Polycaprolactone/gelatin-QAS/bioglass nanofibres accelerate diabetic chronic wound healing by improving dysfunction of fibroblasts.

Worldwide, more than 25 % of patients with diabetes develop chronic diabetic wounds in their lifetime. Infection and dysfunctional fibroblasts represent two significant etiological factors contributing to impaired wound healing in patients with diabetes. It is therefore evident that the development of wound dressings with both anti-infective and DM fibroblast modulating functions has the potential for clinical applications. In this study, a PCL/gelatine-quaternary ammonium salts (QAS)/bioglass (BG) electrospun nanofibrous membrane was developed with physico-chemical and biological properties that not only meet the clinical requirements for wound dressings but also exhibit remarkable moisturising (water adsorption rate of 382.39 ±â€¯4.36 %) and tear-resistance properties (a tear strength of ~5.5 MPa). The incorporation of QAS and BG has enhanced the biocompatibility and bioactivity of the nanofibres, while also imparting remarkable antimicrobial properties. The antibacterial efficacy of PGQ-BG against E. coli and S. aureus was found to be 92.8 ±â€¯0.78 % and 99.3 ±â€¯0.55 %, respectively. Moreover, it was demonstrated that PGQ-BG nanofibers exerted a promoting effect on the extracellular matrix (ECM) in dysfunctional fibroblasts and upregulated the expression level of α-smooth muscle actin (α-SMA), a marker of their differentiation to myofibroblasts in vitro and in vivo. Furthermore, the COL-III/COL-I ratio was significantly increased, indicating that PGQ-BG may also accelerate wound healing. The nanofibrous dressing reduced scar formation by increasing the COL-III/COL-I ratio. This is the first report of BG improving fibroblast dysfunction via COL-III and COL-I promotion in fibroblasts, both in vitro and in vivo. Therefore, this novel bioactive nanofibrous dressing represents an effective and safe therapeutic strategy for improving chronic wound healing in patients with diabetes.

Phenolic Compound Profiles, Antioxidant and Cytoprotective Activity of Elaeagnus conferta Roxb. Fruit.

In this paper, three varieties of Elaeagnus conferta Roxb fruits prepared by ultrasonic-assisted extraction from a subtropical region southwest of China were utilized as raw materials to investigate their phenolic profiles, antioxidant activities, and protective effects on injured human umbilical vein endothelial cells (HUVECs). The ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) findings revealed that fifteen substances, including seven phenolic acids, seven flavonoids, and one gallic acid derivative, were discovered. The dihydromyricetin, ellagic acid, gallic acid were the predominant phenolic compounds in all E.conferta fruits. These E.conferta fruits extracts shown excellent antioxidant activity varied from 2.258 ± 0.03 ~ 7.844 ± 0.39 µM Trolox/g and protective effect on HUVECs injured by H2O2 through decrease the level of ROS, MDA, LDH and enhance the SOD level. These finding indicate that E.conferta is a valuable source of high-capacity antioxidants that might be used as an alternative material for food industries.

Risks of infectious disease hospitalisations in the aftermath of tropical cyclones: a multi-country time-series study.

BACKGROUND: The proportion of intense tropical cyclones is expected to increase in a changing climate. However, there is currently no consistent and comprehensive assessment of infectious disease risk following tropical cyclone exposure across countries and over decades. We aimed to explore the tropical cyclone-associated hospitalisation risks and burden for cause-specific infectious diseases on a multi-country scale. METHODS: Hospitalisation records for infectious diseases were collected from six countries and territories (Canada, South Korea, New Zealand, Taiwan, Thailand, and Viet Nam) during various periods between 2000 and 2019. The days with tropical cyclone-associated maximum sustained windspeeds of 34 knots or higher derived from a parametric wind field model were considered as tropical cyclone exposure days. The association of monthly infectious diseases hospitalisations and tropical cyclone exposure days was first examined at location level using a distributed lag non-linear quasi-Poisson regression model, and then pooled using a random-effects meta-analysis. The tropical cyclone-attributable number and fraction of infectious disease hospitalisations were also calculated. FINDINGS: Overall, 2·2 million people who were hospitalised for infectious diseases in 179 locations that had at least one tropical cyclone exposure day in the six countries and territories were included in the analysis. The elevated hospitalisation risks for infectious diseases associated with tropical cyclones tended to dissipate 2 months after the tropical cyclone exposure. Overall, each additional tropical cyclone day was associated with a 9% (cumulative relative risk 1·09 [95% CI 1·05-1·14]) increase in hospitalisations for all-cause infectious diseases, 13% (1·13 [1·05-1·21]) for intestinal infectious diseases, 14% (1·14 [1·05-1·23]) for sepsis, and 22% (1·22 [1·03-1·46]) for dengue during the 2 months after a tropical cyclone. Associations of tropical cyclones with hospitalisations for tuberculosis and malaria were not significant. In total, 0·72% (95% CI 0·40-1·01) of the hospitalisations for all-cause infectious diseases, 0·33% (0·15-0·49) for intestinal infectious diseases, 1·31% (0·57-1·95) for sepsis, and 0·63% (0·10-1·04) for dengue were attributable to tropical cyclone exposures. The attributable burdens were higher among young populations (aged ≤19 years) and male individuals compared with their counterparts, especially for intestinal infectious diseases. The heterogeneous spatiotemporal pattern was further revealed at the country and territory level-tropical cyclone-attributable fractions showed a decreasing trend in South Korea during the study period but an increasing trend in Viet Nam, Taiwan, and New Zealand. INTERPRETATION: Tropical cyclones were associated with persistent elevated hospitalisation risks of infectious diseases (particularly sepsis and intestinal infectious diseases). Targeted interventions should be formulated for different populations, regions, and causes of infectious diseases based on evidence on tropical cyclone epidemiology to respond to the increasing risk and burden. FUNDING: Australian Research Council, Australian National Health, and Medical Research Council.

