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Abstract Background Porcine acute diarrhea syndrome coronavirus (SADS-CoV) is one of the novel pathogens responsible for piglet diarrhea, contributing to substantial economic losses in the farming sector. The broad host range of SADS-CoV raises concerns regarding its potential for cross-species transmission. Currently, there are no effective means of preventing or treating SADS-CoV infection, underscoring the urgent need for identifying efficient antiviral drugs. This study focuses on evaluating quercetin as an antiviral agent against SADS-CoV. Results In vitro experiments showed that quercetin inhibited SADS-CoV proliferation in a concentration-dependent manner, targeting the adsorption and replication stages of the viral life cycle. Furthermore, quercetin disrupts the regulation of the P53 gene by the virus and inhibits host cell cycle progression induced by SADS-CoV infection. In vivo experiments revealed that quercetin effectively alleviated the clinical symptoms and intestinal pathological damage caused by SADS-CoV-infected piglets, leading to reduced expression levels of inflammatory factors such as TLR3, IL-6, IL-8, and TNF-α. Conclusions Therefore, this study provides compelling evidence that quercetin has great potential and promising applications for anti- SADS-CoV action.

Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus (PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear, and no antiviral studies have been reported. Therefore, we investigated the pathogenic mechanism and antiviral drugs of PEAV. The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways. In lipid metabolism, steady-state energy processes, which can be mediated by lipid droplets (LDs), are the main functions of organelles. LDs are also important in viral infection and inflammation. In infected cells, PEAV increased LD accumulation, upregulated NF-κB signaling, promoted the production of the inflammatory cytokines IL-1β and IL-8, and induced cell death. Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication. Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV, and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury. These findings contribute new targets for developing treatments for PEAV infections.

Nitrogen (N) fertilization is critical for spike and floret development, which affects the number of fertile florets per spike (NFFs). However, the physiological regulation of the floret development process by N fertilization is largely unknown. A high temporal-resolution investigation of floret primordia number and morphology, dry matter, and N availability was conducted under three N fertilization levels: 0 (N0), 120 (N1) and 240 (N2) kg ha−1. Interestingly, fertile florets at anthesis stage were determined by those floret primordia with meiotic ability at booting stage: meiotic ability was a threshold that predicted whether a floret primordium became fertile or abortive florets. Because the developmental rate of the 4th floret primordium in the central spikelet was accelerated and then they acquired meiotic ability, the NFFs increased gradually as N application increased, but the increase range decreased under N2. There were no differences in spike N concentration among treatments, but leaf N concentration was increased in the N1 and N2 treatments. Correspondingly, dry matter accumulation and N content of the leaf and spike in the N1 and N2 treatments was increased as compared to N0. Clearly, optimal N fertilization increased leaf N availability and transport of assimilates to spikes, and allowed more floret primordia to acquire meiotic ability and become fertile florets, finally increasing NFFs. There was no difference in leaf N concentration between N1 and N2 treatment, whereas soil N concentration at 0–60 cm soil layers was higher in N2 than in N1 treatment, implying that there was still some N fertilization that remained unused. Therefore, improving the leaf’s ability to further use N fertilizer is vital for greater NFFs.

Abstract Background With the increasing frequency of climatic anomalies, high temperatures and long-term rain often occur during the rice-harvesting period, especially for early rice crops in tropical and subtropical regions. Seed dormancy directly affects the resistance to pre-harvest sprouting (PHS). Therefore, in order to increase rice production, it is critical to enhance seed dormancy and avoid yield losses to PHS. The elucidation and utilization of the seed dormancy regulation mechanism is of great significance to rice production. Preliminary results indicated that the OsMKKK62-OsMKK3-OsMPK7/14 module might regulate ABA sensitivity and then control seed dormancy. The detailed mechanism is still unclear. Results The overexpression of OsMKK3 resulted in serious PHS. The expression levels of OsMKK3 and OsMPK7 were upregulated by ABA and GA at germination stage. OsMKK3 and OsMPK7 are both located in the nucleus and cytoplasm. The dormancy level of double knockout mutant mkk3/mft2 was lower than that of mkk3, indicating that OsMFT2 functions in the downstream of MKK3 cascade in regulating rice seeds germination. Biochemical results showed that OsMPK7 interacted with multiple core ABA signaling components according to yeast two-hybrid screening and luciferase complementation experiments, suggesting that MKK3 cascade regulates ABA signaling by modulating the core ABA signaling components. Moreover, the ABA response and ABA responsive genes of mpk7/14 were significantly higher than those of wild-type ZH11 when subjected to ABA treatment. Conclusion MKK3 cascade mediates the negative feedback loop of ABA signal through the interaction between OsMPK7 and core ABA signaling components in rice.

Abstract Background The benefits of combining benzoic acid and essential oils (BAO) to mitigate intestinal impairment during the weaning process have been well established, while the detailed underlying mechanism has not been fully elucidated. Previous research has primarily focused on the reparative effects of BAO on intestinal injury, while neglecting its potential in enhancing intestinal stress resistance. Methods In this study, we investigated the pre-protective effect of BAO against LPS-induced stress using a modified experimental procedure. Piglets were pre-supplemented with BAO for 14 d, followed by a challenge with LPS or saline to collect blood and intestinal samples. Results Our findings demonstrated that BAO supplementation led to significant improvements in piglets' final weight, average daily gain, and feed intake/body gain ratio. Additionally, BAO supplementation positively influenced the composition of intestinal microbiota, increasing beneficial Actinobacteriota and Alloprevotella while reducing harmful Desulfobacterota, Prevotella and Oscillospira. Furthermore, BAO supplementation effectively mitigated oxidative disturbances and inflammatory responses induced by acute LPS challenge. This was evidenced by elevated levels of T-AOC, SOD, and GSH, as well as decreased levels of MDA, TNF-α, and IL-6 in the plasma. Moreover, piglets subjected to LPS challenge and pre-supplemented with BAO exhibited significant improvements in intestinal morphological structure and enhanced integrity, as indicated by restored expression levels of Occludin and Claudin-1 compared to the non-supplemented counterparts. Further analysis revealed that BAO supplementation enhanced the jejunal antioxidative capacity by increasing GSH-Px levels and decreasing MDA levels under the LPS challenge and stimulated the activation of the Nrf2 signaling pathway. Additionally, the reduction of TLR4/NF-κB/MAPK signaling pathways activation and proinflammatory factor were also observed in the jejunal of those piglets fed with BAO. Conclusions In summary, our study demonstrates that pre-supplementation of BAO enhances the anti-stress capacity of weaned piglets by improving intestinal microbiota composition, reinforcing the intestinal barrier, and enhancing antioxidative and anti-inflammatory capabilities. These effects are closely associated with the activation of Nrf2 and TLR4/NF-κB/MAPK signaling pathways.

