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Abstract Background The risk of liver fibrosis in HBeAg-positive chronic hepatitis B (CHB) patients with indeterminate phase is not well characterized. We aimed to compare the presence of liver fibrosis in HBeAg-positive CHB patients between indeterminate phase and immune-tolerant phase. Methods This multi-center, retrospective cohort study included 719 treatment-naïve HBeAg-positive CHB patients with normal alanine aminotransferase (ALT). Patients with HBV DNA > 106 IU/mL were categorized into immune-tolerant phase, whereas those with HBV DNA ≤ 106 IU/mL were classified into indeterminate phase. Significant liver fibrosis and cirrhosis were determined by APRI, FIB-4, transient elastography, or liver biopsy. Results The median age of patients was 33.0 years and 59.8% of patients were male. 81.5% and 18.5% of patients were in the immune-tolerant phase and indeterminate phase, respectively. The APRI (0.33 vs. 0.27, P

The extreme heavy rainfall weather under the long-term influence of MCS can easily cause serious disasters such as flash floods in complex terrain areas. Detailed study of its characteristics and causes can help better understand and defend against similar disaster weather. In this paper, we use multi-source meteorological observation data to study the MCS evolution characteristics and mechanism of two rainstorm processes on 10-11 August 2020 (process 1) and 4-5 August 2021 (process 2) in the complex terrain area of the eastern slope of the Qinghai Tibet Plateau. The results are as follows. (1) The two processes are warm rainstorm weather processes under the influence of weak weather scale system, and the strong precipitation areas are located in the Pingba River valley to the west of Luochun Mountains. The terrain has a very obvious impact on the strong precipitation areas. Compared with process 2, process 1 has larger precipitation intensity, wider range and more concentrated distribution of precipitation areas. (2) The MCS that caused the two rainstorm both originated in the high altitude windward slope terrain in the west of Ya'an, and maintained development in the west side of Luochun Mountains, but the MCS of process 1 was larger in scale, intensity and duration. (3) The heavy precipitation in process 1 is mainly caused by a larger scale convective (mainly cumulus clouds) MCS with stable and less movement, while process 2 is caused by two successively developing mixed (cumulus layer cloud mixing) MCS passing through the same area. (4) The maintenance mechanism of MCS during the two processes is different. The main mechanism of Process 1 is the continuous formation of deep convective cells under the forced uplift of the Luochun Mountain terrain, which merge with the original MCS1_A and maintain it on the western side of Luochun Mountain for a long time, forming a quasi stationary backward established MCS echo zone; At the same time, the blocking effect of the terrain on the outflow of the cold pool and the bypass effect on the warm and humid air flow also promote the stability and less movement of MCS1_A to a certain extent. The main mechanism for maintaining MCS in process 2 is the feedback effect of high-altitude windward slope terrain.

Abstract Purpose The essence of this scholarly work was to carefully outline the key factors intensifying the virulence and protracted contagion of COVID-19, particularly among individuals afflicted with hematologic malignancies (HM), in an epoch predominantly governed by the Omicron variant. Methods Adults with HM diagnosed with COVID-19 from November 2022 to February 2023 were monitored in this retrospective study. Patient blood samples yielded biochemical data, and COVID-19 was confirmed through RNA or antigen testing. The factors affecting severity and infection duration were examined using both univariate and multivariate logistic regression analyses. For calculating the overall survival probabilities, the Kaplan–Meier product limit approach was employed. Results In the examined cohort, 133 individuals diagnosed with HM and concomitantly infected with COVID-19 were scrutinized. Of the participants, 29.3% (39 patients) were classified as Severe/Critical, while the other 70.7% (94 patients) were categorized as Non-severe. A significant difference was observed in vaccination status: 61.7% of patients in the Non-severe group had received at least a two-dose vaccine regimen, whereas 61.5% of the Severe/Critical group had either minimal or only one dose of vaccination. The data analysis revealed that elevated C-reactive protein levels (≥ 100 mg/L) significantly raised the risk of severe/critical conditions in HM patients with COVID-19, as determined by advanced multivariate logistic regression. The odds ratio was 3.415 with a 95% confidence interval of 1.294–9.012 (p = 0.013). Patients who continued to have positive nucleic acid tests and ongoing symptoms beyond 30 days were categorized as having a persistent infection, whereas those who achieved infection control within this timeframe were categorized as having infection recovery. Of the HM cohort, 11 did not survive beyond 30 days after diagnosis. The results from a competing risk model revealed that increased interleukin-6 levels (HR: 2.626, 95% CI: 1.361–5.075; p = 0.004) was significantly associated with persistent infection. Conversely, receiving more than two vaccine doses (HR: 0.366, 95% CI: 0.158–0.846; p = 0.019), and having high IgG levels (≥ 1000 mg/dl) (HR: 0.364, 95% CI: 0.167–0.791; p = 0.011), were associated with infection recovery. There was a notable disparity in survival rates between patients with persistent infections and infection recovery, with those in the non-persistent group demonstrating superior survival outcomes (P

Abstract Background Cold is an important environmental limiting factor affecting plant yield and quality. Capsicum (chili pepper), a tropical and subtropical vegetable crop, is extremely sensitive to cold. Although H2S is an important signaling regulator in the responses of plant growth and development to abiotic stress, few studies have examined its effects on cold-sensitive capsicum varieties. Through biotechnology methods to enhance the cold resistance of peppers, to provide some reference for pepper breeding, investigated molecular regulation by H2S of responses to cold stress in cold-sensitive capsicum plants, via physiological and transcriptomic analyses. Results In capsicum seedlings, exogenous H2S enhanced relative electrical conductivity (REC) and levels of malondialdehyde (MDA) under cold stress, maintained membrane integrity, increased the activity of enzymatic and non-enzymatic antioxidants, balanced reactive oxygen species levels (O2 ·− and H2O2), and improved photosynthesis, mitigating the damage caused by cold. In addition, 416 differentially expressed genes (DEGs) were involved in the response to cold stress after H2S treatment. These DEGs were mainly enriched in the ascorbate–glutathione and starch–sucrose metabolic pathways and plant hormone signal-transduction pathways. Exogenous H2S altered the expression of key enzyme-encoding genes such as GST, APX, and MDHAR in the ascorbate–glutathione metabolism pathway, as well as that of regulatory genes for stimulatory hormones (auxin, cytokinins, and gibberellins) and inhibitory hormones (including jasmonate and salicylic acid) in the plant hormone signal-transduction pathway, helping to maintain the energy supply and intracellular metabolic stability under cold stress. Conclusions These findings reveal that exogenous H2S improves cold tolerance in cold-sensitive capsicum plants, elucidating the molecular mechanisms underlying its responses to cold stress. This study provides a theoretical basis for exploring and improving cold tolerance in capsicum plants.

Abstract Recent advances in the search for room-temperature superconductors have focused on high-temperature superconductivity in compressed hydrides, though sustaining this at ambient pressure remains challenging. Concurrently, s p 3-bonded frameworks comprising lightweight elements offer another avenue for ambient-pressure superconductors. However, their critical temperatures (T c) still fall short of those in hydrides. Here we propose a design strategy for achieving high-temperature superconductivity at ambient pressure by integrating hydride units into B–C clathrate structures. This approach exploits the beneficial properties of hydrogen, the lightest element, to enhance superconductivity beyond that of the parent compounds. Our computational predictions indicate that doping SrB3C3 with ammonium (NH4) produces SrNH4B6C6, with an estimated T c of 85 K at ambient pressure—over twice that of its precursor (31 K). Further substitutions yield a family of MNH4B6C6 superconductors, with PbNH4B6C6 predicted to reach a T c of 115 K. These findings offer a promising route to high-T c superconductors at ambient pressure.

