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Abstract TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels.

Abstract Background The association between the triglyceride-glucose (TyG) index and clinical outcomes in patients with both coronary artery disease (CAD) and psoriasis is unclear. This study investigated the association between the TyG index and major adverse cardiovascular events (MACE) in patients with both CAD and psoriasis. Methods This retrospective cohort study included patients diagnosed with both CAD and psoriasis who underwent coronary angiography at the Fuwai Hospital, Beijing, China, between January 2017 and May 2022. The study endpoint was the occurrence of MACE or end of follow-up time. Multivariate Cox proportional analysis and restricted cubic splines (RCS) were used to determine the association between the TyG index and MACE. Receiver operating characteristic (ROC) curves were used to determine the optimal threshold value of the TyG index for predicting MACE. Results This study enrolled 293 patients with both CAD and psoriasis, including 258 (88.1%) males with a mean age of 58.89 ± 9.61 years. Patients were divided into four groups based on the TyG quartiles: Q1 (N = 74), Q2 (N = 73), Q3 (N = 73), and Q4 (N = 73). After adjusting for the potential confounders, the TyG index was independently associated with MACE, both as a continuous variable (HR = 1.53, 95% CI = 1.03–2.28, P = 0.035) and as a categorical variable (Q1: reference; Q2: HR = 1.85, 95% CI = 0.88–3.87, P = 0.105; Q3: HR = 2.39, 95% CI = 1.14-5.00, P = 0.021; Q4: HR = 2.19, 95% CI = 1.001–4.81, P = 0.0497; P for trend = 0.039). RCS analysis showed an linear association between the TyG index and MACE (P-overall = 0.027, P-non-linear = 0.589). ROC curve analysis showed that the TyG index of ≥ 8.73 was the optimal threshold value (area under the ROC curve = 0.60, 95% CI 0.53–0.67). TyG index ≥ 8.73 was significantly associated with MACE (HR = 2.10, 95% CI = 1.32–3.34, P = 0.002). After adjustment for confounders, the TyG index showed independent association with MACE (HR = 2.00, 95% CI = 1.17–3.42, P = 0.011). Conclusions The TyG index showed a positive linear correlation with MACE in patients with both CAD and psoriasis. The TyG index of ≥ 8.73 might be the optimal threshold for predicting MACE. Graphical Abstract

Abstract Background The combined association of physical activity (PA) and alcohol use (AU) with long-term mortality is yet to be investigated. Methods For the current study, 12,621 participants aged ≥ 20 years were enrolled from the National Health and Nutrition Examination Survey (1999–2004). The study endpoint was all-cause mortality. Cox proportional hazards regression models were used to examine the combined effect of PA and AU on long-term mortality. Results The study population was divided into young (

Abstract Optimizing the structure of deep neural networks is essential in many applications. Especially in the object detection tasks of Unmanned Aerial Vehicles. Due to the constraints of the onboard platform, a more efficient network is required to meet practical demands. Nevertheless, existing lightweight detection networks exhibit excessive redundant computations and may yield in a certain level of accuracy loss. To address these issues, this paper proposes a new lightweight network structure named Cross-Stage Partially Deformable Network (CSPDNet). The initial proposal consists of a Deformable Separable Convolution Block (DSCBlock), separating feature channels, greatly reducing the computational load of convolution, and applying adaptive sampling to the separated feature map. Subsequently, to establish information interaction between feature layers, a channel weighting module is proposed. This module calculates weights for the separated feature map, facilitating information exchange across channels and resolutions. Moreover, it compensates for the effect of point-wise (1 $$\times$$ × 1) convolutions, filtering out more important feature information. Furthermore, a new CSPDBlock is designed, primarily composed of DSCBlock, establishing multidimensional feature correlations for each separated feature layer. This approach improves the ability to capture critical feature information and reconstruct gradient paths, thereby preserving detection accuracy. The proposed technology achieves a balance between model parameter size and detection accuracy. Furthermore, experimental results on object detection datasets demonstrate that our designed network, using fewer parameters, achieves competitive detection performance results compared to existing lightweight networks YOLOv5n, YOLOv6n, YOLOv8n, NanoDet and PP-PicoDet. The optimization effect of the designed CSPDBlock, using the VisDrone dataset, is validated when incorporated into advanced detection algorithms YOLOv5m, PPYOLOEm, YOLOv7, RTMDetm and YOLOv8m. In more detail, by incorporating the designed modules it was achieved that the parameters were reduced by 10–20% while almost maintaining detection accuracy.

Objective: This study evaluates the AI-assisted diagnostic potential of computed tomography (CT) for bone cancer and its influence on patient care during the pre- and post-treatment phases. It compares patient management approaches based on CT severity levels and identifies distinct CT phenotypes linked to disease severity. Methodology: We retrospectively examined 50 patients diagnosed with bone cancer between December 2022 and June 2023. The CT scans were analyzed according to the Radiological Society of North America (RSNA) guidelines. This study was performed using the deep convolutional neutral network (DCNN) model to assist doctors in diagnosing bone tumors through CT scanning. Patients’ management approaches were compared based on the severity levels indicated by CT scans. Results: Fifty patients participated in this study, with a median age of 67.2 years, ranging from 32 to 89 years. Of them, 38 % were female and 62 % were male. In 2022, 19 individuals (13 males and 6 females, ages 32 to 84) were assessed, with a mean age of 59.9 years. In 2023, 31 individuals, aged 54 to 89 with a mean age of 71.6 years, were assessed; among them were 18 men and 13 women. SPECT scans revealed the following key diagnostic features: 85.9 % of patients exhibited bone lesions with ground-glass opacities, 88 % had multipolar involvement, 92.8 % had bilateral involvement, and 92.8 % showed peripheral involvement. The severity scores based on CT scans were significantly higher in patients requiring intensive care, with scores above 14 being more common in this group. Conclusion: Distinct CT findings during the AI-assisted diagnosis and treatment of bone cancer provided prompt and sensitive examination capabilities. Notably, two CT phenotypes emerged, associated with large consolidation patterns and high severity scores, offering crucial insights into disease severity and aiding in clinical decision-making for intensive care requirements. The study underscores the importance of CT in the effective monitoring and management of bone cancer pre- and post-treatment.

Abstract Background The relationship between triglyceride glucose-body mass index (TyG-BMI) index and mortality in elderly patients with diabetes mellitus (DM) are still unclear. This study aimed to investigate the association between TyG-BMI with all-cause and cardiovascular mortality among elderly DM patients in the United States (US). Methods Patients aged over 60 years with DM from the National Health and Nutrition Examination Survey (2007–2016) were included in this study. The study endpoints were all-cause and cardiovascular mortality and the morality data were extracted from the National Death Index (NDI) which records up to December 31, 2019. Multivariate Cox proportional hazards regression model was used to explore the association between TyG-BMI index with mortality. Restricted cubic spline was used to model nonlinear relationships. Results A total of 1363 elderly diabetic patients were included, and were categorized into four quartiles. The mean age was 70.0 ± 6.8 years, and 48.6% of them were female. Overall, there were 429 all-cause deaths and 123 cardiovascular deaths were recorded during a median follow-up of 77.3 months. Multivariate Cox regression analyses indicated that compared to the 1st quartile (used as the reference), the 3rd quartile demonstrated a significant association with all-cause mortality (model 2: HR = 0.64, 95% CI 0.46–0.89, P = 0.009; model 3: HR = 0.65, 95% CI 0.43–0.96, P = 0.030). Additionally, the 4th quartile was significantly associated with cardiovascular mortality (model 2: HR = 1.83, 95% CI 1.01–3.30, P = 0.047; model 3: HR = 2.45, 95% CI 1.07–5.57, P = 0.033). The restricted cubic spline revealed a U-shaped association between TyG-BMI index with all-cause mortality and a linear association with cardiovascular mortality, after adjustment for possible confounding factors. Conclusions A U-shaped association was observed between the TyG-BMI index with all-cause mortality and a linear association was observed between the TyG-BMI index with cardiovascular mortality in elderly patients with DM in the US population.

