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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.

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.

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.

Spanish-speaking students constitute the largest subgroup of emergent bilingual (EB) students in the United States. Using longitudinal data on a nationally representative sample of Spanish-English EBs, we explore profiles of English reading trajectories and how early individual differences (i.e., early Spanish reading and English oral proficiency) influence English reading development. Latent class growth analysis revealed five distinct growth trajectories of English reading scores across elementary grades. Results showed a fan-spread effect, indicating that children with higher mean reading scores in kindergarten also had faster growth in English reading from kindergarten to Grade 5. Results also showed that children with high early Spanish reading were more likely to be a member of the classes with the highest initial English reading scores and fastest growth rates. However, kindergarten English oral proficiency was not related to trajectories of English reading. Our findings highlight that early Spanish reading skill is an important factor in identifying EB children who may be at risk for reading difficulties later in elementary school.

Phospholipase A2 (PLA2) catalyzes the hydrolysis of the sn-2 acyl ester linkage in phospholipid, producing lysophospholipid and fatty acid in the presence of Ca2+. The hydrolysis mediated by PLA2 has attracted much interest in various fields, such as pharmacy and biotechnology. It is recognized that PLA2 cannot hydrolyze phospholipid monolayers at high surface coverage. However, the origin of different PLA2 activities is not fully understood yet. The present study investigated the interaction between DPPC (16:0 PC) monolayer and PLA2 using heterodyne-detected sum frequency generation spectroscopy, which is interface-specific spectroscopy and highly sensitive to molecular symmetry based on a second-order nonlinear optical process. It was revealed that PLA2 adsorbs to the DPPC monolayer on the aqueous solution surface only when the surface coverage is low. The adsorption at the low surface coverage significantly changes the interfacial structures of PLA2 and the hydration, which are stabilized by the presence of Ca2+. Therefore, the restriction of the hydrolysis of phospholipid monolayers at high surface coverage can be rationalized by the inhabitation of the PLA2 adsorption. The present study deepens our molecular-level understanding of the hydrolysis of phospholipids by PLA2. [ABSTRACT FROM AUTHOR]

