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Porcine deltacoronavirus (PDCoV) is an emerging pathogen that can cause severe diarrhoea and high mortality in suckling piglets. Moreover, evidence of PDCoV infection in humans has raised concerns regarding potential public health risks. To identify potential therapeutic targets for PDCoV, we performed a genome-wide CRISPR/Cas9 library screening to find key host factors important to PDCoV infection. Several host genes in this screen were enriched, including ANPEP, which encodes the PDCoV receptor aminopeptidase N (APN). Furthermore, we discovered C16orf62, also known as the VPS35 endosomal protein sorting factor like (VPS35L), as an important host factor required for PDCoV infection. C16orf62 is an important component of the multiprotein retriever complex involved in protein recycling in the endosomal compartment and its gene knockout led to a remarkable decrease in the binding and internalization of PDCoV into host cells. While we did not find evidence for direct interaction between C16orf62 and the viral s (spike) protein, C16orf62 gene knockout was shown to downregulate APN expression at the cell surface. This study marks the first instance of a genome-wide CRISPR/Cas9-based screen tailored for PDCoV, revealing C16orf62 as a host factor required for PDCoV replication. These insights may provide promising avenues for the development of antiviral drugs against PDCoV infection.

The pathogens responsible for porcine viral diarrhea are diverse, causing significant economic losses to the pig industry. PEDV and TGEV are well-known pathogens causing diarrheal diseases in pigs, leading to significant economic losses in the breeding industry. In contrast, the newly identified diarrhea virus, PKV, has not garnered as much attention. However, co-infection of PKV with PEDV results in more severe symptoms in piglets, such as acute gastroenteritis, and promotes increased replication of PEDV. Rapid and accurate diagnosis of viral diarrhea is essential for farms to identify pathogens early and mitigate economic losses. This study describes the development of a triplex real-time fluorescent quantitative RT-qPCR technique that can simultaneously detect three RNA viruses associated with porcine viral diarrhea: PEDV, TGEV, and PKV. To establish the triplex RT-qPCR method for the simultaneous detection and identification of the above three diarrhea viruses, conserved regions of the M gene of TGEV, the N gene of PEDV, and the 3D gene of PKV were selected to design specific primers and probes. After optimizing the reaction conditions, the method’s specificity, sensitivity, and reproducibility were evaluated. The triplex RT-qPCR method did not show a significant difference in PCR efficiency compared to the single RT-qPCR method. The method is specific to TGEV, PKV, and PEDV, exhibits no cross-reactivity with other pathogens, and demonstrates satisfactory sensitivity and reproducibility; the limit of detection (LOD) of PEDV, TGEV, and PKV is 11.42 copies/μL. Furthermore, the performance of the triplex RT-qPCR assay was compared with the Chinese standard single-assay method for detecting TGEV, PKV, and PEDV, showing complete consistency between the two methods (100% compliant). Subsequently, 1502 clinical diarrhea samples were collected from the Guangxi Zhuang Autonomous Region to investigate the local prevalence of TGEV, PKV, and PEDV and the positive rates were 16.38% (246/1502), 1.46% (22/1502), and 45.14% (678/1502), respectively. Co-infection of PEDV and PKV were most common, with a rate of 12.12% (182/1502). This study presents a valuable method for the rapid and simultaneous identification of PEDV, TGEV, and PKV in clinical animal farming practices, and provides a reassessment of the epidemiology of these diarrhea-causing viral pathogens in the Guangxi Zhuang Autonomous Region.

