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Abstract Endometrial cancer (UCEC) is one of three major malignant tumors in women. The HOX gene regulates tumor development. However, the potential roles of HOX in the expression mechanism of multiple cell types and in the development and progression of tumor microenvironment (TME) cell infiltration in UCEC remain unknown. In this study, we utilized both the The Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) database to analyze transcriptome data of 529 patients with UCEC based on 39 HOX genes, combing clinical information, we discovered HOX gene were a pivotal factor in the development and progression of UCEC and in the formation of TME diversity and complexity. Here, a new scoring system was developed to quantify individual HOX patterns in UCEC. Our study found that patients in the low HOX score group had abundant anti-tumor immune cell infiltration, good tumor differentiation, and better prognoses. In contrast, a high HOX score was associated with blockade of immune checkpoints, which enhances the response to immunotherapy. The Real-Time quantitative PCR (RT-qPCR) and Immunohistochemistry (IHC) exhibited a higher expression of the HOX gene in the tumor patients. We revealed that the significant upregulation of the HOX gene in the epithelial cells can activate signaling pathway associated with tumour invasion and metastasis through single-cell RNA sequencing (scRNA-seq), such as nucleotide metabolic proce and so on. Finally, a risk prognostic model established by the positive relationship between HOX scores and cancer-associated fibroblasts (CAFs) can predict the prognosis of individual patients by scRNA-seq and transcriptome data sets. In sum, HOX gene may serve as a potential biomarker for the diagnosis and prediction of UCEC and to develop more effective therapeutic strategies.

Abstract Transient Receptor Potential Vanilloid 1 (TRPV1) plays a central role in pain sensation and is thus an attractive pharmacological drug target. SAF312 is a potent, selective, and non-competitive antagonist of TRPV1 and shows promising potential in treating ocular surface pain. However, the precise mechanism by which SAF312 inhibits TRPV1 remains poorly understood. Here, we present the cryo-EM structure of human TRPV1 in complex with SAF312, elucidating the structural foundation of its antagonistic effects on TRPV1. SAF312 binds to the vanilloid binding pocket, preventing conformational changes in S4 and S5 helices, which are essential for channel gating. Unexpectedly, a putative cholesterol was found to contribute to SAF312’s inhibition. Complemented by mutagenesis experiments and molecular dynamics simulations, our research offers substantial mechanistic insights into the regulation of TRPV1 by SAF312, highlighting the interplay between the antagonist and cholesterol in modulating TRPV1 function. This work not only expands our understanding of TRPV1 inhibition by SAF312 but also lays the groundwork for further developments in the design and optimization of TRPV1-related therapies.

Abstract Objectives The performance of the new Respiratory Pathogen panel (fluorescent probe melting curve, FPMC) for the qualitative detection of 12 organisms (chlamydia pneumoniae, mycoplasma pneumoniae, adenovirus, influenza A virus, influenza B virus, parainfluenza virus, rhinovirus, etc.) was assessed. Methods Prospectively collected nasopharyngeal swab (NPS) and sputum specimens (n = 635) were detected by using the FPMC panel, with the Sanger sequencing method as the comparative method. Results The overall percent concordance between the FPMC analysis method and the Sanger sequencing method was 100% and 99.66% for NPS and sputum specimens, respectively. The FPMC testified an overall positive percent concordance of 100% for both NPS and sputum specimens. The FPMC analysis method also testified an overall negative percent concordance of 100% and 99.38% for NPS and sputum specimens, respectively. Conclusions The FPMC analysis method is a stable and accurate assay for rapid, comprehensive detecting for respiratory pathogens.

Abstract Background Carbon monoxide (CO) poisoning is now one of the leading causes of poisoning-related mortality worldwide. The central nervous system is the most vulnerable structure in acute CO poisoning. MRI is of great significance in the diagnosis and prognosis of CO toxic encephalopathy. The imaging features of CO poisoning are diverse. We report atypical hippocampal lesions observed on MRI in four patients after acute CO exposure. Case presentations We report four patients who presented to the emergency department with loss of consciousness. The diagnosis of CO poisoning was confirmed on the basis of their detailed history, physical examination and laboratory tests. Brain MRI in all of these patients revealed abnormal signal intensity in hippocampi bilaterally. They all received hyperbaric oxygen therapy. The prognosis of all four patients was poor. Conclusion Hippocampi, as a relatively rare lesion on MRI of CO poisoning, is of important significance both in the early and delayed stages of acute CO poisoning. In this article, we summarize the case reports of hippocampal lesions on MRI in patients with CO poisoning in recent years, in order to provide reference for the diagnosis and prognosis of CO poisoning.

Abstract Coix lacryma-jobi L. is one of the most economically and medicinally important corns. This study constructed a high-density genetic linkage map of C. lacryma-jobi based on a cross between the parents 'Qianyi No. 2' × 'Wenyi No. 2' and their F2 progeny through high-throughput sequencing and the construction of a specific-locus amplified fragment (SLAF) library. After pre-processing, 325.49 GB of raw data containing 1628 M reads were obtained. A total of 22,944 high-quality SLAFs were identified, among which 3952 SLAFs and 3646 polymorphic markers met the requirements for the construction of a genetic linkage map. The integrated map contained 3605 high-quality SLAFs, which were grouped into ten genetic linkage groups. The total length of the map was 1620.39 cM, with an average distance of 0.45 cM and an average of 360.5 markers per linkage group. This report presents the first high-density genetic map of C. lacryma-jobi. This map was constructed using an F2 population and SLAF-seq approach, which allows the development of a large number of polymorphic markers in a short period. These results provide a platform for precise gene/quantitative trait locus (QTL) mapping, map-based gene separation, and molecular breeding in C. lacryma-jobi. They also help identify a target gene for tracking, splitting quantitative traits, and estimating the phenotypic effects of each QTL for QTL mapping. They are of great significance for improving the efficiency of discovering and utilizing excellent gene resources of C. lacryma-jobi.

ObjectiveTo integrate pharmacovigilance and network toxicology methods to explore the potential adverse drug events (ADEs) and toxic mechanisms of selumetinib, and to provide a reference for quickly understanding the safety and toxicological mechanisms of newly marketed drugs.MethodsTaking selumetinib as an example, this study integrated pharmacovigilance methods based on real-world data and network toxicology methods to analyze its ADE and its potential toxicological mechanism. First, the ADE reports of selumetinib were extracted from the US Food and Drug Administration (FDA) adverse event reporting system (FAERS), and the ADE signals were detected by reporting odds ratio (ROR) and UK medicines and healthcare products regulatory agency (MHRA) methods. The ADE signals were classified and described according to the preferred terms (PTs) and system organ class (SOC) derived from the Medical Dictionary for Regulatory Activities (MedDRA). The network toxicology method was used to analyze the toxicological mechanism of the interested SOCs. The specific steps included predicting the potential targets of selumetinib using TOXRIC, STITCH, ChEMBL, CTD, SwissTargetPreditcion, and Super-PRED databases, collecting the targets of SOC using GeneCards database, conducting protein-protein interaction (PPI) analysis through STRING database, conducting gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis through DAVID database, and testing the molecular affinity using AutoDock software.ResultsA total of 1388 ADE reports related to selumetinib were extracted, and 53 positive signals were detected by ROR and MHRA methods, of which 20 signals were not mentioned in the package insert, including ingrowing nail, hyperphosphatemia, cardiac valve disease, hematuria, neutropenia, etc. Analysis of the toxicological mechanism of six SOCs involved in positive ADE signals revealed that the key targets included EGFR, STAT3, AKT1, IL6, BCL2, etc., and the key pathways included PI3K/Akt pathway, apoptosis, ErbB signaling pathway, and EGFR tyrosine kinase inhibitor resistance, etc. Molecular docking assays showed spontaneous binding of selumetinib to key targets in these pathways.ConclusionThe pharmacovigilance analysis identified some new potential ADEs of selumetinib, and the network toxicology analysis showed that the toxic effects of selumetinib may be related to PI3K/Akt pathway, apoptosis, ErbB signaling pathway, EGFR tyrosine kinase inhibitor resistance and other pathways.

