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To clarify differences in the aroma components and characteristics between traditional and wild Dianhong Congou black teas, five traditional and five wild Dianhong Congou black teas were investigated using headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) to measure and analyze the aroma characteristics of the two types of tea. A total of 180 aroma components were detected in the 10 tea samples, including 31 alcohols, 19 ketones, 33 aldehydes, 32 esters, 11 acids, 35 hydrocarbons, and 19 other categories. Thirty-six components with odor activity values greater than 1 were identified in traditional Dianhong Congou and wild Dianhong Congou black teas, with nine components common to both. Linalool was found to be the major contributor to aroma in traditional Dianhong Congou black tea, which was characterized by a floral and sweet aroma, while linalool, hexanal, and nonanal were the most significant aroma components in wild Dianhong Congou black tea, which had floral, sweet, woody, and fruity aromas. The results of this study provide a data reference for understanding the aroma characteristics of traditional and wild Dianhong Congou black teas.

Abstract The diversity of secondary metabolites is an important means for plants to cope with the complex and ever‐changing terrestrial environment. Plant biosynthetic gene clusters (BGCs) are crucial for the biosynthesis of secondary metabolites. The domestication and evolution of BGCs and how they affect plant secondary metabolites biosynthesis and environmental adaptation are still not fully understood. Buckwheat exhibits strong resistance and abundant secondary metabolites, especially flavonoids, allowing it to thrive in harsh environments. A non‐canonical BGC named UFGT3 cluster is identified, which comprises a phosphorylase kinase (PAK), two transcription factors (MADS1/2), and a glycosyltransferase (UFGT3), forming a complete molecular regulatory module involved in flavonoid biosynthesis. This cluster is selected during Tartary buckwheat domestication and is widely present in species of the Fagopyrum genus. In wild relatives of cultivated buckwheat, a gene encoding anthocyanin glycosyltransferase (AGT), which glycosylates pelargonidin into pelargonidin‐3‐O‐glucoside, is found inserted into this cluster. The pelargonidin‐3‐O‐glucoside can help plants resist UV stress, endowing wild relatives with stronger high‐altitude adaptability. This study provides a new research paradigm for the evolutionary dynamics of plant BGCs, and offers new perspectives for exploring the mechanism of plant ecological adaptability driven by environmental stress through the synthesis of secondary metabolites.

Abstract The multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus.

Abstract The liver is the largest internal organ of the human body. It has a complex structure and function and plays a vital role in drug metabolism. In recent decades, extensive research has aimed to develop in vitro models that can simulate liver function to demonstrate changes in the physiological and pathological environment of the liver. Animal models and in vitro cell models are common, but the data obtained from animal models lack relevance when applied to humans, while cell models have limited predictive ability for metabolism and toxicity in humans. Recent advancements in tissue engineering, biomaterials, chip technology, and 3D bioprinting have provided opportunities for further research in in vitro models. Among them, liver-on-a-Chip (LOC) technology has made significant achievements in reproducing the in vivo behavior, physiological microenvironment, and metabolism of cells and organs. In this review, we discuss the development of LOC and its research progress in liver diseases, hepatotoxicity tests, and drug screening, as well as chip combinations. First, we review the structure and the physiological function of the liver. Then, we introduce the LOC technology, including general concepts, preparation materials, and methods. Finally, we review the application of LOC in disease modeling, hepatotoxicity tests, drug screening, and chip combinations, as well as the future challenges and directions of LOC.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease mainly caused by insulin resistance, which can lead to a series of complications such as cardiovascular disease, retinopathy, and its typical clinical symptom is hyperglycaemia. Glucosidase inhibitors, including Acarbose, Miglitol, are commonly used in the clinical treatment of hypoglycaemia. In addition, Protein tyrosine phosphatase 1B (PTP1B) is also an important promising target for the treatment of T2DM. Gynostemma pentaphyllum is a well-known oriental traditional medicinal herbal plant, and has many beneficial effects on glucose and lipid metabolism. In the present study, three new and nine known dammarane triterpenoids isolated from G. pentaphyllum, and their structures were elucidated by spectroscopic methods including HR-ESI-MS,1H and 13C NMR and X-ray crystallography. All these compounds were evaluated for inhibitory activity against α-glucosidase, α-amylase and PTP1B. The results suggested that compounds 7∼10 were potential antidiabetic agents with significantly inhibition activity against PTP1B in a dose-dependent manner.

Agricultural drought is a major natural disaster affecting biomass accumulation and causing food loss, exacerbated by the increasing frequency of flash droughts and compounded drought-heatwave events. Traditional optical remote sensing indices cannot directly represent the water content of vegetation, resulting in a limited understanding of crop response to drought. To address this gap, we investigated the responsiveness of microwave Vegetation Optical Depth (VOD) with four bands (L-, C-, X-, KU-) and four emerging VOD-derived products to drought conditions in crops in the Midwest US. These products include the normalized Difference Between Night and Day VOD (nVOD), Slope of the Regression of Day and Night VOD (σ), Standardized VOD Index (SVODI), and VOD to estimate Gross Primary Productivity (VOD2GPP). They employ different theoretical modeling approaches to crop growth and water use strategies. We comprehensively analyzed the trend, seasonality, and residual of VODs, using Leaf Area Index (LAI) for comparison, and further assessed the lagged and cumulative effects, quantified drought sensitivity, and captured responsiveness to cumulative drought using thresholds. The results showed a time lag in the response of VOD series to drought as indicated by the Standardized Precipitation Evapotranspiration Index (SPEI). VODs achieved faster responses and higher correlations compared to LAI. Among them, VOD_L exhibited the most statistically significant pixels (39.84%) and positive Rmax-lag with 96.81% of all pixels. For cumulative effects, VOD_L, VOD_C, VOD_X, VOD_KU, and SVODI were highly correlated in the early stages of droughts. We also found that crops in Iowa exhibited medium to high drought sensitivity (average values of 0.55 to 0.74), with the highest drought sensitivity calculated using the isohydricity indicator, σ. Based on threshold comparison, σ showed a timely response in the first month of drought (average of −0.62), whereas VOD_L and VOD_C performed best in the second month (both averaging −1.85), and VOD2GPP (−2.94) was the most responsive in the third month. Due to water use strategy, maize responded more quickly to the onset of drought compared to soybeans. Overall, the results demonstrated that VOD is promising for crop phenology and drought research. This study provides the first comprehensive investigation of the diverse capabilities of multiple VOD-based indices in drought monitoring across various timescales and croplands.

Abstract Background Tartary buckwheat, Fagopyrum tataricum, is a pseudocereal crop with worldwide distribution and high nutritional value. However, the origin and domestication history of this crop remain to be elucidated. Results Here, by analyzing the population genomics of 567 accessions collected worldwide and reviewing historical documents, we find that Tartary buckwheat originated in the Himalayan region and then spread southwest possibly along with the migration of the Yi people, a minority in Southwestern China that has a long history of planting Tartary buckwheat. Along with the expansion of the Mongol Empire, Tartary buckwheat dispersed to Europe and ultimately to the rest of the world. The different natural growth environments resulted in adaptation, especially significant differences in salt tolerance between northern and southern Chinese Tartary buckwheat populations. By scanning for selective sweeps and using a genome-wide association study, we identify genes responsible for Tartary buckwheat domestication and differentiation, which we then experimentally validate. Comparative genomics and QTL analysis further shed light on the genetic foundation of the easily dehulled trait in a particular variety that was artificially selected by the Wa people, a minority group in Southwestern China known for cultivating Tartary buckwheat specifically for steaming as a staple food to prevent lysine deficiency. Conclusions This study provides both comprehensive insights into the origin and domestication of, and a foundation for molecular breeding for, Tartary buckwheat.

