Early identification of stroke through deep learning with multi-modal human speech and movement data.

JOURNAL/nrgr/04.03/01300535-202501000-00031/figure1/v/2024-05-14T021156Z/r/image-tiff Early identification and treatment of stroke can greatly improve patient outcomes and quality of life. Although clinical tests such as the Cincinnati Pre-hospital Stroke Scale (CPSS) and the Face Arm Speech Test (FAST) are commonly used for stroke screening, accurate administration is dependent on specialized training. In this study, we proposed a novel multimodal deep learning approach, based on the FAST, for assessing suspected stroke patients exhibiting symptoms such as limb weakness, facial paresis, and speech disorders in acute settings. We collected a dataset comprising videos and audio recordings of emergency room patients performing designated limb movements, facial expressions, and speech tests based on the FAST. We compared the constructed deep learning model, which was designed to process multi-modal datasets, with six prior models that achieved good action classification performance, including the I3D, SlowFast, X3D, TPN, TimeSformer, and MViT. We found that the findings of our deep learning model had a higher clinical value compared with the other approaches. Moreover, the multi-modal model outperformed its single-module variants, highlighting the benefit of utilizing multiple types of patient data, such as action videos and speech audio. These results indicate that a multi-modal deep learning model combined with the FAST could greatly improve the accuracy and sensitivity of early stroke identification of stroke, thus providing a practical and powerful tool for assessing stroke patients in an emergency clinical setting.

Tumor-related factor complement Clq/TNF-related protein 6 affects the development of digestive system tumors through the phosphatidylinositol 3-kinase pathway.

In this editorial, we review the work of Razali et al published in World J Gastroenterology, with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase (PI3K) pathway and buparlisib on colitis-associated cancer. The role of PI3K in promoting cancer progression has been widely recognized, as it is involved in regulating the survival, differentiation, and proliferation of cancer cells. The complement Clq/TNF-related protein 6 (CTRP6) is a newer tumor-associated factor. Recent studies have revealed the pro-tumor effect of CTRP6 in gastric cancer, hepatocellular carcinoma, colorectal cancer, and other gastrointestinal tumors through the PI3K pathway. This article attempts to reveal the mechanism through which the CTRP6 affects the development of digestive system tumors through the PI3K pathway by summarizing recent research.

Formation mechanism and regulation analysis of trumpet leaf in Ginkgo biloba L.

Introduction: The research on plant leaf morphology is of great significance for understanding the development and evolution of plant organ morphology. As a relict plant, the G. biloba leaf morphology typically exhibits bifoliate and peltate forms. However, throughout its long evolutionary history, Ginkgo leaves have undergone diverse changes. Methods: This study focuses on the distinct "trumpet" leaves and normal fan-shaped leaves of G. biloba for analysis of their phenotypes, photosynthetic activity, anatomical observations, as well as transcriptomic and metabolomic analyses. Results: The results showed that trumpet-shaped G. biloba leaves have fewer cells, significant morphological differences between dorsal and abaxial epidermal cells, leading to a significantly lower net photosynthetic rate. Additionally, this study found that endogenous plant hormones such as GA, auxin, and JA as well as metabolites such as flavonoids and phenolic acids play roles in the formation of trumpet-shaped G. biloba leaves. Moreover, the experiments revealed the regulatory mechanisms of various key biological processes and gene expressions in the trumpet-shaped leaves of G. biloba. Discussion: Differences in the dorsal and abdominal cells of G. biloba leaves can cause the leaf to curl, thus reducing the overall photosynthetic efficiency of the leaves. However, the morphology of plant leaves is determined during the primordia leaf stage. In the early stages of leaf development, the shoot apical meristem (SAM) determines the developmental morphology of dicotyledonous plant leaves. This process involves the activity of multiple gene families and small RNAs. The establishment of leaf morphology is complexly regulated by various endogenous hormones, including the effect of auxin on cell walls. Additionally, changes in intracellular ion concentrations, such as fluctuations in Ca2+ concentration, also affect cell wall rigidity, thereby influencing leaf growth morphology.

