Magnetic Resonance Imaging-Based Vertebral Bone Quality Score for Prediction of Cage Subsidence and Screw Loosening in Patients Undergoing Degenerative Lumbar Surgery: A Meta-analysis.

OBJECTIVE: Poor bone quality is a risk factor for postoperative complications after degenerative lumbar fusion surgery. The magnetic resonance imaging-based vertebral bone quality (VBQ) score is a good tool for assessing bone quality, and this is the first meta-analysis performed to summarize the predictive value of the VBQ score for cage subsidence and screw loosening in patients undergoing degenerative lumbar surgery. METHODS: Studies were comprehensively searched in electronic databases. The quality of the studies was assessed. The pooled sensitivity, specificity and summary receiver operating characteristic curve were calculated. Publication bias was assessed and meta-regression was conducted. RESULTS: We ultimately included 9 studies with a total of 1,404 patients with a mean age of 60.4 years and a percentage of females of 57.0%. According to the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool to assess methodological quality, the quality of the included studies was relatively low and risks of bias might exist. Results showed that a high VBQ was significantly associated with cage subsidence and screw loosening, and risk factor analysis revealed that the merged odds ratio was 5.37 for cage subsidence and 3.87 for screw loosening. With a VBQ cutoff value of 3.34±0.45, the pooled sensitivity and specificity for the diagnosis of postoperative complications were 0.75 and 0.75, respectively, and the area under the curve was 0.82 (95% confidence interval, 0.78-0.85). CONCLUSION: A high VBQ was associated with a high risk of cage subsidence and screw loosening in patients who underwent degenerative lumbar surgery. The VBQ score could be considered for identifying high-risk patients for further evaluation.

Strong and efficient bismuth telluride-based thermoelectrics for Peltier microcoolers.

Thermoelectric Peltier coolers (PCs) are being increasingly used as temperature stabilizers for optoelectronic devices. Increasing integration drives PC miniaturization, requiring thermoelectric materials with good strength. We demonstrate a simultaneous gain of thermoelectric and mechanical performance in (Bi, Sb)2Te3, and successfully fabricate micro PCs (2 × 2 mm2 cross-section) that show excellent maximum cooling temperature difference of 89.3 K with a hot-side temperature of 348 K. A multi-step process involving annealing, hot-forging and composition design, is developed to modify the atomic defects and nano- and microstructures. The peak ZT is improved to ∼1.50 at 348 K, and the flexural and compressive strengths are significantly enhanced to ∼140 MPa and ∼224 MPa, respectively. These achievements hold great potential for advancing solid-state refrigeration technology in small spaces.

Z/E configuration controlled by a Taxus sesquiterpene synthase facilitating the biosynthesis of (3Z,6E)-α-farnesene.

Plant enzymes often present advantages in the synthesis of natural products with specific configurations. Farnesene is a pharmacologically active sesquiterpene with three natural Z/E configurations, among which the enzyme selectively responsible for the biosynthesis of (3Z,6E)-α-farnesene remains elusive. Herein, a sesquiterpene synthase TwSTPS1 biosynthesizing (3Z,6E)-α-farnesene as the major product was identified from Taxus wallichiana through genome mining. Utilizing molecular dynamics simulations and mutation analysis, the catalytic mechanism of TwSTPS1, especially Z/E configuration control, was explored. Moreover, the crucial residues associated with the specific catalytic activity of TwSTPS1 was elucidated through mutagenesis experiments. The findings contribute to our understanding of the Z/E configuration control by plant terpene synthases and also provide an alternative tool for manipulating (3Z,6E)-α-farnesene production using synthetic biology.

High Temperature-Insensitive Electrostrain Obtained in (K, Na)NbO3-Based Lead-Free Piezoceramics.

