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Abstract Background Bactrian camel is one of the important economic animals in northwest China. They live in arid desert, and their gestation period is about 13 months, which is longer than other ruminants (such as cattle and sheep). The harsh living conditions have made its unique histological characteristics a research focus. Aggregated lymphoid nodules area (ALNA) in the abomasum of Bactrian camels, as one of the most important sites for the induction of the immune response, provide a comprehensive and effective protective role for the organism, and their lack of information will affect the feeding management, reproduction and epidemic prevention of Bactrian camels. In this study, the histological characteristics of the fetal ALNA in the abomasum of Bactrian camels at different developmental gestation have been described by using light microscopy and histology . Results The ALNA in the abomasum of the Chinese Alashan Bactrian camel is a special immune structure that was first discovered and reported by Wen-hui Wang. To further establish the developmental characteristics of this special structure in the embryonic stage, the abomasum ALNA of 8 fetuses of Alashan Bactrian camels with different gestational ages (5~13 months) were observed and studied by anatomy and histology. The results showed that the aggregation of reticular epithelial cells (RECs) surrounded by a very small number of lymphoid cells was detected for the first time in the abomasum of fetal camel at 5 months gestation, which was presumed to be primitive ALNA. At 7 months gestation, the reticular mucosal folds region (RMFR) appeared, but the longitudinal mucosal folds region (LMFR) was not significant, and histological observations showed that there were diffusely distributed lymphocytes around the RECs. At 10months gestation, RMFR and LMFR were clearly visible, lymphoid follicles appeared in histological observation, lymphocytes proliferated vigorously. By 13 months, the volume of lymphoid follicles increased, forming the subepithelial dome (SED), and there was a primitive interfollicular area between the lymphoid follicles, which contained high endothelial vein (HEV), but no germinal center (GC) was found. In summary, ALNA of Bactrian camels is not fully mature before birth. Conclusions Generally, the small intestine PPs of ruminants (such as cattle and sheep) is already mature before birth, while the ALNA in the abomasum of Bactrian camels is not yet mature in the fetal period. During the development of ALNA in Bactrian camel, the development of lymphoid follicles extends from submucosa to Lamina propria. Interestingly, the deformation of FAE changes with age from simple columnar epithelium at the beginning of pregnancy to Simple cuboidal epithelium, which is opposite to the FAE deformation characteristics of PPs in the small intestine of fetal cattle and sheep. These results are the basis of further research on the specificity of ALNA in the abomasum of Bactrian camels.

Abstract Background Evidences of comparison of sex difference in Chinese irritable bowel syndrome (IBS) patients were few. We aim to compare gender difference in the biopsychosocial characteristics of Chinese patients of IBS predominant with diarrhea (IBS-D). Methods IBS-D patients meeting Rome III criteria were enrolled. We administered IBS symptom questionnaires, evaluation of psychological status (HAMD and HAMA scales) and IBS quality of life (IBS-QOL), dietary habits, healthcare seeking behaviors, and compared biopsychosocial characteristics between male and female patients. Results Four hundred and ninety patients were enrolled including 299 males and 191 females. More female patients reported abdominal pain associated with defecation (84.3% vs. 74.9%, P = 0.014) while males reported more abdominal discomfort (39.8% vs. 26.7%, P = 0.003). Females had higher IBS symptom score (9.7 ± 1.7 vs. 9.4 ± 1.4, P = 0.025) and more of females had severe abdominal pain/discomfort (17.8% vs. 12.4%, P = 0.013) while there were no significant differences of other bowel symptoms. Females reported higher incidence of comorbid anxiety state (64.9% vs. 52.8%, P = 0.008) and depression state (35.6% vs. 19.7%, P

Background: Cancer stem cells (CSCs) are pivotal in tumor resistance to chemotherapy and gastric cancer's rapid proliferation and metastasis. We aimed to explore the CSCs-related genes in gastric cancer epithelial cells. Methods: The mRNA expression profile and single-cell sequencing data of gastric cancer were downloaded from the public database. Results: We identified WDR72 as a CSCs-related gene in gastric cancer epithelial cells. WDR72 was highly expressed in gastric cancer tissues, and high expression of WDR72 was associated with inferior prognosis of patients. WDR72 expression had a significant negative correlation with the infiltration of CD8 + T cells and activated memory CD4 + T cells. PD-L1 expression was significantly reduced in gastric cancer patients with high WDR72 expression. WDR72 was correlated with IC50 of multiple small-molecule drugs. Conclusion: We identified a novel CSCs-related gene in gastric cancer epithelial cells, WDR72, which was highly expressed in patients with high stemness scores.

In an arid region, water shortage limits agricultural development, and worse, soil salinization is accompanied by soil moisture drought. In this region, hydraulic lift occurs due to the drying upper layer caused by high precipitation and the wet lower layer. Hydraulic lift is defined as water redistribution from wetter, deeper soil layers to drier, shallower soil layers near the soil surface through the plant roots. To examine the effects of water and salt stresses on tomato yield and fruit quality under the condition of hydraulic lift, a 2year experiment was conducted. Different water and salt treatments were designed, including three water levels (W1, W2 and W3 indicating soil moisture contents of 60%–70%, 50%–60% and 40%–50% of the field capacity, respectively) and four salt levels (S0, S1, S2 and S3 indicating NaCl addition of 0%, 0.2%, 0.4% and 0.6% of the dry soil weight, respectively) of the upper pot, and water and salt levels of control treatment (CK) were W1 and S0, respectively. The yield under other treatments significantly decreased by 4.59%–58.39% and 5.12%–62.96% in 2018 and 2019, respectively, compared with that under CK, and the yield under W1S1 treatment had no significance with that under CK in 2018. The firmest fruit quality was observed in the plant under W3S1 treatment, and the percentage increases were 28.67% and 28.89% in both years compared with that under CK. Water, salt stress and their interactions had significant effects on tomato taste quality and vitamin C. Tomato taste quality and vitamin C decreased under the W3 and S3 treatments. In both years, the total magnitudes of hydraulic lift during the entire growth period were higher under the W1S2 treatment (65.20% and 76.06%, respectively) than that under CK. Whereas yield and total magnitudes of hydraulic lift were significantly both correlated with single fruit weight, single fruit volume, fruit shape index and taste qualities, no correlations were observed between hydraulic lift and yield. Mild waterdeficit and salt stresses could improve tomato quality with negligible yield loss, and hydraulic lift had positive effects on fruit quality. Principal component analysis revealed that the combination of W1 and S1 treatments increased fruit quality and total hydraulic lift magnitudes with an acceptable yield decline. These results are important for tomato production in arid saline-alkali region where hydraulic lift is positively corelated with fruit quality and famers may consider this trait to resist drought and soil salinization. Future studies focusing on the effects of the internal mechanisms of hydraulic lift caused by changes in sap flow on tomato quality and yield are warranted.

Multi-factor screenings are commonly used in diverse applications in medicine and bioengineering, including optimizing combination drug treatments and microbiome engineering. Despite the advances in high-throughput technologies, large-scale experiments typically remain prohibitively expensive. Here we introduce a machine learning platform, structure-augmented regression (SAR), that exploits the intrinsic structure of each biological system to learn a high-accuracy model with minimal data requirement. Under different environmental perturbations, each biological system exhibits a unique, structured phenotypic response. This structure can be learned based on limited data and once learned, can constrain subsequent quantitative predictions. We demonstrate that SAR requires significantly fewer data comparing to other existing machine-learning methods to achieve a high prediction accuracy, first on simulated data, then on experimental data of various systems and input dimensions. We then show how a learned structure can guide effective design of new experiments. Our approach has implications for predictive control of biological systems and an integration of machine learning prediction and experimental design.

