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Abstract Tumor-associated macrophages play a crucial role in the tumor microenvironment. Tripartite motif 59 (TRIM59), a member of the tripartite motif (TRIM) family, is known to be associated with immunological diseases and macrophage activation. The functional and molecular mechanisms by which TRIM59 affects the occurrence and development of colorectal cancer (CRC) through macrophages are still not well understood. To address this, we generated macrophage-specific TRIM59 conditional knockout mice and utilized these mice to establish colitis-associated cancer and MC38 transplanted CRC models for further investigation. We found that the deficiency of TRIM59 in macrophages inhibited colorectal tumorigenesis in mice. This tumor-suppressive effect was achieved by promoting the activation of M1 macrophages via STAT1 signaling pathway. Further mechanistic studies revealed that TRIM59 could regulate macrophage polarization by ubiquitinating and degrading STAT1. These findings provide evidence that TRIM59 deficiency promotes M1 macrophage activation and inhibits CRC through the STAT1 signaling pathway, suggesting that the TRIM59/STAT1 signaling pathway may be a promising target for CRC.

Abstract The three-dimensional genome structure organized by CTCF is required for development. Clinically identified mutations in CTCF have been linked to adverse developmental outcomes. Nevertheless, the underlying mechanism remains elusive. In this investigation, we explore the regulatory roles of a clinically relevant R567W point mutation, located within the 11th zinc finger of CTCF, by introducing this mutation into both murine models and human embryonic stem cell-derived cortical organoid models. Mice with homozygous CTCFR567W mutation exhibit growth impediments, resulting in postnatal mortality, and deviations in brain, heart, and lung development at the pathological and single-cell transcriptome levels. This mutation induces premature stem-like cell exhaustion, accelerates the maturation of GABAergic neurons, and disrupts neurodevelopmental and synaptic pathways. Additionally, it specifically hinders CTCF binding to peripheral motifs upstream to the core consensus site, causing alterations in local chromatin structure and gene expression, particularly at the clustered protocadherin locus. Comparative analysis using human cortical organoids mirrors the consequences induced by this mutation. In summary, this study elucidates the influence of the CTCFR567W mutation on human neurodevelopmental disorders, paving the way for potential therapeutic interventions.

Abstract In recent years, the issue of energy consumption in farm buildings has received much attention. The roofs of farm buildings in Northwest China have a variety of roof forms. This paper presents the implementation of first fully confirmed the indoor thermal environment of different roof construction was significantly effected by periodic thermogenesis. In order to determine the indoor temperature distribution of the farmhouse in summer in Ningxia Hui Autonomous Region, we provided the heat transfer coefficient data of the farmhouse envelope, also detailed in the manuscript. Model of Thermal Mass Transport enables fast and accurately simulates the indoor temperature distribution of farmhouses with different roof forms on the same day, taking into account the climate zone of the region. This is despite the phase delay time of indoor temperatures for different roof forms caused by periodic initial temperature boundaries ranged from 1.55 to 2.78 $$\text{h}$$ h , and the phase delay angle ranged from 23.25 $$^{\circ }$$ ∘ to 41.7 $$^{\circ }$$ ∘ . Extensive simulated results revealed individual variability in the role of roof form, demonstrating indoor temperatures in farmhouses corresponding to different climatic zones. In addition, by analyzing and discussing the indoor temperature phase delay angle and delay time for each type of roof forms, statistical results identified the advantages of Non-equal-sloped roof as a local farmhouse roof.

Oleanolic acid (OA) is a pentacyclic triterpene with reported protective effects against various diseases, including diabetes, hepatitis, and different cancers. However, the effects of OA on obesity‐induced muscle atrophy remain largely unknown. This study investigated the effects of OA on skeletal muscle production and proliferation of C2C12 cells. We report that OA significantly increased skeletal muscle mass and improved glucose intolerance and insulin resistance. OA inhibited dexamethasone (Dex)‐induced muscle atrophy in C2C12 myoblasts by regulating the PI3K/Akt signaling pathway. In addition, it also inhibited expression of MuRF1 and Atrogin1 genes in skeletal muscle of obese mice suffering from muscle atrophy, and increased the activation of PI3K and Akt, thereby promoting protein synthesis, and eventually alleviating muscle atrophy. Taken together, these findings suggest OA may have potential for the prevention and treatment of muscle atrophy.

Due to its asymptotic optimality, the Rapidly-exploring Random Tree star (RRT*) algorithm is widely used for robotic operations in complex environments. However, the RRT* algorithm suffers from poor path quality, slow convergence, and unstable generation of high-quality paths in the path planning process. This paper proposes an Improved Bi-Tree Obstacle Edge Search Artificial Potential Field RRT* algorithm (IBPF-RRT*) to address these issues. First, based on the RRT* algorithm, this paper proposes a new obstacle edge search artificial potential field strategy (ESAPF), which speeds up the path search and improves the path quality simultaneously. Second, a bi-directional pruning strategy is designed to optimize the bi-directional search tree branch nodes and combine the bi-directional search strategy to reduce the number of iterations for convergence speed significantly. Third, a novel path optimization strategy is proposed, which enables high-quality paths to be generated stably by creating an entirely new node between two path nodes and then optimizing the paths using a pruning strategy based on triangular inequalities. Experimental results in three different scenarios show that the proposed IBPF-RRT* algorithm outperforms other methods in terms of optimal path quality, algorithm stability, and the number of iterations when compared to the RRT*, Q-RRT*, PQ-RRT*, F-RRT* and CCPF-RRT* algorithms, and proves the effectiveness of the proposed three strategies.

Heavy metal pollution of the soil affects the environment and human health. Masson pine is a good candidate for phytoremediation of heavy metal in mining areas. Microorganisms in the rhizosphere can help with the accumulation of heavy metal in host plants. However, studies on its rhizosphere bacterial communities under heavy metal pollution are still limited. Therefore, in this study, the chemical and bacterial characteristics of Masson pine rhizosphere under four different levels of heavy metal pollution were investigated using 16 S rRNA gene sequencing, soil chemistry and analysis of plant enzyme activities. The results showed that soil heavy metal content, plant oxidative stress and microbial diversity damage were lower the farther they were from the mine dump. The co-occurrence network relationship of slightly polluted soils (C1 and C2) was more complicated than that of highly polluted soils (C3 and C4). Relative abundance analysis indicated Sphingomonas and Pseudolabrys were more abundant in slightly polluted soils (C1 and C2), while Gaiella and Haliangium were more abundant in highly polluted soils (C3 and C4). LEfSe analysis indicated Burkholderiaceae, Xanthobacteraceae, Gemmatimonadaceae, Gaiellaceae were significantly enriched in C1 to C4 site, respectively. Mantel analysis showed that available cadmium (Cd) contents of soil was the most important factor influencing the bacterial community assembly. Correlation analysis showed that eight bacterial genus were significantly positively associated with soil available Cd content. To the best of our knowledge, this is the first study to investigate the rhizospheric bacterial community of Masson pine trees under different degrees of heavy metal contamination, which lays the foundation for beneficial bacteria-based phytoremediation using Masson pines in the future.

Abstract Background Enterocytozoon bieneusi is a zoonotic pathogen widely distributed in animals and humans. It can cause diarrhea and even death in immunocompromised hosts. Approximately 800 internal transcribed spacer (ITS) genotypes have been identified in E. bieneusi. Farmed foxes and raccoon dogs are closely associated to humans and might be the reservoir of E. bieneusi which is known to have zoonotic potential. However, there are only a few studies about E. bieneusi genotype identification and epidemiological survey in foxes and raccoon dogs in Henan and Hebei province. Thus, the present study investigated the infection rates and genotypes of E. bieneusi in farmed foxes and raccoon dogs in the Henan and Hebei provinces. Result A total of 704 and 884 fecal specimens were collected from foxes and raccoon dogs, respectively. Nested PCR was conducted based on ITS of ribosomal RNA (rRNA), and then multilocus sequence typing (MLST) was conducted to analyze the genotypes. The result showed that infection rates of E. bieneusi in foxes and raccoon dogs were 18.32% and 5.54%, respectively. Ten E. bieneusi genotypes with zoonotic potential (NCF2, NCF3, D, EbpC, CHN-DC1, SCF2, CHN-F1, Type IV, BEB4, and BEB6) were identified in foxes and raccoon dogs. Totally 178 ITS-positive DNA specimens were identified from foxes and raccoon dogs and these specimens were then subjected to MLST analysis. In the MLST analysis, 12, 2, 7 and 8 genotypes were identified in at the mini-/ micro-satellite loci MS1, MS3, MS4 and MS7, respectively. A total of 14 multilocus genotypes were generated using ClustalX 2.1 software. Overall, the present study evaluated the infection of E. bieneusi in foxes and raccoon dogs in the Henan and Hebei province, and investigated the zoonotic potential of the E. bieneusi in foxes and raccoon dogs. Conclusions These findings expand the geographic distribution information of E. bieneusi’ host in China and was helpful in preventing against the infection of E. bieneusi with zoonotic potential in foxes and raccoon dogs.