Over the last decades, notable progress is achieved in (K, Na)NbO3 (KNN)-based lead-free piezoceramics. However, more studies are conducted to increase its piezoelectric charge coefficient (d33). For actuator applications, piezoceramics need high electric-field induced strain under low electric fields while maintaining exceptional temperature stability across a wide temperature range. In this study, this work developes Li/Sb-codoped KNN (LKNNS) ceramics with high electrostrain by defect engineering and domain engineering. A remarkable strain of 0.43%, along with a giant d33* value of 2177 pm V-1, is attained in the LKNNS ceramic at 20 kV cm-1. The ceramic exhibits a minimal performance decrease of less than 15% over a temperature range from room temperature to 150 °C. The exceptional strain is attributed to the presence of A-site vacancy-oxygen vacancy ( V A ' - V O • • ${\mathrm{V}}_{\mathrm{A}}^{{\prime}}{\mathrm{ - V}}_{\mathrm{O}}^{{\mathrm{ \bullet \bullet }}}$ ) defect dipoles and the increase in nano-domains. The hierarchical domain configuration and V A ' - V O • • ${\mathrm{V}}_{\mathrm{A}}^{{\prime}}{\mathrm{ - V}}_{\mathrm{O}}^{{\mathrm{ \bullet \bullet }}}$ defect dipoles impede the switched domains from reverting to their original state as temperature increases, furthermore, the elongated dipole moments of V A ' - V O • • ${\mathrm{V}}_{\mathrm{A}}^{{\prime}}{\mathrm{ - V}}_{\mathrm{O}}^{{\mathrm{ \bullet \bullet }}}$ caused by rising temperatures compensate for strain reduction results in exceptional temperature stability. This study provides a model for designing piezoelectric materials with exceptional overall performance under low electric fields and across a wide temperature range.

Occurrence and risk assessment of p-phenylenediamines and their quinones in aquatic environment: From city wastewater to deep sea.

p-Phenylenediamines (PPDs) and PPD-derived quinones (PPD-Qs) have been considered emerging pollutants recently. Their available data on sediment and sewage sludge are limited, especially the ecological risks. Here, typical PPDs and PPD-Qs were measured in the sludge of wastewater treatment plants and surface sediment of a developed river basin (including reservoirs, estuaries, and rivers) and deep-sea troughs. The total concentrations of PPDs (∑PPD) were highest in sludge (range: 9.06-248 ng g-1), followed by surface sediment of the Dongjiang River basin, China (3.33-85.3 ng g-1), and lowest in sediment of the Okinawa Trough (0.01-7.46 ng g-1). The median value of ∑PPD in surface sediment of rivers (9.54 ng g-1) was higher than those in reservoirs (4.28 ng g-1) and estuaries (5.26 ng g-1). N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) was the major congener in all samples, accounting for over 60 % of ∑PPD. For quinones, 6PPD-Q and IPPD-Q were frequently detected in sludge, only trace 6PPD-Q was detected in the sediment of estuaries (nd-0.62 ng g-1) and rivers (nd-5.24 ng g-1), and both of them were absent from the sediment of the Okinawa Trough. The occurrence of PPDs in the trough may be the in-situ release of microplastics, and due to the low-light and weak alkaline conditions of deep-sea water, quinones may hardly photodegrade from PPDs. The PPD concentrations in sludge were positively correlated with local GDP, and the annual PPD emission from sludge will exceed 1370 kg in China. The results of ecological risk assessments indicated low risks for PPDs in sludge-amended soil, median risks for several PPDs in river sediment, but median to high risks for 6PPD-Q contamination sludge-amended soil. For the first time, we explored the potential environmental risk of PPDs and related quinones in sludge used as a soil conditioner.

Variability in Lipid Profiles During Young Adulthood and the Risk of Coronary Artery Calcium Incidence in Midlife: Insights From the CARDIA Study.