Background: Porcine bile powder (PBP) is a traditional Chinese medicine that has been used for centuries in various therapeutic applications. However, PBP has not previously undergone comprehensive component analysis and not been evaluated for safety through standard in vivo toxicological studies.Methods: In our study, we characterized the component of PBP by liquid chromatography-mass spectrometry. The acute and subchronic oral toxicity, genotoxicity, and teratogenicity studies of PBP were designed and conducted in Kunming mice and Sprague-Dawley (SD) rats.Results: The chemical analysis of PBP showed that the main components of PBP were bile acids (BAs), especially glycochenodeoxycholic acid. There were no signs of toxicity observed in the acute oral test and the subchronic test. In the genotoxicity tests, no positive results were observed in the bacterial reverse mutation test. Additionally, in the mammalian micronucleus test and mouse spermatocyte chromosomal aberration test, no abnormal chromosomes were observed. In the teratogenicity test, no abnormal fetal development was observed.Conclusion: Our findings demonstrate that PBP, composed mainly of BAs, is non-toxic and safe based on the conditions tested in this study.

Reports indicate that an interaction between TRPV4 and anoctamin 1 (ANO1) could be widely involved in water efflux of exocrine glands, suggesting that the interaction could play a role in perspiration. In secretory cells of sweat glands present in mouse foot pads, TRPV4 clearly colocalized with cytokeratin 8, ANO1, and aquaporin-5 (AQP5). Mouse sweat glands showed TRPV4-dependent cytosolic Ca2+ increases that were inhibited by menthol. Acetylcholine-stimulated sweating in foot pads was temperature-dependent in wild-type, but not in TRPV4-deficient mice and was inhibited by menthol both in wild-type and TRPM8KO mice. The basal sweating without acetylcholine stimulation was inhibited by an ANO1 inhibitor. Sweating could be important for maintaining friction forces in mouse foot pads, and this possibility is supported by the finding that wild-type mice climbed up a slippery slope more easily than TRPV4-deficient mice. Furthermore, TRPV4 expression was significantly higher in controls and normohidrotic skin from patients with acquired idiopathic generalized anhidrosis (AIGA) compared to anhidrotic skin from patients with AIGA. Collectively, TRPV4 is likely involved in temperature-dependent perspiration via interactions with ANO1, and TRPV4 itself or the TRPV4/ANO 1 complex would be targeted to develop agents that regulate perspiration.

Abstract The nonselective calcium‐permeable Transient Receptor Potential Cation Channel Subfamily V Member4 (TRPV4) channel regulates various physiological activities. Dysfunction of TRPV4 is linked to many severe diseases, including edema, pain, gastrointestinal disorders, lung diseases, and inherited neurodegeneration. Emerging TRPV4 antagonists show potential clinical benefits. However, the molecular mechanisms of TRPV4 antagonism remain poorly understood. Here, cryo‐electron microscopy (cryo‐EM) structures of human TRPV4 are presented in‐complex with two potent antagonists, revealing the detailed binding pockets and regulatory mechanisms of TRPV4 gating. Both antagonists bind to the voltage‐sensing‐like domain (VSLD) and stabilize the channel in closed states. These two antagonists induce TRPV4 to undergo an apparent fourfold to twofold symmetry transition. Moreover, it is demonstrated that one of the antagonists binds to the VSLD extended pocket, which differs from the canonical VSLD pocket. Complemented with functional and molecular dynamics simulation results, this study provides crucial mechanistic insights into TRPV4 regulation by small‐molecule antagonists, which may facilitate future drug discovery targeting TRPV4.

Abstract There are a lot of temperature-sensitive proteins including transient receptor potential (TRP) channels. Some TRP channels are temperature receptors having specific activation temperatures in vitro that are within the physiological temperature range. Mice deficient in specific TRP channels show abnormal thermal behaviors, but the role of TRP channels in these behaviors is not fully understood. The Thermal Gradient Ring is a new apparatus that allows mice to freely move around the ring floor and not stay in a corner. The system can analyze various factors (e.g., ‘Spent time’, ‘Travel distance’, ‘Moving speed’, ‘Acceleration’) associated with temperature-dependent behaviors of TRP-deficient mice. For example, the Ring system clearly discriminated differences in temperature-dependent phenotypes between mice with diabetic peripheral neuropathy and TRPV1 −/− mice, and demonstrated the importance of TRPV3 in temperature detection in skin. Studies using the Thermal Gradient Ring system can increase understanding of the molecular basis of thermal behaviors in mice and in turn help develop strategies to affect responses to different temperature conditions in humans.

COVID-19 patients often suffer from post-COVID-19 acute sequelae (PASC). Pulmonary fibrosis has the most significant long-term impact on the respiratory health of patients, known as post-COVID-19 pulmonary fibrosis (PC19-PF). PC19-PF can be caused by acute respiratory distress syndrome (ARDS) or COVID-19-induced pneumonia. Individuals who experience COVID-19 pneumonia symptoms (including cough, shortness of breath, dyspnea on exertion, and desaturation) for at least 12 weeks after diagnosis, almost all develop PC19-PF. Extracellular matrix molecules: laminin (LN), type IV collagen (IV Col), procollagen III N-terminal peptide (PIIINP), and hyaluronic acid (HA) are involved in the development and progression of PC19-PF. This study aimed to investigate the relationship between the progression of PC19-PF and serum levels of laminin, IV COL, PIIINP, and hyaluronic acid. This retrospective study included 162 PC19-PF patients treated and 160 healthy controls who received treatment at Shenzhen Longgang District Third People’s Hospital, Hebei PetroChina Central Hospital and Changzhi People’s Hospital from January 2021 to December 2023. Serum levels of LN, IV COL, PIIINP, and HA were detected by chemiluminescence immunoassay using commercial kits. Predicted forced vital capacity percentage (FVC% pred), predicted carbon monoxide lung diffusion capacity percentage (DLCO% pred), high-resolution computed tomography (HRCT) scores were assessed, and patient mortality was compared with healthy controls. Serum levels of LN, IV Col, PIIINP, and HA were significantly higher in PC19-PF or CTD-ILD patients than in healthy controls (all p < 0.05), and they were further elevated in acute exacerbation cases (all p < 0.01). In patients, HA was positively associated with HRCT scores and negatively associated with FVC% pred and DLCO% pred (all p < 0.05). Serum levels of LN, IV COL, PIIINP, and HA were significantly lower in surviving patients than in those who deceased (all p > 0.05). Serum levels of LN, IV C, PIIINP, and HA may affect the progression of PC19-PF and may serve as indicators of PC19-PF severity.

BackgroundAcne vulgaris, a chronic inflammatory skin condition predominantly seen in teenagers, impacts more than 640 million people worldwide. The potential use of lipid-lowering medications as a treatment for acne vulgaris remains underexplored. This study seeks to investigate the impact of lipid-lowering therapies on the risk of developing acne vulgaris using two-sample Mendelian randomization (MR) analysis.MethodThe two-sample MR method was employed for analysis, and information on lipid-lowering drugs was obtained from the DrugBank and ChEMBL databases. The summary data for blood low-density lipoprotein (LDL) and triglycerides were sourced from the Global Lipids Genetics Consortium, while genome-wide association studies (GWAS) summary data for acne vulgaris were obtained from the FinnGen database. Heterogeneity was examined using the Q-test, horizontal pleiotropy was assessed using MR-Presso, and the robustness of analysis results was evaluated using leave-one-out analysis.ResultsThe MR analysis provided robust evidence for an association between lowering LDL cholesterol through two drug targets and acne vulgaris, with PCSK9 showing an odds ratio (OR) of 1.782 (95%CI: 1.129–2.812, p = 0.013) and LDL receptor (LDLR) with an OR of 1.581 (95%CI: 1.071–2.334, p = 0.021). Similarly, targeting the lowering of triglycerides through lipoprotein lipase (LPL) was significantly associated with an increased risk of acne vulgaris, indicated by an OR of 1.607 (95%CI: 1.124–2.299, p = 0.009).ConclusionThe current MR study presented suggestive evidence of a positive association between drugs targeting three genes (PCSK9, LDLR, and LPL) to lower lipids and a reduced risk of acne vulgaris.

Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) leaf has abundant rhamnogalacturonan-I enriched pectic polysaccharides, which exert various health-promoting effects. Nevertheless, the potential relationship between the chemical structure and the biological function of pectic polysaccharides from Tartary buckwheat leaves (TBP) remains unclear. Therefore, to bridge the gap between the chemical structure and the biological function of TBP, the impacts of ultrasound-assisted Fenton degradation (UFD) and mild alkaline de-esterification (MAD) on structural properties and biological effects of TBP were systematically studied. Compared with the native TBP (molecular mass, 9.537 × 104 Da), the molecular masses of degraded TBPs (TBP-MMW, 4.811 × 104 Da; TBP-LMW, 2.101 × 104 Da) were significantly reduced by the UFD modification, while their primary chemical structures were overall stable. Besides, compared with the native TBP (esterification degree, 22.73 %), the esterification degrees of de-esterified TBPs (TBP-MDE, 14.27 %; TBP-LDE, 6.59 %) were notably reduced by the MAD modification, while their primary chemical structures were also overall stable. Furthermore, the results revealed that both UFD and MAD modifications could significantly improve the antioxidant, antiglycation, and immunostimulatory effects of TBP. Indeed, TBP’s biological effects were negatively correlated to its molecular mass and esterification degree, while positively linked to its free uronic acids. The findings demonstrate that both UFD and MAD modifications are promising techniques for the structural modification of TBP, which can remarkedly promote its biological effects. Besides, the present results are conducive to better understanding TBP’s structure-bioactivity relationship.

Abstract A novel channel code, the low‐density algebra‐check (LDAC) code, is introduced in this letter. LDAC code is constructed by combining sparse matrice with algebraic constraints from two types of subcodes. Detailed explanations for the encoding and decoding process of the LDAC codes are provided in the paper. Simulation results demonstrate that LDAC codes offer advantages over LDPC codes in constructing low rate codes. The proposed ultra‐low rate LDAC code can achieve approximately 0.4 and 0.2 dB improvement in SNR compared to CA‐polar and 5G LDPC, respectively, at the 10−6 block error rate (BER) over the additive white Gaussian noise (AWGN) channel. LDAC codes demonstrate superior performance over LDPC codes at low rates, due to the enhanced error correction capabilities of the two types of subcodes and reduced rates without introducing short cycles.

AbstractBackground Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with an increased risk of death, but its underlying mechanisms are not fully understood. Circular RNAs (circRNAs) have recently been implicated in various biological processes. The aim of this study was to investigate the key circRNAs related to RA.Methods A microarray assay was used to identify the differentially expressed circRNAs (DEcircRNAs) in peripheral blood mononuclear cells (PBMCs) from patients with RA compared to patients with osteoarthritis (OA) and healthy controls. Then, quantitative real-time PCR was applied to verify the DEcircRNAs, and correlations between the levels of DEcircRNAs and laboratory indices were analysed. We also performed extensive bioinformatic analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG) pathway and potential circRNA–miRNA–mRNA network analyses to predict the function of these DEcircRNAs.Results A total of 35,342 and 6146 DEcircRNAs were detected in RA patients compared to controls and OA patients, respectively. Nine out of the DEcircRNAs in RA were validated by real-time PCR. There were correlations between the levels of DEcircRNAs and some of the laboratory indices. GO analyses revealed that these DEcircRNAs in RA were closely related to cellular protein metabolic processes, gene expression, the immune system, cell cycle, posttranslational protein modification and collagen formation. Functional annotation of host genes of these DEcircRNAs was implicated in several significantly enriched pathways, including metabolic pathways, ECM–receptor interaction, the PI3K–Akt signalling pathway, the AMPK signalling pathway, leukocyte transendothelial migration, platelet activation and the cAMP signalling pathway, which might be responsible for the pathophysiology of RA.Conclusions The findings of this study may help to elucidate the role of circRNAs in the specific mechanism underlying RA.Key messagesMicroarray assays showed that a total of 35,342 and 6146 DEcircRNAs were detected in RA patients compared to controls and OA patients, respectively.Nine out of the DEcircRNAs in RA were validated by real-time PCR, and the levels of the DEcircRNAs were related to some of the laboratory indices.GO analyses revealed that the DEcircRNAs in RA were closely related to cellular protein metabolic processes, gene expression, the immune system, etc.Functional annotation of host genes of the DEcircRNAs in RA was implicated in several significantly enriched pathways, including metabolic pathways, ECM–receptor interaction, the PI3K–Akt signalling pathway, etc.

In order to identify a Lactobacillus sp. strain with efficient and safe in starch degradation, this study analyzed five distinct strains: Lactiplantibacillus plantarum JYI-3913 and AS1.555, Lactobacillus amylovorus CGMCC1.3395, Lactobacillus amylophilus CGMCC1.3394, and Lactobacillus paracasei CGMCC1.12731. The preliminary screening and re-screening for amylase production capabilities, the determination of enzyme production curve and growth curve were carried out to select the strain with the best ability to produce amylase. Subsequently, a detailed safety evaluation of the strain was carried out, including drug sensitivity test, drug resistance genetic testing, plasmid detection, hemolysis test, nitroreductase production, azoreductase production and amine production capacity detection, and acute oral toxicity test in mice. Results showed that, under the same culture conditions, the starch degradation transparent zone of L. amylovorus CGMCC1.3395 exhibited a clear transparent zone of starch degradation. Its starch degradation rate and amylase activity were 97.28% and 36.94 U/mL, respectively. And this strain displayed a relatively brief lag phase, while extending the log phase and stationary phase. Overall, this strain demonstrated superior integrated amylase production capabilities when compared to the other strains under investigation. In terms of antibiotic sensitivity, the selected strain exhibited sensitivity or intermediate sensitivity to the majority of the 22 tested antibiotics, with resistance observed for ampicillin, kanamycin, and four fluoroquinolone antibiotics. Moreover, this strain showed no associated drug-resistance genes and plasmids, thereby eliminating the risk of antibiotic-resistance gene transmission. It also lacked a hemolytic effect and did not produce potentially harmful metabolites such as nitroreductase, azoreductase, histamine, and tyramine. Mice displayed normal growth and weight gain over a 14 day feeding period, indicating the non-toxicity of the strain. In conclusion, L. amylovorus CGMCC1.3395 demonstrated a potent and safe capability for amylase production. These findings provide a theoretical foundation for the safe employment of this strain in the fermentation of starch-rich foods.

To improve the delightful flavor of mulberry wine through semi-artificial inoculation fermentation with Saccharomyces cerevisiae, we studied the dynamics change of microbiota, along with the physicochemical properties and metabolite profiles and their interaction relationship during the fermentation process. The abundance of lactic acid bacteria (Weissella, Lactobacillus, Fructobacillus, and Pediococcus) increased significantly during fermentation, while yeasts gradually established dominance. The inter-kingdom network of the dominant genera analysis further identified the following as core microbiota: Alternaria, Botrytis, Kazachstania, Acremonium, Mycosphaerella, Pediococcus, Gardnerella, and Schizothecium. Additionally, pH, alcohol, and total acid were significantly affected by microbiota variation. Fourteen of all identified volatile compounds with key different aromas were screened using PCA, OPLS-DA, and rOAV. The network of interconnected core microbiota with key different aromas revealed that Kazachstania and Pediococcus had stronger correlations with 1-butanol, 3-methyl-, propanoic acid, and 2-methyl-ethyl ester.

