Helicobacter pylori-Induced Angiopoietin-Like 4 Promotes Gastric Bacterial Colonization and Gastritis.

Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a -/-, Angptl4 -/-, and Il17a -/- Angptl4 -/- mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB, resulting in increased gastric influx of regulatory CD4+ T cells (Tregs) via CCL5-CCR4-dependent migration. In turn, ANGPTL4 induced Treg proliferation by binding to ITGAV to activate PI3K-AKT-NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.

Alkynyl nicotinamides show antileukemic activity in drug-resistant acute myeloid leukemia.

Activating mutations of FLT3 contribute to deregulated hematopoietic stem and progenitor cell (HSC/Ps) growth and survival in patients with acute myeloid leukemia (AML), leading to poor overall survival. AML patients treated with investigational drugs targeting mutant FLT3, including Quizartinib and Crenolanib, develop resistance to these drugs. Development of resistance is largely due to acquisition of cooccurring mutations and activation of additional survival pathways, as well as emergence of additional FLT3 mutations. Despite the high prevalence of FLT3 mutations and their clinical significance in AML, there are few targeted therapeutic options available. We have identified 2 novel nicotinamide-based FLT3 inhibitors (HSN608 and HSN748) that target FLT3 mutations at subnanomolar concentrations and are potently effective against drug-resistant secondary mutations of FLT3. These compounds show antileukemic activity against FLT3ITD in drug-resistant AML, relapsed/refractory AML, and in AML bearing a combination of epigenetic mutations of TET2 along with FLT3ITD. We demonstrate that HSN748 outperformed the FDA-approved FLT3 inhibitor Gilteritinib in terms of inhibitory activity against FLT3ITD in vivo.

High-Resolution Mass Spectrometry for Human Exposomics: Expanding Chemical Space Coverage.

In the modern "omics" era, measurement of the human exposome is a critical missing link between genetic drivers and disease outcomes. High-resolution mass spectrometry (HRMS), routinely used in proteomics and metabolomics, has emerged as a leading technology to broadly profile chemical exposure agents and related biomolecules for accurate mass measurement, high sensitivity, rapid data acquisition, and increased resolution of chemical space. Non-targeted approaches are increasingly accessible, supporting a shift from conventional hypothesis-driven, quantitation-centric targeted analyses toward data-driven, hypothesis-generating chemical exposome-wide profiling. However, HRMS-based exposomics encounters unique challenges. New analytical and computational infrastructures are needed to expand the analysis coverage through streamlined, scalable, and harmonized workflows and data pipelines that permit longitudinal chemical exposome tracking, retrospective validation, and multi-omics integration for meaningful health-oriented inferences. In this article, we survey the literature on state-of-the-art HRMS-based technologies, review current analytical workflows and informatic pipelines, and provide an up-to-date reference on exposomic approaches for chemists, toxicologists, epidemiologists, care providers, and stakeholders in health sciences and medicine. We propose efforts to benchmark fit-for-purpose platforms for expanding coverage of chemical space, including gas/liquid chromatography-HRMS (GC-HRMS and LC-HRMS), and discuss opportunities, challenges, and strategies to advance the burgeoning field of the exposome.

Comparing Transbrachial and Transradial as Alternatives to Transfemoral Access for Large-Bore Neuro Stenting: Insights From a Propensity-Matched Study.