IntroductionFetal heart rate monitoring during labor can aid healthcare professionals in identifying alterations in the heart rate pattern. However, discrepancies in guidelines and obstetrician expertise present challenges in interpreting fetal heart rate, including failure to acknowledge findings or misinterpretation. Artificial intelligence has the potential to support obstetricians in diagnosing abnormal fetal heart rates.MethodsEmploy preprocessing techniques to mitigate the effects of missing signals and artifacts on the model, utilize data augmentation methods to address data imbalance. Introduce a multi-scale long short-term memory neural network trained with a variety of time-scale data for automatically classifying fetal heart rate. Carried out experimental on both single and multi-scale models.ResultsThe results indicate that multi-scale LSTM models outperform regular LSTM models in various performance metrics. Specifically, in the single models tested, the model with a sampling rate of 10 exhibited the highest classification accuracy. The model achieves an accuracy of 85.73%, a specificity of 85.32%, and a precision of 85.53% on CTU-UHB dataset. Furthermore, the area under the receiver operating curve of 0.918 suggests that our model demonstrates a high level of credibility.DiscussionCompared to previous research, our methodology exhibits superior performance across various evaluation metrics. By incorporating alternative sampling rates into the model, we observed improvements in all performance indicators, including ACC (85.73% vs. 83.28%), SP (85.32% vs. 82.47%), PR (85.53% vs. 82.84%), recall (86.13% vs. 84.09%), F1-score (85.79% vs. 83.42%), and AUC(0.9180 vs. 0.8667). The limitations of this research include the limited consideration of pregnant women’s clinical characteristics and disregard the potential impact of varying gestational weeks.

Covert speech (CS) refers to speaking internally to oneself without producing any sound or movement. CS is involved in multiple cognitive functions and disorders. Reconstructing CS content by brain-computer interface (BCI) is also an emerging technique. However, it is still controversial whether CS is a truncated neural process of overt speech (OS) or involves independent patterns. Here, we performed a word-speaking experiment with simultaneous EEG-fMRI. It involved 32 participants, who generated words both overtly and covertly. By integrating spatial constraints from fMRI into EEG source localization, we precisely estimated the spatiotemporal dynamics of neural activity. During CS, EEG source activity was localized in three regions: the left precentral gyrus, the left supplementary motor area, and the left putamen. Although OS involved more brain regions with stronger activations, CS was characterized by an earlier event-locked activation in the left putamen (peak at 262 ms versus 1170 ms). The left putamen was also identified as the only hub node within the functional connectivity (FC) networks of both OS and CS, while showing weaker FC strength towards speech-related regions in the dominant hemisphere during CS. Path analysis revealed significant multivariate associations, indicating an indirect association between the earlier activation in the left putamen and CS, which was mediated by reduced FC towards speech-related regions. These findings revealed the specific spatiotemporal dynamics of CS, offering insights into CS mechanisms that are potentially relevant for future treatment of self-regulation deficits, speech disorders, and development of BCI speech applications.

Abstract Extramedullary multiple myeloma (EMM) is defined as the presence of plasma cells outside the bone marrow of multiple myeloma patients, and its prognosis is poor. High-dose chemotherapy with autologous stem cell transplantation, as a good option on early lines of therapy, has retained the survival benefit of youny EMM patients, but is intolerant for the majority of old patients because of drug cytotoxicity. To essentially address the intolerance above, we designed a CXCR4-PEG-CdTe-DOX (where CXCR4: chemokine receptor 4; PEG-CdTe: polyethylene glycol-modified cadmium telluride; DOX:doxorubicin) nanoplatform. First, CXCR4 is highly expressed in extramedullary plasma cells. Second, PEG-CdTe a drug carrier that controls drug release, can reduce adverse reactions, prolong drug (e.g, DOX) circulation time in the body, and form a targeting carrier after connecting antibodies. In vitro experiments showed CXCR4-PEG-CdTe-DOX facilitated intracellular drug accumulation through active CXCR4 targeting and released DOX into the microenvironment in a pH-controlled manner, enhancing the therapeutic efficacy and apoptosis rate of myeloma cells (U266). Therefore, targeted chemotherapy mediated by CXCR4-PEG-CdTe-DOX is a promising option for EMM treatment. Graphical abstract Figure 1 Action mechanism of drug delivery pathway: CXCR4-PEG-CdTe-DOX nanocomplex can be targeted and close to MM cell membranes, effectively transport DOX into MM cells, and promote MM cell apoptosis.

This paper examines biosafety management in high-biosafety-risk workshops for vaccine production in China, focusing on the context of SARS-CoV-2 inactivated vaccine production. It addresses various aspects, including biosafety management, personnel, virus seed, facilities, and equipment, and compliance with relevant biosafety laws and regulations. The aim is to promote the use of high-level biosafety facilities when dealing with emerging infectious diseases.

Abstract Objective To investigate the effect of therapeutic hypercapnia on the expression and function of gamma delta T (γδ T) cells during ischemia‐reperfusion injury (IRI) after lung transplantation. Methods We randomly divided male Wistar rats into three groups (n = 6 in each group), the control group (group N), the IRI group (group I), and the therapeutic hypercapnia group (group H). We then assessed pulmonary edema, neutrophil infiltration, wet‐to‐dry (W/D) weight ratio, and microscopic histopathology and separately measured the levels of γδT cell surface antigen (TCR) and Interleukin‐17 (IL‐17) using flow cytometry and enzyme‐linked immunosorbent assays (ELISAs). Results The infiltration of neutrophils and the expression of TCR and IL‐17 were significantly increased in the I group compared to the control, and the biopsy edema in group I was more severe. Arterial partial pressure of oxygen (PaO2) was decreased after reperfusion in group I compared with the control group. W/D weight ratio, neutrophil infiltration, and the expression of TCR and IL‐17 decreased drastically in the H group compared to the I group. Conclusion Our findings suggest that γδ T lymphocytes were directly involved in lung injury. In addition, therapeutic hypercapnia effectively reduced the expression of γδ T cells and IL‐17, and this has the potential to become a treatment strategy for IRI and an intervention to improve lung function.

Abstract Background In Asia, the proportion of patients with irritable bowel syndrome (IBS) with abdominal discomfort alone is significantly higher than that in western countries. The purposes of this study are to understand the cognition of abdominal pain and abdominal discomfort in Chinese patients with IBS and to compare the clinical characteristics of patients with abdominal pain alone and with abdominal discomfort alone. Methods Patients with IBS with diarrhea (IBS-D) who met the Rome III diagnostic criteria and had episodes of at least one day/week were consecutively enrolled. The cognition of abdominal pain and abdominal discomfort were investigated through face-to-face unstructured interview. Patients were divided into a pain group and a discomfort group according to the cognition interviews, then the characteristics and severity of symptoms (IBS symptom severity scale, IBS-SSS), IBS quality of life (IBS-QOL) and psychological state were compared between groups. Results A total of 88 patients with IBS-D were enrolled. Most of the patients with self-reported abdominal pain described their pain as spasm/cramping; patients with self-reported abdominal discomfort had as many as 24 different descriptions of discomfort. Most patients having abdominal pain and discomfort could accurately distinguish the two symptoms. The degree of abdominal pain in the pain group was higher than abdominal discomfort in the discomfort group (P = 0.002). There was no significant difference in IBS-SSS, extra-intestinal pain, IBS-QOL, and psychological state between the two groups. Conclusions For Chinese patients with IBS-D, abdominal pain and abdominal discomfort are two different symptoms, but they have similar clinical features. Trial registration ChiCTR, ChiCTR1900028082. Registered 11 December 2019 - Retrospectively registered, http://www.chictr.org.cn .