Abstract TRPV3, a non-selective cation transient receptor potential (TRP) ion channel, is activated by warm temperatures. It is predominantly expressed in skin keratinocytes, and participates in various somatic processes. Previous studies have reported that thermosensation in mice lacking TRPV3 was impaired. Here, we identified a transmembrane protein, TMEM79, that acts as a negative regulator of TRPV3. Heterologous expression of TMEM79 was capable of suppressing TRPV3-mediated currents in HEK293T cells. In addition, TMEM79 modulated TRPV3 translocalization and promoted its degradation in the lysosomes. TRPV3-mediated currents and Ca2+ influx were potentiated in primary mouse keratinocytes lacking TMEM79. Furthermore, TMEM79-deficient male mice preferred a higher temperature than did wild-type mice due to elevated TRPV3 function. Our study revealed unique interactions between TRPV3 and TMEM79, both in vitro and in vivo. These findings support roles for TMEM79 and TRPV3 in thermosensation.

Healthy, nutritious, and delicious mulberry wine is loved by everyone, but there is no specific yeast for mulberry wine. To screen for yeasts with low-yield higher alcohols for the fermentation of mulberry wine, we tested five commonly used commercial yeasts available on the market to ferment mulberry wine. All five yeasts were able to meet the requirements in terms of yeast fermentation capacity, speed, and physical and chemical markers of mulberry wine. The national standards were met by the fermentation requirements and the fermented mulberry wine. We identified yeast DV10 as a yeast with low-yield higher alcohols suitable for mulberry wine fermentation. The total higher alcohol content in fermented mulberry wine was 298 mg/L, which was 41.9% lower than that of fermented mulberry wine with yeast EC118. The contents of 17 free amino acids and five sugars in mulberry juice and five yeast-fermented mulberry wines were tested. The results showed that the higher the amino acid and sugar content in yeast-fermented mulberry wine, the higher the content of higher alcohols produced by fermentation. A correlation analysis performed on each higher alcohol produced when yeast DV10 fermented the mulberry wine indicated decreased sugar and related amino acids. The findings demonstrated a substantial negative correlation among the levels of increased alcohol, decreased sugar, and matching amino acid content. Considering the correlation values among increased alcohol, decreased sugar, and related amino acids, the very slight difference suggests that both sugar anabolism and amino acid catabolism pathways have an equivalent impact on the synthesis of higher alcohols during the fermentation of mulberry wine. These results provide a theoretical basis for reducing the content of higher alcohols in mulberry wines, given the history and foundation for producing mulberry wine.

Raisins, known for their delicious taste and high nutritional value, are among the most widely consumed dried fruits globally. The natural waxy layer on the surface of grapes impedes water migration, making pretreatment necessary before drying. This study evaluated the effects of various pretreatment methods on the nutritional and functional quality of seedless purple raisins. By using non-pretreated dry seedless purple raisins as a control, the impact of physical and chemical pretreatment methods on the nutritional and functional qualities of seedless purple raisins was assessed through the analysis of nutrient content, phenolic compounds, and antioxidant activity. Our results demonstrate that physical pretreatment significantly increases the levels of vitamin C, fructose, glucose, total acid, total phenolics, total flavonoids, total anthocyanins, and antioxidant activity compared to chemical pretreatment and the control group. The correlation analysis revealed that phenolic substances were closely linked to antioxidant capacity. Additionally, phenolic compounds, including resveratrol, ferulic acid, chlorogenic acid, ethyl coumarate, and cinnamic acid, were more abundant following physical pretreatment. The OPLS-DA model effectively differentiated the three groups of processed samples, showing that different pretreatments significantly affect the nutritional and functional quality of seedless purple raisins. These findings suggest that physical pretreatment offers considerable potential for improving the drying quality of seedless purple raisins.

Abstract To describe the clinical spectrum and prognosis of atypical tumefactive demyelinating lesions (TDLs), which were confirmed by pathology. A total of 11 patients were diagnosed with atypical TDLs confirmed by brain biopsy and surgery between January 2006 and December 2017. The clinical spectrum and prognosis in these patients were analyzed. The patients’ ages ranged from 29 to 62 years, with a mean age of 48.9 years; 72.7% were males. The Expanded Disability Status Scale (EDSS) of the patients with first onset was 2.36. Most of the patients started with limb numbness and weakness (45.5%) or alalia (27.2%). The mean time from symptom onset to biopsy or surgery was 12.9 days (3–30 days). Most of the patients had solitary lesions (72.7%), supratentorial lesions (90.9%, particularly predominant in the frontal, temporal, and parietal lobes), moderate edema (63.6%), mild mass effect (54.5%), and patchy lesions (54.5%). Among them, three patients were positive for myelin basic protein (MBP) and one patient was positive for myelin oligodendrocyte glycoprotein (MOG). The patients were followed up for an average of 6.9 years (2–14 years), and recurrent TDLs were observed in 2 patients. Except for the 2 patients who relapsed, only 1 of the 9 patients died; the other 8 patients improved or maintained the status quo (the EDSS scores were lower or unchanged). The patients did not have any serious nervous system injury at onset, and the main presentation included extremity weakness, headache or dizziness, and alalia. The most common form was patchy on MRI enhancement. Cerebrospinal fluid and demyelination test can be an indicator of TDLs, and seizures may be a poor prognostic indicator. Most atypical TDLs have monophasic courses and good outcomes. The effect of neurosurgery alone was good in our group, and the effect of surgery on atypical TDLs can be further studied.

Abstract In this paper, a joint detection strategy of Willie based on two phases observation is proposed and an energy‐efficient covert communication scheme with an adaptive assist nodes group (AANG) based on uniform jamming power (UJP) strategy is proposed to against the joint‐phase detection of Willie, which achieves covert communication with lower energy cost and higher average covert rate (ACR). The probability of detection error (PDE) at Willie with joint‐phase detection and ACR are derived. Furthermore, the optimal power allocation of legitimate transmitters is resolved to maximize ACR. Numerical results demonstrate the benefit of the proposed scheme over the covert rate and consumed jamming power.

Abstract The East Asian winter monsoon (EAWM) is a crucial climate system in Asia, with significant social and economic impacts. Orbital‐scale variability of the EAWM during the Holocene and its associated mechanisms, however, are still not fully understood. Based on a high‐resolution transient simulation by a coupled climate model, we present here a continuous climate evolution of the EAWM in response to orbital forcing. Our simulated springtime EAWM variations, consistent with grain size records of loess, exhibit an obvious strengthening trend since the mid‐Holocene. In winter, a similar increasing trend is also simulated although not statistically significant. Our results suggest that the Holocene EAWM is basically controlled by meridional temperature gradients between high and low latitudes in both seasons. Other than northern insolation forcing, the feedbacks from Arctic sea ice and Eurasian snow cover also modulate the meridional temperature gradients, highlighting their important roles in driving EAWM evolution during the Holocene.

The chloride channel anoctamin1, upon activation by calcium influx through transient receptor potential vanilloid 3, mediates chloride influx and enhances wound healing in keratinocytes.

Tartary buckwheat green leaves are considered to be among the most important by-products in the buckwheat industry. Although Tartary buckwheat green leaves are abundant in pectic polysaccharides, their potential applications in the food industry are quite scarce. Therefore, to promote their potential applications as functional or fortified food ingredients, both deep-eutectic-solvent-assisted extraction (DESE) and high-pressure-assisted deep eutectic solvent extraction (HPDEE) were used to efficiently and selectively extract pectic polysaccharides from Tartary buckwheat green leaves (TBP). The results revealed that both the DESE and HPDEE techniques not only improved the extraction efficiency of TBP but also regulated its structural properties and beneficial effects. The primary chemical structures of TBP extracted using different methods were stable overall, mainly consisting of homogalacturonan and rhamnogalacturonan-I (RG-I) pectic regions. However, both the DESE and HPDEE methods could selectively extract RG-I-enriched TBP, and the proportion of the RG-I pectic region in TBP obviously improved. Additionally, both the DESE and HPDEE methods could improve the antioxidant and anti-glycosylation effects of TBP by increasing its proportion of free uronic acids and content of bound polyphenolics and reducing its molecular weight. Moreover, both the DESE and HPDEE methods could partially intensify the immunostimulatory effect of TBP by increasing its proportion of the RG-I pectic region. These findings suggest that DES-based extraction techniques, especially the HPDEE method, can be promising techniques for the efficient and selective extraction of RG-I-enriched TBP.

