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Abstract Objective This study aims to construct and evaluate an individualized nomogram for predicting the risk of lower limb lymphedema after cervical cancer surgery. Healthcare professionals can utilize line chart models to predict the probability of postoperative lower limb lymphedema in different patients, allowing for the early identification of high-risk patients and facilitating early prevention and treatment. Methods A retrospective study was conducted among 411 cervical cancer patients treated at our hospital from May 2021 to December 2023. The patients were randomly divided into a modeling group (313 cases) and a validation group (98 cases) according to an approximate 3:1 ratio. The modeling group was further divided into a lower limb lymphedema group (61 cases) and a non-lower limb lymphedema group (252 cases) based on the presence of postoperative lower limb lymphedema. Multiple factors Logistic regression was used to identify risk factors, and a nomogram was constructed using R software version 4.0.2, with internal and external validation performed. Results Risk factors for lower limb lymphedema following cervical cancer surgery include age 60 years or older, a Body Mass Index (BMI) of 24 kg/m² or higher, hypertension, the removal of 30 or more lymph nodes, adjuvant radiotherapy and chemotherapy, and prolonged standing for six hours or more (P

Abstract Background Vital pulp therapy (VPT) has recently been reported as an effective approach for preventing and treating carious pulp injury in permanent teeth. Compared with root canal treatment (RCT), which involves complete removal of the pulp tissue, VPT effectively maintains pulp vitality and retains the physiological functions of the pulp. In the research pool, large-scale randomized controlled trials evaluating the treatment outcome of VPT using calcium silicate cements and RCT in cariously exposed permanent teeth are lacking. Here, we present a monocentric clinical protocol to compare the effects of VPT using iRoot BP Plus (Innovative Bioceramix, Vancouver, BC, Canada) as a pulp-capping material with RCT. Methods The proposed trial is an open-label, single-centre, randomized, controlled, noninferiority trial. In total, 462 patients will be included in this trial according to the following criteria: adult patients (18–50 years old), pulp exposure during the treatment of deep caries in mature permanent teeth, a diagnosis of reversible or partially irreversible pulpitis without apical translucency on X-ray, without periodontitis or systemic disease. Patients with signed informed consent forms will be enrolled and randomly divided into two groups (VPT and RCT) with a balanced treatment allocation (1:1). Clinical evaluations will be conducted at baseline and at 3, 6, 12, and 24 months after treatment, with the potential for extension. The primary outcome measure will be the duration of success. The secondary outcomes will include the success rate at the 1-year follow-up and any adverse reactions. The Kaplan‒Meier method and log-rank test will be used to compare the duration of success of both treatments. For other outcomes, the χ 2 test or Fisher’s exact test will be used for categorical variables, and the t test or Mann‒Whitney U test will be used for continuous variables to assess the differences between groups. Discussion The results of this trial will provide a clinical reference for selecting treatments for carious pulp injuries in permanent teeth. Trial registration ClinicalTrials.gov ChiCTR2100051369. The study has been registered in the Chinese Clinical Trial Registry (ChiCTR) ( www.chictr.org.cn ). Registered on 21 September 2021

Abstract Background Staphylococcus aureus is one of the most important bacteria in human colonization and infection. Clonal complex1 (CC1) is one of the largest and most important S. aureus CCs, and it is a predominant clone in S. aureus colonization and can cause a series of S. aureus infections including bloodstream infections. No studies on the relationship of CC1 S. aureus between colonization and infection have been published. Methods To figure out if there are some significant factors in CC1 S. aureus help its colonization or infection, 15 CC1 S. aureus isolates including ten from colonization and five from bloodstream infections were enrolled in this study. Whole-genome sequencing and bioinformatics analysis were performed. Results Virulence factor regulators XdrA, YSIRK signal peptide, CPBP family and OmpR family specifically found in infection isolates can promote virulence factors and enhance the pathogenicity of S. aureus. In addition, some significant differences in metabolism and human diseases were discovered between colonization and infection. Fst family of type I toxin–antitoxin system that mainly maintains stable inheritance was specifically found in CC1 S. aureus colonization isolates and might help S. aureus survive for colonization. No significant differences in genomic evolutionary relationship were found among CC1 S. aureus isolates between colonization and infection. Conclusions Virulence factor regulators and metabolic state can promote CC1 S. aureus pathogenic process compared with colonization, and it seems that the strains of colonization origin cannot have pathogenic potential. Experimental confirmation and a bigger number of CC1 S. aureus strains are necessary for further study about the details and mechanism between colonization and infection.

Abstract Since October 2023, a significant outbreak of Mycoplasma Pneumoniae Pneumonia (MPP) has been observed in children in northern China. Chinese health authorities have attributed this epidemiological to immune debt resulting from the relaxation of coronavirus disease 2019 (COVID-19) control measures. This study described the epidemiological features of Mycoplasma pneumoniae (MP) prevalence in children and developed a straightforward prediction model to differentiate between MPP and viral pneumonia in children. The infection rate of MP in children notably increased from 8.12 in 2022 to 14.94% in 2023, peaking between October and November, especially among school-age children. Logistic regression screening identified four key indicators: Age, D-Dimer levels, erythrocyte sedimentation rate, and gender. The developed nomogram exhibited a receiver operator characteristic curve-area under the curve (ROC-AUC) of 0.858, with external validation confirming an ROC-AUC of 0.794. This study examined the epidemiological characteristics of MPP prevalence in children in Shandong Province during and after the COVID-19 pandemic. An early predict model was developed and validated to differentiate between Mycoplasma Pneumoniae and viral infections.

Abstract Anaplastic thyroid cancer (ATC) is among the most aggressive and metastatic malignancies, often resulting in fatal outcomes due to the lack of effective treatments. Prosapogenin A (PA), a bioactive compound prevalent in traditional Chinese herbs, has shown potential as an antineoplastic agent against various human tumors. However, its effects on ATC and the underlying mechanism remain unclear. Here, we demonstrate that PA exhibits significant anti-ATC activity both in vitro and in vivo by inducing GSDME-dependent pyroptosis in ATC cells. Mechanistically, PA promotes lysosomal membrane permeabilization (LMP), leading to the release of cathepsins that activate caspase 8/3 to cleave GSDME. Remarkably, PA significantly upregulates three key functional subunits of V-ATPase—ATP6V1A, ATP6V1B2, and ATP6V0C—resulting in lysosomal over-acidification. This over-acidification exacerbates LMP and subsequent lysosomal damage. Neutralization of lysosomal lumen acidification or inhibition/knockdown of these V-ATPase subunits attenuates PA-induced lysosomal damage, pyroptosis and growth inhibition of ATC cells, highlighting the critical role for lysosomal acidification and LMP in PA’s anticancer effects. In summary, our findings uncover a novel link between PA and lysosomal damage-dependent pyroptosis in cancer cells. PA may act as a V-ATPase agonist targeting lysosomal acidification, presenting a new potential therapeutic option for ATC treatment.

Abstract Single‐atom catalysts (SACs) with edge‐located metal active sites exhibit superior oxygen reduction reaction (ORR) performance due to their narrower energy gap and higher electron density. However, controllably designing such active sites to fully reveal their advantages remains challenging. Herein, rich edge‐located Fe‐N4 active sites anchored in hierarchically porous carbon nanofibers (denoted as e1‐Fe‐N‐C) are fabricated via an in situ zinc‐assisted thermal etching strategy. The e1‐Fe‐N‐C catalyst demonstrates superior alkaline ORR activity compared to counterparts with fewer edge‐located Fe‐N4 sites and commercial Pt/C. Density functional theory calculations show that the accumulation of more negative charges near the Fe‐N and the formation of partially reduced Fe state in the edge‐located Fe‐N4 sites reduce the energy barrier for the ORR process. Additionally, the unique hierarchically porous structures with mesopores and macropores facilitate full utilization of the active sites and enhance long‐range mass transfer. The zinc–air battery (ZAB) assembled with e1‐Fe‐N‐C has a peak power density of 198.9 mW cm−2, superior to commercial Pt/C (152.3 mW cm−2). The present strategy by facile controlling the amount of the zinc acetate template systematically demonstrates the superiority of edge‐located Fe‐N4 sites, providing a new design avenue for rational defect engineering to achieve high‐performance ORR.