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.1.351 variant inactivated vaccine candidate (B.1.351V) generated strong binding and neutralizing antibody responses in BALB/c mice against the B.1.351 virus and other SARS-CoV-2 variants after two doses within 28 days. Immunized K18-hACE2 mice also exhibited elevated levels of live virus-neutralizing antibodies against various SARS-CoV-2 viruses. Following infection with these viruses, K18-hACE2 mice displayed a stable body weight, a high survival rate, minimal virus copies in lung tissue, and no lung damage compared to the control group. These findings indicate that B.1.351V offered protection against infection with multiple SARS-CoV-2 variants in mice, providing insights for the development of a vaccine targeting SARS-CoV-2 VOCs for human use.

Summary: Corneal alkali burn remains a clinical challenge in ocular emergency, necessitating the development of effective therapeutic drugs. Here, we observed the arachidonic acid metabolic disorders of corneas induced by alkali burns and aimed to explore the role of Prostaglandin E2 (PGE2), a critical metabolite of arachidonic acid, in the repair of alkali-burned corneas. We found a moderate dosage of PGE2 promoted the alkali-burned corneal epithelial repair, whereas a high dosage of PGE2 exhibited a contrary effect. This divergent effect is attributed to different dosages of PGE2 regulating ANXA1 expression differently. Mechanically, a high dosage of PGE2 induced higher GATA3 expression, followed by enhanced GATA3 binding to the ANXA1 promoter to inhibit ANXA1 expression. In contrast, a moderate dosage of PGE2 increased CREB1 phosphorylation and reduced GATA3 binding to the ANXA1 promoter, promoting ANXA1 expression. We believe PGE2 and its regulatory target ANXA1 could be potential drugs for alkali-burned corneas.

ABSTRACTSince May 2022, human mpox cases have increased unexpectedly in non-endemic countries. The first imported case of human mpox in Hong Kong was reported in September 2022. Here we report the isolation and identification of MPXV from the vesicle swabs of this patient. In this research, the vesicle swabs were inoculated in Vero and Vero E6 cells. In addition to observing cytopathic effects (CPEs) in Vero or Vero E6 cells, the isolated virus was identified as mpox virus (MPXV) using quantitative Real-Time PCR (RT–PCR), transmission electron microscopy, and high-throughput sequencing. The experiment also assessed the cross-protective efficacy of sera from the smallpox vaccinated population and preliminarily assessed the inhibitory effect of anti-smallpox virus drugs against MPXV. CPEs can be observed on Vero E6 cells at 24 h and Vero cells at 48 h. The virus particles could be observed by transmission electron microscope, showing typical orthopoxvirus morphology. In addition, F3L and ATI genes which from MPXV A39R, B2R, HA genes which from orthopoxvirus were confirmed by conventional PCR and Sanger sequencing. The next generation sequencing (NGS) suggests that the MPXV strain belongs to B.1 branch of the West African linage, and has a high identity with the sequence of the 2022 ongoing outbreak. PRNT50 results showed that 26.7% of sera from individuals born before 1981 who had been immunized with smallpox were positive, but no MPXV-neutralizing antibodies were found in sera from individuals born later. All four anti-smallpox virus drugs evaluated demonstrated inhibition of mpox virus.

Seagrass beds are a typical coastal ecosystem. To understand the temporal and spatial variation characteristics of the plankton community structure in a Zostera marina seagrass bed and an adjacent area of bare sand in Swan Lake, Rongcheng City, Shandong Province, an investigation of plankton diversity and abundance, ecological characteristics of the seagrass bed, and key environmental factors in the Z. marina seagrass bed and its adjacent bare sand area was conducted in February, May, August, and November in 2019. Canonical correspondence analysis (CCA) and redundancy analysis (RDA) were used to explore the influence of environmental factors on the diversity of plankton species. The results showed that there were 38 species of phytoplankton, belonging to 25 genera and three phyla, among which diatom species were the most abundant (89.4%), followed by dinoflagellates (7.8%). A total of 18 species of zooplankton and three species of larvae were identified (mainly crustaceans: 71.4%), and the number of plankton species was the highest in November. The annual average abundance of phytoplankton and zooplankton in the seagrass bed was 5.4×104 cells/m3 and 1.6×104 ind./m3, respectively, which were 1.4 times and 1.5 times higher than those in the bare sand area. The CCA and RDA analyses showed that the dominant plankton species in the seagrass bed were significantly correlated with water temperature, plant density, and biomass of seagrass beds, while the dominant plankton species in the bare sand area were mainly correlated with environmental factors such as water temperature, pH value, and ammonia nitrogen content. The results showed that the seagrass bed in Swan Lake supported a higher abundance and diversity of plankton compared with the bare sand area. This study provides baseline data for further elucidating the structure and function of the seagrass bed ecosystem.

As SARS-CoV-2 continues to evolve and COVID-19 cases rapidly increase among children and adults, there is an urgent need for a safe and effective vaccine that can elicit systemic and mucosal humoral immunity to limit the emergence of new variants. Using the Chinese Hu191 measles virus (MeV-hu191) vaccine strain as a backbone, we developed MeV chimeras stably expressing the prefusion forms of either membrane-anchored, full-length spike (rMeV-preFS), or its soluble secreted spike trimers with the help of the SP-D trimerization tag (rMeV-S+SPD) of SARS-CoV-2 Omicron BA.2. The two vaccine candidates were administrated in golden Syrian hamsters through the intranasal or subcutaneous routes to determine the optimal immunization route for challenge. The intranasal delivery of rMeV-S+SPD induced a more robust mucosal IgA antibody response than the subcutaneous route. The mucosal IgA antibody induced by rMeV-preFS through the intranasal routine was slightly higher than the subcutaneous route, but there was no significant difference. The rMeV-preFS vaccine stimulated higher mucosal IgA than the rMeV-S+SPD vaccine through intranasal or subcutaneous administration. In hamsters, intranasal administration of the rMeV-preFS vaccine elicited high levels of NAbs, protecting against the SARS-CoV-2 Omicron BA.2 variant challenge by reducing virus loads and diminishing pathological changes in vaccinated animals. Encouragingly, sera collected from the rMeV-preFS group consistently showed robust and significantly high neutralizing titers against the latest variant XBB.1.16. These data suggest that rMeV-preFS is a highly promising COVID-19 candidate vaccine that has great potential to be developed into bivalent vaccines (MeV/SARS-CoV-2).

Abstract Wireless capsule endoscopy (WCE) is becoming more popular in clinical settings as a safe and painless gastrointestinal examination. Existing studies on automatic detection of lesions in WCE images have the problems of small dataset size and uneven distribution of numbers in terms of categories, which often leads to overfitting of the model and severely limits the performance improvement of the object detection network on WCE images. The traditional data enhancement methods such as flipping and local erasure have limitations and cannot achieve good generalization results. Therefore, a WCE‐DCGAN network was proposed in this paper to generate WCE images from existing WCE images. Using the images generated by this network and the original images as the input of the object detection network, there are different degrees of performance improvement on SSD, YOLOv5, and YOLOv4, and the average recognition accuracy of 97.25% can be achieved on SSD. Meanwhile, images generated by WCE‐DCGAN not only enlarge the size of the data set, but also have the characteristics of diversity, which makes the model have a good generalization effect.

Cascade hydropower producers face two stages of risk when participating in medium and long-term market transactions: transaction risk during the bidding stage; and the operational risk during the scheduling and operation stage due to the uncertainty of runoff and market-clearing prices. Therefore, how to measure the above risks and make corresponding decisions has become an urgent problem for producers.This paper combines the real market structure and rules of a certain hydropower dominated market in Southwest China, and establishes a mid-term operation and trading decision-making method based on the Joint Information Gap Decision Theory (IGDT) and Prospect Theory. To address the main uncertainty variables that producers face in participating in transactions, this paper obtains the maximum fluctuation range of variables that satisfy the expected revenue in a robust model based on IGDT. Then, using Prospect Theory, a bidding strategy model that takes into account the psychological factors of producers is constructed within this range.To solve the nonlinear programming problem and address the accuracy issues caused by curve fitting during the solution process, a nonlinear programming combined with an improved stepwise optimization hybrid algorithm is employed.Using actual data from a hydropower grid in southwest China participating in the market as an example. The results indicate that the method provides the fluctuation range of runoff and market prices under different expected return targets, and can formulate reasonable bidding decisions and operation plans based on producers different risk preferences within this range.

