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Abstract Age-related hearing loss (ARHL) is the most prevalent sensory impairment in the elderly. However, the pathogenesis of ARHL remains unclear. This study was aimed to explore the potential inflammation-related genes of ARHL and suggest novel therapeutic targets for this condition. Initially, a total of 105 Inflammatory related differentially expressed genes (IRDEGs) were obtained by overlapping the differentially expressed genes from the GSE49522 and GSE49543 datasets with Inflammatory related genes. The IRDEGs were mainly enriched in MAPK, PI3K-Akt, Hippo and JAK-STAT pathways by analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. We then identified 10 key IRDEGs including Alox5ap, Chil1, Clec7a, Dysf, Fcgr3, etc. using Least absolute shrinkage and selection operator regression analysis and converted them into human genes. The ROC curve indicated that Alox5ap expression presented a high accuracy in distinguishing between different groups. By CIBERSORT algorithm, 8 humanized key IRDEGs were correlated with the infiltration abundance of 3 immune cells. Finally, it showed that the Alox5ap expression was significantly more effective compared to other variables in the diagnostic model of ARHL. This study suggests that inflammation might play a role in the development of ARHL, providing a deeper understanding of the underlying causes of this disease.

Abstract Background Nephrology referral has been recognized as a modifiable factor influencing patient outcomes. The study aimed to compare clinical outcomes among patients referred early versus late to nephrologists. Methods We searched online database from inception to June 1, 2022, to obtain all eligible literature reporting outcomes of patients referred early versus late to nephrologists. The early and late referral was defined by the time at which patients were referred to nephrologists before dialysis onset. Results Seventy-two studies with over 630,000 patients met the inclusion criteria. A lower likelihood of all-cause mortality (HR = 0.67, 95% CI: 0.62–0.72) was achieved among patients referred early to nephrologists. The survival advantage of early referral was apparent in the first 6 months and extended to the 5th year after dialysis onset (6 months: HR = 0.52, 95% CI: 0.40–0.68; 5 years: HR = 0.67, 95% CI: 0.60–0.74). The early referral was associated with shorter durations of initial hospitalization, a higher rate of kidney transplantation (RR = 1.41, 95% CI: 1.12–1.78), a lower likelihood of emergency start (RR = 0.39, 95% CI: 0.28–0.54), a higher likelihood of permanent access creation (RR = 3.34, 95% CI: 2.43–4.59), increased initial use of permanent access (RR = 2.60, 95% CI: 2.18–3.11), and reduced initial catheter use (RR = 0.43, 95% CI: 0.32–0.58). Conclusions Our study showed a lower risk of mortality, shorter lengths of initial hospitalization, and better preparations for renal replacement therapy among patients referred early to nephrologists. Early nephrology care should be promoted to improve the management of advanced chronic kidney disease.

This review summarizes the current research advances and guideline updates in neurocritical care. For the therapy of ischemic stroke, the extended treatment time window for thrombectomy and the emergence of novel thrombolytic agents and strategies have brought greater hope for patient recovery. Minimally invasive hematoma evacuation and goal-directed bundled management have shown clinical benefits in treating cerebral hemorrhage. In the treatment of aneurysmal subarachnoid hemorrhage (aSAH), early lumbar drainage can reduce the risk of infarction. Decompressive craniectomy for severe traumatic brain injury has also obtained high-quality evidence support. However, multimodal brain monitoring strategies for patients with traumatic brain injury need further optimization. For patients with cardiac arrest, extracorporeal cardiopulmonary resuscitation can reduce in-hospital mortality and improve long-term neurological prognosis. For neurocritical care patients, abundant high-quality studies have emerged in areas including multimodal neuromonitoring, hemodynamic management, airway management and respiratory therapy, and antiepileptic treatment. In 2023, the guidelines for aSAH have been updated for the first time in the past decade, aiming to provide evidence-based practice recommendations for clinical care. Chinese expert consensuses have also been formulated to guide analgesia and sedation for neurocritical care patients and developed a set of medical quality indicators on neurocritical care, which will enhance standardization and homogenization improvement in neurocritical care quality.

Abstract To compare the efficacy and safety of gecacitinib (also known as jaktinib) with hydroxyurea (HU) in treating myelofibrosis (MF) patients. In this multicenter, randomized phase 3 trial (ZGJAK016), intermediate- or high-risk primarily JAK inhibitor naïve MF patients were assigned in a 2:1 ratio to receive either gecacitinib (100 mg twice a day, BID) or HU (500 mg BID). The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) from baseline at week 24. Secondary endpoints included the best spleen response rate, the proportion of patients with a ≥50% reduction in total symptom score (TSS50), anemia improvement, and safety profile. At 24 weeks, the SVR35 was reached by 64.8% of patients on gecacitinib (46/71), compared to 26.5% on HU (9/34), P = 0.0002. The best spleen response rates were also superior for gecacitinib at 81.7%, vs 32.4% for HU, P

Abstract Our previous manuscript showed that thrombocytopenia predicts all-cause mortality in Chinese hemodialysis (HD) patients. Based on the role of platelets in coagulation, clot formation, and systemic inflammation, we speculate that high platelets increase risk of thrombo-embolic events, hence the mortality. However, research evidence is currently lacking. Therefore, we utilized data from a very large international cohort study to explore the association of platelet counts with mortality and cardiovascular (CV) death in hemodialysis (HD) patients. International data from 396 facilities enrolled in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 5 (2012–2015) were analyzed. Participants were divided into 3 groups according to their platelet counts (low: 300*109). Associations between platelet counts and all-cause and CV mortality were analyzed using Cox regression, adjusted for confounders. There were 13,631 patients with median age of 65 years old. Males accounted for 61.2%. Mean platelet count was 205*109/L overall and ranged from 173 *109/L in China to 227 *109/L in Sweden. Overall, 2,348 (17.2%) patients died and 1017 (7.5%) died from CV disease. Both low (HR:1.48, 95% CI 1.21–1.80, p

In terms of prevalence, 11β-hydroxylase deficiency (11β-OHD), a common form of congenital adrenal hyperplasia, closely follows 21-hydroxylase deficiency. 11β-OHD has been attributed to diminished enzymatic activity owing to CYP11B1 gene variants, mainly encompassing single nucleotide variations and insertions-deletions. The involvement of chimeric CYP11B2/CYP11B1 genes in 11β-OHD has rarely been reported. We conducted a genetic investigation on a male infant with generalized pigmentation and abnormal steroid hormone levels. Whole-exome sequencing revealed a heterozygous variant in CYP11B1 inherited from the mother (NM_000497.4: c.1391_1393dup [p.Leu464dup]). Long-range polymerase chain reaction revealed an additional allele, a chimeric CYP11B2/CYP11B1 gene, inherited from the father. The current case report highlights the need to consider the occurrence of gene fusion variants in the diagnosis of neonatal or early infantile 11β-OHD.

Socioeconomic status (SES) has received great attention in learning a second or foreign language (SL/FL). However, little research has investigated the association between SES and SL/FL pragmatic learning, let alone the influencing pathways of SES on SL/FL pragmatic awareness (PA). Therefore, this research aimed to address the link between learners’ SES and PA with the mediating effects of learning motivation based on the L2 motivation self-system (L2MSS) theory by surveying 292 Chinese EFL university students. Structural equation modeling analyses indicated that: (1) SES had no significant effect on ought-to L2 self and intended learning efforts; (2) ought-to L2 self and intended learning efforts had significant predictive effects on PA; (3) SES positively and directly predicted EFL learners’ PA; and (4) ideal L2 self, attitudes toward L2 community, and attitudes toward learning English mediated the relationship between SES and Chinese EFL learners’ PA significantly.

