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Diabetic retinopathy (DR) is a leading cause of blindness and vision impairment worldwide and represents one of the most common complications among diabetic patients. Current treatment modalities for DR, including laser photocoagulation, intravitreal injection of corticosteroid, and anti-vascular endothelial growth factor (VEGF) agents, target primarily vascular lesions. However, these approaches are invasive and have several limitations, such as potential loss of visual function, retinal scars and cataract formation, and increased risk of ocular hypertension, vitreous hemorrhage, retinal detachment, and intraocular inflammation. Recent studies have suggested mitochondrial dysfunction as a pivotal factor leading to both the vascular and neural damage in DR. Given that Coenzyme Q10 (CoQ10) is a proven mitochondrial stabilizer with antioxidative properties, this study investigated the effect of CoQ10 eyedrops [in conjunction with vitamin E d-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS)] on DR-induced neurodegeneration using a type 2 diabetes mouse model (C57BLKsJ-db/db mice). Utilizing a comprehensive electroretinography protocol, supported by immunohistochemistry, our results revealed that topical application of CoQ10 eyedrops conjugated with vitamin E TPGS produced a neuroprotective effect against diabetic-induced neurodegeneration by preserving the function and histology of various retinal neural cell types. Compared to the control group, mice treated with CoQ10 exhibited thicker outer and inner nuclear layers, higher densities of photoreceptor, cone cell, and rod-bipolar cell dendritic boutons, and reduced glial reactivity and microglial cell density. Additionally, the CoQ10 treatment significantly alleviated retinal levels of MMP-9 and enhanced mitochondrial function. These findings provide further insight into the role of mitochondrial dysfunction in the development of DR and suggest CoQ10 eyedrops, conjugated with vitamin E TPGS, as a potential complementary therapy for DR-related neuropathy.

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is one of the most destructive fungal diseases threatening global wheat production. Exploring powdery mildew resistance (Pm) gene(s) and dissecting the molecular mechanism of the host resistance are critical to effectively and reasonably control this disease. Durum wheat (Triticum turgidum L. var. durumDesf.) is an important gene donor for wheat improvement against powdery mildew. In this study, a resistant durum wheat accession W762 was used to investigate its potential resistance component(s) and profile its expression pattern in responding to Bgt invasion using bulked segregant RNA-Seq (BSR-Seq) and further qRT-PCR verification. Genetic analysis showed that the powdery mildew resistance in W762 did not meet monogenic inheritance and complex genetic model might exist within the population of W762 × Langdon (susceptible durum wheat). After BSR-Seq, 6,196 consistently different single nucleotide polymorphisms (SNPs) were called between resistant and susceptible parents and bulks, and among them, 763 SNPs were assigned to the chromosome arm 7B. Subsequently, 3,653 differentially expressed genes (DEGs) between resistant and susceptible parents and bulks were annotated and analyzed by Gene Ontology (GO), Cluster of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The potential regulated genes were selected and analyzed their temporal expression patterns following Bgt inoculation. As a result, nine disease-related genes showed distinctive expression profile after Bgt invasion and might serve as potential targets to regulate the resistance against powdery mildew in W762. Our study could lay a foundation for analysis of the molecular mechanism and also provide potential targets for the improvement of durable resistance against powdery mildew.

BackgroundPrevious epidemiological studies have found a link between colorectal cancer (CRC) and human dietary habits. However, the inherent limitations and inevitable confounding factors of the observational studies may lead to the inaccurate and doubtful results. The causality of dietary factors to CRC remains elusive.MethodsWe conducted two-sample Mendelian randomization (MR) analyses utilizing the data sets from the IEU Open GWAS project. The exposure datasets included alcoholic drinks per week, processed meat intake, beef intake, poultry intake, oily fish intake, non-oily fish intake, lamb/mutton intake, pork intake, cheese intake, bread intake, tea intake, coffee intake, cooked vegetable intake, cereal intake, fresh fruit intake, salad/raw vegetable intake, and dried fruit intake. In our MR analyses, the inverse variance weighted (IVW) method was employed as the primary analytical approach. The weighted median, MR-Egger, weighted mode, and simple mode were also applied to quality control. Heterogeneity and pleiotropic analyses were implemented to replenish the accuracy of the results.ResultsMR consequences revealed that alcoholic drinks per week [odds ratio (OR): 1.565, 95% confidence interval (CI): 1.068–2.293, p = 0.022], non-oily fish intake (OR: 0.286; 95% CI: 0.095–0.860; p = 0.026), fresh fruit intake (OR: 0.513; 95% CI: 0.273–0.964; p = 0.038), cereal intake (OR: 0.435; 95% CI: 0.253–0.476; p = 0.003) and dried fruit intake (OR: 0.522; 95% CI: 0.311–0.875; p = 0.014) was causally correlated with the risk of CRC. No other significant relationships were obtained. The sensitivity analyses proposed the absence of heterogeneity or pleiotropy, demonstrating the reliability of the MR results.ConclusionThis study indicated that alcoholic drinks were associated with an increased risk of CRC, while non-oily fish intake, fresh fruit intake, cereal intake, and dried fruit were associated with a decreased risk of CRC. This study also indicated that other dietary factors included in this research were not associated with CRC. The current study is the first to establish the link between comprehensive diet-related factors and CRC at the genetic level, offering novel clues for interpreting the genetic etiology of CRC and replenishing new perspectives for the clinical practice of gastrointestinal disease prevention.