RATIONALE AND OBJECTIVES: This study aimed to evaluate the safety and effectiveness of transbrachial access (TBA) and transradial access (TRA) compared to transfemoral access (TFA) for large-bore neuro stenting (≥7 F). METHODS: From January 2019 to January 2024, 4752 patients received large-bore neuro stenting in our center. The primary outcomes were procedural metrics. Safety outcomes were significant access site complications, including substantial hematoma, pseudoaneurysm, artery occlusion, and complications requiring treatment (medicine, intervention, or surgery). After propensity score matching with a ratio of 1:1:2 (TBA: TRA: TFA), adjusting for age, gender, aortic arch type, and neuro stenting as covariates, outcomes were compared between groups. RESULTS: 46 TBA, 46 TRA and 92 TFA patients were enrolled. The mean age was 67.8 ± 11.2 years, comprising 127 (69.0%) carotid artery stenting and 57 (31.0%) vertebral artery stenting. The rates of technical success (TBA: 100%, TRA: 95.7%, TFA: 100%) and significant access site complications (TBA: 4.3%, TRA: 6.5%, TFA: 1.1%) were comparable between the groups (P > 0.05). Compared to TFA, the TRA cohort exhibited significant delays in angiosuite arrival to puncture time (14 vs. 8 min, P = 0.039), puncture to angiography completion time (19 vs. 11 min, P = 0.027), and procedural duration (42 vs. 29 min, P = 0.031). There were no substantial differences in procedural time metrics between TBA (10, 14, and 31 min, respectively) and TFA. CONCLUSION: TBA and TRA as the primary access for large-bore neuro stenting are safe and effective. Procedural delays in TRA may favor TBA as the first-line alternative access to TFA.

Percutaneous coronary intervention leads to microplastics entering the blood: Interventional devices are a major source.

Microplastics (MPs) is an emerging pollutant potentially harmful to health. Medical practices using plastic devices, such as percutaneous coronary interventions (PCI), may result in MPs entering into the blood. The purpose of this study was to quantify the effect of PCI on microplastic levels in patients' blood. Laser direct infrared (LDIR) was used to detect MPs in the blood of 23 patients before and after PCI. MPs in the water in which devices used in PCI were washed were also examined. The concentration of MPs in the blood was significantly elevated (93.57 ± 35.95 vs. 4.96 ± 3.40 particles/10 mL of blood, P < 0.001) after PCI compared to before, and the increased MPs were polyamide (PA), polyethylene (PE), polyurethane (PU), and polyethylene terephthalate (PET), which was consistent with the types of MPs detected in the device washing water. The maximum diameter of MPs in blood before PCI was 50 µm, whereas after PCI it was 213 µm, and even 336 µm in device washing water. These findings indicated that PCI will cause MPs to enter the blood, and devices used during PCI were a major source, a range of medical practices that use plastic devices may be a new route for MPs to enter the human body.

Endovascular treatment for basilar artery occlusion: whether the "weekend effect" affects time metrics and clinical outcomes at a comprehensive stroke center.

Objectives: This study aimed to evaluate whether the "weekend effect" would affect the time metrics and the prognosis of acute ischemic stroke (AIS) patients who underwent endovascular treatment (EVT) due to basilar artery occlusion (BAO). Methods: Clinical data of AIS patients who underwent EVT due to BAO between December 2019 and July 2023 were retrospectively analyzed. At the time when the patients were admitted, the study population was divided into the weekdays daytime group and weekends nighttime group. In the subgroup analysis, the study cohort was divided into four groups: the weekdays daytime group, weekdays nighttime group, weekend daytime group, and weekend nighttime group. A good outcome was defined as a modified Rankin Scale score of ≤3 at 90 days after EVT. Time metrics [e.g. onset-to-door time (ODT) and door-to-puncture time (DPT)] and clinical outcomes were compared using appropriate statistical methods. Results: A total of 111 patients (88 male patients, mean age, 67.7 ± 11.7 years) were included. Of these, 37 patients were treated during weekdays daytime, while 74 patients were treated during nights or weekends. There were no statistically significant differences in ODT (P = 0.136), DPT (P = 0.931), and also clinical outcomes (P = 0.826) between the two groups. Similarly, we found no significant differences in the time metrics and clinical outcomes among the four sub-groups (all P > 0.05). Conclusion: This study did not reveal any influence of the "weekend effect" on the time metrics and clinical outcomes in AIS patients who underwent EVT due to BAO at a comprehensive stroke center.

Three-year results of central corneal stromal thickness reduction in small-incision lenticule extraction for high myopia correction.