Abstract Background In December 2022, a large‐scale epidemic occurred in China due to Omicron variant of SARS‐CoV‐2. This study explored risk factors for Omicron infection in transplant recipients at our institution and investigated the factors influencing the severity of SARS‐CoV‐2 Omicron infection among recipients of allo‐HSCT. Methods This single‐center study investigated totally 63 allogeneic hematopoietic stem cell transplant patients infected with Omicron variant at the Beijing GoBroad Boren Hospital Transplant Center during December 2022 and analyzed their risk factors. Results The study included 63 allogeneic hematopoietic stem cell transplant patients who developed Omicron infection. There were 34 mild and 29 moderate to severe cases. Their median age was 22 years (range, 1–65 years), with the male‐to‐female ratio being 1:1.1. Acute myeloid leukemia (53.97%), acute lymphoblastic leukemia (42.86%), and non‐Hodgkin lymphoma (3.17%) were underlying diseases. The median time between HCT and Omicron infection was 8.45 months. Significant predictive factors for moderate to severe Omicron infection included older age (p

Scope: Qi-invigorating herbs have been shown to have a tonic-like effect and to improve the body's immune system function. This study explores how high-dose Ginseng and Astragalus, two representative Qi-invigorating herbs, affect the immunes system of SD rats by regulating their gut microbiota. Method and results: We divided thirteen SD rats randomly into two groups, namely the control group and the Qi-invigorating group (Shenqi). The Shenqi rats received a mixture of Ginseng and Astragalus (Ginseng: 5 mg/kg, Astragalus: 15 mg/kg) for 28 days, once a day. After the treatment, we recorded the blood pressure and the heart rate of the rats. Metabolites of each group were detected via LC-MS, and we conducted gut microbiota profiling via 16 s rRNA sequencing. The blood pressure of the rats in the Shenqi group significantly increased compared with the control group (p

Porcine epidemic diarrhea virus (PEDV) is a highly infectious pathogen that targets pig intestines to cause disease. It is globally widespread and causes huge economic losses to the pig industry. PEDV N protein is the protein that constitutes the core of PEDV virus particles, and most of it is expressed in the cytoplasm, and a small part can also be expressed in the nucleus. However, the role of related proteins in host nucleotide metabolic pathways in regulating PEDV replication have not been fully elucidated. In this study, PEDV-N-labeled antibodies were co-immunoprecipitated and combined with LC-MS to screen for host proteins that interact with N proteins. Bioinformatics analyses showed that the selected host proteins were mainly enriched in metabolic pathways. Moreover, co-immunoprecipitation and confocal microscopy confirmed that the second-largest subunit of RNA polymerase II (RPB2) and uridine phosphorylase 1 (UPP1) interacted with the N protein. RPB2 is the main subunit of RNA polymerase II and plays an important role in eukaryotic transcription. UPP1 is an enzyme that catalyzes reversible phosphorylation of uridine to uracil and ribo-1-phosphate to promote catabolism and bio anabolism. RPB2 overexpression significantly promoted viral replication, whereas UPP1 overexpression significantly inhibited viral replication. Studies on interactions between the PEDV N and host proteins are helpful in elucidating the pathogenesis and immune escape mechanism of PEDV.

ObjectiveSeveral observational studies have shown that high-volume and high-intensity exercise training increases the prevalence and severity of coronary atherosclerosis, but the causal effect still remains uncertain. This study aims to explore the causal relationship between the volume of strenuous exercise (SE) and coronary atherosclerosis (CA) using the Mendelian randomization (MR) method.MethodThe exposure factors were two basic parameters of the volume of strenuous exercise (duration and frequency of strenuous exercise), the outcome factor was coronary atherosclerosis, and the relevant genetic loci were extracted from the summary data of the genome-wide association study (GWAS) as the instrumental variables, and MR analyses were performed using the inverse variance weighting (IVW) method, the weighted median method, and the MR-egger method. Sensitivity analyses were performed using heterogeneity analysis, pleiotropy analysis, and the “leave-one-out” method. The original results were tested using other coronary atherosclerosis data sets.ResultIVW results showed no causal association between duration of strenuous exercise (DOSE) [OR = 0.9937, 95% CI (0.9847, 1.0028), P = 0.1757] and frequency of strenuous exercise (FOSE) in the last 4 weeks [OR = 0.9930, 95% CI (0.9808, 1.0054), P = 0.2660] and coronary atherosclerosis. All of the above results were validated with other coronary atherosclerosis data sets.ConclusionThe present study supports that the causal association of duration and frequency of SE with CA was not found, and provides valuable insights into the choice of scientific and correct volume of SE to cardiac rehabilitation (CR).

Summary: Uropathogenic Escherichia coli (UPEC) is the most common causative agent of urinary tract infection (UTI). UPEC invades bladder epithelial cells (BECs) via fusiform vesicles, escapes into the cytosol, and establishes biofilm-like intracellular bacterial communities (IBCs). Nucleoside-diphosphate kinase (NDK) is secreted by pathogenic bacteria to enhance virulence. However, whether NDK is involved in UPEC pathogenesis remains unclear. Here, we find that the lack of ndk impairs the colonization of UPEC CFT073 in mouse bladders and kidneys owing to the impaired ability of UPEC to form IBCs. Furthermore, we demonstrate that NDK inhibits caspase-1-dependent pyroptosis by consuming extracellular ATP, preventing superficial BEC exfoliation, and promoting IBC formation. UPEC utilizes the reactive oxygen species (ROS) sensor OxyR to indirectly activate the regulator integration host factor, which then directly activates ndk expression in response to intracellular ROS. Here, we reveal a signaling transduction pathway that UPEC employs to inhibit superficial BEC exfoliation, thus facilitating acute UTI.

Objective: To study the improving effect of Eupatilin (Eptl) on ethanol withdrawal (EtOHWI)-induced anxiety-like behavior in rats and probe the mechanisms related to ventral hippocampus (vHippo). Methods: Thirty-two adult male Sprague-Dawley rats were randomly divided into four groups, 8 rats per group: Saline-treated control group, EtOHWI model group, low-dose Eptl treatment group and high-dose Eptl treatment group. The EtOHWI was established by intraperitoneal injection of 3 g/kg of ethanol (20% volume/volume, dissolved in saline) once a day for 28 days followed by 3 days of withdrawal, during the withdrawal period, the low-and the high-dose Eptl treatment groups were respectively given 10 and 30 mg/kg Eptl through oral route once a day, while the saline control group was administered with an equal volume of saline. Thirty minutes after the third Eptl, all the rats were subjected to open filed (OF) and elevated plus maze (EPM) tests to detect anxiety-like behaviors. The serum coritosterone (CORT) concentration and vHippo γ-aminobutyric acid (GABA) secretion were measured by enzyme linked immunosorbent assay (ELISA), and vHippo glutamic acid decarboxylase 67 (GAD 67) mRNA relative expression was assayed by real-time quantitative polymerase chain reaction. The protein expression of GABAa receptor α1 (GABAaRα1), GABAaRα2, nuclear factor E2-related factor 2 (Nrf2), heme oxygense-1 (HO-1) in the vHippo were analyzed by Western blot. The levels of MDA, T-SOD, CAT and GSH, IL-6 and TNF-α were measured by commercial kits. Meanwhile, in the in vitro experiment, the nuclear levels of Nrf2 in HT22 cells were detected via immunofluorescent technique. Results: Compared with the rats in the EtOHWI group, the rats in low and high-dose Eptl treatment groups moving distance increased significantly (P

