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Abstract African swine fever virus is highly contagious and causes a fatal infectious disease in pigs, resulting in a significant global impact on pork supply. The African swine fever virus RNA polymerase serves as a crucial multifunctional protein complex responsible for genome transcription and regulation. Therefore, it is essential to investigate its structural and functional characteristics for the prevention and control of African swine fever. Here, we determine the structures of endogenous African swine fever virus RNA polymerase in both nucleic acid-free and elongation states. The African swine fever virus RNA polymerase shares similarities with the core of typical RNA polymerases, but possesses a distinct subunit M1249L. Notably, the dynamic binding mode of M1249L with RNA polymerase, along with the C-terminal tail insertion of M1249L in the active center of DNA-RNA scaffold binding, suggests the potential of M1249L to regulate RNA polymerase activity within cells. These results are important for understanding the transcription cycle of the African swine fever virus and for developing antiviral strategies.

The assessment of lightning disaster-causing hazards is the key to risk survey of lightning disasters. Following the technical route of the national meteorological disasters comprehensive risk survey since 2020, and based on the lightning location data from 2010 to 2020, lightning disaster data from 2000 to 2020, digital elevation data, and soil conductivity data in Anhui Province, a model diagram of disaster-causing hazard zoning was constructed according to"Specification for meteorological disasters investigation and risk assessment: Lightning". The Analytic Hierarchy Process was used to determine the weight of each index, and the lightning disaster-causing hazard index was then calculated. The zoning of lightning disaster-causing hazards in Anhui Province was completed by combining with GIS technology. The results are as follows. (1) The distributions of lightning strike density and lightning peak current amplitude are closely related to the topography. The altitude and terrain have a positive driving effect on the lightning disaster-causing hazard. (2) The high and relatively high sensitivity of lightning disaster-pregnant areas are mainly located in mountainous regions, along the Yangtze River, and parts of the Huai River basin. (3) The areas of high lightning disasters are mainly located in most regions along the Yangtze River and southern mountainous regions in Anhui Province. The areas of relatively high lightning disasters are mainly located in the southern mountainous region, between the Yangtze River and Huai River, and parts of the Jiangnan region. The areas of low and relatively low lightning disasters are mainly located in the plain and hilly areas in the northern Anhui region and the Jiang-huai region. By comparing the zoning results with historical disaster data, it is found that the distribution of lightning disaster-causing hazard zoning agrees well with the true distribution of disaster, which can provide a reference for future lightning disaster prevention in Anhui Province.

Based on the technical specifications for the national comprehensive risk survey of meteorological disasters, and in view of the characteristics of snow disaster impacts in Anhui Province, the observation element of snow pressure is considered and combined with other disaster causative factors, such as the annual maximum snow depth and annual average snow-covered days to establish a risk assessment model. Using the data of snow depth, snow pressure, and geographic information from 81 national meteorological observation stations in Anhui Province from 1978 to 2020, the spatiotemporal distribution characteristics of various disaster-causing factors are analyzed, and the terrain correction for snow-covered days is performed to obtain a refined assessment of snow disaster risk in Anhui Province. The results are as follows. The annual variation and differences of the average maximum snow depth, average snow-covered days, and maximum snow pressure are significant, but the top three years for all these factors are 2008, 1984, and 2018. The areas with high annual maximum snow depth are mainly concentrated between the Dabie Mountains, the southern Anhui Mountains, and the regions between the Yangtze River and the Huai River. Considering the significant correlation between the annual snow-covered days and elevation in the area above 100 meters and the appropriate sample size, after terrain correction, the high-value areas of snow-covered days are located in the Dabie Mountains and the southern Anhui Mountains, followed by the northwest of Huaibei to the northern foothills of Dabie Mountains. After interpolation calculation of missing measurements, the maximum snow pressure in Xuancheng, Tongling, northern Mount Huangshan, and other places is increased, with distinct localized characteristics. The high-risk areas caused by snow disasters in Anhui Province are mainly located in high-altitude regions such as the Dabie Mountains and the mountainous areas in southern Anhui, while the low-risk areas are mainly located in the eastern part of the Huaibei region, the eastern part of the region between the Yangtze River and Huai River, and the southwestern part along the Yangtze River.

Foot-and-mouth disease virus (FMDV) are small, icosahedral viruses that cause serious clinical symptoms in livestock. The FMDV VP1 protein is a key structural component, facilitating virus entry. Here, we find that the E3 ligase RNF5 interacts with VP1 and targets it for degradation through ubiquitination at the lys200 of VP1, ultimately inhibiting virus replication. Mutations at this lysine site have been found to increase the replication of FMDV in mice. Importantly, the RNF5 pharmacological activator Analog-1 alleviates disease development in a mouse infection model. Furthermore, RNF5 recognizes the VP1 protein from several picornaviruses, suggesting that targeting RNF5 may be a broad-spectrum antiviral strategy. These findings shed light on the role of the ubiquitin-proteasome system in controlling virus replication, offering potential new strategies for treating viral infections.

Rattus tanezumi (Niethammer, 1975) is one of the commensal rodent species in South China. With the development of transportation and climate change, R. tanezumi has gradually migrated north and become the dominant rat species for the past few years. In this study, we assembled a complete mitochondrial genome of R. tanezumi, captured from North China. The mitogenome contains 16,307 nucleotide pairs, including 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes, as well as one non-coding control region. Based on whole mitogenome phylogenetical analysis showed that R. tanezumi captured from North China had a close phylogenetic relationship with that from Japan and South Korea. These findings are valuable for further studies on the evolution, genetic diversity, and taxonomy of Asian commensal rodent.

Abstract The incidence of lung cancer has become the highest among all cancer types globally, also standing as a leading cause of cancer-related deaths. Lung cancer is broadly divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with the latter accounting for 85% of total cases. SRY-box transcription factor 4 (SOX4), a crucial transcription factor, has been found to play a key role in the development of various cancers. However, the association between SOX4 and NSCLC is still unclear. This study investigated the clinical relevance of SOX4 and its potential mechanisms in the progression of NSCLC. Analysis of our NSCLC patient cohort revealed a significant increase in SOX4 levels in cancerous tissues, indicating its role as an independent prognostic indicator for NSCLC. In vitro experiments demonstrated that elevated SOX4 expression facilitated NSCLC cell migration, invasion, and EMT. Functionally, SOX4 drives NSCLC progression by enhancing the transcription and expression of B-cell-specific moloney leukemia virus insertion site 1 (BMI1). The oncogenic impact of SOX4-induced BMI1 expression on NSCLC advancement was validated through both in vivo and in vitro studies. In addition, our findings showed that BMI1 promoted the ubiquitination of histone H2A (H2Aub), leading to decreased zinc finger protein 24 (ZNF24) expression, which subsequently triggered vascular endothelial growth factor A (VEGF-A) secretion in NSCLC cells, thereby promoting NSCLC angiogenesis. Moreover, we evaluated the therapeutic potential of a BMI1 inhibitor in combination with Bevacizumab for NSCLC treatment using orthotopic models. The data presented in our study reveal a previously unrecognized role of the SOX4-BMI1 axis in promoting NSCLC progression and angiogenesis. This research significantly contributes to our knowledge of the interplay between SOX4 and BMI1 in NSCLC, potentially paving the way for the development of targeted therapies for this disease.

ABSTRACT Senecavirus A (SVA) is an emerging viral pathogen that threatens the global swine industry significantly. The major clinical symptoms of SVA-infected animals are vesicular lesions, but various diseases can cause the same symptoms, which makes it difficult to distinguish SVA from other vesicular diseases clinically. The absence of an effective and safe vaccine necessitates the development of a simple, specific, and sensitive serological detection method for SVA antibodies. The VP2 protein of SVA, characterized by high immunogenicity and sequence conservatism, is an essential target for serological diagnosis. In this study, a double-antigen sandwich enzyme-linked immunosorbent assay [ELISA (DAgS-ELISA)] based on VP2 protein expressed by Escherichia coli was established for SVA antibody detection. With a cut-off value of 0.237, this assay demonstrated outstanding performance, showing high sensitivity and sharp specificity, which is manifested in the absence of cross-reaction with classical swine fever virus (CSFV), African swine fever virus (ASFV), pseudorabies virus (PRV), and porcine reproductive and respiratory syndrome virus (PRRSV), and foot-and-mouth disease virus (FMDV) serotype A and O. Additionally, the repeatability of the method is remarkable, as shown by the coefficients variation (CV) of both the intra- and inter-assay below 10%. By detecting 166 clinical sera, it was found that the kappa value of the DAgS-ELISA was 0.78 compared with that of the virus neutralization test (VNT), indicating a high level of consistency. In general, this method has high sensitivity, sharp specificity, remarkable repeatability, sound consistency, and low cost, making it a reliable and effective tool for detecting SVA antibodies.IMPORTANCESVA has rapidly become prevalent in many countries, and its outbreaks have threatened the global swine industry significantly. The major clinical symptoms of SVA-infected animals are vesicular lesions that are similar to other vesicular diseases, making it difficult to distinguish SVA. Currently, no commercial vaccines are available for SVA; therefore, effective diagnosis of SVA infection is vital for its prevention and control. In this study, VP2 protein of SVA was expressed by E. coli, and a double-antigen sandwich enzyme-linked immunosorbent assay [ELISA (DAgS-ELISA)] for SVA antibodies detection was successfully established based on the VP2 protein. The DAgS-ELISA has a high sensitivity, sharp specificity, remarkable repeatability, sound consistency, and low cost for detecting SVA antibodies. Therefore, the DAgS-ELISA established in this study may be a reliable and effective tool for detecting SVA antibodies and may be used to strengthen the monitoring and prevention of SVA epidemic in the long run.

