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Abstract β-1,4-N-acetylgalactosaminyltransferase I (B4GALNT1) is a key glycosyltransferase for gangliosides. Its aberrant expression has been observed in various cancers, and its potential roles in tumor immunity were suggested recently. However, how B4GALNT1 regulate tumor progression and tumor immunity remains largely unknown. In this study, we aimed to investigate the roles of B4GALNT1 in hepatocellular carcinoma (HCC), particularly in reshaping the tumor immune microenvironment, and evaluate the potential beneficial effects of targeting B4GALNT1 in immunotherapy. Our data verified the aberrant upregulation of B4GALNT1 in HCC tumor tissues and tumor cells, which could be utilized as an independent prognostic factor and improve the predicting performance of traditional tumor node metastasis (TNM) system. We also demonstrated that B4GALNT1 increased the phosphorylation of Hes Family BHLH Transcription Factor 4 (HES4) via p38 mitogen-activated protein kinase (p38)/ c-Jun N-terminal kinase (JNK) signaling in tumor cells, thus increasing the transcriptional activity of HES4, which upregulated the synthesis and secretion of secreted phosphoprotein 1 (SPP1), modulated the composition of tumor-associated macrophages (TAMs) and T helper type 2 (Th2) cells, and eventually reshaped the immunosuppressive microenvironment. In addition, silencing B4GALNT1 was proved to enhance the tumor-killing efficiency of the programmed cell death protein 1 (PD-1)-targeting strategy in mouse model. In conclusion, this study evaluated B4GALNT1 as a prognostic predictor for HCC patients and revealed the mechanism of B4GALNT1 in microenvironmental remodeling, which extends the understanding of HCC progression and provides a novel auxiliary strategy for HCC immunotherapy.

Abstract Background The epidemiology of fungi identified via next-generation sequencing in bronchoalveolar lavage fluid among patients with COVID-19 is unknown. Methods De-identified information, including age, SARS-CoV-2 reads and fungi from bronchoalveolar lavage fluid, were used to analysis. Results A total of 960 patients with COVID-19 were included. Gender was unknown in 38 patients, and 648 (70.3%) of the rest patients were male. For 876 patients with information on age, their mean ± standard age was 63.4 ± 21.3 years, with the minimum being 0.2 years and the maximum being 101 years. For all the patients, their median [interquartile range] SARS-CoV-2 reads were 26,038 [4421.5, 44,641.5]. The Aspergilli were identified in 159 (16.6%) patients, with Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger in 103 (10.7%), 81 (8.4%) and 17 (1.8%), respectively. The Mucoraceae were identified in 14 (1.5%) patients. Pneumocystis jirovecii was identified in 65 (6.8%) patients, among whom 12 (18.5%) patients also had Aspergilli. The Cryptococcaceae and the Dematiaceae were also identified in some patients, including Cryptococcus in 11 (1.1%) patients. Conclusions In bronchoalveolar lavage fluid among patients with COVID-19, the Aspergilli were very commonly identified, as were the Mucoraceae, Pneumocystis jirovecii and Cryptococcus via next-generation sequencing.

Abstract The cost fluctuations associated with chemotherapy, radiotherapy, and immunotherapy, as primary modalities for treating malignant tumors, are closely related to medical decision-making and impose financial burdens on patients. In response to these challenges, China has implemented the Diagnosis-Related Group (DRG) payment system to standardize costs and control expenditures. This study collected hospitalization data from patients with malignant tumors who received chemotherapy, radiotherapy, and immunotherapy at Hospital H from 2018 to 2022. The dataset was segmented into two groups: the intervention group, treated with traditional Chinese medicine (TCM) alongside standard therapies, and the control group, treated with standard therapies alone. Changes and trends in hospitalization costs under the DRG policy were analyzed using propensity-score matching (PSM), standard deviation (SD), interquartile range (IQR), and concentration index (CI). Findings showed a decreasing trend in the standard deviation of hospitalization costs across all treatment modalities. Radiotherapy exhibited the most significant decrease, with costs reducing by 2547.37 CNY in the control group and 7387.35 CNY in the intervention group. Following the DRG implementation, the concentration indexes for chemotherapy and radiotherapy increased, while those for immunotherapy did not exhibit this pattern. Costs were more concentrated in patients who did not receive TCM treatment. In summary, DRG reform positively impacted the cost homogeneity of inpatient treatments for malignant tumors, particularly in the control group not receiving TCM treatment. The effects of DRG reform varied across different treatment modalities. Although short-term fluctuations in hospitalization costs may occur, initial evidence during the study period shows the positive impact of DRG reform on cost homogeneity.

Summary: Background: Mpox has spread to many countries around the world. While the existing live attenuated mpox vaccines are effective, advances in 21st century technologies now enable the development of vaccines with more specific antigens, clearer mechanisms, and more controllable side effects. Methods: We systematically evaluated the immunogenicity and protective efficacy of the A35R, M1R and B6R antigens of the mpox virus (MPXV). With these findings, we designed three single-chain trivalent mRNA vaccines (AMAB-wt, AMAB-C140S and AMB-C140S) by integrating the soluble regions of these antigens into single mRNA-encoded polypeptides based on their protein structures. Then, the immunogenicity and protective efficacy of these single-chain mRNA vaccines were evaluated in mice models against both VACV and MPXV. Findings: The three single-chain vaccines elicited neutralising antibodies that effectively neutralised both VACV and MPXV. The single-chain vaccines or cocktail vaccine containing mRNAs encoding soluble antigen (sA35R + sM1R + sB6R) exhibited 100% or 80% protection against a lethal dose of VACV challenge, while the cocktail of full-length antigens (A35 + M1 + B6) and the live attenuated vaccine, VACV Tian Tan (VACV-VTT), completely failed to protect mice. Moreover, the single-chain vaccines significantly reduced viral load in the lungs and ovaries of MPXV-challenged mice. Interpretation: Compared with the cocktail vaccines, our single-chain designs demonstrated similar or superior immunogenicity and protective efficacy. Importantly, the simplicity of the single-chain vaccines enhances both the controllability and accessibility of mpox vaccines. We believe these single-chain vaccines qualify as the next-generation mpox vaccines. Funding: National Natural Science Foundation of China and Youth Innovation Promotion Association of the CAS.

Abstract Alzheimer's disease (AD) is a neurodegenerative disorder characterized primarily by cognitive impairment. The motivation of this paper is to explore the impact of the visual information transmission pathway (V–H pathway) on AD, and the following feature were observed: Hemoglobin expression on the V–H pathway becomes dysregulated as AD occurs so as to the pathway becomes dysfunctional. According to the feature, the following conclusion was proposed: As AD occurs, abnormal tau proteins penetrate bloodstream and arrive at the brain regions of the pathway. Then the tau proteins or other toxic substances attack hemoglobin molecules. Under the attack, hemoglobin expression becomes more dysregulated. The dysfunction of V–H pathway has an impact on early symptoms of AD, such as spatial recognition disorder and face recognition disorder.

Abstract 2-Hydroxyoleic acid (2-OHOA) has gained attention as a membrane lipid therapy (MLT) anti-cancer drug. However, in the viewpoint of anti-cancer drug, 2-OHOA shows poor water solubility and its effectiveness still has space for improvement. Thus, this study aimed to overcome the problems by formulating 2-OHOA into liposome dosage form. Furthermore, in the context of MLT reagents, the influence of 2-OHOA on the biophysical properties of the cytoplasmic membrane remains largely unexplored. To bridge this gap, our study specifically focused the alterations in cancer cell membrane fluidity and lipid packing characteristics before and after treatment. By using a two-photon microscope and the Laurdan fluorescence probe, we noted that liposomes incorporating 2-OHOA induced a more significant reduction in cancer cell membrane fluidity, accompanied by a heightened rate of cellular apoptosis when compared to the non-formulated 2-OHOA. Importantly, the enhanced efficacy of 2-OHOA within the liposomal formulation demonstrated a correlation with its endocytic uptake mechanism. In conclusion, our findings underscore the significant influence of 2-OHOA on the biophysical properties of cancer plasma membranes, emphasizing the potential of liposomes as an optimized delivery system for 2-OHOA in anti-cancer therapy.