A sudden angle change between the Y-shaped diversion channel and the inlet tank of the circular pump station often leads to boundary layer separation and large vortex formation. These flow patterns can cause significant sediment deposition in sediment-laden rivers, reducing pump efficiency. A mixture model is introduced to describe water-sediment two-phase flows. Simulation results analyze vortex characteristics and formation mechanisms, and evaluate potential sediment deposition areas. Without rectification, vortex areas cause significant sediment migration towards the sidewalls of the Y-shaped diversion channel and pump inlet. Diversion measures like sills and pressure plates are introduced to reduce flow vortices. Results show that sills generally optimize flow structures. Sills in the main Y-shaped diversion channel outperform those in other channels in terms of optimization. Pressure plates also optimize flow structures. Vortex structure and position are closely related to the distance between the pressure plate and the circular intake tank. Optimized measures with pressure plates significantly reduce the flow deviation angle and improve flow velocity uniformity. Numerical simulation accuracy is validated through experiments. Results reveal the formation mechanism of adverse vortices and their sedimentation effects, which are detrimental to pump stations. The proposed rectification scheme provides theoretical support for optimizing pump station operation.

At present, the state has introduced the policy of forest Chinese herbal medicine planting planning, strictly prohibiting the planting of Chinese herbal medicine in basic farmland, coupled with the fact that the continuous cropping obstacles of Panax notoginseng have not yet been solved, which makes the area of arable land suitable for planting become less and less. However, the effect of soil moisture regulation on the growth of Panax notoginseng cultivated on sloping arable land has not been reported. Thus, the aim of this study was to investigate the impact of various irrigation levels and slopes on Panax notoginseng agronomic traits, physiological characteristics, disease attributes, biomass, and quality characteristics. During 2018–2020, a field experiment was conducted in the Panax notoginseng growing seasons with three irrigation levels (I1: 70–75% θFC, I2: 75–80% θFC, I3: 80–85% θFC) and three slopes (S1: 2.43°, S2: 6.38°, S3: 16.38°). The results evidenced that the photosynthetic characteristics, root hydraulic conductivity characteristics, biomass and PNS of Panax notoginseng reached the maximum value in the I2S2 treatment, and at the same time, the incidence rate of Panax notoginseng root rot was the lowest. Therefore, based on the results of this study, irrigation volume I2S2 should be regarded as the optimal slope and irrigation management strategies for reducing Panax notoginseng diseases and realizing stable yield and quality improvement of Panax notoginseng. A multi-objective optimization model was established through binary quadratic regression analysis. The findings evidenced that when the irrigation interval was 187–203 mm and the slope interval was 5–10.7°, Panax notoginseng had the lowest incidengce rate, and the root biomass and saponin content reached > 95% of the maximum values at the same time.

Study DesignRetrospective radiological analysis.ObjectiveThe aim of this study is to evaluate the distribution of bone mineral density (BMD) in lumbar vertebrae using the Hounsfield unit (HU) measurement method and investigate the clinical implications of HU values for assessing lumbar vertebrae BMD.MethodTwo hundred and ninety-six patients were retrospectively reviewed and divided into six groups according to age: Group 1(20–29 years old), Group 2 (30–39 years old), Group 3 (40–49 years old), Group 4 (50–59 years old), Group 5 (60–69 years old), Group 6 (70–79 years old). Six different locations from each vertebra of L1-L5 were selected as regions of interest: the anterior, middle and posterior parts of the upper and lower slices of the vertebrae. HU values were measured for the six regions of interest, followed by statistical analysis.ResultsThe HU values of vertebrae showed a decreasing trend from young patients to elderly patients in Group 1 to Group 5. There was no significant difference in HU values among different vertebrae in the same age group. In all age groups, the HU values of the anterior and posterior part of the vertebral body were significantly different from L1 to L3, with the anterior part of the vertebral body having lower HU values than the posterior part. The HU values of the anterior and posterior part of the vertebral body of L4 and L5 were statistically significant only in Group 5 and Group 6, and the HU values of the anterior part of the vertebral body were lower than those of the posterior part. The HU values of posterior part of L4 and L5 in Group6 were higher than those in Group5.ConclusionBone mineral density in the lumbar vertebrae is not uniformly distributed, potentially attributed to varying stress stimuli. The assessment of local HU values in the lumbar spine is of significant importance for surgical treatment.

The whole-genome sequence of an African swine fever virus (ASFV) strain (HuB/HH/2019) isolated from Hubei, China, was highly similar to that of the Georgia 2007/1 strain ASFV. After infection with strong strains, domestic pigs show typical symptoms of infection, including fever, depression, reddening of the skin, hemorrhagic swelling of various tissues, and dysfunction. The earliest detoxification occurred in pharyngeal swabs at 4 days post-infection. The viral load in the blood was extremely high, and ASFV was detected in multiple tissues, with the highest viral loads in the spleen and lungs. An imbalance between pro- and anti-inflammatory factors in the serum leads to an excessive inflammatory response in the body. Immune factor expression is suppressed without effectively eliciting an immune defense. Antibodies against p30 were not detected in acutely dead domestic pigs. Sequencing of the peripheral blood mononuclear cell transcriptome revealed elevated transcription of genes associated with immunity, defense, and stress. The massive reduction in lymphocyte counts in the blood collapses the body’s immune system. An excessive inflammatory response with a massive reduction in the lymphocyte count may be an important cause of mortality in domestic pigs. These two reasons have inspired researchers to reduce excessive inflammatory responses and stimulate effective immune responses for future vaccine development.

In order to clarify the gas-phase carrying capacity after the atomization of water from the bottom of deep coalbed wells, considering characteristics of atomization-assisted production and the dynamic equilibrium principle of gas–liquid two-phase flow in the wellbore, the gas-phase liquid-carrying drop model was established, and the solution method of the upstream and downstream driving force of liquid drop flow was studied. We also verified the theoretical model through physical simulation. Then, the law for the influence of droplet size, wellbore inclination, wellbore diameter, and wellhead back pressure of the critical liquid-carrying velocity in the gas phase is analyzed using the model. The results show the following: ① the larger the diameter of atomized droplets, the greater the gravity force applied to it, the worse the ability to be carried by the gas phase, a onefold increase in droplet diameter corresponds to the increase in the minimum critical velocity of the gas phase by 1.45 times; ② with the increase in wellbore inclination, the liquid-carrying capacity of the gas phase decreases, and the minimum critical liquid-carrying velocity of equal diameter droplets increases by 0.01438 m/s or 1.27 times for the increase in wellbore inclination by 10°; ③ with the increase in wellbore diameter, both the driving force of a droplet of equal diameter and the flow resistance through the gas phase in the wellbore decrease within the range of a driving pressure difference of 0.2 Mpa; the decrease in liquid-carrying velocity caused by the decrease in received flow resistance can reach the maximum value of 0.0473 m/s; ④ with the increase in wellhead back pressure, the driving force of equal-diameter droplets decreases, the resistance against passing through the high-concentration gas phase increases, and the gas-phase-carrying droplets start the game; ⑤ the atomization-assisted production has the function of drainage gas recovery, and the adoption of atomization-assisted production technology can increase the production time of a coalbed gas flowing well, enabling the wells to have a good transition time interval for the conversion of flowing wells to pumping ones, which provides a precise production dynamic basis for the efficient design and implements the overall strategy of drainage gas recovery by deep-well pumping. In short, this technology has the high-efficiency liquid-carrying function of “water atomization to help liquid-phase flow and increase gas production”, as well as obvious technical advantages, which can provide a new idea for the development of deep coalbed methane wells and other types of gas wells with water.