BACKGROUND: To investigate the long-term corneal stromal remodeling and central stromal thickness (CST) reduction accuracy after small-incision lenticule extraction (SMILE) for high myopia correction. METHODS: This prospective study included 30 patients (50 eyes) who had undergone SMILE. Measurements of CST reduction using optical coherence tomography were performed at 1 month, 6 months, 1 year, and 3 years after surgery. Correlations were performed between planned and achieved CST reductions. RESULTS: The study enrolled 50 eyes of 30 patients. The mean spherical equivalent was -9.25±1.52 D(diopters). The postoperative CST increased in the first month after surgery and remained stable for a year. Thereafter, it remained stable during follow-up from 1 to 3 years postoperatively. The predicted CST reduction was 146.4±10.3 µm. The achieved CST reductions at 1 month, 6 months, 1 year, and 3 years after surgery were 135.3±12.1 µm, 130.8±10.6 µm, 125.9±9.4 µm, and 122.2±10.6 µm, respectively. An overestimation of CST reduction was observed three years after surgery. Correlation analysis revealed a strong correlation between planned and achieved CST reductions; however, no correlation was found between CST reductions predicted error and the planned CST reductions. CONCLUSION: During long-term follow-up, our findings revealed a significant stromal remodeling following SMILE in patients with high myopia. Therefore, clinicians should consider it when screening patients with high myopia for SMILE.

Study on Mechanical Properties of Nanopores in CoCrFeMnNi High-Entropy Alloy Used as Drug-Eluting Stent.

The CoCrFeMnNi high-entropy alloy is commonly used for vascular stents due to its excellent mechanical support and ductility. However, as high-entropy alloy stents can cause inflammation in the blood vessels, leading to their re-narrowing, drug-eluting stents have been developed. These stents have nanopores on their surfaces that can carry drug particles to inhibit inflammation and effectively prevent re-narrowing of the blood vessels. To optimize the mechanical properties and drug-carrying capacity of high-entropy alloy stents, a high-entropy alloy system with different wide and deep square-shaped nanopore distributions is created using molecular dynamics. The mechanical characteristics and dislocation evolution mechanism of different nanopore high-entropy alloy systems under tensile stress were studied. The results showed that the CoCrFeMnNi high-entropy alloy with a rational nanopore distribution can effectively maintain the mechanical support required for a vascular stent. This research provides a new direction for the manufacturing process of nanopores on the surfaces of high-entropy alloy stents.

Vibration Analysis of Porous Cu-Si Microcantilever Beams in Fluids Based on Modified Couple Stress Theory.

The vibrations in functionally graded porous Cu-Si microcantilever beams are investigated based on physical neutral plane theory, modified coupled stress theory, and scale distribution theory (MCST&SDT). Porous microcantilever beams define four pore distributions. Considering the physical neutral plane theory, the material properties of the beams are computed through four different power-law distributions. The material properties of microcantilever beams are corrected by scale effects based on modified coupled stress theory. Considering the fluid driving force, the amplitude-frequency response spectra and resonant frequencies of the porous microcantilever beam in three different fluids are obtained based on the Euler-Bernoulli beam theory. The quality factors of porous microcantilever beams in three different fluids are derived by estimating the equation. The computational analysis shows that the presence of pores in microcantilever beams leads to a decrease in Young's modulus. Different pore distributions affect the material properties to different degrees. The gain effect of the scale effect is weakened, but the one-dimensional temperature field and amplitude-frequency response spectra show an increasing trend. The quality factor is decreased by porosity, and the degree of influence of porosity increases as the beam thickness increases. The gradient factor n has a greater effect on the resonant frequency. The effect of porosity on the resonant frequency is negatively correlated when the gradient factor is small (n<1) but positively correlated when the gradient factor is large (n>1).

Establishing nomograms for predicting disease-free survival and overall survival in patients with breast cancer.

