Donor-Acceptor Interactions Enhanced Colorimetric Sensors for Both Acid and Base Vapor Based on Two-Dimensional Covalent Organic Frameworks.

Due to the high surface area and uniform porosity of covalent organic frameworks (COFs), they exhibit superior properties in capturing and detecting even trace amounts of gases in the air. However, the COFs materials that possess dual detected functionality are still less reported. Here, an imine-based COF containing thiophene as a donor and triazine as an acceptor to form spatial-distribution-defined D-A structures was prepared. D-A system between thiophene and triazine facilitates the charge transfer process during the protonation process of the imine and the triazine units. The obtained COF exhibits simultaneous sensing ability toward both acidic and alkaline vapors with obvious colorimetric sensing functionality.

SYNBIP: synthetic binding proteins for research, diagnosis and therapy.

The success of protein engineering and design has extensively expanded the protein space, which presents a promising strategy for creating next-generation proteins of diverse functions. Among these proteins, the synthetic binding proteins (SBPs) are smaller, more stable, less immunogenic, and better of tissue penetration than others, which make the SBP-related data attracting extensive interest from worldwide scientists. However, no database has been developed to systematically provide the valuable information of SBPs yet. In this study, a database named 'Synthetic Binding Proteins for Research, Diagnosis, and Therapy (SYNBIP)' was thus introduced. This database is unique in (a) comprehensively describing thousands of SBPs from the perspectives of scaffolds, biophysical & functional properties, etc.; (b) panoramically illustrating the binding targets & the broad application of each SBP and (c) enabling a similarity search against the sequences of all SBPs and their binding targets. Since SBP is a human-made protein that has not been found in nature, the discovery of novel SBPs relied heavily on experimental protein engineering and could be greatly facilitated by in-silico studies (such as AI and computational modeling). Thus, the data provided in SYNBIP could lay a solid foundation for the future development of novel SBPs. The SYNBIP is accessible without login requirement at both official (https://idrblab.org/synbip/) and mirror (http://synbip.idrblab.net/) sites.

VARIDT 2.0: structural variability of drug transporter.

The structural variability data of drug transporter (DT) are key for research on precision medicine and rational drug use. However, these valuable data are not sufficiently covered by the available databases. In this study, a major update of VARIDT (a database previously constructed to provide DTs' variability data) was thus described. First, the experimentally resolved structures of all DTs reported in the original VARIDT were discovered from PubMed and Protein Data Bank. Second, the structural variability data of each DT were collected by literature review, which included: (a) mutation-induced spatial variations in folded state, (b) difference among DT structures of human and model organisms, (c) outward/inward-facing DT conformations and (d) xenobiotics-driven alterations in the 3D complexes. Third, for those DTs without experimentally resolved structural variabilities, homology modeling was further applied as well-established protocol to enrich such valuable data. As a result, 145 mutation-induced spatial variations of 42 DTs, 1622 inter-species structures originating from 292 DTs, 118 outward/inward-facing conformations belonging to 59 DTs, and 822 xenobiotics-regulated structures in complex with 57 DTs were updated to VARIDT (https://idrblab.org/varidt/ and http://varidt.idrblab.net/). All in all, the newly collected structural variabilities will be indispensable for explaining drug sensitivity/selectivity, bridging preclinical research with clinical trial, revealing the mechanism underlying drug-drug interaction, and so on.

NPCDR: natural product-based drug combination and its disease-specific molecular regulation.

Natural product (NP) has a long history in promoting modern drug discovery, which has derived or inspired a large number of currently prescribed drugs. Recently, the NPs have emerged as the ideal candidates to combine with other therapeutic strategies to deal with the persistent challenge of conventional therapy, and the molecular regulation mechanism underlying these combinations is crucial for the related communities. Thus, it is urgently demanded to comprehensively provide the disease-specific molecular regulation data for various NP-based drug combinations. However, no database has been developed yet to describe such valuable information. In this study, a newly developed database entitled 'Natural Product-based Drug Combination and Its Disease-specific Molecular Regulation (NPCDR)' was thus introduced. This database was unique in (a) providing the comprehensive information of NP-based drug combinations & describing their clinically or experimentally validated therapeutic effect, (b) giving the disease-specific molecular regulation data for a number of NP-based drug combinations, (c) fully referencing all NPs, drugs, regulated molecules/pathways by cross-linking them to the available databases describing their biological or pharmaceutical characteristics. Therefore, NPCDR is expected to have great implications for the future practice of network pharmacology, medical biochemistry, drug design, and medicinal chemistry. This database is now freely accessible without any login requirement at both official (https://idrblab.org/npcdr/) and mirror (http://npcdr.idrblab.net/) sites.