Abstract Background Concerns have been raised regarding changes in lipid profiles among patients with chronic hepatitis B (CHB) during tenofovir alafenamide fumarate (TAF) treatment. We aimed to evaluate the effect of TAF treatment on the lipid profiles of patients with CHB. Methods A total of 430 patients with CHB from three hospitals were retrospectively included, including 158 patients treated with TAF and 272 patients treated with tenofovir disoproxil fumarate (TDF). Results In this multicenter cohort, the cumulative incidence of dyslipidemia was notably higher in the TAF group than in the TDF group (P

Abstract Blowouts are a common type of wind-eroded landform found in sandy and desertified areas. They also represent a major degradative surface process affecting grassland ecosystems. Blowouts exacerbate changes in surface morphology through their effects on other surface phenomena including vegetation. In this paper, Xilingol League sandy grassland blowouts are taken as the research object, and the U.S. Keyhole satellite data and China’s Gaofen-1 satellite data are used as the data source, and the blowouts are extracted based on the 3 S technology for a total of six periods of high-resolution remote sensing image data in the study area from 1962 to 2023. The Landscape Pattern Index method and Fuzzy Land Use Simulation (FLUS) modelling applied to changes over the last six decades provided spatial evolution parameters for predicting future blowout distributions. Results showed that blowouts affecting the Xilingol grassland area increased by 16.81% over the past 60 years. The patch density (PD) increased by 0.9 per hectare. The mean proximity index (PROX_MN) and mean Euclidean nearest neighbour distance (ENN_MN) showed a tendency to decrease and then increase indicating initial expansion and then merging of adjacent blowouts to create the present landscape. The FLUS model used ten factors to predict changes in blowout distributions from 2023 to 2033. Factors included digital elevation model (DEM), slope, aspect, normalized difference vegetation index (NDVI), mean annual temperature, mean annual precipitation, population density, real GDP, distance to water, and distance to impervious surfaces. It was found that grassland area decreased by 6217.12 hm2 and blowout area decreased by 102.91 hm2. Results of this study can expand understanding of blowout morphodynamics in ecologically sensitive areas.

Abstract Background There has been no consensus on what power of radiofrequency energy can be used to produce the best surgical results in patients with atrial fibrillation. In addition, patients undergoing local anesthesia and fentanyl analgesia may experience pain when radiofrequency ablation is performed. This study investigated the effect of different power radiofrequency ablations in treatment and postoperative pain in patients with atrial fibrillation. Methods A retrospective study was performed with 60 patients who underwent radiofrequency ablation for atrial fibrillation between January and June 2023. Patients were divided into 2 groups according to the power of the radiofrequency ablation catheter used, with 30 patients in the conventional power group (35 W) and 30 patients in the high-power group (50 W). The cardiac electrophysiological indexes and postoperative pain of the 2 groups were compared. Results Most of the procedural key parameters between the 2 groups had no significant differences. However, the total application time during radiofrequency ablation and pulmonary vein isolation time in the high-power group were significantly shorter than those in the conventional power group (p

Abstract Background Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases. However, it is still not well understand about the relationship between PCDH15 variants and RP. Methods In this study, we enrolled a Chinese autosomal recessive retinitis pigmentosa (arRP) pedigree and identified the causative gene in the proband by targeted whole exome sequencing (WES). The variants were validated in the family members by Sanger sequencing and co-segregation analysis. Results Novel compound heterozygous, Frame shift variants of the PCDH15 gene, NM_001384140.1:c.4368 − 2147_4368-2131del and NM_001384140.1:c exon19:c.2505del: p. T836Lfs*6 were identified in the arRP pedigree, which co-segregated with the clinical RP phenotypes. The PCDH15 protein is highly conserved among species. Conclusion This is the first study to identify novel compound heterozygous variants c.4368 − 2147_4368-2131del and c.2505del(p.T836Lfs*6) in the PCDH15 gene which might be disease-causing variants, and extending the variant spectra. All above findings may be contribute to genetic counseling, molecular diagnosis and clinical management of arRP disease.

Abstract The testis serves as the primary site for spermatogenesis in mammals and is a crucial organ for the secretion of male hormones. Heat stress (HS) can have adverse effects on the seminiferous tubules, sperm quality, and sperm fertilization capability within the testis. Despite numerous previous studies describing various time points after heat stress in mice, a systematic and comprehensive dataset on heat stress and recovery in mice has been lacking. This study aimed to explore the gene expression changes in the recovery of multiple seminiferous epithelial cycles and spermatogenic cycles in mouse testicles after heat stress. We obtained high-throughput bulk RNA-seq data from testicular tissue of 4 NC mice and 32 HS mice (divided into 9 groups: NC, 30 min, 2 h, 6 h, 24 h, 3d, 8d, 24d, 47d, and 95d) and illustrated the dynamic changes in differential genes. This data set provides valuable insights into the detailed dynamic changes of one or more spermatogenic cycles after heat stress in mouse testicles, as well as the molecular mechanisms involved.

Abstract Background This study aimed to identify the differentially expressed proteins in the vitreous humor (VH) of eyes with and without pathologic myopia (PM), providing insights into the molecular pathogenesis. Methods A cross-sectional, observational study was conducted. VH samples were collected from patients undergoing vitrectomy for idiopathic epiretinal membrane (ERM), macular hole (MH), or myopic retinoschisis (MRS). Label-free quantitative proteomic analysis identified differential protein expression, with validation using ELISA. Results The proteomic profiling revealed significantly higher expressions of tubulin alpha 1a (TUBA1A) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) in PM groups (MH-PM, MRS-PM) compared to controls (MH, ERM). Conversely, xylosyltransferase 1 (XYLT1), versican core protein (VCAN), and testican-2 (SPOCK2) expressions were lower in PM. ELISA validation confirmed these findings. Conclusions Our study provides novel insights into the molecular mechanisms of PM. The differentially expressed proteins EEF1A1, TUBA1A, XYLT1, VCAN, and SPOCK2 may play crucial roles in chorioretinal cell apoptosis, scleral extracellular matrix (ECM) synthesis, and scleral remodeling in PM. These proteins represent potential new targets for therapeutic intervention in PM, highlighting the importance of further investigations to elucidate their functions and underlying mechanisms in disease pathogenesis.

Abstract The time-dependent effects in steel-concrete composite beam bridges can intensify track irregularities, subsequently leading to amplified train-bridge coupling vibrations. This phenomenon may increase the stress amplitudes in the bridge steel, thereby impacting the fatigue performance of the composite structures. This paper employs multiple rigid body dynamics to construct a high-speed train model and utilizes the finite element method to develop a steel-concrete composite beam element model that accounts for time-dependent effects, interfacial slip, and shear hysteresis. This approach enables the computational analysis of the train-bridge coupling system, facilitating an investigation into the influence of concrete’s time-dependent effects on the fatigue performance of railway steel-concrete composite bridges. Focusing on a 40-m simply supported composite bridge, the train-bridge coupling dynamic responses were computed for each operational year within a decade of the completion of construction. Applying the P-M linear fatigue damage accumulation theory, statistical analysis of stress history data across various operational periods was conducted to quantify the fatigue damage induced by a single eight-car high-speed train on the lower flange of the mid-span steel beam and the beam-end studs. The findings reveal that the beam-end studs sustain greater damage than the mid-span steel beam. Moreover, the detrimental impact of time-dependent effects diminishes with the increase of operational years. Notably, compared to the initial year, the fatigue damage to the lower flange of the mid-span steel beam by an eight-car train in the tenth year has surged by 39.3%. Conversely, the damage to the beam-end studs has decreased by 47.5%.