Tea (Camellia sinensis) falls into the family Theaceae, is a valuable commercial crop, and tea products made from its buds and young leaves are favored by consumers all over the world. The more common Thea plant is Camellia sinensis (C. sinensis), but its most important relative, Camellia taliensis (C. taliensis), is also utilized by locals in the area of cultivation to manufacture tea. In this investigation, C. taliensis (DL) and C. sinensis (QJZ) were characterized in terms of their agronomic traits, physicochemical indices, metabolomics, and transcriptomics. The leaf area of DL is larger than that of QJZ; the color of DL’s buds and leaves is yellowish-green, while that of QJZ’s is green. DL’s buds and leaves are more densely velvety than those of QJZ. The HPLC results indicated that the physicochemical contents varied considerably between the two samples, with DL having greater concentrations of EGCG and GABA than QJZ, while QJZ had remarkably higher concentrations of C, CA, and EGC than DL. A total of 2269 metabolites and 362,190,414 genes were positively identified, with the number of DAMs and DEGs being 1001 and 34,026, respectively. The flavonoids, phenolic acids, and alkaloid metabolites were dramatically different between the two tea group plants. Bioinformatics profiling revealed that the DAMs and DEGs of the two tea group plants interacted with each other and were involved in metabolic pathways, including “biosynthesis of secondary metabolites”, “biosynthesis of amino acids”, “biosynthesis of cofactors”, “phenylpropanoid biosynthesis”, and “flavonoid biosynthesis”. Overall, these results provide statistical support for germplasm conservation and production for both C. taliensis and C. sinensis.

Abstract Microchromosome maintenance (MCM) proteins are a number of nuclear proteins with significant roles in the development of cancer by influencing the process of cellular DNA replication. Of the MCM protein family, MCM10 is a crucial member that maintains the stability and extension of DNA replication forks during DNA replication and is significantly overexpressed in a variety of cancer tissues, regulating the biological behaviour of cancer cells. But little is understood about MCM10’s functional role and regulatory mechanisms in a range of malignancies. We investigate the impact of MCM10 in human cancers by analyzing data from databases like the Gene Expression Profiling Interaction Analysis (GEPIA2), Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA), among others. Possible relationships between MCM10 and clinical staging, diagnosis, prognosis, Mutation burden (TMB), microsatellite instability (MSI), immunological checkpoints, DNA methylation, and tumor stemness were identified. The findings demonstrated that MCM10 expression was elevated in the majority of cancer types and was connected to tumor dryness, immunocytic infiltration, immunological checkpoints, TMB and MSI. Functional enrichment analysis in multiple tumors also identified possible pathways of MCM10 involvement in tumorigenesis. We also discovered promising MCM10-targeting chemotherapeutic drugs. In conclusion, MCM10 may be a desirable pan-cancer biomarker and offer fresh perspectives on cancer therapy.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic diseases encountered in clinical practice, which is characterized by the excessive accumulation of triglycerides (steatosis), and a variety of metabolic abnormalities including lipid metabolism and bile acid metabolism are closely related to NAFLD. In China, Gynostemma pentaphyllum is used as functional food and Chinese medicine to treat various diseases, especially NAFLD, for a long time. However, the active components that exert the main therapeutic effects and their mechanisms remain unclear. In this study, Gypensapogenin A was isolated from the total saponins of G. pentaphyllum and prepared as a liposomal delivery system. Gypensapogenin A liposomes could activate FXR, inhibit the expression of CYP7A1 and CYP8B1, increase the expression of CYP27A1, modulate the ratio of CA and CDCA, decrease the content of CA, and increase the content of CDCA, thus forming a virtuous cycle of activating FXR to play a role in lowering blood lipid levels.

Abstract Background Lotus corniculatus is a widely distributed perennial legume whose great adaptability to different environments and resistance to barrenness make it an excellent forage and ecological restoration plant. However, its molecular genetics and genomic relationships among populations are yet to be uncovered. Result Here we report on a genomic variation map from worldwide 272 L. corniculatus accessions by genome resequencing. Our analysis suggests that L. corniculatus accessions have high genetic diversity and could be further divided into three subgroups, with the genetic diversity centers were located in Transcaucasia. Several candidate genes and SNP site associated with CNglcs content and growth traits were identified by genome-wide associated study (GWAS). A non-synonymous in LjMTR was responsible for the decreased expression of CNglcs synthesis genes and LjZCD was verified to positively regulate CNglcs synthesis gene CYP79D3. The LjZCB and an SNP in LjZCA promoter were confirmed to be involved in plant growth. Conclusion This study provided a large number of genomic resources and described genetic relationship and population structure among different accessions. Moreover, we attempt to provide insights into the molecular studies and breeding of CNglcs and growth traits in L. corniculatus.

Abstract Backgrounds The incidence of gastric cardiac cancer (GCC) has obviously increased recently with poor prognosis. It’s necessary to compare GCC prognosis with other gastric sites carcinoma and set up an effective prognostic model based on a neural network to predict the survival of GCC patients. Methods In the population-based cohort study, we first enrolled the clinical features from the Surveillance, Epidemiology and End Results (SEER) data (n = 31,397) as well as the public Chinese data from different hospitals (n = 1049). Then according to the diagnostic time, the SEER data were then divided into two cohorts, the train cohort (patients were diagnosed as GCC in 2010–2014, n = 4414) and the test cohort (diagnosed in 2015, n = 957). Age, sex, pathology, tumor, node, and metastasis (TNM) stage, tumor size, surgery or not, radiotherapy or not, chemotherapy or not and history of malignancy were chosen as the predictive clinical features. The train cohort was utilized to conduct the neural network-based prognostic predictive model which validated by itself and the test cohort. Area under the receiver operating characteristics curve (AUC) was used to evaluate model performance. Results The prognosis of GCC patients in SEER database was worse than that of non GCC (NGCC) patients, while it was not worse in the Chinese data. The total of 5371 patients were used to conduct the model, following inclusion and exclusion criteria. Neural network-based prognostic predictive model had a satisfactory performance for GCC overall survival (OS) prediction, which owned 0.7431 AUC in the train cohort (95% confidence intervals, CI, 0.7423–0.7439) and 0.7419 in the test cohort (95% CI, 0.7411–0.7428). Conclusions GCC patients indeed have different survival time compared with non GCC patients. And the neural network-based prognostic predictive tool developed in this study is a novel and promising software for the clinical outcome analysis of GCC patients.

Dendrobium nobile Lindl. (D.nobile) contributes to an hepatoprotective effect. Unfortunately, the active components and molecular mechanism of D.nobile in alcoholic liver injury is still elusive. Here, we investigated the function of main active ingredients in D.nobile aqueous extract (DNAE) in vivo on regulating the expression of E74-like factor 4 (ELF4) in liver macrophages to against alcoholic liver injury through reducing inflammatory response. The differential expressed genes (DEGs) and transcription factors (TFs) in mouse liver immune cells were determined by single-cell transcriptome analysis, and ELF4 expression in macrophages was determined by RT-PCR and Western blot. The main metabolites of DNAE in vivo were determined by LC-MS/MS analysis. The molecular docking was used to analyze the interactions between metabolites of DNAE and ELF4 signaling. The results showed that DNAE administration showed a reduction of oxidative damage and inflammatory response when mice were treatment with a daily alcoholic intragastric for 14 days. What is more, alcohol primarily affected the expression of macrophages genes among liver immune cells and the DEGs were mainly regulated by transcription factor ELF4, which was relevant to inflammation reaction in macrophages. Meanwhile, DNAE upregulated ELF4 expression through the RTK/ERK1/2 axis. ELF4 inhibits macrophage inflammatory responses via transactivating its upstream target genes S100A9. Furthermore, the main metabolites of DNAE were sesquiterpenoids and alkaloids in vivo, and sesquiterpenoids are more strongly correlated with the cell membrane cascade response RTK/ERK1/2 signaling pathway, which could regulate the expression of ELF4. This study explores the essentiality of sesquiterpenoids to regulate ELF4 in macrophages and indicates that sesquiterpenoids could be as an anti-inflammation drug or a daily functional healthcare product to alcoholic liver disease.