Pyrolytic Depolymerization of Polyolefins Catalyzed by Zirconium-based UiO-66 Metal-Organic Frameworks.

Polyolefins such as polyethylenes and polypropylenes are the most-produced plastic waste globally, yet are difficult to convert into useful products due to their unreactivity. Pyrolysis is a practical method for large-scale treatment of mixed, contaminated plastic, allowing for their conversion into industrially-relevant petrochemicals. Metal-organic frameworks (MOFs), despite their tremendous utility in heterogenous catalysis, have been overlooked for polyolefin depolymerization due to their perceived thermal instabilities and inability of polyethylenes and polypropylenes to penetrate their pores. Herein, we demonstrate the viability of UiO-66 MOFs containing coordinatively-unsaturated zirconia nodes, as effective catalysts for pyrolysis that significantly enhances the yields of valuable liquid and gas hydrocarbons, whilst halving the amounts of residual solids produced. Reactions occur on the Lewis-acidic UiO-66 zirconia nodes, without the need for noble metals, and yields aliphatic product distributions distinctly different from the aromatic-rich hydrocarbons from zeolite catalysis. We also demonstrate the first unambiguous characterization of polyolefin penetration into UiO-66 pores at pyrolytic temperatures, allowing access to the abundant Zr-oxo nodes within the MOF interior for efficient C-C cleavage. Our work highlights the potential of MOFs as highly-designable heterogeneous catalysts for depolymerization of plastics which can complement conventional catalysts in reactivity.

Optimization of CRISPR/Cas12a detection assay and its application in the detection of Echinococcus granulosus.

Cystic echinococcosis, resulting from infection with Echinococcus granulosus, poses a significant challenge as a neglected tropical disease owing to the lack of any known effective treatment. Primarily affecting under-resourced, remote, and conflict-ridden regions, the disease is compounded by the limitations of current detection techniques, such as microscopy, physical imaging, ELISA, and qPCR, which are unsuitable for application in these areas. The emergence of CRISPR/Cas12a as a promising tool for nucleic acid detection, characterized by its unparalleled specificity, heightened sensitivity, and rapid detection time, offers a potential solution. In this study, we present a one-pot CRISPR/Cas12a detection method for E. granulosus (genotype G1, sheep strain) integrating recombinase polymerase amplification (RPA) with suboptimal protospacer adjacent motif (PAM) and structured CRISPR RNA (crRNA) to enhance reaction efficiency. The evaluation of the assay's performance using hydatid cyst spiked dog feces and the examination of 62 dog fecal samples collected from various regions of Western China demonstrate its efficacy. The assay permits visual observation of test results about 15 minutes under blue light and displays superior portability and reaction speed relative to qPCR, achieving a sensitivity level of 10 copies of standard plasmids of the target gene. Analytic specificity was verified against four tapeworm species (E. multilocularis, H. taeniaeformis, M. benedeni, and D. caninum) and two other helminths (T. canis and F. hepatica), with negative results also noted for Mesocestoides sp. This study presents a rapid, sensitive, and time-efficient DNA detection method for E. granulosus of hydatid cyst spiked and clinical dog feces, potential serving as an alternative tool for field detection. This novel assay is primarily used to diagnose the definitive host of E. granulosus. Further validation using a larger set of clinical fecal samples is warranted, along with additional exploration of more effective approaches for nucleic acid release.

A handy way for forming N-doped TiO2/carbon from pectin and d,l-serine hydrazide hydrochloride.

N-doped TiO2/carbon composites (N-TiPC) have shown excellent photodegradation performances to the organic contaminants but are limited by the multistage preparation (i.e., preparation of porous carbon, preparation of N-doped TiO2, and loading of N-doped TiO2 on porous carbon). Here, we develop a handy way by combining the Pickering emulsion-gel template route and chelation reaction of polysaccharides. The N-TiPC is obtained by calcinating pectin/Dl-serine hydrazide hydrochloride (SHH)-Ti4+ chelate and is further described by modern characterization techniques. The results show that the N atom is successfully doped into the TiO2 lattice, and the bandgap value of N-TiPC is reduced to 2.3 eV. Moreover, the particle size of N-TiPC remains about 10 nm. The configurations of the composites are simulated using DFT calculation. The photocatalytic experiments show that N-TiPC has a high removal efficiency for methylene blue (MB) and oxytetracycline hydrochloride (OTC-HCL). The removal ratios of MB (20 mg/L, 50 mL) and OTC-HCL (30 mg/L, 50 mL) are 99.41 % and 78.29 %, respectively. The cyclic experiments show that the photocatalyst has good stability. Overall, this study provides a handy way to form N-TiPC with enhanced photodegradation performances. It can also be promoted to other macromolecules such as cellulose and its derivatives, sodium alginate, chitosan, lignin, etc.