Abstract In the current study, we aimed to investigate whether disulfiram (DSF) exerts a neuroprotective role in cerebral ischemiareperfusion (CI-RI) injury by modulating ferredoxin 1 (FDX1) to regulate copper ion (Cu) levels and inhibiting inflammatory responses. To simulate CI-RI, a transient middle cerebral artery occlusion (tMCAO) model in C57/BL6 mice was employed. Mice were administered with or without DSF before and after tMCAO. Changes in infarct volume after tMCAO were observed using TTC staining. Nissl staining and hematoxylin–eosin (he) staining were used to observe the morphological changes of nerve cells at the microscopic level. The inhibitory effect of DSF on initial inflammation was verified by TUNEL assay, apoptosis-related protein detection and iron concentration detection. FDX1 is the main regulatory protein of copper death, and the occurrence of copper death will lead to the increase of HSP70 stress and inflammatory response. Cuproptosis-related proteins and downstream inflammatory factors were detected by western blotting, immunofluorescence staining, and immunohistochemistry. The content of copper ions was detected using a specific kit, while electron microscopy was employed to examine mitochondrial changes. We found that DSF reduced the cerebral infarction volume, regulated the expression of cuproptosis-related proteins, and modulated copper content through down regulation of FDX1 expression. Moreover, DSF inhibited the HSP70/TLR-4/NLRP3 signaling pathway. Collectively, DSF could regulate Cu homeostasis by inhibiting FDX1, acting on the HSP70/TLR4/NLRP3 pathway to alleviate CI/RI. Accordingly, DSF could mitigate inflammatory responses and safeguard mitochondrial integrity, yielding novel therapeutic targets and mechanisms for the clinical management of ischemia–reperfusion injury.

ObjectiveTo analyze the monitoring results and trends of Oncomelania in Songjiang District of Shanghai from 2007 to 2023， and to provide reference for future monitoring work.MethodsThe data of snail monitoring in Songjiang District from 2007 to 2023 were collected， including the location of snail spots， the number of survey frames， the area with snails， the number of frames with snails， the total number of snails， etc. The density of living snails and the occurrence rate of living snail frames were calculated.ResultsFrom 2007 to 2023， a total of 158 snail spots were found in 22 administrative villages in 4 towns in Songjiang District， including 131 emerging snail habitats （82.91%） and 27 reemerging snail habitats （17.09%）. The total snail area was 175 980 m2， the number of snail frames was 10 061， and 33 302 snails were captured. The highest density was 260/0.11 m2， and 15 662 snails were dissected. No positive snails were found. The average density of living snails was 0.60/0.11 m2 and the average occurrence rate of living snail frames was 17.99%. The snail areas in different areas were Yexie Town 126 000 m2 （71.60%）， Maogang Town 26 470 m2 （15.04%）， Xinbang Town 17 040 m2 （9.68%）， and Shihudang Town 6 470 m2 （3.68%）. The average density of living snails in different areas was 0.89/0.11 m2 in Yexie Town， 0.65/0.11 m2 in Maogang Town， 0.26/0.11 m2 in Shihudang Town and 0.24/0.11 m2 in Xinbang Town. The snail areas of different snail habitats were as follows： woodland 151 250 m2（85.95%）， river 13 810 m2（7.85%）， ditch 6 910 m2（3.93%）， farmland 4 010 m2（2.28%）. The average density of living snails in different snail habitats： ditch 1.01/0.11 m2， beach 0.86/0.11 m2， woodland 0.57/0.11 m2， river 0.40/0.11 m2. The occurrence rate of living snail frames in different regions and different snail environment types showed a downward trend and the difference was statistically significant.ConclusionAlthough the snail monitoring indicators such as snail area， average living snail density and average living snail frame occurrence rate in Songjiang District are still at its historically low level， the average living snail density and average living snail frame occurrence rate are still high compared with other regions or the national average. We should focus on the upper reaches and tributaries of the Huangpu River， especially the key areas of seedling transplantation， and strengthen monitoring and supervision to reduce the risk of snail input.

Objective Analysing and evaluating how efficiently health resources are allocated to county-level Traditional Chinese Medicine (TCM) hospitals in Zhejiang Province, this study aims to provide empirical evidence for improving operational efficiency and optimising resource allocation in these hospitals.Design and setting The study employed a three-stage Data Envelopment Analysis (DEA) model to assess efficiency, using data from 68 county-level TCM hospitals. Four input and five output variables related to TCM services were selected for the analysis.Results The first-stage DEA results indicated that in 2022, the technical efficiency (TE) of TCM hospitals in Zhejiang Province was 0.788, the pure technical efficiency (PTE) was 0.876 and the scale efficiency (SE) was 0.903. The classification of hospitals into four groups based on the bed size showed statistically significant differences in returns to scale (p East (0.844) > South (0.805) > North (0.796) > Central (0.731).Conclusion There is an imbalance between the inputs and outputs of county-level TCM hospitals. Each region must consider factors such as the local economy, population and medical service levels, along with the specific development characteristics of hospitals, to reasonably determine the scale of county-level TCM hospital construction. Emphasis should be placed on improving hospital management and technical capabilities, coordinating regional development, promoting the rational allocation and efficient use of TCM resources and enhancing the efficiency of resource allocation in county-level TCM hospitals.

ObjectiveTo observe the clinical effect of articular needling therapy combined with proprioceptive training on patients with knee osteoarthritis (KOA).MethodsA total of 90 KOA patients in the Foshan Traditional Chinese Medicine Hospital Affiliated to Guangzhou University of Medicine from February 2021 to October 2022 were randomly divided into control group and observation group, with 45 cases in each group. The control group received routine treatments such as stretching therapy, joint loosening, muscle strength training and intermediate frequency therapy, with each treatment was 10 minutes a time, once a day, six days a week, lasting for four weeks. The observation group received articular needling therapy combined with proprioceptive training on the basis of the control group, articular needling therapy was performed 20 minutes a time, once a day, six days a week, lasting for four weeks; proprioception training was performed 10 minutes a time, once a day, six days a week, lasting for four weeks. Before and after treatment, visual analog scale (VAS) score was used to evaluate the pain degree of knee joint; Western Ontario and McMaster University osteoarthritis index (WOMAC) was used to evaluate knee joint function; average trajectory error of the affected limb and Berg balance scale (BBS) score was used to evaluate balance function of lower limb.ResultsCompared with that before treatment, VAS score, WOMAC and average trajectory error of the affected limb of the both groups after treatment decreased significantly, while BBS score increased significantly, the difference was statistically significant(P

Abstract The objective of this study was to evaluate and compare the effectiveness of three different types of bariatric surgeries, namely, sleeve gastrectomy (SG), one-anastomotic gastric bypass (OAGB), and single anastomosis sleeve ileal (SASI) bypass, in the treatment of metabolic syndrome (MS). The optimal approach for managing MS remains uncertain, and thus this study aimed to provide a recent analysis of the efficacy of these surgical procedures. This retrospective study evaluated data of individuals who underwent SG, OAGB, and SASI bypass. The primary outcome measures included weight, body mass index (BMI), glucolipid metabolic index, and the occurrence of treatment-related complications within 6 to 12 months post-surgery. A total of 324 patients were included in this study. Of these, 264 patients underwent SG, 30 underwent OAGB, and 30 underwent SASI bypass. A significant decrease in weight was observed at the 6-month and 12-month marks following all three surgical procedures. Of these, patients who underwent SASI bypass exhibited the greatest reduction in weight and BMI post-surgery. Furthermore, the SASI bypass was associated with a significantly higher percentage of total weight loss (%TWL) and excess body mass index loss (%EBMIL) compared to SG and OAGB. Patients who underwent OAGB and SASI bypass demonstrated notable improvements in type 2 diabetes mellitus (T2DM). Patients who underwent SASI bypass and OAGB experienced greater postoperative comfort and reported fewer complaints of discomfort compared to the other procedure. Based on the retrospective analysis of the data, SASI bypass was associated with greater reductions in weight and BMI, higher percentages of %TWL and %EBMIL, and better improvement in T2DM compared to SG and OAGB. Therefore, both SASI bypass and OAGB were found to be more effective than SG in the treatment of MS.