BACKGROUND: Prognostic factors-based nomograms have been utilised to detect the likelihood of the specific cancer events. We have focused on the roles of aldehyde dehydrogenase 1 (ALDH1) and p-AKT in predicting the prognosis of BC patients. This study was designed to establish nomograms based on the integration of aldehyde dehydrogenase 1 (ALDH1) and p-AKT in predicting the disease-free survival (DFS) and overall survival (OS) of breast cancer (BC) patients. METHODS: Demographic and clinical data were obtained from BC patients admitted to our hospital between September 2015 and August 2016. Univariate and multivariate Cox regression analyses were utilised to analyse the risk factors of recurrence and mortality. The nomograms for predicting the DFS and OS were established using the screened risk factors. Stratified analysis was performed with the cut-off value of exp (pi) of 4.0-fold in DFS and OS, respectively. RESULTS: Multivariate Cox regression analysis indicated that ALDH, p-AKT and pathological stage III were independent risk factors for the recurrence among BC patients. ALDH1, p-AKT, pathological stage III and ER-/PR-/HER2- were independent risk factors for the mortality among BC patients. The established nomograms based on these factors were effective for predicting the DFS and OS with good agreement to the calibration curve and acceptable area under the receiver operating characteristic (ROC) curve. Finally, stratified analyses showed patients with a low pi showed significant decrease in the DFS and OS compared with those of high risk. CONCLUSION: We established nomograms for predicting the DFS and OS of BC patients based on ALDH1, p-AKT and pathological stages. The ER-/PR-/HER2- may be utilised to predict the OS rather than DFS in the BC patients.

Many breast cancer patients show poor response after treatment due to recurrence and metastasis. Therefore, early prediction of the disease-free survival and overall survival is crucial to the treatment outcome and clinical decision-making. In this study, we established nomograms with the demographic and clinical data from breast cancer patients admitted to our hospital between September 2015 and August 2016. Univariate and multivariate Cox regression analyses showed that some important proteins and signalling pathways were risk factors for decreased disease-free survival and overall survival of breast cancer patients. On this basis, we established an effective nomogram for predicting the disease-free survival and overall survival of these patients based on these factors. This study offers new options in the predicting the treatment outcome of breast cancer patients.

Structural insights into the molecular effects of the anthelmintics monepantel and betaine on the Caenorhabditis elegans acetylcholine receptor ACR-23.

Anthelmintics are drugs used for controlling pathogenic helminths in animals and plants. The natural compound betaine and the recently developed synthetic compound monepantel are both anthelmintics that target the acetylcholine receptor ACR-23 and its homologs in nematodes. Here, we present cryo-electron microscopy structures of ACR-23 in apo, betaine-bound, and betaine- and monepantel-bound states. We show that ACR-23 forms a homo-pentameric channel, similar to some other pentameric ligand-gated ion channels (pLGICs). While betaine molecules are bound to the classical neurotransmitter sites in the inter-subunit interfaces in the extracellular domain, monepantel molecules are bound to allosteric sites formed in the inter-subunit interfaces in the transmembrane domain of the receptor. Although the pore remains closed in betaine-bound state, monepantel binding results in an open channel by wedging into the cleft between the transmembrane domains of two neighboring subunits, which causes dilation of the ion conduction pore. By combining structural analyses with site-directed mutagenesis, electrophysiology and in vivo locomotion assays, we provide insights into the mechanism of action of the anthelmintics monepantel and betaine.

Automated radiotherapy treatment planning guided by GPT-4Vision.

Radiotherapy treatment planning is a time-consuming and potentially subjective process that requires the iterative adjustment of model parameters to balance multiple conflicting objectives. Recent advancements in large foundation models offer promising avenues for addressing the challenges in planning and clinical decision-making. This study introduces GPT-RadPlan, a fully automated treatment planning framework that harnesses prior radiation oncology knowledge encoded in multi-modal large language models, such as GPT-4Vision (GPT-4V) from OpenAI. GPT-RadPlan is made aware of planning protocols as context and acts as an expert human planner, capable of guiding a treatment planning process. Via in-context learning, we incorporate clinical protocols for various disease sites as prompts to enable GPT-4V to acquire treatment planning domain knowledge. The resulting GPT-RadPlan agent is integrated into our in-house inverse treatment planning system through an API. The efficacy of the automated planning system is showcased using multiple prostate and head & neck cancer cases, where we compared GPT-RadPlan results to clinical plans. In all cases, GPT-RadPlan either outperformed or matched the clinical plans, demonstrating superior target coverage and organ-at-risk sparing. Consistently satisfying the dosimetric objectives in the clinical protocol, GPT-RadPlan represents the first multimodal large language model agent that mimics the behaviors of human planners in radiation oncology clinics, achieving remarkable results in automating the treatment planning process without the need for additional training.

