Identification of diagnostic signature and immune infiltration for ischemic cardiomyopathy based on cuproptosis-related genes through bioinformatics analysis and experimental validation.

BACKGROUND: Ischemic cardiomyopathy (IC) is primarily due to long-term ischemia/hypoxia of the coronary arteries, leading to impaired cardiac contractile or diastolic function. A new form of cell death induced by copper, called "cuproptosis" is related to the development and progression of multiple diseases. The cuproptosis-related gene (CuGs) plays an important role in acute myocardial infarction, while the specific mechanisms of CuGs in ischemic cardiomyopathy remain unclear. METHODS: The expressions of CuGs and their immune characteristics were analyzed with the IC datasets obtained from the Gene Expression Omnibus, namely GSE5406 and GSE57338, identifying core genes associated with IC development. By comparing RF, SVM, GLM and XGB models, the optimal machine learning model was selected. The expression of marker genes was validated based on the GSE57345, GSE48166 and GSE42955 datasets. Construct a CeRNA network based on core genes. Therapeutic chemiacals targeting core genes were acquired using the CTD database, and molecular docking was performed using Autodock vina software. By ligating the left anterior descending (LAD) coronary artery, an IC mouse model is established, and core genes were experimentally validated using Western blot (WB) and immunohistochemistry (IHC) methods. RESULTS: We identified 14 CuGs closely associated with the onset of IC. The SVM model exhibited superior discriminative power (AUC = 0.914), with core genes being DLST, ATP7B, FDX1, SLC31A1 and DLAT. Core genes were validated on the GSE42955, GSE48166 and GSE57345 datasets, showing excellent performance (AUC = 0.943, AUC = 0.800, and AUC = 0.932). The CeRNA network consists of 218 nodes and 264 lines, including 5 core diagnostic genes, 52 miRNAs, and 161 lncRNAs. Chemicals predictions indicated 8 chemicals have therapeutic effects on the core diagnostic genes, with benzo(a)pyrene molecular docking showing the highest affinity (-11.3 kcal/mol). Compared to the normal group, the IC group,which was established by LAD ligation, showed a significant decrease in LVEF as indicated by cardiac ultrasound, and increased fibrosis as shown by MASSON staining, WB results suggest increased expression of DLST and ATP7B, and decreased expression of FDX1, SLC31A1 and DLAT in the myocardial ischemic area (p < 0.05), which was also confirmed by IHC in tissue sections. CONCLUSION: In summary, this study comprehensively revealed that DLST, ATP7B, FDX1, SLC31A1 and DLAT could be identified as potential immunological biomarkers in IC, and validated through an IC mouse model, providing valuable insights for future research into the mechanisms of CuGs and its diagnostic value to IC.

Superfine Nanodomain Engineering Unleashing Ferroelectricity in Incipient Ferroelectrics.

Incipient ferroelectrics have emerged as an attractive class of functional materials owing to their potential to be engineered for exotic ferroelectric behavior, holding great promise for expanding the ferroelectric family. However, thus far, their artificially engineered ferroelectricity has fallen far short of rivaling classic ferroelectrics. In this study, we address this challenge by developing a superfine nanodomain engineering strategy. By applying this approach to representative incipient ferroelectric of SrTiO3-based films, we achieve unprecedentedly strong ferroelectricity, not only surpassing previous records for incipient ferroelectrics but also being comparable to classic ferroelectrics. The remanent polarization of the thin film reaches up to 17.0 µC cm-2 with an ultrahigh Curie temperature of 973 K. Atomic-scale investigations elucidate the origin of this robust ferroelectricity in the emergent high-density superfine nanodomains spanning merely 3-10 unit cells. Combining experimental results with theoretical assessments, we unveil the underlying mechanism, where the intentionally introduced diluted foreign Fe element creates a deeper Landau energy well and promotes a short-range ordering of polarization. Our developed strategy significantly streamlines the design of unconventional ferroelectrics, providing a versatile pathway for exploring new and superior ferroelectric materials.

Point-of-Care Testing of Whole Blood for Liver Injury Auxiliary Diagnosis with Biothiols Activable Chemiluminescent Probe.