Alzheimer’s disease: Protein-activating chili extract improves brain’s immune function A chili pepper extract that activates a sensory protein helps to improve lipid metabolism in immune cells in the brain, leading to better nerve cell health in a mouse model of Alzheimer’s disease. A team led by Zhihua Yu and Hongzhuan Chen from the Shanghai Jiao Tong University School of Medicine, China, showed that mice carrying the ApoE4 risk factor gene for Alzheimer’s exhibited defects in how well their brain’s immune cells, known as microglia, processed lipids. These problems were exacerbated when the microglia lacked a working version of a sensory protein called TRPV1. Boosting the activity of this protein with capsaicin, a TRPV1-stimulating molecule found in hot chili peppers, reversed the metabolic defects, leading to improved microglial function, reduced Alzheimer’s-associated brain pathology and enhanced memory in the mice.

Traditional Chinese medicine (TCM) has been successfully applied worldwide in the treatment of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pharmacological mechanisms underlying this success remain unclear. Hence, the aim of this review is to combine pharmacological assays based on the theory of TCM in order to elucidate the potential signaling pathways, targets, active compounds, and formulas of herbs that are involved in the TCM treatment of COVID-19, which exhibits combatting viral infections, immune regulation, and amelioration of lung injury and fibrosis. Extensive reports on target screening are elucidated using virtual prediction via docking analysis or network pharmacology based on existing data. The results of these reports indicate that an intricate regulatory mechanism is involved in the pathogenesis of COVID-19. Therefore, more pharmacological research on the natural herbs used in TCM should be conducted in order to determine the association between TCM and COVID-19 and account for the observed therapeutic effects of TCM against COVID-19.

Abstract The immunity of patients who recover from coronavirus disease 2019 (COVID-19) could be long lasting but persist at a lower level. Thus, recovered patients still need to be vaccinated to prevent reinfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or its mutated variants. Here, we report that the inactivated COVID-19 vaccine can stimulate immunity in recovered patients to maintain high levels of anti-receptor-binding domain (RBD) and anti-nucleocapsid protein (NP) antibody titers within 9 months, and high neutralizing activity against the prototype, Delta, and Omicron strains was observed. Nevertheless, the antibody response decreased over time, and the Omicron variant exhibited more pronounced resistance to neutralization than the prototype and Delta strains. Moreover, the intensity of the SARS-CoV-2-specific CD4+ T cell response was also increased in recovered patients who received COVID-19 vaccines. Overall, the repeated antigen exposure provided by inactivated COVID-19 vaccination greatly boosted both the potency and breadth of the humoral and cellular immune responses against SARS-CoV-2, effectively protecting recovered individuals from reinfection by circulating SARS-CoV-2 and its variants.

Background: Mpox virus (MPXV) infections have increased in many countries since May 2022, increasing demand for diagnostic tests and research on the virus. To ensure personnel safety, appropriate and reliable measures are needed to disinfect and inactivate infectious samples; Methods: We evaluated the stability of infectious MPXV cultures stored at different temperatures and through freeze–thaw cycles. Heat physical treatment (56 °C, 70 °C, 95 °C), chemical treatment (beta-propiolactone (BPL)) and two commercialized disinfectants (Micro-Chem Plus (MCP) and ethanol) were tested against infectious MPXV cultures; Results: The results indicated that MPXV stability increases with lower temperatures. The MPXV titer was stable within three freeze–thaw cycles and only decreased by 1.04 log10 (lg) 50% cell culture infective dose (CCID50) per milliliter (12.44%) after twelve cycles. MPXV could be effectively inactivated at 56 °C for 40 min, 70 °C for 10 min, and 95 °C for 5 min. For BPL inactivation, a 1:1000 volume ratio (BPL:virus) could also effectively inactivate MPXV. A total of 2% or 5% MCP and 75% ethanol treated with MPXV for at least 1 min could reduce >4.25 lg; Conclusions: MPXV shows high stability to temperature and freeze–thaw. Heat and BPL treatments are effective for the inactivation of MPXV, while MCP and ethanol are effective for disinfection, which could help laboratory staff operate the MPXV under safer conditions and improve operational protocols.

Plant height and biomass are important indicators of rice yield. Here we combined measured plant physiological traits with a crop growth model driven by unmanned aerial vehicle spectral data to quantify the changes in rice plant height and biomass under different irrigation and fertilizer treatments. The study included two treatments: I—water availability factor (i.e., three drought objects, optimal, and excess water); and II—two levels of deep percolation and five nitrogen fertilization doses. The introduced model is extreme learning machine (ELM), back propagation neural network (BPNN), and particle swarm optimization-ELM (PSO-ELM), respectively. The results showed that: (1) Proper water level regulation (3~5 cm) significantly increased the accumulation of spike biomass, which was about 6% higher compared to that under flooded conditions. (2) For plant height inversion, the ELM model was optimal with a mean coefficient of determination of 0.78, a mean root mean square error of 0.26 cm, and a mean performance deviation rate of 2.08. For biomass inversion, the PSO-ELM model was optimal with a mean coefficient of determination of 0.88, a mean root mean square error of 3.8 g, and a mean performance deviation rate of 3.29. This study provided the possible opportunity for large-scale estimations of rice yield under environmental disturbances.

Dry topsoil and relatively moist subsoil can occur in specific areas and times, limiting plant growth but creating conditions for hydraulic lift (HL). There is a lack of a rational water and nitrogen (N) strategy to improve cotton growth and maintain HL. This study investigated the effects of three topsoil water conditions (W0.6: 60–70%, W0.5: 50–60%, and W0.4: 40–50% of field capacity) and three N rates (N120-120, N240-240, and N360-360 kg N ha−1) plus one control treatment on cotton growth and HL under dry topsoil conditions in 2020 and 2021. The results showed that plant height and leaf area increased with increasing N rate, but the differences among topsoil water conditions were relatively small, except for leaf area in 2021. The HL water amount of all treatments increased gradually and then continued to decline during the observation period. There was a trend that the drier the topsoil or the more N applied, the greater the amount of HL water. Additionally, topsoil water conditions and N rate significantly affected the total HL water amount and root morphological characteristics (root length, surface area, and volume). Seed and lint cotton yield tended to decrease with increasing topsoil dryness at N240 or N360, except for lint yield in 2021, or with decreasing N rate, especially under W0.6. As topsoil became drier, the total evapotranspiration (ET) decreased, while with the increase in N rate, ET showed small differences. Water use efficiency increased with a higher N rate, while N partial factor productivity (PFPN) did the opposite. Furthermore, the PFPN under W0.4 was significantly lower than that under W0.6 at N240 or N120. These findings could be useful for promoting the utilization of deep water and achieving sustainable agricultural development.

SARS-CoV-2 variants of concern (VOCs) show increasing transmissibility and infectivity and induce substantial injuries to human health and the ecology. Therefore, it is vital to understand the related features for controlling infection. In this study, SARS-CoV-2 WIV04 (prototype) and five VOCs (Beta, Delta, Omicron BA.1, BA.2 and BA.5 variants) were inoculated in Vero cells to observe their growth activities. Apart from evaluating the environmental stability at different temperatures, residual virus titers and infectivity at different temperatures (4 °C, room temperature (RT) and 37 °C) were measured over 7 days. The experiment also assessed the infectivity for different incubation durations. The growth capacity assay suggested that the WIV04, Beta and Delta variants replicated efficiently in Vero cells compared with Omicron Variants, and BA.2 replicated more efficiently in Vero cells than BA.1 and BA.5. In addition, all variants exhibited longer survivals at 4 °C and could remain infectious after 7 days, compared to RT’ survival after 5 days and at 37 °C after 1 day. The virus infection assay indicated that the Omicron variant had a weaker ability to infect cells compared to the WIV04, Beta and Delta strains, and a longer infection time was required for these strains, except for BA.2.

