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Abstract Single-cell RNA sequencing methods focusing on the 5′-end of transcripts can reveal promoter and enhancer activity and efficiently profile immune receptor repertoire. However, ultra-high-throughput 5′-end single-cell RNA sequencing methods have not been described. We introduce FIPRESCI, 5′-end single-cell combinatorial indexing RNA-Seq, enabling massive sample multiplexing and increasing the throughput of the droplet microfluidics system by over tenfold. We demonstrate FIPRESCI enables the generation of approximately 100,000 single-cell transcriptomes from E10.5 whole mouse embryos in a single-channel experiment, and simultaneous identification of subpopulation differences and T cell receptor signatures of peripheral blood T cells from 12 cancer patients.

Abstract Background Homer1, an immediate early gene, is related to sleep deprivation (SD), and its protein products are involved in synaptic plasticity affecting the cognitive process. This study aimed to identify the SD-associated key Homer1 gene in the brain and explore the value of Homer1 proteins acting on synaptic plasticity in SD. Methods GSE9441 was extracted from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between SD and Control samples were achieved by R software and were analyzed by the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and gene set enrichment analysis (GSEA). Protein–protein interactions (PPI) network was built by the GeneMANIA databases. In animal experiments, male C57BL/6 J mice (aged 12–13 weeks) were sleep deprived for 6 h, followed by independent behavioral tests and in vitro assays. Morris water maze (MWM) was used to evaluate learning and memory function. The expression of hippocampal Homer1 proteins was detected by Western blot analysis and its distribution in CA1 by immunohistochemistry and immunofluorescence staining. Synaptic plasticity was assessed by Golgi staining and long-term potentiation (LTP) testing in the hippocampal CA1 region. Results Homer1 was the hub gene most associated with SD, and its protein products specifically acted on the regulation of synaptic plasticity in bioinformatics. SD mice exhibited spatial memory impairment accompanied by increased Homer1a expression in hippocampal tissue and CA1 region. SD did not induce Homer1b/c overexpression of mice in the hippocampus. SD impaired the hippocampal synaptic plasticity of mice by reducing the density of dendritic spines and inhibiting LTP in the hippocampal CA1 region, which may involve the overexpression of Homer1a in the hippocampus. Conclusion Homer1 gene is a core brain molecule associated with acute SD, and its protein product Homer1a is involved in the changes in cognitive brain function following short-term SD, especially the impact on hippocampal synaptic plasticity.

Sequencing-based genetic association analysis is typically performed by first generating genotype calls from sequence data and then performing association tests on the called genotypes. Standard approaches require accurate genotype calling (GC), which can be achieved either with high sequencing depth (typically available in a small number of individuals) or via computationally intensive multi-sample linkage disequilibrium (LD)-aware methods. We propose a computationally efficient two-stage combination approach for association analysis, in which single-nucleotide polymorphisms (SNPs) are screened in the first stage via a rapid maximum likelihood (ML)-based method on sequence data directly (without first calling genotypes), and then the selected SNPs are evaluated in the second stage by performing association tests on genotypes from multi-sample LD-aware calling. Extensive simulation- and real data-based studies show that the proposed two-stage approaches can save 80% of the computational costs and still obtain more than 90% of the power of the classical method to genotype all markers at various depths d≥2.

Abstract Background Esophageal diverticulum is a rare condition that requires treatment only when symptoms are present. Surgery has been considered to be the only curative option for symptomatic cases. The most popular procedure is diverticulectomy. Clear and intact exposure of the diverticulum’s neck is the basis for safe and effective diverticulectomy. Case presentation We herein report a case of a 57 year-old woman with an epiphrenic diverticulum. VATS diverticulectomy was scheduled. To better identify the diverticulum neck, we injected indocyanine green (ICG) into the diverticulum through the endoscopic channel, and the diverticulum wall and neck were clearly visible under near-infrared (NIR) fluorescence. With the help of this method, diverticulectomy was successfully performed. Conclusion This case shows that NIR fluorescence with ICG is safe, simple and reliable and can be used for diverticulectomy.

Abstract Metabolic reprogramming is one of the hallmarks of cancer. As nutrients are scarce in the tumor microenvironment (TME), tumor cells adopt multiple metabolic adaptations to meet their growth requirements. Metabolic reprogramming is not only present in tumor cells, but exosomal cargos mediates intercellular communication between tumor cells and non-tumor cells in the TME, inducing metabolic remodeling to create an outpost of microvascular enrichment and immune escape. Here, we highlight the composition and characteristics of TME, meanwhile summarize the components of exosomal cargos and their corresponding sorting mode. Functionally, these exosomal cargos-mediated metabolic reprogramming improves the "soil" for tumor growth and metastasis. Moreover, we discuss the abnormal tumor metabolism targeted by exosomal cargos and its potential antitumor therapy. In conclusion, this review updates the current role of exosomal cargos in TME metabolic reprogramming and enriches the future application scenarios of exosomes.

Objectives: To slow down the chemical fixation of phosphate fertilizer, reduce the risk of active phosphorus leaching, stimulate the inherent phosphorus resource activity of soil, and improve phosphorus supply capacity. Methods: This study utilized a combination of field experiments and indoor chemical analysis. Six types of exogenous organic matter (fulvic acid, biochar, compound microbial fertilizer, high-energy microbial inoculum, pig manure-vermicompost, cow manure-vermicompost) were added based on conventional fertilization. The experiment was conducted under the wheat-maize rotation system in the Huang-Huai-Hai region. Results: Compared with control (CK) without exogenous organic matter (EOM), all the other treatments with EOM had an enhancing effect on the available phosphorus of the cultivated soil. During the maize harvest, the combined application of biochar, pig manure-vermicompost and cow manure-vermicompost treatment significantly increased the content of available phosphorus in 0–20 cm soil by 45.87–56.59% compared with CK. The combined application of fulvic acid, biochar, pig manure-vermicompost and cow manure-vermicompost treatment significantly increased the content of Ca2-P in 0–20 cm soil by 34.04–65.14%. The content of Ca10-P in each treatment with EOM exhibited a lower level compared to CK. EOM could slow down the fixation of phosphorus to some degree. Correlation analysis revealed significant associations between Ca2-P, Ca8-P, Al-P, Fe-P, neutral phosphatase activity, acid phosphatase activity, and the available phosphorus content in the soil. The combined application of fulvic acid, biochar, and cow manure-vermicompost could enhance the activity of neutral and acid phosphatase in topsoil to a certain extent, thereby facilitating the conversion of phosphorus into highly available Ca2-P. EOM could enhance the soil phosphorus availability and decelerate the conversion of soil phosphorus into O-P and Ca10-P forms with low availability. Among all treatments, biochar exhibited the most pronounced efficiency in mitigating phosphorus leaching downward. Conclusions: All the EOMs had the potential to enhance the conversion of phosphorus into soluble phosphorus (Ca2-P), thereby mitigating the chemical fixation of soil phosphorus and ameliorating non-point source pollution caused by phosphorus. EOM enhanced the activity of neutral and acid phosphatase, which was beneficial to the conversion of organic phosphorus to inorganic phosphorus and increasing the content of available phosphorus. All EOMs had good effects on the retention of soil effective phosphorus, among which biochar had the best effect on retaining effective phosphorus in the tillage layer and blocking phosphorus leaching downward.

The distribution and diversity of calanoid copepods were investigated using samples collected from 37 lakes in North-eastern (NE) China in 2019. A total of 10 calanoid copepods belonging to eight genera and three families were identified. Among them, Heterocope soldatovi Rylov, 1922 was recorded for the first time in China. Species from the family Centropagidae were more widespread than those from the families Temoridae and Diaptomidae. Sinocalanus doerrii (Brehm, 1909), previously not recorded in NE China, is now widespread alongside Boeckella triarticulata (Thomson G.M., 1883), and the latter species is also prevalent in that region. Canonical correspondence analysis (CCA) and redundancy analysis (RDA) revealed that calanoid copepods were significantly correlated with total phosphorus (TP), total nitrogen, conductivity, nitrate nitrogen, altitude, and dissolved organic carbon. TP was the most important environmental variable that impacted the distribution of calanoid copepods, including both fresh and saline–alkaline lakes. Integrating historical records, a total of 21 calanoid copepods were distributed in NE China, and we also gave comments on the ecology and distribution of these species.

