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Hydrocolloids have been widely used to adjust properties of natural starches, but related research on kudzu starch is still rare. In this study, we investigated the effects of gum arabic (AG), sodium alginate (SA), locust bean gum (LG), and guar gum (GG) on kudzu starch from the perspective of its particle size, pasting, texture, rheology, dehydration rate, thermal properties, microstructure, and sensitivity to amyloglucosidase. Results showed that GG significantly increased the particle size of starch. Addition of AG led to lower peak-, final- and holding-viscosity. SA increased the retention viscosity of kudzu starch, while LG and GG increased its peak viscosity. Addition of hydrocolloids increased the hardness, chewiness, and cohesiveness of starch-hydrocolloid complexes, and reduced the dehydration rate of complex gels. Dynamic rheological data showed that the energy storage modulus (G′) was significantly higher than the loss modulus (G″). The magnitude of modulus increased with frequency, and elastic properties were better than viscous properties. Thermal analysis showed that hydrocolloids increased the starting temperature (To), and the final temperature (Tc). With addition of each of these four hydrocolloids, a more regular and porous thick-wall dense structure was formed, which effectively lowered kudzu starch's sensitivity to amyloglucosidase. It indicated that the binding of hydrocolloid to starch may slow down glucose release into blood during digestion. These results will help understand effects of natural hydrocolloid on kudzu starch, as well as expanding its application in food industry.

Purpose. To investigate whether wogonin, a key bioactive ingredient of Huangqi Guizhi formula (HQGZ formula; a Traditional Chinese Medicine herbal formula) according to network pharmacology analysis, has analgesic effects on discogenic low back pain (LBP) via regulating the nerve growth factor (NGF) in intervertebral discs (IVDs). Methods. The lumbar IVDs of rats were punctured to discogenic LBP, and the therapeutic effect of orally administrated HQGZ for discogenic LBP was investigated by measuring mechanical and cold allodynia and histological analysis. A network pharmacology analysis was conducted to search for bioactive ingredients from the HQGZ formula, and wogonin was suggested to be the most possible bioactive ingredient for LBP treatment. Subsequently, the analgesic effect of wogonin was investigated in the LBP model, and the gene expression of propain peptides in the bilateral dorsal root ganglia was analyzed using RT-PCR. Finally, immunohistochemical staining was performed for NGF expression of NGF in the IVDs to determine whether wogonin treatment would ameliorate NGF-induced LBP. Results. Oral administration of HQGZ for two weeks significantly ameliorated puncture-induced IVD degeneration (IDD) and LBP. In addition, the network pharmacology analysis revealed that wogonin, quercetin, and kaempferol were the potential candidate components of HQGZ for LBP treatment. Furthermore, we proved that wogonin had significant analgesic effects in the LBP model. Finally, wogonin was demonstrated to suppress the upregulated NGF in the IVD and ameliorate NGF-induced LBP in rats. Conclusions. The HQGZ formula has significant analgesic effects for LBP. In addition, the bioactive ingredient of wogonin was extracted from HQGZ and ameliorated LBP by suppressing the overexpressed NGF in degenerated IVDs. Therefore, wogonin has potential to be alternative treatment for LBP in clinical.

Background: Wound healing is a complicated process involving multiple cell components and can help the re-establishment of the skin’s barrier function. Previous studies have pointed out that bacterial infection and sustained inflammatory reactions are the main causes of the delay of wound closure and scar formation during wound healing. The effect of current approaches for scar-free wound repair still faces many challenges, and alternative therapeutic methods are urgently needed to be established.Methods: The basic characteristics of the new-designed nanoparticles were clarified through the characterization of the material. The biocompatibility of the nanoparticles, as well as its effect on fibroblast function, anti-bacterial capacity, inflammation suppressive role, and the underlying mechanism were further verified by a panel of biochemical assays in vitro. Ultimately, pre-clinical rat model was employed to testify its role in wound healing and scar formation in vivo.Results: Firstly, gallium-modified gelatin nanoparticles loaded with quercetin was successfully established, displaying good biocompatibility and facilitative effect on fibroblast function. In addition, the nanoparticles showed prominent anti-bacterial and inflammation-suppressive effects. What’s more important, the nanoparticles could also induce the polarization of macrophages from M1 to M2 phenotype to exert its inflammatory inhibitory role through TGF-β/Smad signaling pathway. Ultimately, in vivo experiment showed that the nanoparticles could effectively promote wound repair and inhibit scar formation during the process of wound healing.Conclusion: Taken together, the new nanoparticles have good anti-bacterial and anti-scar formation effects and great potential in the field of skin wound repair, which provides a promising therapeutic strategy for wound treatment.

The soluble solid content (SSC) is one of the important parameters depicting the quality, maturity and taste of fruits. This study explored hyperspectral imaging (HSI) and fluorescence spectral imaging (FSI) techniques, as well as suitable chemometric techniques to predict the SSC in kiwifruit. 90 kiwifruit samples were divided into 70 calibration sets and 20 prediction sets. The hyperspectral images of samples in the spectral range of 387 nm~1034 nm and the fluorescence spectral images in the spectral range of 400 nm~1000 nm were collected, and their regions of interest were extracted. Six spectral pre-processing techniques were used to pre-process the two spectral data, and the best pre-processing method was selected after comparing it with the predicted results. Then, five primary and three secondary feature extraction algorithms were used to extract feature variables from the pre-processed spectral data. Subsequently, three regression prediction models, i.e., the extreme learning machines (ELM), the partial least squares regression (PLSR) and the particle swarm optimization - least square support vector machine (PSO-LSSVM), were established. The prediction results were analyzed and compared further. MASS-Boss-ELM, based on fluorescence spectral imaging technique, exhibited the best prediction performance for the kiwifruit SSC, with the Rp2, Rc2 and RPD of 0.8894, 0.9429 and 2.88, respectively. MASS-Boss-PLSR based on the hyperspectral imaging technique showed a slightly lower prediction performance, with the Rp2, Rc2, and RPD of 0.8717, 0.8747, and 2.89, respectively. The outcome presents that the two spectral imaging techniques are suitable for the non-destructive prediction of fruit quality. Among them, the FSI technology illustrates better prediction, providing technical support for the non-destructive detection of intrinsic fruit quality.

Acinetobacter baumannii is a gram-negative bacterium and a crucial opportunistic pathogen in hospitals. A. baumannii infection has become a challenging problem in clinical practice due to the increasing number of multidrug-resistant strains and their prevalence worldwide. Vaccines are effective tools to prevent and control A. baumannii infection. Many researchers are studying subunit vaccines against A. baumannii. Subunit vaccines have the advantages of high purity, safety, and stability, ease of production, and highly targeted induced immune responses. To date, no A. baumannii subunit vaccine candidate has entered clinical trials. This may be related to the easy degradation of subunit vaccines in vivo and weak immunogenicity. Using adjuvants or delivery vehicles to prepare subunit vaccines can slow down degradation and improve immunogenicity. The common immunization routes include intramuscular injection, subcutaneous injection, intraperitoneal injection and mucosal vaccination. The appropriate immunization method can also enhance the immune effect of subunit vaccines. Therefore, selecting an appropriate adjuvant and immunization method is essential for subunit vaccine research. This review summarizes the past exploration of A. baumannii subunit vaccines, hoping to guide current and future research on these vaccines.