In this study, we reported the first long-term monitoring of SARS-CoV-2 in wastewater in Mainland China from November 2021 to October 2023. The city of Shijiazhuang was employed for this case study. We developed a triple reverse transcription droplet digital PCR (RT-ddPCR) method using triple primer-probes for simultaneous detection of the N1 gene, E gene, and Pepper mild mottle virus (PMMoV) to achieve accurate quantification of SARS-CoV-2 RNA in wastewater. Both the RT-ddPCR method and the commercial multiplex reverse transcription quantitative polymerase chain reaction (RT-qPCR) method were implemented for the detection of SARS-CoV-2 in wastewater in Shijiazhuang City over a 24-month period. Results showed that SARS-CoV-2 was detected for the first time in the wastewater of Shijiazhuang City on 10 November 2022. The peak of COVID-19 cases occurred in the middle of December 2022, when the concentration of SARS-CoV-2 in the wastewater was highest. The trend of virus concentration increases and decreases forming a “long-tailed” shape in the COVID-19 outbreak and recession cycle. The results indicated that both multiplex RT-ddPCR and RT-qPCR are effective in detecting SARS-CoV-2 in wastewater, but RT-ddPCR is capable of detecting low concentrations of SARS-CoV-2 in wastewater which is more efficient. The SARS-CoV-2 abundance in wastewater is correlated to clinical data, outlining the public health utility of this work.HighlightsFirst long-term monitoring of SARS-CoV-2 in wastewater in Mainland ChinaCOVID-19 outbreak was tracked in Shijiazhuang City from outbreak to containmentWastewater was monitored simultaneously using RT-ddPCR and RT-qPCR methodsTriple primer-probe RT-ddPCR detects N1 and E genes of SARS-CoV-2 and PMMoV

Typhoon disaster factors show multiplicity, so the risk assessment of typhoon-related disasters is more difficult than other hazards. Using the typhoon precipitation and maximum wind speed data of 81 national meteorological stations and 1 035 regional automatic meteorological stations in Anhui Province, a comprehensive typhoon wind and rain intensity index is first constructed. Then the typhoon wind and rain intensity index and disaster pregnant environment impact coefficient are used to assess the risk of typhoon disasters. According to the theory of natural disaster risk assessment, the risk assessment of housing damage by typhoon disaster in Anhui Province is conducted by integrating disaster-causing hazards, exposure level and vulnerability of disaster-bearing bodies. The results show that Anhui Province is affected by about 1.9 typhoons per year on average, with a duration of 2-4 days. The results are as follows. The southern part and mountainous areas usually have more typhoon precipitation than the northern part and plain areas. The high-hazard region caused by typhoon disasters is mainly located in the southern mountainous and Dabie Mountains in Anhui Province, with the relatively high-hazard region in the east of Jianghuai region, and the low-hazard area in most of the regions to the north of the Huaihe River and in the northwest of Jianghuai region. The high and relatively high-risk area of housing damage caused by typhoon disasters is located in the Dabie Mountains, the eastern part of the Jianghuai region, and the southern mountainous area in Anhui Province. These areas are generally high in elevation, and easily suffer from geological disasters and mountain floods during typhoon transit. In addition, the vulnerability of houses is high, which further causes a high risk of house collapse and damage. The medium-risk region is scattered in the Huaihe River region and Jiangnan region. Lower and low-risk areas are located in the central and western parts to the north of the Huaihe River, regions along the Yangtze River, and main urban areas. Using reports on house damage caused by typhoons from different counties in Anhui Province, the zoning results are verified through spatial consistency and scatter correlation. A high degree of spatial consistency between the risk zoning results and the actual damage, with scatter correlation between them passing a significance test of 0.01, indicating that the risk zoning results of housing damage by typhoon disaster in Anhui Province are basically consistent with the actual situation.

We developed ligandomics for the in vivo profiling of vascular ligands in mice, discovering secretogranin III (Scg3) as a novel angiogenic factor that selectively binds to retinal vessels of diabetic but not healthy mice. This discovery led to the development of anti-Scg3 therapy for ocular vasculopathies. However, in vivo ligandomics requires intracardial perfusion to remove unbound phage clones, limiting its use to vascular endothelial cells (ECs). To extend ligandomics to non-vascular cells, we investigated ex vivo ligandomics. We isolated ECs and retinal ganglion cells (RGCs) from diabetic and healthy mouse retinas by immunopanning. We quantified the binding of clonal phages displaying Scg3 and vascular endothelial growth factor (VEGF), confirming that their binding patterns to isolated diabetic versus healthy ECs matched in vivo patterns. Additionally, Scg3 and VEGF binding to isolated RGCs reflected their in vivo activity. These results support the feasibility of ex vivo ligandomics. We further mapped ligands binding to immunopanned diabetic and healthy ECs and RGCs by ligandomics, confirming that Scg3 was enriched with selective binding to diabetic ECs but not healthy ECs or diabetic/healthy RGCs. These findings demonstrate the feasibility of ex vivo ligandomics, which can be broadly applied to various cell types, tissues, diseases, and species.

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus that undergoes rapid mutation. Based on viral whole genome sequencing analysis in Hebei Province, China, we identified several essential single nucleotide variants (SNVs) on primer-probe regions accumulating within some Omicron variants’ genomes. In this study, we focused on three SNVs, C28290T, T28297C, and C28311T emerging on 2019-nCoV-N1 (CDC-N1) primer-probe regions, recommended by CDC in 2020, and two SNVs, C26270T, A26275G emerging on E (Charité-E) primer-probe regions recommended by Charité, Germany. Our findings revealed that the presence of one or two SNVs in the primer or probe region affected the sensitivity of reverse transcription-quantitative polymerase chain reaction and droplet digital PCR to varying extents. This discovery underscores the importance of continuously monitoring the whole genome sequences of SARS-CoV-2 variants, especially the primer-probe targeting regions, and correspondingly updating commercial test kits or recommended primer-probe sequence sets.IMPORTANCEThe emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has resulted in a growing number of mutations in its genome, presenting new challenges for the diagnosis of SARS-CoV-2 using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and droplet digital PCR (RT-ddPCR) methods. There is an urgent need to develop refined methods for modifying primers and probes to improve the detection of these emerging variants. In this study, our focus was on the SNVs that have emerged in the CDC-N1 and Charité-E primer-probe regions. Our research has confirmed that the presence of these SNVs in the primer or probe region can significantly affect the results of coronavirus disease 2019 tests. we have developed and validated a modified detection method that can provide higher sensitivity and specificity. This study emphasizes the importance of refining the primer-probe sets to ensure the diagnostic accuracy of RT-qPCR and RT-ddPCR detection.

