Search

IntroductionMonkeypox virus (MPXV) hosts are of multiple species, with a risk of cross-species transmission. This phenomenon poses a threat to unreported affected domestic animals and increases the risk to human public health. Clinical diagnostics continue to face challenges regarding specificity among poxviruses. The need for a rapid and precise assay to differentiate between MPXV clades I and II, as well as goatpox virus (GTPV) is essential for enhancing our capacity for disease prevention, control, and epidemiological investigation.MethodsTo address this need, we have successfully developed a multiplex real-time PCR assay targeting MPXV D14L gene for clade I, MPXV D18L gene for clade II, and GTPV RPO30 gene, which can simultaneously detect MPXV clades I and II as well as GTPV.ResultsThe developed assay demonstrated high sensitivity, with limits of detection at 207.83 copies/reaction for MPXV clade I, 252.07 copies/reaction for MPXV clade II, and 208.72 copies/reaction for GTPV. Importantly, there was no cross-reactivity with other non-pox viruses which infect goats. The assay exhibited excellent repeatability, with coefficients of variation (CV%) for intra-assay and inter-assay ranging from 0.17% to 0.89% and 0.58% to 1.09%, respectively.DiscussionThis assay can serve as a vital resource to safeguard against the MPXV epidemic posing a threat to the life safety of goats, to mitigate potential risks to the sheep farming industry, and to prevent the transmission of MPXV to humans through sheep, which could act as a potential transmission vector for infection.

BackgroundInvestigation into the immune heterogeneity linked with atherosclerosis remains understudied. This knowledge gap hinders the creation of a robust theoretical framework essential for devising personalized immunotherapies aimed at combating this disease.MethodsSingle-cell RNA sequencing (scRNA-seq) analysis was employed to delineate the immune cell-type landscape within atherosclerotic plaques, followed by assessments of cell-cell interactions and phenotype characteristics using scRNA-seq datasets. Subsequently, pseudotime trajectory analysis was utilized to elucidate the heterogeneity in cell fate and differentiation among macrophages. Through integrated approaches, including single-cell sequencing, Weighted Gene Co-expression Network Analysis (WGCNA), and machine learning techniques, we identified hallmark genes. A risk score model and a corresponding nomogram were developed and validated using these genes, confirmed through Receiver Operating Characteristic (ROC) curve analysis. Additionally, enrichment and immune characteristic analyses were conducted based on the risk score model. The model’s applicability was further corroborated by in vitro and in vivo validation of specific genes implicated in atherosclerosis.ResultThis comprehensive scRNA-seq analysis has shed new light on the intricate immune landscape and the role of macrophages in atherosclerotic plaques. The presence of diverse immune cell populations, with a particularly enriched macrophage population, was highlighted by the results. Macrophage heterogeneity was intricately characterized, revealing four distinct subtypes with varying functional attributes that underscore their complex roles in atherosclerotic pathology. Intercellular communication analysis revealed robust macrophage interactions with multiple cell types and detailed pathways differing between proximal adjacent and atherosclerotic core groups. Furthermore, pseudotime trajectories charted the developmental course of macrophage subpopulations, offering insights into their differentiation fates within the plaque microenvironment. The use of machine learning identified potential diagnostic markers, culminating in the identification of RNASE1 and CD14. The risk score model based on these biomarkers exhibited high accuracy in diagnosing atherosclerosis. Immune characteristic analysis validated the risk score model’s efficacy in defining patient profiles, distinguishing high-risk individuals with pronounced immune cell activities. Finally, experimental validation affirmed RNASE1’s involvement in atherosclerotic progression, suggesting its potential as a therapeutic target.ConclusionOur findings have advanced our understanding of atherosclerosis immunopathology and paved the way for novel diagnostic and therapeutic strategies.

Tree productivity is not only determined by stand structure, but also influenced by soil chemical properties, climate and topography. However, the relative importance of each indicator on larch (Larix principis-rupprechtii) productivity were uncertain. In this study, 76 pure larch forest plots were selected based on national forest inventory (NFI) data in Hebei Province, China. Structural equation model (SEM) was used to analyze the direct and indirect effects of stand structure, soil chemical properties, climate and topography on larch productivity, and to quantify the relative importance of each indicator in determining productivity. The results showed that stem volume growth (SVG) of larch was influenced by a combination of stand density, diameter at breast height (DBH), mean winter snow (PAS), annual temperature range (TD), slope, and alkali-hydrolysis nitrogen (AN). SVG tended to increase with decreasing stand density and AN content and increasing DBH. Stand density, DBH and AN were more important than PAS, TD, and slope in explaining SVG variation. The results can provide a scientific basis for adaptive management of larch forests.

The ability of Deinococcus bacteria to survive in harsh environments, such as high radiation, extreme temperature, and dryness, is mainly attributed to the generation of unique pigments, especially carotenoids. Although the limited number of natural pigments produced by these bacteria restricts their industrial potential, metabolic engineering and synthetic biology can significantly increase pigment yield and expand their application prospects. In this study, we review the properties, biosynthetic pathways, and functions of key enzymes and genes related to these pigments and explore strategies for improving pigment production through gene editing and optimization of culture conditions. Additionally, studies have highlighted the unique role of these pigments in antioxidant activity and radiation resistance, particularly emphasizing the critical functions of deinoxanthin in D. radiodurans. In the future, Deinococcus bacterial pigments will have broad application prospects in the food industry, drug production, and space exploration, where they can serve as radiation indicators and natural antioxidants to protect astronauts’ health during long-term space flights.