The risk of lightning exposure increases as wind turbine size increases, and lightning accidents have grown up to be a severe threat to wind turbines. The present paper focuses on the influence of the changes in atmospheric conditions around the rotating blade for the upward leader initiation. A 2D computational fluid dynamics model was established to obtain the air pressure distribution around the blades, and the simplified inception model was used to determine the initiation of the upward leader mechanism. In this paper, two significant factors of velocity and attack angle were studied. The results show that the trigger height is about an 11.2% difference for 120 m/s with the peak current of return stroke at 30 kA; the difference has reached about 28% for the attack angle of 10°. The research indicates that the area with higher air pressure is exposed to a greater risk of lightning strikes, and the probability of lightning strikes will increase as the blade attack angle increases.

Background Hepatocellular carcinoma (HCC) development is a complex pathological process. Tubulin gamma 1 (TUBG1) plays an oncogenic role in several human cancers; however, its functional role in HCC tumorigenesis remains unknown. Methods Herein we first evaluated the gene expression levels of TUBG1 in HCC using data from The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis databases. We then elucidated the association between TUBG1 gene expression levels and survival rates of patients with HCC. Cell cycle, proliferation, transwell migration, and matrigel invasion assays were used to study the effects of TUBG1 on the malignant phenotypes of HCC cells. Results Based on the data obtained from the aforementioned databases and our in vitro experiments, TUBG1 was found to be overexpressed in HCC and patients with high TUBG1 expression levels showed a remarkably poor overall survival rate. In addition, the expression of TUBG1 significantly promoted the malignant phenotypes of HCC cells in vitro. Gene ontology term enrichment analysis revealed that co-regulated genes were enriched in biological processes mainly involved in chromosome segregation, chromosomal region, and chromatin binding; moreover, Kyoto Encyclopedia of Genes and Genome pathway analysis showed that they were mainly involved in cell cycle, oocyte meiosis, platinum drug resistance, and the p53 signaling pathway. Conclusions We report that TUBG1 is an important oncogene in HCC. It promotes HCC progression and may serve as a potential prognostic biomarker for HCC. Future studies are warranted to unveil molecular biological mechanisms underlying TUBG1 carcinogenesis.

Improving feed efficiency is one of the main goals of chicken breeding and production. The function of the digestive system, where feed is digested and nutrients are absorbed, is closely related to feed efficiency. However, the association between feed efficiency and the development of different digestive organs in chickens remains unclear. Here, we investigated the individual feed efficiency of 207 broilers during the fast-growing period with an electronic feeder and examined the characteristics of 8 organs of their digestive system (the liver, bile, proventriculus, gizzard, duodenum, jejunum, ileum, and cecum) at market age. Both the feed conversion ratio (FCR) and residual feed intake (RFI) were significantly negatively correlated with the gizzard weight (GW) and significantly positively correlated with the relative weight of the liver (RLW). Additionally, we found an obvious negative relationship between the FCR and cecal length (CL). A two-tailed t test further confirmed these correlation analysis results. Specifically, compared to birds with the lowest feed efficiencies, the GW of broilers with the highest feed efficiencies (the lowest FCR or RFI) was 22.74% and 17.97% higher, respectively. The RLW of chickens with the highest feed efficiencies was 10.82 to 13.73% less than that of chickens with the lowest feed efficiencies. In addition, we found that increased CL (5.42–12.09%) was significantly associated with better feed efficiency. Thus, our study showed that the feed efficiency of broilers was related to the development of the gizzard, liver, and cecum. These findings provide new insight into the genetic and physiological regulation of feed efficiency in broilers.

Rainwater adversely affects the interlayer bonding quality of layered concrete. This study tested the influences of different treatment measures (i.e., discharging the rainwater accumulated on the layer and covering the insulation quilt) on the interlayer mechanical properties of concrete under the condition of short-term heavy rainfall, including compressive strength (CS), splitting tensile strength (STS), and shear strength (SS). Meanwhile, the influence of short-term heavy rainfall on the interlayer microstructure of concrete was analyzed using a scanning electron microscope (SEM) and mercury intrusion porosimetry (MIP). In addition, the ultrasonic non-destructive testing method was employed to quantify the deterioration degree of the concrete layer under the condition of short-term heavy rainfall. The results show that short-term heavy rainfall can reduce the CS, STS, and SS of concrete by 50%, 70%, and 37%, respectively. Meanwhile, the porosity and damage degree near the concrete interlayer were also increased by short-term heavy rainfall. This is mainly because rainfall increases the water-binder ratio (w/b) of concrete, resulting in the deterioration of concrete microstructure. The increase of w/b is not conducive to the development of concrete mechanical properties. Concrete with a large w/b will retain more water after hydration. The water not involved in hydration leaves more pores after evaporation, increasing the total porosity of concrete. Moreover, there is a linear relationship between the concrete damage degree and the interlayer STS and SS loss rate, as well as the correlation coefficients are 0.959 and 0.983, respectively. The porosity of concrete is linearly correlated with the interlayer STS and SS, and the correlation coefficients are 0.973 and 0.909, respectively. Draining the rainwater accumulated on the layer and covering the insulation quilt can improve the interlayer CS, STS, and SS of concrete. This is mainly because the above measures reduce the influence of rainwater on the interlayer.

Legume/cereal intercropping has the potential to maximize the use of resources to raise yields due to enhanced nitrogen (N) fixation by legume root nodules, while high N fertilization may inhibit the nodulation of legume. However, whether legume/cereal intercropping can promote the accumulation of soil N storage with N fertilization and its underlying mechanism are less clear. Here, we evaluated the long-term (5 years) effects of maize/peanut intercropping and mineral N fertilization on peanut soil total N content and soil N cycling functional genes. The experiment includes two planting patterns (peanut maize intercropping and peanut monocropping) with three N fertilization rates (0, 150, and 300 kg N ha−1). Intercropping increased soil total N content (STN) by average 18.2%, and the positive effect of intercropping on STN decreased with N application rate. Highest N application decreased the nodule fresh weight (NFW) by 64.3% and 46.0% in intercropping and monocropping system, respectively. However, intercropping has no effect on NFW. Intercropping increased the nifH gene abundance by average 26.5%. SEM analysis indicated that NFW and nifH gene abundance combined can explain 46% of the variance of STN. Our results indicate that biological N fixation but not mineral N fertilization enhances the accumulation of N in soil planted with peanut in maize/peanut intercropping system.

IntroductionDeep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective for the treatment of Parkinson's disease (PD). Moreover, remote programming is widely used in Mainland China. This necessitates evaluating the ability of remote programming to achieve the ideal postoperative effect. Therefore, we aimed to retrospectively evaluate the effects of different programming modes on the effectiveness of STN-DBS 12 months postoperatively in patients with PD.MethodsClinical data were collected retrospectively, before and 12 months after surgery, in 83 patients with PD. Based on the programming modes voluntarily selected by the patients during 12 months postoperatively, they were divided into three groups, namely remote programming alone, hospital programming alone, and hospital + remote programming. We compared the programming data and the effects of different programming methods on STN-DBS-related improvements 12 months postoperatively among these groups. Furthermore, we analyzed STN-DBS-related improvements at 12 months postoperatively in 76 patients.ResultsThe effectiveness of STN-DBS was not influenced by the three programming modes. The postoperative Movement Disorder Society Unified Parkinson's Disease Rating Scale scores did not reveal statistically significant differences between the remote alone and hospital alone programming groups, except for motor examination. The postoperative decline in the levodopa equivalent daily dose was most apparent in the hospital programming alone group. The programming frequency of the hospital + remote programming group was considerably higher than that of the remaining groups. Seventy-six patients with PD displayed good STN-DBS surgical efficacy.ConclusionProgramming modes do not influence the short-term efficacy of STN-DBS, and remote programming can yield a satisfactory surgical effect.