Terrain correction is a key step to ensure the accuracy of risk zoning for hail disasters. This study utilizes the hail observations from 81 national meteorological stations in Anhui Province spanning from 1978 to 2020, along with geographic information data, gross domestic product (GDP), and historical disaster data, to identify causative factors for hail disasters and calculate the hazard-inducing intensity indices by employing statistical methods of correlation analysis and regression analysis. Then, a terrain-involved correction method for hail frequency is established, with the combination of hazard-inducing intensity and frequency, to conduct disaster risk evaluation. According to the theory of natural disaster risk assessment, the Geographic Information System-based economic risk zonation of hail disaster is performed by integrating the hazard-inducing factors and vulnerability factors. The feasibility of zoning results is further verified through the direct economic losses caused by hail disasters. The results show that: (1) the maximum hail diameter and duration of hailfall can be used as hail hazard-inducing factors, as both are significantly correlated with the damage index of hail disaster. The terrain-corrected spatial distributions of hail frequency are well consistent with the actual observations, which better represent spatial distribution variations in high-altitude mountainous areas. (2) the hail-prone areas, as well as the high-risk areas, are located in several regions along the main paths of hail disaster, such as to the north of the Huaihe River, in the eastern regions between the Yangtze River and Huai River, as well as in the mountainous areas of Dabie Mountains and the south part in Anhui Province. (3) The overall economic risk of hail disasters gradually decreases from north to south. The validation by direct economic losses suggests that the correlation coefficient between the economic risk index of hail disaster and the average of direct economic losses over multiple years in Anhui province has passed the significance test with a confidence level of 99%, and the zoning results agree well with the true situations.

C1GALT1 plays a pivotal role in colorectal cancer (CRC) development and progression through its involvement in various molecular mechanisms. This enzyme is central to the O-glycosylation process, producing tumor-associated carbohydrate antigens (TACA) like Tn and sTn, which are linked to cancer metastasis and poor prognosis. The interaction between C1GALT1 and core 3 synthase is crucial for the synthesis of core 3 O-glycans, essential for gastrointestinal health and mucosal barrier integrity. Aberrations in this pathway can lead to CRC development. Furthermore, C1GALT1's function is significantly influenced by its molecular chaperone, Cosmc, which is necessary for the proper folding of T-synthase. Dysregulation in this complex interaction contributes to abnormal O-glycan regulation, facilitating cancer progression. Moreover, C1GALT1 affects downstream signaling pathways and cellular behaviors, such as the epithelial-mesenchymal transition (EMT), by modifying O-glycans on key receptors like FGFR2, enhancing cancer cell invasiveness and metastatic potential. Additionally, the enzyme's relationship with MUC1, a mucin protein with abnormal glycosylation in CRC, highlights its role in cancer cell immune evasion and metastasis. Given these insights, targeting C1GALT1 presents a promising therapeutic strategy for CRC, necessitating further research to develop targeted inhibitors or activators. Future efforts should also explore C1GALT1's potential as a biomarker for early diagnosis, prognosis, and treatment response monitoring in CRC, alongside investigating combination therapies to improve patient outcomes.

Sewage sludge odorous gas release is a key barrier to resource utilization, and conditioners can mitigate the release of sulfur-containing gases. The gas release characteristics and sulfur compound distribution in pyrolysis products under both single and composite conditioning strategies of CaO, Fe2O3, and FeCl3 were investigated. This study focused on the inhibition mechanisms of these conditioners on sulfur-containing gas emissions and compared the theoretical and experimental sulfur content in the products to evaluate the potential synergistic effects of the composite conditioners. The findings indicated that at 650 °C, CaO, Fe2O3, and FeCl3 inhibited H2S release by 35.8%, 23.2%, and 9.1%, respectively. Notably, the composite of CaO with FeCl3 at temperatures ranging from 350 to 450 °C and the combination of Fe2O3 with FeCl3 at 650 °C were found to exert synergistic suppression on H2S emissions. The strongly alkaline CaO inhibited the metathesis reaction between HCl, a decomposition product of FeCl3, and the sulfur-containing compounds within the sewage sludge, thereby exerting a synergistic suppression on the emission of H2S. Conversely, at temperatures exceeding 550 °C, the formation of Ca-Fe compounds, such as FeCa2O4, appeared to diminish the sulfur-fixing capacity of the conditioners, resulting in increased H2S emissions. For instance, the combination of CaO and FeCl3 at 450 °C was found to synergistically reduce H2S emissions by 56.3%, while the combination of CaO and Fe2O3 at 650 °C synergistically enhances the release of H2S by 23.6%. The insights gained from this study are instrumental in optimizing the pyrolysis of sewage sludge, aiming to minimize its environmental footprint and enhance the efficiency of resource recovery.

IntroductionpH is one of the important factors affecting the growth and performance of microorganisms.MethodsWe studied the pH response and plant growth-promoting (PGP) ability of Rhizopus delemar using cultivation experiments and transcriptomics, and verified the expression profiles using quantitative real-time PCR.ResultspH affected the growth and PGP properties of R. delemar. At pH 7, the growth rate of R. delemar was rapid, whereas pH 4 and 8 inhibited mycelial growth and PGP ability, respectively. In the pot experiment, the plant height was the highest at pH 7, 56 cm, and the lowest at pH 4 and pH 5, 46.6 cm and 47 cm, respectively. Enzyme activities were highest at pH 6 to pH 7. Enzyme activities were highest at pH 6 to pH 7. Among the 1,629 differentially expressed genes (DEGs), 1,033 genes were up-regulated and 596 were down-regulated. A total of 1,623 DEGs were annotated to carbohydrate-active enzyme coding genes.DiscussionThe PGP characteristics, e.g., Phosphorus solubilization ability, of R. delemar were strongest at pH 7. The results provide useful information regarding the molecular mechanism of R. delemar pH response.

While utilizing hydrothermal resources, it is necessary to reinject wastewater into the reservoir through reinjection wells to extract heat without mining groundwater. Chemical clogging is a serious problem in the process of reinjection. The precipitation of minerals can lead to reservoir clogging and the reduction of permeability. Therefore, to study the effect of chemical clogging on permeability, the weakly consolidated sandstone of the Neogene Guantao Formation geothermal reservoir in northern Shandong (Eastern China) was taken as the research object. A long-term thermal-hydro-mechanical-chemistry (THMC) coupling reinjection experiment was carried out. The results showed that when the temperature of wastewater was higher than 45 °C, there was a temporary phase of permeability enhancement in the first 10 min of reinjection. However, wastewater with higher temperatures would cause more chemical clogging eventually. XRD and ion analysis results showed that the precipitation of minerals was mainly potash feldspar, illite, calcite, and other carbonate minerals during reinjection. According to the characteristics of low-TDS wastewater in the Guantao Formation, it is recommended to adopt low-temperature wastewater reinjection and reduce the concentration of Ca2+ and Mg2+ in wastewater before reinjection. HIGHLIGHTS Water–rock chemical reactions cause the precipitation of minerals.; Permeability is an important parameter to characterize blockage.; XRD and ion concentration were used to analyze chemical blockage.; There was a temporary phase of permeability enhancement in the first 10 min of reinjection.; Tailwater with higher temperatures will cause more blockage eventually.;

ObjectivesOscillatory patterns in local field potentials (LFPs) have been recognized as disease-specific physiomarkers, particularly in the context of Parkinson’s disease and cervical dystonia. This characteristic oscillatory feature is currently employed in adaptive deep brain stimulation (aDBS). However, for other types of dystonia, especially Meige syndrome, a distinct physiomarker of this nature is yet to be identified.MethodsLocal field potentials were recorded during microelectrode-guided deep brain stimulation surgery from 28 patients with primary Meige syndrome. Before surgery, the severity of patients’ motor syndrome were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale-Motor (BFMDRS-M). An instantaneous oscillation detection method was employed to identify true narrowband oscillations. Subsequently, a linear mixed effects model was utilized to examine the relationship between oscillatory activities (including power amplitude and burst duration) and symptom severity.ResultsThe focal peaks of “oscillatory activities” detected were predominantly concentrated in the narrow theta band (4–8 Hz), constituting 81.5% of the total detected oscillations in all recording sites near active DBS contacts in the globus pallidus internus (GPi). The linear mixed effects model revealed a positive correlation between the theta burst duration and the severity of preoperative motor impairment, but no correlation with postoperative motor scores. Additionally, there was no significant lateralization effect observed between the left and right GPi.ConclusionOur findings suggest that the exaggerated narrowband theta activity (mainly the burst duration) in the GPi is predictive of dystonia symptom severity and may be used as a physiomarker for optimized DBS target during surgery and adaptive DBS for the treatment of Meige syndrome.

Cancer presents a formidable threat to human health, with the majority of cases currently lacking a complete cure. Frequently, chemotherapy drugs are required to impede its progression. However, these drugs frequently suffer from drawbacks such as poor selectivity, limited water solubility, low bioavailability, and a propensity for causing organ toxicity. Consequently, a concerted effort has been made to seek improved drug delivery systems. Nano-drug delivery systems based on biodegradable polyesters have emerged as a subject of widespread interest in this pursuit. Extensive research has demonstrated their potential for offering high bioavailability, effective encapsulation, controlled release, and minimal toxicity. Notably, poly (ε-caprolactone) (PCL), poly (lactic-co-glycolic acid) (PLGA), and polylactic acid (PLA) have gained prominence as the most widely utilized options as carriers of the nano drug delivery system. This paper comprehensively reviews recent research on these materials as nano-carriers for delivering chemotherapeutic drugs, summarizing their latest advancements, acknowledging their limitations, and forecasting future research directions.

