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Palladium-catalyzed cross-coupling of ortho-alkenyl bromobenzenes and α-aryl-α-diazoesters was realized. The reactions proceeded in moderate to excellent yields with broad substrate scope, providing a straightforward method for the synthesis of 1,1-disubstituted indenes. The reaction is thought to undergo a tandem alkenyl C–H activation/carbene insertion sequence, in which a C,C-pallada(II)cycle is the key intermediate.

Tuberculosis (TB) remains one of the deadliest infectious diseases in the world. Previous genome-wide association studies suggested that single-nucleotide polymorphisms (SNPs) in some genes could indicate the susceptibility to TB in some populations. Herein, we studied the association of SNPs in the immunity-related genes, i.e., ASAP1 and SP110 genes with the susceptibility to TB in a Mongolian population in China. A case–control study was performed with 197 TB patients and 217 healthy controls. Six SNPs in ASAP1 and six SNPs in SP110 were selected for genotyping test by second-generation sequencing technique. A SNP in SP110 gene (rs722555) was identified to be associated with susceptibility to TB in the Mongolian population ( p < 0.05 ). The T allele of rs722555 in SP110 gene was associated with a 36% increase of risk at TB (OR 1.36, 95% CI 1.03–1.81), and the CT+TT genotype of rs722555 was associated with a 74% increase of risk at TB (OR 1.74, 95% CI 1.16–2.60) in the dominant genetic model. None of SNPs in ASAP1 gene tested in this study were significantly associated with TB susceptibility, while some individuals with SNPs (rs10956514, rs4733781, rs2033059, rs12680942, rs1017281, rs1469288, and rs17285138) in the ASAP1 gene tended to have a reduced risk at TB. In conclusion, this study suggested that the rs722555 SNP in SP110 gene might be a risk factor for TB in a Mongolian population.

BACKGROUND: Bladder cancer (BCa) is one of the most prevalent malignancies and more common in men. An aberrantly expressed long noncoding RNA (lncRNA) hepatocellular carcinoma up-regulated EZH2-associated lncRNA (HEIH) has been reported to be implicated in the progression of many cancers, but its role in BCa remains little known. Our study intended to uncover whether and how HEIH regulates BCa progression. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (RT-qPCR) was adopted to determine HEIH expression in BCa cell lines. Functional experiments were performed to examine the effects of HEIH on BCa cell proliferation, apoptosis, migration, invasion and stemness. Bioinformatics analysis and mechanism experiments were conducted to investigate the regulatory relationship between HEIH and related molecules in BCa. RESULTS: HEIH expression was observed to be significantly increased in BCa cell lines. HEIH depletion significantly hindered BCa cell proliferation, migration and invasion. Besides, HEIH up-regulated MYC proto-oncogene, and bHLH transcription factor (c-Myc) expression to promote BCa cell stemness. Moreover, HEIH served as a sponge for miR-4500 to modulate insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) expression, thereby stabilizing c-Myc mRNA level. CONCLUSION: Our study demonstrated a positive feedback loop of HEIH/miR-4500/IGF2BP1/c-Myc in BCa progression, offering a novel insight into a possible BCa therapy.

Hepatic ischemia-reperfusion (IR) injury is a clinically significant process that frequently occurs in liver transplantation, partial hepatectomy, and hemorrhagic shock. The aim of this study was to explore the effectiveness of luteolin in hepatic IR injury and the underlying mechanism. BALB/c mice were randomly divided into six groups, including normal controls (NC), luteolin (50 mg/kg), sham procedure, IR+25 mg/kg luteolin, and IR+50 mg/kg luteolin group. Serum and tissue samples were collected at 6 and 24 h after reperfusion to assay liver enzymes, inflammatory factors, expression of proteins associated with apoptosis and autophagy, and factors associated with the extracellular signal-regulated kinase/peroxisome proliferator-activated receptor alpha (ERK/PPARα) pathway. Luteolin preconditioning decreased hepatocyte injury caused by ischemia-reperfusion, downregulated inflammatory factors, and inhibited apoptosis and autophagy. Luteolin also inhibited ERK phosphorylation and activated PPARα.

