liver axis, and attenuate the decreased intestinal tight junction expression caused by ETEC, which might help maintain intestinal homeostasis in weaned piglets.

Structure and molecular-level transformation for oxidation of effluent organic matters by manganese oxides.

As important organic components in water environments, effluent organic matters (EfOMs) from wastewater treatment plants are widely present in Mn-rich environments or engineered treatment systems. The redox interaction between manganese oxides (MnOx) and EfOMs can lead to their structural changes, which are crucial for ensuring the safety of water environments. Herein, the reactivities of MnOx with EfOMs were evaluated, and it was found that MnOx with high specific surface area, active high-valent manganese content and lattice oxygen content (i.e., amorphous MnO2) possessed stronger oxidizing ability towards EfOMs. Accompanying by EfOMs oxidation, Mn(IV) and Mn(III) were reduced into Mn(II), with Mn(III) as the significant active species. Through molecular-level transformation analysis by ultrahigh mass spectrometry (FT-ICR MS), the highly reactive compounds in EfOMs were clearly determined to be that with more aromatic and unsaturated structures, especially lignin-like compounds (the highest content in EfOMs (over 60 %)). EfOMs were oxidized by amorphous MnO2 into products with lower humification index (0.60 vs. 0.46), smaller apparent molecular weight (388.17 Da vs. 369.31 Da), and higher biodegradability (BOD5/COD: 0.12 vs. 0.78). This finding suggested that redox reactions between MnOx and EfOMs might alter their abiotic and biotic behaviors in receiving water environments.

Adherence to a planetary health diet, genetic susceptibility, and incident cardiovascular disease: a prospective cohort study from the UK Biobank.

BACKGROUND: The influence of adherence to a planetary health diet (PHD) proposed by the EAT-Lancet Commission on cardiovascular disease (CVD) is inconclusive. Besides, whether genetic susceptibility to CVD can modify the association of PHD with CVD remains unknown. OBJECTIVE: We aimed to investigate the association between adherence to PHD and CVD, and to evaluate the interaction between PHD and genetic predisposition to CVD. METHODS: This study included 114,165 participants who completed at least two 24-h dietary recalls and were initially free of CVD from the UK Biobank. PHD score was calculated to assess adherence to PHD. Genetic risk was evaluated using the polygenic risk score. Incidence of total CVD, ischemic heart disease (IHD), atrial fibrillation (AF), heart failure (HF), and stroke were identified via electronic health records. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 9.9 y, 10,071 (8.8%) incident CVD cases were documented. Compared with participants with the lowest adherence to PHD, HRs (95% CIs) for total CVD, IHD, AF, HF, and stroke among those with the highest adherence were 0.79 (0.74, 0.84), 0.73 (0.67, 0.79), 0.90 (0.82, 0.99), 0.69 (0.59, 0.82), and 0.88 (0.75, 1.04), respectively. No significant interaction between the genetic risk of CVD and PHD was observed. Participants with high genetic risk and low PHD score, as compared with those with low genetic risk and high PHD score, had a 48% (95% CI: 40%, 56%) higher risk of CVD. The population-attributable risk (95% CI) of CVD for poor adherence to PHD ranged from 8.79% (5.36%, 12.51%) to 14.00% (9.00%, 18.88%). CONCLUSIONS: These findings suggest that higher adherence to PHD was associated with lower risk of total CVD, IHD, AF, and HF in populations across all genetic risk categories.

[Species of Chinese materia medica resources based on the fourth national survey of Chinese materia medica resources].