BackgroundThe increased risks for cardiovascular comorbidities and cardiovascular diseases (CVD) in populations with normal weight obesity (NWO) have not been well-identified. We aimed to study their associations in an adult population in South China.MethodsBased on the CVD prevalence of 4% in Shenzhen and a calculated sample size of 6,000, a cross-sectional study with a multi-stage stratified cluster sampling method was conducted in Shenzhen City. The cardiovascular comorbidities being studied were abdominal obesity (AO), diabetes, hypertension, dyslipidemia, metabolic syndrome, and chronic kidney disease, while the CVD events were occurrences of myocardial infarction and strokes. Questionnaire surveys, physical examinations, and laboratory tests were performed. NWO was defined as a condition with the highest tertile of body fat percentage (BF%) among the normal body mass index (BMI) range (18.5-23.9 kg/m2). Continuous data were reported as mean [standard deviation (SD)] and categorical data as percentages (%). CVD comorbidities and CVD events and their detection rates in different groups were compared using ANONA analysis and Chi-squared test. Spearman's correlation coefficients between BF% and cardiometabolic abnormalities were calculated by partial correlation analysis. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for BF%, CVD comorbidities, and CVD events, adjusted for multiple confounders.ResultsAmong the total 6,240 subjects who completed the study and had BMI and BF% data available, 3,086 had normal BMI. The prevalence of NWO was 16.36%, with 13.15% for men and 19.54% for women. With confounders adjusted, the risks of AO (OR = 6.05, 95%CI = 3.40-10.75), essential hypertension (OR = 1.56, 95%CI = 1.09-2.22), dyslipidemia (OR = 1.85, 95%CI = 1.49-2.29), and metabolic syndrome (OR = 4.61, 95%CI = 2.32-9.18) were significantly increased in the populations with NWO compared with the population without NWO (P < 0.05). BF% was not significantly associated with the risk of CVD events in the total (OR = 1.56, 95%CI = 0.83-2.93), male (OR = 1.00, 95%CI = 0.44-2.30), and female populations (OR = 2.53, 95%CI = 0.91-7.06).ConclusionNWO was found to be positively associated with CVD comorbidities but not with CVD events. The current study provides a ground to conduct further studies on whether body fat affects the risk of occurrence of CVD events and the underlying mechanisms in the future.

Soil organic carbon (SOC) plays a vital role in regulating atmospheric CO2 levels. As global climate change intensifies, understanding the dynamics of the SOC pool becomes the key to assessing the potential for carbon sequestration in terrestrial ecosystems. However, the long-term response mechanisms of SOC density in desert regions to climate change remain unclear, increasing uncertainty in estimating the carbon sequestration potential of these ecosystems. This study aims to construct a comprehensive SOC database for the lower reaches of the Heihe River (HRL) and simulate the spatiotemporal distribution of SOC density within the 0 – 100 cm soil profile. The results indicate that the key indicators of different soil layers are not consistent for SOC density mapping in arid regions. Latitude (LAT), Elevation (ELE) and Normalized difference salinity index (NDSI) are particularly important in shallow soil layers (0–20 and 20–40 cm). Spatially, SOC density in the HRL is primarily distributed along river corridors, aligning closely with vegetation patterns. Additionally, SOC density shows a positive correlation with temperature and a negative correlation with precipitation. The period from the 2050 s to the 2060 s is a critical period for SOC changes in the HRL. Under the low-emission scenario (SSP 119), soil in the HRL shifted from being a carbon sink to a carbon source in the 2050 s. Under the medium-emission (SSP 245) and high-emission scenarios (SSP 585), soil remained a carbon sink overall but began transitioning around the 2060 s and 2050 s, respectively, before stabilizing. This study demonstrates significant carbon sequestration potential in arid region soils, highlighting their essential role in soil carbon storage that cannot be overlooked. The findings of this study provide data references and foundations for understanding the response of SOC in arid regions to climate change.

ObjectiveThe relationship between tinnitus in the elderly with hearing loss remains elusive. This study aimed to reveal the association between tinnitus and hearing impairment among older adults with age-related hearing loss (ARHL).MethodsThis cross-sectional study was conducted among a population of outpatients diagnosed with ARHL at four medical centers in different regions of China, from June 2020 to June 2023. ARHL patients were divided into two groups based on their self-reported tinnitus: tinnitus and non-tinnitus. Multivariable linear regression models were used to assess the association between tinnitus and hearing impairment in ARHL patients. Subgroup analyses, stratified by gender and age, were performed to further evaluate the association.ResultsA total of 418 older adults with ARHL were included in the study. Compared to the non-tinnitus group, ARHL patients with tinnitus had lower hearing thresholds (β = −5.07; 95% confidence interval (CI) −9.32 to −0.81; p = 0.020). On subgroup analyses stratified by gender and age, the male ARHL patients with tinnitus still had lower hearing thresholds compared to those without tinnitus (β = −6.96; 95% CI −12.70 to 1.22; p = 0.018). In females, tinnitus was not associated with hearing thresholds (β = −3.69; 95% CI −10.11 to 2.74, p = 0.262). There was no association between tinnitus and hearing thresholds in both the age group of ≥70 years (β = −4.31; 95% CI −9.65 to 1.03; p = 0.116) and the age group of

Objective Thyroid-associated ophthalmopathy (TAO) is a prevalent orbital disease significantly affecting patients’ daily lives. Nowadays, TikTok acts as a novel tool for healthcare but involved videos need to be further assessed. Many individuals search for disease information on TikTok before professional consultation. This study aimed to assess the quality of TAO-related TikTok videos and correlations between video variables and quality. Methods The top 150 TikTok videos were collected using the keyword TAO. Duplicate, too-short, irrelevant videos and similar videos from the same source were excluded. Two raters evaluated the included videos’ overall quality, reliability, understandability, and actionability on different sources and content focuses. Results Ninety videos had received nearly 15,000 likes and 2000 shares. Ophthalmologists and treatment focus were two primary parts among categorized groups, whose quality scores were much higher than others. The average Patient Education Materials Assessment Tool for Audiovisual Materials scores, Global Quality Scores, and DISCERN scores indicated that these videos were easy to understand (87.6%), actionable (74.5%), and fair in quality (44.97). The number of added hashtags was an essential variable positively correlated with video understandability. Additionally, popularity showed negative correlations with the overall quality, while video length positively correlated with its reliability and negatively correlated with the uploaded days. Conclusion Certified healthcare professionals uploaded most TAO videos, resulting in acceptable quality with minimal misinformation. To serve as a qualified source of patient educational materials, TikTok is supposed to promote longer disease-related videos and enhance reliability and understandability simultaneously.

Food allergies manifest as systemic or digestive allergic responses induced by food allergens, and their progression has been demonstrated to be intimately associated with the host’s gut microbiota. Our preceding investigation has revealed that the probiotic strains Lactiplantibacillus plantarum CCFM1189 and Limosilactobacillus reuteri CCFM1190 possess the capability to mitigate the symptoms of food allergy in mice. However, the underlying mechanisms and material foundations through which these probiotic strains exert their effects remain enigmatic. Here, we initially compared the ameliorative effects of these two probiotic strains on food allergy mice subjected to antibiotic cocktail (ABX) treatment. It is indicated that ABX treatment was ineffective in alleviating weight loss, diarrhea, and allergic symptoms in mice, and it also inhibited the reduction of histamine and T helper cell 2 (Th2) cytokines mediated by effective strains, suggesting that effective strains must operate through the gut microbiota. Then, building upon the outcomes of prior non-targeted metabolomics studies, by quantifying the content of indoleacrylic acid (IA) in single-strain fermentation of probiotic strains and mouse feces, it was ascertained that effective strains do not synthesize IA themselves but can augment the concentration of IA in the gut by modulating the gut microbiota. Ultimately, we discovered that direct intervention with IA could mitigate diarrhea, allergic symptoms, and intestinal damage by modulating immunoglobulin E (IgE) levels, histamine, Th2 cytokines, and tight junction proteins, thereby corroborating that IA is a pivotal metabolite for the alleviation of food allergies. These observations underscore the significance of gut microbiota and metabolites like IA in the management of food allergies and hold potential implications for the development of novel therapeutic strategies.

ABSTRACT Respiratory tract infections (RTIs) caused by viruses are prevalent and significant conditions in clinical settings. Accurate and effective detection is of paramount importance in the diagnosis, treatment, and prevention of viral RTIs. With technological advancements, multiplex real-time reverse transcription polymerase chain reaction (rRT-PCR) assays have been developed and extensively adopted for the diagnosis of viral RTIs. Given the potential challenges in the detection performance of multiplex assays, this study evaluated the analytical sensitivity and competitive interference of the six most commonly used multiplex rRT-PCR kits for detection of respiratory viruses in China. The results revealed that the limits of detection were variable across the viruses and kits. Most of the evaluated multiplex kits demonstrated comparable or enhanced analytical sensitivity compared with singleplex kits for clinically significant viruses, including human adenovirus (HAdV)-3, HAdV-7, Omicron BA.5, H1N1pdm09, H3N2, B/Victoria, respiratory syncytial virus subtype A, and respiratory syncytial virus subtype B, whereas multiplex kits showed relatively less analytical sensitivity for human rhinovirus-B72, human metapneumovirus-A2, parainfluenza virus (PIV)-1, and PIV-3. In addition, most multiplex kits successfully identified co-infections when one analyte was present at a low concentration and another analyte was present at a high concentration.IMPORTANCEThe complexity and severity of viral respiratory tract infections (RTIs) emphasize the pivotal role of precise diagnosis for viral RTIs in guiding effective public health responses and ensuring appropriate medical interventions, given the substantial population at risk. This study highlights the necessity and importance of evaluating the analytical validity of multiplex real-time reverse transcription polymerase chain reaction assays, offering valuable insights into their optimization and application.

