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Tea's popularity and flavor are influenced by factors like cultivation and processing methods and shaping techniques also have an impact on tea flavor. This study employed targeted metabolomics and chemometrics to investigate how shaping techniques affect the flavor of milk-flavored white tea (MFWT). The results showed that the tea cake sample with the shortest pressing time (Y90) has the highest amino acid content and milky aroma intensity. There were variations in amino acids, catechins, and soluble sugars among MFWT samples with different shaping techniques. The total contents of amino acids and catechins in tea cake sample (Y90) were significantly lower than those in the loose tea sample (SC) and bundle-like tea sample (SG), while the total sugar content was significantly higher than that in SC (P<0.05). Additionally, the content of volatiles presenting milky aroma (VIP&OAV>1) in Y90 remained lower relative to SC and SG (P<0.05), but the proportion was not different from that in SC and SG, minimally affecting the overall flavor. The short-time pressing method might be suitable for mass production of MFWT. These findings provide insights into improving the tightness of the appearance of MFWT with minimal impact on tea flavor.

Liquid biopsy is of great significance in tumor early diagnosis and treatment stratification. PD-L1-positive small extracellular vesicles (PD-L1+sEVs) are closely related to tumor growth and immunotherapy response, which are considered valuable liquid biopsy biomarkers. In contrast to conventional in vitrodetection, in vivodetection has the ability to improve the detection efficiency and enable continuous or real-time dynamic monitoring. However, in vivodetection of PD-L1+sEVs has multiple difficulties, such as high cell background, complex blood environments, and lack of a specific and stable detection method. Herein, the in vivodetection of PD-L1+sEVs method was constructed, which efficiently separated sEVs based on the microfluidic device and quantitatively analyzed PD-L1+sEVs by aptamer recognition and hybridization chain reaction. The concentration of PD-L1+sEVs was continuously monitored, and significant differences at different stages of tumor as well as a correlation with tumor volume were found. Diseased and healthy individuals could also be effectively distinguished based on the concentration of PD-L1+sEVs. The method with good stability, biocompatibility, and detection performance provided a powerful means for in vivodetection of PD-L1+sEVs, contributing to the clinical diagnosis and treatment of tumor.

Chinese chestnut (Castanea mollissimaBL.) is a well-known fruit tree that has been cultivated in East Asia for millennia. Leaves and buds of the plant can become seriously infested by the gall wasp Dryocosmus kuriphilus(GWDK), which results in gall formation and associated significant losses in fruit production. Herbivore-induced terpenes have been reported to play an important role in plant–herbivory interactions, and in this study, we show that upon herbivory by GWDK, four terpene-related compounds were significantly induced, while the concentrations of these four compounds in intact buds were relatively low. Among these compounds, (E)-nerolidol and (E, E)-α-farnesene have frequently been reported to be involved in plant herbivory defenses, which suggests direct and/or indirect functions in chestnut GWDK defenses. Candidate terpene synthase (TPS) genes that may account for (E)-nerolidol and (E, E)-α-farnesene terpene biosynthesis were characterized by transcriptomics and phylogenetic approaches, which revealed altered transcript levels for two TPSs: CmAFS, a TPS-g subfamily member, and CmNES/AFS, a TPS-b clade member. Both genes were dramatically upregulated in gene expression upon GWDK infestation. Furthermore, Agrobacterium tumefaciens-mediated transient overexpression in Nicotiana benthamianashowed that CmAFScatalyzed the formation of (E, E)-α-farnesene, while CmNES/AFSshowed dual (E)-nerolidol and (E, E)-α-farnesene synthase activity. Biochemical assays of the recombinant CmAFSand CmNES/AFSproteins confirmed their catalytic activity in vitro, and the enzymatic products were consistent with two of the major volatile compounds released upon GWDK-infested chestnut buds. Subcellular localization demonstrated that CmAFSand CmNES/AFSwere both localized in the cytoplasm, the primary compartment for sesquiterpene synthesis. In summary, we show that two novel sesquiterpene synthase genes CmAFSand CmNES/AFSare inducible by herbivory and can account for the elevated accumulation of (E, E)-α-farnesene and (E)-nerolidol upon GWDK infestation and may be implicated in chestnut defense against GWDK herbivores.

Recently, we proposed in a paper a novel nanomedicine approach based on a versatile bioconjugation linkage (amide, diglycolate, or acylal) between the Leu-enkephalin (LENK), an endogenous neuropeptide, and the squalene (SQ), a natural and biocompatible lipid. The nanoformulation of the resulting bioconjugates allowed the specific delivery of LENK into inflamed tissues for efficient pain control after their intravenous administration. However, the variability of the analgesic profiles exhibited by the three types of LENK-SQ nanoparticles (NPs) remains not well understood. This study investigates the influence of the LENK-SQ NP composition on their supramolecular organization and their interaction with blood proteins. To achieve this objective, a physicochemical study was carried out using complementary techniques such as dynamic light scattering (DLS), small/wide-angle X-ray and neutron scattering (SAXS-WAXS and SANS), and circular dichroism (CD). This study brought together some important information, allowing us to shed light on the crucial link between nanoparticles’ structure, stability, and analgesic activity.