The association of adverse birth outcomes with flood exposure before and during pregnancy in Australia: a cohort study.

BACKGROUND: Exposure to floods might increase the risks of adverse birth outcomes. However, the current evidence is scarce, inconsistent, and has knowledge gaps. This study aims to estimate the associations of flood exposure before and during pregnancy with adverse birth outcomes and to identify susceptible exposure windows and effect modifiers. METHODS: In this cohort study, we obtained all the birth records occurring in Greater Sydney, Australia, from Jan 1, 2001, to Dec 31, 2020, from the New South Wales Midwives Data Collection and in the Brisbane metropolitan region, Australia, from Jan 1, 1995, to Dec 31, 2014, from the Queensland Health Perinatal Data Collection. For each birth, residential address and historical flood information from the Dartmouth Flood Observatory were used to estimate the numbers of days with floods during five exposure windows (Pre-1 was defined as 13-24 weeks before the last menstrual period [LMP], Pre-2 was 0-12 weeks before the LMP, trimester 1 [Tri-1] was 0-12 weeks after the LMP, trimester 2 [Tri-2] was 13-28 weeks after the LMP, and trimester 3 [Tri-3] was ≥29 weeks after the LMP). We estimated the hazard ratios (HRs) of adverse birth outcomes (preterm births, stillbirths, term low birthweight [TLBW], and small for gestational age [SGA]) associated with flood exposures in the five exposure windows using Cox proportional hazards regression models. FINDINGS: 1 338 314 birth records were included in our analyses, which included 91 851 (6·9%) preterm births, 9831 (0·7%) stillbirths, 25 567 (1·9%) TLBW, and 108 658 (8·1%) SGA. Flood exposure in Pre-1 was associated with increased risks of TLBW (HR 1·06 [95% CI 1·01-1·12]) and SGA (1·04 [1·01-1·06]); flood exposure during Tri-1 was associated with increased risks of preterm births (1·03 [1·002-1·05]), stillbirth (1·11 [1·03-1·20]), and SGA (1·03 [1·01-1·06]). In contrast, flood exposures during Pre-2 and Tri-3 were associated with reduced risks. INTERPRETATION: Exposures to floods in Pre-1 and Tri-1 are both associated with increased risks of adverse birth outcomes, and the risks increase with a higher exposure. Upon planning for conception and prenatal care, individuals and health practitioners should raise awareness of the increased risks of adverse birth outcomes after experiencing floods. FUNDING: The Australian Research Council and the Australian National Health and Medical Research Council.

Short-term ozone exposure and cancer mortality in Brazil: A nationwide case-crossover study.