Abstract The rapid expansion of large-scale pig farming has brought about a surge in viral diseases with high morbidity rates and diverse manifestations. This widespread occurrence of multiple viral diseases in pig farms has inflicted severe economic losses on the global swine industry. Consequently, there is an urgent need for eco-friendly and efficient antiviral drugs that can effectively combat viruses and prevent diseases such as PEDV, PRRSV, PRV, and other viral infections. To this end, we conducted a study on the antiviral activity and cytotoxicity of eleven different Chinese herbal extracts (CHE) against PRV. In vitro testing of several extracts, namely, Echinacea, Ilex purpurea Hassk, Ganoderma lucidum Kars, Taraxacum mongolicum, and Ilex rotunda Thunb, exhibited remarkable inhibition of PRV infection without causing any cytotoxic effects. Specifically, their antiviral selectivity indexes were significantly higher, with values ranging from 6- to 144-fold. The antiviral efficacy of five CHEs was evaluated against other RNA viruses, including PRRSV and PEDV. The extracts showed substantial inhibition of PEDV and PRRSV proliferation. Echinacea and Ilex purpurea Hassk extracts exhibited the highest virus inhibitory effects. To understand the antiviral mechanisms underlying their potent activity, a time-of-addition experiment was conducted. The results indicated that these extracts effectively targeted the early infection and postinfection stages of PRV, PEDV, and PRRSV. The study found that the Chinese herbal extracts, Echinacea and Ilex purpurea Hassk, had both direct and indirect effects on virus particles and cellular targets, demonstrating broad-spectrum antiviral activity against multiple clinical strains of PRV and PEDV. These findings provide a strong foundation for the development of herbal medicines to prevent and treat infections caused by PRV, PEDV and PRRSV in the swine industry. The identified extracts show great promise for the formulation of effective and environmentally friendly antiviral interventions. Graphical Abstract

Abstract Aim To explore the physical and mental health status of community residents and to identify the risk factors of chronic diseases. Design A cross‐sectional, descriptive correlational study was conducted. Methods A total of 579 participants were recruited from 15 communities in Tianjin. The demographic information sheet, 7‐item Generalized Anxiety Disorder scale (GAD‐7) and Patient Health Questionnaire (PHQ‐9) were used. Data collection was undertaken based on the health management system on mobile phones from April to May 2019. Results Eighty‐four participants of the total number of surveyed were with chronic disease. The incidence of depression and anxiety in participants was 44.2% and 41.3%. Logistic regression analysis showed that age (OR = 4.905, 95%CI: 2.619–9.187), religious belief (OR = 0.445, 95%CI: 1.510–11.181) and working condition (OR = 0.161, 95%CI: 0.299–0.664) entered the regression equation. Old age is a risk factor for chronic diseases. No religious belief and working condition are protective factors for chronic diseases.

Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus (CoV) that mainly causes acute diarrhea/vomiting, dehydration, and mortality in piglets, possessing economic losses and public health concerns. However, there are currently no proven effective antiviral agents against PDCoV. Cepharanthine (CEP) is a naturally occurring alkaloid used as a traditional remedy for radiation-induced symptoms, but its underlying mechanism of CEP against PDCoV has remained elusive. The aim of this study was to investigate the anti-PDCoV effects and mechanisms of CEP in LLC-PK1 cells. The results showed that the antiviral activity of CEP was based on direct action on cells, preventing the virus from attaching to host cells and virus replication. Importantly, Surface Plasmon Resonance (SPR) results showed that CEP has a moderate affinity to PDCoV receptor, porcine aminopeptidase N (pAPN) protein. AutoDock predicted that CEP can form hydrogen bonds with amino acid residues (R740, N783, and R790) in the binding regions of PDCoV and pAPN. In addition, RT-PCR results showed that CEP treatment could significantly reduce the transcription of ZBP1, cytokine (IL-1β and IFN-α) and chemokine genes (CCL-2, CCL-4, CCL-5, CXCL-2, CXCL-8, and CXCL-10) induced by PDCoV. Western blot analysis revealed that CEP could inhibit viral replication by inducing autophagy. In conclusion, our results suggest that the anti-PDCoV activity of CEP is not only relies on competing the virus binding with pAPN, but also affects the proliferation of the virus in vitro by downregulating the excessive immune response caused by the virus and inducing autophagy. CEP emerges as a promising candidate for potential anti-PDCoV therapeutic development.