Rice straw (RS) is the residue obtained during the rice processing process, and is recognized as one of the most abundant biomass resources in the world. Approximately 800 million to 1 billion tons of rice straw are produced globally every year, and most of them are considered general waste and typically end up in landfills or incineration. This approach wastes resources and can also lead to environmental pollution. In the current study, the RS was used as the source of biodiesel production and a comprehensive process model of the RS valorization process was developed to evaluate the energy flow, production efficiency, production costs, and greenhouse gas emissions in Hunan Province, China. The evaluation results showed that the energy efficiency of biodiesel production from rice straw and the overall energy efficiency of the rice straw valorization process are reported as 52.1% and 56.1%, respectively. The minimum selling price of biodiesel, which is CNY 3.03/kg, is considerably lower than the current market prices for similar products in China. The largest proportion of the production cost of biodiesel is the cost of natural gas, followed by utilities, capital, transportation, plant maintenance and overheads, consumables, labor, and waste disposal. For the current RS valorization plant with a 5000 kg/h RS feed rate, the investment payback times are 8.9 yr and 7.1 yr when the biodiesel is sold at the lowest (CNY 4/kg) and highest (CNY 4.6/kg) market price, respectively. Environmental analysis shows that the greenhouse gas emissions intensity of biodiesel production is 75.8 g CO2eq/MJ, which is only about 52% of traditional fossil diesel and indicating that biodiesel is an environmentally friendly energy source.

Homologous ventricular electrical separation is a rare electrocardiogram manifestation; it is defined as a specific subtype of ventricular separation caused by excitation that originates from the supraventricular rhythm and travels through the His-Pukenje system, resulting in severe asynchrony of biventricular depolarization and production of 2 QRS complexes. It always indicates irreversible cardiac impairment and electrical instability. (Level of Difficulty: Advanced.)

The present study aims to investigate the relationship between sustainable leadership styles and frugal innovation in SMEs in the Chinese context. We also investigate the role of knowledge sharing as a mediator in the relationship between SL-FI. Furthermore, this study introduces the situational variable organizational innovation climate to explore its moderating role between KS-FI. The data were collected from corporate employees of SMEs in China’s manufacturing and service industries, with a 67.7% response rate on the questionnaire. The hypotheses were tested in this study using SmartPLS 4.0.8.7, and the empirical findings of this study revealed that sustainable leadership positively affects frugal innovation, with the knowledge-sharing process serving as a partial mediating effect. In addition, the results revealed that a higher level of organizational innovation climate will result in a higher effect of knowledge sharing on frugal innovation. The results of the current study provide insights and empirical evidence on the importance of frugal innovation in emerging markets and the ability to improve firms’ frugal innovation through leadership practices and knowledge resources. The current study provides a new contribution as it links sustainable leadership, knowledge sharing, and frugal innovation in the context of China as an emerging country. The research findings contribute to expanding the literature in the area of leadership styles and innovation, and provide practical insights for policymakers, entrepreneurs, and others in developing countries and emerging market SMEs.

To investigate the control mechanisms of NOx precursors and the synergistic effects of composite catalysts during proline pyrolysis, a systematic series of experiments was conducted utilizing composite catalysts with varying Fe-Ca ratios. Product distribution analysis was employed to elucidate the catalysts’ mechanisms in reducing NOx precursor emissions. The synergistic interactions between Fe and Ca were quantitatively assessed through comparative theoretical and experimental release calculations. The results indicate that an increase in the Fe content in the catalyst led to a rise in amine concentrations from 0.9% to 2.95%, implying that Fe facilitates the generation of amine-N through ring-opening and substitution reactions. When the Fe to Ca ratio was balanced at 1:1, nitrogen predominantly participated in the formation of purines via cyclization and substitution reactions. Additionally, all composite catalysts exhibited a suppressive effect on the release of NOx precursors, attributed to their significant enhancement of solid product retention. Fe-Ca composite catalyst synergistically inhibits the release of gaseous nitrogen. Notably, the strongest synergistic effect was observed with a 1:3 Fe to Ca ratio, which reduced the release of NH3 by 38.7% and HCN by 53.6% during proline pyrolysis. This study offers valuable insights into the control of NOx precursors and the optimization of nitrogen-rich biomass pyrolysis processes.

Identifying objectively the processes of regional climate events and evaluating quantitatively their intensity are the basis for accurately monitoring and assessing the impacts of events. Using the data of daily mean precipitation and temperature from 80 national meteorological stations in Anhui Province during 1961-2020, the processes of regional extreme climate events are identified. According to the averaged intensity, duration and average influence range, the intensity evaluation model of regional process is constructed and the intensity grade is divided by the percentile method. The 775 regional rainstorm events are captured, and the annual average frequency is 12.9 times during 1961-2020, including 34 extremely strong regional events, about once in two years. The average duration of single regional rainstorm event is about 1-2 days, and the daily average spatial coverage of a single event covers 37 stations. The frequency and intensity of regional rainstorm event has increased significantly in nearly 60 years. In the past 60 years, there have been 152 regional drought events in Anhui Province, including 9 extremely strong regional events with a return period of about 6~7 years. The average duration of single regional drought event is about 15-60 days. The linear change trend of annual frequency of regional drought event is not obvious, but the inter-annual variation is large. Compared with the summary of climate monitoring services and historical cases, the assessment model is reasonable and consistent with historical extreme cases, having good correspondence with historical disaster data in time, range, and intensity. This index will provide a reference for the quantitative assessment of regional extreme climate events in other areas, and it is also an important technical support for timely monitoring and early warning for the extreme climate events.

ABSTRACT Senecavirus A (SVA) is a type of nonenveloped single-stranded, positive-sense RNA virus. The VP2 protein is a structural protein that plays an important role in inducing early and late immune responses of the host. However, its antigenic epitopes have not been fully elucidated. Therefore, defining the B epitopes of the VP2 protein is of great importance to revealing its antigenic characterization. In this study, we analyzed B-cell immunodominant epitopes (IDEs) of the VP2 protein from the SVA strain CH/FJ/2017 using the Pepscan approach and a bioinformatics-based computational prediction method. The following four novel IDEs of VP2 were identified: IDE1, 41TKSDPPSSSTDQPTTT56; IDE2, 145PDGKAKSLQELNEEQW160; IDE3, 161VEMSDDYRTGKNMPF175; and IDE4, 267PYFNGLRNRFTTGT280. Most of the IDEs were highly conserved among the different strains. To our knowledge, the VP2 protein is a major protective antigen of SVA that can induce neutralizing antibodies in animals. Here, we analyzed the immunogenicity and neutralization activity of four IDEs of VP2. Consequently, all four IDEs showed good immunogenicity that could elicit specific antibodies in guinea pigs. A neutralization test in vitro showed that the peptide-specific guinea pig antisera of IDE2 could neutralize SVA strain CH/FJ/2017, and IDE2 was identified as a novel potential neutralizing linear epitope. This is the first time VP2 IDEs have been identified by using the Pepscan method and a bioinformatics-based computational prediction method. These results will help elucidate the antigenic epitopes of VP2 and clarify the basis for immune responses against SVA. IMPORTANCE The clinical symptoms and lesions caused by SVA are indistinguishable from those of other vesicular diseases in pigs. SVA has been associated with recent outbreaks of vesicular disease and epidemic transient neonatal losses in several swine-producing countries. Due to the continuing spread of SVA and the lack of commercial vaccines, the development of improved control strategies is urgently needed. The VP2 protein is a crucial antigen on the capsids of SVA particles. Furthermore, the latest research showed that VP2 could be a promising candidate for the development of novel vaccines and diagnostic tools. Hence, a detailed exploration of epitopes in the VP2 protein is necessary. In this study, four novel B-cell IDEs were identified using two different antisera with two different methods. IDE2 was identified as a new neutralizing linear epitope. Our findings will help in the rational design of epitope vaccines and further understanding of the antigenic structure of VP2.