BackgroundYoung children have a great disease burden and are particularly vulnerable to influenza. This study aimed to assess the direct effect of influenza vaccination among children and to evaluate the indirect benefit of immunizing children.MethodsThe influenza vaccination records for all children born during 2013–2019 in Minhang District and surveillance data for reported influenza cases were obtained from the Minhang CDC. 17,905 children were recorded in the vaccination system and included in this study. Descriptive epidemiology methods were used for data analysis, including an ecological approach to estimate the number of influenza cases averted by vaccination and linear regression to estimate the reduction in influenza cases in the general population per thousand additional childhood vaccination doses.ResultsDuring the study period, the annual vaccination coverage rate ranged from 10.40% in 2013–2014 to 27.62% in 2015–2016. The estimated number of influenza cases averted by vaccination ranged from a low of 0.28 (range: 0.23–0.34) during 2013–2014 (PF: 6.15%, range: 5.11–7.38%) to a high of 15.34 (range: 12.38–18.51) during 2017–2018 (PF: 16.54%, range: 13.79–19.30%). When increasing vaccination coverage rate by 10% in each town/street, a ratio of 7.27–10.69% cases could be further averted on the basis of observed cases. In four selected periods, the number of influenza cases in the general population was most significantly correlated with the cumulative childhood vaccination doses in the prior 2–5 months, and the reduction in influenza cases ranged from 0.73 to 3.18 cases per thousand additional childhood vaccination doses.ConclusionInfluenza vaccination among children is estimated to have direct effects in terms of averted cases and might provide an underlying indirect benefit to the general population. Vaccination coverage in high-coverage areas should be further expanded to avert more influenza cases.

Since May 2022, mutant strains of mpox (formerly monkeypox) virus (MPXV) have been rapidly spreading among individuals who have not traveled to endemic areas in multiple locations, including Europe and the United States. Both intracellular and extracellular forms of mpox virus have multiple outer membrane proteins that can stimulate immune response. Here, we investigated the immunogenicity of MPXV structural proteins such as A29L, M1R, A35R, and B6R as a combination vaccine, and the protective effect against the 2022 mpox mutant strain was also evaluated in BALB/c mice. After mixed 15 μg QS-21 adjuvant, all four virus structural proteins were administered subcutaneously to mice. Antibody titers in mouse sera rose sharply after the initial boost, along with an increased capacity of immune cells to produce IFN-γ alongside an elevated level of cellular immunity mediated by Th1 cells. The vaccine-induced neutralizing antibodies significantly inhibited the replication of MPXV in mice and reduced the pathological damage of organs. This study demonstrates the feasibility of a multiple recombinant vaccine for MPXV variant strains.

Multiple studies have documented low human papillomavirus (HPV) vaccine uptake among Chinese girls. It remains crucial to determine the parental willingness to pay (WTP) HPV vaccine for girls. We conducted a cross-sectional study recruiting 3904 parents with girls aged 9–14 in Shanghai, China, employing an online questionnaire with a convenience sampling strategy. Parental WTP, both range of payment and estimated point value, were determined for themselves (or wives) and daughters. HPV vaccine uptake was 22.44% in mothers and 3.21% in daughters. Respondents favored WTP ≤ 1000 CNY/138 USD for themselves (or wives), whereas showed increasing WTP along with valency of HPV vaccine for daughters (2-valent: 68.62% ≤1000 CNY/138 USD; 4-valent: 56.27% 1001–2000 CNY/138–277 USD; 9-valent: 65.37% ≥2001 CNY/277 USD). Overall, respondents showed higher WTP for daughters (median 2000 CNY/277 USD; IQR 1000–3600 CNY/138–498 USD) than for themselves (2000 CNY/277 USD; 1000–3500 CNY/138–483 USD) or wives (2000 CNY/277 USD; 800–3000 CNY/110–414 USD) (each p

This study aimed to assess the attitudes and willingness of pregnant women to receive the influenza vaccine and the factors influencing their decisions. A sample survey was conducted among pregnant women receiving prenatal care at various medical institutions in Minhang District, Shanghai, from March to June 2023. The survey included inquiries about demographic information, knowledge, and perception of influenza disease and influenza vaccine. Logistic regression models and chi-square tests were used to analyze the data. 6.9% (78/1125) of participants considered receiving the influenza vaccine during pregnancy. Participants with graduate education or above (OR = 4.632, 95%CI: 1.046–20.517), non-office workers (OR = 2.784, 95%CI: 1.560–4.970), and participants whose spouses were not office workers (OR = 0.518, 95% CI: 0.294–0.913) were significantly associated with high intent to vaccinate. Participants with superior knowledge (>30 points) exhibited greater willingness (p

ABSTRACTGenerating an infectious non-human primate (NHP) model using a prevalent monkeypox virus (MPXV) strain has emerged as a crucial strategy for assessing the efficacy of vaccines and antiviral drugs against human MPXV infection. Here, we established an animal model by infecting cynomolgus macaques with the prevalent MPXV strain, WIBP-MPXV-001, and simulating its natural routes of infection. A comprehensive analysis and evaluation were conducted on three animals, including monitoring clinical symptoms, collecting hematology data, measuring viral loads, evaluating cellular and humoral immune responses, and examining histopathology. Our findings revealed that initial skin lesions appeared at the inoculation sites and subsequently spread to the limbs and back, and all infected animals exhibited bilateral inguinal lymphadenopathy, eventually leading to a self-limiting disease course. Viral DNA was detected in post-infection blood, nasal, throat, rectal and blister fluid swabs. These observations indicate that the NHP model accurately reflects critical clinical features observed in human MPXV infection. Notably, the animals displayed clinical symptoms and disease progression similar to those of humans, rather than a lethal outcome as observed in previous studies. Historically, MPXV was utilized as a surrogate model for smallpox. However, our study contributes to a better understanding of the dynamics of current MPXV infections while providing a potential infectious NHP model for further evaluation of vaccines and antiviral drugs against mpox infection. Furthermore, the challenge model closely mimics the primary natural routes of transmission for human MPXV infections. This approach enhances our understanding of the precise mechanisms underlying the interhuman transmission of MPXV.

Studying the cell composition of acral melanoma at the single-cell level could provide some clues about its poor response to immunotherapy. Here, the authors analyse acral and cutaneous melanoma patient samples using single-cell RNA-sequencing, and reveal a severe immunosuppressive state in acral melanomas

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs), especially the latest Omicron, have exhibited severe antibody evasion. Broadly neutralizing antibodies with high potency against Omicron are urgently needed for understanding the working mechanisms and developing therapeutic agents. In this study, we characterized the previously reported F61, which was isolated from convalescent patients infected with prototype SARS-CoV-2, as a broadly neutralizing antibody against all VOCs including Omicron BA.1, BA.1.1, BA.2, BA.3 and BA.4 sublineages by utilizing antigen binding and cell infection assays. We also identified and characterized another broadly neutralizing antibody D2 with epitope distinct from that of F61. More importantly, we showed that a combination of F61 with D2 exhibited synergy in neutralization and protecting mice from SARS-CoV-2 Delta and Omicron BA.1 variants. Cryo-Electron Microscopy (Cryo-EM) structures of the spike-F61 and spike-D2 binary complexes revealed the distinct epitopes of F61 and D2 at atomic level and the structural basis for neutralization. Cryo-EM structure of the Omicron-spike-F61-D2 ternary complex provides further structural insights into the synergy between F61 and D2. These results collectively indicated F61 and F61-D2 cocktail as promising therapeutic antibodies for combating SARS-CoV-2 variants including diverse Omicron sublineages.