Peste des petits ruminants virus (PPRV) is a morbillivirus that causes the acute and highly pathogenic infectious disease peste des petits ruminants (PPR) in small ruminants and poses a major threat to the goat and sheep industries. Currently, there is no effective treatment for PPRV infection. Here, we propose Carboplatin, a platinum-based regimen designed to treat a range of malignancies, as a potential antiviral agent. We showed that Carboplatin exhibits significant antiviral activity against PPRV in a cell culture model. The mechanism of action of Carboplatin against PPRV is mainly attributed to its ability to block STING mediated autophagy. Together, our study supports the discovery of Carboplatin as an antiviral against PPRV and potentially other closely related viruses, sheds light on its mode of action, and establishes STING as a valid and attractive target to counteract viral infection.

Porcine reproductive and respiratory syndrome (PRRS), an important viral disease of swine caused by PRRS virus (PRRSV) was first confirmed in Nepal in 2013. Since then, the virus has spread throughout the country and has now become endemic affecting the pig production nationally. However, molecular characterization of circulating strains has not been done in Nepal yet. In the present study, serum samples were collected from outbreak areas of different districts of Nepal and samples positive for PRRSV by ELISA were sent to Animal and Plant Health Agency (APHA), United Kingdom for sequence analysis. Out of 35 samples that were sent to APHA, only one sample was found positive by PCR and subjected to sequence analysis based on ORF5, ORF7 and Nsp2. The results from the phylogenetic analysis demonstrated that the PRRSV strain belongs to PRRSV-2 and lineage 8 strain. The sequences from the Nepalese PRRSV strain revealed a high degree of similarity with the strains isolated from India, China and Vietnam, with the closest genetic relatedness to the Indian isolates from 2020 and 2018. This is the first study on molecular characterization of PRRS virus circulating in Nepal. Further studies on strains circulating in Nepal are very essential to understand the virus diversity, its spread and evolution.

Forest landscape fragmentation poses a significant challenge to the conservation of species diversity. Evaluating the suitability of forest landscape restoration (FLR) becomes essential as it promotes effective management of forest resources and protects species diversity. This study focused on deploying and testing a suitability evaluation framework system for FLR in the Saihanba area of Hebei, China. The framework system incorporated factors such as land cover type, landscape structure, soil quality, and topography. Using the matter-element model, the study evaluated the restoration suitability and identified priority restoration areas. The results revealed that land cover type and landscape structure were the primary factors influencing FLR in the study area. The suitable area for FLR in the study area was about 519.20 km2, accounting for 55.55% of the total area. The area of moderate, marginal, and unsuitable restoration accounted for 17.30%, 23.96%, and 3.18% of the study area, respectively. The suitable restoration areas predominantly consisted of natural secondary forest characterized by large patch areas, short distances between patches, and complex patch shapes. In the study area, the objective of FLR should be protect large and complex shaped patches of natural secondary forests for better conservation of species diversity. The FLR suitability evaluation conducted in this study provide a valuable guidance for promoting species-diversity conservation and restoration of forest ecosystems at the landscape scale in the study area and other similar regions.

Under-canopy afforestation using different tree species is a key approach in close-to-nature management to improve the structural and functional stability of plantation forests. However, current research on understory afforestation mainly focuses on the seedling stage, with limited attention to saplings or young trees. In this study, we evaluated the growth characteristics and leaf traits of 14-year-old Pinus sylvestris var. Mongolica trees under four different upper forest density (UFD) treatments: 0 trees/hm2 (canopy openness 100%, CK), 150 trees/hm2 (canopy openness 51.9%, T1), 225 trees/hm2 (canopy openness 43.2%, T2), and 300 trees/hm2 (canopy openness 28.4%, T3). We found that the survival rate of P. sylvestris in the T3 was significantly lower than in the other treatments, with a decrease of 30.2%, 18.3%, and 19.5% compared to CK, T1, and T2, respectively. The growth of P. sylvestris in the T1 treatment exhibited superior performance. Specifically, T1 showed a significant increase of 18.8%, 5.5%, and 24.1% in tree height, diameter at breast height, and crown width, respectively, compared to the CK. The mean trunk biomass ratio in the understory was significantly higher than that in full light by 15.4%, whereas the mean leaf biomass ratio was significantly lower by 12.3%. Understory P. sylvestris trees tended to allocate more biomass to the trunk at the expense of decreasing leaf biomass, which would facilitate height growth to escape the shading environment, although the promotion was relatively limited. Leaf length, leaf width, leaf area, leaf thickness, mesophyll tissue thickness, epidermis thickness, and leaf carbon content were the highest in the CK and tended to decrease with increasing UFD, indicating that a high-light environment favored leaf growth and enhanced carbon accumulation. In summary, young P. sylvestris trees adapted to moderate shading conditions created by the upper canopy, and the T1 treatment was optimal for the growth of understory P. sylvestris. This study provides insights into different adaptive strategies of young P. sylvestris trees to changes in light environment, providing practical evidence for under-canopy afforestation using light-demanding trees during pure plantation transformation.

ObjectiveTo analyze the recurrence and metastasis patterns and prognosis after complete resection of retroperitoneal liposarcoma.MethodsThe clinical postoperative follow-up data and results of patients who underwent complete resection of retroperitoneal liposarcoma from September 10, 2014, to September 8, 2021, at Hebei Medical University hospital were collected retrospectively.ResultsA total of 60 patients with complete resection of retroperitoneal liposarcoma, including 33 cases of retroperitoneal liposarcoma recurrence, 2 cases of liver metastasis, and 1 case of lung metastasis, were included. The results showed that 100% of the recurrent sites were located in the primary region of the tumor, with most recurrences located near the kidney, paracolic sulci, and iliac vessels. Three patients had distant metastasis without obvious recurrence on imaging examination. The pathological type of retroperitoneal liposarcoma, Ki67 expression, and presence of serum albumin were risk factors for recurrence and metastasis after complete resection of retroperitoneal liposarcoma. The malignancy and Ki67 expression were independent risk factors for recurrence and metastasis as well as for overall survival of patients undergoing complete resection of retroperitoneal liposarcoma.ConclusionComplete resection remains the most effective method to treat retroperitoneal liposarcoma. Patients with pathological types of retroperitoneal liposarcoma showing dedifferentiation, pleomorphism, mixed type, and high Ki67 expression should be closely monitored and observed after complete resection, especially for imaging changes in the primary tumor area.