Organic pollutant exposure may alter sex steroid hormone levels in both animals and humans, but studies on mixture effects have been lacking and mainly limited to persistent organic pollutants, with few hormones being investigated. Moreover, measurements from a single blood or urine sample may not be able to reflect long-term status. Using hair analysis, here, we evaluated the relationship between multiclass organic pollutants and sex steroid hormones in 196 healthy Chinese women aged 25–45 years. Associations with nine sex steroid hormones, including progesterone, androstenedione (AD), testosterone (T), estrone (E1), and 17β-estradiol (E2), and eight related hormone ratios were explored on 54 pollutants from polychlorinated biphenyl (PCB), pesticide, and bisphenol families using stability-based Lasso regression analysis. Our results showed that each hormone was associated with a mixture of at least 10 examined pollutants. In particular, hair E2 concentration was associated with 19 pollutants, including γ-hexachlorocyclohexane, propoxur, permethrin, fipronil, mecoprop, prochloraz, and carbendazim. There were also associations between pollutants and hormone ratios, with pentachlorophenol, dimethylthiophosphate, 3-phenoxybenzoic acid, and flusilazole being related to both E1/AD and E2/T ratios. Our results suggest that exposure to background levels of pesticides PCB180 and bisphenol S may affect sex steroid hormone homeostasis among women of reproductive age.

•An IncHI5 plasmid co-carrying blaKPC-2 and blaNDM-1 was first identified in K. michiganensis.•The CRKM isolates carrying multiple carbapenemase genes were potentially spreading in China.•A comparison of blaKPC-2 and/or blaNDM-1 carrying Tn1696-related transposons was performed.

Liquid biopsy technology involves taking samples from body fluids in a minimally invasive way and analyzing tumor markers to achieve early diagnosis and efficacy evaluation of tumors. The development of real-time cancer diagnosis and treatment strategies based on liquid biopsy technology is of great significance to cancer management. This paper described an extracorporeal circulation based on a three-dimensional (3D) magnetic chip (3DMC-system) for in vivo detection and real-time monitoring of circulating tumor cells (CTCs). Utilizing biofunctionalized magnetic nanospheres (MNs) with CTC recognition function, this 3DMC-system could effectively achieve the real-time monitoring of CTCs in vivo with good stability and strong anti-interference. Compared with in vitro CTC detection, in vivo detection could not only detect more CTCs but also detect the presence of CTCs in the blood at an early stage of the tumor, when tumor metastasis is not observed in imaging. In addition, due to the flexibility of the chip design, the system can easily add a treatment module to integrate cancer diagnosis and treatment together. With good biocompatibility and high stability, this 3DMC-system is expected to provide a new personalized medical program for cancer patients.

Extracellular vesicles (EVs), acting as important mediators of intercellular communication, play an essential role in physiological processes, which have unique potential in the medical field. However, the heterogeneity of EVs limits their development for disease diagnosis and therapy, making the EV subpopulation analysis extremely valuable. In this article, a simple microfluidic approach was presented for the on-chip specific isolation and detection of two phenotypes of EVs (Annexin V+EGFR+EVs and Annexin V–EGFR+EVs) based on different biomolecule-modified magnetic nanospheres and a fluorescence labeling technique. Combined with the control of the magnetic field in the microzone and fluid flow, it was easy to form two separate functional regions in the chip to capture different EV subpopulations. This method was successfully applied to the tests of clinical saliva samples in 75 oral squamous cell carcinoma (OSCC) patients and 10 healthy people. The results showed that the total level of EGFR+EVs was much higher in OSCC patients that in healthy people. Meantime, the ratio of Annexin V+EGFR+EVs to Annexin V–EGFR+EVs was found to be negatively correlated with tumor T stage of OSCC patients with a statistical difference, which suggested the ratio as a clinical index for monitoring the progression of OSCC in real time based on a noninvasive method. The approach provided a novel idea for evaluating the tumor T stage of OSCC and a powerful tool for clinical application.

Fusion selenophene endows the chromophore with more intrinsic and special functions. Herein, nonsymmetric selenophene-fused BODIPYs were designed and synthesized starting from the selenophene unit. The fused ring of selenophene not only maintains the rigid structure of BODIPY but also further modulates its spectral properties. The newly prepared dyes possessed many promising properties including large molar extinction coefficients, low fluorescence quantum yields, and moderate singlet oxygen generation. Quantum calculations affirmed that the smaller singlet-triplet energy gap and larger spin–orbit coupling cause efficient intersystem crossing, thus enhancing the singlet oxygen generation yield. Furthermore, selenophene-fused BODIPY exhibited significant phototoxicity with negligible dark cytotoxicity, based on the fluorescence imaging of the reactive oxygen species detection experiment.

This work aimed to investigate the effect of the physical properties of urea-desilicated HZSM-5 on the catalytic performance of the lignite pyrolysis volatiles upgrading to aromatics. A mild urea treatment can create more secondary mesoporous and Brønsted acid sites while well-preserving micropores, of which the first two promoted the diffusion and active cleavage of macromolecules into more small fragments, while the latter ensured the shape selectivity to form aromatics. Consequently, the urea-desilicated catalysts exhibited better performance for the production of aromatics, especially benzene and toluene in monocyclic aromatic hydrocarbons (MAHs), compared to the parent HZSM-5. Among the catalysts, HZSM-5 treated with 5 wt % urea solution for 5 h gave the highest light aromatic (LA) yield of 25.8 mg/g, in which the increased MAH yield accounted for 77% of the total increased LAs. However, excessive desilication with a higher urea concentration or longer treatment time significantly reduced the aromatic yield as a result of a considerable loss of micropores and mesoporous and Brønsted acid sites. The strategy of preserving micropores and optimizing mesoporous and Brønsted acid sites provides a new way to enhance the formation of aromatics.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, primarily due to its late diagnosis, high propensity to metastasis, and the development of resistance to chemo-/radiotherapy. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are intimately involved in the treatment resistance of pancreatic cancer cells via interacting with critical signaling pathways and may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC.