IntroductionHelicobacter pylori (H.pylori, Hp) affects billions of people worldwide. However, the emerging resistance of Hp to antibiotics challenges the effectiveness of current treatments. Investigating the genotype-phenotype connection for Hp using next-generation sequencing could enhance our understanding of this resistance.MethodsIn this study, we analyzed 52 Hp strains collected from various hospitals. The susceptibility of these strains to five antibiotics was assessed using the agar dilution assay. Whole-genome sequencing was then performed to screen the antimicrobial resistance (AMR) genotypes of these Hp strains. To model the relationship between drug resistance and genotype, we employed univariate statistical tests, unsupervised machine learning, and supervised machine learning techniques, including the development of support vector machine models.ResultsOur models for predicting Amoxicillin resistance demonstrated 66% sensitivity and 100% specificity, while those for Clarithromycin resistance showed 100% sensitivity and 100% specificity. These results outperformed the known resistance sites for Amoxicillin (A1834G) and Clarithromycin (A2147), which had sensitivities of 22.2% and 87%, and specificities of 100% and 96%, respectively.DiscussionOur study demonstrates that predictive modeling using supervised learning algorithms with feature selection can yield diagnostic models with higher predictive power compared to models relying on single single-nucleotide polymorphism (SNP) sites. This approach significantly contributes to enhancing the precision and effectiveness of antibiotic treatment strategies for Hp infections. The application of whole-genome sequencing for Hp presents a promising pathway for advancing personalized medicine in this context.

IntroductionDendrobium nobile (D. nobile), a valued Chinese herb known for its diverse pharmacological effects, owes much of its potency to the bioactive compound dendrobine. However, dendrobine content varies significantly with plant age, and the mechanisms governing this variation remain unclear. This study delves into the potential role of endophytic fungi in shaping host-microbe interactions and influencing plant metabolism.MethodsUsing RNA-seq, we examined the transcriptomes of 1-year-old, 2-year-old, and 3-year-old D. nobile samples and through a comprehensive analysis of endophytic fungal communities and host gene expression in D. nobile stems of varying ages, we aim to identify associations between specific fungal taxa and host genes.ResultsThe results revealing 192 differentially expressed host genes. These genes exhibited a gradual decrease in expression levels as the plants aged, mirroring dendrobine content changes. They were enriched in 32 biological pathways, including phagosome, fatty acid degradation, alpha-linolenic acid metabolism, and plant hormone signal transduction. Furthermore, a significant shift in the composition of the fungal community within D. nobile stems was observed along the age gradient. Olipidium, Hannaella, and Plectospherella dominated in 1-year-old plants, while Strelitziana and Trichomerium prevailed in 2-year-old plants. Conversely, 3-year-old plants exhibited additional enrichment of endophytic fungi, including the genus Rhizopus. Two gene expression modules (mediumpurple3 and darkorange) correlated significantly with dominant endophytic fungi abundance and dendrobine accumulation. Key genes involved in dendrobine synthesis were found associated with plant hormone synthesis.DiscussionThis study suggests that the interplay between different endophytic fungi and the hormone signaling system in D. nobile likely regulates dendrobine biosynthesis, with specific endophytes potentially triggering hormone signaling cascades that ultimately influence dendrobine synthesis.

Protein tyrosine phosphatase 1B (PTP1B) is a key factor and regulator of glucose, lipid metabolism throughout the body, and a promising target for treatment of type 2 diabetes mellitus (T2DM). Gynostemma pentaphyllum is a famous oriental traditional medicinal herbal plant and functional food, which has shown many beneficial effects on glucose and lipid metabolism. The aim of the present study is to assess the inhibitory activity of five new and four known dammarane triterpenoids isolated from the hydrolysate product of total G. pentaphyllum saponins. The bioassay data showed that all the compounds exhibited significant inhibitory activity against PTP1B. The structure-activity relationship showed that the strength of PTP1B inhibitory activity was mainly related to the electron-donating group on its side chain. Molecular docking analysis suggested that its mechanism may be due to the formation of competitive hydrogen bonding between the electron-donating moiety and the Asp48 amino acid residues on the PTP1B protein.

Rosiglitazone (RL), a second-generation thiazolidinedione (TZD), is an oral antidiabetic agent that is reportedly associated with hepatotoxicity. However, the molecular mechanism of Rosiglitazone induced hepatotoxicity has not been reported yet. To minimize clinical risk, in the present study, toxicity was evaluated initially in C57BL/6 mice to confirm the hepatotoxicity of Rosiglitazone. Subsequently, the transcription of genes, the up-regulated expression of proteins and changes of metabolite spectrum in bile acid system in accordance with system pharmacology and multi-omics profiling strategy were investigated to reveal its toxic mechanism. Results show an obvious Rosiglitazone induced hepatocyte injury in our experiment. Changes in bile acid profiles revealed that Rosiglitazone administration increased the concentration of deoxycholic acid (DCA) in the liver, but decreased those of other bile acids. Transcriptomic and proteomic data showed that while the expression of efflux transporters ABCC3, ABCC4 and ABCB11 was upregulated following Rosiglitazone treatment, the expression of two hepatic uptake transporters, OATP1A1 and OATP1A4, which were negatively associated with DCA accumulation, were significantly downregulated. These results indicated that cholestasis, especially the accumulation of DCA in the liver, is the primary factors responsible for Rosiglitazone induced hepatocyte injury. The mechanism of Rosiglitazone induced DCA accumulation in the liver may be the result of stimulated intestinal permeability and increased biosynthesis and uptake of DCA and weakening of DCA amidation to reduce DCA efflux due to the inhibition of OATP1A1 and OATP1A4 expression in the liver.

Dendrobium, which belongs to the family of Orchidaceae, is a highly valuable traditional Chinese medicine commonly used in China. It exerts pharmacological activities such as antitumor and hypoglycemia effects, and its main components are alkaloids, polysaccharides, and terpenoids, among others. In recent years, research on the clinical application of Dendrobium in antitumor therapy has gained increasing attention. Accumulating evidence suggests that the active components of Dendrobium possess significant inhibitory effects on the viability of cancer cells as evident from in vivo and in vitro experiments, which indicates that Dendrobium exerts significant anticancer effect in treating and preventing cancer development, inhibiting the underlying potential molecular mechanisms, including suppression of cancer cell growth and proliferation, epithelial-mesenchymal transition (EMT), apoptosis induction, tumor angiogenesis, and reinforcement of cisplatin (DDP) -induced apoptosis. We herein present a review that summarizes the research progress of the application of Dendrobium in cancer therapy and its molecular mechanisms. This review describes the positive aspects of the active ingredients of Dendrobium in the treatment of cancers in various systems of the human body, their inhibitory effects on tumor survival and tumor microenvironment, and their potential mechanisms. Additionally, this review proposes future application prospects of Dendrobium in cancer therapy to promote further research and future extensive clinical applications of Dendrobium in cancer therapy.