IntroductionTo achieve effective conservation objectives, it is crucial to map biodiversity patterns and hotspots while considering multiple influencing factors. However, focusing solely on biodiversity hotspots is inadequate for species conservation on a landscape scale. This emphasizes the importance of integrating hotspots with the home ranges of species to identify priority conservation areas.MethodsCompiling the vegetation data with environmental and anthropogenic disturbance data collected from kilometer-grid plots in Bawangling Nature Reserve, Hainan, China, we analyzed the spatial distribution of plant diversity (species richness and Shannon-Wiener index), as well as the main drivers affecting these patterns. We also investigated the spatial distribution of hotspots using a threshold approach and compared them with the home ranges of the flagship species, Hainan gibbon (Nomascus hainanus).ResultClimate and soil are predominant drivers shaping the spatial pattern of plant diversity in Bawangling Nature Reserve, surpassing the influence of anthropogenic disturbance and topographic factors. Both diversity indices exhibit a generally similar pattern with exceptions in surrounding areas of Futouling and Elongling. The hotspots identified by the Shannon-Wiener index showed a higher spatial overlap with the home ranges of Hainan gibbon compared to the species richness hotspots. The recently established Hainan gibbon Group E in 2019, located 8 km away from the original Futouling habitat, does not coincide with identified hotspots.DiscussionOur findings indicate that the hotspots of plant diversity within the habitat of Hainan gibbon Group E are relatively limited, emphasizing the necessity of giving precedence to its conservation. Integrating hotspots with the home ranges of critically endangered species offers decision-makers valuable information to establish rational conservation networks in the context of changing environments, as well as a reference for habitat restoration of species.

Turpan Basin located in the eastern Xinjiang is a typical arid inland basin with extremely scarce water resources and a fragile ecosystem. Prokaryotic communities with unique genetic and physiological modifications can survive and function in such harsh environments, offering diverse microbial resources. However, numerous microbes can enter the viable but non-culturable state because of drought stress in the desert soil. In this work, next generation sequencing (NGS) technology based on DNA nanoball sequencing platform (DNBSEQ-G400) and sequencing-by-synthesis platform (NovaSeq 6000) were applied to analyze the prokaryotic diversity in three hyper-arid Gobi soils from Flaming Mountain, Toksun, and Kumtag. The comparison between two platforms indicated that DNBSEQ-G400 had better repeatability and could better reflect the prokaryotic community of this hyper-arid region. The diversity analysis based on DNBSEQ-G400 identified a total of 36 bacterial phyla, including Pseudomonadota, Bacteroidota, Bacillota, Actinomycetota, Methanobacteriota, Acidobacteriota, Nitrososphaerota, and Planctomycetota. The environmental factors, including soluble salt, available potassium, total nitrogen, and organic matter, were positively correlated with the abundance of most prokaryote. In addition, the prokaryotic community assembly in hyper-arid soil was well described by neutral-based models, indicating that the community assembly was mainly controlled by stochastic processes. Finally, the phylogenetic analysis of Actinomycetota proved that such extremophiles played an important role in the ecosystems they colonize. Overall, our result provides a reference for choosing the appropriate sequencing platform and a perspective for the utilization of soil microbial resources from hyper-arid regions.

For the razor clam Solen grandis, siphonal autotomy and regeneration is a necessary means of facing external stress, which is accompanied by a large amount of energy consumption. To explore the function of the ENO4 gene in the siphonal autotomy and regeneration of S. grandis, the full-length cDNA of the ENO4 in S. grandis was cloned and characterized. The full-length cDNA of SgENO4 was 2,773 base pairs (bp), with an 1,851 bp coding sequence (CDS) encoding 616 amino acids. ​Bioinformatic analysis revealed a slightly lower codon usage bias and a relatively stable nucleotide composition in the SgENO4 sequence. Three conserved motifs were found from the SgENO4 sequence. These conserved motifs vary in length from 14 to 27 amino acids. Moreover, in the siphonal pre-autotomy of razor clams, expression level of the SgENO4 gene was significantly higher in the hepatopancreas and siphonal base than other tissues (P < 0.05). However, the expression of the SgENO4 gene in the siphonal base decreased significantly in the siphonal post-autotomy 7 hours and gradually recovered as the regeneration process continued. ​Linear correlation analysis showed that there was a significant linear correlation between specific weight of siphon and relative expression levels of SgENO4 (R2 = 0.826). RNA interference (RNAi) result showed that the specific weight (the proportion of siphonal weight to body weight) is significantly lower than other groups on the seventh day (P < 0.05), suggesting that interfering with the expression of the SgENO4 gene could inhibit the siphonal regeneration of S. grandis. These results further demonstrate that SgENO4 is a conserved sequence and that it plays a crucial role in the siphonal autotomy and regeneration of S. grandis, advancing further understanding in exploring molecular mechanisms in the siphonal autotomy and regeneration.

