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Cognitive frailty (CF) is an important geriatric syndrome and is reversible. It is crucial to develop preventive interventions for CF. We aimed to explore the associations between CF and its associated factors in Chinese aged 45 years and above. Based on the available data of 3 waves in China Health and Retirement Longitudinal Study from 2011 to 2015, 16,071 individuals aged 45 years and above from 3 waves were included. Based on the health ecology model, the associated factors were classified as downstream, midstream and upstream factors. Generalized hierarchical linear model including time level, individual level, and province level was applied to analyze the associations between factors and CF. Multilevel factors have different effects on physical and cognitive function. In the downstream, old age, female, underweight, chronic diseases, and depression were risk factors of reversible CF and potentially reversible CF, and overweight was their protective factor. In the midstream, short or long night sleep duration was their risk factor, and > 30 and ≤ 60 min afternoon naps, alcohol drinking, and participation in social activities were their protective factors. In the upstream, living in rural areas was their risk factor, and high educational level, household consumption and GDP per capita were their protective factors. Physical function and cognitive function are affected differently by multiple factors. The occurrence and development of physical frailty and cognitive impairment may have some common mechanisms. CF can be influenced by multilevel factors, and multilevel and comprehensive management of CF should be achieved. Cognitive frailty was correlated with multilevel factors, including downstream, midstream, and upstream factors. It is crucial to focus on individual interventions such as physiological factors, psychological factors and health behaviors, especially the elderly, women and those with depression. Socioeconomic status was associated with the lower prevalence of cognitive frailty. • Physical function and cognitive function were affected differently by multiple factors. • Cognitive frailty was associated with multilevel factors, including downstream, midstream, and upstream factors. • It is crucial to focus on individual interventions such as physiological, psychological, and health behavior factors. • Socioeconomic status was associated with the lower risk of cognitive frailty. [ABSTRACT FROM AUTHOR]

Odontoblastic differentiation of human stem cells from the apical papilla (hSCAPs) is crucial for continued root development and dentin formation in immature teeth with apical periodontitis (AP). Fat mass and obesity-associated protein (FTO) has been reported to regulate bone regeneration and osteogenic differentiation profoundly. However, the effect of FTO on hSCAPs remains unknown. This study aimed to identify the potential function of FTO in hSCAPs' odontoblastic differentiation under normal and inflammatory conditions and to investigate its underlying mechanism preliminarily. Histological staining and micro-computed tomography were used to evaluate root development and FTO expression in SD rats with induced AP. The odontoblastic differentiation ability of hSCAPs was assessed via alkaline phosphatase and alizarin red S staining, qRT-PCR, and Western blotting. Gain- and loss-of-function assays and online bioinformatics tools were conducted to explore the function of FTO and its potential mechanism in modulating hSCAPs differentiation. Significantly downregulated FTO expression and root developmental defects were observed in rats with AP. FTO expression notably increased during in vitro odontoblastic differentiation of hSCAPs, while lipopolysaccharide (LPS) inhibited FTO expression and odontoblastic differentiation. Knockdown of FTO impaired odontoblastic differentiation, whereas FTO overexpression alleviated the inhibitory effects of LPS on differentiation. Furthermore, FTO promoted the expression of secreted modular calcium-binding protein 2 (SMOC2), and the knockdown of SMOC2 in hSCAPs partially attenuated the promotion of odontoblastic differentiation mediated by FTO overexpression under LPS-induced inflammation. This study revealed that FTO positively regulates the odontoblastic differentiation ability of hSCAPs by promoting SMOC2 expression. Furthermore, LPS-induced inflammation compromises the odontoblastic differentiation of hSCAPs by downregulating FTO, highlighting the promising role of FTO in regulating hSCAPs differentiation under the inflammatory microenvironment. [ABSTRACT FROM AUTHOR]

Non‐native plants are typically released from specialist enemies but continue to be attacked by generalists, albeit at lower intensities. This reduced herbivory may lead to less investment in constitutive defences and greater investment in induced defences, potentially reducing defence costs. We compared herbivory on 27 non‐native and 59 native species in the field and conducted bioassays and chemical analyses on 12 pairs of non‐native and native congeners. Non‐natives suffered less damage and had weaker constitutive defences, but stronger induced defences than natives. For non‐natives, the strength of constitutive defences was correlated with the intensity of herbivory experienced, whereas induced defences showed the reverse. Investment in induced defences correlated positively with growth, suggesting a novel mechanism for the evolution of increased competitive ability. To our knowledge, these are the first linkages reported among trade‐offs in plant defences related to the intensity of herbivory, allocation to constitutive versus induced defences, and growth. [ABSTRACT FROM AUTHOR]

