Electro-Induced Phase Transformation of a Conductive Metal-Organic Framework Film for Nonlinear Optical Switching.

Achieving metal-organic frameworks (MOFs) with nonlinear optical (NLO) switching is profoundly important. Herein, the conductive MOFs Cu-TCNQ phase I (Ph-I) and phase II (Ph-II) films were prepared using the liquid-phase-epitaxial layer-by-layer spin-coating method and steam heating method, respectively. Electronic experiments showed that the Ph-II film could be changed into the Ph-I film under an applied electric field. The third-order NLO results revealed that the Ph-I film had a third-order nonlinear reverse saturation absorption (RSA) response and the Ph-II film displayed a third-order nonlinear saturation absorption (SA) response. With increases in the heating time and applied voltage, the third-order NLO response realized the reversible transition between SA and RSA. The theoretical calculations indicated that Ph-I possessed more interlayer charge transfer, resulting in a third-order nonlinear RSA response that was stronger than that of Ph-II. This work applies phase-transformed MOFs to third-order NLO switching and provides new insights into the nonlinear photoelectric applications of MOFs.

Chiral Liquid Crystalline Metal-Organic Framework Thin Films for Highly Circularly Polarized Luminescence.

Combining metal-organic frameworks (MOFs) with liquid crystals to construct liquid crystalline MOFs (LCMOF) offers the advantage of endowing and enhancing their functionality, yet it remains a challenging task. Herein, we report chiral liquid crystalline MOF (CLCMOF) thin films by cross-linking the chiral liquid crystals (CLC) with MOF thin films to realize highly circular polarization luminescence (CPL) performance with photo and thermal switching. By layer by layer cross-linking stilbene-containing CLC with stilbene-based MOF (CLC/MOF) thin film, the CLCMOF thin films were successfully obtained after UV irradiation due to the abundant [2 + 2] photocycloaddition. The resulted CLCMOF thin films have strong chirality, obvious photochromic fluorescent, and strong CPL performance (the asymmetry factor reaches to 0.4). Furthermore, due to the photochromic fluorescent MOF and thermotropic CLC, the CPL can be reversed and red-shifted after heating and UV irradiation treatment, showing photo- and thermal CPL switching. Such MOF-based CPL thin films with photo/thermal CPL switching were prepared to patterns and codes for the demonstration of potential application in advanced information anticounterfeit and encryption. This study not only opens a strategy for developing chiral thin films combining MOFs and liquid crystals but also offers a new route to achieve CPL switching in optical applications.

Sex-determining region Y gene promotes liver fibrosis and accounts for sexual dimorphism in its pathophysiology.

BACKGROUND & AIMS: Men are more prone to develop and die from liver fibrosis than women. In this study, we aim to investigate how sex-determining region Y gene (SRY) in hepatocytes promotes liver fibrosis. METHODS: Hepatocyte-specific Sry knock-in (KI), Sry knockout (KO), and Sry KI with platelet-derived growth factor receptor α (Pdgfrα) KO mice were generated. Liver fibrosis was induced in mice by bile duct ligation for 2 weeks or carbon tetrachloride treatment for 6 weeks. In addition, primary hepatocytes, hepatic stellate cells (HSCs), and immortalized cell lines were used for in vitro studies and mechanistic investigation. RESULTS: Compared to females, the severity of toxin- or cholestasis-induced liver fibrosis is similarly increased in castrated and uncastrated male mice. Among all Y chromosome-encoded genes, SRY was the most significantly upregulated and consistently increased gene in fibrotic/cirrhotic livers in male patients and in mouse models. Sry KI mice developed exacerbated liver fibrosis, whereas Sry KO mice had alleviated liver fibrosis, compared to age- and sex-matched control mice after bile duct ligation or administration of carbon tetrachloride. Mechanistically, both our in vivo and in vitro studies illustrated that SRY in hepatocytes can transcriptionally regulate Pdgfrα expression, and promote HMGB1 (high mobility group box 1) release and subsequent HSC activation. Pdgfrα KO or treatment with the SRY inhibitor DAX1 in Sry KI mice abolished SRY-induced HMGB1 secretion and liver fibrosis. CONCLUSIONS: SRY is a strong pro-fibrotic factor and accounts for the sex disparity observed in liver fibrosis, suggesting its critical role as a potentially sex-specific therapeutic target for prevention and treatment of the disease. IMPACT AND IMPLICATION: We identified that a male-specific gene, sex-determining region Y gene (SRY), is a strong pro-fibrotic gene that accounts for the sex disparity observed in liver fibrosis. As such, SRY might be an appropriate target for surveillance and treatment of liver fibrosis in a sex-specific manner. Additionally, SRY might be a key player in the sexual dimorphism observed in hepatic pathophysiology more generally.