BackgroundBread wheat is one of the most important food crops associated with ensuring food security and human nutritional health. The starch quality is an important index of high-quality wheat. It is affected by a complex series of factors; among which, suitable sowing time is a key factor.Aim and methodsTo analyze the integrative effects of sowing time on the starch quality of high-quality wheat, in the present study, we selected a high-quality bread wheat cultivar Jinan 17 and investigated the effect of different sowing times on the starch properties and the related genes by analyzing X-ray diffraction patterns, apparent amylose content, thermal properties, pasting properties, in vitro starch digestibility, and qRT-PCR. Meanwhile, we also investigated the agronomic and yield performance that may be associated with the starch properties.ResultsDelayed sowing had little effect on starch crystalline morphology, but there was a tendency to reduce the formation of crystals within wheat starch granules: (1) delayed sowing for 15 days altered the thermal properties of starch, including onset, peak and termination temperatures, and enthalpy changes; (2) delayed sowing for 30 days changed the thermal characteristics of starch relatively insignificant; (3) significant differences in pasting characteristics occurred: peak viscosity and hold-through viscosity increased, while final viscosity, breakdown viscosity, and setback viscosity tended to increase and then decrease, suggesting that delayed sowing caused changes in the surface of the starch granules resulting in a decrease in digestibility. Analysis of related genes showed that several key enzymes in starch biosynthesis were significantly affected by delayed sowing, leading to a reduction in apparent straight-chain starch content. In addition to starch properties, thousand-kernel weight also increased under delayed sowing conditions compared with normal sowing.ConclusionThe impact of delayed sowing on starch quality is multifaceted and complex, from the fine structure, and functional properties of the starch to the regulation of key gene expression. Our study holds significant practical value for optimizing wheat planting management and maximizing the potential in both quality and yield.

BackgroundSeveral studies have confirmed the direct relationship between extracellular acidification and the occurrence of pain. As an effective pain management approach, the mechanism of electroacupuncture (EA) treatment of acidification-induced pain is not fully understood. The purpose of this study was to assess the analgesic effect of EA in this type of pain and to explore the underlying mechanism(s).MethodsWe used plantar injection of the acidified phosphate-buffered saline (PBS; pH 6.0) to trigger thermal hyperalgesia in male Sprague–Dawley (SD) rats aged 6–8 weeks. The value of thermal withdrawal latency (TWL) was quantified after applying EA stimulation to the ST36 acupoint and/or chemogenetic control of astrocytes in the hindlimb somatosensory cortex.ResultsBoth EA and chemogenetic astrocyte activation suppressed the acid-induced thermal hyperalgesia in the rat paw, whereas inhibition of astrocyte activation did not influence the hyperalgesia. At the same time, EA-induced analgesia was blocked by chemogenetic inhibition of astrocytes.ConclusionThe present results suggest that EA-activated astrocytes in the hindlimb somatosensory cortex exert an analgesic effect on acid-induced pain, although these astrocytes might only moderately regulate acid-induced pain in the absence of EA. Our results imply a novel mode of action of astrocytes involved in EA analgesia.

BackgroundThe first-line standard treatment option for patients with NSCLC complicated with Chronic obstructive pulmonary disease (COPD) is still unclear and relies on the treatment option of NSCLC alone. To date, a limited number of retrospective studies have explored the efficacy and safety of immunotherapy in patients with NSCLC complicated with COPD. We therefore designed this study to further explore the efficacy and safety of first-line immunotherapy in patients with NSCLC complicated with COPD.MethodsThis study was designed as a single-armed, single-center, prospective, phase II clinical study. It will include 30 advanced (stage IV) NSCLC combined with COPD primary treatment subjects. Each subject’s diagnosis will be confirmed by clinical, radiographic, pathologic, and pulmonary function evaluation. A fixed dose of 200 mg pembrolizumab will be administered by intravenous infusion on day1 every 3 weeks (Q3W). The management of stable and acute exacerbations of COPD include home oxygen therapy, and the use of conventional medications are also administered. Imaging evaluation will be performed every 6 weeks for 6 months from the first pembrolizumab dose and approximately every 12 weeks thereafter until disease progression or early withdrawal. COPD status will be evaluated every 3 months by pulmonary function, GOLD grading, mMRC score, CAT score, ABCD grouping, and AECOPD severity. The primary outcome is Progression-free survival. The secondary outcome measures include objective response rate, overall survival, rate of acute exacerbations of COPD (times/year), lung function, mMRC score, CAT score, impact of treatment on patient’s health-related quality of life, antibiotic use (including duration and classes), and adverse events associated with immune checkpoint inhibitors. Exploratory endpoint is to explore the association between COPD grade and the degree of immune cell (CD4+ T lymphocytes and CD8+ T lymphocytes) infiltration, as well as the association between COPD grade and the efficacy of immune checkpoint inhibitors.Clinical trial registrationClinicalTrials.gov, identifier NCT05578222.

Abstract Background Sarcopenia and obesity are two abnormal body composition phenotypes, and sarcopenic obesity (SO) is characterized by both low skeletal muscle mass (sarcopenia) and high adiposity (obesity). SO negatively influences the clinical status of patients with chronic obstructive pulmonary disease (COPD). However, the studies exploring the prevalence and clinical effects of SO in COPD patients are limited. Our study aimed to elucidate the prevalence and impact of SO on COPD patients. Methods In this cross-sectional study, the pulmonary function, St. George’s Respiratory Questionnaire, exercise tolerance, body composition, and serum levels of resistin and TNF-α were assessed in 198 COPD patients. The clinical value of serum resistin and TNF-α for predicting SO in patients with COPD was evaluated. Results In the 198 patients with COPD, the prevalence rates of sarcopenia, obesity, and SO in COPD patients were 27.27%, 29.8%, and 9.6%, respectively. Patients with SO experienced more severe symptoms of dyspnea and worse health related quality of life. The expression of resistin increased in patients with SO compared to other patients. The AUC value of serum resistin level for predicting SO was 0.870 (95% CI: 0.799–0.940). BMI (OR: 1.474, 95% CI: 1.124–1.934) and resistin (OR: 1.001, 95% CI: 1.000-1.002) levels were independent risk factors of SO in patients with COPD in Multivariate analysis. Conclusion The prevalence rates of SO in COPD patients was 9.6%. COPD accompanied by SO is significantly associated with worse pulmonary function and poor physical performance. Serum resistin may be a potential adjunct for predicting SO in COPD patients.