Genome-wide identification and expression analysis of EPF/EPFL gene family in Populus trichocarpa.

The Epidermal Patterning Factor/EPF-like (EPF/EPFL) family encodes a specific type of secreted protein in plants and plays an important role in plant growth and development, especially in the process of morphogenesis. To investigate the characteristics of EPF/EPFL gene family members and their regulatory functions in stomatal development of Populus trichocarpa, a total of 15 EPF/EPFL family genes were identified. Then the gene structure, chromosome location, phylogenetic relationship, protein conserved domain and gene expression profile were analyzed. According to phylogenetic analysis, PtEPF/EPFL can be classified into four groups. The gene structure and protein conservation motifs within the EPF family indicate the high conservation of the PtEPF/EPFL sequence. The promoter region of PtEPF/EPFL was found to contain cis-elements in response to stress and plant hormones. In addition, RT-qPCR results indicated that the PtEPF/EPFL have a differentially expressed in different tissues. Under drought stress treatment, a substantial upregulation was observed in the majority of PtEPF/EPFL members, suggesting their potential involvement in drought response. These results provide a theoretical basis for future exploration of the characteristics and functions of more PtEPF/EPFL genes.

Global, regional, national epidemiology and trends of neglected tropical diseases in youths and young adults aged 15-39 years from 1990 to 2019: findings from the global burden of disease study 2019.

BACKGROUND: In recent years, the escalating concern for neglected tropical diseases (NTDs) has been recognized as a pressing global health issue. This concern is acutely manifested in low- and middle-income countries, where there is an escalating prevalence among adolescents and young adults. The burgeoning of these conditions threatens to impair patients' occupational capabilities and overall life quality. Despite the considerable global impact of NTDs, comprehensive studies focusing on their impact in younger populations remain scarce. Our study aims to describe the global prevalence of neglected tropical diseases among people aged 15 to 39 years over the 30-year period from 1990 to 2019, and to project the disease burden of the disease up to 2040. METHODS: Annual data on incident cases, mortality, and disability-adjusted life years (DALYs) for NTDs were procured from the Global Burden of Disease Study 2019 (GBD 2019). These data were stratified by global and regional distribution, country, social development index (SDI), age, and sex. We computed age-standardized rates (ASRs) and the numbers of incident cases, mortalities, and DALYs from 1990 to 2019. The estimated annual percentage change (EAPC) in the ASRs was calculated to evaluate evolving trends. RESULTS: In 2019, it was estimated that there were approximately 552 million NTD cases globally (95% Uncertainty Interval [UI]: 519.9 million to 586.3 million), a 29% decrease since 1990. South Asia reported the highest NTD prevalence, with an estimated 171.7 million cases (95% UI: 150.4 million to 198.6 million). Among the five SDI categories, the prevalence of NTDs was highest in the moderate and low SDI regions in 1990 (approximately 270.5 million cases) and 2019 (approximately 176.5 million cases). Sub-Saharan Africa recorded the most significant decline in NTD cases over the past three decades. Overall, there was a significant inverse correlation between the disease burden of NTDs and SDI. CONCLUSION: NTDs imposed over half a billion incident cases and 10.8 million DALYs lost globally in 2019-exerting an immense toll rivaling major infectious and non-communicable diseases. Encouraging declines in prevalence and disability burdens over the past three decades spotlight the potential to accelerate progress through evidence-based allocation of resources. Such strategic integration could substantially enhance public awareness about risk factors and available treatment options.