Herein, a combined multipoint picking scheme was proposed, and the sizes of the end of the bud picker were selectively designed. Firstly, the end of the bud picker was abstracted as a fixed-size picking box, and it was assumed that the tea buds in the picking box have a certain probability of being picked. Then, the picking box coverage and the greedy algorithm were designed to make as few numbers of picking box set as possible to cover all buds to reduce the numbers of picking. Furthermore, the Graham algorithm and the minimum bounding box were applied to fine-tune the footholds of each picking box in the optimal coverage picking box set, so that the buds were concentrated in the middle of the picking boxes as much as possible. Moreover, the geometric center of each picking box was taken as a picking point, and the ant colony algorithm was used to optimize the picking path of the end of the bud picker. Finally, by analyzing the influence of several parameters on the picking performance of the end of the bud picker, the optimal sizes of the picking box were calculated successfully under different conditions. The experimental results showed that the average picking numbers of the combined multipoint picking scheme were reduced by 31.44%, the shortest picking path was decreased by 11.10%, and the average consumed time was reduced by 50.92% compared to the single-point picking scheme. We believe that the proposed scheme can provide key technical support for the subsequent design of intelligent bud-picking robots.

BackgroundVisfatin is considered to be a “novel pro-inflammatory cytokine.” Neuroinflammatory response is one of the important mechanisms of postoperative delirium (POD). The relationship between preoperative plasma visfatin and POD is unclear.ObjectiveTo investigate the relationship between preoperative plasma visfatin concentrations and POD (primary outcome) in older hip fracture patients and to explore whether it affects POD through inflammatory factors.Materials and methodsThis prospective cohort study enrolled 176 elderly patients who were scheduled for hip fracture surgery. Preoperative plasma was collected on the morning of surgery, and visfatin levels were measured. Interleukin (IL)-1 and IL-6 were measured using patients’ plasma collected on the first day after surgery. We used the 3-min diagnostic interview for Confusion Assessment Method-defined delirium (3D-CAM) twice daily within the 2 days after surgery to assess whether POD had occurred. Restricted cubic splines and piecewise regression were used to explore the relationship between preoperative plasma visfatin concentrations and POD, and further mediation analysis was used to verify whether visfatin plays a role in POD through regulating inflammatory factors.ResultsThe incidence of POD was 18.2%. A J-shaped association was observed between preoperative plasma visfatin levels and POD. The risk of POD decreased within the lower visfatin concentration range up to 37.87 ng/ml, with a hazard ratio of 0.59 per 5 ng/ml [odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.37–0.95], but the risk increased above this concentration (P for non-linearity < 0.001, with a hazard ratio of 1.116 per 10 ng/ml; OR = 1.10, 95% CI = 1.02–1.23). Mediation effect analysis showed that when the plasma visfatin concentration was higher than 37.87 ng/ml, the effect of visfatin on POD was mediated by IL-6 (p < 0.01). A significant indirect association with postoperative plasma IL-6 was observed between preoperative plasma visfatin and POD (adjusted β = 0.1%; 95% CI = 4.8∼38.9%; p < 0.01).ConclusionVisfatin is the protective factor in POD when the preoperative plasma visfatin concentration is below 37.87 ng/ml, but when it exceeds 37.87 ng/ml, the visfatin concentration is a risk factor for POD, which is mediated by postoperative plasma IL-6. The results suggest that preoperative visfatin may have a dual effect on the POD occurrence.Clinical trial registration[www.ClinicalTrials.gov], identifier [ChiCTR21 00052674].

Parkinson’s disease (PD) is a nervous disorder that can cause motor impairment. PD severity assessment based on a series of motor movements illustrated in Unified Parkinson’s Disease Rating Scale (UPDRS) is an important part of clinical PD diagnosis. However, the current quantifying method heavily relies on human observation, which is time-consuming and subjective. Therefore, automatic severity estimation stemming from machine learning methods is receiving an increasing amount of research attention. However, these advances are still limited by data availability and interpretability. In this paper, we release a large PD motor dataset of over 300 real PD patients collected under doctors’ instructions and propose a pipeline to automatically quantify the motor severity of PD in finger tapping and postural stability. These two selected movements are representative of local and global motor control, exhibiting great clinical importance. The pipeline contains three-stage: pose estimation, domain knowledge extraction, and classification stage. The pose estimation uses deep-learning-based methods to extract 21 and 17 key points for finger tapping and postural stability respectively. The domain knowledge extraction stage extracts several explicit features pre-defined by experienced neuro-physicians. Finally, a classifier is trained to infer PD severity under MDS-UPDRS. To combine deep-learning-based features from pose estimation and domain features from the expert, the pipeline achieves a better trade-off between the model efficiency and clinical interpretability. Experiments show that our method achieves a micro average f1-score of 88%, 84%, and 84%, respectively on left finger tapping, right finger tapping, and postural stability, outperforming previous methods by a large margin. In addition, involving expert knowledge in the feature extraction stage greatly improves our model’s interpretability, which is essential in automatic PD detection.

Mental stress has been recognized as an essential risk factor for hypertension. Therefore, experts specializing in cardiology, psychiatry, and Traditional Chinese Medicine organized by the Psycho-Cardiology Group of College of Cardiovascular Physicians of Chinese Medical Doctor Association and Hypertension Group of Chinese Society of Cardiology proposed the expert consensus on the diagnosis and treatment of adult mental stress-induced hypertension in March 2021, which includes the epidemiology, etiology, diagnosis, and treatment of the mental stress-induced hypertension. This consensus will hopefully facilitate the clinical practice of this disorder. In addition, the COVID-19 pandemic has become one of the primary global sources of psychosocial stressors since the beginning of 2020, and the revision of this expert consensus in 2022 has increased the relevant content. This consensus consists of Part A and Part B. Part A includes (I) Background and epidemiological characteristics, (II) Pathogenesis, and (III) Diagnosis and Part B includes (IV) Treatment recommendations and (V) Prospects. This part presents the content of Part A.

Mental stress has been recognized as an essential risk factor for hypertension. Therefore, experts specializing in cardiology, psychiatry, and Traditional Chinese Medicine organized by the Psycho-cardiology Group, College of Cardiovascular Physicians of Chinese Medical Doctor Association, and Hypertension Group of the Chinese Society of Cardiology proposed the expert consensus on the diagnosis and treatment of adult mental stress-induced hypertension in March 2021, which includes the epidemiology, etiology, diagnosis, and treatment of the mental stress-induced hypertension. This consensus will hopefully facilitate the clinical practice of this disorder. In addition, the COVID-19 pandemic has become one of the primary global sources of psychosocial stressors since the beginning of 2020, and the revision of this expert consensus in 2022 has increased the relevant content. This consensus consists of two parts. The sections of Part A include (I) Background and epidemiological characteristics, (II) Pathogenesis, and (III) Diagnosis. The sections of Part B contain (IV) Treatment recommendations, and (V) Prospects. This article presents Part B of the consensus.