Abstract Background Myopia control interventions, such as defocus incorporated multiple segments (DIMS) spectacle lenses, have been adopted in school-aged children to reduce the prevalence of myopia and its complications. This study aimed to investigate the effect of DIMS spectacle lenses on subfoveal choroidal thickness (SfChT) over a period of two years, as the choroidal response to myopic control is a crucial factor in exploring its potential effect on predicting myopia progression. Methods This study involved a secondary analysis of our previous randomized clinical trial. Myopic school-aged children aged 8–13 years were recruited in a two-year study investigating the effect of DIMS spectacle lenses on myopia progression. The treated group received DIMS spectacle lenses (n = 78), while the control group was treated with a pair of single vision (SV) spectacle lenses (n = 80). SfChT was monitored at 1 week, 1, 3, 6, 12, 18 and 24 months post lens wear using spectral-domain optical coherence tomography and a custom made auto-segmentation algorithm utilizing convolutional neural networks. Results SfChT increased significantly after one week of DIMS spectacle lens wear compared to those wearing SV spectacle lenses (adjusted mean change relative to baseline ± SEM at one week; DIMS vs. SV, 6.75 ± 1.52 µm vs. − 3.17 ± 1.48 µm; P

Abstract Background Accurate analysis of quantitative PET data plays a crucial role in studying small, specific brain structures. The integration of PET and MRI through an integrated PET/MR system presents an opportunity to leverage the benefits of precisely aligned structural MRI and molecular PET images in both spatial and temporal dimensions. However, in many clinical workflows, PET studies are often performed without the aid of individually matched structural MRI scans, primarily for the sake of convenience in the data collection and brain segmentation possesses. Currently, two commonly employed segmentation strategies for brain PET analysis are distinguished: methods with or without MRI registration and methods employing either atlas-based or individual-based algorithms. Moreover, the development of artificial intelligence (AI)-assisted methods for predicting brain segmentation holds promise but requires further validation of their efficiency and accuracy for clinical applications. This study aims to compare and evaluate the correlations, consistencies, and differences among the above-mentioned brain segmentation strategies in quantification of brain metabolism in 18F-FDG PET/MR analysis. Results Strong correlations were observed among all methods (r = 0.932 to 0.999, P

Abstract Background Diabetic retinopathy (DR), one of the leading causes of blindness and vision impairment, is suggested to exhibit functional and structural changes in retinal neurons as the earliest manifestation, which could be used to predict the progression of related angiopathy. While neural function and survival rely on proper mitochondrial function, and a growing body of literature has supported the role of mitochondrial dysfunction in the development of DR, how diabetes affects mitochondrial function in retinal tissue remains elusive. This study primarily aimed to investigate mitochondrial functional changes in a diabetic rodent model. We also characterized the early DR phenotype, in particular, neurodegeneration. Methods C57BLKsJ-db/db (db/db) mice (a type 2 diabetic mouse model) were used with their normoglycemic heterozygous littermates (db/+) serving as controls. Longitudinal changes in retinal function and morphology were assessed with electroretinography (ERG) and optical coherence tomography (OCT), respectively, at 9, 13, 17, and 25 weeks of age. At 25 weeks, the retinas were harvested for immunohistochemistry and ex vivo mitochondrial bioenergetics. Results Decreased ERG responses were observed in db/db mice as early as 13 weeks of age. OCT revealed that db/db mice had significantly thinner retinas than the controls. Immunohistochemistry showed that the retinas of the db/db mice at 25 weeks were thinner at the outer and inner nuclear layers, with lower photoreceptor and cone cell densities compared with the db/+ mice. The number of rod-bipolar cell dendritic boutons and axon terminals was significantly reduced in db/db mice relative to the db/+ mice, suggesting that diabetes may lead to compromised synaptic connectivity. More importantly, the retinas of db/db mice had weaker mitochondrial functions than the controls. Conclusions Our longitudinal data suggest that diabetes-induced functional deterioration and morphological changes were accompanied by reduced mitochondrial function in the retina of db/db mice. These findings suggest that mitochondrial dysfunction may be a contributing factor triggering the development of DR. While the underlying mechanistic cause remains elusive, the db/db mice could be a useful animal model for testing potential treatment regimens targeting neurodegeneration in DR.

Supercooled water in mixed-phase clouds plays a significant role in precipitation formation, atmospheric radiation, weather modification, and aircraft flight safety. Identifying supercooled water in mixed-phase clouds is a crucial-frontier scientific issue in atmospheric detection research. In this study, we propose a new algorithm for identifying supercooled water based on the multi-spectral peak characteristics in cloud radar power spectra, combined with radar reflectivity factor and mean Doppler velocity. Using microwave radiometer data, we conducted retrieval analyses on two stratocumulus cases in the spring over the northeastern Daxing’anling region, China. The retrieval results show that the supercooled water in the spring stratocumulus clouds over the region is widespread, with liquid water content (LWC) ranging around 0.1 ± 0.05 g/m3, and particle sizes not exceeding 10 μm. The influence of updrafts on supercooled water is evident, with both showing good consistency in spatiotemporal variation trends. Comparing the liquid water path (LWP) variations retrieved from cloud radar and microwave radiometer, both showed good consistency in variation trends and high LWC areas, indicating the reliability of the identification algorithm developed in this study.

Camellia oleifera Abel, one of the most valuable woody oil plants, has been widely cultivated for extracting edible oil. The shell of C. oleifera is a by-product generated in the processing of edible oil extraction. However, there is still limited research on the maturity and high-value resource utilization of shell by-products. We found that the C. oleifera ‘Huashuo’ (HS) fruit shells contained a high content of catechins. Abscisic acid (ABA) and methyl jasmonate (MeJA) enhanced the accumulation of catechins in C. oleifera fruit shells, providing a basis for production and application of the catechins in fruit shells of C. oleifera. We further found that 500 μM ABA and 900 μM MeJA significantly promoted the accumulation of catechin (C) and epicatechin (EC) in fruit shells. Following treatment with 900 μM MeJA, the expressions of CoPAL1, CoC4H1, CoC4H2, CoC4H3, Co4CL1, Co4CL2, CoF3′H1, CoLAR1, CoLAR2, CoLAR3, CoANR2, and CoANRL2 were significantly upregulated, while after 500 μM ABA treatment the expressions of CoPAL3, CoCHS1, CoCHS4, CoF3′H1, CoDFR, CoLAR1, CoLAR2, CoLAR3, CoANS1, CoANR1, and CoANR2 increased dramatically. These results indicate that appropriate concentrations of ABA and MeJA activate C and EC biosynthesis and promote their accumulation in fruit shells. Our results provide new ideas and guidance for promoting the resource utilization of C. oleifera fruit shells.