Objective: Sarcomas are a group of rare malignancies with various subtypes. Patients with metastatic sarcoma who have failed traditional treatments can possibly achieve better prognoses from using novel therapies, including anti-programmed death-1 (PD-1)-based therapies. Methods: We retrospectively analyzed clinical data of 24 metastatic sarcoma patients from June 15, 2016 to December 30, 2019. These patients mainly received angiogenesis inhibitors combined with anti-PD-1 therapy after they became resistant to traditional treatments. Furthermore, 8 patients underwent panel DNA and whole transcript sequencing. Results: Six patients received 2 cycles of anti-PD-1 therapy and were included in the safety evaluation only group. The median follow-up time was 5.77 months. The median progression-free survival was 7.59 months, the overall response rate was 16.7% and the disease control rate was 55.6%. Based on whole exome and transcript sequencing data, there was no association between TMB, TNB, MSI, HLA-LOH, and PD-L1 expressions and sarcoma types with clinical responses. Immunotherapy efficacy and bioinformatics analyses indicated higher intratumoral heterogeneity (ITH) in progressive disease (PD) patients and lower ITH in partial response (PR) and stable disease patients. A higher percentage of immune cell infiltration, especially monocytes, was observed in PR patients. Active stromal gene expression was increased in PD patients but decreased in PR patients. Enrichment analysis revealed that an increased TGF-β signaling pathway was reversely correlated with anti-PD-1 efficacy, while a decreased inflammatory response signaling pathway was positively correlated with anti-PD-1 efficacy. Conclusions: Our study showed PD-1 inhibitors combined with anti-angiogenesis agents were effective and well-tolerated. ITH, monocyte ratio, stroma subtypes, and the status of immune-associated signaling pathways may be related with anti-PD-1 based therapy.

The rapid growth of wind and solar energy sources in recent years has brought challenges to power systems. One challenge is surging wind and solar electric generation, understanding how to consume such generation is important. Achieving the complementarity of hydropower and renewable energies such as wind and solar power by utilizing the flexible regulation performance of hydropower is helpful to provide firm power to help renewable energy consumption. However, the multi-energy complementary operation mode will change the traditional hydropower operation mode, causing challenges to the comprehensive utilization of hydropower. In this paper, a multi-objective optimal scheduling model is built by considering coordinated hydro-wind-solar system peak shaving and downstream navigation. First, the Gaussian mixture model is adopted to quantify the uncertainty of wind and solar power. Then, a hydro-wind-solar coordinated model was built to obtain the standard deviation of the residual load and the standard deviation of the downstream water level. Finally, the ε-constraint method is used to solve for the Pareto optimality. The results demonstrate the following: 1) The proposed model can effectively determine hydropower output schemes that can coordinate wind and solar power output to reconcile peak shaving and navigation; 2) The downstream hydropower stations’ reverse regulation of the upstream hydropower station is a positive factor in reconciling conflicts; and 3) Reasonable planning of wind power and solar power is helpful for hydro-wind solar power complement operation.

ObjectivesThe purpose of this study was to develop and validate an CT-based radiomics nomogram for the preoperative differentiation of focal-type autoimmune pancreatitis from pancreatic ductal adenocarcinoma.Methods96 patients with focal-type autoimmune pancreatitis and pancreatic ductal adenocarcinoma have been enrolled in the study (32 and 64 cases respectively). All cases have been confirmed by imaging, clinical follow-up and/or pathology. The imaging data were considered as: 70% training cohort and 30% test cohort. Pancreatic lesions have been manually delineated by two radiologists and image segmentation was performed to extract radiomic features from the CT images. Independent-sample T tests and LASSO regression were used for feature selection. The training cohort was classified using a variety of machine learning-based classifiers, and 5-fold cross-validation has been performed. The classification performance was evaluated using the test cohort. Multivariate logistic regression analysis was then used to develop a radiomics nomogram model, containing the CT findings and Rad-Score. Calibration curves have been plotted showing the agreement between the predicted and actual probabilities of the radiomics nomogram model. Different patients have been selected to test and evaluate the model prediction process. Finally, receiver operating characteristic curves and decision curves were plotted, and the radiomics nomogram model was compared with a single model to visually assess its diagnostic ability.ResultsA total of 158 radiomics features were extracted from each image. 7 features were selected to construct the radiomics model, then a variety of classifiers were used for classification and multinomial logistic regression (MLR) was selected to be the optimal classifier. Combining CT findings with radiomics model, a prediction model based on CT findings and radiomics was finally obtained. The nomogram model showed a good sensitivity and specificity with AUCs of 0.87 and 0.83 in training and test cohorts, respectively. The areas under the curve and decision curve analysis showed that the radiomics nomogram model may provide better diagnostic performance than the single model and achieve greater clinical net benefits than the CT finding model and radiomics signature model individually.ConclusionsThe CT image-based radiomics nomogram model can accurately distinguish between focal-type autoimmune pancreatitis and pancreatic ductal adenocarcinoma patients and provide additional clinical benefits.

Oil tea (Camellia oleifera Abel.), an important edible oil tree found in the acidic soil of south China, is tolerant to aluminum (Al); however, the mechanism via which it detoxifies Al remains unclear. The present study investigated the accumulation and distribution of Al and the changes in antioxidant components in C. oleifera leaves at different stages of growth. The analysis revealed that the content of Al in young, mature, and old leaves was 1.53, 7.49, and 12.04 g kg−1, respectively. In the leaves, Al was mainly accumulated in the cell wall, which accounted for 66.03%, 79.94%, and 86.51% of the total Al accumulation in young, mature, and old leaves, respectively. In the leaf cell wall, the Al content in hemicellulose increased from 54.22% to 81.72% with leaf age. The proportion of Al in the upper epidermis, lower epidermis, palisade, and spongy parenchyma cell walls increased with leaf age. The activity of antioxidant enzymes increased and showed a synergistic effect on Al stress with leaf age. The peroxidase activity was the highest in mature leaves, 2.3 times that in young leaves. Meanwhile, catalase and superoxide dismutase activities and total phenol content were the highest in young leaves. Correlation analysis showed that antioxidant system composed of catalase, superoxide dismutase and total phenol (CAT, SOD, and TP) was negatively correlated with the Al content in C. oleifera leaves. The malondialdehyde (MDA) content was positively correlated with Al content in C. oleifera leaves, indicating that the MDA in the leaves helped resist Al stress in C. oleifera. Thus, our findings suggest that the increase in antioxidant properties and modification of the cell wall contributed to Al detoxification in the Al hyperaccumulator C. oleifera.

To evaluate the impact of a two-dose VarV program on varicella incidence among the whole population, considering the influence of public health and social measures (PHSMs), we extracted surveillance data on varicella cases during 2013–2022 in Minhang, Shanghai. Then, we estimated the incidence trend of varicella through interrupted time-series analyses and quantified the impact of the immunization program and PHSMs using Serfling regression. We also explored the associations between PHSMs and varicella cases. The implementation of the two-dose VarV strategy was followed by a significant decrease in varicella incidence (−1.84% per month). After one year of the program, varicella incidence was estimated at a 45.25% reduction, which was higher in children (59.12% and 54.09%) than in adults (19.49%). The decrease attributed to PHSMs was 31.26% during 2020–2022, and school closing was identified as the most relevant PHSM (b = −8.03 cases, r = −0.67 with a 1-week lag). These findings indicate that the two-dose immunization program has more effectively reduced the varicella incidence compared with the one-dose vaccine, and interventions like school closings are also encouraged to serve as supplementary measures to prevent varicella epidemics.