Objective To determine the relationship of napping with incident diabetes risk and glycaemic control in people with diabetes.Design Systematic review and meta-analysis.Data sources MEDLINE (PubMed), EMBASE, Web of Science and the Cochrane Library were searched for studies published from database inception to 9 May 2023.Eligibility criteria Observational studies reporting the relationship of napping with diabetes or glycaemic control in patients with diabetes in adult populations were included.Data extraction and synthesis Two reviewers independently screened the literature, extracted data and assessed the quality of the included studies. The results were reported as ORs and 95% CIs, which were pooled by using fixed and random effects models, and subgroup analyses were performed. The Grading of Recommendations Assessment, Development and Evaluation method was used to assess the quality of the evidence.Results Forty studies were included in our review. Habitual napping was associated with an increased diabetes risk (OR 1.20, 95% CI 1.14 to 1.27) and poor glycaemic control in patients with diabetes (OR 2.05, 95% CI 1.55 to 2.73). Nap durations less than 30 min were unrelated to diabetes (OR 1.05, 95% CI 0.97 to 1.14). Nap durations of 30–60 min were associated with diabetes risk (OR 1.09, 95% CI 1.02 to 1.17), but there were differences in the subgroup analysis results. Nap durations of more than 60 min significantly increased the risk of diabetes (OR 1.31, 95% CI 1.20 to 1.44).Conclusions Napping is associated with increased diabetes risk and poor glycaemic control, and future research will need to confirm whether there are sex and regional differences. Nap durations of more than 60 min significantly increases the risk of diabetes, and the relationship between nap duration and glycaemic control in patients with diabetes needs to be further explored in the future.PROSPERO registration number CRD42021292103.

12 μm thick rolled copper foil is the thinnest rolled copper foil that can be stably produced at present, which can be used for the production of high-end Flexible Printed Circuit (FPC) boards. With the miniaturized and multi-functional of various electronic components in the age of 5th Generation (5G) communication, higher requirements have been put forward for the etching performance of rolled copper foil. The microstructure of 12 μm thick rolled copper foil was obtained through thermal treatment at 180 °C for different times, and then the relationship between microstructure and etching performance was systematically studied. The research results show that the etching performance of rolled copper foil improves with the increasing of annealing time. But the etching performance of copper foil annealed for 10 min is better than that annealed for 30 min. Due to the low energy of Low Angle Grain Boundaries (LAGBs), the etching performance of copper foil gradually becomes better with the decreasing of LAGBs proportion. The etching performance of copper foil improves with the decreasing of work-hardening and dislocation density. The lower proportion of {001} crystal planes is the key reason for higher etching rate. The etching performance of copper foil is better with higher Random High Angle Grain Boundaries Network (RHGBN). The amount of grain boundaries decreases with the increasing of grain size, resulting in the decreasing of etching performance. In addition, it is found that the release of residual compressive stress on copper foil surface can also obviously improve the etching performance.

A meta-analysis of wheat aphid populations obtained from 120 studies from 1970 to 2017 reveals that pest loads increased in China but decreased in Europe and suggests this is due to differences in pesticide use, fertilization, land use, and natural enemies.

Melatonin is a biogenic amine that can be found in plants, animals and microorganism. The metabolic pathway of melatonin is different in various organisms, and biosynthetic endogenous melatonin acts as a molecular signal and antioxidant protection against external stress. Microbial synthesis pathways of melatonin are similar to those of animals but different from those of plants. At present, the method of using microorganism fermentation to produce melatonin is gradually prevailing, and exploring the biosynthetic pathway of melatonin to modify microorganism is becoming the mainstream, which has more advantages than traditional chemical synthesis. Here, we review recent advances in the synthesis, optimization of melatonin pathway. l-tryptophan is one of the two crucial precursors for the synthesis of melatonin, which can be produced through a four-step reaction. Enzymes involved in melatonin synthesis have low specificity and catalytic efficiency. Site-directed mutation, directed evolution or promotion of cofactor synthesis can enhance enzyme activity and increase the metabolic flow to promote microbial melatonin production. On the whole, the status and bottleneck of melatonin biosynthesis can be improved to a higher level, providing an effective reference for future microbial modification.