Abstract Objectives Observational studies indicated a controversial relationship between periodontitis (PD) and Sjogren’s syndrome (SS). To overcome restrictions in conventional observational studies, we conducted a two-sample Mendelian randomization (MR) analysis to assess the potential bidirectional relationship between PD and SS. Methods We utilized the largest available genome-wide association study (GWAS) of European ancestry on both PD (17,353 cases-28,210 controls) and SS (2495 cases-365,533 controls) for MR genetic instrument selection. The random-effect inverse-variance weighted (IVW) method complemented by Causal Analysis Using Summary Effect (CAUSE), weighted median, weighted mode, simple mode, MR-Egger regression, and MR-pleiotropy residual sum and outlier (MR-PRESSO) was used for MR analysis. Subsequent pleiotropy and heterogeneity tests were conducted. Results IVW analysis exhibited neither an effect of PD on SS (OR = 0.939, 95%CI = 0.525–1.677, P = 0.8304) nor that of SS on PD (OR = 1.007, 95%CI = 0.977–1.038, P = 0.6440). The other five complementary methods further recognized the null association with an effect size close to one. No significant pleiotropy was detected in the relationship between PD and SS (P > 0.05). Heterogeneity existed in the effect of PD on SS but not vice versa. Conclusions No genetic causality between PD and SS or vice versa was supported by our results under MR assumptions and limitations. The study results provided new insights into the relationship between periodontal status and sjogren’s syndrome, highlighting the need for a more prudent medical intervention.

Abstract Glaucoma drainage devices (GDDs) are prosthetic-treatment devices for treating primary open-angle glaucoma. Despite their effectiveness in reducing intraocular pressures (IOP), endothelial cell damage (ECD) is a commonly known side-effect. There have been different hypotheses regarding the reasons for ECD with one being an induced increase in shear on the corneal wall. A computational fluid dynamics (CFD) model was used to investigate this hypothesis in silico. The Ahmed Glaucoma Valve (AGV) was selected as the subject of this study using an idealised 3D model of the anterior chamber with insertion angles and positions that are commonly used in clinical practice. It was found that a tube-cornea distance of 1.27 mm or greater does not result in a wall shear stress (WSS) above the limit where ECD could occur. Similarly, a tube-cornea angle of 45° or more was shown to be preferable. It was also found that the ECD region has an irregular shape, and the aqueous humour flow fluctuates at certain insertion angles and positions. This study shows that pathological amounts of WSS may occur as a result of certain GDD placements. Hence, it is imperative to consider the associated fluid force interactions when performing the GDD insertion procedure.

Abstract A modified non‐linear magnetic equivalent circuit (MEC) model is presented for double‐stator single‐rotor axial flux permanent magnet (AFPM) (DSSR‐AFPM) machine considering stator radial‐end flux‐leakage, which is severer under a heavier load. Compared to the conventional MEC model for DSSR‐AFPM machine, the proposed model can predict the electromagnetic performance more accurately when the machine operates under a heavy load. The proposed MEC model is verified by the finite element analysis (FEA) on a 24‐slot/20‐pole DSSR‐AFPM machine. The comparison results show that the relative error between the proposed MEC model and FEA is

ABSTRACTBrain metastasis is the most devasting form of lung cancer. Recent studies highlight significant differences in the tumor microenvironment (TME) between lung cancer brain metastasis (LCBM) and primary lung cancer, which contribute significantly to tumor progression and drug resistance. Cancer-associated fibroblasts (CAFs) are the major component of pro-tumor TME with high plasticity. However, the lineage composition and function of CAFs in LCBM remain elusive. By reanalyzing single-cell RNA sequencing (scRNA-seq) data (GSE131907) from lung cancer patients with different stages of metastasis comprising primary lesions and brain metastasis, we found that CAFs undergo distinctive lineage transition during LCBM under a hypoxic situation, which is directly driven by hypoxia-induced HIF-2α activation. Transited CAFs enhance angiogenesis through VEGF pathways, trigger metabolic reprogramming, and promote the growth of tumor cells. Bulk RNA sequencing data was utilized as validation cohorts. Multiplex immunohistochemistry (mIHC) assay was performed on four paired samples of brain metastasis and their primary lung cancer counterparts to validate the findings. Our study revealed a novel mechanism of lung cancer brain metastasis featuring HIF-2α-induced lineage transition and functional alteration of CAFs, which offers potential therapeutic targets.

The double stator high-temperature superconducting field modulated (DS-HTS-FM) machine with a dual-stator configuration and high-temperature superconducting materials includes numerous cryogenic components that establish the required operating temperature for superconducting magnets. This abundance of cryogenic elements introduces complexity to the process of conducting a modal analysis of the entire machine. However, the conventional trial-and-error approach employed to achieve precise modal analysis results for the entire-machine suffers from the drawback of lacking a clear direction for adjustment elastic modulus which has a great influence on the modal analysis results. Therefore, it is difficult to obtain accurate modal analysis results of the entire-machine. In response to this challenge, this study focuses on a 10 kW DS-HTS-FM machine as its subject and presents an elastic modulus adjustment method based on the entire-machine modal analysis, aiming to obtain accurate finite element (FE) modal analysis results of the entire-machine. Initially, the FE method is used to find the components that have a great influence on the outer stator modals while the components that have less influence on the outer stator modal are equivalent to the front and rear end cover in the form of additional mass, thus establishing an entire-machine equivalent model for elastic modulus adjustment. Subsequently, an examination is conducted to ascertain the relative impact proportions of the elastic modulus associated with the outer stator, casing, end cover, and armature windings on the natural frequencies of the outer stator, which can lead to a precise determination of the optimal direction for adjusting the elastic modulus parameters. Lastly, based on the entire-machine modal experiment, the elastic modulus of the equivalent model is modified in a definite direction. Consequently, the elastic modulus values for various components of the DS-HTS-FM machine can be accurately identified. Experimental outcomes affirm the efficacy of this approach in attaining precise FE modal results for the DS-HTS-FM machine and reducing the computational time required for FE analysis.