Drought hardening could promote the development of plant roots, potentially improving the resistance of crops to other adversities. To investigate the response and resistance of physiological and growth characteristics induced by drought hardening to salt stress in the later stages, a greenhouse experiment was carried out from 2021 to 2022 with one blank control treatment and twelve treatments that comprised combinations of four irrigation regimes (W1 = 85%, W2 = 70%, W3 = 55%, and W4 = 40% of the field capacity) and three irrigation water salinity levels (S2, S4, and S6, referring to 2 g, 4 g, and 6 g of sodium chloride added to 1000 mL of tap water, respectively). The results show that saline water irrigation introduced a large amount of salt into the soil, resulting in the deterioration of tomato growth, physiology, yield, and water use efficiency (WUE), but had a positive, significant effect on fruit quality. When the irrigation water salinity was 2 g L−1, the W2 treatment could reduce soil salt accumulation, even at the end of the maturation stage; consequently, enhancing the increments in plant height and leaf area index during the whole growing stage. The physiological activity of tomato plants under the W2 and W3 treatments showed a promoting effect. Correspondingly, the maximum values of the fruit quality of tomato plants irrigated with the same saline water were all obtained with the W2 or W3 treatment. However, the yield and WUE of the W3 treatment were lower than that of the W2 treatment, which was the highest among the same saline water irrigation treatments, consistent with the reflection of the changing trend of the ratio of fresh weight to dry weight. Overall, drought hardening can be considered an economically viable approach to mitigate the hazards of saline water irrigation, and the W2S2 combination is recommended for tomato production due to the maximum values of yield and WUE with a higher fruit quality among the twelve saline water irrigation treatments.

Abstract Background The α-synuclein released by neurons activates microglia, which then engulfs α-synuclein for degradation via autophagy. Reactive microglia are a major pathological feature of Parkinson’s disease (PD), although the exact role of microglia in the pathogenesis of PD remains unclear. Transient receptor potential vanilloid type 1 (TRPV1) channels are nonselective cation channel protein that have been proposed as neuroprotective targets in neurodegenerative diseases. Methods Using metabolic profiling, microglia energy metabolism was measured including oxidative phosphorylation and aerobic glycolysis. The mRFP-GFP-tagged LC3 reporter was introduced to characterize the role of TRPV1 in microglial autophagy. α-synuclein preformed fibril (PFF) TRPV1 flox/flox ; Cx3cr1Cre mouse model of sporadic PD were employed to study the capacity of TRPV1 activation to attenuate neurodegeneration process. Results We found that acute exposure to PFF caused microglial activation as a result of metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis via the AKT–mTOR–HIF-1α pathway. Activated microglia eventually reached a state of chronic PFF-tolerance, accompanied by broad defects in energy metabolism. We showed that metabolic boosting by treatment with the TRPV1 agonist capsaicin rescued metabolic impairments in PFF-tolerant microglia and also defects in mitophagy caused by disruption of the AKT–mTOR–HIF-1α pathway. Capsaicin attenuated phosphorylation of α-synuclein in primary neurons by boosting phagocytosis in PFF-tolerant microglia in vitro. Finally, we found that behavioral deficits and loss of dopaminergic neurons were accelerated in the PFF TRPV1 flox/flox ; Cx3cr1Cre mouse model of sporadic PD. We identified defects in energy metabolism, mitophagy and phagocytosis of PFF in microglia from the substantia nigra pars compacta of TRPV1 flox/flox ; Cx3cr1Cre mice. Conclusion The findings suggest that modulating microglial metabolism might be a new therapeutic strategy for PD.

Given the problems of unclear division of evaluation factors, inadequate utilization of objective data and unreasonable distribution of weight in college performance measurement, this study extracts relevant indicators and quantitative data from the survey report of administrational institutions, and constructs a comprehensive performance measurement model based on the integration of fuzzy Delphi method (FDM), Entropy weight method (EWM), and grey relational analysis (GRA). The study seeks to identify differences in measurement analysis by comparing the weights, the performance and the rankings of the alternatives about higher vocational colleges in Zhejiang province. Finally, the results show the following: (1) by FDM, 33 indicators about colleges' performance are selected to form the evaluation system of the college’s performance, (2) the indicators' weights are obtained through EWM and GRA, and a nonparametric test shows that there is no significant difference between the two types of weights, (3) the grey relational degrees of the alternatives are obtained and ranked on the basis of comprehensive evaluation model. By nonparametric test, there is a significant difference between the two types of relational degrees. On the contrary, no significant difference is found in the ranking of relational degrees, (4) based on the analysis results, this study further compares the performance of alternatives in different forms. There are significant differences between the performance of public colleges and private colleges, while no significant differences are observed between the performance of vocational colleges in Hangzhou and non-Hangzhou. Given the reliability and validity of the model, the comprehensive measurement model provides a relatively objective reference for college governance and administrational institutions, and also becomes an effective tool of colleges' evaluation to assist and improve the management practice in educational institutions.

Gastrointestinal associated lymphoid tissue (GALT) is an important component of the mucosal immune system. It is the largest mass of lymphoid tissues in the body and makes up more than 70% immune cells of entire body. GALT is considered to be the origin of systemic mucosal immunity and consists of solitary lymphoid nodules, aggregated lymphoid nodules (Peyer’s patches, PPs), scattered lymphoid tissues, and follicular associated epithelia. PPs play important roles as antigen inductive sites of the mucosal immune system, which are mainly distributed in the intestine of animals and humans (especially ileum and appendix). However, a special area of well-developed aggregated lymphoid nodules in the abomasum of Dromedary camel was found in our laboratory. Its existence was rarely described in the stomach before. In the present study, we investigated this special structure with the dromedary camels of different ages (young, 0.5–2 years; pubertal, 3–5 years; middle-aged, 6–16 years; old, 17–20 years), by the anatomical, histological and immunohistochemical approaches. The results showed that the special structure was mainly distributed in the cardiac glandular area of the abomasum, forming a triangular area. The mucosal folds in this area were significantly thicker than those in the surrounding region. These mucosal folds had two different forms, namely reticular mucosal folds (RMF) and longitudinal mucosal folds (LMF). There were abundant lymphoid nodules in the submucosa of RMF and LMF, which were arranged in one or multiple rows. The statistical analysis of the height and thickness of RMF and LMF showed that the structure was most developed in pubertal dromedary camels. The histological characteristics of the structure were the same as PPs in the intestine of the Dromedary camel, while anatomical appearance showed some difference. The immunohistochemical examination revealed that both immunoglobulin A (IgA) and G (IgG) antibodies-producing cells (APCs) were extensively distributed in the gastric lamina propria (LP) in all age group. Our finding suggest that camel stomach not only performs digestive functions, but also involves parts of body immunity.

Deep fluid activity is widespread in large oil-gas basins around the world. Deep fluids, as the links between internal and external factors of a basin, run in the way of organic-inorganic interactions through the oil-gas formation and aggregation. Herein, the identification characteristics of deep fluids in sedimentary basins as well as their influence on oil-gas reservoir formation and geothermal resource are summarized. The deep fluids of sedimentary basins are identified from three aspects, including mineral composition, fluid inclusions, and geochemical characteristics. The effects of deep fluid activities on oil-gas reservoir formation are manifested in two key aspects of matter and energy. As for the matter effects, deep fluids can improve the primary productivity of sedimentary basins and carry abundant inorganic hydrogen, which contributes to improving the hydrocarbon productivity through hydrogenation. As for the energy effects, the heat energy of deep fluids can promote the mature evolution from organic matter to oil and gas. During this process, the heating of deep fluids will cause the oil-generation window depth of the hydrocarbon source rocks to become thinner, and it will also generate very high pressure, which will promote the discharge of abundant hydrocarbons formed by the hydrocarbon source rocks. Furthermore, deep fluids can directly form volcanic rock oil-gas reservoirs. And another manifestation of deep fluid energy is geothermal. And the thermal energy of deep fluids can directly form hot dry rocks, which is the most important existing form of geothermal resources. The geological exploration of hot dry rocks should be supported by further geochemical and geophysical research.