Abstract Arterial occlusion-induced ischemic stroke (IS) is a highly frequent stroke subtype. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that modulates antioxidant genes. Its role in IS is still unelucidated. The current study focused on constructing a transient middle cerebral artery occlusion (tMCAO) model for investigating the NRF2-related mechanism underlying cerebral ischemia/reperfusion (I/R) injury. Each male C57BL/6 mouse was injected with/with no specific NRF2 activator post-tMCAO. Changes in blood–brain barrier (BBB)-associated molecule levels were analyzed using western-blotting, PCR, immunohistochemistry, and immunofluorescence analysis. NRF2 levels within cerebral I/R model decreased at 24-h post-ischemia. NRF2 activation improved brain edema, infarct volume, and neurological deficits after MCAO/R. Similarly, sulforaphane (SFN) prevented the down-regulated tight junction proteins occludin and zonula occludens 1 (ZO-1) and reduced the up-regulated aquaporin 4 (AQP4) and matrix metalloproteinase 9 (MMP9) after tMCAO. Collectively, NRF2 exerted a critical effect on preserving BBB integrity modulating ferroptosis and inflammation. Because NRF2 is related to BBB injury regulation following cerebral I/R, this provides a potential therapeutic target and throws light on the underlying mechanism for clinically treating IS.

Background Long-acting antipsychotics are currently important therapeutic options for the long-term treatment of schizophrenia. Risperidone microspheres for injection (Ⅱ) has been modified in dosage form to ensure fast acting without oral antipsychotic supplementation during treatment, however, there is a lack of studies on the efficacy and safety of it. Objective To evaluate the efficacy and safety of risperidone microspheres for injection (Ⅱ) in patients with acute schizophrenia. Methods This is a single-arm multicenter prospective study. The patients aged 18-55 years with acute schizophrenia from August 2021 to April 2022 at five study centers including Peking University Sixth Hospital, Hebei Provincial Mental Health Center, the Fourth People's Hospital in Urumqi, Taiyuan Psychiatric Hospital and Tianjin Anding Hospital were included and given variable dose of risperidone microspheres for injection (Ⅱ) of 25.0 mg/2 weeks, 37.5 mg/2 weeks or 50.0 mg/2 weeks and followed up for 8 weeks. The Positive and Negative Symptom Scale (PANSS), Clinical Global Impression Scale (CGI-S) and the Udvalg for Kliniske Undersogelser (UKU) Side Effects Rating Scale were used for evaluation at baseline and the end of week 2, 4, 6 and 8. In addition, Personal and Social Performance (PSP) Scale were evaluated and laboratory tests were collected at baseline and the end of week 8. Results A total of 58 patients were included in the study. PANSS total score, PANSS-positive score, PANSS-negative score, PANSS-general psychopathology score and CGI-S score were significantly reduced at the end of week 2, 4, 6 and 8 compared to baseline (P

Abstract Triphenyltin (TPT) is a widespread synthetic chemical used in many fields and its potential risk to organisms has been comprehensively investigated using different animal models and species. Currently, little is known about the effects of TPT exposure on microbial midgut diversity, therefore we explored these effects in the lepidopterous silkworm model using 16S rDNA sequencing. In total, 5273 and 5065 operational taxonomic units (OTUs) were identified in control and TPT-exposure group samples, ranging from 424 to 728 OTUs/sample. Alpha-diversity analyses revealed that TPT exposure induced the fluctuations of gut microbial diversity and abundance while beta-diversity analyses identified a distinct impact on major gut microbiota components. In our microbiome analyses, 23 phyla and 353 genera were recognized in the control group, while 20 phyla and 358 genera were recognized in the TPT exposure group. At the genus level, midgut microbiota were composed of several predominant bacterial genera, including Muribaculaceae, Lactobacillus, and UCG-010. In the TPT exposure group, o__Bacillales, f__Bacillaceae, and f__Caldicoprobacteraceae abundance was relatively high, while f__Oscillospiraceae, f__Fusobacteriaceae, and f__SC_I_84 abundance was relatively high in the control group. Gene function analyses in silkworm microbiota after TPT exposure showed that biosynthesis of ansamycins, fructose and mannose metabolism, glycerolipid metabolism, type II diabetes mellitus, glycolysis/gluconeogenesis, lipid metabolism, translation proteins, atrazine degradation, DNA repair and recombination proteins, nicotinate and nicotinamide metabolism were significantly increased. Collectively, our silkworm model identified gut microbial diversity risks and the adverse effects from TPT exposure, which were similar to other aquatic animals. Therefore, TPT levels in environmental samples must be monitored to prevent ecological harm.

Objective To explore potential function of IKAROS family zinc finger 1 (Ikzf1) in terminal erythroid differentiation. Methods Single-cell regulatory network inference and clustering (SCENIC) was used to predict transcription factors of terminal erythroid differentiation based on single cell transcriptomes of human and mouse bone marrow erythroid cells. Expression of the predicted Ikzf1 during terminal erythroid differentiation was acquired from public RNA-seq data and validated by RT-qPCR. Short hairpin RNA (shRNA) interference was performed to knock down Ikzf1 in mouse erythroid cells from fetal liver with a GFP cassette to mark successfully transfected cells. The knockdown efficiency in GFP+ cells was verified by RT-qPCR. The effect of Ikzf1 knockdown on erythroid differentiation and enucleation was analyzed by flow cytometry. Results SCENIC predicted that the transcription factor Ikzf1 regulated both human and mouse erythroid differentiation. RNA-seq data and RT-qPCR showed highly expressed Ikzf1 at proerythroblast and basophilic erythroblast stages of terminal erythroid differentiation. Ikzf1 expression was indeed down-regulated by shRNA in erythroid cells from mouse fetal liver. Flow cytometry analysis showed that knockdown of Ikzf1 affected terminal differentiation and significantly reduced the ratio of erythroid enucleation (P＜ 0.05). Conclusions Transcription factor Ikzf1 is highly expressed in early stage erythroblasts and involved in terminal erythroid differentiation as well as enucleation.

Many picornaviruses require the myristoylation of capsid proteins for viral replication. Myristoylation is a site-specific lipidation to the N-terminal G residue of viral proteins, which is catalyzed by the ubiquitous eukaryotic enzyme N-myristoyltransferase (NMT) by allocating the myristoyl group to the N-terminal G residue. IMP-1088 and DDD85646 are two inhibitors that can deprive NMT biological functions. Whether Senecavirus A (SVA) uses NMT to modify VP0 and regulate viral replication remains unclear. Here, we found that NMT inhibitors could inhibit SVA replication. NMT1 knock-out in BHK-21 cells significantly suppressed viral replication. In contrast, the overexpression of NMT1 in BHK-21 cells benefited viral replication. These results indicated that VP0 is a potential NMT1 substrate. Moreover, we found that the myristoylation of SVA VP0 was correlated to the subcellular distribution of this protein in the cytoplasm. Further, we evaluated which residues at the N-terminus of VP0 are essential for viral replication. The substitution of N-terminal G residue, the myristoylation site of VP0, produced a nonviable virus. The T residue at the fifth position of the substrates facilitates the binding of the substrates to NMT. And our results showed that the T residue at the fifth position of VP0 played a positive role in SVA replication. Taken together, we demonstrated that SVA VP0 myristoylation plays an essential role in SVA replication.