Rotary kiln has been widely used in hazardous waste treatment because of its strong adaptability to raw materials, high productivity, and simple processing technology. However, the formation of deposits reduces its performance period and profitability. This study characterized the deposit mineralogy and thermodynamically and experimentally investigated its formation mechanism. The results show that the main phases of the deposit are magnetite, monolithic iron, olivine, and yellow feldspar. They indicate that the deposit formation process was accompanied by the participation of alkaline and iron oxides. The intermediate product Ca2SiO4 can promote the generation of low melting point phases, such as CaFeSiO4 and Ca2Al2SiO7, which are the main phases of deposit materials. Additionally, the reduction intermediate product FeO facilitated the generation of a liquid ferrous mixture (Fe3O4-FeO and Fe3O4-FeO-Fe mixture), which in turn further promoted the growth of the initial deposit phase. The solid deposit formed and attached to the kiln inner wall, along with a decrease in temperature. These results are expected to provide an idea or approach for fundamentally solving the problem of deposits in the rotary kiln.

Strain differences have been reported for motor behaviors, and only a subset of spinal cord injury (SCI) patients develop neuropathic pain, implicating genetic or genomic contribution to this condition. Here, we evaluated neuropsychiatric behaviors in A/J, BALB/c, and C57BL/6 male mice and tested genetic or genomic alterations following SCI. A/J and BALB/c naive mice showed significantly less locomotor activity and greater anxiety-like behavior than C57BL/6 mice. Although SCI elicited locomotor dysfunction, C57BL/6 and A/J mice showed the best and the worst post-traumatic recovery, respectively. Mild (m)-SCI mice showed deficits in gait dynamics. All moderate/severe SCI mice exhibited similar degrees of anxiety/depression. mSCI in BALB/c and A/J mice resulted in depression, whereas C57BL/6 mice did not exhibit depression. mSCI mice had significantly lower mechanical thresholds than their controls, indicating high cutaneous hypersensitivity. C57BL/6, but not A/J and BLAB/c mice, showed significantly lower heat thresholds than their controls. C57BL/6 mice exhibited spontaneous pain. RNAseq showed that genes in immune responses and wound healing were upregulated, although A/J mice showed the largest increase. The cell cycle and the truncated isoform of trkB genes were robustly elevated in SCI mice. Thus, different genomics are associated with post-traumatic recovery, underscoring the likely importance of genetic factors in SCI.

Climate change affects the geographical distribution of plant species. Rare Trachycarpus nanus with a narrow distribution range, high medicinal value and extremely small population is facing increasing extinction risks under global climate change. In this study, 96 recorded occurrences and 23 environmental factors are used to predict the potential suitable area of T. nanus based on the optimized MaxEnt (3.4.4) model and ArcGIS (10.7) software. The results show that when the parameters are FC = LQ and RM = 1, the MaxEnt model is optimal and AUC = 0.946. The distribution patterns were predicted in the past, present, and four future phases, i.e., 2021–2040 (2030), 2041–2060 (2050), 2061–2080 (2070), and 2081–2100 (2090). The main factors are the annual precipitation (bio12), mean temperature of the coldest quarter (bio11), temperature seasonality (bio4), precipitation of the wettest quarter (bio16), and isothermality (bio3). The potential distribution of T. nanus is primarily concentrated in central Chuxiong, encompassing a total potential suitable area of 5.65 × 104 km2. In historical periods, the total habitat area is smaller than that in the present. In the future, the potential suitable area is generally increased. The centroid analysis shows that T. nanus will move to a high-altitude area and to the southeast. But its dispersal capacity may not keep up with the climate change rate. Therefore, additional protection sites for this species should be appropriately established and the habitat connectivity should be enhanced.

A fungal strain (X21156) collected in Tibet was used as the material, identified based on its morphological characteristics and internal transcribed spacer (ITS) sequence; its optimal culture conditions were analyzed by single-factor experiments; artificial domestication and cultivation were carried out; its nutrient composition was determined; and the bioactivities of its polysaccharides were detected using chemical antioxidant assays and MTT assays. The results showed that the strain was Pleurotus citrinopileatus Sing. Its optimal culture conditions were a pH of 7, a temperature of 25 °C, glucose (20 g·L−1) as the carbon source, and yeast powder (20 g·L−1) as the nitrogen source. The fresh weight of a single domesticated fruiting body was 41.16 g. The strain had high protein (28.5%), high fiber (34%), and low fat (1.4%) contents, with high proportions of fresh and sweet amino acids. Polysaccharides had good scavenging ability on ABTS+, DPPH, and OH free radicals (EC50 0.06 mg/mL, 1.21 mg/mL, and 3.62 mg/mL, respectively), and the cytotoxicity of polysaccharides to hepatocellular carcinoma cells (HepG2) (IC50: 1.69 mg/mL) was higher than that of triple-negative breast cancer cells (MDA-MB-468) (IC50: 1.76 mg/mL). In conclusion, the study provides a reference on the optimal culture conditions, domestication and cultivation, and dietary and medicinal values of wild P. citrinopileatus Sing.

Adaptive cruise control (ACC) enables efficient, safe, and intelligent vehicle control by autonomously adjusting speed and ensuring a safe following distance from the vehicle in front. This paper proposes a novel adaptive cruise system, namely the Safety-First Reinforcement Learning Adaptive Cruise Control (SFRL-ACC). This system aims to leverage the model-free nature and high real-time inference efficiency of Deep Reinforcement Learning (DRL) to overcome the challenges of modeling difficulties and lower computational efficiency faced by current optimization control-based ACC methods while simultaneously maintaining safety advantages and optimizing ride comfort. Firstly, we transform the ACC problem into a safe DRL formulation Constrained Markov Decision Process (CMDP) by carefully designing state, action, reward, and cost functions. Subsequently, we propose the Projected Constrained Policy Optimization (PCPO)-based ACC Algorithm SFRL-ACC, which is specifically tailored to solve the CMDP problem. PCPO incorporates safety constraints that further restrict the trust region formed by the Kullback–Leibler (KL) divergence, facilitating DRL policy updates that maximize performance while keeping safety costs within their limit bounds. Finally, we train an SFRL-ACC policy and compare its computation time, traffic efficiency, ride comfort, and safety with state-of-the-art MPC-based ACC control methods. The experimental results prove the superiority of the proposed method in the aforementioned performance aspects.

An increasing number of scholars are researching underwater acoustic sensor networks (UASNs), including the physical layer, the protocols of the routing layer, the MAC layer, and the cross-layer. In UASNs, the ultimate goal is to transmit data from the seabed to the surface, and a well-performed routing protocol can effectively achieve this goal. However, the nodes in the network are prone to drift, and the topology is easily changed because of the movement caused by ocean currents, resulting in a routing void. The data cannot be effectively aggregated to the sink terminal on the surface. Thus, it is extremely important to determine how to find an alternative node as a relay node after node drift and how to rebuild a reliable transmission path. Although many relay routing protocols have been proposed to avoid routing voids, few of them consider the relay node selection between the outage probability and the ocean current model. Therefore, we propose an ocean current motion model based routing (OCMR) protocol to avoid the routing void in UASNs. We predicted underwater node movement based on the ocean current motion model and designed a protection radius to construct a limited search coverage based on the optimal outage probability; then, the node with the best fitness value within the protection radius was selected as the alternative relay node using an improved WOA. In OCMR, the problem of the routing void caused by ocean current motion is effectively suppressed. The simulation results show that, compared with VBF, HH-VBF, and QELAR, the proposed OCMR platform performs well in terms of the PDR (packet delivery ratio), average end-to-end delay, and average energy consumption.