The bioaccumulation of the neurotoxin methylmercury (MeHg) in rice is a significant concern due to its potential risk to humans. Thiols have been known to affect MeHg bioavailability in microorganisms, but how thiols influence MeHg accumulation in rice plants remains unknown. Here, we investigated effects of common low-molecular-weight thiols, including cysteine (Cys), glutathione (GSH), and penicillamine (PEN), on MeHg uptake and translocation by rice plants. Results show that rice roots can rapidly take up MeHg, and this process is influenced by the types and concentrations of thiols in the system. The presence of Cys facilitated MeHg uptake by roots and translocation to shoots, while GSH could only promote MeHg uptake, but not translocation, by roots. Conversely, PEN significantly inhibited MeHg uptake and translocation to shoots. Using labeled

Extended-spectrum beta-lactamase-producing Gram-negative bacteria are common in the community and hospitals. To monitor ESBLs mediated by the CTX-M genotype, we collected clinical ESBL pathogenic strains from a hospital in central China and observed a strain of Escherichia coli, namely Ec15103 carrying blaCTX–M–14, blaCTX–M–64 and blaTEM–1, isolated from the blood of a 7-day-old infant in 2015. Strain Ec15103 contains two drug resistance plasmids: pEc15103A, an IncFI-type plasmid that cannot be conjugatively transferred and carries the drug resistance genes blaTEM–1, aacC2, aadA5, sul1, mph(A), sul2, strAB, and tetA(A); and pEc15103B, an IncK2/Z-type plasmid that carries the conjugation transfer gene and blaCTX–M–14. In addition, blaCTX–M–64 is located on the chromosome of Ec15103, and it is the first report of pathogen with blaCTX–M–64 located on its chromosome (the search terms used “blaCTX-M-64” and “chromosome”). blaCTX–M–14 and blaCTX–M–64 are carried by ISEcp1-mediated transposon Tn6503a and Tn6502, respectively. The conjugation transfer ability of pEc15103B was significantly inhibited by zidovudine (AZT) and linoleic acid (LA) and that expression of blaCTX–M–14, blaCTX–M–64 and blaTEM–1 at the mRNA level did not change based on the concentration of cefotaxime or ampicillin. Co-occurrence of blaCTX–M–14 and blaCTX–M–64 in a single isolate will enhance the drug resistance of bacteria, and the presence of blaCTX–M–64 in the chromosome may make the resistance more maintain. This fact will facilitate its dissemination and persistence under different antimicrobial selection pressures. It is essential to prevent these strains from further spreading in a hospital environment.

10 páginas- 4 figuras.- referencias.- Additional supporting information can be found online in the Supporting Information section at the end of this article, Microbial residues contribute to the long-term stabilization of carbon in the entire soil profile, helping to regulate the climate of the planet; however, how sensitive these residues are to climatic seasonality remains virtually unknown, especially for deep soils across environmental gradients. Here, we investigated the changes of microbial residues along soil profiles (0–100 cm) from 44 typical ecosystems with a wide range of climates (~3100 km transects across China). Our results showed that microbial residues account for a larger portion of soil carbon in deeper (60–100 cm) vs. shallower (0–30 and 30–60 cm) soils. Moreover, we find that climate especially challenges the accumulation of microbial residues in deep soils, while soil properties and climate share their roles in controlling the residue accumulation in surface soils. Climatic seasonality, including positive correlations with summer precipitation and maximum monthly precipitation, as well as negative correlations with temperature annual range, are important factors explaining microbial residue accumulation in deep soils across China. In particular, summer precipitation is the key regulator of microbial-driven carbon stability in deep soils, which has 37.2% of relative independent effects on deep-soil microbial residue accumulation. Our work provides novel insights into the importance of climatic seasonality in driving the stabilization of microbial residues in deep soils, challenging the idea that deep soils as long-term carbon reservoirs can buffer climate change. © 2023 John Wiley & Sons Ltd., This research was supported by the National Natural Science Foundation of China (42207391, 32071595 and 42177022). M.D‐B. is also supported by a project from the Spanish Ministry of Science and Innovation (PID2020‐115813RA‐I00), and a project of the Fondo Europeo de Desarrollo Regional (FEDER) and the Consejería de Transformación Económica, Industria, Conocimiento y Universidades of the Junta de Andalucía (FEDER Andalucía 2014‐2020 Objetivo temático “01—Refuerzo de la investigación, el desarrollo tecnológico y la innovación”) associated with the research project P20_00879 (ANDABIOMA).