Cultivated beet (Beta vulgaris L. ssp. vulgaris) originated from sea beet (B. vulgaris ssp. maritima (L.) Arcang), a wild beet species widely distributed along the coasts of the Mediterranean Sea and Atlantic Ocean, as well as northern Africa. Understanding the evolution of sea beet will facilitate its efficient use in sugarbeet improvement. We used SNPs (single nucleotide polymorphisms) covering the whole genome to analyze 599 sea beet accessions collected from the north Atlantic Ocean and Mediterranean Sea coasts. All B. maritima accessions can be grouped into eight clusters with each corresponding to a specific geographic region. Clusters 2, 3 and 4 with accessions mainly collected from Mediterranean coasts are genetically close to each other as well as to Cluster 6 that contained mainly cultivated beet. Other clusters were relatively distinct from cultivated beets with Clusters 1 and 5 containing accessions from north Atlantic Ocean coasts, Clusters 7 and Cluster 8 mainly have accessions from northern Egypt and southern Europe, and northwest Morocco, respectively. Distribution of B. maritima subpopulations aligns well with the direction of marine currents that was considered a main dynamic force in spreading B. maritima during evolution. Estimation of genetic diversity indices supported the formation of B. maritima subpopulations due to local genetic drift, historic migration, and limited gene flow. Our results indicated that B. maritima originated from southern Europe and then spread to other regions through marine currents to form subpopulations. This research provides vital information for conserving, collecting, and utilizing wild sea beet to sustain sugarbeet improvement.

To ensure optimal use of images while preserving privacy, it is necessary to partition the shared image into public and private areas, with public areas being openly accessible and private areas being shared in a controlled and privacy-preserving manner. Current works only facilitate image-level sharing and use common cryptographic algorithms. To ensure efficient, controlled, and privacy-preserving image sharing at the area level, this paper proposes an image partition security-sharing mechanism based on blockchain and chaotic encryption, which mainly includes a fine-grained access control method based on Attribute-Based Access Control (ABAC) and an image-specific chaotic encryption scheme. The proposed fine-grained access control method employs smart contracts based on the ABAC model to achieve automatic access control for private areas. It employs a Cuckoo filter-based transaction retrieval technique to enhance the efficiency of smart contracts in retrieving security attributes and policies on the blockchain. The proposed chaotic encryption scheme generates keys based on the private areas' security attributes, largely reducing the number of keys required. It also provides efficient encryption with vector operation acceleration. The security analysis and performance evaluation were conducted comprehensively. The results show that the proposed mechanism has lower time overhead than current works as the number of images increases.

Since the issuance of the "Guiding Opinions on Vigorously Developing Sports Tourism" in 2016, the integration of sports and tourism has become a strategy in regional economic development. It creates new economic growth points, enhances local images, and promotes cultural communication. In the context of the "Tourism Makes Xinjiang Thrive" strategy, quantitatively investigating the integration of the sports and tourism industries helps people to better understand their interaction which can serve as the valuable input in policy-making for the comprehensive development of a region. This paper uses entropy weight method, stochastic frontier analysis and coupling coordination model to quantitatively analyze the effect of sports tourism industry integration in Xinjiang from the perspective of integration path. Meanwhile, the Dagum Gini coefficient and nuclear density estimation were used to analyze the regional differences and dynamic evolution of industrial integration quality. The result shows that (1) The sports and tourism integration quality in Xinjiang has not reached the optimal goal of complete integration. In the process of mutual industrial promotion, tourism promotes a higher degree of integration with the sports industry. (2) The industrial integration quality shows a phenomenon of "imbalance and inadequacy" among the regions. The regions with high quality of industrial integration were Urumqi, Ili, Kashgar, Altay and Changji, which have rich sports tourism resources. (3) The overall spatial difference in the quality of industrial integration presented a fluctuation downtrend. The difference between the tourism industrial belts was very significant.

Temperature is one of the most important environmental factors for plant growth, as low-temperature freezing damage seriously affects the yield and distribution of plants. The Lanzhou lily (Lilium davidii, var. unicolor) is a famous ornamental plant with high ornamental value. Using an Illumina HiSeq transcriptome sequencing platform, sequencing was conducted on Lanzhou lilies exposed to two different temperature conditions: a normal temperature treatment at 20°C (A) and a cold treatment at -4°C (C). After being treated for 24 hours, a total of 5848 differentially expressed genes (DEGs) were identified, including 3478 significantly up regulated genes and 2370 significantly down regulated genes, accounting for 10.27% of the total number of DEGs. Quantitative real-time PCR (QRT-PCR) analysis showed that the expression trends of 10 randomly selected DEGs coincided with the results of high-throughput sequencing. In addition, genes responding to low-temperature stress were analyzed using the interaction regulatory network method. The anti-freeze pathway of Lanzhou lily was found to involve the photosynthetic and metabolic pathways, and the key freezing resistance genes were the OLEO3 gene, 9 CBF family genes, and C2H2 transcription factor c117817_g1 (ZFP). This lays the foundation for revealing the underlying mechanism of the molecular anti-freeze mechanism in Lanzhou lily.

Abstract Exosomes mediate intercellular communication by transmitting active molecules. The function of long noncoding RNA (lncRNA) H19 in autoimmune liver injury is unclear. Concanavalin A (ConA)‐induced liver injury is well‐characterized immune‐mediated hepatitis. Here, we showed that lncRNA H19 expression was increased in the liver after ConA treatment, accompanied by increased exosome secretion. Moreover, injection of AAV‐H19 aggravated ConA‐induced hepatitis, with an increase in hepatocyte apoptosis. However, GW4869, an exosome inhibitor, alleviated ConA‐induced liver injury and inhibited the upregulation of lncRNA H19. Intriguingly, lncRNA H19 expression in the liver was significantly downregulated, after macrophage depletion. Importantly, the lncRNA H19 was primarily expressed in type I macrophage (M1) and encapsulated in M1‐derived exosomes. Furthermore, H19 was transported from M1 to hepatocytes via exosomes, and exosomal H19 dramatically induced hepatocytes apoptosis both in vitro and vivo. Mechanistically, H19 upregulated the transcription of hypoxia‐inducible factor‐1 alpha (HIF‐1α), which accumulated in the cytoplasm and mediated hepatocyte apoptosis by upregulating p53. M1‐derived exosomal lncRNA H19 plays a pivotal role in ConA‐induced hepatitis through the HIF‐1α–p53 signaling pathway. These findings identify M1 macrophage‐derived exosomal H19 as a novel target for the treatment of autoimmune liver diseases.

When the skin is damaged, accelerating the repair of skin trauma and promoting the recovery of tissue function are crucial considerations in clinical treatment. Previously, we isolated and identified an active peptide (livisin) from the skin secretion of the frog Odorrana livida. Livisin exhibited strong protease inhibitory activity, water solubility, and stability, yet its wound-healing properties have not yet been studied. In this study, we assessed the impact of livisin on wound healing and investigated the underlying mechanism contributing to its effect. Our findings revealed livisin effectively stimulated the migration of keratinocytes, with the underlying mechanisms involved the activation of CaSR as a peptide calcium mimetic. This activation resulted in the stimulation of the CaSR/E-cadherin/EGFR/ERK signaling pathways. Moreover, the therapeutic effects of livisin were partially reduced by blocking the CaSR/E-cadherin/EGFR/ERK signaling pathway. The interaction between livisin and CaSR was further investigated by molecular docking. Additionally, studies using a mouse full-thickness wound model demonstrated livisin could accelerate skin wound healing by promoting re-epithelialization and collagen deposition. In conclusion, our study provides experimental evidence supporting the use of livisin in skin wound healing, highlighting its potential as an effective therapeutic option.