Trace Small Molecular/Nano-Colloidal Multiscale Electrolyte Additives Enable Ultra-Long Lifespan of Zinc Metal Anodes.

Electrolyte additives are efficient to improve the performance of aqueous zinc-ion batteries (AZIBs), yet the current electrolyte additives are limited to fully water-soluble additives (FWAs) and water-insoluble additives (WIAs). Herein, trace slightly water-soluble additives (SWAs) of zinc acetylacetonate (ZAA) were introduced to aqueous ZnSO4 electrolytes. The SWA system of ZAA is composed of a FWA part and a WIA part in a dynamic manner of dissolution equilibrium. The FWA part exists as soluble small molecules, which efficiently regulate Zn2+ ion solvation structure, while the WIA part exists as insoluble nano-colloids, which in-situ form a thick and robust solid electrolyte interface film on zinc metal anodes (ZMAs). Such small molecular/nano-colloidal multiscale electrolyte additives of ZAA are capable to not only improve ionic conductivity and transference number but also inhibit corrosion, hydrogen evolution, and Zn dendrite on ZMAs. The SWA-based Zn∥Zn half battery delivers a superb cumulative plating capacity of 15 Ah cm-2 under 1 mAh cm-2 and 20 mA cm-2, and the SWA-based NH4V4O10∥Zn pouch cell obtains a capacity retention of 67.8% within 4000 cycles under 4 A g-1. The study provides innovative insights for rational design of electrolyte additives, which may pave the way for the practicality of AZIBs.

Research on bearing fault diagnosis based on improved genetic algorithm and BP neural network.

Health monitoring and fault diagnosis of rolling bearings are crucial for the continuous and effective operation of mechanical equipment. In order to improve the accuracy of BP neural network in fault diagnosis of rolling bearings, a feature model is established from the vibration signals of rolling bearings, and an improved genetic algorithm is used to optimize the initial weights, biases, and hyperparameters of the BP neural network. This overcomes the shortcomings of BP neural network, such as being prone to local minima, slow convergence speed, and sample dependence. The improved genetic algorithm fully considers the degree of concentration and dispersion of population fitness in genetic algorithms, and adaptively adjusts the crossover and mutation probabilities of genetic algorithms in a non-linear manner. At the same time, in order to accelerate the optimization efficiency of the selection operator, the elite retention strategy is combined with the hierarchical proportional selection operation. Using the rolling bearing dataset from Case Western Reserve University in the United States as experimental data, the proposed algorithm was used for simulation and prediction. The experimental results show that compared with the other seven models, the proposed IGA-BPNN exhibit superior performance in both convergence speed and predictive performance.

Bilateral optic neuritis and encephalopathy as the atypical presentations of multiple sclerosis following severe acute respiratory syndrome coronavirus 2 infection.

Numerous evidence suggests coronavirus disease 2019 (COVID-19) potentially triggers demyelinating diseases, inclusive of multiple sclerosis (MS), and acute disseminated encephalomyelitis (ADEM), and various mechanisms have been proposed. We report a 42-year-old male presented with bilateral optic neuritis and encephalopathy, 2 weeks following COVID-19 infection. He denied any history or family history of neurological and ocular diseases. Severe bilateral visual impairment (only light perception) and pain with eye movement were reported. Fundoscopy revealed bilateral optic disc swelling. Magnetic resonance imaging showed tortuous bilateral optic nerves with optic nerve and nerve sheath enhancement. Multiple hyperintense nodules in bilateral cerebral white matter were noted on fluid-attenuated inversion recovery T2-weighted imaging without diffusion restriction or gadolinium contrast enhancement. Hypointense nodules in cerebral white matter were also noted on T1-weighted imaging, which implied some old lesions. Dissemination in space and time and cerebrospinal fluid-specific oligoclonal bands confirmed the diagnosis of MS. Both serum aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies were negative. He received pulse steroid therapy for 5 days, followed by slowly tapering oral prednisolone. His vision, ocular motion pain, and encephalopathy improved gradually. However, the visual outcome was still poor (bilateral 20/400), and optic atrophy was noticed during 1-year follow-up. To our knowledge, this is the first case of MS following severe acute respiratory syndrome coronavirus 2 infection presented with bilateral optic neuritis and encephalopathy. Since these manifestations are exceedingly rare in MS, we suspect acute immune reactions induced by COVID-19 could bring about the atypical ADEM-like presentations of MS.