This article outlined the composition and species characteristics of Chinese materia medica(CMM) resources identified in the fourth national survey of CMM resources. The survey was conducted based on field investigations and office collation, adhering to the "four principles", which emphasized the existence of survey records, voucher specimens, actual photographs, and evidence of medicinal use, so as to summarize the species of CMM resources and ensure the scientific integrity and accuracy of the results. According to the results, China had a total of 18 817 CMM resources, including 15 321 medicinal plants, 826 medicinal fungi, 2 517 medicinal animals, and 153 medicinal minerals. Additionally, the fourth national survey of CMM resources also conducted specialized investigations on 3 151 species of unique medicinal plants, 464 species of rare and endangered medicinal plants, and 196 new species in China. These latest statistics on these CMM resources will provide the most up-to-date foundational data for the protection, management, development, and utilization of these resources over an extended period, offering scientific guidance for the development of the traditional Chinese medicine(TCM) industry.

Filler found in bone: Surgical removal of polyacrylamide hydrogel (Amazingel) from the mandible after 24 years: A case report and literature review.

Polyacrylamide hydrogel (PAAG) is widely regarded as a safe soft tissue filler and has been extensively utilized for cosmetic enhancements, such as breast and facial augmentation in China from 1997 until its ban in 2006. Common complications associated with its use include inflammation, infection, granulomas, fibrosis, gel migration, and facial and soft tissue deformities. This case report describes a 45-year-old Chinese woman who experienced PAAG migration into her mandible 24 years after facial augmentation, causing irritation of the mandibular alveolar nerve - apparently the first documented instance of this occurrence. Surgical intervention was necessary to remove the migrated gel and associated calcifications. A literature review explored adverse events and management strategies for PAAG complications in cosmetic procedures. While generally considered safe, this report underscores the importance of meticulous injection techniques and careful anatomical site selection to prevent such severe complications.

PGC1α enhances macrophage efferocytosis in ox-LDL-stimulated RAW264.7 cells by regulating the NLRP3/PPARα axis.

BACKGROUND: Defective clearance of apoptotic and foam cells achieved by arterial macrophage efferocytosis propels the progression of inflammatory atherosclerosis, but related molecular mechanisms in this process remain unclear. Herein, this study is engineered to probe into the mechanism of peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC1α) on atherosclerosis. METHODS: The PGC1α/NLR family pyrin domain containing 3 (NLRP3)/peroxisome proliferator activated receptor alpha (PPARα) axis in oxidized low-density lipoprotein (ox-LDL)-induced RAW264.7 cells was verified using Western blot. Inflammatory response, NLRP3 activation, efferocytotic efficiency and lipid uptake of the ox-LDL-stimulated cells overexpressing PGC1α or/and silencing PPARα were detected by enzyme-linked immunosorbent assay, immunofluorescence, tracing of apoptotic Jurkat cells and Oil red O staining. RESULTS: PGC1α and PPARα levels were decreased, but NLRP3 level was increased in ox-LDL-stimulated RAW264.7 cells (P<0.001). PGC1α overexpression repressed the levels of IL-1ß, IL-6 and TNF-α, NLRP3 expression or activation and foam cell formation (P<0.05), but enhanced efferocytosis as well as expressions of AXL, MERTK and TYRO3 in ox-LDL-stimulated cells (P<0.001). PGC1α overexpression increased PPARα expression. However, PPARα silencing reversed the effects of PGC1α overexpression on protecting macrophages against ox-LDL-induced inflammation, efferocytotic impairment and foam cell formation (P<0.05). CONCLUSION: Overexpression PGC1α decreased NLRP3 activation to promoted the expression of PPARα, which alleviated the impairment of macrophage efferocytosis and inhibited the development of atherosclerosis development.

Pt Loading of Phosphorus-Doped Carbon Nanotube Aerogels in Fuel Cell-Type Gas Sensors for Ultrasensitive H2 Detection.