Abstract Background Insulin resistance (IR) had been reported to be associated with age; however, few studies have explored the association between IR and biological age (BA). The HOMA-IR value is a useful indicator of the extent of IR. This cross-sectional study is to explore the relationship between HOMA-IR and BA/advanced aging in the US population. Methods This study is a cross-sectional analysis of National Health and Nutrition Examination Survey (NHANES) data. The survey comprised 12,266 people from the NHANES, and their full HOMA-IR data as well as BA data were extracted. Four multiple linear regressions were performed to analyze the association between HOMA-IR and BA, and four multiple logistic regression models were performed to analyze the association between HOMA-IR and advanced aging. In addition, trend tests and stratified analysis were performed and smoothed fitted curves were plotted to test the robustness of the results. Results HOMA-IR was positively correlated with BA [β: 0.51 (0.39, 0.63)], and it was the same to advanced aging [OR: 1.05 (1.02, 1.07)], and both showed a monotonically increasing trend. The trend tests showed that the results were stable (all P for trend

As a new type of high-performance material, gradient structural steel is widely used in engineering fields due to its unique microstructure and excellent mechanical properties. For the prevalent fatigue failure problem, the rate of change in the local grain size gradients along the structure (referred to as the gradient rate) is a key parameter in the design of gradient structures, which significantly affects the fatigue performance of gradient structural steel. In this study, a new method of ‘Voronoi primary + secondary modeling’ is adopted to successfully establish three typical high-strength steel models corresponding to the convex-, linear-, and concave-type gradient rates for gradient structures, focusing on the stress–strain response and crack propagation in structural steel with different gradient rates under cyclic loading. It was found that the concave gradient rate structural model is dominated by finer grains with larger volume fraction, which is conducive to hindering fatigue crack propagation and has the longest fatigue life, which is 16.16% longer than that of the linear gradient rate structure and 23.66% longer than that of the convex gradient rate structure. The simulation results in this study are consistent with the relevant experimental phenomena. Therefore, when regulating the gradient rate, priority should be given to increasing the volume fraction of fine grains and designing a gradient rate structure dominated by fine grains to improve the fatigue life of the material. This study presents a new strategy for designing engineering materials with better service performance.

IntroductionPorcine epidemic diarrhea (PED) is an acute, highly contagious, and high-mortality enterophilic infectious disease caused by the porcine epidemic diarrhea virus (PEDV). PEDV is globally endemic and causes substantial economic losses in the swine industry. The PEDV E protein is the smallest structural protein with high expression levels that interacts with the M protein and participates in virus assembly. However, how the host proteins interact with E proteins in PEDV replication remains unknown.MethodsWe identified host proteins that interact with the PEDV E protein using a combination of PEDV E protein-labeled antibody co-immunoprecipitation and tandem liquid-chromatography mass-spectroscopy (LC-MS/MS).ResultsBioinformatical analysis showed that in eukaryotes, ribosome biogenesis, RNA transport, and amino acid biosynthesis represent the three main pathways that are associated with the E protein. The interaction between the E protein and isocitrate dehydrogenase [NAD] β-subunit (NAD-IDH-β), DNA-directed RNA polymerase II subunit RPB9, and mRNA-associated protein MRNP 41 was validated using co-immunoprecipitation and confocal assays. NAD-IDH-β overexpression significantly inhibited viral replication.DiscussionThe antiviral effect of NAD-IDH-β suggesting that the E protein may regulate host metabolism by interacting with NAD-IDH-β, thereby reducing the available energy for viral replication. Elucidating the interaction between the PEDV E protein and host proteins may clarify its role in viral replication. These results provide a theoretical basis for the study of PEDV infection mechanism and antiviral targets.

Abstract The complex pathogenesis of castration-resistant prostate cancer (CRPC) makes it challenging to identify effective treatment methods. Matrix metalloproteinase (MMP)-12 can degrade elastin as well as various extracellular matrix (ECM) components, which is associated with cancer progression. However, the relationship between MMP-12 and CRPC progression is poorly understood. In this study, we observed the effect of MMP-12 on the progression of CRPC and further explored its potential mechanism of action. High levels of MMP-12 were observed in patients with CRPC. We therefore developed cell co-culture and mouse models to study the function of MMP-12. Silencing MMP-12 in CRPC cells disrupted lipid utilization and autophagy marker expression via the CD36/CPT1 and P62/LC3 pathways, respectively, leading to reduced CRPC cell migration and invasion. Moreover, animal experiments confirmed that MMP-12-knockdown CRPC xenograft tumors exhibited reduced tumor growth, and the mechanisms involved the promotion of cancer cell autophagy and the inhibition of lipid catabolism. According to our results, MMP-12 played important roles in the progression of CRPC by disrupting adipocyte maturation and regulating cancer migration and invasion via the modulation of autophagy and lipid catabolism pathways.

IntroductionAfrican swine fever virus (ASFV) is a highly contagious virus that spreads rapidly and has a mortality rate of up to 100% in domestic pigs, leading to significant economic losses in the pig industry. The major capsid protein p72 of ASFV plays a critical role in viral invasion and immune evasion.MethodsIn this study, we used yeast two-hybrid screening to identify host proteins interacting with p72 in porcine alveolar macrophages (PAMs) and verified these proteins using confocal microscopy and immunoprecipitation techniques.Results and DiscussionWe validated 13 proteins that interact with p72, including CD63, B2M, YTHDF2, FTH1, SHFL, CDK5RAP3, VIM, PELO, TIMP2, PHYH, C1QC, CMAS, and ERCC1. Enrichment analysis and protein-protein interaction network analysis of these interacting proteins revealed their involvement in virus attachment, invasion, replication, assembly, and immune regulation. These findings provide new insights into the function of p72 and valuable information for future research on the interaction between ASFV and host proteins.

A thorough understanding of the degradation of chemical biomarkers in wastewater after the sampling is critical in the surveillance of illicit drug use based on the back-calculation technique. Herein, three temperatures, eight groups of matrices, and acidification were applied to simulate the preservation condition of 21 illicit drugs, their metabolites, and cotinine for a 240-day stability study. It was proved that the temperature, matrices, and acidification play vital roles in their stability in wastewater. Most of them demonstrated high stability (transformation rates < 20%) during room temperature for 45 days, and the transformation rates decreased while the storage temperature reduced. The stability of the target compounds such as cocaine (COC), 6-monoacetylmorphine (6-MAM), and amphetamine (AM) is influenced by matrices. Acidification prevented the majority of analytes from transforming, making it a feasible solution for preservation after sampling. A model that combined the effects of temperature and matrix was developed to back-calculate the concentration of target compounds during the postsampling process. The feasibility of this model was validated by correcting the loss of COC and 6-MAM from 24.2% and 16.2% to 2.98% and 2.77%. This study simulated a typical large-scale sampling and storage scenario. The effect of the temperature, pH, and matrix on in-sample stability and the postsampling analysis of selected target compounds was investigated for the first time in this study.

The performance of lithium-ion batteries declines rapidly over time, inducing anxiety in their usage. Ascertaining the capacity of these batteries is difficult to measure directly during online remaining useful life (RUL) prediction, and a single deep learning model falls short of accuracy and applicability in RUL predictive analysis. Hence, this study proposes a lithium-ion battery RUL indirect prediction model, fusing convolutional neural networks and bidirectional gated recurrent units (CNN-BiGRU). The analysis of characteristic parameters of battery life status reveals the selection of pressure discharge time, average discharge voltage and average temperature as health factors of lithium-ion batteries. Following this, a CNN-BiGRU model for lithium-ion battery RUL indirect prediction is established, and the Tree-structured Parzen Estimator (TPE) adaptive hyperparameter optimization method is used for CNN-BiGRU model hyperparameter optimization. Overall, comparison experiments on single-model and other fusion models demonstrate our proposed model's superiority in the prediction of RUL in terms of stability and accuracy.

