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Abstract Background The integration of multi-omics data through deep learning has greatly improved cancer subtype classification, particularly in feature learning and multi-omics data integration. However, key challenges remain in embedding sample structure information into the feature space and designing flexible integration strategies. Results We propose MoAGL-SA, an adaptive multi-omics integration method based on graph learning and self-attention, to address these challenges. First, patient relationship graphs are generated from each omics dataset using graph learning. Next, three-layer graph convolutional networks are employed to extract omic-specific graph embeddings. Self-attention is then used to focus on the most relevant omics, adaptively assigning weights to different graph embeddings for multi-omics integration. Finally, cancer subtypes are classified using a softmax classifier. Conclusions Experimental results show that MoAGL-SA outperforms several popular algorithms on datasets for breast invasive carcinoma, kidney renal papillary cell carcinoma, and kidney renal clear cell carcinoma. Additionally, MoAGL-SA successfully identifies key biomarkers for breast invasive carcinoma.

Abstract This study aimed to identify the specific site of pulmonary vein conduction recovery after radiofrequency ablation (RFA) of atrial fibrillation (AF) for improved outcomes and reduced recurrence. Patients who underwent RFA for AF at our institution were included. The ablation procedure was guided by the ablation index (AI) and left, and right atrial pressures were monitored before and after ablation. Additionally, the recovery time of the sinoatrial node under Burst 400/300 ms stimulation was examined. Among 60 repeat procedure patients, 48 had paroxysmal and 12 had persistent AF. The recovery sites were 36.6% in the left anterior superior, 35% in the right anterior superior, 20% in the left anterior inferior, 20% in the right anterior inferior, 13.3% in the right top, and 11.6% in the left top. Preoperative and postoperative left and right atrial pressures were significantly higher in the persistent AF group compared with the paroxysmal AF group (P

The distribution of oil and gas phases around ball–raceway local regions is an important basis and foundation for determining whether a bearing is sufficiently lubricated. To obtain the oil phase distribution law in the inner raceway–ball contact local region (IBCR) and outer raceway–ball contact local region (OBCR) of the ball bearing with under-race lubrication, the numerical simulation method is used. The effects of bearing rotation speed, oil flow rate, oil viscosity, and oil density on these two regions are studied. The results indicate that the oil phase exhibited significant periodic changes in both time and space. Compared with that in the IBCR, the oil phase distribution in the OBCR is more uniform. Increasing the bearing rotation speed and reducing the oil flow rate made the IBCR and OBCR more uniform. Changing the oil viscosity only alters the distribution pattern of the OBCR. The oil density may not affect the fluid flow state or the oil phase distribution in the bearing.

Abstract Aim To analyze the clinicopathological features of schistosomal and non-schistosomal colorectal cancer in Central China and compare them with other areas of the Yangtze River Basin. Method The 501 cases of colorectal cancer (CRC) were retrospectively analyzed from 2020 to 2022. They were divided into two groups: 406 cases of colorectal cancer without schistosomiasis (CRC-NS) and 95 cases of colorectal cancer with schistosomiasis (CRC-S).The clinicopathological characteristics included the distribution of schistosomiasis eggs, patient age, sex, tumor differentiation, lymph node metastasis, and clinical stage. By retrieving the database, this study compared the clinicopathological differences of colorectal cancer with schistosomiasis in other areas of the Yangtze River basin. Results The cases of colorectal cancer with schistosomiasis accounted for 18.9%(95/501) in the study. The patients of CRC-S were older than the patients of CRC-NS (P = 0.002, P

When 2-chloro-6-(trichloromethyl) pyridine (nitrapyrin) is applied alone, it typically does not significantly increase crop yield. Therefore, we combined gamma-aminobutyric acid (GABA) with nitrapyrin to address the limitations of nitrapyrin in enhancing yield. We conducted indoor incubation experiments and pot experiments in Chernozem and Calcic Kastanozem, respectively. The results demonstrated that GABA exerted an influence on the effectiveness of nitrapyrin by altering its degradation rate. In Chernozem, GABA accelerated nitrapyrin degradation, whereas, in Calcic Kastanozem, the results were the opposite. The pot experiment results showed that the combination of nitrapyrin and GABA increased rice total biomass by 5%, grain yield by 18 ± 2%, and plant nitrogen (N) uptake by 9 ± 1% compared to nitrapyrin applied alone. The increase in yield was attributed to the combined effect of nitrapyrin and GABA, which elevated root biomass and leaf area. In contrast, the effect of GABA on yield through altering the degradation rate of nitrapyrin was weaker. Therefore, the combination of nitrapyrin and GABA combined with urea increases rice yields in Chernozem and Calcic Kastanozem. The aim of this endeavour was to foster the development of a novel fertiliser product that offers both favourable agronomic outcomes and environmental benefits.

Abstract Background Breeding polled goats is a welfare-friendly approach for horn removal in comparison to invasive methods. To gain a comprehensive understanding of the genetic basis underlying polledness in goats, we conducted whole-genome sequencing of 106 Xinong Saanen dairy goats, including 33 horned individuals, 70 polled individuals, and 3 polled intersexuality syndrome (PIS) individuals. Methods The present study employed a genome-wide association study (GWAS) and linkage disequilibrium (LD) analysis to precisely map the genetic locus underlying the polled phenotype in goats. Results The analysis conducted in our study revealed a total of 320 genome-wide significant single nucleotide polymorphisms (SNPs) associated with the horned/polled phenotype in goats. These SNPs exhibited two distinct peaks on chromosome 1, spanning from 128,817,052 to 133,005,441 bp and from 150,336,143 to 150,808,639 bp. The present study identified three genome-wide significant SNPs, namely Chr1:129789816, Chr1:129791507, and Chr1:129791577, as potential markers of PIS-affected goats. The results of our LD analysis suggested a potential association between MRPS22 and infertile intersex individuals, as well as a potential association between ERG and the polled trait in goats. Conclusion We have successfully identified three marker SNPs closely linked to PIS, as well as several candidate genes associated with the polled trait in goats. These results may contribute to the development of SNP chips for early prediction of PIS in goats, thereby facilitating breeding programs aimed at producing fertile herds with polled traits.

ObjectiveThe prevalence of osteoporosis and its resultant healthcare challenges are escalating, posing significant burdens on public health systems. Studies have introduced immunoinflammatory indices, which are recognized for effectively reflecting the systemic immunoinflammatory status. Despite their potential, the exploration of these indices in the context of osteoporosis remains limited. The study sought to explore the relationship between immune inflammation-related indices and osteoporosis in non-diabetic elderly populations.MethodsThe clinical data of 438 non-diabetic elderly subjects were retrospectively analyzed and all statistical analyses were performed using SPSS 27.0.ResultsDifferences were observed between the osteoporosis group and the normal bone density group in terms of age, neutrophil, lymphocyte, monocyte, hemoglobin, and platelet. A review of prior studies revealed a close association between osteoporosis and chronic inflammation. Immunological indices such as Platelet to Lymphocyte Ratio (PLR), Neutrophil to Lymphocyte Ratio (NLR), Monocyte to Lymphocyte Ratio (MLR), Systemic Immuno-Inflammatory Index (SII), Systemic Inflammatory Response Index (SIRI) and Peripheral Immunity Index (PIV) were calculated. The analysis indicated significant differences in MLR, SII, SIRI and PIV. A multifactorial binary logistic regression model was established, incorporating age, MLR, SII, SIRI, and PIV as variables. The results identified age and SIRI as independent risk factors for bone abnormalities in non-diabetic elderly populations, while PIV served as an independent protective factor. Receiver operating characteristic analysis demonstrated that SIRI and PIV predicted osteoporosis with areas under the curve (AUC) of 0.609 and 0.620, respectively. The diagnostic value was enhanced when combined with age, yielding AUC values of 0.725 for PIV combined with age. PIV combined with age was particularly effective as a biomarker for bone abnormalities in this population. The optimal Youden’s index was calculated to be 0.367, corresponding to a sensitivity of 63.8% and a specificity of 72.9%.ConclusionsFor non-diabetic elderly populations, SIRI is a risk factor, while PIV serves as a protective factor against bone abnormalities. Combined with previous studies, we suggest that people at high risk of osteoporosis should avoid or minimize the intake of pro-inflammatory dietary patterns. Meanwhile, research from an immune perspective is expected to open new avenues for osteoporosis treatment.