Abstract Background In Tibet, the two most important breeds are Tibetan chicken and Lhasa white chicken, and the duo exhibit specific adaptations to the high altitude thereby supplying proteins for humans living in the plateau. These breeds are partly included in the conservation plans because they represent important chicken genetic resources. However, the genetic diversity of these chickens is rarely investigated. Based on whole-genome sequencing data of 113 chickens from 4 populations of Tibetan chicken including Shigatse (SH), Nyemo (NM), Dagze (DZ) and Nyingchi (LZ), as well as Lhasa white (LW) chicken breed, we investigated the genetic diversity of these chicken breeds by genetic differentiation, run of homozygosity (ROH), genomic inbreeding and selection signature analyses. Results Our results revealed high genetic diversity across the five chicken populations. The linkage disequilibrium decay was highest in LZ, while subtle genetic differentiation was found between LZ and other populations (Fst ranging from 0.05 to 0.10). Furthermore, the highest ROH-based inbreeding estimate (FROH) of 0.11 was observed in LZ. In other populations, the FROH ranged from 0.04 to 0.06. In total, 74, 111, 62, 42 and 54 ROH islands containing SNPs ranked top 1% for concurrency were identified in SH, NM, DZ, LZ and LW, respectively. Genes common to the ROH islands in the five populations included BDNF, CCDC34, LGR4, LIN7C, GLS, LOC101747789, MYO1B, STAT1 and STAT4. This suggested their essential roles in adaptation of the chickens. We also identified a common candidate genomic region harboring AMY2A, NTNG1 and VAV3 genes in all populations. These genes had been implicated in digestion, neurite growth and high-altitude adaptation. Conclusions High genetic diversity is observed in Tibetan native chickens. Inbreeding is more intense in the Nyingchi population which is also genetically distant from other chicken populations. Candidate genes in ROH islands are likely to be the drivers of adaptation to high altitude exhibited by the five Tibetan native chicken populations. Our findings contribute to the understanding of genetic diversity offer valuable insights for the genetic mechanism of adaptation, and provide veritable tools that can help in the design and implementation of breeding and conservation strategies for Tibetan native chickens.

It is vital for the annotation of uncharacterized proteins by protein function prediction. At present, Deep Neural Network based protein function prediction is mainly carried out for dataset of small scale proteins or Gene Ontology, and usually explore the relationships between single protein feature and function tags. The practical methods for large-scale multi-features protein prediction still need to be studied in depth. This paper proposes a DNN based protein function prediction approach IGP-DNN. This method uses Grasshopper Optimization Algorithm (GOA) and Intuitionistic Fuzzy c-Means clustering (IFCM) based protein function modules extracting algorithm to extract the features of protein modules, utilizing Kernel Principal Component Analysis (KPCA) method to reduce the dimensionality of the protein attribute information, and integrating module features and attribute features. Inputting integrated data into DNN through multiple hidden layers to classify proteins and predict protein functions. In the experiments, the F-measure value of IGP-DNN on the DIP dataset reaches 0.4436, which shows better performance.

Abstract NRF2 is the master transcriptional activator of cytoprotective genes and Kelch-like ECH-associated protein 1 (Keap1), a biosensor for electrophiles and oxidation, promotes NRF2 degradation in unstressed conditions. SQSTM1/p62, an oncogenic protein aberrantly accumulated in hepatocellular carcinoma (HCC), binds and sequestrates Keap1, leading to the prevention of NRF2 degradation. Here, we show that p15INK4b-related sequence/regulation of nuclear pre-mRNA domain-containing protein 1A (RPRD1A) is highly expressed in HCC tumors and correlated with aggressive clinicopathological features. RPRD1A competitively interacts with TRIM21, an E3 ubiquitin ligase of p62, resulting in the decrease of p62 ubiquitination and the increased sequestration for Keap1. Therefore, RPRD1A enhances the nuclear translocation of NRF2, which induces gene expression for counteracting oxidative stress, maintaining cancer cells survival, and promoting HCC development. Moreover, disturbing the redox homeostasis of cancer cells by genetic knockdown of RPRD1A sensitizes cancer cells to platinum-induced cell death. Our study reveals RPRD1A is involved in the oxidative stress defense program and highlights the therapeutic benefits of targeting pathways that support antioxidation.

Abstract Due to its suddenness and unpredictability, COVID-19 caused strife and effects on public mental health, resulting in a surge of negative emotions. The study explores the relationship between physical exercise and negative emotions in home-based college students during the COVID-19 epidemic, as well as the mediating role of resilience, thus providing a new basis for understanding the role of physical exercise in improving negative emotions in college students; A total of 1214 college students were investigated with the Physical Exercise Questionnaire, Negative Emotion Scale and Resilience Scale; Both physical exercise and resilience were significantly negatively correlated with negative emotions in college students (r = − 0.25, − 0.33, P

Abstract Background Eggshell is a bio-ceramic material comprising columnar calcite (CaCO3) crystals and organic proteinaceous matrix. The size, shape and orientation of the CaCO3 crystals influence the microstructural properties of chicken eggshells. However, the genetic architecture underlying eggshell crystal polymorphism remains to be elucidated. Results The integral intensity of the nine major diffraction peaks, total integral intensity and degree of orientation of the crystals were measured followed by a genome-wide association study in 839 F2 hens. The results showed that the total integral intensity was positively correlated with the eggshell strength, eggshell thickness, eggshell weight, mammillary layer thickness and effective layer thickness. The SNP-based heritabilities of total integral intensity and degree of orientation were 0.23 and 0.06, respectively. The 621 SNPs located in the range from 55.6 to 69.1 Mb in GGA1 were significantly associated with TA. PLCZ1, ABCC9, ITPR2, KCNJ8, CACNA1C and IAPP, which are involved in the biological process of regulating cytosolic calcium ion concentration, can be suggested as key genes regulating the total integral intensity. Conclusions The findings greatly advance the understanding of the genetic basis underlying the crystal ultrastructure of eggshell quality and thus will have practical significance in breeding programs for improving eggshell quality.

Metal-organic frameworks—through the use of creative synthetic designs—could produce MOF materials with excellent porosity, stability, particle microstructures, and conductivity, and their inherent characteristics—including their porosity and controllable structure—may result in an immense number of prospects for energy storage. In this paper, a nanosphere-like NiCo-MOF was effectively manufactured via an ultra-fast microwave technique. Additionally, the ideal synthesis conditions of the NiCo-MOF were investigated by adjusting the microwave output power and microwave reaction time. Under the reaction conditions of a 600 W microwave and a 210 s microwave reaction time, the NiCo-MOF exhibited an excellent capacitance of 1348 F/g at a current density of 1 A/g and an 86.1% capacity retention rate at 10 A/g. In addition, self-assembled NiCo-MOF/AC asymmetric capacitors showed a splendid energy density of 46.6 Wh/kg and a power density of 8000 W/kg.

Crude oil resource scheduling is one of the critical issues upstream in the crude oil industry chain. It aims to reduce transportation and inventory costs and avoid alerts of inventory limit violations by formulating reasonable crude oil transportation and inventory strategies. Two main difficulties coexist in this problem: the large problem scale and uncertain supply and demand. Traditional operations research (OR) methods, which rely on forecasting supply and demand, face significant challenges when applied to the complicated and uncertain short-term operational process of the crude oil supply chain. To address these challenges, this paper presents a novel hierarchical optimization framework and proposes a well-designed hierarchical reinforcement learning (HRL) algorithm. Specifically, reinforcement learning (RL), as an upper-level agent, is used to select the operational operators combined by various sub-goals and solving orders, while the lower-level agent finds a viable solution and provides penalty feedback to the upper-level agent based on the chosen operator. Additionally, we deploy a simulator based on real-world data and execute comprehensive experiments. Regarding the alert number, maximum alert penalty, and overall transportation cost, our HRL method outperforms existing OR and two RL algorithms in the majority of time steps.