Abstract Nanoscale optoelectrodes hold the potential to stimulate optically individual neurons and intracellular organelles, a challenge that demands both a high-density of photoelectron storage and significant charge injection. Here, we report that zinc porphyrin, commonly used in dye-sensitized solar cells, can be self-assembled into nanorods and then coated by TiO2. The J-aggregated zinc porphyrin array enables long-range exciton diffusion and allows for fast electron transfer into TiO2. The formation of TiO2(e−) attracts positive charges around the neuron membrane, contributing to the induction of action potentials. Far-field cranial irradiation of the motor cortex using a 670 nm laser or an 850 nm femtosecond laser can modulate local neuronal firing and trigger motor responses in the hind limb of mice. The pulsed photoelectrical stimulation of neurons in the subthalamic nucleus alleviates parkinsonian symptoms in mice, improving abnormal stepping and enhancing the activity of dopaminergic neurons. Our results suggest injectable nanoscopic optoelectrodes for optical neuromodulation with high efficiency and negligible side effects.

Abstract Harvesting biomechanical energy from cardiac motion is an attractive power source for implantable bioelectronic devices. Here, we report a battery-free, transcatheter, self-powered intracardiac pacemaker based on the coupled effect of triboelectrification and electrostatic induction for the treatment of arrhythmia in large animal models. We show that the capsule-shaped device (1.75 g, 1.52 cc) can be integrated with a delivery catheter for implanting in the right ventricle of a swine through the intravenous route, which effectively converts cardiac motion energy to electricity and maintains endocardial pacing function during the three-week follow-up period. We measure in vivo open circuit voltage and short circuit current of the self-powered intracardiac pacemaker of about 6.0 V and 0.2 μA, respectively. This approach exhibits up-to-date progress in self-powered medical devices and it may overcome the inherent energy shortcomings of implantable pacemakers and other bioelectronic devices for therapy and sensing.

Background: Insufficient clinicians' auscultation ability delays the diagnosis and treatment of valvular heart disease (VHD); artificial intelligence provides a solution to compensate for the insufficiency in auscultation ability by distinguishing between heart murmurs and normal heart sounds. However, whether artificial intelligence can automatically diagnose VHD remains unknown. Our objective was to use deep learning to process and compare raw heart sound data to identify patients with VHD requiring intervention. Methods: Heart sounds from patients with VHD and healthy controls were collected using an electronic stethoscope. Echocardiographic findings were used as the gold standard for this study. According to the chronological order of enrollment, the early-enrolled samples were used to train the deep learning model, and the late-enrollment samples were used to validate the results. Results: The final study population comprised 499 patients (354 in the algorithm training group and 145 in the result validation group). The sensitivity, specificity, and accuracy of the deep-learning model for identifying various VHDs ranged from 71.4 to 100.0%, 83.5–100.0%, and 84.1–100.0%, respectively; the best diagnostic performance was observed for mitral stenosis, with a sensitivity of 100.0% (31.0–100.0%), a specificity of 100% (96.7–100.0%), and an accuracy of 100% (97.5–100.0%). Conclusions: Based on raw heart sound data, the deep learning model effectively identifies patients with various types of VHD who require intervention and assists in the screening, diagnosis, and follow-up of VHD.

Abstract Background Intracranial plasmacytomas are rare tumors arising from plasma cells with approximately half of the cases progressing to multiple myeloma (MM). However, there is a lack of comprehensive clinical cohort analysis on the clinical and pathological features, progression, and outcomes of intracranial plasmacytomas. Methods A retrospective analysis of 190 cases was conducted, combining data from 38 cases in a single institution and 152 cases from the literature. Patient demographics, clinical presentations, tumor locations, imaging features, surgical treatments, and follow‐up outcomes were collected and analyzed. Survival analysis and Cox regression analysis were performed to identify prognostic factors. Results A total of 190 intracranial plasmacytoma patients with an average age of 55.4 years were included in the study. The preoperative misdiagnosis ratio was high at 55.3%, and 59.7% of the tumors affected the calvaria convexity, compared to 40.3% located at the skull base. Resection and biopsy were achieved in 72.4% and 27.6% patients, respectively. Among them, 34.2% (65/190) of patients were initially diagnosed with MM with intracranial plasmacytoma as their first presentation (MM‐IPFP), while 63.2% (120/190) of patients were diagnosed with solitary intracranial plasmacytoma (SIP), including 61 extramedullary plasmacytomas and 59 solitary bone plasmacytomas. In the SIP group, 22.4% (24/107) of patients experienced disease progression leading to the development of MM during a median follow‐up time of 42.6 months (range 1–230 months). Multivariate analysis unveiled that radiotherapy (HR, 0.05; 95% CI, 0.00–0.87; p = 0.04), not surgery, was a protective prognostic factor for overall survival in MM‐IPFP patients. Comparison between the SIP progression group and non‐progression group revealed a significant difference of Ki‐67 index (non‐progression vs. SIP progression, 8.82% ± 7.03 vs. 16.5% ± 10.5, p

Electrical energy is becoming more popular due to the fact that it is economic, practical, clean, and easy to control and convert energy compared to other forms of energy. Currently, however, most of the electrical energy is converted from or to mechanical energy based on the well-known Faraday’s law of electromagnetic induction, which states that a current will be induced in a closed conductive coil exposed to a changing magnetic field. For that purpose, either the magnetic field itself must be changing or the magnetic field must be moving relative to the closed conductive coil. While investigating the physical significance of magductance (or magnetic-inductance), we unearthed a new electromagnetic induction mechanism that the electrical current is induced in a closed conductive coil with the invariant magnetic field by changing the magnetic parameter of magductance of the closed coil. Time-varying magductance is achieved by changing the conductivity of the coil. To demonstrate the feasibility of the electromagnetic induction, both theoretical validation and experimental verification are undertaken. We built a closed superconducting coil and successfully measured the induced electrical currents in the cooling process of the closed superconducting coil under an invariant magnetic field, thus verifying the new law of electromagnetic induction.

The melon fly, Bactrocera cucurbitae (Coquillett) (Tephritidae: Diptera), is an invasive pest that poses a significant threat to agriculture in Africa and other regions. Flies are known to use their olfactory systems to recognise environmental chemical cues. However, the molecular components of the chemosensory system of B. cucurbitae are poorly characterised. To address this knowledge gap, we have used next-generation sequencing to analyse the antenna transcriptomes of sexually immature B. cucurbitae adults. The results have identified 160 potential chemosensory genes, including 35 odourant-binding proteins (OBPs), one chemosensory protein (CSP), three sensory neuron membrane proteins (SNMPs), 70 odourant receptors (ORs), 30 ionotropic receptors (IRs), and 21 gustatory receptors (GRs). Quantitative real-time polymerase chain reaction quantitative polymerase chain reaction was used to validate the results by assessing the expression profiles of 25 ORs and 15 OBPs. Notably, high expression levels for BcucOBP5/9/10/18/21/23/26 were observed in both the female and male antennae. Furthermore, BcucOROrco/6/7/9/13/15/25/27/28/42/62 exhibited biased expression in the male antennae, whereas BcucOR55 showed biased expression in the female antennae. This comprehensive investigation provides valuable insights into insect olfaction at the molecular level and will, thus, help to facilitate the development of enhanced pest management strategies in the future.