Metric learning for comparing genomic data with triplet network.

Many biological applications are essentially pairwise comparison problems, such as evolutionary relationships on genomic sequences, contigs binning on metagenomic data, cell type identification on gene expression profiles of single-cells, etc. To make pair-wise comparison, it is necessary to adopt suitable dissimilarity metric. However, not all the metrics can be fully adapted to all possible biological applications. It is necessary to employ metric learning based on data adaptive to the application of interest. Therefore, in this study, we proposed MEtric Learning with Triplet network (MELT), which learns a nonlinear mapping from original space to the embedding space in order to keep similar data closer and dissimilar data far apart. MELT is a weakly supervised and data-driven comparison framework that offers more adaptive and accurate dissimilarity learned in the absence of the label information when the supervised methods are not applicable. We applied MELT in three typical applications of genomic data comparison, including hierarchical genomic sequences, longitudinal microbiome samples and longitudinal single-cell gene expression profiles, which have no distinctive grouping information. In the experiments, MELT demonstrated its empirical utility in comparison to many widely used dissimilarity metrics. And MELT is expected to accommodate a more extensive set of applications in large-scale genomic comparisons. MELT is available at https://github.com/Ying-Lab/MELT.

Long-term survivors after curative-intent resection for intrahepatic cholangiocarcinoma.

OBJECTIVES: The objective of the current study was to characterize prognostic factors related to long-term recurrence-free survival after curative-intent resection of intrahepatic cholangiocarcinoma (ICC). METHODS: Data on patients who underwent curative-intent resection for ICC between 2000 and 2020 were collected from an international multi-institutional database. Prognostic factors were investigated among patients who recurred within 5 years versus long-term survivors who survived more than 5 years with no recurrence. RESULTS: Among 635 patients who underwent curative-intent resection for ICC, 104 (16.4%) patients were long-term survivors with no recurrence beyond 5 years after surgery. Patients who survived for more than 5 years with no recurrence were more likely to have less aggressive tumor features, as well as have undergone an R0 resection versus patients who recurred within 5 years after resection. On multivariable analysis, tumor size (>5 cm) (HR: 1.535, 95% CI: 1.254-1.879), satellite lesions (HR: 1.253, 95% CI: 1.003-1.564), and lymph node metastasis (HR: 1.733, 95% CI: 1.349-2.227) were independently associated with recurrence within 5 years. Patients who recurred beyond 5 years (n = 23), 2-5 years (n = 60), and within 2 years (n = 471) had an incrementally worse post-recurrence survival (PRS, 28.0 vs. 20.0 vs. 12.0 months, p = 0.032). Among patients with N0 status, tumor size (>5 cm) (HR: 1.612, 95% CI: 1.087-2.390) and perineural invasion (PNI) (HR: 1.562,95% CI: 1.081-2.255) were risk factors associated with recurrence. Among patients with N1 disease, only a minority (5/128, 3.9%) of patients survived with no recurrence to 5 years. CONCLUSION: Roughly 1 in 6 patients survived for more than 5 years with no recurrence following curative-intent resection of ICC. Among N0 patients, tumor recurrence was associated with tumor size and PNI. Only a small subset of N1 patients experienced long-term survival.

TWIK-related acid-sensitive potassium channels TASK-1 and TASK-3 may participate in the process of the coexistence of asthma and OSA.