We report a case and follow-up of an adult male with intracranial yolk sac tumor (YST). Initially, the patient presented with abnormal high signals in the right basal ganglia on MRI, misdiagnosed as a cavernous hemangioma. However, within 2 years, the condition rapidly progressed into a large, hypervascular solid neoplasm leading to a basal ganglia hemorrhage. Comprehensive evaluation of clinical symptoms, imaging, surgical findings, serology, histopathology, and genetic analysis confirmed the diagnosis of a yolk sac tumor. The patient underwent prompt surgical resection followed by radiotherapy and chemotherapy. Six months post-treatment, his condition remains stable, with no recurrence. Notably, early MRI revealed Wallerian degeneration in the brainstem suggesting that benign-appearing basal ganglia lesions may sometimes result from malignant infiltration by germ cell tumors or other cancers. To prevent misdiagnosis and ensure timely treatment, a stereotactic biopsy is recommended. We hope this case provides a valuable reference for diagnosing and treating YSTs and contributes to ongoing research aimed at improving patient survival.

Anemia is a common complication of chronic kidney disease with major option treatment of erythropoiesis-stimulating agents (ESAs). This study aimed to investigate the influencing factors of erythropoietin resistance index (ERI) and its association with mortality in maintenance hemodialysis (MHD) patients. Patients enrolled from China Dialysis Outcomes and Practice Patterns Study (DOPPS) 5 were included. ERI was calculated as follows: ESA (IU/week)/weight (kg, post-dialysis)/hemoglobin level (g/dL). The Cox regression model was used to analyze the influencing factors on survival outcomes. Stepwise multivariate logistic regression was used to identify the related risk factors, and subgroup analyses were performed. A total of 1270 MHD subjects (687 males and 583 females) were included, with an average age of 60 (49.0, 71.0) years. All subjects were divided into two groups by the median ERI of 14.03. Multivariate logistic regression showed that dialysis vintage (OR 0.957, 95% CI: 0.929–0.986), white blood cells (OR 0.900, 95% CI: 0.844–0.960), high flux dialyzer use (OR 0.866, 95% CI: 0.755–0.993), body mass index (OR 0.860, 95% CI: 0.828–0.892), males (OR 0.708, 95% CI: 0.625–0.801), and albumin (OR 0.512, 95% CI: 0.389–0.673) had a negative association with high ERI baseline (all p

Chlamydia psittaci is an obligate intracellular gram-negative bacterium with a unique biphasic developmental cycle. It is a zoonotic pathogen with a wide range of hosts and can cause avian chlamydiosis in birds and psittacosis in humans. The pathogen is transmitted mainly through horizontal transmission between birds. Cross-species transmission sometimes occurs and human-to-human transmission has recently been confirmed. This review provides an updated overview of C. psittaci from the perspective of both avian chlamydiosis and psittacosis. We include the aspects of genotype, host–pathogen interaction, transmission, epidemiology, detection and diagnosis, clinical manifestation, management, and prevention, aiming to provide a basic understanding of C. psittaci and offer fresh insights focused on zoonosis and cross-species transmission.

Abstract. Background:. Digestive system cancers constitute a significant number of cancer cases, but their burden is not uniform. As Global Cancer Observatory (GLOBOCAN) 2022 has recently updated its estimates of cancer burden, we aimed to investigate the burden of six major digestive system cancers both worldwide and in China, along with geographical and temporal variations in cancer-specific incidence and mortality. Methods:. We extracted data on primary cancers of the esophagus, stomach, colorectum, liver, pancreas, and gallbladder from the GLOBOCAN database for 2022. Age-standardized incidence and mortality rates were calculated and stratified by sex, country, region, and human development index (HDI). We used the 2022 revision of the World Population Prospects (United Nations) to obtain demographic data for various age groups in China from 1988 to 2012 and used the joinpoint model and the average annual percentage change (AAPC) to analyze cancer incidence trends in China. Results:. In 2022, the estimated global incidence of digestive system cancers reached 4,905,882, with an estimated 3,324,774 cancer-related deaths. Colorectal cancer was most prevalent in terms of incidence and mortality. There was a significant correlation between the burden of gastrointestinal cancers and country HDI. From 1988 to 2012, the incidence of esophageal, gastric, and liver cancers declined in China, whereas colorectal and pancreatic cancer incidences continued to increase. By 2050, colorectal and liver cancers are projected to remain the leading cancer types in China in terms of incidence and mortality, respectively. Conclusions:. Digestive system cancers remain a significant public health challenge globally and in China. Although progress has been made in the prevention and control of some cancers, the burden of digestive system cancers persists. The implementation of tertiary prevention strategies must be intensified to reduce the incidence and mortality of digestive system cancers, mitigating their impact on public health.

Abstract Background The inhalational anesthetic isoflurane is commonly utilized in clinical practice, particularly in the field of pediatric anesthesia. Research has demonstrated its capacity to induce neuroinflammation and long-term behavioral disorders; however, the underlying mechanism remains unclear [1]. The cation-chloride cotransporters Na+–K+–2Cl−–1 (NKCC1) and K+–2Cl−–2 (KCC2) play a pivotal role in regulating neuronal responses to gamma-aminobutyric acid (GABA) [2]. Imbalances in NKCC1/KCC2 can disrupt GABA neurotransmission, potentially leading to neural circuit hyperexcitability and reduced inhibition following neonatal exposure to anesthesia [3]. Therefore, this study postulates that anesthetics have the potential to dysregulate NKCC1 and/or KCC2 during brain development. Methods We administered 1.5% isoflurane anesthesia to neonatal rats for a duration of 4 h at postnatal day 7 (PND7). Anxiety levels were assessed using the open field test at PND28, while cognitive function was evaluated using the Morris water maze test between PND31 and PND34. Protein levels of NKCC1, KCC2, BDNF, and phosphorylated ERK (P-ERK) in the hippocampus were measured through Western blotting analysis. Pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were quantified using ELISA. Results We observed a decrease in locomotion trajectories within the central region and a significantly shorter total distance in the ISO group compared to CON pups, indicating that isoflurane induces anxiety-like behavior. In the Morris water maze (MWM) test, rats exposed to isoflurane exhibited prolonged escape latency onto the platform. Additionally, isoflurane administration resulted in reduced time spent crossing in the MWM experiment at PND34, suggesting long-term impairment of memory function. Furthermore, we found that isoflurane triggered activation of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; downregulated KCC2/BDNF/P-ERK expression; and increased the NKCC1/KCC2 ratio in the hippocampus of PND7 rats. Bumetadine (NKCC1 specific inhibitors) reversed cognitive damage and effective disorder induced by isoflurane in neonatal rats by inhibiting TNF-α activation, normalizing IL-6 and IL-1β levels, restoring KCC2 expression levels as well as BDNF and ERK signaling pathways. Based on these findings, it can be speculated that BDNF, P-ERK, IL-1β, IL-6 and TNF - α may act downstream of the NKCC1/KCC2 pathway. Conclusions Our findings provide evidence that isoflurane administration in neonatal rats leads to persistent cognitive deficits through dysregulation of the Cation-Chloride Cotransporters NKCC1 and KCC2, BDNF, p-ERK proteins, as well as neuroinflammatory processes.