Liver injury significantly affects a patient's health and quality of life. However, timely and convenient diagnosis of this disease via whole blood detection remains challenging due to the lack of user-friendly and fast readout blood test methods. Herein, we developed such a method for the swift auxiliary diagnosis of liver injury via whole blood detection using a customed point-of-care testing (POCT) system consisting of a biothiols-activatable chemiluminescent probe and a hand-held POCT device. Biothiols served as the target to build the activable chemiluminescence probe due to their abnormal level in liver injury. Compared with fluorescent and electrical POCTs, this method is more convenient and has strong universality. By incorporating cyclodextrin via host-guest chemistry, we intensified chemiluminescence while mitigating chemical hemolysis caused by the dissolution of organic molecules, making this system suitable for whole blood analysis. Preliminary assessments in aqueous solutions, living cells, and mouse models confirmed its sensitivity, reliability, and feasibility. Simply mixing blood with the probe for 30 min yielded a clear signal readout within 15 s on the POCT device. Utilizing this portable detector, the reduced biothiol level was tested in 18 liver injury patient blood samples, and the results were similar to those measured by a commercial kit and in vivo imaging system. Thus, this work provides a universal platform for the fast and convenient detection of other biomarkers in whole blood samples and opens up possibilities for the rapid clinical diagnosis of diseases, enabling patients to conduct home self-examinations with ease.

Integrating muti-omics data to identify tissue-specific DNA methylation biomarkers for cancer risk.

The relationship between tissue-specific DNA methylation and cancer risk remains inadequately elucidated. Leveraging resources from the Genotype-Tissue Expression consortium, here we develop genetic models to predict DNA methylation at CpG sites across the genome for seven tissues and apply these models to genome-wide association study data of corresponding cancers, namely breast, colorectal, renal cell, lung, ovarian, prostate, and testicular germ cell cancers. At Bonferroni-corrected P < 0.05, we identify 4248 CpGs that are significantly associated with cancer risk, of which 95.4% (4052) are specific to a particular cancer type. Notably, 92 CpGs within 55 putative novel loci retain significant associations with cancer risk after conditioning on proximal signals identified by genome-wide association studies. Integrative multi-omics analyses reveal 854 CpG-gene-cancer trios, suggesting that DNA methylation at 309 distinct CpGs might influence cancer risk through regulating the expression of 205 unique cis-genes. These findings substantially advance our understanding of the interplay between genetics, epigenetics, and gene expression in cancer etiology.

Distribution of scoliosis in 2.22 million adolescents in mainland China: A population-wide analysis.

Background: The characteristics of scoliosis afflicting school children and adolescents in mainland China are still unclear. Therefore, we conducted a systematic review to estimate scoliosis's prevalence and characterise its distribution in China. Methods: We screened PubMed, Scopus, WanFang, China National Knowledge Infrastructure, National Science and Technology Library, and WeiPu databases for mainland China articles published between 1 January 1980 and 31 October 2022. Among them, we identified population-wide scoliosis studies in school children and adolescents. The main outcomes were the positive rate of primary screening and the prevalence of final screening. Primary screening mainly included general examination with/without the forward bending test in school. The final screening entailed clinical diagnosis by Röntgen radiation in a hospital (based on primary screening). A meta-analysis of scoliosis distribution by gender was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Further, we analysed the distributions of scoliosis by age, region, aetiological type, and severity of curvature, in addition to the correlation between its prevalence and altitude or latitude. Results: 77 studies with 2 224 320 participants were included. The positive rate through primary screening was 3.97%, whereas the prevalence of scoliosis at final screening was 1.20%. Analysing the data revealed a higher prevalence of scoliosis in girls (OR = 1.57; 95% CI = 1.38-1.81). The age-wise peak rate of scoliosis was 15-16 years (1.07%) in boys and 13-14 years (1.42%) in girls. The mean prevalence of scoliosis was 1.07% in the western region, 1.54% in the central, and 1.35% in the eastern. Scoliosis prevalence was not correlated with either altitude or latitude. The prevalence of idiopathic and congenital scoliosis was 1.18 and 0.03%. Among all subjects with scoliosis, 79.10 and 16.80% had mild and medium disease severity. Conclusions: According to this comprehensive study using data sets of scoliosis in adolescents across mainland China, the mean prevalence of scoliosis is 1.20%, yet 1.57 times higher in girls than boys, and is most prevalent in the middle region. Overall, scoliosis in adolescents could pose a burden to public health in mainland China. Registration: PROSPERO CRD42021231987.

