Objective: To quantify the spatiotemporal factors and built environment effects on daily blood collection volumes at fixed sites using multi-source spatiotemporal data, explore the influence radii of different point of interest(POI) categories, and develop a classification framework for sites, thereby providing data references for efficiency diagnosis and network optimization of blood collection sites. Methods: We collected daily blood donation records from 16 fixed whole blood collection sites in Guangzhou in 2023, constructing a balanced “site-day” panel dataset (16 sites × 365 days = 5 840 observations). Multi-source geospatial data, including Amap POI, OpenStreetMap (OSM) road network, and meteorological data were integrated to establish 300 m, 500 m, 800 m, and 1 000 m buffer zones around each site. Variables extracted included counts of surrounding commercial facilities, distance to the nearest subway station, rainfall, and temperature. A two-way fixed effects panel model was employed with a first-order lag term of the dependent variable to capture the inertial effect of blood donation behavior. Based on the significant regression coefficients, a "Structure-Function Index (SFI)" was constructed for each site to identify its optimal buffer radius. Combining inherent site capacity (fixed effects) with the optimal SFI, a two-dimensional quadrant diagram was created to classify the sites. Results: The optimized model showed an adjusted R of 0.89 and a Durbin-Watson statistic of 1.90, with the lag term coefficient stable at 0.36 (P<0.05). Temporal effects were significant: campaign days increased blood collection by 1 717.75 mL, holidays by 3 755.53 mL, and overlapping holidays with campaign days by 5 650.49 mL (P<0.05). Rainy days reduced collection by approximately 419 mL (P<0.05), and each 1℃ rise in daily average temperature decreased collection by approximately 31 mL (P<0.05). Distance to the nearest subway station was significantly positive (coefficient 0.95-1.39, P<0.05). POI effects showed scale-dependent differences: within 300 m, leisure and entertainment (+173.65 mL/unit) and shopping (+2.95 mL/unit) were significantly positive; within 500 m, tourist attractions (+72.55 mL/unit) and hotels (+40.09 mL/unit) were significantly positive; within 1 000 m, these effects diminished. Based on the two-dimensional classification of inherent collection capacity and optimal SFI, sites were categorized into four types: core, potential, adjustment, and resource-dependent. Conclusion: This study elucidates the multidimensional determinants of blood collection site efficiency, and provides quantitative evidence for performance diagnosis. It proposes a "concentric-zone planning" approach for site selection assessment alongside a" station-specific strategy" classification framework, offering data-driven references for network planning and resource allocation in blood collection and supply institutions. It should be noted that blood donation site selection also involves complex factors such as budgetary constraints, interdepartmental coordination, and venue conditions. This study provides a spatial econometric perspective for the quantitative optimization of blood collection networks.

Chemical constituents of n-butanol fraction of ethanol extract from the leaves of Cyclocarya paliurus (Batalin) Iljinskaja were studied. Ten compounds were purified by silica gel, MCI, ODS, Sephadex LH-20 column chromatography and semi-preparative high-performance liquid chromatography. Based on the physicochemical properties and spectroscopic data, these compounds were identified as (4S)-4,8-dihydroxy-α-tetralone-5-[6′-(3′′,5′′-dimethoxy-(E)-p-coumaroyl)]-β-D-glucopyranoside (1), (4S)-4,8-dihydroxy-α-tetralone-5-[6′-(E)-feruloyl]-β-D-glucopyranoside (2), (1S,3R,4S,5R)-4,5-di-O-caffeoyl quinic acid methyl ester (3), (1R,3R,4S,5R)-3,4-di-O-caffeoyl quinic acid methyl ester (4), (3R,5R)-3,4,5-tri-O-caffeoylquinic acid methyl ester (5), (1R,3R,4S,5R)-3-O-caffeoyl-5-O-p-coumaroyl quinic acid methyl ester (6), (1R,3R,4S,5R)-3-O-p-coumaroy-4-O-caffeoyl quinic acid methyl ester (7), (1R,3R,4S,5R)-3-O-caffeoyl-4-O-p-coumaroy quinic acid methyl ester (8), (3R,5R)-3,5-di-O-caffeoyl quinic acid methyl ester (9) and (1S,3R,4R,5R)-4-O-caffeoyl-5-O-feruloyl quinic acid methyl ester (10). Among them, compound 1 was a new compound, and compounds 3–10 were isolated from the genus Cyclocarya for the first time.

