Time trends in the incidence of interstitial lung disease across Brazil, Russia, India, China and South Africa (BRICS) from 1990 to 2019: An age-period-cohort analysis.

BACKGROUND AND OBJECTIVE: The global incidence of interstitial lung disease (ILD) has risen over the past few decades. However, few studies have evaluated the status and incidence trends of ILD in Brazil, Russia, India, China and South Africa (BRICS). This study assesses the trends of ILD incidence across the BRICS with an emphasis on ILD changes from 1990 to 2019. METHODS: Incidence rates were estimated by the data obtained from the Global Burden of Disease Study 2019 (GBD 2019). Age-period-cohort modelling was used to estimate the effects on ILD from 1990 to 2019, and the net drift and local drift were calculated. RESULTS: In 2019, a total of 11.4 million cases of ILD were reported in the BRICS countries. From 1990 to 2019, the incidence rate of ILD in BRICS showed an upward trend. India consistently reported the highest incidence rate, while China showed the fastest growth rate (107.6%). Russia reported a similar incidence rates for men and women, with a lower age of peak incidence compared to the other four countries. We found the time effect was unfavourable for BRICS in the first decade, especially for Brazil; in China and Brazil, the risk of people born after 1960 has rapidly decreased. CONCLUSION: ILD shows a rising incidence in BRICS. with the trends varying based on age and other environmental factors. BRICS should strengthen specific public health approaches and policies for different stages and populations.

Triptolide regulates neutrophil function through the Hippo signaling pathway to alleviate rheumatoid arthritis disease progression.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammatory changes in the joints, the etiology of which is unclear. It is now well established that regulated cell death (RCD) and migration of neutrophils play an important role in the pathogenesis of RA. Tripterygium wilfordii Hook.f (TwHF) is a total saponin extracted from the root of Tripterygium wilfordii Hook.f, a plant of the family Wesleyanaceae, which has strong anti-inflammatory and immunomodulatory effects and has been used as a basic drug in the clinical treatment of RA. Despite the good efficacy of TwHF treatment, the mechanism of action of TwHF remains unclear. Several studies have demonstrated that the drug tripterygium glycosides, in which TwHF is the main ingredient, has achieved excellent efficacy in the clinical treatment of RA. Investigations have also found that TwHF can affect cellular RCD, cell migration, cell proliferation, and the apoptosis-related Hippo signaling pathway. In this study, we first analyzed the RCD and migration differences of neutrophils in patients with RA through network pharmacology and transcriptome analysis. Subsequently, we used electron microscopy, immunofluorescence, and other methods to identify the RCD phenotype of neutrophils. In collagen-induced arthritis (CIA) model, we demonstrated that Triptolide (the main active ingredient in TwHF) could alleviate the progression of arthritis by reducing the bone destruction and the infiltration of neutrophils. Furthermore, in vitro experiments showed that Triptolide induced neutrophil apoptosis, inhibited the formation of neutrophil extracellular traps (NETs), and impeded the neutrophil migration process in a Hippo pathway-dependent manner. Taken together, these findings indicate that Triptolide has potential for treating RA and provide theoretical support for the clinical application of TwHF, as a traditional Chinese medicine, in RA.

Stabilization of NCM811 cathode interface through macromolecular compound protective film formed by 2,5-bis(2,2,2-trifluoroethoxy)-benzoic acid additive in lithium metal batteries.

Lithium metal batteries (LMBs) offer substantial promise for next-generation energy storage owing to lithium metal's low reduction potential (-3.045 V vs. the standard hydrogen electrode) and its high specific capacity of 3860 mA h g-1. Among various cathode materials in LMBs, LiNi0.8Co0.1Mn0.1O2 (NCM811) is extensively employed because of its notably high specific capacity (over 200 mA h g-1) and comparatively lower cost. However, structural stress, nickel ions migration, and uneven Li+ deposition in NCM811 particles lead to cracking, irreversible decomposition of active substances, and the growth of mossy Li dendrites, causing severe capacity decline and low Coulomb efficiency in LMBs. In this study, we introduce an effective ethoxyl additive, 2,5-bis(2,2,2-trifluoroethoxy)-benzoic acid (2,5BTBA), directly into the carbonate electrolyte. This additive forms a dense and conductive macromolecular protective film on the NCM811 cathode and lithium metal anode during initial cycles, preventing electrode contact with the electrolyte. Consequently, it safeguards the cathode's structural integrity and enables dense lithium deposition. Adding 3 wt% 2,5BTBA, the Li/NCM811 battery retains a high capacity of 150.60 mA h g-1 and 89.41% retention after 700 cycles at 0.5C, maintaining an average Coulomb efficiency of 99.13%. This study presents an efficient and straightforward strategy to enhance the capacity retention of LMBs.