ABSTRACT African swine fever virus (ASFV) causes acute hemorrhagic infectious disease in pigs. The ASFV genome encodes various proteins that enable the virus to escape innate immunity; however, the underlying mechanisms are poorly understood. The present study found that ASFV MGF-360-10L significantly inhibits interferon (IFN)-β-triggered STAT1/2 promoter activation and the production of downstream IFN-stimulated genes (ISGs). ASFV MGF-360-10L deletion (ASFV-Δ10L) replication was impaired compared with the parental ASFV CN/GS/2018 strain, and more ISGs were induced by the ASFV-Δ10L in porcine alveolar macrophages in vitro. We found that MGF-360-10L mainly targets JAK1 and mediates its degradation in a dose-dependent manner. Meanwhile, MGF-360-10L also mediates the K48-linked ubiquitination of JAK1 at lysine residues 245 and 269 by recruiting the E3 ubiquitin ligase HERC5 (HECT and RLD domain-containing E3 ubiquitin protein ligase 5). The virulence of ASFV-Δ10L was significantly lower than that of the parental strain in vivo, which indicates that MGF-360-10L is a novel virulence factor of ASFV. Our findings elaborate the novel mechanism of MGF-360-10L on the STAT1/2 signaling pathway, expanding our understanding of the inhibition of host innate immunity by ASFV-encoded proteins and providing novel insights that could contribute to the development of African swine fever vaccines. IMPORTANCE African swine fever outbreaks remain a concern in some areas. There is no effective drug or commercial vaccine to prevent African swine fever virus (ASFV) infection. In the present study, we found that overexpression of MGF-360-10L strongly inhibited the interferon (IFN)-β-induced STAT1/2 signaling pathway and the production of IFN-stimulated genes (ISGs). Furthermore, we demonstrated that MGF-360-10L mediates the degradation and K48-linked ubiquitination of JAK1 by recruiting the E3 ubiquitin ligase HERC5. The virulence of ASFV with MGF-360-10L deletion was significantly less than parental ASFV CN/GS/2018. Our study identified a new virulence factor and revealed a novel mechanism by which MGF-360-10L inhibits the immune response, thus providing new insights into the vaccination strategies against ASFV.

Carbon dioxide blasting provides a new technical idea and way to stimulate hot dry rock reservoirs. To explore the effect of carbon dioxide blasting-induced cracking on dry-hot rock reservoirs, a numerical simulation for the action range of carbon dioxide blasting-induced cracking of hot dry rock was carried out. Considering the cooling effect of drilling fluid on the hot dry rock reservoir near the wellbore in the actual mining process, the fitting functions with temperature difference as a variable were adopted to set the material parameters of the reservoir in the damaged area, and the temperature distribution functions of the reservoir near the wellbore after well washing were adopted to set the temperature field of the reservoir in the damaged area. The blasting load was set by the relevant theories and formulas of explosive blasting. Combined with COMSOL software, the process of carbon dioxide blasting to stimulate hot dry rock reservoirs was simulated. The results showed that there were multiple stress concentrations in the process of the dry hot rock cracking caused by carbon dioxide blasting, the compressive stress concentration near the blast hole produced the crushing zone, and the tensile stress outside the crushing zone formed the fracture zone. In addition, the initial temperature of the reservoir and the thickness of the pressure plate would affect the effect of carbon dioxide blasting fracturing to stimulate dry and hot rock reservoirs. The initial temperature had a great influence on the scope of the blasting crushing zone and had little influence on the scope of the fracture zone. The thickness of the pressure plate had little influence on the scope of the crushing zone, which mainly affected the distribution of the blasting fracture zone. The research results could provide a theoretical support and a reference for the subsequent exploitation and utilization of dry-hot rock geothermal energy.

In commercial dairy farms, mastitis is associated with increased antimicrobial use and associated resistance, which may affect milk production. This study aimed to develop sensor-based prediction models for naturally occurring clinical bovine mastitis using nine machine learning algorithms with data from 447 mastitic and 2146 healthy cows obtained from five commercial farms in Northeast China. The variables were related to daily activity, rumination time, and daily milk yield of cows, as well as milk electrical conductivity. Both Z-standardized and non-standardized datasets pertaining to four specific stages of lactation were used to train and test prediction models. For all four subgroups, the Z-standardized dataset yielded better results than those of the non-standardized one, with the multilayer artificial neural net algorithm showing the best performance. Variables of importance had a similar rank in this algorithm, indicating the consistency of these variables as predictors for bovine mastitis in commercial farms with similar automatic systems. Moreover, the peak milk yield (PMY) of mastitic cows was significantly higher than that of healthy cows (p < 0.005), indicating that high-yielding cattle are more prone to mastitis. Our results show that machine learning algorithms are effective tools for predicting mastitis in dairy cows for immediate intervention and management in commercial farms.

The horizontal well multi-fracture development technology, which is well-developed in the oil and gas industry, can significantly improve the economics of enhanced geothermal systems (EGS). In this paper, a three-dimensional horizontal-well multi-fracture physical model is established for EGS. The performances of EGS under different reservoir characteristics of well spacing and fracture spacing are analyzed by CFX simulation, and the influence mechanism of different reservoir characteristics on the heat recovery process of the EGS reservoir is revealed. The results show that: ①The fracture spacing is the key factor affecting the operating life and mining rate of EGS engineering. Under the same water injection flow, the larger the fracture spacing, the smaller the possibility of forming thermal permeability, the longer the system operation life, but the lower the reservoir recovery rate. The smaller the fracture spacing, the higher the thermal permeability, the shorter the system life, and the higher the reservoir recovery.②The well spacing has a significant effect on the fluid velocity in the fracture. As the well spacing increases, the temperature of the flow-producing fluid increases continuously during the same mining time, and the life of the system also increases. The increase in well spacing also means that the reservoir volume becomes large, so there is more geothermal energy for exploitation and longer life for the system for operating. The research can provide theoretical guidance for the construction of EGS reservoirs and provide theoretical preparation for the commercial exploitation of geothermal energy.

High-temperature rock cooling can occur in the whole process of the drilling, fracturing, and heat exchange during the geothermal energy exploitation in hot dry rock. To reveal the evolution law of rock damage, based on the Brazilian splitting test and acoustic emission technology, the effects of different high temperatures and cooling methods on the tensile properties of granite were studied. The results showed that: ①The tensile strength of granite decreases with increasing temperature from 25℃ to 600℃, and the temperature threshold, at which it decreases greatly, is advanced to 200℃ after cooling with water. After 500℃, the tensile strength is more sensitive to water cooling. ②When the load reaches the peak value, the cumulative ringing count of acoustic emission suddenly increases, and the fracture zone forms in the rock sample. Under the influence of water cooling, the ringing count peak value and energy peak value of the rock sample decrease, which indirectly reflects that the internal cracks of the rock are more developed, and both of their decrease range is larger at 200~300℃. The granite is more sensitive to heat treatment at 300℃ and after 500℃. ③With the increase in temperature, the fracture surface of granite changes from flat to rough and tortuous, from brittle to ductile; Cooling in water promotes rock fracture and advances the temperature range from brittleness to ductility. The research results provide a theoretical reference for the stability evaluation of high-temperature rocks in geothermal exploitation.

IntroductionMeige syndrome (MS) is an adult-onset segmental dystonia disease, mainly manifested as blepharospasm and involuntary movement caused by dystonic dysfunction of the oromandibular muscles. The changes of brain activity, perfusion and neurovascular coupling in patients with Meige syndrome are hitherto unknown.MethodsTwenty-five MS patients and thirty age- and sex-matched healthy controls (HC) were prospectively recruited in this study. All the participants underwent resting-state arterial spin labeling and blood oxygen level-dependent examinations on a 3.0 T MR scanner. The measurement of neurovascular coupling was calculated using cerebral blood flow (CBF)-functional connectivity strength (FCS) correlations across the voxels of whole gray matter. Also, voxel-wised analyses of CBF, FCS, and CBF/FCS ratio images between MS and HC were conducted. Additionally, CBF and FCS values were compared between these two groups in selected motion-related brain regions.ResultsMS patients showed increased whole gray matter CBF-FCS coupling relative to HC (t = 2.262, p = 0.028). In addition, MS patients showed significantly increased CBF value in middle frontal gyrus and bilateral precentral gyrus.ConclusionThe abnormal elevated neurovascular coupling of MS may indicate a compensated blood perfusion in motor-related brain regions and reorganized the balance between neuronal activity and brain blood supply. Our results provide a new insight into the neural mechanism underlying MS from the perspective of neurovascular coupling and cerebral perfusion.