Abstract Background Fatigue is a common complication of stroke that has a significant impact on quality of life. The biological mechanisms that underly post-stroke fatigue are currently unclear, however, reactivation of latent viruses and their impact on systemic immune function have been increasingly reported in other conditions where fatigue is a predominant symptom. Epstein-Barr virus (EBV) in particular has been associated with fatigue, including in long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome, but has not yet been explored within the context of stroke. Aims We performed an exploratory analysis to determine if there is evidence of a relationship between EBV reactivation and post-stroke fatigue. Methods In a chronic ischemic stroke cohort (> 5 months post-stroke), we assayed circulating EBV by qPCR and measured the titres of anti-EBV antibodies by ELISA in patients with high fatigue (FACIT-F 41). Statistical analysis between two-groups were performed by t-test when normally distributed according to the Shapiro-Wilk test, by Mann-Whitney test when the data was not normally distributed, and by Fisher’s exact test for categorical data. Results We observed a similar incidence of viral reactivation between people with low versus high levels of post-stroke fatigue (5 of 22 participants (24%) versus 6 of 22 participants (27%)). Although the amount of circulating EBV was similar, we observed an altered circulating anti-EBV antibody profile in participants with high fatigue, with reduced IgM against the Viral Capsid Antigen (2.244 ± 0.926 vs. 3.334 ± 2.68; P = 0.031). Total IgM levels were not different between groups indicating this effect was specific to anti-EBV antibodies (3.23 × 105 ± 4.44 × 104 high fatigue versus 4.60 × 105 ± 9.28 × 104 low fatigue; P = 0.288). Conclusions These data indicate that EBV is not more prone to reactivation during chronic stroke recovery in those with post-stroke fatigue. However, the dysregulated antibody response to EBV may be suggestive of viral reactivation at an earlier stage after stroke.

Abstract The optimal treatment endpoints and duration of continuous therapy for multicentric Castleman disease (MCD) remain controversial. We retrospectively analyzed data from 123 patients with Human Herpesvirus (HHV)-8 negative MCD. We demonstrated that continuous therapy significantly enhanced progression-free survival (PFS) in patients who achieved an optimal response after initial treatment. These findings underscore the critical role of continuous therapy in HHV-8 negative MCD. Further studies with larger cohorts are required to validate these findings.

Three mole percent yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) ceramics are exemplary materials for dental restoration due to their high mechanical strength, fracture toughness, chemical endurance, and biocompatibility. Nevertheless, 3Y-TZP ceramics are opaque and their CAD/CAM manufacturing process may cause micro-cracks in conventional clinical practice. In this study, 3Y-TZP ceramic samples were prepared using vat photopolymerization, pre-sintering, external staining, and final high-temperature sintering. The microstructures, mechanical properties, optical properties, and cytotoxicity of the 3Y-TZP ceramic samples were investigated. The results indicate that with increasing Fe3+ concentration of staining solution from 0.1 mol/L to 0.3 mol/L and increasing staining time from 5 s to 30 min, the 3Y-TZP ceramic samples showed a tetragonal crystal structure of zirconia with densely packed grains and a slight increase in grain size. The flexural strength, Vickers hardness, and fracture toughness of 3Y-TZP ceramic samples stained in 0.1–0.3 mol/L Fe3+ solution for 5 s to 3 min were all greater than 665 MPa, 11.9 GPa, and 5 MPa m1/2, respectively, meeting the mechanical requirements for clinical application. Colorimetric analysis revealed a decrease in L* (black-white index) from 90.4 to 81.3, an increase in a* (green-red index) from −1.5 to 3.2, and an increase in b* (blue-yellow index) from 11.6 to 20.3, approximating the commercial VITA 3D-Master Shade Guide chromaticity. Furthermore, the 3Y-TZP ceramic samples exhibited a cell viability of 90% or higher toward L929 cells.

Abstract Background This study aimed to investigate risk factors for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) based on baseline high-resolution computed tomography (HRCT). Methods This prospective observational study enrolled patients with IPF treated at the General Hospital of Ningxia Medical University between January 2019 and January 2021. HRCT-derived quantitative parameters at baseline were analyzed. Results A total of 102 patients [92 (90.2%) males with a mean age of 67 years] with IPF were included, with a median follow-up of 32 (24-40.5) months. AE occurred in 30 (29.4%) IPF patients. Multivariable logistic regression analysis identified Doppler transthoracic echocardiography suggestive of pulmonary hypertension (PH) (13.43; 95% CI: 4.18–41.09; P

Abstract Infertility, a worldwide reproductive health concern, impacts approximately one in five couples. Male infertility, stemming from spermatogenic dysfunction and reduced sperm quality, stands as a primary factor contributing to infertility. Given the global decrease in male fertility linked to environmental factors like the greenhouse effect, it is crucial to develop a comprehensive understanding of how increased temperatures impact both the quantity and quality of sperm. In this study, we utilized Pandora-seq technology to detect the small non-coding RNAs (sncRNAs) expression profile in the testicular tissue of heat-stressed mice. The investigation explores the dynamic shifts in sncRNAs within the mouse testis under heat stress, including miRNAs, tsRNAs, piRNAs, rsRNAs and other sncRNAs. Furthermore, we successfully identified differentially expressed sncRNAs in testicular tissues before and after heat stress. Subsequently, we conducted functional enrichment analysis on the potential predicted target genes of differentially expressed miRNAs and tsRNAs. These datasets will constitute a valuable foundational resource for further investigations into the decline in male reproductive capacity triggered by heat stress.

Abstract Objective To reveal the contributing effects of MTDH gene SNPs in the risk of invasive ductal breast cancer (IDC). Patients and methods A case–control study was conducted, recruiting a total of 300 cases of IDC and 565 cancer-free controls from East China. Genotyping of three single-nucleotide polymorphisms (SNPs) in the MTDH gene was performed. Genomic DNA was extracted from peripheral blood samples of patients. The three SNPs (rs1311 T > C, rs16896059 G > A, rs2449512 A > G) in the MTDH gene were selected for detection using a TaqMan real-time polymerase chain reaction assay. The association between MTDH and the risk of IDC was analyzed employing an epidemiology case–control study and a multinomial logistic regression model. Results Among the three evaluated SNPs, rs1311 T > C, rs16896059 G > A, and rs2449512 A > G demonstrated a significant association with an increased risk of IDC. Furthermore, stratified analysis revealed that individuals carrying the rs1311 CC genotype, rs16896059 GA/AA genotypes, and rs2449512 GG genotype were more susceptible to developing IDC in subgroups of patients younger than 53 years, without family history of IDC, pre-menopause status, clinical stage 2, high grade, with no distant metastasis or invasion, Her2-positive type, ER positive, PR positive, and Ki67 cells less than 10%. However, carriers of the rs16896059 GA/AA genotypes and rs2449512 GG genotype had an elevate the risk of IDC in patients with tumor size larger than 2 cm, post-menopause status, clinical stage 3, with invasion, lymph node infiltration, ER negative, PR negative, Her2 negative, and Ki67 cells exceeding 10%. Compared to the reference haplotype TGA, haplotypes TAA, TAG, and TGG were significantly associated with an increased IDC risk. Conclusion In this study, we demonstrated a significant association between MTDH gene polymorphisms and an increased risk of IDC. Moreover, our findings suggested that MTDH gene polymorphisms could serve as a potential biomarker for IDC subtyping and therapeutic selection.

Abstract Background Previous studies evaluating the association between prediabetes the prognosis of patients with acute myocardial infarction (AMI) showed inconsistent results. The aim of the meta-analysis was to compare the long-term incidence of major adverse cardiovascular events (MACEs) between AMI patients with prediabetes and normoglycemia. Methods Relevant prospective cohort studies were obtained by searching Medline, Web of Science, and Embase databases. Only studies with follow-up duration of at least one year were included. A random-effects model was utilized to pool the results by incorporating the influence of heterogeneity. Results Twelve studies with 6972 patients with AMI were included. Among them, 2998 were with prediabetes and 3974 were with normoglycemia. During a mean follow-up of 52.6 months, 2100 patients developed MACEs. Compared to those with normoglycemia, AMI patients with prediabetes were associated with a higher incidence of MACEs (risk ratio [RR]: 1.30, 95% confidence interval: 1.07 to 1.58, p = 0.008; I2 = 67%). Subgroup analysis showed a stronger association between prediabetes and MACEs in studies of patients with mean age ≥ 60 years compared to