Association of ambient ozone exposure and greenness exposure with hemorrhagic stroke mortality at different times: A cohort study in Shandong Province, China.

Evidence on the association between long-term ozone exposure and greenness exposure and hemorrhagic stroke (HS) is limited, with mixed results. One potential source of this inconsistency is the difference in exposure time metrics. This study aimed to investigate the association between long-term exposure to ambient ozone, greenness, and mortality from HS using exposure metrics at different times. We also examined whether greenness exposure modified the relationship between ozone exposure and mortality due to HS. The study population consisted of 45771 participants aged ≥40 y residing in 20 counties in Shandong Province who were followed up from 2013 to 2019. Ozone exposure metrics (annual mean and warm season) and the normalized difference a measure of greenness exposure, were calculated. The relationship between environmental exposures (ozone and greenness exposures) and mortality from HS was assessed using time-dependent Cox proportional hazards models, and the modification of greenness exposure was examined using stratified analysis with interaction terms. The person-years at the end of follow-up were 90,663. With full adjustments, the risk of death from hemorrhagic stroke increased by 5% per interquartile range increase in warm season ozone [hazard ratio =1.05; 95 % confidence interval: 1.01-1.08]. No clear association was observed between annual ozone and mortality HS. Both the annual and summer NDVI were found to reduce the risk of HS mortality. The relationships were influenced by age, sex, and residence (urban or rural). Furthermore, greenness exposure was shown to have a modifying effect on the relationship between ozone exposure and the occurrence of HS mortality (P for interaction = 0.001). Long-term exposure to warm season O3 was positively associated with HS mortality, while greenness exposure was inversely associated with HS mortality. Greenness exposure may mitigate the negative effects of warm season ozone exposure on HS mortality.

Autonomous Needle Navigation in Subretinal Injections via iOCT.

Subretinal injection is an effective method for direct delivery of therapeutic agents to treat prevalent subretinal diseases. Among the challenges for surgeons are physiological hand tremor, difficulty resolving single-micron scale depth perception, and lack of tactile feedback. The recent introduction of intraoperative Optical Coherence Tomography (iOCT) enables precise depth information during subretinal surgery. However, even when relying on iOCT, achieving the required micron-scale precision remains a significant surgical challenge. This work presents a robot-assisted workflow for high-precision autonomous needle navigation for subretinal injection. The workflow includes online registration between robot and iOCT coordinates; tool-tip localization in iOCT coordinates using a Convolutional Neural Network (CNN); and tool-tip planning and tracking system using real-time Model Predictive Control (MPC). The proposed workflow is validated using a silicone eye phantom and ex vivo porcine eyes. The experimental results demonstrate that the mean error to reach the user-defined target and the mean procedure duration are within an acceptable precision range. The proposed workflow achieves a 100% success rate for subretinal injection, while maintaining scleral forces at the scleral insertion point below 15mN throughout the navigation procedures.

Sulfur-containing substances in sewers: Transformation, transportation, and remediation.

Sulfur-containing substances in sewers frequently incur unpleasant odors, corrosion-related economic loss, and potential human health concerns. These observations are principally attributed to microbial reactions, particularly the involvement of sulfate-reducing bacteria (SRB) in sulfur reduction process. As a multivalent element, sulfur engages in complex bioreactions in both aerobic and anaerobic environments. Organic sulfides are also present in sewage, and these compounds possess the potential to undergo transformation and volatilization. In this paper, a comprehensive review was conducted on the present status regarding sulfur transformation, transportation, and remediation in sewers, including both inorganic and organic sulfur components. The review extensively addressed reactions occurring in the liquid and gas phase, as well as examined detection methods for various types of sulfur compounds and factors affecting sulfur transformation. Current remediation measures based on corresponding mechanisms were presented. Additionally, the impacts of measures implemented in sewers on the subsequent wastewater treatment plants were also discussed, aiming to attain better management of the entire wastewater system. Finally, challenges and prospects related to the issue of sulfur-containing substances in sewers were proposed to facilitate improved management and development of the urban water system.