OBJECTIVE: To investigate the role of TWIK-related acid-sensitive potassium channels TASK-1 and TASK-3 in the mechanism of asthma combined with obstructive sleep apnea (OSA) in mice. METHOD: C57BL/6 mice were randomly divided into four groups: control group (NS-RA), asthma group (OVA-RA), OSA group (NS-IH), and asthma combined with OSA group (OVA-IH). After monitoring lung function in each group, the expression levels of TASK-1 and TASK-3 mRNA and protein in lung tissues were measured, and the correlation between the changes of both and lung function was analyzed. RESULTS: A total of 64 male mice were studied. Penh, serum IgE concentrations, and the percentage of eosinophils in bronchoalveolar lavage fluid (BALF) were higher in OVA-RA and OVA-IH mice compared with NS-RA (P < 0.05),while the above indexes were slightly elevated in NS-IH mice compared with NS-RA (P > 0.05), where the Penh and the percentage of eosinophils in BALF was higher in OVA-IH mice than NS-IH (P < 0.05).Increased TASK-3 mRNA expression (P < 0.05) as well as TASK-1 and TASK-3 protein expression (P > 0.05) in lung tissues of OVA-RA and NS-IH mice compared with NS-RA, and TASK-3 mRNA expression was slightly more in the OVA-IH group compared with NS-RA (P > 0.05), but less compared with OVA-RA (P < 0.05) or NS-IH (P > 0.05), while TASK-1 and TASK-3 protein expression was increased in the OVA-IH group compared with the remaining three groups, and TASK-3 protein expression was associated with lung function impairment was positively correlated with the degree of lung function impairment (P < 0.05). CONCLUSION: Task-1 and Task-3 may be involved in the pathogenesis of asthma with OSA by affecting lung function.

The association between human papillomavirus infection, vaginal microecology, and cervical intraepithelial neoplasia in women from Xinjiang, China.

PURPOSE: This study analyzes the relationship between human papillomavirus (HPV) infection, vaginal microecology, and cervical lesions to provide a basis for the prevention and treatment of cervical cancer (CC) in the Xinjiang region. METHODS: Real-time quantitative PCR was used for HPV genotyping and viral load. The Gram staining and dry biochemical enzyme kit were utilized to diagnose vaginal secretions. The χ2 test and Logistic regression analysis were used for statistical analysis. RESULTS: The HPV infection rate among women in the Xinjiang region was 30.29%, of which the single HPV infection accounts for 77%. HPV16 and HPV52 were the main infection types. There was significant differences in the HPV infection rate and infection types among the Han, Uighur, Hui, and Kazakh ethnic groups. The viral load of HPV16 and HPV52 increases with the upgrade of cervical lesions. There were significant differences in vaginal microecology evaluation indicators H2O2, SNA, LE, GUS, trichomonas, clue cells, and lactobacilli among different ethnic groups. HPV negative patients with varying grades of cervical lesions exhibit a notable variance in H2O2 and LE, which is statistically significant. Single HPV infection and high viral load HPV significantly increase the risk of CC. CONCLUSIONS: This study indicates that HPV infection and vaginal microecology differ among ethnic groups, which have a strong correlation with the progression of CC, offering guidance on CC screening and interventions in the Xinjiang area.

Ambient Pressure Drying of Freeze-Cast Ceramics from Aqueous Suspension.

Freeze-casting has been wildly exploited to construct porous ceramics but usually requires costly and demanding freeze-drying (high vacuum, size limit, and supercooled chamber), which can be avoided by the ambient pressure drying (APD) technique. However, applying APD to freeze-cast ceramic based on an aqueous suspension is still challenging due to inert surface chemistry. Herein, a modified APD strategy is developed to improve the drying process of freeze-cast ceramics by exploiting the simultaneous ice etching, ionic cross-linking, and solvent exchange under mild conditions (-10-0 °C, ambient pressure). This versatile strategy is applicable to various ceramic species, metal ions, and freezing techniques. The incorporated metal ions not only enhance liquid-phase sintering, producing ceramics with higher density and mechanical properties than freeze-cast counterparts, but also render customizable coloration and antibacterial property. The cost-/time-efficient APD is promising for mass production and even successive production of large-size freeze-cast ceramics that exceed the size of commercial freeze-dryers.

Antimicrobial Activities of α-Helix and ß-Sheet Peptides against the Major Bovine Respiratory Disease Agent, Mannheimia haemolytica.