Succession characteristics of phytoplankton functional groups and ecological assessment in a cold spring-type urban lake, China.

Phytoplankton functional groups have been increasingly utilized in elucidating and predicting the response of phytoplankton species to environmental conditions and seasonal succession in various aquatic systems including lakes, rivers and reservoirs. However, it is still unclear whether the trait-based functional classification can be applied to spring-type lakes. To understand the temporal and spatial characteristics of phytoplankton functional groups and their responses to environmental factors in spring-type urban lake in northern China, an investigation was conducted in Daming Lake from May 2020 to September 2021. The findings revealed the identification of 98 phytoplankton taxa belonging to 6 phyla, predominantly being Chlorophyta (39.8%), Bacillariophyta (35.7%) and Cyanophyta (15.3%). The dominant species were Microcystis sp., Merismopedia minima, Synedra acus and Scenedesmus quadricauda. These phytoplankton taxa were categorized into 21 functional groups, with 6 dominant functional groups (abbreviated as D, MP, P, J, Lo, and W1). Among them, the functional group D, primarily constituted by S. acus, exhibited absolute predominance. The seasonal succession sequence of the dominant functional groups was as follows: D/P/J/MP/ Lo →→ D/P/W1/MP/Lo/J → D/P/J → D/MP → D/P/MP. Throughout the investigation period, the trophic level index (TLI) ranged from 39.10 to 71.13, and the Q index was from 1.91 to 2.91, both indicating a medium health state for Daming Lake, which was consistent with the evaluation results of the diversity index. The results of redundancy analysis revealed that the main driving factors of phytoplankton FG biomass and composition were water temperature (WT), total nitrogen (TN), transparency (SD), TN:TP (N:P), redox potential (ORP), chemical oxygen demand (CODMn) and pH. The dominance of the functional group D positively correlated with water temperature, TN, CODMn, pH and N:P but negatively correlated with SD. It was observed that functional groups and the Q index can objectively indicate the seasonal succession of phytoplankton and the water quality status of Daming Lake. Our discoveries have significant implications for the comprehension of the effects of urbanization on phytoplankton dynamics and for enhancing lake management practices to foster sustainable urban development.

Clinical efficacy of endovascular revascularization combined with vacuum-assisted closure for the treatment of diabetic foot.

BACKGROUND: The diabetic foot is a common cause of disability and death, and comorbid foot infections usually lead to prolonged hospitalization, high healthcare costs, and a significant increase in amputation rates. And most diabetic foot trauma is complicated by lower extremity arteriopathy, which becomes an independent risk factor for major amputation in diabetic foot patients. AIM: To establish the efficacy and safety of endovascular revascularization (ER) combined with vacuum-assisted closure (VAC) for the treatment of diabetic foot. METHODS: Clinical data were collected from 40 patients with diabetic foot admitted to the Second Affiliated Hospital of Soochow University from April 2018 to April 2022. Diabetic foot lesions were graded according to Wagner's classification, and blood flow to the lower extremity was evaluated using the ankle-brachial index test and computerized tomography angiography of the lower extremity arteries. Continuous subcutaneous insulin infusion pumps were used to achieve glycemic control. Lower limb revascularization was facilitated by percutaneous tran-sluminal balloon angioplasty (BA) or stenting. Wounds were cleaned by nibbling debridement. Wound granulation tissue growth was induced by VAC, and wound repair was performed by skin grafting or skin flap transplantation. RESULTS: Of the 35 cases treated with lower limb revascularization, 34 were successful with a revascularization success rate of 97%. Of these, 6 cases underwent stenting after BA of the superficial femoral artery, and 1 received popliteal artery stent implantation. In the 25 cases treated with infrapopliteal artery revascularization, 39 arteries were reconstructed, 7 of which were treated by drug-coated BA and the remaining 32 with plain old BA. VAC was performed in 32 wounds. Twenty-four cases of skin grafting and 2 cases of skin flap transplantation were performed. Two patients underwent major amputations, whereas 17 had minor amputations, accounting for a success limb salvage rate of 95%. CONCLUSION: ER in combination with VAC is a safe and effective treatment for diabetic foot that can significantly improve limb salvage rates. The use of VAC after ER simplifies and facilitates wound repair.