Based on recent multiregional epidemiological investigations of Monkeypox (MPX), on 24 July 2022, the World Health Organization declared it a global public health threat. Retrospectively MPX was an ignored zoonotic endemic infection to tropical rainforest regions of Western and Central African rural communities until a worldwide epidemic in May 2022 verified the potential threat of monkeypox virus (MPXV) to be propagated across the contemporary world via transnational tourism and animal movements. During 2018–2022, different cases of MPX diagnosed in Nigerian travelers have been documented in Israel, the United Kingdom, Singapore, and the United States. More recently, on 27 September 2022, 66,000 MPX cases have been confirmed in more than 100 non-endemic countries, with fluctuating epidemiological footprinting from retrospective epidemics. Particular disease-associated risk factors fluctuate among different epidemics. The unpredicted appearance of MPX in non-endemic regions suggests some invisible transmission dynamic. Hence, broad-minded and vigilant epidemiological attention to the current MPX epidemic is mandatory. Therefore, this review was compiled to highlight the epidemiological dynamic, global host ranges, and associated risk factors of MPX, concentrating on its epidemic potential and global public health threat.

The transformation of engineered microbial cells is a pivotal link in green biomanufacturing. Its distinctive research application involves genetic modification of microbial chassis to impart targeted traits and functions for effective synthesis of the desired products. Microfluidics, as an emerging complementary solution, focuses on controlling and manipulating fluid in channels at the microscopic scale. One of its subcategories is droplet-based microfluidics (DMF), which can generate discrete droplets using immiscible multiphase fluids at kHz frequencies. To date, droplet microfluidics has been successfully applied to a variety of microbes, including bacteria, yeast, and filamentous fungi, and the detection of massive metabolites of strain products, such as polypeptides, enzymes, and lipids, has been realized. In summary, we firmly believe that droplet microfluidics has evolved into a powerful technology that will pave the way for high-throughput screening of engineered microbial strains in the green biomanufacturing industry.

Geosmin is one of the most common earthy-musty odor compounds, which is mainly produced by Streptomyces. Streptomyces radiopugnans was screened in radiation-polluted soil, which has the potential to overproduce geosmin. However, due to the complex cellular metabolism and regulation mechanism, the phenotypes of S. radiopugnans were hard to investigate. A genome-scale metabolic model of S. radiopugnans named iZDZ767 was constructed. Model iZDZ767 involved 1,411 reactions, 1,399 metabolites, and 767 genes; its gene coverage was 14.1%. Model iZDZ767 could grow on 23 carbon sources and five nitrogen sources, which achieved 82.1% and 83.3% prediction accuracy, respectively. For the essential gene prediction, the accuracy was 97.6%. According to the simulation of model iZDZ767, D-glucose and urea were the best for geosmin fermentation. The culture condition optimization experiments proved that with D-glucose as the carbon source and urea as the nitrogen source (4 g/L), geosmin production could reach 581.6 ng/L. Using the OptForce algorithm, 29 genes were identified as the targets of metabolic engineering modification. With the help of model iZDZ767, the phenotypes of S. radiopugnans could be well resolved. The key targets for geosmin overproduction could also be identified efficiently.

Larix principis-rupprechtii Mayr (larch) is one of the main afforestation and timber production species used in North China. Climate change has led to a change in its suitable distribution and growth. However, the impact of climate change on its growth suitability is not clear. In this study, using forest resource inventory data and spatially continuous environmental factor data (temperature, precipitation, topography, and soil) in Hebei and Shanxi Provinces, China, the random forest model (RF) was used to simulate the larch site index (SI) and growth suitability under three shared socioeconomic pathways (SSPs: SSP1-2.6, SSP2-4.5, and SSP5-8.5) for the current and future (2021–2040, 2041–2060 and 2080–2100). The results revealed that (1) RF had excellent performance in predicting the regional SI (R2 = 0.73, MAE = 0.93 m, RMSE = 1.35 m); (2) the main factors affecting the productivity of larch were the mean temperature of the warmest quarter (BIO10), elevation (ELEV), mean diurnal range (BIO2), and annual precipitation (BIO12); and (3) larch currently had a higher SI in the Bashang areas and in the high-altitude mountains. The areas characterized as unsuitable, poorly suitable, moderately suitable, and highly suitable accounted for 15.45%, 42.12%, 31.94%, and 10.49% of the total area, respectively. (4) Future climate warming had an obvious inhibitory effect on the SI, and the effect strengthened with increasing radiation intensity and year. (5) The moderately suitable and highly suitable areas of larch growth showed a downward trend under future climate scenarios. By the end of this century, the suitable growth areas would decrease by 14.14% under SSP1-2.6, 15.17% under SSP2-4.5, and 19.35% under SSP5-8.5. The results revealed the impact of climate change on larch growth suitability, which can provide a scientific basis for larch forest management.

The diameter at breast height (DBH) is the most important independent variable in biomass allometry models based on metabolic scaling theory (MST) or geometric theory. However, the fixed position DBH can be misleading in its use of universal scaling laws and lead to some deviation for the biomass model. Therefore, it is still an urgent scientific problem to build a high-precision biomass model system. A dataset of 114 trees was destructively sampled to obtain dry biomass components, including stems, branches, and foliage, and taper measurements to explore the applicability of biomass components to allometric scaling laws and develop a new system of additive models with the diameter in relative height (DRH) for each component of a Larch (Larix principis-rupprechtii Mayr) plantation in northern China. The variable exponential taper equations were modelled using nonlinear regression. In addition, applying nonlinear regression and nonlinear seemingly unrelated regression (NSUR) enabled the development of biomass allometric models and the system of additive models with DRH for each component. The results showed that the Kozak’s (II) 2004 variable exponential taper equation could accurately describe the stem shape and diameter in any height of stem. When the diameters in relative height were D0.2, D0.5, and D0.5 for branches, stems, and foliage, respectively, the allometric exponent of the stems and branches was the closest to the scaling relations predicted by the MST, and the allometric exponent of foliage was the most closely related to the scaling relations predicted by geometry theory. Compared with the nonlinear regression, the parameters of biomass components estimated by NSUR were lower, and it was close to the theoretical value and the most precise at forecasting. In the study of biomass process modelling, utilizing the DRH by a variable exponential taper equation can confirm the general biological significance more than the DBH of a fixed position.