Abstract Background Sedentary behavior and vitamin D deficiency are independent risk factors for mortality in cancer survivors, but their joint association with mortality has not been investigated. Methods We analyzed data from 2914 cancer survivors who participated in the National Health and Nutrition Examination Survey (2007–2018) and followed up with them until December 31, 2019. Sedentary behavior was assessed by self-reported daily hours of sitting, and vitamin D status was measured by serum total 25-hydroxyvitamin D (25(OH)D) levels. Results Among 2914 cancer survivors, vitamin D deficiency was more prevalent in those with prolonged daily sitting time. During up to 13.2 years (median, 5.6 years) of follow-up, there were 676 deaths (cancer, 226; cardiovascular disease, 142; other causes, 308). The prolonged sitting time was associated with a higher risk of all-cause and noncancer mortality, and vitamin D deficiency was associated with a higher risk of all-cause and cancer mortality. Furthermore, cancer survivors with both prolonged sitting time (≥ 6 h/day) and vitamin D deficiency had a significantly higher risk of all-cause (HR, 2.05; 95% CI: 1.54–2.72), cancer (HR, 2.33; 95% CI, 1.47–3.70), and noncancer mortality (HR, 1.91; 95% CI, 1.33–2.74) than those with neither risk factor after adjustment for potential confounders. Conclusions In a nationally representative sample of U.S. cancer survivors, the joint presence of sedentary behavior and vitamin D deficiency was significantly associated with an increased risk of all-cause and cancer-specific mortality.

Plant height is a key plant architectural trait that affects the seed yield, harvest index and lodging resistance in Brassica napus L., although the genetic mechanisms affecting plant height remain unclear. Here, a semi-dwarf mutant, df34, was obtained by ethyl methanesulphonate-induced mutagenesis. Genetic analysis showed that the semi-dwarf phenotype is controlled by one semi-dominant gene, which was located on chromosome C03 using a bulked segregant analysis coupled with whole-genome sequencing, and this gene was named BnaSD.C3. Then BnaSD.C3 was fine-mapped to a 297.35-kb segment of the “Darmor-bzh” genome, but there was no potential candidate gene for the semi-dwarf trait underlying this interval. Furthermore, the interval was aligned to the Zhongshuang 11 reference genome. Finally, combining structural variation analysis, transcriptome sequencing, phytohormone analyses and gene annotation information, BnaC03G0466900ZS and BnaC03G0478900ZS were determined to be the most likely candidate genes affecting the plant height of df34. This study provides a novel major locus for breeding and new insights into the genetic architecture of plant height in B. napus.

Abstract Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing‐induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre‐procedure evaluation and preparation, implant procedure management, follow‐up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

Abstract Astrocytoma and glioblastoma (GB) are reclassified subtypes of adult diffuse gliomas based on distinct isocitrate dehydrogenase (IDH) mutation in the fifth edition of the WHO Classification of Tumors of the Central Nervous System. The recurrence of gliomas is a common and inevitable challenge, and analyzing the distinct genomic alterations in astrocytoma and GB could provide insights into their progression. This study conducted a longitudinal investigation, utilizing whole-exome sequencing, on 65 paired primary/recurrent gliomas. It examined chromosome arm aneuploidies, copy number variations (CNVs) of cancer-related genes and pathway enrichments during the relapse. The veracity of these findings was verified through the integration of our data with multiple public resources and by corroborative immunohistochemistry (IHC). The results revealed a greater prevalence of aneuploidy changes and acquired CNVs in recurrent lower grade astrocytoma than in relapsed grade 4 astrocytoma and GB. Larger aneuploidy changes were predictive of an unfavorable prognosis in lower grade astrocytoma (P

In this paper, a gap nonlinear compensation strategy is proposed for the full closed-loop control structure of non-direct-drive servo motor systems. Firstly, an improved deadband model containing the initial value of the gap is proposed, and two gap amplitude identification methods, namely, incremental torque and velocity difference integral, are compared. Then, for the full closed-loop structure, based on the describing function and the stability theory of the nonlinear system, the limit-loop oscillating frequency and the influencing factors are predicted, which are related to the system control stiffness and independent of the gap amplitude; finally, the state-feedback control is proposed, and the feedback coefficients are designed by using the pole configuration, making the system a pseudo-linear system. Simulation and experimental verification show that the method can suppress the limit loop oscillation, attenuate the system shock, and have a certain robustness.

High-molecular-weight glutenin subunits (HMW-GS) are an important component of total cereal proteins in wheat. It is closely related to the processing quality of flour. Here, we analyzed allelic variations at the Glu-1 locus in 163 wheat accessions from Hubei Province, China with SDS-PAGE. Among the 15 alleles detected, alleles 1, 7+8, and 2+12 were the major alleles, and 7, 6+8, and 2+10 were rare alleles. The breeding lines had higher genetic diversity than the commercial varieties. Alleles 7 and 6+8 significantly reduced the grain protein content and wet gluten content of wheat. The “1, 7+9, 5+10” and “1, 14+15, and 2+12” allelic combinations significantly increased the grain protein content, hardness index, test weight, and wet gluten content of wheat. Alleles 7+9, 14+15, and 5+10 were identified as alleles related to high wheat quality. The “1, 7, 5+10”, “1, 6+8, 5+10”, “null, 7+9, 2+12”, “1, 14+15, 2+12”, and “1, 7+9, 5+10” allelic combinations had greater effects on wheat grain quality traits. These results demonstrate the effects of HMW-GS on wheat grain quality traits and provide a reference for the genetic improvement of wheat quality.

Almond hull, a substantial byproduct comprising more than half of almond fresh weight, has recently gained attention due to its functionality and sustainability benefits. Despite heightened interest, information regarding its toxicity remains limited. In order to assess its genotoxic potential, we conducted Good Laboratory Practice-compliant in vitro and in vivo studies following Organization for Economic Co-operation and Development (OECD) guidelines. No evidence of toxicity or mutagenicity was observed in a bacterial reverse mutation assay using five tester strains, evaluating almond hull at concentrations up to 5 mg/plate, with or without metabolic activation. Almond hull did not induce chromosome structural damage in a chromosome aberration assay using Chinese hamster ovary cells, nor did it cause any spermatogonial chromosomal aberration in tested male BALB/c mice. To evaluate its ability to induce DNA damage in rodents, a combined micronucleus assay was conducted in KM mice of both sexes. Almond hull was administered at doses of 1250, 2500, and 5000 mg/kg/day via gavage once daily for 2 days. No adverse effects of almond hull were observed in the micronucleus assay. Our results indicate no evidence of the genotoxic potential of almond hull administered up to the maximum concentrations of 5 g/kg, as recommended by OECD guidelines.

Background: The tissue response viewer (TRV) is a multiparametric index that incorporates time, power, tissue pressure, impedance, and wall thickness data during radiofrequency catheter ablation (RFCA) and is used to predict the transmurality of lesions. This study aimed to evaluate the feasibility and accuracy of the TRV in a porcine model. Methods: Twelve pigs underwent preablation high-density voltage and activation mapping of two atria, and both were repeated after linear RFCA. Intentional gaps were kept in the left atrium (LA) and were touched up in the right atrium (RA). Standard and high powers were, respectively, performed in the LA ablation. Six pigs were immediately sacrificed for pathological examination after the mapping and ablation procedure (acute study). Another six pigs were kept for 4 weeks before remapping and pathological examination (chronic study). Results: All animals completed the planned procedure. The TRV function showed a sensitivity of 97.1% and a specificity of 76.9% in the acute study, and a sensitivity of 95.9% and a specificity of 72.5% in the chronic study to predict the transmural lesion. All positive and negative predictive values were over 80%. In addition, the TRV achieved higher sensitivity (92.3% vs. 85.0%) and specificity (88.2% vs. 78.9%) to predict the transmural lesion in LA ablation with high power compared with standard ablation. Conclusions: This study presents the histopathological validation of TRV to predict transmural lesions. The use of TRV may guide a more individual ablation and a more precise touch-up of gaps for atrial arrhythmias.