BackgroundVisuospatial dysfunction and cognitive impairment are common in Parkinson’s disease (PD), which draw increasing attention in the current literature. But clinicians still lack rapid, effective and unified cognitive battery for visuospatial assessment.ObjectiveA new approach was studied to explore the feasibility of using mobile application software (APP) to evaluate visuospatial dysfunction in patients with PD and compared with traditional assessment tools. We aimed to verify the threshold score of the APP for early diagnosis.Materials and methodsA total of 41 patients with PD underwent assessments using several test modules including Digit Symbol Test (DST), Visual Organization Test (VOT), Facial Recognition Test (FRT), Vocabulary Memory Test (VMT) of this APP, as well as Clock Drawing Test (CDT), Cube Copying Test (CCT) and the Mini-Mental State Examination (MMSE) for comparison. Among the 41 PD patients, 30 individuals were found to have visuospatial dysfunction based on CDT score

Acquired amegakaryocytic thrombocypenia (AAMT) is an extremely rare hematologic disorder and standard treatment strategy has not been established. We described herein two cases of AAMT who were fully responded to eltrombopag and immunosuppressant. Patient 1 was refractory to steroid, IVIG and recombinant human thrombopoietin (rhTPO). Patient 2 did not respond to high dosage of steroid, IVIG, rhTPO and rituximab. Moreover, his AAMT progressed to aplastic anemia in 5 months. Both patients took eltrombopag and immunosuppressant, then they achieved long-term remission without obvious side effects. Our findings suggest that this combination can be a valuable alternative in AAMT.

Abstract Coronaviruses (CoVs) are a group of related enveloped RNA viruses that have severe consequences in a wide variety of animals by causing respiratory, enteric or systemic diseases. Porcine epidemic diarrhea virus (PEDV) is an economically important CoV distributed worldwide that causes diarrhea in pigs. nsp14 is a nonstructural protein of PEDV that is involved in regulation of innate immunity and viral replication. However, the function and mechanism by which nsp14 modulates and manipulates host immune responses remain largely unknown. Here, we report that PEDV nsp14 is an NF-κB pathway antagonist. Overexpression PEDV nsp14 protein remarkably decreases SeV-, poly (I:C)- and TNF-α-induced NF-κB activation. Meanwhile, expression of proinflammatory cytokines is suppressed by nsp14. nsp14 inhibits the phosphorylation of IKKs by interacting with IKKs and p65. Furthermore, nsp14 suppresses TNF-α-induced phosphorylation and nuclear import of p65. Overexpression nsp14 considerably increases PEDV replication. These results suggest a novel mechanism employed by PEDV to suppress the host antiviral response, providing insights that can guide the development of antivirals against CoVs.

Abstract Plants and soil interactions greatly affect ecosystems processes and properties. Ecological stoichiometry is an effective means to explore the C, N, P correlation between plants and soil and the relationship between plant growth and nutrient supply. Serious soil erosion on China’s Loess Plateau has further barrenness the soil. Fertilization solves the problem of ecosystem degradation by improving soil fertility and regulating the ecological stoichiometric between soil and plants. No fertilization (CK), nitrogen fertilization (N), phosphorus fertilization (P) and N and P combined fertilization (NP) treatments were set in an alfalfa grassland. Organic carbon (C), nitrogen (N) and phosphorus (P) nutrients and their stoichiometry were measured in shoot and soil. P and NP fertilization increased shoot C concentration (3.12%, 0.91%), and all fertilization decreased shoot N concentration (6.96%). The variation of shoot C and N concentrations resulted in a greater increase in shoot C:N under the fertilization treatment than that under CK (8.24%). Most fertilization treatments increased shoot P concentration (4.63%) at each cut, which induced a decrease of shoot C:P. Shoot N:P of most treatments were greater than 23, but it was lower under N and NP fertilization than that under CK. Fertilization only increased soil C in 2014, but had no effect on soil N. Soil P content was significantly higher under P fertilization in 2014 (34.53%), and all fertilization in the second cut of 2015 (124.32%). Shoot and soil C:P and N:P having the opposite changes to shoot and soil P, respectively. Our results suggest that the change of P after fertilization largely drove the changes of stoichiometric. The growth of alfalfa in the Loess Plateau was severely restricted by P. It is an effective method to increase the biomass of alfalfa by increasing the addition of N or NP fertilizer to alleviate P limitation.

Neovascular age-related macular degeneration (nAMD) with choroidal neovascularization (CNV) is a leading cause of blindness in the elderly in developed countries. The disease is currently treated with anti-angiogenic biologics, including aflibercept, against vascular endothelial growth factor (VEGF) but with limited efficacy, treatment resistance and requirement for frequent intravitreal injections. Although anti-VEGF gene therapy may provide sustained therapy that obviates multiple injections, the efficacy and side effects related to VEGF pathway targeting remain, and alternative strategies to block angiogenesis independently of VEGF are needed. We recently reported that secretogranin III (Scg3) induces only pathological angiogenesis through VEGF-independent pathways, and Scg3-neutralizing antibodies selectively inhibit pathological but not physiological angiogenesis in mouse proliferative retinopathy models. Anti-Scg3 antibodies synergize dose-dependently with VEGF inhibitors in a CNV model. Here, we report that an adeno-associated virus-8 (AAV8) vector expressing anti-Scg3 Fab ameliorated CNV with an efficacy similar to that of AAV-aflibercept in a mouse model. This study is the first to test an anti-angiogenic gene therapy protocol that selectively targets pathological angiogenesis via a VEGF-independent mechanism. The findings support further safety/efficacy studies of anti-Scg3 gene therapy as monotherapy or combined with anti-VEGF to treat nAMD.

Objective: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has been shown to be a safe and effective alternative therapy for ameliorating medically refractory primary Meige syndrome. However, the associations between DBS target position and surrounding electrophysiological properties as well as patients’ clinical outcomes remains largely unknown. In a large number of patients, we investigated electrophysiological features around stimulation targets and explored their roles in predicting clinical outcomes following bilateral GPi-DBS. Methods: The locations of DBS active contacts along the long axis of the GPi in a standard space were calculated and compared among three groups with different clinical outcomes. The firing rates of individual neurons within the GPi were calculated for each patient and compared across the three groups. Results: Compared with the bad group (poor clinical outcome), active contacts in the good group (good clinical outcome) and the best group (best clinical outcome) were located in the more posterior GPi. The average firing rates in the good and best groups were significantly higher than in the bad group, and this difference was pronounced within the ventral GPi. For the bad group, the average firing rates were significantly lower in the ventral than in the dorsal GPi. Conclusions: This study suggests that DBS of the posterior GPi may produce better clinical outcomes during primary Meige syndrome treatment and that higher GPi neuronal activity, particularly within the ventral part, can be used as a biomarker to guide DBS electrode implantation during surgery.

Background: Aplasia cutis congenita (ACC) and terminal transverse limb defects (TTLDs) are the most common features of Adams-Oliver syndrome (AOS). ARHGAP31 is one of the causative genes for autosomal dominant forms of AOS, meanwhile its variants may only cause isolated TTLD. Here, we report a proband presented with apparent TTLD but not ACC.Methods: Whole exome sequencing (WES) and Sanger sequencing were applied to identify causative genes. Expression vectors were constructed for transfections in mammalian cell cultures followed by biochemical and functional analysis including immunoblotting, immunofluorescence staining, and cell counting kit-8 assay.Results: WES and Sanger sequencing suggested that the proband inherited rare ARHGAP31 variant [c.2623G > A (p.Glu875Lys)] and a rare FBLN1 variant [c.1649G > A (p.Arg550His)] from one of her asymptomatic parents, respectively. Given FBLN1 variation has also been linked to syndactyly, we suspected that the two genes together contributed to the TTLD phenotype and explored their possible roles in vitro. Mutant FBLN1 showed reduced expression resulted from impaired protein stability, whereas ARHGAP31 protein expression was unaltered by mutation. Functional assays showed that only in the co-transfected group of two mutants cell viability was decreased, cell proliferation was impaired, and apoptosis was activated. Cdc42 activity was declined by both ARHGAP31 mutation and FBLN1 mutation alone, and the two together. Furthermore, the MAPK/ERK pathway was only activated by two mutants co-transfected group compared with two wild-type transfections.Conclusion: We report a case carrying two rare variants of limb defects associated genes, ARHGAP31 and FBLN1, and provide in vitro evidence that synergistic disruption of cellular functions attributed by the two mutants may potentiate the penetrance of clinical manifestations, expanding our knowledge of clinical complexity of causal gene interactions in TTLD and other genetic disorders.

