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Intravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcome of such treatment remains unclear. This study evaluated the effectiveness of IVIG treatment in severe COVID-19 patients. This retrospective multicentre study evaluated 28-day mortality in severe COVID-19 patients with or without IVIG treatment. Each patient treated with IVIG was matched with one untreated patient. Logistic regression and inverse probability weighting (IPW) were used to control confounding factors. The study included 850 patients (421 IVIG-treated patients and 429 non-IVIG-treated patients). After matching, 406 patients per group remained. No significant difference in 28-day mortality was observed after IPW analysis (average treatment effect (ATE) = 0.008, 95% CI –0.081 to 0.097, p 0.863). There were no significant differences between the IVIG group and non-IVIG group for acute respiratory distress syndrome, diffuse intravascular coagulation, myocardial injury, acute hepatic injury, shock, acute kidney injury, non-invasive mechanical ventilation, invasive mechanical ventilation, continuous renal replacement therapy and extracorporeal membrane oxygenation except for prone position ventilation (ATE = –0.022, 95% CI –0.041 to –0.002, p 0.028). IVIG treatment was not associated with significant changes in 28-day mortality in severe COVID-19 patients. The effectiveness of IVIG in treating patients with severe COVID-19 needs to be further investigated through future studies. [ABSTRACT FROM AUTHOR]

In recent years, the low sensitivity caused by plasma quenching has restricted the development of LIBS technology in practical applications. In order to improve the sensitivity of the LIBS analysis method, we proposed a nanoparticle-assisted metal–organic framework (MOF) enhanced laser-induced breakdown spectroscopy, which combines a metal–organic framework (MOF), Au nanoparticles (AuNPs), and a portable LIBS instrument. Common metal ions in water were selected as the research objects to be tested by the proposed method. First, the synthesized three-dimensional (3D) MOF, namely [Zn2(L2)]2DMA·3H2O (complex 1) [H2L = 2-(imidazole-1-yl)terephthalic acid], was used to capture metal ions. Second, complex 1 loaded with metal ions induced AuNPs to aggregate on its surface. Third, the samples were attached to the glass substrate with double-sided tape and analyzed by LIBS. As a result, the limits of detection (LODs) for Pb and Cr obtained in this work were 8.0 and 4.2 ng mL−1, respectively, which were notably 8–10 times lower than those of the complex 1 enrichment method alone and 4 orders of magnitude lower than those of traditional LIBS methods. The significant improvement in LODs was also a new breakthrough for LIBS in liquid analysis. The great improvement in sensitivity can be mainly attributed to the unique microporous structure and the exposed metal binding sites of complex 1, which provide a huge space to accommodate metal ions. Also, the coupling action between laser electromagnetic fields and the surface plasmon of AuNPs greatly improved the laser ablation efficiency in the process of laser–matter interaction. Finally, the analysis of actual samples yielded good recoveries (92.8–99.0%) and reproducibility (lower than 11.9%), which shows the great potential of the combination of this method and portable LIBS in-field detection. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: A detailed chemical study on the Hainan soft coral Sinularia crass has resulted in the isolation and characterization of eleven casbane‐type diterpenoids, named sinucrassins A—K (1—11), along with six known related ones (12—17). Their structures were elucidated by extensive spectroscopic analyses and comparison with the reported data. The absolute configurations of new compounds were determined by the X‐ray diffraction analysis and computer‐assisted structural elucidation including 13C NMR data calculation and time‐dependent density functional theory/electronic circular dichroism calculation. [ABSTRACT FROM AUTHOR]

Anonymous authentication is an important step to protect vehicular privacy and security in VANETs. To improve the efficiency of anonymous authentication in multiple security domains, VANETs integrated with blockchain attracts extensive attention. However, the existing blockchain-based authentication schemes cannot effectively achieve anonymity because colluded RSUs or vehicles can achieve linkability via the same retrieved record to destroy anonymity. To address the issue, we propose an unlinkable authenticated key agreement with collusion resistant for VANETs. For the unlinkability of V2R, firstly, a trusted authority generates multiple tickets that hide the vehicle's identity and shares them by the blockchain network. Then, vehicle generates different pseudonyms by homomorphic encryption, and RSU uses different tickets to authenticate them. Meanwhile, in view of the unlinkability of the V2V, anonymous authenticated key agreement based on homomorphic properties is designed to enable vehicles to achieve authentication without retrieving any vehicular information. Security analysis and performance evaluation show that our scheme has strict unlinkability and enhanced anonymity as well as improves the efficiency of V2R and V2V by 10% and 50%, respectively. [ABSTRACT FROM AUTHOR]

T reg plays a pivotal role in the suppression of Th2 cell and the maintenance of immune homeostasis. The precise molecular mechanism underlying the disruption of T reg suppression of Th2 cell and the promotion of Th2 type inflammation in allergic diseases remains elusive. This study aims to investigate the molecular mechanism underlying quantitative and functional changes of T reg in AD. The molecular mechanism was investigated using flow cytometry, mRNA sequencing, co-culture experiments, co-immunoprecipitation, chromatin immunoprecipitation, and bisulfite sequencing in vitro or in AD mice model and patients with AD. Increased proportion of T reg was detected in mild and moderate AD. Conversely, characteristic decrease in both the number and CTLA-4 expression of T reg was relevant to serum IL-4 level in severe AD patients, which was verified under a high concentration of IL-4 treatment in vitro. The underlying mechanism is that IL-4/pSTAT6 pathway recruits DNMT1 and HDAC2 to inhibit transcriptional regulation of Foxp3 and CTLA-4 loci. High level of IL-4 impaired the suppression of T reg against Th2 cell differentiation mediated by CTLA-4, and blockade of IL-4Rα signaling in T reg restored T reg number and suppression of Th2 cell in AD model mice and patients with AD. The number of T reg is relevant to stratification of severity and serum IL-4 level in patients with AD. Abnormal high level of IL-4 epigenetically triggers a decrease in both the number and CTLA-4 expression of T reg. The reduced expression of CTLA-4 on T reg induced by IL-4 impairs suppression of Th2 cell differentiation. • The number of T reg is relevant to stratification of severity and serum IL-4 level in patients with AD. • High level of IL-4 epigenetically triggers a decrease in both the number and CTLA-4 expression of T reg in severe AD. • IL-4-induced reduction in both number and CTLA-4 expression of T reg impaired CTLA-4-mediated suppression of Th2 cell. • Blockade of IL-4Rα signaling in T reg restores T reg expression and its suppression of Th2 type inflammation in severe AD. [ABSTRACT FROM AUTHOR]