Abstract Background The evidence on the association between the triglyceride glucose (TyG) index and the risk of death in the general population remains controversial. This study aims to investigate the relationship between the TyG index and all-cause and cardiovascular mortality in the general population, with a focus on sex differences. Methods This prospective cohort study analyzed data from the National Health and Nutrition Examination Survey (1999–2002), comprising 7,851 US adults. The study employed multivariate Cox proportional hazards regression and two-segment Cox hazard regression models to evaluate the sex-specific differences in the relationship between the TyG index and all-cause and cardiovascular mortality. Results After 11,623 person-years of follow-up, there were 539 deaths, with 10.56% due to all-cause mortality and 2.87% due to cardiovascular mortality. After adjusting for multiple variables, our study found a U-shaped association of the TyG index with all-cause and cardiovascular mortality, with inflection points at 9.36 and 9.52. A significant sex difference was observed in the association between the TyG index and mortality. Below the inflection point, the relationship between the TyG index and mortality was consistent in males and females. However, above the inflection point, only males exhibited a positive association between the TyG index and all-cause mortality (adjusted hazard risk [HR], 1.62, 95% confidence interval [CI], 1.24–2.12) and cardiovascular mortality (adjusted HR, 2.28, 95% CI, 1.32–3.92). Conclusions Our study showed a U-shaped association between the TyG index and all-cause and cardiovascular mortality in the general population. Furthermore, sex differences were observed in the association between the TyG index and mortality once it exceeded a certain threshold.

Abstract Background Glioblastoma (GBM) is the most malignant primary tumor in the brain, with poor prognosis and limited effective therapies. Although Bevacizumab (BEV) has shown promise in extending progression-free survival (PFS) treating GBM, there is no evidence for its ability to prolong overall survival (OS). Given the uncertainty surrounding BEV treatment strategies, we aimed to provide an evidence map associated with BEV therapy for recurrent GBM (rGBM). Methods PubMed, Embase, and the Cochrane Library were searched for the period from January 1, 1970, to March 1, 2022, for studies reporting the prognoses of patients with rGBM receiving BEV. The primary endpoints were overall survival (OS) and quality of life (QoL). The secondary endpoints were PFS, steroid use reduction, and risk of adverse effects. A scoping review and an evidence map were conducted to explore the optimal BEV treatment (including combination regimen, dosage, and window of opportunity). Results Patients with rGBM could gain benefits in PFS, palliative, and cognitive advantages from BEV treatment, although the OS benefits could not be verified with high-quality evidence. Furthermore, BEV combined therapy (especially with lomustine and radiotherapy) showed higher efficacy than BEV monotherapy in the survival of patients with rGBM. Specific molecular alterations (IDH mutation status) and clinical features (large tumor burden and double-positive sign) could predict better responses to BEV administration. A low dosage of BEV showed equal efficacy to the recommended dose, but the optimal opportunity window for BEV administration remains unclear. Conclusions Although OS benefits from BEV-containing regimens could not be verified in this scoping review, the PFS benefits and side effects control supported BEV application in rGBM. Combining BEV with novel treatments like tumor-treating field (TTF) and administration at first recurrence may optimize the therapeutic efficacy. rGBM with a low apparent diffusion coefficient (ADCL), large tumor burden, or IDH mutation is more likely to benefit from BEV treatment. High-quality studies are warranted to explore the combination modality and identify BEV-response subpopulations to maximize benefits.

Abstract This research proposes a deep-learning paradigm, termed functional learning (FL), to physically train a loose neuron array, a group of non-handcrafted, non-differentiable, and loosely connected physical neurons whose connections and gradients are beyond explicit expression. The paradigm targets training non-differentiable hardware, and therefore solves many interdisciplinary challenges at once: the precise modeling and control of high-dimensional systems, the on-site calibration of multimodal hardware imperfectness, and the end-to-end training of non-differentiable and modeless physical neurons through implicit gradient propagation. It offers a methodology to build hardware without handcrafted design, strict fabrication, and precise assembling, thus forging paths for hardware design, chip manufacturing, physical neuron training, and system control. In addition, the functional learning paradigm is numerically and physically verified with an original light field neural network (LFNN). It realizes a programmable incoherent optical neural network, a well-known challenge that delivers light-speed, high-bandwidth, and power-efficient neural network inference via processing parallel visible light signals in the free space. As a promising supplement to existing power- and bandwidth-constrained digital neural networks, light field neural network has various potential applications: brain-inspired optical computation, high-bandwidth power-efficient neural network inference, and light-speed programmable lens/displays/detectors that operate in visible light.

The purple nonsulfur bacteria, Rhodospirillum rubrum, is recognized as a potential strain for PHAs bioindustrial processes since they can assimilate a broad range of carbon sources, such as syngas, to allow reduction of the production costs. In this study, we comparatively analyzed the biomass and PHA formation behaviors of R. rubrum under 100% CO and 50% CO gas atmosphere and found that pure CO promoted the PHA synthesis (PHA content up to 23.3% of the CDW). Hydrogen addition facilitated the uptake and utilization rates of CO and elevated 3-HV monomers content (molar proportion of 3-HV up to 9.2% in the presence of 50% H2). To elucidate the genetic events culminating in the CO assimilation process, we performed whole transcriptome analysis of R. rubrum grown under 100% CO or 50% CO using RNA sequencing. Transcriptomic analysis indicated different CO2 assimilation strategy was triggered by the presence of H2, where the CBB played a minor role. An increase in BCAA biosynthesis related gene abundance was observed under 50% CO condition. Furthermore, we detected the α-ketoglutarate (αKG) synthase, converting fumarate to αKG linked to the αKG-derived amino acids synthesis, and series of threonine-dependent isoleucine synthesis enzymes were significantly induced. Collectively, our results suggested that those amino acid synthesis pathways represented a key way for carbon assimilation and redox potential maintenance by R. rubrum growth under syngas condition, which could partly replace the PHA production and affect its monomer composition in copolymers. Finally, a fed-batch fermentation of the R. rubrum in a 3-l bioreactor was carried out and proved H2 addition indeed increased the PHA accumulation rate, yielding 20% ww-1 PHA production within six days.