BACKGROUND: Intraindividual variability in lipid profiles is recognized as a potential predictor of cardiovascular events. However, the influence of early adulthood lipid profile variability along with mean lipid levels on future coronary artery calcium (CAC) incidence remains unclear. METHODS: A total of 2395 participants (41.6% men; mean±SD age, 40.2±3.6 years) with initial CAC =0 from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included. Serial lipid measurements were obtained to calculate mean levels and variability of total cholesterol, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides. CAC incidence was defined as CAC >0 at follow-up. RESULTS: During a mean follow-up of 9.0 years, 534 individuals (22.3%) exhibited CAC incidence. Higher mean levels of total cholesterol, LDL-C, and non-HDL-C were associated with a greater risk of future CAC incidence. Similarly, 1-SD increment of lipid variability, as assessed by variability independent of the mean, was associated with an increased risk of CAC incidence (LDL-C: hazard ratio, 1.139 [95% CI, 1.048-1.238]; P=0.002; non-HDL-C: hazard ratio, 1.102 [95% CI, 1.014-1.198]; P=0.022; and triglycerides: hazard ratio, 1.480 [95% CI, 1.384-1.582]; P<0.001). Combination analyses demonstrated that participants with both high lipid levels and high variability in lipid profiles (LDL-C and non-HDL-C) faced the greatest risk of CAC incidence. Specifically, elevated variability of LDL-C was associated with an additional risk of CAC incidence even in low mean levels of LDL-C (hazard ratio, 1.396 [95% CI, 1.106-1.763]; P=0.005). These findings remained robust across a series of sensitivity and subgroup analyses. CONCLUSIONS: Elevated variability in LDL-C and non-HDL-C during young adulthood was associated with an increased risk of CAC incidence in midlife, especially among those with high mean levels of atherogenic lipoproteins. These findings highlight the importance of maintaining consistently low levels of atherogenic lipids throughout early adulthood to reduce subclinical atherosclerosis in midlife. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005130.

Effect of concentration, temperature, and time on the stability of hepatitis C virus nucleic acid in serum.

To explore the influence of storage temperature and time on the stability of different concentrations of hepatitis C virus nucleic acid (HCV RNA) samples and to provide data reference for laboratory quality control. Serum samples of 10 patients with HCV RNA detection quantitation of 106-108 IU/mL were collected. The samples of each patient were diluted into three concentrations: high, medium, and low. Then the samples of each concentration were divided into 21, which were divided into three groups according to the storage conditions of -20°C, 4°C, and 25°C, with seven samples in each group. The samples were selected from each group for quantitative detection of HCV RNA on day 0, day 1, day 3, day 5, day 7, day 14, and day 30. The results of each concentration and storage temperature sample remained stable within 5 days. Based on the mixed-effect linear model, the main effects of temperature, time, and concentration were statistically significant (P < 0.01). There was an interaction effect between concentration and time (P = 0.0448), and there was also an interaction effect between temperature and time (P < 0.01). There was no interaction effect between concentration and temperature (P = 0.11) or between concentration, temperature, and time (P = 0.90). The results of serum samples with different concentrations of the HCV RNA remained stable within 5 days. The lower the initial concentration of HCV RNA serum sample, the worse the stability; the higher the storage temperature, the worse the stability. If conditions permit, the laboratory should store such samples at -20°C. IMPORTANCE: Previously, there were few reports about the influence of different concentrations of sample nucleic acid on the stability of samples at various temperatures and times in various literatures. Therefore, it is necessary to analyze the influence of concentration factors on the stability of samples and test results at different storage times and temperatures. This study took the concentration of hepatitis C virus nucleic acid as the research object to further understand the stability of hepatitis C virus nucleic acid test samples under various storage conditions, to provide data reference for the treatment of hepatitis C virus nucleic acid and RNA test samples before clinical laboratory test, and provide guidance and help for the improvement of laboratory quality control.

Different Etiological Entities of Liver Cancer Across Populations: Implications From Age-Period-Cohort Analysis on Incidence Trends.