High-speed trains (HSTs) positioning is a critical technology that affects the safety and operational efficiency of trains. The unique operating environment of HSTs, coupled with the limitations of real data collection, poses challenges in obtaining large-scale and diverse positioning data. To tackle this problem, we introduce a comprehensive method for generating virtual position data for HSTs. Utilizing virtual simulation technology and expert expertise, this method constructs a HST operating simulation environment on the Unity 3D platform, effectively simulating a range of operating scenarios and complex scenes. Positioning data is collected using virtual sensors, while error characteristics are incorporated to emulate real data collection behavior. The contribution of this paper lies in providing abundant, reliable, controllable and diverse positioning data for HSTs, thereby offering novel insights and data support for the evaluation and optimization of positioning algorithms. This method is not only applicable to various routes and scenarios, but also delivers fresh perspectives on data generation for research in other domains, boasting a broad scope of application.

Abstract African swine fever (ASF) is an acute infectious haemorrhagic fever of pigs caused by African swine fever virus (ASFV). Aloe-emodin (Ae) is an active ingredient of Chinese herbs with antiviral, anticancer, and anti-inflammatory effects. We investigated the antiviral activity and mechanism of action of Ae against ASFV using Real-time quantitative PCR (qPCR), western blotting, and indirect immunofluorescence assays. Ae significantly inhibited ASFV replication. Furthermore, transcriptomic analysis revealed that ASFV infection activated the NF-κB signaling pathway in the early stage and the apoptosis pathway in the late stage. Ae significantly downregulated the expression levels of MyD88, phosphor-NF-κB p65, and pIκB proteins as well as the mRNA levels of IL-1β and IL-8 in porcine alveolar macrophages (PAMs) infected with ASFV, thereby inhibiting the activation of the NF-κB signaling pathway induced by ASFV. Flow cytometry and western blot analysis revealed that Ae significantly increased the percentage of ASFV-induced apoptotic cells. Additionally, Ae promoted apoptosis by upregulating the expression levels of cleaved-caspase3 and Bax proteins and downregulating the expression levels of Bcl-2 proteins. This suggests that Ae promotes apoptosis by inhibiting the NF-κB pathway, resulting in inhibition of ASFV replication. These findings have further improved therapeutic reserves for the prevention and treatment of ASF.

Disabled older adults exhibited a higher risk for cognitive impairment. Early identification is crucial in alleviating the disease burden. This study aims to develop and validate a prediction model for identifying cognitive impairment among disabled older adults. A total of 2138, 501, and 746 participants were included in the development set and two external validation sets. Logistic regression, support vector machine, random forest, and XGBoost were introduced to develop the prediction model. A nomogram was further established to demonstrate the prediction model directly and vividly. Logistic regression exhibited better predictive performance on the test set with an area under the curve of 0.875. It maintained a high level of precision (0.808), specification (0.788), sensitivity (0.770), and F1-score (0.788) compared with the machine learning models. We further simplified and established a nomogram based on the logistic regression, comprising five variables: age, daily living activities, instrumental activity of daily living, hearing impairment, and visual impairment. The areas under the curve of the nomogram were 0.871, 0.825, and 0.863 in the internal and two external validation sets, respectively. This nomogram effectively identifies the risk of cognitive impairment in disabled older adults.

In this Comment, we point out that statements made in the paper ‘Computing the Closest Approach Distance of Two Ellipsoids’ by Min Gyu Choi are incorrect and misleading. We provide the needed corrections and suggest an explanation for the observations which gave rise to the incorrect claims.

Porcine epidemic diarrhea (PED) is an enterophilic infectious disease caused by the porcine epidemic diarrhea virus (PEDV), which can lead to dehydration-like diarrhea in piglets with a mortality rate of up to 100%, causing huge economic losses to the global pig industry. In this study, we isolated two PEDV strains, FS202201 and JY202201, from diarrheal samples collected from two new PED outbreak farms in 2022. We performed phylogenetic analysis of the S gene and whole gene sequence. The effects of the different mutations on viral pathogenicity were investigated using piglet challenge experiments. The results showed that both strains belong to the G2c subtype, a widely prevalent virulent strain. Compared with FS202201, JY202201 harbored substitution and deletion mutations in nsp1. Both FS202201 and JY202201 infected piglets showed severe diarrhea and significant intestinal tissue lesions at an infection dose of 104 TCID50/mL, with a mortality rate of 50%; however, JY202201 required an additional day to reach mortality stabilization. An infection dose of 103 TCID50/mL reduced diarrhea and intestinal tissue lesions in piglets, with mortality rates of the two strains at 16.7% and 0%, respectively. In addition, PEDV was detected in the heart, liver, spleen, lungs, kidneys, mesenteric lymph nodes, stomach, large intestine, duodenum, jejunum, and ileum, with the highest levels in the intestinal tissues. In conclusion, this study enriches the epidemiology of PEDV and provides a theoretical basis for the study of its pathogenic mechanism and prevention through virus isolation, identification, and pathogenicity research on newly identified PED in the main transmission hub area of PEDV in China (Guangdong).

The performance of lithium-ion batteries will decline dramatically with the increase in usage time, which will cause anxiety in using lithium-ion batteries. Some data-driven models have been employed to predict the remaining useful life (RUL) model of lithium-ion batteries. However, there are limitations to the accuracy and applicability of traditional machine learning models or just a single deep learning model. This paper presents a fusion model based on convolutional neural network (CNN) and long short-term memory network (LSTM), named CNN-LSTM, to measure the RUL of lithium-ion batteries. Firstly, this model uses the grey relational analysis to extract the main features affecting the RUL as the health index (HI) of the battery. In addition, the fusion model can capture the non-linear characteristics and time-space relationships well, which helps find the capacity decay and failure threshold of lithium-ion batteries. The experimental results show that: 1) Traditional machine learning is less effective than LSTM. 2) The CNN-LSTM fusion model is superior to the single LSTM model in predicting performance. 3) The proposed model is superior to other comparable models in error indexes, which could reach 0.36% and 0.38e-4 in mean absolute percentage error (MAPE) and mean square error (MSE), respectively. 4) The proposed model can accurately find the failure threshold and the decay fluctuation for the lithium-ion battery.

Highlights An efficient and general strategy for ultrafast synthesis of seven transition metal layered hydroxides on conductive substrates is proposed, which avoids the use of additional reagents, multiple steps and long production time in the traditional bottom-up method. The whole synthesis process only takes as fast as approximately 13 s, and its synthesis rate reaches ~ 0.46 cm2 s−1. The NiCo LDH@CC as a demonstration example is selected as cathode material for aqueous alkaline Zn (micro-) battery, which exhibits an outstanding performance.