Exposure to ambient ozone (O3) is linked to increased mortality risks from various diseases, but epidemiological investigations delving into its potential implications for cancer mortality are limited. We aimed to examine the association between short-term O3 exposure and site-specific cancer mortality and investigate vulnerable subgroups in Brazil. In total 3,459,826 cancer death records from 5570 Brazilian municipalities between 2000 and 2019, were included. Municipal average daily O3 concentration was calculated from a global estimation at 0.25°×0.25° spatial resolution. The time-stratified case-crossover design was applied to assess the O3-cancer mortality association. Subgroup analyses by age, sex, season, time-period, region, urban hierarchy, climate classification, quantiles of GDP per capita and illiteracy rates were performed. A linear and non-threshold exposure-response relationship was observed for short-term exposure to O3 with cancer mortality, with a 1.00% (95% CI: 0.79%-1.20%) increase in all-cancer mortality risks for each 10-µg/m3 increment of three-day average O3. Kidney cancer was most strongly with O3 exposure, followed by cancers of the prostate, stomach, breast, lymphoma, brain and lung. The associated cancer risks were relatively higher in the warm season and in southern Brazil, with a decreasing trend over time. When restricting O3 concentration to the national minimum value during 2000-2019, a total of 147,074 (116,690-177,451) cancer deaths could be avoided in Brazil, which included 17,836 (7014-28,653) lung cancer deaths. Notably, these associations persisted despite observed adaptation within the Brazilian population, highlighting the need for a focus on incorporating specific measures to mitigate O3 exposure into cancer care recommendations.

Short-term Exposure to Wildfire-Specific PM2.5 and Diabetes Hospitalization: A Study in Multiple Countries and Territories.

OBJECTIVE: To evaluate associations of wildfire fine particulate matter ≤2.5 mm in diameter (PM2.5) with diabetes across multiple countries and territories. RESEARCH DESIGN AND METHODS: We collected data on 3,612,135 diabetes hospitalizations from 1,008 locations in Australia, Brazil, Canada, Chile, New Zealand, Thailand, and Taiwan during 2000-2019. Daily wildfire-specific PM2.5 levels were estimated through chemical transport models and machine-learning calibration. Quasi-Poisson regression with distributed lag nonlinear models and random-effects meta-analysis were applied to estimate associations between wildfire-specific PM2.5 and diabetes hospitalization. Subgroup analyses were by age, sex, location income level, and country or territory. Diabetes hospitalizations attributable to wildfire-specific PM2.5 and nonwildfire PM2.5 were compared. RESULTS: Each 10 µg/m3 increase in wildfire-specific PM2.5 levels over the current day and previous 3 days was associated with relative risks (95% CI) of 1.017 (1.011-1.022), 1.023 (1.011-1.035), 1.023 (1.015-1.032), 0.962 (0.823-1.032), 1.033 (1.001-1.066), and 1.013 (1.004-1.022) for all-cause, type 1, type 2, malnutrition-related, other specified, and unspecified diabetes hospitalization, respectively. Stronger associations were observed for all-cause, type 1, and type 2 diabetes in Thailand, Australia, and Brazil; unspecified diabetes in New Zealand; and type 2 diabetes in high-income locations. An estimate of 0.67% (0.16-1.18%) and 1.02% (0.20-1.81%) for all-cause and type 2 diabetes hospitalizations were attributable to wildfire-specific PM2.5. Compared with nonwildfire PM2.5, wildfire-specific PM2.5 posed greater risks of all-cause, type 1, and type 2 diabetes and were responsible for 38.7% of PM2.5-related diabetes hospitalizations. CONCLUSIONS: We show the relatively underappreciated links between diabetes and wildfire air pollution, which can lead to a nonnegligible proportion of PM2.5-related diabetes hospitalizations. Precision prevention and mitigation should be developed for those in advantaged communities and in Thailand, Australia, and Brazil.

Association of the High-Sensitivity C-Reactive Protein-to-Albumin Ratio with Carotid Atherosclerotic Plaque: A Community-Based Cohort Study.

Background: The inflammatory response is a pivotal factor in accelerating the progression of atherosclerosis. The high-sensitivity C-reactive protein-to-albumin ratio (CAR) has emerged as a novel marker of systemic inflammation. However, few studies have shown the CAR to be a promising prognostic marker for carotid atherosclerotic disease. This study aimed to analyse the predictive role of the CAR in carotid atherosclerotic disease. Methods: This community-based cohort study recruited 2003 participants from the Rose asymptomatic IntraCranial Artery Stenosis (RICAS) study who were free of stroke or transient ischemic attack. Carotid atherosclerotic plaques and their stability were identified via carotid ultrasound. Logistic regression models were utilized to investigate the association between CAR and the presence of carotid atherosclerotic plaques. Results: The prevalence of carotid atherosclerotic plaques was 38.79% in this study. After adjusting for clinical risk factors, including sex, age, dyslipidemia, hypertension, diabetes mellitus (DM), and smoking and drinking habits, a high CAR-level was independently associated with carotid plaque (odds ratio [OR] of upper: 1.46, 95% confidence interval [CI]: 1.13-1.90, P = 0.004; P for trend = 0.011). The highest CAR tertile was still significantly associated with carotid plaques among middle-aged (40-64 years) or female participants. Notably, an elevated CAR may be an independent risk factor for vulnerable carotid plaques (OR of upper: 2.06, 95% CI: 1.42-2.98, P < 0.001; P for trend <0.001). Conclusion: A high CAR may be correlated with a high risk of carotid plaques, particularly among mildly aged adults (40-64 years) or females. Importantly, the CAR may be associated with vulnerable carotid plaques, suggesting that the CAR may be a new indicator for stroke prevention.