Abstract Background Workplace violence has always been a critical issue worldwide before and after the COVID-19 pandemic, which can lead to burnout and turnover. In addition, the burnout and mental stress of nurses during the COVID-19 period have been widely described. To our knowledge, no studies have examined the mediating effect of the sense of coherence on the relationship between workplace violence and burnout among Chinese nurses over time. Therefore, this study aimed to explore the relationship between workplace violence and burnout among Chinese nurses and how the sense of coherence mediates the association. Methods Using a convenience sampling method, 1190 nurses from 4 tertiary grade-A comprehensive hospitals were investigated between September 2021 and December 2021 in 3 provinces of China. The Workplace Violence Scale, Burnout Inventory, and Sense of Coherence scale were used to collect data. Data analysis was conducted using descriptive statistics, Pearson correlation, and regression analysis to estimate direct and indirect effects using bootstrap analysis. Results The mean total scores for workplace violence and burnout were 1.67 ± 1.08 and 47.36 ± 18.39, respectively. Workplace violence was significantly negatively correlated with the sense of coherence (r = -0.25) and positively correlated with burnout (r = 0.27). Additionally, a higher level of workplace violence was associated with higher burnout (β = 1.13, 95% CI: 0.68 ~ 1.56). A higher sense of coherence was also associated with lower burnout (β = -0.98, 95% CI: -1.03 ~ -0.92). Workplace violence showed an effect on burnout through a sense of coherence. The direct, indirect and total effects were 1.13, 1.88 and 3.01, respectively. The mediating effect of the sense of coherence accounted for 62.45% of the relationship between workplace violence and burnout. Conclusion We found that the sense of coherence mediated most workplace violence on burnout. It is imperative for hospital managers to improve nurses’ sense of coherence to reduce the occurrence of burnout during COVID-19. Future intervention studies should be designed to strengthen nurses’ sense of coherence.

Abstract Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed drugs for mental disorders in critically ill patients. We performed a retrospective cohort study to investigate the association between pre-ICU use of SSRIs and mortality in critically ill adults with mental disorders. We identified critically ill adults with mental disorders based on the Medical Information Mart in Intensive Care-IV database. The exposure was the use of SSRIs during the period after hospital admission and before ICU admission. The outcome was in-hospital mortality. Time-dependent Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) with 95% confidence interval (CI). To further test the robustness of the results, we performed propensity score matching and marginal structural Cox model estimated by inverse probability of treatment weighting. The original cohort identified 16601 patients. Of those, 2232 (13.4%) received pre-ICU SSRIs, and 14369 (86.6%) did not. Matched cohort obtained 4406 patients, with 2203 patients in each group (SSRIs users vs. non-users). In the original cohort, pre-ICU use of SSRIs was associated with a 24% increase in the hazard for in-hospital mortality (aHR, 1.24; 95% CI, 1.05–1.46; P = 0.010). The results were robust in the matched cohort (aHR, 1.26; 95% CI, 1.02–1.57; P = 0.032) and the weighted cohort (aHR, 1.43; 95% CI, 1.32–1.54; P

We used low and high molecular weight fluorescence tracers to investigate the entry of foreign solutes into the brain parenchyma and their exit from it by the glymphatic system, during experimentally induced depressive-like behavior in rats. The tail suspension test (TST), as an acute stressor, is known to induce such a type of behavior, considered to model the human major depressive disorder (MDD). Electroacupuncture (EAP) relieves both depressive-like behavior in rodents and the symptoms of MDD in humans. Here we report that 180 min after the intracisternal injection of the low molecular weight tracer Fluorescein-5-Isothiocianate Conjugated Dextran (FITC-d3), a 15-min duration TST tended to increase the control fluorescence in the brain of rats. Both EAP and sham EAP decreased the fluorescence of FITC-d3 in comparison with the TST, but not the control value. In addition, EAP and sham EAP counteracted the effects of TST. The high molecular weight tracer Ovalbumin Alexa Fluor 555 Conjugate (OA-45) failed to enter the brain parenchyma and accumulated at more superficial sites; however, EAP or sham EAP modified the distribution of fluorescence under TST application in a similar manner as that observed during the use of FITC-d3. It is concluded that EAP is possibly a valid treatment to slow down the entry of foreign solutes into the brain; in view of the comparable effects of EAP on FITC-d3 and OA-45 distribution, EAP seems to act before FITC-d3 passes the astroglial aquaporin-4 water channels, which are a critical constituent of the glymphatic system.

Abstract In mixed‐phase cumulus clouds, droplets and ice crystals are inhomogeneously distributed, such spatial inhomogeneity can be enhanced by inhomogeneous entrainment as it can strengthen the particle clustering, which may further influence the phase partitioning and interactions among hydrometeors. However, the scale of particle clustering induced by inhomogeneous entrainment is not well known. Utilizing high‐resolution in‐situ aircraft measurements in mixed‐phase cumulus clouds, this study shows due to inhomogeneous entrainment‐mixing, the cluster scales of droplets and ice crystals decrease by approximately 10 m from the cloud center to the edge. Changes in the clustering are correlated with the intensity of entrainment‐mixing. Clouds that are significantly affected by entrainment exhibit stronger enhancement of particle clustering and a more noticeable reduction in cluster scale. The findings from this study improve our understanding of the scale of particle clustering induced by entrainment‐mixing, and are potentially helpful in evaluating models.

Pharmaceuticals are receiving increasing attention as emerging contaminants in the aquatic environment. Herein, we investigated the occurrence of 11 antidepressants, 6 antihistamines and 4 metabolites in treated wastewater effluents, rivers, stormwater, and seawater in Hong Kong, with special focus on chirality. The average levels of ∑pharmaceuticals ranged from 0.525 to 1070 ng/L in all samples and the total annual mass load of target pharmaceuticals in the marine environment of Hong Kong was 756 kg/y. Antihistamines accounted for >80 % of ∑pharmaceuticals, with diphenhydramine and fexofenadine being predominant. The occurrence and enantiomeric profiles of brompheniramine and promethazine sulfoxide were reported in global natural waters for the first time. Among chiral pharmaceuticals, mirtazapine and fexofenadine exhibited R-preference, while others mostly exhibited S-preference, implying that the ecological risks derived from achiral data for chiral pharmaceuticals may be biased. The joint probabilistic risk assessment of fluoxetine revealed that R-fluoxetine and rac-fluoxetine presented different ecological risks from that of S-fluoxetine; Such assessment also revealed that target pharmaceuticals posed only minimal to low risks, except that diphenhydramine posed an intermediate risk. As estimated, 10 % aquatic species will be affected when the environmental level of diphenhydramine exceeds 7.40 ng/L, which was seen in 46.9 % samples. Collectively, this study highlights further investigations on the enantioselectivity of chiral pharmaceuticals, particularly on environmental behavior and ecotoxicity using local aquatic species as target organisms.