Osteostaticytes: A novel osteoclast subset couples bone resorption and bone formation.

Background: Osteomyelitis (OM) is an inflammatory condition of bone characterized by cortical bone devascularization and necrosis. Dysregulation of bone remodelling is triggered by OM. Bone remodelling is precisely coordinated by bone resorption and formation via a reversal phase. However, the cellular and molecular mechanisms underlying bone remodelling failure after osteomyelitis remain elusive. Methods: To elucidate the cellular and molecular mechanism underlying bone healing after osteomyelitis, we employed single-cell RNA sequencing (scRNA-seq) to depict the atlas of human cortical bone in normal, infected and reconstructed states. Dimensionality reduction by t-stochastic neighbourhood embedding (t-SNE) and graph-based clustering were applied to analyse the detailed clusters of osteoclast lineages. After trajectory analysis of osteoclast lineages over pseudotime, real-time PCR and immunofluorescence (IF) staining were applied to identify marker gene expression of various osteoclast lineages in the osteoclast induction model and human bone sections, respectively. The potential function and communication of osteoclasts were analysed via gene set enrichment analysis (GSEA) and CellChat. The chemotactic ability of mesenchymal stem cells (MSCs) and osteoclast lineage cells in various differentiation states was determined by transwell assays and coculture assays. The effects of various osteoclast lineages on the osteogenic differentiation potential of MSCs were also determined by using this coculture system. A normal mouse tibia fracture model and an osteomyelitis-related tibia fracture model were generated via injection of luciferase-labelled Staphylococcus aureus to verify the relationships between a novel osteoclast lineage and MSCs. Then, the infection was detected by a bioluminescence imaging system. Finally, immunofluorescence staining was used to detect the expression of markers of MSCs and novel osteoclast lineages in different remodelling phases in normal and infected bone remodelling models. Results: In this study, we constructed a cell atlas encompassing normal, infected, and reconstructed cortical bone. Then, we identified a novel subset at the earlier stage of the osteoclast lineage that exhibited increased expression of IDO1, CCL3, and CCL4. These IDO1highCCL3highCCL4high cells, termed osteostaticytes (OSCs), were further regarded as the reservoir of osteoclasts in the reversal phase. Notably, OSCs exhibited the highest chemotactic activity, surpassing other lineage subsets. We also discovered that cells at the earlier stage of the osteoclast lineage play a significant role in recruiting mesenchymal stem cells (MSCs). Finally, the data revealed that OSCs might be positively related to the occurrence of bone MSCs and the contribution of bone remodelling. Conclusion: Collectively, our findings revealed a novel stage (OSC) within the osteoclast lineage, potentially representing elusive bone reversal cells due to its increased chemotactic ability towards MSCs and potential contribution to bone remodelling. This study provides valuable insights into the intricate mechanisms of the reversal phase during bone remodelling and unveils potential therapeutic strategies for diseases associated with bone uncoupling. Translational potential of this article: This study identified a new subset, referred to as IDO1(plus symbol) CCL3(plus symbol) CCL4(plus symbol) osteostaticytes which displayed the highest chemotactic activity among all osteoclast lineages and may serve as reversal cells in bone remodelling. These findings offer new insights and insights for understanding bone reversal-related diseases and may serve as novel therapeutic targets for conditions such as osteomyelitis and delayed bone healing.

Flexible Substrate-Compatible and Efficiency-Improved Quantum-Dot Light-Emitting Diodes with Reduced Annealing Temperature of NiOx Hole-Injecting Layer.

The growing demand for wearable and attachable displays has sparked significant interest in flexible quantum-dot light-emitting diodes (QLEDs). However, the challenges of fabricating and operating QLEDs on flexible substrates persist due to the lack of stable and low-temperature processable charge-injection/-transporting layers with aligned energy levels. In this study, we utilized NiOx nanoparticles that are compatible with flexible substrates as a hole-injection layer (HIL). To enhance the work function of the NiOx HIL, we introduced a self-assembled dipole modifier called 4-(trifluoromethyl)benzoic acid (4-CF3-BA) onto the surface of the NiOx nanoparticles. The incorporation of the dipole molecules through adsorption treatment has significantly changed the wettability and electronic characteristics of NiOx nanoparticles, resulting in the formation of NiO(OH) at the interface and a shift in vacuum level. The alteration of surface electronic states of the NiOx nanoparticles not only improves the carrier balance by reducing the hole injection barrier but also prevents exciton quenching by passivating defects in the film. Consequently, the NiOx-based red QLEDs with interfacial modification demonstrate a maximum current efficiency of 16.1 cd/A and a peak external quantum efficiency of 10.3%. This represents a nearly twofold efficiency enhancement compared to control devices. The mild fabrication requirements and low annealing temperatures suggest potential applications of dipole molecule-modified NiOx nanoparticles in flexible optoelectronic devices.