Bamboo resources have garnered significant global attention due to their excellent capacity for regeneration and high yield. Rhombic-spot disease, a substantial threat to fishscale bamboo (Phyllostachys heteroclada), is primarily caused by Neostagonosporella sichuanensis. This study first reported the genome assemblies and characteristics of two N. sichuanensis isolates using PacBio and Illumina sequencing platforms. The genomes of N. sichuanensis strain SICAUCC 16–0001 and strain SICAUCC 23–0140, with sizes of 48.0 Mb and 48.4 Mb, respectively, revealed 10,289 and 10,313 protein-coding genes. Additionally, they contained 34.99 and 34.46% repetitive sequences within AT-rich regions, with notable repeat-induced point mutation activity. Comparative genome analysis identified 1,049 contracted and 45 expanded gene families in the genome of N. sichuanensis, including several related to pathogenicity. Several gene families involved in mycotoxin metabolism, secondary metabolism, sterol biosynthesis and transport, and cell wall degradation were contracted. Compared to most analyzed necrotrophic, hemibiotrophic, and phaeosphaeriacous pathogens, the genomes of two N. sichuanensis isolates exhibited fewer secondary metabolite enzymes, carbohydrate-active enzymes, plant cell wall degrading enzymes, secreted proteins, and effectors. Comparative genomics analysis suggested that N. sichuanensis shares more similar characteristics with hemibiotrophic pathogens. Based on single carbon source tests, N. sichuanensis strains demonstrated a higher potential for xylan decomposition than pectin and cellulose. The proportion of cell wall-degrading enzyme effectors occupied a high proportion of the total effectors of the N. sichuanensis genomes. These findings provide valuable insights into uncovering the pathogenesis of N. sichuanensis toward the efficient management of rhombic-spot disease of fishscale bamboo.

Abstract Background Idiopathic pulmonary fibrosis is a persistent disease of the lung interstitium for which there is no efficacious pharmacological therapy. Protodioscin, a steroidal saponin, possesses diverse pharmacological properties; however, its function in pulmonary fibrosis is yet to be established. Hence, in this investigation, it was attempted to figure out the anti-pulmonary fibrosis influences of protodioscin and its pharmacological properties related to oxidative stress. Methods A mouse lung fibrosis model was generated using tracheal injections of bleomycin, followed by intraperitoneal injection of different concentrations of protodioscin, and the levels of oxidative stress and fibrosis were detected in the lungs. Multiple fibroblasts were treated with TGF-β to induce their transition to myofibroblasts. It was attempted to quantify myofibroblast markers’ expression levels and reactive oxygen species levels as well as Nrf2 activation after co-incubation of TGF-β with fibroblasts and different concentrations of protodioscin. The influence of protodioscin on the expression and phosphorylation of p62, which is associated with Nrf2 activation, were detected, and p62 related genes were predicted by STRING database. The effects of Nrf2 inhibitor or silencing of the Nrf2, p62 and NBR1 genes, respectively, on the activation of Nrf2 by protodioscin were examined. The associations between p62, NBR1, and Keap1 in the activation of Nrf2 by protodioscin was demonstrated using a co-IP assay. Nrf2 inhibitor were used when protodioscin was treated in mice with pulmonary fibrosis and lung tissue fibrosis and oxidative stress levels were detected. Results In vivo, protodioscin decreased the levels of fibrosis markers and oxidative stress markers and activated Nrf2 in mice with pulmonary fibrosis, and these effects were inhibited by Nrf2 inhibitor. In vitro, protodioscin decreased the levels of myofibroblast markers and oxidative stress markers during myofibroblast transition and promoted Nrf2 downstream gene expression, with reversal of these effects after Nrf2, p62 and NBR1 genes were silenced or Nrf2 inhibitors were used, respectively. Protodioscin promoted the binding of NBR1 to p62 and Keap1, thereby reducing Keap1-Nrf2 binding. Conclusion The NBR1-p62-Nrf2 axis is targeted by protodioscin to reduce oxidative stress and inhibit pulmonary fibrosis. Graphical Abstract

Abstract Gastric cancer is a highly prevalent disease that poses a serious threat to public health. In clinical practice, gastroscopy is frequently used by medical practitioners to screen for gastric cancer. However, the symptoms of gastric cancer at different stages of advancement vary significantly, particularly in the case of early gastric cancer (EGC). The manifestations of EGC are often indistinct, leading to a detection rate of less than 10%. In recent years, researchers have focused on leveraging deep learning algorithms to assist medical professionals in detecting EGC and thereby improve detection rates. To enhance the ability of deep learning to detect EGC and segment lesions in gastroscopic images, an Improved Mask R-CNN (IMR-CNN) model was proposed. This model incorporates a “Bi-directional feature extraction and fusion module” and a “Purification module for feature channel and space” based on the Mask R-CNN (MR-CNN). Our study includes a dataset of 1120 images of EGC for training and validation of the models. The experimental results indicate that the IMR-CNN model outperforms the original MR-CNN model, with Precision, Recall, Accuracy, Specificity and F1-Score values of 92.9%, 95.3%, 93.9%, 92.5% and 94.1%, respectively. Therefore, our proposed IMR-CNN model has superior detection and lesion segmentation capabilities and can effectively aid doctors in diagnosing EGC from gastroscopic images.

We generated an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells (PBMCs) of a healthy 40-year-old Chinese Han female, using non-integrated reprogramming technology. The established iPSC line, SDCHi011-A, expressed pluripotency marker and could differentiate into cells of three germ layers in vitro with normal karyotype. This cell line is a valuable resource as a control line for stem cell research of disease models and molecular pathogenesis.

Abstract Integrated multimodal imaging in theranostics nanomaterials offers extensive prospects for precise and noninvasive cancer treatment. Precisely controlling the structural evolution of plasmonic nanoparticles is crucial in the development of photothermal agents. However, previous successes have been limited to static assemblies and single‐component structures. Here, an activatable plasmonic theranostics system utilizing self‐assembled 1D silver‐coated gold nanochains (1D nanochains) is presented for precise tumor diagnosis and effective treatment. The absorbance of the adaptable core–shell chain structure can shift from visible to near‐infrared (NIR) regions due to the fusion between nearby Au@Ag nanoparticles induced by elevated H2O2 levels in the tumor microenvironment (TME), resulting in the creation of a novel 3D aggregates with strong NIR absorption. With a high photothermal conversion efficiency of 60.2% at 808 nm, nanochains utilizing the TME‐activated characteristics show remarkable qualities for photoacoustic imaging and significantly limit tumor growth in vivo. This study may pave the way for precise tumor diagnosis and treatment through customizable, optically tunable adaptive plasmonic nanostructures.