BackgroundMyopia, characterized by excessive axial elongation of the eyeball, increases risks of having sight-threatening diseases and impose a financial burden to healthcare system. Although myopic control interventions showed their effectiveness in slowing progression, the efficacy varies between individuals and does not completely halt progression. The study aims to investigate the efficacy of combining 0.01% atropine administered twice daily with optical defocus for myopia control in schoolchildren.Methods and designThis is a prospective, parallel-group, single-blinded, randomized, active-control trial (ClinicalTrials.gov identifier: NCT06358755). Myopic schoolchildren with no previous myopic control interventions aged between 7 to 12 years will be recruited. They will be randomly allocated into two groups (n = 56 per group) after baseline measurement. Both groups will receive 0.01% atropine twice per day for 18 months (one drop in the morning and the other drop at night before bedtime). Defocus incorporated multiple segments (DIMS) spectacle lenses will be prescribed in atropine plus optical defocus (ATD) treatment group while single vision spectacle lenses will be given in atropine only (AT) group. Cycloplegic refraction and axial lengths will be monitored every 6 months over 18-month study period. The primary outcomes are changes in cycloplegic refraction and axial lengths relative to the baseline over the study period.DiscussionThe result will examine the combination effect of low dose atropine and myopic defocus on myopia control in a randomized controlled study. The findings will also explore the potential benefits of applying 0.01% atropine twice per day on myopic control and its potential side effects.

The mesenchymal feature, dominated by epithelial mesenchymal transition (EMT) and stromal cell activation, is one of the main reasons for the aggressive nature of tumors, yet it remains poorly understood. In gastric cancer (GC), the fermitin family homolog-2 (FERMT2) is involved in macrophage signaling, promoting migration and invasion. However, the function of FERMT2 in fibroblasts remains unclear. Here, we demonstrated that downregulation of FERMT2 expression can block EMT in GC cells by inhibiting fibroblast activation in vitro. Furthermore, we found that, in addition to the known pathways, fibroblast-derived FERMT2 promotes M2-like macrophage growth and that in human GC samples, there is a strong positive correlation between FERMT2 and CD163 and CD206 levels. Notably, high FERMT2 expression was significantly associated with poor clinical outcomes and was upregulated in patients with advanced disease. Taken together, our results provide evidence that the fibroblast-FERMT2-EMT-M2 macrophage axis plays a critical role in the GC mesenchymal phenotype and may be a promising target for the treatment of advanced GC.

Neuroinflammation is a pathological event associated with many neurological disorders, including dementia and stroke. The choroid plexus (ChP) is a key structure in the ventricles of the brain that secretes cerebrospinal fluid (CSF), forms a blood-CSF barrier, and responds to disease conditions by recruiting immune cells and maintaining an immune microenvironment in the brain. Despite these critical roles, the exact structural and functional changes to the ChP over post-stroke time remain to be elucidated. We induced ischemic stroke in C57BL/6J mice via transient middle cerebral artery occlusion which led to reduction of cerebral blood flow and infarct stroke. At 1–7 days post-stroke, we detected time-dependent increase in the ChP blood-CSF barrier permeability to albumin, tight-junction damage, and dynamic changes of SPAK-NKCC1 protein complex, a key ion transport regulatory system for CSF production and clearance. A transient loss of SPAK protein complex but increased phosphorylation of the SPAK-NKCC1 complex was observed in both lateral ventricle ChPs. Most interestingly, stroke also triggered elevation of proinflammatory Lcn2 mRNA and its protein as well as infiltration of anti-inflammatory myeloid cells in ChP at day 5 post-stroke. These findings demonstrate that ischemic strokes cause significant damage to the ChP blood-CSF barrier, contributing to neuroinflammation in the subacute stage.

Abstract One of the major factors controlling the phase partitioning in mixed‐phase cloud is entrainment mixing, but it is still poorly understood. In this study, the liquid‐ice mass partitioning across the edge of shallow to moderately deep cumulus clouds are analyzed using airborne measurements. The results show the concentration and water content of both liquid and ice decrease toward the cloud edge. However, the liquid mass fraction remains similar across the cloud. The mechanism responsible for the phase partitioning is that extreme inhomogeneous entrainment‐mixing dominates. This is evident as both the droplet and ice sizes remain similar with changing concentrations. The comparison between the time scale of turbulent mixing and the phase relaxation time of water also suggests the turbulence strength is too low to homogenize the cloud. The findings from this study improve our understanding on the role of entrainment in phase partitioning, and are useful in evaluating model simulations.

ABSTRACTDietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95–1.05 in group A to D (all P

BackgroundLong working hours are a common occupational health risk factor. The problem of long working hours and its impact on health of medical staff cannot be ignored. ObjectiveTo investigate long working hours in medical staff of tertiary grade A hospitals in Shanghai, and evaluate the relationships of long working hours with occupational stress and fatigue accumulation. MethodsA total of 1531 medical staff in departments of emergency, internal medicine, surgery, intensive care unit (ICU), anesthesiology, and obstetrics and gynecology from 6 hospitals in 6 districts of Shanghai were selected using stratified random sampling. A structured questionnaire was used to collect information on social demographics, occupational characteristics, andbehavior and lifestyle. The Core Occupational Stress Scale (COSS) and the Self-diagnostic Questionnaire on the Accumulation of Fatigue of Laborers were used to assess occupational stress and fatigue accumulation condition. Chi-square test and Kruskal-Wallis H test were used to analyze the distributions of long working hours, occupational stress, and fatigue accumulation, log-binomial models were used to analyze the relationships of long working hours with occupational stress and fatigue accumulation, and job title stratified models were also constructed. ResultsThe average weekly working hours of the study subjects was (47.84±11.40) h, 65.90% of the medical staff worked more than 40 h every week. The percentages of the weekly working hours categories of 41-48 h, 49-54 h, and ≥55 h were 31.42%, 13.46%, and 21.03%, respectively. The positive rates of occupational stress and fatigue accumulation were 25.87% and 65.64% respectively, and the differences among different age, gender, job title, education, length of service, and shift system groups were statistically significant (P