Survival Outcomes and Safety of Programmed Cell Death/Programmed Cell Death Ligand 1 Inhibitors for Unresectable Hepatocellular Carcinoma: Result From Phase III Trials.

Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. The aim of this study was conducted a meta-analysis to assess the efficacy and safety of PD-1/PD-L1 inhibitors in patients with unresectable hepatocellular carcinoma (uHCC). A total of 1657 patients were included. The completed phase III trials with details data, such as overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse effects (AEs) were included. The pooled hazard ratio (HR) of OS and PFS were .75 (95% CI: .61-.92) and .74 (95% CI: .56-.97) with heterogeneity between PD-1/PD-L1 inhibitors groups and control groups. Sensitivity analysis revealed IMbrave-150 could be the most important factor of heterogeneity for OS, while CheckMate-459 was the main fact of heterogeneity for PFS. In addition, the relative risk (RR) of ORR and DCR were 2.43 (95% CI: 1.80-3.26) and 1.26 (95% CI: 1.11-1.43) with low heterogeneity in PD-1/PD-L1 inhibitors groups. The therapeutic effect of PD-1/PD-L1 inhibitors was better in females, Asia without Japan, BCLC status C and infected hepatitis groups. The RR of AEs from any cause and serious adverse events (SAEs) for patients receiving PD-1/PD-L1 inhibitors were 1.03 (95% CI: .93-1.13) and 1.13 (95% CI: .89-1.44), respectively. Pruritus was the most common AEs reported in 10% of patients or more (RR = 1.69, 95% CI: 1.33-2.15). In conclusion, PD-L1 inhibitor combined with anti-VEGF antibody could improve the prognosis of patients with uHCC. However, caution should be taken for AEs during patients receiving PD-1/PD-L1 inhibitors.

Pancreas grafts for transplantation from donors with hypertension: an analysis of the scientific registry of transplant recipients database.

BACKGROUND: With the rising demands for pancreas transplantation, surgeons are trying to extend the donors pool and set up a more appropriate assessment system. We aim to evaluate the effect of donor hypertension on recipient overall and graft survival rates. METHODS: Twenty-four thousand one hundred ninety-two pancreas transplantation patients from the Scientific Registry of Transplant Recipients database were subdivided into hypertension group (HTN, n = 1531) and non-hypertension group (non-HTN, n = 22,661) according to the hypertension status of donors. Recipient overall and graft survival were analyzed and compared by log rank test, and hazard ratios of predictors were estimated using Cox proportional hazard models. RESULTS: Patient overall and graft survival of non-HTN group were higher than that of the HTN group (both p < 0.001). The duration of hypertension negatively influenced both overall and graft survival rates (both p < 0.001). Multivariate analyses demonstrated that hypertension was an independent factor for reduced survival (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.01-1.18; p < 0.001). Other independent factors included recipient body mass index (HR, 1.02; 95% CI, 1.01-1.05; p < 0.001) and transplant type (pancreas after kidney transplants / pancreas transplant alone vs. simultaneous pancreas-kidney transplants; HR, 1.41; 95% CI, 134-1.55; p < 0.001). CONCLUSIONS: Donor hypertension is an independent factor for recipient survival after pancreas transplantation and could be considered in donor selection as well as post-transplant surveillance in clinical practice.

Accelerating two-dimensional nuclear magnetic resonance correlation spectroscopy via selective coherence transfer.