Effect of surface viscoelasticity on top jet drops produced by bursting bubbles.

Jet drops resulting from bubble bursting at a liquid surface play a key role in various mass transfer processes across the interface, including sea spray aerosol generation and pathogen transmission. However, the impact of structurally compound interfaces, characterized by complex surface rheology introduced by surface-active contaminants, on the jet drop ejection still remains unclear. Here, we experimentally investigate the influence of surface viscoelasticity on the size and velocity of the top jet drops from surface bubble bursting, examining both pure protein and mixed protein-surfactant solutions. We document that for bubble bursting at a pure-protein-laden surface where surface elasticity dominates, the increase in Ec, i.e. the interfacial elastocapillary number as the ratio between the effects of interfacial elasticity and capillarity, efficiently increases the radius and decreases the velocity of the top jet drop, ultimately inhibiting the jet drop ejection. On the other hand, considering the mixed protein-surfactant solution, we show that the top jet drop radius and velocity exhibit a different variation trend with Ec, which is attributed to the additional dissipation on the capillary waves as well as the retardation and resistance on the converging flow for jet formation from surface viscoelasticity. Our work may advance the understanding of bubble bursting dynamics at contaminated liquid surfaces and shed light on the potential influence of surface viscoelasticity on the generation of bubble bursting aerosols.

Ambient fine particulate matter and daily mortality: a comparative analysis of observed and estimated exposure in 347 cities.

BACKGROUND: Model-estimated air pollution exposure products have been widely used in epidemiological studies to assess the health risks of particulate matter with diameters of ≤2.5 µm (PM2.5). However, few studies have assessed the disparities in health effects between model-estimated and station-observed PM2.5 exposures. METHODS: We collected daily all-cause, respiratory and cardiovascular mortality data in 347 cities across 15 countries and regions worldwide based on the Multi-City Multi-Country collaborative research network. The station-observed PM2.5 data were obtained from official monitoring stations. The model-estimated global PM2.5 product was developed using a machine-learning approach. The associations between daily exposure to PM2.5 and mortality were evaluated using a two-stage analytical approach. RESULTS: We included 15.8 million all-cause, 1.5 million respiratory and 4.5 million cardiovascular deaths from 2000 to 2018. Short-term exposure to PM2.5 was associated with a relative risk increase (RRI) of mortality from both station-observed and model-estimated exposures. Every 10-µg/m3 increase in the 2-day moving average PM2.5 was associated with overall RRIs of 0.67% (95% CI: 0.49 to 0.85), 0.68% (95% CI: -0.03 to 1.39) and 0.45% (95% CI: 0.08 to 0.82) for all-cause, respiratory, and cardiovascular mortality based on station-observed PM2.5 and RRIs of 0.87% (95% CI: 0.68 to 1.06), 0.81% (95% CI: 0.08 to 1.55) and 0.71% (95% CI: 0.32 to 1.09) based on model-estimated exposure, respectively. CONCLUSIONS: Mortality risks associated with daily PM2.5 exposure were consistent for both station-observed and model-estimated exposures, suggesting the reliability and potential applicability of the global PM2.5 product in epidemiological studies.

Cancer mortality risk from short-term PM2.5 exposure and temporal variations in Brazil.

Although some studies have found that short-term PM2.5 exposure is associated with lung cancer deaths, its impact on other cancer sites is unclear. To answer this research question, this time-stratified case-crossover study used individual cancer death data between January 1, 2000, and December 31, 2019, extracted from the Brazilian mortality information system to quantify the associations between short-term PM2.5 exposure and cancer mortality from 25 common cancer sites. Daily PM2.5 concentration was aggregated at the municipality level as the key exposure. The study included a total of 34,516,120 individual death records, with the national daily mean PM2.5 exposure 15.3 (SD 4.3) µg/m3. For every 10-µg/m3 increase in three-day average PM2.5 exposure, the odds ratio (OR) for all-cancer mortality was 1.04 (95% CI 1.03-1.04). Apart from all-cancer deaths, PM2.5 exposure may impact cancers of oesophagus (1.04, 1.00-1.08), stomach (1.05, 1.02-1.08), colon-rectum (1.04, 1.01-1.06), lung (1.04, 1.02-1.06), breast (1.03, 1.00-1.06), prostate (1.07, 1.04-1.10), and leukaemia (1.05, 1.01-1.09). During the study period, acute PM2.5 exposure contributed to an estimated 1,917,994 cancer deaths, ranging from 0 to 6,054 cases in each municipality. Though there has been a consistent downward trend in PM2.5-related all-cancer mortality risks from 2000 to 2019, the impact remains significant, indicating the continued importance of cancer patients avoiding PM2.5 exposure. This nationwide study revealed a notable association between acute PM2.5 exposure and heightened overall and site-specific cancer mortality for the first time to our best knowledge. The findings suggest the importance of considering strategies to minimize such exposure in cancer care guidelines. ENVIRONMENTAL IMPLICATION: The 20-year analysis of nationwide death records in Brazil revealed that heightened short-term exposure to PM2.5 is associated with increased cancer mortality at various sites, although this association has gradually decreased over time. Despite the declining impact, the research highlights the persistent adverse effects of PM2.5 on cancer mortality, emphasizing the importance of continued research and preventive measures to address the ongoing public health challenges posed by air pollution.