Context • Chromosomal abnormalities in embryos are the most common cause of early spontaneous abortions. Chromosome 1p36 deletion syndrome (OMIM 607872) is the most common subtelomeric, terminal microdeletion syndrome. Objective • The study intended to analyze miscarriage samples using chromosomal microarray analysis (CMA), to explore the mechanism of chromosomal aberrations, and to identify the recurrence risk and a prenatal diagnostic strategy for couples experiencing spontaneous abortions. Design • The research team performed a narrative review by searching PubMed databases. The search used the keywords 1p36 deletion, CMA, karyotype analysis, FISH and aborted fetus. The team also conducted case studies using genetic analyses. Setting • The study took place at Wuxi Maternity and Child Health Care Hospital in Wuxi, Jiangsu, PR China. Participants • Out of 673 abortion samples, six had 1p36 deletions (0.89%). Participants were the six families who had had those spontaneous abortions. Outcome Measures • The research team evaluated the fetal samples using: (1) CMA, (2) karyotype analysis, and (3) novel fluorescence in-situ hybridization (FISH). Results • The CMA showed that: (1) fetus 1 had a 1.75 MB microdeletion at the 1p36.32p36.31 band, which testing didn’t detect in fetus 1’s parents, but the research team couldn’t exclude the possibility that one of the parents was a carrier of a chromosomal insertional translocation; and (2) fetus 2 had a 5.10 MB microdeletion at the 1p36.13p36.12 segment, and fetus 3 had a 9.21 MB deletion at the 1p36.33p36.22 band, and the high-resolution karyotype analysis and FISH of the parents of both fetuses appeared normal, indicating that the chromosomal abnormalities were de novo; (3) fetus 4 had a 9.28 MB deletion at 1p36.33p36.22, although the high-resolution karyotype analysis of fetus 4’s parent was normal; (4) fetuses 5 and 6 had a 7.64 MB microdeletion at 1p36.33p36.23 and a 4.45 MB deletion at 1p36.33p36.32, respectively, although the parents of both fetuses waived further testing. Conclusions • This study provides the first report of recurrent spontaneous and sporadic abortions with 1p36 deletion syndrome. The CMA combined with a reasonable family-pedigree investigation can detect cryptic chromosomal aberrations in miscarriages and can determine the mechanism of the chromosomal variations. It thus is invaluable in assessing recurrence risk and providing appropriate prenatal diagnostic strategies for affected families. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to examine the measurement structure of the linguistic features of speech-language pathologists' (SLPs) talk during business-as-usual therapy sessions in the public schools and to test the longitudinal stability of a theorized dimensional structure consisting of quantity, grammatical complexity, and lexical complexity. Method: Seventy-five SLPs' talk during therapy sessions with primary-grade students was automatically transcribed and coded for linguistic features from a corpus of 579 videotaped therapy session videos collected at the beginning, middle, and end of one school year with an approximately 12-week interval. We explored video characteristics and conducted descriptive statistics on eight linguistic indices of SLP talk to examine the variability in SLP talk between therapy sessions. Confirmatory factor analyses were used to explore the dimensional structure of SLP talk at each time point separately for the theorized three dimensions, and we conducted longitudinal measurement invariance analyses to test the stability of the three-factor structural model across the academic year. Results: There were considerable variabilities among SLPs in the characteristics of SLP talk during therapy sessions. The proposed three-factor structure of SLP talk consisting of quantity, grammatical complexity, and lexical complexity had good model fit at all three time points. The linguistic measurement properties representing the three factors were invariant over time. Conclusions: Results provided robust evidence of between-SLP variability in their child-directed talk, established a three-dimensional structure of the linguistic features in SLP talk, and identified that the linguistic features in SLP talk stably measured the same constructs across one school year, based on measurement invariance. The dimensions of SLP talk during therapy with students may represent important, malleable features of therapy that influence child language gains. [ABSTRACT FROM AUTHOR]

This article is concerned with constructing a confidence interval for a target policy's value offline based on a pre-collected observational data in infinite horizon settings. Most of the existing works assume no unmeasured variables exist that confound the observed actions. This assumption, however, is likely to be violated in real applications such as healthcare and technological industries. In this article, we show that with some auxiliary variables that mediate the effect of actions on the system dynamics, the target policy's value is identifiable in a confounded Markov decision process. Based on this result, we develop an efficient off-policy value estimator that is robust to potential model misspecification and provide rigorous uncertainty quantification. Our method is justified by theoretical results, simulated and real datasets obtained from ridesharing companies. A Python implementation of the proposed procedure is available at. [ABSTRACT FROM AUTHOR]

In aprotic lithium–oxygen (Li–O2) batteries, solvent properties are crucial in the charge/discharge processes. Therefore, a thorough understanding of the solvent stability at the cathode surface during the oxygen reduction/evolution reactions (ORR/OER) is essential for the rational design of high-performance electrolytes. In this study, the stability of typical solvents, a series of glyme solvents with different chain lengths, has been investigated during the ORR/OER by in situ vibrational spectroscopy measurements of sum frequency generation (SFG) spectroscopy and infrared reflection absorption spectroscopy (IRRAS). The structural evolution and decomposition mechanism of the solvents during ORR/OER have been discussed based on the observations. Our results demonstrate that superoxide (O2−) generated during the ORR plays a critical role in the stability of the solvents. [ABSTRACT FROM AUTHOR]