Genetically predicted waist circumference and risk of atrial fibrillation.

INTRODUCTION: Observational studies have revealed an association between waist circumference (WC) and atrial fibrillation (AF). However, it is difficult to infer a causal relationship from observational studies because the observed associations could be confounded by unknown risk factors. Therefore, the causal role of WC in AF is unclear. This study was designed to investigate the causal association between WC and AF using a two-sample Mendelian randomization (MR) analysis. METHODS: In our two-sample MR analysis, the genetic variation used as an instrumental variable for MR was acquired from a genome-wide association study (GWAS) of WC (42 single nucleotide polymorphisms with a genetic significance of P <5 × 10 -8 ). The data of WC (from the Genetic Investigation of ANthropometric Traits consortium, containing 232,101 participants) and the data of AF (from the European Bioinformatics Institute database, containing 55,114 AF cases and 482,295 controls) were used to assess the causal role of WC on AF. Three different approaches (inverse variance weighted [IVW], MR-Egger, and weighted median regression) were used to ensure that our results more reliable. RESULTS: All three MR analyses provided evidence of a positive causal association between high WC and AF. High WC was suggested to increase the risk of AF based on the IVW method (odds ratio [OR] = 1.43, 95% confidence interval [CI], 1.30-1.58, P = 2.51 × 10 -13 ). The results of MR-Egger and weighted median regression exhibited similar trends (MR-Egger OR = 1.40 [95% CI, 1.08-1.81], P = 1.61 × 10 -2 ; weighted median OR = 1.39 [95% CI, 1.21-1.61], P = 1.62 × 10 -6 ). MR-Egger intercepts and funnel plots showed no directional pleiotropic effects between high WC and AF. CONCLUSIONS: Our findings suggest that greater WC is associated with an increased risk of AF. Taking measures to reduce WC may help prevent the occurrence of AF.

Robotic Navigation Autonomy for Subretinal Injection via Intelligent Real-Time Virtual iOCT Volume Slicing.

In the last decade, various robotic platforms have been introduced that could support delicate retinal surgeries. Concurrently, to provide semantic understanding of the surgical area, recent advances have enabled microscope-integrated intraoperative Optical Coherent Tomography (iOCT) with high-resolution 3D imaging at near video rate. The combination of robotics and semantic understanding enables task autonomy in robotic retinal surgery, such as for subretinal injection. This procedure requires precise needle insertion for best treatment outcomes. However, merging robotic systems with iOCT introduces new challenges. These include, but are not limited to high demands on data processing rates and dynamic registration of these systems during the procedure. In this work, we propose a framework for autonomous robotic navigation for subretinal injection, based on intelligent real-time processing of iOCT volumes. Our method consists of an instrument pose estimation method, an online registration between the robotic and the iOCT system, and trajectory planning tailored for navigation to an injection target. We also introduce intelligent virtual B-scans, a volume slicing approach for rapid instrument pose estimation, which is enabled by Convolutional Neural Networks (CNNs). Our experiments on ex-vivo porcine eyes demonstrate the precision and repeatability of the method. Finally, we discuss identified challenges in this work and suggest potential solutions to further the development of such systems.

Autonomous Needle Navigation in Retinal Microsurgery: Evaluation in ex vivo Porcine Eyes.

Important challenges in retinal microsurgery include prolonged operating time, inadequate force feedback, and poor depth perception due to a constrained top-down view of the surgery. The introduction of robot-assisted technology could potentially deal with such challenges and improve the surgeon's performance. Motivated by such challenges, this work develops a strategy for autonomous needle navigation in retinal microsurgery aiming to achieve precise manipulation, reduced end-to-end surgery time, and enhanced safety. This is accomplished through real-time geometry estimation and chance-constrained Model Predictive Control (MPC) resulting in high positional accuracy while keeping scleral forces within a safe level. The robotic system is validated using both open-sky and intact (with lens and partial vitreous removal) ex vivo porcine eyes. The experimental results demonstrate that the generation of safe control trajectories is robust to small motions associated with head drift. The mean navigation time and scleral force for MPC navigation experiments are 7.208 s and 11.97 mN, which can be considered efficient and well within acceptable safe limits. The resulting mean errors along lateral directions of the retina are below 0.06 mm, which is below the typical hand tremor amplitude in retinal microsurgery.