Anthropogenic warming is a key climate indicator of rising urban fire activity in China.

China, one of the most populous countries in the world, has suffered the highest number of natural disaster-related deaths from fire. On local scales, the main causes of urban fires are anthropogenic in nature. Yet, on regional to national scales, little is known about the indicators of large-scale co-varying urban fire activity in China. Here, we present the China Fire History Atlas (CFHA), which is based on 19 947 documentary records and represents fires in urban areas of China over the twentieth century (1901-1994). We found that temperature variability is a key indicator of urban fire activity in China, with warmer temperatures being correlated with more urban fires, and that this fire-temperature relationship is seasonally and regionally explicit. In the early twentieth century, however, the fire-temperature relationship was overruled by war-related fires in large urban areas. We further used the fire-temperature relationship and multiple emissions scenarios to project fire activity across China into the twenty-first century. Our projections show a distinct increase in future urban fire activity and fire-related economic loss. Our findings provide insights into fire-climate relationships in China for densely-populated areas and on policy-relevant time scales and they contribute spatial coverage to efforts to improve global fire models.

Ferroelectric Order Evolution in Freestanding PbTiO3 Films Monitored by Optical Second Harmonic Generation.

The demand for low-dimensional ferroelectric devices is steadily increasing, however, the thick substrates in epitaxial films impede further size miniaturization. Freestanding films offer a potential solution by eliminating substrate constraints. Nevertheless, it remains an ongoing challenge to improve the stability in thin and fragile freestanding films under strain and temperature. In this work, the structure and ferroelectric order of freestanding PbTiO3 (PTO) films are investigated under continuous variation of the strain and temperature using nondestructive optical second harmonic generation (SHG) technique. The findings reveal that there are both out-of-plane and in-plane domains with polarization along out-of-plane and in-plane directions in the orthorhombic-like freestanding PTO films, respectively. In contrast, only out-of-plane domains are observed in the tetragonal epitaxial PTO films. Remarkably, the ferroelectricity of freestanding PTO films is strengthened under small uniaxial tensile strain from 0% up to 1.66% and well-maintained under larger biaxial tensile strain up to 2.76% along the [100] direction and up to 4.46% along the [010] direction. Moreover, a high Curie temperature of 630 K is identified in 50 nm thick freestanding PTO films by wide-temperature-range SHG. These findings provide valuable understanding for the development of the next-generation electronic nanodevices with flexibility and thermostability.

Capture of armA by a novel ISCR element, ISCR28.

ISCR28 is a fully functional and active member of the IS91-like family of insertion sequences. ISCR28 is 1,708-bp long and contains a 1,293-bp long putative open reading frame that codes a transposase. Sixty ISCR28-containing sequences from GenBank generated 27 non-repeat genetic contexts, all of which represented naturally occurring biological events that had occurred in a wide range of gram-negative organisms. Insertion of ISCR28 into target DNA preferred the presence of a 5'-GXXT-3' sequence at its terIS (replication terminator) end. Loss of the first 4 bp of its oriIS (origin of replication) likely caused ISCR28 to be trapped in ISApl1-based transposons or similar structures. Loss of terIS and fusion with a mobile element upstream likely promoted co-transfer of ISCR28 and the downstream resistance genes. ArmA and its downstream intact ISCR28 can be excised from recombinant pKD46 plasmids forming circular intermediates, further elucidating its activity as a transposase.

Association between atherogenic index of plasma and new-onset stroke in individuals with different glucose metabolism status: insights from CHARLS.