The finite element method has been widely used in property simulations and the design of cemented carbides, but most of the simulations have focused on individual properties of the alloy, and few studies were done on multiple properties to explore the micromechanical properties simultaneously. In this work, a finite element model is established based on the real microstructure from scanning electron microscopy images of cemented carbide, and elastoplastic properties are imparted to both WC and Co phases. The residual thermal stress, fracture toughness, and hardness of WC-10 wt.%Co cemented carbide were subject to different external stresses. The average normal stresses of the WC and Co phases obtained by the residual thermal stress simulation are −170 and 920 MPa at 25 °C, respectively. The crack initiation and propagation due to the fracture toughness model tend to concentrate on the WC/WC boundary where the stress is concentrated. The alloy hardness (HV30) calculated from the load-displacement curve is 1850. These simulation results are in good agreement with the experimental results, which proves the feasibility of the models. The present work provides a simulation basis for further exploring the relationship between the microstructure and mechanical properties of cemented carbide and optimizing several mechanical properties simultaneously.

Abstract Background Intrauterine growth restriction (IUGR) is a major inducer of higher morbidity and mortality in the pig industry and catch-up growth (CUG) before weanling could significantly restore this negative influence. But there was limited knowledge about the underlying mechanism of CUG occurrence. Methods Eighty litters of newborn piglets were divided into normal birth weight (NBW) and IUGR groups according to birth weight. At 26 d, those piglets with IUGR but over average body weight of eighty litters of weaned piglets were considered as CUG, and the piglets with IUGR still below average body weight were considered as NCUG. This study was conducted to systemically compare the intestinal difference among NBW, CUG and NCUG weaned piglets considering the crucial role of the intestine for piglet growth. Results The results indicated that the mRNA expression of nutrients (amino acids, glucose, and fatty acids) transporters, and mitochondrial electron transport chain (ETC) I were upregulated in CUG piglets’ gut with improved morphology compared with those NCUG, as well as the ratio of P-AMPK/AMPK protein expression which is the indicator of energy metabolism. Meanwhile, CUG piglet’s gut showed higher antioxidative capacity with increased SOD and GSH-Px activity, decreased MDA levels, as well as higher mRNA expressions of Nrf2, Keap1, SOD, and GSH-Px. Furthermore, inflammatory parameters including TNF-α, IL-1β, IL-6, and IL-12 factors, and the activation of MAPK and NF-κB signaling pathways were significantly elevated in the NCUG intestine, while the protein expression of ZO-1, Occludin and Claudin-1 was reduced. The alpha diversity of fecal microbiota was higher in CUG piglets in contrast with NCUG piglets, and the increased beneficial bacteria and decreased pathogenic bacteria was also observed in CUG piglets. Conclusions CUG piglet’s intestine showed comprehensive restoration including higher nutrients transport, energy metabolism, antioxidant capacity, and intestinal physical barrier, while lower oxidative stress, inflammatory response, and pathogenic microbiota.

Abstract Background Our previous study identified miR-99a as a negative regulator of early chondrogenic differentiation. However, the functional role of miR-99a in the pathogenesis of osteoarthritis (OA) remains unclear. Methods We examined the levels of miR-99a and Frizzled 8 (FZD8) expression in tissue specimens. Human SW1353 chondrosarcoma cells were stimulated with IL-6 and TNF-α to construct an in vitro OA environment. A luciferase reporter assay was performed to analyze the relationship between miR-99a and FZD8. CCK-8 assays, flow cytometry, and ELISA assays were used to assess cell viability, apoptosis, and inflammatory molecule expression, respectively. Percutaneous intra-spinal injections of papain mixed solution were performed to create an OA Sprague–Dawley rat model. Alcian Blue staining, Safranin O Fast Green staining, and Toluidine Blue O staining were performed to detect the degrees of cartilage injury. Results MiR-99a expression was downregulated in the severe spine OA patients when compared with the mild spine OA patients, and was also decreased in the experimentally induced in vitro OA environment when compared with the control environment. Functionally, overexpression of miR-99a significantly suppressed cell apoptosis and extracellular matrix degradation stimulated by IL-6 and TNF-α. FZD8 was identified as a target gene of miR-99a. Furthermore, the suppressive effects of miR-99a on cell injury induced by IL-6 and TNF-α were reversed by FZD8 overexpression. Moreover, the levels of miR-99a expression were also reduced in the induced OA model rats, and miR-99a agomir injection relieved the cartilage damage. At the molecular level, miR-99a overexpression downregulated the levels of MMP13, β-catenin, Bax, and caspase-3 protein expression and upregulated the levels of COL2A1 and Bcl-2 protein expression in the in vitro OA-like chondrocyte model and also in the experimental OA model rats. Conclusions Our data showed that miR-99a alleviated apoptosis and extracellular matrix degradation by targeting FZD8, and thereby suppressed the development and progression of experimentally induced spine osteoarthritis.

BackgroundSeveral clinical trials of corticosteroids have been carried out in the treatment of septic shock, however, the therapeutic effect of the most widely used hydrocortisone is still controversial, and no studies have directly compared hydrocortisone versus hydrocortisone plus fludrocortisone for patients with septic shock.MethodsBaseline characteristics and treatment regimens of patients with septic shock treated with hydrocortisone from the Medical Information Mart for Intensive Care-IV database were collected. Patients were divided into hydrocortisone treatment groups and hydrocortisone plus fludrocortisone treatment groups. The primary outcome was 90-day mortality, and secondary outcomes included 28-day mortality, in-hospital mortality, length of hospital stay, and length of intensive care unit (ICU) stay. Binomial Logistic regression analysis was performed to identify independent risk factors for mortality. Survival analysis was performed and Kaplan–Meier curves were drawn for patients in different treatment groups. Propensity score matching (PSM) analysis was performed to reduce bias.ResultsSix hundred and fifty three patients were enrolled, of which 583 were treated with hydrocortisone alone, and 70 with hydrocortisone plus fludrocortisone. After PSM, 70 patients were included in each group. The proportion of patients with acute kidney injury (AKI) and the proportion of renal replacement therapy (RRT) treatment in the hydrocortisone plus fludrocortisone group were higher than those in the hydrocortisone alone group, and there was no significant difference in other baseline characteristics. Compared with hydrocortisone alone, hydrocortisone plus fludrocortisone did not reduce the 90-day mortality (after PSM, relative risk/RR = 1.07, 95%CI 0.75–1.51), 28-day mortality (after PSM, RR = 0.82, 95%CI 0.59–1.14) and in-hospital mortality (after PSM, RR = 0.79, 95%CI 0.57–1.11) of the enrolled patients, nor did it affect the length of hospital stay (after PSM, 13.9 days vs. 10.9 days, p = 0.34) and ICU stay (after PSM, 6.0 days vs. 3.7 days, p = 0.14), and the survival analysis showed no statistically significant difference in the corresponding survival time. After PSM, binomial Logistic regression analysis showed that SAPS II score was an independent risk factor for 28-day morality (OR = 1.04, 95%CI 1.02–1.06, p

Cleft palate (CP) is a common congenital birth defect. Cellular and morphological processes change dynamically during palatogenesis, and any disturbance in this process could result in CP. However, the molecular mechanisms steering this fundamental phase remain unclear. One study suggesting a role for miRNAs in palate development via maternal small extracellular vesicles (SEVs) drew our attention to their potential involvement in palatogenesis. In this study, we used an in vitro model to determine how SEVs derived from amniotic fluid (ASVs) and maternal plasma (MSVs) influence the biological behaviors of mouse embryonic palatal mesenchyme (MEPM) cells and medial edge epithelial (MEE) cells; we also compared time-dependent differential expression (DE) miRNAs in ASVs and MSVs with the DE mRNAs in palate tissue from E13.5 to E15.5 to study the dynamic co-regulation of miRNAs and mRNAs during palatogenesis in vivo. Our results demonstrate that some pivotal biological activities, such as MEPM proliferation, migration, osteogenesis, and MEE apoptosis, might be directed, in part, by stage-specific MSVs and ASVs. We further identified interconnected networks and key miRNAs such as miR-744-5p, miR-323-5p, and miR-3102-5p, offering a roadmap for mechanistic investigations and the identification of early CP biomarkers.