Temperature has a large influence on insect abundances, thus under climate change, identifying major drivers affecting pest insect populations is critical to world food security and agricultural ecosystem health. Here, we conducted a meta-analysis with data obtained from 120 studies across China and Europe from 1970 to 2017 to reveal how climate and agricultural practices affect populations of wheat aphids. Here we showed that aphid loads on wheat had distinct patterns between these two regions, with a significant increase in China but a decrease in Europe over this time period. Although temperature increased over this period in both regions, we found no evidence showing climate warming affected aphid loads. Rather, differences in pesticide use, fertilization, land use, and natural enemies between China and Europe may be key factors accounting for differences in aphid pest populations. These long-term data suggest that agricultural practices impact wheat aphid loads more than climate warming. 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. [ABSTRACT FROM AUTHOR]

• CEP can significantly inhibits PDCoV binding, entry, and replication in LLC-PK1 cells. • In silico data and SPR results indicate that CEP targets pAPN and PDCoV binding sites in cells to inhibits PDCoV infection. • CEP reduces inflammatory signaling caused by PDCoV infection. • CEP inhibits PDCoV replication by inducing autophagy. • CEP confers broad-spectrum resistance to other coronaviruses (TGEV and MHV). 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. [Display omitted] [ABSTRACT FROM AUTHOR]

Similarity-based approaches have made significant progress in visual object tracking (VOT). Although these methods work well in simple scenes, they ignore the continuous spatio-temporal connection of the object in the video sequence. For this reason, tracking by spatial matching solely can lead to tracking failures because of distractors and occlusion. In this paper, we propose a spatio-temporal joint-modeling tracker named STTrack which implicitly builds continuous connections between the temporal and spatial aspects of the sequence. Specifically, we first design a time-sequence iteration strategy (TSIS) to concentrate on the temporal connection of the object in the video sequence. Then, we propose a novel spatial temporal interaction Transformer network (STIN) to capture the spatio-temporal correlation of the object between frames. The proposed STIN module is robust in object occlusion because it explores the dynamic state change dependencies of the object. Finally, we introduce a spatio-temporal query to suppress distractors by iteratively propagating the target prior. Extensive experiments on six tracking benchmark datasets demonstrate that the proposed STTrack achieves excellent performance while operating in real-time. The code is publicly available at https://github.com/nubsym/STTrack. [ABSTRACT FROM AUTHOR]

• We generated a pig genome-wide gRNA library for loss function of pig genes. • We achieved some genes related to PRRSV replication using genome-wide CRISPR/Cas9 screening. • We found loss of KXD1 inhibited replication PRRSV through prevented the fusion of lysosome and autophagosome. Porcine reproductive and respiratory syndrome (PRRS), a viral infection caused by PRRS virus (PRRSV) can result in severe reproductive failure, and respiratory disease in the pigs thus causing enormous economic losses to the global swine industry. Although the cellular receptors for PRRSV have been identified, but mechanisms underlying PPRSV replication remain obscure. Here, we have performed a genome-scale CRISPR/Cas9 knockout screen in the pig kidney cells with PRRSV. Several genes were found to be highly enriched post-PRRSV selection, just like KxDL Motif Containing 1(KXD1), Proteasome 26S Subunit, Non-ATPase 3 (PSMD3) and Galectin 2 (LGALS2) and soon on. Importantly, we have identified that loss of KXD1 resulted in the restricted autophagy and inhibited replication of PRRSV. Therefore, our study demonstrates that CRISPR/Cas9 system can be effectively used for the screening of pig factors responsible for PRRSV replication. [ABSTRACT FROM AUTHOR]

• Quercetin inhibits multiple PRV strains infection of Vero cells. • Quercetin mainly interacts with PRV and inhibit the viral adsorption on the cell. • In silico data indicated that quercetin may interaction with PRV gD protein. • Quercetin protects against PRV infection in mouse models Pseudorabies virus (PRV) accounts for a critical swine disease incurring economic losses worldwide. Several PRV vaccines are commercially available but these vaccines are effective against only certain prevalent PRV strains in China. To prevent PRV-induced latent infection and decrease the pathogenicity, novel anti-PRV drugs are required to prevent PRV infection. Natural products show exceptional structural diversity representing an important source for developing novel therapeutic agents. Quercetin is a flavonoid with anti-oxidant, anti-cancer, anti-bacterial and anti-viral activities. This study involved quercetin for studying the anti-PRV function in vitro and in vivo. Quercetin was found to significantly decrease the PRV virulent strain HNX at a half-maximal inhibitory concentration (IC 50) of 2.618 μM and selectivity index 229. This anti-PRV activity of quercetin was found to be dose-dependent. Furthermore, quercetin also inhibited a wide the infections by a spectrum of PRV strains like HNX, Ea, Bartha and Fa strain. These virucidal effects of quercetin suggest the interaction between these molecules and viral particles, and quercetin is responsible for inhibiting the adsorption of PRV infections. The silico assays suggesting that quercetin might interact with the gD-protein on the surface of the PRV important for viral infection. Additional, the quercetin plantar injection protected the mice from the lethal challenge, decreasing the PRV-infected mice's brain viral loads and mortality. These results provides a anti-PRV strategy and contribute to drug discovery and development. [Display omitted] Schematic diagram of quercetin interaction with Pseudorabies viruses in Vero cells [ABSTRACT FROM AUTHOR]