Although recent evidence has revealed that a body shape index (ABSI) is correlated with the incidence of death among different ethnicities, there remains a paucity of studies investigating the impact of ABSI on mortality within the Chinese elderly. Our objective was to ascertain the link between ABSI, as well as its alterations over time, and all-cause mortality among Chinese aged 65 y and above. A total of 3789 participants were enrolled from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Cox regressions and restricted cubic splines were employed to assess the association of ABSI and relative changes with all-cause mortality. When nonlinearity was detected, a restricted cubic spline regression was subsequently conducted to compute hazard ratios and 95% confidence intervals. The median survival time was 46 months, and 1342 individuals (35.4%) were reported to have died. ABSI contributed independently to rising death rates among Chinese old populations according to univariate and multivariate Cox regressions. Statistically significant associations were also found stratified by age, sex, and lifestyle. A U-shaped association of ABSI changes with all-cause mortality (p = 0.027) was observed, indicating that old adults with stable ABSI during the follow-up period experienced the lowest risk of mortality. After multivariable adjustment, participants with a 10% reduction in ABSI changes had an increased 9.4% risk of death, while participants with a 10% rise in ABSI changes had an increased 1.9% risk. ABSI and its changes are predictors for all-cause mortality among the elderly Chinese population, which emphasizes the clinical importance of monitoring ABSI and keeping it stable over time.

The propagation of electromagnetic waves beyond the line of sight can be caused by atmospheric ducts, which are significant concerns in the fields of radar and communication. This paper utilizes data from seven automatic weather stations and five radio-sounding stations to statistically analyze the characteristics of the atmospheric ducts in the northwest region of the South China Sea (SCS). After verifying the practicality of numerical analysis data from NCEP CFSv2 and ECMWF in studying atmospheric ducts using measured data, we analyzed the spatial–temporal distribution characteristics of the height of the regional evaporation duct and the bottom height of the elevated duct. The study found that the NCEP CFSv2 data accurately capture the evaporation duct height and duct occurrence rate in the study area, and the elevated duct bottom height calculated from ERA5 and the measured data have good consistency. The occurrence rate and height of the evaporation duct in coastal stations in the northwest of the SCS vary significantly by month, demonstrating clear monthly distribution patterns; conversely, changes in the Xisha station are minimal, indicating good temporal uniformity. For lower atmospheric ducts, the difference in occurrence rates between 00:00 and 12:00 (UTC) is negligible. The occurrence probability of elevated ducts in the Beibu Gulf area is relatively high, mainly concentrated from January to April, and the Xisha area is dominated by surface ducts without foundation layers, mainly concentrated from June to August. Monsoons play a critical role in the generation and evolution of atmospheric ducts in the northwest of the SCS, with the height of the evaporation duct increasing and the bottom height of the elevated duct decreasing after the onset of the summer monsoon. In the end, we simulated electromagnetic propagation loss under different frequencies and radiation elevation angles in various duct environments within a typical atmospheric duct structure.

Optical coherence tomography is a new promising chromatographic imaging technique with the advantages of noncontact and high resolution without damage, which is widely used in the field of biological tissue detection and imaging. As an important optical element in the system, the wide-angle depolarizing reflector plays a key role in the accurate acquisition of optical signals. Ta2O5 and SiO2 are selected as the coating materials for the technical parameter requirements of the reflector in the system. Based on the basic theory of optical thin film and combined with MATLAB and OptiLayer software, the design of 0~60° incident 1064 ± 40 nm depolarizing reflective film is realized by establishing the evaluation function of the film system. To optimize the oxygen-charging distribution scheme during film deposition, the weak absorption properties of the film materials are characterized by optical thermal co-circuit interferometry. According to the sensitivity distribution of the film layer, the optical control monitoring scheme with a thickness error of less than 1% is designed rationally. “Crystal control + optical control” is used to precisely control the thickness of each film layer and complete the preparation of resonant cavity film. The measurement results show that the average reflectance is more than 99.5%, and the deviation of P-light and S-light is less than 1% in the 1064 ± 40 nm wavelength band range from 0° to 60°, which meets the requirements of optical coherence tomography system.

The actual protective performance of the coated reinforcement in coral concrete was investigated by measuring the chloride ion diffusion coefficient, electrochemical analysis, and numerical simulation. The test results show that the corrosion rate of coated reinforcement in coral concrete under the action of wet and dry cycles is kept at a low level, and the Rp value is always greater than 250 kΩ·cm2 during the test period, which is in the uncorroded state and has good protection performance. Moreover, the chloride ion diffusion coefficient D is in accordance with the power function relationship with the wet and dry cycle time, and a time-varying model of chloride ion concentration on the surface of coral concrete is established. The surface chloride ion concentration of coral concrete reinforcement was modeled as a time-varying model; the cathodic zone of coral concrete members was the most active, increasing from 0 V to 0.14 V from 0 to 20 years, with a large increase in potential difference before the 7th year, and a significant decrease in the increase after the 7th year.

Hybrid nanogenerators based on the principle of surface charging of functional films are significant in self-powering sensing and energy conversion devices due to their multiple functions and high conversion efficiency, although applications remain limited due to a lack of suitable materials and structures. Here, we investigate a triboelectric-piezoelectric hybrid nanogenerator (TPHNG) in the form of a mousepad for computer user behavior monitoring and energy harvesting. Triboelectric and piezoelectric nanogenerators with different functional films and structures work independently to detect sliding and pressing movements, and the profitable coupling between the two nanogenerators leads to enhanced device outputs/sensitivity. Different mouse operations such as clicking, scrolling, taking-up/putting-down, sliding, moving rate, and pathing can be detected by the device via distinguishable patterns of voltage ranging from 0.6 to 36 V. Based on operation recognition, human behavior monitoring is realized, with monitoring of tasks such as browsing a document and playing a computer game being successfully demonstrated. Energy harvesting from mouse sliding, patting, and bending of the device is realized with output voltages up to 37 V and power up to 48 μW while exhibiting good durability up to 20,000 cycles. This work presents a TPHNG utilizing surface charging for self-powered human behavior sensing and biomechanical energy harvesting.

Due to the long synthetic aperture time, the large squint angle, and the large imaging width of medium Earth orbit (MEO) and high Earth orbit (HEO) SAR satellites, it is difficult to simulate the geometric positioning accuracy of MEO- and HEO-SAR satellites through the SAR image simulation methods. In this paper, one non-zero Doppler simulation method of geometric positioning accuracy was proposed without simulating SAR images. In order to simulate the geometric positioning accuracy under different errors and imaging observation conditions, the virtual simulation geometric model was constructed by the simulated satellite ephemeris and the coordinates of ground control points (GCPs). On this basis, one geometric accuracy simulation method based on mean value compensation was proposed to simulate the geometric positioning accuracy with GCPs. The experimental results showed that the impact of Doppler center frequency error and velocity error of MEO- and HEO-SAR satellites on geometric positioning accuracy is significant compared with the LEO-SAR satellites, and the maximum error they affect can reach about 1597 m. In addition, the geometric positioning accuracies of MEO- and HEO-SAR satellites with GCPs can be achieved to 1~10 m and 7~29 m, respectively.