Abstract Background Type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) are mutual risk factors, with both conditions inducing cognitive impairment and anxiety. However, whether OSA exacerbates cognitive impairment and anxiety in patients with T2DM remains unclear. Moreover, TREM2 upregulation has been suggested to play a protective role in attenuating microglia activation and improving synaptic function in T2DM mice. The aim of this study was to explore the regulatory mechanisms of TREM2 and the cognitive and anxiety-like behavioral changes in mice with OSA combined with T2DM. Methods A T2DM with OSA model was developed by treating mice with a 60% kcal high-fat diet (HFD) combined with intermittent hypoxia (IH). Spatial learning memory capacity and anxiety in mice were investigated. Neuronal damage in the brain was determined by the quantity of synapses density, the number and morphology of brain microglia, and pro-inflammatory factors. For mechanism exploration, an in vitro model of T2DM combined with OSA was generated by co-treating microglia with high glucose (HG) and IH. Regulation of TREM2 on IFNAR1-STAT1 pathway was determined by RNA sequencing and qRT-PCR. Results Our results showed that HFD mice exhibited significant cognitive dysfunction and anxiety-like behavior, accompanied by significant synaptic loss. Furthermore, significant activation of brain microglia and enhanced microglial phagocytosis of synapses were observed. Moreover, IH was found to significantly aggravate anxiety in the HFD mice. The mechanism of HG treatment may potentially involve the promotion of TREM2 upregulation, which in turn attenuates the proinflammatory microglia by inhibiting the IFNAR1-STAT1 pathway. Conversely, a significant reduction in TREM2 in IH-co-treated HFD mice and HG-treated microglia resulted in the further activation of the IFNAR1-STAT1 pathway and consequently increased proinflammatory microglial activation. Conclusions HFD upregulated the IFNAR1-STAT1 pathway and induced proinflammatory microglia, leading to synaptic damage and causing anxiety and cognitive deficits. The upregulated TREM2 inT2DM mice brain exerted a negative regulation of the IFNAR1-STAT1 pathway. Mice with T2DM combined with OSA exacerbated anxiety via the downregulation of TREM2, causing heightened IFNAR1-STAT1 pathway activation and consequently increasing proinflammatory microglia. Graphical Abstract

Abstract Purpose Preserved ratio impaired spirometry (PRISm) and chronic obstructive pulmonary disease (COPD) belong to lung function injury. PRISm is a precursor to COPD. We compared and evaluated the different basic information, imaging findings and survival curves of 108 lung cancer patients with different pulmonary function based on high resolution computed tomography (HRCT). Methods This retrospective study was performed on 108 lung cancer patients who did pulmonary function test (PFT) and thoracic HRCT. The basic information was evaluated: gender, age, body mass index (BMI), smoke, smoking index (SI). The following pulmonary function findings were evaluated: forced expiratory volume in 1s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio. The following computed tomography (CT) findings were evaluated: appearance (bronchiectasis, pneumonectasis, atelectasis, ground-glass opacities [GGO], interstitial inflammation, thickened bronchial wall), diameter (aortic diameter, pulmonary artery diameter, MPAD/AD ratio, inferior vena cava diameter [IVCD]), tumor (volume, classification, distribution, staging [I, II, III, IV]). Mortality rates were calculated and survival curves were estimated using the Kaplan-Meier method. Results Compared with normal pulmonary function group, PRISm group and COPD group were predominantly male, older, smoked more, poorer lung function and had shorter survival time after diagnosis. There were more abnormal images in PRISm group and COPD group than in normal lung function group (N-C group). In PRISm group and COPD group, lung cancer was found late, and the tumor volume was larger, mainly central squamous carcinoma. But the opposite was true for the N-C group. The PRISm group and COPD group had significant poor survival probability compared with the normal lung function group. Conclusions Considerable differences regarding basic information, pulmonary function, imaging findings and survival curves are found between normal lung function group and lung function injury group. Lung function injury (PRISm and COPD) should be taken into account in future lung cancer screening studies.

Abstract The incidence of ulcerative colitis (UC) is on the rise globally. Shen-Zhu-Lian-Bai decoction (SZLBD) can relieve the clinical symptoms of UC. This study aimed to investigate the underlying molecular mechanism of SZLBD in the treatment of UC. The key treatment targets of SZLBD for UC were obtained based on the online database, and combined with the STRING database and Cytoscape 3.7.2 software, PPI network was constructed and visualized. The GEO database was utilized to validate the expression levels of core targets in UC. Metascape database GO functional annotation and KEGG pathway enrichment analysis. Molecular docking technology was used to verify the docking of core compounds with key targets. RT-qPCR and Western Blot were used to detect the expression of key targets in HCoEpiC cells for verification. After screening, 67 targets shared by SZLBD and UC were obtained. It is predicted that IL-6, IL-1B, and AKT1 might be the key targets of SZLBD in the treatment of UC. Quercetin was the main active ingredient. GEO results showed that the expression levels of IL-6, IL-1B and AKT1 were higher in the UC group compared to the control group. GO and KEGG analyses showed that these targets were related to apoptosis and inflammation. The results of molecular docking demonstrated that the AKT1 gene, a key target of quercetin, had the highest affinity of -9.2 kcal/mol. Cell experiments found that quercetin could affect the expression of IL-6, IL-1B, and AKT1. This study preliminarily explored and verified the mechanism of action of SZLBD in the treatment of UC, which provides a theoretical basis for subsequent in vivo mechanism studies.

Abstract Objectives To investigate the diagnostic performance of the apparent diffusion coefficient (ADC) for low to intermediate-risk prostate cancer (PCa), as well as its correlation with the prognostic Gleason score (GS). Materials and methods Retrospective analysis of MRI images and relevant clinical data from patients with prostate disease. The differences in ADC between different GS groups were compared, and the efficacy of ADC in PCa diagnosis were analyzed. Furthermore, the diagnostic performance of the mean ADC (ADCmean) and minimum ADC (ADCmin) values was compared. Results There were 1414 patients with 1631 lesions. In terms of GS, both ADCmin and ADCmean values of the GS 4 + 3 group were significantly lower than those of the GS 3 + 4 group, GS 3 + 3 group, and the benign group, with all differences being statistically significant (p

Abstract Background The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA. Methods Six hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA

Abstract Background Beta-amyloid (Aβ) deposition in the brain parenchyma is a crucial initiating step in the amyloid cascade hypothesis of Alzheimer’s disease (AD) pathology. Furthermore, dysfunction of plaque-associated microglia, also known as disease-associated microglia (DAM) has been reported to accelerate Aβ deposition and cognitive impairment. Our previous research demonstrated that intermittent hypoxia training (IHT) improved AD pathology by upregulating autophagy in DAM, thereby enhancing oligomeric Aβ (oAβ) clearance. Considering that oAβ internalization is the initial stage of oAβ clearance, this study focused on the IHT mechanism involved in upregulating Aβ uptake by DAM. Methods IHT was administered to 8-month-old APP/PS1 mice or 6-month-old microglial vacuolar protein sorting 35 (VPS35) knockout mice in APP/PS1 background (MG VPS35 KO: APP/PS1) for 28 days. After the IHT, the spatial learning-memory capacity of the mice was assessed. Additionally, AD pathology was determined by estimating the nerve fiber and synapse density, Aβ plaque deposition, and Aβ load in the brain. A model of Aβ-exposed microglia was constructed and treated with IHT to explore the related mechanism. Finally, triggering receptor expressed on myeloid cells 2 (TREM2) intracellular recycling and Aβ internalization were measured using a fluorescence tracing technique. Results Our results showed that IHT ameliorated cognitive function and Aβ pathology. In particular, IHT enhanced Aβ endocytosis by augmenting the intracellular transport function of microglial TREM2, thereby contributing to Aβ clearance. Furthermore, IHT specifically upregulated VPS35 in DAM, the primary cause for the enhanced intracellular recycling of TREM2. IHT lost ameliorative effect on Aβ pathology in MG VPS35 KO: APP/PS1 mice brain. Lastly, the IHT mechanism of VPS35 upregulation in DAM was mediated by the transcriptional regulation of VPS35 by transcription factor EB (TFEB). Conclusion IHT enhances Aβ endocytosis in DAM by upregulating VPS35-dependent TREM2 recycling, thereby facilitating oAβ clearance and mitigation of Aβ pathology. Moreover, the transcriptional regulation of VPS35 by TFEB demonstrates a close link between endocytosis and autophagy in microglia. Our study further elucidates the IHT mechanism in improving AD pathology and provides evidence supporting the potential application of IHT as a complementary therapy for AD. Graphical abstract