Abstract Background The COVID-19 has caused significant toll over the globe. Pregnant women are at risk of infection. The present study examined the frequency of washing hands with soap and wearing face mask when going out, prevalence of depression and anxiety, and identified their associated factors among pregnant women during the early phase of COVID-19 outbreak in China. Methods A cross-sectional online survey was conducted between 24 February and 3 March 2020. A total of 15 428 pregnant women who were using maternal health care services in China completed a questionnaire which assessed their socio-demographic and pregnancy-related characteristics, contextual, cognitive and social factors related to COVID-19, frequency of washing hands and wearing face masks, and depression and anxiety. Logistics regression analyses were performed to identify the associated factors of preventive behaviours and mental health. Results The prevalence of probable anxiety and depression was 28.2% and 43.6% respectively. 19.8% reported always wearing face mask when going out, and 19.1% reported washing hands with soap for more than 10 times per day. Results from logistic regression analyses showed that older age was associated with lower levels of depression and anxiety (OR = 0.42–0.67) and higher frequency of washing hands (OR = 1.57–3.40). Higher level of education level was associated with probable depression (OR = 1.31–1.45) and higher frequency of wearing face mask (OR = 1.50–1.57). After adjusting for significant socio-demographic and pregnancy-related factors, place of residence being locked down (aOR = 1.10–1.11), being quarantined (aOR = 1.42–1.57), personally knowing someone being infected with COVID-19 (aOR = 1.80–1.92), perception that COVID-19 would pose long term physical harm to human (aOR = 1.25–1.28) were associated with higher levels of depression and anxiety, while the perception that the disease will be under control in the coming month was associated with lower levels of depression and anxiety (aOR = 0.59–0.63) and lower tendency of always wearing face mask (aOR = 0.85). Social support was associated with lower levels of depression and anxiety (aOR = 0.86–0,87) and higher frequency of washing hands (aOR = 1.06). Conclusions The mental health and preventive behaviours of pregnant women during COVID-19 outbreak was associated with a range of socio-demographic, pregnancy-related, contextual, cognitive and social factors. Interventions to mitigate their mental health problems and to promote preventive behaviours are highly warranted.

Based on precipitation data at Anhui meteorological stations and NCEP reanalysis data, in this paper we analyze the characteristics and the causes of Meiyu climate anomaly in Anhui Province in 2020, and evaluate the skill of climate prediction and the effectiveness of prediction precursor signals. The main conclusions are as following. (1) In Anhui Province, Meiyu onset date was June 2 and outset date was August 1. Meiyu duration was 60 days. Meiyu precipitation was 1 057 mm in South along the Yangtze River and 810 mm between Yangtze River and Huaihe Rive, and the rainfall intensity in many places reached the historical extreme value in 2020. On the whole, the length of Meiyu period, the wide coverage, the large amount of accumulated rainfall and the intensity of Meiyu reached the top level since 1961. (2) The main reason for the abnormal Meiyu is that the blocking high is active near the Ural Mountain and the East Siberian-Okhotsk Sea from June to July. The EAP wave train on the 500 hPa geopotential height anomaly field along the East Asian coast is obvious. The summer monsoon is weak. The Western Pacific Subtropical High is abnormally strong and located too far to west and south, which is conducive to the convergence of cold and warm air in Anhui Province. The water vapor transport from the west side of the subtropical high to the province is extremely strong. The reason for the longer Meiyu period is that the ridge line of subtropical high is northward in June and southward in July, which leads to the early onset and late demise of Meiyu. (3) In the previous winter and spring, there was a weak El Niño event in the equatorial central Pacific Ocean. Although the indication of ist influence on Meiyu in Anhui Province is not clear, the response signal is that the Indian Ocean SST and subtropical high are abnormally warm and strong. According to historical statistics, if the equatorial Middle East Pacific Ocean is basically in El Niño state in previous winter, the probability of more intensive Meiyu in these years is very high. Therefore, the Indian Ocean SST and Western Pacific Subtropical High response factors can be used as the starting points to improve the prediction ability of Meiyu in weak El Niño years.

Follicular Th (Tfh) cells are key CD4+ Th cells involved in regulating B cell differentiation in the germinal center. Mice with conditional KO (CKO) of B lymphocyte-induced maturation protein-1 (BLIMP-1) expression in CD11chi DCs (Prdm1 CKO) spontaneously develop a lupus-like disease. We found an increase in the number of Tfh cells in secondary lymphoid organs in lupus-prone Prdm1-CKO mice. B cells stimulated with Tfh cells become Ab-secreting cells (ASCs); there was an increase in ASC differentiation mediated by Tfh cells from Prdm1-CKO mice compared with Tfh cells from control mice. This was mainly due to the increased expression of molecules within the IL-23/IL-17 pathway in Tfh cells from Prdm1-CKO mice. There was an increased frequency of IL-17A+ Tfh cells in Prdm1-CKO mice. These Tfh cells secrete IL-17A and an increased amount of IL-21. Furthermore, neutralizing IL-17A and IL-21 reduced ASC differentiation induced by Tfh cells. Lastly, we found the expression of IL-1β and IL-6 was increased in BLIMP-1–deficient DCs, which are key for Th17 induction. Altogether, the lack of BLIMP-1 expression in DCs induces not only an increased number of Tfh cells, but also functionally distinct Tfh cells that lead to increased ASC differentiation.

A new approach to preparing the cesium antimonide photocathode has been developed. A tungsten sponge diffusion barrier layer, instead of the conventional nickel pipe, was used as the evaporation source so that a slow and uniform evaporation of the photoemissive materials, whose direction and amount could be well controlled, was realized. Then, the cathode substrate surface was modified with a nanoparticle layer, resulting in better photoemissive material adsorption and higher light absorbance. A new technique of treating the tungsten sponge, which worked as the barrier layer to the diffusion of the photoemissive materials, was studied. The tungsten–copper alloy was subjected to direct high-frequency heating in a vacuum chamber so that the copper in the alloy evaporated rapidly, resulting in smooth and shiny tungsten sponge. In comparison with the conventional method for fabricating the tungsten sponge, in which the copper in the tungsten–copper alloy was removed chemically, the new method removed the copper more completely, took less time, and caused less pollution. By means of direct-current magnetic sputtering, a layer of osmium nanoparticles of 50 nm diameter was deposited on the photocathode substrate surface. Then, a diode tube for the photocathode emission test equipped with a small titanium ion pump, whose pressure was as low as 5 × 10−8 Pa, was developed. A comparative emission performance test was carried out on the photocathode with the substrate surface covered with an osmium film vs that covered with osmium nanoparticles. The highest quantum efficiencies of the stable photoemission from the two photocathodes were 1.80 × 10−3 and 5.13 × 10−3, respectively. Moreover, the light absorptivity of the osmium nanoparticle-coated photocathode was 2.16 times that of the osmium film-coated photocathode, and the quantum efficiency of the former was 2.85 times that of the latter. Therefore, the improvement in the quantum efficiency of the osmium nanoparticle-coated photocathode is mainly attributed to the increase in the light absorptivity.

ABSTRACT African swine fever (ASF)—an aggressive infectious disease caused by the African swine fever virus (ASFV)—is significantly unfavorable for swine production. ASFV has a complex structure and encodes 150–167 proteins; however, the function of most of these proteins is unknown. This study identified ASFV MGF360-9L as a negative regulator of the interferon (IFN)-β signal. Further evidence showed that MGF360-9L interacts with signal transducer and activator of transcription (STAT) 1 and STAT2 and degrades STAT1 and STAT2 through apoptosis and ubiquitin–proteasome pathways, respectively. Subsequently, the activation of IFN-β signaling was inhibited. Naturally isolated or genetically manipulated live attenuated viruses are known to protect against the virulent parental ASFV strains. Therefore, through homologous recombination, we deleted MGF360-9L from the virulent ASFV CN/GS/2018 strain to construct a recombinant strain, ASFV-Δ360-9L. Compared with the parent ASFV CN/GS/2018 strain, the replication level of ASFV-Δ360-9L decreased in primary porcine alveolar macrophage cultures at 24 h postinfection, but the difference is unlikely to be biologically relevant. Notably, ASFV-Δ360-9L was partially attenuated in pigs. To our knowledge, this study is the first to uncover the function of MGF360-9L during ASFV infection. MGF360-9L inhibits IFN-β signaling through the targeted degradation of STAT1 and STAT2. Furthermore, MGF360-9L is a key virulence gene of ASFV. Our findings reveal a new mechanism by which ASFV inhibits host antiviral response; this might facilitate the development of live attenuated ASFV vaccines. IMPORTANCE African swine fever—an acute, febrile, hemorrhagic, highly contacting, and highly lethal disease caused by African swine fever virus (ASFV)—jeopardizes the global pig industry. Understanding the mechanism ASFV employs to evade host defense during infection is essential for developing targeted drugs and vaccines against ASFV. To our knowledge, this study identifies the mechanism of innate immunity against by MGF360-9L and the effect of MGF360-9L on ASFV pathogenicity. The results showed that MGF360-9L may help ASFV escape the host immunity by degrading STAT1 and STAT2 and thus inhibiting IFN-β signaling. MGF360-9L is also an important virulence factor of ASFV. The deletion of MGF360-9L reduces ASFV virulence in pigs. This study explored a new mechanism of ASFV against innate immunity and identified a new ASFV virulence factor; these findings may guide the development of live attenuated ASFV vaccines.