This article proposes a video prediction network called STMP-Net that addresses the problem of the inability of Recurrent Neural Networks (RNNs) to fully extract spatiotemporal information and motion change features during video prediction. STMP-Net combines spatiotemporal memory and motion perception to make more accurate predictions. Firstly, a spatiotemporal attention fusion unit (STAFU) is proposed as the basic module of the prediction network, which learns and transfers spatiotemporal features in both horizontal and vertical directions based on spatiotemporal feature information and contextual attention mechanism. Additionally, a contextual attention mechanism is introduced in the hidden state to focus attention on more important details and improve the capture of detailed features, thus greatly reducing the computational load of the network. Secondly, a motion gradient highway unit (MGHU) is proposed by combining motion perception modules and adding them between adjacent layers, which can adaptively learn the important information of input features and fuse motion change features to significantly improve the predictive performance of the model. Finally, a high-speed channel is provided between layers to quickly transmit important features and alleviate the gradient vanishing problem caused by back-propagation. The experimental results show that compared with mainstream video prediction networks, the proposed method can achieve better prediction results in long-term video prediction, especially in motion scenes.

Sex determination and differentiation are processes by which a bipotential gonad adopts either a testicular or ovarian cell fate, and secondary sexual characteristics adopt either male or female developmental patterns. In birds, although genetic factors control the sex determination program, sex differentiation is sensitive to hormones, which can induce sex reversal when disturbed. Although these sex-reversed birds can form phenotypes opposite to their genotypes, none can experience complete sex reversal or produce offspring under natural conditions. Promising evidence indicates that the incomplete sex reversal is associated with cell autonomous sex identity (CASI) of avian cells, which is controlled by genetic factors. However, studies cannot clearly describe the regulatory mechanism of avian CASI and sex development at present, and these factors require further exploration. In spite of this, the abundant findings of avian sex research have provided theoretical bases for the progress of gender control technologies, which are being improved through interdisciplinary co-operation and will ultimately be employed in poultry production. In this review, we provide an overview of avian sex determination and differentiation and comprehensively summarize the research progress on sex reversal in birds, especially chickens. Importantly, we describe key issues faced by applying gender control systems in poultry production and chronologically summarize the development of avian sex control methods. In conclusion, this review provides unique perspectives for avian sex studies and helps scientists develop more advanced systems for sex regulation in birds.

Domestic ducks are descended from the Mallard and have been bred for several purposes. Here the authors present three high-quality duck genome assemblies which recover previously missing genes and provide a rich resource of variants potentially related to domestication.

Abstract Background Poultry is the major reservoir of Campylobacter that contributes to human campylobacteriosis and threatens food safety. Litter contact has been linked to Campylobacter colonization, but the gut microecological impact underlying this link remains not fully clear. Here, we sought to investigate the impact of the gut microecology on the presence of Campylobacter by examining the microbiota in the duodenum, jejunum, ileum, ceca, and feces from chickens raised on commercial litter and in individual cages at 0–57 days of age. Results Through litter contact, the presence of Campylobacter was found to benefit from microecological competition among Lactobacillus, Helicobacter, and genera that are halotolerant and aerobic or facultatively anaerobic in the upper intestine, such as Corynebacterium and Brachybacterium. The presence was also promoted by the increased abundance in obligate anaerobic fermentation microbes, especially members of the orders Clostridiales and Bacteroidales. The longitudinal analysis supported the vertical or pseudo-vertical transmission but suggested that colonization might occur immensely at 7–28 days of age. We observed a host genetic effect on the gut microecology, which might lead to increased heterogeneity of the microecological impact on Campylobacter colonization. Conclusions The findings advance the understanding of the gut microecological impact on Campylobacter presence in the chicken gut under conditions of litter contact and suggest that manipulations of the gut microecology, as well as the microbes identified in the Campylobacter association networks, might be important for the development of intervention strategies.

Abstract In glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH), downregulated osteogenic ability and damaged blood supply are two key pathogenic mechanisms. Studies suggested that cannabinoid receptor 2 (CB2) is expressed in bone tissue and it plays a positive role in osteogenesis. However, whether CB2 could enhance bone formation and blood supply in GC-induced ONFH remains unknown. In this study, we focused on the effect of CB2 in GC-induced ONFH and possible mechanisms in vitro and in vivo. By using GC-induced ONFH rat model, rat-bone mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) to address the interaction of CB2 in vitro and in vivo, we evaluate the osteogenic and angiogenic effect variation and possible mechanisms. Micro-CT, histological staining, angiography, calcein labeling, Alizarin red staining (ARS), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) staining, TUNEL staining, migration assay, scratch assay, and tube formation were applied in this study. Our results showed that selective activation of CB2 alleviates GC-induced ONFH. The activation of CB2 strengthened the osteogenic activity of BMSCs under the influence of GCs by promotion of GSK-3β/β-catenin signaling pathway. Furthermore, CB2 promoted HUVECs migration and tube-forming capacities. Our findings indicated that CB2 may serve as a rational new treatment strategy against GC-induced ONFH by osteogenesis activation and maintenance of blood supply.

Abstract Background Tuberculosis (TB) is a chronic infectious disease, common in China. TB bacteria can invade multiple organs throughout the body, but they rarely cause critical illness. We present a complex critically ill case in this report. Case presentation A 40-year-old man suffered sudden cardiac arrest during an emergency room visit. Spontaneous circulation resumed after emergency cardiopulmonary resuscitation (CPR), but recurrent ventricular fibrillation and refractory cardiac shock emerged. Thereafter, extracorporeal membrane oxygenation (ECMO) was implemented to maintain hemodynamic stability. Blood test results revealed that the patient had severe electrolyte imbalance and adrenal insufficiency. Further imaging examination showed multiple tuberculosis lesions throughout the body, including the lungs, adrenal glands, and lumbar spine. In the end, the patient was successfully moved from the ICU after weaning from ECMO and the ventilator, and then transferred to an infectious disease specialist hospital for standard anti-tuberculosis therapy. Conclusions ECMO has won the opportunity for the diagnosis and treatment of this young patient who suffered from a rare cause of cardiac arrest and finally achieved a good prognosis.

Abstract We propose a classification method using the radiomics features of CT chest images to identify patients with coronavirus disease 2019 (COVID-19) and other pneumonias. The chest CT images of two groups of participants (90 COVID-19 patients who were confirmed as positive by nucleic acid test of RT-PCR and 90 other pneumonias patients) were collected, and the two groups of data were manually drawn to outline the region of interest (ROI) of pneumonias. The radiomics method was used to extract textural features and histogram features of the ROI and obtain a radiomics features vector from each sample. Then, we divided the data into two independent radiomic cohorts for training (70 COVID-19 patients and 70 other pneumonias patients), and validation (20 COVID-19 patients and 20 other pneumonias patients) by using support vector machine (SVM). This model used 20 rounds of tenfold cross-validation for training. Finally, single-shot testing of the final model was performed on the independent validation cohort. In the COVID-19 patients, correlation analysis (multiple comparison correction—Bonferroni correction, P

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a broad clinical spectrum of coronavirus disease 2019 (COVID-19). The development of COVID-19 may be the result of a complex interaction between the microbial, environmental, and host genetic components. To reveal genetic determinants of susceptibility to COVID-19 severity in the Chinese population, we performed a genome-wide association study on 885 severe or critical COVID-19 patients (cases) and 546 mild or moderate patients (controls) from two hospitals, Huoshenshan and Union hospitals at Wuhan city in China. We identified two loci on chromosome 11q23.3 and 11q14.2, which are significantly associated with the COVID-19 severity in the meta-analyses of the two cohorts (index rs1712779: odds ratio [OR] = 0.49; 95% confidence interval [CI], 0.38–0.63 for T allele; P = 1.38 × 10−8; and index rs10831496: OR = 1.66; 95% CI, 1.38–1.98 for A allele; P = 4.04 × 10−8, respectively). The results for rs1712779 were validated in other two small COVID-19 cohorts in the Asian populations (P = 0.029 and 0.031, respectively). Furthermore, we identified significant eQTL associations for REXO2, C11orf71, NNMT, and CADM1 at 11q23.3, and CTSC at 11q14.2, respectively. In conclusion, our findings highlight two loci at 11q23.3 and 11q14.2 conferring susceptibility to the severity of COVID-19, which might provide novel insights into the pathogenesis and clinical treatment of this disease.