Impact of dexmedetomidine on mortality in critically ill patients with acute kidney injury: a retrospective propensity score matching analysis.

OBJECTIVES: This study sought to estimate the effect of dexmedetomidine (DEX) administration on mortality in critically ill patients with acute kidney injury (AKI). DESIGN: A retrospective cohort study. SETTING: The study sourced its data from the Multiparameter Intelligent Monitoring in Intensive Care Database IV (MIMIC-IV), a comprehensive database of intensive care unit patients. PARTICIPANTS: A total of 15 754 critically ill patients with AKI were enrolled from the MIMIC-IV database. PRIMARY AND SECONDARY OUTCOME: Primary outcome was in-hospital mortality and secondary outcome was 180-day mortality. RESULTS: 15 754 critically ill AKI patients were included in our analysis. We found that DEX use decreased in-hospital mortality risk by 38% (HR 0.62, 95% CI 0.55 to 0.70) and 180-day mortality risk by 23% (HR 0.77, 95% CI 0.69 to 0.85). After adjusting for confounding factors, DEX can reduce all three stages of AKI in in-hospital mortality. CONCLUSIONS: Our retrospective cohort study suggests that DEX significantly correlates with decreased risk-adjusted in-hospital and 180-day mortality in critically ill AKI patients. Nonetheless, future randomised controlled trials are warranted to validate our findings.

Effects of greenness in university campuses on test anxiety among Chinese university students during COVID-19 lockdowns: a correlational and mediation analysis.

The purpose of this study is to investigate the correlations of greenness exposure with test anxiety among university students during COVID-19 lockdowns and to explore their mechanisms. We conducted a cross-sectional study with 2609 university students in Anhui and Shandong provinces, China. We assessed perceived campus greenness using a five-point Likert scale for quality, visibility, abundance, usage, and accessibility. Objective greenness was estimated via average normalised difference vegetation index (NDVI) in 1,000-, 1,500-, and 2,000-m radius zones around each of the campuses. A generalised linear mixed model examined the associations between greenness and test anxiety and to evaluate the mediation effects of physical activity, body mass index (BMI), and air pollution. Results showed that higher NDVI1500-m correlated with lower test anxiety (OR = 0.871; 95% CI: 0.851, 0.891), physical activity may partially mediate this association. Increased campus greenness may alleviate test anxiety among Chinese university students.

Cardiovascular metrics on CT pulmonary angiography in patients with pulmonary hypertension - re-evaluation under the updated guidelines of pulmonary hypertension.

PURPOSE: To re-assess cardiovascular metrics on computed tomography pulmonary angiography (CTPA) in predicting pulmonary hypertension (PH) under the 2022 ESC/ERS guidelines. MATERIALS AND METHODS: This observational study retrospectively included 272 patients (female 143, mean age = 54.9 ± 12.5 years old) with suspected PH. 218 patients were grouped to evaluate cardiovascular metrics on CTPA and develop a binary logistic regression model. The other 54 patients were grouped into the validation group to assess the performance of the prediction model under the updated criteria. Based on mean pulmonary artery pressure (mPAP), patients were divided into three groups: group A consisted of patients with mPAP ≤ 20 mmHg, group B included patients with 20 mmHg < mPAP < 25 mmHg, and group C comprised patients with mPAP ≥ 25 mmHg. Cardiovascular metrics among the three groups were compared, and receiver operating characteristic curves (ROCs) were used to evaluate the performance of cardiovascular metrics in predicting mPAP > 20 mmHg. RESULTS: The main pulmonary arterial diameter (MPAd), MPAd/ascending aorta diameter ratio (MPAd/AAd ratio), and right ventricular free wall thickness (RVFWT) showed significant differences among the three groups (p < 0.05). The area under curve (AUC) of MPAd was larger than MPAd/AAd ratio and RVFWT. A MPAd cutoff value of 30.0 mm has a sensitivity of 83.1% and a specificity of 90.4%. The AUC of the binary logistic regression model (Z = - 12.98187 + 0.31053 MPAd + 1.04863 RVFWT) was 0.938 ± 0.018. In the validation group, the AUC, sensitivity, specificity, and accuracy of the prediction model were 0.878, 92.7%, 76.9%, and 88.9%, respectively. CONCLUSION: Under the updated criteria, MPAd with a threshold value of 30.0 mm has better sensitivity and specificity in predicting PH. The binary logistic regression model may improve the diagnostic accuracy. CRITICAL RELEVANCE STATEMENT: Under the updated criteria, the main pulmonary arterial diameter with a threshold value of 30.0 mm has better sensitivity and specificity in predicting pulmonary hypertension. The binary logistic regression model may improve diagnostic accuracy. KEY POINTS: • According to 2022 ESC/ERS guidelines, a MPAd cutoff value of 30.0 mm has better sensitivity and specificity in predicting mPAP > 20 mmHg • A binary logistic regression model (Z = - 12.98187 + 0.31053 MPAd + 1.04863 RVFWT) was developed and had a sensitivity, specificity, and accuracy of 92.7%, 76.9%, and 88.9% in predicting mPAP > 20 mmHg. • A binary logistic regression prediction model outperforms MPAd in predicting mPAP > 20 mmHg.