BackgroundFibrinogen plays a pivotal role in the inflammatory cascade and is intricately linked to the pathogenesis of sepsis. Nevertheless, its significance as a prognostic marker for sepsis-associated acute kidney injury (SA-AKI) remains uncertain. This study aimed to investigate the association between fibrinogen levels and 28-day mortality with sepsis-associated acute kidney injury.MethodThe fibrinogen levels of patients admitted to the intensive care unit of Beth Israel Deaconess Medical Center between 2008 and 2019 were retrospectively assessed, and those diagnosed with SA-AKI were divided into low, middle and high fibrinogen level groups according to tertiles. Multivariate Cox proportional hazards model was used to assess the 28-day mortality risk of the SA-AKI patients.ResultsA total of 3,479 patients with SA-AKI were included in the study. Fibrinogen demonstrated an independent association with 28-day mortality, yielding a hazard ratio (HR) of 0.961 (95% confidence interval [CI]: 0.923-0.999, P = 0.0471). Notably, a non-linear relationship between fibrinogen levels and 28-day mortality was observed, with the threshold observed at approximately 1.6 g/l. The effect sizes and corresponding CIs below and above this threshold were 0.509 (0.367, 0.707) and 1.011 (0.961, 1.064), respectively. Specifically, the risk of mortality among SA-AKI patients decreased by 49.1% for every 1 g/l increment in fibrinogen, provided that fibrinogen levels were less than 1.6 g/l.ConclusionIn patients with SA-AKI, a non-linear relationship was identified between fibrinogen levels and 28-day mortality. Particularly, when their fibrinogen levels were less than 1.6 g/l, a concomitant decrease in 28-day mortality was observed as fibrinogen levels increased.

ObjectiveThis study aims to explore the correlation between patients with Hashimoto’s thyroiditis and food intolerance.MethodsA total of 172 subjects who visited Guangdong Provincial Hospital of Traditional Chinese Medicine between January 2020 and March 2023 were selected and tested for 90 food-specific IgG antibodies. The study group composed 85 individuals diagnosed with Hashimoto’s thyroiditis, while the control group consisted of 87 healthy individuals. Data were analyzed to determine the correlation between Hashimoto’s thyroiditis and food intolerance.ResultsAmong the 85 patients with Hashimoto’s thyroiditis, 97.65% exhibited food intolerance, with an average of 15.76 ± 10.61 types of food intolerances. The most common intolerances were to eggs (75.29%), bok choy (71.76%), and milk (65.88%), each exceeding a 60% intolerance rate. In the control group of 87 healthy individuals, the intolerance rate was 95.40%, with an average of 9.57 ± 8.90 types of food intolerances. The most prevalent intolerances in the control group were to bok choy (54.02%) and eggs (52.87%), each exceeding a 50% intolerance rate.ConclusionThe findings suggest that patients with Hashimoto’s thyroiditis are more likely to develop food intolerance compared to the healthy population, which may indicate a correlation between Hashimoto’s thyroiditis and food intolerance. Different dietary patterns may affect the activity of the thyroid axis and may even be the cause of autoimmune thyroid disease. The technique of detecting food intolerance IgG antibodies has the potential to be an important reference for dietary interventions in patients with Hashimoto’s thyroiditis.

ABSTRACT: Semen quality is an important indicator that can directly affect fertility. In mammals, miRNAs in seminal plasma extracellular vesicles (SPEVs) and sperms can regulate semen quality. However, relevant regulatory mechanism in duck sperms remains largely unclear. In this study, duck SPEVs were isolated and characterized by transmission electron microscopy (TEM), western blot (WB), and nanoparticle tracking analysis (NTA). To identify the important molecules affecting semen quality, we analysed the miRNA expression in sperms and SPEVs of male ducks in high semen quality group ((DHS, DHSE) and low semen quality group (DLS, DLSE). We identified 94 differentially expressed (DE) miRNAs in the comparison of DHS vs. DLS, and 21 DE miRNAs in DHSE vs. DLSE. Target genes of SPEVs DE miRNAs were enriched in ErbB signaling pathway, glycometabolism, and ECM-receptor interaction pathways (P < 0.05), while the target genes of sperm DE miRNAs were enriched in ribosome (P < 0.05). The miRNA-target-pathway interaction network analyses indicated that 5 DE miRNAs (miR-34c-5p, miR-34b-3p, miR-449a, miR-31-5p, and miR-128-1-5p) targeted the largest number of target genes enriched in MAPK, Wnt and calcium signaling pathways, of which FZD9 and ANAPC11 were involved in multiple biological processes related to sperm functions, indicating their regulatory effects on sperm quality. The comparison of DE miRNAs of SPEVs and sperms found that mir-31-5p and novel-273 could potentially serve as biomarkers for semen quality detection. Our findings enhance the insight into the crucial role of SPEV and sperm miRNAs in regulating semen quality and provide a new perspective for subsequent studies.

Drought, excessive use of nitrogen fertilizer, and decline in soil organic matter threaten corn production. This study investigated the potential of water retaining agents, inhibitors, and corn stalks in enhancing soil physicochemical properties to bolster corn yield in semi-arid farmlands. In our study, polyacrylamide addition increased the content of ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) in the seedling stage, exchangeable potassium (K) in the mature stage but decreased the content of available phosphorus (P) in the seedling stage. Potassium polyacrylate addition increased the content of NH4+-N and decreased the content of available P in the seedling stage. The addition of inhibitors decreased the content of NH4+-N and available P in the seedling stage, NO3--N and available P in the jointing stage, and NH4+-N in the mature stage, respectively. Corn stalks returning could maintain soil moisture, decrease the content of NH4+-N in the seedling stage and exchangeable K in the mature stage, and increase the content of available P and exchangeable K in the seedling stage. Combined application of inhibitors and corn stalks could increase soil organic carbon (SOC) and ensure corn yield, which was the best fertilization mode in semi-arid cropland.

Objective:. Real-world diagnostic and treatment data for pancreatic cancer in China are lacking. As such, the present study investigated the clinical characteristics, diagnosis, and treatment of advanced pancreatic cancer (including locally advanced and metastatic disease) in the Hospital-based Advanced Pancreatic Cancer Cohort in China of the China Pancreas Data Center database. Methods:. A total of 5349 Chinese patients with advanced pancreatic cancer were identified from a database. The entire course of real-world pancreatic cancer management was analyzed. Results:. The proportion of patients with advanced pancreatic cancer was higher among males than females (62.4% vs 37.6%, respectively). Patients typically had a history of hypertension (30.8%), diabetes (21.6%), and cholangitis (20.2%). Abdominal pain (51.6%), abdominal distension (27.1%), jaundice (20.1%), and weight loss (16.3%) were the main symptoms observed in patients with advanced pancreatic cancer in this cohort. Serum carbohydrate antigen (CA)19-9 is one of the most common tumor markers. In the present study, 2562 patients underwent first-line therapy. The median progression-free survival (PFS) for patients undergoing first-line therapy was 4.1 months. The major options for first-line therapy included gemcitabine (GEM) plus S-1 (GS/X) (23.4%), nab-paclitaxel plus GEM (AG) (18.1%), oxaliplatin, irinotecan, and leucovorin-modulated fluorouracil (FOLFIRINOX; 11.9%), nab-paclitaxel plus S-1 (AS) (8.9%), and GEM combined with oxaliplatin/cisplatin (GEMOX/GP) (7.6%). The AS and GS/X regimens were associated with the highest PFS rates. Conclusion:. This is the first study to report multicenter, real-world data regarding advanced pancreatic cancer in China. Results revealed that real-world treatment options differed from guideline recommendations, and PFS was shorter than that in previously reported data. Improving intelligent follow-up systems and standardizing diagnosis and treatment of pancreatic cancer is recommended.