The pattern of itching in patients with atopic dermatitis has not been systematically studied. Therefore, this study aimed to assess the pattern of itching in adults with atopic dermatitis using questionnaires to assess for a circadian rhythm of itching in participating patients at a single institution (n = 241). A self-report questionnaire was used to assess circadian rhythm and intensity of itching in patients. In addition, the patients’ disease severity (Eczema Area and Severity Index [EASI]) and quality of life (Dermatology Life Quality Index [DLQI]) were assessed. Itching occurred most frequently (74.69%) and with the greatest severity (62.66%) between 20:00 and 00:00, and the least number of patients (25.31%) experienced itching between 04:00 and 08:00. The DLQI and EASI scores both correlated with the average and maximum itch intensity (r = 0.582, r = 0.533, respectively; r = 0.539, r = 0.517, respectively; p

Pyruvate dehydrogenase kinase 1 (PDK1) phosphorylates the pyruvate dehydrogenase complex, which inhibits its activity. Inhibiting pyruvate dehydrogenase complex inhibits the tricarboxylic acid cycle and the reprogramming of tumor cell metabolism to glycolysis, which plays an important role in tumor progression. This study aims to elucidate how PDK1 promotes breast cancer progression. We found that PDK1 was highly expressed in breast cancer tissues, and PDK1 knockdown reduced the proliferation, migration, and tumorigenicity of breast cancer cells and inhibited the HIF-1α (hypoxia-inducible factor 1α) pathway. Further investigation showed that PDK1 promoted the protein stability of HIF-1α by reducing the level of ubiquitination of HIF-1α. The HIF-1α protein levels were dependent on PDK1 kinase activity. Furthermore, HIF-1α phosphorylation at serine 451 was detected in wild-type breast cancer cells but not in PDK1 knockout breast cancer cells. The phosphorylation of HIF-1α at Ser 451 stabilized its protein levels by inhibiting the interaction of HIF-1α with von Hippel-Lindau and prolyl hydroxylase domain. We also found that PDK1 enhanced HIF-1α transcriptional activity. In summary, PDK1 enhances HIF-1α protein stability by phosphorylating HIF-1α at Ser451 and promotes HIF-1α transcriptional activity by enhancing the binding of HIF-1α to P300. PDK1 and HIF-1α form a positive feedback loop to promote breast cancer progression.

Phospholipase C (PLC) is an essential enzyme involved in lipid signaling pathways crucial for regulating plant growth and responding to environmental stress. In sorghum, 11 PLC genes have been identified, comprising 6 PI-PLCs and 5 NPCs. Through phylogenetic and interspecies collinearity analyses, structural similarities between SbPLCs and ZmPLCs proteins have been observed, with a particularly strong collinearity between SbPLCs and OsPLCs. Promoter function analysis has shown that SbPLCs are significantly enriched under abiotic stress and hormonal stimuli, like ABA, jasmonic acid, drought, high temperature, and salt. Gene co-expression networks, constructed using a weighted gene co-expression network analysis (WGCNA), highlight distinct expression patterns of SbPLC1, SbPLC3a, and SbPLC4 in response to abiotic stress, providing further insights into the expression patterns and interactions of SbPLCs under various environmental stimuli. qRT-PCR results reveal variations in expression levels among most SbPLCs members under different stress conditions (drought, NaCl, NaHCO3), hormone treatments (ABA), and developmental stages, indicating both specific and overlapping expression patterns. This comprehensive analysis offers valuable insights into the roles of SbPLCs in sorghum, shedding light on their specific expression patterns, regulatory elements, and protein interactions across different environmental stimuli and developmental stages.

This work was conducted mainly to provide a healthy and safe monitoring system for the elderly living in the home environment. In this paper, two different target fall detection schemes are proposed based on whether the target is visible or not. When the target is visible, a vision-based fall detection algorithm is proposed, where an image of the target captured by a camera is transmitted to the improved You Only Look Once version 5s (YOLOv5s) model for posture detection. In contrast, when the target is invisible, a WiFi-based fall detection algorithm is proposed, where channel state information (CSI) signals are used to estimate the target’s posture with an improved long short-term memory (LSTM) model. In the improved YOLOv5s model, adaptive picture scaling technology named Letterbox is used to maintain consistency in the aspect ratio of images in the dataset, and the weighted bidirectional feature pyramid (BiFPN) and the attention mechanisms of squeeze-and-excitation (SE) and coordinate attention (CA) modules are added to the Backbone network and Neck network, respectively. In the improved LSTM model, the Hampel filter is used to eliminate the noise from CSI signals and the convolutional neural network (CNN) model is combined with the LSTM to process the image made from CSI signals, and thus the object of the improved LSTM model at a point in time is the analysis of the amplitude of 90 CSI signals. The final monitoring result of the health status of the target is the result of combining the fall detection of the improved YOLOv5s and LSTM models with the physiological information of the target. Experimental results show the following: (1) the detection precision, recall rate, and average precision of the improved YOLOv5s model are increased by 7.2%, 9%, and 7.6%, respectively, compared with the original model, and there is almost no missed detection of the target; (2) the detection accuracy of the improved LSTM model is improved by 15.61%, 29.36%, and 52.39% compared with the original LSTM, CNN, and neural network (NN) models, respectively, while the convergence speed is improved by 90% compared with the original LSTM model; and (3) the proposed algorithm can meet the requirements of accurate, real-time, and stable applications of health monitoring.

Background and objectivesPrevious observational studies have established a connection between bronchiectasis and inflammatory bowel disease (IBD), but none of these studies have provided a clear explanation for the underlying cause of this relationship. The present study thus implemented Mendelian randomization (MR) design to explore possible bidirectional relationships between IBD and bronchiectasis risk, with an additional focus on Crohn’s disease (CD) and ulcerative colitis (UC) as IBD subtypes.Materials and methodsA large genome-wide association study (GWAS)-derived data pool was leveraged to examine the relationships between bronchiectasis and IBD, CD, and UC. Two-sample MR analyses were performed with an inverse variance weighted (IVW) approach supplemented with the MR-Egger and weighted median methods. Sensitivity analyses were used to further assess the reliability of the main MR study findings. The possibility of reverse causation was also evaluated using a reverse MR approach.ResultsThe IVW MR analytical approach revealed that IBD (p = 0.074), UC (p = 0.094), and CD (p = 0.644) had no significant impact on the incidence of bronchiectasis, with the converse also being true (p = 0.471, p = 0.700, and p = 0.099, respectively).ConclusionThis MR analysis demonstrated that the higher occurrence of bronchiectasis in patients with IBD is not caused by genetic predisposition.

Abstract Background Acute lung injury (ALI) is a severe disease that can lead to acute respiratory distress syndrome (ARDS), characterized by intractable hypoxemia, poor lung compliance, and respiratory failure, severely affecting patients' quality of life. The pathogenesis of ALI has not been fully elucidated yet, and sepsis is an important cause of ALI. Among the organ injuries caused by sepsis, the lungs are the earliest damaged ones. Radix cyathulae is reported to have analgesic, anti-inflammatory, and anti-aging effects. Cyasterone is extracted from Radix cyathulae. However, it is not known whether cyasterone has protective effects for ALI. This study aims to investigate the effect of cyasterone on sepsis-related ALI and its mechanism. Methods We used the cecal ligation peferation (CLP) method to establish a mouse sepsis model, and cyasterone was given intraperitoneally on days 1–3 to observe its preventive effect on sepsis-related acute lung injury. Primary murine peritoneal macrophages were used to investigate the molecular mechanism of cyasterone in vitro. Results Cyasterone pretreatment inhibits pro-inflammatory cytokine production, NLRP3 inflammasome activation, and oxidative stress in vivo and in vitro. In addition, cyasterone attenuates sepsis-induced ALI by activating nuclear factor erythroid2-related factor (Nrf2), which may be associated with AKT(Ser473)/GSK3β(Ser9) pathway activation. Conclusions Cyasterone defends against sepsis-induced ALI by inhibiting inflammatory responses and oxidative stress, which depends heavily on the upregulation of the Nrf2 pathway through phosphorylation of AKT(Ser473)/GSK3β(Ser9). These results suggest cyasterone may be a valuable drug candidate for preventing sepsis-related ALI.

