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Abstract Purpose Bietti crystalline dystrophy (BCD) is an inherited retinal degeneration disease caused by mutations in the CYP4V2 gene. Currently, there is no clinical therapy approach available for BCD patients. Previous research has suggested that polyunsaturated fatty acids (PUFAs) may play a significant role in the development of BCD, implicating the involvement of ferroptosis in disease pathogenesis. In this work, we aimed to investigate the interplay between ferroptosis and BCD and to detect potential therapeutic strategies for the disease. Methods Genetic-edited RPE cell line was first established in this study by CRISPR-Cas9 technology. Cyp4v3 (the homologous gene of human CYP4V2) knock out (KO) mice have also been used. Lipid profiling and transcriptome analysis of retinal pigment epithelium (RPE) cells from Cyp4v3 KO mice have been conducted. Ferroptosis phenotypes have been first investigated in BCD models in vitro and in vivo, including lipid peroxidation, mitochondrial changes, elevated levels of reactive oxygen species (ROS), and altered gene expression. Additionally, an iron chelator, deferiprone (DFP), has been tested in vitro and in vivo to determine its efficacy in suppressing ferroptosis and restoring the BCD phenotype. Results Cyp4v3 KO mice exhibited progressive retinal degeneration and lipid accumulation, similar to the BCD phenotype, which was exacerbated by a high-fat diet (HFD). Increased levels of PUFAs, such as EPA (C22:5) and AA (C20:4), were observed in the RPE of Cyp4v3 KO mice. Transcriptome analysis of RPE in Cyp4v3 KO mice revealed changes in genes involved in iron homeostasis, particularly an upregulation of NCOA4, which was confirmed by immunofluorescence. Ferroptosis-related characteristics, including mitochondrial defects, lipid peroxidation, ROS accumulation, and upregulation of related genes, were detected in the RPE both in vitro and in vivo. Abnormal accumulation of ferrous iron was also detected. DFP, an iron chelator administration suppressed ferroptosis phenotype in CYP4V2 mutated RPE. Oral administration of DFP also restored the retinal function and morphology in Cyp4v3 KO mice. Conclusion This study represented the first evidence of the substantial role of ferroptosis in the development of BCD. PUFAs resulting from CYP4V2 mutation may serve as substrates for ferroptosis, potentially working in conjunction with NCOA4-regulated iron accumulation, ultimately leading to RPE degeneration. DFP administration, which chelates iron, has demonstrated its ability to reverse BCD phenotype both in vitro and in vivo, suggesting a promising therapeutic approach in the future.

Abstract Background Depression is a prevalent issue among older adults, affecting their quality of life and overall well-being. Exercise is an effective means of relieving depressive symptoms in older adults, but the optimal dose for different exercise types remains unclear. As such, the aim of this meta-analysis was to examine the dose–response relationship between overall and specific types of exercise with depression symptoms in older adults. Methods This systematic review and network meta-analysis included a search of PubMed, Medline, Embase, PsycINFO, Cochrane library, and Web of Science for randomized controlled trials of exercise in older adults with depression symptoms from inception to 15 July 2023. Comprehensive data extraction covered dose, treatment regimen, demographics and study duration. Dosage metrics, encompassing METs-min/week, were scrutinized in correlation with the Minimal Clinically Importance Difference (MCID). Results A total of 47 studies involving 2895 participants and 7 kinds of exercise were included in the review. Without considering the dose, the results of our network meta-analysis indicated that Walking was the most effective in alleviating depression in older adults, in addition to Aerobic exercise (AE), Yoga, Qigong, Resistance training (RT), and Tai Chi (TC), which were equally effective. However, the results of the dose–response analysis found that Aerobic exercise was most effective at a dose of 1000 METs-min/week. It is noteworthy that Walking is significantly effective in alleviating depressive symptoms in older adults at very low doses. In terms of clinical benefits, we found that overall exercise doses in the range of 600 ~ 970 METs-min/week were clinically effective. Considering the specific types of exercise, Aerobic exercise, Resistance training, Walking, and Yoga were found to be effective at doses ranging from 820 ~ 1000 METs-min/week, 520 ~ 1000 METs-min/week, 650 ~ 1000 METs-min/week, 680 ~ 1000 METs-min/week, respectively. At the same time, we found that when the age exceeded 81 years, even when participating in exercise, it did not achieve the effect of alleviating depressive symptoms in older adults. Conclusions In conclusion, including Walking, AE, Yoga, Qigong, RT, and TC, effectively alleviate depressive symptoms in older adults. Furthermore, we established statistically and clinically significant threshold doses for various exercise types. Early initiation of exercise is beneficial, but its efficacy diminishes from the age of 80, and beyond 81, exercise no longer significantly alleviates depressive symptoms.

In recent years, concerns have escalated regarding eye health problems arising from Light-emitting diode (LED), which emits high-energy blue light (BL), potentially causing corneal epithelial dysfunctions (CEpD). Nevertheless, the mechanisms underlying this damage remain poorly comprehended. This study endeavors to explore the specific mechanisms through which BL exposure induces CEpD. The study carried out diverse assays and treatments to investigate the toxicological effects of BL exposure. 48 hours (h) of 440 nm of BL exposure decreased the migration of human corneal epithelial cells (hCEpCs) while augmenting reactive oxygen species (ROS) production and apoptosis. RNA-Sequencing and bioinformatic analysis indicated that cellular oxidation and reduction equilibrium, wound healing, the positive regulation of the apoptotic process, and the Phosphoinositide 3-kinase (PI3K)/AKT pathway were significantly influenced by BL exposure. Treatment with N-acetylcysteine (NAC), a ROS scavenger, restored cell viability and AKT/S6 kinase (S6K) activation, suggesting the involvement of ROS in BL-induced damage. NAC also reversed BL-induced apoptosis and migration. Blocking AKT/S6K replicated detrimental effects, while pre-treatment with SC79 (SC), an AKT activator, alleviated the changes caused by BL exposure in hCEpCs. Furthermore, in mice, the combination of AKT inhibition and BL exposure led to CEpD. However, treatment with SC and NAC restored CEpD caused by BL exposure. These results imply that the regulation of the ROS/PI3K/AKT/S6K axis is implicated in BL-induced CEpD. Collectively, this study offers insights into the molecular mechanisms of BL-induced CEpD and proposes targeting the ROS/PI3K/AKT/S6K cascade as a potential therapeutic approach. The findings contribute to ocular health knowledge and establish the basis for developing interventions to safeguard the cornea from the detrimental effects of excessive BL exposure.

Abstract Growing urban population and the distinct strategies to accommodate them lead to diverse urban development patterns worldwide. While local evidence suggests the presence of urban signatures in rainfall anomalies, there is limited understanding of how rainfall responds to divergent urban development patterns worldwide. Here we unveil a divergence in the exposure to extreme rainfall for 1790 inland cities globally, attributable to their respective urban development patterns. Cities that experience compact development tend to witness larger increases in extreme rainfall frequency over downtown than their rural surroundings, while the anomalies in extreme rainfall frequency diminish for cities with dispersed development. Convection-permitting simulations further suggest compact urban footprints lead to more pronounced urban-rural thermal contrasts and aerodynamic disturbances. This is directly responsible for the divergent rainfall responses to urban development patterns. Our analyses offer significant insights pertaining to the priorities and potential of city-level efforts to mitigate the emerging climate-related hazards, particularly for countries experiencing rapid urbanization.