A physics-guided neural network (PGNN) is proposed to predict the fatigue life of materials. In order to reduce the complexity of fatigue life prediction and reduce the data required for network training, the PGNN only predicts the fatigue performance parameters under a specific loading environment, and calculates the fatigue life by substituting the load into the fatigue performance parameters. The advantage of this is that the network does not need to evaluate the effect of numerical changes in the load on fatigue life. The load only needs to participate in the error verification, which reduces the dimension of the function that the neural network needs to approximate. The performance of the PGNN is verified using published data. Due to the reduction in the complexity of the problem, the PGNN can use fewer training samples to obtain more accurate fatigue life prediction results and has a certain extrapolation ability for the changes in trained loading environment parameters. The prediction process of the PGNN for fatigue life is not completely a black box, and the prediction results are helpful for scholars to further study the fatigue phenomenon.

Many clinical studies have shown that embryos of in vitro fertilization (IVF) are often prone to developmental arrest, which leads to recurrent failure of IVF treatment. Early embryonic arrest has always been an urgent clinical problem in assisted reproduction centers. However, the molecular mechanisms underlying early embryonic development arrest remain largely unknown. The objective of this study is to investigate potential candidate hub genes and key signaling pathways involved in early stages of embryonic development. RNA-seq analysis was performed on normal and arrest embryos to study the changes of gene expression during early embryonic development. A total of 520 genes exhibiting differential expression were identified, with 174 genes being upregulated and 346 genes being downregulated. Upregulated genes show enrichment in biosynthesis, cellular proliferation and differentiation, and epigenetic regulation. While downregulated genes exhibit enrichment in transcriptional activity, epigenetic regulation, cell cycle progression, cellular proliferation and ubiquitination. The STRING (search tool for the retravel of interacting genes/proteins) database was utilized to analyze protein-protein interactions among these genes, aiming to enhance comprehension of the potential role of these differentially expressed genes (DEGs). A total of 22 hub genes (highly connected genes) were identified among the DEGs using Cytoscape software. Of these, ERBB2 and VEGFA were upregulated, while the remaining 20 genes (CCNB1, CCNA2, DICER1, NOTCH1, UBE2B, UBE2N, PRMT5, UBE2D1, MAPK3, SOX9, UBE2C, UB2D2, EGF, ACTB, UBA52, SHH, KRAS, UBE2E1, ADAM17 and BRCA2) were downregulated. These hub genes are associated with crucial biological processes such as ubiquitination, cellular senescence, cell proliferation and differentiation, and cell cycle. Among these hub genes, CCNA2 and CCNB1 may be involved in controlling cell cycle, which are critical process in early embryonic development.

Naturally existing polyphenols in virgin olive oil possess significative biological activities and are potential nutraceutical therapeutic for breast cancer. In the present study, we investigated the anti-breast cancer activity of oleuropein and its hydrolysates, and further explored their molecular mechanisms. A similar cellular viability was observed in MCF-7 and MDA-MB-231 cells both treated with oleocanthal (3 μg/mL), hydroxytyrosol (30 μg/mL) and oleuropein (200 μg/mL) showed the same cellular viability, indicating oleocanthal structure may be the main structural component part of the physiological activity of oleuropein. Results showed that olive polyphenols produced reactive oxygen species and suppressed breast cancer cells. For flow cytometry analysis, the three polyphenols impacted the MCF-7 cell and MDA-MB-231 cycle, stagnated in the G1 phase and S phase, respectively, via reducing Cyclin D protein expression and promoting cell apoptosis. The pro-apoptosis, anti-proliferation capacity and delaying cell cycle of the three olive oil polyphenols could be achieved through the PI3K-AKT signaling pathway, mainly inhibited phosphorylation of AKT, PI3K protein.

Background Chronic obstructive pulmonary disease (COPD) has been considered a disease of the elderly, but it could also occur in young people aged 20–50 years. However, the characteristics and prognosis of COPD in such young people remain unclear.Methods Our retrospective cohort study was based on the National Health and Nutrition Examination Survey (NHANES). Participants who 20–50 years old at baseline and completed the pulmonary function test were enrolled in our study cohort. These participants were followed up to 31 December 2019. The sample weight and Taylor Linearization Procedures were adapted to make representative estimations of prevalence and baseline characteristics. The weighted logistic regression model was used to assess the risk factors. The propensity score method and Cox proportional hazard models were applied to calculate the risk of mortality.Results The weighted prevalence of COPD in young people in the USA was 1.64% and it increased with age, with a higher prevalence in males than females (2.59% vs 0.72%, p

A synthetic octoploid rapeseed, Y3380, induces maternal doubled haploids when used as a pollen donor to pollinate plant. However, the mechanism underlying doubled haploid formation remains elusive. We speculated that double haploid induction occurs as the inducer line’s chromosomes pass to the maternal egg cell, and the zygote is formed through fertilization. In the process of zygotic mitosis, the paternal chromosome is specifically eliminated. Part of the paternal gene might have infiltrated the maternal genome through homologous exchange during the elimination process. Then, the zygote haploid genome doubles (early haploid doubling, EH phenomenon), and the doubled zygote continues to develop into a complete embryo, finally forming doubled haploid offspring. To test our hypothesis, in the current study, the octoploid Y3380 line was back bred with the 4122-cp4-EPSPS exogenous gene used as a marker into hexaploid Y3380-cp4-EPSPS as paternal material to pollinate three different maternal materials. The fertilization process of crossing between the inducer line and the maternal parent was observed 48 h after pollination, and the fertilization rate reached 97.92% and 98.72%. After 12 d of pollination, the presence of cp4-EPSPS in the embryo was detected by in situ PCR, and at 13–23 d after pollination, the probability of F1 embryos containing cp4-EPSPS gene was up to 97.27%, but then declined gradually to 0% at 23–33 d. At the same time, the expression of cp4-EPSPS was observed by immunofluorescence in the 3rd to 29th day embryo. As the embryos developed, cp4-EPSPS marker genes were constantly lost, accompanied by embryonic death. After 30 d, the presence of cp4-EPSPS was not detected in surviving embryos. Meanwhile, SNP detection of induced offspring confirmed the existence of double haploids, further indicating that the induction process was caused by the loss of specificity of the paternal chromosome. The tetraploid-induced offspring showed infiltration of the induced line gene loci, with heterozygosity and homozygosity. Results indicated that the induced line chromosomes were eliminated during embryonic development, and the maternal haploid chromosomes were synchronously doubled in the embryo. These findings support our hypothesis and lay a theoretical foundation for further localization or cloning of functional genes involved in double haploid induction in rapeseed.

IntroductionSoil quality plays an irreplaceable role in plant growth for restored grassland. However, few studies investigate the comprehensive effects considering soil and vegetation properties during the restoration of desertified grassland, which restrict the virtuous circle of restored grassland ecosystem.MethodsBy setting three restoration patterns of enclosure plus grass (EG), enclosure intercropping shrub-grass (ESG), and enclosure plus sand-barrier and shrub-grass (ESSG) with three different restoration years (≤5, 7–9, and ≥15 years), we selected 28 physicochemical and microbial indicators, and constructed a minimum data set (MDS) to analyze the influences of restoration measurements on soil quality and ecological benefits in alpine desertified grassland.ResultsThe results showed that the MDS comprised seven soil quality indicators: silt, total nitrogen (TN), carbon–nitrogen ratio (C/N), total potassium (TK), microbial biomass carbon (MBC), microbial biomass phosphorus (MBP), and fungi. Soil quality index (SQI) and ecological restoration effect index (EREI) in restored grasslands significantly increased by 144.83–561.24% and 87.21–422.12%, respectively, compared with unrestored grassland, and their positive effects increased with extending restoration years. The increasing effects of SQI and EREI were the highest in ESSG, followed by EG and ESG. The increasing rate of SQI began to decrease after 5 years in EG and ESG, while it decreased after 7–9 years in ESSG, and that of EREI in EG was lower than ESSG in each restoration year. Our work revealed that ESSG was the optimum restoration pattern for desertified grassland, and anthropogenic monitoring and management measurements such as applying organic fertilization and mowing return reasonably should be carried out at the beginning of 5 years in EG and ESG as well as 7 years in ESSG to maintain sustainable ecological benefits.DiscussionThe study highlights that soil quality, including microbial properties, is a key factor to evaluate the restoration effects of desertified grassland.