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that lacks effective treatment modalities. Once patients are diagnosed with IPF, their median survival is approximately 3–5 years. PPARγ is an important target for the prevention and treatment of pulmonary fibrosis. Asarinin is a lignan compound that can be extracted from food plant Asarum heterotropoides. In this study, we investigated the therapeutic effects of asarinin in a pulmonary fibrosis model constructed using bleomycin in mice and explored the underlying mechanisms. Intraperitoneal administration of asarinin to mice with pulmonary fibrosis showed that asarinin effectively attenuated pulmonary fibrosis, and this effect was significantly inhibited by the PPARγ inhibitor GW9662. Asarinin inhibited TGF-β1-induced fibroblast-to-myofibroblast transition in vitro, while GW9662 and PPARγ gene silencing significantly inhibited this effect. In addition, asarinin inhibited not only the canonical Smad pathway of TGF-β but also the non-canonical AKT and MAPK pathways by activating PPARγ. Our study demonstrates that asarinin can be used as a therapeutic agent for pulmonary fibrosis, and that PPARγ is its key target.

Abstract GBA1 variants are important risk factors for Parkinson’s disease (PD). Most studies assessing GBA1-related PD risk have been performed in European-derived populations. Although the coding region of the GBA1 gene in the Chinese population has been analyzed, the sample sizes were not adequate. In this study, we aimed to investigate GBA1 variants in a large Chinese cohort of patients with PD and healthy control and explore the associated clinical characteristics. GBA1 variants in 4034 patients and 2931 control participants were investigated using whole-exome and whole-genome sequencing. The clinical features of patients were evaluated using several scales. Regression analysis, chi-square, and Fisher exact tests were used to analyze GBA1 variants and the clinical symptoms of different groups. We identified 104 variants, including 8 novel variants, expanding the spectrum of GBA1 variants. The frequency of GBA1 variants in patients with PD was 7.46%, higher than that in the control (1.81%) (P

Information transmission plays a crucial role across various fields, including physics, engineering, biology, and society. The efficiency of this transmission is quantified by mutual information and its associated information capacity. While studies in closed systems have yielded significant progress, understanding the impact of non-equilibrium effects on open systems remains a challenge. These effects, characterized by the exchange of energy, information, and materials with the external environment, can influence both mutual information and information capacity. Here, we delve into this challenge by exploring non-equilibrium effects using the memoryless channel model, a cornerstone of information channel coding theories and methodology development. Our findings reveal that mutual information exhibits a convex relationship with non-equilibriumness, quantified by the non-equilibrium strength in transmission probabilities. Notably, channel information capacity is enhanced by non-equilibrium effects. Furthermore, we demonstrate that non-equilibrium thermodynamic cost, characterized by the entropy production rate, can actually improve both mutual information and information channel capacity, leading to a boost in overall information transmission efficiency. Our numerical results support our conclusions.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease for which there is a lack of effective pharmacological treatments. Hirudin, a natural peptide extracted from leeches, has been used for broad pharmacological purposes. In this study, we investigated the therapeutic effects of hirudin on IPF and its related mechanism of action. By constructing a mouse model of pulmonary fibrosis and treating it with hirudin in vivo, we found that hirudin exerted anti-fibrotic, anti-oxidative, and anti-fibroblast senescence effects. Moreover, using an in vitro model of stress-induced premature senescence in primary mouse lung fibroblasts and treating with hirudin, we observed inhibition of fibroblast senescence and upregulation of PGC1-alpha and Sirt3 expression. However, specific silencing of PGC1-alpha or Sirt3 suppressed the anti-fibroblast senescence effect of hirudin. Thus, the PGC1-alpha/Sirt3 pathway mediates the anti-fibroblast senescence effect of hirudin, potentially serving as a molecular mechanism underlying its anti-fibrosis and anti-oxidative stress effects exerted on the lungs.

Urbanization accelerates habitat fragmentation and leads to the decline of biodiversity in cities. Urban greenway landscapes provide not only social functions but also important ecological services. In this study, taxonomic richness, abundance, diversity, and the distribution of soil meso- and microfauna were investigated in three different urban greenway landscapes to assess their environmental quality. Urban greenway landscapes that had a richer tree species composition, higher deciduous tree ratios, wider ecological greenspace, moderate soil temperature and moisture, and lower soil bulk density and less lead were conducive to the survival and development of the soil meso- and microfauna community. Different soil fauna groups had varied responses to different environmental conditions in urban greenway landscapes. Microarthropods were more sensitive to plant communities; in contrast, soil moisture was the most important abiotic driver for hygrophilous meso-micro fauna. Our study highlights the importance of deciduous trees for their rich litter input, and the wide ecological greenspace for its buffering effect on various disturbances, which promote the conservation of biodiversity in urban greenway landscapes.

We recruited a healthy 6-year-old Chinese Han male, obtained his peripheral blood mononuclear cells (PBMCs) and successfully established induced pluripotent stem cells (iPSC) line using non-integrated reprogramming technology. The iPSC line possessed normal karyotype, expressed pluripotency markers and could differentiate into three germ layers in vitro. This cell line will serve as an available control in the research of molecular pathogenesis and a basis for disease modeling.

Sargentodoxa cuneata is a traditional Chinese herb commonly used for the treatment of ulcerative colitis (UC) in clinical practice. However, the effects of total flavonoids of Sargentodoxa cuneata (TFSc) remain unclear. In this study, we explored the effects and mechanisms of action of TFSc in mice with dextran sulfate sodium-induced UC. The TFSc components were identified using liquid chromatography-tandem mass spectrometry. Mice with UC were orally administered TFSc to evaluate its effects on colon and liver damage. Changes in gut microbiota were analyzed using 16S rRNA gene sequencing. Moreover, the levels of short-chain fatty acids (SCFAs) and few organic acids in the intestinal contents were measured. Furthermore, the correlation amongst gut flora, SCFAs, and organic acids was studied. A total of 304 compounds were identified. TFSc alleviated the symptoms of UC in mice, inhibited weight loss, reduced the disease activity index, and improved colon shortening along with cardiac and hepatic indices. Furthermore, TFSc mitigated pathological changes in the colon and liver, and reduced the TNF-α levels in colon tissues of mice with UC. TFSc also modulated intestinal flora disorders, increased the levels of four SCFAs (isocaproic acid, 3-hydroxyisovaleric acid, isobutyric acid, and ethylmethylacetic acid), and decreased the levels of two organic acids (malonic acid and succinic acid). The differential regulation of SCFAs and organic acids by TFSc was strongly associated with specific gut flora. TFSc showed potential for improving colon and liver injury in mice with UC by regulating the intestinal flora and associated metabolites (SCFAs and organic acids). These findings provide new evidence for developing TFSc as a drug for treating UC and UC-related liver injuries.

BackgroundUlcerative colitis (UC) is a refractory disease worldwide. Liver injury can be found clinically with UC, and now, it is found that gut dysbiosis is an important mechanism in the pathogenesis of UC. Sargentodoxa cuneata has been used as a traditional Chinese medicine and is commonly used clinically for the treatment of UC. The main objective of this study was to investigate the intrinsic mechanisms of Sargentodoxa cuneata in the treatment of UC and its associated liver injuries from the perspective of intestinal flora and related metabolites.MethodsUltra-performance liquid chromatography-mass spectrometry was used to identify the components in the aqueous extract of Sargentodoxa cuneata (AESc). Mice with UC induced by dextran sulfate sodium were used to study the effects of AESc on UC and its associated liver injuries. Furthermore, 16S rRNA gene sequencing and analysis were performed on intestinal contents, and correlation analysis of intestinal flora with short-chain fatty acids (SCFAs) and organic acids was performed.ResultsA total of 114 compounds were identified in AESc. AESc improved disease activity index scores, liver index, and colon length in mice with UC and had a good protective effect on intestine and liver injuries. Moreover, the administration of AESc regulated gut microbiota dysbiosis and the levels of a few SCFAs and organic acids in mice with UC. In addition, the correlation analysis results showed that the Megamonas and Bifidobacterium were the key intestinal flora related to the levels of differential SCFAs and organic acids in mice with UC after AESc intervention.ConclusionAESc has a good protective effect on UC and UC related liver injuries. Modulation of the intestinal flora and its metabolites (SCFAs and a few organic acids) is an important pathway for AESc in the treatment of UC and also provides a rationale for the clinical use of Sargentodoxa cuneata in the treatment of UC.