A phosphorus-doped carbon nanotube (CNT) aerogel as the support material was loaded with Pt nanoparticles in fuel cell-type gas sensors for ultrasensitive H2 detection. The high surface area of the CNT scaffold is favorable to providing abundant active sites, and the high electrical conductivity facilitates the transport of carriers generated by electrochemical reactions. In addition, the CNT aerogel was doped with phosphorus (P) to further enhance the conductivity and electrochemical catalytic activity. As a result, the fuel cell-type gas sensor using the Pt/CNT aerogel doped with the optimal P content as the sensing material shows considerable performance for H2 detection at room temperature. The sensor exhibits an ultrahigh response of -921.9 µA to 15,000 ppm of H2. The sensitivity is -0.063 µA/ppm, which is 21 times higher than that of the conventional Pt/CF counterpart. The sensor also exhibits excellent repeatability and humidity resistance, as well as fast response/recovery; the response/recovery times are 31 and 4 s to 3000 ppm of H2, respectively. The modulation of the structure and catalytic properties of the support material is responsible for the improvement of the sensor performance, thus providing a feasible solution for optimizing the performance of fuel cell-type gas sensors.

Catalytic Asymmetric Aza-Electrophilic Additions of 1,1-Disubstituted Styrenes.

Electrophilic addition of alkenes is a textbook reaction that plays a pivotal role in organic chemistry. In the past decades, catalytic asymmetric variants of this important type of reaction have witnessed great achievements by the development of novel catalytic systems. However, enantioselective aza-electrophilic additions of unactivated alkenes, which could provide a transformative strategy for the preparation of synthetically significant nitrogen-containing compounds, still remain a formidable challenge. Herein, we have developed unprecedented Au(I)/NHC-catalyzed asymmetric aza-electrophilic additions of unactivated 1,1-disubstituted styrenes by the utilization of readily available dialkyl azodicarboxylates as electrophilic nitrogen sources. Based on this approach, a series of transformations, including [2 + 2] cycloaddition, intermolecular 1,2-oxyamination, and several types of intramolecular hydrazination-induced cyclizations, have been realized. These transformations provide a previously unattainable platform for the divergent synthesis of hydrazine derivatives, which could also be converted to other nitrogen-containing chiral synthons. Experimental and computational studies support the idea that carbocation intermediates are involved in reaction pathways.

Vitamin D and Heart Failure Risk among Individuals with Type 2 Diabetes: Observational and Mendelian Randomization Studies.

BACKGROUND: Evidence is limited and inconsistent regarding vitamin D and heart failure (HF) risk in people with type 2 diabetes (T2D), among whom vitamin D insufficiency or deficiency is common. OBJECTIVE: This study aimed to investigate the associations of serum 25-hydroxyvitamin D (25[OH]D) with HF risk among individuals with T2D, in observational and Mendelian randomization (MR) frameworks. METHODS: Observational analyses were performed among 15,226 T2D participants aged 40-72 from the UK Biobank. HF incidence was ascertained through electronic health records. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between serum 25(OH)D and HF risk among people with T2D. MR analyses were conducted among 11,260 unrelated participants with T2D. A weighted genetic risk score (GRS) for genetically predicted 25(OH)D concentration was instrumented using 62 confirmed genome-wide variants. RESULTS: The mean ± standard deviation of serum 25(OH)D was 43.4 ± 20.4 nmol/L. During a median follow-up of 11.3 years, 836 incident HF events occurred. Serum 25(OH)D was nonlinearly and inversely associated with HF and the decreasing risk tended to plateau at around 50 nmol/L. Comparing those with 25(OH)D <25 nmol/L, the multivariable-adjusted HR (95% CI) was 0.67 (0.54, 0.83) for participants with 25(OH)D of 50.0-74.9 nmol/L and was 0.71 (0.52, 0.98) for 25(OH)D >75 nmol/L. In MR analysis, each 7% increment in genetically predicted 25(OH)D was associated with 36% lower risk of HF among people with T2D (HR: 0.64, 95% CI: 0.41, 0.99). CONCLUSIONS/INTERPRETATION: Higher serum 25(OH)D was associated with lower HF risk among individuals with T2D and the MR analysis suggested a potential causal relationship. These findings indicate a role of maintaining adequate vitamin D status in the prevention of HF among individuals with T2D.