INTRODUCTION: The incidence of liver cancer has shown different temporal trends across populations, while the underlying reasons remain unclear. METHODS: We examined temporal trends in the incidence of liver cancer in Hong Kong, Sweden, and the United States since the 1970s through 2021 using joinpoint regression and age-period-cohort analysis. RESULTS: The age-standardized incidence rate of liver cancer in Hong Kong steadily decreased (average annual percentage change [AAPC] -2.2%, 95% confidence interval [CI] -2.8% to -1.7% in men; AAPC -2.1%, 95% CI -3.1% to -1.1% in women) in 1983-2020. The rate in Sweden increased on average by 0.8% (95% CI 0.2%-1.4%) per year in men and was stable in women (AAPC 0.2%, 95% CI -0.9%-1.4%) in 1970-2021. The rate in the United States increased by 2.1% (95% CI 1.5%-2.8%) per year in men and by 2.1% (95% CI 1.6%-2.5%) in women in 1975-2020, but decreasing trends were noted in 2015-2020 (AAPC -6.6%, 95% CI -8.3% to -4.9% in men; AAPC -4.2%, 95% CI -7.5% to -0.8% in women). Stratified analysis by histological type showed such decrease in recent years was limited to hepatocellular carcinoma, rather than intrahepatic cholangiocarcinoma. We observed distinct changes in trends across age groups and different trends across birth cohorts. DISCUSSION: The incidence of liver cancer has decreased in Hong Kong but increased in Sweden and in the United States since the 1980s, despite the decreasing incidence in the United States since 2015. Such disparities may be explained by different etiology and implementation of preventive measures across populations.

Establishment and validation of circulating cell-free DNA signatures for nasopharyngeal carcinoma detection.

BACKGROUND: Early detection of nasopharyngeal carcinoma (NPC) poses a significant challenge. The absence of highly sensitive and specific diagnostic biomarkers for nasopharyngeal carcinoma contributes to the unfavourable prognosis of NPC patients. Here, we aimed to establish a non-invasive approach for detecting NPC using circulating cell-free DNA (cfDNA). METHODS: We investigated the potential of next-generation sequencing (NGS) of peripheral blood cells as a diagnostic tool for NPC. We collected data on genome-wide nucleosome footprint (NF), 5'-end motifs, fragmentation patterns, CNV information, and EBV content from 553 Chinese subjects, including 234 NPC patients and 319 healthy individuals. Through case-control analysis, we developed a diagnostic model for NPC, and validated its detection capability. FINDINGS: Our findings revealed that the frequencies of NF, fragmentation, and motifs were significantly higher in NPC patients compared to healthy controls. We developed an NPC score based on these parameters that accurately distinguished NPC from non-NPC cases according to the American Joint Committee on Cancer staging system from non-NPC (validation set: area under curve (AUC) = 99.9% (95% CI: 99.8%-100%), se: 98.15%, sp: 100%). This model showed superior performance over plasma EBV DNA. Additionally, the NPC score effectively differentiated between NPC patients and healthy controls, even after clinical treatment. Furthermore, the NPC score was found to be independent of potential confounders such as age, sex, or TNM stage. INTERPRETATION: We have developed and verified a non-invasive approach with substantial potential for clinical application in detecting NPC. FUNDING: A full list of funding bodies that contributed to this study can be found in Funding section.

Application of biochar and selenium together at low dose efficiently reduces mercury and methylmercury accumulation in rice grains.

Irrespective of cost and ecological risk, literatures have reported that both biochar and selenium (Se) alone at high application rate exhibited positive effects on decreasing rice mercury (Hg) uptake in high Hg contaminated paddy soil. In this study, we investigated whether biochar and Se together at low dose could efficiently reduce the rice grain Hg and MeHg accumulation in the slight Hg-contaminated soil. Compared with control (CK), the Hg concentration of grains in the BC3, Se0.5, and BC3 + Se0.5 treatments decreased by 5.4 %, 38.3 %, and 48.5 %, respectively. Co-application of biochar and Se also decreased the methylmercury (MeHg) concentration in rice grains by 29.1-91.6 %. The decrease of Hg and MeHg level in rice grains for biochar and Se treatments could be attributed to the following mechanisms: (1) high Hg (primarily inorganic Hg) adsorption on biochar through its high hydroxyl groups and large specific surface area; (2) Increased dissolved organic carbon and cysteine contents in pore water after biochar application, which reduced the availability of soil Hg through complexation; (3) Decreased bioavailability of Hg in soil due to the formation of HgSe precipitation which inhibited Hg uptake and translation by rice plant; (4) Both biochar and Se facilitated the reduction of MeHg in soil. Our results indicate that co-application of biochar and Se at low dose is a promising method to effectively mitigate Hg accumulation in rice grains from the slight Hg-contaminated soil.