The purpose of this trial was to evaluate the pharmacokinetics (PK), bioequivalence (BE), and safety of 2 preparations of hydroxychloroquine (200‐mg tablet) under fasting and fed conditions. A total of 180 subjects (fasting condition: n = 80; fed condition: n = 100) were randomly enrolled in this randomized, open, single‐dose, single‐cycle parallel phase Ⅰ clinical study. Under the 2 conditions, the subjects were randomly administered the test (T) or reference (R) tablet, both at a dose of 200 mg (1 tablet). Liquid chromatography–tandem mass spectrometry was used to determine the concentration of hydroxychloroquine in healthy subjects after oral administration of the T or R preparation to evaluate the PK characteristics. In this trial, the T and R preparations of hydroxychloroquine were bioequivalent under both conditions within the range of 80%–125%. No serious adverse events (SAEs) were found in the safety assessments for either condition, and all adverse events (AEs) were mild, except for 2 moderate AEs in the fed condition, indicating good safety.

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. 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. 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. 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.

The high-carbohydrate, low-fat, low-protein (HC-LFP) and low-carbohydrate, high-fat, high-protein (LC-HFP) diets are the main dietary patterns worldwide. The influence of dietary patterns on bioavailable metals, gut microbes, and their interaction is still unknown. A biomimetic digestive tract with full functions is constructed to transform the diets into chyme, and the gut microbes are cultured with the corresponding chyme. The diet species-specificity in bioavailable metal content and the positive and negative correlations between bioavailable metals and microbial reproductions are disclosed. The safe dosage and maximum consumption are 369.5 and 858.6 g/d and 268.6 and 3119.0 g/d for LC-HFP and HC-LFP, respectively. When replacing HC-LFP with LC-HFP for 21 days, the bioavailability of Fe and Cr is increased 83.2% and 268.4%, respectively; the reproductions of harmful and benefical microbes are significantly increased and decreased. The prevalences of obesity, inflammation, septicemia, and cancer are increased, and then the risk of dietary pattern shift is disclosed.

Curcumenol, an effective ingredient of Wenyujin, has been reported that exerted its antitumor potential in a few cancer types. However, the effect and molecular mechanism of curcumenol in lung cancer are largely unknown. Here, we found that curcumenol induced cell death and suppressed cell proliferation in lung cancer cells. Next, we demonstrated that ferroptosis was the predominant method that contributed to curcumenol-induced cell death of lung cancer in vitroand vivofor the first time. Subsequently, using RNA sequencing, we found that the long non-coding RNA H19 (lncRNA H19) was significantly downregulated in lung cancer cells treated with curcumenol, when compared to untreated controls. Overexpression of lncRNA H19 eliminated the anticancer effect of curcumenol, while lncRNA H19 knockdown promoted ferroptosis induced by curcumenol treatment. Mechanistically, we showed that lncRNA H19 functioned as a competing endogenous RNA to bind to miR-19b-3p, thereby enhanced the transcription activity of its endogenous target, ferritin heavy chain 1 (FTH1), a marker of ferroptosis. In conclusion, our data show that the natural product curcumenol exerted its antitumor effects on lung cancer by triggering ferroptosis, and the lncRNA H19/miR-19b-3p/FTH1 axis plays an essential role in curcumenol-induced ferroptotic cell death. Therefore, our findings will hopefully provide a valuable drug for treating lung cancer patients.

Organoboron complexes have gained considerable attention owing to their versatile chemical structures and excellent optical properties. Nevertheless, stable seven-membered organoboron complexes have rarely been reported because of their challenging synthesis. Herein, seven-membered N,O-boron-chelated dyes, whose photophysical properties have been thoroughly studied via spectroscopic tests and theoretical calculations, were synthesized from commercially available materials via a facile method. Single-crystal X-ray diffraction studies provided evidence of their seven-membered ring N,O-boron-chelated skeleton. These complexes produced singlet oxygen species under laser irradiation, endowing them with potential application as a photosensitizer to treat superficial tumors (B16 cells). Our study provided a new skeleton to construct versatile organoboron compounds and offered a strategy to design heavy-atom-free photosensitizers.

ABSTRACTGraves’ disease (GD) is a kind of autoimmune diseases. The development of GD is closely related to the imbalance of Th1/Th2 generated by the differentiation of CD4+T cells. This study was sought to clarify the role of lncRNA RUNX1-IT1 and explore the mechanism of its function. The expressions of RUNX1-IT1 and Neural cell adhesion molecule (NrCAM) in the peripheral blood of GD patients were detected by qRT-PCR and Western blot. We performed RNA pull down, RIP, and ChIP experiments to verify the correlation between p53 and RUNX1-IT1, p53 and NrCAM. The levels of Th1 cells differentiation markers were detected by Flow cytometry assay and ELISA. The expressions of lncRNA RUNX1-IT1 and NrCAM were most significantly up-regulated in CD4+T cells of GD patients, and NrCAM expression was significantly positively correlated with RUNX1-IT1 expression. Furthermore, p53 was a potential transcription factor of NrCAM, which could interact with NrCAM. NrCAM level was up-regulated after the overexpression of p53 in CD4+T cells, while knockdown of RUNX1-IT1 reversed this effect. Down-regulation of NrCAM and RUNX1-IT1 could decrease the mRNA and protein levels of transcriptional regulator T-bet and CXC chemokine ligand 10 (CXCL10) in CD4+T cells. Our results suggested that RUNX1-IT1 regulated the expressions of the important Th1 factor T-bet, CXCL10, and interferon γ (IFN-γ) by regulating NrCAM transcription, thus participating in the occurrence and development of specific autoimmune disease GD.