Abstract Concrete repair and rehabilitation prolong the effective service lives of structures and are important topics in the building field worldwide. Epoxy latex-modified cementitious materials have shown promise for a number of applications in building and construction, but the mix design processes remain arbitrary because their pore structures are not well understood. Porosity and pore size distributions are pore structure parameters that have direct effects on the mechanical properties and durability of concrete. In this paper, mercury intrusion porosimetry (MIP) was used to analyze the porosities and pore size distributions of epoxy latex-modified mortars. The effects of the polymer-to-cement ratio on the pore structures of epoxy latex-modified mortars were investigated. Mortars with polymer-to-cement ratios of 0%, 5%, 10%, 15%, and 20% were cured for 7, 28, 60, and 90 days in this study. Images of specimen microstructures were obtained by scanning electron microscopy (SEM), which showed that increases in the amount of epoxy latex added caused the proportion of micropores in the mortar to decrease, while the proportion of macropores and gel pores increased. The pore size distribution of epoxy latex-modified mortar was described with a composite logarithmic model. Relationships between the pore size distribution and the polymer-to-cement ratio and the curing age were obtained. The method described herein might be sufficiently accurate and convenient to evaluate or predict the pore size distribution of an epoxy latex-modified mortar, i.e., by determining the statistical distribution and analyzing the probability. The process for design of the polymer concrete mix ratio will be facilitated by methods that accurately describe the structure of the epoxy latex-modified mortar.

Abstract The total alkaloids extracted from the seeds of Sophora moorcroftiana (TAs-SM) have the potential to treat alveolar echinococcosis, a disease included by the WHO in a list of 17 key neglected diseases world-wide. The aims of the current study were first to develop a supercritical fluid extraction (SFE) method for optimizing TAs-SM extraction, and second, to develop an optimized method for evaluating TAs-SM pharmacokinetics in vivo. The Box–Behnken response surface method was used to optimize the extraction process, and ultra-high liquid chromatography coupled with high resolution electrospray mass spectrometry (UPLC-HR-ESI-MS) was used to determine the pharmacokinetics of TAs-SM in SD rats. The results indicated the following optimal SFE extraction conditions: pressure = 31 MPa, temperature = 70 °C, time = 162.18 min. With these parameters, total alkaloids could be extracted from each gram of S. moorcroftiana, with the total content being 68.88 μg. The linear range of UPLC-HR-ESI-MS is 0.78–200.00 ng/ml, R2 > 0.99, and the sample recovery is 99–113%. The precision, accuracy, selectivity and stability of the method meet the requirements of US FDA guidelines. To our knowledge this study is the first to establish an SFE method for extracting TAs-SM and the first to employ UPLC-HR-ESI-MS for measuring TAs-SM in rats. These findings provide important contributions for using TAs-SM in further drug development and clinical applications.

The purpose of this study was to compare the outcome of anterolateral thigh perforator flap and abdominal pedicled flap repair for treating traumatic tissue defects of the hand. A total of 140 patients with hand trauma tissue defects were randomly divided (random number table) into Group A and Group B, with 70 cases in each group. Group A was given anterolateral thigh perforator flap repair, while Group B was given abdominal pedicled flap repair. The healing time of wounds in Group A was noted to be shorter than that in Group B (P

Background Tannins are the main bottlenecks restricting the transformation efficiency of plants. Hongyingzi is a special tannin-containing sorghum cultivar used in brewing. Methods In this study, a highly efficient microprojectile transformation system for tannin-containing sorghum was successfully exploited using immature embryos (IEs) of Hongyingzi as explants. Results Hongyingzi presented two types of calli. Type II calli were found to be the most suitable and effective explants for transformation. After optimization of the geneticin (G418) concentration and tissue culture medium, an average transformation frequency of 27% was achieved. Molecular analyzis showed that all transgenic plants were positive and showed transgenes expression. The inheritance analyzis confirmed that the transgenes could be inherited into the next generation. Thus, we successfully established an efficient transformation system for tannin-containing sorghum and demonstrated the possibility of breaking the restriction imposed by tannins in plants.

NADC34-like porcine reproductive and respiratory syndrome virus (PRRSV) strains were first detected in China in 2017 and became major circulating strains in 2021. Our previous study showed that the live-attenuated vaccine candidate SD-R strain could provide broad cross-protection against different NADC30-like PRRSVs (sublineage 1.8). However, the protective effect of SD-R against NADC34-like PRRSV is unclear. Here, a novel NADC34-like PRRSV, LNTZJ1341-2012, was isolated from a pig farm experiencing disease in 2020. Sequence analysis revealed that LNTZJ1341-2012 belonged to PRRSV-2 sublineage 1.5, exhibited the same Nsp2 amino-acid deletion characteristics as IA/2014/NADC34, and had not recombined with other strains. Additionally, a good challenge model was established to evaluate the protection afforded by the candidate SD-R vaccine against infection with a representative NADC34-like strain (LNTZJ1341-2012). The control piglets in the challenge experiment displayed clinical signs typical of PRRSV infection, including transient fever, high viremia, mild clinical symptoms, and histopathological changes in the lungs and submaxillary lymph nodes. In contrast, SD-R vaccination significantly reduced serum and lung tissue viral loads, and vaccinated piglets did not show any clinical symptoms or histopathological changes. Our results demonstrated that LNTZJ1341-2012 is a mildly virulent NADC34-like PRRSV and that the live-attenuated vaccine SD-R can prevent the onset of clinical signs upon challenge with the NADC34-like PRRSV LNTZJ1341-2012 strain, indicating that SD-R is a promising vaccine candidate for the swine industry.

Abstract Constructive remodeling of focal esophageal defects with biodegradable acellular grafts relies on the ability of host progenitor cell populations to repopulate implant regions and facilitate growth of de novo functional tissue. Intrinsic molecular mechanisms governing esophageal repair processes following biomaterial-based, surgical reconstruction is largely unknown. In the present study, we utilized mass spectrometry-based quantitative proteomics and in silico pathway evaluations to identify signaling cascades which were significantly activated during neoepithelial formation in a Sprague Dawley rat model of onlay esophagoplasty with acellular silk fibroin scaffolds. Pharmacologic inhibitor and rescue experiments revealed that epithelialization of neotissues is significantly dependent in part on pro-survival stimuli capable of suppressing caspase activity in epithelial progenitors via activation of hepatocyte growth factor receptor (c-MET), tropomyosin receptor kinase A (TrkA), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) signaling mechanisms. These data highlight the molecular machinery involved in esophageal epithelial regeneration following surgical repair with acellular implants.

Abstract Aiming at the problem encountered in the previous research: during the electrical activity of cardiomyocytes, the influent ions do not seem to be directly derived from the extracellular fluid. We chose to cut in from the colloidal properties of the cells, follow the basic principles of physical chemistry, and establish hypotheses along the derivation of the structural characteristics of cardiomyocytes. Through the surface ion adsorption experiment and patch clamp experiment of living cells, under the condition of sequentially reducing the concentration of Na+ in the extracellular fluid, we observed the exchange and diffusion of adsorbed ions on the cell surface; the changes of inflow I Na, I Ca-L and action potential; and correlation between results. The results showed that the hypothesis is true. The observed parameter changes were consistent with the fact that during depolarization of cardiomyocytes, the ions of influx were derived from the inference of adsorbed ions on the cell surface; at the same time, it also provided an objective and realistic explanation for the generation of electrocardiogram.