Sugarcane (Saccharum spp. hybrids) is a worldwide acclaimed important agricultural crop used primarily for sugar production and biofuel. Sugarcane’s genetic complexity, aneuploidy, and extreme heterozygosity make it a challenging crop in developing improved varieties. The molecular breeding programs promise to develop nutritionally improved varieties for both direct consumption and commercial application. Therefore, to address these challenges, the development of simple sequence repeats (SSRs) has been proven to be a powerful molecular tool in sugarcane. This study involved the collection of 285216 expressed sequence tags (ESTs) from sugarcane, resulting in 23666 unigenes, including 4547 contigs. Our analysis identified 4120 unigenes containing a total of 4960 SSRs, with the most abundant repeat types being monomeric (44.33%), dimeric (13.10%), and trimeric (39.68%). We further chose 173 primers to analyze the banding pattern in 10 sugarcane accessions by PAGE analysis. Additionally, functional annotation analysis showed that 71.07%, 53.6%, and 10.3% unigenes were annotated by Uniport, GO, and KEGG, respectively. GO annotations and KEGG pathways were distributed across three functional categories: molecular (46.46%), cellular (33.94%), and biological pathways (19.6%). The cluster analysis indicated the formation of four distinct clusters among selected sugarcane accessions, with maximum genetic distance observed among the varieties. We believe that these EST-SSR markers will serve as valuable references for future genetic characterization, species identification, and breeding efforts in sugarcane.

Physical activity serves as a pivotal mediator in previous theoretical frameworks that link greenspace and human health. However, it remains unclear whether the domain of physical activity within and around greenspaces can alter the pathway. The present study recruited 668 participants online and examined a conceptual framework that explores the associations between residential greenspace and mental well-being, with a particular focus on the mediation effect of green physical activity (physical activity undertaken in and around greenspaces). Moreover, socio-demographic characteristics, including gender, age, household income, education status, marital status, and student status, were controlled for during the examination. The investigated green physical activities included leisure activities, transportation walking, and transportation cycling, and they were measured by a pre-established questionnaire. Meanwhile, mental well-being was measured by the WHO-5 well-being index, and residential greenspace was indicated by self-reported perceived greenspace and mean Normalized Difference Vegetation Index (NDVI) values within 500 meters (m) of residential radius. We found that both perceived greenspace (B = 1.852, p 0.05), mediated the relationship between perceived greenspace and mental well-being. Our findings reinforce previous studies on “greenspace-health” frameworks and underline the importance of leisure physical activity in promoting mental well-being.

Estrogen pollution is a persistent issue in rivers. This study investigated the occurrence, spatiotemporal variation mechanisms, sources, and ecological risks of estrone (E1), 17β-estradiol (E2), estriol (E3), 17α-ethinylestradiol (EE2), diethylstilbestrol (DES), and bisphenol-A (BPA) in the waters of the Zijiang River, a tributary of the middle Yangtze River. The results revealed elevated detection frequencies and estrogen concentrations in the dry season compared to the wet season, mainly due to the precipitation dilution effect. Total estrogen concentration ranged from 21.2 to 97.5 ng/L in the dry season, which was significantly correlated to spatial distributions of animal husbandry and population. Among the estrogens studied in the river, E2, BPA, and EE2 were predominant. The collective sources of E1, E2, E3, and EE2 were traced back to human and husbandry excrement, whereas BPA emitted from daily life products, contributing to 55.5% and 42.7% of the total estrogen concentration, respectively. Particularly, the average and median E1, E2, and EE2 concentrations in the river exceeded the environmental quality standards of the European Union. The total estrogenic activity dominated by EE2 exceeded the 1 ng E2/L threshold, with levels exceeding 10 ng E2/L during the dry season. The risk quotients exhibited a high ecological risk of E1 and EE2 to fish and a moderate to high ecological risk of E1 to crustaceans, EE2 to mollusks, and E2 to fish. Therefore, E1, E2, and EE2 pollution of the river may lead to both high estrogenic potency and moderate or high ecological risk; thus, they should be considered priority pollutants in the river. These results yield valuable insights into the spatiotemporal change mechanisms, sources, and ecological risks of estrogens in river water of low-urbanization and rural watersheds.

BackgroundThe association between mean arterial pressure (MAP) trajectory in young adults and risk of cardiovascular diseases (CVD) and all-cause mortality is not well-characterized. The objective of this study was to investigate the effects of different MAP trajectory on the risk of CVD and all-cause mortality among the young.MethodsIn the Kailuan cohort study, 19,171 participants aged 18–40 years were enrolled without CVD (including myocardial infarction, stroke, atrial fibrillation and heart failure). The potential hybrid model was used to fit different trajectory patterns according to longitudinal changes of MAP. Hazard ratios and 95% confidence intervals for risk of CVD and all-cause mortality were analyzed using Cox proportional hazard regression models for participants with different trajectories.ResultsFive distinct MAP trajectories were identified during 2006–2013. Each of the trajectories was labelled as low-stable, middle-stable, decreasing, increasing, or high-stable. With the low-stable trajectory group as the reference, the multivariate adjusted HR (95%CI) of CVD for the middle-stable, decreasing, increasing and high-stable groups were 2.49 (1.41–4.40), 5.18 (2.66–10.06), 5.91 (2.96–11.80) and 12.68 (6.30–25.51), respectively. The HR (95%CI) for all-cause deaths were 1.27 (0.84–1.94), 2.01 (1.14–3.55), 1.96 (1.04–4.3.72), and 3.28 (1.69–6.37), respectively.ConclusionIn young adults, MAP trajectories were associated with the risk of CVD or all-cause mortality and increasing MAP trajectories within the currently designated “normal” range may still increase the risk for CVD.

Profound congenital sensorineural hearing loss (SNHL) prevents children from developing spoken language. Cochlear implantation and auditory brainstem implantation can provide partial hearing sensation, but language development outcomes can vary, particularly for patients with inner ear malformations and/or cochlear nerve deficiency (IEM&CND). Currently, the peripheral auditory structure is evaluated through visual inspection of clinical imaging, but this method is insufficient for surgical planning and prognosis. The central auditory pathway is also challenging to examine in vivo due to its delicate subcortical structures. Previous attempts to locate subcortical auditory nuclei using fMRI responses to sounds are not applicable to patients with profound hearing loss as no auditory brainstem responses can be detected in these individuals, making it impossible to capture corresponding blood oxygen signals in fMRI. In this study, we developed a new pipeline for mapping the auditory pathway using structural and diffusional MRI. We used a fixel-based approach to investigate the structural development of the auditory-language network for profound SNHL children with normal peripheral structure and those with IEM&CND under 6 years old. Our findings indicate that the language pathway is more sensitive to peripheral auditory condition than the central auditory pathway, highlighting the importance of early intervention for profound SNHL children to provide timely speech inputs. We also propose a comprehensive pre-surgical evaluation extending from the cochlea to the auditory-language network, showing significant correlations between age, gender, Cn.VIII median contrast value, and the language network with post-implant qualitative outcomes.