Abstract Corneal diseases are among the primary causes of blindness and vision loss worldwide. However, the pathogenesis of corneal diseases remains elusive, and diagnostic and therapeutic tools are limited. Thus, identifying new targets for the diagnosis and treatment of corneal diseases has gained great interest. Methylation, a type of epigenetic modification, modulates various cellular processes at both nucleic acid and protein levels. Growing evidence shows that methylation is a key regulator in the pathogenesis of corneal diseases, including inflammation, fibrosis, and neovascularization, making it an attractive potential therapeutic target. In this review, we discuss the major alterations of methylation and demethylation at the DNA, RNA, and protein levels in corneal diseases and how these dynamics contribute to the pathogenesis of corneal diseases. Also, we provide insights into identifying potential biomarkers of methylation that may improve the diagnosis and treatment of corneal diseases.

Budd-Chiari syndrome (BCS) is a life-threatening disease characterized by the partial or complete obstruction of hepatic venous outflow anywhere from the liver to the heart. In China, secondary BCS is rare. We present a case of secondary BCS caused by compression of the suprahepatic inferior vena cava (IVC), mainly due to local bile accumulation in the caudate lobe of the liver. This case highlights the scarcity of secondary BCS worldwide and the importance of point-of-care ultrasound (POCUS) in the diagnosis and treatment, especially in critical and comatose patients. Prompt diagnosis and recanalization with POCUS-guided puncture and drainage help improve patient prognosis.

Background: Exosomes, one of small extracellular vesicles, play a vital role in cell to cell communication and contribute to the advancement of tumors through their cargo molecules. Exosomal circRNAs have emerged as significant players in various types of tumors. Thus, this study aimed to investigate how exosomal circRNAs are involved in the diagnosis and progression of gastric cancer (GC). Methods: Serum exosomes were characterized using transmission electron microscopy, nanoparticle tracking analysis and Western blot. CCK-8, colony formation and transwell assays were conducted to study the function of hsa_circ_0050547 (named as circ50547). qRT-PCR was used to quantify the expression of circ50547 in GC tissues and serum exosomes. Fluorescence in situ hybridization was applied to detect the cellular distribution of circ50547. Stemness and drug-resistance were detected by sphere formation, WB, flow cytometry and half-maximal inhibitory concentration analyses. Bioinformatic analyses, luciferase experiments, qRT-PCR and WB were used to investigate molecular mechanisms. Results: We discovered for the first time a new type of GC-derived exosomal circRNA, circ50547. We found that circ50547 is highly expressed in both GC tissues and serum exosomes. Interestingly, we observed that the diagnostic value of exosomal circ50547 is superior to that of serum circ50547. Circ50547 overexpression enhanced the proliferation, migration, invasion, stemness and drug resistance of GC cells, while knockdown of circ50547 showed the opposite effect. Mechanistically, circ50547 acted as a sponge for miR-217 to regulate the expression of HNF1B, which promoted gastric cancer progression. Conclusion: Exosomal circ50547 may be a promising marker for the diagnosis and prognosis prediction of GC. These findings suggest that it plays an oncogenic role through miR-217/HNF1B signaling pathway in GC.

ABSTRACT A dysfunction of human host genes and proteins in coronavirus infectious disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key factor impacting clinical symptoms and outcomes. Yet, a detailed understanding of human host immune responses is still incomplete. Here, we applied RNA sequencing to 94 samples of COVID-19 patients with and without hematological tumors as well as COVID-19 uninfected non-tumor individuals to obtain a comprehensive transcriptome landscape of both hematological tumor patients and non-tumor individuals. In our analysis, we further accounted for the human-SARS-CoV-2 protein interactome, human protein interactome, and human protein complex subnetworks to understand the mechanisms of SARS-CoV-2 infection and host immune responses. Our data sets enabled us to identify important SARS-CoV-2 (non-)targeted differentially expressed genes and complexes post-SARS-CoV-2 infection in both hematological tumor and non-tumor individuals. We found several unique differentially expressed genes, complexes, and functions/pathways such as blood coagulation (APOE, SERPINE1, SERPINE2, and TFPI), lipoprotein particle remodeling (APOC2, APOE, and CETP), and pro-B cell differentiation (IGHM, VPREB1, and IGLL1) during COVID-19 infection in patients with hematological tumors. In particular, APOE, a gene that is associated with both blood coagulation and lipoprotein particle remodeling, is not only upregulated in hematological tumor patients post-SARS-CoV-2 infection but also significantly expressed in acute dead patients with hematological tumors, providing clues for the design of future therapeutic strategies specifically targeting COVID-19 in patients with hematological tumors. Our data provide a rich resource for understanding the specific pathogenesis of COVID-19 in immunocompromised patients, such as those with hematological malignancies, and developing effective therapeutics for COVID-19.IMPORTANCEA majority of previous studies focused on the characterization of coronavirus infectious disease 2019 (COVID-19) disease severity in people with normal immunity, while the characterization of COVID-19 in immunocompromised populations is still limited. Our study profiles changes in the transcriptome landscape post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hematological tumor patients and non-tumor individuals. Furthermore, our integrative and comparative systems biology analysis of the interactome, complexome, and transcriptome provides new insights into the tumor-specific pathogenesis of COVID-19. Our findings confirm that SARS-CoV-2 potentially tends to target more non-functional host proteins to indirectly affect host immune responses in hematological tumor patients. The identified unique genes, complexes, functions/pathways, and expression patterns post-SARS-CoV-2 infection in patients with hematological tumors increase our understanding of how SARS-CoV-2 manipulates the host molecular mechanism. Our observed differential genes/complexes and clinical indicators of normal/long infection and deceased COVID-19 patients provide clues for understanding the mechanism of COVID-19 progression in hematological tumors. Finally, our study provides an important data resource that supports the increasing value of the application of publicly accessible data sets to public health.

Background & Aims: Functional cure is achieved by a limited number of patients with chronic hepatitis B (CHB) after nucleotide analogue(s) and interferon treatment. It is urgent to develop therapies that can help a larger proportion of patients achieve functional cure. The present study was designed to explore the anti–hepatitis B virus (HBV) potency of interleukin-6 family cytokines and to characterize the underlying mechanisms of the cytokine displaying the highest anti-HBV potency. Methods: HBV-infected cells were used to screened the anti-HBV potency of interleukin-6 family cytokines. The concentration of oncostatin M (OSM) in patients with chronic HBV infection was examined by enzyme-linked immunosorbent assay. The underlying mechanism of OSM anti-HBV was explored through RNA-seq. C57BL/6 mice injected with rAAV8-1.3HBV were used to explore the suppression effect of OSM on HBV in vivo. Results: OSM is the most effective of the interleukin-6 family cytokines for suppression of HBV replication (percentage of average inhibition: hepatitis B surface antigen, 34.44%; hepatitis B e antigen, 32.52%; HBV DNA, 61.57%). Hepatitis B e antigen–positive CHB patients with high OSM levels had lower hepatitis B surface antigen and hepatitis B e antigen than those with low levels. OSM activated JAK-STAT signaling pathway promoting the formation of STAT1-IRF9 transcription factor complex. Following this, OSM increased the expression of various genes with known functions in innate and adaptive immunity, which was higher expression in patients with CHB in immune clearance phase than in immune tolerance phase (data from GEO: GSE65359). Interferon-induced transmembrane protein 1, one of the most differentially expressed genes, was identified as an HBV restriction factor involved in OSM-mediated anti-HBV effect. In vivo, we also found OSM significantly inhibited HBV replication and induced expression of antiviral effector interferon-induced transmembrane protein 1. Conclusions: Our study shows that OSM remodels the immune response against HBV and exerts potent anti-HBV activity, supporting its further development as a potential therapy for treating CHB.