Introduction Colorectal cancer (CRC) is the third most common cancer. Precise prediction of CRC patients’ overall survival (OS) probability could offer advice on its treatment. Neural network (NN) is the first-class algorithm, but a consensus on which NN survival models are better has not been established yet. A predictive model on CRC using Asian data is also lacking. Material and methods We conducted 8 NN survival models of CRC (n = 416) with different theories and compared them using Asian data. Results DeepSurv performed best with a C-index value of 0.8300 in the training cohort and 0.7681 in the test cohort. Conclusions The deep learning survival model for CRC patients (DeepCRC) could predict CRC’s OS accurately.

Preparation of calcined phosphogypsum (CPG) is an important utilization way for phosphogypsum (PG) on a large scale. In this paper, the effects of grinding fineness on the phase transformation rate, mechanical strength and structure of hardened body of the CPG were studied. The results show that increasing calcination temperature is beneficial to accelerating the dehydration of PG, the appropriate calcination temperature is 120℃. With the increase of grinding fineness, the conversion rate of PG into CPG first increases and then decreases; the flexural strength and compressive strength of the prepared CPG first increase and then decrease; the hardened body of the CPG prepared from non-grinding PG has loose structure, many holes and serious pulverization, and the flexural strength and compressive strength are only 0.24 MPa and 0.57 MPa, respectively. When the average particle size of PG is reduced to 49.95 μm, the dehydration rate is accelerated, the crystal size of dihydrate gypsum is uniform, the hardened structure is dense, and the pores are less, the flexural strength and compressive strength are increased to 1.02 MPa and 2.62 MPa, respectively. Therefore, grinding modification is not only beneficial to increasing the dehydration rate of PG, but also to effectively improving the structure of hardened gypsum and increasing the mechanical strength of CPG.

Abstract Introduction The Gelao people are a unique minority in Southwest China with a unique culture for the utilization of edible plants, including a large number of medicinal plants. They believe that at least 61 species are edible and have medicinal value. Ethnobotany research can reveal the local knowledge of the Gelao people regarding the traditional use of plants and the relationship between this minority and their living environment to help retain and pass on this traditional knowledge forever. Methods Edible wild plants and their applied ethnic knowledge were investigated in three counties in northern Guizhou. Gelao residents were the main informants, and literature search, village interviews, participatory observation and quantitative ethnobotany evaluation were used. Results A total of 151 species of wild plants in 67 families are collected and eaten by Gelao residents, among which 61 species were considered to have medicinal value, accounting for 40.4% of the total, and 43 were listed in the Chinese Pharmacopoeia. There were 57 plant species with fruits as their edible parts, which are consumed as snacks, followed by 54 species whose young seedlings and leaves are the edible parts, most of which are consumed cold or stir-fried. Other edible parts included roots or rhizomes (bulbs), flowers, whole plants, seeds, fruiting bodies and stems. There were two consumption modes: raw and cooked. Raw foods were mainly consumed as snacks, which mainly comprise fruits. Cooked foods were mainly vegetables consumed cold or stir-fried. Some plants were used as seasonings, infused wines, condiments and grains. The main medicinal functions were nourishing and reducing heatiness. Nourishing plants were mainly “shen” plants and Liliaceae, while plants able to reduce heatiness were mainly Asteraceae. Others functions included anti-hangover, anticancer and insecticidal. There were 38 species of important edible wild plants (CFSI > 500) in northern Guizhou, which had a high utilization rate. Houttuynia cordata Thunb. and Mentha suaveolens Ehrh. were the most representative edible wild plants in this area. The species, edible parts, edible categories, consumption modes and medicinal functions of edible wild plants in this area are diverse, and the traditional knowledge on their uses is rich. However, the number of wild plant species eaten by the informants and their related knowledge were positively correlated with age, which indicates that the rich traditional knowledge in this area is gradually disappearing with urbanization. Conclusions The Gelao have a rich history of consuming wild plants. With the development of the social economy, the traditional knowledge passed from older generations is gradually being lost and its inheritance is facing great risks. This study collects, sorts and spreads this precious traditional knowledge, which is of great value to its protection and inheritance and fully demonstrates the value and importance of our work.

Abstract Background Emerging evidence suggests that gut microbiota plays a predominant role in Crohn’s disease (CD). However, the microbiome alterations in the early stage of CD patients still remain unclear. The present study aimed to identify dysbacteriosis in patients with early CD and explore specific gut bacteria related to the progression of CD. Methods This study was nested within a longitudinal prospective Chinese CD cohort, and it included 18 early CD patients, 22 advanced CD patients and 30 healthy controls. The microbiota communities were investigated using high-throughput Illumina HiSeq sequencing targeting the V3–V4 region of 16S ribosomal DNA (rDNA) gene. The relationship between the gut microbiota and clinical characteristics of CD was analyzed. Results Differential microbiota compositions were observed in CD samples (including early and advanced CD samples) and healthy controls samples. Notably, Lachnospiracea_incertae_sedis and Parabacteroides were enriched in the early CD patients, Escherichia/Shigella, Enterococcus and Proteus were enriched in the advanced CD patients, and Roseburia, Gemmiger, Coprococcus, Ruminococcus 2, Butyricicoccus, Dorea, Fusicatenibacter, Anaerostipes, Clostridium IV were enriched in the healthy controls [LDA score (log10) > 2]. Furthermore, Kruskal–Wallis Rank sum test results showed that Blautia, Clostridium IV, Coprococcus, Dorea, Fusicatenibacter continued to significantly decrease in early and advanced CD patients, and Escherichia/Shigella and Proteus continued to significantly increase compared with healthy controls (P 2]. Some genera were significantly correlated with various clinical parameters, such as fecal calprotectin, erythrocyte sedimentation rate, C-reactive protein, gland reduce, goblet cells decreased, clinical symptoms (P

Although a growing body of research has recently shown how crucial inflammation and infection are to all major diseases, several of the medications currently available on the market have various unfavourable side effects, necessitating the development of alternative therapeutic choices. Researchers are increasingly interested in alternative medications or active components derived from natural sources. Naringenin is a commonly consumed flavonoid found in many plants, and since it was discovered to have nutritional benefits, it has been utilized to treat inflammation and infections caused by particular bacteria or viruses. However, the absence of adequate clinical data and naringenin's poor solubility and stability severely restrict its usage as a medicinal agent. In this article, we discuss naringenin’s effects and mechanisms of action on autoimmune-induced inflammation, bacterial infections, and viral infections based on recent research. We also present a few suggestions for enhancing naringenin's solubility, stability, and bioavailability. This paper emphasizes the potential use of naringenin as an anti-inflammatory and anti-infective agent and the next prophylactic substance for the treatment of various inflammatory and infectious diseases, even though some mechanisms of action are still unclear, and offers some theoretical support for its clinical application.

Introduction: Cross-court and the long-line topspin forehand is the common and basic stroke skill in table tennis. The purpose of this study was to investigate the differences in lumbar and pelvis movements between cross-court and long-line topspin forehand strokes in table tennis based on musculoskeletal demands using OpenSim.Materials and Methods: The eight-camera Vicon system and Kistler force platform were used to measure kinematics and kinetics in the lumbar and pelvis movement of sixteen participants (Weight: 69.89 ± 1.58 kg; Height: 1.73 ± 0.03 m; Age: 22.89 ± 2.03 years; BMI: 23.45 ± 0.69 kg/m2; Experience: 8.33 ± 0.71 years) during cross-court and long-line topspin forehand play. The data was imputed into OpenSim providing the establishment of the Giat2392 musculoskeletal model for simulation. One-dimensional statistical parametric mapping and independent samples t-test was performed in MATLAB and SPSS to analyze the kinematics and kinetics.Results: The results show that the range of motion, peak moment, and maximum angle of the lumbar and pelvis movement in cross-court play were significantly higher than in the long-line stroke play. The moment of long-line in the sagittal and frontal plane was significantly higher than cross-court play in the early stroke phase.Conclusion: The lumbar and pelvis embody greater weight transfer and greater energy production mechanisms when players performed cross-court compared to long-line topspin forehand. Beginners could enhance their motor control strategies in forehand topspin skills and master this skill more easily based on the results of this study.