Abstract DNA methylation plays a crucial role in the survival of bacteriophages (phages), yet the understanding of their genome methylation remains limited. In this study, DNA methylation patterns are analyzed in 8848 metagenome‐assembled high‐quality phages from 104 fecal samples using single‐molecule real‐time sequencing. The results demonstrate that 97.60% of gut phages exhibit methylation, with certain factors correlating with methylation densities. Phages with higher methylation densities appear to have potential viability advantages. Strikingly, more than one‐third of the phages possess their own DNA methyltransferases (MTases). Increased MTase copies are associated with higher genome methylation densities, specific methylation motifs, and elevated prevalence of certain phage groups. Notably, the majority of these MTases share close homology with those encoded by gut bacteria, suggesting their exchange during phage–bacterium interactions. Furthermore, these MTases can be employed to accurately predict phage–host relationships. Overall, the findings indicate the widespread utilization of DNA methylation by gut DNA phages as an evasion mechanism against host defense systems, with a substantial contribution from phage‐encoded MTases.

BackgroundStroke-associated pneumonia (SAP) is associated with a poor prognosis and a high mortality rate in stroke patients. However, the accuracy of early prediction of SAP is insufficient, and there is a lack of effective prognostic evaluation methods. Therefore, in this study, we investigated the predictive value of the Oxford Acute Severity of Illness Score (OASIS) in SAP to provide a potential reference index for the incidence and prognosis of SAP.MethodsWe recruited a total of 280 patients with acute ischemic stroke who had been diagnosed and treated in the Zhumadian Central Hospital between January 2021 and January 2023. These patients were divided into an SAP group (86 cases) and a non-SAP group (194 cases) according to SAP diagnostic criteria by expert consensus on the diagnosis and treatment of SAP. We collated general and clinical data from all patients, including the survival of SAP patients during the follow-up period. Multivariate logistic regression was used to analyze the risk factors for SAP. Kaplan–Meier and multivariate COX regression analyses were used to investigate the relationship between OASIS and the prognosis of SAP, and a receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of OASIS for SAP.ResultsOur analyses identified body temperature, C-reactive protein, procalcitonin, OASIS, and a prolonged length of intensive care unit (ICU) stay as the main risk factors for SAP (all Ps < 0.05). Advanced age and an elevated OASIS were identified as the main risk factors for death in SAP patients (all Ps < 0.05). The risk of death in patients with OASIS of 31–42 points was significantly higher than that in patients with OASIS of 12–20 points (HR = 5.588, 95% CI = 1.531–20.401, P = 0.009). ROC curve analysis further showed that OASIS had a high predictive value for morbidity and the incidence of death in SAP patients.ConclusionOASIS can effectively predict the onset and death of SAP patients and provides a potential reference index for early diagnosis and the prediction of prognosis in patients with SAP. Our findings should be considered in clinical practice.

Background: Co-stimulatory molecules have been shown to enhance antitumor immune responses, but their role in Diffuse Large B-cell Lymphoma (DLBCL) remains unexplored. Methods: This study aimed to explore the molecular typing of DLBCL with co-stimulatory molecule genes and to construct a prognostic profile to improve treatment decisions and clinical outcomes. Results: We conducted the first comprehensive analysis of co-stimulatory molecules in DLBCL patients and identified five co-stimulatory molecule genes with prognostic and diagnostic values. Consensus cluster analysis based on these five co-stimulatory molecule genes revealed that the two identified clusters had different distribution patterns and prognostic differences. Co-stimulatory molecular correlation signatures were then constructed based on these five co-stimulatory molecular genes and validated in an external dataset, showing good performance in predicting patient prognosis. The signature is an independent risk factor for DLBCL patients and significantly correlates with clinical factors in patients and can be used as a complement to clinical factors. Furthermore, the signature was associated with the tumor immune microenvironment. Patients identified as being at high risk according to our signature exhibit high levels of immune cell infiltration microenvironment. Conclusions: In conclusion, our signature can provide clinicians with prognostic predictions and help guide the treatment of patients with DLBCL.

Summary: Background: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases. Methods: We performed an epigenome-wide association study using whole blood from Framingham Heart Study (FHS; n = 3,471, 46% females) participants and validated results using the Childhood Asthma Management Program (CAMP; n = 674, 39% females) and the Genetic Epidemiology of Asthma in Costa Rica Study (CRA; n = 787, 41% females). Using the closest gene to each IgE-associated CpG, we highlighted biologically plausible pathways underlying IgE regulation and analyzed the transcription patterns linked to IgE-associated CpGs (expression quantitative trait methylation loci; eQTMs). Using prior UK Biobank summary data from genome-wide association studies of asthma and allergy, we performed Mendelian randomization (MR) for causal inference testing using the IgE-associated CpGs from FHS with methylation quantitative trait loci (mQTLs) as instrumental variables. Findings: We identified 490 statistically significant differentially methylated CpGs associated with IgE in FHS, of which 193 (39.3%) replicated in CAMP and CRA (FDR < 0.05). Gene ontology analysis revealed enrichment in pathways related to transcription factor binding, asthma, and other immunological processes. eQTM analysis identified 124 cis-eQTMs for 106 expressed genes (FDR < 0.05). MR in combination with drug-target analysis revealed CTSB and USP20 as putatively causal regulators of IgE levels (Bonferroni adjusted P

Abstract Left ventricular hypertrophy (LVH), the most common target organ damage in patients with hypertension, is closely related to excessive visceral adipose tissue (VAT) accumulation in the body. The hypertriglyceridemic waist (HTHW) phenotype can act as a surrogate marker of excessive VAT. However, the relationship between the HTHW phenotype and LVH in patients with hypertension remains unknown. The present study aimed to investigate whether the HTHW phenotype is associated with LVH, using echocardiography in a cross‐sectional study involving 4470 middle‐aged and older Chinese patients with hypertension. Logistic regression analysis revealed that patients with the HTHW phenotype were 1.52‐fold more likely to experience LVH than those with normal triglyceride levels and normal waist circumference. This association was independent of age, sex, and other potentially confounding factors. In the stratified analysis, a stronger correlation was found among women, people of at least 70 years of age, and people with hyperuricemia. These results suggest that distinguishing the HTHW phenotype in patients with hypertension could serve as a simple and effective screening strategy for identifying people with a higher risk of developing LVH.

Este artículo propone una mirada comparativa e interdisciplinaria, mediante herramientas históricas, en particular el modelo de historia social, a algunos conceptos jurídicos, como el Derecho Civil, la obligación y el contrato. El derecho de un país nunca ha existido independientemente, forma parte de su cultura y está influido profundamente por su historia y el modo de pensar particular. Tomamos estos conceptos básicos del derecho de contratos como ejemplo y muestra. Los conceptos más importantes con los que vamos a trabajar son los siguientes: ¿Qué se entiende por Civil Law? Y, en particular, ¿qué se entiende por obligación y contrato en los sistemas chino y latinoamericano? ¿La tradición jurídica china es igual que la de Europa y de América Latina? Para el Derecho chino, la evolución histórica de los conceptos del Derecho civil, la obligación y el contrato fue un proceso de recepción del Derecho extranjero, lo cual fue en todo caso complicado, pues siempre existían conflictos y debates sobre ello, por lo tanto, estos conceptos del derecho chino, comparados con los del derecho extranjero, muestran características particulares.