Luteolin-7-diglucuronide, a novel PTP1B inhibitor, ameliorates hepatic stellate cell activation and liver fibrosis in mice.

Liver fibrosis, one of the leading causes of morbidity and mortality worldwide, lacks effective therapy. The activation of hepatic stellate cells (HSCs) is the dominant event in hepatic fibrogenesis. Luteolin-7-diglucuronide (L7DG) is the major flavonoid extracted from Perilla frutescens and Verbena officinalis. Their beneficial effects in the treatment of liver diseases were well documented. In this study we investigated the anti-fibrotic activities of L7DG and the potential mechanisms. We established TGF-ß1-activated mouse primary hepatic stellate cells (pHSCs) and human HSC line LX-2 as in vitro liver fibrosis models. Co-treatment with L7DG (5, 20, 50 µM) dose-dependently decreased TGF-ß1-induced expression of fibrotic markers collagen 1, α-SMA and fibronectin. In liver fibrosis mouse models induced by CCl4 challenge alone or in combination with HFHC diet, administration of L7DG (40, 150 mg·kg-1·d-1, i.g., for 4 or 8 weeks) dose-dependently attenuated hepatic histopathological injury and collagen accumulation, decreased expression of fibrogenic genes. By conducting target prediction, molecular docking and enzyme activity detection, we identified L7DG as a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 2.10 µM. Further studies revealed that L7DG inhibited PTP1B activity, up-regulated AMPK phosphorylation and subsequently inhibited HSC activation. This study demonstrates that the phytochemical L7DG may be a potential therapeutic candidate for the treatment of liver fibrosis.

[Inhibitory effect and mechanism of sodium cantharidate on human tongue squamous cell carcinoma CAL27 cells].

PURPOSE: To investigate the inhibitory effect of sodium cantharidate (SCA) on human tongue squamous cell carcinoma CAL27 cells and its mechanism. METHODS: CAL27 cells were pretreated with different concentrations of SCA. Cell viability was analyzed by CCK-8 method. The migration and invasion of CAL27 cells were measured by scratch test and Transwell chamber, and the apoptosis rate was measured by flow cytometry. p53 protein and its phosphorylation sites Ser33, Ser37, Ser46, expression of BCL-2, BAX, and cleaved caspase 3 in CAL27 cells were detected by Western blot. Statistical analysis was performed with Graphpad Prism 9.0 software package. RESULTS: Compared with the blank control group, the proliferation, migration and invasion of CAL27 cells in sodium cantharidate group were significantly decreased, and the apoptosis rate was significantly increased(P＜0.01) in a dose-dependent manner. The expression of p53 protein and its phosphorylation sites Ser33, Ser37, Ser46 protein was significantly up-regulated(P＜0.05 or P＜0.01). The expression of BCL-2 protein was down-regulated and the expression of BAX protein was significantly up-regulated(P＜0.05 or P＜0.01). The ratio of BCL-2/BAX was significantly decreased and the expression of cleaved caspase 3 protein was significantly up-regulated(P＜0.05 or P＜0.01). CONCLUSIONS: SCA can inhibit the proliferation, migration and invasion of human tongue squamous cell carcinoma CAL27 cells. It also down-regulates the ratio of BCL-2/BAX and up-regulates the expression of cleaved caspase 3 protein by regulating the phosphorylation of p53 protein, which induces apoptosis.

Synergistic promotion of nitrogen vacancies and single atomic dopants on Pt/C3N4 for photocatalytic hydrogen evolution.

C3N4 is widely applied in the synthesis of single-atom catalysts. However, understanding on the active site and the reaction mechanism is not fully in consensus. Especially, bare studies have considered the coordination environment of the single-atomic dopant and the effect of nitrogen vacancy on C3N4. In this study, we found that the presence of nitrogen vacancies promotes the activation of water and reduces the activation energy barrier for hydrogen generation. The results show that a synergistic effect between single-atom Pt and nitrogen vacancies enables the catalyst to achieve a superior hydrogen production rate of 3,890 µmol/g/h, which is 16.8 times higher than that of pristine C3N4. Moreover, the catalyst is also applicable for photocatalytic hydrogen production from seawater without significantly decreased hydrogen production rate. This study paves the way for the rational design and optimization of next-generation photocatalysts for sustainable energy applications, particularly in solar-driven hydrogen production.