Pseudorabies is a highly contagious viral disease caused by the pseudorabies virus (PRV), and it is one of the most devastating diseases for the swine industry worldwide. However, the host-virus interaction and virus-related host factors at the mRNA level in virus natural host (pig) cells, are not fully understood. Here, we performed time-course RNA sequencing of the PK-15 cells infected with a recombinant strain PRV-Becker-GFP to study the dynamic competition between the host and the virus. At early stage of infection (3 hpi), our results suggested that the activation of cytosolic DNA-sensing pathway and NOD-like receptor signaling pathway might play a role in recognition of PRV, and the activation of NF-kappa B signaling pathway and TNF signaling pathway might be involved in immune response against the virus. However, all these pathways were subsequently inhibited by PRV. Additionally, our data indicated the fatty acid degradation pathway was significantly downregulated during late stage of infection (9 hpi), which was likely to accumulate fatty acids for viral envelope synthesis. Moreover, we verified the expression of 5 representative genes (ALDH1B1, ACAA2, ACSL3, ADH5, and EHHADH) related to fatty acid degradation pathway by RT-qPCR. Overall, our findings provide valuable information to better understand host-virus interactions and the immune escape mechanism of PRV-Becker as a virulent strain, offering novel targets for porcine anti-PRV breeding research and potential clinical treatment.

Objectives: First-year college students had exposure to unhealthy lifestyle behaviors that correlate with a high prevalence of anxiety and depression. Regarding to the modifiable lifestyle behaviors factors, this study investigated the prevalence and correlation of multiple lifestyle behaviors, anxiety and depression in a sample of Chinese first-year college students. Methods: Cross-sectional data were extracted from Residents eHealth app of health lifestyle behaviors survey from September to October 2019. Anxiety, depression, eating regular meals, consumption of snacks in-between meals, consumption of fruit, dessert and sugar-sweetened beverages, smoking and secondhand smoke exposure, consuming alcohol, physical activity, sedentary time were assessed by self-report. Socio-demographic including age, gender, education, family income, religion, and health condition were captured. Logistic regression was used to explore the association of multiple lifestyle behaviors, anxiety and depression. Results: Totally 1,017 participants were included in the study. The prevalence of anxiety and depression (from mild to severe) were 40.3% and 45.3%, respectively. In multivariable analyses, religion (believe in Buddhism, OR = 2.438, 95%CI: 1.097–5.421; believe in Christian, OR = 5.886, 95%CI: 1.604–21.597), gender (Female, OR = 1.405, 95%CI: 1.001–1.971), secondhand smoke exposure (OR = 1.089, 95%CI: 1.001–1.184), and eating regular meals (OR = 0.513, 95%CI: 0.346–0.759) were associated with anxiety. Family income (OR = 0.732, 95%CI: 0.596–0.898), eating regular meals (OR = 0.641, 95%CI: 0.415–0.990), frequency of breakfast (OR = 0.813, 95%CI: 0.690–0.959), with a chronic disease (OR = 1.902, 95%CI: 1.335–2.712), and consumption of nocturnal snack (OR = 1.337, 95%CI: 1.108–1.612) were associated with depression. Conclusions: These results highlighted the need for early lifestyle behavior intervention, especially modifying diet patterns considering the background of religion, health condition, and social-economic status in first-year college students to improve their mental health.