A novel copper-based metal-organic framework (Cu-MOF) with a large specific surface area and high porosity was synthesized. The Cu-MOF was a good peroxidase-mimicking enzyme and showed a high affinity with hydrogen peroxide in a wide pH range. The catalytic mechanism of Cu-MOF has been studied further based on comparing the characteristic of the Cu-MOF with some isomorphic MOFs. The catalytic activity center of Cu-MOF was determined to be the cupric ion rather than the ligand, which effectively promoted the generation of free radicals and electron transfer in the reaction progress. The high affinity of Cu-MOF to hydrogen peroxide proved it as an ideal catalyst for the chemiluminescence (CL) reaction involving hydrogen peroxide. Therefore, the CL method with high sensitivity could be established for detecting various substrates. A double-enzyme CL glucose biosensing platform was constructed for the determination of serum glucose employing the peroxidase-mimicking properties of Cu-MOF as well as glucose oxidase (GOx). [ABSTRACT FROM AUTHOR]

Venetoclax is a highly selective BCL2 inhibitor widely used in the treatment of leukemia, especially chronic lymphocytic leukemia and acute myeloid leukemia (AML). However, long-term use of venetoclax may lead to secondary drug resistance, which constitutes an important obstacle to prolonging the duration of the therapeutic response. Here, we show that the acquired resistance to venetoclax in human AML cell lines depends on NF-κB activation rather than on the upregulation of anti-apoptotic BCL2L1 expression. Moreover, alkaliptosis induced by the small molecular compound JTC801, but not necroptosis and ferroptosis, inhibits the growth of venetoclax-resistant AML cells in vitro and in xenograft mouse models. Mechanistically, NF-κB–mediated CA9 downregulation is required for intracellular pH upregulation, thereby inducing alkaliptosis in venetoclax-resistant cells. These findings provide a new strategy to selectively remove venetoclax-resistant AML cells. • BCL2L1 is not required for acquired resistance to venetoclax. • NF-κB is required for acquired resistance to venetoclax. • NF-κB–dependent alkaliptosis inhibits the growth of venetoclax-resistant cells. • JTC801 inhibits the growth of venetoclax-resistant cells in vivo. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a broad-spectrum antineoplastic drug; however, its serious cardiotoxic side effects in inflammatory responses limit its use in clinical applications. Dopamine D1 receptor (DRD1), a G protein-coupled receptor, is crucial for the development and function of the nervous system; additionally, it also play a role in immune regulation. However, the specific role of DRD1 in DOX-induced cardiac inflammation has not yet been clarified. Here, we discovered that DRD1 expression was induced by DOX treatment in H9C2 cardiomyocytes. DRD1 activation by A-68930, a DRD1-specific agonist, decreased DOX-induced nucleotide-binding domain-like receptor protein 3 (NLRP3) expression, caspase-1 activation, and IL-1β maturation in H9C2 cells. Expression of the cytokines IL-1β and IL-18 in the supernatants was also inhibited by A-68930 treatment. DRD1 knockdown, using siRNA, abolished the effects of A-68930 on the DOX-induced NLRP3 inflammasome. Furthermore, we found that DRD1 signaling downregulated the NLRP3 inflammasome in H9C2 cells through cyclic adenosine monophosphate (cAMP). Moreover, application of A-68930 to activate DRD1 reduced cardiac injury and fibrosis in a DOX-treated mouse model by suppressing the NLRP3 inflammasome in the heart. These findings indicate that DRD1 signaling may protect against DOX-induced cardiac injury by inhibiting the NLRP3 inflammasome-mediated inflammation. • DRD1 signaling protects against DOX-induced NLRP3 inflammasome-mediated inflammation in cardiomyocytes. • DRD1 inhibits NLRP3 inflammasome-mediated inflammation through cAMP signaling. • DRD1 agonist A-68930 treatment decreases DOX-induced cardiac injury and fibrosis by suppressing NLRP3 inflammasome. [ABSTRACT FROM AUTHOR]

The remarkable ability of certain molecules with a bent molecular shape to form hierarchically self-assembled helical building blocks with negative Gaussian or cylindrical curvature featuring in-layer hexatic ordering– so-called B4 phases – has quickly transformed these molecules into desirable building blocks for a variety of potential applications in optics, energy harvesting, and metamaterials. We here demonstrate that these building blocks, helical nanofilaments, helical microfilaments, and heliconical-layered nanocylinders, can to some degree be predictably blended. Supported by scanning as well as transmission electron microscopy and variable angle x-ray scattering data, the three bent-core compounds, each forming exactly one of these B4 morphologies, in binary mixtures at a 1:1 molar ratio, form either the third missing, or one of the two but with opposite handedness, or a random mixture of the two selected morphologies with larger overall dimensions. Furthermore, for two of the mixtures the a priori predicted handedness of the chiral filaments was experimentally confirmed. The third mixture with a priori predicted antagonistic handedness of the initial morphologies forms a combination of the two, one apparently achiral and the other one with opposite handedness. [ABSTRACT FROM AUTHOR]