BackgroundThe use of lymph node (LN) tracers can help obtain a complete dissection of the lymph nodes and increase the detection rate of LNs and metastatic LNs. Carbon nanoparticle suspension injection (CNSI) and indocyanine green (ICG) have been widely used in radical gastrectomy in recent years. Nevertheless, the comparison of their clinical effects has not been studied.Method/designThe FUTURE-01 trial will be the first randomized, open-label, single-center trial to compare CNSI and ICG. The study started in 2021 and enrolled 96 patients according to a prior sample size calculation. The primary outcome is the number of LNs retrieved. The secondary outcomes are LN staining rate, LN metastasis rate, stained LN metastasis rate, perioperative recovery and survival.ConclusionBy comparing the safety and efficacy of CNSI and ICG tracer-guided LN dissection in patients with gastric cancer, we can determine the most appropriate LN tracer at present. With the help of LN tracers, the operation is simplified, and the prognosis of these patients is improved. Our study is a prospective exploration of the safety, efficacy, and prognosis of CNSI and ICG.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT05229874?cond=NCT05229874&draw=2&rank=1, identifier NCT05229874.

Stem form is the shape of the trunk, differs among tree species and mainly affected by stand density factor. Accurate taper equations are crucial for estimating the stem diameter, form and tree volume, which is conducive to timber utilization and sustainable forest management and planning. Larch (Larix principis-rupprechtii Mayr.) is a valuable afforestation species under large-scale development in North China, but no study on the effect of density on its stem taper has been reported yet. The dataset included 396 analytical trees from 132 standard plots of larch plantation in Saihanba, Hebei Province. Based on 12 different forms of models, we explored the optimal basic equation for plantations and the effects of the stand density, basal area, canopy density and different forms of stand density on the prediction accuracy of the variable-exponent models. The variable-exponent taper equation that includes Sd (stand density) was constructed by using nonlinear regression, a nonlinear mixed effect model and the nonlinear quantile regression method. The results indicate that the Kozak’s 2004 variable-exponent taper equation was the best basic model for describing changes in the stem form of larch plantations, and the density factor in the form of Sd improved the prediction accuracy of the basic model. Among the three regression methods, the quantile regression method had the highest fitting accuracy, followed by the nonlinear mixed effect model. When the quantile was 0.5, the nonlinear quantile regression model exhibited the best performance which provides a scientific basis for the rational management of larch plantations.

BackgroundNeoadjuvant chemotherapies have been widely recommended in patients with locally advanced gastric cancer (LAGC). However, the evidence of combining neoadjuvant chemotherapy with anti–programmed death 1 (anti–PD-1) antibody therapy for patients with LAGC is lacking. Thus, we conducted a single-arm phase II trial to evaluate the efficacy and safety of the anti–PD-1 antibody sintilimab plus XELOX regimen (capecitabine plus oxaliplatin) in patients with LAGC.MethodsPatients with LAGC (cT3-4 N+ M0, CY0, P0) were enrolled and received four preoperative cycles of sintilimab (200 mg, IV, Q21d) plus XELOX (oxaliplatin 130 mg/m2, IV, d1 with capecitabine 1,000 mg/m2, bid, d1–d14, Q21d) therapy. The primary endpoint was the pathological complete response (pCR) rate. This clinical trial was registered at Chictr.org.cn (trial number: ChiCTR2000030414).ResultsThirty patients were enrolled from March 2020 to July 2021, with a median age of 62 years (range, 30–72), and 18 (60.0%) were men. There were 19 (63.3%) patients with PD-L1 CPS ≥1.The pCR rate was 33.3% [95% confidence interval (CI), 17.3%–52.8%], and the major pathologic response (MPR) rate was 63.3% (95% CI, 43.9%–80.1%). All the patients underwent R0 resection. The objective response rate (ORR) and the disease control rate (DCR) were 70.0% (95% CI, 50.6%–85.3%) and 100% (95% CI, 88.4%–100%), respectively. Downstaging of the overall TNM stage was observed in 22 (73.3%) patients. The pCR rate in patients with PD-L1 CPS ≥1 and patients with PD-L1 CPS

African swine fever (ASF), caused by the African swine fever virus (ASFV), is an acute, deadly, infectious disease of domestic pigs and wild boars and has a tremendous negative socioeconomic impact on the swine industry. ASF is a notifiable disease to the World Organization for Animal Health (OIE). Currently, no effective vaccine or treatment against ASF is available. Early detection and rapid diagnosis are potentially significant to control ASF spread with the emerging ASFV mutant strains and non-classical symptoms. In this study, we developed a real-time recombinase-aid amplification (RAA) assay to detect the ASFV genome rapidly. Thirty samples were detected using commercial lysis buffer for DNA extraction and equipped with a portable testing instrument. The results showed that the sensitivity of RAA was 103 copies per reaction at 95% probability in 9 min at 39°C. The method was universally specific for three strains of ASFV, and there was no cross-reaction with other pathogens, including foot-and-mouth disease virus (FMDV), classical swine fever virus (CSFV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus 2 (PCV2), pseudorabies virus (PRV), and porcine parvovirus (PPV). The coefficient of variation (C.V) of repetitive experiments was 0%, and the coincidence rate was 100% compared to the real-time qPCR. 123 field samples were detected by the real-time RAA assay, and the results showed that the clinical coincidence rate of the real-time RAA assay was 98% compared to the real-time qPCR assay. The advantages of this method were as follows: the extraction of DNA can be performed on site, the DNA template is directly used, a small battery-powered instrument is easily available, and the on-site diagnostic process is finished within an hour. These suggest that this assay could be used to detect different genotypes of ASFV and play a vital role in the control of ASF.