The excessive rainfall and irrigation amount in the facility herbal medicine production system (FHmPS) in China leading to a severe root rot disease of Panax notoginseng, which endangers root yield and quality, compromise economic profit and waste resources. Therefore, the objective of our research was to seek optimal irrigation and cultivation management strategy for FHmPS to improve Panax notoginseng production and economic benefit. A three-year (2019, 2020 and 2021) field experiment was conducted on Panax notoginseng under two shelter-cultivation [rain-shelter cultivation (Sr) and unrain-shelter cultivation (NSr)] at three deficit irrigation levels [I1= 65%W, I2= 75%W, I3= 85% W, where W was the irrigation quota when the upper and lower limits of irrigation are (100% ∼ 40%)θFC under shelter-cultivation] to explore the combined practices effects on yield, quality, economic benefit, water productivity (WP) and nutrients uptake of Panax notoginseng, and to obtain the optimal irrigation and cultivation supply practice by the technique for order preference by similarity to ideal solution (TOPSIS). The results showed that SrI2 obtained relatively high plant nutrient uptake, net profit, WP, and quality. SrI2 significantly decreased the root rot incidence by 6–17.5% in comparison to other treatments. However, compared with rain-shelter cultivation, unrain-shelter cultivation weaken these effects in Panax notoginseng. Deficit irrigation promoted Sr to obtain higher WP than NSr. According to the result of TOPSIS, the comprehensive ranking of SrI2 and SrI3 were first and second among the practices, regardless of growing seasons and planting years. The SrI2 significantly decreased the yield of Panax notoginseng by 5.4%− 20.8% in comparison to other treatments. SrI2 and SrI3 were highly recommended for facility herbal medicine production system (FHmPS) in the semi-arid area of Southwest China.

Panax notoginseng cultivation planting conditions are harsh and require high soil moisture and slope of cultivated land, plus it takes 3–7 years from planting to harvesting. At present, the continuous crop barrier of Panax notoginseng has not been solved, which makes the arable land suitable for planting significantly reduced. And yet, there is almost no report on the impact of coupling water and slope on the growth of Panax notoginseng. Therefore, this study aims to explore the effects of different irrigation levels and slopes on soil water content (SWC) in the root zone, soil nutrient content, root characteristics, yield, water use efficiency (WUE), partial fertilizer productivity (PFP) and economic benefits of Panax notoginseng. During 2018–2020, a field experiment was conducted in the Panax notoginseng growing seasons with three irrigation levels (I1: 70–75% θFC, I2: 75–80% θFC, I3: 80–85% θFC) and three slopes (S1: 2.43°, S2: 6.38°, S3: 16.38°). The results evidenced that soil water and nutrient content increased with increasing irrigation and decreased with increasing slope. The yield of Panax notoginseng, root morphological characteristics, WUE, PFP, and economic benefits showed a trend of increasing first and then decreasing with the increase of irrigation amount and slope, which increased with the increase of planting years. These parameters reached their maximum at the irrigation I2 (75–80% θFC) and slope S2 (6.38°) treatments. Thus, based on the results of this study, medium irrigation I2 (75–80% θFC) and slope S2 (6.38°) should be considered as the best slope and water management strategy to obtain both high Panax notoginseng yield and economic benefits. Through establishing a multi-objective optimization model with binary quadratic regression analysis. It was indicated that Panax notoginseng yield, WUE, PFP, and economic benefits simultaneously reached ≥ 98% of their maximum values when irrigation interval was 152–193 mm and slope interval was 5.4–9°. In summary, the results obtained in this study have important practical significance for the water management of Panax notoginseng cultivation in slope farmland in Yunnan Province, China.

Image data augmentation plays a crucial role in data augmentation (DA) by increasing the quantity and diversity of labeled training data. However, existing methods have limitations. Notably, techniques like image manipulation, erasing, and mixing can distort images, compromising data quality. Accurate representation of objects without confusion is a challenge in methods like auto augment and feature augmentation. Preserving fine details and spatial relationships also proves difficult in certain techniques, as seen in deep generative models. To address these limitations, we propose OFIDA, an object-focused image data augmentation algorithm. OFIDA implements one-to-many enhancements that not only preserve essential target regions but also elevate the authenticity of simulating real-world settings and data distributions. Specifically, OFIDA utilizes a graph-based structure and object detection to streamline augmentation. Specifically, by leveraging graph properties like connectivity and hierarchy, it captures object essence and context for improved comprehension in real-world scenarios. Then, we introduce DynamicFocusNet, a novel object detection algorithm built on the graph framework. DynamicFocusNet merges dynamic graph convolutions and attention mechanisms to flexibly adjust receptive fields. Finally, the detected target images are extracted to facilitate one-to-many data augmentation. Experimental results validate the superiority of our OFIDA method over state-of-the-art methods across six benchmark datasets.

Abstract Background Originating in Africa, African swine fever (ASF) was introduced to China in 2018. This acute and highly virulent infectious disease affects domestic pigs. The World Organization for Animal Health has listed it as a statutory reportable disease, and China has listed it as a category A infectious disease. Methods Primers and probes were designed for four ASFV genes (B646L, EP402R, MGF505-3R, and A137R). The primers/probes were highly conserved compared with the gene sequences of 21 ASFV strains. Results After optimization, the calibration curve showed good linearity (R2 > 0.99), the minimum concentration of positive plasmids that could be detected was 50 copies/µL, and the minimum viral load detection limit was 102 HAD50/mL. Furthermore, quadruple quantitative polymerase chain reaction (qPCR) with nucleic acids from three porcine-derived DNA viruses and cDNAs from eight RNA viruses did not show amplification curves, indicating that the method was specific. In addition, 1 × 106, 1 × 105, and 1 × 104 copies/µL of mixed plasmids were used for the quadruple qPCR; the coefficient of variation for triplicate determination between groups was

In this study, we investigated the effect of monobutyrin (MB) on the gut microbiota and intestinal health of weaned mice. MB was administered via gavage to 21-day-old weaned mice. Samples of small intestinal and ileal contents were collected on day 1, day 7, and day 21 post-administration. Seven days of MB administration enhanced the mucin layer and morphological structure of the intestine and the integrity of the intestinal brush border. Both MB and sodium butyrate (SB) accelerated tight junction development. Compared to SB, MB modulated intestinal T cells in a distinct manner. MB increased the ratio of Treg cells in the small intestine upon the cessation of weaning. After 21 days of MB administration, enhancement of the villus structure of the ileum was observed. MB increased the proportion of Th17 cells in the ileum. MB facilitated the transition of the small intestinal microbiota toward an adult microbial community structure and enhanced the complexity of the microbial community structure. An increase in Th17 cells enhanced intestinal barrier function. The regulatory effect of MB on Th17 cells may occur through the intestinal microbiota. Therefore, MB can potentially be used to promote intestinal barrier function, especially for weaning animals, with promising application prospects.

Abstract Objective The purpose of this study was to quantify the degree of lumbar spinal stenosis by assessing the anterior and posterior vertebral canal diameter and dural area, determine the sensitivity of the anterior and posterior spinal canal diameter, dural area and dural occupying rate in predicting the postoperative efficacy of oblique lumbar interbody fusion (OLIF) for patients with single-stage lumbar spinal stenosis, and identify the corresponding indicators suggesting that OLIF surgery should not be performed. Methods In a retrospective analysis of patients who had previously undergone OLIF surgery in our hospital, we included a total of 104 patients with lumbar spinal stenosis who had previously undergone single-stage surgery in our hospital. Three independent observers were employed to measure the anterior and posterior diameter of the spinal canal (AD, mm), dural area (CSA, mm2), the spinal canal area (SCA, mm2), and the ratio of the dural area to the spinal canal area (DM, %) at the disc level with the most severe stenosis on MRI. According to the values of AD and CSA in preoperative MRI, patients were divided into three groups: A, B, and C (Group A: AD > 12 and 100

Obesity is a common chronic metabolic disease that induces chronic systemic inflammation in the body, eventually leading to related complications such as insulin resistance (IR), type 2 diabetes mellitus, and metabolic syndromes such as cardiovascular disease. Exosomes transfer bioactive substances to neighboring or distal cells through autosomal, paracrine, or distant secretion, regulating the gene and protein expression levels of receptor cells. In this study, we investigated the effect of mouse bone marrow mesenchymal stem cell‐derived exosomes (BMSC‐Exos) on high‐fat diet obese mice and mature 3T3‐L1 adipocyte models of IR. BMSC‐Exo treatment of obese mice promoted their metabolic homeostasis, including reduction of obesity, inhibition of M1‐type proinflammatory factor expression, and improvement of insulin sensitivity. In vitro analysis revealed that BMSC‐Exos improved IR and lipid droplet accumulation in mature 3T3‐L1 adipocytes treated with palmitate (PA). Mechanistically, BMSC‐Exos cause increased glucose uptake and improved IR in high‐fat chow‐fed mice and PA‐acting 3T3‐L1 adipocytes by activating the phosphoinositide 3‐kinases/protein kinase B (PI3K/AKT) signaling pathway and upregulating glucose transporter protein 4 (GLUT4) expression. This study offers a new perspective for the development of treatments for IR in obese and diabetic patients.