Abstract Vitamin K2 (menaquinone, MK) is an essential lipid-soluble vitamin with critical roles in blood coagulation and bone metabolism. Chemically, the term vitamin K2 encompasses a group of small molecules that contain a common naphthoquinone head group and a polyisoprenyl side chain of variable length. Among them, menaquinone-7 (MK-7) is the most potent form. Here, the biosynthetic pathways of vitamin K2 and different types of MK produced by microorganisms are briefly introduced. Further, we provide a new aspect of MK-7 production, which shares a common naphthoquinone ring and polyisoprene biosynthesis pathway, by analyzing strategies for expanding the product spectrum. We review the findings of metabolic engineering strategies targeting the shikimate pathway, polyisoprene pathway, and menaquinone pathway, as well as membrane engineering, which provide comprehensive insights for enhancing the yield of MK-7. Finally, the current limitations and perspectives of microbial menaquinone production are also discussed. This article provides in-depth information on metabolic engineering strategies for vitamin K2 production by expanding the product spectrum.

In this paper, the measurement data loss is considered and two data-driven stochastic optimal iterative learning control (DDSOILC) methods are presented directly for nonlinear network systems. Specifically, an iterative dynamic linearization (IDL) is adopted to construct the linear incremental input output relationship of the repetitive nonlinear network system between two consecutive iterations. In the sequel, a lifted IDL is obtained by defining two super vectors of inputs and outputs over the entire finite time interval. Then, a lifted IDL-based DDSOILC scheme is proposed where the random data loss is described by a Bernoulli distribution of random variable. The results are extended by using a non-lifted IDL where the input-output relationship is described pointwisely. The learning gains of the proposed two methods are iteration-time-variant and can be iteratively estimated using real-time data. The proposed two methods do not depend on any explicit model. Moreover, the proposed non-lifted IDL-based DDSOILC can use more control information than the proposed lifted IDL-based one, and thus it can achieve a better control performance. Both theoretical analysis and simulations verify the efficiency and applicability of the two proposed methods.

The problem of finite time adaptive control for stochastic nonlinear system is studied in this paper, where the system has a non-strict feedback structure. Under the sense of finite time stability, the authors propose a new neural network (NN) adaptive controller for stochastic nonlinear systems by backstepping technique. To overcome the difficulties that arise from the non-strict feedback structure of system, a key lemma is introduced. All the signals of the closed-loop systems are bounded in finite time in probability under the adaptive controller. At the same time good tracking performance can be achieved. A simulation example further shows the effectiveness of the control strategy in this thesis.

This paper exploits the outer synchronization between two dynamic networks with diversely varying node behaviours at the presence of noise. Aiming to obtain a generic technical solution for network outer synchronization, the problem is addressed for the dynamic network scenarios with non-identical topological structures, nonlinear inner coupling connections and time-delayed node characteristics. The impact of noise is fully considered in the theoretical and performance analysis which makes the derived synchronization criteria be able to be adopted in practical engineering deployment with minimized hurdles. By using a Lyapunov–Krasovskii energy function, the synchronization criteria and adaptive control solution are presented and the convergence of the system error states is also proved. Finally, the numerical analysis is carried out based on the simulation study and the result verifies the correctness and effectiveness of the suggested control solution.

The nucleocapsid (N) protein is a major structural component of porcine epidemic diarrhea virus (PEDV), which is predicted to be a multifunctional protein in viral replication. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a cellular protein participating in the splicing of pre-mRNA in the nucleus and translation regulation in the cytoplasm. According to our previous proteomic study about PEDV infection in vivo, hnRNP A1 was thought to be a cellular factor influencing PEDV replication. In this report, PEDV N protein was discovered to colocalize with cellular hnRNP A1 in perinuclear region of PEDV infected cells. Co-immunoprecipitation (CO-IP) results clearly demonstrated that PEDV N protein could bind to human hnRNP A1. Replication of PEDV was inhibited by silencing the expression of hnRNP A1 in CCL-81 cells, suggesting the positive effect of hnRNP A1 on PEDV infection.