Cultivating Suaeda salsa (S. salsa) is a promising strategy for the improvement and development of saline wastelands. However, the absence of a scientifically reasonable water and fertilizer management system has long hindered the large-scale improvement and utilization of saline wastelands. Therefore, we performed field experiments for two consecutive years to investigate the effects of water-nitrogen coupling on biomass, forage quality, salt absorption capacity, soil improvement effect, and economic benefits of S. salsa. The optimal water and nitrogen dosages for multi-objective optimization were determined using multiple regression and spatial analysis methods. Three irrigation levels were established for the experiment based on 0.35 (W1), 0.50 (W2), and 0.65 (W3) of the local ETo (Where ETo denotes the reference evapotranspiration calculated based on the FAO-56 recommended by the Food and Agriculture Organization). The three nitrogen application levels were 150 (F1), 250 (F2), and 350 (F3) kg ha−1 in the complete combination design. At the same nitrogen application level, the biomass and economic benefits of the W3 irrigation level were the highest. However, the forage quality, salt absorption capacity, salt reduction, and water productivity at the W3 irrigation level were lower than those at the W2 irrigation level, and the water productivity at the W1 irrigation level was the highest. At the same irrigation level, when the nitrogen application level was F2, the biomass, forage quality, salt absorption, salt reduction, and net profit, all reached their maximum values, and water productivity was the highest at the F3 level. The optimal amount of water and nitrogen applied for each parameter was different, so it was impossible to obtain the highest biomass, forage quality, salt absorption, salt reduction, water productivity, and net profit at the same time. Therefore, multi-objective optimization was needed, the optimal irrigation volume range was 3350.11–3485.97 m3 ha−1, and the nitrogen application rate range was 273.49–326.66 kg ha−1. These findings provide a scientific basis for the large-scale cultivation of S. salsa in extreme arid region, which is helpful for the improvement and utilization of saline-alkali land.

Bloodstream infections (BSIs) are a critical medical concern, characterized by elevated morbidity, mortality, extended hospital stays, substantial healthcare costs, and diagnostic challenges. The clinical outcomes for patients with BSI can be markedly improved through the prompt identification of the causative pathogens and their susceptibility to antibiotics and antimicrobial agents. Traditional BSI diagnosis via blood culture is often hindered by its lengthy incubation period and its limitations in detecting pathogenic bacteria and their resistance profiles. Surface-enhanced Raman scattering (SERS) has recently gained prominence as a rapid and effective technique for identifying pathogenic bacteria and assessing drug resistance. This method offers molecular fingerprinting with benefits such as rapidity, sensitivity, and non-destructiveness. The objective of this study was to integrate deep learning (DL) with SERS for the rapid identification of common pathogens and their resistance to drugs in BSIs. To assess the feasibility of combining DL with SERS for direct detection, erythrocyte lysis and differential centrifugation were employed to isolate bacteria from blood samples with positive blood cultures. A total of 12,046 and 11,968 SERS spectra were collected from the two methods using Raman spectroscopy and subsequently analyzed using DL algorithms. The findings reveal that convolutional neural networks (CNNs) exhibit considerable potential in identifying prevalent pathogens and their drug-resistant strains. The differential centrifugation technique outperformed erythrocyte lysis in bacterial isolation from blood, achieving a detection accuracy of 98.68% for pathogenic bacteria and an impressive 99.85% accuracy in identifying carbapenem-resistant Klebsiella pneumoniae. In summary, this research successfully developed an innovative approach by combining DL with SERS for the swift identification of pathogenic bacteria and their drug resistance in BSIs. This novel method holds the promise of significantly improving patient prognoses and optimizing healthcare efficiency. Its potential impact could be profound, potentially transforming the diagnostic and therapeutic landscape of BSIs.

Understanding the differences in genetic variation between local Chinese dairy goat breeds and imported breeds can help germplasm innovation and molecular breeding. However, the research is limited in this area. In this study, whole-genome resequencing data from 134 individuals of both local and imported dairy goat breeds were analyzed, and their differences in genomic genetic variation, genetic diversity, and population structure were subsequently identified. We also screened candidate genes associated with important traits of dairy goats such as milk production (STK3, GHR, PRELID3B), reproduction (ATP5E), growth and development (CTSZ, GHR), and immune function (CTSZ, NELFCD). Furthermore, we examined allele frequency distributions for the genes of interest and found significant differences between the two populations. This study provides valuable resources for the study of genetic diversity in dairy goats and lays the foundation for the selective breeding of dairy goats in the future.

Abstract High thermal conductive polymers have become more important because equipment requires high performance, high-energy density, and high integration. There are different strategies to make high thermal conductive polymers, among which is the synthesis of polymers in the liquid crystal phase. However, the thermal conductivity of such material is rarely beyond 1 W m−1 K−1 because of the disordered molecular directionality. The disordered directionality between crystal zones limits the thermal conductivity in a specific direction. Here, we show a method for unifying the direction of crystal zones by applying an external electric field on the liquid crystal monomers. Meanwhile, by exposing the transparent equipment and specially designed photopolymerisable monomer in UV light, the liquid crystal monomer is in situ polymerised into a liquid crystal polymer with a high intrinsic thermal conductivity of 1.02 W m−1 K−1. The molecular alignment was characterised and resulted in the resultant high conductivity.

Abstract How climate change will influence the accumulation of pollutants in remote mountainous lakes is poorly understood. Here we collected sediment cores from two glacial lakes (one is small and close to glacier, and the other is large and far from glacier) in the Third Pole and quantified deposition fluxes of perfluoroalkyl substances. The trends of perfluoroalkyl substances fluxes broadly correspond with their historical emissions and phase-out. Besides of emission, glacial meltwater strongly impacts the accumulation of perfluoroalkyl substances in the small lake, while precipitation exhibits great impact on that of the big lake. We then modified the Quantitative Water Air Sediment Interaction model to explore how perfluoroalkyl substances transport along proglacial rivers before entering the big lake and found that river sediments intercept ~13% of perfluoroalkyl substances from glacial meltwater. With climate warming and increased glacial meltwater, proglacial river sediments will play an important role in retaining perfluoroalkyl substances.