Abstract Background Clostridioides difficile infection (CDI) is associated with considerable morbidity and mortality in hospitalized patients, especially among older adults. Probiotics have been evaluated to prevent hospital-acquired (HA) CDI in patients who are receiving systemic antibiotics, but the implementation of timely probiotic administration remains a challenge. We evaluated methods for effective probiotic implementation across a large health region as part of a study to assess the real-world effectiveness of a probiotic to prevent HA-CDI (Prevent CDI-55 +). Methods We used a stepped-wedge cluster-randomized controlled trial across four acute-care adult hospitals (n = 2,490 beds) to implement the use of the probiotic Bio-K + ® (Lactobacillus acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2®; Laval, Quebec, Canada) in patients 55 years and older receiving systemic antimicrobials. The multifaceted probiotic implementation strategy included electronic clinical decision support, local site champions, and both health care provider and patient educational interventions. Focus groups were conducted during study implementation to identify ongoing barriers and facilitators to probiotic implementation, guiding needed adaptations of the implementation strategy. Focus groups were thematically analyzed using the Theoretical Domains Framework and the Consolidated Framework of Implementation Research. Results A total of 340 education sessions with over 1,800 key partners and participants occurred before and during implementation in each of the four hospitals. Site champions were identified for each included hospital, and both electronic clinical decision support and printed educational resources were available to health care providers and patients. A total of 15 individuals participated in 2 focus group and 7 interviews. Key barriers identified from the focus groups resulted in adaptation of the electronic clinical decision support and the addition of nursing education related to probiotic administration. As a result of modifying implementation strategies for identified behaviour change barriers, probiotic adherence rates were from 66.7 to 75.8% at 72 h of starting antibiotic therapy across the four participating acute care hospitals. Conclusions Use of a barrier-targeted multifaceted approach, including electronic clinical decision support, education, focus groups to guide the adaptation of the implementation plan, and local site champions, resulted in a high probiotic adherence rate in the Prevent CDI-55 + study.

Background: Sivelestat, a selective inhibitor of neutrophil elastase (NE), can mitigate sepsis-related acute lung injury. However, the role of sivelestat in inhibiting oxidative stress and attenuating sepsis-related acute kidney injury (AKI) remains unclear. Here, we reported the effects of sivelestat against oxidative stress-induced AKI by suppressing the production of oxidative stress indicators. Materials and methods: A male Sprague-Dawley rat model of sepsis was established by cecal ligation and puncture (CLP). Sivelestat or normal saline was administered into jugular vein with a sustained-release drug delivery system. Indicators of inflammation and AKI, including white blood cells (WBC), neutrophils, lymphocytes, C-reactive proteins (CRP), procalcitonin (PCT), blood urea nitrogen (BUN), creatinine (Cr) and uric acid (UA), were assessed at 24 h post-sivelestat treatment. Indicators of liver injury, including direct bilirubin (DBIL), indirect bilirubin (IBIL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), were also assessed at 24 h post-sivelestat treatment. Indicators of oxidative stress, including superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px), were assessed at 12 h and 24 h post-sivelestat treatment. At 24 h post-sivelestat treatment, H&E staining of kidney and liver tissue was performed to observe pathological alterations. Results: At 24 h post normal saline or sivelestat (0.2 g/kg body weight) treatment, WBC, neutrophil, CRP, PCT, MDA, BUN, Cr, UA, AST, ALT, DBIL and IBIL were increased, while SOD and GSH-Px were decreased, in septic rats treated with normal saline compared with that in non-septic rats treated with normal saline (all p

Background: Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality. Methods: We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors. Results: Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend

Efferocytosis of apoptotic neutrophils (PMNs) by macrophages is helpful for inflammation resolution and injury repair, but the role of efferocytosis in intrinsic nature of macrophages during septic acute kidney injury (AKI) remains unknown. Here we report that CD47 and signal regulatory protein alpha (SIRPα)—the anti-efferocytotic ‘don't eat me’ signals—are highly expressed in peripheral blood mononuclear cells (PBMCs) from patients with septic AKI and kidney samples from mice with polymicrobial sepsis and endotoxin shock. Conditional knockout (CKO) of SIRPA in macrophages ameliorates AKI and systemic inflammation response in septic mice, accompanied by an escalation in mitophagy inhibition of macrophages. Ablation of SIRPA transcriptionally downregulates solute carrier family 22 member 5 (SLC22A5) in the lipopolysaccharide (LPS)-stimulated macrophages that efferocytose apoptotic neutrophils (PMNs). Targeting SLC22A5 renders mitophagy inhibition of macrophages in response to LPS stimuli, improves survival and deters development of septic AKI. Our study supports further clinical investigation of CD47-SIRPα signalling in sepsis and proposes that SLC22A5 might be a promising immunotherapeutic target for septic AKI.

Liver cancer, a global menace, ranked as the sixth most prevalent and third deadliest cancer in 2020. The challenge of early diagnosis and treatment, especially for hepatocellular carcinoma (HCC), persists due to late-stage detections. Understanding HCC's complex pathogenesis is vital for advancing diagnostics and therapies. This study combines bioinformatics and machine learning, examining HCC comprehensively. Three datasets underwent meticulous scrutiny, employing various analytical tools such as Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein interaction assessment, and survival analysis. These rigorous investigations uncovered twelve pivotal genes intricately linked with HCC's pathophysiological intricacies. Among them, CYP2C8, CYP2C9, EPHX2, and ESR1 were significantly positively correlated with overall patient survival, while AKR1B10 and NQO1 displayed a negative correlation. Moreover, the Adaboost prediction model yielded an 86.8 % accuracy, showcasing machine learning's potential in deciphering complex dataset patterns for clinically relevant predictions. These findings promise to contribute valuable insights into the elusive mechanisms driving liver cancer (HCC). They hold the potential to guide the development of more precise diagnostic methods and treatment strategies in the future. In the fight against this global health challenge, unraveling HCC's intricacies is of paramount importance.

Abstract In the early stages of diabetic retinopathy (DR), diabetes-related hyperglycemia directly inhibits the AKT signaling pathway by increasing oxidative stress or inhibiting growth factor expression, which leads to retinal cell apoptosis, nerve proliferation and fundus microvascular disease. However, due to compensatory vascular hyperplasia in the late stage of DR, the vascular endothelial growth factor (VEGF)/phosphatidylinositol 3 kinase (PI3K)/AKT cascade is activated, resulting in opposite levels of AKT regulation compared with the early stage. Studies have shown that many factors, including insulin, insulin-like growth factor-1 (IGF-1), VEGF and others, can regulate the AKT pathway. Disruption of the insulin pathway decreases AKT activation. IGF-1 downregulation decreases the activation of AKT in DR, which abrogates the neuroprotective effect, upregulates VEGF expression and thus induces neovascularization. Although inhibiting VEGF is the main treatment for neovascularization in DR, excessive inhibition may lead to apoptosis in inner retinal neurons. AKT pathway substrates, including mammalian target of rapamycin (mTOR), forkhead box O (FOXO), glycogen synthase kinase-3 (GSK-3)/nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor kappa-B (NF-κB), are a research focus. mTOR inhibitors can delay or prevent retinal microangiopathy, whereas low mTOR activity can decrease retinal protein synthesis. Inactivated AKT fails to inhibit FOXO and thus causes apoptosis. The GSK-3/Nrf2 cascade regulates oxidation and inflammation in DR. NF-κB is activated in diabetic retinas and is involved in inflammation and apoptosis. Many pathways or vital activities, such as the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and mitogen-activated protein kinase (MAPK) signaling pathways, interact with the AKT pathway to influence DR development. Numerous regulatory methods can simultaneously impact the AKT pathway and other pathways, and it is essential to consider both the connections and interactions between these pathways. In this review, we summarize changes in the AKT signaling pathway in DR and targeted drugs based on these potential sites.