Background: The relationship between short-term cardiac function changes and long-term outcomes in heart failure (HF) patients undergoing cardiac resynchronization therapy (CRT) remains uncertain, especially when stratified by diabetes status. Objectives: This study aims to assess the association between short-term cardiac function changes and outcomes such as all-cause mortality and HF hospitalization in patients undergoing CRT, stratified by diabetes status. Design: This is a cohort longitudinal retrospective study. Methods: A total of 666 HF patients, treated with CRT between March 2007 and March 2019, were included in this study. Among them, 166 patients (24.9%) were diagnosed with diabetes. Cardiac function was assessed at baseline and again at 6 months, incorporating evaluations of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left atrial diameter (LAD), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and QRS duration. The QRS duration represents the time required for a stimulus to spread through the ventricles (ventricular depolarization). The primary endpoints of the study were all-cause mortality and HF-related hospitalization. Results: During a median follow-up of 2.51 years, 172 (25.8%) patients died and 197 (29.6%) were hospitalized for HF. Changes in LVEF, LVEDD, and LAD within 6 months had similar effects on adverse outcomes in both diabetic and nondiabetic patients. However, the presence of diabetes significantly modified the association between changes in NT-proBNP and QRS duration and adverse outcomes. Short-term changes in NT-proBNP and QRS duration were positively associated with all-cause mortality and HF hospitalization in patients without diabetes. However, the relationship between short-term changes in NT-proBNP and QRS duration and adverse outcomes was non-linear in diabetic patients. Conclusion: Improvement of cardiac function after CRT implantation can reduce long-term risk of all-cause mortality and HF hospitalization in HF patients. However, the presence of diabetes may affect the association between short-term changes in NT-proBNP and QRS duration and adverse outcomes.

Rolling circle amplification is a widely used biosensing technique. Although various secondary structures have been employed in RCA, their effects on RCA efficiency have seldom been reported. Here, we find that stems in circular templates can strongly inhibit RCA, and the primer-stem distance is responsible for the inhibition. Based on the results, we propose an initiation inhibition mechanism and present a design principle for a general RCA assay. Inspired by this mechanism, we further propose a new nucleic acid detection method. The results verify that this method can increase RCA detection sensitivity according to the target recycling principle. Besides DNA detection, it can also achieve single mismatch discrimination of miRNA detection after optimization. This method also shows convenient visualization detection. The initiation inhibition of RCA could be helpful for RCA applications as promising detection techniques.

Objective To investigate the application of nurse-led chain management in extended care of children undergoing surgical treatment for Hirschsprung’s disease. Methods Totally 60 children with Hirschsprung’s disease were divided into control group and observation group according to the sequence of hospital admission, with 30 cases in each group. The control group received routine perioperative nursing management, and a nurse-led chain management model was adopted in perioperative nursing management and extended care of children in the observation group. Intervention efficacy was evaluated via incidence of postoperative complications and satisfaction of children’s parents. Results The incidence of postoperative complications in the observation group was lower than that in the control group(P＜0. 05). Parents of children in the observation group were more satisfied with nursing service compared with those in the control group(P＜0. 01). Conclusion The nurse-led chain management in extended care is potentially effective to reduce the risk of postoperative complications and improve the quality of life of children with Hirschsprung’s disease. (目的 探讨以护士为主导的链式管理模式在先天性巨结肠患儿术后延续性护理中的应用效果。方法 将60例先天性巨结肠患儿按照入院时间分为对照组与观察组, 各30例。对照组接受常规先天性巨结肠围手术期管理模式, 观察组采用链式管理协同延续护理模式。干预6个月后评价效果。结果 观察组术后并发症发生率低于对照组, 差异有统计学意义(P＜0. 05)。观察组患儿家属对护理工作的满意度高于对照组, 差异有统计学意义(P＜0. 01)。结论 以护士为主导的链式管理模式有利于减少术后并发症的发生, 对提升先天性巨结肠患儿术后生活质量具有积极意义。)

Abstract Background Dysregulated long non-coding RNAs participate in the development of diabetic cerebral ischemia. This study aimed to investigate the underlying mechanism of lncRNA MALAT1 in diabetic cerebral ischemia. Method Middle cerebral artery occlusion (MCAO) was performed to establish diabetic cerebral I/R in vivo. TTC and neurological deficits assessment were performed to assess cerebral ischemic injury. LDH was conducted to detect cytotoxicity. RT-qPCR and western blotting assays were applied to determine mRNA and protein expression. Flow cytometry was performed to detect the pyroptosis of BV2 cells. Immunofluorescence and FISH were conducted for subcellular localization of MALAT1 and STAT1. ELISA was performed to determine cytokine release. Dual luciferase reporter, RIP, and ChIP assays were used to validate the interaction between STAT1 and MALAT1/NLRP3. Diabetes aggravated cerebral injury in vivo and in vitro. Diabetic cerebral ischemia induced inflammatory response and inflammation-induced cell pyroptosis. Result MALAT1 was overexpressed in diabetic cerebral ischemia models in vivo and in vitro. However, knockdown of MALAT1 suppressed inflammatory response and the pyroptosis of BV2 cells. Moreover, MALAT1 interacted with STAT1 to transcriptionally activate NLRP3. Knockdown of STAT1 significantly reversed the effects of MALAT1. Furthermore, STAT1 promotes the MALAT1 transcription. MALAT1 interacts with STAT1 to promote the pyroptosis of microglias induced by diabetic cerebral ischemia through activating NLRP3 transcription. Conclusion Thus, knockdown of MALAT1 may be a potential promising therapy target for diabetic cerebral ischemia.

Abstract The usage of antiretroviral treatment (ART) has considerably decreased the morbidity and mortality related to HIV-1 (human immunodeficiency virus type 1) infection. However, ART is ineffective in eradicating the virus from the persistent cell reservoirs (e.g., microglia), noticeably hindering the cure for HIV-1. Microglia participate in the progression of neuroinflammation, brain aging, and HIV-1-associated neurocognitive disorder (HAND). Some methods have currently been studied as fundamental strategies targeting microglia. The purpose of this study was to comprehend microglia biology and its functions in HIV-1 infection, as well as to look into potential therapeutic approaches targeting microglia.

Krister Stendahl’s article, “The Apostle Paul and the Introspective Conscience of the West”, argues that Paul has a “robust conscience” both before and after his conversion. Martin Luther misinterprets this as a “plagued conscience” in accordance with his own religious experience, and this misinterpretation can be traced back even to Augustine. This paper examines the context for the ancient Greek and Hellenistic theory of conscience, in order to understand Augustine’s transformation of Paul’s doctrine of justification by faith and the consequent discovery of the concept of introspective conscience in Western intellectual history. This paper also clarifies aspects of Augustine’s “plagued conscience”, which it analyses across two stages: the first after the descent of grace but before the conversion of a believer, and the second after conversion. In the first stage, Augustine implies a continuous spiritual conflict between good will and evil will within the inner self; however, in the second stage, the inner self experiences a deeper spiritual struggle, owing to its certainty of God’s predestined plan alongside its uncertainty over personal salvation. The concept of introspective conscience has shaped the deep consciousness of sin for many Western Christians. This paper compares Pauline and Augustinian conscience with the same concept in the Confucian author Mencius. For Mencius, conscience is self-sufficient even in the earliest stages of its development and does not require the support of God’s grace or the power of Heaven. The constant expansion of Mencius’s operative conscience is sufficient for self-cultivation and the correction of the distorted world.