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in cattle raised in North America. At the feedlot, cattle are subject to metaphylactic treatment with macrolides to prevent BRD, a practice that may promote antimicrobial resistance and has resulted in an urgent need for novel strategies. Mannheimia haemolytica is one of the major bacterial agents of BRD. The inhibitory effects of two amphipathic, α-helical (PRW4, WRL3) and one ß-sheet (WK2) antimicrobial peptides were evaluated against multidrug-resistant (MDR) M. haemolytica isolated from Alberta feedlots. WK2 was not cytotoxic against bovine turbinate (BT) cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. All three peptides inhibited M. haemolytica, with WK2 being the most efficacious against multiple isolates. At 8-16 µg/mL, WK2 was bactericidal against Mh 330 in broth, and at 32 µg/mL in the presence of BT cells, it reduced the population by 3 logs CFU/mL without causing cytotoxic effects. The membrane integrity of Mh 330 was examined using NPN (1-N-phenylnaphthylamine) and ONPG (o-Nitrophenyl ß-D-galactopyranoside), with both the inner and outer membranes being compromised. Thus, WK2 may be a viable alternative to the use of macrolides as part of BRD prevention and treatment strategies.

Bioinspired Total Synthesis of Cephalotaxus Diterpenoids and Their Structural Analogues.

Herein, we present a unified chemical synthesis of three subgroups of cephalotaxus diterpenoids. Key to the success lies in adopting a synthetic strategy that is inspired by biosynthesis but is opposite in nature. By employing selective one-carbon introduction and ring expansion operations, we have successfully converted cephalotane-type C18 dinorditerpenoids (using cephanolide B as a starting material) into troponoid-type C19 norditerpenoids and intact cephalotane-type C20 diterpenoids. This synthetic approach has enabled us to synthesize cephinoid H, 13-oxo-cephinoid H, 7-oxo-cephinoid H, fortalpinoid C, 7-epi-fortalpinoid C, cephanolide E, and 13-epi-cephanolide E. Furthermore, through the development of an intermolecular asymmetric Michael reaction between ß-oxo esters and ß-substituted enones, we have achieved the enantioselective synthesis of advanced intermediates within our synthetic sequence, thus formally realizing the asymmetric total synthesis of the cephalotaxus diterpenoids family.

Sialyl Lewis X mediates interleukin-1 beta-induced trophoblast adhesion to endometrial cells during human embryo implantation.

Cell surface carbohydrate antigens sialyl Lewis X (sLeX) and Lewis Y (LeY) are paramount glycoconjugates and are abundantly expressed in the receptive endometrium. Furthermore, among the important biological functions of both antigens is their role in leukocytes adhesion and extravasation. Interleukin-1 beta (IL-1ß) is involved in the process of human embryo implantation and placenta development. Here, we used an in vitro model to investigate whether sLeX and LeY are playing a role in the embryo implantation process mediated by IL-1ß. Our results are showing that the expression of cell surface sLeX was enhanced in endometrial RL95-2 cells after exposure to IL-1ß. RT-qPCR detection indicated that the transcript level of glycosyltransferase gene fucosyltransferase 3 (FUT3) was significantly elevated and that of FUT4/7 and ST3 beta-galactoside alpha-2,3-sialyltransferase 3/4 (ST3GAL3/4) were decreased by treatment with IL-1ß. Modulatory role of glycosyltransferase FUT3 on sLeX biosynthesis was determined by FUT3 siRNA transfection in RL95-2 cells. Results showed that the expression level of sLeX was suppressed, but no change was observed in regard to LeY. Moreover, IL-1ß promoted the HTR-8/SVneo trophoblast spheroids attachment to the RL95-2 endometrial monolayer, which was partially blocked by anti-sLeX antibody and FUT3 knockdown. Gene expression analysis of the RNA-seq transcriptome data from human secretory endometrium demonstrated a significantly higher level of FUT3 in the mid-secretory phase compared to the early secretory phase, which was correlated with the expression of IL1B. In summary, the inflammatory microenvironment at the fetomaternal interface can regulate the glycosylation pattern of endometrial cells at the time of implantation. SLeX can be significantly induced by IL-1ß via increasing FUT3 expression, which facilitates the trophoblast adhesion during embryo implantation.