(1) Background: The effect of Dendrobium nobile Lindl. (D. nobile) on hyperglycemic syndrome has only been recently known for several years. Materials of D. nobile were always collected from the plants cultivated in various growth ages. However, regarding the efficacy of D. nobile on hyperglycemic syndrome, it was still unknown as to which cultivation age would be selected. On the other hand, with the lack of quality markers, it is difficult to control the quality of D. nobile to treat hyperglycemic syndrome. (2) Methods: The effects of D. nobile cultivated at year 1 and year 3 were checked on alloxan-induced diabetic mice while their body weight, diet, water intake, and urinary output were monitored. Moreover, levels of glycosylated serum protein and insulin were measured using Elisa kits. The constituents of D. nobile were identified and analyzed by using UPLC-Q/trap. Quality markers were screened out by integrating the data from UPLC-Q/trap into a network pharmacology model. (3) Results: The D. nobile cultivated at both year 1 and year 3 showed a significant effect on hyperglycemic syndrome at the high dosage level; however, regarding the significant level, D. nobile from year 1 showed the better effect. In D. nobile, most of the metabolites were identified as alkaloids and sesquiterpene glycosides. Alkaloids, represented by dendrobine, were enriched in D. nobile from year 1, while sesquiterpene glycosides were enriched in D. nobile from year 3. Twenty one metabolites were differentially expressed between D. nobile from year 1 and year 3. The aforementioned 21 metabolites were enriched to 34 therapeutic targets directly related to diabetes. (4) Conclusions: Regarding the therapy for hyperglycemic syndrome, D. nobile cultivated at year 1 was more recommended than that at year 3. Alkaloids were recommended to be used as markers to control the quality of D. nobile for hyperglycemic syndrome treatment.

Abstract Background The development of diabetes vascular calcification (VC) is tightly associated with the inhibition of vascular smooth muscle cell (VSMC) autophagy. Previously, our team found that miR-32-5p (miR-32) promotes macrophage activation, and miR-32 is expressed at higher level in the plasma of patients with coronary calcification. However, whether miR-32 mediates the function of macrophages in type 2 diabetes (T2D) VC is still unclear. Methods Wild-type (WT) and miR-32−/− mice were used in this study. qRT-PCR and western blotting were used to analyze gene expression. Flow cytometry was used to analyze the influence of glucose concentration on macrophage polarization. Nanoparticle tracking analysis (NTA), transmission electron microscopy, and confocal microscopy were used to identify macrophage extracellular vehicles (EVs). Immunofluorescence, in situ hybridization (ISH), immunohistochemistry, and alizarin red staining were used to analyze the influence of macrophage EVs on autophagy and calcification of the aorta of miR-32−/− mice. A luciferase assay was used to analyze the effect of miR-32 on myocyte enhancer factor 2D (Mef2d) expression. Co-IP combined with mass spectrometry (MS) and transcriptome sequencing was used to analyze the signalling pathway by which Mef2d acts in VSMC autophagy. Results We found that high glucose conditions upregulate miR-32 expression in macrophages and their EVs. Importantly, macrophages and their EVs promote VSMC osteogenic differentiation and upregulate miR-32 expression in VSMCs. Moreover, miR-32 mimics transfection promoted osteogenic differentiation and inhibited autophagy in VSMCs. In vitro and in vivo experiments showed that Mef2d is the key target gene of miR-32 that inhibits VSMC autophagy. Furthermore, MS and transcriptome sequencing found that cGMP-PKG is an important signalling pathway by which Mef2d regulates VSMC autophagy. In addition, after T2D miR-32−/− mice were injected with macrophage EVs via the caudal vein, miR-32 was detected in aortic VSMCs of miR-32−/− mice. Moreover, autophagy was significantly inhibited, and calcification was significantly enhanced in aorta cells. Conclusions These results reveal that EVs are the key pathway by which macrophages promote T2D VC, and that EVs miR-32 is a key cause of autophagy inhibition in VSMCs.

BackgroundNeuroimaging studies have identified aberrant activity patterns in multiple brain regions in functional dyspepsia (FD) patients. However, due to the differences in study design, these previous findings are inconsistent, and the underlying neuropathological characteristics of FD remain unclear.MethodsEight databases were systematically searched for literature from inception to October 2022 with the keywords “Functional dyspepsia” and “Neuroimaging.” Thereafter, the anisotropic effect size signed the differential mapping (AES-SDM) approach that was applied to meta-analyze the aberrant brain activity pattern of FD patients.ResultsA total of 11 articles with 260 FD patients and 202 healthy controls (HCs) were included. The AES-SDM meta-analysis demonstrated that FD patients manifested increased activity in the bilateral insula, left anterior cingulate gyrus, bilateral thalamus, right precentral gyrus, left supplementary motor area, right putamen, and left rectus gyrus and decreased functional activity in the right cerebellum compared to the HCs. Sensitivity analysis showed that all these above regions were highly reproducible, and no significant publication bias was detected.ConclusionThe current study demonstrated that FD patients had significantly abnormal activity patterns in several brain regions involved in visceral sensation perception, pain modulation, and emotion regulation, which provided an integrated insight into the neuropathological characteristics of FD.

Dendrobium nobile is a well-known famous traditional Chinese medicine and nourishing food in China and/or other subtropical areas. Alkaloids represented by dendrobine were considered to be the main active components in D. nobile, especially dendrobine was used as the quality marker of D. nobile in the Chinese Pharmacopoeia. Previous literature reported that the content of dendrobine in D. nobile would decrease with increasing growth years. In the present study, we analyzed the secondary metabolites in the stems of 1-year and 3-year grown D. nobile by UPLC-Q/TOF-MS. The results showed that the content of several alkaloid components, except dendrobine, decreased with the increase of growth years. Interestingly, the sesquiterpene glycosides components showed opposite accumulation patterns compared to alkaloids in D. nobile. Based on the biosynthetic pathway of dendrobine, we hypothesized that the decrease in alkaloids contents was due to the glycosylation of sesquiterpenes, the synthetic precursor compounds of alkaloids in D. nobile. The plausibility of this hypothesis was confirmed in the next transcriptome sequencing combined with RT-PCR and molecular docking. The results suggested that UDP-glycosyltransferases play a crucial role in regulating the accumulation of alkaloids and sesquiterpene glycosides in D. nobile. And it is likely that multiple UDP-glycosyltransferases act together in the glycosylation of sesquiterpenes in D. nobile. These results will provide the important information for the good agricultural practice (GAP) production of D. nobile.

IntroductionAltitude, as a comprehensive ecological factor, regulates the growth and development of plants and microbial distribution. Dendrobium nobile (D. nobile) planted in habitats at different elevations in Chishui city, also shows metabolic differences and endophytes diversity. What is the triangular relationship between altitude, endophytes, and metabolites?MethodsIn this study, the diversity and species of endophytic fungi were tested by ITS sequencing and metabolic differences in plants were tested by UPLC–ESI–MS/MS. Elevation regulated the colonization of plant endophytic fungal species and fatty acid metabolites in D. nobile.ResultsThe results indicate that and high altitude was better for the accumulation of fatty acid metabolites. Therefore, the high-altitude characteristic endophytic floras were screened, and the correlation with fatty acid metabolites of plants was built. The colonization of T. rubrigenum, P. Incertae sedis unclassified, Phoma. cf. nebulosa JZG 2008 and Basidiomycota unclassified showed a significantly positive correlation with fatty acid metabolites, especially 18-carbon-chain fatty acids, such as (6Z,9Z,12Z)-octadeca-6,9,12-trienoic acid, 3,7,11,15-tetramethyl-12-oxohexadeca-2,4-dienoic acid and Octadec-9-en-12-ynoic acid. What is more fascinating is these fatty acids are the essential substrates of plant hormones.DiscussionConsequently, it was speculated that the D. nobile- colonizing endophytic fungi stimulated or upregulated the synthesis of fatty acid metabolites and even some plant hormones, thus affecting the metabolism and development of D. nobile.