IntroductionThe objective of this study is to thoroughly analyze the detailed genomic characteristics of clinical strain 211703 of Aeromonas caviae, which co-carrying blaRSA-1 and blaNDM-1 genes. 211703 was isolated from the patient’s cerebrospinal fluid drainage sample in a Chinese tertiary hospital.MethodsCarbapenemase NDM was detected by the immunocolloidal gold technique. The MIC values were determined by VITEK2. The whole genome sequence of 211703 was analyzed using phylogenetics, genomic comparison, and extensive dissection.ResultsThis study revealed that 211703 only contained a single 4.78 Mb chromosome (61.8% GC content), and no plasmids were discovered in 211703. 15 different types of resistant genes were detected in the genome of 211703, including blaRSA-1 harbored on integrative and mobilizable element (IME) Tn7413a, and blaNDM-1 harbored on integrative and conjugative element (ICE). The ICE and IME were all carried on the chromosome of 211703 (c211703). Detailed comparison of related IMEs/ICEs showed that they shared similar conserved backbone regions, respectively. Comprehensive annotation revealed that blaRSA-1 was carried by the gene cassette of a novel integron In2148 on Tn7413a, and blaNDM-1 was captured by an insertion sequence ISCR14-like on the ICE of 211703. We speculated that mobile genetic elements (MGEs) such as ICE and IME facilitated the spread of resistance genes such as blaRSA-1 and blaNDM-1.DiscussionIn conclusion, this study provides an overall understanding of the genomic characterization of clinically isolated A. caviae 211703, and an in-depth discussion of multiple acquisition methods of drug resistance genes in Aeromonas. To the best of our knowledge, this is the first report of A. caviae carrying blaRSA-1 even both blaRSA-1 and blaNDM-1, and this is the first bacterium carrying blaRSA-1 isolated from the clinical setting.

Synthetic microorganisms capable of using one-carbon compounds, such as methanol, formic acid or carbon dioxide, are of increasing interest. In this study, we converted the yeasts of Pichia pastoris and Saccharomyces cerevisiae to both synthetic methylotroph and formatotroph, allowing them to grow on methanol and formic acid alone coupled with CO2 fixation through a synthetic C1-compound assimilation pathway (MFORG pathway). This pathway consists of a methanol-formic acid oxidation module and the reductive glycine pathway. We first assembled the MFORG pathway in P. pastoris using only native enzymes, followed by overexpression of genes in the reductive glycine pathway, blocking the native methanol assimilation pathway, and compartmentalizing the methanol oxidation module. These modifications successfully redesigned the native methylotrophic yeast P. pastoris to grow on both methanol and formic acid, where higher growth rate and yield on methanol was obtained compared to the wild-type strain. We then introduced the MFORG pathway from P. pastoris into the model yeast S. cerevisiae, establishing full synthetic methylotrophy and formatotrophy in this organism. The resulting strain was able to successfully grow on methanol or formic acid alone with consumption rates of 24 mg/L*h and 15.2 mg/L*h, respectively. The CO2 fixation ability of synthetic P. pastoris and S. cerevisiae through the MFORG pathway was confirmed by 13C-tracer analysis. Finally, production of 5-aminolevulinic acid and lactic acid with methanol as the sole carbon source was demonstrated using synthetic P. pastoris and S. cerevisiae, indicating the potential of yeasts as promising hosts for biochemical production from various one-carbon compounds.

Biochar amendment is one of the most promising agricultural approaches to tackle climate change by enhancing soil carbon (C) sequestration. Microbial-mediated decomposition processes are fundamental for the fate and persistence of sequestered C in soil, but the underlying mechanisms are uncertain. Here, we synthesise 923 observations regarding the effects of biochar addition (over periods ranging from several weeks to several years) on soil C-degrading enzyme activities from 130 articles across five continents worldwide. Our results showed that biochar addition increased soil ligninase activity targeting complex phenolic macromolecules by 7.1%, but suppressed cellulase activity degrading simpler polysaccharides by 8.3%. These shifts in enzyme activities explained the most variation of changes in soil C sequestration across a wide range of climatic, edaphic and experimental conditions, with biochar-induced shift in ligninase:cellulase ratio correlating negatively with soil C sequestration. Specifically, short-term (

Cardiac glycosides (CGs) are good candidates as drug leads in the treatment of cancer because of their structural diversities and potent biological activities.

A palladium catalyzed synthesis of tetrasubstituted allenes through a 1,4-palladium migration/carbene insertion/β-H elimination sequence has been developed.