Background and objective Previous studies have shown that lymph node metastasis only occurs in some mixed ground-glass nodules (mGGNs) which the pathological results were invasive adenocarcinoma (IAC). However, the presence of lymph node metastasis leads to the upgrading of tumor-node-metastasis (TNM) stage and worse prognosis of the patients, so it is important to perform the necessary evaluation before surgery to guide the operation method of lymph node. The aim of this study was to find suitable clinical and radiological indicators to distinguish whether mGGNs with pathology as IAC is accompanied by lymph node metastasis, and to construct a prediction model for lymph node metastasis. Methods From January 2014 to October 2019, the patients with resected IAC appearing as mGGNs in computed tomography (CT) scan were reviewed. All the lesions were divided into two groups (with lymph node metastasis or not) according to their lymph node status. Lasso regression model analysis by applying R software was used to evaluate the relationship between clinical and radiological parameters and lymph node metastasis of mGGNs. Results A total of 883 mGGNs patients were enroled in this study, among which, 12 (1.36%) showed lymph node metastasis. Lasso regression model analysis of clinical imaging information in mGGNs with lymph node metastasis showed that previous history of malignancy, mean density, mean density of solid components, burr sign and percentage of solid components were informative. Prediction model for lymph node metastasis in mGGNs was developed based on the results of Lasso regression model with area under curve=0.899. Conclusion Clinical information combined with CT imaging information can predict lymph node metastasis in mGGNs.

Abstract Background The current study aimed to investigate the dynamic alteration and prognostic significance of tumor‐infiltrating lymphocytes (TILs), tumor‐associated macrophages (TAMs), and PD‐L1 status of immune cells in muscle‐invasive bladder cancer (MIBC) treated with neoadjuvant chemotherapy (NAC). Methods Multiplex immunofluorescence staining was performed to examine CD68+ TAM, CD4+ T cell, CD8+ T cell, FOXP3+ Treg cell, and PD‐L1 expression in paired MIBC tissues (n = 54) before and after NAC. Patients were then divided into definite responders (DR), (≤pT1) and incomplete responders (IR). Results There was no significant difference between DR and IR cohorts for the immune cell infiltration levels at the baseline status. Tobacco history was identified to be associated with worse NAC efficacy. CD68+ (stroma area: p = 0.025; tumor area: p = 0.028; total area: p = 0.013) and CD68+PD‐L1− (stroma area: p = 0.035; tumor area: p = 0.013 total area: p = 0.014) TAMs infiltration levels decreased significantly after NAC, while there was no significant difference of CD68+PD‐L1+ and TILs. The infiltration of CD68+ (p = 0.033), CD68+PD‐L1− (p = 0.033), and CD68+PD‐L1+ (p

Abstract Background Agrobacterium tumefaciens-mediated leaf disc genetic transformation is an important way to achieve transgenics or gene editing. Ensuring stable and efficient genetic transformation is still an important problem in modern biology. It is assumed that the difference in the development status of genetic transformation cells of receptor materials is the main reason for the difference and instability of genetic transformation efficiency; the stable and efficient genetic transformation rate can be obtained by defining the appropriate treatment period of the receptor material and applying genetic transformation in a timely manner. Results Based on these assumptions, we studied and established an efficient and stable Agrobacterium-mediated plant transformation system with hybrid poplar (Populus alba × Populus glandulosa, 84 K) leaves, stem segments and tobacco leaves as the research objects. There were differences in the development process of leaf bud primordial cells from different explants, and the genetic transformation efficiency was significantly related to the cell development stage of the in vitro cultured materials. Among them, the genetic transformation rate of poplar and tobacco leaves was the highest on the 3rd and 2nd day of culture, reaching 86.6% and 57.3%, respectively. The genetic transformation rate of poplar stem segments was the highest on the 4th day of culture, reaching 77.8%. The best treatment period was from the development of leaf bud primordial cells to the S phase of the cell cycle. The number of cells detected using flow cytometry and 5-ethynyl-2ʹ-deoxyuridine (EdU) staining, the expression of cell cycle-related protein CDKB1; 2, CDKD1; 1, CYCA3; 4, CYCD1; 1, CYCD3; 2, CYCD6; 1, and CYCH; 1 of explants, and morphological changes of explants can be used as indicators to determine the appropriate treatment period for genetic transformation. Conclusions Our study provides a new and universal set of methods and characteristics to identify the S phase of the cell cycle and apply genetic transformation treatments at the appropriate time. Our results are of great significance for improving the efficiency and stability of plant leaf disc genetic transformation.

Abstract Background This study aimed to explore the effect of a prior cancer history on the survivals of resected non-small cell lung cancer (NSCLC) patients. Methods Kaplan–Meier method with a log-rank test was used to compare overall survival (OS) and disease-free survival (DFS) between groups. Propensity score matching (PSM) method was used to reduce bias. The least absolute shrinkage and selection operator (LASSO)-penalized Cox multivariable analysis was used to identify the prognostic factors. Results A total of 4,102 eligible cases were included in this study. The rate of patients with a prior cancer was 8.2% (338/4,102). Patients with a prior cancer tended to be younger and have early-stage tumors when compared with those without prior cancer. Before PSM, the survivals of the patients with a prior cancer were similar to those of the patients without prior cancer (OS: P = 0.591; DFS: P = 0.847). After PSM, patients with a prior cancer and those without prior cancer still had comparable survival rates (OS: P = 0.126; DFS: P = 0.054). The LASSO-penalized multivariable Cox analysis further confirmed that a prior cancer history was not a prognostic factor for both OS and DFS. Conclusions A prior cancer history was not associated with resected NSCLC patients’ survivals, and we proposed that it might be reasonable for clinical trials to enroll the NSCLC patients with a prior cancer.

Abstract Background Patients with tuberculosis (TB) and HIV often present with impairments in lung function and exercise capacity after treatment. We evaluated clinical and immunologic variables associated with a minimum clinically important difference (MCID) in the change in the 6 min walk test distance during the first 24 weeks of antiretroviral (ART) and anti-tubercular therapy. Methods Adults initiating ART and anti-TB treatment in the setting of newly-diagnosed HIV and pulmonary TB were enrolled in a prospective cohort study in South Africa. Patients underwent 6 min walk tests and spirometry at weeks 0, 4, 12, and 24 and biomarker level measurements early during treatment, at weeks 0, 4, and 12, when inflammation levels are typically elevated. Biomarkers included matrix metalloproteinases-1 (MMP-1), tissue inhibitor of MMP (TIMP)-1, collagen 1a, IL-6, IL-8, vascular cell adhesion molecule 1 (VCAM-1), C-X-C motif chemokine 10 (CXCL-10), CXCL-11, macrophage colony-stimulating factor (M-CSF), plasminogen activator, vascular endothelial growth factor, and chemokine (C-C) motif-2 (CCL-2). An MCID was derived statistically, and achievement of an MCID was modeled as the outcome using logistic regression model. Results Eighty-nine patients walked an average of 393 (± standard deviation = 69) meters at baseline, which increased by an average of 9% (430 ± 70 m) at week 24. The MCID for change in walk distance was estimated as 41 m. Patients experiencing an MCID on treatment had worse lung function, lower 6 min walk test distance, higher levels of proinflammatory biomarkers including TIMP-1 and M-CSF, and lower levels of collagen 1a at baseline. Experiencing an MCID during treatment was associated with increases in forced expiratory volume in 1-s [odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.05–1.33] and increases in blood collagen 1a levels (OR = 1.31, 95%CI 1.06–1.62). Conclusions ART and TB treatment are associated with substantial improvements in 6 min walk test distance over time. Achievement of an MCID in the 6 min walk test in this study was associated with more severe disease at baseline and increases in collagen 1a levels and lung function during therapy.

Abstract Acute lung injury is a major cause of death in sepsis. Tofacitinib (TOFA), a JAK inhibitor, has anti-inflammatory activity in autoimmune diseases, but its role in acute lung injury in sepsis remains unclear. The purpose of this study is to establish a septic rat model by cecal ligation and perforation, and to evaluate the effect of tofacitinib on the survival rate of septic rat model and its role in acute lung injury in septic rats and the possible mechanism of action. In this study, TOFA (1 mg/kg, 3 mg/kg, 10 mg/kg) was used to observe the survival rate of septic rats. It was found that TOFA (10 mg/kg) significantly improved the survival rate of septic rats. We selected TOFA (10 mg/kg) and focused on the protective effect of TOFA on acute lung injury. The results confirmed that TOFA significantly inhibited the expression of TNF-α, IL-1β, IL-6 and IFN-γ inflammatory factors, reduced the W/D weight ratio of septic lung tissue, and significantly improved lung histopathological damage. These results may be related to the inhibitory effect of TOFA on JAK-STAT/NF-κ B signaling pathway. In conclusion, for the first time, we found that TOFA has a protective effect against sepsis-induced acute lung injury, and it may be a promising drug for the treatment of acute lung injury in sepsis.