Abstract Mental health issues have increased substantially since the onset of the COVID-19 pandemic. However, health policymakers do not have adequate data and tools to predict mental health demand, especially amid a crisis. Using time-series data collected in Singapore, this study examines if and how algorithmically measured emotion indicators from Twitter posts can help forecast emergency mental health needs. We measured the mental health needs during 549 days from 1 July 2020 to 31 December 2021 using the public’s daily visits to the emergency room of the country’s largest psychiatric hospital and the number of users with “crisis” state assessed through a government-initiated online mental health self-help portal. Pairwise Granger-causality tests covering lag length from 1 day to 5 days indicated that forecast models using Twitter joy, anger and sadness emotions as predictors perform significantly better than baseline models using past mental health needs data alone (e.g., Joy Intensity on IMH Visits, χ2 = 14·9, P < ·001***; Sadness Count on Mindline Crisis, χ2 = 4·6, P = ·031*, with a one-day lag length). The findings highlight the potential of new early indicators for tracking emerging public mental health needs.

Abstract The main objective of this study is to examine the relationship of emotional intelligence with psychological well-being and academic achievement through positive psychological characteristics among university students in China. The study was conducted with postgraduate and undergraduate students. The integration of emotional intelligence theory and positive psychological theory was used in this study. The introduced framework included emotional intelligence as the main independent variable, self-efficacy, motivation, and resilience as three mediators, and psychological well-being and academic achievement as two dependent variables. A survey was conducted among 518 students, and structural equation modelling was used to analyse the data. The study found that emotional intelligence was positively related to positive psychological characteristics, psychological well-being, and academic achievement, and the effects were stronger among postgraduate students. Also, positive psychological characteristics, which include self-efficacy, motivation, and resilience, mediate the relationship between emotional intelligence and psychological well-being and academic achievement, and the relationship was stronger among postgraduate students. Proper coping strategies and mechanisms can be helpful to improve both psychological well-being and academic achievement at the same time among university students.

Abstract Purpose To explore the predictive potential of intratumoral and multiregion peritumoral radiomics features extracted from multiparametric MRI for predicting pathological differentiation in hepatocellular carcinoma (HCC) patients. Methods A total of 265 patients with 277 HCCs (training cohort n = 193, validation cohort n = 84) who underwent preoperative MRI were retrospectively analyzed. The risk factors identified through stepwise regression analysis were utilized to construct a clinical model. Radiomics models based on MRI (arterial phase, portal venous phase, delayed phase) across various regions (entire tumor, Peri_5mm, Peri_10mm, Peri_20mm) were developed using the LASSO approach. The features obtained from the intratumoral region and the optimal peritumoral region were combined to design the IntraPeri fusion model. Model performance was assessed using the area under the curve (AUC). Results Larger size, non-smooth margins, and mosaic architecture were risk factors for poorly differentiated HCC (pHCC). The clinical model achieved AUCs of 0.77 and 0.73 in the training and validation cohorts, respectively, while the intratumoral model achieved corresponding AUC values of 0.92 and 0.82. The Peri_10mm model demonstrated superior performance to the Peri_5mm and Peri_20mm models, with AUC values of 0.87 vs. 0.84 vs. 0.73 in the training cohort and 0.80 vs. 0.77 vs. 0.68 in the validation cohort, respectively. The IntraPeri model exhibited remarkable AUC values of 0.95 and 0.86 in predicting pHCC in the training and validation cohorts, respectively. Conclusions Our study highlights the potential of a multiparametric MRI-based radiomic model that integrates intratumoral and peritumoral features as a tool for predicting HCC differentiation. Critical relevance statement Both clinical and multiparametric MRI-based radiomic models, particularly the intratumoral radiomic model, are non-invasive tools for predicting HCC differentiation. Importantly, the IntraPeri fusion model exhibited remarkable predictiveness for individualized HCC differentiation. Key points • Both the intratumoral radiomics model and clinical features were useful for predicting HCC differentiation. • The Peri_10mm radiomics model demonstrated better diagnostic ability than other peritumoral region-based models. • The IntraPeri radiomics fusion model outperformed the other models for predicting HCC differentiation. Graphical Abstract