Abstract Non-hydraulic root source signaling (nHRS) is a unique positive response to soil drying in the regulation of plant growth and development. However, it is unclear how the nHRS mediates the tradeoff between source and sink at the late growth stages and its adaptive mechanisms in primitive wheat. To address this issue, a root-splitting design was made by inserting solid partition in the middle of the pot culture to induce the occurrence of nHRS using four wheat cultivars (MO1 and MO4, diploid; DM22 and DM31, tetraploid) as materials. Three water treatments were designed as 1) both halves watered (CK), 2) holistic root system watered then droughted (FS), 3) one-half of the root system watered and half droughted (PS). FS and PS were designed to compare the role of the full root system and split root system to induce nHRS. Leaves samples were collected during booting and anthesis to compare the role of nHRS at both growth stages. The data indicated that under PS treatment, ABA concentration was significantly higher than FS and CK, demonstrating the induction of nHRS in split root design and nHRS decreased cytokinin (ZR) levels, particularly in the PS treatment. Soluble sugar and proline accumulation were higher in the anthesis stage as compared to the booting stage. POD activity was higher at anthesis, while CAT was higher at the booting stage. Increased ABA (nHRS) correlated with source-sink relationships and metabolic rate (i.e., leaf) connecting other stress signals. Biomass density showed superior resource acquisition and utilization capabilities in both FS and PS treatment as compared to CK in all plants. Our findings indicate that nHRS-induced alterations in phytohormones and their effect on source-sink relations were allied with the growth stages in primitive wheat.

Abstract The prevalence of thyroid dysfunction diseases (TDFDs) and osteoporosis (OP) is high. Previous studies have indicated a potential association between TDFDs and OP, yet the causal direction remains unclear. This study aimed to investigate the potential causal relationship between TDFDs and the risk of developing OP and related fractures. We obtained pooled data from genome-wide association studies (GWASs) conducted on TDFDs and OP in European populations and identified single-nucleotide polymorphisms (SNPs) with genome-wide significance levels associated with exposure to TDFDs as instrumental variables. Inverse variance weighted (IVW) was employed as the primary method for Mendelian randomization (MR) analysis, supplemented by MR‒Egger, weighted median, simple mode and weighted mode methods. Sensitivity analyses were conducted to evaluate the robustness of the findings. The IVW method demonstrated an increased risk of OP in patients with TDFDs, including hyperthyroidism and hypothyroidism (TDFDs: OR = 1.11; 95% CI 1.09, 1.13; hypothyroidism: OR = 1.14; 95% CI 1.10, 1.17; hyperthyroidism: OR = 1.09; 95% CI 1.06, 1.12). These findings were supported by supplementary analysis, which revealed a positive correlation between TDFDs and the risk of OP. Multiple sensitivity analyses confirmed the absence of horizontal pleiotropy in the study, thus indicating the robustness of our results. The causal relationship between TDFDs and increased risk of OP implies the need for early bone mineral density (BMD) screening and proactive prevention and treatment strategies for individuals with TDFDs.

BackgroundRecurrent ischemic stroke in patients with symptomatic intracranial atherosclerotic stenosis (sICAS) can be attributed to two main causes: intracranial atherosclerotic stenosis (ICAS) and cerebral small vessel disease (CSVD). This study investigates the potential associations between stroke recurrence and the modified cerebral small vessel disease (mCSVD) burden score, as well as the characteristics of culprit plaques related to intracranial artery high-resolution vessel wall imaging (HR-VWI).MethodsA total of 145 patients presenting sICAS underwent intracranial artery HR-VWI and routine cranial MRI at two large Chinese hospitals from December 2019–2022 were participants of this retrospective analysis. Standard MRI scans were used to calculate the mCSVD score. Following a 12-month observation period, the patients were categorized into two distinct groups depending on whether or not they experienced a subsequent stroke.ResultsWithin 12 months, 32 patients experienced stroke recurrence. The recurrence group’s mCSVD score was higher compared to the non-recurrence group (p

IntroductionLong-term domestication in high-altitude environments has led to unique changes in the gut microbiota of Tibetan Pigs. This study aims to investigate specific alterations in the intestinal flora of Tibetan Pigs compared to Yorkshire pigs.MethodsWe employed 16S rRNA and metagenomic sequencing technologies for comprehensive analysis of the gut microbiota. The data collected allowed us to assess microbial community structures and functional capabilities.ResultsOur analysis revealed that Tibetan Pigs raised under a “free-range + supplementary feeding” model exhibited increased abundance of microbial communities associated with short-chain fatty acid synthesis and the digestion of cellulose and hemicellulose. Notably, the characteristic bacterium Rhodococcus, commonly found in high-altitude environments, was enriched in the gut microbiota of Tibetan Pigs, facilitating the efficient utilization of natural compounds and degradation of toxic substances. Additionally, the increased abundance of probiotics in these pigs enhances their immunity, which may involve mechanisms such as disrupting the structure of pathogenic bacteria and detoxifying harmful metabolites.DiscussionThese findings underscore the advantages of Tibetan Pigs over common commercial breeds, highlighting their unique gut microbiota adaptations. Furthermore, they open new avenues for screening potential probiotics and developing genetic breeding strategies for improved livestock varieties.ConclusionUnderstanding the distinct gut microbiota of Tibetan Pigs provides valuable insights into their health benefits and resilience, contributing to future research on breed improvement and microbiome applications in agriculture.

ABSTRACT HIV-1 envelope glycoprotein (Env) conformation substantially impacts antibody-dependent cellular cytotoxicity (ADCC). Envs from primary HIV-1 isolates adopt a prefusion “closed” conformation, which is targeted by broadly neutralizing antibodies (bnAbs). CD4 binding drives Env into more “open” conformations, which are recognized by non-neutralizing Abs (nnAbs). To better understand Env–Ab and Env–CD4 interaction in CD4+ T cells infected with HIV-1, we simultaneously measured antibody binding and HIV-1 mRNA expression using multiparametric flow cytometry and RNA flow fluorescent in situ hybridization (FISH) techniques. We observed that env mRNA is almost exclusively expressed by HIV-1 productively infected cells that already downmodulated CD4. This suggests that CD4 downmodulation precedes env mRNA expression. Consequently, productively infected cells express “closed” Envs on their surface, which renders them resistant to nnAbs. Cells recognized by nnAbs were all env mRNA negative, indicating Ab binding through shed gp120 or virions attached to their surface. Consistent with these findings, treatment of HIV-1-infected humanized mice with the ADCC-mediating nnAb A32 failed to lower viral replication or reduce the size of the viral reservoir. These findings confirm the resistance of productively infected CD4+ T cells to nnAbs-mediated ADCC and question the rationale of immunotherapy approaches using this strategy.IMPORTANCEAntibody-dependent cellular cytotoxicity (ADCC) represents an effective immune response for clearing virally infected cells, making ADCC-mediating antibodies promising therapeutic candidates for HIV-1 cure strategies. Broadly neutralizing antibodies (bNAbs) target epitopes present on the native "closed" envelope glycoprotein (Env), while non-neutralizing antibodies (nnAbs) recognize epitopes exposed upon Env–CD4 interaction. Here, we provide evidence that env mRNA is predominantly expressed by productively infected cells that have already downmodulated cell-surface CD4. This indicates that CD4 downmodulation by HIV-1 precedes Env expression, making productively infected cells resistant to ADCC mediated by nnAbs but sensitive to those mediated by bnAbs. These findings offer critical insights for the development of immunotherapy-based strategies aimed at targeting and eliminating productively infected cells in people living with HIV.