Objective: To investigate and analyze the post-marketing adverse event (AE) data of multiple sclerosis (MS) therapeutic drug dalfampridine using the US Food and Drug Administration Adverse Event Reporting System (FAERS) for its clinical safety application.Methods: Use OpenVigil2.1 platform to obtain AE data of dalfampridine from FAERS from February 2010 to September 2022. Match “adverse drug reaction” with preferred term (PT) and system organ class (SOC) according to the Medical Dictionary for Regulatory Activities (MedDRA), then merge the same PT and delete non-AE PT. Positive signals were identified by the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) methods. When AE signals met the criteria of those three methods, they were identified as positive signals.Results: A total of 44,092 dalfampridine-related AE reports were obtained, and 335 AE signals were identified, including 11,889 AE reports. AEs were more common in females and in the 45–65 age group, which is consistent with the epidemiological characteristics of MS. The 335 AE signals involved 21 SOCs, including investigations, infections and infestations, eye disorders, etc. Among the top 20 PTs in signal strength, 10 were associated with abnormal lymphocyte percentage and count, and 5 were associated with abnormal urine tests, some of which were not described in the instruction, such as spinal cord injury cauda equina, haemoglobin urine present, urinary sediment abnormal and so on. The most frequently reported AE signals were urinary tract infection, dizziness, condition aggravated. In addition, 23 AE signals with death outcomes were identified, with an incidence of less than 0.1%.Conclusion: Data mining of FAERS was conducted to analyze the AEs of dalfampridine, and new AE signals were found. This study provides a reference for the safe use of dalfampridine in the treatment of MS.

Rice (Oryza sativa L.) consumption represents a major route of human exposure to cadmium (Cd) and arsenic (As), especially in Asia. This study investigated the effects of adding MnSO4 (0, 200, 400, and 800 mg kg‐1−1) on the formation of soil Fe/Mn oxides and Cd and As uptake in rice. The application of MnSO4 reduced soil pH, increased Eh, increased the contents of Fe/Mn oxides in the soil, and decreased the total Fe and Mn2+ contents in the porewater. It also led to lower contents of available Cd and As, higher levels of Cd and As bound to Fe/Mn oxides, and higher abundances of Thiobacillus and Syntrophobacter. Furthermore, Mn application increased the Fe and Mn contents in the root Fe/Mn plaque and decreased the grain Cd and As contents. Therefore, Mn application may modify the microbial community and porewater composition in soil, resulting in higher levels of Fe/Mn oxides in soil and Fe/Mn plaque at the root surface and in a lower accumulation of Cd and As in rice grains. Thus, Mn application can be a promising strategy for Cd and As stabilization in soils.

Long non-coding RNAs have recently attracted considerable attention due to their aberrant expression in human diseases. LncMIR31HG is a novel lncRNA that is abnormally expressed in multiple diseases and implicated in various stages of disease progression. A large proportion of recent studies have indicated that MIR31HG has biological functions by triggering various signalling pathways in the pathogenesis of human diseases, especially cancers. More importantly, the abnormal expression of MIR31HG makes it a potential biomarker in diagnosis and prognosis, as well as a promising target for treatments. This review aims to systematically summarize the gene polymorphism, expression profiles, biological roles, underlying mechanisms, and clinical applications of MIR31HG in human diseases.

Abstract In order to counter the double attack with wardens and eavesdroppers in the practical scenario, a distributed transmission scheme with security and covertness is proposed, which combines coding techniques and transmission protocol. The covert message is encoded by rateless codes and transmitted embedded in normal frames. The security is based on the random essence of rateless coding, and the covertness is achieved by ignoring the error frames and maintaining the signal waveform. The inter‐collusion between multiple wardens and eavesdroppers greatly increases the potential security hazards, which is first discussed in this paper. The authors can counter the inter‐collusion attack by adjusting the ratio of covert frame transmission in the distributed transmission scheme with security and covertness. Compared with the related work, this paper has many advantages, such as good robustness, lower extra complexity, and the insurance of the performance for both normal message and covert message. The analysis and simulation results show that our distributed transmission scheme with security and covertness can achieve both covertness and security based on the effective design under the existing communication system.

Abstract This letter proposes a joint weighted power detector based on maximum a posteriori probability criterion for Willie aiming at two‐hop covert communication scenario, which is a near optimal detector. Instead of only supervising one single phase, Willie combines the observations of two phases to make joint decision in the proposed scheme. The proposed scheme achieves lower probability of detection error than adding‐power‐directly‐detector scheme and the existing single‐phase‐detector scheme due to sufficient utilization of the two‐phase observations. Numerical results demonstrate the benefit of authors' proposed scheme.

Abstract The strain-temperature cross-sensitivity problem easily occurs in the engineering strain monitoring of the self-sensing embedded with fiber Bragg grating (FBG) sensors. In this work, a theoretical investigation of the strain-temperature cross-sensitivity has been performed using the temperature reference grating method. To experimentally observe and theoretically verify the problem, the substrate materials, the preloading technique, and the FBG initial central wavelength were taken as main parameters. And a series of sensitivity coefficients calibration tests and temperature compensation tests have been designed and carried out. It was found that when the FBG sensors were embedded on different substrates, their coefficients of the temperature sensitivity were significantly changed. Besides, the larger the coefficients of thermal expansion (CTE) of substrates were, the higher the temperature sensitivity coefficients would be. On the other hand, the effect of the preloading technique and FBG initial wavelength was negligible on both the strain monitoring and temperature compensation. In the case of similar substrates, we did not observe any difference between temperature sensitivity coefficients of the temperature compensation FBG with one free end or two free ends. The curves of the force along with temperature were almost overlapped with minor differences (less than 1%) gained by FBG sensors and pressure sensors, which verified the accuracy of the temperature compensation method. We suggest that this work can provide efficient solutions to the strain-temperature cross-sensitivity for engineering strain monitoring with the self-sensing element embedded with FBG sensors.

Abstract Background Current data indicate that supplements such as folic acid and vitamin B may be beneficial in halting and even reversing atrophic gastritis, intestinal metaplasia and intraepithelial neoplasia, generally referred to as gastric precancerous conditions(GPC). However, there is no Meta-analysis article to evaluate the prevention and treatment of folic acid in the gastric precancerous conditions. We therefore conducted a meta-analysis to confirm the efficacy of folic acid in treating GPC. Methods Using a systematic review method, consider randomized controlled trials (RCT), including clinical trial reports, unpublished clinical trial data, and conference papers. The search time was been set from the database’s establishment to June 2, 2021. The language was not limited, using PubMed, SinoMed, Lancet, Web of Science, CNKI, Cochrane, Ovid, Science Direct, Embase, and EBSCO databases. Data were extracted using a pre-designed extraction tool and analysis was undertaken using RevMan5.2.Besides,we use Origin software to construct the Time-dose interval analysis. Results Of the 225 records identified, 13 studies involving 1252 patients (including 11 clinical controlled trials, 1 conference paper report and 1 unpublished research report) met the inclusion conditions. Folic acid dose maintained at 20–30 mg / d for 3–6 months may be beneficial to pathological changes of GPC. Moreover, in the 3 month treatment of 5 trials, the effect was more obvious when the folic acid dose was maintained at 30 mg / d. In the 7 trials, the symptom ineffective rate of GPC treated with folic acid was 32% (RR:0.32, 95% confidence interval CI:0.21–0.48), which was combined using a fixed analysis model; The effect of folic acid on gastric mucosal atrophy in 5 trials (RR: 1.61, 95%CI 1.07–2.41). The changes of folic acid on intestinal metaplasia in the 2 experiments (RR: 1.77, 95% CI: 1.32–2.37).The 2 results are combined using a fixed analytical model. However, the subgroup analysis of 9 trials revealed no significant effectiveness of symptom. Conclusions Our research showed that folic acid supplementation brings benefits in preventing and even reversing the progression of GPC in the stomach, and provided evidence for its potential clinical use in management of GPC. Registration: The logn number of our Meta-anlysis on PROSPERO is CRD420223062.