Alpha-1 antitrypsin-overexpressing mesenchymal stromal/stem cells (AAT-MSCs) showed improved innate properties with a faster proliferation rate when studied for their protective effects in mouse models of diseases. Here, we investigated the potential mechanism(s) by which AAT gene insertion increases MSC proliferation. Human bone marrow-derived primary or immortalized MSCs (iMSCs) or AAT-MSCs (iAAT-MSCs) were used in the study. Cell proliferation was measured by cell counting and cell cycle analysis. Possible pathways involved in the pro-proliferation effect of AAT were investigated by measuring mRNA and protein expression of key cell cycle genes. Interval cell counting showed increased proliferation in AAT-MSCs or iAAT-MSCs compared to their corresponding MSC controls. Cell cycle analysis revealed more cells progressing into the S and G2/M phases in iAAT-MSCs, with a notable increase in the cell cycle protein, Cyclin D1. Moreover, treatment with Cyclin D1 inhibitors showed that the increase in proliferation is due to Cyclin D1 and that the AAT protein is upstream and a positive regulator of Cyclin D1. Furthermore, AAT’s effect on Cyclin D1 is independent of the Wnt signaling pathway as there were no differences in the expression of regulatory proteins, including GSK3β and β-Catenin in iMSC and iAAT-MSCs. In summary, our results indicate that AAT gene insertion in an immortalized MSC cell line increases cell proliferation and growth by increasing Cyclin D1 expression and consequently causing cells to progress through the cell cycle at a significantly faster rate.

With the increasing demands for battery safety management, data-driven method becomes a promising solution for highly accurate battery state of health (SOH) estimation. However, the data-driven method faces problems of poor interpretability and high dependence on input features. This paper proposes a SOH estimation method that integrates data-driven model and signal analysis method. Specifically, the differential thermal voltammetry (DTV) analysis method is used to analyze aging characteristics to obtain features strongly related to battery aging and solve the problem of poor interpretability of data-driven methods. The use of local linear embedding method (LLE) for feature extraction has improved model efficiency. A data-driven model is constructed with the Bi-directional long short-term memory (Bi-LSTM) as the core, and the attention mechanism (AM) is added to focus on important parts of the sequence to further improve the accuracy of the model. The proposed method is validated based on the Oxford battery degradation dataset, and the results show that the proposed method achieves high accuracy and strong robustness in SOH estimation with a root mean square error (RMSE) maintained at about 0.4%. This method has the potential to be employed on cloud platforms or end-cloud collaboration systems for online implementation.

Due to the presence of the new magnetic component of magductance (or magnetic-inductace), the traditional scalar magnetic circuit theory is evolved into the vector magnetic circuit theory. Further research is still required to determine whether the vector magnetic circuit theory and the current electromagnetic theory are compatible with one another. In this paper, the reluctance and magductance parameters of the magnetic circuit are derived using electromagnetic field theory, vector magnetic circuit theory, and electrical circuit theory by taking a laminated magnetic core as an example. Additionally, based on the derived general expressions for the magnetic circuit parameters, the law of magnetic circuit parameters changing with magnetic circuit frequency is plotted and summarized, and the compatibility of electromagnetic field theory, vector magnetic circuit theory, and electrical circuit theory is analyzed. Finally, combined with the magnetoelectric power law, the derived general expressions for the magnetic circuit parameters have been verified by the experiments with the Epstein frame.

Abstract. Background:. Single-tablet regimen (STR) provides a convenient once-daily regimen for the prevention of human immunodeficiency virus (HIV) infection. Here, we investigated the safety and tolerability of coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a three-drug, STR for post-exposure prophylaxis (PEP) in Chinese individuals. Methods:. This was a prospective, open-label, single-arm trial conducted in a sexually transmitted diseases and acquired immunodeficiency syndrome clinic of a tertiary hospital in Beijing, China. Adults requiring PEP were prescribed BIC/FTC/TAF one pill once a day for 28 days. Clinical and laboratory data were collected and analyzed at baseline, weeks 2, 4, 8, 12, and 24. Results:. Of 112 participants enrolled in the study, 109 (97.3%) were male and the mean age was 30 ± 8 years. PEP completion was 96.4% (95% confidence interval: 91.1–99.0%). Two participants stopped PEP after 2 days because the source partner was identified as HIV uninfected. One participant was excluded due to hepatitis B virus infection according to the exclusion criteria. One discontinued due to the participant's decision. No participant acquired HIV through week 24. Adherence was 98.9% (standard deviation [SD]: 3.3%) by self-reporting and 98.5% (SD: 3.5%) by pill count. Only five participants experienced mild clinical adverse events attributed to the study drug (including headache, diarrhea, and nausea) and four participants had elevated serum creatinine (grade 1). Conclusions:. A once daily, STR of BIC/FTC/TAF used as PEP was safe and well-tolerated with a high rate of completion and adherence in Chinese. BIC/FTC/TAF may be a good option for PEP. Trial Registration:. ChiCTR.org.cn, ChiCTR2100048080

Abstract Background Intensive care is of great significance for very low birth weight infants (VLBWI). The Yangtze River Delta is the most ecomonically developed area in China. However, there are few data on the care practices and survival of VLBWI in this region. Objectives To investigate the prevalence, care practices and motality of VLBWI in Yangtze River Delta in China. Methods A multi-center retrospective investigation study was conducted at five tertiary hospitals within the Yangtze River Delta in China from January to December 2017. Clinical data included the general characteristics of the infants and the mothers, clinical prognosis, care practices in NICUs was collected by trained research members. Results During the study period, 1059 VLBWIs were included. Infants with birth weight

Abstract Background The combined association of triglyceride-glucose (TyG) index and different systolic blood pressure (SBP) levels with all-cause and cardiovascular mortality among the general population remains unclear. Methods In this study, 6245 individuals were from the National Health and Nutrition Examination Survey (1999–2002). The study endpoints were all-cause and cardiovascular mortality. Multivariate Cox proportional hazards regression models were used to explore the combined association of TyG index and different SBP levels with all-cause and cardiovascular mortality. Results During a mean follow-up period of 66.8 months, a total of 284 all-cause deaths (331/100000 person-years) and 61 cardiovascular deaths (66/100000 person-years) were recorded. Multivariate Cox regression analysis revealed that the combination of low TyG index and low SBP (

Abstract Background Acquired immunodeficiency syndrome (AIDS) is a chronic infectious disease characterized by consistent immune dysfunction. The objective of this study is to determine whether immune cell-related genes can be used as biomarkers for the occurrence of AIDS and potential molecular mechanisms. Methods A weighted gene co-expression network analysis was performed using the GSE6740 dataset from the Gene Expression Synthesis Database to identify the Hub gene, which contained microarray data from HIV-1 positive (HIV-1+) and HIV-1 negative (HIV-1−) individuals. The HIV-1+-related differentially expressed genes were then identified using the limma package. Subsequently, the characteristic immune cell-related genes were identified as diagnostic biomarkers for HIV-1+ using the random forest model (RF), support vector machine model, and generalized linear model. Results MEdarkgreen exhibited the strongest correlation with HIV clinical features of any of these modules. As the best model for diagnosing HIV-1±, RF was used to select four critical immune cell-related genes, namely, ARRB1, DPEP2, LTBP3, and RGCC, and a nomogram model was created to predict the occurrence of HIV-1 infection based on four key immune cell-related genes. Diagnostic genes were shown to be engaged in immune-related pathways, suggesting that immunological molecules, immune cells, and immune pathways all have a role in HIV-1 infection. The CTD database was explored for prospective medications or molecular compounds that might be utilized to treat HIV-1+ patients. = Moreover, in HIV-1+ individuals, the ceRNA network revealed that ARRB1, DPEP2, LTBP3, and RGCC could be regulated by lncRNAs through the corresponding miRNAs. Ultimately, RT-PCR results from clinical blood samples demonstrated that the four diagnostic genes were significantly downregulated in HIV-1+ patients. Conclusion We screened four immune cell-related genes, ARRB1, DPEP2, LTBP3, and RGCC, which may be considered as the diagnostic markers for HIV-1/AIDS. Our findings reveal that immune related genes and pathways involved in HIV-1 pathogenesis were regulated on both genetic and epigenetic levels by constructing a ceRNA network associated with lncRNA.