Objective: Runt‐related transcription factor 2 (Runx2) plays an important role in bone metabolism; however, the relationship between Runx2 and periodontitis remains unclear. We investigated Runx2 expression in the gingiva of patients to explore its role in periodontitis. Methods: Gingival samples of patients were collected, including healthy samples (control group) and periodontitis samples (P group). Periodontitis samples were divided into three groups based on the periodontitis stage. Samples with stage I and grade B periodontitis were in the P1 group, stage II and grade B in the P2 group, and stage III or IV and grade B in the P3 group. Immunohistochemistry and western blotting were performed to detect Runx2 levels. The probing (PD) and clinical attachment loss (CAL) were recorded. Results: Runx2 expression levels in the P and P3 groups were higher than those in the control group. In addition, Runx2 expression was positively correlated with CAL and PD (r1 = 0.435, r2 = 0.396). Conclusion: The high expression level of Runx2 in the gingiva of patients with periodontitis may be correlated with the pathogenesis of periodontitis. [ABSTRACT FROM AUTHOR]

• 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. • 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. 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. [ABSTRACT FROM AUTHOR]

Objective. This work is aimed at revealing the role and the molecular mechanism of connective tissue growth factor 2 (CTGF) in the osteoblast differentiation of periodontal ligament stem cells (PDLSCs). Methods. The osteogenic differentiation of PDLSCs was induced by osteogenic induction medium (OM), and the expression level of osteogenic related proteins ALP, RUNX2, OCN, and CTGF was estimated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analysis. We constructed cell lines with CTGF overexpression or knockdown to verify the role of CTGF in the osteoblast differentiation of PDLSCs. Alkaline phosphatase (ALP) staining was introduced to measure the osteoblasts activity, and alizarin red S (ARS) staining was employed to test matrix mineralization. The interaction between CTGF and bone morphogenetic protein-2 (BMP-2) was determined by endogenous coimmunoprecipitation (Co-IP). Results. The expression level of CTGF was increased during the osteogenic induction of PDLSCs. Additionally, CTGF overexpression effectively maintained the stemness and facilitated the osteoblast differentiation in PDLSCs, and CTGF knockdown exerted opposite effects. Moreover, at molecular mechanism, CTGF increased the activity of BMP-2/Smad signaling pathway. Conclusion. This investigation verified that CTGF promotes the osteoblast differentiation in PDLSCs at least partly by activating BMP-2/Smad cascade signal. [ABSTRACT FROM AUTHOR]

Streptococcus suis (S. suis) is a significant zoonotic microorganism that causes a severe illness in both pigs and humans and is characterized by severe meningitis and septicemia. Suilysin (SLY), which is secreted by S. suis , plays a crucial role as a virulence factor in the disease. To date, the interaction between SLY and host cells is not fully understood. In this study, we identified the interacting proteins between SLY and human brain microvascular endothelial cells (HBMECs) using the TurboID-mediated proximity labeling method. 251 unique proteins were identified in TurboID-SLY treated group, of which six plasma membrane proteins including ARF6, GRK6, EPB41L5, DSC1, TJP2, and PNN were identified. We found that the proteins capable of interacting with SLY are ARF6 and PNN. Subsequent investigations revealed that ARF6 substantially increased the invasive ability of S. suis in HBMECs. Furthermore, ARF6 promoted SLY-induced the activation of p38 MAPK signaling pathway in HBMECs. Moreover, ARF6 promoted the apoptosis in HBMECs through the activation of p38 MAPK signaling pathway induced by SLY. Finally, we confirmed that ARF6 could increase the virulence of SLY in C57BL/6 mice. These findings offer valuable insights that contribute to a deeper understanding of the pathogenic mechanism of SLY. [ABSTRACT FROM AUTHOR]