Background: The large inter-individual variability in immune-cell composition and function determines immune responses in general and susceptibility o immune-mediated diseases in particular. While much has been learned about the genetic variants relevant for type 1 diabetes (T1D), the pathophysiological mechanisms through which these variations exert their effects remain unknown. Methods: Blood samples were collected from 243 patients with T1D of Dutch descent. We applied genetic association analysis on >200 immune-cell traits and >100 cytokine production profiles in response to stimuli measured to identify genetic determinants of immune function, and compared the results obtained in T1D to healthy controls. Results: Genetic variants that determine susceptibility to T1D significantly affect T cell composition. Specifically, the CCR5+ regulatory T cells associate with T1D through the CCR region, suggesting a shared genetic regulation. Genome-wide quantitative trait loci (QTLs) mapping analysis of immune traits revealed 15 genetic loci that influence immune responses in T1D, including 12 that have never been reported in healthy population studies, implying a disease-specific genetic regulation. Conclusions: This study provides new insights into the genetic factors that affect immunological responses in T1D. Funding: This work was supported by an ERC starting grant (no. 948207) and a Radboud University Medical Centre Hypatia grant (2018) to YL and an ERC advanced grant (no. 833247) and a Spinoza grant of the Netherlands Association for Scientific Research to MGN CT received funding from the Perspectief Biomarker Development Center Research Programme, which is (partly) financed by the Netherlands Organisation for Scientific Research (NWO). AJ was funded by a grant from the European Foundation for the Study of Diabetes (EFSD/AZ Macrovascular Programme 2015). XC was supported by the China Scholarship Council (201706040081).

Objectives Several studies have demonstrated the association between gamma-glutamyl transferase (GGT) and hyperuricaemia, but little is known about such relation in less-developed ethnic minority regions.Design We cross-sectionally analysed data from the China Multi-Ethnic Cohort (Yunnan region).Setting Cross-sectional study.Participants 22 020 participants aged 30–79 years from Han ethnicity, Yi ethnicity and Bai ethnicity.Outcomes The serum level of uric acid, GGT and other metabolic parameters were tested. Weight, height and blood pressure were measured. Smoking, drinking, ethnicity, education and medical history were obtained from questionnaires.Results In the crude model, compared with the lowest quintile, the second, third, fourth and fifth quintiles of serum GGT exhibited a positive association with hyperuricaemia risk (OR=1.69, 2.90, 4.34 and 7.70, 95% CI=1.42 to 2.01, 2.47 to 3.42, 3.71 to 5.09 and 6.60 to 8.98, respectively, p-trend

Abstract Interleukin-17 receptor D (IL17RD or IL-17RD) also known as Sef (similar expression to fibroblast growth factor), is a single pass transmembrane protein that is reported to regulate several signaling pathways . IL17RD was initially described as a feedback inhibitor of fibroblast growth factor (FGF) signaling during zebrafish and frog development. It was subsequently determined to regulate other receptor tyrosine kinase signaling cascades as well as several proinflammatory signaling pathways including Interleukin-17A (IL17A), Toll-like receptors (TLR) and Interleukin-1α (IL1α) in several vertebrate species including humans. This review will provide an overview of IL17RD regulation of signaling pathways and functions with emphasis on regulation of development and pathobiological conditions. We will also discuss gaps in our knowledge about IL17RD function to provide insight into opportunities for future investigation. Video Abstract

Objective Heart failure (HF) and atrial fibrillation (AF) are often coexisting. They have common risk factors and pathophysiologic mechanisms. Sacubitril/valsartan has shown efficacy and tolerability in patients with HF. Thus, the study was performed to evaluate the impact of sacubitril/valsartan on AF occurrence in patients with HF. Methods The Embase and PubMed were searched from their inception date to June 2021 for all relevant randomized controlled trials (RCTs) evaluating the efficacy of sacubitril/valsartan in HF. The outcome of interest was the AF occurrence during the follow-up. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Results Six trials involving a total of 15,512 patients were included (7,750 randomized to sacubitril/valsartan and 7,762 to control). All trials were randomized, double-blind, and active-control. There was no significant difference in the prevention of AF occurrence between the sacubitril/valsartan group and the control group (enalapril or valsartan) in patients with HF (RR 1.07, 95%CI 0.95 to 1.19; I2 4%). Conclusions Sacubitril/valsartan was similar to either enalapril or valsartan in preventing the occurrence of AF in patients with HF.

Porcine circovirus type 2 (PCV2) is a highly prevalent virus in pig farms worldwide that causes significant economic losses in the swine industry. The PCV2 virus-like particles (VLPs) are potent subunit vaccines that are widely used. Currently, the adopted quality control of VLPs vaccines is mainly based in animal testing, the titration of neutralizing antibodies, or other biochemical/biophysical assays. In this study, we generated a monoclonal antibody that can distinguish assembled PCV2 VLPs from the capsid proteins. Subsequently, a convenient Sandwich ELISA was developed based on the monoclonal antibody (mAb) that recognizes the PCV2 VLPs specifically. This assay can be used for the quantity and quality control of PCV2 VLPs vaccines for both the intermediate or final products with high accuracy.

Lung cancer with loss-of-function of the LKB1 tumor suppressor is a common aggressive subgroup with no effective therapies. LKB1-deficiency induces constitutive activation of cAMP/CREB-mediated transcription by a family of three CREB-regulated transcription coactivators (CRTC1-3). However, the significance and mechanism of CRTC activation in promoting the aggressive phenotype of LKB1-null cancer remain poorly characterized. Here, we observed overlapping CRTC expression patterns and mild growth phenotypes of individual CRTC-knockouts in lung cancer, suggesting functional redundancy of CRTC1-3. We consequently designed a dominant-negative mutant (dnCRTC) to block all three CRTCs to bind and co-activate CREB. Expression of dnCRTC efficiently inhibited the aberrantly activated cAMP/CREB-mediated oncogenic transcriptional program induced by LKB1-deficiency, and specifically blocked the growth of human and murine LKB1-inactivated lung cancer. Collectively, this study provides direct proof for an essential role of the CRTC-CREB activation in promoting the malignant phenotypes of LKB1-null lung cancer and proposes the CRTC-CREB interaction interface as a novel therapeutic target.

Purpose: To report the clinical characteristics of ocular adverse events that have occurred, in China, after vaccination with inactivated COVID-19 vaccines. Methods: A retrospective cross-sectional observational study was conducted of ocular disorders that occurred within 15 days from any dose of an inactivated COVID-19 vaccine. Information on gender, age, the interval between the vaccination and ocular symptoms, laterality, duration of the ocular symptoms, primary visual acuity, and clinical diagnosis were retrospectively collected. Results: Twenty-four patients were involved in the study, including 15 females and 9 males, with a mean age of 41 ± 16 years (range of 8–71 years). The patients all denied a prior history of COVID-19 infection. Ocular adverse events occurred after the first dose of vaccine in 18 patients and, after the second or third doses, in six patients. The interval between vaccination with the inactivated COVID-19 vaccine and ocular symptoms was 6 ± 5 days; six patients were bilaterally involved and 18 patients were unilaterally involved. Regarding the diagnosis, 10 patients were diagnosed with white dot syndrome (WDS), 9 patients were diagnosed with uveitis, and 5 patients were diagnosed with retinal vascular disorders. The ages of patients with WDS were younger than those with uveitis or retinal vascular disorders (32 ± 10 vs. 48 ± 18, p < 0.05). For patients diagnosed with WDS, the best-corrected visual acuity (BCVA) was 0.74 ± 0.73 LogMAR. For patients diagnosed with retinal vascular disorders or uveitis, the BCVA was 1.44 ± 1.26 LogMAR. There was no significant difference (p > 0.05). Conclusions: A relationship cannot be established between inactivated COVID-19 vaccines and ocular disorders; therefore, further investigation of the clinical spectrum of ocular adverse events after vaccination with an inactivated COVID-19 vaccine is necessary.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen that endangers the swine industry worldwide. Recently, lineage 1 PRRSVs, especially NADC30-like PRRSVs, have become the major endemic strains in many pig-breeding countries. Since 2016, NADC30-like PRRSV has become the predominant strain in China. Unfortunately, current commercial vaccines cannot provide sufficient protection against this strain. Here, an attenuated lineage 1 PRRSV strain, named SD-R, was obtained by passaging an NADC30-like PRRSV strain SD in Marc-145 cells for 125 passages. Four-week-old PRRSV-free piglets were vaccinated intramuscularly with 105.0TCID50 SD-R and then challenged intramuscularly (2 mL) and intranasally (2 mL) with homologous NADC30-like PRRSV SD (1 × 105.0TCID50/mL) and heterologous NADC30-like PRRSV HLJWK108-1711 (1 × 105.0TCID50/mL). The results showed that antibodies against specific PRRSVs in 5 of 5 immunized piglets were positive after a 14-day post-vaccination and did not develop fever or clinical diseases after NADC30-like PRRSV challenges. Additionally, compared with challenge control piglets, vaccinated piglets gained significantly more weight and showed much milder pathological lesions. Furthermore, the viral replication levels of the immunized group were significantly lower than those of the challenge control group. These results demonstrate that lineage 1 PRRSV SD-R is a good candidate for an efficacious vaccine, providing complete clinical protection for piglets against NADC30-like PRRSVs.