Purpose: The purpose of the study is to evaluate the effects of 0.01% atropine eye drops on accommodative system parameters among teenagers with low myopia.Methods: Ninety-five myopic teenagers [39 boys (8.69 ± 2.473) and 56 girls (8.54 ± 2.054) aged 5–17 years] with no history of eye disease were enrolled. Biometric and accommodative system parameters were evaluated before and at 1 week, 1 month, 3 months, and 6 months of 0.01% atropine eye drop instillation.Results: Participants without accommodative demand at 6 months demonstrated insignificant changes after the atropine instillation (all p > 0.05). Nevertheless, there were significant differences in accommodative sensitivity, accommodative amplitude, accommodative responsiveness, and negative relative accommodation (NRA) at 3 months compared with baseline after atropine instillation (all p < 0.05). Except spherical equivalent refraction, cornea thickness, intraocular pressure, and axial length were stable after the 0.01% atropine instillation (all p > 0.05).Conclusion: Morphologically, current measurements suggested that 0.01% atropine had favorable reduction of accommodation for childhood low myopia over a half-year period.

The study was designed to explore a clinical manifestation-based quantitative scoring model to assist the differentiation between psychogenic pseudosyncope (PPS) and vasovagal syncope (VVS) in children. In this retrospective case-control study, the training set included 233 pediatric patients aged 5–17 years (183 children with VVS and 50 with PPS) and the validation set consisted of another 138 patients aged 5–15 years (100 children with VVS and 38 with PPS). In the training set study, the demographic characteristics and clinical presentation of patients were compared between PPS and VVS. The independent variables were analyzed by binary logistic regression, and the score for each variable was given according to the approximate values of odds ratio (OR) to develop a scoring model for distinguishing PPS and VVS. The cut-off scores and area under the curve (AUC) for differentiating PPS and VVS cases were calculated using receiver operating characteristic (ROC) curve. Then, the ability of the scoring model to differentiate PPS from VVS was validated by the true clinical diagnosis of PPS and VVS in the validation set. In the training set, there were 7 variables with significant differences between the PPS and VVS groups, including duration of loss of consciousness (DLOC) (p < 0.01), daily frequency of attacks (p < 0.01), BMI (p < 0.01), 24-h average HR (p < 0.01), upright posture (p < 0.01), family history of syncope (p < 0.05) and precursors (p < 0.01). The binary regression analysis showed that upright posture, DLOC, daily frequency of attacks, and BMI were independent variables to distinguish between PPS and VVS. Based on the OR values of each independent variable, a score of 5 as the cut-off point for differentiating PPS from VVS yielded the sensitivity and specificity of 92.0% and 90.7%, respectively, and the AUC value was 0.965 (95% confidence interval: 0.945–0.986, p < 0.01). The sensitivity, specificity, and accuracy of this scoring model in the external validation set to distinguish PPS from VVS were 73.7%, 93.0%, and 87.7%, respectively. Therefore, the clinical manifestation-based scoring model is a simple and efficient measure to distinguish between PPS and VVS.

Objective: Anxiety symptoms are persistent in Parkinson’s disease (PD), but the underlying neural substrates are still unclear. In the current study, we aimed to explore the underlying neural mechanisms in PD patients with anxiety symptoms. Methods: 42 PD-A patients, 41 PD patients without anxiety symptoms (PD-NA), and 40 healthy controls (HCs) were recruited in the present study. All the subjects performed 3.0T fMRI scans. The fractional amplitude of low-frequency fluctuation (fALFF) analysis was used to investigate the alterations in neural activity among the three groups. A Pearson correlation analysis was performed between the altered fALFF value of the PD-A group and anxiety scores. Results: Compared with HCs, PD-A patients had higher fALFF values in the left cerebellum, cerebellum posterior lobe, bilateral temporal cortex, and brainstem and lower fALFF values in the bilateral inferior gyrus, bilateral basal ganglia areas, and left inferior parietal lobule. Moreover, between the two PD groups, PD-A patients showed higher fALFF values in the right precuneus and lower fALFF values in the bilateral inferior gyrus, bilateral basal ganglia areas, left inferior parietal lobule, and left occipital lobe. Furthermore, Pearson’s correlation analysis demonstrated that the right precuneus and left caudate were correlated with the Hamilton Anxiety Rating Scale scores. Conclusion: Our study found that anxiety symptoms in PD patients may be related to alterations of neurological activities in multiple brain regions. Furthermore, these may be critical radiological biomarkers for PD-A patients. Therefore, these findings can improve our understanding of the pathophysiological mechanisms underlying PD-A.

Acute leukemia during pregnancy (P-AL) is a rare disease with limited data regarding the management and outcomes of mothers and fetuses. We retrospectively analyzed the characteristics, pregnancy outcomes and maternal and neonatal prognoses of 52 patients with P-AL collected from January 2013 to December 2020 in our center. Seventeen (32.7%) patients received chemotherapy during pregnancy (exposed cohort), while 35 (67.3%) received chemotherapy after abortion/delivery (nonexposed cohort). Twenty-six (50.0%) pregnancies ended with abortion, and 26 (50.0%) babies were born through spontaneous delivery or cesarean section. Seven infants (26.9%) were born in the exposed cohort, while 19 infants (73.1%) were born in the nonexposed cohort. Fetuses in the exposed cohort had lower gestational ages (P=0.030) and birth weights (P=0.049). Considering the safety of the fetus, seven patients in the exposed cohort received low-dose chemotherapy, one patient received all-trans retinoic acid (ATRA) and one patient only received corticosteroids as induction therapy. Patients received low-dose chemotherapy as induction therapy had a lower complete remission (CR) rate (P=0.041), and more patients in this group received HSCT (P=0.010) than patients received intensive chemotherapy. Patients who delayed chemotherapy in the nonexposed cohort experienced a trend toward a higher mortality rate than patients who received timely chemotherapy (P=0.191). The CR (P = 0.488), OS (P=0.655), and DFS (P=0.453) were similar between the exposed and nonexposed cohorts. Overall, the 4-year overall survival (OS) and disease-free survival (DFS) rates were estimated at 49.1% and 57.8%, respectively. All newborns were living, without deformities, or developmental and intellectual disabilities. Our study indicated that P-AL patients in the first trimester might tend to receive chemotherapy after abortion. Both the status of disease and patients’ willingness should be taken into consideration when clinicians were planning treatment strategies in the second or third trimester. Low-dose or delayed chemotherapy might decrease the efficacy of induction therapy and survival rate of patients, but HSCT could improve the prognosis.

The osteoclast-dependent bone resorption process is a crucial part of the bone regulatory system. The excessive function of osteoclasts can cause diseases of bone, joint, and other tissues such as osteoporosis and osteoarthritis. Greenshell mussel oil (GSM), a good source of long chain omega-3 polyunsaturated fatty acids (LCn-3PUFAs), was fractionated into total lipid, polar lipid, and non-polar lipid components and their anti-osteoclastogenic activity tested in RAW 264.7 cell cultures. Osteoclast differentiation process was achieved after 5 days of incubation with RANKL in 24-well culture plates. Introducing the non-polar lipid fraction into the culture caused a lack of cell differentiation, and a reduction in tartrate-resistant acid phosphatase (TRAP) activity and TRAP cell numbers in a dose-dependent manner (50% reduction at the concentration of 20 μg/mL, p

This article shows a global gradient estimate in the framework of Orlicz spaces for general parabolic obstacle problems with p(t,x)-Laplacian in a bounded rough domain. It is assumed that the variable exponent p(t,x) satisfies a strong log-Holder continuity, that the associated nonlinearity is measurable in the time variable and have small BMO semi-norms in the space variables, and that the boundary of the domain has Reifenberg flatness.