AIM: To evaluate the clinical application value of the artificial intelligence assisted pathologic myopia (PM-AI) diagnosis model based on deep learning. METHODS: A total of 1156 readable color fundus photographs were collected and annotated based on the diagnostic criteria of Meta-pathologic myopia (PM) (2015). The PM-AI system and four eye doctors (retinal specialists 1 and 2, and ophthalmologists 1 and 2) independently evaluated the color fundus photographs to determine whether they were indicative of PM or not and the presence of myopic choroidal neovascularization (mCNV). The performance of identification for PM and mCNV by the PM-AI system and the eye doctors was compared and evaluated via the relevant statistical analysis. RESULTS: For PM identification, the sensitivity of the PM-AI system was 98.17%, which was comparable to specialist 1 (P=0.307), but was higher than specialist 2 and ophthalmologists 1 and 2 (P0.05), and was higher than ophthalmologist 1. The specificity of the PM-AI system was 95.31%, which was lower than specialists 1 and 2, but higher than ophthalmologists 1 and 2. The PM-AI system gave the Kappa value of 0.624, while the Kappa values of specialists 1, 2 and ophthalmologists 1 and 2 were 0.864, 0.732, 0.304 and 0.238, respectively. CONCLUSION: In comparison to the senior ophthalmologists, the PM-AI system based on deep learning exhibits excellent performance in PM and mCNV identification. The effectiveness of PM-AI system is an auxiliary diagnosis tool for clinical screening of PM and mCNV.

Abstract Background To explore differential metabolites in the aqueous humor of patients with different axial lengths and their correlations with axial length and choroidal parameters. Methods In this study, we included 12 patients with axial lengths less than 24 mm, 11 patients with axial lengths between 24 and 26 mm, and 11 patients with axial lengths greater than 26 mm. We collected their aqueous humor samples during cataract surgery for liquid chromatography-mass spectrometry metabolomic analysis. Simultaneously, we collected relevant clinical parameters such as axial length, subfoveal choroidal thickness, and choroidal vascular index. Correlations between clinical data, differential metabolites, and clinical indicators were analyzed. In addition, we plotted receiver operating characteristic curves. Results The results showed that axial length was significantly negatively correlated with choroidal thickness (r=-0.7446, P

The effect of norovirus dose on outcomes such as virus shedding and symptoms after initial infection is not well understood. We performed a secondary analysis of a human challenge study by using Bayesian mixed-effects models. As the dose increased from 4.8 to 4,800 reverse transcription PCR units, the total amount of shed virus in feces increased from 4.5 × 1011 to 3.4 × 1012 genomic equivalent copies; in vomit, virus increased from 6.4 × 105 to 3.0 × 107 genomic equivalent copies. Onset time of viral shedding in feces decreased from 1.4 to 0.8 days, and time of peak viral shedding decreased from 2.3 to 1.5 days. Time to symptom onset decreased from 1.5 to 0.8 days. One type of symptom score increased. An increase in norovirus dose was associated with more rapid shedding and symptom onset and possibly increased severity. However, the effect on virus load and shedding was inconclusive.

Abstract Background The Behavioral Risk Factor Surveillance System (BRFSS) is an annual survey designed to identify trends in the public’s health. In its 2019 field survey, the U.S. state of GA tested a new 3 – item module to measure the numbers of bereaved, resident adults aged 18 years and older. Participants were eligible if they answered ‘Yes’ to the item ‘Have you experienced the death of a family member or close friend in the years 2018 or 2019?’. This analysis explores two research questions. Can estimates for bereavement prevalence be derived without large sampling errors, low precision, and small subsamples? Can multiple imputation techniques be applied to overcome non-response and missing data to support multivariate modeling? Methods BRFSS is a non-institutionalized sample of adults aged 18 years and older living in the U.S. state of Georgia. Analyses in this study were conducted under two scenarios. Scenario 1 applies the complex sample weights created by the Centers for Disease Control and imputes values for missing responses. Scenario 2 treats the data as a panel – no weighting combined with removal of persons with missing data. Scenario 1 reflects the use of BRFSS data for public health and policy, while Scenario 2 reflects data as it is commonly used in social science research studies. Results The bereavement screening item has a response rate (RR) of 69.1% (5206 of 7534 persons). Demographic subgroups and categories of health have RR of 55% or more. Under Scenario 1, the estimated prevalence of bereavement is 45.38%, meaning that 3,739,120 adults reported bereaved in 2018 or 2019. The estimated prevalence is 46.02% with Scenario 2 which removes persons with any missing data (4,289 persons). Scenario 2 overestimates the bereavement prevalence by 1.39%. An illustrative logistic model is presented to show the performance of exposure to bereavement under the two data scenarios. Conclusions Recent bereavement can be ascertained in a surveillance survey accounting for biases in response. Estimating bereavement prevalence is needed for measuring population health. This survey is limited to one US state in a single year and excludes persons aged 17 years and younger.

ImportanceUnderstanding the susceptibility and infectiousness of children and adolescents in comparison to adults is important to appreciate their role in the COVID-19 pandemic.ObjectiveTo determine SARS-CoV-2 susceptibility and infectiousness of children and adolescents with adults as comparator for three variants (wild-type, alpha, delta) in the household setting. We aimed to identify the effects independent of vaccination or prior infection.Data sourcesWe searched EMBASE, PubMed and medRxiv up to January 2022.Study selectionTwo reviewers independently identified studies providing secondary household attack rates (SAR) for SARS-CoV-2 infection in children (0-9 years), adolescents (10-19 years) or both compared with adults (20 years and older).Data extraction and synthesisTwo reviewers independently extracted data, assessed risk of bias and performed a random-effects meta-analysis model.Main outcomes and measuresOdds ratio (OR) for SARS-CoV-2 infection comparing children and adolescents with adults stratified by wild-type (ancestral type), alpha, and delta variant, respectively. Susceptibility was defined as the secondary attack rate (SAR) among susceptible household contacts irrespective of the age of the index case. Infectiousness was defined as the SAR irrespective of the age of household contacts when children/adolescents/adults were the index case.ResultsSusceptibility analysis: We included 27 studies (308,681 contacts), for delta only one (large) study was available. Compared to adults, children and adolescents were less susceptible to the wild-type and delta, but equally susceptible to alpha. Infectiousness analysis: We included 21 studies (201,199 index cases). Compared to adults, children and adolescents were less infectious when infected with the wild-type and delta. Alpha -related infectiousness remained unclear, 0-9 year old children were at least as infectious as adults. Overall SAR among household contacts varied between the variants.Conclusions and relevanceWhen considering the potential role of children and adolescents, variant-specific susceptibility, infectiousness, age group and overall transmissibility need to be assessed.

Introduction: Environmental regulation, as a vital component of public regulation in China, plays a crucial role in coordinating regional eco-efficiency, while the traditional hypothesis, Porter hypothesis, and uncertainty hypothesis offer three different perspectives for understanding the relationship between industry performance and environmental regulations.Methods: Based on the assumption of industry heterogeneity, 81 public-private partnership (PPP) waste-to-energy (WTE) incineration projects are analyzed using panel data from 66 cities within China during the period from 2013 to 2017 with the aims to reveal the underlying mechanism behind environmental regulation and the government subsides of public-private partnership waste-to-energy incineration projects by using multiple regression modeling.Results: The results show that the impact of environmental regulation on government subsides of PPP WTE projects has demonstrated an “Inverted-U”-shaped relationship with an inflection point, of which an increase in environmental regulation is positively correlated with an increase in subsidies at first then a negative correlation developing later.Discussion: The findings are significant in setting flexible environmental regulations according to the needs of regional economic and social development. In addition, they also supply a theoretical reference for promoting the WTE incineration industry’s sustainable and healthy development.

Summary: This study aimed to investigate the effects of long-term pollution from different wavelengths of light on the corneal epithelium (CE) and identify potential biomarkers. Rabbits were exposed to red, green, blue, white, and environmental light for 6 weeks. The CE was assessed using various techniques such as fluorescein sodium staining, transcriptome sequencing, electron microscopy, and molecular assays. In human corneal epithelial cells (hCECs), the downregulation of vascular cell adhesion molecule 1 (VCAM1) in response to blue light (BL) pollution was observed. This downregulation of VCAM1 inhibited migration, increased reactive oxygen species (ROS) levels, and apoptosis, and inhibited the AKT/p70 S6 kinase cascade in hCECs. Animal experiments confirmed that BL pollution caused similar effects on the rabbit cornea, including increased ROS production, apoptosis, delayed wound healing, and decreased VCAM1 expression. Overall, BL-induced VCAM1 downregulation may impair CE and wound healing and promote ROS and apoptosis in vitro and in vivo.