The social internet of things （SIoT） is a new paradigm that combines social networks and the internet of things to enhance network scalability and navigability.However, with increased openness and mobility of intelligent objects, there are rising security risks related to information security and reliable service delivery, which poses a significant challenge to the SIoT.Trust is a critical factor in providing secure and reliable services.Therefore, a new trust assessment model was proposed from the perspective of social relationships.A trust transfer algorithm was proposed based on the explicit social relationships and potential features between nodes.The algorithm can tap and establish the implicit social relationships among nodes to solve the SIoT sparsity and cold start problem.Additionally, the social relations were fine-grained and divided to build a single-relationship sub-network.Multiple single-relationship sub-networks were fused to build a multiple-relationship composite network.Thus, the impact of multiple dynamically changing social relationships among nodes on trust evaluation can be effectively fused.The comprehensive trust assessment of intelligent objects was conducted based on three indicators: direct trust, indirect recommendation trust, and service satisfaction.The experimental results on real smart city datasets demonstrate the model’s robustness in non-sparse and sparse network scenarios.It can effectively evaluate trusted and untrusted objects in the network and improve the accuracy and convergence of trust evaluation.

Abstract This study evaluated the long-term myopia control effect and safety in children wearing Defocus Incorporated Multiple Segments (DIMS) spectacle lenses. Participants who completed the 2-year RCT were followed for a total of 6 years; their cycloplegic refractions and axial length were measured. Group 1 (n = 36) wore DIMS spectacles for 6 years; Group 2 (n = 14) wore DIMS lens for the first 3.5 years and SV spectacles afterwards; Group 3 (n = 22) wore SV spectacles in the first 2 years and switched to DIMS; Group 4 (n = 18) wore SV spectacles in the first 2 years, switched to DIMS for 1.5 years and then SV spectacles again. Group 1 showed no significant differences in myopia progression (− 0.52 ± 0.66 vs. − 0.40 ± 0.72D) and axial elongation (0.32 ± 0.26 vs. 0.28 ± 0.28 mm, both p > 0.05) between the first and the later 3 years. In the last 2.5 years, DIMS lens groups (Groups 1 and 3) had less myopia progression and axial elongation than the single vision groups (Groups 2 and 4). There was no evidence of rebound after stopping the treatment. Post-wear visual functions in all groups were within norms. The results supported that DIMS lenses provided sustained myopia control without adverse effects over the 6-year study period. Trial registration: clinicaltrials.gov; NCT02206217.

Abstract Background In the past decade and during the COVID pandemic, the prevalence of myopia has reached epidemic proportions. To address this issue and reduce the prevalence of myopia and its complications, it is necessary to develop more effective interventions for controlling myopia. In this study, we investigated the combined effects of narrowband lights and competing defocus on eye growth and refraction in chicks, an important step in understanding the potential for these interventions to control myopia. This is the first time these effects have been characterized. Methods Three groups of five-day-old chicks (n = 8 per group) were raised in three different lighting conditions: white, red, and blue for 13 days in a 12/12-h light/dark diurnal cycle. One eye was randomly selected for applications of a dual-power optical lens (− 10 D/ + 10 D, 50∶50), while another eye was left untreated as control. Vitreous chamber depth (VCD), axial length (AL), choroidal thickness (CT) and refractive errors were measured at pre-exposure (D0) and following 3 (D3), 7 (D7), 10 (D10), and 13 days (D13) of light exposure. Results Under white light, the dual-power lens induced a hyperopic shift [at D13, mean spherical equivalent refraction (SER), treated vs. control: 4.81 ± 0.43 D vs. 1.77 ± 0.21 D, P

This article presents a 39 GHz transceiver front-end chipset for 5G multi-input multi-output (MIMO) applications. Each chip includes two variable-gain frequency-conversion channels and can support two simultaneous independent beams, and the chips also integrate a local-oscillator chain and digital module for multi-chip extension and gain-state control. To improve the radio-frequency performance, several circuit-level improvement techniques are proposed for the key building blocks in the front-end system. Furthermore, an advanced low-temperature co-fired ceramic process is developed to package the 39 GHz dual-channel transceiver chipset, and it achieves low packaging loss and high isolation between the two transmitting (TX)/receiving (RX) channels. Both the chip-level and system-in-package (SIP)-level measurements are conducted to demonstrate the performance of the transceiver chipset. The measurement characteristics show that the TX SIP provides 11 dB maximum gain and 10 dBm saturated output power, while the RX SIP achieves 52 dB maximum gain, 5.4 dB noise figure, and 7.2 dBm output 1 dB compression point. Single-channel communication link testing of the transceiver exhibits an error vector magnitude (EVM) of 3.72% and a spectral efficiency of 3.25 bit·s−1·Hz−1 for 64-quadrature amplitude modulation (QAM) modulation and an EVM of 3.76% and spectral efficiency of 3.90 bit·s−1·Hz−1 for 256-QAM modulation over a 1 m distance. Based on the chipset, a 39 GHz multi-beam prototype is also developed to perform the MIMO operation for 5G millimetre wave applications. The over-the-air communication link for one- and two-stream transmission indicates that the multi-beam prototype can cover a 5–150 m distance with comparable throughput.