BACKGROUND: Circulating atherogenic index of plasma (AIP) levels has been proposed as a novel biomarker for dyslipidemia and as a predictor of insulin resistance (IR) risk. However, the association between AIP and the incidence of new-onset stroke, particularly in individuals with varying glucose metabolism status, remains ambiguous. METHODS: A total of 8727 participants aged 45 years or older without a history of stroke from the China Health and Retirement Longitudinal Study (CHARLS) were included in this study. The AIP was calculated using the formula log [Triglyceride (mg/dL) / High-density lipoprotein cholesterol (mg/dL)]. Participants were divided into four groups based on their baseline AIP levels: Q1 (AIP ≤ 0.122), Q2 (0.122 < AIP ≤ 0.329), Q3 (0.329 < AIP ≤ 0.562), and Q4 (AIP > 0.562). The primary endpoint was the occurrence of new-onset stroke events. The Kaplan-Meier curves, multivariate Cox proportional hazard models, and Restricted cubic spline analysis were applied to explore the association between baseline AIP levels and the risk of developing a stroke among individuals with varying glycemic metabolic states. RESULTS: During an average follow-up of 8.72 years, 734 participants (8.4%) had a first stroke event. The risk for stroke increased with each increasing quartile of baseline AIP levels. Kaplan-Meier curve analysis revealed a significant difference in stroke occurrence among the AIP groups in all participants, as well as in those with prediabetes mellitus (Pre-DM) and diabetes mellitus (DM) (all P values < 0.05). After adjusting for potential confounders, the risk of stroke was significantly higher in the Q2, Q3, and Q4 groups than in the Q1 group in all participants. The respective hazard ratios (95% confidence interval) for stroke in the Q2, Q3, and Q4 groups were 1.34 (1.05-1.71), 1.52 (1.19-1.93), and 1.84 (1.45-2.34). Furthermore, high levels of AIP were found to be linked to an increased risk of stroke in both pre-diabetic and diabetic participants across all three Cox models. However, this association was not observed in participants with normal glucose regulation (NGR) (p > 0.05). Restricted cubic spline analysis also demonstrated that higher baseline AIP levels were associated with higher hazard ratios for stroke in all participants and those with glucose metabolism disorders. CONCLUSIONS: An increase in baseline AIP levels was significantly associated with the risk of stroke in middle-aged and elderly individuals, and exhibited distinct characteristics depending on the individual's glucose metabolism status.

Molecular subtypes of ischemic heart disease based on circadian rhythm.

Coronary atherosclerotic heart disease (CAD) is among the most prevalent chronic diseases globally. Circadian rhythm disruption (CRD) is closely associated with the progression of various diseases. However, the precise role of CRD in the development of CAD remains to be elucidated. The Circadian rhythm disruption score (CRDscore) was employed to quantitatively assess the level of CRD in CAD samples. Our investigation revealed a significant association between high CRDscore and adverse prognosis in CAD patients, along with a substantial correlation with CAD progression. Remarkably distinct CRDscore distributions were also identified among various subtypes. In summary, we have pioneered the revelation of the relationship between CRD and CAD at the single-cell level and established reliable markers for the development, treatment, and prognosis of CAD. A deeper understanding of these mechanisms may offer new possibilities for incorporating "the therapy of coronary heart disease based circadian rhythm" into personalized medical treatment regimens.

Early admission is better-the time to admission (TTA) is associated with one-year mortality in hip fracture.

OBJECTIVE: This study evaluated the probable association between time to admission (TTA) and one-year mortality in geriatric hip fractures. METHODS: Older adult patients with hip fractures were screened between January 2015 and September 2019. The demographic and clinical characteristics of the patients were collected at the largest trauma center in northwest China. TTA can be obtained from the medical record system and converted into a categorical variable. Multivariate binary logistic regression and generalized additive model were used to identify the linear and nonlinear association between TTA and one-year mortality. Analyses were performed using EmpowerStats and the R software. RESULTS: Two thousand three hundred and sixty-one patients who met the criteria were finally included. There were 1618 (68.53%) female and 743 (31.47%) male patients. All patients were divided into three groups according to their TTA. The proportions of patients with low (<=6 h), middle (>6, <=24 h), and high (>24 h) waiting times were 995, 654, and 712, respectively, and the corresponding one-year mortality rates were 62 (6.23%), 72 (11.01%), and 82 (11.52%). We found a curve relationship between TTA and one-year mortality by two-piecewise linear regression, and 9 hours was an inflection point. When TTA was less than 9 hours, the one-year mortality of patients increased by 9% for every 1-hour increase in TTA (OR=1.09, 95%CI: 1.03-1.16; P<0.01). When TTA was greater than 9 hours, the mortality of patients no longer increased with the rise of TTA (OR=1.00, 95%CI:1.00-1.00; P=0.26). CONCLUSION: TTA is a probable predictor of one-year mortality. We found that 9 hours is an inflection point. If TTA is less than 9 hours, the mortality rate of patients will be lower. If it takes more than 9 hours, the mortality will be higher. Therefore, the elderly who are found to have possible hip fractures should be admitted to the hospital as soon as possible.