Gypenosides (GP), extracted from the traditional Chinese herb Gynostemma pentaphyllum (Thunb.) Makino, have been used to treat metabolic disorders, including lipid metabolism disorders and diabetes. Although recent studies have confirmed their beneficial effects in nonalcoholic fatty liver disease (NAFLD), the underlying therapeutic mechanism remains unclear. In this study, we explored the protective mechanism of GP against NAFLD in mice and provided new insights into the prevention and treatment of NAFLD. Male C57BL6/J mice were divided into three experimental groups: normal diet, high-fat diet (HFD), and GP groups. The mice were fed an HFD for 16 weeks to establish an NAFLD model and then treated with GP for 22 weeks. The transcriptome and proteome of the mice livers were profiled using RNA sequencing and high-resolution mass spectrometry, respectively. The results showed that GP decreased serum lipid levels, liver index, and liver fat accumulation in mice. Principal component and heatmap analyses indicated that GP significantly modulated the changes in the expression of genes associated with HFD-induced NAFLD. The 164 differentially expressed genes recovered using GP were enriched in fatty acid and steroid metabolism pathways. Further results showed that GP reduced fatty acid synthesis by downregulating the expression of Srebf1, Fasn, Acss2, Acly, Acaca, Fads1, and Elovl6; modulated glycerolipid metabolism by inducing the expression of Mgll; promoted fatty acid transportation and degradation by inducing the expression of Slc27a1, Cpt1a, and Ehhadh; and reduced hepatic cholesterol synthesis by downregulating the expression of Tm7sf2, Ebp, Sc5d, Lss, Fdft1, Cyp51, Nsdhl, Pmvk, Mvd, Fdps, and Dhcr7. The proteomic data further indicated that GP decreased the protein expression levels of ACACA, ACLY, ACSS2, TM7SF2, EBP, FDFT1, NSDHL, PMVK, MVD, FDPS, and DHCR7 and increased those of MGLL, SLC27A1, and EHHADH. In conclusion, GP can regulate the key genes involved in hepatic lipid metabolism in NAFLD mice, providing initial evidence for the mechanisms underlying the therapeutic effect of GP in NAFLD.

Introduction: Alisol B 23-acetate (AB23A), a major bioactive constituent in the Chinese herb Zexie (Rhizoma Alismatis), has been found with multiple pharmacological activities. AB23A can be readily hydrolyzed to alisol B in mammals, but the hydrolytic pathways of AB23A in humans and the key enzymes responsible for AB23A hydrolysis are still unrevealed. This study aims to reveal the metabolic organs and the crucial enzymes responsible for AB23A hydrolysis in human biological systems, as well as to decipher the impact of AB23A hydrolysis on its biological effects.Methods: The hydrolytic pathways of AB23A in human plasma and tissue preparations were carefully investigated by using Q-Exactive quadrupole-Orbitrap mass spectrometer and LC-UV, while the key enzymes responsible for AB23A hydrolysis were studied via performing a set of assays including reaction phenotyping assays, chemical inhibition assays, and enzyme kinetics analyses. Finally, the agonist effects of both AB23A and its hydrolytic metabolite(s) on FXR were tested at the cellular level.Results: AB23A could be readily hydrolyzed to form alisol B in human plasma, intestinal and hepatic preparations, while human butyrylcholinesterase (hBchE) and human carboxylesterases played key roles in AB23A hydrolysis in human plasma and tissue preparations, respectively. It was also found that human serum albumin (hSA) could catalyze AB23A hydrolysis, while multiple lysine residues of hSA were covalently modified by AB23A, suggesting that hSA catalyzed AB23A hydrolysis via its pseudo-esterase activity. Biological tests revealed that both AB23A and alisol B exhibited similar FXR agonist effects, indicating AB23A hydrolysis did not affect its FXR agonist effect.Discussion: This study deciphers the hydrolytic pathways of AB23A in human biological systems, which is very helpful for deep understanding of the metabolic rates of AB23A in humans, and useful for developing novel prodrugs of alisol B with desirable pharmacokinetic behaviors.

Dolutegravir, cabotegravir, and bictegravir are three integrase inhibitors, which were used for HIV-1 in the clinic. In this paper, a continuous three-step synthetic strategy was developed to prepare dolutegravir, cabotegravir, and bictegravir in a better yield, compared to the initial step-by-step procedure. Different solvents, temperature, and times were optimized. In the course of industrial production of active pharmaceutical ingredient (API), this three-step synthetic protocol has several advantages, including low cost, time-saving, and better yield. This process was successfully scaled up to tens of grams.

The retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) play a crucial role as pattern-recognition receptors within the innate immune system. These receptors, present in various cell and tissue types, serve as essential sensors for viral infections, enhancing the immune system’s capacity to combat infections through the induction of type I interferons (IFN-I) and inflammatory cytokines. RLRs are involved in a variety of physiological and pathological processes, including viral infections, autoimmune disorders, and cancer. An increasing body of research has examined the possibility of RLRs or microRNAs as therapeutic targets for antiviral infections and malignancies, despite the fact that few studies have focused on the regulatory function of microRNAs on RLR signaling. Consequently, our main emphasis in this review is on elucidating the role of microRNAs in modulating the signaling pathways of RLRs in the context of cancer and viral infections. The aim is to establish a robust knowledge base that can serve as a basis for future comprehensive investigations into the interplay between microRNAs and RIG-I, while also facilitating the advancement of therapeutic drug development.

ABSTRACTAn unusual NBS promoted cascade reaction of β-anhydroicaritine and alcohols was successfully developed to prepare chromane-3,4-dione 3 in a moderate yield. A mechanism was also put forward to explain this reaction. These chromane-3,4-dione derivatives showed a potent cytotoxicity against HepG2 and MCF-7 cell lines, which were expected to be a potential lead candidate for the treatment of liver cancer and breast cancer.

BackgroundDrug metabolism genes are involved in the in vivo metabolic processing of drugs. In previous research, we found that a high-fat diet affected the transcript levels of mouse hepatic genes responsible for drug metabolism.AimsOur research intends to discover the drug metabolism genes that are dysregulated at the transcriptome level in nonalcoholic fatty liver disease (NAFLD).MethodsWe analyzed the transcriptome for drug metabolism genes of 35 human liver tissues obtained during laparoscopic cholecystectomy. Additionally, we imported transcriptome data from mice fed a high-fat diet in previous research and two open-access Gene Expression Omnibus (GEO) datasets (GSE63067 and GSE89632). Then, using quantitative real-time polymerase chain reaction (qRT-PCR), we cross-linked the differentially expressed genes (DEGs) in clinical and animal samples and validated the common genes.ResultsIn this study, we identified 35 DEGs, of which 33 were up-regulated and two were down-regulated. Moreover, we found 71 DEGs (39 up- and 32 down-regulated), 276 DEGs (157 up- and 119 down-regulated), and 158 DEGs (117 up- and 41 down-regulated) in the GSE63067, GSE89632, and high-fat diet mice, respectively. Of the 35 DEGs, nine co-regulated DEGs were found in the Venn diagram (CYP20A1, CYP2U1, SLC9A6, SLC26A6, SLC31A1, SLC46A1, SLC46A3, SULT1B1, and UGT2A3).ConclusionNine significant drug metabolism genes were identified in NAFLD. Future research should investigate the impacts of these genes on drug dose adjustment in patients with NAFLD.Clinical Trial Registrationhttp://www.chictr.org.cn, identifier ChiCTR2100041714.