An industrial process usually has multiple operating conditions or periods due to various factors such as the fluctuation of raw material quality, differences of worker levels, and changes of product specifications. Industrial data from different operating conditions or periods have different statistical characteristics, namely multimode behavior. In fact, multimode recognition of industrial processes is the first problem to develop effective intelligent manufacturing strategies for engineers. The clustering-based methods can help them characterize multimode behavior in historical databases and group them together with little detailed knowledge of the process. However, these methods are facing the challenges of massive high-dimensional industrial big data and unknown mode number. This study proposes a construction method of complex network to describe the potential relationship in industrial big data. The topological structure of complex network can be acquired by taking the correlation matrix of multi-variables as nodes and the similarity between correlation matrices as edges. On this basis, community detection technology is employed to reveal the aggregation behavior of nodes in network. It takes the maximum modularity as the optimization objective, and partitions each node into one community through greedy search algorithm, where a community denotes a mode of industrial process. Finally, case studies have demonstrated the proposed method has good performance and application prospects.

Design the adenosine phosphate hydrolysis (APH) pathway multienzyme cascade system for the biosynthesis of nicotinamide mononucleotide (NMN) in vitro.

PurposeThe high-quality development of the real estate industry is crucial to the transformation of China's economy. However, few studies apply the productivity to explore the development path of the real estate industry in China. To fill this gap, this study mainly investigates the total factor productivity (TFP) of the real estate industry of 30 sample provinces in mainland China from 2007 to 2016.Design/methodology/approachThe Malmquist index is applied to estimate the productivity (i.e. TFP) of the real estate industry, based on the data envelopment analysis (DEA). Then, the truncated tobit regression analysis explores the external influencing factors on the TFP of the real estate industry.FindingsThrough empirical analysis, it is found that the high-quality development of the real estate industry depends on the technological innovation by the real estate enterprises and the targeted policies by the provincial government. Moreover, the development of the real estate industry has a positive correlation with the growth of China's economy but a negative correlation with the development of other industries.Practical implicationsTFP mainly reveals the development status of the provincial real estate industry and identifies the driving force for exploring the high-quality development mode of the real estate sector. Furthermore, the fluctuation rule of TFP can be applied to predict the development trend of the real estate industry in the future.Originality/valueAs an application, this study measures the TFP of the Chinese real estate industry in different provinces and periods. The results have meaningful policy implications for policymakers regulating the real estate industry.

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in Scutellaria baicalensis Georgi with anticancer potential various cancer types; however, the effects of baicalein on bladder cancer and the underlying molecular mechanisms remain largely unknown. In the study, we investigated the effect of baicalin on bladder cancer cells 5637 and KU-19-19. As a result, we show baicalin exerted its anticancer activity by inducing apoptosis and cell death in bladder cancer cells. Subsequently, we for the first time demonstrate baicalin-induced ferroptotic cell death in vitro and in vivo, accompanied by reactive oxygen species (ROS) accumulation and intracellular chelate iron enrichment. The ferroptosis inhibitor deferoxamine but not necrostatin-1, chloroquine (CQ), N-acetyl-l-cysteine, l-glutathione reduced, or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK) rescued baicalin-induced cell death, indicating ferroptosis contributed to baicalin-induced cell death. Mechanistically, we show that ferritin heavy chain 1 (FTH1) was a key determinant for baicalin-induced ferroptosis. Overexpression of FTH1 abrogated the anticancer effects of baicalin in both 5637 and KU19-19 cells. Taken together, our data for the first time suggest that the natural product baicalin exerts its anticancer activity by inducing FTH1-dependent ferroptosis, which will hopefully provide a prospective compound for bladder cancer treatment., Graphical abstract Baicalin exerts its anticancer activity in bladder cancer by inducing ferritin heavy chain 1 (FTH1)-dependent ferroptosis, which will hopefully provide great therapeutic potential for bladder cancer treatment.Image 1

Carbapenem-resistant Klebsiella pneumoniae is one of the primary bacterial pathogens that pose a significant threat to global public health because of the lack of available therapeutic options. Phage therapy shows promise as a potential alternative to current antimicrobial chemotherapies. In this study, we isolated a new Siphoviridae phage vB_KpnS_SXFY507 against KPC-producing K. pneumoniae from hospital sewage. It had a short latent period of 20 min and a large burst size of 246 phages/cell. The host range of phage vB_KpnS_SXFY507 was relatively broad. It has a wide range of pH tolerance and high thermal stability. The genome of phage vB_KpnS_SXFY507 was 53,122 bp in length with a G + C content of 49.1%. A total of 81 open-reading frames (ORFs) and no virulence or antibiotic resistance related genes were involved in the phage vB_KpnS_SXFY507 genome. Phage vB_KpnS_SXFY507 showed significant antibacterial activity in vitro. The survival rate of Galleria mellonella larvae inoculated with K. pneumoniae SXFY507 was 20%. The survival rate of K. pneumonia-infected G. mellonella larvae was increased from 20 to 60% within 72 h upon treatment with phage vB_KpnS_SXFY507. In conclusion, these findings indicate that phage vB_KpnS_SXFY507 has the potential to be used as an antimicrobial agent for the control of K. pneumoniae.