Abstract Background Aging is an inevitable process associated with impairments in multiple organ systems, which increases the risk of comorbidity and disability, and reduces the health-span. Metabolomics is a powerful tool in aging research, which can reflect the characteristics of aging at the level of terminal metabolism, and may contribute to the exploration of aging mechanisms and the formulation of anti-aging strategies. Methods To identify possible biomarkers and pathways associated with aging using untargeted metabolomics methods, we performed liquid chromatography–mass spectrometry (LC–MS)-based untargeted metabolomics profiling on serum samples from 32 older adults and 32 sex-matched young controls. Results Metabolite profiling could distinguish the two groups. Among the 349 metabolites identified, 80—including lysophospholipids whose levels gradually decline—are possible candidate aging biomarkers. Valine, leucine and isoleucine degradation and biosynthesis were important pathways in aging, with reduced levels of l-isoleucine (r = − 0.30, p = 0.017) and l-leucine (r = − 0.32, p = 0.010) observed in older adults. Conclusions We preliminarily revealed the metabolite changes associated with aging in Chinese adults. Decreases in mitochondrial membrane-related lysophospholipids and dysfunction of branched-chain amino acid metabolism were determined to be the characteristics and promising research targets for aging.

Abstract Background Diabetes is an independent risk factor of frailty, which increases adverse outcomes in patients with diabetes. Metformin is a common antidiabetic drug in clinical practice. Insulin resistance and chronic inflammation are the two common mechanisms of diabetes and frailty, as well as the main targets of metformin. Research suggested that metformin has anti-aging potential. However, few studies focus on the relationship between metformin and frailty. Thus, we aimed to explore whether metformin was associated with a low risk of frailty and other adverse outcomes in diabetic patients. Methods A total of 422 patients (≥ 40 years old) with type 2 diabetes were recruited. Frailty was defined by the Fried phenotype. General information and metformin exposure data were collected, and comprehensive geriatric assessment and laboratory tests were performed. Follow-up was conducted after 4.5 years. The primary outcome was the combined endpoint of cardiovascular events, cerebrovascular events, readmission, and death. Binary logistic regression analysis was used to analyze the association of metformin with frailty. Survival analysis was performed using Cox proportional hazards models. Results The total prevalence of frailty was 19.4% among the participants with diabetes. 13.1% of patients in the metformin group and 28.2% in the non-metformin group had frailty. Metformin was inversely associated with frailty after adjusting for age, sex, duration, blood glucose levels, target organ damage, comorbidities, and polypharmacy. Further longitudinal analysis showed that metformin was also independently associated with a low risk of combined primary outcomes after adjusting for multiple covariables, while frailty was related to an increased risk of the combined primary outcomes. In the non-frail group, metformin was associated with a decreased risk of combined primary outcomes after adjustment for age and sex. However, the protective effect of metformin on adverse outcomes was not found in frail participants with diabetes. Conclusions Metformin use is associated with a reduced risk of frailty. In addition, frailty may attenuate the protective effects of metformin on adverse outcomes in diabetic patients. The early identification and prevention of frailty progression may help enhance the benefits of metformin in patients with diabetes.

Background: Neurocysticercosis (NCC), a predominant parasitic disease that affects the central nervous system and presents with diverse clinical manifestations, is a major contributor to acquired epilepsy worldwide, particularly in low-, middle-, and upper middle-income nations, such as China. In China, the Yunnan Province bears a significant burden of this disease. Objective: To describe the demographic, clinical, and radiological features as well as serum and cerebrospinal fluid antibodies to cysticercus in patients with NCC from Dali, Yunnan Province, China. Materials and Methods: This retrospective study included patients who were diagnosed with NCC at The First Affiliated Hospital of Dali University between January 2018 and May 2023 and were residing in Dali, Yunnan Province, China. Results: A total of 552 patients with NCC were included, of which 33.3% belonged to Bai ethnicity. The clinical presentation of NCC exhibited variability that was influenced by factors such as the number, location, and stage of the parasites. Epilepsy/seizure (49.9%) was the most prevalent symptom, with higher occurrence in the degenerative stage of cysts (P < 0.001). Compared with other locations, cysticerci located in the brain parenchyma are more likely to lead to seizures/epilepsy (OR = 17.45, 95% CI: 7.96–38.25) and headaches (OR = 3.02, 95% CI: 1.23–7.41). Seizures/epilepsy are more likely in patients with cysts in the vesicular (OR = 2.71, 95% CI: 1.12–6.61) and degenerative (OR = 102.38, 95% CI: 28.36–369.60) stages than those in the calcified stage. Seizures was not dependent on the number of lesions. All NCC patients underwent anthelminthic therapy, with the majority receiving albendazole (79.7%). Conclusion: This study provides valuable clinical insights into NCC patients in Dali and underscores the significance of NCC as a leading preventable cause of epilepsy.

Healthcare for truck drivers is an important issue. To prevent fatigue-related collisions among drivers, objective assessments of their physiological states are essential. A simple and quantitative evaluation method for fatigue involves the use of autonomic nerve function (ANF) indices obtained from heart rate variability analysis. However, predicting the occurrence of crashes using only physiological data is challenging. In most previous studies, the targets of driving situations have been often limited, or the prediction targets have been set as the driver’s internal state rather than the accident. In this paper, we propose a novel collision risk prediction model using ANF and several simple external information types, which can be extracted from standard in-vehicle sensors without limiting the driving scene. Our experiments using actual truck drivers’ data reveal that the proposed model can achieve collision risk prediction for the following 30 min with an accuracy of 74.9% recall and 0.79 AUC. Furthermore, we discover that simple external information obtained based on the vehicle speed significantly contributes to the prediction accuracy. As our prediction method only requires commonly equipped sensors as the sources of external information, this method is expected to be easily implemented not only for truck driving but also for general vehicle driving, where crashes are often likely.

High-throughput chromatin conformation capture technologies, such as Hi-C and Micro-C, have enabled genome-wide view of chromatin spatial organization. Most recently, Hi-C-derived enrichment-based technologies, including HiChIP and PLAC-seq, offer attractive alternatives due to their high signal-to-noise ratio and low cost. While a series of computational tools have been developed for Hi-C data, methods tailored for HiChIP and PLAC-seq data are still under development. Here we present HPTAD, a computational method to identify topologically associating domains (TADs) from HiChIP and PLAC-seq data. We performed comprehensive benchmark analysis to demonstrate its superior performance over existing TAD callers designed for Hi-C data. HPTAD is freely available at https://github.com/yunliUNC/HPTAD.

The limitation in metal-semiconductor contact has been a major challenge for high-performance organic field-effect transistors. Here, the authors fabricate the contact by transferring platinum electrode on solution-processed organic films, realizing ultralow total contact resistance down to 14 Ω ∙ cm.

It is well-known that mosquito control is one of the effective methods to reduce and prevent the transmission of mosquito-borne diseases. In this paper, we formulate a reaction-diffusion impulsive hybrid model incorporating Wolbachia, impulsively spraying of insecticides, spatial heterogeneity, and seasonality to investigate the control of mosquito population. The sufficient conditions for mosquito extinction or successful Wolbachia persistence in a population of natural mosquitoes are derived. More importantly, we give the estimations of the spraying times of insecticides during a period for achieving the mosquito extinction and population replacement in a special case. A global attractivity of the positive periodic solution is analyzed under appropriate conditions. Numerical simulations disclose that spatial heterogeneity and seasonality have significant impacts on the design of mosquitoes control strategies. It is suggested to combine biological control and chemical pulse control under certain situations to reduce the natural mosquitoes. Further, our results reveal that the establishment of a higher level of population replacement depends on the strain type of the Wolbachia and the high initial occupancy of the Wolbachia-infected mosquitoes.