Distribution patterns of reef-building corals in the Northwest Pacific and their environmental drivers.

Understanding species distribution and the related driving processes is a fundamental issue in ecology. However, incomplete data on reef-building corals in the ecoregions of the South China Sea have hindered a comprehensive understanding of coral distribution patterns and their ecological drivers in the Northwest Pacific (NWP). This study investigated the coral species diversity and distribution patterns in the NWP by collecting species presence/absence data from the South China Sea and compiling an extensive species distribution database for the region, and explored their major environmental drivers. Our NWP coral database included 612 recorded coral species across 15 ecoregions. Of these, 536 coral species were recorded in the South China Sea Oceanic Islands after compilation, confirming the extraordinary coral species diversity in this ecoregion. Coral alpha diversity was found to decrease with increasing latitude in the whole NWP, while the influence of the Kuroshio Current on environmental conditions in its path results in a slower decline in species richness with latitude compared to regions within the South China Sea. Beta-diversity decomposition revealed that nestedness patterns mainly occurred between low and high latitude ecoregions, while communities within similar latitudes exhibited a turnover component, particularly pronounced at high latitudes. The impact of environmental factors on coral assemblage structure outweighed the effects of spatial distance. Temperature, especially winter temperature, and light intensity strongly influenced alpha diversity and beta diversity's nestedness component. Additionally, turbidity and winter temperature variations at high latitudes contributed to the turnover pattern observed among communities in the NWP. These findings elucidate the assembly processes and major environmental drivers shaping different coral communities in the NWP, highlighting the significant role of specific environmental filtering in coral distribution patterns and providing valuable insights for coral species conservation efforts.

Silencing of CircTRIM25/miR-138-5p/CREB1 axis promotes chondrogenesis in osteoarthritis.

BACKGROUND: Dysregulated circular RNAs (circRNAs) are involved in osteoarthritis (OA) progression. OBJECTIVE: We aimed to explore the effect of hsa_circ_0044719 (circTRIM25) on the ferroptosis of chondrocytes. METHODS: Chondrocytes were treated with interleukin (IL)-1ß to generate cell model. Cellular behaviours were measured using cell counting kit-8, enzyme-linked immunosorbent assay, relevant kits, propidium iodide staining, and immunofluorescence assay. Quantitative real-time polymerase chain reaction was performed to examine the expression of circTRIM25, miR-138-5p, and cAMP responsive element binding protein 1 (CREB1), and their interactions were assessed using luciferase reporter analysis and RNA pull-down assay. RESULTS: CircTRIM25 was upregulated in OA tissues and IL-1ß-stimulated chondrocytes. Knockdown of circTRIM25 facilitated the viability and suppressed ferroptosis and inflammation of IL-1ß-induced cells. CircTRIM25 served as a sponge of miR-138-5p, which directly targets CREB1. Downregulation of miR-138-5p abrogated the effect induced by knockdown of circTRIM25. Furthermore, enforced CREB1 reversed the miR-138-5p induced effect. Moreover, knockdown of circTRIM25 attenuated cartilage injury in vivo. CONCLUSION: Silencing of circTRIM25 inhibited ferroptosis of chondrocytes via the miR-138-5p/CREB axis and thus attenuated OA progression.

Design, synthesis, and anti-oomycete activity of 3-acyloxymaltol/ethyl maltol derivatives.

Twenty 3-acyloxymaltol/ethyl maltol derivatives (7a-j and 8a-j) were synthesized and evaluated in vitro for their anti-oomycete activity against Phytophthora capsici, respectively. Among all of twenty derivatives, more than half of the compounds 7f, 7h, 8a-h and 8j had anti-oomycete activity higher than the positive control zoxamide (EC50 = 22.23 mg/L), and the EC50 values of 18.66, 20.32, 12.80, 16.18, 10.59, 14.98, 16.80, 10.36, 15.32, 12.64, and 13.59 mg/L, respectively. Especially, compounds 8c and 8f exhibited the best anti-oomycete activity against P. capsici with EC50 values of 10.59 and 10.36 mg/L, respectively. Overall, hydroxyl group of maltol/ethyl maltol is important active modification site.