Background Sorafenib resistance is a key impediment to successful treatment of patients with advanced hepatocellular carcinoma (HCC) and recent studies have reported reversal of drug resistance by targeting ferroptosis. The present study aimed to explore the association of fatty acid synthase (FASN) with sorafenib resistance via regulation of ferroptosis and provide a novel treatment strategy to overcome the sorafenib resistance of HCC patients. Methods Intracellular levels of lipid peroxides, glutathione, malondialdehyde, and Fe2+ were measured as indicators of ferroptosis status. Biological information analyses, immunofluorescence assays, western blot assays, and co-immunoprecipitation analyses were conducted to elucidate the functions of FASN in HCC. Both in vitro and in vivo studies were conducted to examine the antitumor effects of the combination of orlistat and sorafenib and CalcuSyn software was used to calculate the combination index. Results Solute carrier family 7 member 11 (SLC7A11) was found to play an important role in mediating sorafenib resistance. The up-regulation of FASN antagonize of SLC7A11-mediated ferroptosis and thereby promoted sorafenib resistance. Mechanistically, FASN enhanced sorafenib-induced ferroptosis resistance by binding to hypoxia-inducible factor 1-alpha (HIF1α), promoting HIF1α nuclear translocation, inhibiting ubiquitination and proteasomal degradation of HIF1α, and subsequently enhancing transcription of SLC7A11. Orlistat, an inhibitor of FASN, with sorafenib had significant synergistic antitumor effects and reversed sorafenib resistance both in vitro and in vivo. Conclusion Targeting the FASN/HIF1α/SLC7A11 pathway resensitized HCC cells to sorafenib. The combination of orlistat and sorafenib had superior synergistic antitumor effects in sorafenib-resistant HCC cells.

The present study examined potential association between the daily intake and serum levels of copper (Cu), selenium (Se) and zinc (Zn) and the risk of osteoarthritis (OA) and rheumatoid arthritis (RA) using data from the National Health and Nutrition Examination Survey (NHANES). Daily intake and serum concentrations of Cu, Zn and Se in 4200 adults from the 2011–2016 NHANES were examined and divided into normal, OA patients and RA patients. The level of serum Cu was higher in OA and RA than in non- arthritis, while the level of serum Se and Zn were no difference in the three group. Serum Se and Zn, but not Cu, concentrations were highly correlated with daily intake. Cu, Se and Zn intake was independently associated with increased risk of OA, but not with RA. And there was a trend for higher odds of OA among participants in the higher Cu, Se and Zn intake. Future large longitudinal studies are warranted to confirm these findings.

Background Itaconic acid, an unsaturated C5 dicarbonic acid, has significant market demand and prospects. It has numerous biological functions, such as anti-cancer, anti-inflammatory, and anti-oxidative in medicine, and is an essential renewable platform chemical in industry. However, the development of industrial itaconic acid production by Aspergillus terreus, the current standard production strain, is hampered by the unavoidable drawbacks of that species. Developing a highly efficient cell factory is essential for the sustainable and green production of itaconic acid. Results This study employed combinatorial engineering strategies to construct Escherichia coli cells to produce itaconic acid efficiently. Two essential genes (cis-aconitate decarboxylase (CAD) encoding gene cadA and aconitase (ACO) encoding gene acn) employed various genetic constructs and plasmid combinations to create 12 recombination E. coli strains to be screened. Among them, E. coli BL-CAC exhibited the highest titer with citrate as substrate, and the induction and reaction conditions were further systematically optimized. Subsequently, employing enzyme evolution to optimize rate-limiting enzyme CAD and synthesizing protein scaffolds to co-localize ACO and CAD were used to improve itaconic acid biosynthesis efficiency. Under the optimized reaction conditions combined with the feeding control strategy, itaconic acid titer reached 398.07 mM (51.79 g/L) of engineered E. coli BL-CAR470E-DS/A-CS cells as a catalyst with the highest specific production of 9.42 g/g(DCW) among heterologous hosts at 48 h. Conclusions The excellent catalytic performance per unit biomass shows the potential for high-efficiency production of itaconic acid and effective reduction of catalytic cell consumption. This study indicates that it is necessary to continuously explore engineering strategies to develop high-performance cell factories to break through the existing bottleneck and achieve the economical commercial production of itaconic acid.