IntroductionL-arginine is an α-amino acid and a semi-essential nutrient of significant biological interest. It plays a role in influencing various aspects of animal meat traits, gut microbiota composition, and physiological metabolism.MethodsThis study aimed to investigate the combined effects of L-arginine supplementation on gut microbiota composition and the metabolism of the longissimus dorsi muscle in fattening pigs. Eighteen Yorkshire commercial pigs were divided into two groups: a control group that received no supplements and a treatment group that was given 1% L-arginine for 52 days. The diversity and composition of microorganisms in the feces of the control (NC) and L-arginine (Arg) groups were analyzed by sequencing the 16S rRNA V3 -V4 region of the bacterial genome.ResultsThe findings indicated that L-arginine supplementation increased both the abundance and diversity of gut microbiota, particularly affecting the Firmicutes and Bacteroidetes phyla. KEGG enrichment analysis revealed significant changes in several metabolism-related pathways, including amino acid, carbohydrate, and lipid metabolism. Metabolomic analysis identified 85 differential metabolites between the arginine and control groups, with phospholipids ranking among the top 20. Additionally, functional predictions indicated an increased abundance in the glycerophospholipid metabolism pathway. Correlation analysis linked changes in gut microbiota to phospholipid levels, which subsequently influenced post-slaughter meat color and drip loss.DiscussionThese results suggest that L-arginine supplementation positively impacts gut microbiota composition and the metabolic profile of the longissimus dorsi muscle in fattening pigs, with potential implications for meat quality.

Purpose: To investigate the effects of hydroxybutyl chitosan (HBCS) with and without 5-fluorouracil (5-FU) during endoscopic endonasal dacryocystorhinostomy (Endo-DCR). In addition, the present study observed the impact of HBCS and 5-FU on the functions of the nasal mucosal cell population in vivo. Methods: Patients were randomized into HBCS (group A), HBCS combined with 5-FU (group B), and gelatin sponge control group (group C). 16S rRNA high-throughput sequencing technology examined the conjunctival sac and nasal flora changes. In addition, CCK8, cell scratching, and flow cytometry were used to investigate the effects of HBCS and 5-FU on the nasal mucosal cell populations. Results: Subjects in groups A, B, and C had anastomotic areas of 21.83 ± 12.69 mm2, 21.57 ± 14.53 mm2, and 12.45 ± 8.16 mm2, respectively (P = 0.0359). Group A had less severe epiphora than the other two groups at 1-, 2-, and 12-week postoperative follow-up (P < 0.05). Complications around the anastomosis in group A were the least severe of the three groups (P = 0.0259). After surgery, the proportion of pathogenic bacteria in the conjunctival sac and nasal cavity was higher in groups A and B than in healthy adults. At the 2-week follow-up, the structure of nasal flora in group A was more similar to that of the healthy adults compared to group B. Conclusion: Intraoperative use of HBCS at the anastomose improves the postoperative outcome of En-DCR. 5-FU cannot give better postoperative results in En-DCR and is detrimental to the normalization of the postoperative flora in patients with chronic dacryocystitis. At the cellular level, both HBCS and 5-FU inhibit the migration of nasal mucosal cell populations, and 5-FU inhibits proliferation but does not promote apoptosis.

Academics have long debated the similarities and differences between translation and transcreation. Despite extensive discussion, few studies have examined these distinctions through the lens of the strategies adopted. In response, this study explores how strategies of translation and transcreation are utilized to render gender stereotypes within a specific text type. The theoretical framework is grounded in Karoubi’s categorization of translating gender and Ketola’s types of transcreation strategies, which focus on how gender is interpreted and represented across languages and cultures. Utilizing a qualitative approach, this research analyzes English fragrance product descriptions and their Chinese versions across 12 brands, comprising 224 pairs of descriptions. The findings reveal significant differences in the use of target culture-oriented strategies, with transcreation employing these strategies in approximately 90% of cases, compared to only about 50% in translation. The results suggest that the primary distinction between translation and transcreation lies in the extent to which practitioners alter the source text when creating new content. Moreover, identifying strategies of translation and transcreation based on the established framework could also help distinguish transcreation from translation. These findings contribute new empirical insights to the ongoing debates about the distinctions between translation and transcreation.

BackgroundThe global prevalence of Metabolic Syndrome (MetS) is increasing, primarily characterized by abdominal obesity, which significantly heightens the risk of cardiovascular diseases, gastrointestinal disorders, and cancers. Constipation is a common gastrointestinal issue that impacts both physiological and psychological health and worsens with age. Calcium, an essential mineral vital for human health, has been proven to be crucial not only for bone health but also beneficial for gastrointestinal health. However, the results regarding its impact on constipation are inconsistent. This study aimed to investigate the relationship between dietary calcium intake and constipation in individuals with MetS.MethodsThis cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. Participants were assessed for MetS based on the International Diabetes Federation (IDF) criteria. Dietary calcium intake was evaluated through 24-h dietary recalls, and constipation was defined based on the frequency of bowel movements recorded in the bowel health questionnaire. The relationship between calcium intake and constipation was explored using logistic regression models with adjustment for covariates, and restricted cubic spline analyses were also used to investigate nonlinear relationships.ResultsThe study included 4,838 adult participants with MetS. Adjusted logistic regression revealed that an increase in dietary calcium intake was significantly associated with a reduced risk of constipation (OR: 0.562, 95% CI: 0.379 to 0.835, p = 0.006). Compared to the lowest quartile, the highest quartile of dietary calcium intake significantly decreased the risk of constipation (OR: 0.282, 95% CI: 0.115 to 0.691, p = 0.008). Results from the restrictive cubic spline analysis indicated a negative linear association between dietary calcium intake and constipation risk (non-linearity p = 0.704).ConclusionThe findings suggested that increased dietary calcium intake is associated with a decreased risk of constipation among MetS patients, emphasizing dietary calcium as a potentially modifiable factor for managing gastrointestinal symptoms in this population.

IntroductionTo establish a high myopia model in C57BL/6J mice with monocular form deprivation myopia (FDM) and investigate its ocular structure pathological trajectory.MethodsHealthy 3-week-old C57BL/6J mice were divided into an FDM group (n = 36) and a control group (n = 24). The left eyes of the FDM group were patched, while the right eyes served as controls. Biometric parameters and fundus morphology were assessed at baseline and after 4, 8, and 12 weeks of form deprivation.ResultsSignificant differences were observed in the deprived eyes, including longer axial length, higher refractive power, deeper vitreous chambers, thinner retina, choroid, and sclera, and smaller scleral fibers’ diameters under a transmission electron microscope. Retinal vascular area proportion in covered eyes decreased significantly (P < 0.05), with a decline rate of 11% from weeks 4 to 8 and a faster decline of 19% from weeks 8 to 12, while this proportion increased significantly in control eyes.DiscussionThis study successfully induced a high myopia model in mice with long-term form deprivation. The axial length grew dramatically in FDM in the first 8 weeks, while the pathological progress of the fundus accelerated from weeks 8 to 12.

ABSTRACT Chinese serow (Capricornis milneedwardsii) is mainly distributed in the south of Yellow River in China, which has been listed as vulnerable by the International Union for Conservation of Nature (IUCN). However, the reference genome of serow has not been reported and its taxonomic status is still unclear. Here, we first constructed a high‐quality chromosome‐level reference genome of C. milneedwardsii using PacBio long HiFi reads combined with Hi‐C technology. The assembled genome was ~2.83 Gb in size, with a contig N50 of 100.96 Mb and scaffold N50 of 112.75 Mb, which were anchored onto 24 chromosomes. Furthermore, we found that the Chinese serow was more closely related to muskox, which diverged from ~4.85 million years ago (Mya). Compared to the karyotype of goat (2n = 60), we found the Chinese serow (2n = 48) experienced six chromosome fusions, which resulted in the formation of six central centromere chromosomes. We also identified two positively selected genes (MYH6 and DCSTAMP) specific to Chinese serow, which were involved in ‘viral myocarditis’ and ‘Cardiac muscle contraction’. Interestingly, compared to other Caprinae animals, the MYH6 protein of Chinese serow occurred two mutations (E1520S and G1521S), which might be related to hypoxia tolerance. The high‐quality reference genome of C. milneedwardsii provides a valuable information for protection of serows and insights into its evolution.