Abstract Background Synaptosomal-associated protein 25 (SNAP25) exerts protective effects against postoperative cognitive dysfunction (POCD) by promoting PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy and repressing caspase-3/gasdermin E (GSDME)-mediated pyroptosis. However, the regulatory mechanisms of SNAP25 protein remain unclear. Methods We employed recombinant adeno-associated virus 9 (AAV9)-hSyn to knockdown tumor necrosis factor α-induced protein 1 (TNFAIP1) or SNAP25 and investigate the role of TNFAIP1 in POCD. Cognitive performance, hippocampal injury, mitophagy, and pyroptosis were assessed. Co-immunoprecipitation (co-IP) and ubiquitination assays were conducted to elucidate the mechanisms by which TNFAIP1 stabilizes SNAP25. Results Our results demonstrated that the ubiquitin ligase TNFAIP1 was upregulated in the hippocampus of mice following isoflurane (Iso) anesthesia and laparotomy. The N-terminal region (residues 1–96) of TNFAIP1 formed a conjugate with SNAP25, leading to lysine (K) 48-linked polyubiquitination of SNAP25 at K69. Silencing TNFAIP1 enhanced SH-SY5Y cell viability and conferred antioxidant, pro-mitophagy, and anti-pyroptosis properties in response to Iso and lipopolysaccharide (LPS) challenges. Conversely, TNFAIP1 overexpression reduced HT22 cell viability, increased reactive oxygen species (ROS) accumulation, impaired PINK1/Parkin-dependent mitophagy, and induced caspase-3/GSDME-dependent pyroptosis by suppressing SNAP25 expression. Neuron-specific knockdown of TNFAIP1 ameliorated POCD, restored mitophagy, and reduced pyroptosis, which was reversed by SNAP25 depletion. Conclusions In summary, our findings demonstrated that inhibiting TNFAIP1-mediated degradation of SNAP25 might be a promising therapeutic approach for mitigating postoperative cognitive decline. Video Abstract

This study addresses the low water productivity (WP) of traditional flood irrigation (FI) and the mismatch between the wet zone of surface drip irrigation (SDI) and the root activity layer of fragrant pear. A fixed field experiment was conducted in Xinjiang, northwest China in 2021 − 2023. The experiment was designed as a two-factor, completely randomized trial with three lateral depths of Subsurface drip irrigation (SSDI) gradients set at 20 cm (D1), 30 cm (D2) and 40 cm (D3) and three irrigation gradients: W1 (3750 m³ ha−1); W2 (5250 m³ ha−1); and W3 (6750 m³ ha−1), using SDI (6750 m³ ha−1) and FI (9750 m³ ha−1) as the controls. The effects of these factors on soil moisture, crop water consumption (ETc), fruit quality, yield, WP and net profit were analyzed. The results revealed that the average soil moisture content increased with the lateral depth and irrigation amount. Principal component analysis determined D2W3 to be the treatments with the best overall quality in 2021–2023. On average, compared with SDI and FI, SSDI increased yield by 13.14% and 17.03%, and WP by 44.65% and 137.23%, respectively. A comprehensive Moisture-Yield-Quality-Efficiency evaluation model was established using the Projection Pursuit Classification model based on the Real Coded Accelerating Genetic Algorithm (RAGA-PPC). The comprehensive evaluation was optimized at the lateral depth of 30 cm and an irrigation amount of 6750 m³ ha−1. This study is a crucial reference for further research on perennial fruit trees to improve fruit quality and WP.

Angiogenesis plays a key role in bone regeneration. The role of neurons of peripheral nerves involved in angiogenesis of bone defects needs to be explored. The transient receptor potential vanilloid 1 (TRPV1), a nociceptor of noxious stimuli, is expressed on sensory neurons. Apart from nociception, little is known about the role of sensory innervation in angiogenesis. Calcitonin gene-related peptide (CGRP), a neuropeptide secreted by sensory nerve terminals, has been associated with vascular regeneration. We characterized the reinnervation of vessels in bone repair and assessed the impact of TRPV1-CGRP signaling on early vascularization. We investigated the pro-angiogenic effect of neuronal TRPV1 in the mouse model of femur defect. Micro-CT analysis with Microfil® reagent perfusion demonstrated neuronal TRPV1 activation enhanced angiogenesis by increasing vessel volume, number, and thickness. Meanwhile, TRPV1 activation upregulated the mRNA and protein expression of vascular endothelial growth factor A (VEGF-A), cell adhesion molecule-1 (CD31), and CGRP. Immunostaining revealed the co-localization of TRPV1 and CGRP in dorsal root ganglia (DRG) sensory neurons. By affecting neuronal TRPV1 channels, the release of neuronal and local CGRP was controlled. We demonstrated that TRPV1 influenced on blood vessel development by promoting CGRP release from sensory nerve terminals. Our results showed that neuronal TRPV1 played a crucial role in regulating angiogenesis during bone repair and provided important clinical implications for the development of novel therapeutic approaches for angiogenesis.

Background: Thyroid Dysfunction (TD) is a common immune-related adverse events (irAEs) in the treatment of advanced lung cancer with programmed cell death protein 1 (PD-1) and programmed death 1 ligand (PD-L1) inhibitors, with incidence accounting for 6–8% of all irAEs. The incidence of TD is receiving increasing attention from clinicians, given its potential impact on clinical efficacy. However, the molecular mechanisms, biomarkers, and clinical impact of TD resulting from PD-1/PD-L1 inhibitor treatment in advanced lung cancer are unclear. Objective: To present a comprehensive review of current advancements in research about the molecular mechanisms, influential factors, and clinical manifestations in the treatment of advanced lung cancer with PD-1 and PD-L1 inhibitors, as well as the correlation between TD and the efficacy of PD-1 and PD-L1 inhibitors. Methods: A systematic search was conducted using PubMed, Web of Science, Cochrane Library, Embase and Google Scholar databases, with the keywords including thyroid dysfunction, efficacy, mechanisms, immune checkpoint inhibitors, PD-1/PD-L1 inhibitors, and advanced lung cancer. Results: PD-1/PD-L1 inhibitors can induce T cell-mediated destructive thyroiditis, thyroid autoantibody-mediated autoimmunity, and a decrease in the number of immunosuppressive monocytes (circulating cluster of differentiation (CD)14+ human leukocyte antigen (HLA)-DRlow/negatives monocytes, CD14+ HLA-DR + lo/neg), leading to TD. Several factors, including peripheral blood inflammatory markers, body mass index (BMI), baseline thyroid-stimulating hormone (TSH) level, gender, smoking history, hypertension, and previous opioid use, may also contribute to the development of TD. However, there is currently a lack of reliable predictive biomarkers for TD, although anti-thyroid antibodies, TSH levels, and peripheral blood inflammatory markers are expected to be predictive.Interestingly, some studies suggested a positive correlation between TD and clinical efficacy, i.e., patients experiencing TD showed better outcomes in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS), compared with those without TD. However, most of these studies were single-center and had small sample sizes, so more multi-center studies are needed to provide further data support. Conclusion: TD resulting from PD-1/PD-L1 inhibitor treatment in advanced lung cancer may be associated with good clinical outcomes. The clarification of the molecular mechanisms underlying TD and the identification of reliable predictive biomarkers will guide clinicians in managing TD in this patient population.

Soil microbial carbon use efficiency (CUE) is a key parameter controlling the short-term carbon (C) cycle in terrestrial ecosystems. The effect of urea application (156 kg N ha-1) and corn stalks returning (9.0 tons ha-1) on soil microbial CUE and corn yield in semi-arid cropland was studied using the 18O-labeled water approach during a one-year experiment. In semi-arid cropland, applying urea reduced soil microbial CUE by 44%, while the soil microbial CUE was increased significantly by 34% after returning corn stalks to the field. The application of urea increased the total nitrogen content of soil by 23%, and corn stalks returning further increased nitrate nitrogen (NO3--N) by 45%, dissolved organic carbon (DOC) by 53%, and dissolved organic nitrogen (DON) by 122%. Compared with no fertilization, urea application increased the corn height by 4% and the corn yield by 21%. Corn stalks returning combined with urea reduced the corn stalks by 37% compared with no fertilizer. There was no significant difference in corn yield between corn stalks returning combined with urea and single urea application. Therefore, corn stalks returning combined with urea may be an effective agronomic measure to increase soil carbon sequestration, improve soil fertility, maintain corn yield, restore soil fertility, and improve production capacity.