Abstract Previous research has found that parenting style influences academic resilience. Nonetheless, few studies have focused on the mechanism underlying the relationship between parenting style and academic resilience. This study aims to examine the relationship between adolescents' parenting style and academic resilience, drawing upon the framework of Social Cognitive Theory. Specifically, it wants to explore the mediating roles of self-efficacy and academic motivation in this relationship. The participants were 518 students chosen at random from educational institutions in the Chinese provinces of Zhejiang, Shanghai, and Jiangsu. Social Cognitive Theory was the theoretical foundation for the study, and the Parental Authority Questionnaire was used to measure parenting style. Out of the respondents, 55.5% were male and 45.5% female. The student allocation in the study sample was as follows: 62.34% undergraduate, 28.22% master’s, and 9.44% PhD. More than 60% of participants were over 25 years old. Moreover, the findings revealed that parenting style was directly and positively related to academic resilience. Parenting style was also found to be indirectly and positively related to academic resilience via self-efficacy and academic motivation, respectively, and sequentially. More crucially, it was discovered that the direct association was far lower than the indirect effects, with self-efficacy being the most effective. The study indicates a relationship between parenting style and academic resilience in adolescents, with self-efficacy and academic motivation acting as the main mediators. These findings emphasize the significance of these intermediary elements, implying that they play a larger role than the direct influence of parenting style alone.

BackgroundSingapore, like the rest of Asia, faces persistent challenges to mental health promotion, including stigma around unwellness and seeking treatment and a lack of trained mental health personnel. The COVID-19 pandemic, which created a surge in mental health care needs and simultaneously accelerated the adoption of digital health solutions, revealed a new opportunity to quickly scale innovative solutions in the region. ObjectiveIn June 2020, the Singaporean government launched mindline.sg, an anonymous digital mental health resource website that has grown to include >500 curated local mental health resources, a clinically validated self-assessment tool for depression and anxiety, an artificial intelligence (AI) chatbot from Wysa designed to deliver digital therapeutic exercises, and a tailored version of the website for working adults called mindline at work. The goal of the platform is to empower Singapore residents to take charge of their own mental health and to be able to offer basic support to those around them through the ease and convenience of a barrier-free digital solution. MethodsWebsite use is measured through click-level data analytics captured via Google Analytics and custom application programming interfaces, which in turn drive a customized analytics infrastructure based on the open-source platforms Titanium Database and Metabase. Unique, nonbounced (users that do not immediately navigate away from the site), engaged, and return users are reported. ResultsIn the 2 years following launch (July 1, 2020, through June 30, 2022), the website received >447,000 visitors (approximately 15% of the target population of 3 million), 62.02% (277,727/447,783) of whom explored the site or engaged with resources (referred to as nonbounced visitors); 10.54% (29,271/277,727) of those nonbounced visitors returned. The most popular features on the platform were the dialogue-based therapeutic exercises delivered by the chatbot and the self-assessment tool, which were used by 25.54% (67,626/264,758) and 11.69% (32,469/277,727) of nonbounced visitors. On mindline at work, the rates of nonbounced visitors who engaged extensively (ie, spent ≥40 seconds exploring resources) and who returned were 51.56% (22,474/43,588) and 13.43% (5,853/43,588) over a year, respectively, compared to 30.9% (42,829/138,626) and 9.97% (13,822/138,626), respectively, on the generic mindline.sg site in the same year. ConclusionsThe site has achieved desired reach and has seen a strong growth rate in the number of visitors, which required substantial and sustained digital marketing campaigns and strategic outreach partnerships. The site was careful to preserve anonymity, limiting the detail of analytics. The good levels of overall adoption encourage us to believe that mild to moderate mental health conditions and the social factors that underly them are amenable to digital interventions. While mindline.sg was primarily used in Singapore, we believe that similar solutions with local customization are widely and globally applicable.