Phylogenomic analyses using a new 1013-gene Vitaceae bait-set support major groups of North American Vitis.

A set of newly designed Vitaceae baits targeting 1013 genes was employed to explore phylogenetic relationships among North American Vitis. Eurasian Vitis taxa including Vitis vinifera were found to be nested within North American Vitis subgenus Vitis. North American Vitis subgenus Vitis can be placed into nine main groups: the Monticola group, the Occidentales group, the Californica group, the Vinifera group (introduced from Eurasia), the Mustangensis group, the Palmata group, the Aestivalis group, the Labrusca group, and the Cinerea group. Strong cytonuclear discordances were detected in North American Vitis, with many species non-monophyletic in the plastid phylogeny, while monophyletic in the nuclear phylogeny. The phylogenomic analyses support recognizing four distinct species in the Vitis cinerea complex in North America: V. cinerea, V. baileyana, V. berlandieri, and V. simpsonii. Such treatment will better serve the conservation of wild Vitis diversity in North America. Yet the evolutionary history of Vitis is highly complex, with the concordance analyses indicating conflicting signals across the phylogeny. Cytonuclear discordances and Analyses using the Species Networks applying Quartets (SNaQ) method support extensive hybridizations in North American Vitis. The results further indicate that plastid genomes alone are insufficient for resolving the evolutionary history of plant groups that have undergone rampant hybridization, like the case in North American Vitis. Nuclear gene data are essential for species delimitation, identification and reconstructing evolutionary relationships; therefore, they are imperative for plant phylogenomic studies.

Practical security analysis of a continuous-variable source-independent quantum random number generator based on heterodyne detection.

Heterodyne-based continuous-variable source-independent quantum random number generator (CV-SI-QRNG) can produce true random numbers without any assumptions on source. However, practical implementations always contain imperfections, which will greatly influence the extractable randomness and even open loopholes for eavesdroppers to steal information about the final output. In this work, based on the theoretical model, we systematically analyzed the effects of imperfect implementations on the practical security of heterodyne-based CV-SI-QRNG. The influences of local oscillator (LO) fluctuation under imbalanced heterodyne detection are first analyzed. The simulation results show that the lower bound of extractable randomness will be overestimated without considering the influence of LO fluctuation, which will threaten the practical security of CV-SI-QRNG system. Moreover, we analyze the effects of the degree of imbalance and the magnitude of LO fluctuation on evaluating the extractable randomness. Finally, we investigate the impact of an imperfect phase modulator on the practical security of CV-SI-QRNG and find it will reduce the extractable randomness. Our analysis reveals that one should carefully consider the imperfections in the actual implementations of CV-SI-QRNGs.

Sodium Tanshinone IIA Sulfonate Ameliorates Oxygen-glucose Deprivation/Reoxygenation-induced Neuronal Injury via Protection of Mitochondria and Promotion of Autophagy.

Sodium tanshinone IIA sulfonate (STS) has shown significant clinical therapeutic effects in cerebral ischemic stroke (CIS), but the molecular mechanisms of neuroprotection remain partially known. The purpose of this study was to explore whether STS plays a protective role in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury by regulating microglia autophagy and inflammatory activity. Co-cultured microglia and neurons were subjected to OGD/R injury, an in vitro model of ischemia/reperfusion (I/R) injury with or without STS treatment. Expression of protein phosphatase 2 A (PP2A) and autophagy-associated proteins Beclin 1, autophagy related 5 (ATG5), and p62 in microglia was determined by Western blotting. Autophagic flux in microglia was observed with confocal laser scanning microscopy. Neuronal apoptosis was measured by flow cytometric and TUNEL assays. Neuronal mitochondrial function was determined via assessments of reactive oxygen species generation and mitochondrial membrane potential integrity. STS treatment markedly induced PP2A expression in microglia. Forced overexpression of PP2A increased levels of Beclin 1 and ATG5, decreased the p62 protein level, and induced autophagic flux. Silencing of PP2A or administration of 3-methyladenine inhibited autophagy and decreased the production of anti-inflammatory factors (IL-10, TGF-ß and BDNF) and induced the release of proinflammatory cytokines (IL-1ß, IL-2 and TNF-α) by STS-treated microglia, thereby inducing mitochondrial dysfunction and apoptosis of STS-treated neurons. STS exerts protection against neuron injury, and the PP2A gene plays a crucial role in improving mitochondrial function and inhibiting neuronal apoptosis by regulating autophagy and inflammation in microglia.