BackgroundCurrently, gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract, and surgical resection is the main treatment. Malnutrition after gastrointestinal surgery is not uncommon, which may have adverse effects on postoperative recovery and prognosis. However, the nutritional status of GIST patients after surgical resection and its impact on clinical outcomes have received less attention. Therefore, the aim of this study was to dynamically evaluate the nutritional status of GIST patients undergoing surgical resection, and to analyze the correlation between nutritional status and clinical outcomes.MethodsWe retrospectively analyzed the clinical data of GIST patients who underwent surgical resection in the Fourth Hospital of Hebei Medical University from January 2016 to January 2020. Nutritional risk screening 2002 (NRS2002) and Patient-Generated Subjective Global Assessment (PG-SGA) were used to assess the nutritional status of all patients at admission and discharge, and the correlation between nutritional risk and clinical outcomes was analyzed.ResultsA total of 413 GIST patients were included in this study, among which 114 patients had malnutrition risk at admission (NRS2002 score ≥ 3), and 65 patients had malnutrition (PG-SGA score ≥ 4). The malnutrition risk rate (27.60 vs. 46.73%, p < 0.001) and malnutrition incidence (15.73 vs. 37.29%, p < 0.001) at admission were lower than those at discharge. Compared with the laboratory results at admission, the albumin, prealbumin, and total protein of the patients at discharge were significantly lower (all p < 0.05). And there was a negative correlation between PG-SGA and clinical outcome (all p < 0.05).ConclusionThe nutritional status of GIST patients after surgical resection at discharge was worse than that at admission, and malnutrition is an important risk factor leading to poor clinical outcomes.

The integrated stress response (ISR) is an adaptational signaling pathway induced in response to different stimuli, such as accumulation of unfolded and misfolded proteins, hypoxia, amino acid deprivation, viral infection, and ultraviolet light. It has been known that viral infection can activate the ISR, but the role of the ISR during viral infection is still unclear. In some cases, the ISR is a protective mechanism of host cells against viral infection, while viruses may hijack the ISR for facilitating their replication. This review highlighted recent advances on the induction of the ISR upon viral infection and the downstream responses, such as autophagy, apoptosis, formation of stress granules, and innate immunity response. We then discussed the molecular mechanism of the ISR regulating viral replication and how viruses antagonize this cellular stress response resulting from the ISR.

BackgroundHerein, we aimed to analyze cardiac metabolic reprogramming in patients with tetralogy of Fallot (ToF).MethodsCardiac metabolic reprogramming was analyzed through comprehensive bioinformatics analysis, which included gene set enrichment, gene set variation, and consensus clustering analyses, so as to assess changes in metabolic pathways. In addition, full-spectrum metabolomics analysis was performed using right atrial biopsy samples obtained from patients with ToF and atrial septal defect (ASD) before cardiopulmonary bypass; ultrahigh performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) was used to construct a metabolic map of cardiac metabolic reprogramming in cyanotic congenital heart disease.ResultsThe metabolic maps of carbohydrate metabolic process and heme metabolism were significantly activated, while bile acid metabolism, lipid droplet, and lipid binding were primarily restrained in ToF samples as compared with that in ASD samples. The reprogramming of butanoate metabolism was identified basing on the UPLC–MS/MS detection and analysis in myocardial hypoxia damage in cyanotic heart disease. Finally, the butanoate metabolism–related hub regulators ALDH5A1 and EHHADH were identified and they were significantly downregulated in ToF samples.ConclusionsThe metabolic network of butanoate metabolism involved ALDH5A1 and EHHADH, which could contribute to myocardial tissue damage in cyanotic congenital heart of ToF. Our results provide further insights into the mechanisms underlying metabolic reprogramming in cyanotic congenital heart disease and could lead to the identification of potential therapeutic targets.

BackgroundReports have shown that neoadjuvant concurrent chemoradiotherapy (nCRT) increases the R0 resection rate for patients with Siewert type II or III adenocarcinoma of the gastroesophageal junction (AEG). However, the long-term efficacy of nCRT for AEG patients remains unclear. In this multicenter study, we investigated the long-term results of AEG patients treated with nCRT.MethodsA total of 149 patients with potentially resectable advanced AEG (T3/4, Nany, M0) were randomly divided into two groups: the nCRT-treated group (treated group) (n = 76) and the surgery group (control group) (n = 73). The primary endpoint was disease-free survival (DFS), and the secondary outcome indexes included the R0 resection rate, HER-2 expression, tumor regression grade (TRG), objective response rate (ORR), disease control rate (DCR), overall survival (OS), and adverse events.ResultsIn the treated group, the overall therapeutic efficacy rate was 40.8%, and the pathological complete response (pCR) rate was 16.9%. The rates of patients who underwent R0 resection in the treated and control groups were 97.0% and 87.7%, respectively (p < 0.05). The toxic effects were mainly graded 1–2 in the treated group. The median DFS times in the treated and control groups were 33 and 27 months, respectively (p = 0.08), whereas the median OS times were 39 and 30 months, respectively (p = 0.01). The median DFS times of patients with positive and negative HER-2 expression in the treated group were 13 and 43 months, respectively (p = 0.01), and the median OS times were 27 and 41 months, respectively (p = 0.01).ConclusionSurgery after nCRT improved the efficacy of treatment for AEG patients and thus provided a better prognosis.Clinical Trial RegistrationThe trial is registered with ClinicalTrials.gov (number NCT01962246).