Two new three-dimensional (3D) metal–organic frameworks (MOFs), namely {[Cu2(L)(4,4′-bipy)(OH)]·H2O}n (1) and {[Mn3(L)2(4,4′-bipy)(DMA)2]·H2O}n (2), were constructed by a newly synthesized thioether carboxylic acid ligand 5-((formic acid-3-sulfur)methyl)isophthalic acid (H3L) and 4,4′-bipyridine (4,4′-bipy). Thioether bonds in H3L can rotate freely in space, which are conducive in constructing MOFs with rich and stable structures. Simultaneously, the uncoordinated sulfur atoms affect the polarity of the framework and play an important role in adsorption. Gas adsorption results indicated that 1 can selectively adsorb CO2 from the mixture of CH4/CO2. Moreover, due to the high catalytic activity of [Cu4(COO)6N4O2] clusters, 1 is also an excellent recyclable catalyst that can chemically fix CO2 into cyclic carbonate under mild solvent-free conditions. Therefore, 1 may be explored as a dual-functional material for industrial adsorption and catalysis. [ABSTRACT FROM AUTHOR]

The stability analysis issue of switched positive systems (SPSs) with an impulse interval is discussed in this paper for the first time. All subsystems are allowed to be unstable. Unlike previous studies, the impulse is restricted to an interval, that is, the impulse interval. By dividing the state space on the nonnegative orthant and establishing multiple linear copositive Lyapunov functions, sufficient linear programming conditions are obtained to ensure that SPSs with an impulse interval are asymptotically stable. A hysteresis state-dependent switching law is designed to prevent the chattering behavior caused by frequent switching. Finally, two numerical examples are given to validate the theoretical findings. [ABSTRACT FROM AUTHOR]

The oral route of protein and peptide drugs has been a popular method of drug delivery in recent years, although it is often a challenge to achieve effective drug release and minimize the barrier functions of the gastrointestinal tract. Gastrointestinal mucosa can capture and remove harmful substances; similarly, it can limit the absorption of drugs. Many drugs are effectively captured by the mucus and rapidly removed, making it difficult to control the release of drugs in the gastrointestinal tract. The use of drug carrier systems can overcome the mucosal barrier and significantly improve bioavailability. Nanoparticle drug carriers can protect the drug from degradation, transporting it to a predetermined location in the gastrointestinal tract to achieve more efficient and sustained drug delivery. It is becoming clearer that the characteristics of nanoparticles, such as particle size, charge, and hydrophobicity, are related to permeability of the mucosal barrier. This review focuses on the latest research progress of nanoparticles to penetrate the mucosal barrier, including the delivery methods of nanoparticles on the surface of gastrointestinal mucosa, and aims to summarize how successful oral nanoparticle delivery systems can overcome this biological barrier in the human body. In addition, the in vitro model based on gastrointestinal mucus is an important tool for drug research and development. Here, we discuss different types of drug delivery systems and their advantages and disadvantages in design and potential applications. Similarly, we reviewed and summarized various methods for evaluating oral nanoparticles in in vitro and in vivo models. [ABSTRACT FROM AUTHOR]

The cap 'n' collar (Cnc) belongs to the Basic Leucine Zipper (bZIP) transcription factor super family. Cap 'n' collar isoform C (CncC) is highly conserved in the animal kingdom. CncC contributes to the regulation of growth, development, and aging and takes part in the maintenance of homeostasis and the defense against endogenous and environmental stress. Insect CncC participates in the regulation of various kinds of stress-responsive genes and is involved in the development of insecticide resistance. In this study, one full-length CncC sequence of Locusta migratoria was identified and characterized. Upon RNAi silencing of LmCncC , insecticide bioassays showed that LmCncC played an essential role in deltamethrin and imidacloprid susceptibility. To fully investigate the downstream genes regulated by LmCncC and further identify the LmCncC -regulated genes involved in deltamethrin and imidacloprid susceptibility, a comparative transcriptome was constructed. Thirty-five up-regulated genes and 73 down-regulated genes were screened from ds LmCncC -knockdown individuals. We selected 22 LmCncC -regulated genes and verified their gene expression levels using RT-qPCR. Finally, six LmCYP450 genes belonging to the CYP6 family were selected as candidate detoxification genes, and LmCYP6FD1 and LmCYP6FE1 were further validated as detoxification genes of insecticides via RNAi, insecticide bioassays, and metabolite identification. Our data suggest that the locust CncC gene is associated with deltamethrin and imidacloprid susceptibility via the regulation of LmCYP6FD1 and LmCYP6FE1 , respectively. [Display omitted] • LmCncC played an essential role in deltamethrin and imidacloprid susceptibility. • 35 up-regulated genes and 73 down-regulated genes were screened from dsLmCncC-knockdown locusts. • LmCncC is associated with deltamethrin and imidacloprid susceptibility via the LmCYP6FD1 and LmCYP6FE1. • LmCYP6FE1 participates in the detoxification of imidacloprid by producing hydroxy imidacloprid. [ABSTRACT FROM AUTHOR]