In March 2024, three male and two female specimens of the genus Lispe were intercepted on cargo ships inbound for Wan Zai Port under Gongbei Customs. Based on morphological characteristics and molecular analysis, the specimens were identified as Lispe pumila. In this study, we describe the morphological features, diagnostic characteristics, and geographical distribution of L. pumila, with the aim of providing a reference for the identification of this species when intercepted at ports.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

Arginine methylation is a critical post-translational modification that plays multifaceted biological functions. However, the manipulation of protein arginine methylation largely depends on genetic or pharmaceutic inhibition of the regulatory enzymes, protein arginine methyltransferases (PRMTs), or non-methylation substitution of corresponding arginine residue to lysine or alanine of protein of interest (POI), which inevitably affects other substrates, or disrupts the structure of POI. Thus, it urges an approach to specifically modulate the arginine methylation of a POI under physiological conditions. To this end, we report the discovery of a methylation tagging system (MeTAG), that enables targeted modification of protein arginine methylation. Through bridging the methyltransferase PRMT5 proximity to a POI, MeTAG facilitates the arginine methylation of POIs, including known arginine methylated proteins, androgen receptor (AR) and protein kinase B (AKT), as well as a neo-substrate E1A binding protein (p300), in a reversible and PRMT5-dependent manner. Moreover, MeTAG can regulate downstream signaling in a methylation dependent manner, leading to downregulation of PSMA mRNA level and activation of AKT. Therefore, MeTAG represents a feasible approach to modulate protein methylation and thereby perturbs protein function in biological and therapeutic contexts.

Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

Transformer models have emerged as pivotal tools within the realm of drug discovery, distinguished by their unique architectural features and exceptional performance in managing intricate data landscapes. Leveraging the innate capabilities of transformer architectures to comprehend intricate hierarchical dependencies inherent in sequential data, these models showcase remarkable efficacy across various tasks, including new drug design and drug target identification. The adaptability of pre-trained transformer-based models renders them indispensable assets for driving data-centric advancements in drug discovery, chemistry, and biology, furnishing a robust framework that expedites innovation and discovery within these domains. Beyond their technical prowess, the success of transformer-based models in drug discovery, chemistry, and biology extends to their interdisciplinary potential, seamlessly combining biological, physical, chemical, and pharmacological insights to bridge gaps across diverse disciplines. This integrative approach not only enhances the depth and breadth of research endeavors but also fosters synergistic collaborations and exchange of ideas among disparate fields. In our review, we elucidate the myriad applications of transformers in drug discovery, as well as chemistry and biology, spanning from protein design and protein engineering, to molecular dynamics (MD), drug target identification, transformer-enabled drug virtual screening (VS), drug lead optimization, drug addiction, small data set challenges, chemical and biological image analysis, chemical language understanding, and single cell data. Finally, we conclude the survey by deliberating on promising trends in transformer models within the context of drug discovery and other sciences.

OBJECTIVE: To explore the epidemiological characteristics of knee osteoarthritis (KOA) among the elderly in the community, and its correlation with bone mass loss. METHODS: A cross-sectional study was conducted on elderly community population over 50 year old from 12 community health service centers in Zhejiang province. Their gender, age, body mass index (BMI), T value and KOA diagnosis were collected using face to face questionnaire survey. Univariate regression was used to analyze the influence of age, gender, BMI and bone loss on KOA. Logistic multivariate regression model was used to analyze the independent effect of bone mass loss on KOA. RESULTS: Among 4 173 subjects in this study, 1 710 of them were had a KOA. The prevalence rate was 40.9%. The mean age, the proportion of females and the mean BMI in KOA patients were (65.5±3.8) years old, 67.7%(1 158/1 710) and(24.59±1.28) kg·m^-2, respectively, which were significantly higher than (58.5±3.2) years old, 51.3%(1 263/2 463), and (23.48±1.25) kg·m^-2 in non-KOA subjects (P<0.001). In the population aged from 60 to 69 years old, the influence of osteopenia and osteoporosis on the prevalence of KOA was[OR=1.21, 95%CI(1.00, 1.46), P=0.053 2], [OR=1.42, 95%CI(1.14, 1.78), P=0.002 2]. The influence of male and female osteoporosis on the prevalence of KOA was [OR=1.52, 95%CI(1.16, 1.99), P=0.002 7] and [OR=1.87, 95%CI(1.51, 2.32), P<0.000 1], respectively. In the population of 24 kg·m^-2≤BMI<28 kg·m^-2, the influence of osteopenia and osteoporosis on the prevalence of KOA was [OR=1.47, 95%CI(1.21, 1.80), P=0.000 1], [OR=2.69, 95%CI(2.11, 3.42), P<0.000 1], respectively. After controlling the confounding factors of age, gender and BMI, compared with people with normal bone mass, the effect of osteopenia on the prevalence of KOA was [OR=1.34, 95%CI(1.08, 1.67), P=0.009 2], and the effect of osteoporosis on the prevalence of KOA was [OR=1.38, 95%CI(1.06, 1.79), P=0.017 9]. CONCLUSION Elderly overweight women are more likely to develop KOA. Bone mass loss is an independent risk factor for KOA, which will significantly increase the prevalence of KOA in people overweight or aged 60 to 69 years old.
Humans ; Female ; Male ; Aged ; Osteoarthritis, Knee/etiology* ; Middle Aged ; Cross-Sectional Studies ; Bone Density ; Aged, 80 and over ; Incidence ; Body Mass Index ; China/epidemiology* ; Osteoporosis/epidemiology*

PURPOSE: The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery. METHODS: A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications. RESULTS: In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram. CONCLUSION Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans ; COVID-19/complications* ; Male ; Female ; Middle Aged ; Postoperative Complications/epidemiology* ; SARS-CoV-2 ; Orthopedic Procedures/adverse effects* ; Aged ; Nomograms ; Adult ; Retrospective Studies ; Risk Factors