Reliable assessment of landslide susceptibility in broad areas of terrain remains challenging due to complex topography and poor representation of randomly selected negative samples. Assessment in broad areas is now primarily based on grid units, which do not have a clear physical meaning like slope units, and their accuracy is not ideal. Nevertheless, the large amount of manual editing, due to the incorrectly generated horizontal and vertical lines during slope unit partitioning, limits using slope units for rapid assessment over large areas. Hence, this paper proposes a reliable susceptibility assessment approach to solve this problem based on optimal slope units and negative samples involving prior knowledge. Precisely, an algorithm to automatically extract slope units is designed to eliminate fragmented and erroneous units. Second, a samples labeling index (SLI) is defined based on the certainty factors model to select negative samples reasonably. Sichuan Province, China is selected for experimental analysis, with the results demonstrate that the optimized slope unit and the negative samples selection strategy consider prior knowledge achieve better results in the random forest model, support vector machine model, and artificial neural network model. In particular, the composite performance index AUC of artificial neural network model improved from 0.81 to 0.90.

Abstract Lasing is observed in Bragg lasers formed through conformal contact of a patterned PDMS stamp with a plain active film, spincoated on glass. The thresholds, output efficiencies and spectral characteristics are compared to standard substrate patterned gratings and is discussed in relation to the coupling coefficient $$\upkappa $$ κ . The reported thresholds are highly sensitive in distributed feedback (DFB) lasers to grating duty cycles, for both PDMS-air and substrate–film lasers. Overall, laser thresholds of PDMS-air (PA) DFB lasers are found to be significantly higher than substrate–film (SF) lasers, which is attributed to an approximate three-fold reduction of optical-confinement in the grating region. Slope output efficiencies are found to be comparatively higher in PA lasers relative to SF lasers for both DFB and DBR configurations and is attributed to several competing factors. The PDMS can be removed from the surface of the active film repeatedly and conformal contact is limited mainly by the particle build up on the PDMS surface. The proposed PA system is expected to be useful in rapid laser metrology of new gain materials and in practical applications of optically pumped lasers.

Abstract Objective This article aims to propose a new surgical method for the treatment of pyriform fistula, especially for the complex pyriform fistula. Methods A total of 36 patients with pyriform fistula underwent the procedure between August 2017 to October 2020. Surgery was performed by the senior authors using the same technique at the same clinical center for all patients. The median follow‐up time was 33 months. Meantime, we collected information on patients with pyriform fistula using traditional surgical methods in our hospital from April 2015 to November 2018 for comparison. Results The surgery was successfully completed in 36 patients. In all, 32 patients had a history of multiple incisions and drainage, 16 patients had a history of surgical resections, and two patients had a history of cauterization of the internal fistula. Compared with traditional surgical methods, our new surgical method greatly shortens the length of the surgical incision (4.3 vs. 5.5, p

Abstract Background Liquid biopsy has been widely researched for early diagnosis, prognostication and disease monitoring in lung cancer, but there is a need to investigate its clinical utility for early-stage non-small cell lung cancer (NSCLC). Methods We performed a meta-analysis and systematic review to evaluate diagnostic and prognostic values of liquid biopsy for early-stage NSCLC, regarding the common biomarkers, circulating tumor cells, circulating tumor DNA (ctDNA), methylation signatures, and microRNAs. Cochrane Library, PubMed, EMBASE databases, ClinicalTrials.gov, and reference lists were searched for eligible studies since inception to 17 May 2022. Sensitivity, specificity and area under the curve (AUC) were assessed for diagnostic values. Hazard ratio (HR) with a 95% confidence interval (CI) was extracted from the recurrence-free survival (RFS) and overall survival (OS) plots for prognostic analysis. Also, potential predictive values and treatment response evaluation were further investigated. Results In this meta-analysis, there were 34 studies eligible for diagnostic assessment and 21 for prognostic analysis. The estimated diagnostic values of biomarkers for early-stage NSCLC with AUCs ranged from 0.84 to 0.87. The factors TNM stage I, T1 stage, N0 stage, adenocarcinoma, young age, and nonsmoking contributed to a lower tumor burden, with a median cell-free DNA concentration of 8.64 ng/ml. For prognostic analysis, the presence of molecular residual disease (MRD) detection was a strong predictor of disease relapse (RFS, HR, 4.95; 95% CI, 3.06–8.02; p

Most genetic association studies have been done on single nucleotide polymorphisms and small indels, while other types of variants have been less studied. Here, the authors use whole genome sequencing in a diverse population to identify and provide experimental evidence for associations between structural variants and blood-cell traits.

In this study, we examined the expression of 11 cytokines in liver and serum of C57BL/6 mice upon single or co-exposed to Aflatoxin B1 and Microcystin-LR at low-dose and sub-chronic conditions. The objective is to elucidate the potential combined hepatotoxic effects induced by AFB1+MC-LR, and we aim to provide references for further immune impacts in the liver. Luminex-based cytokine examination was applied, and we found that most of the cytokine expression increased with time. The level of IL-18, GM-CSF, IFN-γ, IL-1β and IL-4 in the liver showed a significant rise. However, some cytokines (IL-13) showed an upward trend after being suppressed during the middle stage of exposure. The level of IFN-γ and IL-12p70 generally represented the immune response in the combined exposure group. Conclusionally, there are many uncertainties due to sub-chronic and low-dose exposure. Therefore, the occurrence of subsequent irreversible liver injury and liver cancer is a probabilistic event.

ABSTRACT: Objectives: XNW4107 is a novel β-lactamase inhibitor that possesses broad activity against serine-β-lactamases. XNW4107 in combination with imipenem exhibited potent in vitro activity against carbapenem-resistant bacteria and particularly against carbapenem-resistant Acinetobacter baumannii. This study aimed to evaluate the in vitro and in vivo antibacterial activities of imipenem/XNW4107. Methods: The minimum inhibitory concentrations, minimum bactericidal concentrations, time-kill curves, post-antibiotic effects, and spontaneous frequency of resistance were used to investigate the imipenem/XNW4107 in vitro activity. A mouse systemic infection model was used to evaluate the imipenem/XNW4107 in vivo efficacy. Results: MIC90 of imipenem/XNW4107 against imipenem-nonsusceptible A. baumannii (n = 106) was 8 mg/L, which was 16-fold lower than the MIC90 of imipenem; the resistance rate decreased from 90% to 20% applying the CLSI imipenem breakpoint. MIC90 of imipenem/XNW4107 against imipenem-resistant Klebsiella pneumoniae (n = 54) was 2 mg/L, which was 128-fold lower than the MIC90 of imipenem; 80% imipenem-nonsusceptible Pseudomonas aeruginosa (n = 101) exhibited MICs of imipenem/XNW4107 from 2 to 8 mg/L, which were 4- to 8-fold lower than the MICs of imipenem. Imipenem/XNW4107 was bactericidal against A. baumannii, K. pneumoniae, and Escherichia coli. The time-kill curves showed that increasing concentrations did not result in progressively increased killing at concentrations >4 × MIC. Imipenem/XNW4107 has a low potential for resistance development in tested strains except for K. pneumoniae. Imipenem/XNW4107 provided good protection against imipenem-resistant A. baumannii and K. pneumoniae in vivo. Conclusions: The broad-spectrum profile and potent in vitro and in vivo antibacterial activities support imipenem/XNW4107 as a promising investigational candidate.