Probiotics play beneficial roles in improving the host intestinal microecological balance and improving the host health level and health state. It mainly affects the host health by regulating the intestinal microbiota and participating in the immune regulation of various diseases, thus improving the gastrointestinal physiology. Probiotics have considerable potential in the prevention and treatment of gastrointestinal diseases, and a deeper understanding of the mechanisms of their interaction with gut flora and immune regulation are needed. In this paper, the distribution and colonization of probiotics in the intestinal tract, the regulation of probiotics on intestinal flora and intestinal function, and the relationship between probiotics and immune regulation are briefly discussed, in order to provide reference for the future research on the interaction between probiotics and intestinal flora and the clinical application of probiotics.

Objectives: Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiomyopathy. However, few studies have investigated the prognosis of familial HCM (FHCM) through clinical data. The purpose of this study was to compare the clinical outcomes of FHCM and non-FHCM through propensity score matching analysis. Methods and results: The cohort study included 1243 patients with HCM between 1996 and 2013 in Fuwai Hospital, Chinese Academy of Medical Sciences, among whom 125 patients had FHCM. During a mean follow-up of 7.6 ± 3.8 years (interquartile range: (IQR) 5.0–10.0 years), 217 (16.57%) of the 1243 patients had died, including 3 patients who underwent cardiac transplantation. Using 30 demographic and clinical variables, a 4:1 propensity score matched cohort for FHCM was established. The stepwise variable selection procedure for the Cox proportional hazards model was performed to identify the factors associated with mortality and competing risk regression analysis was performed to analyze the competitive risk of cardiovascular and non-cardiovascular mortality. The results showed that FHCM patients had a higher risk of cardiovascular mortality/cardiac transplantation (log-rank χ2 = 6.8, P = 0.0084) and an increased tendency of sudden cardiac death (SCD) (log-rank χ2 = 3.2, P = 0.074) compared with non-FHCM patients, but there was no difference in all-cause mortality (log-rank χ2 = 2.7, P = 0.1) between the two groups. Moreover, the Cox model showed that FHCM was an independent prognostic predictor for cardiovascular mortality/cardiac transplantation in HCM patients. Conclusion: FHCM patients had a higher risk of cardiovascular mortality/cardiac transplantation and a higher tendency of SCD than non-FHCM patients, but there was no difference in all-cause mortality. Moreover, FHCM was an independent prognostic predictor for cardiovascular mortality/cardiac transplantation in HCM patients.

Diverse molecular processes regulate the interactions between insect herbivores and their host plants. When plants are exposed to insects, elicitors induce plant defenses, and complex physiological and biochemical processes are triggered, such as the activation of the jasmonic acid (JA) and salicylic acid (SA) pathways, Ca2+ flux, reactive oxygen species (ROS) burst, mitogen-activated protein kinase (MAPK) activation, and other responses. For better adaptation, insects secrete a large number of effectors to interfere with plant defenses on multiple levels. In plants, resistance (R) proteins have evolved to recognize effectors and trigger stronger defense responses. However, only a few effectors recognized by R proteins have been identified until now. Multi-omics approaches for high-throughput elicitor/effector identification and functional characterization have been developed. In this review, we mainly highlight the recent advances in the identification of the elicitors and effectors secreted by insects and their target proteins in plants and discuss their underlying molecular mechanisms, which will provide new inspiration for controlling these insect pests.

Over the last two decades, there has been increasing interest in investigating the connection between the Asian-Pacific Oscillation (APO) and weather and climate on regional and global scales, but the impacts of the APO on sea surface temperature (SST) remains unclear. Using the multisource reanalysis dataset and observed SST data, we evaluated the interannual relationship between the APO and SST in the North Atlantic (NASST) during the period 1979–2016. The results show that there exists a statistically significant positive interannual relationship between APO and NASST and this connection can be attributed to the Rossby wave train that originates in Asia and propagates to Europe, which is triggered by the APO forcing. Further examination revealed that the cloud radiation, air–sea heat exchange and oceanic dynamic process induced by APO are crucial in modulating the interannual variability of the NASST. Additionally, the numerical simulation results from the linear baroclinic model also provide additional evidence for this linkage.

The two-component system (TCS), consisting of histidine kinases (HKs), histidine phosphotransfer proteins (HPs) and response regulators (RRs) in eukaryotes, plays pivotal roles in regulating plant growth, development, and responses to environment stimuli. However, the TCS genes were poorly characterized in rapeseed, which is an important tetraploid crop in Brassicaceae. In this work, a total of 182 BnaTCS genes were identified, including 43 HKs, 16 HPs, and 123 RRs, which was more than that in other crops due to segmental duplications during the process of polyploidization. It was significantly different in genetic diversity between the three subfamilies, and some members showed substantial genetic differentiation among the three rapeseed ecotypes. Several hormone- and stress-responsive cis-elements were identified in the putative promoter regions of BnaTCS genes. Furthermore, the expression of BnaTCS genes under abiotic stresses, exogenous phytohormone, and biotic stresses was analyzed, and numerous candidate stress-responsive genes were screened out. Meanwhile, using a natural population with 505 B. napus accessions, we explored the genetic effects of BnaTCS genes on salt tolerance by association mapping analysis and detected some significant association SNPs/genes. The result will help to further understand the functions of TCS genes in the developmental and stress tolerance improvement in B. napus.

Prussian blue analogs (PBAs) are effective precatalysts for the oxygen evolution reaction (OER); however, the underlying mechanism of their electrochemical activation is still not well elucidated. In this study, we designed and constructed PBA-based precatalysts to determine the electrochemical activation mechanism and achieve high-efficiency OER. The PBAs undergo in situ electrochemical transformation to form the corresponding metal (oxy)hydroxides (M(O)OH) as the true OER catalyst. More importantly, the hexacyanoferrate ligands undergo repetitive interfacial coordination/etching with/from M(O)OH during the activation process. The distinct mechanism could achieve in situ Fe doping and enable defect incorporation. The defect-enriched Fe-NiOOH derived from a well-designed NiHCF/Ni(OH)2 precatalyst requires a low overpotential of 227 mV to reach a current density of 10 mA cm−2 and works stably at 130 mA cm−2 over 100 h. This study provides fundamental insights into the electrochemical activation mechanism for developing advanced precatalysts for OER.