The internal quality of eggs is critical for human consumption and embryonic development. However, microorganisms inside eggs have not been thoroughly investigated for their roles in determining the egg’s internal quality. Here, a total of 21 hens were selected from more than 1,000 chickens based on their hatching results and were divided into high- and low-hatchability groups. Then, we collected 72 eggs from these 21 hens to obtain egg whites and yolks, including 54 fresh eggs and 18 eggs after 12 days of incubation. We characterized the microbial composition of egg yolks and whites, the microbial change along incubation, and differences in microbial abundance between the high- and low-hatchability groups. The results indicated that egg whites are not sterile. Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were the dominant phyla in egg yolk and white. There was a large difference in the microbial composition between egg whites and yolks, and this difference increased after 12 days of incubation. Egg whites have lower microbial diversity than egg yolks owing to the presence of antibacterial substances such as lysozyme in the egg white. After a 12-day incubation, the microbial diversity decreased in egg whites but increased slightly in egg yolks. Meanwhile, the microbes in egg white can migrate to egg yolk during incubation. Additionally, Genus Muribaculaceae was identified as a biomarker in egg yolks incubated for 12 days and was more often detected in healthy groups. On the contrary, more genus Rothia were found in the fresh egg yolk of the low hatchability groups and was considered to have low virulence. These findings shed light on the composition and differences in microbiota between egg yolks and whites and may open new avenues for studying embryonic development in chickens.

To evaluate the patient safety culture status of the ECMO team in the emergency department of a tertiary care hospital. A cross-sectional survey was conducted in the emergency department of Xiangya Hospital from September 1st to 30th, 2021. The Chinese version of HSOPSC electronic questionnaire was administered to all staff involved in ECMO management and initiation. A total of 152 ECMO team members completed the survey. Among the 12 dimensions of patient safety culture, 4 dimensions recorded relatively high positive response rates (>50%): organizational learning-continuous improvement (87.1%), teamwork within units (86.8%), feedback and communication about errors (58.5%), and supervisor/manager expectations and actions promoting patient safety (55.6%). 8 dimensions recorded relatively low positive response rates (

Accurate recognition method of pitaya in natural environment provides technical support for automatic picking. Aiming at the intricate spatial position relationship between pitaya fruits and branches, a pitaya recognition method based on improved YOLOv4 was proposed. GhostNet feature extraction network was used instead of CSPDarkNet53 as the backbone network of YOLOv4. A structure of generating a large number of feature maps through a small amount of calculation was used, and the redundant information in feature layer was obtained with lower computational cost, which can reduce the number of parameters and computation of the model. Coordinate attention was introduced to enhance the extraction of fine-grained feature of targets. An improved combinational convolution module was designed to save computing power and prevent the loss of effective features and improve the recognition accuracy. The Ghost Module was referenced in Yolo Head to improve computing speed and reduce delay. Precision, Recall, F1, AP, detection speed and weight size were selected as performance evaluation indexes of recognition model. 8800 images of pitaya fruit in different environments were used as the dataset, which were randomly divided into the training set, the validation set and the test set according to the ratio of 7:1:2. The research results show that the recognition accuracy of the improved YOLOv4 model for pitaya fruit is 99.23%. Recall, F1 and AP are 95.10%, 98% and 98.94%, respectively. The detection speed is 37.2 frames·s-1, and the weight size is 59.4MB. The improved YOLOv4 recognition algorithm can meet the requirements for the accuracy and the speed of pitaya fruit recognition in natural environment, which will ensure the rapid and accurate operation of the picking robot.

Immune checkpoint blockade (ICB) has demonstrated clinical success in “inflamed” tumors with substantial T cell infiltrates, but tumors with an immune-desert tumor microenvironment (TME) fail to benefit. The tumor cell–intrinsic molecular mechanisms of the immune-desert phenotype remain poorly understood. Here, we demonstrated that inactivation of the polycomb-repressive complex 2 (PRC2) core components embryonic ectoderm development (EED) or suppressor of zeste 12 homolog (SUZ12), a prevalent genetic event in malignant peripheral nerve sheath tumors (MPNSTs) and sporadically in other cancers, drove a context-dependent immune-desert TME. PRC2 inactivation reprogramed the chromatin landscape that led to a cell-autonomous shift from primed baseline signaling-dependent cellular responses (e.g., IFN-γ signaling) to PRC2-regulated developmental and cellular differentiation transcriptional programs. Further, PRC2 inactivation led to diminished tumor immune infiltrates through reduced chemokine production and impaired antigen presentation and T cell priming, resulting in primary resistance to ICB. Intratumoral delivery of inactivated modified vaccinia virus Ankara (MVA) enhanced tumor immune infiltrates and sensitized PRC2-loss tumors to ICB. Our results identify molecular mechanisms of PRC2 inactivation–mediated, context-dependent epigenetic reprogramming that underline the immune-desert phenotype in cancer. Our studies also point to intratumoral delivery of immunogenic viruses as an initial therapeutic strategy to modulate the immune-desert TME and capitalize on the clinical benefit of ICB.

Human esophageal cancer has a global impact on human health due to its high incidence and mortality. Therefore, there is an urgent need to develop new drugs to treat or prevent the prominent pathological subtype of esophageal cancer, esophageal squamous cell carcinoma (ESCC). Based upon the screening of drugs approved by the Food and Drug Administration, we discovered that Arbidol could effectively inhibit the proliferation of human ESCC in vitro. Next, we conducted a series of cell-based assays and found that Arbidol treatment inhibited the proliferation and colony formation ability of ESCC cells and promoted G1-phase cell cycle arrest. Phosphoproteomics experiments, in vitro kinase assays and pull-down assays were subsequently performed in order to identify the underlying growth inhibitory mechanism. We verified that Arbidol is a potential ataxia telangiectasia and Rad3-related (ATR) inhibitor via binding to ATR kinase to reduce the phosphorylation and activation of minichromosome maintenance protein 2 at Ser108. Finally, we demonstrated Arbidol had the inhibitory effect of ESCC in vivo by a patient-derived xenograft model. All together, Arbidol inhibits the proliferation of ESCC in vitro and in vivo through the DNA replication pathway and is associated with the cell cycle.