Abstract Objective To explore the association of delivery mode and the number of pregnancies with anorectal manometry data in patients with postpartum constipation. Methods This retrospective study included women with postpartum constipation treated at the pelvic floor rehabilitation department of Huzhou Maternity & Child Health Care Hospital between January 2018 and December 2019. Results Among 127 patients included, 55 (43.3%) had one pregnancy, 72 (56.7%) had two pregnancies, 96 (75.6%) delivered spontaneously, 25 (16.7%) underwent Cesarean section, and six (4.7%) needed a Cesarean section despite spontaneous labor. The median duration of constipation was 12 months (range, 6–12). There were no differences between the two groups for any manometry parameters (all P > 0.05). The patients with a spontaneous delivery had a lower change in maximal contracting sphincter pressure compared with those with Cesarean section (14.3 (4.5–25.0) vs. 19.6 (13.4–40.0), P = 0.023). Only the delivery mode (Cesarean vs. spontaneous) independently affected the changes in contracting sphincter pressure (B = 10.32, 95%CI: 2.95–17.69, P = 0.006); age (P = 0.201), number of pregnancies (P = 0.190), and constipation duration (P = 0.161) were not associated. Conclusion The patients with a spontaneous delivery had a lower change in maximal contracting sphincter pressure compared with those with a Cesarean section, suggesting that patients with Cesarean may retain a better “push” function during defecation.

Atmospheric ice nucleation particles (INPs) play a crucial role in influencing cloud formation and microphysical properties, which in turn impact precipitation and Earth’s radiation budget. However, the influence of anthropogenic activities on the properties and concentrations of INPs remains an area of significant uncertainty. This study investigated the physical and chemical characteristics of atmospheric ice nucleation particles in Huangshan, China during the May Day labor holiday period (spanning 8 days, from April 27th to May 5th). INP concentrations were measured at temperatures from −17 °C to −26 °C and relative humidities (RHw) from 95% to 101%. Average INP concentrations reached 13.7 L−1 at −26 °C and 101% RH, 137 times higher than at −17 °C and 95% RH. INP concentrations showed exponential increases with decreasing temperature and exponential increases with increasing RH. Concentration fluctuations were observed over time, with a peak of ~30 L−1 (t = −26 °C, RHw = 101%) around the start and end of the holiday period. Aerosol number concentrations were monitored simultaneously. The peak in aerosols larger than 0.5 μm aligned with the peak in INP concentrations, suggesting a link between aerosol levels and INPs. Chemical composition analysis using SEM–EDX revealed the distinct elemental makeup of INPs based on the activation temperature. INPs active at warmer temperatures contained N, Na, and Cl, indicating possible biomass and sea salt origins, while those active at colder temperatures contained crustal elements like Al and Ca.

SPL (SQUAMOSA promoter binding protein-like), as one family of plant transcription factors, plays an important function in plant growth and development and in response to environmental stresses. Despite SPL gene families having been identified in various plant species, the understanding of this gene family in peanuts remains insufficient. In this study, thirty-eight genes (AhSPL1-AhSPL38) were identified and classified into seven groups based on a phylogenetic analysis. In addition, a thorough analysis indicated that the AhSPL genes experienced segmental duplications. The analysis of the gene structure and protein motif patterns revealed similarities in the structure of exons and introns, as well as the organization of the motifs within the same group, thereby providing additional support to the conclusions drawn from the phylogenetic analysis. The analysis of the regulatory elements and RNA-seq data suggested that the AhSPL genes might be widely involved in peanut growth and development, as well as in response to environmental stresses. Furthermore, the expression of some AhSPL genes, including AhSPL5, AhSPL16, AhSPL25, and AhSPL36, were induced by drought and salt stresses. Notably, the expression of the AhSPL genes might potentially be regulated by regulatory factors with distinct functionalities, such as transcription factors ERF, WRKY, MYB, and Dof, and microRNAs, like ahy-miR156. Notably, the overexpression of AhSPL5 can enhance salt tolerance in transgenic Arabidopsis by enhancing its ROS-scavenging capability and positively regulating the expression of stress-responsive genes. These results provide insight into the evolutionary origin of plant SPL genes and how they enhance plant tolerance to salt stress.

The mitogen-activated protein kinase (MAPK) cascades act as crucial signaling modules that regulate plant growth and development, response to biotic/abiotic stresses, and plant immunity. MAP3Ks can be activated through MAP4K phosphorylation in non-plant systems, but this has not been reported in plants to date. Here, we identified a total of 234 putative TaMAPK family members in wheat (Triticum aestivum L.). They included 48 MAPKs, 17 MAP2Ks, 144 MAP3Ks, and 25 MAP4Ks. We conducted systematic analyses of the evolution, domain conservation, interaction networks, and expression profiles of these TaMAPK–TaMAP4K (representing TaMAPK, TaMAP2K, TaMAP3K, and TaMAP4K) kinase family members. The 234 TaMAPK–TaMAP4Ks are distributed on 21 chromosomes and one unknown linkage group (Un). Notably, 25 of these TaMAP4K family members possessed the conserved motifs of MAP4K genes, including glycine-rich motif, invariant lysine (K) motif, HRD motif, DFG motif, and signature motif. TaMAPK3 and 6, and TaMAP4K10/24 were shown to be strongly expressed not only throughout the growth and development stages but also in response to drought or heat stress. The bioinformatics analyses and qRT-PCR results suggested that wheat may activate the MAP4K10–MEKK7–MAP2K11–MAPK6 pathway to increase drought resistance in wheat, and the MAP4K10–MAP3K8–MAP2K1/11-MAPK3 pathway may be involved in plant growth. In general, our work identified members of the MAPK–MAP4K cascade in wheat and profiled their potential roles during their response to abiotic stresses and plant growth based on their expression pattern. The characterized cascades might be good candidates for future crop improvement and molecular breeding.

IntroductionFood allergies have a substantial impact on patient health, but their mechanisms are poorly understood, and strategies for diagnosing, preventing, and treating food allergies are not optimal. This study explored the levels of and relationship between IL-17A and IFN-γ in the saliva of children with food allergies, which will form the basis for further mechanistic discoveries as well as prevention and treatment measures for food allergies.MethodsA case–control study with 1:1 matching was designed. Based on the inclusion criteria, 20 case–control pairs were selected from patients at the Skin and Allergy Clinic and children of employees. IL-17A and IFN-γ levels in saliva were measured with a Luminex 200 instrument. A general linear model was used to analyze whether the salivary IL-17A and IFN-γ levels in the food allergy group differed from those in the control group.ResultsThe general linear model showed a significant main effect of group (allergy vs. healthy) on the levels of IL-17A and IFN-γ. The mean IL-17A level (0.97 ± 0.09 pg/ml) in the food allergy group was higher than that in the healthy group (0.69 ± 0.09 pg/ml). The mean IFN-γ level (3.0 ± 0.43 pg/ml) in the food allergy group was significantly higher than that in the healthy group (1.38 ± 0.43 pg/ml). IL-17A levels were significantly positively related to IFN-γ levels in children with food allergies (r=0.79) and in healthy children (r=0.98).DiscussionThe salivary IL-17A and IFN-γ levels in children with food allergies were higher than those in healthy children. This finding provides a basis for research on new methods of diagnosing food allergies and measuring the effectiveness of treatment.