Floods and cause-specific mortality in the UK: a nested case-control study.

BACKGROUND: Floods are the most frequent weather-related disaster, causing significant health impacts worldwide. Limited studies have examined the long-term consequences of flooding exposure. METHODS: Flood data were retrieved from the Dartmouth Flood Observatory and linked with health data from 499,487 UK Biobank participants. To calculate the annual cumulative flooding exposure, we multiplied the duration and severity of each flood event and then summed these values for each year. We conducted a nested case-control analysis to evaluate the long-term effect of flooding exposure on all-cause and cause-specific mortality. Each case was matched with eight controls. Flooding exposure was modelled using a distributed lag non-linear model to capture its nonlinear and lagged effects. RESULTS: The risk of all-cause mortality increased by 6.7% (odds ratio (OR): 1.067, 95% confidence interval (CI): 1.063-1.071) for every unit increase in flood index after confounders had been controlled for. The mortality risk from neurological and mental diseases was negligible in the current year, but strongest in the lag years 3 and 4. By contrast, the risk of mortality from suicide was the strongest in the current year (OR: 1.018, 95% CI: 1.008-1.028), and attenuated to lag year 5. Participants with higher levels of education and household income had a higher estimated risk of death from most causes whereas the risk of suicide-related mortality was higher among participants who were obese, had lower household income, engaged in less physical activity, were non-moderate alcohol consumers, and those living in more deprived areas. CONCLUSIONS: Long-term exposure to floods is associated with an increased risk of mortality. The health consequences of flooding exposure would vary across different periods after the event, with different profiles of vulnerable populations identified for different causes of death. These findings contribute to a better understanding of the long-term impacts of flooding exposure.

Discovery of Hepatitis B Virus Surface Antigen Suppressor GS-8873.

Chronic hepatitis B (CHB) virus infection afflicts hundreds of millions of people and causes nearly one million deaths annually. The high levels of circulating viral surface antigen (HBsAg) that characterize CHB may lead to T-cell exhaustion, resulting in an impaired antiviral immune response in the host. Agents that suppress HBsAg could help invigorate immunity toward infected hepatocytes and facilitate a functional cure. A series of dihydropyridoisoquinolizinone (DHQ) inhibitors of human poly(A) polymerases PAPD5/7 were reported to suppress HBsAg in vitro. An example from this class, RG7834, briefly entered the clinic. We set out to identify a potent, orally bioavailable, and safe PAPD5/7 inhibitor as a potential component of a functional cure regimen. Our efforts led to the identification of a dihydropyridophthalazinone (DPP) core with improved pharmacokinetic properties. A conformational restriction strategy and optimization of core substitution led to GS-8873, which was projected to provide deep HBsAg suppression with once-daily dosing.

Spatiotemporal characteristics and influencing factors for joint events of air pollution wave and cold wave in China.

Climate change triggered more environmental extremes. The joint events of air pollution wave and cold wave showed higher health risks than independent events, but little evidence is available for the spatiotemporal features of their co-occurrence. To better understand and forecast the joint events, a method framework was developed in this study. The temporal trend and spatial distribution of count and duration for joint events were measured at each grid cell (0.5°×0.5°) by integrating the PM2.5 air pollution wave and cold wave. The generalized linear mixed model was used to screen influencing variables that took into account socioeconomic characteristics, meteorological variables, and annual PM2.5 levels. During 2000 and 2018, the average annual count of joint events was 4.1 ± 6.8 days and the average duration ranged from 1.0 to 9.7 days. High spatial heterogeneity was observed throughout China, with a significant increase in joint events observed in Xinjiang area (the largest province in China). The most average count of joint events was observed in Henan province (one of the most populous provinces), while the longest duration was in Chongqing (a municipality, one of the megacities). Areas with higher PM2.5 levels, prolonged air pollution wave, and cold wave durations would experience more joint events. These findings can assist China in locating vulnerable areas and establishing effective local early warning systems. The method framework offers broader perspectives on mitigating health risks associated with extreme events in other countries and regions.