Hydrodeoxygenation (HDO) is an important chemical process to convert lignin to high-energy-density cycloalkanes by removing oxygen-containing functional groups. Herein, a bifunctional metal/acid catalyst of Ru/SHZSM-5-100 (Ru/SHZ5-100) with a large specific surface area, a large average pore diameter, and more external pores was successfully prepared by combining the hydrothermal and simple incipient wetness impregnation methods. The resulting Ru/SHZ5-100 catalyst exhibited the best HDO performance for lignin-derived diphenyl ether (DPE) under extremely mild conditions (150 °C, 1 MPa H2, 2 h). The results revealed that DPE was hydrogenated to oxydicyclohexane first and then quickly converted to the target product cyclohexane. Furthermore, other lignin model compounds could also be converted successfully to corresponding cycloalkanes over Ru/SHZ5-100 in this reaction system. Finally, the relationship between the structure and high performance of Ru/SHZ5-100 was studied. The construction of the Ru/SHZ5-100 catalytic system highlighted a promising way to convert lignin model compounds to oxygen-free fuels and chemicals.

In this study, the influence of hydrogen charging and deformation on the tensile behavior of a 60Fe–12Cr–10Mn–15Cu–3Mo multi-component alloy was investigated using electron microscopy and positron annihilation lifetime spectroscopy. The results show that hydrogen-induced vacancy clusters found in the electrochemically charged hydrogen specimens are responsible for crack initiation. Upon ingress to the microstructure, hydrogen promotes the formation of cell-structured dislocations that are beneficial for the improvement of tensile strength. In addition, hydrogen embrittlement can be mitigated by dislocations that can hinder hydrogen mobility in the deformed specimens.

For the biosynthesis of nicotinamide mononucleotide (NMN), three artificial pathways including the nicotinamide ribose phosphorylation pathway, adenosine phosphate pyrophosphorylation pathway, and adenosine phosphate hydrolysis (APH) pathway were designed and successfully conducted to produce NMN in vitro. The APH pathway, using AMP nucleosidase, ribose-phosphate diphosphokinase, and nicotinamide phosphoribosyltransferase (NAMPT), exhibited the highest level of NMN synthesis. To further improve NMN production viathe APH pathway, various NAMPT orthologues were screened. The effects of temperature, pH, metal ions and enzyme ratios were further systematically investigated, and the accumulation of ADP was identified limiting pathway efficiency. Subsequently, an ATP recycling process was achieved by adding polyphosphate kinase 2 to convert ADP to ATP. With the optimized four multienzyme cascade catalysis systems, the NMN titer was increased to 9 mmol L−1(3.0 g L−1) from 600 μmol L−1(0.2 g L−1) in vitro. This is the first study to use a multienzyme cascade catalysis process for NMN biosynthesis.

Leydig cells (LCs) apoptosis is responsible for the deficiency of serum testosterone in Late-onset hypogonadism (LOH), while its specific mechanism is still unknown. This study focuses on the role of long noncoding RNA (lncRNA) MIR22HG in LC apoptosis and aims to elaborate its regulatory mechanism. MIR22HG was up-regulated in the testicular tissues of mice with LOH and H2O2-treated TM3 cells (mouse Leydig cell line). Interference of MIR22HG ameliorated cell apoptosis and upregulated miR-125a-5p expression in H2O2-treated TM3 cells. Then, the interaction between MIR22HG and miR-125a-5p was confirmed with RIP and RNA pull-down assay. Further study showed that miR-125a-5p downregulated N-Myc downstream-regulated gene 2 (NDRG2) expression by targeting its 3′-UTR of mRNA. What's more, MIR22HG overexpression aggravated cell apoptosis and reduced testosterone production in TM3 cells via miR-125a-5p/NDRG2 pathway. MIR22HG knockdown elevated testosterone levels in LOH mice. In conclusion, MIR22HG up-regulated NDRG2 expression through targeting miR-125a-5p, thus promoting LC apoptosis in LOH.

• Soil abundant taxa diversity positively related to multifunctionality under Hg stress.

The engineering practice shows that the application of grouting technology to treat underground engineering has strong applicability and is one of the most commonly used technical means at present. Based on the underground engineering, this paper introduces the research achievements of grouting materials in recent years, including cement-based grouting materials, mixed grouting materials, anti-scouring grouting materials, and ultra-fine cement grouting materials. Current demand of grouting materials in underground engineering, there exists large dosage of cement, high content, high cost, serious environmental pollution problems, such as looking for alternatives or mixed with other raw materials for preparation of cementation material become the development trend, compared with the cement grouting material, chemical grouting material with higher performance, but in smaller projects within the scope of application. How to reduce the production cost of chemical grouting materials, simplify the production process, overcome the existing toxicity, reduce environmental pollution and improve the durability of solidified body has become the bottleneck of its popularization and application. Some achievements have been made in the modification of cement or chemical materials by nanometer components, but there is still a long way to go before the large-scale application of grouting engineering.

Dysregulation of the long intergenic noncoding RNA 01315 (LINC01315) has recently been demonstrated in cancer. However, the role of LINC01315 in papillary thyroid cancer (PTC) has not been determined. We attempted to determine the function of LINC01315 in PTC. The levels of LINC01315 were higher in thyroid carcinoma tissues and cell lines compared with that in noncancerous tissues or normal cells, respectively. LINC01315 knockdown significantly inhibited the in vitro colony formation and invasion of PTC cells. Upregulation of LINC01315 produced opposite effects. Bioinformatic analysis and luciferase reporter assays indicated direct binding of miR‐497‐5p to LINC01315. Gain‐ and loss‐of‐function assays indicated that miR‐497‐5p acts as a suppressive miRNA in PTC. Furthermore, LINC01315 facilitated the growth and invasion of PTC cells by sponging miR‐497‐5p. Our results demonstrated the critical role of the LINC01315‐miR‐497‐5p axis in the growth and invasion of PTC cells.