Background: Apatinib exhibits a synergistic effect with transarterial chemoembolization (TACE) by inhibiting TACE-induced neoangiogenic reaction in hepatocellular carcinoma (HCC) patients. But apatinib plus drug-eluting bead TACE (DEB-TACE) is rarely reported as a bridging therapy to surgery. This study aimed to evaluate the efficacy and safety of apatinib plus DEB-TACE as a bridge to surgical resection in intermediate-stage HCC patients. Materials and Methods: Thirty-one intermediate-stage HCC patients who received apatinib plus DEB-TACE as a bridging therapy to surgery were enrolled. After the bridging therapy, complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), and objective response rate (ORR) were evaluated; meanwhile, relapse-free survival (RFS) and overall survival (OS) were determined. Results: After the bridging therapy, three (9.7%), twenty one (67.7%), seven (22.6%), and twenty four (77.4%) patients achieved CR, PR, SD, and ORR, respectively; besides, PD did not occur. The successful downstaging rate was 18 (58.1%). The median (95% confidence interval [CI]) accumulating RFS was 33.0 (19.6 - 46.6) months. Besides, the median (95% CI) accumulating OS was 37.0 (24.8 - 49.2) months. HCC patients with successful downstaging showed a higher accumulating RFS rate (P = 0.038) and similar accumulating OS rate (P = 0.073) compared to those without successful downstaging. The overall incidence of adverse events was relatively low. Besides, all the adverse events were mild and controllable. The most frequent adverse events included pain (14 [45.2%]) and fever (9 [29.0%]). Conclusion: Apatinib plus DEB-TACE as a bridging therapy to surgical resection displays good efficacy and safety profile in intermediate-stage HCC patients. [ABSTRACT FROM AUTHOR]

Background: Athletes and fitness enthusiasts often encounter thoracolumbar compression fractures due to rigorous physical activities. Combining calcium (Ca) and zoledronic acid (ZOL) with percutaneous kyphoplasty (PKP) has shown promising clinical efficacy in elderly patients with osteoporotic thoracolumbar compression fractures (OTCF). However, the potential benefits of this approach in athletes and fitness enthusiasts require further investigation. Methods: We conducted a retrospective analysis of 295 athletes and fitness enthusiasts (mean age 75.91±3.74 years) with OTCF who underwent PKP. Patients were divided into three groups: PKP+Ca (n=92), receiving 1500mg/d Ca carbonate post-surgery; PKP+ZOL (n=98), receiving 5mg ZOL intravenously post-surgery; and PKP+Ca+ZOL (n=105), administered with a combination of Ca and ZOL post-surgery. A two-year follow-up was conducted, and clinical and imaging data were recorded and analyzed before and after treatment. Results: There were no significant differences in general information, lumbar bone mineral density (BMD), visual analog scale (VAS), Oswestry dysfunction index (ODI), and bone marker levels among the three groups before treatment. In the 3rd, 6th, 12th, and 24th months post-treatment, the PKP+Ca+ZOL group exhibited higher vertebral heights compared to the PKP+Ca and PKP+ZOL groups. Additionally, in the 6th, 12th, and 24th months post-treatment, the PKP+Ca+ZOL group demonstrated lower kyphosis than the PKP+Ca and PKP+ZOL groups. Furthermore, in the 12th and 24th months post-treatment, the PKP+Ca+ZOL group had higher BMD values than the PKP+ZOL and PKP+Ca groups. VAS scores in the PKP+Ca+ZOL and PKP+ZOL groups were significantly lower than those in the PKP+Ca group. ODI scores and bone marker concentrations were also lower in the PKP+Ca+ZOL group compared to the other groups. Importantly, the incidence of postoperative vertebral refracture was 1.02% in the PKP+ZOL group and 7.60% in the PKP+Ca group, while no refractures were observed in the PKP+Ca+ZOL group. The incidence of adverse reactions was similar between the PKP+ZOL (39.04%) and PKP+Ca+ZOL (34.69%) groups. Conclusion: The combination of PKP and Ca and ZOL demonstrates a high clinical efficacy in the treatment of OTCF among athletes and fitness enthusiasts. This approach offers potential benefits for individuals engaged in rigorous physical activities and warrants further exploration. [ABSTRACT FROM AUTHOR]