Background & Aims: HBV infection is a global health burden. Covalently closed circular DNA (cccDNA) transcriptional regulation is a major cause of poor cure rates of chronic hepatitis B (CHB) infection. Herein, we evaluated whether targeting host factors to achieve functional silencing of cccDNA may represent a novel strategy for the treatment of HBV infection. Methods: To evaluate the effects of Jumonji C domain-containing (JMJD2) protein subfamily JMJD2A-2D proteins on HBV replication, we used lentivirus-based RNA interference to suppress the expression of isoforms JMJD2A-2D in HBV-infected cells. JMJD2D-knockout mice were generated to obtain an HBV-injected model for in vivo experiments. Co-immunoprecipitation and ubiquitylation assays were used to detect JMJD2D-HBx interactions and HBx stability modulated by JMJD2D. Chromatin immunoprecipitation assays were performed to investigate JMJD2D-cccDNA and HBx-cccDNA interactions. Results: Among the JMJD2 family members, JMJD2D was significantly upregulated in mouse livers and human hepatoma cells. Downregulation of JMJD2D inhibited cccDNA transcription and HBV replication. Molecularly, JMJD2D sustained HBx stability by suppressing the TRIM14-mediated ubiquitin-proteasome degradation pathway and acted as a key co-activator of HBx to augment HBV replication. The JMJD2D-targeting inhibitor, 5C-8-HQ, suppressed cccDNA transcription and HBV replication. Conclusion: Our study clarified the mechanism by which JMJD2D regulates HBV transcription and replication and identified JMJD2D as a potential diagnostic biomarker and promising drug target against CHB, and HBV-associated hepatocarcinoma. Impact and implications: HBV cccDNA is central to persistent infection and is a major obstacle to healing CHB. In this study, using cellular and animal HBV models, JMJD2D was found to stabilise and cooperate with HBx to augment HBV transcription and replication. This study reveals a potential novel translational target for intervention in the treatment of chronic hepatitis B infection.

Nearly all modern life depends on artificial light; however, it does cause health problems. With certain restrictions of artificial light emitting technology, the influence of the light spectrum is inevitable. The most remarkable problem is its overload in the short wavelength component. Short wavelength artificial light has a wide range of influences from ocular development to mental problems. The visual neuronal pathway, as the primary light-sensing structure, may contain the fundamental mechanism of all light-induced abnormalities. However, how the artificial light spectrum shapes the visual neuronal pathway during development in mammals is poorly understood. We placed C57BL/6 mice in three different spectrum environments (full-spectrum white light: 400–750 nm; violet light: 400 ± 20 nm; green light: 510 ± 20 nm) beginning at eye opening, with a fixed light time of 7:00–19:00. During development, we assessed the ocular axial dimension, visual function and retinal neurons. After two weeks under short wavelength conditions, the ocular axial length (AL), anterior chamber depth (ACD) and length of lens thickness, real vitreous chamber depth and retinal thickness (LLVR) were shorter, visual acuity (VA) decreased, and retinal electrical activity was impaired. The density of S-cones in the dorsal and ventral retinas both decreased after one week under short wavelength conditions. In the ventral retina, it increased after three weeks. Retinal ganglion cell (RGC) density and axon thickness were not influenced; however, the axonal terminals in the lateral geniculate nucleus (LGN) were less clustered and sparse. Amacrine cells (ACs) were significantly more activated. Green light has few effects. The KEGG and GO enrichment analyses showed that many genes related to neural circuitry, synaptic formation and neurotransmitter function were differentially expressed in the short wavelength light group. In conclusion, exposure to short wavelength artificial light in the early stage of vision-dependent development in mice delayed the development of the visual pathway. The axon terminus structure and neurotransmitter function may be the major suffering.

Purpose – With the increasing requirements for intelligence in the field of aviation manufacturing, manual assembly can hardly adapt to the trend of future production. The purpose of this study is to realize the semi-automatic assembly of the movable airfoil by proposing a human-robot collaborative assembly strategy based on adaptive admittance control. Design/methodology/approach – A logical judgment system for operating intentions is introduced in terms of different situations of the movements; hence, a human cognition-based adaptive admittance control method is developed to curb the damage of inertia; then virtual limit walls are raised on the periphery of the control model to ensure safety; finally, simulated and experimental comparisons with other admittance control methods are conducted to validate the proposed method. Findings – The proposed method can save at least 28.8% of the time in the stopping phase which effectively compensates for inertia during the assembly process and has high robustness concerning data disturbances. Originality/value – Due to the human-robot collaboration to achieve compliant assembly of movable airfoils can preserve human subjectivity while overcoming the physical limits of humans, which is of great significance to the investigation of intelligent aircraft assembly, the proposed method that reflects the user's naturalness and intuitiveness can not only enhance the stability and the flexibility of the manipulation, but also contribute to applications of industrial robots in the field of human-robot collaboration.

Rice-based products exported from China to Europe have repeatedly encountered technical trade barriers. Using panel data from 24 states of the European Union during 2001–2017, this study builds a theoretical model to investigate the impact of implementation, intensity and structure of the Rapid Alert System for Food and Feed (RASFF) on China-EU rice-based product trade. The study found that RASFF has a serious inhibitory effect on the trade of traditional rice-based products because of detecting GM ingredients, showing an obvious lag effect, diffusion effect and structure effect. The negative effect occurs in entry process, and the inhibitory effect of border rejection and information notifications results in time lag, but the marginal effect of alerts for market links is insignificant. Moreover, the positive information disclosure effect of technical barriers implemented by individual members is much smaller than the negative diffusion effect. Finally, countermeasures and suggestions are proposed, including the source supervision of the test, the supervision of GM variety approval and GM seed production, the establishment of an early-warning and rapid-response mechanism to technical barriers of agricultural products, and food enterprise information.

Abstract Background Pathogenesis of posterior capsular opacification (PCO) was related to pathological epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). It has been reported that blue light could have an effect on EMT. This study aims to elucidate the role and potential mechanism of autophagy in EMT after blue light exposure in LECs. Methods HLE-B3 cells were treated with TGF-β2 with different concentration and time to induce EMT as a model of PCO in vitro. Cells were exposed to blue light with or without TGF-β2. The expression levels of EMT-associated markers were analyzed by qRT-PCR, western blotting and cell migration ability was determined by transwell migration assay and wound healing assay. The expressions of autophagy-related proteins were analyzed by western blotting, immunofluorescence and transmission electron microscopy. Rapamycin and chloroquine were utilized in cells for autophagy activation and inhibition. Results TGF-β2 induced autophagy activation during EMT progression in HLE-B3 cells in a dose- and time-dependent manner. Blue light exposure inhibited TGF-β2-induced EMT characterized by inhibited expression of EMT related markers and reduced migration capacity. Meanwhile, blue light exposure impaired autophagy activated by TGF-β2. Furthermore, Autophagy activation with rapamycin rescued EMT attenuated by blue light. Autophagy inhibition with chloroquine reduced TGF-β2-induced EMT in HLE-B3 cells. Conclusion Blue light exposure had inhibited effects on TGF-β2-induced EMT in LECs through autophagy impairment, which provides a new insight on prevention and treatment of PCO.