Associations of air pollution and greenness with global burden of breast cancer: an ecological study.

Despite the significance of the associations of air pollution and greenness with the risk of breast cancer, this topic has not been investigated on a global scale. We conducted an ecological study using 7 years of data from 162 countries. Disability-adjusted life years (DALYs) and incidence data were used to represent the breast cancer disease burden. Particulate matter with a diameter < 2.5 µm (PM2.5), ozone (O3), nitrogen dioxide (NO2), and the normalized difference vegetation index (NDVI) were adopted as our exposures. We employed generalized linear mixed models to explore the relationship between air pollution and greenness on breast cancer disease burden. The rate ratio (RR) and its 95% confidence interval (CI) indicate the effect size. There is a positive association between air pollution and the burden of breast cancer disease. Contrarily, per interquartile range increment in NDVI was negatively associated with DALYs and incidence. In terms of air pollutants and breast cancer, NDVI seems to have a significant influence on the relationship between these two conditions. A higher amount of greenness helps to alleviate the negative association of air pollution on breast cancer. PM2.5 and O3 play a mediating role in the relationship between greenness and breast cancer disease burden. In areas with higher levels of greenness, there is a possibility that the inverse association between air pollutants and the burden of breast cancer may be influenced.

Exosomes derived from LPS-preconditioned bone marrow-derived MSC modulate macrophage plasticity to promote allograft survival via the NF-κB/NLRP3 signaling pathway.

OBJECTIVES: This study investigated whether exosomes from LPS pretreated bone marrow mesenchymal stem cells (LPS pre-MSCs) could prolong skin graft survival. METHODS: The exosomes were isolated from the supernatant of MSCs pretreated with LPS. LPS pre-Exo and rapamycin were injected via the tail vein into C57BL/6 mice allografted with BALB/c skin; graft survival was observed and evaluated. The accumulation and polarization of macrophages were examined by immunohistochemistry. The differentiation of macrophages in the spleen was analyzed by flow cytometry. For in vitro, an inflammatory model was established. Specifically, bone marrow-derived macrophages (BMDMs) were isolated and cultured with LPS (100 ng/ml) for 3 h, and were further treated with LPS pre-Exo for 24 h or 48 h. The molecular signaling pathway responsible for modulating inflammation was examined by Western blotting. The expressions of downstream inflammatory cytokines were determined by Elisa, and the polarization of macrophages was analyzed by flow cytometry. RESULTS: LPS pre-Exo could better ablate inflammation compared to untreated MSC-derived exosomes (BM-Exo). These loaded factors inhibited the expressions of inflammatory factors via a negative feedback mechanism. In vivo, LPS pre-Exo significantly attenuated inflammatory infiltration, thus improving the survival of allogeneic skin graft. Flow cytometric analysis of BMDMs showed that LPS pre-Exo were involved in the regulation of macrophage polarization and immune homeostasis during inflammation. Further investigation revealed that the NF-κB/NLRP3/procaspase-1/IL-1ß signaling pathway played a key role in LPS pre-Exo-mediated regulation of macrophage polarization. Inhibiting NF-κB in BMDMs could abolish the LPS-induced activation of inflammatory pathways and the polarization of M1 macrophages while increasing the proportion of M2 cells. CONCLUSION: LPS pre-Exo are able to switch the polarization of macrophages and enhance the resolution of inflammation. This type of exosomes provides an improved immunotherapeutic potential in prolonging graft survival.