Precipitates are the primary source of strength for the Al-Mg-Si alloy. Aluminum alloy in the peak-aged state mainly contains β” and β’ precipitates. Most of the literature has only considered the strengthening effect of β”. Here, we develop a single-crystal intensity model including both precipitate enhancement effects for the first time. This model was subsequently implemented into a crystal plastic finite-element method to model the uniaxial tensile process of a polycrystalline aggregate model of Al-Mg-Si alloy. The simulation results for uniaxial stretching are in good agreement with the experimental results, confirming that the constitutive parameters used for the single-crystal strength model with two precipitates are based on realistic physical implications. Furthermore, by comparing the uniaxial tensile simulation results of a peak-aged alloy considering the actual precipitated phase composition of the alloy with those assuming that the precipitated phase is only the β” phase, the predicted tensile strength of the former is around 5.65% lower than that of the latter, suggesting that the two kinds of precipitation should be separately considered when simulating the mechanical response of Al-Mg-Si alloy. It is highly expected that the present simulation strategy is not limited to Al-Mg-Si alloys, and it can be equally applied to the other age-enhanced alloys.

BackgroundPatients with refractory/relapsed (r/r) acute B lymphocytic leukemia (B-ALL) can achieve complete response (CR) after chimeric antigen receptor T-cell (CAR-T) therapy, but recurrence occurs in the short term. To reduce recurrence and improve survival, CAR-T therapy followed by transplantation is a feasible option. We analyzed the long-term follow-up outcomes and the risk factors for allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR by CAR-T therapy in this study.MethodsA total of 144 patients who underwent allo-HSCT after CAR-T therapy in our hospital were enrolled in this study. Target gene analysis was performed in 137 r/r B-ALL patients receiving allo-HSCT after CR by CAR-T therapy. Among the 137 patients, 87 were evaluated for germline predisposition gene mutations, and 92 were evaluated for tumor somatic gene mutations using NGS. The clinical factors, germline predisposition gene and somatic gene mutations associated with the prognosis of patients receiving transplantation after CAR-T therapy were analyzed using univariate Cox regression. Factors related to disease-free survival (DFS) and overall survival (OS) were analyzed using multivariate Cox regression analysis.ResultsIn 137 r/r B-ALL patients, the 2-year cumulative incidence of recurrence (CIR), OS and DFS in patients receiving allo-HSCT after CAR-T therapy was 31.5%, 71.4%, and 60.5%, respectively. The 2-year OS and DFS in MRD-negative patients were 80.9% and 69.3%, respectively. Univariate Cox analysis showed that pretransplant MRD positivity, fungal infection, germline EP300 mutation and somatic TP53 mutation were associated with a poor prognosis after transplantation; a TBI-based regimen was a protective factor for survival and recurrence after transplantation. Multivariate Cox regression analysis showed that the TBI-based regimen was an independent protective factor for DFS, fungal infection and MRD positivity were independent risk factors for DFS, and tumor somatic TP53 mutation and germline EP300 mutation were independent risk factors for DFS and OS.ConclusionGermline EP300 mutation and tumor somatic TP53 mutation are poor prognostic factors for posttransplant recurrence and survival in r/r B-ALL patients achieving CR after CAR-T therapy. The prognostic risk factors should be considered in adjusting treatment strategies to improve the efficacy of clinical diagnosis and treatment.

Built-up area change detection (CD) plays an important role in city management, which always uses very high spatial resolution (VHR) remote sensing data to extract refined spatial information. Recently, many CD models based on deep learning with VHR data have been proposed. However, due to the complex background information and natural landscape changes, VHR with optical RGB features is hard to extract changes exactly. To this end, we tend to explore the abundant channel information of multispectral and SAR data as a supplement to the refined spatial features of VHR images. We propose a new deep learning framework called multisource CD UNet++ (MSCDUNet), integrating multispectral, SAR, and VHR data for built-up area CD. First, we label and reform two new built-up area CD datasets containing multispectral, SAR, and VHR data: multisource built-up change (MSBC) and multisource OSCD (MSOSCD) datasets. Second, a feature selection method based on random forest is introduced to choose effective features from multispectral and SAR images. Finally, a multilevel heterogeneous feature fusion module is embedded in MSCDUNet to combine multifeatures for CD. Experiments are conducted on both the MSOSCD and the MSBC datasets. Compared to other CD methods based on VHR images, our proposal achieves the highest accuracy on both datasets and proves the effectiveness of multispectral, SAR, and VHR data fusion for CD. The dataset in the article will be available for download from the following link.1

Floral organ development determines agricultural productivity by affecting seed development, seed quality, and final yield. In this study, we described the novel ogl mutant in rice (Oryza sativa L.), which is characterized by an open-glume phenotype, increased pistil number, reduced stamen number, decreased seed setting rate, and smaller rice grains. Genetic analysis showed that the open-glume phenotype might be controlled by a recessive qualitative trait locus. Employing bulked segregant analysis (BSA), one candidate region was identified on rice chromosome 1. The glume opening phenotype cosegregated with SNP (Chr1:1522703), which was located at the start codon of one transcript of OsJAG, resulting in partial loss of OsJAG function. cDNA analysis revealed that OsJAG encodes two transcript variants. Compared to normal plants, the expression of OsJAG.1 was upregulated in open-glume plants. When investigating the glume phenotype, we found that the expression of genes related to floral development changed greatly in open-glume plants. Taken together, this work increases our understanding of the developmental role of OsJAG in rice floral development.

Many processes take place during embryogenesis, and the development of the palate mainly involves proliferation, migration, osteogenesis, and epithelial–mesenchymal transition. Abnormalities in any of these processes can be the cause of cleft palate (CP). There have been few reports on whether C-X-C motif chemokine receptor 4 (CXCR4), which is involved in embryonic development, participates in these processes. In our study, the knockdown of Cxcr4 inhibited the migration of mouse embryonic palatal mesenchymal (MEPM) cells similarly to the use of its inhibitor plerixafor, and the inhibition of cell migration in the Cxcr4 knockdown group was partially reversed by supplementation with C-X-C motif chemokine ligand 12 (CXCL12). In combination with low-dose retinoic acid (RA), plerixafor increased the incidence of cleft palates in mice by decreasing the expression of Cxcr4 and its downstream migration-regulating gene Rac family small GTPase 1 (RAC1) mediating actin cytoskeleton to affect lamellipodia formation and focal complex assembly and ras homolog family member A (RHOA) regulating the actin cytoskeleton to affect stress fiber formation and focal complex maturation into focal adhesions. Our results indicate that the disruption of cell migration and impaired normal palatal development by inhibition of Cxcr4 expression might be mediated through Rac1 with RhoA. The combination of retinoic acid and plerixafor might increase the incidence of cleft palate, which also provided a rationale to guide the use of the drug during conception.