Antimicrobial resistance has become a severe threat to global public health. According to statistics, nearly 700,000 people die from bacterial infections worldwide (J.

Humulus scanden, rich in flavonoids, is a traditional Chinese medicine. It is widely used in China to treat tuberculosis, dysentery and chronic colitis. In this study, Humulus scandens (H.S) was extracted in different solvents (water, n-butanol, acetic ether and chloroform) and the antioxidant, anti-inflammatory activities of extracts were investigated by four assays including DPPH, reducing power, xylene-induced mouse ear edema and cotton pellet-induced granuloma methods. And then, the acute oral toxicity of extracts and biochemical parameters such as superoxide dismutase (SOD) and catalase (CAT) in blood serum and edematous tissue of rats were also evaluated. Moreover, the active compounds were identified by LC-ESI-QTOF-MS-MS. Results showed that ethyl acetate and n-butanol extracts had the stronger antioxidant activities, while water extract appeared to be weakest among them. The anti-inflammatory test showed that the extract of n-butanol and chloroform had significant anti-inflammatory effects and could improve the activity of SOD and CAT in mice. In general, the site of n-butanol has a stronger antioxidant and anti-inflammatory activity, and 15 compounds were analyzed by LC/Q-TOF-MS/MS technology. The present study confirms the ethnobotanical use of H.S extracts as natural antioxidant, anti-inflammatory, and the composition of the active compound was preliminarily identified.

This is the first report of extensively drug-resistant C. portucalensis harboring both bla KPC-2 and bla NDM-1 . This study will not only extend the understanding of the structural dissection of plasmids and chromosomes carried in C. portucalensis , but also expand knowledge of the genetic environment of the bla KPC-2 and bla NDM-1 genes. bla KPC-2 and bla NDM-1 genes have been suggested to facilitate the propagation and persistence of their host bacteria under different antimicrobial selection pressures.

Phenolic compounds and their derivatives play a major role in the intensity and characteristics of grape (Vitis vinifera) astringency. The present study investigated the relationship between phenolic composition and astringency of six commercial table grape varieties (two of each white-, red-, and black-skinned). Qualitative and quantitative liquid chromatography-mass spectrometry analysis was used to identify the variety-specific phenolic profiles in the skins and total astringency intensity was assessed and described by a trained sensory panel. Thirty phenolic compounds were identified among the six varieties. Principal component analysis of the phenolic profiles revealed that the intensity of astringency of grape skin was positively correlated with catechin, epicatechin, epicatechin-3-O-gallate, and proanthocyanidin dimers B1, B2, and B3. A further orthogonal partial least-squares discrimination analysis of these compounds showed that catechin was the substance most strongly and positively correlated (R = 0.904) with grape skin astringency. PRACTICAL APPLICATION: This study provided a better understanding of the relationships between phenolic composition and table grape astringency and highlighted a potential metabolic marker that could be used as a predictor for the complex astringency sensory attributes of table grape berries.

Background: Suppressor of cytokine signaling (SOCS) is a family of proteins that respond to cytokine, growth factor and other signals, and can regulate various functions of tumor cells. The purpose of our study was to investigate the prognostic performance and biological function of SOCS3 in bladder cancer. Methods: The clinical information of 80 patients with bladder cancer at Zhejiang Provincial People’s Hospital was collected and the SOCS3 protein level was detected by immunohistochemistry. The relationship between SOCS3 status and clinical parameters and the prognosis was analyzed. Besides, we explored the biological function of SOCS3 in bladder cancer. Results: The expression of SOCS3 in bladder cancer tissues was lower than that in normal tissues at the protein level and transcription level (P < 0.001). The low expression group of SOCS3 was more inclined to high staging and high grading. The prognosis of the high expression group of SOCS3 was significantly better than that of the low expression group of SOCS3 in non-muscle-invasive bladder cancer patients (P = 0.037). Also, ectopic expression of SOCS3 reduced the cell proliferation and migration ability of the bladder cancer cell line. Conclusions: Our findings imply that SOCS3 is a potential prognostic factor for non-muscle-invasive bladder cancer, and plays a tumor suppressor role in bladder cancer.