Fat-soluble vitamin malabsorption may occur due to low dietary fat content, even in the presence of an adequate supply of fat-soluble vitamins. Bile acids (BAs) have been confirmed as emulsifiers to promote fat absorption in high-fat diets. However, there are no direct evidence of exogenous BAs promoting the utilization of fat-soluble vitamins associated with fat absorption in vitro and in vivo. Therefore, we chose laying hens as model animals, as their diet usually does not contain much fat, to expand the study of BAs. BAs were investigated in vitro for emulsification, simulated intestinal digestion, and release rate of fat-soluble vitamins. Subsequently, a total of 450 healthy 45-week-old Hy-Line Gray laying hens were chosen for an 84-day feeding trial. They were divided into five treatments, feeding diets supplemented with 0, 30, 60, 90, and 120 mg/kg BAs, respectively. No extra fat was added to the basic diet (crude fat was 3.23%). In vitro, BAs effectively emulsified the water-oil interface. Moreover, BAs promoted the hydrolysis of fat by lipase to release more fatty acids. Although BAs increased the release rates of vitamins A, D, and E from vegetable oils, BAs improved for the digestion of vitamin A more effectively. Dietary supplementation of 60 mg/kg BAs in laying hens markedly improved the laying performance. The total number of follicles in ovaries increased in 30 and 60 mg/kg BAs groups. Both the crude fat and total energy utilization rates of BAs groups were improved. Lipase and lipoprotein lipase activities were enhanced in the small intestine in 60, 90, and 120 mg/kg BAs groups. Furthermore, we observed an increase in vitamin A content in the liver and serum of laying hens in the 60, 90, and 120 mg/kg BAs groups. The serum IgA content in the 90 and 120 mg/kg BAs groups was significantly improved. A decrease in serum malondialdehyde levels and an increase in glutathione peroxidase activity were also observed in BAs groups. The present study concluded that BAs promoted the absorption of vitamin A by promoting the absorption of fat even under low-fat diets, thereupon improving the reproduction and health of model animals.

Inositol hexaphosphate (IP6) is a phytochemical widely found in grains and legumes that plays an anti-cancer role. However, the mechanism underlying the inhibition of colorectal cancer metastasis by IP6 through host genes, gut microbiota, and their interactions remain elusive. In this study, 16S rRNA sequencing was used to study the effect of IP6 on gut microbiota in an orthotopic transplantation model of colorectal cancer mice. The transcriptome was used to study the changes of host genes in metastasis and the relationship with gut microbiota. The results showed that the gut microbiota composition of model mice was significantly different from that of normal mice. The beta diversity partly tended to return to the normal level after IP6 intervention. Especially, Lactobacillus helveticus and Lactococcus lactis were recovered after IP6-treated. Enrichment analysis showed that the enrichment score of the Cytokine-Cytokine receptor interaction signal pathway decreased after IP6 treatment compared to the model group. Further analysis of differentially expressed genes (DEGs) in this pathway showed that IP6 reduced the expression of the Tnfrsf1b gene related to the area of liver metastasis, and the Tnfrsf1b gene was negatively correlated with the relative abundance of Lactobacillus helveticus. Our results presented that host gene, microbiome and their interaction may serve as promising targets for the mechanism of IP6 intervention in colorectal cancer metastasis.

Abstract Background α‐1,6 Fucosyltransferase (FUT8) appears to play an essential role in the pathogenesis of renal fibrosis. However, it remained unknown whether FUT8 also contributed to renal fibrosis in immunoglobulin A nephropathy (IgAN). In the present study, we explored the association of serum FUT8 activity with renal tubulointerstitial injury in IgAN patients. Methods Serum FUT8 activity was measured in 135 IgAN patients and 68 healthy controls from January 2016 to December 2018. The relationships of serum FUT8 activity with clinical and pathological features were analyzed. Results Relative to healthy controls, IgAN patients had significantly higher serum FUT8 activity and upregulation of renal FUT8 protein (p 12.2 pmol/h/ml, n = 95). The high serum FUT8 activity group had a higher Oxford T score, increased inflammatory cell infiltration, more severe fibrosis and poor renal function (p

Neural tissue is an important soft tissue; for instance, craniofacial nerves govern several aspects of human behavior, including the expression of speech, emotion transmission, sensation, and motor function. Therefore, nerve repair to promote functional recovery after craniofacial soft tissue injuries is indispensable. However, the repair and regeneration of craniofacial nerves are challenging due to their intricate anatomical and physiological characteristics. Currently, nerve transplantation is an irreplaceable treatment for segmental nerve defects. With the development of emerging technologies, transplantation donors have become more diverse. The present article reviews the traditional and emerging alternative materials aimed at advancing cutting-edge research on craniofacial nerve repair and facilitating the transition from the laboratory to the clinic. It also provides a reference for donor selection for nerve repair after clinical craniofacial soft tissue injuries. We found that autografts are still widely accepted as the first options for segmental nerve defects. However, allogeneic composite functional units have a strong advantage for nerve transplantation for nerve defects accompanied by several tissue damages or loss. As an alternative to autografts, decellularized tissue has attracted increasing attention because of its low immunogenicity. Nerve conduits have been developed from traditional autologous tissue to composite conduits based on various synthetic materials, with developments in tissue engineering technology. Nerve conduits have great potential to replace traditional donors because their structures are more consistent with the physiological microenvironment and show self-regulation performance with improvements in 3D technology. New materials, such as hydrogels and nanomaterials, have attracted increasing attention in the biomedical field. Their biocompatibility and stimuli-responsiveness have been gradually explored by researchers in the regeneration and regulation of neural networks.

Glioma is the most common primary malignant tumor in the central nervous system, and directly affects the quality of life and cognitive function of patients. Ferroptosis, is a new form of regulated cell death characterized by iron-dependent lipid peroxidation. Ferroptosis is mainly due to redox imbalance and involves multiple intracellular biology processes, such as iron metabolism, lipid metabolism, and antioxidants synthesis. Induction of ferroptosis could be a new target for glioma treatment, and ferroptosis-related processes are associated with chemoresistance and radioresistance in glioma. In the present review, we provide the characteristics, key regulators and pathways of ferroptosis and the crosstalk between ferroptosis and other programmed cell death in glioma, we also proposed the application and prospect of ferroptosis in the treatment of glioma.

ABSTRACT Iron is essential to the virulence of Aspergillus species, and restricting iron availability is a critical mechanism of antimicrobial host defense. Macrophages recruited to the site of infection are at the crux of this process, employing multiple intersecting mechanisms to orchestrate iron sequestration from pathogens. To gain an integrated understanding of how this is achieved in aspergillosis, we generated a transcriptomic time series of the response of human monocyte-derived macrophages to Aspergillus and used this and the available literature to construct a mechanistic computational model of iron handling of macrophages during this infection. We found an overwhelming macrophage response beginning 2 to 4 h after exposure to the fungus, which included upregulated transcription of iron import proteins transferrin receptor-1, divalent metal transporter-1, and ZIP family transporters, and downregulated transcription of the iron exporter ferroportin. The computational model, based on a discrete dynamical systems framework, consisted of 21 3-state nodes, and was validated with additional experimental data that were not used in model generation. The model accurately captures the steady state and the trajectories of most of the quantitatively measured nodes. In the experimental data, we surprisingly found that transferrin receptor-1 upregulation preceded the induction of inflammatory cytokines, a feature that deviated from model predictions. Model simulations suggested that direct induction of transferrin receptor-1 (TfR1) after fungal recognition, independent of the iron regulatory protein-labile iron pool (IRP-LIP) system, explains this finding. We anticipate that this model will contribute to a quantitative understanding of iron regulation as a fundamental host defense mechanism during aspergillosis. IMPORTANCE Invasive pulmonary aspergillosis is a major cause of death among immunosuppressed individuals despite the best available therapy. Depriving the pathogen of iron is an essential component of host defense in this infection, but the mechanisms by which the host achieves this are complex. To understand how recruited macrophages mediate iron deprivation during the infection, we developed and validated a mechanistic computational model that integrates the available information in the field. The insights provided by this approach can help in designing iron modulation therapies as anti-fungal treatments.