Abstract Background Postoperative lung cancer patients belong to the high-risk group for venous thromboembolism (VTE). The standardized preventive measures for perioperative VTE in lung cancer are not perfect, especially for the prevention and treatment of catheter-related thrombosis (CRT) caused by carried central venous catheters (CVCs) in lung cancer surgery. Patients and methods This study included 460 patients with lung cancer undergoing video-assisted thoracic surgery (VATS) in our center from July 2020 to June 2021. Patients were randomized into two groups, and intraoperatively-placed CVCs would be carried to discharge. During hospitalization, the control group was treated with low-molecular-weight heparin (LMWH), and the experimental group with LMWH + intermittent pneumatic compression (IPC). Vascular ultrasound was performed at three time points which included before surgery, before discharge, and one month after discharge. The incidence of VTE between the two groups was studied by the Log-binomial regression model. Results CRT occurred in 71.7% of the experimental group and 79.7% of the control group. The multivariate regression showed that the risk of developing CRT in the experimental group was lower than in the control group (Adjusted RR = 0.889 [95%CI0.799–0.989], p = 0.031), with no heterogeneity in subgroups (P for Interaction > 0.05). Moreover, the fibrinogen of patients in the experimental group was lower than control group at follow-up (P = 0.019). Conclusion IPC reduced the incidence of CRT during hospitalization in lung cancer patients after surgery. Trial registration No. ChiCTR2000034511.

Coinfection of porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) is common in pig farms, but there is currently no effective vaccine to prevent this co-infection. In this study, we used immunoinformatics tools to design a multi-epitope vaccine against PEDV and PDCoV co-infection. The epitopes were screened through a filtering pipeline comprised of antigenic, immunogenic, toxic, and allergenic properties. A new multi-epitope vaccine named rPPMEV, comprising cytotoxic T lymphocyte-, helper T lymphocyte-, and B cell epitopes, was constructed. To enhance immunogenicity, the TLR2 agonist Pam2Cys and the TLR4 agonist RS09 were added to rPPMEV. Molecular docking and dynamics simulation were performed to reveal the stable interactions between rPPMEV and TLR2 as well as TLR4. Additionally, the immune stimulation prediction indicated that rPPMEV could stimulate T and B lymphocytes to induce a robust immune response. Finally, to ensure the expression of the vaccine protein, the sequence of rPPMEV was optimized and further performed in silico cloning. These studies suggest that rPPMEV has the potential to be a vaccine candidate against PEDV and PDCoV co-infection as well as a new strategy for interrupting the spread of both viruses.

Soil mulching has been widely used to improve crop productivity around the world, but how various mulching practices affect soil hydrothermal conditions, water-temperature-radiation utilization and finally grain yield of rainfed maize has been poorly understood. A two-season field experiment was conducted on rainfed summer maize in 2021 and 2022 on the Loess Plateau of China, with six soil mulching practices: flat planting with non-mulching (FPNM), flat planting with full straw mulching (FPSM), flat planting with full black film mulching (FPBF), flat planting with full transparent film mulching (FPTF), ridge-furrow planting with black film mulching on the ridge (RFBF) and ridge-furrow planting with transparent film mulching on the ridge (RFTF). The results showed that compared with the traditional FPNM, the five mulching treatments (FPSM, FPBF, FPTF, RFBF and RFTF) greatly regulated root-zone soil hydrothermal conditions and resulted in obvious soil drying-wetting alternation, which significantly changed the daytime average root-zone soil temperature in the 0 – 25 cm soil layer (by − 1.1 ℃, − 1.9 ℃, + 2.7 ℃, − 1.6℃ and + 0.8 ℃, respectively) and significantly reduced crop evapotranspiration. The five mulching treatments promoted the root growth, leaf area index and canopy light interception rate due to the improved soil water and/or temperature conditions. The structural equation modeling indicated that soil hydrothermal condition and water-temperature-radiation use efficiency could directly or indirectly explain 98% of the grain yield variation under various soil mulching practices; radiation use efficiency (RUE) determined maize production in the water-sufficient year (2021), whereas maize production was mainly determined by crop water productivity (WP) in the water-limited year (2022). The RFBF increased maize production most, followed by RFTF. Compared with FPNM, RFBF increased leaf area index by 45.4%, canopy light interception rate by 19.1%, aboveground biomass by 68.8%, 1000-grain weight by 15.1%, grain yield by 58.6%, WP by 71.8%, thermal time use efficiency by 64.6% and RUE by 30.5%. In conclusion, RFBF optimized the root-zone soil hydrothermal conditions for root growth, which in turn promoted aboveground growth and water-temperature-radiation use efficiency, and finally improved the gain yield of rainfed summer maize on the Loess Plateau of China. Therefore, RFBF was considered as a promising agricultural practice to improve rain-fed summer maize production and resource utilization efficiency on the Loess Plateau of China.

Introduction: Depression is a common comorbidity in Parkinson's Disease (PD) and treatment of depression can significantly support PD management. Zishen pingchan granules (ZPG), a traditional Chinese herbal formula, may help ameliorate depressive symptoms in PD patients. However, the molecular mechanisms underlying the effects of ZPG remain unclear. This study aimed to investigate the impact of ZPG on serum levels of brain-derived neurotrophic factor (BDNF), interleukin-1β (IL-1β), interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) in PD patients with depression. Methods: Eighty PD patients treated with pramipexole but still experiencing mild to moderate depression symptoms were randomly allocated to a group receiving 12-week ZPG treatment (n = 40) or placebo (n = 40). The Hamilton Depression Scale 17 items (HAM-D-17) was utilized to evaluate changes in depressive symptoms from baseline over 12 weeks, while the Unified Parkinson's Disease Rating Scales (UPDRS) part 3 was employed to assess changes in motor symptoms over the same duration. Serum levels of BDNF, IL-1β, IL-6, CRP, and TNF-α were measured at baseline and post-treatment. Results: Seventy-one participants completed the study. Following treatment, both groups showed significantly reduced HAMD scores. The placebo group demonstrated a decrease in BDNF levels, while the ZPG group showed an increase in IL-6 levels post-treatment. In the examination of the group-time interaction, the ZPG group exhibited a greater decrease in HAMD scores and increase in IL-6 levels compared to the placebo group. Conversely, the placebo group showed a greater decrease in BDNF levels compared to the ZPG group. However, no significant group differences were observed in UPDRS part 3 change scores or serum levels of IL-1β, CRP, or TNF-α change from baseline. Conclusion: ZPG may potentially ameliorate depressive symptoms in PD patients, with the potential mechanism involving mitigation of reductions in serum BDNF level and an increase in IL-6 level.

Obesity and its complications constitute a main threat to global human health. The purpose of this investigation was to explore the influences of Clostridium tyrobutyricum (Ct) on lipid metabolism, intestinal barrier function, and intestinal microbiome in obese mice induced by a high-fat diet (HFD). After establishing the obesity model, 107 CFU/mL and 108 CFU/mL C. tyrobutyricum were used to intervene in HFD-fed mice by gavage for six weeks, and indexes related to obesity were measured. In the liver of HFD-fed mice, the results revealed that C. tyrobutyricum reduced liver weight and the levels of triglyceride (TG), total cholesterol (TC), and nonesterified fatty acid (NEFA), along with decreasing red lipid droplets and fat vacuoles. After C. tyrobutyricum intervention, the mRNA expression of peroxisome proliferator-activated receptor-γ (PPARγ) was downregulated, and AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-α (PPARα), adipose triglyceride lipase (ATGL), and hormone-sensitive lipase (HSL) were upregulated in the liver. Additionally, C. tyrobutyricum alleviated intestinal morphology injury caused by HFD, decreased the expression of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and IL-1β in the colon, and upregulated tight junction protein expression. In addition, 16S rRNA sequencing revealed that C. tyrobutyricum increases the diversity of intestinal microbiota. Overall, C. tyrobutyricum improved HFD-induced lipid metabolism disorders, preserved the intestinal barrier’s integrity, and modulated the structure of the intestinal microbiome. These findings provide a novel insight into the role of C. tyrobutyricum as a probiotic in regulating lipid metabolism.

Porcine epidemic diarrhea virus (PEDV), a continuously evolving pathogen, causes severe diarrhea in piglets with high mortality rates. However, current vaccines cannot provide complete protection against PEDV, so vaccine development is still necessary and urgent. Here, with the help of immunoinformatics approaches, we attempted to design a multi-epitope vaccine named rPMEV to prevent and control PEDV infection. The epitopes of rPMEV were constructed by 9 cytotoxic T lymphocyte epitopes (CTLs), 11 helper T lymphocyte epitopes (HTLs), 6 linear B cell epitopes (LBEs), and 4 conformational B cell epitopes (CBEs) based on the S proteins from the four representative PEDV G2 strains. To enhance immunogenicity, porcine β-defensin-2 (PBD-2) was adjoined to the N-terminal of the vaccine as an adjuvant. All of the epitopes and PBD-2 were joined by corresponding linkers and recombined into the multivalent vaccine, which is stable, antigenic, and non-allergenic. Furthermore, we adopted molecular docking and molecular dynamics simulation methods to analyze the interaction of rPMEV with the Toll-like receptor 4 (TLR4): a stable interaction between them created by 13 hydrogen bonds. In addition, the results of the immune simulation showed that rPMEV could stimulate both cellular and humoral immune responses. Finally, to raise the expression efficiency, the sequence of the vaccine protein was cloned into the pET28a (+) vector after the codon optimization. These studies indicate that the designed multi-epitope vaccine has a potential protective effect, providing a theoretical basis for further confirmation of its protective effect against PEDV infection in vitro and in vivo studies.