Nuclear magnetic resonance (NMR) spectroscopy serves as an important tool for both qualitative and quantitative analyses of various systems in chemistry, biology, and medicine. However, applications of one-dimensional 1H NMR are often restrained by the presence of severe overlap among different resonances. The advent of two-dimensional (2D) 1H NMR constitutes a promising alternative by extending the crowded resonances into a plane and thereby alleviating the spectral congestions. However, the enhanced ability in discriminating resonances is achieved at the cost of extended experimental duration due to necessity of various scans with progressive delays to construct the indirect dimension. Therefore, in this study, we propose a selective coherence transfer (SECOT) method to accelerate acquisitions of 2D correlation spectroscopy by converting chemical shifts into spatial positions within the effective sample length and then performing an echo planar spectroscopic imaging module to record the spatial and spectral information, which generates 2D correlation spectrum after 2D Fourier transformation. The feasibility and effectiveness of SECOT have been verified by a set of experiments under both homogeneous and inhomogeneous magnetic fields. Moreover, evaluations of SECOT for quantitative analyses are carried out on samples with a series of different concentrations. Based on these experimental results, the SECOT may open important perspectives for fast, accurate, and stable investigations of various chemical systems both qualitatively and quantitatively.

Relationship between Insulin Levels and Nonpsychotic Dementia: A Systematic Review and Meta-Analysis.

Objectives: To explore the relationship between insulin levels and nonpsychotic dementia. Methods: Six electronic databases (PubMed, Cochrane, SCI, CNKI, VIP, and Wanfang) were searched from January 1, 2007, to March 1, 2017. Experimental or observational studies that enrolled people with nonpsychotic dementia or abnormal insulin levels in which insulin levels or MMSE scores (events in nonpsychotic dementia) were the outcome measures. Random-effects models were chosen for this meta-analysis. Sample size, mean, s.d., and events were primarily used to generate effect sizes (with the PRIMA registration number CRD42017069860). Results: 50 articles met the final inclusion criteria. Insulin levels in cerebrospinal fluid were lower (Hedges' g = 1.196, 95% CI = 0.238 to 2.514, and P = 0.014), while the levels in peripheral blood were higher in nonpsychotic dementia patients (Hedges' g = 0.853 and 95% CI = 0.579 to 1.127), and MMSE scores were significantly lower in the high insulin group than in the healthy control group (Hedges' g = 0.334, 95% CI = 0.249 to 0.419, and P = 0.000). Conclusions: Our comprehensive results indicate that blood insulin levels may increase in patients with nonpsychotic dementia.

Effects of Refined Xiaoyaosan on Depressive-Like Behaviors in Rats with Chronic Unpredictable Mild Stress through Neurosteroids, Their Synthesis and Metabolic Enzymes.

Abstract: To observe the effects of refined Xiaoyaosan (XYS) on the depressive-like behaviors in rats with chronic unpredictable mild stress (CUMS), and to explore the relationship between the changes of neurosteroids and mRNA expressions of their synthesis and metabolic enzymes, and the mechanism of XYS in the treatment of depression. Methods: Eighty-four healthy male Sprague-Dawley rats were randomly divided into normal group, model group, XYS group and fluoxetine group. The latter three groups were subjected to 21 days of CUMS to prepare the stress depression model. Rats in the XYS group, and fluoxetine group were given intragastric administration with refined XYS and fluoxetine, respectively. The behavioral changes of the rats were observed after 21 days. The contents of pregnenolone (PREG), progesterone (PROG) and alloprognanolone (ALLO) in the plasma of rats were measured by ELISA. The levels of PREG, PROG and ALLO in the hippocampus and amygdala tissues were measured by LC-MS/MS. The mRNA expressions of 3α-hydroxysteroid dehydrogenase (3α-HSD), 3ß-hydroxysteroid dehydrogenase (3ß-HSD), cholesterol side-chain cleavage enzyme (P450scc) and 5α-reductase (5a-R) in the hippocampus and amygdala were detected by RT-qPCR methods. Results: There were changes in the model rats. The contents of PREG, PROG and ALLO changed similarly, which reflected in the decrease of PROG and ALLO, and the increase of PREG. The mRNA expression of P450scc was increased, and the mRNA expressions of 3α-HSD, 3ß-HSD and 5a-R were decreased. Refined XYS could improve the behaviors of rats and the biological indicators. Conclusions: There is a neurosteroid dysfunction in the brain region of depression rat model animals, and the mechanism of refined XYS depression treatment may be related to the regulation of the control of mRNA expression of related synthesis and metabolic enzymes in the hippocampus and amygdala, further affecting the contents of neurosteroids.