Understanding the targets and interactions of long non-coding RNAs (lncRNAs) related to the retinoic acid-inducible gene-I (RIG-I) signaling pathway is essential for developing interventions, which would enable directing the host inflammatory response regulation toward protective immunity. In the RIG-I signaling pathway, lncRNAs are involved in the important processes of ubiquitination, phosphorylation, and glycolysis, thus promoting the transport of the interferon regulatory factors 3 and 7 (IRF3 and IRF7) and the nuclear factor kappa B (NF-κB) into the nucleus, and activating recruitment of type I interferons (IFN-I) and inflammatory factors to the antiviral action site. In addition, the RIG-I signaling pathway has recently been reported to contain the targets of coronavirus disease-19 (COVID-19)-related lncRNAs. The molecules in the RIG-I signaling pathway are directly regulated by the lncRNA–microRNAs (miRNAs)–messenger RNA (mRNA) axis. Therefore, targeting this axis has become a novel strategy for the diagnosis and treatment of cancer. In this paper, the studies on the regulation of the RIG-I signaling pathway by lncRNAs during viral infections and cancer are comprehensively analyzed. The aim is to provide a solid foundation of information for conducting further detailed studies on lncRNAs and RIG-I in the future and also contribute to clinical drug development.

Dendrobium nobile, an epiphytic plant, is a traditional medicinal herb with abundant endophytes. It is unclear whether the variation in the diversity and abundance of endophytes could stimulate the biosynthesis of medicinal compounds in the plant. In this study, we collected fresh stems of D. nobile from four habitats for investigating the fungal community structure, dendrobine content, and environment factors and their correlations. The results indicated no significant difference in endophytic fungal diversity among the habitats; however, different dominant or special endophytic genera were observed in the hosts from different habitats. The altitude was observed to be positively related to the dendrobine content, as the stems collected from the altitude of 692 m exhibited the highest level of dendrobine. Furthermore, the relative abundance of Toxicocladosporium was found to be positively correlated with the altitude and dendrobine content. The epiphytic matrix exhibited a significant negative correlation with the relative abundance of the endophytic fungus Gibberella but did not exhibit any significant correlation with the dendrobine content. The results indicated that the abundance of endophytes in D. nobile was affected by the altitude and epiphytic matrix and that high Toxicocladosporium abundance and high altitude were conducive to dendrobine production.

Bile acids are acknowledged as signaling molecules involved in metabolic syndrome. The Takeda G protein-coupled receptor 5 (TGR5) functions as a significant bile acid receptor. The accumulated evidence suggests that TGR5 involves lipid homeostasis, glucose metabolism, and inflammation regulation. In line with this, recent preclinical studies also demonstrate that TGR5 plays a significant role in the generation and progression of metabolic syndrome, encompassing type 2 diabetes mellitus, obesity, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). In this review, we discuss the role of TGR5 in metabolic syndrome, illustrating the underlying mechanisms and therapeutic targets.

Considering the influence of fabric on the critical state of sandy soil, an anisotropic hypoplastic constitutive model is developed by introducing the anisotropic critical state line that takes into account the rotation of the principal stress axes. With the introduction of new anisotropic state variables defined by the joint invariants of the stress tensor and fabric tensor, the critical state equation of sandy soil is established to describe the effects of three factors, namely, anisotropic parameters, stress states, and the relationship between principal stresses and fabric directions, on the critical state. The mechanical response of sandy soil under different deposition angles can be described by considering the rotation of principal stresses relative to the fabric. The application range of Wu et al.’s isotropic hypoplastic model (2017) is extended by incorporating the effect of principal stress rotation on the stress–strain relationship of sandy soil. Based on a series of Toyoura sand plane strain tests, the effects of void ratio, confining pressure, and principal stress axis rotation angle on anisotropic strength and deformation characteristics are simulated under low confining pressure. Furthermore, a comparison with Wu’s transversely isotropic hypoplastic model (1998) is made regarding their simulation performances. The proposed model exhibits a balanced performance when simulating the variation of anisotropy in both strength and deformation with respect to the rotation angle, without being overestimated within a certain range of rotation angles. The prediction results demonstrate, to a certain degree, the validity and effectiveness of the proposed model.

Endophytes is a kind of microorganism resource with great potential medicinal value. The interactions between endophytes and host not only promote the growth and development of each other but also drive the biosynthesis of many new medicinal active substances. In this review, we summarized recent reports related to the interactions between endophytes and hosts, mainly regarding the research progress of endophytes affecting the growth and development of host plants, physiological stress and the synthesis of new compounds. Then, we also discussed the positive effects of multiomics analysis on the interactions between endophytes and their hosts, as well as the application and development prospects of metabolites synthesized by symbiotic interactions. This review may provide a reference for the further development and utilization of endophytes and the study of their interactions with their hosts.

Osteoarthritis and rheumatoid arthritis are the most ubiquitous joint disorders which cause tremendous loss of life quality and impose an economic burden on society. At present, the treatment options for these two diseases comprise non-operative and surgical treatments, amongst those total knee arthroplasties (TKA). Various studies have recognized smoking as a significant risk factor for postoperative complications. Therefore, the purpose of this study was to examine the impact of smoking on the incidence and postoperative complications after a total knee arthroplasty by a systematic review and meta-analysis. The research was performed using PUBMED, Cochrane Library and EMBASE, extracting data from thirteen suitable studies and incorporating 2,109,482 patients. Cohort studies evaluating the impact of smoking on TKA with sufficient data were included for the study, and cohort studies without a proper control group and complete data were excluded. A fixed-effects or random-effects model was used to measure the pooled risk ratio (RR) or hazard ratio (HR) with 95% confidence interval (CI). Compared to non-smokers, smokers had a significantly lower incidence of TKA (p

Dendrobium officinale Kimura et Migo is a famous plant with a high medicinal value which has been recorded in the Chinese Pharmacopoeia (2020 Edition). The medicinal properties of D. officinale are based on its chemical composition. However, there are no reports on how different cultivation methods affect its chemical composition. In order to reveal this issue, samples of the D. officinale were collected in this study through tree epiphytic cultivation, stone epiphytic cultivation, and greenhouse cultivation. Polysaccharides were determined by phenol sulfuric acid method and secondary metabolites were detected by the UPLC-MS technique. In addition, with regards to metabolomics, we used multivariate analyses including principal component analysis (PCA) and orthogonal partial least squares analysis (OPLS-DA) to screen for differential metabolites which met the conditions of variable importance projection values >1, fold change >4, and p < 0.05. The differential metabolites were taken further for metabolic pathway enrichment analysis, which was based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and validated by antioxidant activity. Comparing the three groups of samples according to the standards of the ChP (2020 edition), the results showed that the polysaccharide content of the samples from stony epiphytic cultivation and greenhouse cultivation was significantly higher than that of the samples from live tree epiphytic cultivation. Metabolomic analysis revealed that there were 185 differential metabolites among the 3 cultivation methods, with 99 of the differential metabolites being highest in the stone epiphytic cultivation. The results of the metabolic pathway enrichment analysis showed that the different cultivation strategies mainly effected four carbohydrate metabolic pathways, five secondary metabolite synthesis pathways, six amino acid metabolic pathways, one nucleotide metabolism pathway, three cofactor and vitamin metabolism pathways, and one translation pathway in genetic information processing. Furthermore, D. officinale from stone epiphytic cultivation which had the best antioxidant activity was implicated in differential metabolite production. This study revealed the effects of different cultivation methods on the chemical composition of D. officinale and also provided a reference for establishing the quality control standards to aid its development and utilization.