Senecavirus A (SVA) is a picornavirus that causes vesicular disease in swine, and the inactivated vaccine is used to prevent and control SVA infection. To develop a new chromatography strategy for the purification and concentration of SVA vaccine antigens, we inserted a 6×His-tag at the VP1 C-terminal of the SVA/HLJ/CHA/2016 in an infectious clone to rescue a His-tagged SVA. The constructed and rescued recombinant virus, named as rSVA-His, exhibited similar growth kinetics to that of its parental virus. In addition, the expression of a 6×His-tag on the surface of SVA showed genetic stability in cell passages in vitro, which allowed one-step purification of SVA antigens by Ni2+ affinity columns. Furthermore, the immunogenicity of the inactivated rSVA-His was evaluated by inoculating rabbits and detecting neutralizing antibodies. The animals receiving two doses of the inactivated rSVA-His emulsified with oil adjuvant developed a high titer of neutralizing antibodies, indicating that SVA VP1 is tolerant to His-tag insertion without detriment to its antigenicity. In summary, the constructed 6×His-tagged SVA may offer a feasible approach to the affinity purification and concentration of antigens in the process of SVA inactivated vaccine production.

The newly emerged sublineage 1.5 (NADC34-like) porcine reproductive and respiratory syndrome virus (PRRSV) has posed a direct threat to the Chinese pig industry since 2018. However, the prevalence and impact of NADC34-like PRRSV on Chinese pig farms is unclear. In the present study, we continuously monitored pathogens—including PRRSV, African swine fever virus (ASFV), classical swine fever virus (CSFV), pseudorabies virus (PRV), and porcine circovirus 2 (PCV2)—on a fattening pig farm with strict biosecurity practices located in Heilongjiang Province, China, from 2020 to 2021. The results showed that multiple types of PRRSV coexisted on a single pig farm. NADC30-like and NADC34-like PRRSVs were the predominant strains on this pig farm. Importantly, NADC34-like PRRSV—detected during the period of peak mortality—was one of the predominant strains on this pig farm. Sequence alignment suggested that these strains shared the same 100 aa deletion in the NSP2 protein as IA/2014/NADC34 isolated from the United States (U.S.) in 2014. Phylogenetic analysis based on open reading frame 5 (ORF5) showed that the genetic diversity of NADC34-like PRRSV on this farm was relatively singular, but it had a relatively high rate of evolution. Restriction fragment length polymorphism (RFLP) pattern analysis showed that almost all ORF5 RFLPs were 1-7-4, with one 1-4-4. In addition, two complete genomes of NADC34-like PRRSVs were sequenced. Recombination analysis and sequence alignment demonstrated that both viruses, with 98.9% nucleotide similarity, were non-recombinant viruses. This study reports the prevalence and characteristics of NADC34-like PRRSVs on a large-scale breeding farm in northern China for the first time. These results will help to reveal the impact of NADC34-like PRRSVs on Chinese pig farms, and provide a reference for the detection and further prevention and control of NADC34-like PRRSVs.

Abstract NZ17074 (N1), an arenicin-3 derivative isolated from the lugworm, has potent antibacterial activity and is cytotoxic. To reduce its cytotoxicity, seven N1 analogues with different structures were designed by changing their disulfide bonds, hydrophobicity, or charge. The “rocket” analogue-N2 and the “kite” analogue-N6 have potent activity and showed lower cytotoxicity in RAW264.7 cells than N1. The NMR spectra revealed that N1, N2, and N6 adopt β-sheet structures stabilized by one or two disulfide bonds. N2 and N6 permeabilized the outer/inner membranes of E. coli, but did not permeabilize the inner membranes of S. enteritidis. N2 and N6 induced E. coli and S. enteritidis cell cycle arrest in the I-phase and R-phase, respectively. In E. coli and in S. enteritidis, 18.7–43.8% of DNA/RNA/cell wall synthesis and 5.7–61.8% of DNA/RNA/protein synthesis were inhibited by the two peptides, respectively. Collapsed and filamentous E. coli cells and intact morphologies of S. enteritidis cells were observed after treatment with the two peptides. Body weight doses from 2.5–7.5 mg/kg of N2 and N6 enhanced the survival rate of peritonitis- and endotoxemia-induced mice; reduced the serum IL-6, IL-1β and TNF-α levels; and protected mice from lipopolysaccharide-induced lung injury. These data indicate that N2 and N6, through multiple selective actions, may be promising dual-function candidates as novel antimicrobial and anti-endotoxin peptides.

Low temperature induces changes in plants at physiological and molecular levels, thus affecting growth and development. The Lanzhou lily (Lilium davidii, var. unicolor) is an important medicinal plant with high economic value. However, the molecular mechanisms underlying its photosynthetic and antioxidation responses to low temperature still remain poorly understood. This study subjected the Lanzhou lily to the two temperatures of 20°C (control) and 4°C (low temperature) for 24 h. Physiological parameters related to membrane integrity, photosynthesis, antioxidant system, and differentially expressed genes were investigated. Compared with control, low temperature increased the relative electrical conductivity by 43.2%, while it decreased net photosynthesis rate, ratio of variable to maximal fluorescence, and catalase activity by 47.3%, 10.1%, and 11.1%, respectively. In addition, low temperature significantly increased the content of soluble protein, soluble sugar, and proline, as well as the activity of superoxide dismutase and peroxidase. Comparative transcriptome profiling showed that a total of 238,109 differentially expressed genes were detected. Among these, 3,566 were significantly upregulated while 2,982 were significantly downregulated in response to low temperature. Gene Ontology enrichment analysis indicated that in response to low temperature, the mostly significantly enriched differentially expressed genes were mainly involved in phosphorylation, membrane and protein kinase activity, as well as photosynthesis, light harvesting, light reaction, and alpha,alpha-trehalose-phosphate synthase activity. Kyoto Encyclopedia of Genes and Genomes enrichment analysis also indicated that the most significantly enriched pathways involved ribosome biogenesis in eukaryotes, phenylalanine metabolism, circadian rhythm, porphyrin and chlorophyll metabolism, photosynthesis of antenna proteins, photosynthesis, and carbon fixation in photosynthetic organisms. Moreover, the expression patterns of 10 randomly selected differentially expressed genes confirmed the RNA-Seq results. These results expand the understanding of the physiological and molecular mechanisms underlying the response of the Lanzhou lily to low temperature stress.