Nocardia implantans sp. nov. isolated from a patient with pulmonary infection.

TwoGram-stain-positive and rod-shaped actinomycetes (strains CDC186T and CDC192) were isolated from sputum samples of a patient in Chongqing, PR China, and were investigated to determine their taxonomic status. The results of phylogenetic analysis based on the 16S rRNA gene indicated that CDC186T and CDC192 represented members of the genus Nocardia, and the sequence similarity with Nocardia beijingensis DSM 44636T was the highest, at 99.71 and 99.78 %, respectively. The DNA G+C content of both CDC186T and CDC192 was 69.1 %. Genomic diversity analysis revealed that the average nucleotide identity and in silico DNA‒DNA hybridisation values between the two novel strains and closely related species were significantly below the thresholds of 95-96 and 70 %, respectively, but these values between the two novel strains were 99.96 and 99.90 %, respectively. The phylogenetic relationship based on the dapb1 gene and the single-copy core genes further indicated that the two novel strains were clustered in separate branch adjacent to N. beijingensis DSM 44636T. Growth occurred within the ranges of 20-42 °C, pH 6.0-9.0 and NaCl concentrations of 0.5-4.5 % (w/v). The major fatty acids of CDC186T and CDC192 were C16 : 0 and C18 : 0 10-methyl [tuberculostearic acid (TBSA)]. The predominant respiratory menaquinone was MK-9. The polar lipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol mannoside, one unidentified glycolipid, one unidentified phospholipid and one unidentified phosphoglycolipid. All the genomes of the studied strains were annotated with virulence factor (VF)-associated genes homologous to those of Mycobacterium tuberculosis, and the results of susceptibility testing indicated that CDC186T and CDC192 were resistant to amoxicillin-clavulanic acid and tigecycline. On the basis of chemotaxonomic characteristics and the results of phylogenetic analyses, strains CDC186T and CDC192 represent a novel species within the genus Nocardia, for which the name Nocardia implantans sp. nov. is proposed. The type strain is CDC186T (=GDMCC 4.206T= JCM 34959T).

Generation of an integration-free induced pluripotent stem cell (iPSC) line (SDHI001-A) from a 65-year old adult mitral valve prolapse (MVP) patient.

Human iPSC line, SDHi001-A, was generated from 65-year-old male patient with mitral valve prolapse, using non-integrative reprogramming method. This cell line shows pluripotency both in vitro and in vivo, and has a normal karyotype.

Bruceine A alleviates alcoholic liver disease by inhibiting AIM2 inflammasome activation via activating FXR.