The knowledge of seasonal nutrient demand is necessary for maximizing potato yield and resources use efficiency under drip fertigation, and it also can effectively mitigate the risk of nutrient leaching caused by excessive fertilization. To explore the coupling effects of irrigation level and fertilization rate on drip-fertigated potato growth, nutrient accumulation and determine the multi-objective optimal irrigation and fertilization regimes, a two-year (2018 and 2019) field experiment was conducted in the sandy regions of northern China. The experiments included three irrigation levels (I60, 60% ETC; I80, 80% ETC and I100, 100% ETC, where ETc is the crop evapotranspiration) and five fertilization rates (N0P0K0, 0 kg ha−1; N1P1K1, 100–17.5–124.5 kg ha−1; N2P2K2, 150–26.2–186.7 kg ha−1; N3P3K3, 200–34.9–248.9 kg ha−1 and N4P4K4, 250–43.7–311.2 kg ha−1, where the ratio of N, P and K was 1:0.17:1.24). The results showed that N, P and K accumulated rapidly from 42th to 95th, 50th to 96th and 46th to 91th days after sowing, respectively. For producing 1000 kg tuber yield, the required amounts of N, P and K were 1.97–4.16 kg, 0.55–0.81 kg and 4.83–7.65 kg, respectively. The uptakes of N, P and K in 1000 kg tubers across all treatments were 1:0.18–0.34:1.61–2.59, with the average N:P:K ratio of 1:0.23:2.05. Besides, irrigation level, fertilization rate and their interaction had significant effects on potato leaf area index, biomass, N, P and K accumulation. Deficit irrigation reduced seasonal LAI, biomass, N, P and K accumulation, tuber yield and apparent fertilizer recovery (AFR), but increased water productivity. High fertilization rate was conducive to promoting nutrient absorption, plant growth and improving tuber yield, while it reduced the unit nutrient productivity. The AFR increased first and then decreased with the increase of fertilization rate. To simultaneously achieve high potato yield and resources use efficiency, a multi-objective optimization model was established using the binary quadratic regression analysis between tuber yield, net income, water productivity, AFR and water–fertilizer regimes, which showed that tuber yield, net income, water productivity, and AFR could obtained ≥ 90% of their maximum values simultaneously when the irrigation interval was 204–262 mm and fertilization (N-P-K) interval ranged from 200–24–248 to 247–42–306 kg ha−1. The findings can provide useful information for optimizing irrigation and fertilization regimes in sandy regions of northern China.

Background: Dural ossification (DO) is strongly correlated with an increased incidence of complications during the surgery for the patients with thoracic ossification of the ligamentum flavum (OLF). Some methods for predicting DO have emerged, but the accuracy remains to be improved. We aimed to find a more accurate way to predict the appearance of DO. Methods: Retrospective study was adopted in this study. According to the intraoperative findings, ninety-one patients with thoracic OLF were ultimately included and divided into two groups based on the presence or absence of DO. Patient characteristics and radiographic data were recorded. The residual area ratio (RAR, residual area/cross-section area of normal spinal canal × 100%) and the short shaft ratio (SSR, the length of short shaft of the ellipse-like shape/the length of the spinal canal × 100%) were measured and calculated by 2 independent observers, followed by statistical analysis. The receiver operating characteristic curve was used to evaluate the accuracy of the SSR and RAR in predicting DO. Results: No significant differences were found in sex, age and BMI between the DO group and the non-DO group. The mean RAR (and standard deviation) in the Non-DO group (62.6% ± 10.2%) was significantly higher (p

Objective: To optimize the enzymatic hydrolysis process of Pueraria protein and study its antioxidant properties. Methods: DPPH radical scavenging ability and DH were used as the index to screen the best hydrolytic protease. Base on the single factor experiments, the Box-Behnken response surface design was used to optimize the enzymatic hydrolysis process of Pueraria protein, and the antioxidant properties of the optimum hydrolysate in vitro was analyzed. Results: The optimal hydrolysis conditions for alkaline protease were as follows: Temperature 55 ℃, pH9 and enzyme substrate ratio 2%. Under these conditions, the IC50 of DPPH·, ABTS+·, and ·OH radicals were 0.15, 0.38, 1.41 mg/mL and a reduction capacity of 0.553. Conclusion: Under these conditions, Pueraria protein hydrolysate had remarkable antioxidant properties.

When skeletal muscle is damaged, satellite cells (SCs) are activated to proliferate rapidly and fuse with the damaged muscle fibers to form new muscle fibers, thereby promoting muscle growth and remodeling and repair of trauma. Exosomes from differentiating human skeletal muscle cells trigger myogenesis of stem cells and provide biochemical cues for skeletal muscle regeneration. Therefore, we hypothesized that, when muscles are injured, myoblast‐derived exosomes may regulate muscle repair and regeneration. Here, we investigated the underlying mechanism by applying C2C12‐derived exosomes to injured mouse skeletal muscles. The expression levels of skeletal muscle regeneration factors paired box 7 and lipid‐promoting factor peroxisome proliferator‐activated receptor γ were upregulated, whereas the expression levels of fibrosis factors collagen‐1 and α‐smooth muscle actin decreased. The expression of proliferating cell nuclear antigen was elevated after applying C2C12‐derived exosomes to SCs. Application of C2C12‐derived exosomes to fibro‐adipogenic progenitors resulted in an increase in peroxisome proliferator‐activated receptor γ expression and adipogenesis capacity, whereas α‐smooth muscle actin expression and fibrosis capacity decreased. Analysis of the transcriptome and proteome of SCs after treatment with exosomes showed the involvement of multiple biological processes, including proliferation and differentiation of SCs, muscle regeneration, skeletal muscle atrophy, and the inflammatory response after muscle injury. Hence, our data suggest that C2C12‐derived exosomes can promote the regeneration of skeletal muscle fibers, accelerate the production of fat from damaged muscles, inhibit the fibrosis of damaged muscles, and accelerate injury repair, which is related to exosome‐mediated regulation of the proliferation of SCs, differentiation of fibro‐adipogenic progenitors, and modulation of SC mRNA expression and protein formation and decomposition.

Superhydrophobic behavior of liquid droplets on a surface typically results from chemical and surface topography considerations. Here, contact angles approaching 180° are observed for condensation-induced droplets on suspended monolayer graphene.

Abstract Background and objective Zishen Pingchan granule (ZPG), a traditional Chinese herbal recipe for treating Parkinson’s disease (PD), is usually used as an add-on drug with some antiparkinsonian drugs in China. The objectives of this study were to evaluate the efficacy, safety, and tolerability of ZPG combined with pramipexole in the treatment of depression in PD (dPD). Methods A 12-week, multicenter, randomized, double-blind, and placebo-controlled study on ZPG was performed on a total of 200 patients who were treated with pramipexole but still had mild to moderate depressive symptoms. Patients were randomly divided into ZPG (n = 100) or placebo (n = 100). The primary effective result was the mean change from the baseline on the Hamilton Depression Scale 17 items (HAM-D-17) over 12 weeks and the clinical efficacy rate. Secondary endpoints were the mean change from the baseline in the Geriatric Depression Scale (GDS-15), Unified Parkinson's disease rating scale Part III (UPDRS III), Parkinson's quality of life scale (PDQ-8), and Parkinson's disease sleep scale (PDSS-2) over 12 weeks. Results After 12 weeks of treatment, ZPG significantly reduced the mean [95% confidence interval] HAMD score vs. placebo (− 1.43 scores [− 2.50, − 0.36]; p = 0.009). The clinical remission rate and responders of the ZPG group were higher than those of the placebo (46.1% vs. 31.0%; p = 0.041; 34.8% vs. 18.4%; p = 0.014). A significant improvement in the PDSS-2 score was also observed in the ZPG group compared with that in the placebo group (− 3.56 scores [− 5.77, − 1.35]; p = 0.002). A total of 7 patients (7.1%) in the ZPG group had mild adverse events (AEs) vs 9 patients (9%) in the placebo group. No severe AEs were observed in either group. The randomization and controlled clinical study revealed that ZPG was effective, safe, and well-tolerated. Conclusion ZPG combined with pramipexole further reduced the depressive symptoms and improved the sleeping quality of PD patients. Trial registration The protocol was retrospectively registered at the Chinese Clinical Trial Registry, Unique identifier: ChiCTR1800019942, date of registration: December 9, 2018; http://www.chictr.org.cn/showproj.aspx?proj=30432

This study monitors the open/closed states of the windows in 16 residential apartments in representative cities of the hot summer and cold winter zone of China, along with outdoor air temperature, outdoor relative humidity and outdoor PM2.5 concentration in 2017, to investigate the window opening/closing behavior. Three window opening models are developed. All the models are validated by modeling a typical residential apartment to compare the predicted indoor CO2 concentration with monitored data. It is found that the window opening probability is negatively correlated to both outdoor PM2.5 concentration and outdoor relative humidity, and the probability of window opening reaches the peak value when the outdoor air temperature is 23.7 °C. In terms of season, the shortest window opening duration occurs in winter due to the cold outdoor air temperature and high outdoor PM2.5 concentration. Finally, by comparing the correlation between the measured date and simulation results of indoor CO2 concentration, this study provides an appropriate window opening model for reference.