Potential of body mass index as a screening indicator for extracranial-intracranial bypass surgery in patients with symptomatic artery occlusion: a post-hoc analysis of the CMOSS trial.

BACKGROUND: To investigate the association between body mass index (BMI) and the incidence of ischemic stroke in patients with symptomatic artery occlusion, and further to evaluate the utility of BMI as a screening tool for identifying candidates for extracranial-intracranial bypass surgery. MATERIALS AND METHODS: We analyzed the relationship between BMI and the occurrence of ipsilateral ischemic stroke (IIS) among patients receiving only medical management in the Carotid or Middle cerebral artery Occlusion Surgery Study (CMOSS). Additionally, we compared the primary endpoint of CMOSS-stroke or death within 30 days, or IIS after 30 days up to two years-among patients with varying BMIs who underwent either surgery or medical treatment. RESULTS: Of the 165 patients who treated medically only, 16 (9.7%) suffered an IIS within two years. BMI was independently associated with the incidence of IIS (hazard ratio: 1.16 per kg/m2; 95% confidence interval: 1.06-1.27). The optimal BMI cutoff for predicting IIS was 24.5 kg/m2. Patients with BMI ≥24.5 kg/m2 experienced a higher incidence of IIS compared to those with BMI <24.5 kg/m2 (17.4% vs. 0.0%, P<0.01). The incidence of the CMOSS primary endpoint was significantly different between the surgical and medical groups for patients with BMI ≥24.5 kg/m2 (5.3% vs. 19.8%, P<0.01) and those with BMI <24.5 kg/m2 (10.6% vs. 1.4%; P=0.02). Surgical intervention was independently associated with a reduced rate of the CMOSS primary endpoint in patients with BMI ≥24.5 kg/m2. CONCLUSION: Data from the CMOSS trial indicate that patients with BMI ≥24.5 kg/m2 are at a higher risk of IIS when treated medically only and appear to derive greater benefit from bypass surgery compared to those with lower BMIs. Given the small sample size and the inherent limitations of retrospective analyses, further large-scale, prospective studies are necessary to confirm these findings.

Dams alter the control pattern of watershed land use to riverine nutrient distribution: Comparison of three major rivers under different hydropower development levels in Southwestern China.

Land use plays a critical role in managing water quality in a watershed, as it governs the import and distribution of nutrients. In addition to the land use, some rivers in Southwest China are encountering a new environmental stressor of damming, which is being driven by the national strategy of hydropower development. However, the coupling effect of land use and dams on nutrients remains poorly understood, challenging the effective management of riverine water quality. Therefore, this study examined the nutrients in the Nu, Yarlung Tsangpo (YT), and Lancang (LC) Rivers, which have no dam, 1 dam, and 11 dams, respectively, during different regulatory periods (spring and fall) to identify variations in nutrient control patterns influenced by land use and dams. The findings suggested that an increase in hydropower development contributed to a notable shift in nutrient patterns from land use regulation towards dam regulation and coupling effects. Land use dominated the nutrient variations of the Nu (27.4 %-32.8 %) and low hydropower development YT (25.2 %-30.9 %) Rivers during both seasons, but the primary contributors to the nutrient variations of the high hydropower development LC River were dams (17.9 %-41.6 %) and coupling effects (16.5 %-29.0 %). Dams transform nutrient levels and compositions through internal reservoir cycling, decoupling land use and nutrients. Partial least-squares structural equation model analysis further suggested that the coupling effects of the LC River were seasonal-specific, which was primarily attributed to hydrological variations that affected their interactions. During spring, the reservoir underwent a drainage mode characterized by high-level nutrients in the bottom water. Combined with the import of riverine nutrients, it exacerbated the increase of nutrients (synergistic effect). In contrast, the reservoir transitioned into a storage mode where it intercepted nutrients from the upstream and watershed during the fall, leading to a reduction in the previously observed increasing trend and an increase in nutrient variability (antagonism effect).