Objective: In order to improve the situation that existing fruit recognition and classification methods rely on manual operation and complex equipment. Methods: A lightweight model YOLO-FFD (YOLO with fruit and freshen detection) was proposed, which based on the YOLOv5 framework. Firstly, LightweightC3 was designed as the basic unit of the backbone feature extraction network based on the depth separable convolution and GELU activation function, which reduced the number of model parameters and computation, and speeds up the convergence of the model. Secondly, EnhancedC3, a large kernel depth separable convolution module, was used to improve the neck of the original model, suppressed information loss and enhance the feature fusion ability of the model, so as to improve the detection accuracy of the model. Finally, GSConv was used to replace the common convolution in the feature fusion network to further lighten the model. Results: The experimental results showed that the average accuracy of the proposed model reached 96.12%, the FPS on RTX 3090 was 172, and the speed on the embedded Jetson TX2 was 20 frames per second. Compared with the original YOLOv5 model, the mAP was improved by 2.21%, the calculation amount was reduced by 26%, and the speed was increased by two times. Conclusion: YOLO-FFD can meet the requirement of identifying fruit varieties and freshness, and improve the falsely detection and missing detection in complex scenes.

Abstract Following the Materials Genome Initiative project, materials research has embarked a new research paradigm centered around material repositories, significantly accelerating the discovery of novel materials, such as thermoelectrics. Thermoelectric materials, capable of directly converting heat into electricity, are garnering increasing attention in applications like waste heat recovery and refrigeration. To facilitate research in this emerging paradigm, we have established the Materials Hub with Three‐Dimensional Structures (MatHub‐3d) repository, which serves as the foundation for high‐throughput (HTP) calculations, property analysis, and the design of thermoelectric materials. In this review, we summarize recent advancements in thermoelectric materials powered by the MatHub‐3d, specifically HTP calculations of transport properties and material design on key factors. For HTP calculations, we develop the electrical transport package for HTP purpose, and utilize it for materials screening. In some works, we investigate the relationship between transport properties and chemical bonds for particular types of thermoelectric compounds based on HTP results, enhancing the fundamental understanding about interested compounds. In our work associated with material design, we primarily utilize key factors beyond transport properties to further expedite materials screening and speedily identify specific materials for further theoretical/experimental analyses. Finally, we discuss the future developments of the MatHub‐3d and the evolving directions of database‐driven thermoelectric research.

Objective To explore the influence of apical dense bone islands on tooth movement during orthodontic treatment and its complications, and to provide a reference for orthodontic clinical treatment. Methods This study obtained approval from the hospital ethics committee. A retrospective analysis was conducted on 33 patients with apical dense bone islands who received full-mouth fixed orthodontic treatment in the Orthodontics Department of Huizhou Stomatological Hospital from 2018 to 2022. Cone-beam CT (CBCT) was used to determine the location, distribution, and wrapping severity of the apical dense bone islands before treatment. The number of loose teeth located in the apical dense bone islands and the degree of external apical root resorption in the apical area of teeth were analyzed before treatment, immediately after treatment, and 12 months after treatment. Results There were 33 orthodontic patients (aged 11 to 42 years, with an average age of 16.7 years and a median age of 15 years) included in this study, including 12 males (36.4%) and 21 females (63.6%). All apical dense bone islands involved a single tooth located in the mandible, mainly in the premolar-molar area. No gender differences were present in the location of the dense bone islands (P>0.05). The apical dense bone islands were mildly wrapped in 23 cases (69.7%), moderately wrapped in 10 cases (30.3%), and severely wrapped in no cases. No difficulty in tooth movement or incomplete closure of extraction space was found in the apical dense bone islands with different degrees of wrapping during orthodontic treatment. For teeth located in apical dense bone islands, 1 patient (3.0%) had loose teeth before treatment, 6 patients (18.2%) had loose teeth after treatment, and 2 patients (6.1%) had loose teeth 12 months after treatment. The number of patients with grade I loose teeth increased after treatment and 12 months after treatment. There was a statistically significant difference in the number of loose teeth before and after treatment (PP>0.05), and no statistically significant difference in the number of loose teeth after treatment and 12 months after treatment (P>0.05). After treatment, apical dense bone islands showed mild resorption in 26 cases (78.8%), moderate resorption in 7 cases (21.2%), and severe resorption in no cases. The apical dense bone islands showed mild resorption in 25 cases (75.8%), moderate resorption in 8 cases (24.2%), and severe resorption in no cases 12 months after treatment. For the severity of root resorption, there was a statistically significant difference between before and after treatment (PPP>0.05). Conclusion Apical dense bone islands were not found to affect tooth movement during orthodontic treatment. After orthodontic treatment, the number of loose teeth increased and mild-to-moderate tooth external apical root resorption occurred, which may be a potential risk of external apical root resorption. Thus, it is recommended to pay close attention during the orthodontic process.