Partial-Homogeneity-Based Two-Dimensional High-Resolution Nuclear Magnetic Resonance Spectroscopy under Inhomogeneous Magnetic Fields.

High-resolution multidimensional nuclear magnetic resonance (NMR) spectroscopy serves as an irreplaceable and versatile tool in various chemical investigations. In this study, a method based on the concept of partial homogeneity is developed to offer two-dimensional (2D) high-resolution NMR spectra under inhomogeneous fields. Oscillating gradients are exerted to encode the high-resolution information, and a field-inhomogeneity correction algorithm based on pattern recognition is designed to recover high-resolution spectra. Under fields where inhomogeneity primarily distributes along a single orientation, the proposed method will improve performances of 2D NMR spectroscopy without increasing the experimental duration or significant loss in sensitivity, and thus may open important perspectives for studies of inhomogeneous chemical systems.

A method based on covariance and pattern recognition for improving resolutions of spatially encoded NMR spectra.

The spatially encoded technique enables the fast acquisition of two-dimensional (2D) nuclear magnetic resonance spectrum within a single scan, serving as a powerful tool for studying various systems and phenomena in short time scales. In spatially encoded spectroscopy, the resolution in the direct dimension can be enhanced by increasing effective acquisition times. However, spectral widths and resolutions in indirect dimensions are no longer independent of each other with wider spectral widths yielding lower resolution. The covariance method, which has achieved success in enhancing resolutions in the indirect dimensions of conventional 2D spectroscopy, is employed here to improve resolutions in the spatially encoded dimension. Moreover, an algorithm is developed based on pattern recognition to eliminate artifacts arising from the employment of the covariance method and experimental imperfections in recording the spatially encoded spectra. Therefore, high-resolution homonuclear 2D correlated spectra are obtained. Experiments are performed to show the feasibility and effectiveness of this proposed method in providing high-resolution spectra within greatly shortened times.

Non-coding RNAs in hepatocellular carcinoma metastasis: Remarkable indicators and potential oncogenic mechanism.

Non-coding RNAs (ncRNAs), as key regulators involving in intercellular biological processes, are more prominent in many malignancies, especially for hepatocellular carcinoma (HCC). Herein, we conduct a comprehensive review to summarize diverse ncRNAs roles in HCC metastatic mechanism. We focus on four signaling pathways that predominate in HCC metastatic process, including Wnt/ß-catenin, HIF-1α, IL-6, and TGF-ß pathways. MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) employed different mechanisms to participate in the regulation of the key genes in these pathways, typical as interaction with DNA to control transcription, with RNA to control translation, and with protein to control stability. Therefore, ncRNAs may become potential biomarkers and therapeutic targets for HCC metastasis.

Methicillin-resistant Staphylococcus aureus bacteremia during the coronavirus disease 2019 (COVID-19) pandemic: Trends and distinguishing characteristics among patients in a healthcare system in New York City.

During the pandemic, the rate of healthcare facility-onset methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was 5 times greater in patients admitted with coronavirus disease 2019 (COVID-19). The presence of central lines and mechanical ventilation likely contribute to this increased rate. The number of central-line-associated bacteremia cases may be underestimated in patients with COVID-19.

Xiaoyaosan ameliorates depressive-like behavior and susceptibility to glucose intolerance in rat: involvement of LepR-STAT3/PI3K pathway in hypothalamic arcuate nucleus.