The nucleation and growth mechanism of electrodeposited Ni−W alloy were investigated. Cyclic voltammetry (CV) and chronoamperometry (CA) were used to examine the electrochemical behavior and nucleation mechanism of the electrodeposited Ni−W alloy. The nucleation type and kinetic parameters of the electrodeposited Ni−W alloy were obtained from the CA analysis results. SEM, AFM, and TEM were also used to investigate the nucleation and growth process of the electrodeposition of Ni−W alloy. The results demonstrate that the nucleation and initial stages of the growth phase of the Ni−W alloy undergo the formation, movement, and aggregation of atoms, single crystals, and nanoclusters. When the size of single crystal increases up to approximately 10 nm and the average size of the crystal granules is approximately 68 nm, they no longer grow. Increasing the applied potential increases the number of nuclei but does not affect the size of the final crystal granules. Therefore, the electrodeposited Ni−W alloy shows a nanocrystalline structure.

Terpenes and their derivatives are important biomarkers of grape quality as they contribute to the flavor and aroma of grapes. However, the molecular basis of terpene biosynthesis throughout the grapevine phenological developmental cycle remains elusive. Our current study investigates the free and bound terpene biosynthesis of berries at different phenological stages from preveraison to harvest. Detailed gene expression (transcriptomics) analysis, terpenoid volatile production by gas chromatography–mass spectrometry (GC–MS), and in plantatransient expression were employed. Our results show that concentrations of most individual terpenes at different stages are distinctive and increase from preveraison to the veraison stage followed by a decrease from veraison to maturity. The combined transcriptomic analysis and terpene profiling revealed that 22 genes belonging to the MEP pathway and multiple classes of transcription factor family members including bHLH and several hormone biosynthesis- or signaling-related genes likely participate in the regulation of terpenoid biosynthesis according to their specific expression patterns in berries. Quantitative real-time polymerase chain expression analysis of 8 key differentially expressed genes in MEP pathways and further 12 randomly selected genes was performed during 8 sampling stages and validated the RNA-seq-derived expression profiles. To further confirm the function of a subset of the differentially expressed genes, we investigated the effects of combined overexpression of 1-deoxy-d-xylulose-5-phosphate synthase (VvDXS1-LOC100249323), 1-deoxy-d-xylulose-5-phosphate reductoisomerase (VvDXR-LOC100248516), and terpene synthase (VvTPS56-LOC100266449) on the production of terpenes by transient overexpression in Nicotiana benthamianaleaves. The overall developmental patterns of total terpenes and gene expression profiles will help guide the functional analyses of further candidate genes important for terpene biosynthesis of grape as well as identifying the master transcriptional and hormonal regulators of this pathway in the future.

Bioaccumulation of the neurotoxin methylmercury (MeHg) in rice has raised worldwide concerns because of its risks to human health. Certain microorganisms are able to degrade MeHg in pure cultures, but the roles and diversities of the microbial communities in MeHg degradation in rice paddy soils are unknown. Using a series of microcosms, we investigated MeHg degradation in paddy soils from Hunan, Guizhou, and Hubei provinces, representing three major rice production regions in China, and further characterized one of the soils from the Hunan Province for microbial communities associated with MeHg degradation. Microbial demethylation was observed in all three soils, demonstrated by significantly more MeHg degraded in the unsterilized soils than in the sterilized controls. More demethylation occurred in water-saturated soils than in unsaturated soils, but the addition of molybdate and bromoethanesulfonic acid as the respective inhibitors of sulfate reducing bacteria and methanogens showed insignificant effects on MeHg degradation. However, the addition of Cu enhanced MeHg degradation and the enrichment of Xanthomonadaceae in the unsaturated soil. 16S rRNA Illumina sequencing and metatranscriptomic analyses of the Hunan soil consistently revealed that Catenulisporaceae, Frankiaceae, Mycobacteriaceae, and Thermomonosporaceae were among the most likely microbial taxa in influencing MeHg degradation in the paddy soil, and they were confirmed by combined analyses of the co-occurrence network, random forest modeling, and linear discriminant analysis of the effect size. Our results shed additional light onto the roles of microbial communities in MeHg degradation in paddy soils and its subsequent bioaccumulation in rice grains.

The physicochemical properties of the prepared bimetallic NiFe/γ-Al2O3catalysts can be affected by reduction temperature, which can change the hydrogenation activity and product selectivity for methyl laurate catalytic hydrogenation. The metal Ni active sites mainly promote the decarbonylation/decarboxylation (DCO/DCO2) reaction, and the addition of Fe can promote the hydrodeoxygenation (HDO) reaction of methyl laurate to produce C12alkanes. The results of H2-TPR, XRD, H2-TPD and BET indicate that high reduction temperature is beneficial to the formation of metal or alloy active centers. The hydrogenation activity of bimetallic catalysts depends on the content of metal Ni, Fe and NiFe alloy. The ability of NiFe bimetallic catalyst to adsorb and activate H2is obviously affected by reduction temperature. In the studied temperature range, Ni active centers have excellent hydrogenation and cracking performances, and the introduction of Fe species can effectively inhibit the cracking performance. The sequence of catalytic hydrogenation activity for these bimetallic catalysts is: NF420 > NF360 > NF450 > NF300. When the reduction temperature is 420°C, the prepared NF420 catalyst owns the best catalytic hydrogenation performances. The conversion of methyl laurate and the selectivity of alkanes are 93.3% and 90.0% at the reaction temperature of 380°C, respectively.

