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Abstract The convergence of blockchain and immersive technologies has resulted in the popularity of Metaverse platforms and their cryptocurrencies, known as Metaverse tokens. There has been little research into tokenomics in these emerging tokens. Building upon the information dissemination theory, this research examines the role of trading volume in the returns of these tokens. An empirical study was conducted using the trading volumes and returns of 197 Metaverse tokens over 12 months to derive the latent grouping structure with spectral clustering and to determine the relationships between daily returns of different token clusters through augmented vector autoregression. The results show that trading volume is a strong predictor of lead–lag patterns, which supports the speed of adjustment hypothesis. This is the first large-scale study that documented the lead–lag effect among Metaverse tokens. Unlike previous studies that focus on market capitalization, our findings suggest that trade volume contains vital information concerning cross-correlation patterns.

Abstract Background Cervical cancer (CC) is one of the most common gynecologic tumors among women around the world. Although the etiological role of human papillomavirus (HPV) in CC is well established, other factors in CC carcinogenesis remains unclear. Here, we performed a systematic review and meta-analysis to explore the association between infections of human herpesvirus (HHVs) and CC risk. Methods Embase and PubMed databases were utilized to search the relevant studies. The revised JBI Critical Appraisal Tool was used to assess the quality of the included studies. Prevalence and odds ratios (ORs) with 95% confidence intervals (CI) were calculated to evaluate the association between viral infection and CC or precancerous cervical lesions (PCL). Results Totally 67 eligible studies involving 7 different HHVs were included in meta-analysis. We found an increased risk of CC or PCL that was associated with the overall infection of HHVs (CC, OR = 2.74, 95% CI 2.13–3.53; PCL, OR = 1.95, 95% CI 1.58–2.41). Subgroup analysis showed a trend towards positive correlations between herpes simplex virus type 2 (HSV-2) infection and CC (OR = 3.01, 95% CI 2.24 to 4.04) or PCL (OR = 2.14, 95% CI 1.55 to 2.96), and the same is true between Epstein-Barr virus (EBV) infection and CC (OR = 4.89, 95% CI 2.18 to 10.96) or PCL (OR = 3.55, 95% CI 2.52 to 5.00). However, for HSV-1 and cytomegalovirus (HCMV), there was no association between viral infection and CC or PCL. By contrast, the roles of HHV-6, HHV-7, and Kaposi sarcoma–associated herpesvirus (KSHV) in cervical lesions were unclear due to the limited number of studies. Conclusions This study provided evidence that HHVs infection as a whole increase the risk of CC incidence. In addition, some types of HHVs such as EBV and HSV-2 may serve as potential targets in the development of new interventions or therapeutic strategies for cervical lesions.

MET protooncogene (MET) alterations are known driver oncogenes in NSCLC. Since the identification of MET as a potential therapeutic target, extensive clinical trials have been performed. As a result, MET-targeted therapies, including MET tyrosine kinase inhibitors, monoclonal antibodies, and MET antibody–drug conjugates now play important roles in the standard treatment of MET-altered NSCLC; they have considerably improved the outcomes of patients with tumors that harbor MET oncogenic drivers. Although clinical agents are currently available and numerous other options are in development, particular challenges in the field require attention. For example, the therapeutic efficacy of each drug remains unsatisfactory, and concomitantly, the resistance mechanisms are not fully understood. Thus, there is an urgent need for optimal drug sequencing and combinations, along with a thorough understanding of treatment resistance. In this review, we describe the current landscape of pertinent clinical trials focusing on MET-targeted strategies and discuss future developmental directions in this rapidly expanding field.