Synthesis of α-Difluoromethylene Ethers via Photoredox-Induced Hyperconjugative Ring Opening of gem-Difluorocyclopropanes.

Fluorinated compounds have found widespread applications in pharmaceuticals, agrochemicals, and materials science. Precise construction of α-difluoromethylene ether (CF2-O) moiety in organic molecules is of high demand. Herein, a visible light-promoted reaction protocol for the synthesis of α-difluoromethylene ether from gem-difluorocyclopropane is described. The key ring-opening step is induced by hyperconjugative interaction of cyclopropane with photo-oxidized aromatic rings. This reaction is easy scale-up, and the products bearing a synthetic handle enable their further manipulation.

Quercetin inhibits the amphiregulin/EGFR signaling-mediated renal tubular epithelial-mesenchymal transition and renal fibrosis in obstructive nephropathy.

Quercetin is a widely distributed, bioactive flavonoid compound, which displays potential to inhibit fibrosis in several diseases. The purpose of our study was to determine the effect of quercetin treatment on renal fibrosis and investigate the mechanism. Human proximal tubular epithelial cells (HK-2) stimulated by transforming growth factor-ß1 (TGF-ß1) and a rat model of unilateral ureter obstruction (UUO) that contributes to fibrosis were used to investigate the role and molecular mechanism of quercetin. PD153035 (N-[3-Bromophenyl]-6,7-dimethoxyquinazolin-4-amine) was used to inactivate EGFR (epidermal growth factor receptor). The level of fibrosis, proliferation, apoptosis, and oxidative stress in HK-2 were measured. All data are presented as means ± standard deviation (SD). p-value < .05 was considered statistically significant. In UUO rats, quercetin reduced the area of fibrosis as well as inflammation, oxidative stress, and cell apoptosis. In cultured HK-2 cells, quercetin significantly ameliorated the EMT induced by TGF-ß1, which was accompanied by increased amphiregulin (AREG) expression. Moreover, quercetin inhibited AREG binding to the EGFR receptor, thereby further affecting other downstream pathways. Quercetin may alleviate fibrosis in vitro and in vivo by inhibiting the activation of AREG/EGFR signaling indicating a potential therapeutic effect of quercetin in renal fibrosis.

Effects of Three Essential Oil Fumigation Treatments on the Postharvest Control of Botrytis cinerea and Their Efficacy as Preservatives of Cherry Tomatoes.

Cherry tomatoes (Solanum lycopersicum) are becoming increasingly popular due to their nutrition and delicious flavor. However, cherry tomatoes are highly perishable and susceptible to various pathogenic microorganisms after harvest, such as Botrytis cinerea. In the pretest experiment, we screened out three kinds of plant essential oils (EOs) (Torreya grandis oil, Eriobotrya japonica oil, and Citrus medica oil) that have strong fungicidal activity on B. cinerea from cherry tomatoes. To further evaluate the postharvest preservation application prospect of these three oils for cherry tomatoes, the oils were extracted from different parts of three plants by hydrodistillation, and their chemical constituents were analyzed by gas chromatography-mass spectrometry. The main representative components of T. grandis oil, E. japonica oil, and C. medica oil were δ-cadinene (11.76%), transnerolidol (9.70%), and 5,7-dimethoxycoumarin (23.22%), respectively. These three EOs effectively inhibited the mycelial growth of B. cinerea in vitro, with EC50 values of 81.672, 144.046, and 221.500 µl/liter, respectively. Compared with the blank control and other oil treatments, the T. grandis oil (at a concentration of 200 µl/liter) fumigation treatment was more effective at inhibiting the growth rate of the pathogen. In addition, the phenolic content and phenylalanine ammonia lyase, ß-1,3-glucanase, chitinase, and peroxidase activities of tomatoes significantly increased on the seventh day due to the T. grandis oil treatment. The present study shows that these three oils with high extraction rates have preservation potential for cherry tomatoes. Among these three EOs, T. grandis oil can be used to further develop preservative products as a fumigant.