A new 3D luminescent Ba-organic framework {[Ba3L2(NMP)2(H2O)2]·2NMP·H2O}n (1) was first synthesized based on Ba(II) and a triangular-shaped bridging rigid ligand, namely 1,3,5-tris(4-carboxyphenly)benzene (H3L), via solvothermal reaction (NMP = N-methyl pyrrolidone), thereby forming a stabilized network including a one-dimensional (1D) infinite rod-like helical metal chain. 1 may be explored as a recyclable heterogeneous catalyst for the efficient fixation of CO2 to form serviceable cyclic carbonate since 1D channels remain decorated with abundant open metal sites (OMSs), and the catalytic efficiency of 1 was up to 98% for 1-bromo-2,3-propylene oxide. Simultaneously, the luminescence sensing shows that 1 has excellent response and sensitivity towards pollutants such as Fe3+, Cr2O72−, CrO42−, and [Fe(CN)6]3− ions. Moreover, 1 exhibits the particularly selective sorption towards the Congo red (CR) dye. Consequently, this study may provide a facile synthetic route for the construction of multi-functional Ba-MOF materials. [ABSTRACT FROM AUTHOR]

Ferroptosis is a type of non-apoptotic regulated cell death that involves excessive iron accumulation and subsequent lipid peroxidation. Although the antioxidant mechanisms of ferroptosis have been extensively studied recently, little is known about the interactions between the different organelles that control ferroptosis. Here, we show that the translocation of lysosomal cysteine protease cathepsin B (CTSB) into the nucleus is an important molecular event that mediates organelle-specific initiation of ferroptosis in human pancreatic cancer cells. Iron-dependent lysosomal membrane permeability triggers the release of CTSB from the lysosome to nucleus during ferroptosis. Mechanistically, nuclear CTSB accumulation causes DNA damage and subsequent activation of the stimulator of interferon response CGAMP interactor 1 (STING1/STING)-dependent DNA sensor pathway, which ultimately leads to autophagy-dependent ferroptosis. Consequently, the genetic inhibition of CTSB-dependent STING1 activation by RNAi prevents ferroptosis in cell culture and animal models. These new findings not only enhance our understanding of the mechanism by which organelles specifically trigger ferroptosis, but also may provide a potential way to enhance the anticancer activity of ferroptosis therapy. • Increased CTSB expression, activity, and translocation during ferroptosis • CTSB triggers DNA damage and STING1 activation during ferroptosis • CTSB mediates autophagy-dependent ferroptosis • CTSB regulates ferroptosis therapy in vivo [ABSTRACT FROM AUTHOR]

5-Fluorouracil (5-Fu) is an effective anticarcinogenic agent, however, continuous use of 5-Fu may cause severe side effects. The goal of this study was to investigate the effectiveness of Sarcodon aspratus polysaccharides (SATP) in alleviating 5-Fu-induced toxicity in Lewis tumor-bearing mice. Lewis tumor-bearing mice were treated with saline, SATP, 5-Fu or 5-Fu + SATP. The results indicated that compared to the 5-Fu group, the 5-Fu + SATP group showed effective amelioration of the liver, kidney and small intestine injury caused by 5-Fu and decreases in the levels of related biochemical indicators, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and urea nitrogen (BUN). Additionally, the combination therapy enhanced the quality of life and immune organ indexes of mice. Further mechanistic studies indicated that the 5-Fu + SATP group showed a decrease in hepatotoxicity caused by 5-Fu via a reduction in the levels of interleukin-1β (IL-1β), an increase in the expression of Bcl-2 and decreases in the expression of p-p38, p-JNK and Bax. Collectively, the results indicated that SATP could significantly alleviate the toxicity of 5-Fu in Lewis tumor-bearing mice and showed the hepatoprotective capability of SATP via its effect on the expression levels of inflammatory factors and components of the MAPK/P38/JNK pathway, which shows that it may be a potential adjuvant for the chemotherapeutic drug 5-Fu in cancer treatment. • SATP could alleviate the toxicity of 5-Fu on tumor bearing mice organs. • SATP could enhance the immune functions during the tumor inhibition process of 5-Fu. • SATP has shown hepatoprotective ability by affecting MAPK/P38/JNK pathway. [ABSTRACT FROM AUTHOR]

Remote sensing image scene classification refers to assigning semantic labels according to the content of the remote sensing scenes. Most machine learning-based scene classification methods assume that training and testing data share the same distributions. However, in real application scenarios, this assumption is difficult to guarantee. Domain adaptation (DA) is a promising approach to address this problem by aligning the feature distribution of training and testing data. Inspired by the idea DA, in this article, we propose a correlation subspace dynamic distribution alignment (CS-DDA) method for remote sensing image scene classification. Aiming at the characteristics of remote sensing scenes, we introduce two strategies to balance the effects of source and target domains: subspace correlation maximization (SCM) and dynamic statistical distribution alignment (DSDA). On the one hand, SCM tries to avoid mapping source domain data into irrelevant subspace to preserve the representation information of the source domain. On the other hand, DSDA is proposed to reduce the data distribution discrepancy between aligned source and target domains. Specifically, DSDA is a dynamic adjustment process where an adaptive factor is learned to balance the interclass and intraclass distribution between domains. Moreover, we integrate SCM and DSDA into a uniform optimization framework, and the optimal solution can be converted to the generalized eigendecomposition problem by derivation. The experimental results indicate that the proposed method can generate better results when compared with other feature distribution alignment methods. [ABSTRACT FROM AUTHOR]