Aim:To characterize two plasmids p13294-KPC and pA1966-NR from clinical Klebsiella pneumoniaestrains. Materials & methods:Plasmids p13294-KPC and pA1966-NR were fully sequenced and then detailed genomic analysis was performed in this work. The antimicrobial resistance phenotypes were determined. Results:p13294-KPC and pA1966-NR displayed IncpA1763-KPC:IncFIIK7dual-replicon structures. The backbone of these two plasmids were closely related to each other. p13294-KPC contained two accessory modules, namely ΔISKpn25and blaKPC-2region, and the blaKPC-2region carried a range of mobile elements and resistance gene blaKPC-2. while pA1966-NR contained four individual IS elements in its backbone and carried no resistance genes. Conclusion:This study provided a deeper insight into the genomic characterization of IncpA1763-KPC: IncFIIK7type plasmids p13294-KPC and pA1966-NR.

The organic fluorescent probes for temperature have received increasing interest due to their extremely high spatial and temporal resolution. A few of triarylboron derivatives, as almost the only molecular probes consisting of a single luminophore, have the ability to change their luminescent color at different temperatures. The mechanism of their luminescence thermochromism is controversial. Herein, several spectral experiments, along with time-dependent density functional theory (TDDFT) and coupled-cluster (CC) calculations, are carried out to elucidate the temperature-dependent luminescence. The CC rather than the TDDFT methods give a relatively reasonable explanation for the experimental results. Consequently, the thermochromism is now considered as the result of conformational thermal equilibria that occur in both the excited and ground states. Besides, an unusual conformer with intramolecular excimer characteristic plays a crucial role in the attractive luminescence behavior.

Single-entity electrochemistry (SEEC), a promising method for biosensing, has an intrinsic limitation on sensitivity since at most one colliding entity can be successfully triggered by one target. Here, we take advantage of one-to-many (1:n) signal amplification to develop a new single-entity electrochemistry biosensing (SEECBS), integrating satellite magnetic nanoparticle (MN)-DNA-Pt nanoparticle (NP) conjugates, duplex-specific nuclease (DSN) assisted Pt NPs releasing with stabilization, and effective collision of small sized and nearly naked Pt NPs. Compared with conventional SEECBS, the 1:nSEECBS can successfully enrich ∼2 nM Pt NPs by adding 50 aM microRNA (miRNA), in other words, ∼4 × 107Pt NPs can be triggered by one target. The proposed SEECBS allows the detection of 47 aM miRNA-21, nearly 6 orders of magnitude lower than the previous work, and discrimination of nontarget miRNAs containing even single-nucleotide mismatch. Besides, this method has also been successfully demonstrated for quantification of miRNA in different cell lines. Therefore, the proposed method holds great potential for the application of SEECBS in early diagnosis and prognosis monitoring of cancer.

•This study isolated the clinical E. hormaecheistrain K432 carrying multiple resistance genes.•The genome of strain K432 consisted of chromosome cK432 and plasmids pK432-IMP, pK432-TEM and pK432-NR.•pK432-IMP belonged to a novel incompatibility group, which has the potential to acquire different antimicrobial resistance genes.•pK432-TEM was an IncR plasmid.•pK432-IMP could be transferred from strain K432 into E. coliEC600 through conjugation.

Astringency influences the sensory characteristics and flavor quality of table grapes. We tested the astringency sensory attributes of berries and investigated the concentration of flavan-3-ols/proanthocyanidins (PAs) in skins after the application of the plant growth regulators CPPU and GA3to the flowers and young berries of the “Summer Black” grape. Our results showed that CPPU and GA3applications increase sensory astringency perception scores and flavan-3-ol/proanthocyanidin concentrations. Using integrated transcriptomic and proteomic analysis, differentially expressed transcripts and proteins associated with growth regulator treatment were identified, including those for flavonoid biosynthesis that contribute to the changes in sensory astringency levels. Transient overexpression of candidate astringency-related regulatory genes in grape leaves revealed that VvWRKY71, in combination with VvMYBPA1and VvMYC1, could promote the biosynthesis of proanthocyanidins, while overexpression of VvNAC83reduced the accumulation of proanthocyanidins. However, in transient promoter studies in Nicotiana benthamiana, VvWRKY71repressed the promoter of VvMYBPA2, while VvNAC83had no significant effect on the promoter activity of four PA-related genes, and VvMYBPA1was shown to activate its own promoter. This study provides new insights into the molecular mechanisms of sensory astringency formation induced by plant growth regulators in grape berries.

Cardiometabolic health is complex and characterized by an ensemble of correlated and/or co-occurring conditions including obesity, dyslipidemia, hypertension, and diabetes mellitus. It is affected by social, lifestyle, and environmental factors, which in-turn exhibit complex correlation patterns. To account for the complexity of (i) exposure profiles and (ii) health outcomes, we propose to use a multitrait Bayesian variable selection approach and identify a sparse set of exposures jointly explanatory of the complex cardiometabolic health status. Using data from a subset (N= 941 participants) of the nutrition, environment, and cardiovascular health (NESCAV) study, we evaluated the link between measurements of the cumulative exposure to (N= 33) pollutants derived from hair and cardiometabolic health as proxied by up to nine measured traits. Our multitrait analysis showed increased statistical power, compared to single-trait analyses, to detect subtle contributions of exposures to a set of clinical phenotypes, while providing parsimonious results with improved interpretability. We identified six exposures that were jointly explanatory of cardiometabolic health as modeled by six complementary traits, of which, we identified strong associations between hexachlorobenzene and trifluralin exposure and adverse cardiometabolic health, including traits of obesity, dyslipidemia, and hypertension. This supports the use of this type of approach for the joint modeling, in an exposome context, of correlated exposures in relation to complex and multifaceted outcomes.