How to improve and regulate coffee bean yield and quality through split fertilization in the whole life cycle of coffee is still unclear and deserves further study. A field experiment of 5-year-old Arabica coffee trees was conducted for 2 consecutive years from 2020 to 2022. The fertilizer (750 kg ha-1 year-1, N-P2O5-K2O:20%-20%-20%) was split in three times at early flowering (FL), the berry expansion (BE), and the berry ripening (BR). Taking equal fertilization throughout the growth cycle (FL250BE250BR250) as the control check, variable fertilizations including FL150BE250BR350, FL150BE350BR250, FL250BE150BR350, FL250BE350BR150, FL350BE150BR250, and FL350BE250BR150. Leaf net photosynthetic rate (Anet), stomatal conductance (gs), transpiration rate (Tr), leaf water use efficiency (LWUE), carboxylation efficiency (CE), partial factor productivity of fertilizer (PFP), bean yield, crop water use efficiency (WUE), bean nutrients, volatile compounds and cup quality, and the correlation of nutrients with volatile compounds and cup quality was evaluated. FL350BE250BR150 had the maximum Anet and gs, followed by FL250BE350BR150. The highest dry bean yield and WUE were obtained from FL250BE350BR150, which increased by 8.86% and 8.47% compared with FL250BE250BR250 in two-year average. The ash, total sugar, fat, protein, caffeine and chlorogenic acid in FL250BE350BR150 were 6.47%, 9.48%, 3.60%, 14.02%, 4.85% and 15.42% higher than FL250BE250BR250. Cluster analysis indicated FL150BE350BR250, FL250BE350BR150, FL350BE150BR250 and FL350BE250BR150 under medium roasted degree increased pyrazines, esters, ketones and furans, FL150BE350BR250 and FL250BE350BR150 under dark roasted degree increased ketones and furans. The aroma, flavor, acidity and overall score of medium roasted coffee were higher than dark roasted coffee, while the body score of dark roasted coffee was higher than medium roasted coffee. The nutrient contents were correlated with the volatile compounds and cup quality. TOPSIS indicated that FL250BE350BR150 was the optimal fertilization mode in the xerothermic regions. The obtained optimum fertilization mode can provide a scientific basis for coffee fertilization optimization and management.

Intermediate mafic lava is a special oil and gas reservoir. While its internal structure is an important factor affecting the reservoir properties, the identification of facies and understanding of the relationship between facies architecture and reservoir are limited. This study evaluated the intermediate mafic lava flows of the Yingcheng Formation in the Dongling area of Songliao Basin by analyzing drilling cores, corresponding thin sections, and scanning electron microscope (SEM) images, as well as well-logging and seismic attributes. We also performed helium gas experiments and high-pressure mercury intrusion (HPMI) analysis to assess the physical properties and pore structure of the reservoir, respectively. The results showed that intermediate mafic lava flows develop tabular lava flow, compound lava flow, and hyaloclastite. Three facies showed present diverse well-logging and seismic responses. The intermediate mafic lava facies architecture was divided into crater-proximal facies (CF-PF), medial facies (MF), and distal facies (DF), which were characterized by their vesicles and joints and could be identified through their seismic attributes. The reservoir spaces including vesicles, amygdale inner pores, joint fissures, and dissolution pores predominantly showed oil and gas accumulation. The results of the tests of the reservoir’s physical properties showed that the reservoir quality was best in the CF-PF, which is the main target of oil and gas exploration.

Usutu virus (USUV) is a mosquito-borne flavivirus of African origin. Over the past decades, USUV has spread through Europe causing mass die-offs among multiple bird species. The natural transmission cycle of USUV involves Culex spp. mosquitoes as vectors and birds as amplifying hosts. Next to birds and mosquitoes, USUV has also been isolated from multiple mammalian species, including humans, which are considered dead-end hosts. USUV isolates are phylogenetically classified into an African and European branch, subdivided into eight genetic lineages (Africa 1, 2, and 3 and Europe 1, 2, 3, 4, and 5 lineages). Currently, multiple African and European lineages are co-circulating in Europe. Despite increased knowledge of the epidemiology and pathogenicity of the different lineages, the effects of co-infection and transmission efficacy of the co-circulating USUV strains remain unclear. In this study, we report a comparative study between two USUV isolates as follows: a Dutch isolate (USUV-NL, Africa lineage 3) and an Italian isolate (USUV-IT, Europe lineage 2). Upon co-infection, USUV-NL was consistently outcompeted by USUV-IT in mosquito, mammalian, and avian cell lines. In mosquito cells, the fitness advantage of USUV-IT was most prominently observed in comparison to the mammalian or avian cell lines. When Culex pipiens mosquitoes were orally infected with the different isolates, no overall differences in vector competence for USUV-IT and USUV-NL were observed. However, during the in vivo co-infection assay, it was observed that USUV-NL infectivity and transmission were negatively affected by USUV-IT but not vice versa.

Source location identification methods are typically applied to steady-state conditions under pure indoor or outdoor environments, but under time-varying wind conditions and coupled indoor and outdoor environments, the applicability is not clear. In this study, we proposed an improved adjoint probability method to identify the pollutant source location with time-varying inflows in street canyons and used scaled outdoor experiment data to verify the accuracy. The change in inflow velocity will affect the airflow structure inside the street canyons. Outdoor wind with a lower temperature will exchange heat with the air with a higher temperature inside the street canyon, taking away part of the heat and reducing the heat of the air inside the street canyons. Moreover, the room opening will produce some air disturbance, which is conducive to the heat exchange between the air near the opening and the outdoor wind. Furthermore, the fluctuations of the upper wind will influence the diffusion of the tracer gas. We conducted three cases to verify the accuracy of the source identification method. The results showed that the conditioned adjoint location probability (CALP) of each case was 0.06, 0.32, and 0.28. It implies that with limited pollutant information, the improved adjoint probability method can successfully identify the source location in the dynamic wind environments under coupled indoor and outdoor conditions.

Two-dimensional nanomaterials have obvious advantages in thermoelectric device development. It is rare to use the same experimental system to accurately measure multiple thermoelectrical parameters of the same sample. Therefore, scholars have developed suspended microdevices, T-type and H-type methods to fulfill the abovementioned requirements. These methods usually require a direct-current voltage signal to detect in Seebeck coefficient measurement. However, the thermoelectric potential generated by the finite temperature difference is very weak and can be easily overwritten by the direct-current voltage, thereby affecting the measurement accuracy. In addition, these methods generally require specific electrodes to measure the thermoelectric potential. We propose a measurement method that combines laser heating with an H-type device. By introducing a temperature difference in two-dimensional materials through laser heating, the thermoelectric potential can be accurately measured. This method does not require specific electrodes to simplify the device structure. The thermoelectrical parameters of supported graphene are successfully measured with this method; the results are in good agreement with the literature. The proposed method is unaffected by material size and characteristics. It has potential application value in the characterization of thermoelectric physical properties.

Colorectal cancer liver metastasis (CRLM) is a highly heterogeneous disease. Therapies that target both primary foci and liver metastasis are severely lacking. Therefore, understanding the features of metastatic tumor cells in the liver is valuable for the overall control of CRLM patients. In this review, we summarize the heterogeneity exhibited in CRLM from five aspects (gene, transcriptome, protein, metabolism, and immunity). In addition to genetic heterogeneity, the other four aspects exhibit significant heterogeneity. Compared to primary CRC, the dysregulation of epithelial–mesenchymal transition (EMT)-related proteins, the enhanced metabolic activity, and the increased infiltration of immunosuppressive cells are detected in CRLM. Preclinical evidence shows that targeting the EMT process or enhancing cellular metabolism may represent a novel approach to increasing the therapeutic efficacy of CRLM.