BACKGROUND: Alcoholic liver disease (ALD), a public health challenge worldwide caused by long-term persistent drinking, is life-threatening with minimal approved therapies. Hepatic steatosis accompanied by inflammation is an initial and inevitable stage in the complex progression of simple alcoholic liver injury to more severe liver diseases such as hepatitis, liver fibrosis, cirrhosis and liver cancer. PURPOSE: We aimed to identify the therapeutic role of Bruceine A (BA) in ALD whilst attempting to explore whether its protective effects depend specifically on the farnesoid X receptor (FXR). METHODS: Autodock was applied to detect the affinity between BA and FXR. Lieber-DeCarli liquid diet with 5 % ethanol (v/v) was adopted to establish the mouse ALD model. The lentivirus mediating FXR (LV-FXR) was injected into mice via the tail vein to establish FXR-overexpressed mice. FXR silencing or overexpression plasmids were transfected into AML-12 cells prior to ethanol stimulation. Quantitative real-time PCR, Western blotting and immunofluorescence assays were employed to determine the expression of related genes. We subjected liver sections to H&E and Oil Red O staining to evaluate the liver histological injury and the deposition of lipid droplets. RESULTS: BA significantly reduced body weight and liver-to-body weight ratios as well as biochemical indexes in mice. Ethanol-induced liver damage and lipid accumulation could be alleviated by BA treatment. BA bound to FXR by two hydrogen bonds. There was a positive correlation between BA administration and FXR expression. BA inhibited the expression of lipid synthesis genes and enhanced the expression of lipid metabolism genes by activating FXR, thus alleviating steatosis in ALD. Moreover, BA exerted an ameliorative effect against inflammation by inhibiting the activation of absent in melanoma 2 (AIM2) inflammasome by activating FXR. FXR overexpression possessed the ability to counter the accumulation of lipid and the activation of AIM2 inflammasome caused by ethanol. FXR deficiency exacerbated ethanol-induced liver steatosis and inflammation. The hepatoprotective effect of BA could be disrupted by FXR antagonist guggulsterone (GS) in vivo and FXR siRNA in vitro. CONCLUSION: BA alleviated alcoholic liver disease by inhibiting AIM2 inflammasome activation through an FXR-dependent mechanism. This study may potentially represent a new therapeutic approach for ALD.

Characterisation of a Novel Insect-Specific Virus Discovered in Rice Thrips, Haplothrips aculeatus.

Insects constitute the largest proportion of animals on Earth and act as significant reservoirs and vectors in disease transmission. Rice thrips (Haplothrips aculeatus, family Phlaeothripidae) are one of the most common pests in agriculture. In this study, the full genome sequence of a novel Ollusvirus, provisionally named "Rice thrips ollusvirus 1" (RTOV1), was elucidated using transcriptome sequencing and the rapid amplification of cDNA ends (RACE). A homology search and phylogenetic tree analysis revealed that the newly identified virus is a member of the family Aliusviridae (order Jingchuvirales). The genome of RTOV1 contains four predicted open reading frames (ORFs), including a polymerase protein (L, 7590 nt), a glycoprotein (G, 4206 nt), a nucleocapsid protein (N, 2415 nt) and a small protein of unknown function (291 nt). All of the ORFs are encoded by the complementary genome, suggesting that the virus is a negative-stranded RNA virus. Phylogenetic analysis using polymerase sequences suggested that RTOV1 was closely related to ollusvirus 1. Deep small RNA sequencing analysis reveals a significant accumulation of small RNAs derived from RTOV1, indicating that the virus replicated in the insect. According to our understanding, this is the first report of an Ollusvirus identified in a member of the insect family Phlaeothripidae. The characterisation and discovery of RTOV1 is a significant contribution to the understanding of Ollusvirus diversity in insects.

A randomized controlled double-blinded split-face prospective clinical trial to assess the efficacy, safety, and tolerability of a novel 3-step routine compared to benzoyl peroxide for the treatment of mild to moderate acne vulgaris.

Adult acne vulgaris affects up to 43-51% of individuals. While there are numerous treatment options for acne including topical, oral, and energy-based approaches, benzoyl peroxide (BPO) is a popular over the counter (OTC) treatment. Although BPO monotherapy has a long history of efficacy and safety, it suffers from several disadvantages, most notably, skin irritation, particularly for treatment naïve patients. In this prospective, randomized, controlled, split-face study, we evaluated the comparative efficacy, safety, and tolerability of a novel 3-step azelaic acid, salicylic acid, and graduated retinol regimen versus a common OTC BPO-based regimen over 12 weeks. A total of 37 adult subjects with self-reported mild to moderate acne vulgaris were recruited. A total of 21 subjects underwent a 2-week washout period and completed the full study with 3 dropping out due to product irritation from the BPO routine, and 13 being lost to follow-up. Detailed tolerability surveys were conducted at Week 4. Additional surveys on tolerability and product preferences were collected monthly, at Week 4, Week 8, and Week 12. A blinded board-certified dermatologist objectively scored the presence and type of acne lesions (open or closed comedones, papules, pustules, nodules, and cysts) at baseline, Week 4, Week 8, and Week 12. Patients photographed themselves and uploaded the images using personal mobile phones. Detailed Week 4 survey results showed across 25 domains of user-assessed product performance, the novel routine outperformed the BPO routine in 19 (76%) which included domains in preference (e.g. "I would use this in the future) and performance ("my skin improved" and "helped my acne clear up faster"). Users of the novel routine reported less facial redness, itching, and burning, though differences did not reach statistical significance. In terms of efficacy, both products performed similarly, reducing total acne lesions by 36% (novel routine) and 40% (BPO routine) by Week 12. Overall, accounting for user preferences and tolerability the novel routine was more preferred than the BPO routine in 79% of domains (22/28). Differences in objective acne lesion reduction were not statistically significant (p = 0.97). In a randomized split-face study, a 3-step azelaic acid, salicylic acid, and graduated retinol regimen delivered similar acne lesion reduction, fewer user dropouts, greater user tolerability, and higher use preference compared to a 3-step BPO routine based in a cohort of participants with mild-to-moderate acne vulgaris.