BACKGROUND:As an essential component in reducing anthropogenic CO2 emissions to the atmosphere, tree planting is the key to keeping carbon dioxide emissions under control. In 1992, the United Nations agreed to take action at the Earth Summit to stabilize and reduce net zero global anthropogenic CO2 emissions. Tree planting was identified as an effective method to offset CO2 emissions. A high net photosynthetic rate (Pn) with fast-growing trees could efficiently fulfill the goal of CO2 emission reduction. Net photosynthetic rate model can provide refernece for plant's stability of photosynthesis productivity. METHODS AND RESULTS:Using leaf phenotype data to predict the Pn can help effectively guide tree planting policies to offset CO2 release into the atmosphere. Tree planting has been proposed as one climate change solution. One of the most popular trees to plant are poplars. This study used a Populus simonii (P. simonii) dataset collected from 23 artificial forests in northern China. The samples represent almost the entire geographic distribution of P. simonii. The geographic locations of these P. simonii trees cover most of the major provinces of northern China. The northwestern point reaches (36°30'N, 98°09'E). The northeastern point reaches (40°91'N, 115°83'E). The southwestern point reaches (32°31'N, 108°90'E). The southeastern point reaches (34°39'N, 113°74'E). The collected data on leaf phenotypic traits are sparse, noisy, and highly correlated. The photosynthetic rate data are nonnormal and skewed. Many machine learning algorithms can produce reasonably accurate predictions despite these data issues. Influential outliers are removed to allow an accurate and precise prediction, and cluster analysis is implemented as part of a data exploratory analysis to investigate further details in the dataset. We select four regression methods, extreme gradient boosting (XGBoost), support vector machine (SVM), random forest (RF) and generalized additive model (GAM), which are suitable to use on the dataset given in this study. Cross-validation and regularization mechanisms are implemented in the XGBoost, SVM, RF, and GAM algorithms to ensure the validity of the outputs. CONCLUSIONS:The best-performing approach is XGBoost, which generates a net photosynthetic rate prediction that has a 0.77 correlation with the actual rates. Moreover, the root mean square error (RMSE) is 2.57, which is approximately 35 percent smaller than the standard deviation of 3.97. The other metrics, i.e., the MAE, R2, and the min-max accuracy are 1.12, 0.60, and 0.93, respectively. This study demonstrates the ability of machine learning models to use noisy leaf phenotype data to predict the net photosynthetic rate with significant accuracy. Most net photosynthetic rate prediction studies are conducted on herbaceous plants. The net photosynthetic rate prediction of P. simonii, a kind of woody plant, illustrates significant guidance for plant science or environmental science regarding the predictive relationship between leaf phenotypic characteristics and the Pn for woody plants in northern China.

This study was conducted to explore specific chill models and the mechanisms underlying rhizome bud dormancy break in Polygonatum kingianum. Rhizome buds were subjected to various chilling temperatures for different duration and then transferred to warm conditions for germination and subsequent evaluation of their response to temperature and chilling requirements. A CUkingianum model was constructed to describe the contribution of low temperature to the chill unit, and it was suggested that 2.97°C was the optimum temperature and that 11.54°C was the upper limit for bud release. The CASkingianum model showed the relationship between chilling accumulation and sprouting percentage; therefore, rhizome bud development could be predicted through the model. Weighted correlation network analysis (WGCNA) of transcriptomic data of endo-, eco- and nondormant rhizome buds generated 33 gene modules, 6 of which were significantly related to bud sprouting percentage. In addition, 7 significantly matched transcription factors (TFs) were identified from the promoters of 17 "real" hub genes, and DAG2 was the best matched TF that bound to AAAG element to regulate gene expression. The current study is valuable for developing a highly efficient strategy for seedling cultivation and provides strong candidates for key genes related to rhizome bud dormancy in P. kingianum.

Streptococcus suis causes disease in pigs and is implicated increasingly in human disease worldwide. Although most clinical cases are associated with serotype 2, infections by other serotypes have sometimes been reported. Here, we sequenced the genome of a multidrug-resistant S. suis serotype 28 (strain 11313) and a multidrug-resistant S. suis serotype 31 (strain 11LB5). Strain 11313 was apathogenic in mouse infection models, whereas strain 11LB5 displayed ganglion demyelination, meningeal thickening, congestion, mononuclear cell infiltration, massive proliferation of cortical glial cells, and bacteria (>104 CFU/g) in the spinal cord and ganglia in mice. Furthermore, immunohistochemistry found that the heavily infiltrated glial cells were astrocytes. Strain 11313 harbored the resistance genes ant(6)-Ia, erm(B), optrA, tet(l), tet(o), and strain 11LB5 harbored the resistance genes ant(6)-Ia, erm(B), tet(40), tet(o/w/32/o), aac(6′)-aph(2″). Mouse studies showed that strain 11LB5 exhibited a similar virulence to serotype 2 strain 700794, highlighting the need for surveillance of the other serotype S. suis isolates, in addition to serotype 2, in farms. This is the first report of the aminoglycoside resistance gene ant(6)-Ia in S. suis from animals. This suggests that S. suis might serve as an antibiotic resistance reservoir, which spreads the resistance gene ant(6)-Ia or optrA to other streptococcal pathogens on farms.

Canine adenovirus (CAdV) has a high prevalence in canine populations. High affinity neutralizing antibodies against conserved epitopes can provide protective immunity against CAdV and protect against future outbreaks. In this study, we identified two CAdV-2-specific neutralizing monoclonal antibodies (mAbs), 2C1 and 7D7, which recognized two linear-dependent epitopes. MAb 2C1 potently neutralized CAdV-2 with a 50% neutralization titer (NT50) of 4096, and mAb 7D7 partially neutralized CAdV-2 with a 50% NT50 of 64. Immunoprecipitation, Western blot and protein spectral analysis indicated that both neutralizing mAbs recognized the hexon protein (Hex) of CAdV-2. Through a 12-mer random peptide phage display and synthetic peptides analysis, we finely mapped the neutralizing epitopes to two 10-amino acid (aa) peptides within the CAdV Hex: 634RIKQRETPAL643 located on the surface region; and 736PESYKDRMYS745 located in the inner region of the expected 3D structure of trimeric Hex. Importantly, the two epitopes are highly conserved among all CAdV isolates by sequence alignment analysis. Thus, these results provide insights into the interaction between virus and mAbs at the aa level and may have potential applications in the development of novel therapeutic or epitope-based vaccines, antibody therapeutics and a diagnostic method suitable for the rapid detection of all CAdVs.

It is difficult to simulate both the flow field and the chemical reaction using, respectively, the flow state and kinetics calculations and actually reflect the influence of the gas flow state on the chemical change in a selective catalytic reduction (SCR) system. In this study, the flow field and the chemical reaction were therefore coupled to simulate a full Cu-Zeolite SCR system and the boundary conditions of the simulation were set by a relevant diesel engine bench test which included the exhaust temperature, the mass flow, and the exhaust pressure. Then, the influence of the gas flow state on the NOx conversion efficiency was investigated. Specifically, an orthogonal experimental design was used to study the influence of the injection parameters (position, angle, and speed) on the NH3 distribution by establishing the NH3 uniformity coefficient γ at the SCR catalyst capture surface in the flow field simulation. Then, the velocity capture surface of the SCR catalyst front section was sliced into coupled data transfer interfaces to study the effects of exhaust temperature, ammonia to NOx ratio (ANR), and the NO2/NOx on the NOx conversion efficiency. This was used as guidelines to optimize the SCR system control strategy. The results showed that a 1150 mm injection position, a 45°injection angle, and a 23 m/s injection velocity provided the most uniform NH3 distribution on the SCR catalyst capture surface. For constant injection parameters, the NOx conversion efficiency was the highest when the exhaust temperature was 200°C-400°C, the ANR was 1.1, and NO2/NOx was 0.5.

There is great debate surrounding the demographic impact of China's population control policies, especially the one-birth restrictions, which ended only recently. We apply an objective, data-driven method to construct the total fertility rates and population size of a 'synthetic China', which is assumed to be not subjected to the two major population control policies implemented in the 1970s. We find that while the earlier, less restrictive 'later-longer-fewer' policy introduced in 1973 played a critical role in driving down the fertility rate, the role of the 'one-child policy' introduced in 1979 and its descendants was much less significant. According to our model, had China continued with the less restrictive policies that were implemented in 1973 and followed a standard development trajectory, the path of fertility transition and total population growth would have been statistically very similar to the pattern observed over the past three decades.