Microbiological Characteristics of Clinically Isolated Staphylococcus aureus with Different Hemolytic Phenotypes in China.

Purpose: This study aimed to investigate the microbiological characteristics of clinically isolated Staphylococcus aureus with different hemolytic phenotypes in China. Materials and Methods: Using the three-point inoculation method, the hemolytic phenotypes of 1295 clinically isolated S. aureus strains were detected and categorized. Antimicrobial susceptibility testing of all strains was performed using a VITEK 2 Compact System. After sample size matching, plasma coagulase activity, catalase activity, mRNA expression of hemolysin genes (hla, hlb, hlc, and hld), biofilm formation, growth kinetics, inflammatory response of macrophages and cytotoxicity of S. aureus with different hemolytic phenotypes using the rabbit plasma kit, the catalase test on slides, qRT-PCR, crystal violet staining, the microcultivation assay, the ELISA kits, and the CCK-8 assay, respectively. Results: Seven categories of hemolytic phenotypes were identified. Accordingly, strains were categorized into seven different groups, including S. aureus with complete hemolytic phenotype (SCHP), S. aureus with weak hemolytic phenotype (SWHP), S. aureus with incomplete hemolytic phenotype 1 (SIHP-1), SIHP-2, SIHP-3, SIHP-4 and SIHP-5, the last three of which were reported for the first time. Except for the hemolytic phenotype, all seven groups differed in clinical isolation rates, antibiotic resistance profile, plasma coagulase activity, mRNA expression of hemolysin genes, biofilm formation, growth kinetics, inflammatory response of macrophages, and cytotoxicity. Conclusion: S. aureus with different hemolytic phenotypes have distinctive microbiological characteristics. Clinical microbiologists need to be vigilant about the hemolytic phenotypes when culturing S. aureus strains, and actively enhance communication with clinicians to optimize the treatment of infection.

Eu3+-functionalized covalent organic framework for ratiometric fluorescence detection and adsorption of tetracycline and information steganography.

Functional materials with organic/inorganic composites as the main matrix and rare earth ion complexes as the guest have shown a very broad application prospect for antibiotic sensors. However, Eu3+-complex often relies on a single fluorescence response signal, which is susceptible to changes in the detection environment and cannot simultaneously detect and remove tetracycline (TC). Herein, green fluorescent covalent two-dimensional organic framework (COF-TD) is synthesized, followed by modification of Eu3+ to synthesize COF-TD@Eu3+. In the ratiometric sensor, Eu3+ serves as the recognition site and specific response probe for TC, while COF-TD is the fluorescence reference and carrier for Eu3+. Due to the antenna effect, TC enhances the red fluorescence of Eu3+, while the green fluorescence of COF-TD remains almost stable. Based on the change of fluorescence intensity and fluorescence color from green to red, the efficient ratiometric sensing can be finished in 1 min. The developed method shows high sensitivity with a detection limit of 0.3 µM and high selectivity to TC which makes the method applicable to detect TC in traditional Chinese medicine preparations. In addition, due to the high specific surface area of COFs and specific adsorption sites, COF-TD@Eu3+ also shows good performance for TC removal. The findings show that the maximum adsorption capacity is 137.3 mg g-1 and the adsorption equilibrium is reached in 30 min. Smartphone assisted COF-TD@Eu3+ for both ratiometric fluorescence detection and detecting the absorption of TC is proposed for the first time. The molecular cryptosteganography that transforms the selective response of COF-TD@Eu3+ to binary strings is anticipated to advance utilization of nanomaterials in logic sensing and information safety.

Electron-Efficient Co-electrosynthesis of Formates from CO2 and Methanol Feedstocks.