Comprehensive Multiple Risk Factor Control in Type 2 Diabetes to Mitigate Heart Failure Risk: Insights From a Prospective Cohort Study.

OBJECTIVE: The impact of comprehensive risk factor control on heart failure (HF) risk and HF-free survival time in individuals with type 2 diabetes (T2D) was evaluated in this study. RESEARCH DESIGN AND METHODS: This prospective study included 11,949 individuals diagnosed with T2D, matched with 47,796 non-T2D control study participants from the UK Biobank cohort. The degree of comprehensive risk factor control was assessed on the basis of the major cardiovascular risk factors, including blood pressure, BMI, LDL cholesterol, hemoglobin A1c, renal function, smoking, diet, and physical activity. Cox proportional hazards models were used to measure the associations between the degree of risk factor control and HF risk. Irwin's restricted mean was used to evaluate HF-free survival time. RESULTS: During a median follow-up of 12.3 years, 702 individuals (5.87%) with T2D and 1,402 matched control participants (2.93%) developed HF. Each additional risk factor controlled was associated with an average 19% lower risk of HF. Optimal control of at least six risk factors was associated with a 67% lower HF risk (hazard ratio [HR] 0.33; 95% CI 0.20, 0.54). BMI was the primary attributable risk factor for HF. Notably, the excess risk of HF associated with T2D could be attenuated to levels comparable to those of non-T2D control participants when individuals had a high degree of risk factor control (HR 0.66; 95% CI 0.40, 1.07), and they exhibited a longer HF-free survival time. CONCLUSIONS: Comprehensive management of risk factors is inversely associated with HF risk, and optimal risk factor control may prolong HF-free survival time among individuals with T2D.

FTMT-dependent mitophagy is crucial for ferroptosis resistance in cardiac fibroblast.

Metabolic responses to cellular stress are pivotal in cell ferroptosis, with mitophagy serving as a crucial mechanism in both metabolic processes and ferroptosis. This study aims to elucidate the effects of high glucose on cardiomyocytes (CMs) and cardiac fibroblasts (CFs) regarding ferroptosis and to uncover the underlying mechanisms involved. We examined alterations in glycolysis, mitochondrial oxidative phosphorylation (OXPHOS), and mitophagy, which are essential for metabolic adaptations and ferroptosis. High glucose exposure induced ferroptosis specifically in CMs, while CFs exhibited resistance to ferroptosis, increased glycolytic activity, and no change in OXPHOS. Moreover, high glucose treatment enhanced mitophagy and upregulated mitochondrial ferritin (FTMT). Notably, the combination of FTMT and the autophagy-related protein nuclear receptor coactivator 4 (NCOA4) increased under high glucose conditions. Silencing FTMT significantly impeded mitophagy and eliminated ferroptosis resistance in CFs cultured under high glucose conditions. The transcription factor forkhead box A1 (FOXA1) was upregulated in CFs upon high glucose exposure, playing a crucial role in the increased expression of FTMT. Within the 5'-flanking sequence of the FTMT mRNA, approximately -500 nt from the transcription initiation site, three putative FOXA1 binding sites were identified. High glucose augmented the binding affinity between FOXA1 and these sequences, thereby promoting FTMT transcription. In summary, high glucose upregulated FOXA1 expression and stimulated FTMT promoter activity in CFs, thereby promoting FTMT-dependent mitophagy and conferring ferroptosis resistance in CFs.

Mechanism research of non-coding RNA in immune checkpoint inhibitors therapy.

Immune checkpoint inhibitor (ICI) therapies for tumors of different systems have attained significant achievements and have changed the current situation of tumor treatment due to their therapeutic characteristics of high specificity and low side effects. The immune checkpoint Programmed death 1/Programmed cell death-Ligand 1 (PD-1/PD-L1) axis exerts a vital role in the immune escape of tumor cells. As a result, it has become a key target for tumor immunotherapy. Therefore, to perfect research into potential regulatory factors for the PD-1/PD-L1 axis, in order to understand and illustrate tumor ICI therapy mechanisms, is a significant goal. Moreover, ncRNA has been verified to regulate the PD-1/PD-L1 axis in the tumor immune microenvironment to regulate tumor genesis and development. ncRNAs can improve or decrease the efficacy of ICI therapy by modulating PD-L1 expression. This review aimed to investigate the mechanisms of action of ncRNA in regulating the PD-1/PD-L1 axis in ICI therapy, to provide more efficient immunotherapy for tumors of different systems.