Background Excessive proliferation of orbital fibroblasts (OFs) is an essential factor in the pathogenesis of thyroid eye disease (TED). While existing evidence indicates that various microRNAs (miRNAs) significantly contribute to TED development, the precise function and targets of miR-101-3p in TED pathogenesis remain unknown. This research aims to elucidate the effects of miR-101-3p on TED-OFs and identify its potential targets. Methods Orbital adipose tissues were harvested from both TED patients and healthy controls to culture their fibroblasts. MiR-101-3p mimic or mimic negative control (mimic NC) was transfected into OFs from TED patients, with untreated OFs serving as an additional blank control group. Cell proliferation was assessed using cell counting kit-8 (CCK-8) assay, Ki-67 immunofluorescence staining, and the EdU assay, while apoptosis was evaluated via flow cytometry. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure the expression levels of miR-101-3p and pentraxin-3 (PTX3), and PTX3 protein levels were quantified using western blot. A dual-luciferase assay was conducted to ascertain how miR-101-3p and PTX3 interacted. Results The results demonstrated a significant downregulation of miR-101-3p in fibroblasts and TED orbital adipose tissues. Transfection with the miR-101-3p mimic upregulated miR-101-3p levels, significantly reducing OFs proliferation without affecting apoptosis. Overexpression of miR-101-3p led to the downregulation of PTX3 in OFs. The dual-luciferase assay validated miR-101-3p binding to PTX3’s 3’UTR, thereby repressing its expression. Moreover, overexpression of PTX3 partially rescued the miR-101-3p mimic’s inhibitory effect on TED-OFs proliferation. Conclusion Our findings illustrate miR-101-3p’s role in targeting PTX3 to regulate TED-OFs proliferation, providing novel insights into the pathological mechanisms underlying TED development.

IntroductionEndoplasmic reticulum stress (ERS) is a prominent etiological factor in the pathogenesis of diabetes. Nevertheless, the mechanisms through which ERS contributes to the development of diabetes remain elusive.MethodsTranscriptional expression profiles from the Gene Expression Omnibus (GEO) datasets were analyzed and compared to obtain the differentially expressed genes (DEGs) in T2DM. Following the intersection with ERS associated genes, the ERS related T2DM DEGs were identified. Receiver operating characteristic (ROC) and Least Absolute Shrinkage and Selection Operator (LASSO) analysis were performed to screen out the ERS related biomarker genes and validate their diagnostic values. Gene expression level was detected by qPCR and Elisa assays in diabetic mice and patient serum samples.ResultsBy analyzing the transcriptional expression profiles of the GEO datasets, 49 T2DM-related DEGs were screened out in diabetic islets. RTN1, CLGN, PCSK1, IAPP, ILF2, IMPA1, CCDC47, and PTGES3 were identified as ERS-related DEGs in T2DM, which were revealed to be involved in protein folding, membrane composition, and metabolism regulation. ROC and LASSO analysis further screened out CLGN, ILF2, and IMPA1 as biomarker genes with high value and reliability for diagnostic purposes. These three genes were then demonstrated to be targeted by the transcription factors and miRNAs, including CEBPA, CEBPB, miR-197-5p, miR-6133, and others. Among these miRNAs, the expression of miR-197-5p, miR-320c, miR-1296-3P and miR-6133 was down-regulated, while that of miR-4462, miR-4476-5P and miR-7851-3P was up-regulated in diabetic samples. Small molecular drugs, including D002994, D001564, and others, were predicted to target these genes potentially. qPCR and Elisa analysis both validated the same expression alteration trend of the ERS-related biomarker genes in diabetic mice and T2DM patients.DiscussionThese findings will offer innovative perspectives for clinical diagnosis and treatment strategies for T2DM.

BackgroundLacrimal gland enlargement is a common pathological change in patients with thyroid eye disease (TED). Tear fluid has emerged as a new source of diagnostic biomarkers, but tear-based diagnostic biomarkers for TED with high efficacy are still lacking.ObjectiveWe aim to investigate genes associated with TED-associated lacrimal gland lesions. Additionally, we seek to identify potential biomarkers for diagnosing TED in tear fluid.MethodsWe obtained two expression profiling datasets related to TED lacrimal gland samples from the Gene Expression Omnibus (GEO). Subsequently, we combined the two separate datasets and conducted differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) on the obtained integrated dataset. The genes were employed for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The genes were intersected with the secretory proteins profile to get the potential proteins in the tear fluid. Machine learning techniques were then employed to identify optimal biomarkers and develop a diagnostic nomogram for predicting TED. Finally, gene set enrichment analysis (GSEA) and immune infiltration analysis were conducted on screened hub genes to further elucidate their potential mechanisms in TED.ResultsIn our analysis of the integrated TED dataset, we identified 2,918 key module genes and 157 differentially expressed genes and finally obtained 84 lacrimal-associated key genes. Enrichment analysis disclosed that these 84 genes primarily pertain to endoplasmic reticulum organization. After intersecting with the secretory proteins, 13 lacrimal gland-associated secretory protein genes (LaSGs) were identified. The results from machine learning indicated the substantial diagnostic value of dyslexia associated gene (KIAA0319) and peroxiredoxin4 (PRDX4) in TED-associated lacrimal gland lesions. The two hub genes were chosen as candidate biomarkers in tear fluid and employed to establish a diagnostic nomogram. Furthermore, single-gene GSEA results and immune cell infiltration analysis unveiled immune dysregulation in the lacrimal gland of TED, with KIAA0319 and PRDX4 showing significant associations with infiltrating immune cells.ConclusionsWe uncovered the distinct pathophysiology of TED-associated lacrimal gland enlargement compared to TED-associated orbital adipose tissue enlargement. We have demonstrated the endoplasmic reticulum-related pathways involved in TED-associated lacrimal gland lesions and established a diagnostic nomogram for TED utilizing KIAA0319 and PRDX4 through integrated bioinformatics analysis. This contribution offers novel insights for non-invasive, prospective diagnostic approaches in the context of TED.

Limited therapeutic options are available for patients with breast cancer brain metastases (BCBM), and thus there is an urgent need for novel treatment approaches. We previously engineered an effective oncolytic herpes simplex virus 1 (oHSV) expressing a full-length anti-CD47 monoclonal antibody (mAb) with a human IgG1 scaffold (OV-αCD47-G1) that was used to treat both ovarian cancer and glioblastoma. Here, we demonstrate that the combination of OV-αCD47-G1 and temozolomide (TMZ) improve outcomes in preclinical models of BCBM. The combination of TMZ with OV-αCD47-G1 synergistically increased macrophage phagocytosis against breast tumor cells and led to greater activation of NK cell cytotoxicity. In addition, the combination of OV-αCD47-G1 with TMZ significantly prolonged the survival of tumor-bearing mice when compared with TMZ or OV-αCD47-G1 alone. Combination treatment with the mouse counterpart of OV-αCD47-G1, termed OV-A4-IgG2b, also enhanced mouse macrophage phagocytosis, NK cell cytotoxicity, and survival in an immunocompetent model of mice bearing BCBM compared with TMZ or OV-A4-IgG2b alone. Collectively, these results suggest that OV-αCD47-G1 combined with TMZ should be explored in patients with BCBM.

Abstract Background Assessing mechanical properties of the respiratory system (Cst) during mechanical ventilation necessitates an end-inspiration flow of zero, which requires an end-inspiratory occlusion maneuver. This lung model study aimed to observe the effect of airflow obstruction on the accuracy of respiratory mechanical properties during pressure-controlled ventilation (PCV) by analyzing dynamic signals. Methods A Hamilton C3 ventilator was attached to a lung simulator that mimics lung mechanics in healthy, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD) models. PCV and volume-controlled ventilation (VCV) were applied with tidal volume (VT) values of 5.0, 7.0, and 10.0 ml/kg. Performance characteristics and respiratory mechanics were assessed and were calibrated by virtual extrapolation using expiratory time constant (RCexp). Results During PCV ventilation, drive pressure (DP) was significantly increased in the ARDS model. Peak inspiratory flow (PIF) and peak expiratory flow (PEF) gradually declined with increasing severity of airflow obstruction, while DP, end-inspiration flow (EIF), and inspiratory cycling ratio (EIF/PIF%) increased. Similar estimated values of Crs and airway resistance (Raw) during PCV and VCV ventilation were obtained in healthy adult and mild obstructive models, and the calculated errors did not exceed 5%. An underestimation of Crs and an overestimation of Raw were observed in the severe obstruction model. Conclusion Using the modified dynamic signal analysis approach, respiratory system properties (Crs and Raw) could be accurately estimated in patients with non-severe airflow obstruction in the PCV mode.