Abstract Background Changes in the retina and choroid blood vessels are regularly observed in myopia. However, if the retinal glial cells, which directly contact blood vessels, play a role in mammalian myopia is unknown. We aimed to explore the potential role and mechanism of retinal glial cells in form deprived myopia. Methods We adapted the mice form-deprivation myopia model by covering the right eye and left the left eye open for control, measured the ocular structure with anterior segment optical coherence tomography, evaluated changes in the morphology and distribution of retinal glial cells by fluorescence staining and western blotting; we also searched the online GEO databases to obtain relative gene lists and confirmed them in the form-deprivation myopia mouse retina at mRNA and protein level. Results Compared with the open eye, the ocular axial length (3.54 ± 0.006 mm v.s. 3.48 ± 0.004 mm, p = 0.027) and vitreous chamber depth (3.07 ± 0.005 mm v.s. 2.98 ± 0.006 mm, p = 0.007) in the covered eye became longer. Both glial fibrillary acidic protein and excitatory amino acid transporters 4 elevated. There were 12 common pathways in human myopia and anoxic astrocytes. The key proteins were also highly relevant to atropine target proteins. In mice, two common pathways were found in myopia and anoxic Müller cells. Seven main genes and four key proteins were significantly changed in the mice form-deprivation myopia retinas. Conclusion Retinal astrocytes and Müller cells were activated in myopia. They may response to stimuli and secretory acting factors, and might be a valid target for atropine.

Abstract Salvia miltiorrhiza Bunge (danshen in Chinese) is one of the most important medicinal cash crops in China. Previously, we showed that arbuscular mycorrhizal fungi (AMF) can promote S. miltiorrhiza growth and the accumulation of bioactive compounds. Fertilization may affect mycorrhizal efficiency, and appropriate doses of phosphate (P) and nitrogen (N) fertilizers are key factors for obtaining mycorrhizal benefits. However, the optimal fertilization amount for mycorrhizal S. miltiorrhiza remains unclear. In this study, we studied the effects of AMF on the growth and bioactive compounds of S. miltiorrhiza under different doses (low, medium, and high) of P and N fertilizer. The results showed that the mycorrhizal growth response (MGR) and mycorrhizal response of bioactive compounds (MBC) decreased gradually with increasing P addition. Application of a low (N25) dose of N fertilizer significantly increased the MGR of mycorrhizal S. miltiorrhiza, and a medium (N50) dose of N fertilizer significantly increased the MBC of phenolic acids, but decreased the MBC of tanshinones. Our results also showed that the existence of arbuscular mycorrhiza changes nutrient requirement pattern of S. miltiorrhiza. P is the limiting nutrient of non-mycorrhizal plants whereas N is the limiting nutrient of mycorrhizal plants.

Continuous monoculture of crops has resulted in reduced yields and quality, as well as soil deterioration. Although traditional Chinese medicine residues (TCMRs) are known to promote plant growth and soil health, few studies have investigated their effectiveness in continuous monoculture soils. Here, we studied the impact of chemical fertilizers (CF) and four TCMRs with antibacterial activities on the growth of S. miltiorrhiza (a widely used medicinal plant in China), accumulation of active ingredients in plants, and soil health under continuous monoculture conditions. Compared with no fertilizer (CK) and CF, fermented Sophora flavescens radix residue (SFRf) and fermented and unfermented Moutan cortex residue (MCRf and MCRu, respectively) resulted in a reduction of the disease index of root rot, while CF did not. The CF and four TCMR treatments increased the accumulation of nitrogen (N) (42.8-124.6% and 17.0-101.7%), phosphorous (P) (19.8-74.7% and 8.3-27.4%), and potassium (K) (104.1-212.0% and 9.3-51.8%) in shoots and roots compared to CK. The differences in nutrient accumulation between the CF and TCMR treatments were statistically insignificant, excepted for the N accumulation in the roots. All fertilization treatments increased plant biomass compared to CK, with increases of 25.57-89.86% and 2.62-35.28% in shoots and roots, respectively. The SFRf treatment exhibited the most significant enhancement in both shoot and root biomass. CF significantly reduced the accumulation of seven active ingredients in roots by 23.90-78.95% compared to CK, whereas each TCMR increased accumulation of certain active ingredients. The TCMR treatments effectively improved the health of deteriorated soil by enhancing soil physicochemical properties, restoring the balance of the microbial community, recruiting beneficial bacteria, and reducing the relative abundance of the pathogen Fusarium. The SFRf treatment exhibited superior performance in improving soil health than other treatments. Overall, the TCMRs outperformed CF in restoring soil health and promoting the yield and quality of S. miltiorrhiza. These findings offer guidance for improving the health of continuous cropping soil and recycling TCMRs.

ObjectiveThis study aimed to evaluate the prevalence of HPV and genotype distribution among female populations in Xiamen, Fujian Province, China, which can be conducive for local governments to formulate cervical cancer screening and HPV vaccine strategies.MethodsCervical swabs were collected from 47,926 participants aged 16–92 years at the Women and Children’s Hospital, Xiamen University, from November 2019 to June 2020. HPV DNA was extracted and detected using conventional PCR, followed by HPV subtype-specific hybridisation. HPV infection rates based on different groups were compared using the χ2 test. HPV prevalence and the corresponding 95% confidence intervals (95% CI) were calculated using SPSS 19.0.ResultsThe overall HPV prevalence among the 47,926 cervical swabs that were analysed was 15.13%, of which single, double, and multiple infections accounted for 76.83, 16.70 and 6.47%, respectively. The age-specific prevalence of HPV infection presented a “U” curve with a HPV prevalence peak observed in women aged

IntroductionThe efficacy and safety of 3% diquafosol sodium eye drops in Chinese patients with dry eye in the real-world setting remains unclear.Methods3099 patients with dry eye symptoms were screened according to Asia Dry Eye Society latest recommendation. Among them, 3000 patients were enrolled for a phase IV study. We followed up with multiple clinical characteristics including corneal fluorescein staining, tear break up time, Schirmer’s tests, visual acuity, intraocular pressure, and others. The follow ups were performed at baseline, 2 weeks and 4 weeks after treatment.ResultsBased on the results of corneal fluorescein staining and tear break up time, all age and gender subgroups exhibited obvious alleviation of the symptoms among the patients with dry eye, and the data in elderly group showed the most significant alleviation. All the adverse drug reactions (ADRs, 6.17%) were recorded, among which 6% local ocular ADRs were included. Meanwhile, mild ADRs (91.8%) accounted for the most. Most of the ADRs (89.75%) got a quick and full recovery, with an average time at 15.6 days. 1.37% of patients dropped out of the study due to ADRs.DiscussionThe use of 3% diquafosol sodium eye drop is effective and safe in the treatment of dry eye, with a low incidence of ADRs showing mild symptoms. This trial was registered at Chinese Clinical Trial Registry ID: ChiCTR1900021999 (Registration Date: 19/03/2019).

Abstract Diverse urban‐induced rainfall anomalies across different cities highlight the need for additional insights into land‐atmosphere interactions over complex urban environments. Based on empirical analyses of 144 warm‐season storms and high‐resolution numerical simulations over Nanjing, China, we show divergent patterns of urban‐induced rainfall anomalies for storms with contrasting synoptic conditions, despite of rainfall enhancement over downtown from a climatological perspective. We propose two simple gage‐based metrics to characterize both the thermal and turbulent conditions in pre‐storm environment, and classify storms into different groups. Our results show that elevated rainfall magnitudes and heavy rainfall frequency are equally expected in either downtown or suburb regions (upwind or downwind). This is mainly dictated by the relative dominance of urban‐induced thermal perturbations and mechanical turbulence (i.e., related to surface roughness) under different synoptic conditions. We develop four paradigms of urban rainfall modification, and thus provide a predictive understanding of rainfall anomalies in urban environments.