Outcrops of late Paleozoic magmatic rocks are common in the Southern Beishan Orogenic Belt (SBOB), Southern Central Asian Orogenic Belt (CAOB), which is a key object for the understanding of regional tectonism and defining the final closure time of the Paleo-Asian Ocean (PAO). We present zircon U-Pb chronology and whole-rock geochemistry data for late Paleozoic granodiorites and bimodal volcanic rocks from the Shuangyingshan-Huaniushan unit in the north Huitongshan-Zhangfangshan ophiolitic belt in the SBOB. The Zhangfangshan granodiorites (LA-ICP-MS, Ca. 288 Ma) are A2-type granite enriched in Rb, Th, Pb and LREEs and depleted in Nb, Ta, Ti, Sr, Ba and HREEs. They have varying MgO and TFe2O3 contents with high Mg# (38.56~48.97) values; the Lu/Yb ratios (0.14~0.15) of these granodiorites are similar to mantle-derived magma. A clear plagioclase zoning structure and acicular apatite occur in mineral assemblages derived from magma mixing between mafic and felsic magmas. The Baishantang bimodal volcanic rocks (272 Ma) consist of rhyolite and basaltic andesite. Baishantang rhyolites are A2-type felsic rock enriched in Rb, Th, Pb and LREEs and depleted in Nb, Ta, Ti, Sr, Ba and HREEs, with negative εNd(t) and εHf(t) (−5.2~−4.8 and −2.2~−1.9, respectively). Rhyolites originated from the partial melting of the crust, influenced by mantle material. Basaltic andesites belong to calc-alkaline series and have an enrichment of Rb, Ba, Th, U, Pb and LREEs, are weakly enriched in Zr-Hf, and are depleted in Nb, Ta, Ti and HREEs. The Nd-Hf isotopes of these basaltic andesites are not coupled with negative εNd(t) (−2.8~−0.4) and positive εHf(t) (1.8~5.5) values. These characteristics indicate that they originated from the partial melting of the mantle mixed with sediment-derived melts. In combination with previous studies, our findings show that the early Permian Zhangfangshan granodiorites and Baishantang bimodal volcanic rocks formed in a post-collision extensional setting, and the Huitongshan-Zhangfangshan ocean had been closed before early Permian.

Wide-bandgap gallium nitride (GaN)-based semiconductors offer significant advantages over traditional Si-based semiconductors in terms of high-power and high-frequency operations. As it has superior properties, such as high operating temperatures, high-frequency operation, high breakdown electric field, and enhanced radiation resistance, GaN is applied in various fields, such as power electronic devices, renewable energy systems, light-emitting diodes, and radio frequency (RF) electronic devices. For example, GaN-based high-electron-mobility transistors (HEMTs) are used widely in various applications, such as 5G cellular networks, satellite communication, and radar systems. When a current flows through the transistor channels during operation, the self-heating effect (SHE) deriving from joule heat generation causes a significant increase in the temperature. Increases in the channel temperature reduce the carrier mobility and cause a shift in the threshold voltage, resulting in significant performance degradation. Moreover, temperature increases cause substantial lifetime reductions. Accordingly, GaN-based HEMTs are operated at a low power, although they have demonstrated high RF output power potential. The SHE is expected to be even more important in future advanced technology designs, such as gate-all-around field-effect transistor (GAAFET) and three-dimensional (3D) IC architectures. Materials with high thermal conductivities, such as silicon carbide (SiC) and diamond, are good candidates as substrates for heat dissipation in GaN-based semiconductors. However, the thermal boundary resistance (TBR) of the GaN/substrate interface is a bottleneck for heat dissipation. This bottleneck should be reduced optimally to enable full employment of the high thermal conductivity of the substrates. Here, we comprehensively review the experimental and simulation studies that report TBRs in GaN-on-SiC and GaN-on-diamond devices. The effects of the growth methods, growth conditions, integration methods, and interlayer structures on the TBR are summarized. This study provides guidelines for decreasing the TBR for thermal management in the design and implementation of GaN-based semiconductor devices.

Abstract Background Pneumoconiosis refers to a class of serious diseases threatening the health of workers exposed to coal or silicosis dust. However, the burden of pneumoconiosis is unavailable in China. Methods Incident cases, deaths, and disability-adjusted life years (DALYs) from pneumoconiosis and its subtypes in China were estimated from the Global Burden of Disease Study 2019 using a Bayesian meta-regression method. The trend of the burden from pneumoconiosis was analyzed using percentage change and annualized rate of change (ARC) during the period 1990–2019. The relationship between subnational socio-demographic index (SDI) and the ARC of age-standardised death rate was measured using Spearman’s Rank-Order Correlation. Results In 2019, there were 136.8 (95% uncertainty interval [UI] 113.7–162.5) thousand new cases, 10.2 (8.1–13.6) thousand deaths, and 608.7 (473.6–779.4) thousand DALYs from pneumoconiosis in China. Of the global burdens from pneumoconiosis, more than 60% were in China. Both the total number of new cases and DALYs from pneumoconiosis was keeping increasing from 1990 to 2019. In contrast, the age-standardised incidence, death, and DALY rates from pneumoconiosis and its subtypes, except for the age-standardised incidence rate of silicosis, and age-standardised death rate of asbestosis, experienced a significant decline during the same period. The subnational age-standardised death rates were higher in western China than in eastern China. Meanwhile, the subnational ARC of age-standardised death rates due to pneumoconiosis and its subtypes were significantly negatively correlated with SDI in 2019. Conclusion China suffers the largest health loss from pneumoconiosis in the world. Reducing the burden of pneumoconiosis is still an urgent task in China.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation, pannus formation, and bone and cartilage damage. It has a high disability rate. The hypoxic microenvironment of RA joints can cause reactive oxygen species (ROS) accumulation and mitochondrial damage, which not only affect the metabolic processes of immune cells and pathological changes in fibroblastic synovial cells but also upregulate the expression of several inflammatory pathways, ultimately promoting inflammation. Additionally, ROS and mitochondrial damage are involved in angiogenesis and bone destruction, thereby accelerating RA progression. In this review, we highlighted the effects of ROS accumulation and mitochondrial damage on inflammatory response, angiogenesis, bone and cartilage damage in RA. Additionally, we summarized therapies that target ROS or mitochondria to relieve RA symptoms and discuss the gaps in research and existing controversies, hoping to provide new ideas for research in this area and insights for targeted drug development in RA.

BackgroundWhen thyroid cancer invades the trachea, tumor resection and trachea reconstruction are required. Although the traditional way of anesthesia and tracheal intubation can maintain the necessary ventilation function during the operation, tracheal intubation affects the surgical field of vision and is not conducive to the protection of the recurrent laryngeal nerve beside the trachea during the operation.Case presentationExtracorporeal membrane oxygenation (ECMO) is used to replace traditional tracheal intubation in the process of resection and end-to-end anastomosis of tracheal tumors, and complete tracheal tumor resection and trachea reconstruction are achieved.ConclusionUsing ECMO for thyroid carcinoma resection, invaded trachea resection, and trachea reconstruction is safe and effective, which reduces the obstruction of endotracheal intubation on the operative field, guarantees the rapid and efficient end-to-end anastomosis in the upper trachea, and clearly avoids laryngeal recurrent nerve injury in the process of anastomosis.

Background & Aims: As an indispensable component of store-operated Ca2+ entry, stromal interaction molecule 1 (STIM1) is known to promote colorectal cancer and T-cell–mediated inflammatory diseases. However, whether the intestinal mucosal STIM1 is involved in inflammatory bowel diseases (IBDs) is unclear. This study aimed to investigate the role of intestinal epithelial STIM1 in IBD. Methods: Inflammatory and matched normal intestinal tissues were collected from IBD patients to investigate the expression of STIM1. Intestinal epithelium-specific STIM1 conditional knockout mice (STIM1ΔIEC) were generated and induced to develop colitis and colitis-associated colorectal cancer. The mucosal barrier, including the epithelial barrier and mucus barrier, was analyzed. The mechanisms by which STIM1 regulate goblet cell endoplasmic reticulum stress and apoptosis were assessed. Results: STIM1 could regulate intestinal epithelial homeostasis. STIM1 was augmented in the inflammatory intestinal tissues of IBD patients. In dextran sodium sulfate–induced colitis, STIM1 deficiency in intestinal epithelium reduced the loss of goblet cells through alleviating endoplasmic reticulum stress induced by disturbed Ca2+ homeostasis, resulting in the maintenance of the integrated mucus layer. These effects prevented commensal bacteria from contacting and stimulating the intestinal epithelium of STIM1ΔIEC mice and thereby rendered STIM1ΔIEC mice less susceptible to colitis and colitis-associated colorectal cancer. In addition, microbial diversity in dextran sodium sulfate–treated STIM1ΔIEC mice slightly shifted to an advantageous bacteria, which further protected the intestinal epithelium. Conclusions: Our results establish STIM1 as a crucial regulator for the maintenance of the intestinal barrier during colitis and provide a potential target for IBD treatment.