Abstract Background In the era defined by the fourth paradigm of science research, the burgeoning volume of science data poses a formidable challenge. The established data-related requisites within science literacy now fall short of addressing the evolving needs of researchers and STEM students. Consequently, the emergence of science data literacy becomes imperative. However, notwithstanding the escalating importance of science data literacy, a comprehensive definition and conceptual framework are still elusive, posing challenges to effective assessment. Results This study analyzes the science literacy frameworks of six international organizations and countries, including the OECD, and reviews 16 data literacy-related literature sources identified using the PRISMA process. We also consider the characteristics of science data. Based on these sources, we clarify the connotation of science data literacy and construct a tailored conceptual framework for college students majoring in STEM. The framework undergoes two rounds of Delphi method refinement to enhance its applicability. Subsequently, we created and piloted a set of questions using physics, astronomy, geography, and other STEM subjects as examples to assess science data literacy. The revised assessment tool was then used in a formal test with 198 university students, employing Rasch modeling to evaluate its effectiveness. The tool’s validity in assessing science data literacy was confirmed. Conclusions This study offers a systematic and comprehensive conceptual framework for science data literacy tailored to STEM undergraduates. Endorsed by experts, the framework outlines essential literacies for STEM students in handling science data. The developed assessment tool enables educators to measure students’ science data literacy levels and serves as a scientific guide to enhance their competencies in this area.

Since the patients suffering from female lower genital tract diseases are getting younger and younger and the human papilloma virus (HPV) infection is becoming more widespread, the novel non-invasive precise modalities of diagnosis and therapy are required to remain structures of the organ and tissue, and fertility as well, by which the less damage to normal tissue and fewer adverse effects are able to be achieved. In all nucleated mammalian cells, 5-Aminolevulinic acid (5-ALA) is an amino acid that occurs spontaneously, which further synthesizes in the heme biosynthetic pathway into protoporphyrin IX (PpIX) as a porphyrin precursor and photosensitizing agent. Exogenous 5-ALA avoids the rate-limiting step in the process, causing PpIX buildup in tumor tissues. This tumor-selective PpIX distribution after 5-ALA application has been used successfully for tumor photodynamic diagnosis (PDD) and photodynamic therapy (PDT). Several ALA-based drugs have been used for ALA-PDD and ALA-PDT in treating many (pre)cancerous diseases, including the female lower genital tract diseases, yet the ALA-induced fluorescent theranostics is needed to be explored further. In this paper, we are going to review the studies of the mechanisms and applications mainly on ALA-mediated photodynamic reactions and its effectiveness in treating female lower genital tract diseases.

The significant fluctuations in the liquid level of the two-stage tandem separators on FPSOs result in low oil and gas separation efficiency. To address this issue, an improved adaptive smoothing factor weight deep deterministic policy gradient (ASFW-DDPG) control algorithm is proposed to mitigate the separator liquid level fluctuations. The adaptive smoothing factor weight function and the reward function are meticulously designed to improve convergence speed and stability. A two-stage tandem separator liquid level control network, based on the ASFW-DDPG online control algorithm, is developed. Simulation experiments with the ASFW-DDPG algorithm are carried out using monitoring data from the separators on FPSOs. These simulations demonstrate that the learning efficiency of the ASFW-DDPG algorithm is 200% higher than that of the traditional DDPG algorithm. The primary and secondary separator liquid levels stabilize at the set values within 2.4 seconds and 1.8 seconds, while the PID and traditional DDPG algorithms exhibit slight fluctuations in liquid level. The results suggest that the ASFW-DDPG algorithm exhibits superior convergence speed and stability.

To investigate the value of self-developed air-free laparoscopic auxiliary instruments in the clinical application of thyroid diseases. The clinical data of 70 transaxillary and 45 transareolar air-free laparoscopic surgeries for thyroid cancer and 40 conventional open surgeries were retrospectively compared. The transaxillary and transareolar laparoscopic groups had significantly longer operative times than the open group, while the postoperative satisfaction was higher in the endoscopic group than in the open group. This set of instruments has advantage of novel design, scientific structure, safe application. It can be compatible with a variety of thyroid and breast air-free laparoscopic procedures, which can promote the development and popularization of laparoscopic technology.

The association between human immunodeficiency virus (HIV) status and readmissions and death outcomes in patients with established heart failure (HF) remains unclear. We conducted a systematic search of PubMed, EMBASE, Cochrane Library, and Web of Science up to March 1st, 2023, for cohort studies of adult patients (≥18 years) diagnosed with HF and recorded HIV status at baseline. Our analysis included 7 studies with 10,328 HF patients living with HIV and 48,757 HF patients without HIV. Compared to HF patients without HIV, those with HIV had a higher risk of all-cause deaths (HR: 1.20, 95% CI: 1.15–1.25). HIV infection was also associated with increased risks of HF-associated readmission (HR: 1.34, 95% CI: 1.03–1.75) and all-cause readmission (HR: 1.27, 95% CI: 1.10–1.46). Our study highlights the independent association between HIV and poor HF outcomes, emphasizing the need for improved management in individuals living with HIV.

ObjectiveTo fully utilize the experience of nuclear power plant operation and management to assist nuclear power operators in fault diagnosis, a marine nuclear power plant fault diagnosis expert system is designed. MethodFirst, based on the logical consistency between fault trees and production rules, a method is proposed to transform fault tree knowledge into production rules. The knowledge base and inference machine of the expert system are then optimized by using a mixed forward and backward inference method, and a forward inference strategy is designed to simplify the inference process based on the minimum cut set and importance analysis results of the fault tree. Finally, based on the idea of manually judging the fault status, a status monitoring module is designed to collect key equipment parameters in real time and convert them into equipment information that can be recognized by expert systems. ResultsThe results show that the proposed method solves the problem of difficult knowledge acquisition in expert systems and improves inference efficiency while ensuring inference accuracy, thereby achieving the online fault diagnosis function of expert systems. ConclusionUsing the proposed method can enhance the knowledge acquisition ability and inference efficiency of expert systems, which is of great significance for ensuring the operational management safety of nuclear power plants.

AbstractHuman papillomavirus (HPV) infection and related diseases are clinical challenges. The efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) using red laser (630 ± 5 nm) is remarkable and safe. In this study, we aim to investigate the efficacy of ALA-450 nm PDT comparing with ALA-635 nm PDT. We detected cell proliferation and cell apoptosis through MTT assay and flow cytometry assay respectively. Flow cytometry assay determined the intracellular reactive oxygen species (ROS) generation. Western blotting analysis investigated the protein expression. In vivo, immunohistochemical staining assay and TUNEL assay were performer to detect cell apoptosis. ALA-450 nm PDT inhibited the proliferation of End1 and HeLa cells, promoted cell apoptosis more effectively than ALA-635 nm PDT, and induced cell death probably through increasing the intracellular ROS generation and caspase-dependent apoptosis pathway. In vivo, ALA-450 nm PDT significantly inhibited tumour growth and activated cell apoptosis. The ALA-450 nm PDT had an advantage over ALA-635 nm PDT on inhibiting the proliferation of End1 and HeLa cells and inducing cell apoptosis. The ALA-450 nm PDT might be a promising therapeutic strategy for eradicating the HR-HPV infected cells and promoting the integration of diagnosis and treatment of HR-HPV related diseases.HighlightsWe combined 5-aminolevulinic acid with 450 nm blue laser using as a novel type of photodynamic therapy.The ALA-450 nm PDT had an advantage over ALA-635 nm PDT on inhibition of the proliferation of End1 and HeLa cells and inducing cell apoptosis in vitro and in vivo.The ALA-450 nm PDT may provide a novel alternative therapeutic option in patients with persistent HPV infection and promote the integration of diagnosis and treatment.

ABSTRACTThe effect of cathelicidin hCAP18/LL-37 in hepatocellular carcinoma (HCC) metastasis remains unclear. Here, we confirmed that LL-37 expression enhanced endothelial-mesenchymal transition (EMT), migration and invasion in HCC cells. And the HER2/EGFR-MAPK/ERK signal participated in the process above. More frequent lung metastases were observed in an LL-37-overexpressing hematogenous metastasis model. Interestingly, 1,25(OH)2D3 together with si-LL-37 significantly enhanced 1,25(OH)2D3-induced inhibition of migration and invasion in PLC/PRF-5 cells, and also enhanced reversion of the EMT process. Therefore, LL-37 is involved in HCC metastases, and may act as an important factor to attenuate the inhibitory activity of 1,25(OH)2D3 on HCC metastasis. Targeting hCAP18/LL-37 may offer a potential strategy to improve the anticancer activity of 1,25(OH)2D3 in HCC therapy.