BACKGROUND: Accumulating evidence has demonstrated that arcuate nucleus (ARC) of the hypothalamus is likely responsible for the close association between chronic stress, depression, and diabetes. Xiaoyaosan (XYS), a Chinese herbal formula, remarkably improves depressive-like behavior and glucose intolerance, but the mechanism remains unclear. Leptin receptor (LepR) regulates energy expenditure and depression by mediating the action of leptin on the ARC. Therefore, we hypothesized that XYS may regulate depressive-like behavior and glucose intolerance via the leptin and its cascade LepR-STAT3/PI3K pathway in the ARC. METHODS: A rat model of depressive-like behavior and susceptibility to glucose intolerance was induced by exposure to chronic unpredictable mild stress (CUMS) for six weeks. XYS (2.224 g/kg) was orally gavaged for six weeks, and fluoxetine (2.0 mg/kg) was administrated to the positive control group. Depressive-like behaviors were assessed using the open field test (OFT), sucrose preference test (SPT) and forced swim test (FST). Fasting blood glucose (FBG) and oral glucose tolerance test (OGTT) were performed to evaluate the effects of XYS on blood glucose. Peripheral leptin and blood lipids were detected using enzyme-linked immunosorbent assay and an automatic biochemical analyzer, respectively. The effects of XYS on the LepR-STAT3/PI3K pathway were detected by quantitative real-time PCR and western blotting. RESULTS: XYS ameliorated CUMS-induced depressive-like behaviors and elevated blood glucose. XYS improved the food intake but have no significant effects on the body weight. Peripheral leptin and its central receptor were also suppressed by XYS, accompanied by the downregulation of JAK2/STAT3 and PI3K/AKT pathway in the ARC. Additionally, XYS increased AGRP and NPY expression but inhibited POMC in the ARC. CONCLUSIONS: XYS improves depressive-like behaviors and susceptibility to glucose intolerance induced by CUMS, which may be achieved by the downregulation of the LepR-STAT3/PI3K signaling pathway in the ARC.

The Study on the Influence of Green Inclusive Leadership on Employee Green Behaviour.

As a result of the implementation of the "double carbon" strategy, the issue of how to encourage green behaviour has become a prominent one in society. According to the cognitive-affective processing system theory, this study constructs two paths through which green inclusive leadership influences employee green behaviours: the cognitive pathway mediated by pro-environmental goals clarity and the affective way mediated by green organization identification. Data analysis of 372 employees in chemical enterprises reveals that first, employees' perception of green inclusive leadership positively affects employee green behaviour; second, green inclusive leadership enhances employee awareness of environmental goals and green organization identification so that employees are more likely to behave environmentally; furthermore, green HRM practices positively moderate the relationship between green inclusive leadership and pro-environmental goals clarity, as well as positively moderate the relationship between green inclusive leadership and green organization identification. This study aims to provide theoretical and practical insight into how to promote the green development of organizations from the perspective of leadership style to facilitate green development.

The initial and lingering impact of coronavirus disease 2019 (COVID-19) on catheter-associated infections in a large healthcare system in New York City.

Catheter-related infections increased during surges of coronavirus disease 2019 (COVID-19) in an 11-hospital system in New York City. A disproportionate number of central-line infections occurred in larger hospitals. Patients with COVID-19 had shorter times from catheter insertion to infection and a higher incidence of infections with enterococci.

Trends in Clostridioides difficile infection across a public health hospital system in New York City 2019-2021: A cautionary note.

Contrary to national reports, rates of healthcare facility-onset Clostridioides difficile infection across an 11-hospital system rose after the spring of 2020, when New York City was the epicenter for the COVID-19 pandemic. Antibiotic pressure from an escalation in cephalosporin usage correlated with this increase. The majority of cases of Clostridioides difficile were in patients without COVID-19, suggesting the pandemic has adversely impacted the healthcare of other inpatients.

DeepSPIO: Super Paramagnetic Iron Oxide Particle Quantification Using Deep Learning in Magnetic Resonance Imaging.