Abstract Phosphatidylinositol 3 kinase (PI3K)/AKT (also called protein kinase B, PKB) signalling regulates various cellular processes, such as apoptosis, cell proliferation, the cell cycle, protein synthesis, glucose metabolism, and telomere activity. Corneal epithelial cells (CECs) are the outermost cells of the cornea; they maintain good optical performance and act as a physical and immune barrier. Various growth factors, including epidermal growth factor receptor (EGFR) ligands, insulin-like growth factor 1 (IGF1), neurokinin 1 (NK-1), and insulin activate the PI3K/AKT signalling pathway by binding their receptors and promote antiapoptotic, anti-inflammatory, proliferative, and migratory functions and wound healing in the corneal epithelium (CE). Reactive oxygen species (ROS) regulate apoptosis and inflammation in CECs in a concentration-dependent manner. Extreme environments induce excess ROS accumulation, inhibit PI3K/AKT, and cause apoptosis and inflammation in CECs. However, at low or moderate levels, ROS activate PI3K/AKT signalling, inhibiting apoptosis and stimulating proliferation of healthy CECs. Diabetes-associated hyperglycaemia directly inhibit PI3K/AKT signalling by increasing ROS and endoplasmic reticulum (ER) stress levels or suppressing the expression of growth factors receptors and cause diabetic keratopathy (DK) in CECs. Similarly, hyperosmolarity and ROS accumulation suppress PI3K/AKT signalling in dry eye disease (DED). However, significant overactivation of the PI3K/AKT signalling pathway, which mediates inflammation in CECs, is observed in both infectious and noninfectious keratitis. Overall, upon activation by growth factors and NK-1, PI3K/AKT signalling promotes the proliferation, migration, and anti-apoptosis of CECs, and these processes can be regulated by ROS in a concentration-dependent manner. Moreover, PI3K/AKT signalling pathway is inhibited in CECs from individuals with DK and DED, but is overactivated by keratitis.

Objective: The protective effect of Polygonatum odoratum polysaccharides (POP) on D-galactose (D-gal) induced senescence in rat aortic smooth muscle cells (A7r5) was investigated. Methods: Firstly, the POP was extracted by the water extraction and alcohol precipitation methods. Next, the phenol concentrated sulfuric acid method was applied to further measure the total sugar content of POP. In addition, the A7r5-senescent cell model was established by the D-galactose treatment. Finally, the MTT assay, β-galactosidase staining, reactive oxygen species (ROS) staining as well as JC-1 staining were applied to further detect the protective effect of POP in A7r5-senescent cells induced by D-galactose. Results: This study found an yield of POP was 8.23% and its total sugar content was 76.48%±0.036%. As a result, the MTT assay showed the viability of the A7r5 cells was increased to 174.89%±3.30% after 24 h treatment by 400 μg/mL of POP, while it was decreased to 65.93%±1.63% after 48 h treatment by 40 mg/mL of D-galactose. Interestingly, when a concentration of POP was 100 μg/mL, this study had found the most significant protective effect in A7r5-senescent cells induced by D-galactose, which increased its cell viability to 226.87%±12.58% as compared with the control group (P

Using fist-principles calculations, we study the B atom of diffusion process and the origin of the perpendicular magnetic anisotropy in MgO|CoFe|Ta structures with boron. It is found that B atoms are more likely to enter the Ta layer than FeCo layer and MgO layer. This result is in good agreement with that of the experimental and theoretical results. Furthermore, we elucidate the physical origin of the interfacial PMA Ta|CoFe|MgO structure with B element. We find that interfacial PAM come from both the MgO|CoFe and CoFe|Ta layer interfaces. These findings provide a comprehensive understanding of the PMA and point towards the possibility to achieve the advanced-node STT-MRAM with high thermal stability.

Background Disparities in cardiovascular disease (CVD) outcomes persist across the United States. Social determinants of health play an important role in driving these disparities. The current study aims to identify the most important social determinants associated with CVD mortality over time in US counties. Methods and Results The authors used the Agency for Healthcare Research and Quality's database on social determinants of health and linked it with CVD mortality data at the county level from 2009 to 2018. The age‐standardized CVD mortality rate was measured as the number of deaths per 100 000 people. Penalized generalized estimating equations were used to select social determinants associated with county‐level CVD mortality. The analytic sample included 3142 counties. The penalized generalized estimating equation identified 17 key social determinants of health including rural–urban status, county's racial composition, income, food, and housing status. Over the 10‐year period, CVD mortality declined at an annual rate of 1.08 (95% CI, 0.74–1.42) deaths per 100 000 people. Rural counties and counties with a higher percentage of Black residents had a consistently higher CVD mortality rate than urban counties and counties with a lower percentage of Black residents. The rural–urban CVD mortality gap did not change significantly over the past decade, whereas the association between the percentage of Black residents and CVD mortality showed a significant diminishing trend over time. Conclusions County‐level CVD mortality declined from 2009 through 2018. However, rural counties and counties with a higher percentage of Black residents continued to experience higher CVD mortality. Median income, food, and housing status consistently predicted higher CVD mortality.

Endometrial hyperplasia is caused by an excess of estrogen unopposed by progesterone. Oral progestogens are traditionally used for endometrial hyperplasia without atypia. However oral progestogen is not always successful at causing regression of endometrial hyperplasia. In addition, cyclic progestogens are less effective in delivering progestogen to the endometrium. Therefore, the levonorgestrel-intrauterine device (LNG-IUD), as an alternative option of delivery progestogen has been introduced in clinical practice. The effectiveness of LNG-IUD in causing regression of endometrial hyperplasia in the short-term had moderate-quality evidence, but the long-term (13 months to two years) effectiveness had low-quality evidence. In this study with relatively large sample size, we compared the effectiveness in the regression of endometrial hyperplasia without atypia for short-term and long-term between the treatment with LNG-IUD and oral progestogens or no treatment. Data on histology or ultrasound from 466 cases who received either LNG-IUD or oral progestogens or were untreated were collected. The primary treatment with LNG-IUD showed a 93% regression rate of endometrial hyperplasia, which was significantly higher than oral progestogens showing a 66% regression rate. The odds ratio of regression of endometrial hyperplasia in cases with LNG-IUD treatment was 7.128 (95%CI: 2.94, 16.76, p < 0.0001), compared to the cases with oral progestogen treatment. The regression rate in untreated cases was 16%. In addition, cases without regression by oral progestogens who then received the alternative treatment option by LNG-IUD also showed a 93% regression rate. While continuously receiving oral progestogens showed a 55% regression rate of endometrial hyperplasia, which was significantly lower than LNG-IUD treatment as an alternative option. Our data reports a significant response on regression of endometrial hyperplasia after LNG-IUD treatment in comparison with oral progestogen treatment.

Salvia miltiorrhiza Bunge (Danshen in Chinese) is vulnerable to Fusarium wilt, which severely affects the quality of the crude drug. Mycorrhizal colonization enhances resistance to fungal pathogens in many plant species. In this study, pre-inoculation of S. miltiorrhiza with the arbuscular mycorrhizal fungi (AMF) Glomus versiforme significantly alleviated Fusarium wilt caused by Fusarium oxysporum. Mycorrhizal colonization protected S. miltiorrhiza from pathogen infection, thereby preventing a loss of biomass and photosynthesis. There were greater defense responses induced by pathogen infection in AMF pre-inoculated plants than those in non-treated plants. AMF pre-inoculation resulted in systemic responses upon pathogen inoculation, including significant increases in the protein content and activities of phenylalanine ammonia-lyase (PAL), chitinase, and β-1,3-glucanase in S. miltiorrhiza roots. In addition, mycorrhizal pre-inoculation caused upregulation of defense-related genes, and jasmonic acid (JA) and salicylic acid (SA) signaling pathway genes after pathogen infection. The above findings indicate that mycorrhizal colonization enhances S. miltiorrhiza resistance against F. oxysporum infection by enhancing photosynthesis, root structure, and inducing the expression of defense enzymes and defense-related genes on the other hand.