Objective To find out the suspicious food, pathogenic factors and risk factors of a foodborne disease outbreak in a factory, and to discuss the problems exposed in the investigation of the incident, so as to provide reference for the prevention, control and investigation of similar incidents in the future. Methods A case was defined as the onset of abdominal pain or diarrhea (≥3 times/24 hours) or vomiting in a person who worked in M factory from March 3 to March 4 in 2019. Case interviews and retrospective research was carried out using descriptive and analytical epidemics pathological method. Stool specimens of the cases, leftover food and related environmental samples were gathered for pathogen isolation and toxin gene detection using polymerase chain reaction (PCR). Results 106 cases were identified with a attack rate of 73.6% (106/144). The symptoms were diarrhea (78.3%, 83/106), abdominal cramps (78.3%, 83/106), abdominal gas pains (9.4%, 10/106), and no fever. The epidemic curve showed a point source exposure pattern. The median incubation time was 10 hours (range: 2-22 h). Illness were associated with three food items of the lunch on March 3 in 2019 by univariate analysis and Logistic regression analysis: braised fish pieces [relative risk (RR)=1.55, 95% confidence interval (95%CI): 1.29-1.85], pork stir-fried with garlic sprouts (RR=1.26, 95%CI: 1.01-1.57) and duck blood stir-fried with pickles (RR=1.47, 95%CI: 1.16-1.87). Alpha toxin and enterotoxin CPE genes were positive and beta toxin genes was negative in the Clostridium perfringens strain isolated in anal swabs of three patients, three environmental samples and two leftover food samples. There were possible bacterial contamination and reproduction in the processing and preparation of enterprise D, which delivered food. Conclusion This incident was caused by the food poisoning of Clostridium perfringens caused by the consumption of a meal provided by a catering company. After the meal was delivered, it should be cooled quickly and stored at low temperature. If it cannot be eaten immediately, it should be heated sufficiently before eating.

BackgroundHigh PD-L1 expression in non-small cell lung cancer (NSCLC) is evident to predict elevated immunotherapy efficacy, to which NSCLC with onco-driver gene mutations is probed with poor responsiveness. Thus, it is of great interest to investigate how effective immune monotherapy is in the presence of concurrent high PD-L1 expression and driving gene mutation.Patients and methodsWe present a case of squamous lung cancer with high PD-L1 expression and HER2 exon 20 insertion (20Ins) who presented hyperprogressive disease (HPD) after being treated with PD-1 inhibitor.ResultsA 71-year-old female was diagnosed with advanced squamous lung cancer with 98% tumor proportion score of PD-1 and 20ins. She benefited from first-line docetaxel cisplatin followed by 2 months second-line afatinib. Third-line pembrolizumab monotherapy was then given. Unfortunately, she rapidly progressed with dramatically enlarged primary site as well as mediastinal lymph nodes and pleural effusion only 2 weeks later, presenting severe dyspnea and dysphagia. Re-biopsy was conducted, and we found that compared with the baseline, CD8+ T cells were largely recruited only in tumor stroma but not in tumor parenchyma. Tumor-associated macrophages were notably increased in both tumor stroma and parenchyma. Concomitantly, CD56dim NK cells in tumor parenchyma were decreased.ConclusionsApplication of immune monotherapy in patients with positive driver genes demands extreme caution, even harboring high PD-L1 expression. Abnormality of tumor microenvironment might be critically involved in immune checkpoint inhibitor-induced HPD. Further study in greater depth is required.

H5N6 highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4 not only exhibits unprecedented intercontinental spread in poultry, but can also cause serious infection in humans, posing a public health threat. Phylogenetic analyses show that 40% (8/20) of H5N6 viruses that infected humans carried H9N2 virus-derived internal genes. However, the precise contribution of H9N2 virus-derived internal genes to H5N6 virus infection in humans is unclear. Here, we report on the functional contribution of the H9N2 virus-derived matrix protein 1 (M1) to enhanced H5N6 virus replication capacity in mammalian cells. Unlike H5N1 virus-derived M1 protein, H9N2 virus-derived M1 protein showed high binding affinity for H5N6 hemagglutinin (HA) protein and increased viral progeny particle release in different mammalian cell lines. Human host factor, G protein subunit beta 1 (GNB1), exhibited strong binding to H9N2 virus-derived M1 protein to facilitate M1 transport to budding sites at the cell membrane. GNB1 knockdown inhibited the interaction between H9N2 virus-derived M1 and HA protein, and reduced influenza virus-like particles (VLPs) release. Our findings indicate that H9N2 virus-derived M1 protein promotes avian H5N6 influenza virus release from mammalian, in particular human cells, which could be a major viral factor for H5N6 virus cross-species infection.

The feasibility study of unified power flow controller (UPFC) application in 220 kV Shanghai Grid is conducted based on the analysis of the practical operation of the grid. The location selection method and scheme are proposed for the application of 220 kV UPFC demonstration project. The application effect of the demonstration project of UPFC is evaluated from various perspectives including enhancement of interface transfer capability, improvement of voltage stability performance of the grid and contribution to balancing of reactive power in 220 kV sectionalised systems.