The susceptibility of super paramagnetic iron oxide (SPIO) particles makes them a useful contrast agent for different purposes in MRI. These particles are typically quantified with relaxometry or by measuring the inhomogeneities they produced. These methods rely on the phase, which is unreliable for high concentrations. We present in this study a novel Deep Learning method to quantify the SPIO concentration distribution. We acquired the data with a new sequence called View Line in which the field map information is encoded in the geometry of the image. The novelty of our network is that it uses residual blocks as the bottleneck and multiple decoders to improve the gradient flow in the network. Each decoder predicts a different part of the wavelet decomposition of the concentration map. This decomposition improves the estimation of the concentration, and also it accelerates the convergence of the model. We tested our SPIO concentration reconstruction technique with simulated images and data from actual scans from phantoms. The simulations were done using images from the IXI dataset, and the phantoms consisted of plastic cylinders containing agar with SPIO particles at different concentrations. In both experiments, the model was able to quantify the distribution accurately.

Optimization of metabolomic data processing using NOREVA.

A typical output of a metabolomic experiment is a peak table corresponding to the intensity of measured signals. Peak table processing, an essential procedure in metabolomics, is characterized by its study dependency and combinatorial diversity. While various methods and tools have been developed to facilitate metabolomic data processing, it is challenging to determine which processing workflow will give good performance for a specific metabolomic study. NOREVA, an out-of-the-box protocol, was therefore developed to meet this challenge. First, the peak table is subjected to many processing workflows that consist of three to five defined calculations in combinatorially determined sequences. Second, the results of each workflow are judged against objective performance criteria. Third, various benchmarks are analyzed to highlight the uniqueness of this newly developed protocol in (1) evaluating the processing performance based on multiple criteria, (2) optimizing data processing by scanning thousands of workflows, and (3) allowing data processing for time-course and multiclass metabolomics. This protocol is implemented in an R package for convenient accessibility and to protect users' data privacy. Preliminary experience in R language would facilitate the usage of this protocol, and the execution time may vary from several minutes to a couple of hours depending on the size of the analyzed data.

Postoperative Plasmacytoid Dendritic Cells Secrete IFNα to Promote Recruitment of Myeloid-Derived Suppressor Cells and Drive Hepatocellular Carcinoma Recurrence.

Patients with hepatocellular carcinoma (HCC) confront a high incidence of tumor recurrence after curative surgical resection. Hepatic ischemia-reperfusion injury (IRI) is the major consequence of surgical stress during hepatectomy. Although it has been suggested that hepatic IRI-induced immunosuppression could contribute to tumor relapse after surgery, the underlying mechanisms have not been fully defined. Here, using a multiplex cytokine array, we found that levels of postoperative IFNα serve as an independent risk factor for tumor recurrence in 100 patients with HCC with curative hepatectomy. Plasmacytoid dendritic cells (pDC), the major source of IFNα, were activated after surgery and correlated with poor disease-free survival. Functionally, IFNα was responsible for mobilization of myeloid-derived suppressor cells (MDSC) following hepatic IRI. Conditioned medium from IFNα-treated hepatocytes mediated the migration of MDSCs in vitro. Mechanistically, IFNα upregulated IRF1 to promote hepatocyte expression of CX3CL1, which subsequently recruited CX3CR1+ monocytic MDSCs. Knockdown of Irf1 or Cx3cl1 in hepatocytes significantly inhibited the accumulation of monocytic MDSCs in vivo. Therapeutically, elimination of pDCs, IFNα, or CX3CR1 could restore the tumor-killing activity of CD8+ T cells, hence limiting tumor growth and lung metastasis following hepatic IRI. Taken together, these data suggest that IFNα-producing pDCs drive CX3CR1+ MDSC recruitment via hepatocyte IRF1/CX3CL1 signaling and lead to tumor recurrence after hepatectomy in HCC. Targeting pDCs and the IFNα/CX3CL1/CX3CR1 axis could inhibit surgical stress-induced HCC recurrence by attenuating postoperative immunosuppression. SIGNIFICANCE: IFNα secreted by plasmacytoid dendritic cells drives postoperative immunosuppression and early recurrence of hepatocellular carcinoma, providing new biomarkers and therapeutic targets to improve patient outcomes after surgical resection.