Peste des petits ruminant virus (PPRV) causes a highly contagious disease in small ruminants. The molecular mechanism of PPRV replication and its interactions with hosts are poorly studied. In other paramyxoviruses, the viral phosphoprotein (P) has been associated with multiple functions for key biological processes such as the regulation of transcription, translation, and the control of cell cycle. Phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α) is an important process for gene regulation in host cells under stress, including viral infection. In the present study, molecular mechanisms associated with PPRV replication and viral interaction with host cells were investigated. We describe the ability of PPRV to dephosphorylate eIF2α and the potential of PPRV P protein to induce the host cellular growth arrest DNA damage protein (GADD34), which is known to be associated with eIF2α dephosphorylation. Furthermore, we observed that PPRV P protein alone could block PERK/eIF2α phosphorylation. We speculate that PPRV exploits eIF2α dephosphorylation to facilitate viral replication and that PPRV P protein is involved in this molecular mechanism. This work provides new insights into further understanding PPRV pathobiology and its viral/host interactions.

Gastric cancer (GC), as a common gastrointestinal tumor, is an important cause of death from cancer all around the world. Long non-coding RNAs (lncRNAs), a novel class of transcripts, have attracted great attention of researchers. However, the mechanisms of the clinical significance of most lncRNAs in human cancer are mainly undocumented. This research desires to explore the clinical significance, biological function, and mechanism of Lnc_ASNR (apoptosis suppressing-non-coding RNA) in GC. Cell proliferation, cell cycle, cell migration, and invasion abilities were respectively determined by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), flow cytometry, wound healing, and Transwell assay (Sigma-Aldrich, St. Louis, MO, United States). The association of Lnc_ASNR, miR-519e-5p, and fibroblast growth factor receptor 2 (FGFR2) was evaluated via luciferase reporter experiments. The tumor xenograft assay was conducted to confirm the results of cell experiments. High expressed Lnc_ASNR was detected in both GC cells and tissues using qRT-PCR. Downregulated Lnc_ASNR could reduce proliferation, migration, and invasion in GC cells, while upregulated Lnc_ASNR could promote the cell proliferation, migration, and invasion. Moreover, the effect of Lnc_ASNR on migration and invasion ability is closely related to epithelial-mesenchymal transition (EMT). The bioinformatics analysis, luciferase assay, and Western blot demonstrated that Lnc_ASNR inhibited miR-519e-5p expression but increased FGFR2 expression. Lnc_ASNR and FGFR2 were both targeted to miR-519e-5p, and they were negatively correlated with the expression of miR-519e-5p. All investigations indicated that Lnc_ASNR functioned as a ceRNA targeting miR-519e-5p and facilitated GC development by regulating the pathway of miR-519e-5p/FGFR2.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common antibody-mediated encephalitis. There are several studies on B cell repertoire of anti-NMDAR encephalitis in Caucasians. Here, the cerebrospinal fluid (CSF) samples of 12 Chinese patients with first-episode anti-NMDAR encephalitis were collected to investigate the B cell receptor (BCR) binding to NMDAR by single cell amplification of BCR and Sanger sequencing. BCR data of healthy persons, and of patients with anti-leucine-rich glioma inactivated 1 (anti-LGI1) encephalitis, multiple sclerosis (MS), and neuromyelitis optica spectrum disorder (NMOSD) from the public databases were used as control. A heavy chain common clone IGHV1-18*04,IGHD1-26*01/ IGHD2-2*03/IGHD2-8*01, IGHJ3*02_(CDR3) ARVGSKYGFETFDI was found in 11 of 12 enrolled patients but not in the comparison data set. In addition, 4 shared clonotypes were found among these patients, and three of them contained the common clone. This study also revealed that the antibody gene family usage preference between patients and healthy controls were different, while they had similar antibody mutation rate. Our findings may have potential clinical implications for the diagnosis of anti-NMDAR encephalitis.

Peste des petits ruminant (PPR) is an economically important severe viral disease of small ruminants that affects primarily the respiratory and digestive tract. Specific detection of the PPR virus (PPRV) antigen plays an important role in the disease control and eradication program. In this study, an indirect enzyme-linked immunosorbent assay (ELISA) based on the recombinant goat signaling lymphocyte activation molecule (SLAM) as the capture ligand was successfully developed for the detection of the PPRV antigen (PPRV SLAM-iELISA). The assay was highly specific for PPRV with no cross-reactions among foot and mouth disease virus, Orf virus, sheep pox virus, and goat pox virus and had a sensitivity with a detection limit of 1.56 × 101 TCID50/reaction (50 μl). Assessment of 136 samples showed that the developed PPRV SLAM-iELISA was well correlated with real-time RT-qPCR assays and commercially available sandwich ELISA for detection of PPRV and showed relative sensitivity and specificity of 93.75 and 100.83%, respectively. These results suggest that the developed PPRV SLAM-iELISA is suitable for specific detection of the PPRV antigen. This study demonstrated for the first time that the goat SLAM, the cellular receptor for PPRV, can be used for the development of a diagnostic method for the detection of PPRV.