Abstract Cuproptosis is a recently discovered novel programmed cell death pathway that differs from traditional programmed cell death and has an important role in cancer and immune regulation. Long noncoding RNA (lncRNA) is considered new potential prognostic biomarkers in pancreatic adenocarcinoma (PAAD). However, the prognostic role and immune landscape of cuproptosis-related lncRNA in PAAD remain unclear. The transcriptome and clinical data of PAAD were obtained from The Cancer Genome Atlas (TCGA) database. Cuproptosis-related lncRNA was identified using Pearson correlation analysis. The optimal lncRNA was screened by Cox and the Least Absolute Shrinkage and Selection Operator (LASSO) regression mode, and for the construction of risk scoring system. PAAD patients were divided into high- and low-risk groups according to the risk score. Clinicopathological parameter correlation analysis, univariate and multivariate Cox regression, time-dependent receiver operating characteristic (ROC) curves, and nomogram were performed to evaluate the model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to explore differences in biological function between different risk groups. Single-sample gene set enrichment analysis (ssGSEA) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm were used to analyze the differences in tumor immune microenvironment (TIME) in different risk groups of PAAD. Additionally, the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to predict immunotherapy response and identify potential immune beneficiaries. Immune checkpoints and tumor mutation burden (TMB) were also systematically analyzed. Finally, drug sensitivity analysis was used to explore the reactivity of different drugs in high- and low-risk groups to provide a reference for the selection of precise therapeutic drugs. Six cuproptosis-related lncRNAs (AL117335.1, AC044849.1, AL358944.1, ZNF236-DT, Z97832.2, and CASC8) were used to construct risk model. Survival analysis showed that overall survival and progression-free survival in the low-risk group were better than those in the high-risk group, and it is suitable for PAAD patients with different clinical characteristics. Univariate and multifactorial Cox regression analysis showed that risk score was an independent prognostic factor in PAAD patients. ROC analysis showed that the AUC values of the risk score in 1 year, 3 years and 5 years were 0.707,0.762 and 0.880, respectively. Nomogram showed that the total points of PAAD patients at 1 year, 3 years, and 5 years were 0.914,0.648, and 0.543. GO and KEGG analyses indicated that the differential genes in the high- and low-risk groups were associated with tumor proliferation and metastasis and immune regulatory pathway. Immune correlation analysis showed that the amount of pro-inflammatory cells, including CD8+ T cells, was significantly higher in the low-risk group than in the high-risk group, and the expression of immune checkpoint genes, including PD-1 and CTLA-4, was increased in the low-risk group. TIDE analysis suggests that patients in the low-risk group may benefit from immunotherapy. Finally, there was significant variability in multiple chemotherapeutic and targeted drugs across the risk groups, which informs our clinical drug selection. Our cuproptosis-related lncRNA scoring system (CRLss) could predict the clinical outcome and immune landscape of PAAD patients, identify the potential beneficiaries of immunotherapy, and provide a reference for precise therapeutic drug selection.

3,4-Dimethylpyrazole phosphate (DMPP) is acknowledged as one of the most efficient nitrification inhibitors (NIs); however, researchers have suggested that its effectiveness needs to be further improved. The authors combined the biostimulant seaweed extract (SE) with DMPP and conducted an indoor incubation experiment to initially investigate the impact of the influence of SE on the degradation and effectiveness of DMPP. Meanwhile, a method for the extraction and determination of DMPP was developed. DMPP performed better, with a longer effective time in loess than black soil, and SE showed a delayed effect on DMPP degradation of DMPP at the beginning of the incubation and then accelerated the degradation process. This was attributed to the adsorption effect of SE on DMPP, consequently reducing its effectiveness. The SE delayed the hydrolysis of urea in various soils; however, no significant impact on urease activity was observed (P < 0.05) (P < 0.05). Furthermore, it also increased potential nitrification rate (PNR) from 10 to 21 days and promoting the rapid transformation of NH4+-N in black soil. The SE reduced PNR within 21 days and inhibited nitrification in loess. In addition, the SE appeared to mitigate the adverse effects of excessive nitrogen on microorganisms The combination of DMPP and SE was not conducive to the inhibition of soil nitrification, and this formulation in field applications requires further investigation.

As of 31 October 2023, there have been 771,795,258 confirmed cases of COVID-19 globally. Developing simple, portable, and reliable testing devices has become increasingly important. This paper presents a point-of-care testing (POCT) device for COVID-19 based on the dual-excitation fluorescence RT-LAMP method, which is derived from the principles of RT-LAMP-based COVID-19 detection kits available in the market. The key design solutions of the device were simulated and modeled. Key performance metrics such as detection repeatability and linearity were validated. Comparative experiments with the RT-qPCR detection method were conducted to verify the accuracy and reliability of the device. Additionally, the device’s detection sensitivity and accuracy were assessed. Experimental results show that the repeatability coefficient of variation (CV) value is ≤0.09%; the linearity R2 for the FAM channel is 0.9977 and that for the HEX channel is 0.9899; it exhibits good anti-interference performance, with negligible cross-channel interference; the temperature stability is ±0.062 °C, the temperature accuracy is less than 0.2 °C, and there is no significant temperature overshoot during the heating process. Compared with the real-time quantitative PCR (RT-qPCR) instrument, the positive agreement rate is 100% and the negative agreement rate is 95.0%. This research provides a foundational basis for the development of equipment for the prevention of infectious diseases and clinical diagnostics.

Phosphate plays a crucial role in microbial proliferation, and the regulation of the phosphate concentration can modulate the fermentation efficiency. In this study, based on Lambert–Beer’s Law and the selective absorption characteristics of substances under light, a dual-light-type photoelectric colorimetric device for phosphate determination was designed. The device’s main components, such as the excitation light path and incubation stations, were modeled and simulated. The primary performance of the instrument was verified, and comparative experiments with a UV-1780 spectrophotometer were conducted to validate its performance. The experimental results demonstrate that this device exhibits a high degree of linearity with an R2 value of 0.9956 and a repeatability of ≤1.72%. The average temperature rise rate at the incubation stations was measured at 0.44 °C/s, with a temperature uniformity ≤ ±0.1 °C (temperature set at 37.3 °C). Consistently observed trends in the measurement of 23 CHO cell suspensions using the UV-1780 spectrophotometer further validated the accuracy and reliability of the device’s detection results.

Abstract Structural variations (SVs) are a major source of domestication and improvement traits. We present the first duck pan‐genome constructed using five genome assemblies capturing ∼40.98 Mb new sequences. This pan‐genome together with high‐depth sequencing data (∼46.5×) identified 101,041 SVs, of which substantial proportions were derived from transposable element (TE) activity. Many TE‐derived SVs anchoring in a gene body or regulatory region are linked to duck's domestication and improvement. By combining quantitative genetics with molecular experiments, we, for the first time, unraveled a 6945 bp Gypsy insertion as a functional mutation of the major gene IGF2BP1 associated with duck bodyweight. This Gypsy insertion, to our knowledge, explains the largest effect on bodyweight among avian species (27.61% of phenotypic variation). In addition, we also examined another 6634 bp Gypsy insertion in MITF intron, which triggers a novel transcript of MITF, thereby contributing to the development of white plumage. Our findings highlight the importance of using a pan‐genome as a reference in genomics studies and illuminate the impact of transposons in trait formation and livestock breeding.