Development and validation of a prenatal predictive nomogram for the risk of NICU admission in infants born to Chinese mothers over 35 years of age: a retrospective cohort study.

BACKGROUND: The rising number of women giving birth at advanced maternal age has posed significant challenges in obstetric care in recent years, resulting in increased incidence of neonatal transfer to the Neonatal Intensive Care Unit (NICU). Therefore, identifying fetuses requiring NICU transfer before delivery is essential for guiding targeted preventive measures. OBJECTIVE: This study aims to construct and validate a nomogram for predicting the prenatal risk of NICU admission in neonates born to mothers over 35 years of age. STUDY DESIGN: Clinical data of 4218 mothers aged ≥ 35 years who gave birth at the Department of Obstetrics of the Second Hospital of Shandong University between January 1, 2017 and December 31, 2021 were reviewed. Independent predictors were identified by multivariable logistic regression, and a predictive nomogram was subsequently constructed for the risk of neonatal NICU admission. RESULTS: Multivariate logistic regression demonstrated that the method of prenatal screening, number of implanted embryos, preterm premature rupture of the membranes, preeclampsia, HELLP syndrome, fetal distress, premature birth, and cause of preterm birth are independent predictors of neonatal NICU admission. Analysis of the nomogram decision curve based on these 8 independent predictors showed that the prediction model has good net benefit and clinical utility. CONCLUSION: The nomogram demonstrates favorable performance in predicting the risk of neonatal NICU transfer after delivery by mothers older than 35 years. The model serves as an accurate and effective tool for clinicians to predict NICU admission in a timely manner.

Short­ and long­term outcomes after laparoscopic and open pancreatoduodenectomy for elderly patients: a propensity score­matched study.

BACKGROUND: The feasibility and safety of laparoscopic pancreatoduodenectomy (LPD) in elderly patients is still controversial. This study aimed to compare the clinical outcomes of LPD and open pancreatoduodenectomy (OPD) in elderly patients. METHODS: Clinical and follow-up data of elderly patients (≥ 65 years) who underwent LPD or OPD between 2015 and 2022 were retrospectively analyzed. A 1:1 propensity score-matching (PSM) analysis was performed to minimize differences between groups. Univariate and multivariate logistic regression analysis were used to select independent prognostic factors for 90-day mortality. RESULTS: Of the 410 elderly patients, 236 underwent LPD and 174 OPD. After PSM, the LPD group had a less estimated blood loss (EBL) (100 vs. 200 mL, P < 0.001), lower rates of intraoperative transfusion (10.4% vs. 19.0%, P = 0.029), more lymph node harvest (11.0 vs. 10.0, P = 0.014) and shorter postoperative length of stay (LOS) (13.0 vs. 16.0 days, P = 0.013). There were no significant differences in serious complications, reoperation, 90-day readmission and mortality rates (all P > 0.05). Multivariate logistic regression analysis showed that post-pancreatectomy hemorrhage (PPH) was an independent risk factor for 90-day mortality. Elderly patients with pancreatic ductal adenocarcinoma (PDAC) who underwent LPD or OPD had similar overall survival (OS) (22.5 vs.20.4 months, P = 0.672) after PSM. CONCLUSIONS: It is safe and feasible for elderly patients to undergo LPD with less EBL and a shorter postoperative LOS. There was no statistically significant difference in long-term survival outcomes between elderly PDAC patients who underwent LPD or OPD.