Fish Oil, Plasma n-3 PUFAs, and Risk of Macro- and Microvascular Complications among Individuals with Type 2 Diabetes.

OBJECTIVE: To evaluate associations of fish oil supplementation and plasma omega 3 polyunsaturated fatty acids (n-3 PUFAs) with risks of macrovascular and microvascular complications among people with type 2 diabetes, and to further explore the potential mediating role of metabolism-related biomarkers. RESEARCH DESIGN AND METHODS: This study included 20,338 participants with type 2 diabetes from UK Biobank. Diabetic complications were identified through hospital inpatient records. RESULTS: During 13.2 years of follow-up, 5,396 people developed macrovascular complications, and 4,868 people developed microvascular complications. After multivariable adjustment, hazard ratios (HRs) and 95% confidence intervals (CIs) for patients with fish oil were 0.90 (0.85, 0.97) for composite macrovascular complications, 0.91 (0.84, 0.98) for coronary heart disease (CHD), 0.72 (0.61, 0.83) for peripheral artery disease; and 0.89 (0.83, 0.95) for composite microvascular complications, 0.87 (0.79, 0.95) for diabetic kidney disease, and 0.88 (0.80, 0.97) for diabetic retinopathy. In addition, higher n-3 PUFA levels, especially docosahexaenoic acid (DHA), were associated with lower risks of macrovascular and microvascular complications. Comparing extreme quartiles of plasma DHA, the HRs (95% CIs) were 0.68 (0.57, 0.81) for composite macrovascular complications, 0.63 (0.51, 0.77) for CHD; and 0.59 (0.38, 0.91) for diabetic neuropathy. Moreover, biomarkers including lipid profile and inflammation collectively explained 54.4% and 63.1% of associations of plasma DHA with risks of composite macrovascular complications and CHD. CONCLUSIONS: Habitual use of fish oil supplementation and higher plasma n-3 PUFA levels, especially DHA, were associated with lower risks of macrovascular and microvascular complications among individuals with type 2 diabetes, and the favorable associations were partially mediated through improving biomarkers of lipid profile and inflammation.

COL5A1 overexpression correlates with poor prognosis in human cervical cancer.

BACKGROUND: Cervical cancer is the most prevalent malignant tumor in women. This study aims to detect collagen type V α1 chain (COL5A1) expression and its clinical relevance in the prognosis of patients with cervical cancer. METHODS: Cervical cancer tissues and their paired adjacent normal tissues were prepared for tissue microarray. The expression of COL5A1 protein and the scores of the expression were evaluated by immunohistochemistry (IHC) staining. The prognostic value of COL5A1 was analyzed by R software version 4.2.1 with "survival, survminer, ggplot2" packages and Gene Expression Profiling Interactive Analysis (GEPIA). The cBioPortal database was utilized for the analysis of COL5A1 gene mutations. RESULTS: COL5A1 protein was overexpressed in human cervical cancer tissues compared to their paired adjacent normal tissues detected by IHC (P < 0.001). High expression of COL5A1 tends to be in elderly patients with cervical cancer. Survival analyses of clinical data of patients with cervical cancer showed that a high level of COL5A1 expression was significantly correlated with shorter overall survival (P = 0.031) and disease-free survival (P = 0.042) of patients. Further analyses of The Cancer Genome Atlas-Cervical Squamous Cell Carcinoma and the GEPIA survival datasets confirmed the association of high COL5A1 expression with poor overall survival of patients (P = 0.040 and P = 0.018, respectively). The analysis of genomic alterations of COL5A1 using the cBioPortal tool revealed that the COL5A1 gene was altered in 4% of cervical cancer patients and COL5A1 corresponding protein alterations with post-translational modifications were hydroxylation. CONCLUSION: COL5A1 is a tissue biomarker correlated with the poor prognosis of patients with cervical cancer, which may lead to a new clinical application.

Correlating the crystal structure and facet of indium oxides with their activities for CO2 electroreduction.