In this study, we investigated the mechanism of photosynthesis and physiological function of blueberry leaves under low temperature stress (4–6°C) by exogenous hydrogen sulfide (H2S) by spraying leaves with 0.5 mmol·L–1 NaHS (H2S donor) and 200 μmol·L–1 hypotaurine (Hypotaurine, H2S scavenger). The results showed that chlorophyll and carotenoid content in blueberry leaves decreased under low temperature stress, and the photochemical activities of photosystem II (PSII) and photosystem I (PSI) were also inhibited. Low temperature stress can reduce photosynthetic carbon assimilation capacity by inhibiting stomatal conductance (Gs) of blueberry leaves, and non-stomatal factors also play a limiting role at the 5th day of low temperature stress. Low temperature stress leads to the accumulation of Pro and H2O2 in blueberry leaves and increases membrane peroxidation. Spraying leaves with NaHS, a donor of exogenous H2S, could alleviate the degradation of chlorophyll and carotenoids in blueberry leaves caused by low temperature and reduce the photoinhibition of PSII and PSI. The main reason for the enhancement of photochemical activity of PSII was that exogenous H2S promoted the electron transfer from QA to QB on PSII acceptor side under low temperature stress. In addition, it promoted the accumulation of osmotic regulator proline under low temperature stress and significantly alleviated membrane peroxidation. H2S scavengers (Hypotaurine) aggravated photoinhibition and the degree of oxidative damage under low temperature stress. Improving photosynthetic capacity as well as alleviating photosynthetic inhibition and oxidative stress with exogenous H2S is possible in blueberry seedlings under low temperature stress.

Peste des petits ruminants (PPR) is a severe respiratory and digestive tract disease of domestic small ruminants caused by PPR virus (PPRV) of the genus Morbillivirus. Although the primary hosts of PPRV are goats and sheep, the host range of PPRV has been continuously expanding and reported to infect various animal hosts over the last decades, which could bring a potential challenge to effectively control and eradicate PPR globally. In this review, we focused on current knowledge about host expansion and interspecies infection of PPRV and discussed the potential mechanisms involved.

Porcine reproductive and respiratory syndrome (PRRS), an important viral disease of swine caused by PRRS virus (PRRSV) was first confirmed in Nepal in 2013. Since then, the virus has spread throughout the country and has now become endemic affecting the pig production nationally. However, molecular characterization of circulating strains has not been done in Nepal yet. In the present study, serum samples were collected from outbreak areas of different districts of Nepal and samples positive for PRRSV by ELISA were sent to Animal and Plant Health Agency (APHA), United Kingdom for sequence analysis. Out of 35 samples that were sent to APHA, only one sample was found positive by PCR and subjected to sequence analysis based on ORF5, ORF7 and Nsp2. The results from the phylogenetic analysis demonstrated that the PRRSV strain belongs to PRRSV-2 and lineage 8 strain. The sequences from the Nepalese PRRSV strain revealed a high degree of similarity with the strains isolated from India, China and Vietnam, with the closest genetic relatedness to the Indian isolates from 2020 and 2018. This is the first study on molecular characterization of PRRS virus circulating in Nepal. Further studies on strains circulating in Nepal are very essential to understand the virus diversity, its spread and evolution. [ABSTRACT FROM AUTHOR]

Introduction: To achieve effective conservation objectives, it is crucial to map biodiversity patterns and hotspots while considering multiple influencing factors. However, focusing solely on biodiversity hotspots is inadequate for species conservation on a landscape scale. This emphasizes the importance of integrating hotspots with the home ranges of species to identify priority conservation areas. Methods: Compiling the vegetation data with environmental and anthropogenic disturbance data collected from kilometer-grid plots in Bawangling Nature Reserve, Hainan, China, we analyzed the spatial distribution of plant diversity (species richness and Shannon-Wiener index), as well as the main drivers affecting these patterns. We also investigated the spatial distribution of hotspots using a threshold approach and compared them with the home ranges of the flagship species, Hainan gibbon (Nomascus hainanus). Result: Climate and soil are predominant drivers shaping the spatial pattern of plant diversity in Bawangling Nature Reserve, surpassing the influence of anthropogenic disturbance and topographic factors. Both diversity indices exhibit a generally similar pattern with exceptions in surrounding areas of Futouling and Elongling. The hotspots identified by the Shannon-Wiener index showed a higher spatial overlap with the home ranges of Hainan gibbon compared to the species richness hotspots. The recently established Hainan gibbon Group E in 2019, located 8 km away from the original Futouling habitat, does not coincide with identified hotspots. Discussion: Our findings indicate that the hotspots of plant diversity within the habitat of Hainan gibbon Group E are relatively limited, emphasizing the necessity of giving precedence to its conservation. Integrating hotspots with the home ranges of critically endangered species offers decision-makers valuable information to establish rational conservation networks in the context of changing environments, as well as a reference for habitat restoration of species. [ABSTRACT FROM AUTHOR]

Based on recent multiregional epidemiological investigations of Monkeypox (MPX), on 24 July 2022, the World Health Organization declared it a global public health threat. Retrospectively MPX was an ignored zoonotic endemic infection to tropical rainforest regions of Western and Central African rural communities until a worldwide epidemic in May 2022 verified the potential threat of monkeypox virus (MPXV) to be propagated across the contemporary world via transnational tourism and animal movements. During 2018-2022, different cases of MPX diagnosed in Nigerian travelers have been documented in Israel, the United Kingdom, Singapore, and the United States. More recently, on 27 September 2022, 66,000 MPX cases have been confirmed in more than 100 non-endemic countries, with fluctuating epidemiological footprinting from retrospective epidemics. Particular disease-associated risk factors fluctuate among different epidemics. The unpredicted appearance of MPX in non-endemic regions suggests some invisible transmission dynamic. Hence, broad-minded and vigilant epidemiological attention to the current MPX epidemic is mandatory. Therefore, this review was compiled to highlight the epidemiological dynamic, global host ranges, and associated risk factors of MPX, concentrating on its epidemic potential and global public health threat. [ABSTRACT FROM AUTHOR]