ABSTRACTVibrio anguillarum is a cause of vibriosis in marine fisheries worldwide, but only one previous study reported human pathogenicity of this species. Here, we report a 70-year-old man from Dalian, a coastal city in northeast China, who experienced a severe infection with V. anguillarum due to a bite on his left hand when handling hairtail, a marine fish. This patient had low immunity because of the long-term use of glucocorticoids due to nephrotic syndrome. Despite treatments consisting of a strong antibiotic, continuous veno-venous hemofiltration, debridement, and fasciotomy, his condition deteriorated and he died of septic shock and multiple organ dysfunction syndrome. His death might be partly due to the delayed amputation of the left forearm, because he seemed to get better for the first several days. This case report emphasizes the possibility of human infection by V. anguillarum, which is likely to be more lethal in immunocompromised individuals.

Urease inhibitors (UIs) and nitrification inhibitors (NIs) still have limitations in increasing crop yield. Therefore, to improve the application effect of inhibitors, the combination of seaweed extracts (SE) from different sources and inhibitors was added to urea to provide a theoretical basis for the development of a new generation of efficient stabilized urea fertilizer with both biostimulant and inhibitor technologies. The combinations were tested in outdoor pots with no N- fertilizer (CK), application of urea alone (U) as control, and kelp polysaccharide (KP), margin polysaccharide (MP), N−(n−propyl) thiophosphoric triamide (NPPT), dicyandiamide (DCD), and combinations of SE with inhibitor were added to urea to make eight fertilizer prototypes. Compared with KP, MP showed better application effect, with significantly higher grain yield and nitrogen use efficiency (NUE) (P < 0.05). Compared with the addition of inhibitor alone, the combinations of NPPT with KP and MP, respectively, had opposite effects on urea−N transformation, meanwhile NPPT+KP had a positive effect. However, NPPT+MP significantly decreased yield, plant nitrogen uptake, and NUE (P < 0.05); DCD+MP decreased plant N uptake and NUE to some extent. Therefore, the addition of NPPT with KP and DCD with KP to urea significantly improved yield when planting maize in black soil.

Abstract Background Toll-like receptors (TLRs) may be involved in the natural history of human papillomavirus (HPV) infection. In our study, we aimed to investigate the association of TLR4 (rs10116253, rs1927911, rs10759931) and TLR9 (rs187084, rs352140) gene polymorphisms with cervical persistent high-risk HPV (HR-HPV) infection, as well as multiple HR-HPV infections. Methods A total of 269 study subjects were enrolled and grouped by retrospectively analyzing the HR-HPV testing results and other clinical data of 2647 gynecological outpatients from Jingzhou Hospital Affiliated to Yangtze University. We conducted a case–control study to compare the role of TLR4/TLR9 gene polymorphisms between HR-HPV transient and persistent infections, as well as between HR-HPV single and multiple infections. HR-HPV genotypes were detected using Real-time polymerase chain reaction (RT-PCR). PCR-restriction fragment length polymorphism (PCR–RFLP) was used to determine TLR4 and TLR9 gene polymorphisms. Analyses of the different outcome variables (HR-HPV infection status and time for HR-HPV clearance) with respect to TLR4/TLR9 polymorphisms were carried out. Logistic regression analysis was used to determine the association of TLR4/TLR9 genotypes and alleles with HR-HPV infection status. The Kaplan–Meier method with the log-rank test was used to analyze the relationship between TLR4/TLR9 genotypes and the time for HR-HPV clearance. Results The mutant genotypes of TLR9 rs187084 and rs352140 were associated with persistent (rs187084: CT and CT+CC; rs352140: CT and CT+TT) and multiple (rs187084: CT and CT+CC; rs352140: CT+TT) (all P

The milk flavor can be attributed to the presence of numerous flavor molecules and precursors. In this study, we employed widely targeted metabolomic analysis techniques to analyze the metabolic profiles of various milk samples obtained from goats, sheep, dairy cows, and buffaloes. A total of 631 metabolites were identified in the milk samples, which were further categorized into 16 distinct classes. Principal component analysis (PCA) suggested that the metabolite profiles of samples from the same species exhibit clustering, while separated patterns of metabolite profiles are observed across goat, sheep, cow, and buffalo species. The differential metabolites between the groups of each species were screened based on fold change and variable importance in projection (VIP) values. Five core differential metabolites were subsequently identified, including 3-(3-hydroxyphenyl)-3-hydroxypropanoic acid, inosine 5′-triphosphate, methylcysteine, N-cinnamylglycine, and small peptide (L-tyrosine–L-aspartate). Through multiple comparisons, we also screened biomarkers of each type of milk. Our metabolomic data showed significant inter-species differences in the composition and concentration of some compounds, such as organic acids, amino acids, sugars, nucleotides, and their derivatives, which may affect the overall flavor properties of the milk sample. These findings provided insights into the molecular basis underlying inter-species variations in milk flavor.

In addressing the detection of drug resistance in Helicobacter pylori, we have successfully developed an efficient and highly accurate detection methodology. Initially, we designed and fabricated a microarray chip, which underwent finite element analysis for its optical and thermal characteristics. Ultimately, COC material was chosen as the processing material for the chip, ensuring superior performance. Subsequently, we established a comprehensive detection system and validated its performance. Following that, comparative experiments were conducted for detecting drug resistance in H. pylori. The experimental results indicate that our established methodology aligns with the results obtained using the E-test detection kit, achieving a concordance rate of 100%. In comparison to the E-test detection kit, our methodology reduces the detection time to 1.5 h and provides a more extensive coverage of detection sites.

Objectives: Multi-parametric magnetic resonance imaging (MRI) can provide comprehensive and valuable information for precise diagnosis and treatment evaluation of a number of diseases. In this study, the neuroprotective effects of melatonin (Mel) on a rat model of cerebral ischemia/reperfusion injury (CIRI) were assessed by multi-parametric MRI combined with histopathological techniques for longitudinal monitoring of the lesion microenvironment. Methods: Sixty Sprague Dawley (SD) rats were randomly divided into three groups: the Sham, CIRI and CIRI + Mel groups. At multiple time points after ischemia, MRI scanning was performed on a 7.0 Tesla MRI scanner. Multi-parametric MRI includes T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), and chemical exchange saturation transfer (CEST)-MRI. CEST effects were calculated by the Lorentzian difference method, 3.5 ppm indicates amide protons of mobile proteins/peptide (Amide-CEST) and 2.0 ppm indicates amine protons (Guan-CEST). Multiple histopathological techniques were used to examine the histopathological changes and explore the therapeutic effects of Mel. Results: T2WI and DWI-MRI could localize the infarct foci and areas in CIRI rats, which was further validated by staining, 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) staining. After Mel treatment, T2WI and DWI-MRI showed smaller infarct volume, and neurons displayed improved morphology with less apoptosis rates. Notably, Amide-CEST and Guan-CEST signal decreased as early as 2 h after CIRI (all P

Abstract Sepsis is a difficult‐to‐treat systemic condition in which liver dysfunction acts as both regulator and target. However, the dynamic response of diverse intrahepatic cells to sepsis remains poorly characterized. Capsaicin (CAP), a multifunctional chemical derived from chilli peppers, has recently been shown to potentially possess anti‐inflammatory effects, which is also one of the main approaches for drug discovery against sepsis. We performed single‐cell RNA transcriptome sequencing on 86,830 intrahepatic cells isolated from normal mice, cecal ligation and puncture‐induced sepsis model mice and CAP‐treated mice. The transcriptional atlas of these cells revealed dynamic changes in hepatocytes, macrophages, neutrophils, and endothelial cells in response to sepsis. Among the extensive crosstalk across these major subtypes, KC_Cxcl10 shared strong potential interaction with other cells when responding to sepsis. CAP mitigated the severity of inflammation by partly reversing these pathophysiologic processes. Specific cell subpopulations in the liver act collectively to escalate inflammation, ultimately causing liver dysfunction. CAP displays its health‐promoting function by ameliorating liver dysfunction induced by sepsis. Our study provides valuable insights into the pathophysiology of sepsis and suggestions for future therapeutic gain.