Glycosides of Buyang Huanwu decoction inhibits inflammation associated with cerebral ischemia-reperfusion via the PINK1/Parkin mitophagy pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: A classic stroke formula is Buyang Huanwu Decoction (BYHWD), Glycosides are the pharmacological components found in BYHWD, which are utilized for the prevention and management of cerebral ischemia-reperfusion (CIR), as demonstrated in a previous study. Its neuroprotective properties are closely related to its ability to modulate inflammation, but its mechanism is as yet unclear. AIM OF THE STUDY: A research was undertaken to investigate the impact of glycosides on the inflammation of CIR through the PTEN-induced putative kinase-1 (PINK1)/Parkin mitophagy pathway. MATERIALS AND METHODS: Analyzing glycosides containing serum components was performed with ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS). Glycosides were applied to rat of Middle cerebral artery occlusion/reperfusion (MCAO/R) model and primary neural cell of Oxygen glucose deprivation/reperfusion (OGD/R) model. The neuroprotective effect and the regulation of mitophagy of glycosides were evaluated through neural damage and PINK1/Parkin mitophagy activation. Moreover, the assessment of the relationship between glycosides regulation of mitophagy and its anti-inflammatory effects subsequent to mitophagy blockade was conducted by examining neural damage, PINK1/Parkin mitophagy activation, and levels of pyroptosis. RESULTS: (1) It was observed that the administration of glycosides resulted in a decrease in neurological function scores, a reduction in cerebral infarction volume, an increase in mitochondrial autophagosome, and the maintenance of a high expression status of light chain 3 (LC3) II/LC3Ⅰ protein. Additionally, there was a significant inhibition of p62 protein expression and an enhancement of PINK1 and Parkin protein expression. Furthermore, it was found that the effect of glycosides at a dosage of 0.128 g · kg-1 was significantly superior to that of glycosides at a dosage of 0.064 g · kg-1. Notably, the neuroprotective effect and inhibition of pyroptosis protein of glycosides at a dosage of 0.128 g · kg-1 were attenuated when mitochondrial autophagy was blocked. (2) Glycosides repaired cellular morphological damage, enhanced cell survival, and reduced Lactate dehydrogenase (LDH) leakage, with glycosides (2.36 µg·mL-1 and 4.72 µg·mL-1) neuronal protection being the strongest. Glycosides (4.72 µg·mL-1) maintained LC3II/LC3Ⅰ protein high expression state, inhibited p62 protein expression, and promoted PINK1 and Parkin protein expression, which was stronger than glycosides (2.36 µg·mL-1). The blockade of mitophagy resulted in a reduction of neuroprotection and inhibition of pyroptosis protein exerted by glycosides. CONCLUSION: Glycosides demonstrate the ability to hinder inflammation through the activation of the PINK1/Parkin mitophagy pathway, thereby leading to subsequent neuroprotective effects on CIR.

Tropical cyclone-specific mortality risks and the periods of concern: A multicountry time-series study.

BACKGROUND: More intense tropical cyclones (TCs) are expected in the future under a warming climate scenario, but little is known about their mortality effect pattern across countries and over decades. We aim to evaluate the TC-specific mortality risks, periods of concern (POC) and characterize the spatiotemporal pattern and exposure-response (ER) relationships on a multicountry scale. METHODS AND FINDINGS: Daily all-cause, cardiovascular, and respiratory mortality among the general population were collected from 494 locations in 18 countries or territories during 1980 to 2019. Daily TC exposures were defined when the maximum sustained windspeed associated with a TC was ≥34 knots using a parametric wind field model at a 0.5° × 0.5° resolution. We first estimated the TC-specific mortality risks and POC using an advanced flexible statistical framework of mixed Poisson model, accounting for the population changes, natural variation, seasonal and day of the week effects. Then, a mixed meta-regression model was used to pool the TC-specific mortality risks to estimate the overall and country-specific ER relationships of TC characteristics (windspeed, rainfall, and year) with mortality. Overall, 47.7 million all-cause, 15.5 million cardiovascular, and 4.9 million respiratory deaths and 382 TCs were included in our analyses. An overall average POC of around 20 days was observed for TC-related all-cause and cardiopulmonary mortality, with relatively longer POC for the United States of America, Brazil, and Taiwan (>30 days). The TC-specific relative risks (RR) varied substantially, ranging from 1.04 to 1.42, 1.07 to 1.77, and 1.12 to 1.92 among the top 100 TCs with highest RRs for all-cause, cardiovascular, and respiratory mortality, respectively. At country level, relatively higher TC-related mortality risks were observed in Guatemala, Brazil, and New Zealand for all-cause, cardiovascular, and respiratory mortality, respectively. We found an overall monotonically increasing and approximately linear ER curve of TC-related maximum sustained windspeed and cumulative rainfall with mortality, with heterogeneous patterns across countries and regions. The TC-related mortality risks were generally decreasing from 1980 to 2019, especially for the Philippines, Taiwan, and the USA, whereas potentially increasing trends in TC-related all-cause and cardiovascular mortality risks were observed for Japan. CONCLUSIONS: The TC mortality risks and POC varied greatly across TC events, locations, and countries. To minimize the TC-related health burdens, targeted strategies are particularly needed for different countries and regions, integrating epidemiological evidence on region-specific POC and ER curves that consider across-TC variability.