Abstract The transformer, a type of neural architecture, has demonstrated exceptional performance improvements in vision and natural language tasks. While overcoming the disadvantages of limited perceptual field and non‐adaptive input content exhibited in CNNs, the computational complexity of the Transformer model increases quadratically with spatial resolution. As such, this model is not frequently employed in image processing tasks such as image denoising, and there is a shortage of studies that investigate ultrasonic image multiplication speckle removal. In light of this, we present TranSpeckle, an effective and efficient despeckle architecture that employs Multi‐Dconv Head Transposed Attention and Dconv Feed‐Forward Network as the core components of its Transformer block. Multiple Transformer blocks are then utilized to implement a hierarchical encoder‐decoder network. TranSpeckle architecture considerably reduces the computational complexity of feature maps while also effectively capturing long‐range pixel interactions and local context information. In this study, an edge protection module is combined to augment the edges of ultrasound images. The module incorporates extracted image edge features into the TranSpeckle architecture, which ameliorates the issue of edge information loss engendered by the image despeckling process. Extensive experimental results clearly show that our proposed network outperforms state‐of‐the‐art methods in terms of quantitative metrics and visual quality.

Abstract Visualization of photothermal therapy mediated by photothermal transduction agents (PTAs) is important to promote individual treatment of patients with low side effects. Photoacoustic detection has emerged as a promising noninvasive method for the visualization of PTAs distribution but still has limitations in temperature measurement, including poor measurement accuracy and low tissue penetration depth. In this study, we developed biocompatible semiconducting polymer dots (SPD) for in situ coupling of photothermal and photoacoustic detection in the near-infrared II window. SPD has dual photostability under pulsed laser and continuous-wave laser irradiation with a photothermal conversion efficiency of 42.77%. Meanwhile, a strong correlation between the photoacoustic signal and the actual temperature of SPD can be observed. The standard deviation of SPD-mediated photoacoustic thermometry can reach 0.13 °C when the penetration depth of gelatin phantom is 9.49 mm. Preliminary experimental results in vivo show that SPD-mediated photoacoustic signal has a high signal-to-noise ratio, as well as good performance in temperature response and tumor enrichment. Such a study not only offers a new nanomaterial for the visualization of photothermal therapy but will also promote the theranostic platform for clinical applications.

Abstract Background Non-small cell lung cancer (NSCLC) is a major pathological type of lung cancer. However, its pathogenesis remains largely unclear. MRPL35 is a regulatory subunit of the mitoribosome, which can regulate the assembly of cytochrome c oxidases and plays an important role in the occurrence of NSCLC. Methods The expression of MRPL35 in NSCLC was detected by tissue microarray and immunohistochemistry. H1299 cells were infected with lentivirus to knockdown MRPL35, and the cells were subjected to crystal violet staining to assess the results of colony formation assays. A549 cells were infected by lentiviral particles-expressing shMRPL35 or shControl, and then subcutaneously injected into nude mice. Tumorigenesis in mice was detected by in vivo imaging. The potential pathway of MRPL35 in NSCLC was assessed by Western blotting. Results MRPL35 was over-expressed in NSCLC tissue compared to para-cancerous and normal tissues. Knockdown of MRPL35 suppressed cell proliferation and decreased NSCLC progression both in vitro and in vivo. The possible molecular mechanisms were also clarified, which indicated that MRPL35 could be involved in cell apoptosis and proliferation by modulating the expression levels of CDK1, BIRC5, CHEK1, STMN1 and MCM2. Knockdown of MRPL35 activated p53 signaling pathway and inhibited cell cycle regulation. Conclusions The oncogenic role of MRPL35 in NSCLC was potentially mediated through the cell cycle regulatory genes such as BIRC5, STMN1, CDK1, CHEK1 and MCM2, as well as activation of P53 signaling pathway.

Abstract Low temperatures severely impair the performance of lithium-ion batteries, which demand powerful electrolytes with wide liquidity ranges, facilitated ion diffusion, and lower desolvation energy. The keys lie in establishing mild interactions between Li+ and solvent molecules internally, which are hard to achieve in commercial ethylene-carbonate based electrolytes. Herein, we tailor the solvation structure with low-ε solvent-dominated coordination, and unlock ethylene-carbonate via electronegativity regulation of carbonyl oxygen. The modified electrolyte exhibits high ion conductivity (1.46 mS·cm−1) at −90 °C, and remains liquid at −110 °C. Consequently, 4.5 V graphite-based pouch cells achieve ~98% capacity over 200 cycles at −10 °C without lithium dendrite. These cells also retain ~60% of their room-temperature discharge capacity at −70 °C, and miraculously retain discharge functionality even at ~−100 °C after being fully charged at 25 °C. This strategy of disrupting solvation dominance of ethylene-carbonate through molecular charge engineering, opens new avenues for advanced electrolyte design.

Abstract Objective To evaluate the clinical effectiveness and pregnancy rate after hysteroscopic resection (HR) and/or vaginal repair (VR) in patients with cesarean scar defect (CSD). Methods This prospective observational study enrolled 191 patients who received CSD surgery in the First affiliated hospital of Sun Yat-sen University between September 2019 to February 2022 (96 in HR and 95 in VR, respectively). Patient follow-up were performed three months after surgery in both groups by transvaginal ultrasound to confirm the presence of fluid in the niche, along with the resolution of prolonged menses at the same time. The primary outcome was the clinical effectiveness between HR and VR, identified by the resolution of prolonged menses. Results The rates of niche-fluid disappearance (70.1% vs 60.2%, P = 0.176) and prolonged menses resolution (74.8% vs 80.0%, P = 0.341) were comparable for HR and VR. A subgroup analysis for niche size revealed that HR provides patients with small niche a more favorable rate of menstrual resolution compared to VR (size of niche ≤ 15 mm2, aOR = 3.423, 95% confidence interval [CI] 1.073–10.918), but patients with large niche experience a lower rate of resolution compared to VR (size of niche > 25 mm2, aOR = 0.286, 95% CI 0.087- 0.938). During follow-up, 41 patients who wanted to conceive became pregnant. Kaplan–Meier estimates of the cumulative probability of pregnancy at 12 months and 24 months were 47.1% (95% CI: 34.5%, 58.8%) and 63.8% (95% CI: 52.5%, 72.9%), respectively. The median pregnancy time was 22 months (95% CI: 14.2, 29.8) after VR and 12 months (95% CI: 8.3, 15.7, Gehan-Breslow-Wilcoxon P = 0.021) after HR. Among patients with subsequent infertility, 31.6% achieved pregnancy by unassisted mode and 29.8% by IVF/ICSI. Moreover, among patients with previously failed IVF/ICSI treatment, 60% (12/20) obtained pregnancy, including 71.4% (10/14) after HR and 33.3% (2/6) after VR. Conclusions Hysteroscopic resection is as effective as vaginal repair at relieving symptoms of CSD-associated prolonged menses. Hysteroscopic resection is the modality of choice with an improvement in prolonged menses for small niche, while vaginal might be considered for a large niche. Furthermore, surgical intervention could improve the clinical pregnancy rate of CSD patients. All of these provide evidence for the individualized management of CSD.

When there are two sets of parallel once through-steam generators(OTSG) in the natural circulation loop, the thermal-hydraulic characteristics are complicated. Flow instability often occurs in such loops. In order to alleviate the harm caused by flow instability and enhance the natural circulation capacity, it is necessary to study the characteristics of flow instability in depth. In this paper, a thermal-hydraulic computational model is developed for a two-phase natural circulation loop with two parallel OTSGs based on the RELAP5 program. And the model is validated. The thermal-hydraulic parameters of the loop were calculated for different decay heat conditions. The flow instability of the loop is found to be characterized by a clear division into three zones in the decay heat interval. The concept of “load-flow ratio” is proposed to analyze the critical point of flow instability under different operating conditions. The reason for the flow instability zones of the loop is explained. The conclusions of the relevant research can provide a basis for an in-depth study of the characteristics of flow instability and the development of operational schemes to mitigate flow instability.