BackgroundAdvances in studies using body indicators to predict death risk. Estimating the balance ability of death risk in middle-aged and older Chinese adults with overweight and obesity is still challenging.MethodsA retrospective analysis of the data from the China Health and Retirement Study from January 2011 to December 2018. A total of 8,632 participants were randomly divided into 7:3 a training group and a verification group, respectively. Univariable Cox analysis was used to prescreen 17 potential predictors for incorporation in the subsequent multivariable Cox analysis. Nine variables were included in the nomogram finally and validated with concordance index (C-index), calibration plots, Hosmer-Lemeshow test, and internal validation population.Results287 participants were death in the training group. One hundred and thirteen participants were death in the verification group. A total of nine indicators were included in the modeling group, including gender, age, marriage, hypertension, diabetes, stroke, ADL, IADL, and balance ability to establish a prediction model. The nomogram predicted death with a validated concordance index of (C-index = 0.77, 95% CI: 0.74–0.80). The inclusion of balance ability variables in the nomogram maintained predictive accuracy (C-index = 0.77, 95% CI: 0.73–0.82). The calibration curve graph and Hosmer-Lemeshow test (P > 0.05 for both the modeling group and the verification group) showed the model has a good model consistency.ConclusionIn the present study, we provide a basis for developing a prediction model for middle-aged and older people with overweight and obesity. In most cases, balance ability is more reversible than other predictors.

Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.

MicroRNAs (miRs) are reported to regulate myocardial infarction (MI). This study was performed to investigate the function and mechanism of miR-17-5p in myocardial remodelling after MI. Initially, a mouse model of MI was established and MI mice were infected with lentivirus antago-miR-17-5p vector. High expression of miR-17-5p was found in myocardial tissues after MI. After inhibiting miR-17-5p expression, myocardial fibrosis, scarring, and cardiomyocyte apoptosis were improved, LC3-II/LC3-I ratio and Beclin-1 expression were decreased but p62 expression was increased. The dual-luciferase assay suggested that miR-17-5p targeted STAT3 and negatively regulated its expression. Then, after inhibiting STAT3 expression using STAT3 inhibitor S31-201, the fibrosis, scarring, and cardiomyocyte apoptosis were deteriorated, along with the rise of LC3-II/LC3-I and Beclin-1 expression, the reduction of p62 expression and the reversion of MI attenuation. In conclusion, inhibition of miR-17-5p can inhibit myocardial autophagy through targeting STAT3 and then inhibit myocardial remodelling, thereby protecting the myocardium after MI.

Background In China, premature children in good health may be advised to receive routine immunization programs. However, delayed vaccination is common. This study aimed to characterize vaccination experiences of premature children and determine the impact of vaccination consultation clinic (VCC) assessment. Methods We performed a retrospective cohort study, including premature children visiting VCC at Children’s Hospital of Fudan University in 2017–2019. Data of these children, including demographics, recommendations of vaccination after VCC assessment, vaccination records, adverse events following immunization (AEFI), and incidence of vaccine-preventable diseases in 2017–2019, were collected retrospectively. Results A total of 1124 premature children were included, with vaccination uptake of 46.3% for expanded program of immunization (EPI) vaccines and 15.1% for non-EPI vaccines before VCC assessment. Furthermore, 77.5% of premature children who had not received any EPI vaccine were vaccinated after the assessment; however, most were delayed, regardless of vaccine types and recommendations. In contrast, 67.3% was vaccinated with non-EPI vaccines after the assessment. Majority (n = 35) of recorded AEFI was mild to moderate, in addition to one allergic rash. One each case of pertussis and varicella were recorded in those who had not received the corresponding vaccines. Conclusion Vaccination may be safe and epidemiological effective in premature children. However, it remains mostly delayed in premature children with recommendations of normal vaccination. It warrants improving implementation of VCC recommendations. In addition, there is a need of health promotion on more non-EPI vaccines for premature children.

Auricularia heimuer is a widely cultivated jelly mushroom. The fruiting bodies are categorized into cluster and chrysanthemum types. With changing consumer demands and the need to reduce bio-waste, the demand for clustered fruiting bodies is increasing. Therefore, gene mining for fruiting body types is a matter of urgency. We determined that the A. heimuer locus for fruiting body type was located at one end of the genetic linkage map. The locus was localized between the markers D23860 and D389 by increasing the density of the genetic linkage map. BlastN alignment showed that the marker SCL-18 was also located between D23860 and D389, and a total of 25 coding genes were annotated within this interval. Through parental transcriptome analysis and qRT-PCR verification, the locus g7219 was identified as the gene controlling the fruiting body type. A single-nucleotide substitution in the TATA box of g7219 was detected between the parents. By PCR amplification of the promoter region of g7219, the TATA-box sequences of the cluster- and chrysanthemum-type strains were found to be CATAAAA and TATAAAA, respectively. This study provides a foundation for the breeding of fruiting body types and strain improvement of A. heimuer.

Auricularia heimuer is among China’s most important edible mushrooms and is rich in gum. With the improvement of people’s quality of life, demand is increasing for high-quality and good-tasting food; thus, the texture of A. heimuer is the focus of increasing attention. In this study, we added extra markers to a previously constructed genetic linkage map to generate a high-density genetic linkage map of A. heimuer, resolved the attributes of substrate quality-related traits, and performed quantitative trait locus (QTL) localization. The original genetic linkage map was improved by adding two new linkage groups, merging seven linkage groups into three linkage groups, and increasing the average linkage distance and total linkage estimated length. We anchored the 142 scaffolds of the genome to the improved genetic linkage map. In total, 15 significant QTLs controlling four quality-related traits were detected. Gumminess and chewiness, and cohesiveness and resilience, were linked. Three genes controlled cohesiveness and resilience; one gene controlled gumminess and chewiness. In conclusion, this study lays the foundation for gene localization and chromosome assembly in A. heimuer, elucidation of the mechanism of substrate quality-related trait formation, and provides a basis for precision breeding of A. heimuer.

Analysis of the spatial and temporal variation patterns of surface evapotranspiration is important for understanding global climate change, promoting scientific deployment of regional water resources, and improving crop yield and water productivity. Based on Landsat 8 OIL_TIRS data and remote sensing image data of the lower Yangtze River urban cluster for the same period of 2016–2021, combined with soil and meteorological data of the study area, this paper constructed a multiple linear regression (MLR) model and an extreme learning machine (ELM) inversion model with evapotranspiration as the target and, based on the model inversion, quantitatively and qualitatively analyzed the spatial and temporal variability in surface evapotranspiration in the study area in the past six years. The results show that both models based on feature factors and spectral indices obtained a good inversion accuracy, with the fusion of feature factors effectively improving the inversion ability of the model for ET. The best model for ET in 2016, 2017, and 2021 was MLR, with an R2 greater than 0.8; the best model for ET in 2018–2019 was ELM, with an R2 of 0.83 and 0.62, respectively. The inter-annual ET in the study area showed a “double-peak” dynamic variation, with peaks in 2018 and 2020; the intra-annual ET showed a single-peak cycle, with peaks in July–August. Seasonal differences were obvious, and spatially high-ET areas were mainly found in rural areas north of the Yangtze River and central and western China where agricultural land is concentrated. The net solar radiation, soil heat flux, soil temperature and humidity, and fractional vegetation cover all had significant positive effects on ET, with correlation coefficients ranging from 0.39 to 0.94. This study can provide methodological and scientific support for the quantitative and qualitative estimation of regional ET.