In vivo detection of circulating tumor cells (CTCs) which inspect all of the circulating blood in body seems to have more advantages on cell capture, especially in earlier cancer diagnosis. Herein, based on in vivo microfluidic chip detection system (IV-chip-system), an extracorporeal circulation was constructed to effectively detect and monitor CTCs in vivo. Combined with microfluidic chip and immunomagnetic nanosphere (IMN), this system not only acts as a window for CTC monitoring but also serves as a collector for further cancer diagnosis and research on CTCs. Compared with the current in vivo detection method, this system can capture and detect CTCs in the bloodstream without any pretreatments, and it also has a higher CTC capture efficiency. It is worth mentioning that this system is stable and biocompatible without any irreversible damage to living animals. Taking use of this system, the mimicked CTC cleanup process in the blood vessel is monitored, which may open new insights in cancer research and early cancer diagnosis.

CXC chemokine ligand 12 (CXCL12) is a member of the CXC chemokine family and mainly acts on cell chemotaxis. CXCL12 also elicits a proatherogenic role, but the molecular mechanisms have not been fully defined yet. We aimed to reveal if and how CXCL12 promoted atherosclerosis via regulating lipid metabolism. In vitro, our data showed that CXCL12 could reduce ABCA1 expression, and it mediated cholesterol efflux from THP-1-derived macrophages to apoA-I. Data from the luciferase reporter gene and chromatin immunoprecipitation assays revealed that transcription factor 21 (TCF21) stimulated the transcription of ABCA1 via binding to its promoter region, which was repressed by CXCL12. We found that CXCL12 increased the levels of phosphorylated glycogen synthase kinase 3β (GSK3β) and the phosphorylation of β-catenin at the Thr120 position. Inactivation of GSK3β or β-catenin increased the expression of TCF21 and ABCA1. Further, knockdown or inhibition of CXC chemokine receptor 4 (CXCR4) blocked the effects of CXCL12 on TCF21 and ABCA1 expression and the phosphorylation of GSK3β and β-catenin. In vivo, the overexpression of CXCL12 in Apoe−/−mice via lentivirus enlarged the atherosclerotic lesion area and increased macrophage infiltration in atherosclerotic plaques. We further found that the overexpression of CXCL12 reduced the efficiency of reverse cholesterol transport and plasma HDL-C levels, decreased ABCA1 expression in the aorta and mouse peritoneal macrophages (MPMs), and suppressed cholesterol efflux from MPMs to apoA-I in Apoe−/−mice. Collectively, these findings suggest that CXCL12 interacts with CXCR4 and then activates the GSK-3β/β-cateninT120/TCF21 signaling pathway to inhibit ABCA1-dependent cholesterol efflux from macrophages and aggravate atherosclerosis. Targeting CXCL12 may be a novel and promising strategy for the prevention and treatment of atherosclerotic cardiovascular diseases.

Nitrogenous disinfection by-products (N-DBPs) are more genotoxic and cytotoxic than the currently regulated carbonaceous DBPs (i.e., C-DBPs), and it has become a frontier issue of drinking water safety research. In this paper, the effect of granular activated carbon (GAC) on adsorption and its influencing factors was investigated for a typical N-DBP phenylacetonitrile, which is produced during chlorination of phenylalanine precursor during water treatment. The results showed that GAC had a high adsorption capacity (qmax= 22.92 mg/g) for phenylacetonitrile, and the adsorption isotherm was fitted to the Langmuir isotherm model. Pseudo-second-order equation can well describe the behavior of phenylacetonitrile adsorption on activated carbon (R2> 0.990), and the adsorption rate constant k2= 0.7780–14.12 g/(mg h). Analysis of the influencing factors showed that higher phenylacetonitrile concentration improved the adsorption equilibrium capacity and the adsorption rate. Water temperature and pH had little effect on the capacity or rate of adsorption.

The biological responses of artificial biomaterials are affected strongly by its interfacial topography, especially from nano- to microscale. The structure controllability is essential for the design and synthesis of novel biomedical materials. Herein, the effect of soluble silk fibroin (SF) on the cathodic electrolytic deposition (ELD) behavior of octacalcium phosphate (OCP) coating is studied. It is observed that the addition of soluble SF does not change the inorganic phase of the coating (OCP), but it has a remarkable effect on the microstructure of the deposited coating. As a result, the OCP/SF composite coating possessed a micro/nano multilevel structure is finely constructed on titanium implant by using ELD technology. Such OCP/SF composite coating significantly promotes preosteoblast cells adhesion, spreading and proliferation. In general, effects have been made to produce an in-depth understanding of protein incorporated ELD technology to extend its application in the biomedical field. It provides a promising strategy to design and synthesize biomaterials with specific biomimetic structures and functions.

Photon detection efficiency is a key parameter of PMTs in high-precision neutrino and dark matter experiments, while normally the quantum efficiency is used with a normalization factor and angular response as the detection efficiency, where it is always coupled with detector response from the calibration normalization. Here, the absolute photon detection efficiency of 20′′ PMTs in photon-counting level is further considered rather than the combination of quantum efficiency and normalization factors. In order to have a good understanding of photon detection efficiency of the large-area PMT, we conduct a detailed comparison of relative collection efficiencies of a series of PMTs with spotlight. This study is based on the tests of relative quantum efficiency and relative detection efficiency, checked with several light intensities. All the results are consistent in relative QE and DE measurement with different light intensities, and the error of each parameter is coupled in our studies. Based on the measurements, Hamamatsu R12860 shows the maximum collection efficiency with spotlight at PMT center, and Hamamatsu R12199, R1355 and HZC XP72B22 have the same level of CE within the uncertainty. Following the configuration on incident light and DE definition, we can further define the DE of a large-area PMT with similar algorithms, which will also be used for detector simulation in JUNO.