This paper studies the distributed output-based bipartite consensus problem in a nonlinear fractional-order multi-agent system (FOMAS) subjected to heterogeneous nonlinear functions and disturbances over a signed directed graph. Two types of distributed bipartite consensus algorithms are proposed to solve the bipartite consensus problem by utilizing continuous and intermittent output measurements, respectively. A novel discontinuous algorithm with a nominal controller is first developed to derive that all agents reach the sliding-mode surface in finite time, and meanwhile, each agent’s dynamics can be described by a linear FOMAS with a nominal controller. When each agent can access its neighbors’ output measurements continuously all the time, a continuous output-based nominal controller is designed for the linear FOMAS to realize bipartite consensus asymptotically. When each agent can only access its neighbors’ output measurements intermittently in some disconnected time intervals, an intermittent output-based nominal controller is further designed, where the communication rate is required to be greater than a derived threshold value. Numerical simulations are performed to validate the effectiveness of the main results.

Abstract Background sCD59, as a soluble form of CD59, is observed in multiple types of body fluids and correlated with the cell damage after ischemia/reperfusion injury. This study aims to observe the dynamic changes of serum sCD59 in patients after restoration of spontaneous circulation (ROSC) and explore the association of serum sCD59 with neurological prognosis and all-cause mortality in patients after ROSC. Methods A total of 68 patients after ROSC were prospectively recruited and divided into survivors (n = 23) and non-survivors (n = 45) groups on the basis of 28-day survival. Twenty healthy volunteers were enrolled as controls. Serum sCD59 and other serum complement components, including sC5b-9, C5a, C3a, C3b, C1q, MBL, Bb, and pro-inflammatory mediators tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), neurological damage biomarkers neuron-specific enolase (NSE) and soluble protein 100β (S100β) were measured by enzyme linked immunosorbent assay on day 1, 3, and 7 after ROSC. Neurologic outcome was assessed using cerebral performance category scores, with poor neurologic outcome defined as 3–5 points. Results In the first week after ROSC, serum levels of sCD59, sC5b-9, C5a, C3a, C3b, C1q, MBL, Bb, TNF-α, IL-6, NSE and S100β were significantly elevated in patients after ROSC compared to healthy volunteers, with a significant elevation in the non-survivors compared to survivors except serum C1q and MBL. Serum sCD59 levels were positively correlated with serum sC5b-9, TNF-α, IL-6, NSE, S100β, SOFA score and APACHE II score. Moreover, serum sCD59 on day 1, 3, and 7 after ROSC could be used for predicting poor 28-day neurological prognosis and all-cause mortality. Serum sCD59 on day 3 had highest AUCs for predicting poor 28-day neurological prognosis [0.862 (95% CI 0.678–0.960)] and 28-day all-cause mortality [0.891 (95% CI 0.769–0.962)]. In multivariate logistic regression analysis, the serum level of sCD59D1 was independently associated with poor 28-day neurological prognosis and all-cause mortality. Conclusions The elevated serum level of sCD59 was positively correlated with disease severity after ROSC. Moreover, serum sCD59 could have good predictive values for the poor 28-day neurological prognosis and all-cause mortality in patients after ROSC.

We report a case-series study of 5 patients with Japanese spotted fever from the Three Gorges Area in China, including 1 fatal case. Seroprevalence of Rickettsia japonica was ≈21% among the local population. Our report highlights the emerging potential threat to human health of Japanese spotted fever in the area.

Human papillomavirus (HPV) infection is the primary cause of cervical cancer and its precursor lesions. The overall prevalence of HPV genotypes in Changzhou has previously been reported. However, the distribution of multiple HPV infections and their roles in cervical injury have less been investigated. We aimed to assess the prevalence of multiple HPV infections among the people in Changzhou. Furthermore, we analyzed whether multiple HPV infections comprising the top five prevalent HPVs were more associated with abnormalities in E6 and E7 (E6/E7) mRNA, liquid-based cytology, and cervical histopathology than a single infection. In the current study, HPV 16, 52, 58, 53, and 81 were the top five prevalent HPV types, both in single and multiple infections. Compared to a single infection, multiple infections containing HPV 16/52/58 were closely linked to positivity for E6/E7 mRNA. In addition to HPV 16, multiple infections containing the remaining top four HPVs conferred a significant advantage on atypical squamous cells of undermined significance or worse in comparison to a single infection. Furthermore, women with multiple infections containing the top five prevalent HPV types were more likely to develop cervical intraepithelial neoplasia grade II or worse than those with a single HPV infection. Our results demonstrate the superiority of multiple HPV infections containing the top five prevalent HPV types in cervical disease progression, which should be closely monitored. These findings are conducive for formulating regional preventive strategies for cervical cancer screening and vaccination in Changzhou.

Heavy metals (HMs) are the toxic pollutants in urban environment, and their sources are complex. Dust might be a good carrier of HMs into ecosystem and human. In this study, 48 dust samples were collected in Nanjing, an industrial city and transportation hub in the Yangtze River Delta, China. The concentrations, spatial distribution, sources and risks of heavy metals (Cr, Ni, Cu, Zn, Cd and Pb) in dust were determined and analyzed. The results showed that although the health risks of some HMs had decreased, Cr, Zn, and Cd had high concentrations and high risks on ecosystem/human. And thus, the total risks of the target HMs were higher than the threshold of non-risks. Especially, children may face the highest possible risks due to the frequent hand-oral ingestion when children play. The hot spot regions of the HMs were mainly in the industrial district in the north, urban, and rural region in south, relating with the industrial, traffic, and agricultural sources, respectively. The analysis for the risks of individual sources further confirmed these sources should be further controlled. The results in this study will provide information on the priority of HMs’ monitoring and source management.

With the rapid advancement of nanotechnology and its widespread applications, increasing amounts of manufactured and natural nanoparticles (NPs) have been tested for their potential utilization in treating harmful cyanobacterial blooms (HCBs). NPs can be used as a photocatalyst, algaecide, adsorbent, flocculant, or coagulant. The primary mechanisms explored for NPs to mitigate HCBs include photocatalysis, metal ion-induced cytotoxicity, physical disruption of the cell membrane, light-shielding, flocculation/coagulation/sedimentation of cyanobacterial cells, and the removal of phosphorus (P) and cyanotoxins from bloom water by adsorption. As an emerging and promising chemical/physical approach for HCB mitigation, versatile NP-based technologies offer great advantages, such as being environmentally benign, cost-effective, highly efficient, recyclable, and adaptable. The challenges we face include cost reduction, scalability, and impacts on non-target species co-inhabiting in the same environment. Further efforts are required to scale up to real-world operations through developing more efficient, recoverable, reusable, and deployable NP-based lattices or materials that are adaptable to bloom events in different water bodies of different sizes, such as reservoirs, lakes, rivers, and marine environments.

In this work, an adaptive fuzzy backstepping fault-tolerant control (FTC) issue is tackled for uncertain fractional-order (FO) nonlinear systems with sensor and actuator faults. A fuzzy logic system is exploited to manage unknown nonlinearity. In addition, a novel FO nonlinear filter-based dynamic surface control (DSC) method is constructed, effectively avoiding the inherent complexity explosion problem in the backstepping recursive process, and in the light of the construction of auxiliary functions, compensating the coupling term introduced by faults. On account of certain assumptions, the stability criterion of the FO Lyapunov function is applied to guarantee the stability of the closed-loop system. Finally, the simulation example verifies the validity of the presented control strategy.