Serum creatinine (Cr) is a biosynthetic product of creatine phosphate metabolism in muscles and is closely related to total muscle mass, but it is not easily affected by diet. Several studies have tried to explore the role of serum Cr levels in amyotrophic lateral sclerosis (ALS), but the results were inconsistent. Therefore, our study aims to explore the differences of serum Cr levels between ALS patients and controls and whether serum Cr at baseline is an independent predictor of survival. Methods: We searched all the related studies that probed into the association between Serum Cr levels and ALS based on PubMed, EMBASE and Cochrane library from October 1952 to February 2019. The quality of the included studies was evaluated by using Newcastle-Ottawa Scale (NOS), and all the statistical analysis of this meta-analysis was performed by Stata version 12.0. Results: Eight studies with a total of 11377 ALS patients and 937 controls were included. Among them, five studies indicated that ALS patients had lower serum Cr levels (SMD = −0.78, 95%CI [−0.97, −0.60]) compared to controls, and three studies showed that higher serum Cr levels in ALS patients were related to lower overall mortality (HR 0.89, 95%CI [0.80, 0.99]). Conclusion: The levels of serum Cr in ALS patients are significantly lower than those in controls, and they are inversely related to overall mortality in ALS patients. Therefore, the serum Cr, an easily accessible serological factor, may serve as a prognostic biomarker. [ABSTRACT FROM AUTHOR]

Macroautophagy (hereafter referred to as autophagy) involves an intracellular degradation and recycling system that, in a context-dependent manner, can either promote cell survival or accelerate cellular demise. Ferroptosis was originally defined in 2012 as an iron-dependent form of cancer cell death different from apoptosis, necrosis, and autophagy. However, this latter assumption came into question because, in response to ferroptosis activators (e.g., erastin and RSL3), autophagosomes accumulate, and because components of the autophagy machinery (e.g., ATG3, ATG5, ATG4B, ATG7, ATG13, and BECN1) contribute to ferroptotic cell death. In particular, NCOA4-facilitated ferritinophagy, RAB7A-dependent lipophagy, BECN1-mediated system x c − inhibition, STAT3-induced lysosomal membrane permeabilization, and HSP90-associated chaperone-mediated autophagy can promote ferroptosis. In this review, we summarize current knowledge on the signaling pathways involved in ferroptosis, while focusing on the regulation of autophagy-dependent ferroptotic cell death. The molecular comprehension of these phenomena may lead to the development of novel anticancer therapies. [ABSTRACT FROM AUTHOR]

Signal transducer and activator of transcription 1 (STAT1) is related to the immune microenvironment of tumorigenesis. The programmed cell death 1 (PD-1) and its ligand (PD-L1) have been reported to be important in immunotherapy by mediating tumor immune evasion. Blocking the PD-1/PD-L1 pathway can restore the endogenous anti-tumor immune response. This study aimed to examine the expression of STAT1, PD-1, and PD-L1 and the correlation between selected markers in human epithelial ovarian cancer (EOC). The results showed that malignant tumors contained more STAT1, PD-1, and PD-L1 positive cells. The expression of STAT1 and PD-L1 was associated with age, whereas PD-1 and PD-L1 associated with histopathological type, in patients with ovarian tumors. Moreover, the expression of STAT1 was found to be associated with disease stages and the grade of serous carcinoma. STAT1 expression was higher in OC cells than normal ovarian surface epithelial cells and was positively correlated with PD-L1 expression. The knockdown of STAT1 decreased PD-L1 expression, whereas overexpression of STAT1 increased PD-L1 expression. Furthermore, the expression of STAT1, PD-1, and PD-L1 was lower in paclitaxel-resistant cells than sensitive cells. Finally, STAT1 affected the overall survival and progression-free survival of patients with EOC. These findings suggest that STAT1, PD-1, and PD-L1 are the tissue markers of EOC and imply the possibility that the high level of STAT1, PD-1, and PD-L1 may favor the checkpoint immunotherapy in patients with EOC, but may have a limit in paclitaxel-resistant patients because of the low expression of STAT1, PD-1, and PD-L1 in paclitaxel-resistant cells. [ABSTRACT FROM AUTHOR]

Proteins are important biological molecules whose structures are closely related to their specific functions. Understanding how the protein folds under physical principles, known as the protein folding problem, is one of the main tasks in modern biophysics. Coarse-grained methods play an increasingly important role in the simulation of protein folding, especially for large proteins. In recent years, we proposed a novel coarse-grained method derived from the topological soliton model, in terms of the backbone Cα chain. In this review, we will first systematically address the theoretical method of topological soliton. Then some successful applications will be displayed, including the thermodynamics simulation of protein folding, the property analysis of dynamic conformations, and the multi-scale simulation scheme. Finally, we will give a perspective on the development and application of topological soliton. [ABSTRACT FROM AUTHOR]

In this study, two new monometallic organic frameworks (MOFs), namely {[Zn1.5L(NMP)(H2O)]·H2O}n (1) and {[Pb2L2(H2O)2]·H2O}n (2), were synthesized for the first time by a new bifunctional N,O-containing 2-(1H-tetrazol-5-yl)terephthalic acid (H2L) ligand. Then, based on the HSAB principle, another porous Pb–Zn heterometallic organic framework (HMOF), namely {[PbZn0.5L(H2O)]·0.5NMP·H2O}n (3), was successfully obtained for the first time by combining Pb(II) and Zn(II) ions with H2L. The MOFs 1 and 2 are 3D densely packed frameworks, whereas the HMOF 3 is a porous 3D framework (28.9% porosity) with 1D open channels modified by Lewis basic sites (exposed N atoms) and Lewis acidic sites (unsaturated bimetallic sites). The HMOF 3 has a strong boiling water/acid–base resistance (pH = 2–12) and shows an enhanced high-efficiency catalytic effect for CO2 conversion (98%) under ambient temperature and pressure conditions. In addition, fine color regulations of the MOFs were successfully realized by doping different kinds of metal ions into them. This study aims to provide a new way and field of vision for the construction of HMOFs and their multi-functional materials. [ABSTRACT FROM AUTHOR]