Background: Retinopathy of prematurity (ROP) continues to be a major cause of visual impairment and blindness in premature infants and children. Objectives: To investigate the incidence of severe ROP receiving treatment in extremely preterm (EP) infants in China over time. The risk factors for ROP treatment were also assessed. Methods: This was a multicentre retrospective study and a subanalysis of baseline data from the "Outcomes of EP infants in China 2010–2019" study. This study was conducted in 68 tertiary neonatal care centres from 31 provinces of China. Infants with a gestational age of 230–276 weeks and admitted to a neonatal unit within the first 72 h of life between 2010 and 2019 were enrolled. Incidence of ROP was analysed in infants who survived to 32 weeks postmenstrual age and screened for ROP. Multivariable modified Poisson regression models were used to identify risk factors for ROP treatment. Results: Among 7295 eligible infants, 4701 (64.5%) survived to 32 weeks postmenstrual age and met ROP screening criteria. Of the 3756 infants who screened and with ROP data, 2320 (61.8%) developed ROP of any stage. The overall incidence of ROP treatment was 12.6%, decreasing from 45.5% at 23 weeks to 8.3% at 27 weeks. During the 10‐year period, the incidence of ROP treatment did not change, although the incidence of any ROP increased over time. Independent risk factors associated with ROP treatment included lower gestational age, small for gestational age, multiple birth, severe intraventricular haemorrhage, patent ductus arteriosus and supplemental oxygen duration. Conclusions: The incidence of EP infants receiving ROP treatment showed no change during this 10‐year period in China. Prevention of prematurity and foetal growth restriction, judicious use of oxygen and reducing comorbidities are promising factors that may reduce the incidence of ROP needing treatment in these high‐risk infants. [ABSTRACT FROM AUTHOR]

Curdlan is widely applied in the food and pharmaceutical industries. This review focuses on the biosynthetic pathways, regulatory mechanisms and metabolic engineering strategies for curdlan production. Firstly, curdlan biosynthesis is discussed. Furthermore, various strategies to increase curdlan production are summarized from four aspects, including the overexpression of genes for curdlan biosynthesis, weakening/knockdown of genes from competing pathways, increasing the supply of curdlan precursors, and optimization of fermentation conditions. Moreover, the emerging and advanced applications of curdlan are introduced. Finally, the challenges that are frequently encountered during curdlan biosynthesis are noted with a discussion of directions for curdlan production. • Mechanisms that regulate curdlan biosynthesis are described. • Strategies for increasing the supply of precursors for curdlan synthesis are analyzed. • Applications of curdlan in the food and pharmaceutical industries are summarized. [ABSTRACT FROM AUTHOR]

The wide application of clean energy has promoted the development of microgrids. For direct current (DC) microgrids, power fluctuations are inevitable, because photovoltaics, wind power and other clean energy sources are very unstable, which will bring great trouble to DC microgrids. Hybrid energy storage systems (HESS) are an effective solution to suppress power fluctuations. For a HESS composed of battery and supercapacitor (SC), a low-pass filter is usually used to allocate energy and power requirements to each energy storage unit, but the filter constant of the filter cannot be dynamically adjusted to adapt to different situations. The low-pass filter compensation coefficient used in this paper will change with the state of charge and discharge and dynamically change and allocate different power requirements to the battery and SC according to the actual operating conditions of the HESS. The objective function of DC bus power fluctuation is established, and the optimized particle swarm algorithm (PSO) is used to obtain the output power coefficient of each energy storage unit. The output coefficient of the HESS control strategy has the characteristics of fast convergence speed and high computational efficiency in the optimization process, and it will not fall into the local optimal solution. Through the design experiment, the SC can withstand more high-frequency components, fully utilize the advantages of SC with fast response to power fluctuations, improve the performance of HESS and have great engineering application value. [ABSTRACT FROM AUTHOR]

Background: Little is known about how health behaviors cluster to form meaningful patterns that influence health outcomes in young adult nursing students. Purpose: The purpose of this study was to identify the unique health behavior patterns among young adult nursing students in China and examine the associations between health behaviors and chronic diseases. Methods: Using an electronic app, the achievements of an exercise target, sedentary behavior, smoking and drinking, and dietary patterns were assessed in 1,480 nursing student participants aged 18–24 years from two medical universities in Eastern China. Results: A four-class model was developed using latent class analysis that included the "failure to achieve exercise target, alcohol-drinking, and insufficient fruit and vegetable group" (Group 1, n = 187, 12.6%), the "alcohol-drinking and sedentary behavior group" (Group 2, n = 290, 19.6%), the "sedentary behavior only group" (Group 3, n = 721, 48.7%), and the "failure to achieve exercise target only group" (Group 4, n = 282, 19.1%). Logistic regressions indicated that nursing students in Group 2 (odds ratio [ OR ] = 0.42), Group 3 (OR = 0.51), and Group 4 (OR = 0.30) were less likely to have chronic diseases than those in Group 1 after adjusting for sociodemographic variables. Conclusions: The health behaviors were clustered in different patterns among young adult nursing students. Tailoring interventions to specific groups is suggested to improve health outcomes. [ABSTRACT FROM AUTHOR]