ABSTRACTShiraia-like fungi, which are rare parasitic fungi found around bamboo, play an important role in traditional medicine. Their main active component, hypocrellin, is widely used in medicine, food, and cosmetics. By comparing strains with different hypocrellin yields, we identified a transcription factor (SbTF) in the hypocrellin biosynthesis pathway. SbTF from high-yielding zzz816 and low-yielding CNUCC C72 differed in its protein structure. Subsequently, SbTF from high-yielding zzz816 was overexpressed in several strains. This stabilised the yield in zzz816 and significantly increased the yield in low-yielding CNUCC C72. Comparing downstream non-essential genes between wild type and SbTF-overexpressing CNUCC C72 showed that SbMNF was significantly up-regulated. Therefore, it was selected for further study. SbMNF overexpression increased the hypocrellin yield in low-yielding CNUCC C72 and altered the composition of compounds in high-yielding CNUCC 1353PR and zzz816. This involved an increased elsinochrome C yield in CNUCC 1353PR and an increased hypocrellin B yield in zzz816 (by 2 and 70.3 times that in the corresponding wild type, respectively). This study is the first to alter hypocrellin synthesis to alter the levels of one bioactive agent compared to another. The results provide new insights regarding genetic modification and will help to optimise fungal fermentation.

Pulmonary infection is highly prevalent in patients with acute myocardial infarction undergoing percutaneous coronary intervention. However, the potential mechanism is not well characterized. Myocardial ischemia-reperfusion injury (MIRI) induces acute lung injury (ALI) related to pulmonary infection and inflammation. Recent studies have shown that pyroptosis mediates ALI in several human respiratory diseases. It is not known whether MIRI induces pyroptosis in the lungs. Furthermore, ticagrelor is a clinically approved anti-platelet drug that reduces ALI and inhibits the expression levels of several pyroptosis-associated proteins, but the effects of ticagrelor on MIRI-induced ALI have not been reported. Therefore, we investigated whether ticagrelor alleviated ALI in the rat MIRI model, and its effects on pyroptosis in the lungs. Sprague-Dawley rats were randomly divided into four groups: control, MIRI, MIRI plus low ticagrelor (30 mg/kg), and MIRI plus high ticagrelor (100 mg/kg). Hematoxylin and Eosin (HE) staining was performed on the lung sections, and the HE scores were calculated to determine the extent of lung pathology. The wet-to-dry ratio of the lung tissues were also determined. The expression levels of pyroptosis-related proteins such as NLRP3, ASC, and Cleaved caspase-1 were estimated in the lung tissues using the western blot. ELISA was used to estimate the IL-1β levels in the lungs. Immunohistochemistry was performed to determine the levels of MPO-positive neutrophils as well as the total NLRP3-positive and Cleaved caspase-1-positive areas in the lung tissues. The lung tissues from the MIRI group rats showed significantly higher HE score, wet-to-dry ratio, and the MPO-positive area compared to the control group, but these effects were attenuated by pre-treatment with ticagrelor. Furthermore, lung tissues of the MIRI group rats showed significantly higher expression levels of pyroptosis-associated proteins, including NLRP3 (2.1-fold, P < 0.05), ASC (3.0-fold, P < 0.01), and Cleaved caspase-1 (9.0-fold, P < 0.01). Pre-treatment with the high-dose of ticagrelor suppressed MIRI-induced upregulation of NLRP3 (0.46-fold, P < 0.05), ASC (0.64-fold, P < 0.01), and Cleaved caspase-1 (0.80-fold, P < 0.01). Immunohistochemistry results also confirmed that pre-treatment with ticagrelor suppressed MIRI-induced upregulation of pyroptosis in the lungs. In summary, our data demonstrated that MIRI induced ALI and upregulated pyroptosis in the rat lung tissues. Pre-treatment with ticagrelor attenuated these effects.