Background: Recent studies demonstrate that N6-methyladenosine (m6A) methylation plays a crucial role in colorectal cancer (CRC). Therefore, we conducted a comprehensive analysis to assess the m6A modification patterns and identify m6A-modified genes in patients with CRC recurrence.Methods: The m6A modification patterns were comprehensively evaluated by the NMF algorithm based on the levels of 27 m6A regulators, and tumor microenvironment (TME) cell-infiltrating characteristics of these modification patterns were systematically assessed by ssGSEA and CIBERSORT algorithms. The principal component analysis algorithm based on the m6A scoring scheme was used to explore the m6A modification patterns of individual tumors with immune responses. The weighted correlation network analysis and univariable and multivariable Cox regression analyses were applied to identify m6A-modified gene signatures. The single-cell expression dataset of CRC samples was used to explore the tumor microenvironment affected by these signatures.Results: Three distinct m6A modification patterns with significant recurrence-free survival (RFS) were identified in 804 CRC patients. The TME characterization revealed that the m6A modification pattern with longer RFS exhibited robust immune responses. CRC patients were divided into high- and low-score subgroups according to the m6A score individually, which was obtained from the m6A-related signature genes. The patients with low m6A scores had both longer RFS and overall survival (OS) with altered immune cell infiltration. Notably, m6A-modified genes showed significant differences related to the prognosis of CRC patients in the meta-GEO cohort and TCGA cohort. Single-cell expression indicated that ALVRL1 was centrally distributed in endothelial tip cells and stromal cells.Conclusion: The m6A modification plays an indispensable role in the formation of TME diversity and complexity. Importantly, the signatures (TOP2A, LRRC58, HAUS6, SMC4, ACVRL1, and KPNB1) were identified as m6A-modified genes associated with CRC recurrence, thereby serving as a promising predictive biomarker or therapeutic target for patients with CRC recurrence.

A pot experiment was conducted to investigate the effects of citric acid application and mowing frequency on the remediation of cadmium (Cd) contaminated soil by napier grass (

To compare the clinical efficacy of scraping needling technique combined with western medication and simple western medication for neurogenic tinnitus of kidney essence deficiency.A total of 68 patients with neurogenic tinnitus of kidney essence deficiency were randomly divided into an observation group and a control group, 34 cases in each group. In the control group, oral methylcobalamin tablets were given, 0.5 mg each time, 3 times a day; oral flunarizine hydrochloride capsules were given before bed, 5 mg each time, once a day, 4 weeks in total. On the basis of the treatment as the control group, scraping needling technique was applied at Tinghui (GB 2), Yifeng (TE 17), Yangchi (TE 4) on the affected side and Shenshu (BL 23), Lieque (LU 7), 5 min each acupoint, once a day, 5 times a week for 4 weeks. Before treatment, 2, 4 weeks into treatment and 4 weeks after treatment (follow-up), the tinnitus severity score, tinnitus visual analogue scale (VAS) score and pure tone average (PTA) were observed, and the clinical efficacy was evaluated in the two groups.The tinnitus severity scores, VAS scores and PTA of each time point after treatment in the two groups were lower than those before treatment (Scraping needling technique combined with western medication could improve tinnitus severity, tinnitus volume and hearing in patients with neurogenic tinnitus of kidney essence deficiency, and its curative effect is better than simple western medication.

Afforestation; Soil ecoenzymatic C: N: P; Specific enzyme activities; Soil C and N contents.

Background: The parallel mechanism plays an important role in various fields. The multifunctional integrated innovation experiment platform can improve the utilization rate of the mechanism and be applied in many fields. Objective: The main objective of the study is to establish an integrated innovation experiment platform based on the 3-PRS parallel mechanism, which can be used in typical application and related technology development. Methods: The integrated innovation experiment platform is established and analyzed based on the 3-PRS parallel mechanism. According to the 3D model of the experiment platform, the kinematics and dynamics are analyzed. The force/position control strategy of the system is adopted. According to the function of the experiment platform, two kinds of application and the position and pose measurement technology are developed. The experiment platform is developed by the following methods: (1) The XY table is set up on the fixing platform of the 3-PRS parallel mechanism, so that the mechanism has five degrees of freedom, and the many kinds of workpiece can be easily processed. (2) By selecting the impedance parameter, the experiment platform can realize the compliant control of plantar flexion/dorsiflexion and varus/eversion simultaneously. (3) The binocular vision position and pose measurement method is used to obtain the marked images of the experiment platform through dual cameras, and the position and pose is obtained through image processing, 3D reconstruction and stereo matching, etc. (4) The position and pose detection based on deep learning is divided into two parts: one is to detect the slider height using the regression Convolutional Neural Network (CNN); the other is to compute the position and pose using the Back Propagation Neural Network (BPNN). Results: The experiment results show that the function of the 3-PRS parallel mechanism integrated innovation experiment platform can be effectively realized. The position and pose can be accurately measured in real time using the proposed two measurement methods. The impedance parameters are selected to achieve the rehabilitation training function of the 3-PRS ankle rehabilitation robot and the characters are processed to verify the function of the 3-PRS-XY series-parallel machine tool. Conclusion: The integrated innovation experiment platform based on the 3-PRS parallel mechanism can achieve the function of mechanical processing and rehabilitation training, and can also measure the state of motion in real time through machine vision and deep learning.