The phosphokinase activity of IRE1ɑ prevents the oxidative stress injury through miR-25/Nox4 pathway after ICH.

BACKGROUND: Endoplasmic reticulum (ER) stress and oxidative stress are the major pathologies encountered after intracerebral hemorrhage (ICH). Inositol-requiring enzyme-1 alpha (IRE1α) is the most evolutionarily conserved ER stress sensor, which plays a role in monitoring and responding to the accumulation of unfolded/misfolded proteins in the ER lumen. Recent studies have shown that ER stress is profoundly related to oxidative stress in physiological or pathological conditions. The purpose of this study was to investigate the role of IRE1α in oxidative stress and the potential mechanism. METHODS: A mouse model of ICH was established by autologous blood injection. The IRE1α phosphokinase inhibitor KIRA6 was administrated intranasally at 1 h after ICH, antagomiR-25 and agomiR-25 were injected intraventricularly at 24 h before ICH. Western blot analysis, RT-qPCR, immunofluorescence staining, hematoma volume, neurobehavioral tests, dihydroethidium (DHE) staining, H2O2 content, brain water content, body weight, Hematoxylin and Eosin (HE) staining, Nissl staining, Morris Water Maze (MWM) and Elevated Plus Maze (EPM) were performed. RESULTS: Endogenous phosphorylated IRE1α (p-IRE1α), miR-25-3p, and Nox4 were increased in the ICH model. Administration of KIRA6 downregulated miR-25-3p expression, upregulated Nox4 expression, promoted the level of oxidative stress, increased hematoma volume, exacerbated brain edema and neurological deficits, reduced body weight, aggravated spatial learning and memory deficits, and increased anxiety levels. Then antagomiR-25 further upregulated the expression of Nox4, promoted the level of oxidative stress, increased hematoma volume, exacerbated brain edema and neurological deficits, whereas agomiR-25 reversed the effects promoted by KIRA6. CONCLUSION: The IRE1α phosphokinase activity is involved in the oxidative stress response through miR-25/Nox4 pathway in the mouse ICH brain.

Climate change, environmental extremes, and human health in Australia: challenges, adaptation strategies, and policy gaps.

Climate change presents a major public health concern in Australia, marked by unprecedented wildfires, heatwaves, floods, droughts, and the spread of climate-sensitive infectious diseases. Despite these challenges, Australia's response to the climate crisis has been inadequate and subject to change by politics, public sentiment, and global developments. This study illustrates the spatiotemporal patterns of selected climate-related environmental extremes (heatwaves, wildfires, floods, and droughts) across Australia during the past two decades, and summarizes climate adaptation measures and actions that have been taken by the national, state/territory, and local governments. Our findings reveal significant impacts of climate-related environmental extremes on the health and well-being of Australians. While governments have implemented various adaptation strategies, these plans must be further developed to yield concrete actions. Moreover, Indigenous Australians should not be left out in these adaptation efforts. A collaborative, comprehensive approach involving all levels of government is urgently needed to prevent, mitigate, and adapt to the health impacts of climate change.

Trends and hotspots in research on medical images with deep learning: a bibliometric analysis from 2013 to 2023.