Comparison of biliary protein spectrum in gallstone patients with obesity and those with normal body weight.

BACKGROUND: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile proteomics differences between cholelithiasis patients with obesity and normal body weight. METHODS: Bile samples from 20 patients (10 with obesity and 10 with normal body weight) who underwent laparoscopic cholecystectomy at our center were subjected to tandem mass tag labeling (TMT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), followed by further bioinformatic analysis. RESULTS: Among the differentially-expressed proteins, 23 were upregulated and 67 were downregulated. Bioinformatic analysis indicated that these differentially-expressed proteins were mainly involved in cell development, inflammatory responses, glycerolipid metabolic processes, and protein activation cascades. In addition, the activity of the peroxisome proliferator-activated receptor (PPAR, a subfamily of nuclear receptors) signaling pathway was decreased in the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Two downregulated proteins in the PPAR signaling pathway, APOA-I and APOA-II, were confirmed using enzyme-linked immunosorbent assay. CONCLUSIONS: The PPAR signaling pathway may play a crucial role in the development of cholelithiasis among patients with obesity. Furthermore, biliary proteomics profiling of gallstones patients with obesity is revealed, providing a reference for future research.

Optimization of fermentation medium and conditions for enhancing valinomycin production by Streptomyces sp. ZJUT-IFE-354.

Valinomycin is a cyclodepsipeptide antibiotic with a broad spectrum of biological activities, such as antiviral, antitumor, and antifungal activities. However, the low yield of valinomycin often limits its applications in medicine, agriculture, and industry. In our previous report, Streptomyces sp. ZJUT-IFE-354 was identified as a high-yielding strain of valinomycin. In this study, Plackett-Burman design (PBD) and response surface methodology (RSM) were used to optimize components of medium. The optimal medium contained 31 g/L glucose, 22 g/L soybean meal, and 1.6 g/L K2HPO4·3H2O, which could generate 262.47 ± 4.28 mg/L of valinomycin. Then, the culture conditions were optimized by a one-factor-at-a-time (OFAT) approach. The optimal conditions for the strain included a seed age of 24 h, an inoculum size of 8% (v/v), an incubation temperature of 28 °C, an initial pH of 7.2, an elicitor of 0.1% Bacillus cereus feeding at 24 h cultivation, and the feeding of 0.6% L-valine at 36 h cultivation. The final valinomycin production increased to 457.23 ± 9.52 mg/L, which was the highest yield ever reported. It highlights that RSM and OFAT may be efficient methods to enhance valinomycin production by Streptomyces sp. ZJUT-IFE-354.

Climate-influenced boreotropical survival and rampant introgressions explain the thriving of New World grapes in the north temperate zone.

The north temperate region was characterized by a warm climate and a rich thermophilic flora before the Eocene, but early diversifications of the temperate biome under global climate change and biome shift remain uncertain. Moreover, it is becoming clear that hybridization/introgression is an important driving force of speciation in plant diversity. Here, we applied analyses from biogeography and phylogenetic networks to account for both introgression and incomplete lineage sorting based on genomic data from the New World Vitis, a charismatic component of the temperate North American flora with known and suspected gene flow among species. Biogeographic inference and fossil evidence suggest that the grapes were widely distributed from North America to Europe during the Paleocene to the Eocene, followed by widespread extinction and survival of relicts in the tropical New World. During the climate warming in the early Miocene, a Vitis ancestor migrated northward from the refugia with subsequent diversification in the North American region. We found strong evidence for widespread incongruence and reticulate evolution among nuclear genes within both recent and ancient lineages of the New World Vitis. Furthermore, the organellar genomes showed strong conflicts with the inferred species tree from the nuclear genomes. Our phylogenomic analyses provided an important assessment of the wide occurrence of reticulate introgression in the New World Vitis, which potentially represents one of the most important mechanisms for the diversification of Vitis species in temperate North America and even the entire temperate Northern Hemisphere. The scenario we report here may be a common model of temperate diversification of flowering plants adapted to the global climate cooling and fluctuation in the Neogene.