Background: Emerging studies demonstrate that exposure to brominated flame retardants (BFRs) can have harmful effects on human health. Our study focused on the relationship between exposure to various BFRs and markers of liver function. Methods: To further explore the association between BFR exposure and liver function impairment, we used data from the National Health and Nutrition Examination Surveys (NHANES) for three cycles from 2009 to 2014, leaving 4206 participants (≥20 years of age) after screening. Nine BFRs and eight liver function tests (LFTs) were measured in the participants’ serum to represent BFRs and liver function impairment in vivo. To investigate whether there is a relationship between BFRs and health outcome, statistical research methods such as the weighted linear regression model, restricted cubic spline (RCS), weighted quantile sum (WQS), quantile-based g computing (QGC), and the Bayesian Kernel Machine Regression (BKMR) were used to evaluate the correlation between serum BFRs and LFTs. Results: The studies reveals that exposure to BFRs is associated with liver function biomarkers. In a weighted linear regression model, we found that PBB153, PBDE99, PBDE154, PBDE209, PBDE85 exposure was positively correlated with AST, ALT, GGT, ALP, TP, and SL risk. In RCS model, the nonlinear relationships between PBB153 and AST, ALT, and GGT and PBDE209 and ALT and TP are the most significant. The exposure to combined BFRs was positively correlated with AST, ALT, and GGT in WQS and QGC models. BKMR analysis showed that BFR exposure was positively correlated with AST, ALT, ALP, and GGT. Conclusions: Exposure to BFRs is associated with liver function impairment, suggesting that BFR exposure is potentially toxic to the human liver, but more in-depth studies are needed to explore this correlation.

With the offshore oil–gas fields entering a decline phase, the high-efficiency separation of oil–gas–water mixtures becomes a significant challenge. As essential equipment for separation, the three-phase separators play a key role in offshore oil–gas production. However, level control is critical in the operation of three-phase gravity separators on offshore facilities, as it directly affects the efficacy and safety of the separation process. This paper introduces an advanced deep deterministic policy gradient with the adaptive learning rate weights (ALRW-DDPG) control algorithm, which improves the convergence and stability of the conventional DDPG algorithm. An adaptive learning rate weight function has been meticulously designed, and an ALRW-DDPG algorithm network has been constructed to simulate three-phase separator liquid level control. The effectiveness of the ALRW-DDPG algorithm is subsequently validated through simulation experiments. The results show that the ALRW-DDPG algorithm achieves a 15.38% improvement in convergence rate compared to the traditional DDPG algorithm, and the control error is significantly smaller than that of PID and DDPG algorithms.

The crystal structure has a great influence on the dielectric and piezoelectric performance of poly(vinylidene fluoride) (PVDF). In this work, we prepared PVDF films with two typical crystalline phases (α and β). In situ Kelvin probe force microscopy (KPFM) and Piezoelectric force microscopy (PFM) were employed to investigate the responses of different PVDF crystalline phases to charge mobility, polarization, and piezoelectric properties. We used a homemade Kelvin probe force microscope (KPFM) to inject charges into the two crystalline phases to investigate the differences in the response of different crystalline phases of PVDF to electrical excitation on a microscopic scale. It was found that the α-phase has a lower charge injection barrier and is more susceptible to charge injection and that the α-phase is accompanied by a faster charge dissipation rate, which makes it easier to accumulate charge at the interface between the α-phase and β-phase PVDF. Moreover, the PFM polarization manipulation showed no change in the amplitude and phase diagram of the α-phase under ±10 V bias. In contrast, the β-phase showed a clear polarization reversal phenomenon and a significant increase in piezoelectric amplitude, which is consistent with its polar intrinsic properties. This study provides valuable insights into the multiphase contributions and a reference for designing advanced PVDF dielectrics.

[Introduction] As the country has set ambitious targets in carbon peaking and carbon neutrality for the energy sector, there is a growing demand for technology improvements of low-carbon emission for power station gas turbines. It is urgent to explore the path of the key technology for this goal in China. The lean premixed combustion technology of gas turbine can make the air volume for combustion deviate from the theoretical air volume, which is the main technology to reduce NOx emission at present. At the same time, by mixing hydrogen in natural gas when combusting, it can effectively reduce the consumption of fossil energy and reduce carbon emissions. [Method] In this paper, a one-dimensional premixed free propagation flame model was established by Chemkin-Pro software, and the effects of different equivalent ratios, initial temperatures, initial pressures, and hydrogen-blended ratios on combustion temperatures, combustion rates, pollutant generation concentration, combustion free radicals, and chain reactions were compared. The temperature distribution, fuel component change and emission characteristics of combustion process were simulated. [Result] It is found that by mixing hydrogen in natural gas when combusting, fossil energy consumption and carbon emissions can be effectively reduced. However, the higher flame temperature brought by the lean premixed combustion of natural gas mixed with hydrogen will promote the generation of NOx, and at the same time, more CO will be produced at a lower equivalent ratio. [Conclusion] Based on the above research, the key data of hydrogen-blended combustion are obtained, which lays a foundation for the completion of hydrogen-blended combustion technology route.

In this paper, the differences in mechanical properties and high temperature (HT) deformation behavior between TiBw/Ti65 and TiBw/TA15 composites with network structure were studied. The alloy element distribution and microstructure of TiBw/Ti65 and TiBw/TA15 composites were characterized by the electron probe micro analyzer and transmission electron microscopy. The microstructure evolution during HT deformation was analyzed by electron back scatter diffraction. The mechanical properties of two composites were tested at room temperature and 600–750 °C. Arrhenius and artificial neural network models were developed to predict the peak stress and flow stress, respectively. The results show that the multiple alloying elements and silicide in TiBw/Ti65 refined the grains. TiBw/Ti65 composites had higher deformation activation energy and higher strength under the same deformation conditions. Based on the analysis of differences in microstructure, the strengthening mechanisms of TiBw/Ti65 compared to TiBw/TA15 was mainly from fine grain strengthening, dislocation density strengthening, and Orowan strengthening of silicide. The initial recrystallization temperatures for TiBw/TA15 and TiBw/Ti65 were 700 °C and 750 °C with strain rate of 0.001 s−1, respectively. The above results show that TiBw/Ti65 had better HT deformation resistance.

Thyroid eye disease (TED) is a disfiguring autoimmune disease characterized by changes in the orbital tissues and is caused by abnormal thyroid function or thyroid-related antibodies. It is the ocular manifestation of Graves’ disease. The expression of thyroid-stimulating hormone receptor (TSHR) and the insulin-like growth factor-1 receptor (IGF-1 R) on the cell membrane of orbital fibroblasts (OFs) is responsible for TED pathology. Excessive inflammation is caused when these receptors in the orbit are stimulated by autoantibodies. CD34+ fibrocytes, found in the peripheral blood and orbital tissues of patients with TED, express immune checkpoints (ICs) like MHC II, B7, and PD-L1, indicating their potential role in presenting antigens and regulating the immune response in TED pathogenesis. Immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, it can also lead to the occurrence of TED in some instances, suggesting the abnormality of ICs in TED. This review will examine the overall pathogenic mechanism linked to the immune cells of TED and then discuss the latest research findings on the immunomodulatory role of ICs in the development and pathogenesis of TED. This will offer fresh perspectives on the study of pathogenesis and the identification of potential therapeutic targets.

The Volumetric Homogenization Method (VHM) is one of the most commonly used methods for neutronics calculation in reactors or components. However, the use of VHM for the Double-Heterogeneous (DH) System may lead to a large deviation in reactivity calculation. The deviation of DH System using the VHM can be expressed by the theoretically modified optical length. When the theoretically modified optical length is less than 10−4, the deviation caused by the VHM will be less than 100 pcm. This paper points out that the existing theoretically modified optical length for some cases of DH systems is not accurate, and this method is only for pin cell. In this paper, by calculating a series of DH models and their corresponding VHM models, it is found that the water-uranium ratio and the shape of fuel region seriously affects the reactivity calculation deviation of particle-dispersed fuel, the original modified optical length does not take this into account, resulting in unacceptable errors. On this basis, the application of optical length to physical boundaries for DH system is further discussed and the shape correction factor is taken into consideration. Therefore, an improved optical length is proposed, which greatly expands the range of application of the physical boundary judgment methods for the double heterogeneity of dispersed particle fuel. The numerical results show that the accuracy of the improved optical length in defining the physical boundary of double heterogeneous system is higher than the theoretically modified optical length.