Chromatin structure plays a fundamental role in regulating gene expression, with histone modifiers shaping the structure of chromatin by adding or removing chemical changes to histone proteins. The p53 transcription factor controls gene expression, binds target genes, and regulates their activity. While p53 has been extensively studied in cancer research, specifically in relation to fundamental cellular processes, including gene transcription, apoptosis, and cell cycle progression, its association with histone modifiers has received limited attention. This review explores the interplay between histone modifiers and p53 in regulating gene expression. We discuss how histone modifications can influence how p53 binds to target genes and how this interplay can be disrupted in cancer cells. This review provides insights into the complex mechanisms underlying gene regulation and their implications for potential cancer therapy.

Abstract Background Early and timely fluid treatment or resuscitation are the basic measures for the active treatment of sepsis. Our aim is to further explore the relationship between fluid balance and prognosis in patients with sepsis on a daily basis for 5 days. Methods Sepsis patients in eICU Collaborative Research Database were divided into the negative balance group (NB/−) and the positive balance group (PB/+) according to daily fluid balance. The primary outcome was in-hospital mortality. Survival differences between the groups were analyzed by using Cox regression. Then dose-response relationship between fluid balance and in-hospital mortality was studied using restricted cubic splines (RCSs). Furthermore, patients with fluid balance data for the previous three consecutive days were selected and divided into eight groups (“+/+/+”, “+/+/−”, “+/ −/−”, “+/ −/+”, “−/ −/−”, “−/ −/+”, “−/+/+”, and “−/+/−”). Kaplan–Meier curves and Cox regression were used to show the survival difference between groups. Results Our study, which included 19,557 patients in a multicenter database, showed that positive fluid balances on days 1, 2, and 3 after sepsis diagnosis were associated with poor prognosis with the HRs of 1.29 (1.20,1.40), 1.13 (1.01,1.27), and 1.25 (1.08,1.44), respectively, while the fluid balance on days 4 and 5 had no effect on the primary outcome. Then RCSs showed an overall trend that the risk of in-hospital mortality on days 1, 2, and 3 increased with increasing fluid balance. For three consecutive days of fluid balance, we studied 9205 patients and Kaplan–Meier curves revealed survival differences among patients in the eight groups. The cox model demonstrated that compared with the “+/+/+” group, the “+/ −/−”, “−/ −/−”, “−/ −/+”, “−/+/+”, and “−/+/−” groups had a lower risk of in-hospital mortality, with HRs of 0.65 (0.45,0.93), 0.72 (0.60,0.86), 0.63 (0.43,0.93), 0.69 (0.48,0.98), and 0.63 (0.42,0.96), respectively. Conclusions In patients with sepsis, positive fluid balance on days 1, 2, and 3 was associated with adverse outcomes. For patients with fluid balance for three consecutive days, the “+/−/−”, “−/ −/−”, “−/−/+”, “−/+/+”, and “−/+/−” groups were less likely to die in hospital than the “+/+/+” group.

Abstract Background Granulomatous capillary haemangioma refers to a benign vascular tumour that commonly affects the skin, with occasional involvement of the mucosa. Reports of conjunctival granulomatous capillary haemangioma in children are uncommon. In this article, we present a case of granulomatous capillary haemangioma and a brief review of the relevant literature. Case presentation An 11-year-old girl presented with a conjunctival mass. An excision of the entire lesion was performed. Histopathology showed a granulomatous capillary haemangioma. Conclusions The clinical manifestations of granulomatous capillary haemangioma lack specificity; pathological characteristics and immunohistochemistry are the main basis for diagnosis. We retrospectively analysed the diagnosis and treatment of a patient with conjunctival granulomatous capillary haemangioma to deepen the understanding and facilitate the diagnosis and treatment of this disease.

BackgroundBlood-derived exosomes are involved in developing multiple pathological processes, with platelets being the most well-known source. Related studies have become an area of research with significant value and potential. However, no bibliometric studies in this field have yet been identified. We aimed to analyze the hotspots and academic trends of platelet exosome research through bibliometric visualization to actively grasp the research base in this field and track its developmental orientation.MethodsFrom 2000 to 2022, we screened all relevant publications on platelet exosome-related research from the Web of Science database, generated knowledge maps using VOSviewer and CiteSpace software, and analyzed research trends in the field.ResultsA total of 722 articles were screened for inclusion based on the search strategy. The number of articles on exosome studies in platelets has expanded vastly. The USA and the People’s Republic of China contributed substantially among 69 countries or regions. Amsterdam University and Semmelweis University are the research institutions with the most publications. The most studied and co-cited journals were the International Journal of Molecular Sciences and the Journal of Extracellular Vesicles. We identified 4,598 authors, with Nieuwland Rienk having the highest number of articles and Bruno Stefania having the most cited publications. Keywords of great interest include “thrombosis,” “anti-inflammatory,” “anti-apoptosis,” “angiogenesis,” “microparticles,” “miRNAs,” “stem cells,” and “biomarkers,” which are key research areas for future development.ConclusionWe used bibliometric and visualization methods to identify hotspots and trends in platelet exosome research. Platelet exosome research is widely expanding. Future research will most likely focus on “thrombosis,” “anti-inflammatory,” “anti-apoptosis,” “angiogenesis,” “microparticles,” “miRNAs,” “stem cells,” and “biomarkers.”

BackgroundConventional systemic inflammatory biomarkers could predict prognosis in patients with ischemic stroke (IS) admitted to the intensive care unit (ICU). Acute kidney injury (AKI) is common in patients with IS admitted to ICU, but few studies have used systemic inflammatory biomarkers to predict AKI in critically ill patients with IS. This study aimed to establish a risk model based on white blood cell (WBC)-related biomarkers to predict AKI in critically ill patients with IS.MethodsData were extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) for a training cohort, and data were extracted from the Medical Information Mart for eICU Collaborative Research Database (eICU-CRD) for a validation cohort. Logistic regression analysis was used to determine the significant predictors of WBC-related biomarkers on AKI prediction, and a risk model was established based on those significant indicators in multivariate logistic regression. The receiver operating characteristics (ROC) curve was utilized to obtain the best cut-off value of the risk model. The Kaplan–Meier curve was used to evaluate the prognosis-predictive ability of the risk model.ResultsThe overall incidence of AKI was 28.4% in the training cohort and 33.2% in the validation cohort. WBC to lymphocyte ratio (WLR), WBC to basophils ratio (WBR), WBC to hemoglobin ratio (WHR), and neutrophil to lymphocyte ratio (NLR) could independently predict AKI, and a novel risk model was established based on WLR, WBR, WHR, and NLR. This risk model depicted good prediction performance both in AKI and other clinical outcomes including hemorrhage, persistent AKI, AKI progression, ICU mortality, and in-hospital mortality both in the training set and in the validation set.ConclusionA risk model based on WBC-related indicators exhibited good AKI prediction performance in critically ill patients with IS which could provide a risk stratification tool for clinicians in the ICU.