Abstract In this letter, a velocity measurement algorithm based on auto‐correlation in a single frame for IEEE 802.11ad is proposed. The periodicity of the Golay sequences in the preamble is exploited in the algorithm to estimate the time delay and achieve the velocity measurement at the same time. The improved measuring accuracy is obtained as the effect of noise is suppressed by designing and utilizing the auto‐correlation function.

IntroductionMycobacterium tuberculosis (MTB) identification and drug resistance diagnosis are very important for treatment of drug-resistant tuberculosis (DR-TB). Therefore, high throughput, accurate and low-cost molecular detection techniques are urgently needed. This study aimed to evaluate the clinical application value of MassARRAY in tuberculosis diagnosis and drug resistance screening.MethodsThe limit of detection (LOD) and clinical application value of MassARRAY were evaluated using reference strains and clinical isolates. MTB in bronchoalveolar lavage fluid (BALF) and sputum samples were detected using MassARRAY, quantitative real-time polymerase chain reaction (qPCR) and MGIT960 liquid culture (culture). Using culture as the standard, the efficacy of MassARRAY and qPCR for the detection of TB was analyzed. Mutation of drug resistance genes in MTB clinical isolates was tested using MassARRAY, high-resolution melting curve (HRM), and Sanger sequencing. Using sequencing as the standard, the efficacy of MassARRAY, and HRM for the detection of each drug resistance site of MTB was analyzed. Simultaneously, the mutation of drug resistance genes by the MassARRAY method was compared with the results of drug susceptibility testing (DST), and the genotype–phenotype relationship was analyzed. The ability of MassARRAY to discriminate mixed infections was detected using mixtures of standard strains (M. tuberculosis H37Rv) and drug-resistant clinical isolates and mixtures of wild-type and mutant plasmids.ResultsIn MassARRAY, 20 related gene mutations could be detected by two PCR systems. All genes could be accurately detected when the bacterial load was 104 CFU/mL. When the load of wild-type and drug-resistant MTB mixture was 105 CFU/mL (respectively reached 104 CFU/mL), variants and wild-type genes could be detected simultaneously. The sensitivity of MassARRAY (96.9%) for identification was higher than that of qPCR (87.5%) (p

In order to improve the preservation rate of total phenols and flavonoids, the fermentation technology of grape medicine mulberry wine was explored, and the antioxidant activity and bile acid binding capacity of grape medicine mulberry wine were studied. Using grape and medicine mulberry as raw materials, the optimal fermentation process of grape medicine mulberry wine was determined by single factor (inoculation amount, temperature, time, mass ratio) combined with response test. Three antioxidant systems (DPPH·, ABTS+·, ·OH) were used to evaluate the antioxidant activity of grape medicine mulberry wine, and the binding ability of different concentrations of grape medicine mulberry wine with glycocholic acid and taurocholate was used to evaluate the effect of reducing blood lipid in vitro. The results showed that the optimum technological parameters of grape medicine mulberry fermentation were: Inoculation amount 0.3%, main fermentation time 8 d, fermentation temperature 26 ℃, raw material ratio 1:3. When the volume concentration of grape medicine mulberry wine fermented by this process was 1.0 mL/mL, the scavenging rates for DPPH, ABTS and hydroxyl radicals were 98.83%, 98.38%, and 99.24%, respectively. It showed that it had stronger antioxidant activity compared with similar fruit wines. When the concentration of grape medicine mulberry wine reached 1.0 mL/mL, the binding rate of grape medicine mulberry wine with glycocholic acid and taurocholate reached 69.36% and 73.28% respectively. It was preliminarily confirmed that the grape medicine mulberry wine had better lipid lowering activity in vitro.

Abstract Dopamine receptors are involved in several immunological diseases. We previously found that dopamine D3 receptor (D3R) on mast cells showed a high correlation with disease activity in patients with rheumatoid arthritis, but the mechanism remains largely elusive. In this study, a murine collagen-induced arthritis (CIA) model was employed in both DBA/1 mice and D3R knockout mice. Here, we revealed that D3R-deficient mice developed more severe arthritis than wild-type mice. D3R suppressed mast cell activation in vivo and in vitro via a Toll-like receptor 4 (TLR4)-dependent pathway. Importantly, D3R promoted LC3 conversion to accelerate ubiquitin-labeled TLR4 degradation. Mechanistically, D3R inhibited mTOR and AKT phosphorylation while enhancing AMPK phosphorylation in activated mast cells, which was followed by autophagy-dependent protein degradation of TLR4. In total, we found that D3R on mast cells alleviated inflammation in mouse rheumatoid arthritis through the mTOR/AKT/AMPK-LC3-ubiquitin-TLR4 signaling axis. These findings identify a protective function of D3R against excessive inflammation in mast cells, expanding significant insight into the pathogenesis of rheumatoid arthritis and providing a possible target for future treatment.

Background: Acute pancreatitis (AP) is a common digestive system disease, and its incidence is increasing year by year. Although some clinical studies have indicated that cholecystectomy can reduce the risk of recurrent pancreatitis after acute biliary pancreatitis (ABP), it is not clear whether cholecystectomy would affect the severity of subsequent AP. Methods: In this study, we combined computed tomography scoring index (CTSI), bedside index for severity in AP (BISAP), and clinical manifestations grading of AP with propensity score matching (PSM), after correction for baseline confounding factors, to respectively explore the influence of cholecystectomy on the severity of subsequent pancreatitis in 527 AP patients. Results: The results showed that ABP (231/527) is more common in female patients and elderly patients (P < 0.001). Age, amylase, creatinine, blood urea nitrogen, and aspartate aminotransferase levels of patients with ABP at admission were higher than those of non-biliary pancreatitis (296/527), and the levels of albumin, hematocrit, and blood glucose were lower (P < 0.050). Further, compared with the unresected group (458/527), patients after cholecystectomy (69/527) had less white blood cells and higher level of albumin (P < 0.050). Patients had lower clinical manifestation grade (P = 0.019) and CTSI grade (P < 0.008) after cholecystectomy. After PSM correction, there was no difference in biochemical parameters between the cholecystectomy group and the non-cholecystectomy group, but differences in clinical manifestation grade (P = 0.039) and CTSI grade (P = 0.013) remained. We also found that cholecystectomy reduced the frequency of biliary pancreatitis (30.4% vs. 45.9%, P < 0.050). Finally, we found that cholecystectomy could reduce the severity of subsequent idiopathic AP. Conclusion: Cholecystectomy could reduce the severity of subsequent idiopathic AP and the frequency of biliary pancreatitis.

Background: Studies have reported that the RNA-binding protein Eukaryotic Elongation Factor 1A1 (EEF1A1) is low expressed in the hippocampal region of Alzheimer’s disease (AD). In addition, it is related to PARK2 activity in cells, predicting its importance in neurodegenerative diseases. However, the function of EEF1A1 in Parkinson’s disease (PD) is unclear. Our study’s primary objective was to knock down EEF1A1 in U251 cells and preliminarily explore the role of EEF1A1 in PD neuroinflammation. Methods: To inhibit EEF1A1 from being expressed in U251 cells, siRNA was transfected into those cells. Then, RNA-seq sequencing was used to determine the Differentially Expressed Genes (DEGs) resulting from the EEF1A1 knockdown. Additionally, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed to find the biological processes and signaling pathways engaged in the DEGs, as well as to screen for genes associated with neuroinflammatory processes that influence the development of PD. Further Real Time - quantitative Polymerase Chain Reaction (RT-qPCR) validation experiments were performed to confirm the reliability of the sequencing results. Finally, combined with the support of related literature, the molecular mechanism of EEF1A1 in regulating the neuroinflammatory process of PD was initially explored. Results: Analysis using the RNA-seq technique showed that EEF1A1 knockdown could significantly upregulate the expression of IL-6, GDF15, STC1, MT1E, GPNMB, CCL5, MT1X, A2M, and VIP genes at the transcriptional level. These nine highly elevated genes were enriched to signaling pathways linked to inflammatory processes, according to an analysis of GO and KEGG enrichment. Conclusions: EEF1A1 is involved in the regulating of IL-6, GDF15, STC1, MT1E, GPNMB, CCL5, MT1X, A2M, and VIP genes associated with the neuroinflammatory process of PD. Among them, we found that GDF15, STC1, MT1E, MT1X, GPNMB, VIP, and A2M genes were involved in delaying the neuroinflammatory process of PD, while IL-6 and CCL5 were involved in exacerbating the neuroinflammatory process, implicating that EEF1A1 may participate in the regulation of the PD neuroinflammation.