Broussonetia papyrifera, is a promising fast-growing woody plant for the phytoremediation of heavy metal(loid) (HM)-contaminated soil. In this study, a greenhouse experiment was conducted to explore the tolerance capacities of B. papyrifera and its phytoremediation potential in the HM-contaminated soil. The results indicated that B. papyrifera could effectively decrease malondialdehyde (MDA) content by enhancing the antioxidant enzyme activities along with the cultivation in the HM-contaminated soil. Significant (p

Vaccination is the most economic and effective measure to deal with infectious diseases and protect public health. Nowadays, due to the spread of COVID-19 and the ensuing pandemic, safe, effective vaccines are in urgent need. However, due to concerns about vaccine safety, there is still reluctance to vaccinate. In China, in response to the Changchun Changsheng Vaccine incident, the National People's Congress Standing Committee passed the Vaccine Administration Law in 2019, which marks China's first comprehensive piece of legislation on vaccine regulation. The law establishes a regulatory system covering the entire life cycle of vaccines, introduces the vaccine marketing authorization holder system, stipulates the legal responsibilities of all parties, and further clarifies the compensation system for any individuals who exhibit abnormal reactions to vaccination. In addition, it emphasizes the use of modern technology to build a national vaccine electronic platform for tracing. To balance vaccine efficacy and safety, it is necessary to further improve the vaccine risk management mechanism, promote cooperation between government and non-governmental actors, and avoid improper interventions in the vaccine market.

BACKGROUND Keratosis pilaris is a hereditary abnormal keratosis of the hair follicle orifice. Gray-brown keratotic plugs in the pores and dark red keratotic papules at the openings of hair follicles can be seen, which contain coiled hair and are often accompanied by perifollicular erythema and pigmentation. Glycolic acid can correct the abnormalities of hair follicular duct keratosis and eliminate excessive accumulation of keratinocytes. It also promotes skin metabolism and accelerates the melanin metabolism. The therapeutic effect is related to the glycolic acid concentration. AIM To evaluate the efficacy and safety of a high concentration of glycolic acid in the treatment of keratosis pilaris, and to observe the outcomes at 5-year of follow-up. METHODS Twenty-five participants were recruited and areas with typical keratosis pilaris were selected as testing sites. High concentrations of glycolic acid (50% or 70%) were applied to a circular area (d = 8 cm, S = 50 cm2) and repeated four times, on days 0, 20, 40 and 60. Before each treatment and 20 d after the last treatment, on days 0, 20, 40, 60, and 80 and at a 5-year follow-up, The number of follicular keratotic papules were counted and the extent of perifollicular erythema and pigmentation was determined. At the same time, the participants provided subjective evaluations of treatment efficacy and safety. RESULTS Treatment effectiveness was indicated by the percentage of keratotic papules in the test site, on days 20, 40, 60 and 80, which were 8%, 12%, 36%, and 60%, respectively. Compared with day 0, each difference was significant (P < 0.05). Compared with day 0, differences in melanin content (M) in the skin and skin lightness (L) on days 40, 60 and 80, the were statistically significant (P < 0.05); skin hemoglobin content (E) on days 60 and 80 was statistically different as compared with before treatment (P < 0.05). There were no significant differences in the number of keratotic papules, M, L, and E in 9 participants at the 5-year follow-up compared with before treatment (P > 0.05%). CONCLUSION A high concentration of glycolic acid significantly improved skin roughness as well as follicular hyperpigmentation of patients with keratosis pilaris. The treatment was relatively safe, but there was no significant difference at the 5-year follow-up compared to before treatment.