β-Elemene is the major active ingredient of TCM anticancer drug elemene extracts. To further improve its antitumor activity and poor solubility, a polar HDACi pharmacophore was incorporated its scaffold. Systematic SAR studies led to the discovery of compounds 27f and 39f, which exhibited potent inhibitory activity against HDACs (HDAC1: IC50 = 22 and 9 nM; HDAC6: 8 and 14 nM, respectively). In cellular levels, 27f and 39f significantly inhibited cell proliferation of five tumour cell lines (IC50: 0.79 - 4.42 µM). Preliminary mechanistic studies indicated that 27f and 39f efficiently induced cell apoptosis. Unexpectedly, compound 39f could also stimulate cell cycle arrest in G1 phase. Further in vivo study in WSU-DLCL-2 xenografted mouse model validated the antitumor activities of 27f, without significant toxicity. The results suggest the therapeutic potential of these HDACs inhibitors in lymphoma and provide valuable insight and understanding for further structural optimisation around β-elemene scaffold.

IntroductionIn the face of escalating apprehensions surrounding food security, the sustainability of food systems, and food quality, the ingenuity of resource management strategies becomes paramount. A key component within these strategies is the enhancement of chemical fertilizer utilization, an element that bears significant weight on agricultural yields and the preservation of our environment. The emergence of Integrated Water-Fertilizer Systems (IWFS) thus presents a significant innovation in boosting the efficiency of chemical fertilizer usage, necessitating in-depth examination.MethodsUtilizing a rigorous analytical framework that combines meta-frontier production function with a Two-Stage Residual Inclusion model, this study delves into the multi-dimensional impacts of IWFS adoption on fertilizer use efficiency among cotton growers in Xinjiang, China.ResultsEmpirical evidence demonstrates that those who have adopted IWFS achieve a fertilizer use efficiency score of 0.452, markedly outstripping the mean score of 0.382 among non-adopters. Intriguingly, efficiency increases proportionately with the size of the farm, hinting at a sophisticated interplay between the adoption of technology and operational parameters.DiscussionThe research further unveils additional benefits including augmented cotton yields and diminished labor inputs among adopters. These multifaceted outcomes bear significant policy implications, highlighting the transformative potential of IWFS in promoting sustainable food systems, bolstering food security, and enhancing food quality.

Abstract The overuse of agrochemicals in greenhouse production system has aroused high concerns in China. Existing studies have investigated the status and determinants of agrochemicals overuse for greenhouse vegetables whereas little is known about whether the agrochemicals are allocated efficiently from economic perspective. We use a translog production function and the inputs and outputs data of vegetable production in 34 Chinese cities during 2004–2017 to calculate agrochemicals allocation efficiency for both open-field and greenhouse vegetables. We find that the agrochemicals are allocated inefficiently due to overuse for both open-field and greenhouse vegetables, whereas the overuse degree of chemical fertilizer used in greenhouse vegetables is lower than that of open-field vegetables during a growing duration. In addition, we also find that the application levels of agrochemicals for greenhouse vegetables per mu (15 mu = 1 hectare) are higher than those of open-field vegetables, but the application levels of agrochemicals for per kilogram greenhouse vegetables are significantly lower. We conclude that the overuse of agrochemicals in greenhouse production system may attribute to the year-round production of greenhouse vegetables induced by economic incentives. Therefore, reducing the number of production rotations may be an effective method to alleviate the overuse of agrochemicals in greenhouse vegetables.

Heat-tolerant cucumbers: The graft of life Photosynthesis-related genes and proteins are triggered into action when cucumber is grafted onto another member of the Cucurbitaceae family, helping it to tolerate heat. Shirong Guo of China’s Nanjing Agricultural University and colleagues analysed the genes and proteins of a cucumber plant grafted onto Momordica, a climbing plant from the same family, when it was exposed to high temperatures. Heat stress negatively affects photosynthesis in plants. The team found that cucumber grafted onto Momordica adapted better to heat stress than cucumber grafted onto cucumber. They found this was due to the expression of key enzymes and genes related to photosynthesis. The findings provide insight into the molecular mechanisms involved in enhancing heat stress tolerance in plants by grafting.