BackgroundCoronary care unit (CCU) patients with acute myocardial infarction (AMI) lack effective predictors of in-hospital mortality. This study aimed to investigate the performance of four scoring systems in predicting in-hospital mortality in CCU patients with AMI.MethodsThe baseline data, the logistic organ dysfunction system (LODS), the Oxford acute severity of illness score (OASIS), the simplified acute physiology score II (SAPS II), and the simplified acute physiology score III (SAPS III) scores of the patients were extracted from the fourth edition of the Medical Information Mart for Critical Care (MIMIC-IV) database. Independent risk factors for in-hospital mortality were identified by regression analysis. We performed receiver operating characteristic (ROC) curves and compared the area under the curve (AUC) to clarify the predictive value of the four scoring systems. Meanwhile, Kaplan–Meier curves and decision curve analysis (DCA) were performed to determine the optimal scoring system for predicting in-hospital mortality.ResultsA total of 1,098 patients were included. The SAPS III was an independent risk factor for predicting in-hospital mortality in CCU patients with AMI before and after the propensity score matching (PSM) analysis. The discrimination of in-hospital mortality by SAPS III was superior to that of LODS, OASIS, and SAPS II. The AUC of the SAPS III scoring system was the highest among the four scoring systems, at 0.901 (before PSM) and 0.736 (after PSM). Survival analysis showed that significantly more in-hospital mortality occurred in the high-score SAPS III group compared to the low-score SAPS III group before PSM (HR 7.636, P < 0.001) and after PSM (HR 2.077, P = 0.005). The DCA curve of SAPS III had the greatest benefit score across the largest threshold range compared to the other three scoring systems.ConclusionThe SAPS III was an independent risk factor for predicting in-hospital mortality in CCU patients with AMI. The predictive value for in-hospital mortality with SAPS III is superior to that of LODS, OASIS, and SAPS II. The results of the DCA analysis suggest that SAPS III may provide a better clinical benefit for patients. We demonstrated that SAPS III is an excellent scoring system for predicting in-hospital mortality for CCU patients with AMI.

African swine fever virus (ASFV) is a complex large DNA enveloped virus that causes African swine fever (ASF) with a fatality rate of up to 100%, seriously threatening the global swine industry. Due to the strict cell tropism of ASFV, there is no effective in vitro cell line, which hinders its prevention and control. Herein, we analyzed genome-wide transcriptional profiles of ASFV-susceptible porcine alveolar macrophages (PAMs) and non-susceptible cell lines PK15 and 3D4-21, an found that PAM surface pattern recognition receptors (PRRs) were significantly higher and common differential genes were significantly enriched in phagocytosis compared with that observed in PK15 and 3D4-21 cell lines. Therefore, endocytosis functions of host cell surface PRRs may play key roles in ASFV infection in vitro. ASFV was found to be infective to PK15 and 3D4-21 cell lines overexpressing CD163 and Siglec1, and to the PK15S1-CD163 cell line stably expressing CD163 and Siglec1. However, the PK15 and 3D4-21 cell lines overexpressing CD163 or Siglec1 alone were not infectious. Simultaneous interference of CD163 and Siglec1 in PAMs with small interfering RNA (siRNA) significantly reduced the infectivity of ASFV. However, siRNA interference of CD163 and Siglec1 respectively did not affect ASFV infectivity. ASFV significantly inhibited IFN expression levels in PAMs and PK15S1-CD163 cells, but had no effect on PK15 and 3D4-21 cell lines. These results indicate that CD163 and Siglec1 are key receptors for ASFV-infected host cells, and both play a synergistic role in the process of ASFV infection. ASFV inhibits IFN expression in susceptible cells, thereby downregulating the host immune response and evading the immune mechanism. The discovery of the ASFV receptor provides novel ideas to study ASFV and host cell interactions, pathogenic mechanisms, development of receptor blockers, vaccine design, and disease resistance breeding.

The bacterium Vibrio cholerae can colonize the human intestine and cause cholera, but spends much of its life cycle in seawater. Here, Liu et al. identify a fructose uptake system that is important for the growth of the bacteria in seawater, where fructose concentrations are low.

Comprehensive studies have been conducted to compare the effect of organic and inorganic selenium previously, but there is still limited knowledge about the difference between organic selenium (Se) from varied sources despite the widely use of organic Se in both animal and human being nutrient additives. In the present study, we systemically compared the effect of two different types of organic Se including selenium yeast (SeY) and selenium methionine (Sel-Met) on cell viability, selenoprotein transcriptome, and antioxidant status in porcine mammary epithelial cells (PMECs) and the results indicated that appropriate addition of SeY and Sel-Met both significantly promoted cell viability and up-regulated the mRNA expression of most selenopreoteins including DIOs, GPXs, and TrxRs family et al. (P < 0.05). Besides, two different sources of Se supplementation both greatly improved redox status with higher levels of T-AOC, SOD, and CAT (P < 0.05), while less content of MDA (P < 0.05), and reduced protein expression of cleaved-caspase-3 (P < 0.05) to mitigate cell apoptosis. Furthermore, the key proteins related to p38/JNK pathway including p38, p-p38, JNK, and p-JNK were apparently reduced in the groups with both of SeY and Sel-Met (P < 0.05). Interestingly we found that the changes induced by SeY supplementation in cell viability, selenoprotein transcriptome, antioxidative capacity, and anti-apoptosis were comprehensively greater compared with same levels addition of Sel-Met in PEMCs (P < 0.05). In conclusion, both SeY and Sel-Met promoted cell viability and attenuated cell apoptosis by regulating the selenoprotein expression and antioxidative capacity via p38/JNK signaling pathway in PMEC, but SeY has more efficient benefits than that of Sel-Met.

Many environmental and pathogenic insults induce endoplasmic reticulum (ER) stress in animals, especially in aquatic ecosystems, where these factors are crucial for life. In penaeid shrimp, pathogens and environmental stressors induce hemocyanin expression, but the involvement of hemocyanin in ER stress response is unknown. We demonstrate that in response to pathogenic bacteria (Vibrio parahaemolyticus and Streptococcus iniae), hemocyanin, ER stress proteins (Bip, Xbp1s, and Chop), and sterol regulatory element binding protein (SREBP) are induced to alter fatty acid levels in Penaeus vannamei. Interestingly, hemocyanin interacts with ER stress proteins to modulate SREBP expression, while ER stress inhibition with 4-Phenylbutyric acid or hemocyanin knockdown attenuates the expression of ER stress proteins, SREBP, and fatty acid levels. Contrarily, hemocyanin knockdown followed by tunicamycin treatment (ER stress activator) increased their expression. Thus, hemocyanin mediates ER stress during pathogen challenge, which consequently modulates SREBP to regulate the expression of downstream lipogenic genes and fatty acid levels. Our findings reveal a novel mechanism employed by penaeid shrimp to counteract pathogen-induced ER stress.

In order to reduce the global carbon emission pressure and improve the energy efficiency of the construction industry, this paper establishes the Un-Super-SBM model to measure the total factor energy efficiency of the construction industry in China, which based on the 2012–2019 Chinese provincial panel data with CO _2 emissions as the non-desired output, and uses the panel data model to empirically analyze the impact of formal and informal environmental regulations on the energy efficiency of the construction industry. The results show that, from the national level, the impact of formal environmental regulation on energy efficiency of the construction industry shows an inverted U-shaped trend of promotion followed by inhibition, while the impact of informal environmental regulation on energy efficiency of the construction industry shows a U-shaped trend of inhibition followed by promotion. From the regional level, there are regional differences in the impact of formal and informal environmental regulations on the energy efficiency of the construction industry. Finally, the paper puts forward relevant policy suggestions to promote the improvement of energy utilization efficiency of China’s construction industry and achieve sustainable development.