The electrochemical conversion of CO2 into valuable chemicals using renewable electricity shows significant promise for achieving carbon neutrality and providing alternative energy storage solutions. However, its practical application still faces significant challenges, including high energy consumption, poor selectivity, and limited stability. Here, we propose a hybrid acid/alkali electrolyzer that couples the acidic CO2 reduction reaction (CO2RR) at the cathode with alkaline methanol oxidation reaction (MOR) at the anode. This dual electro-synthesis cell is implemented by developing Bi nanosheets as cathode catalysts and oxide-decorated Cu2Se nanoflowers as anode catalysts, enabling high-efficiency electron utilization for formate production with over 180% coulombic efficiency and more than 90% selectivity for both CO2RR and MOR conversion. The hybrid acid/alkali CO2RR-MOR cell also demonstrates long-term stability exceeding 100 hours of continuous operation, delivers a formate partial current density of 130 mA cm-2 at a voltage of only 2.1 V, and significantly reduces electricity consumption compared to the traditional CO2 electrolysis system. This study illuminates an innovative electron-efficiency and energy-saving techniques for CO2 electrolysis, as well as the development of highly efficient electrocatalysts.

Genome-wide association analysis of hypertension and epigenetic aging reveals shared genetic architecture and identifies novel risk loci.

Hypertension is a disease associated with epigenetic aging. However, the pathogenic mechanism underlying this relationship remains unclear. We aimed to characterize the shared genetic architecture of hypertension and epigenetic aging, and identify novel risk loci. Leveraging genome-wide association studies (GWAS) summary statistics of hypertension (129,909 cases and 354,689 controls) and four epigenetic clocks (N = 34,710), we investigated genetic architectures and genetic overlap using bivariate casual mixture model and conditional/conjunctional false discovery rate methods. Functional gene-sets pathway analyses were performed by functional mapping and gene annotation (FUMA) protocol. Hypertension was polygenic with 2.8 K trait-influencing genetic variants. We observed cross-trait genetic enrichment and genetic overlap between hypertension and all four measures of epigenetic aging. Further, we identified 32 distinct genomic loci jointly associated with hypertension and epigenetic aging. Notably, rs1849209 was shared between hypertension and three epigenetic clocks (HannumAge, IEAA, and PhenoAge). The shared loci exhibited a combination of concordant and discordant allelic effects. Functional gene-set analyses revealed significant enrichment in biological pathways related to sensory perception of smell and nervous system processes. We observed genetic overlaps with mixed effect directions between hypertension and all four epigenetic aging measures, and identified 32 shared distinct loci with mixed effect directions, 25 of which were novel for hypertension. Shared genes enriched in biological pathways related to olfaction.

BACE1 inhibitors from the fruits of Alpinia oxyphylla have efficacy to treat T2DM-related cognitive disorder.

The fruits of Alpinia oxyphylla (Alpiniae Oxyphyllae Fructus, AOF) are one of the "Four Famous South Medicines" in China. In this study, beta-site amyloid protein precursor cleaving enzyme 1 (BACE1) was applied to explore the active components in AOF responsible for type 2 diabetes mellitus (T2DM)-related cognitive disorder. As a result, 24 compounds including three unreported ones (1, 3, 4) were isolated from AOF. Compound 1 is an unusual carbon­carbon linked diarylheptanoid dimer, and compound 4 is the first case of 3,4-seco-eudesmane sesquiterpenoid with a 5/6-bicyclic skeleton. Four diarylheptanoids (3, 5-7), one flavonoid (9) and two sesquiterpenoids (14 and 20) showed BACE1 inhibitory activity, of which the most active 6 was revealed to be a non-competitive and anti-competitive mixed inhibitor. Docking simulation suggested that OH-4' of 6 played important roles in maintaining activity by forming hydrogen bonds with Ser36 and Ile126 residues. Compounds 3, 5, 9 and 20 displayed neuroprotective effects against amyloid ß (Aß)-induced damage in BV2 cells. Mechanism study revealed that compounds 5 and 20 downregulated the expression of BACE1 and upregulated the expression of Lamp2 to exert effects. Thus, the characteristic diarylheptanoids and sesquiterpenoids in AOF had the efficacy to alleviate T2DM-related cognitive disorder by inhibiting BACE1 activity and reversing Aß-induced neuronal damage.