Age-specific disparity in insomnia among COVID-19 patients in Fangcang shelter hospitals: a population-based study in Shanghai, China.

Background: Fangcang shelter hospitals are quarantine facilities offering primary medical treatment for mild and asymptomatic SARS-CoV-2 cases. Little is known about the age-specific prevalence of insomnia among patients in Fangcang shelter hospitals, particularly in older age groups. Methods: This cross-sectional study was conducted in the three largest Fangcang shelter hospitals during the lockdown period, from March to May 2022, in Shanghai. The patients' demographic and medical information was recorded. Insomnia was defined according to the prescriptions for zolpidem and estazolam. The overall and age-specific prevalence and the risk factors of insomnia were investigated through regression models. Results: A total of 2,39,448 patients were included in this study (59.09% of the patients were male, the median age was 42, and 73.41% of the patients were asymptomatic), with the prevalence of insomnia being 3.1%. The prevalence of insomnia varied across different age groups (<18 years: 0.23%, 18-64 years: 2.64%, and ≥65 years: 10.36%). SARS-CoV-2 vaccine, regardless of the number of doses, was significantly associated with a decreased risk of insomnia for the group aged ≥65 years. Three doses of the vaccine reduced the risk of insomnia for patients aged 18-64 years. An extra day in the hospital significantly increased the risk of insomnia by approximately 10% for all age groups. Mild symptoms were significantly associated with a higher risk of insomnia among patients aged <65 years old, while being male and residing in the surrounding area were negatively associated with insomnia for all adults. Conclusion: This study observed that older patients were a high-risk population for developing insomnia in Fangcang shelter hospitals. SARS-CoV-2 vaccination might decrease the risk of insomnia in adults, especially the older adult, which indicates the benefits of vaccination for reducing insomnia among infected patients.

Relative peripheral refraction in school children with different refractive errors using a novel multispectral refraction topographer.

AIM: To compare relative peripheral refraction (RPR) in Chinese school children with different refractive errors using multispectral refraction topography (MRT). METHODS: A total of 713 eyes of primary school children [172 emmetropia (E), 429 low myopia (LM), 80 moderate myopia (MM), and 32 low hypermetropia (LH)] aged 10 to 13y were analyzed. RPRs were measured using MRT without mydriasis. MRT results showed RPR at 0-15° (RPR 0-15), 15°-30° (RPR 15-30), and 30°-45° (RPR 30-45) annular in the inferior (RPR-I), superior (RPR-S), nasal (RPR-N), and temporal (RPR-T) quadrants. Spherical equivalent (SE) was detected and calculated using an autorefractor. RESULTS: There were significant differences of RPR 15-30 between groups MM [0.02 (-0.12; 0.18)] and LH [-0.13 (-0.36; 0.12)] (P<0.05), MM and E [-0.06 (-0.20; 0.10)] (P<0.05), and LM [-0.02 (-0.15; 0.15)] and E (P<0.05). There were also significant differences of RPR 30-45 between groups MM [0.45 (0.18; 0.74)] and E [0.29 (-0.09; 0.67)] (P<0.05), and LM [0.44 (0.14; 0.76)] and E (P<0.001). RPR values increased from the hyperopic to medium myopic group in each annular. There were significant differences of RPR-S between groups MM [-0.02 (-0.60; 0.30)] and E [-0.44 (-0.89; -0.04)] (P<0.001), and LM [-0.28 (-0.71; 0.12)] and E (P<0.05). There were also significant differences of RPR-T between groups MM [0.37 (0.21; 0.78)] and LH [0.14 (-0.52; 0.50)] (P<0.05), LM [0.41 (0.06; 0.84)] and LH (P<0.05), and LM and E [0.29 (-0.10; 0.68), P<0.05]. A Spearman's correlation analysis showed a negative correlation between RPR and SE in the 15°-30° (P=0.005), 30°-45° (P<0.05) annular (P=0.002), superior (P<0.001), and temporal (P=0.001) quadrants. CONCLUSION: Without pupil dilation, values for RPR 15-30, 30-45, RPR-S, and T shows significant differences between myopic eyes and emmetropia, and the differences are negatively correlated with SE.