Activating transcription factor 4 (ATF4), a member of the ATF/cAMP response element-binding (CREB) family, plays a critical role as a stress-induced transcription factor. It orchestrates cellular responses, particularly in the management of endoplasmic reticulum stress, amino acid deprivation, and oxidative challenges. ATF4's primary function lies in regulating gene expression to ensure cell survival during stressful conditions. However, when considering its involvement in ferroptosis, characterized by severe lipid peroxidation and pronounced endoplasmic reticulum stress, the ATF4 pathway can either inhibit or promote ferroptosis. This intricate relationship underscores the complexity of cellular responses to varying stress levels. Understanding the connections between ATF4, ferroptosis, and endoplasmic reticulum stress holds promise for innovative cancer therapies, especially in addressing apoptosis-resistant cells. In this review, we provide an overview of ATF4, including its structure, modifications, and functions, and delve into its dual role in both ferroptosis and cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: An atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon, yet aggressive, pediatric central nervous system neoplasm. Our prognostic study included 316 Surveillance, Epidemiology, and End Results (SEER) repository participants and 27 external validation patients. The incidence of AT/RT consistently increased between 2000 and 2020. Age, SEER stage, tumor size, surgery, chemotherapy, and radiotherapy are closely related to the prognosis of AT/RT. Triple therapy resulted in discernibly enhanced OS and CSS. The most common mutations in AT/RT identified using the COSMIC database were SMARCB1, BRAF, SMARCA4, NF2, and NRAS. Our study identified the clinical determinants of prognosis in patients with AT/RT and mapped the genetic mutation landscape. The prediction model that we devised may offer a valuable tool to address existing clinical challenges. Additionally, analysis based on mutational genomics will facilitate the research regarding molecular-targeted drugs. Background: An atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon and aggressive pediatric central nervous system neoplasm. However, a universal clinical consensus or reliable prognostic evaluation system for this malignancy is lacking. Our study aimed to develop a risk model based on comprehensive clinical data to assist in clinical decision-making. Methods: We conducted a retrospective study by examining data from the Surveillance, Epidemiology, and End Results (SEER) repository, spanning 2000 to 2019. The external validation cohort was sourced from the Children's Hospital Affiliated to Chongqing Medical University, China. To discern independent factors affecting overall survival (OS) and cancer-specific survival (CSS), we applied Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF) regression analyses. Based on these factors, we structured nomogram survival predictions and initiated a dynamic online risk-evaluation system. To contrast survival outcomes among diverse treatments, we used propensity score matching (PSM) methodology. Molecular data with the most common mutations in AT/RT were extracted from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Results: The annual incidence of AT/RT showed an increasing trend (APC, 2.86%; 95% CI:0.75–5.01). Our prognostic study included 316 SEER database participants and 27 external validation patients. The entire group had a median OS of 18 months (range 11.5 to 24 months) and median CSS of 21 months (range 11.7 to 29.2). Evaluations involving C-statistics, DCA, and ROC analysis underscored the distinctive capabilities of our prediction model. An analysis via PSM highlighted that individuals undergoing triple therapy (integrating surgery, radiotherapy, and chemotherapy) had discernibly enhanced OS and CSS. The most common mutations of AT/RT identified in the COSMIC database were SMARCB1, BRAF, SMARCA4, NF2, and NRAS. Conclusions: In this study, we devised a predictive model that effectively gauges the prognosis of AT/RT and briefly analyzed its genomic features, which might offer a valuable tool to address existing clinical challenges. [ABSTRACT FROM AUTHOR]

Simple Summary: In the complex world of cancer, iron and copper play essential roles as trace metal ions that are crucial for cancer cell survival. Disruption in their metabolic functions can be lethal to cancer cells, triggering ferroptosis and cuproptosis, respectively. Given an accelerated proliferation rate, cancer cells exhibit a heightened dependence on iron and copper, exposing vulnerabilities that could potentially be exploited to reverse drug resistance. Notably, mitochondria, the cellular powerhouses, play a crucial role in regulating both ferroptosis and cuproptosis. This review focuses on elucidating the key mechanisms behind ferroptosis and cuproptosis and summarizes recent clinical applications targeting dysfunctional iron and copper metabolic pathways. Drug resistance is a hallmark of cancer development that underscores a critical need to address it, underscoring the critical need to explore novel approaches. Understanding and targeting these metal-related processes offers promising approaches for developing innovative cancer therapies, making use of vulnerabilities specific to cancer cells. Iron (Fe) and copper (Cu), essential transition metals, play pivotal roles in various cellular processes critical to cancer biology, including cell proliferation, mitochondrial respiration, distant metastases, and oxidative stress. The emergence of ferroptosis and cuproptosis as distinct forms of non-apoptotic cell death has heightened their significance, particularly in connection with these metal ions. While initially studied separately, recent evidence underscores the interdependence of ferroptosis and cuproptosis. Studies reveal a link between mitochondrial copper accumulation and ferroptosis induction. This interconnected relationship presents a promising strategy, especially for addressing refractory cancers marked by drug tolerance. Harnessing the toxicity of iron and copper in clinical settings becomes crucial. Simultaneous targeting of ferroptosis and cuproptosis, exemplified by the combination of sorafenib and elesclomol-Cu, represents an intriguing approach. Strategies targeting mitochondria further enhance the precision of these approaches, providing hope for improving treatment outcomes of drug-resistant cancers. Moreover, the combination of iron chelators and copper-lowering agents with established therapeutic modalities exhibits a synergy that holds promise for the augmentation of anti-tumor efficacy in various malignancies. This review elaborates on the complex interplay between ferroptosis and cuproptosis, including their underlying mechanisms, and explores their potential as druggable targets in both cancer research and clinical settings. [ABSTRACT FROM AUTHOR]