This paper presents a compact dual-band and dual-polarized millimeter-wave patch antenna array with satisfactory performance on element mutual coupling and beam scanning capabilities. Using capacitive feed technique and stacked configuration with extra parasitic strips, the proposed antenna array is able to achieve a wide operating bandwidth in both the low- and high-bands. In order to reduce the array’s footprint, and to enhance the beam scanning performance in both bands, the element spacing is shrunk to less than 0.36 wavelength at 26 GHz. To improve the isolation between array elements due to their small spacings, two effective decoupling approaches are adopted, which result in a 6-dB isolation enhancement. The overall size of the proposed antenna array is only 18.2 mm $\times4.1$ mm $\times1.07$ mm, which is smaller than some industrial mm-Wave antenna modules released recently. Our simulation shows that the antenna array can fully cover the 5G NR bands of n258~n261 simultaneously. The four-element array provides ±60° and ±45° beam scanning performance in the low- and high-bands, respectively. The experimental data of reflection coefficient, mutual coupling, and radiation patterns confirm with the simulated results, rendering the proposed array to be a good candidate for 5G mm-Wave communications.

In this paper, a broadband double-ridge horn antenna (DRHA) covering 5G millimeter-wave (mm-wave) band is proposed, which maintains stable radiation pattern and gain in the entire band. By redesigning the transition between coaxial and waveguide, there is no splitting or deterioration in the axis pattern throughout the entire 18–54 GHz frequency band, and the VSWRs are all below 2. Meanwhile, by replacing the H-Side wall of the antenna with metal grid, the variation on 3 dB beamwidth of the radiation pattern also become more stable against frequencies. In order to fabricate the prototype successfully, the method of block processing and assembly is adopted, which can ensure high precision machining and make the assembly simple and easy to operate. Prototype measurement results show that the VSWR of the antenna is in well agreement with the simulation ones, while the gain is stable as well as no pattern splitting in the entire frequency band can be observed. It will find potential applications in 5G mm-wave frequency band, especially in the field of antenna measurement system as a standard calibration antenna or a probe antenna.

In this paper, an effective method for developing a multi-feed multiple-input multiple-output (MIMO) antenna system using the metal rims of a mobile phone without any structural interruption on the long edge frames is proposed. Instead of traditionally designing MIMO antennas with multiple similar antenna structures on the mobile phone frame or its ground plane, the MIMO antennas in this work are realized by reasonably constructing feeding points and grounding points on the entire edge frame. The MIMO antenna system established by such multi-feed technique is capable to achieve much simpler structural configuration, excellent isolation and matching performance while multiple antennas are connected. A planar eight-port MIMO antenna system operating in the 5G frequency band of 3.4~3.6 GHz is investigated initially, and subsequently applied to the curved metal-rims which comply with the industry design of a modern flagship mobile phone. The prototypes are fabricated and measured, evaluation results show that isolations among all ports are better than 15 dB with reflection coefficients below −10 dB within the band of 3.4~3.7 GHz and −6 dB within the band of 3.3~3.8 GHz. In addition, more than 57% total efficiency and envelope correlation coefficient (ECC) of less than 0.3 are obtained. The satisfactory performance reveals the proposed design of multi-feed MIMO antennas can be a promising candidate for 5G metal-rimmed mobile phone applications.

The cultivation medium of Dendrobium nobile has an effect on the contents of its main medicinal components, but the specific mechanism is still unclear. In this study, the callus, seedlings, rhizomes, and leaves of D. nobile were sequenced for the PacBio SMRT. The 2-year-old stems were selected for the Illumina sequencing and metabolome sequencing to analyze the genetic mechanism of metabolic differences under different epiphytic patterns. As a result, a total of 387 differential genes were obtained, corresponding to 66 differential metabolites. Different epiphytic patterns can induce a series of metabolic changes at the metabolome and transcriptome levels of D. nobile, including flavonoid metabolism, purine metabolism, terpenoid backbone biosynthesis, amino acid metabolism, and alpha-linolenic acid metabolic, and related regulatory genes include ALDH2B7, ADC, EPSPS-1, SHKA, DHAPS-1, GES, ACS1, SAHH, ACS2, CHLP, LOX2, LOX2.3, and CYP74B2. The results showed that the genetic mechanism of D. nobile under various epiphytic patterns was different. In theory, the content of metabolites under the epiphytic patterns of Danxia stone is higher, which is more suitable for field cultivation.

Abstract Background High fat diet impact transcription of hepatic genes responsible for drug metabolism and pharmacokinetics. Until now, researches just focused on a couple specific genes without a global profile showing. Age-dependent manner was also not noted well. This study aims to investigate the high fat diet effect on transcriptome of drug metabolism and pharmacokinetic system in mouse livers and show the age-dependent evidence. Methods C57BL/6 male mice were used in this experiment. High fat diet was used to treat mice for 16 and 38 weeks. Serum total cholesterol, low density lipoprotein cholesterol, aspartate transaminase, and alanine transaminaselevels were measured. Meanwhile, Histology, RNA-Seq, RT-PCR analysis and fourteen major hepatic bile acids quantification were performed for the liver tissues. Data was mined at levels of genes, drug metabolism and pharmacokinetic sysem, and genome wide. Results Treatment with high fat diet for 38 weeks significantly increased levels of serum lipids as well as aspartate transaminase, and alanine transaminase. Meanwhile, lipid accumulation in livers was observed. At week 38 of the experiment, the profile of 612 genes involved in drug metabolism and pharmacokinetics was significantly changed, indicated by a heatmap visulization and a principal component analysis. In total 210 genes were significantly regulated. Cyp3a11, Cyp4a10, and Cyp4a14 were down-regulated by 10–35 folds, while these three genes also were highly expressed in the liver. High fat diet regulated 11% of genome-wide gene while 30% of genes involved in the hepatic drug metabolism and pharmacokinetic system. Genes, including Adh4, Aldh1b1, Cyp3a11, Cyp4a10, Cyp8b1, Fmo2, Gsta3, Nat8f1, Slc22a7, Slco1a4, Sult5a1, and Ugt1a9, were regulated by high fat diet as an aging-dependent manner. Bile acids homeostasis, in which many genes related to metabolism and transportation were enriched, was also changed by high fat diet with an aging-dependet manner. Expression of genes in drug metabolism and disposition system significantly correlated to serum lipid profiles, and frequently correlated with each other. Conclusions High fat diet changed the global transcription profile of hepatic drug metabolism and pharmacokinetic system with a age-dependent manner.

This article presents a miniaturized wide-angle scanning phased array for fifth-generation (5G) application. A subarray of two closely packed patch antennas on electromagnetic bandgap structure (EBG) ground with the operating bandwidth of 26–29 GHz is used as the basic module of the linear array, which contains four equally spaced subarrays. The existence of the EBG ground enables the array to be compact in size (3.2 × 0.6 × 0.12λL3), yet the mutual coupling between each element can reach to more than 22 dB within the whole band of interest. The EBG structures also contribute to the wide element radiation pattern of the aperiodic array and consequently the wide scanning angle performance of the array. The range of the main beam scan with EBG structure can reach from −70° to 70° with more than 6 dB side lobe levels (SLLs) at 26.5 GHz with 3 dBi scanning gain loss. This proposed method enabling the array to be compact and wide in scanning angle is very attractive for 5G mobile terminal applications.