Background The objective of this study is to develop a predictive model for the assessment of cervical lymph node metastasis risk in papillary thyroid carcinoma (PTC). Methods A retrospective study was conducted on 212 patients with PTC who underwent initial surgical treatment from August 2022 to April 2023 in 2 hospitals. Data were randomly split into 7:3 training-validation sets. Logistic regression was used for feature selection and predictive model creation. Model performance was assessed using receiver operating characteristic (ROC) and calibration curves. Clinical utility was determined using decision curves. Results Among the 212 patients with PTC, 104 cases (49.1%) exhibited cervical lymph node metastasis, while 108 cases (50.9%) did not. Multivariate logistic regression analysis revealed that age (OR = 0.95), FT3 (OR = 0.41), tumor maximum diameter ≥0.9 cm (OR = 1.85), intratumoral microcalcifications (OR = 1.84), and suspicious lymph node on ultrasound (OR = 2.96) were independent risk factors for lymph node metastasis in PTC patients ( P < 0.05). The constructed model for predicting the risk of cervical lymph node metastasis demonstrated a training set ROC curve area under the curve (AUC) of 0.742 (95% CI: 0.664 - 0.821), with a cut-off value of 0.615, specificity of 87.8%, and sensitivity of 51.4%. The validation set exhibited an AUC of 0.648 (95% CI: 0.501 - 0.788), with a cut-off value of 0.644, specificity of 91.2%, and sensitivity of 43.3%. Including the BRAF V600 E mutation did not improve the model’s diagnostic performance significantly. Decision curve analysis indicated clinical feasibility of the model. Conclusion The predictive model developed in this study effectively predicts lymph node metastasis risk in PTC patients by incorporating ultrasound features, demographic characteristics, and serum parameters. However, including the BRAF V600 E mutation does not significantly improve the model’s diagnostic performance.

The high-altitude, low-oxygen environment of the Qinghai-Tibet Plateau poses significant challenges for the introduction of superior livestock breeds. However, local plateau species have adapted to thrive and reproduce under these harsh conditions. Understanding the molecular mechanisms behind plateau animals’ adaptation to low-oxygen environments is essential for breeding livestock suited to high-altitude regions. Tibetan pigs, which have undergone long-term natural selection and artificial breeding, have developed the ability to survive and reproduce in hypoxic environments. In this study, we conducted whole-genome resequencing of 30 Tibetan pigs from high-altitude regions and 30 Diannan small-ear pigs from low-altitude areas, to identify candidate genes that support Tibetan pigs’ adaptation to hypoxic conditions through selection signal analysis. Additionally, we performed transcriptome sequencing on five tissues (heart, liver, spleen, lung, and bone marrow) from both Tibetan pigs and Diannan small-ear pigs to identify genes with significant differential expression between the two breeds. We then integrated the genomic and transcriptomic data by examining the expression of candidate genes identified in selection signal analysis across different tissues. The selection signal analysis identified 10 genes—HES4, ANGPT1, HIF3A, SPHK2, PCK2, RCN3, HIGD2A, DNM2, IRF9, and SRF—that were under positive selection in the Tibetan pig population and are associated with hypoxia adaptation. When combined with transcriptome data, we found that five of these genes—HIF3A, RCN3, HIGD2A, PCK2, and IRF9—exhibited differential expression. Through an integrated approach of selection signal and transcriptome analysis, we identified five key functional genes that contribute to the adaptation of Tibetan pigs to hypoxic environments. These findings offer new insights into the adaptability of plateau animals.

Alfalfa (Medicago sativa L.) grassland is prone to degradation following multi-year maintenance. Yet, its mechanism regarding the stoichiometry of carbon (C) and nitrogen (N) across plant–soil system is still unclear. To address this issue, the method of space-for-time sampling was employed to investigate alfalfa grasslands with five planting years (5-, 8-, 10-, 15-, and 20-year periods) in the semiarid Loess Plateau. The results showed that the alfalfa above- and underground biomass decreased steadily decrease after the fifth to eighth years, showing a degradation tendency with the extension of planting duration. The mean weight diameter of aggregate registered an increase with planting years. However, the C and N stocks decreased with planting years in five soil aggregate fractions. Specifically, they were the highest in the fifth year and then started to gradually decrease along the 8th, 10th, 15th, and 20th year. Redundancy and correlation analysis confirmed that the C and N stocks of soil aggregates were closely positively associated with those of plant. Overall, the highest stability of soil physical structure was found during the period from the fifth to eighth year, and, afterward, the stability declined. In conclusion, alfalfa plantation improved soil structure stability but aggravated soil C and N stocks, and biomass and soil aggregate indicators accounted for alfalfa field degradation after a certain year of plantation.

Cardiovascular disease (CVD) has now become the leading cause of death worldwide, and its high morbidity and mortality rates pose a great threat to society. Although numerous studies have reported the pathophysiology of CVD, the exact pathogenesis of all types of CVD is not fully understood. Therefore, much more research is still needed to explore the pathogenesis of CVD. With the development of proteomics, many studies have successfully identified the role of posttranslational modifications in the pathogenesis of CVD, including key processes such as apoptosis, cell metabolism, and oxidative stress. In this review, we summarize the progress in the understanding of posttranslational modifications in cardiovascular diseases, including novel protein posttranslational modifications such as succinylation and nitrosylation. Furthermore, we summarize the currently identified histone deacetylase (HDAC) inhibitors used to treat CVD, providing new perspectives on CVD treatment modalities. We critically analyze the roles of posttranslational modifications in the pathogenesis of CVD-related diseases and explore future research directions related to posttranslational modifications in cardiovascular diseases.

Transparent objects are ubiquitous in everyday life, but how to detect them is full of challenges. Transparent objects hardly reflect light, and they usually transmit the appearance of their surroundings, making it difficult to distinguish them from their surroundings. Existing methods usually use only RGB (Red Green Blue) images as input, ignoring the role of depth maps in transparent object detection. In this article, we try to improve the detection performance of transparent objects by fusing RGB and depth information. Specifically, we propose a multimodal fusion network that fuses RGB and depth modalities in a complementary way. Moreover, extensive experiments and ablation studies on the RGB-D (RGB-Depth) transparent object dataset demonstrate the excellent performance of our method.

Citrus diseases caused by fungal pathogens drastically decreased the yield and quality of citrus fruits, leading to huge economic losses. Given the threats of chemical pesticides on the environment and human health, biocontrol agents have received considerable attention worldwide as ecofriendly and sustainable alternative to chemical fungicides. In the present study, we isolated a Bacillus velezensis strain TZ01 with potent antagonistic effect against three citrus pathogenic fungi: Diaporthe citri, Colletotrichum gloeosporioides and Alternaria alternata. The culture supernatant of this strain exhibited remarkable antifungal activity on potato dextrose agar plates and detached leaves of five citrus varieties. Treatment with TZ01 culture supernatant obviously affected the hyphal morphology and caused nucleic acid leakage. The crude lipopeptides (LPs) extracted from the culture supernatant were found as the major active ingredients, and could maintain the activity under a wide range of temperature and pH and ultraviolet radiation. Furthermore, the type of LPs, produced in vitro, were explored. Whole-genome sequencing of TZ01 revealed secondary metabolite gene clusters encoding synthetases for non-ribosomal peptides and polyketide production, and gene clusters responsible for the synthesis of three important LPs (surfactin, iturin, and fengycin) were identified in the genome. The liquid chromatography-mass spectrometry analysis confirmed the presence of various homologs of surfactin A, bacillomycin D, and fengycin A in the extracted LPs. Taken together, these results contribute to the possible biocontrol mechanisms of B. velezensis strain TZ01, as well as providing a promising new candidate strain as a biological control agent for controlling citrus fungal pathogens.