Effect of neighbourhood greenness on the association between air pollution and risk of stroke first onset: A case-crossover study in shandong province, China.

BACKGROUND: Higher neighbourhood greenness is associated with beneficial health outcomes, and short-term exposure to air pollution is associated with an elevated risk of stroke onset. However, little is known about their interactions. METHODS: Daily data on stroke first onset were collected from 20 counties in Shangdong Province, China, from 2013 to 2019. The enhanced vegetation index (EVI) and concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and sulfur dioxide (SO2) were calculated for each individual at the village or community level based on their home address to measure their neighbourhood exposure to greenness and air pollution. EVI was categorised as low or high, and a time-stratified case-crossover design was used to estimate the percent excess risk (ER%) of stroke associated with short-term exposure to air pollution. We further stratified greenness on the basis of EVI values into quartiles and introduced interaction terms between air pollutant concentrations and the median EVI values of the quartiles to assess the effect of greenness on the associations between short-term exposure and stroke. RESULTS: Individuals living in the high-greenness areas had weaker associations between total stroke risk and exposure to NO2 (low greenness: ER% = 1.765% [95% CI 1.205%-2.328%]; high greenness: ER% = 0.368% [95% CI -0.252% to 0.991%]; P = 0.001), O3 (low greenness: 0.476% [95% CI 0.246%-0.706%]; high greenness: ER% = 0.085% [95% CI -0.156% to 0.327%]; P = 0.011), and SO2 (low greenness: 0.632% [95% CI 0.138%-1.129%]; high greenness: ER% = -0.177% [95% CI -0.782% to 0.431%]; P = 0.035). CONCLUSION: Residence in areas with higher greenness was related to weaker associations between air pollution and stroke risk, suggesting that effectively planning green spaces can improve public health.

Acute kidney injury after infant cardiac surgery: a comparison of pRIFLE, KDIGO, and pROCK definitions.

BACKGROUND: KDIGO and pRIFLE classifications are commonly used in pediatric acute kidney injury (AKI). As a novel AKI definition, pROCK considered the high variability of serum creatinine in children. This study aimed to compare the above three definitions for AKI in infants undergoing cardiac surgery. METHODS: We analyzed a clinical cohort of 413 infants undergoing cardiac surgery. AKI was defined and staged according to pRIFLE, KDIGO, and pROCK, respectively. Incidence differences and diagnostic agreement across definitions were assessed. The association between postoperative outcomes and AKI by each definition was investigated. RESULTS: Postoperative AKI was identified in 185 (44.8%), 160 (38.7%), and 77 (18.6%) patients according to pRIFLE, KDIGO, and pROCK, respectively. The agreement between pRIFLE and KDIGO was almost perfect (κ = 0.88), while there was only a slight agreement between pROCK and them. AKI by pROCK was independently associated with adverse outcomes (p = 0.003) and prolonged mechanical ventilation (p = 0.002). CONCLUSIONS: There were considerable differences in AKI incidence and staging among definitions. Compared with pRIFLE and KDIGO, AKI defined by pROCK was significantly reduced and better associated with postoperative adverse outcomes.

Association of greenness with the disease burden of lower respiratory infections and mediation effects of air pollution and heat: a global ecological study.

Exposure to greenness is increasingly linked to beneficial health outcomes, but the associations between greenness and the disease burden of lower respiratory infections (LRIs) are unclear. We used the normalized difference vegetation index (NDVI) and the leaf area index (LAI) to measure greenness and incidence, death, and disability-adjusted life years (DALYs) due to LRIs to represent the disease burden of LRIs. We applied a generalized linear mixed model to evaluate the association between greenness and LRI disease burden and performed a stratified analysis, after adjusting for covariates. Additionally, we assessed the potential mediating effects of fine particulate matter (PM2.5), ozone (O3), nitrogen dioxide (NO2), and heat on the association between greenness and the disease burden of LRIs. In the adjusted model, one 0.1 unit increase of NDVI and 0.5 increase in LAI were significantly inversely associated with incidence, death, and DALYs due to LRIs, respectively. Greenness was negatively correlated with the disease burden of LRIs across 15-65 age group, both sexes, and low SDI groups. PM2.5, O3, and heat mediated the effects of greenness on the disease burden of LRIs. Greenness was significantly negatively associated with the disease burden of LRIs, possibly by reducing exposure to air pollution and heat.