Abstract Background Hepatic steatosis is a big hurdle to treat type 2 diabetes (T2D). Fasting-mimicking diet (FMD) has been shown to be an effective intervention in dyslipidemia of T2D. However, fasting may impair the normal glucose metabolism. Human umbilical cord-derived mesenchymal stem cell (UC-MSC) transplantation has been discovered to regulate immune reactions and reduce hyperglycemia in diabetes. However, the effect of UC-MSCs on improving the lipid metabolism disorder is not quite satisfactory. We have investigated the efficacy comparison and interaction between FMD and UC-MSC infusion, aiming to establish effective T2D therapies and explore its mechanism. Methods C57/BL6 mice were fed with high-fat diet (HFD) to induce a diet-induced obese (DIO) mouse model. Leptin receptor-deficient (db/db) mice were used for follow-up experiments. DIO or db/db mice were divided into 4 groups: phosphate buffer saline (PBS), UC-MSCs, FMD, and UC-MSCs + FMD. At the end of the study period, mice were fasted and sacrificed, with the measurement of physiological and biochemical indexes. In addition, the fresh liver, skin, and white adipose tissue were analyzed by histology. Results FMD restored the lipid metabolism in DIO mice, whereas its capacity to rescue hyperglycemia was uncertain. Infusion of UC-MSCs was effective in T2D glycemic control but the impact on dyslipidemia was insufficient. Furthermore, both the glucose and the lipid alterations of DIO and db/db mice recovered after UC-MSCs combined with FMD. It was proved that UC-MSCs promoted FMD effects on ameliorating hyperglycemia and restoring the lipid metabolism in T2D mice, while FMD had little promotion effect on UC-MSCs. Mechanistically, we discovered that UC-MSC infusion significantly modulated systematic inflammatory microenvironment, which contributed to concerted actions with FMD. Conclusions We established a strategy that combined UC-MSC infusion and FMD and was effective in treating T2D, which provided potential approaches for developing novel clinical T2D therapies.

The World Health Organization declared a public health emergency of international concern in January 2020. The Delta variant became the main epidemic strain on 11 May 2021. Vaccines were proven highly effective in controlling hospitalization and deaths associated with severe acute respiratory syndrome coronavirus 2 infections. Real data on vaccine efficacy against B.1.617.2 infection in the Chinese population were currently limited. This study aimed to evaluate the protective effect of inactivated vaccine injection and immunoglobulin (Ig) G levels in coronavirus disease 2019 (COVID-19) severity. This retrospective study included patients with COVID-19 in Xi’an Chest Hospital from December 2021 to January 2022. The protective effect of inactivated vaccine injection and IgG levels on COVID-19 severity was analyzed using multiple logistic regressions. A total of 580 patients were included in the study, of whom 158 (27.24%) were mild, 412 (71.03%) were moderate, 5 (0.9%) were severe, and 5 (0.86%) were critical. Severe case (including severe and critical) rates were 1.72% (10/580). Compared with the unvaccinated group, the vac+IgG− group had a 0.21 (0.02–2.05)-fold risk of suffering from severe cases, and the vac+IgG+ group had a 0.05 (0–0.63)-fold risk of suffering from severe cases. Of the 10 severe cases, 8 were older than 60 years, 8 were men, 8 had underlying diseases, 6 were in the unvaccinated group, and 2 were in the vac+IgG− group. Vaccination and sufficient IgG antibody production can protect patients with COVID-19 from severe cases. Booster vaccine injection can produce a stronger immune response and protection.

To overcome the fruit’s perishability, mulberry wine has been developed as a method of preservation. However, dynamic changes in metabolites during mulberry wine fermentation have not been reported yet. In the present investigation, UHPLC-QE-MS/MS coupled with multivariate statistical analyses was employed to scrutinize the metabolic profiles, particularly the flavonoid profiles, throughout the process of vinification. In general, the major differential metabolites encompassed organic heterocyclic compounds, amino acids, phenylpropanoids, aromatic compounds, and carbohydrates. The contents of total sugar and alcohol play a primary role that drove the composition of amino acids, polyphenol, aromatic compound, and organic acid metabolites based on the Mantel test. Importantly, among the flavonoids, abundant in mulberry fruit, luteolin, luteolin-7-O-glucoside, (−)-epiafzelechin, eriodictyol, kaempferol, and quercetin were identified as the differential metabolic markers during blackberry wine fermentation and ripening. Flavonoid, flavone and flavonol biosynthesis were also identified to be the major metabolic pathways of flavonoids in 96 metabolic pathways. These results will provide new information on the dynamic changes in flavonoid profiles during black mulberry winemaking.

Dictyophora indusiata is one of the most famous edible mushrooms in China. D. indusiata polysaccharide (DP) has attracted increasing attention because of its multiple beneficial effects. In this study, the in vitro simulated digestion and microbial fermentation were designed to reveal the potential catabolic property of DP and its impacts on the modulation of gut microbial composition. The results showed that the reducing sugar content, total polysaccharides content, molecular weight, and rheological property of DP were not significantly altered under in vitro simulated digestive conditions. However, the molecular weight, apparent viscosity, and total polysaccharides content of indigestible DP (DPI) significantly decreased during in vitro fecal fermentation, and the reducing sugar content and the release of free monosaccharides notably increased, suggesting that DP could be degraded and used by gut microbiota. Additionally, the relative abundances of several beneficial bacteria, such as Bacteroides, Catenibacterium, Parabacteroides, and Megamonas, increased significantly, indicating that DP can regulate the composition and abundance of gut microbiota. Moreover, DP could also promote the production of SCFAs, thus changing the acid–base environment of the large intestine. The results of this study are beneficial for deeply clarifying the catabolic behavior of DP in the gastrointestinal tract, which can provide a theoretical basis for developing microbiota-directed products based on DP.

Abstract Background TGFB‐induced factor homeobox 2 (TGIF2) has been reported to exert essential functions in brain development. This study aimed to elucidate the correlation of TGIF2 with autism, a neurodevelopmental condition which presents with severe communication problems. Methods An autism‐related gene expression dataset GSE36315 was used to analyze aberrantly expressed genes in autistic brain tissues. Maternal mice were treated with valproate (VPA), and their offspring were selected as model mice with autism. The functions of TGIF2 in autism‐like symptoms in mice were examined by behavioral tests and histological examination of their hippocampal tissues. Mouse hippocampal neurons were extracted for in vitro studies. A gene set enrichment analysis was performed to analyze the signaling pathways involved, and the upstream factors influencing TGIF2 expression were explored in the ENCODE database and validated by ChIP‐qPCR assays. Results TGIF2 was poorly expressed in autistic patients in the GSE36315 dataset as well as in the temporal cortex tissues of autistic mice. Adenovirus‐mediated overexpression of TGIF2 suppressed autism‐like symptoms and neuronal apoptosis in autistic mice. TGIF2 activated the Wnt/β‐catenin signaling pathway. TGIF2 could be regulated by monomethylation of histone H3 Lys4 (H3K4me1). The histone demethylase LSD1 was highly expressed in the tissues of autistic mice and bound to TGIF2 promoter, which was possibly responsible for TGIF2 downregulation. Conclusion This research suggests that the downregulation of TGIF2, possibly regulated by LSD1/H3K4me1, is correlated with neuronal apoptosis and development of autism in mice through the inactivation of the Wnt/β‐catenin pathway.