[Clinical Characteristics Analysis of EBV-associated Hemophagocytic Lymphohistiocytosis Patients with Acute Kidney Injury].

OBJECTIVE: To analyze the clinical characteristics of patients with Epstein-Barr virus(EBV)-associated hemophagocytic lymphohistiocytosis(HLH) with acute kidney injury(AKI). METHODS: EBV-HLH patients who were hospitalized in our hospital from January 2014 to December 2020 were collected, and their clinical characteristics, treatment, concurrent acute kidney injury and prognosis were retrospectively analyzed. RESULTS: In this study, the incidence of AKI complicated by EBV-HLH was 65.5%, and the 28-day mortality rate was 15.3%. Compared with non-AKI group, patients in the AKI group had higher levels of bilirubin, lactate dehydrogenase, creatinine, urea nitrogen, and ß2-microglobulin（ß2-MG）, poorer coagulation, and lower soluble IL-2 receptor （sCD25）. Patients in the AKI group had a higher proportion of chemotherapy, transplantation, mechanical ventilation, and the application of vasoactive medications, and were hospitalized for longer periods of time, with higher in-hospital mortality rates and 28-day mortality rates. Patients in the AKI group were analyzed in subgroups according to the Kidney Disease Improving Global Outcomes （KDIGO）classification, and the levels of leukocytes, bilirubin, albumin, creatinine, urea nitrogen, ß2-MG, activated partial thromboplastin time （APTT）, and prothrombin time activity （PTA）were more responsive to the severity of the patient's condition. KDIGO grade 2 and 3 had higher proportions of receiving transplants, diuretics, organ support (mechanical ventilation, application of vasoactive medications, and renal replacement therapy), and admissions to the intensive care unit （ICU）, and with higher in-hospital mortality rates and 28-day mortality rates. Regression analysis found that creatinine, ß2-MG, APTT, transplantation, and chemotherapy were independent risk factors for the development of AKI; the application of vasoactive drugs was both an independent risk factor for the development of AKI and for death at 28 days; and chemotherapy, length of hospitalization, and HGB and fibrinogen levels were protective factors for death at 28 days. CONCLUSION: AKI in EBV-HLH has high incidence and high rate of progression to severe disease and death, early attention should be given and strengthened in order to carry out early treatment and improve the prognosis of patients.

Activation of GPR30 Ameliorates Cerebral Ischemia-Reperfusion Injury by Suppressing Ferroptosis Through Nrf2/GPX4 Signaling Pathway.

The newly identified estrogen receptor, G protein-coupled receptor 30 (GPR30), is prevalent in the brain and has been shown to provide significant neuroprotection. Recent studies have linked ferroptosis, a newly characterized form of programmed cell death, closely with cerebral ischemia-reperfusion injury (CIRI), highlighting it as a major contributing factor. Consequently, our research aimed to explore the potential of GPR30 targeting in controlling neuronal ferroptosis and lessening CIRI impacts. Results indicated that GPR30 activation not only improved neurological outcomes and decreased infarct size in a mouse model but also lessened iron accumulation and malondialdehyde formation post-middle cerebral artery occlusion (MCAO). This protective effect extended to increased levels of Nrf2 and GPX4 proteins. Similar protective results were replicated in PC12 cells subjected to Oxygen Glucose Deprivation and Reoxygenation (OGD/R) using the GPR30-specific agonist G1. Importantly, inhibition of Nrf2 with ML385 curtailed the neuroprotective effects of GPR30 activation, suggesting that GPR30 mitigates CIRI primarily through inhibition of neuronal ferroptosis via upregulation of Nrf2 and GPX4.

Partitioning polar-slush strategy in relaxors leads to large energy-storage capability.