Phospholipase A2 (PLA2) catalyzes the hydrolysis of the sn-2 acyl ester linkage in phospholipid, producing lysophospholipid and fatty acid in the presence of Ca2+. The hydrolysis mediated by PLA2 has attracted much interest in various fields, such as pharmacy and biotechnology. It is recognized that PLA2 cannot hydrolyze phospholipid monolayers at high surface coverage. However, the origin of different PLA2 activities is not fully understood yet. The present study investigated the interaction between DPPC (16:0 PC) monolayer and PLA2 using heterodyne-detected sum frequency generation spectroscopy, which is interface-specific spectroscopy and highly sensitive to molecular symmetry based on a second-order nonlinear optical process. It was revealed that PLA2 adsorbs to the DPPC monolayer on the aqueous solution surface only when the surface coverage is low. The adsorption at the low surface coverage significantly changes the interfacial structures of PLA2 and the hydration, which are stabilized by the presence of Ca2+. Therefore, the restriction of the hydrolysis of phospholipid monolayers at high surface coverage can be rationalized by the inhabitation of the PLA2 adsorption. The present study deepens our molecular-level understanding of the hydrolysis of phospholipids by PLA2., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Obstructive sleep apnea (OSA) is common in surgical patients and associated with worse perioperative outcomes., Objectives: To investigate the effect of mini-dose dexmedetomidine supplemented analgesia on postoperative sleep quality pattern in patients at high risk of OSA., Design: A pilot randomized, double-blind, placebo-controlled trial., Setting: A tertiary university hospital in Beijing, China., Patients: One hundred and fifty-two adult patients who had a STOP-Bang score ≥3 and a serum bicarbonate level ≥28 mmol/L and were scheduled for major noncardiac surgery between 29 January 2021 and 20 September 2022., Intervention: After surgery, patients were provided with high-flow nasal cannula and randomized in a 1:1 ratio to receive self-controlled opioid analgesia supplemented with either mini-dose dexmedetomidine (median 0.02 μg/kg/h) or placebo. We monitored polysomnogram from 9:00 pm to 6:00 am during the first night., Main Outcome Measures: Our primary outcome was the percentage of stage 2 non-rapid eye movement (N2) sleep. Secondary and exploratory outcomes included other postoperative sleep structure parameters, sleep-respiratory parameters, and subjective sleep quality (Richards-Campbell Sleep Questionnaire; 0-100 score range, higher score better)., Results: All 152 patients were included in intention-to-treat analysis; 123 patients were included in sleep structure analysis. Mini-dose dexmedetomidine supplemented analgesia increased the percentage of stage N2 sleep (median difference, 10%; 95% CI, 1 to 21%; p  = 0.029); it also decreased the percentage of stage N1 sleep (median difference, -10%; 95% CI, -20% to -1%; p  = 0.042). Other sleep structure and sleep-respiratory parameters did not differ significantly between the two groups. Subjective sleep quality was slightly improved with dexmedetomidine on the night of surgery, but not statistically significant (median difference, 6; 95% CI, 0 to 13; p  = 0.060). Adverse events were similar between groups., Conclusion: Among patients at high risk of OSA who underwent noncardiac surgery, mini-dose dexmedetomidine supplemented analgesia may improve sleep quality without increasing adverse events., Clinical Trial Registration: Clinicaltrials.gov, identifier NCT04608331., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Liang, Chen, Ma, Zhang, Shen, Zhu and Wang.)