Background: With the rapid development of the internet, the improvement of computer capabilities, and the continuous advancement of algorithms, deep learning has developed rapidly in recent years and has been widely applied in many fields. Previous studies have shown that deep learning has an excellent performance in image processing, and deep learning-based medical image processing may help solve the difficulties faced by traditional medical image processing. This technology has attracted the attention of many scholars in the fields of computer science and medicine. This study mainly summarizes the knowledge structure of deep learning-based medical image processing research through bibliometric analysis and explores the research hotspots and possible development trends in this field. Methods: Retrieve the Web of Science Core Collection database using the search terms "deep learning," "medical image processing," and their synonyms. Use CiteSpace for visual analysis of authors, institutions, countries, keywords, co-cited references, co-cited authors, and co-cited journals. Results: The analysis was conducted on 562 highly cited papers retrieved from the database. The trend chart of the annual publication volume shows an upward trend. Pheng-Ann Heng, Hao Chen, and Klaus Hermann Maier-Hein are among the active authors in this field. Chinese Academy of Sciences has the highest number of publications, while the institution with the highest centrality is Stanford University. The United States has the highest number of publications, followed by China. The most frequent keyword is "Deep Learning," and the highest centrality keyword is "Algorithm." The most cited author is Kaiming He, and the author with the highest centrality is Yoshua Bengio. Conclusion: The application of deep learning in medical image processing is becoming increasingly common, and there are many active authors, institutions, and countries in this field. Current research in medical image processing mainly focuses on deep learning, convolutional neural networks, classification, diagnosis, segmentation, image, algorithm, and artificial intelligence. The research focus and trends are gradually shifting toward more complex and systematic directions, and deep learning technology will continue to play an important role.

Vessel wall MRI characteristics associated with intraprocedural stent thrombosis during angioplasty for intracranial atherosclerotic stenosis.

BACKGROUND: Few studies have so far explored plaque characteristics on high-resolution magnetic resonance vessel wall imaging (HR-VWI) associated with intraprocedural stent thrombosis (IPST) during angioplasty for intracranial atherosclerotic stenosis (ICAS). We aimed to investigate the plaque features on HR-VWI associated with IPST during stenting for ICAS. METHODS: This study recruited 77 patients with ICAS who underwent intracranial stenting using the Gateway-Wingspan system, and were performed with enhanced pre- and post-contrast T1-weighted HR-VWI on a 3.0T MRI scanner before angioplasty. During stenting for ICAS, eight patients (male: 100%, age mean ± standard deviation (SD): 58.7±2.47) developed IPST within 30 minutes after stenting. To ensure comparability, 16 patients who had undergone intracranial stenting but did not develop IPST were matched as controls for this study. Univariable and binary logistic models were used to explore the plaque characteristics on HR-VWI associated with IPST. RESULTS: Patients who developed IPST had less plaque diffusion (37.50% vs 81.25%, p=0.036), a more severe degree of area stenosis (median 96.30% vs 81.65%, p<0.01), and a higher plaque enhancement index (median 37.99 vs 13.12, p<0.01) compared with those who did not. After multivariate adjustment, IPST was independently associated with a more severe degree of area stenosis (adjusted odds ratio (OR) 1.20, 95% confidence interval (CI) 1.01-1.43, p=0.044) and a higher plaque enhancement index (adjusted OR 1.17, 95% CI 1.01 to 1.36, p=0.036). CONCLUSION: Intraprocedural stent thrombosis during intracranial angioplasty for patients with ICAS may be independently associated with a higher plaque enhancement index and a more severe degree of area stenosis on HR-VWI.

Bidirectional Droplet Manipulation on Magnetically Actuated Superhydrophobic Ratchet Surfaces.

Droplet manipulation has garnered significant attention in various fields due to its wide range of applications. Among many different methods, magnetic actuation has emerged as a promising approach for remote and instantaneous droplet manipulation. In this study, we present the bidirectional droplet manipulation on a magnetically actuated superhydrophobic ratchet surface. The surface consists of silicon strips anchored on elastomer ridges with superhydrophobic black silicon structures on the top side and magnetic layers on the bottom side. The soft magnetic properties of the strips enable their bidirectional tilting to form a ratchet surface and thus bidirectional droplet manipulation upon varying external magnetic field location and strength. Computational multiphysics models were developed to predict the tilting of the strips, demonstrating the concept of bidirectional tilting along with a tilting angle hysteresis theory. Experimental results confirmed the soft magnetic hysteresis and consequential bidirectional tilting of the strips. The superhydrophobic ratchet surface formed by the tilting strips induced the bidirectional self-propulsion of dispensed droplets through the Laplace pressure gradient, and the horizontal acceleration of the droplets was found to be positively correlated with the tilting angle of the strips. Additionally, a finite element analysis was conducted to identify the critical conditions for dispensed droplet penetration through the gaps between the strips, which hinder the droplet's self-propulsion. The models and findings here provide substantial insights into the design and optimization of magnetically actuated superhydrophobic ratchet surfaces to manipulate droplets in the context of digital microfluidic applications.