Colorectal cancer has a poor prognosis and is prone to recurrence and metastasis. DPP7, a prolyl peptidase, is reported to regulate lymphocyte quiescence. However, the correlation of DPP7 with prognosis in CRC remains unclear. With publicly available cohorts, the Wilcoxon rank-sum test and logistic regression were employed to analyze the relationship between DPP7 expression and the clinicopathological features of CRC patients. Specific pathways of differentially expressed genes were determined through biofunctional analysis and gene set enrichment analysis (GSEA). qPCR and immunohistochemical staining were used to determine DPP7 expression levels in surgical specimens. The public dataset and analysis of the biospecimens of CRC patients revealed that DPP7, in the CRC samples, was expressed significantly higher than in non-tumor tissues. Moreover, increased DPP7 was significantly associated with a higher N stage, lymphatic invasion, and shorter overall survival. Functionally, DPP7 is involved in neuroactive ligand–receptor interaction and olfactory transduction signaling. We identified a series of targeted drugs and small-molecule drugs with responses to DPP7. To conclude, DPP7 is a valuable diagnostic and prognostic biomarker for CRC and considered as a new therapeutic target.

Vertical agriculture has developed rapidly in recent years, pushing artificial light planting to new heights. Under indoor artificial light, the light supply mode has practical significance in studying the impact of lighting conditions on plants. This experiment involved five intermittent light supply modes (with a light period of 16 h and a dark period of 8 h (16/8) as the control group, with a light period of 8 h and a dark period of 4 h repeated twice a day (8/4), a light period of 4 h and a dark period of 2 h repeated four times a day (4/2), a light period of 2 h and a dark period of 1 h repeated eight times a day (2/1), and a light period of 1 h and a dark period of 0.5 h repeated 16 times a day (1/0.5) (as the experimental groups). A total of ten treatments were combined before the continuous light supply mode (B) and after the continuous light supply mode (A). Through experimental settings, we explored the response mechanisms to intermittent and continuous light supply modes as they pertain to lettuce growth, nutrient content, photosynthetic parameters, and light stress. Through research, it was found that continuous light supply significantly increased plant height, root length, aboveground dry and fresh weight, and the underground dry and fresh weight of lettuce. The treatments with a light period 4 h/dark period 2 h (4/2) and a light period 8 h/dark period 4 h (8/4) significantly increased the N, P, K, and Cu contents. Additionally, continuous light supply helped stabilize the Mg, Ca, and Mn contents across all treatment groups. Stomatal closure has been found to cause a decrease in the rate of net photosynthesis, transpiration, and intercellular CO2 concentration. The energy absorbed by antenna pigments is significantly increased when participating in photochemical reactions; however, continuous light supply has been observed to reduce the absorption flux per reaction center (ABS/RC), trapped energy flux per reaction center (TR0/RC), electron transport flux per reaction center (ET0/RC), and the probability that a trapped exciton moves an electron into the electron transport chain beyond QA− (at t = 0) (ET0/TR0). Conversely, the electron transport flux per cross section (ET0/CS) has been found to increase significantly. In summary, among the intermittent light supply treatment groups, the 2/1 treatment group showed the best response to growth indicators, nutrient absorption, and photosynthesis, and could improve the quality of lettuce without adding additional light energy. Continuous light supply in the short term can improve the growth and nutrient absorption of lettuce; both of the two light supply modes produced light stress on lettuce, and this light stress caused by non-circadian rhythm forced the lettuce to increase its photochemical quenching (qI) and electro transport flux crossover (ET0/CS). This paper may provide a theoretical reference for the use of light supply modes in plant factories to improve vegetable yield, and for the study of the response mechanism of light stress under non-circadian rhythm.

Fgf21 has been identified as playing a regulatory role in muscle growth and function. Although the mechanisms through which endurance training regulates skeletal muscle have been widely studied, the contribution of Fgf21 remains poorly understood. Here, muscle size and function were measured, and markers of fiber type were evaluated using immunohistochemistry, immunoblots, or qPCR in endurance-exercise-trained wild-type and Fgf21 KO mice. We also investigated Fgf21-induced fiber conversion in C2C12 cells, which were incubated with lentivirus and/or pathway inhibitors. We found that endurance exercise training enhanced the Fgf21 levels of liver and GAS muscle and exercise capacity and decreased the distribution of skeletal muscle fiber size, and fast-twitch fibers were observed converting to slow-twitch fibers in the GAS muscle of mice. Fgf21 promoted the markers of fiber-type transition and eMyHC-positive myotubes by inhibiting the TGF-β1 signaling axis and activating the p38 MAPK signaling pathway without apparent crosstalk. Our findings suggest that the transformation and function of skeletal muscle fiber types in response to endurance training could be mediated by Fgf21 and its downstream signaling pathways. Our results illuminate the mechanisms of Fgf21 in endurance-exercise-induced fiber-type conversion and suggest a potential use of Fgf21 in improving muscle health and combating fatigue.

Li-In alloys are widely used as reference materials in the research field of solid-state lithium-based batteries. Here, the authors report and discuss the instability of Li-In electrodes towards sulfide solid electrolytes in all-solid-state batteries.

Abstract Background Cold-inducible RNA binding protein (CIRP) is a newly discovered proto-oncogene. In this study, we investigated the role of CIRP in the progression of non-small cell lung cancer (NSCLC) using patient tissue samples, cultured cell lines and animal lung cancer models. Methods Tissue arrays, IHC and HE staining, immunoblotting, and qRT-PCR were used to detect the indicated gene expression; plasmid and siRNA transfections as well as viral infection were used to manipulate gene expression; cell proliferation assay, cell cycle analysis, cell migration and invasion analysis, soft agar colony formation assay, tail intravenous injection and subcutaneous inoculation of animal models were performed to study the role of CIRP in NSCLC cells; Gene expression microarray was used to select the underlying pathways; and RNA immunoprecipitation assay, biotin pull-down assay, immunopurification assay, mRNA decay analyses and luciferase reporter assay were performed to elucidate the mechanisms. The log-rank (Mantel-Cox) test, independent sample T-test, nonparametric Mann-Whitney test, Spearman rank test and two-tailed independent sample T-test were used accordingly in our study. Results Our data showed that CIRP was highly expressed in NSCLC tissue, and its level was negatively correlated with the prognosis of NSCLC patients. By manipulating CIRP expression in A549, H460, H1299, and H1650 cell lines, we demonstrated that CIRP overexpression promoted the transition of G1/G0 phase to S phase and the formation of an enhanced malignant phenotype of NSCLC, reflected by increased proliferation, enhanced invasion/metastasis and greater tumorigenic capabilities both in vitro and in vivo. Transcriptome sequencing further demonstrated that CIRP acted on the cell cycle, DNA replication and Wnt signaling pathway to exert its pro-oncogenic action. Mechanistically, CIRP directly bound to the 3′- and 5′-UTRs of CTNNB1 mRNA, leading to enhanced stability and translation of CTNNB1 mRNA and promoting IRES-mediated protein synthesis, respectively. Eventually, the increased CTNNB1 protein levels mediated excessive activation of the Wnt/β-catenin signaling pathway and its downstream targets C-myc, COX-2, CCND1, MMP7, VEGFA and CD44. Conclusion Our results support CIRP as a candidate oncogene in NSCLC and a potential target for NSCLC therapy.

Abstract In order to encourage innovative medicine to address Chinese unmet medical needs, China has changed its drug regulatory landscape to speed up access to new medicines. In order to understand the fast‐changing landscape and to enable planning of more global drug development programs and study designs in China, we reviewed 15 published clinical pharmacology‐related guidances by the National Medical Products Administration (NMPA), and compared them with reference guidances from the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), or the International Conference on Harmonization (ICH), to understand the similarities and differences, especially any China‐specific requirements, such as ethnic sensitivity analysis. Overall, by reviewing these clinical pharmacology‐related NMPA guidances, it is clear that NMPA guidances are very similar to FDA, EMA, and ICH guidances. There are no relevant differences in the major principles, but some differences in structure, contents, and focus were noted. The NMPA is adapting flexibility statements into newly published guidances. Ethnic sensitivity analysis needs to be implemented early in drug development plans. The NMPA encourages sponsors to conduct early clinical trials in China or include China early in multiregional clinical trials, and to obtain safety, efficacy, and pharmacokinetic data for ethnic sensitivity analysis. Depending on the stage of development, ethnic sensitivity analysis can be conducted using in vitro or literature data, other Asian clinical data, or Chinese clinical data.