Itaconic acid induces angiogenesis and suppresses apoptosis via Nrf2/autophagy to prolong the survival of multi-territory perforator flaps.

Background: Perforator flaps are widely used in hand microsurgery to reconstruct and repair soft tissue injuries. However, ischemia and subsequent ischemia-reperfusion injury may cause distal necrosis of the flap. Itaconic acid (IA) is a modulator of macrophage function, which exerts anti-inflammatory effects in macrophage activation. Methods: The necrotic area of the flap was detected by measuring the flap temperature with an infrared thermometer. Flap cell apoptosis was detected by TUNEL staining and Western blot analysis of the apoptosis-associated proteins Bcl-2 and Bax. HE staining was used to detect angiogenesis of the skin flaps. CD31 was detected to identify positive vascular expression, and the survival of choke vessels in different areas of the skin flap was assessed by arteriography. In addition, Western blot was performed to quantify the expressions of VEGF, Nrf2, LC3II, SQSTM1, and CTSD. Results: Itaconic acid raises VEGF protein levels in skin flaps and the number of CD31-positive vessels. The skin flaps in the IA treatment group exhibited higher neovascularization and less necrosis than those in the control group. The results of TUNEL staining and Western blot revealed that Itaconic acid attenuated apoptosis in the ischemic area of flap. The combination of itaconic acid and Nrf2 inhibitor ML385 reversed this beneficial effect. The results revealed that itaconic acid attenuated apoptosis, enhanced angiogenesis, and enhanced autophagy. Conclusion: In summary, our findings indicate that itaconic acid might be an effective treatment to reduce flap necrosis. Additionally, this study identified a novel mechanism for the effects of itaconic acid on flap survival.

Ferromagnetism emerged from non-ferromagnetic atomic crystals.

The recently emerged ferromagnetic two-dimensional (2D) materials provide unique platforms for compact spintronic devices down to the atomic-thin regime; however, the prospect is hindered by the limited number  of ferromagnetic 2D materials discovered with limited choices of magnetic properties. If 2D antiferromagnetism could be converted to 2D ferromagnetism, the range of 2D magnets and their potential applications would be significantly broadened. Here, we discovered emergent ferromagnetism by interfacing non-magnetic WS2 layers with the antiferromagnetic FePS3. The WS2 exhibits an order of magnitude enhanced Zeeman effect with a saturated interfacial exchange field ~38 Tesla. Given the pristine FePS3 is an intralayer antiferromagnet, the prominent interfacial exchange field suggests the formation of ferromagnetic FePS3 at interface. Furthermore, the enhanced Zeeman effect in WS2 is found to exhibit a strong WS2-thickness dependence, highlighting the layer-tailorable interfacial exchange coupling in WS2-FePS3 heterostructures, which is potentially attributed to the thickness-dependent interfacial hybridization.

Metformin induces M2 polarization via AMPK/PGC-1α/PPAR-γ pathway to improve peripheral nerve regeneration.

OBJECTIVES: Investigating the effect of metformin on peripheral nerve regeneration and the molecular mechanism. METHODS: In this study, a rat model of sciatic nerve injury and an inflammatory bone marrow-derived macrophage (BMDM) cell model were established. We assessed the sensory and motor function of the hind limbs four weeks after sciatic nerve injury, immunofluorescence was used to detect axonal regeneration and myelin formation, as well as local macrophage subtypes. We investigated the polarizing effect of metformin on inflammatory macrophages, and western blotting was applied to detect the molecular mechanisms behind it. RESULTS: Metformin treatment accelerated functional recovery, axon regeneration and remyelination, and promoted M2 macrophage polarization. In vivo, metformin transformed pro-inflammatory macrophages into pro-regeneration M2 macrophages. Protein expression levels of phosphorylated AMP-activated protein kinase (p-AMPK), proliferator-activated receptor-γ co-activator 1α (PGC-1α), and peroxisome proliferator-activated receptor-γ (PPAR-γ) increased upon metformin treatment. Moreover, inhibition of AMPK abolished the effects of metformin treatment on M2 polarization. CONCLUSION: Metformin promoted M2 macrophage polarization by activating the AMPK/PGC-1α/PPAR-γ signaling axis, thereby promoting peripheral nerve regeneration.