Objective To reveal the prevailing scenarios of cutaneous infections and multidrug resistance of skin lesions, and nosocomial infections among inpatients in dermatology hospital. Methods Clinical data, including pathogens from skin lesions, were collected from inpatients at Dermatology Hospital of Southern Medical University between October 2019 and September 2022. The analyses included multi-drug-resistant organism (MDRO), extensively drug-resistant organisms, and the annual variations and resistance profiles of the top five pathogens. Results Over the three years, 3 331 pathogen strains were cultured from skin lesions, predominantly Gram-positive bacteria (77.72%), Gram-negative bacteria (17.35%) and fungi (4.92%) . Eczematous dermatoses exhibited the highest incidence among positive cultures of skin lesions (27.32%). The top 5 pathogens were Staphylococcus aureus, Coagulase-negative staphylococci, Pseudomonas aeruginosa, Candida albicans and Klebsiella pneumoniae. The proportions of Staphylococcus aureus and Coagulase-negative staphylococci tended to be increased annually (P <0. 05). However, multi-drug-resistant Staphylococcus aureus infections and methiciilin-esistant Staphylococcus aureus (MRSA) tended to be decreased (P <0.05). The overall MDRO detection rate was 45. 39%, with a hospital infection rate of 0.67%. The rate of MDRO in nosocomial infections declined annually (χ² = 26.26, P < 0.05). Conclusions Gram-positive bacteria such as staphylococci are the common pathogens in cutaneous lesion infections, suggesting that the first choice of antibiotics should be those targeting these strains. Declines in MDRO and nosocomial infections of MRSA indicate effective control of infections in the dermatology hospital. However, the increasing prevalence and resistance in coagulase-negative staphylococci underscore the need for heightened management of these infections. [ABSTRACT FROM AUTHOR]

Background: Since December 2019, an outbreak of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) initially emerged in Wuhan, China, and has spread worldwide now. Clinical features of patients with COVID-19 have been described. However, risk factors leading to in-hospital deterioration and poor prognosis in COVID-19 patients with severe disease have not been well identified. Methods: In this retrospective, single-center cohort study, 1190 adult inpatients (≥ 18 years old) with laboratory-confirmed COVID-19 and determined outcomes (discharged or died) were included from Wuhan Infectious Disease Hospital from December 29, 2019 to February 28, 2020. The final follow-up date was March 2, 2020. Clinical data including characteristics, laboratory and imaging information as well as treatments were extracted from electronic medical records and compared. A multivariable logistic regression model was used to explore the potential predictors associated with in-hospital deterioration and death. Results: 1190 patients with confirmed COVID-19 were included. Their median age was 57 years (interquartile range 47–67 years). Two hundred and sixty-one patients (22%) developed a severe illness after admission. Multivariable logistic regression demonstrated that higher SOFA score (OR 1.32, 95% CI 1.22–1.43, per score increase, p < 0.001 for deterioration and OR 1.30, 95% CI 1.11–1.53, per score increase, p = 0.001 for death), lymphocytopenia (OR 1.81, 95% CI 1.13–2.89 p = 0.013 for deterioration; OR 4.44, 95% CI 1.26–15.87, p = 0.021 for death) on admission were independent risk factors for in-hospital deterioration from not severe to severe disease and for death in severe patients. On admission D-dimer greater than 1 μg/L (OR 3.28, 95% CI 1.19–9.04, p = 0.021), leukocytopenia (OR 5.10, 95% CI 1.25–20.78), thrombocytopenia (OR 8.37, 95% CI 2.04–34.44) and history of diabetes (OR 11.16, 95% CI 1.87–66.57, p = 0.008) were also associated with higher risks of in-hospital death in severe COVID-19 patients. Shorter time interval from illness onset to non-invasive mechanical ventilation in the survivors with severe disease was observed compared with non-survivors (10.5 days, IQR 9.25–11.0 vs. 16.0 days, IQR 11.0–19.0 days, p = 0.030). Treatment with glucocorticoids increased the risk of progression from not severe to severe disease (OR 3.79, 95% CI 2.39–6.01, p < 0.001). Administration of antiviral drugs especially oseltamivir or ganciclovir is associated with a decreased risk of death in severe patients (OR 0.17, 95% CI 0.05–0.64, p < 0.001). Conclusions: High SOFA score and lymphocytopenia on admission could predict that not severe patients would develop severe disease in-hospital. On admission elevated D-dimer, leukocytopenia, thrombocytopenia and diabetes were independent risk factors of in-hospital death in severe patients with COVID-19. Administration of oseltamivir or ganciclovir might be beneficial for reducing mortality in severe patients. [ABSTRACT FROM AUTHOR]

Objective: Many noninvasive brain stimulation techniques have been applied to treat depressive disorders. However, the target brain region in most noninvasive brain stimulation studies is the dorsolateral prefrontal cortex. Exploring new stimulation locations may improve the efficacy of noninvasive brain stimulation for depressive disorders. We aimed to explore potential noninvasive brain stimulation locations for depressive disorders through a meta-analysis and a functional connectivity approach. Methods: We conducted a meta-analysis of 395 functional magnetic resonance imaging studies to identify depressive disorder–associated brain regions as regions of interest. Then, we ran resting-state functional connectivity analysis with three different pipelines in 40 depression patients to find brain surface regions correlated with these regions of interest. The 10–20 system coordinates corresponding to these brain surface regions were considered as potential locations for noninvasive brain stimulation. Results: The 10–20 system coordinates corresponding to the bilateral dorsolateral prefrontal cortex, bilateral inferior frontal gyrus, medial prefrontal cortex, supplementary motor area, bilateral supramarginal gyrus, bilateral primary motor cortex, bilateral operculum, left angular gyrus and right middle temporal gyrus were identified as potential locations for noninvasive brain stimulation in depressive disorders. The coordinates were: posterior to F3, posterior to F4, superior to F3, posterior to F7, anterior to C4, P3, midpoint of F7–T3, posterior to F8, anterior to C3, midpoint of Fz–Cz, midpoint of Fz–Fp1, anterior to T4, midpoint of C3–P3, and anterior to C4. Conclusion: Our study identified several potential noninvasive brain stimulation locations for depressive disorders, which may serve as a basis for future clinical investigations. [ABSTRACT FROM AUTHOR]