BackgroundDNMT3A mutations can be detected in premalignant hematopoietic stem cells and are primarily associated with clonal hematopoiesis of indeterminate potential; however, current evidence does not support assigning them to a distinct European Leukemia Net (ELN) prognostic risk stratification. CD7 is a lymphoid antigen expressed on blasts in approximately 30% of acute myeloid leukemia (AML), and its role in AML remains unclear and depends on subgroup evaluation. This study investigated the prognostic value of DNMT3A mutation combined with CD7 expression in AML.MethodsWe retrospectively analyzed the clinical data of 297 newly diagnosed non-M3 AML patients. According to the DNMT3A mutation and CD7 expression in AML cells, patients were divided into the DNMT3A-mutated/CD7-positive (CD7+), DNMT3A-mutated/CD7-negative (CD7-), DNMT3A-wild-type/CD7+, and DNMT3A-wild-type/CD7- groups.ResultsThe DNMT3A-mutated/CD7+ group had lower complete remission rates and higher relapse rates. Importantly, these patients had significantly shorter overall survival (OS) and relapse-free survival (RFS). Furthermore, multivariate analysis showed that CD7+ with DNMT3A mutation was an independent risk factor for OS and RFS.ConclusionCD7+ with DNMT3A mutation predicts a poor prognosis in AML patients, and the immunophenotype combined with molecular genetic markers can help to further refine the current risk stratification of AML.

Abstract Loss of neuromelanin in the midbrain is known in Parkinson’s disease(PD), which can now be directly detected by neuromelanin-sensitive MRI(NM-MRI). This case-control study was to investigate the distribution of neuromelanin in the substantia nigra(SN) and the locus coeruleus(LC) using NM-MRI technique and evaluate its potential as a diagnostic marker for PD. 10 early PD patients(H&Y stage I, II), 11 progressive PD patients(H&Y stage III-V), and 10 healthy controls matched in age and gender were recruited. All participants completed clinical and psychometric assessments as well as NM-MRI scans. Neuromelanin signal intensities in SN and LC were measured by contrast-to-noise ratios(CNRs) derived from NM-MRI scans. There were significant decreases of CNRs in SNpc(including anterior, central, and posterior) and LC in PD patients compared to controls. There were also significant differences of CNR between the left and right sides. CNR in LC had a negative correlation with the Non-Motor Symptoms Scale(NMSS) score in PD patients(|R|=0.49), whereas CNR in SNpc did not correlate with Unified Parkinson Disease Rating Scale(UPDRS) score(|R|

Abstract Microsporidia are a class of obligate intracellular parasitic unicellular eukaryotes that infect a variety of hosts, even including humans. Although different species of microsporidia differ in host range and specificity, they all share a similar infection organelle, the polar tube, which is also defined as the polar filament in mature spores. In response to the appropriate environmental stimulation, the spore germinates with the polar filament everted, forming a hollow polar tube, and then the infectious cargo is transported into host cells via the polar tube. Hence, the polar tube plays a key role in microsporidian infection. Here, we review the origin, structure, composition, function, and application of the microsporidian polar tube, focusing on the origin of the polar filament, the structural differences between the polar filament and polar tube, and the characteristics of polar tube proteins. Comparing the three-dimensional structure of PTP6 homologous proteins provides new insight for the screening of additional novel polar tube proteins with low sequence similarity in microsporidia. In addition, the interaction of the polar tube with the spore wall and the host are summarized to better understand the infection mechanism of microsporidia. Due to the specificity of polar tube proteins, they are also used as the target in the diagnosis and prevention of microsporidiosis. With the present findings, we propose a future study on the polar tube of microsporidia. Graphical Abstract

Internal thermal insulation composite system (ITICS) can be an important measure for the energy-saving retrofitting of buildings. However, ITICS may cause harmful effects on the hygrothermal performance of building envelopes. This work investigated the influence of the materials' hygric properties on the hygrothermal performance of a typical ITICS in different climate conditions in China. Two base wall materials, the traditional concrete and a new type aerated concrete, were tested and compared for their hygric properties firstly. The influence of the hygroscopicity of exterior plasters, the permeability of insulation materials and the climate conditions were then analyzed with WUFI simulations. The hygrothermal performance was evaluated with consideration of the total water content (TWC) of the walls and the moisture flux strength, the relative humidity (RH) and the mould growth risk at the interface between the base wall and the insulation layer (B-I interface). The numerical analysis implies that the TWC of internal insulated walls depends mainly on the hygroscopicity of exterior plaster and the wind-driven rain intensity. The upper limits for the water absorption coefficient of exterior plasters used in Beijing, Shanghai and Fuzhou are 1e-9, 1e-10, 1e-10 m2/s respectively. When such limits are guaranteed, a vapour tight system created by using insulation materials with a large vapour resistance factor or adding a vapour barrier can improve the hygrothermal performance of ITICS, especially for concrete walls in cold climate.

Abstract Background Preoperative differentiation between IgG4-related orbital disease (IgG4-ROD) and orbital mucosa-associated lymphoid tissue (MALT) lymphoma has a significant impact on clinical decision-making. Our research aims to construct and evaluate a magnetic resonance imaging (MRI)-based radiomics model to assist clinicians to better identify IgG4-ROD and orbital MALT lymphoma and make better preoperative medical decisions. Methods MR images and clinical data from 20 IgG4-ROD patients and 30 orbital MALT lymphoma patients were classified into a training (21 MALT; 14 IgG4-ROD) or validation set (nine MALT; six IgG4-ROD). Radiomics features were collected from T1-weighted (T1WI) and T2-weighted images (T2WI). Student’s t-test, the least absolute shrinkage and selection operator (LASSO) and principal component analysis (PCA) were conducted to screen and select the radiomics features. Support vector machine (SVM) classifiers developed from the selected radiomic features for T1WI, T2WI and combined T1WI and T2WI were trained and tested on the training and validation set via five-fold cross-validation, respectively. Diagnostic performance of the classifiers were evaluated with area under the curve (AUC) readings of the receiver operating characteristic (ROC) curve, and readouts for precision, accuracy, recall and F1 score. Results Among 12 statistically significant features from T1WI, four were selected for SVM modelling after LASSO analysis. For T2WI, eight of 51 statistically significant features were analyzed by LASSO followed by PCA, with five features finally used for SVM. Combined analysis of T1WI and T2WI features selected two and four, respectively, for SVM. The AUC values for T1WI and T2WI classifiers separately were 0.722 ± 0.037 and 0.744 ± 0.027, respectively, while combined analysis of T1WI and T2WI classifiers further enhanced the classification performances with AUC values ranging from 0.727 to 0.821. Conclusion The radiomics model based on features from both T1WI and T2WI images is effective and promising for the differential diagnosis of IgG4-ROD and MALT lymphoma. More detailed radiomics features and advanced techniques should be considered to further explore the differences between these diseases.

Abstract Background Respiratory mechanics monitoring provides useful information for guiding mechanical ventilation, but many measuring methods are inappropriate for awake patients. This study aimed to evaluate the accuracy of dynamic mechanics estimation using expiratory time constant (RCexp) calculation during noninvasive pressure support ventilation (PSV) with air leak in different lung models. Methods A Respironics V60 ventilator was connected to an active breathing simulator for modeling five profiles: normal adult, restrictive, mildly and severely obstructive, and mixed obstructive/restrictive. Inspiratory pressure support was adjusted to maintain tidal volumes (VT), achieving 5.0, 7.0, and 10.0 ml/kg body weight. PEEP was set at 5 cmH2O, and the back-up rate was 10 bpm. Measurements were conducted at system leaks of 25–28 L/min. RCexp was estimated from the ratio at 75% exhaled VT and flow rate, which was then used to determine respiratory system compliance (Crs) and airway resistance (Raw). Results In non-obstructive conditions (Raw ≤ 10 cmH2O/L/s), the Crs was overestimated in the PSV mode. Peak inspiratory and expiratory flow and VT increased with PS levels, as calculated Crs decreased. In passive breathing, the difference of Crs between different VT was no significant. Underestimations of inspiratory resistance and expiratory resistance were observed at VT of 5.0 ml/kg. The difference was minimal at VT of 7.0 ml/kg. During non-invasive PSV, the estimation of airway resistance with the RCexp method was accurately at VT of 7.0 ml/kg. Conclusions The difference between the calculated Crs and the preset value was influenced by the volume, status and inspiratory effort in spontaneously breathing.