AbstractThis study was designed to examine the relative safety and efficacy of sevelamer in the treatment of chronic kidney disease (CKD) patients in comparison to placebo, calcium carbonate (CC), or lanthanum carbonate (LC). The PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases were searched for articles published through 18 June 2022. The quality of relevant studies was independently analyzed by two investigators who also extracted data from these manuscripts as per Cochrane Collaboration Handbook 5.3. The safety and efficacy of sevelamer as a treatment for hyperphosphatemia in CKD patients were then examined through a meta-analysis, with the primary patient-level outcomes of interest in this analysis being all-cause mortality and the incidence of gastrointestinal adverse effects. Vascular calcification score was also examined as an intermediate outcome, while serum biochemical parameters including levels of phosphate (P), calcium (Ca), intact parathyroid hormone (iPTH), lipids, C-reactive protein (CRP), or fibroblast growth factor-23 (FGF-23) were additionally assessed. In total, this meta-analysis incorporated data from 34 randomized controlled trials (RCTs) enrolling 2802 patients. Sevelamer was associated with reduced all-cause mortality (RR 0.28, CI 0.19 − 0.41, very low certainty) and Vessel calcification score (RR −0.58, CI −1.11 to −0.04, low certainty) and induced less hypercalcemia (MD −0.28, CI 0.40 to −0.16, low certainty) and hyperphosphatemia (MD −0.22, CI −0.32 to −0.13, low certainty) when compared with Ca-based binders in CKD5D individuals. No significant differences in gastrointestinal adverse events (GAEs) incidence were observed. These data suggest that sevelamer may represent a beneficial means of protecting CKD patients against death and vessel calcification when used to treat hyperphosphatemia, while we found no clinically important benefits in decreasing gastrointestinal adverse effects.

The fungal genus Microcera consists of species mostly occurring as parasites of scale insects, but are also commonly isolated from soil or lichens. In the present study, we surveyed the diversity and assess the taxonomy of entomopathogenic fungi in Sichuan Province, China. Two new species of Microcera, viz. M. chrysomphaludis and M. pseudaulacaspidis, were isolated from scale insects colonising walnut (Juglans regia). Maximum Likelihood and Bayesian Inference analyses of ITS, LSU, tef1-α, rpb1, rpb2, acl1, act, tub2, cmdA and his3 sequence data provide evidence for the validity of the two species and their placement in Nectriaceae (Hypocreales). Microcera pseudaulacaspidis primarily differs from similar species by having more septate and smaller cylindrical macroconidia, as well as DNA sequence data. Meanwhile, Microcera chrysomphaludis has elliptical, one-septate ascospores with acute ends and cylindrical, slightly curved with 4–6 septate macroconidia up to 78 µm long. Morphological descriptions with illustrations of the novel species and DNA-based phylogeny generated from analyses of multigene dataset are also provided to better understand species relationships.

Abstract Background Regulating the pluripotency of human dental pulp stem cells (hDPSCs) is key for the self-repair of injured dental pulp. We previously found that OCT4A promotes the proliferation and odontogenic differentiation of human dental pulp cells (hDPCs). Recent studies have shown the interaction between OCT4A and lncRNAs in pluripotency maintenance of various stem cells. The aim of this study was to explore the underlying roles and mechanisms of OCT4A and its related lncRNAs in the proliferation and multidirectional differentiation of hDPSCs in an inflammatory microenvironment. Methods Human lncRNA microarrays were applied to screen out the differentially expressed lncRNAs in hDPSCs between the OCT4A-overexpressing and vector groups. Lipopolysaccharide (LPS) was used to simulate the inflammatory microenvironment. The effects of OCT4A and the lncRNA FTX on the proliferation and multidifferentiation of hDPSCs were observed by the CCK-8 assay, EdU staining, real-time PCR, western blotting, and Alizarin red and oil red O staining. Bioinformatics analysis and chromatin immunoprecipitation (ChIP) assays were performed to clarify the targeted mechanism of OCT4A on FTX. The regulation by FTX of the expression of OCT4A and its downstream pluripotent transcription factors SOX2 and c-MYC was further detected by real-time PCR and western blotting. Results The microarray results showed that 978 lncRNAs (250 of which were upregulated and 728 downregulated) were potentially differentially expressed genes (fold change ≥ 2, P

Abstract English walnut (Juglans regia), has high economic and ecological value. As an important tree species for eliminating poverty, it is planted in many Provinces of China. In 2021, new pathogenic fungi were observed in English walnut in Guangyuan City, Sichuan Province, China. The initial symptom of leaf infection is that the leaves are covered with small black spots, which gradually expand into larger brown spots. Most of the spots appeared at the edges of the leaves, and yellow whorls were observed at the junction between the spots and the healthy leaves. The pathogenic fungi were isoalted form collecting disease samples and purified by single-spore culturing. In vitro and field experiments showed that the pathogen could cause brown spots on walnut leaves. The inoculation experiment showed that the symptoms in the field experiment were the same as those observed on the spot; however, slight differences were observed in the in vitro experiment. Ten isolates were obtained from walnut leaves with brown spot symptoms, and these were further characterized based on morphology and DNA sequencing. ITS (internal transcribed spacer), LSU (large sub-unit rDNA), rpb2 (second largest subunit of RNA polymerase) and tub2 (beta-tubulin) gene regions were used to construct phylogenetic trees and determine the evolutionary relationships among the collected strains. The isolate was identified as Nothophoma quercina by morphological and polygene analyses. As far as we are aware, the brown spots on walnut leaves caused by N. quercina is the first report of its kind.

Abstract Background Platelet concentrates combined with calcium silicate cements may promote reparative dentin formation. However, few studies have reported their effect on dental pulp inflammation. This study aimed to evaluate the effects of concentrated growth factor (CGF) combined with iRoot BP Plus on inflammatory human dental pulp stem cells (hDPSCs) in vitro and inflamed pulp in rats in vivo. Methods The proliferation of LPS-stimulated hDPSCs treated with 50% CGF with/without 25% iRoot BP Plus was evaluated using Cell Counting Kit-8 on days 1, 4 and 7. The expression of genes associated with inflammation on day 1 and differentiation on day 14 was analysed by real-time polymerase chain reaction. The exposed pulp of rat maxillary molars was injected with 10 mg/mL LPS and directly capped with CGF membrane with/without iRoot BP Plus extract for 1, 7 and 28 days. The teeth were subjected to histologic analyses and immunohistochemistry. Results The proliferation rates of the inflammatory hDPSCs after the combination treatment were significantly higher than those after the other treatments on days 4 and 7 (P