Constructing structure-function relationships is critical for the rational design and development of efficient catalysts for CO2 electroreduction reaction (CO2RR). In2O3 is well-known for its specific ability to produce formic acid. However, how the crystal phase and surface affect the CO2RR activity is still unclear, making it difficult to further improve the intrinsic activity and screen for the most active structure. In this work, cubic and hexagonal In2O3 with different stable surfaces ((111) and (110) for cubic, (120) and (104) for hexagonal) are investigated for CO2RR. Theoretical results demonstrate that the adsorption of reactants on cubic In2O3 is stronger than that on hexagonal In2O3, with the cubic (111) surface being the most active for CO2RR. In experiments, synthesized cubic In2O3 nanosheets with predominantly exposed (111) surfaces exhibited a high HCOO- Faradaic efficiency (87.5%) and HCOO- current density (-16.7 mA cm-2) at -0.9 V vs RHE. In addition, an aqueous Zn-CO2 battery based on a cubic In2O3 cathode was assembled. Our work correlates the phases and surfaces with the CO2RR activity, and provides a fundamental understanding of the structure-function relationship of In2O3, thereby contributing to further improvements in its CO2RR activity. Moreover, the results provide a principle for the directional preparation of materials with optimal phases and surfaces for efficient electrocatalysis.

Efficacy of Repetitive Transcranial Magnetic Stimulation over the Supplementary Motor Area on Motor Function in Parkinson's Disease: A Meta-Analysis.

OBJECTIVES: The objective of this study was to assess the effect of repetitive transcranial magnetic stimulation (rTMS) on the supplementary motor area (SMA) in motor function in Parkinson's disease (PD) patients. METHOD: Databases searched included 5 databases from October 7,2022 to January 4, 2023. The Cochrane Bias Risk Assessment Tool was used for quality assessment. Standardized mean differences (SMDs) were calculated using a random-effects model. Outcome measure is the motor function examination of the motor part of Unified Parkinson's Disease Rating Scale (UPDRS-III). RESULTS: Seven studies totaling 374 patients were included. Meta-analysis showed that stimulation of SMA significantly improved motor function in PD patients compared with sham stimulation (SMD = -1.24; 95% CI, -2.24 to -0.24; P = 0.02; I 2 = 93%). Stimulation of the same target (SMA), subgroup analysis showed that high-frequency rTMS (HF-rTMS) is more effective than low-frequency rTMS (LF-rTMS) in improving motor function in PD (SMD = -1.39; 95% CI, -2.21 to -0.57; P = 0.04; I 2 = 77.2%). CONCLUSIONS: Overall, rTMS over SMA had a statistically significant improvement in motor function in PD patients, and HF-rTMS is statistically significantly more effective than LF-rTMS.

Six undescribed 23-norursane triterpenoids from the biotransformation of ilexgenin a by endophytic fungi and their vascular protective activity.

Biotransformation of ursane-type triterpenoid ilexgenin A by endophytic fungi Lasiodiplodia sp. MQD-4 and Pestalotiopsis sp. ZZ-1, isolated from Ilex pubescences and Callicarpa kwangtungensis respectively, was investigated for the first time. Six previously undescribed metabolites (1-6) with 23-norursane triterpenoids skeleton were isolated and their structures were unambiguously established by the analysis of spectroscopic data and single-crystal X-ray crystallographic experiments. Decarboxylation, oxidation, and hydroxylation reactions were observed on the triterpenoid skeleton. Especially, the decarboxylation of C-23 provided definite evidence to understand the biogenetic process of 23-norursane triterpenoids. Moreover, the qualitative analysis of the extract of I. pubescences showed metabolites 1, 3, 4, and 6 could be detected in the originated plant, indicating biotransformation by endophytic fungi is a practical strategy for the isolation of novel natural products. Finally, all isolates were evaluated for the protective activities against H2O2-induced HUVECs dysfunction in vitro. Compound 5 could improve the viability of endothelial cells and decrease the level of intracellular ROS.