Plant-associated microbial communities are crucial for plant growth and health. However, assembly mechanisms of microbial communities and microbial interaction patterns remain elusive across vary degrees of pathogen-induced diseases. By using 16S rRNA high-throughput sequencing technology, we investigated the impact of wildfire disease on the microbial composition and interaction network in plant three different compartments. The results showed that pathogen infection significantly affect the phyllosphere and rhizosphere microbial community. We found that the primary sources of microbial communities in healthy and mildly infected plants were from the phyllosphere and hydroponic solution community. Mutual exchanges between phyllosphere and rhizosphere communities were observed, but microbial species migration from the leaf to the root was rarely observed in severely infected plants. Moreover, wildfire disease reduced the diversity and network complexity of plant microbial communities. Interactions among pathogenic bacterial members suggested that Caulobacter and Bosea might be crucial “pathogen antagonists” inhibiting the spread of wildfire disease. Our study provides deep insights into plant pathoecology, which is helpful for the development of novel strategies for phyllosphere disease prediction or prevention.

Abstract The liver is a major metastatic site (organ) for gastrointestinal cancers (such as colorectal, gastric, and pancreatic cancers) as well as non-gastrointestinal cancers (such as lung, breast, and melanoma cancers). Due to the innate anatomical position of the liver, the apoptosis of T cells in the liver, the unique metabolic regulation of hepatocytes and other potential mechanisms, the liver tends to form an immunosuppressive microenvironment and subsequently form a pre-metastatic niche (PMN), which can promote metastasis and colonization by various tumor cells(TCs). As a result, the critical role of immunoresponse in liver based metastasis has become increasingly appreciated. T cells, a centrally important member of adaptive immune response, play a significant role in liver based metastases and clarifying the different roles of the various T cells subsets is important to guide future clinical treatment. In this review, we first introduce the predisposing factors and related mechanisms of liver metastasis (LM) before introducing the PMN and its transition to LM. Finally, we detail the role of different subsets of T cells in LM and advances in the management of LM in order to identify potential therapeutic targets for patients with LM.

Abstract Gastric cancer is one of the most common malignant tumors, and chemotherapy is the main treatment for advanced gastric cancer. However, chemotherapy resistance leads to treatment failure and poor prognosis in patients with gastric cancer. Multidrug resistance (MDR) is a major challenge that needs to be overcome in chemotherapy. According to recent research, ferroptosis activation is crucial for tumor therapeutic strategies. In this work, we explored the solution to chemoresistance in gastric cancer by investigating the effects of the Chinese medicine monomer baicalin on ferroptosis. Baicalin with different concentrations was used to treat the parent HGC27 and drug-resistant HGC27/L cells of gastric cancer. Cell viability was measured by CCK8, and synergistic effects of baicalin combined with oxaliplatin were evaluated using Synergy Finder software. The effects of baicalin on organelles and cell morphology were investigated using projective electron microscopy. Iron concentration, MDA production and GSH inhibition rate were measured by colorimetry. ROS accumulation was detected by flow cytometry. The ferroptosis-related genes (IREB2, TfR, GPX4, FTH1), P53, and SLC7A11 were analysed by Western blot, and the expression differences of the above proteins between pretreatment and pretreatment of different concentrations of baicalin, were assayed in both parental HGC27 cells and Oxaliplatin-resistant HGC27/L cells. Mechanically, Baicalin disrupted iron homeostasis and inhibits antioxidant defense, resulting in iron accumulation, lipid peroxide aggregation, and specifically targeted and activated ferroptosis by upregulating the expression of tumor suppressor gene p53, thereby activating the SLC7A11/GPX4/ROS pathway mediated by it. Baicalin activates ferroptosis through multiple pathways and targets, thereby inhibiting the viability of oxaliplatin-resistant gastric cancer HGC27/L cells and enhancing the sensitivity to oxaliplatin chemotherapy.

Abstract While the role of crystal facets is well known in traditional heterogeneous catalysis, this effect has not yet been thoroughly studied in plasmon-assisted catalysis, where attention has primarily focused on plasmon-derived mechanisms. Here, we investigate plasmon-assisted electrocatalytic CO2 reduction using different shapes of plasmonic Au nanoparticles - nanocube (NC), rhombic dodecahedron (RD), and octahedron (OC) - exposing {100}, {110}, and {111} facets, respectively. Upon plasmon excitation, Au OCs doubled CO Faradaic efficiency (FECO) and tripled CO partial current density (jCO) compared to a dark condition, with NCs also improving under illumination. In contrast, Au RDs maintained consistent performance irrespective of light exposure, suggesting minimal influence of light on the reaction. Temperature experiments ruled out heat as the main factor to explain such differences. Atomistic simulations and electromagnetic modeling revealed higher hot carrier abundance and electric field enhancement on Au OCs and NCs than RDs. These effects now dominate the reaction landscape over the crystal facets, thus shifting the reaction sites when comparing dark and plasmon-activated processes. Plasmon-assisted H2 evolution reaction experiments also support these findings. The dominance of low-coordinated sites over facets in plasmonic catalysis suggests key insights for designing efficient photocatalysts for energy conversion and carbon neutralization.

Abstract Background Obesity is the main risk factor leading to the development of various respiratory diseases, such as asthma and pulmonary hypertension. Pulmonary microvascular endothelial cells (PMVECs) play a significant role in the development of lung diseases. Aconitate decarboxylase 1 (Acod1) mediates the production of itaconate, and Acod1/itaconate axis has been reported to play a protective role in multiple diseases. However, the roles of Acod1/itaconate axis in the PMVECs of obese mice are still unclear. Methods mRNA-seq was performed to identify the differentially expressed genes (DEGs) between high-fat diet (HFD)-induced PMVECs and chow-fed PMVECs in mice (|log2 fold change| ≥ 1, p ≤ 0.05). Free fatty acid (FFA) was used to induce cell injury, inflammation and mitochondrial oxidative stress in mouse PMVECs after transfection with the Acod1 overexpressed plasmid or 4-Octyl Itaconate (4-OI) administration. In addition, we investigated whether the nuclear factor erythroid 2-like 2 (Nrf2) pathway was involved in the effects of Acod1/itaconate in FFA-induced PMVECs. Results Down-regulated Acod1 was identified in HFD mouse PMVECs by mRNA-seq. Acod1 expression was also reduced in FFA-treated PMVECs. Acod1 overexpression inhibited cell injury, inflammation and mitochondrial oxidative stress induced by FFA in mouse PMVECs. 4-OI administration showed the consistent results in FFA-treated mouse PMVECs. Moreover, silencing Nrf2 reversed the effects of Acod1 overexpression and 4-OI administration in FFA-treated PMVECs, indicating that Nrf2 activation was required for the protective effects of Acod1/itaconate. Conclusion Our results demonstrated that Acod1/Itaconate axis might protect mouse PMVECs from FFA-induced injury, inflammation and mitochondrial oxidative stress via activating Nrf2 pathway. It was meaningful for the treatment of obesity-caused pulmonary microvascular endotheliopathy.

In this study, the pyrroloquinoline quinone (PQQ) high-yield mutant J1-1 of Methylobacterium glucophilum MP688 was used to do bioinformatics analysis to extract the two methanol dehydrogenase (MDH) genes from the genome, mpq0771 and mpq2496. The effects of Ca2+ and La3+ on bacterial growth, PQQ synthesis, MDH expression, and enzyme activity were explored, as well as the roles of the two enzymes in methanol metabolism. The results showed that Ca2+ and La3+ both increased J1-1 bacteriophage growth and decreased PQQ synthesis in the context of fast viral development. In the presence of Ca2+, mpq0771 expression increased in strain J1-1. La3+ inhibited mpq0771 expression while promoting mpq2496 expression and increasing total bacterial MDH viability. The knockout bacteria J1-1Δmpq0771 could not grow in methanol, but with the addition of La3+, it could grow in methanol and synthesize PQQ, and MDH activity was identified. The product encoded by mpq0771 was a Ca2+-dependent MDH, and the product encoded by mpq2496 was a La3+-dependent MDH, and La3+ could increase the production of mpq2496 and replace mpq0771 as a methanol dehydrogenase.