Abstract Background Although subcutaneous edema is a common symptom of critically ill patients, it is still underreported due to the lack of a systematic method for evaluating it. The present study aims to describe the occurrence and distribution of subcutaneous edema, as well as the risk factors associated with it, in critically ill patients using the focused liquid ultrasonography in dropsy (FLUID) protocol, and to assess their impact on ICU mortality. Methods The FLUID protocol and the pitting test were performed on general ICU patients in China. Cohen’s Kappa coefficient and Bland–Altman plots were used to evaluate the agreement between the two methods at each measurement site and between the whole-body subcutaneous edema scores, respectively, while a repeated measures ANOVA was performed to compare the differences between the two methods in whole-body and body-part measurements. A generalized linear model was used to evaluate the risk factors for subcutaneous edema development and the relationship between subcutaneous edema severity and ICU mortality. Results A total of 145 critically ill patients were evaluated using both approaches, of whom 40 (27.6%) experienced subcutaneous edema. Over 1440 measurements, it was found that ultrasound discovered more subcutaneous edema than the pitting test (ultrasound: 522[36.3%], pitting test: 444[30.8%], χ 2 = 9.477, p = 0.002). The FLUID protocol scored edema severity significantly higher than the pitting test in the whole body and specific body parts, including the abdominal wall, thighs, chest wall, and hands. Subcutaneous edema exhibited gravity-dependent distribution patterns, particularly in the abdominal wall. The APACHE II, NT-proBNP, serum creatinine, and sepsis were independent risk factors for subcutaneous edema development. The score of ultrasonic subcutaneous edema was related to ICU mortality. Conclusions The FLUID protocol provides a comprehensive strategy for the semi-quantitative assessment of subcutaneous edema in critically ill patients. In detecting the onset and severity of edema, ultrasound was found to outperform the pitting test. Subcutaneous edema showed a gravity-dependent distribution pattern, and its severity was associated with mortality.

Idiopathic pulmonary fibrosis is a fatal interstitial lung disease for which effective drug therapies are lacking. Senegenin, an effective active compound from the traditional Chinese herb Polygala tenuifolia Willd, has been shown to have a wide range of pharmacological effects. In this study, we investigated the therapeutic effects of senegenin on pulmonary fibrosis and their associated mechanisms of action. We found that senegenin inhibited the senescence of epithelial cells and thus exerted anti-pulmonary-fibrosis effects by inhibiting oxidative stress. In addition, we found that senegenin promoted the expression of Sirt1 and Pgc-1α and that the antioxidative and antisenescent effects of senegenin were suppressed by specific silencing of the Sirt1 and Pgc–1α genes, respectively. Moreover, the senegenin-induced effects of antioxidation, antisenescence of epithelial cells, and antifibrosis were inhibited by treatment with Sirt1 inhibitors in vivo. Thus, the Sirt1/Pgc-1α pathway exerts its antifibrotic effect on lung fibrosis by mediating the antioxidative and antisenescent effects of senegenin.

The increasing popularity of vehicles has led to traffic congestion and frequent traffic accidents. Intelligent transportation technology is an effective solution to this problem. In order to improve the accuracy and effectiveness of vehicle detection and tracking, this paper combined the improved YOLOv5s model with the optimized DeepSORT tracking algorithm to detect and track vehicles on traffic roads. Firstly, in the detection model of YOLOv5s, the Attention-based Intra-scale Feature Interaction (AIFI) module is introduced to detect vehicles more quickly and accurately. Secondly, the Kalman filtering (KF) algorithm of DeepSORT is optimized to improve the accuracy of predictions of the vehicle state by using the width to replace the length-to-width ratio of the vehicle prediction box in the original KF algorithm. Finally, in the re-recognition network of DeepSORT, the original Convolutional Neural Network (CNN) model is replaced by an improved ResNet36 as the backbone network for feature extraction. The experimental results show that, compared with the original algorithm, when examining the performance of the improved algorithm in terms of target detection, the recall rate, average accuracy (mAP), and detection speed, are increased by 7.7%, 15.5%, and 14.2%, respectively; in terms of multi-object tracking performance, such as multi-object tracking precision (MOTP) and multi-object tracking accuracy (MOTA), improvements of 14.84% and 9.62%, respectively, are obtained and the total number of times a trajectory is fragmented (Frag) is reduced by 32.52%.These results indicate that the proposed algorithm can meet the requirements of accuracy, real-time detection, and stable vehicle detection and tracking on traffic roads.

Tobacco black shank induced by Phytophthora nicotianae causes significant yield losses in tobacco plants. MicroRNAs (miRNAs) play a pivotal role in plant biotic stress responses and have great potential in tobacco breeding for disease resistance. However, the roles of miRNAs in tobacco plants in response to P. nicotianae infection has not been well characterized. In this study, we found that Nta-miR6155, a miRNA specific to Solanaceae crops, was significantly induced in P. nicotianae infected tobacco. Some of predicted target genes of Nta-miR6155 were also observed to be involved in disease resistance. To further investigate the function of miR6155 in tobacco during P. nicotianae infection, Nta-miR6155 overexpression plants (miR6155-OE) were generated in the Honghua Dajinyuan tobacco variety (HD, the main cultivated tobacco variety in China). We found that the Nta-miR6155 overexpression enhanced the resistance in tobacco towards P. nicotianae infections. The level of reactive oxygen species (ROS) was significantly lower and antioxidant enzyme activities were significantly higher in miR6155-OE plants than those in control HD plants during P. nicotianae infection. In addition, we found that the accumulation of salicylic acid and the expression of salicylic acid biosynthesis and signal transduction-related genes is significantly higher in miR6155-OE plants in comparison to the control HD plants. Furthermore, we found that Nta-miR6155 cleaved target genes NtCIPK18 to modulate resistance towards P. nicotianae in tobacco plants. Additionally, phenotypic analysis of miR6155-OE plants showed that Nta-miR6155 could inhibit the growth of tobacco by suppressing nitrogen uptake and photosynthesis. In conclusion, our findings indicated that miR6155 plays a crucial role in the regulation of growth and resistance against P. nicotianae infections in tobacco plants.

To efficiently remove organic and inorganic pollutants from leachate concentrate, an in situ coagulation-electrochemical oxidation (CO-EO) system was proposed using Ti/Ti4O7 anode and Al cathode, coupling the “super-Faradaic” dissolution of Al. The system was evaluated in terms of the removal efficiencies of organics, nutrients, and metals, and the underlying cathodic mechanisms were investigated compared with the Ti/RuO2–IrO2 and graphite cathode systems. After a 3-h treatment, the Al-cathode system removed 89.0% of COD and 36.3% of total nitrogen (TN). The TN removal was primarily ascribed to the oxidation of both ammonia and organic-N to N2. In comparison, the Al-cathode system achieved 3–10-fold total phosphorus (TP) (62.6%) and metal removals (>80%) than Ti/RuO2–IrO2 and graphite systems. The increased removals of TP and metals were ascribed to the in situ coagulation of Al(OH)3, hydroxide precipitation, and electrodeposition. With the reduced scaling on the Al cathode surface, the formation of Al3+ and electrified Al(OH)3 lessened the requirement for cathode cleaning and increased the bulk conductivity, resulting in increased instantaneous current production (38.9%) and operating cost efficiencies (48.3 kWh kgCOD−1). The present study indicated that the in situ CO-EO process could be potentially used for treating persistent wastewater containing high levels of organic and inorganic ions.