Drylands are characterized by stressful conditions with the limitation of both carbon (C) and nutrients, particularly nitrogen (N) and phosphorus (P). Biological C, N, and P releases from soil organic matter by enzymes are essential components for biogeochemical cycles and are sensitive to the climate in drylands. However, how the ecoenzymatic C:N:P stoichiometry responds to environmental factors (i.e., climatic and edaphic factors) over broad geographical scales remains largely unclear. We examined the patterns of ecoenzymatic C:N:P ratios across a 3,700‐km aridity gradient (0.43 < aridity < 0.97) in northern China. In wetter sites (aridity < 0.70), the relative C:N:P acquisition ratios via enzymes remained relatively constant with increasing aridity. In contrast, in drier sites (aridity > 0.70), the enzymatic C:nutrient (N and P) ratios declined as the aridity increased, while the enzymatic P:N ratios were mostly lower than those in the wetter sites. In drier sites with low C availability, the increasing carbon use efficiency and the increasing proportion of C converted to biomass (than the proportion of respiration) contributed to the declines of the enzymatic C:nutrient ratios as the aridity increased. The overall lower enzymatic P:N ratios were related to the higher soil P availability compared with N availability (higher organic P and lower soil NH4+:available P ratios) in drier sites. Overall, our findings indicate that intrinsic linkages of biological C, N, and P acquisitions and cycles were broken at the aridity threshold of 0.70, with higher acquisition efforts for N and P (particularly for N) with increasing aridity in drier sites with aridity > 0.70. Ecoenzymatic C:N:P ratios remained relatively constant in wetter sitesEcoenzymatic C:N and C:P ratios declined with increasing aridity in drier sitesEcoenzymatic P:N ratios varied and were generally lower than 1 in drier sites

AbstractTalaromyces marneffeiis the only dimorphic species in its genus and causes a fatal systemic mycosis named talaromycosis. Our previous study indicated that knockdown of AcuDgene (encodes isocitrate lyase of glyoxylate bypass) of T. marneffeiby RNA interference approach attenuated the virulence of T. marneffei, while the virulence of the AcuDknockout strains was not studied. In this study, T. marneffei-zebrafish infection model was successfully established through hindbrain microinjection with different amounts of T. marneffeiyeast cells. After co-incubated at 28°C, the increasing T. marneffeiinoculum doses result in greater larval mortality; and hyphae generation might be one virulence factor involved in T. marneffei-zebrafish infection. Moreover, the results demonstrated that the virulence of the ΔAcuDwas significantly attenuated in this Zebrafish infection model.

The goal of this study is to systematically assess the effectiveness of acupuncture compared with medication for migraine.

Jiangmen Underground Neutrino Observation (JUNO) is one of the largest experimental facilities for neutrino detecting. As its main structure, the central detector contains 20 kiloton liquid scintillator filled in an acrylic shell, and there are 18,000 20-inch photomultiplier tubes (PMTs) and 25,000 3-inch PMTs covering the shell. As an independent photon detection system, 3-inch PMTs have been required to have excellent resolution for the single photoelectron detection, high quantum efficiency, small transit time spread and low dark noise rate. Two kinds of 3-inch PMTs from HZC Photonics and Hamamatsu have been investigated as candidates. A dedicated test system for 3-inch PMTs has been designed, and various characterization parameters have been studied. The preliminary results show these PMTs can meet the requirements of JUNO.

ABSTRACTFocussing on the problem that redundant nodes in the kernel incremental extreme learning machine (KI-ELM) which leads to ineffective iteration increase and reduce the learning efficiency, a novel improved hybrid intelligent deep kernel incremental extreme learning machine (HI-DKIELM) based on a hybrid intelligent algorithms and kernel incremental extreme learning machine is proposed. At first, hybrid intelligent algorithms are proposed based on differential evolution (DE) and multiple population grey wolf optimization (MPGWO) methods which used to optimize the hidden layer neuron parameters and then to determine the effective hidden layer neurons number. The learning efficiency of the algorithm is improved by reducing the network complexity. Then, we bring in the deep network structure to the kernel incremental extreme learning machine to extract the original input data layer by layer gradually. The experiment results show that the HI-DKIELM methods proposed in this paper with more compact network structure have higher prediction accuracy and better ability of generation compared with other ELM methods.

ABSTRACTCronobacter sakazakii505108 was isolated from a sputum specimen of a neonate with severe pneumonia. C. sakazakii505108 co-harbors 3 resistance plasmids of the IncHI2, IncX3, and IncFIB incomparability groups, respectively. These 3 plasmids have acquired several accessory modules, which carry an extremely large number of resistance genes, especially including those involved in resistance to carbapenems, aminoglycoside, tetracyclines, and phenicols and sulphonamide/trimethoprim. These plasmid-borne antibiotic resistance genes were associated with insertion sequences, integrons, and transposons, indicating that the assembly and mobilization of the corresponding accessory modules with complex chimera structures are facilitated by transposition and/or homologous recombination. This is the first report of fully sequence plasmids in clinical Cronobacter, which provides a deeper insight into plasmid-mediated multi-drug resistance in Cronobacterfrom hospital settings.

AbstractThis study aimed to determine the chemical composition and skin protective effects of essential oil from ginger (Zingiber officinaleRoscoe), a traditional Chinese medicine, spice, and food. Essential oil was extracted from ginger by hydrodistillation. Forty-three compounds were identified in ginger essential oil (GEO) by using gas chromatography-mass spectrometry. GEO comprised α-zingiberene (26.00 %), β-sesquiphyllandrene (8.10 %), α-curcumene (7.99 %), α-bergamotene (7.99 %), β-bisabolene (7.47 %), and ar-turmerone (3.86 %). Skin damage induced by eight-week Ultraviolet B (UVB) irradiation, including erythema, wrinkles, and skin inflammation in nude mice. GEO treatment at three different concentrations ameliorated UVB-induced skin inflammation and inhibited interleukin-1β and tumour necrosis factor-α expression in skin tissues. Therefore, GEO adequately protected the skin from UVB irradiation and photoaging.