Demographic characteristics have been recognized as an important factor affecting public acceptance of waste-to-energy (WTE) incineration facilities. The present study explores whether the differences in public acceptance of WTE incineration facilities caused by demographic characteristics are consistent in residential groups under different perceived stress using data collected by a large-scale questionnaire survey (1,066 samples) conducted in three second-tier cities in China. The result of data analysis using a T-test (one-way ANOVA) shows firstly that people with low perceived stress have higher public acceptance of WTE incineration facilities. Second, the differences in public acceptance of WTE incineration facilities caused by demographic characteristics (gender, educational attainment, and age) vary in residential groups with different perceived stress levels. The findings enrich the knowledge system related to demographic characteristics research on NIMBY infrastructure projects and provide the theoretical basis for the government to formulate more targeted policies about NIMBY infrastructure sitting.

Abstract Background Intraocular lens (IOL) calculation using traditional formulas for post-corneal refractive surgery eyes can yield inaccurate results. This study aimed to compare the clinical accuracy of the newly developed Zhang & Zheng (ZZ) formula with previously reported IOL formulas. Study design Retrospective study. Methods Post-corneal refractive surgery eyes were assessed for IOL power using the ZZ, Haigis-L, Shammas, Barrett True-K (no history), and ray tracing (C.S.O Sirius) IOL formulas, and their accuracy was compared. No pre-refractive surgery information was used in the calculations. Results This study included 38 eyes in 26 patients. ZZ IOL yielded a lower arithmetic IOL prediction error (PE) compared with ray tracing (P = 0.04), whereas the other formulas had values like that of ZZ IOL (P > 0.05). The arithmetic IOL PE for the ZZ IOL formula was not significantly different from zero (P = 0.96). ZZ IOL yielded a lower absolute IOL PE compared with Shammas (P

Objectives: Avian influenza virus A(H7N9) remains a threat to humans and has great potential to cause a pandemic in the foreseeable future. Antiviral treatment with neuraminidase inhibitors has been recommended to treat patients with H7N9 infection as early as possible, although evidence-based research on their effectiveness for H7N9 infection is lacking. Methods: Data from all laboratory-confirmed cases of H7N9 infection in Zhejiang Province between 2013 and 2017 were retrieved, and time-dependent survival models were used to evaluate the effectiveness of treatment with neuraminidase inhibitors to reduce the risk of mortality. Results: The final optimal model found no significant association (odds ratio 1.29, 95% confidence interval 0.78–2.15) between time to treatment with neuraminidase inhibitors and survival after controlling for age and white blood cell count. Sensitivity analyses with multiple imputation for missing data concurred with the primary analysis. Conclusions: No association was found between treatment with neuraminidase inhibitors and survival in patients with H7N9 infection using various adjusted models and sensitivity analyses of missing data imputations.

Abstract Background Myopia is hypothesized to be influenced by environmental light conditions. For example, it has been shown that colour and temporal frequency of flickering light affect emmetropisation in animals. Considering the omnipresence of flickering light in our daily life, we decided to analyze the effect of colour flickers on variability of the accommodation response (VAR) in emmetropes and myopes. Methods We measured the dynamic accommodative responses of 19 emmetropic and 22 myopic adults using a Grand Seiko WAM-5500 open-field autorefractor. The subjects focused for more than 20 s on a black Snellen E target against three different backgrounds made up of three colour flicker combinations (red/green, red/blue and blue/green) and under five frequency conditions (0.20 Hz, 0.50 Hz, 1.00 Hz, 1.67 Hz, and 5.00 Hz). Results Flicker frequency and colour both had a significant effect on VAR. Lower frequencies were associated with larger variability. Colour had an effect only at low frequencies, and red/blue colour flicker resulted in the largest variability. The variability in myopes were larger than those in emmetropes. Conclusions These findings support the hypothesis that further studies on the colour and temporal frequency of flickering light can lead to a better understanding of the development and progression of myopia.

Salvia miltiorrhiza is a medicinal plant that can produce the bioactive tanshinones. Here, the authors report the improved genome assembly and reveal the possible roles of three CYP71Ds in catalyzing the reactions leading to the formation of the characteristic furan D-ring of transhinones.

Introduction Using a cross-sectional population-based survey, electronic vapor product (EVP) use was evaluated in relation to physical activity levels among high school students in Georgia. Methods We used self-reported EVP and cigarette use from the Georgia Student Health Survey 2.0 data from 2018 (N =362 933) and used multi-level multinomial logistic regression models to estimate relative risks of the type of product use relative to no-use by levels of physical activity. Results Nearly 7% of the students were EVP-only users. The relative risks of being an EVP-only user were 11% and 23% higher for those who were physically active 2-3 days/week and 4-5 days/week, respectively, compared to those who were physically active

Roots of Euphorbia fischeriana and Euphorbia ebracteolata are recorded as the source plant of traditional Chinese medicine “Langdu,” containing active ingredients with anticancer and anti-AIDS activity. However, the two species have specific patterns in the graphic distribution. Compared with E. ehracteolata, E. fischeriana distributes in higher latitude and lower temperature areas and might have experienced cold stress adaptation. To reveal the molecular mechanism of environmental adaptation, RNA-seq was performed toward the roots, stems, and leaves of E. fischeriana and E. ehracteolata. A total of 6,830 pairs of putative orthologs between the two species were identified. Estimations of non-synonymous or synonymous substitution rate ratios for these orthologs indicated that 533 of the pairs may be under positive selection (Ka/Ks > 0.5). Functional enrichment analysis revealed that significant proportions of the orthologs were in the TCA cycle, fructose and mannose metabolism, starch and sucrose metabolism, fatty acid biosynthesis, and terpenoid biosynthesis providing insights into how the two closely related Euphorbia species adapted differentially to extreme environments. Consistent with the transcriptome, a higher content of soluble sugars and proline was obtained in E. fischeriana, reflecting the adaptation of plants to different environments. Additionally, 5 primary or secondary metabolites were screened as the biomarkers to distinguish the two species. Determination of 4 diterpenoids was established and performed, showing jolkinolide B as a representative component in E. fischeriana, whereas ingenol endemic to E. ebracteolate. To better study population genetics, EST-SSR markers were generated and tested in 9 species of Euphorbia. A total of 33 of the 68 pairs were screened out for producing clear fragments in at least four species, which will furthermore facilitate the studies on the genetic improvement and phylogenetics of this rapidly adapting taxon. In this study, transcriptome and metabolome analyses revealed the evolution of genes related to cold stress tolerance, biosynthesis of TCA cycle, soluble sugars, fatty acids, and amino acids, consistent with the molecular strategy that genotypes adapting to environment. The key active ingredients of the two species were quantitatively analyzed to reveal the difference in pharmacodynamic substance basis and molecular mechanism, providing insights into rational crude drug use.

ObjectivesAn accurate prognostic score to predict mortality for adults with COVID-19 infection is needed to understand who would benefit most from hospitalizations and more intensive support and care. We aimed to develop and validate a two-step score system for patient triage, and to identify patients at a relatively low level of mortality risk using easy-to-collect individual information.DesignMulticenter retrospective observational cohort study.SettingFour health centers from Virginia Commonwealth University, Georgetown University, the University of Florida, and the University of California, Los Angeles.PatientsCoronavirus Disease 2019-confirmed and hospitalized adult patients.Measurements and Main ResultsWe included 1,673 participants from Virginia Commonwealth University (VCU) as the derivation cohort. Risk factors for in-hospital death were identified using a multivariable logistic model with variable selection procedures after repeated missing data imputation. A two-step risk score was developed to identify patients at lower, moderate, and higher mortality risk. The first step selected increasing age, more than one pre-existing comorbidities, heart rate >100 beats/min, respiratory rate ≥30 breaths/min, and SpO2