Relaxor ferroelectric (RFE) films are promising energy-storage candidates for miniaturizing high-power electronic systems, which is credited to their high energy density (Ue) and efficiency. However, advancing their Ue beyond 200 joules per cubic centimeter is challenging, limiting their potential for next-generation energy-storage devices. We implemented a partitioning polar-slush strategy in RFEs to push the boundary of Ue. Guided by phase-field simulations, we designed and fabricated high-performance Bi(Mg0.5Ti0.5)O3-SrTiO3-based RFE films with isolated slush-like polar clusters, which were realized through suppression of the nonpolar cubic matrix and introduction of highly insulating networks. The simultaneous enhancement of the reversible polarization and breakdown strength leads to a Ue of 202 joules per cubic centimeter with a high efficiency of ~79%. The proposed strategy provides a design freedom for next-generation high-performance dielectrics.

Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma.

BACKGROUND: The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) as neoadjuvant therapy before liver transplantation (LT) for advanced-stage hepatocellular carcinoma (HCC) and to analyze the prognostic factors. AIM: To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC. METHODS: A total of 99 individuals diagnosed with advanced HCC were studied retrospectively. The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT: DEB-TACE group (n = 45) and control group (n = 54). The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus (PVTT). The DEB-TACE group consisted of two subgroups: Group A (n = 31) without PVTT and group B (n = 14) with PVTT. The control group also had two subgroups: Group C (n = 37) without PVTT and group D (n = 17) with PVTT. Data on patient demographics, disease characteristics, therapy response, and adverse events (AEs) were collected. The overall survival (OS) and recurrence-free survival (RFS) rates were assessed using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS. RESULTS: The DEB-TACE group exhibited an overall response rate of 86.6%. Following therapy, there was a significant decrease in the median alpha-fetoprotein (AFP) level (275.1 ng/mL vs 41.7 ng/mL, P < 0.001). The main AE was post-embolization syndrome. The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group (68.9% vs 38.9%, P = 0.003; 86.7% vs 63.0%, P = 0.008). Within the subgroups, group A had higher 2-year rates of RFS and OS compared to group C (71.0% vs 45.9%, P = 0.038; 83.8% vs 62.2%, P = 0.047). The 2-year RFS rate of group B was markedly superior to that of group D (64.3% vs 23.5%, P = 0.002). Results from multivariate analyses showed that pre-LT DEB-TACE [hazard ratio (HR) = 2.73, 95% confidence interval (CI): 1.44-5.14, P = 0.04], overall target tumor diameter ≤ 7 cm (HR = 1.98, 95%CI: 1.05-3.75, P = 0.035), and AFP level ≤ 400 ng/mL (HR = 2.34; 95%CI: 1.30-4.19, P = 0.009) were significant risk factors for RFS. Additionally, pre-LT DEB-TACE (HR = 3.15, 95%CI: 1.43-6.96, P = 0.004) was identified as a significant risk factor for OS. CONCLUSION: DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

Thermoelectric Performance Enhancement in SnS Polycrystals Owing to Hole Doping Combined with Textured Microstructures.

Recently, the earth-abundant tin sulfide (SnS) has emerged as a promising thermoelectric material due to its phonon and electron structure similar to that of tin selenide (SnSe). However, compared with SnSe, limited progress has been achieved in the thermoelectric property enhancement of SnS. Textured SnS polycrystals with an enhanced thermoelectric performance have been developed in this work. The high carrier mobility benefited from the enhanced texture through the repressing strategy of spark plasma sintering, improving the electrical conductivity. In addition, Sn atom deficiencies in the texture sample led to an increased hole concentration, further boosting the electrical conductivity and power factor. The power factor exceeded 4.10 µW/cm·K2 at 423 K and 5.50 µW/cm·K2 at 850 K. The phonon scattering was strengthened by adjusting the multiscale microstructures including dislocations, defect clusters, etc., leading to an ultralow lattice thermal conductivity of 0.23 W/m·K at 850 K. A figure of merit zT > 1.3 at 850 K and an average zTave of 0.58 in the temperature range 373-850 K were achieved in the SnS polycrystal.