Plant-growth-promoting rhizobacteria (PGPR) can both improve plant growth and enhance plant resistance against a variety of environmental stresses. To investigate the mechanisms that PGPR use to protect plants under pathogenic attack, transmission electron microscopy analysis and a proteomic approach were designed to test the effects of the new potential PGPR strain Paenibacillus polymyxa NSY50 on cucumber seedling roots after they were inoculated with the destructive phytopathogen Fusarium oxysporum f. sp. cucumerinum (FOC). NSY50 could apparently mitigate the injury caused by the FOC infection and maintain the stability of cell structures. The two-dimensional electrophoresis (2-DE) approach in conjunction with MALDI-TOF/TOF analysis revealed a total of 56 proteins that were differentially expressed in response to NSY50 and/or FOC. The application of NSY50 up-regulated most of the identified proteins that were involved in carbohydrate metabolism and amino acid metabolism under normal conditions, which implied that both energy generation and the production of amino acids were enhanced, thereby ensuring an adequate supply of amino acids for the synthesis of new proteins in cucumber seedlings to promote plant growth. Inoculation with FOC inhibited most of the proteins related to carbohydrate and energy metabolism and to protein metabolism. The combined inoculation treatment (NSY50+FOC) accumulated abundant proteins involved in defense mechanisms against oxidation and detoxification as well as carbohydrate metabolism, which might play important roles in preventing pathogens from attacking. Meanwhile, western blotting was used to analyze the accumulation of enolase (ENO) and S-adenosylmethionine synthase (SAMs). NSY50 further increased the expression of ENO and SAMs under FOC stress. In addition, NSY50 adjusted the transcription levels of genes related to those proteins. Taken together, these results suggest that P. polymyxa NSY50 may promote plant growth and alleviate FOC-induced damage by improving the metabolism and activation of defense-related proteins in cucumber roots.

With the aim to clarifying the role of the ABA / H2O2 signaling cascade in the regulating the antioxidant capacity of grafted cucumber plants in response to Ca(NO3)2 stress, we investigated the relationship between ABA-mediated H2O2 production and the activities of antioxidant enzymes in the leaves of pumpkin-grafted cucumber seedlings. The results showed that both ABA and H2O2 were detected in pumpkin-grafted cucumber seedlings in response to Ca(NO3)2 treatment within 0.5 h in the leaves and peaked at 3 h and 6 h after Ca(NO3)2 treatment, respectively, compared to the levels under control conditions. The activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), and peroxidase (POD) in pumpkin-grafted cucumber leaves gradually increased over time and peaked at 12 h of Ca(NO3)2 stress. Furthermore, in the leaves of pumpkin-grafted cucumber seedlings, the H2O2 generation, the antioxidant enzyme activities and the expression of SOD, POD and cAPX were strongly blocked by an inhibitor of ABA under Ca(NO3)2 stress, but this effect was eliminated by the addition of exogenous ABA. Moreover, the activities and gene expressions of these antioxidant enzymes in pumpkin-grafted leaves were almost inhibited under Ca(NO3)2 stress by pretreatment with ROS scavengers. These results suggest that the pumpkin grafting-induced ABA accumulation mediated H2O2 generation, resulting in the induction of antioxidant defense systems in leaves exposed to Ca(NO3)2 stress in the ABA/H2O2 signaling pathway.

Soil salinity is a major environmental constraint that threatens agricultural productivity. Different strategies have been developed to improve crop salt tolerance, among which the effects of polyamines have been well reported. To gain a better understanding of the cucumber (Cucumis sativus L.) responses to NaCl and unravel the underlying mechanism of exogenous putrescine (Put) alleviating salt-induced damage, comparative proteomic analysis was conducted on cucumber roots treated with NaCl and/or Put for 7 days. The results showed that exogenous Put restored the root growth inhibited by NaCl. 62 differentially expressed proteins implicated in various biological processes were successfully identified by MALDI-TOF/TOF MS. The four largest categories included proteins involved in defense response (24.2%), protein metabolism (24.2%), carbohydrate metabolism (19.4%) and amino acid metabolism (14.5%). Exogenous Put up-regulated most identified proteins involved in carbohydrate metabolism, implying an enhancement in energy generation. Proteins involved in defense response and protein metabolism were differently regulated by Put, which indicated the roles of Put in stress resistance and proteome rearrangement. Put also increased the abundance of proteins involved in amino acid metabolism. Meanwhile, physiological analysis showed that Put could further up-regulated the levels of free amino acids in salt stressed-roots. In addition, Put also improved endogenous polyamines contents by regulating the transcription levels of key enzymes in polyamine metabolism. Taken together, these results suggest that Put may alleviate NaCl-induced growth inhibition through degradation of misfolded/damaged proteins, activation of stress defense, and the promotion of carbohydrate metabolism to generate more energy.