Objective: This study aimed to explore the mechanism of the Bushen Huoxue Formula (BHF) in treating diminished ovarian reserve (DOR) through the use of metabolomics and integrated network pharmacology. Methods: The study involved 24 non-pregnant female Sprague-Dawley rats, divided into four groups of six rats each: control, model, BHF, and DHEA (n = 6 per group). The model group was induced with DOR by administering Tripterygium glycosides orally [50 mg (kg·d)−1] for 14 days. Subsequently, BHF and Dehydroepiandrosterone (DHEA) treatments were given to the respective groups. Ovarian reserve function was assessed by measuring anti-Müllerian hormone (AMH), estradiol (E2), and follicle-stimulating hormone (FSH) levels and conducting hematoxylin-eosin staining. In addition, UHPLC-QTOF-MS analysis was performed to identify differential metabolites and pathways in DOR rats treated with BHF. In this study, LC-MS was utilized to identify the active ingredients of BHF, while network pharmacology was employed to investigate the correlations between BHF-related genes and DOR-related genes. An integrated analysis of metabonomics and network pharmacology was conducted to elucidate the mechanisms underlying the efficacy of BHF in treating DOR. Results: The model group exhibited a poor general condition and a significant decrease in the number of primordial, primary, and secondary follicles (P

Background: Myocardial infarction is associated with the autophagy and apoptosis of cardiomyocytes, and the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway plays a crucial role in this mechanism. Methods: Acute myocardial infarction rat models were assessed 0.5, 2, 4, and 6 hours after the induction of the myocardial infarction using hematoxylin and eosin staining, triphenyl tetrazolium chloride staining, myocardial enzyme measurements, and levels of autophagic activity. Additionally, diazoxide, 5-hydroxydecanoate, and LY294002 were intraperitoneally administered to rat models at peak myocardial injury to assess their effects on cardiac injury. The expression levels of autophagy-related and apoptosis-related proteins, as well as p-AKT and p-mTOR, were measured. Electron microscopy was used to assess the ultrastructure and the number of autophagosomes in the cardiac tissue. Results: We demonstrated that the degree of myocardial injury and the level of autophagy were significantly elevated in the experimental cohort compared with the control cohort. In addition, the myocardial infarct size was significantly smaller in diazoxide-treated acute myocardial infarction rats compared with untreated rats. Diazoxide also decreased the levels of myocardial injury markers, autophagy, and apoptosis, while it also induced the levels of AKT and mTOR phosphorylation, decreased the number of autophagosomes, and improved the myocardial ultrastructure of the acute myocardial infarction rats. 5-Hydroxydecanoate treatment resulted in an opposite effect to those observed upon diazoxide treatment. LY294002 was also able to reverse diazoxide treatment effects. Conclusion: Peak levels of myocardial tissue injury and autophagy were observed 2 hours post-acute myocardial infarction induction in rats. Diazoxide treatment inhibited myocardial autophagy and apoptosis while protecting cardiac tissue from ischemic injury, which is likely to have proceeded through activation of the AKT/mTOR pathway.

Abstract Background Regenerative endodontic procedures (REPs) have achieved clinical success on the immature permanent teeth with pulp necrosis, and can promote root development. However, preoperative factors and their effects on root development of REPs have not been definitely concluded. The aim of this study was to investigate the preoperative factors that may influence the root development of REPs. Methods A total of 116 teeth in 110 patients treated with REPs in the Paediatric Dentistry Department and Endodontics Department from 2013 to 2017 were included in this study. Preoperative factors including aetiology, age, diagnosis and initial root morphology were collected retrospectively, and the associations between these factors and root development after REPs were analysed by Fisher's exact test and multivariate logistic regression model. Results The overall rate of root development after REPs was 89.7%. The dens evaginatus group showed a higher rate (98.8%) in root development than the trauma group (67.6%) (P 0.05). And it showed in the trauma group that the teeth with apical foramen sizes larger than 3 mm significantly promoted root development than those smaller than 3 mm (P

ObjectiveParkinson's disease (PD) and dystonia are two closely related movement disorders with overlaps in clinical phenotype. Variants in several dystonia-related genes were demonstrated to be associated with PD; however, genetic evidence for the involvement of dystonia-related genes in PD has not been fully studied. Here, we comprehensively investigated the association between rare variants in dystonia-related genes and PD in a large Chinese cohort.MethodsWe comprehensively analyzed the rare variants of 47 known dystonia-related genes by mining the whole-exome sequencing (WES) and whole-genome sequencing (WGS) data from 3,959 PD patients and 2,931 healthy controls. We initially identified potentially pathogenic variants of dystonia-related genes in patients with PD based on different inheritance models. Sequence kernel association tests were conducted in the next step to detect the association between the burden of rare variants and the risk for PD.ResultsWe found that five patients with PD carried potentially pathogenic biallelic variants in recessive dystonia-related genes including COL6A3 and TH. Additionally, we identified 180 deleterious variants in dominant dystonia-related genes based on computational pathogenicity predictions and four of which were considered as potentially pathogenic variants (p.W591X and p.G820S in ANO3, p.R678H in ADCY5, and p.R458Q in SLC2A1). A gene-based burden analysis revealed the increased burden of variant subgroups of TH, SQSTM1, THAP1, and ADCY5 in sporadic early-onset PD, whereas COL6A3 was associated with sporadic late-onset PD. However, none of them reached statistical significance after the Bonferroni correction.ConclusionOur findings indicated that rare variants in several dystonia-related genes are suggestively associated with PD, and taken together, the role of COL6A3 and TH genes in PD is highlighted.

We investigated the impact of nonequilibrium conditions on the transmission and recovery of information through noisy channels. By measuring the recoverability of messages from an information source, we demonstrate that the ability to recover information is connected to the nonequilibrium behavior of the information flow, particularly in terms of sequential information transfer. We discovered that the mathematical equivalence of information recoverability and entropy production characterizes the dissipative nature of information transfer. Our findings show that both entropy production (or recoverability) and mutual information increase monotonically with the nonequilibrium strength of information dynamics. These results suggest that the nonequilibrium dissipation cost can enhance the recoverability of noise messages and improve the quality of information transfer. Finally, we propose a simple model to test our conclusions and found that the numerical results support our findings.

High-efficiency video coding (HEVC) outperforms H.264 in coding efficiency. However, the rate–distortion optimization (RDO) process in coding tree unit (CTU) partitioning requires an exhaustive exploration of all possible quad-tree partitions, resulting in high encoding complexity. To simplify this process, this paper proposed a convolution neural network (CNN) based optimization algorithm combined with a hybrid attention mechanism module. Firstly, we designed a CNN compatible with the current coding unit (CU) size to accurately predict the CU partitions. In addition, we also designed a convolution block to enhance the information interaction between CU blocks. Then, we introduced the convolution block attention module (CBAM) into CNN, called CNN-CBAM. This module concentrates on important regions in the image and attends to the target object correctly. Finally, we integrated the CNN-CBAM into the HEVC coding framework for CU partition prediction in advance. The proposed network was trained, validated, and tested using a large scale dataset covering various scenes and objects, which provides extensive samples for intra-frame CU partition prediction in HEVC. The experimental findings demonstrate that our scheme can reduce the coding time by up to 64.05% on average compared to a traditional HM16.5 encoder, with only 0.09 dB degradation in BD-PSNR and a 1.94% increase in BD-BR.

High-efficiency video coding (HEVC/H.265) is one of the most widely used video coding standards. HEVC introduces a quad-tree coding unit (CU) partition structure to improve video compression efficiency. The determination of the optimal CU partition is achieved through the brute-force search rate-distortion optimization method, which may result in high encoding complexity and hardware implementation challenges. To address this problem, this paper proposes a method that combines convolutional neural networks (CNN) with joint texture recognition to reduce encoding complexity. First, a classification decision method based on the global and local texture features of the CU is proposed, efficiently dividing the CU into smooth and complex texture regions. Second, for the CUs in smooth texture regions, the partition is determined by terminating early. For the CUs in complex texture regions, a proposed CNN is used for predictive partitioning, thus avoiding the traditional recursive approach. Finally, combined with texture classification, the proposed CNN achieves a good balance between the coding complexity and the coding performance. The experimental results demonstrate that the proposed algorithm reduces computational complexity by 61.23%, while only increasing BD-BR by 1.86% and decreasing BD-PSNR by just 0.09 dB.