Anaplastic lymphoma kinase gene (ALK) rearrangement is present in only approximately 5% of non-small cell lung cancers (NSCLCs) and is scarce in LCNEC patients. The conventional first-line treatment options are chemotherapy combined with immunotherapy or chemotherapy followed by palliative radiotherapy. In this report, we present two cases of metastatic LCNEC with EML4-ALK fusion that were treated with ALK-TKI inhibitors and demonstrated a rapid therapeutic response. Both patients were nonsmoking women who declined cytotoxic chemotherapy, underwent Next-Generation Sequencing (NGS), and confirmed EML4-ALK fusion. They were treated with alectinib as first-line therapy, and the tumors showed significant shrinkage after two months, achieving a PR (defined as a more than 30% decrease in the sum of maximal dimensions). The PFS was 22 months and 32 months, respectively, until the last follow-up. A systematic review of all previously reported cases of LCNEC with ALK mutations identified only 21 cases. These cases were characterized by being female (71.4%), nonsmoking (85.7%), diagnosed at a relatively young age (median age 51.1), and stage IV (89.5%), with an overall response rate (ORR) of 90.5%. PFS and OS were significantly longer than those treated with conventional chemotherapy/immunotherapy. Based on the clinical characteristics and the effective therapeutic outcomes with ALK inhibitors in LCNEC patients with ALK fusion, we recommend routine ALK IHC (economical, affordable, and convenient, but with higher false positives) as a screening method in advanced LCNEC patients, particularly nonsmoking females or those who are not candidates for or unwilling to undergo cytotoxic chemotherapy. Further molecular profiling is necessary to confirm these potential beneficiaries. We suggest TKI inhibitors as the first-line treatment for metastatic LCNEC with ALK fusion. Additional studies on larger cohorts are required to assess the prevalence of ALK gene fusions and their sensitivity to various ALK inhibitors.

Abstract Atmospheric black carbon (BC) aerosols have been long‐lasting uncertain components in environmental and climate studies. Global climate models (GCMs) potentially overestimate BC absorption efficiency due to a lack of consideration of complex BC microphysical and mixing properties. We extract multiple BC properties from observations and develop an aerosol optical module known as Advanced Black Carbon (ABC) in the framework of the Modal Aerosol Model version 4 (MAM4). The ABC module is implemented in the Community Atmosphere Model version 6 (CAM6) and evaluated by in situ and remote sensing observations. CAM6‐ABC addresses the shortcomings of CAM6‐MAM4 in terms of BC microphysical and mixing properties, particularly their size, mixing state and optical simulations. Sensitivity simulations show that the global BC absorption aerosol optical depth at 550 nm simulated by CAM6‐ABC is reduced by ∼29% compared with that in CAM6‐MAM4. The BC absorption enhancement simulated by CAM6‐ABC is reduced from ∼2.6 of the default MAM4 to ∼1.4, which is closer to the observed values (mostly less than 1.5). With improved BC absorption estimation, the biases of aerosol single‐scattering coalbedo simulations are reduced by 18%–69% compared with global Aerosol Robotic Network observations. Moreover, the globally averaged BC direct radiative effect is reduced from 0.37 to 0.28 W/m2 at the top of the atmosphere. Our new scheme alleviates the overestimation of BC absorption in GCMs by constraining BC microphysical and mixing properties when assessing aerosol radiative and climate effects, and it can be easily implemented in most modal‐based aerosol modules of climate models.

As a high efficiency hydrogen-to-power device, proton exchange membrane fuel cell (PEMFC) attracts much attention, especially for the automotive applications. Real-time prediction of output voltage and area specific resistance (ASR) via the on-board model is critical to monitor the health state of the automotive PEMFC stack. In this study, we use a transient PEMFC system model for dynamic process simulation of PEMFC to generate the dataset, and a long short-term memory (LSTM) deep learning model is developed to predict the dynamic performance of PEMFC. The results show that the developed LSTM deep learning model has much better performance than other models. A sensitivity analysis on the input features is performed, and three insensitive features are removed, that could slightly improve the prediction accuracy and significantly reduce the data volume. The neural structure, sequence duration, and sampling frequency are optimized. We find that the optimal sequence data duration for predicting ASR is 5 s or 20 s, and that for predicting output voltage is 40 s. The sampling frequency can be reduced from 10 Hz to 0.5 Hz and 0.25 Hz, which slightly affects the prediction accuracy, but obviously reduces the data volume and computation amount.

Proton exchange membrane fuel cell (PEMFC) is regarded as one of the most promising energy conversion devices, but cost and durability are two challenges that hinder its large-scale application. Short-term performance degradation prediction is of great importance for the optimization of operating conditions and maintenance strategies to improve the durability and reduce costs of the PEMFCs. This paper proposes a novel data-driven short-term prediction method combining discrete wavelet transform (DWT), gaussian process regression (GPR) and particle swarm optimization (PSO) algorithm. The DWT decomposes the voltage time series waveform into numerous sub-waveforms with different characteristics. The GPR is utilized to construct individual prediction models for distinct sub-waveforms and the final prediction outcomes are obtained by adding the results of each model. The PSO achieves the automatic hyper-parameters optimization in order to improve the accuracy and robustness of the GPR model. In addition, the effectiveness of the proposed method is fully validated by the degradation datasets of PEMFCs in constant and quasi-dynamic load current conditions as well as real road working conditions. Finally, compared with widely used data-driven models such as artificial neural networks (ANN), support vector machine (SVM), long short-term memory (LSTM) and newly proposed methods in relevant studies, the proposed method exhibits superior accuracy and stability for degradation prediction.