Nonalcoholic fatty liver disease (NAFLD) is prevalent worldwide, while no pharmaceutical treatment has been approved. Natural herbs are promising for their amelioration effect on lipid metabolism. Theabrownin (TB) and Poria cocos polysaccharide (PCP) have been reported to have effect on hyperlipidemia and diabetes. Here, we compared the effect of individual TB or PCP and the combination of TB and PCP (TB + PCP) on NAFLD phenotypes and the alteration of metabolism in the mice with high-fat diet. The results showed that TB, PCP, and TB + PCP reduced serum and hepatic lipid levels, among which TB + PCP was the most effective. Serum metabolomic profile and liver mRNA analyses revealed that the treatments altered metabolic pathways involved in fatty acid metabolism, bile acid metabolism, and tricarboxylic acid cycle, which was also most significant in the TB + PCP group. This study demonstrated that TB, PCP, especially the combination of TB and PCP could be potential therapeutic formula for NAFLD that promoted lipid utilization and inhibited lipid synthesis and absorption.

Biomass, a globally available resource, is a promising alternative feedstock for fossil fuels, especially considering the current energy crisis and pollution. Biomass-derived diols, such as 2,5-bis(hydroxymethyl)furan, 2,5-bis(hydroxymethyl)-tetrahydrofuran, and 1,6-hexanediol, are a significant class of monomers in the polyester industry. Therefore, the catalytic conversion of biomass to valuable diols has received extensive research attention in the field of biomass conversion and is a crucial factor in determining the development of the polyester industry. 5-Hydroxymethylfurfural (HMF) is an important biomass-derived compound with a C6-furanic framework. The hydroconversion of HMF into diols has the advantages of being simple to operate, inexpensive, environmentally friendly, safe, and reliable. Therefore, in the field of diol synthesis, this method is regarded as a promising approach with significant industrialization potential. This review summarizes recent advances in diol formation, discusses the roles of catalysts in the hydroconversion process, highlights the reaction mechanisms associated with the specificities of each active center, and provides an outlook on the challenges and opportunities associated with the research on biomass-derived diol synthesis.

Kiwi starch (KS) is a fruit-derived starch; in order to improve its processing performance and increase its added value, it is necessary to modify KS to enhance the positive attributes and to enlarge its application. In this study, KS was modified by high-power ultrasound treatment (HUT) to reveal the relationship between the structure and function of KS with different treatment powers (0, 200, 400, and 600 W) and different treatment times (0, 10, 20, and 30 min). The results showed that HUT destroyed the granular morphology of KS, formed holes and cracks on the surface, and reduced the particle size and the short-range molecular order of KS. After different HUTs, the apparent amylose content (AAC), swelling power (SP), water solubility index (WSI), viscosity and setback value (SB) of KS were significantly increased, while the gelatinization temperature was significantly decreased. In addition, HUT significantly reduced the content of rapidly digestible starch (RDS) and slowly digestible starch (SDS), while it significantly enhanced the content of resistant starch (RS) (64.08–72.73%). In a word, HUT as a novel physical modification method for KS, enlarged its application, and fulfilled different demands of a starch-based product, which introduces another possibility for kiwi fruit further processing.

Abstract Multiple‐input multiple‐output‐sparse code multiple access, a non‐trivial integration of sparse code multiple access and multiple‐input multiple‐output techniques, is able to achieve high spectrum efficiency and massive user connections. However, this integration also increases the complexity of signal detection. Here, the signal detection problem of multiple‐input multiple‐output sparse code multiple access is transformed into a tree search problem and use sphere decoding to detect the signal. By setting the initial radius to positive infinity, sphere decoding can achieve optimal maximum likelihood performance while the complexity is high. In order to further reduce the complexity of sphere decoding, a block‐wise sorted QR decomposition algorithm is proposed. Based on block‐wise sorted QR decomposition, the improved sphere decoding, namely block‐wise sorted QR decomposition‐sphere decoding, is able to make the tree search more efficient. Since only the detection order of each user's signal has been changed, block‐wise sorted QR decomposition‐sphere decoding can maintain the optimal maximum likelihood performance. Simulation results and complexity analysis show that block‐wise sorted QR decomposition‐sphere decoding can achieve optimal performance and both hard‐output and soft‐output block‐wise sorted QR decomposition‐sphere decoding have much lower complexity than joint message passing algorithm. Furthermore, given the same signal‐to‐noise ratio, the complexity of block‐wise sorted QR decomposition‐sphere decoding decreases with the increase of receiving antennas, while the complexity of joint message passing algorithm increases linearly.

Abstract Background A carotid web is a very rare vascular disease of the carotid artery, leading to thrombosis and ischemic stroke. Case presentation A 65-year-old male patient was admitted due to left limb weakness. On arrival, he had moderate left hemiplegia, neglect, and sensory loss; the National Institutes of Health Stroke Scale score was 8. Computed tomography angiography (CTA) and magnetic resonance (MR) examination were performed to determine the cause of basal ganglia infarction. Thin-section axial CTA showed a membrane-like structure in the posterior wall of the right common carotid artery. The sagittal reconstruction image showed a membrane-like protrusion in the posterior wall of the right common carotid artery under the right carotid sinus. The MR axial T2 image showed a membrane-like high-signal protrusion into the carotid artery lumen, which was diagnosed as a right carotid web. The patient was treated with dual antihypertensive therapy by adjusting blood pressure, controlling brain edema, improving cerebral circulation, and nourishing the nerves. Conclusion Careful comparison of axial thin-layer CTA and MR axial T2 images combined with sagittal reconstruction of CTA images can greatly improve the diagnostic rate of carotid web.

Graph embedding models are widely used in knowledge graph completion (KGC) task. However, most models are based on the assumption that knowledge is completely certain, and this is inconsistent with real-world situations. Although there are multiple studies on uncertain knowledge embedding tasks, they often use knowledge confidence to learn embedding and cannot make full use the structural and uncertain information of knowledge. This paper presents a new embedding model named Structural and Uncertain Knowledge Embedding (SUKE), which comprises two components: an evaluator and a confidence generator. For unknown triples, the evaluator learns the structural and uncertain information to evaluate its rationality and obtain a candidate set. The confidence generator then determines the confidence of the candidate set to achieve KGC. To verify the effectiveness of the proposed model, confidence prediction, triple evaluation, and fact classification tasks are performed on three data sets. Experimental results show that SUKE performs better than mainstream embedding methods. The model proposed in this paper can help advance the research on the embedding of uncertain knowledge graphs.

An association rule mining algorithm is an algorithm that mines the association between things and is often used to mine the association knowledge between things. Association rule mining algorithms can find potential connections between different qualities of college students from the data of college students’ life and learning, which can help teachers discover the problems and their own strengths of different students and achieve teaching according to their aptitude. The purpose of this paper is to solve some problems related to the associative rule extraction algorithm and to investigate the impact of applying the associative rule extraction algorithm in a college student quality assessment system. Based on the algorithm, a quality assessment system for college students has been developed. A modified script-based associative rule extraction algorithm is used to find the correlation between the quality and the ability of college students. The quality assessment data of college students are analyzed and studied. The results show that the use of associative rule extraction algorithms to assess the quality and ability of college students can improve the efficiency of the test by 24% and the accuracy of the test score by 33% and reduce the probability of outliers in the scoring process by 27%. It can be seen that the association rule extraction algorithm can be applied to college students’ quality assessment system and also reduces the probability of encountering obstacles in accuracy and performance assessment. At the same time, this experiment also proves the robustness and feasibility of the algorithm in this paper.