Improving water resources utilization efficiency is conducive to achieving the sustainable development of water resources. It is essential to explore the regional differences and dynamic evolution of agricultural water resources utilization efficiency in China to promote high-quality development of agriculture. In this study, based on the unexpected output, we build a super slack-based measure model to measure agricultural water resources utilization efficiency in China's provinces from 2007 to 2018. In addition, we use the Dagum Gini coefficient to analyze the source of regional differences. Finally, we construct the distributed dynamics model to explore the distribution of the dynamic evolution trend of China's agricultural water resources utilization efficiency. The results reveal that regional difference is the main source of the overall difference in agricultural water resources utilization efficiency in China. Spatial imbalance exists in the development of agricultural water resources utilization efficiency in China. The agricultural water resources utilization efficiency in various provinces and regions of China is relatively stable, having the characteristics of club convergence. The probability of maintaining the initial state is high, and the internal mobility is low. However, with time, the degree of club convergence decreases.

ObjectiveCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease caused by mutations in the NOTCH3 gene. Previous studies have established a link between NOTCH3 variants and Parkinson’s disease (PD) in terms of neuropathology and clinical characteristics. In this study, we aimed to explore the role of NOTCH3 gene in PD in a large Chinese cohort.MethodsA total of 1,917 patients with early-onset or familial PD and 1,652 matched controls were included. All variants were divided into common or rare types by minor allele frequency (MAF) at a threshold of 0.01 (MAF > 0.01 into common variants and others into rare variants). Common variants were subjected to single-variant tests by PLINK, then gene-based analyses were used for rare variants with the optimized sequence kernel association test (SKAT-O). For genotype–phenotype correlation assessment, regression models were conducted to compare clinical features between the studied groups.ResultsThree common variants (rs1044006, rs1043997, and rs1043994) showed a nominal protective effect against PD. However, none of these SNPs survived Bonferroni correction. The results in the validation cohort revealed a significant but opposite association between these variants and PD. The gene-based analyses of rare variants showed no significant associations of NOTCH3 with PD. Although we did not find significant associations in the following genotype–phenotype analysis, the higher clinical scores of motor symptoms in NOTCH3-variant carriers were of interest.ConclusionOur results indicated that NOTCH3 gene may not play an important role in the early-onset or familial PD of Chinese population.

Lack of expression and function of chloride ion-extruding transporter KCC2 in central neurons, a consequence of various forms of neural injury, is strongly suggested to contribute to chronic pain. Here the authors identify from a screen of cancer drugs a kinase-inhibitor, kenpaullone, as an enhancer of Kcc2/KCC2 gene expression and show that it (i) alleviates pain like behaviour in animal models, (ii) repairs neural-circuit disrupting elevated chloride in pain relay neurons in the dorsal spinal cord.

Abstract To test diagnostic accuracy of changes in thickness (TH) and cross-sectional area (CSA) of muscle ultrasound for diagnosis of intensive care unit acquired weakness (ICU-AW). Fully conscious patients were subjected to muscle ultrasonography including measuring the changes in TH and CSA of biceps brachii (BB) muscle, vastus intermedius (VI) muscle, and rectus femoris (RF) muscles over time. 37 patients underwent muscle ultrasonography on admission day, day 4, day 7, and day 10 after ICU admission, Among them, 24 were found to have ICW-AW. Changes in muscle TH and CSA of RF muscle on the right side showed remarkably higher ROC-AUC and the range was from 0.734 to 0.888. Changes in the TH of VI muscle had fair ROC-AUC values which were 0.785 on the left side and 0.779 on the right side on the 10th day after ICU admission. Additionally, Sequential Organ Failure Assessment (SOFA), Acute Physiology, and Chronic Health Evaluation II (APACHE II) scores also showed good discriminative power on the day of admission (ROC-AUC 0.886 and 0.767, respectively). Ultrasonography of changes in muscles, especially in the TH of VI muscle on both sides and CSA of RF muscle on the right side, presented good diagnostic accuracy. However, SOFA and APACHE II scores are better options for early ICU-AW prediction due to their simplicity and time efficiency.

BackgroundAcupuncture is increasingly used as adjuvant therapy for infertile women undergoing frozen-thawed embryo transfer (FET); however, its effects and safety are highly controversial. This study aimed to evaluate the pooled effects of adjuvant acupuncture on FET pregnancy outcomes.MethodsWe considered only randomized controlled trials (RCTs) that compared acupuncture with sham acupuncture or no adjuvant treatment during FET and the primary outcome was clinical pregnancy rate. Two authors separately selected studies, extracted data, and performed a risk of bias assessment. Pooled data were expressed as risk ratio (RR) or mean difference (MD), with a 95% confidence interval (CI). In addition, we conducted subgroup and sensitivity analyses to investigate the sources of heterogeneity, and we also constructed funnel plots to assess the likelihood of publication bias. Finally, Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) was applied to evaluate the quality of evidence.ResultsA total of 14 RCTs with a total of 1,130 participants were included in the study. We found significant effects of acupuncture adjuvant to FET on the outcomes of clinical pregnancy rate (RR = 1.54, 95% CI [1.28, 1.85], I2 = 34%; 14 trials), biochemical pregnancy rate (RR = 1.51, 95% CI [1.21, 1.89]; 5 trials), endometrial thickness (MD = 0.97, 95% CI [0.43, 1.51]; 12 trials), and endometrial pattern (RR = 1.41, 95% CI [1.13, 1.75]; 7 trials). For live birth rate (RR = 1.48, 95% CI [0.90, 2.43], 4 trials), there were no statistical effectiveness. For subgroup analyses, most variables had tolerable heterogeneity (I2 = 0%) except for trials that were sham-controlled, performed acupuncture only after FET, or

Background: Chronic neck pain (CNP) is highly prevalent and complicated, associated with limited movement, and accompanied by shoulder pain and other clinical manifestations such as dizziness, anxiety, and insomnia. Brain structural and functional abnormalities often occur in patients with CNP. However, knowledge of the brain’s functional organization and temporal dynamics in CNP patients is limited. Dynamic functional connectivity density (dFCD) can reflect the ability of brain areas or voxels to integrate information, and could become neuroimaging markers for objectively reflecting pain to a certain extent. Therefore, this study compared the dFCD between CNP patients and healthy controls (HCs) and investigated potential associations of the abnormal density variability in dynamic functional connectivity with pain characteristics in CNP patients.Methods: Resting functional magnetic resonance imaging was performed for 89 CNP patients and 57 HCs. After preprocessing resting-state fMRI images by the Data Processing and Analysis of Brain Imaging toolbox, the sliding window method was applied to investigate dFCD changes in CNP patients and HCs using the DynamicBC toolbox. Then we quantified dFCD variability using their standard deviation. Based on the pain-associated factors collected from the case report form of CNP patients, the mean dFCD variability values of each dFCD from region of interest were extracted to calculate Pearson’s correlation coefficient to study the potential correlation between dFCD abnormal variability and pain.Results: Compared with HCs, the dFCD values of the anterior cingulate cortex, occipital lobe, temporal lobe, and cerebellum were statistically different in patients with CNP. Subsequent correlation analysis showed that the variable dFCD in the related brain region was correlative with the course of the disease and clinical symptoms, such as pain and depression, in patients with CNP.Conclusion: Dynamic functional alterations were observed in the brain regions of CNP patients, and the dFCD of these brain regions could become neuroimaging markers for objectively reflecting pain to a certain extent. This suggests that chronic pain may cause changes in pain processing and emotional feedback and highlights the link between dynamic neural communication in brain regions and disease conditions, deepening our understanding of chronic pain diseases, and guiding clinical practice.