Digital polymerase chain reaction (PCR) technology in microfluidic systems often results in bubble formation post-amplification, leading to microdroplet fragmentation and compromised detection accuracy. To solve this issue, this study introduces a method based on the constant pressure regulation of microdroplets during PCR within microfluidic chips. An ideal pressure reference value for continuous pressure control was produced by examining air solubility in water at various pressures and temperatures as well as modeling air saturation solubility against pressure for various temperature scenarios. Employing a high-efficiency constant pressure device facilitates precise modulation of the microfluidic chip’s inlet and outlet pressure. This ensures that air solubility remains unsaturated during PCR amplification, preventing bubble precipitation and maintaining microdroplet integrity. The device and chip were subsequently utilized for quantitative analysis of the human epidermal growth factor receptor (EGFR) exon 18 gene, with results indicating a strong linear relationship between detection signal and DNA concentration within a range of 101–105 copies/μL (R2 = 0.999). By thwarting bubble generation during PCR process, the constant pressure methodology enhances microdroplet stability and PCR efficiency, underscoring its significant potential for nucleic acid quantification and trace detection.

CHD7 is chromatin remodeler and mutations of CHD7 are the main cause of CHARGE syndrome. Here the authors show that conditional knockout of Chd7 in bone marrow mesenchymal stem cells (MSCs) and pre-osteoblasts leads to a skeletal system development disorder in mice and upregulated PPAR signaling, disrupting the balance between osteogenic and adipogenic differentiation.

Abstract Venetoclax plus cytarabine therapy is approved for elderly acute myeloid leukemia (AML) patients and needs further improvement. We studied the mechanisms of venetoclax plus cytarabine treatment and searched for a third agent to enhance their effects. Cytarabine induces S phase arrest-mediated DNA damage with activation of DNA replication checkpoint kinase 1 (Chk1) through phosphorylation, while venetoclax induces B cell lymphoma 2 (Bcl-2)-interacting mediator of cell death (Bim)-mediated apoptotic DNA damage. Myeloid cell leukemia-1 (Mcl-1) plays negative roles in both events by sequestering Bim and accelerating Chk1 phosphorylation. Venetoclax releases Bim from Bcl-2 with increased Bim binding to Mcl-1. Artesunate, an antimalaria drug, induces Noxa to replace Bim from Mcl-1 and induces synergistic apoptosis with venetoclax accompanied with Mcl-1 reduction. Silencing Mcl-1 or adding venetoclax/artesunate diminishes the cytarabine resistance pathway p-Chk1. The triple combination exhibits S phase arrest with enhanced DNA damage, improves AML colony formation inhibition, and prolongs survival of two mice xenograft models compared to the venetoclax/cytarabine dual combination. Artesunate serves as a bridge for venetoclax and cytarabine combination by Noxa and Bim-mediated apoptosis and Mcl-1 reduction. We provide a new triple combination for AML treatment by targeting the Noxa/Mcl-1/Bim axis to reverse Mcl-1/p-Chk1 resistance of cytarabine therapy.

Abstract High electrical and thermal conductive metals (HETCM) play a key role in smart electronics, green energy, modern communications and healthcare, however, typical HETCM (e.g., Ag, Au, Cu) usually have relatively low mechanical strength, hindering further applications. Selective laser melting (SLM) is a potentially transformative manufacturing technology that is expected to address the issue. Ag is the metal with the highest thermal conductivity, which induces microscale grain refinement, but also leads to high internal stresses by SLM. Here, we select Ag7.5Cu alloy as an example to demonstrate that multi-scale (micro/meso/macro) synergies can take advantage of high thermal conductivity and internal stresses to effectively strengthen Ag alloy. The mimicry of metal-hardened structures (e.g., large-angle boundary) is extended to the mesoscale by controlling the laser energy density and laser scanning strategy to manipulate the macroscale internal stress intensity and mesoscale internal stress direction, respectively, to form mesoscale large-angle "grains", resulting in multiple mutual perpendicular shear bands during fracture. The presented approach achieved a significant enhancement of yield strength (+ 145%) and ductility (+ 28%) without post-treatment. The results not only break the strength-ductility trade-off of conventional SLM alloys, but also demonstrate a multi-scale synergistic enhancement strategy that exploits high thermal conductivity and internal stresses.

This paper investigates the problem of fixed-time distributed time-varying optimization of a nonlinear fractional-order multiagent system (FOMAS) over a weight-unbalanced directed graph (digraph), where the heterogeneous unknown nonlinear functions and disturbances are involved. The aim is to cooperatively minimize a convex time-varying global cost function produced by a sum of time-varying local cost functions within a fixed time, where each time-varying local cost function does not have to be convex. Using a three-step design procedure, a fully distributed fixed-time optimization algorithm is constructed to achieve the objective. The first step is to design a fully distributed fixed-time estimator to estimate some centralized optimization terms within a fixed time T0. The second step is to develop a novel discontinuous fixed-time sliding mode algorithm with nominal controller to derive all the agents to the sliding-mode surface within a fixed time T1, and meanwhile the dynamics of each agent is described by a single-integrator MAS with nominal controller. In the third step, a novel estimator-based fully distributed fixed-time nominal controller for the single-integrator MAS is presented to guarantee all agents reach consensus within a fixed time T2, and afterwards minimize the convex time-varying global cost function within a fixed time T3. The upper bound of each fixed time Tm(m=0,1,2,3) is given explicitly, which is independent of the initial states. Finally, a numerical example is provided to validate the results.

One common problem in omics data analysis is missing values, which can arise due to various reasons, such as poor tissue quality and insufficient sample volumes. Instead of discarding missing values and related data, imputation approaches offer an alternative means of handling missing data. However, the imputation of missing omics data is a non-trivial task. Difficulties mainly come from high dimensionality, non-linear or non-monotonic relationships within features, technical variations introduced by sampling methods, sample heterogeneity, and the non-random missingness mechanism. Several advanced imputation methods, including deep learning-based methods, have been proposed to address these challenges. Due to its capability of modeling complex patterns and relationships in large and high-dimensional datasets, many researchers have adopted deep learning models to impute missing omics data. This review provides a comprehensive overview of the currently available deep learning-based methods for omics imputation from the perspective of deep generative model architectures such as autoencoder, variational autoencoder, generative adversarial networks, and Transformer, with an emphasis on multi-omics data imputation. In addition, this review also discusses the opportunities that deep learning brings and the challenges that it might face in this field.

Red blood cell-derived extracellular vesicles (RBC EVs) are small, spherical fragments released from red blood cells. These vesicles, similar to EVs derived from other cell types, are crucial for intercellular communication processes and have been implicated in various physiological and pathological processes. The diagnostic and therapeutic potential of RBC EVs has garnered increasing attention in recent years, revealing their valuable role in the field of medicine. In this review, we aim to provide a comprehensive analysis of the current research status of RBC EVs. We summarize existing studies and highlight the progress made in understanding the characteristics and functions of RBC EVs, with a particular focus on their biological roles in different diseases. We also discuss their potential utility as diagnostic and prognostic biomarkers in diseases and as vectors for drug delivery. Furthermore, we emphasize the need for further research to achieve selective purification of RBC EVs and unravel their heterogeneity, which will allow for a deeper understanding of their diverse functions and exploration of their potential applications in diagnostics and therapeutics.