The key challenge for CO2 methanation, an eight-electron process under kinetic limitation, relies on the design of non-noble metal catalysts so as to achieve high activity at low reaction temperatures. In this work, four Ni-based catalysts with different supports were prepared and tested for CO2 methanation at 250–550 °C in a fixed bed quartz reactor and further characterized to reveal the structure–function relationship. The Ni-based catalysts followed an activity order of Ni/CeO2 > Ni/Al2O3 > Ni/TiO2 > Ni/ZrO2, especially at temperatures lower than 350 °C. H2-TPR and TPD results indicated that the interaction between nickel and support was strong and the metallic nickel was well dispersed in the Ni/Al2O3 catalyst, while more amount of CO2 was adsorbed on the weak basic sites in the Ni/CeO2 catalyst. By establishing the correlation between the catalytic performance and the catalyst structure, it was found that the Ni nanoparticles and basic support serve as H2 and CO2 active centers respectively and cooperatively catalyze CO2 methanation, resulting in high low-temperature reaction activity. High CO2 conversion was achieved over Ni/CeO2 catalyst at 300 °C for its high H2 uptake on Ni nanoparticles and high CO2 adsorption capacity on the support with weak basic sites and cooperatively to catalyze CO2 methanation. [ABSTRACT FROM AUTHOR]

The coordination preference of different metal ions and ligands have an immense influence on the constructions of functional MOF materials. In this work, two new monometallic complexes, namely [Ag(HL)(bipy)0.5] (1) and {[Tb(L)1.5(H2O)]⋅4 H2O}n (2) (bipy=4,4‐bipyridine), have been synthesized successfully by employing a bifunctional 2‐(imidazol‐1‐yl)terephthalic acid (H2L) ligand. After that, two new different heterometallic–organic frameworks (HMOFs), namely {[TbAg(L)2(H2O)3]⋅H2O}n (3) and [TbAg(L)2(H2O)]n (4), were obtained from complexes 1 and 2 as the precursors based on a rational stepwise construction strategy and the theory of hard and soft acids and bases (HSAB principle), respectively. The HMOFs bearing dual metallic catalytic sites (Tb and Ag) can be used as heterogeneous catalysts without losing performance for the chemical fixation of CO2 with epoxides including the sterically hindered epoxides, demonstrating some of the highest reported catalytic activity values. This work may provide a new synthetic route toward tailoring new HMOFs with excellent catalytic activity. [ABSTRACT FROM AUTHOR]

Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved cellular process capable of degrading various biological molecules (e.g., protein, glycogen, lipids, DNA, and RNA) and organelles (e.g., mitochondria, endoplasmic reticulum [ER] ribosomes, lysosomes, and micronuclei) via the lysosomal pathway. Ferroptosis is a type of oxidative stress-dependent regulated cell death associated with iron accumulation and lipid peroxidation. The recently discovered role of autophagy, especially selective types of autophagy (e.g., ferritinophagy, lipophagy, clockophagy, and chaperone-mediated autophagy), in driving cells toward ferroptotic death motivated us to explore the functional interactions between metabolism, immunity, and cell death. Here, we describe types of selective autophagy and discuss the regulatory mechanisms and signaling pathways of autophagy-dependent ferroptosis. We also summarize chemical modulators that are currently available for triggering or blocking autophagy-dependent ferroptosis and that may be developed for therapeutic interventions in human diseases. Liu et al. describes types of selective autophagy and discuss the regulatory mechanisms and signaling pathways of autophagy-dependent ferroptosis. A deeper understanding of the process and function of autophagy-dependent cell death is critical for creating innovative therapeutic strategies for oxidative stress-related diseases. [ABSTRACT FROM AUTHOR]

Background: Carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with poor patient outcomes. Data on risk factors and molecular epidemiology of CRE in complicated intra-abdominal infections (cIAI) in China are limited. This study examined the risk factors of cIAI with CRE and the associated mortality based on carbapenem resistance mechanisms.Methods: In this retrospective analysis, we identified 1024 cIAI patients hospitalized from January 1, 2013 to October 31, 2018 in 14 intensive care units in China. Thirty CRE isolates were genotyped to identify β-lactamase-encoding genes.Results: Escherichia coli (34.5%) and Klebsiella pneumoniae (21.2%) were the leading pathogens. Patients with hospital-acquired cIAI had a lower rate of E coli (26.0% vs 49.1%; P < .001) and higher rate of carbapenem-resistant Gram-negative bacteria (31.7% vs 18.8%; P = .002) than those with community-acquired cIAI. Of the isolates, 16.0% and 23.4% of Enterobacteriaceae and K pneumoniae, respectively, were resistant to carbapenem. Most carbapenemase-producing (CP)-CRE isolates carried blaKPC (80.9%), followed by blaNMD (19.1%). The 28-day mortality was 31.1% and 9.0% in patients with CRE vs non-CRE (P < .001). In-hospital mortality was 4.7-fold higher for CP-CRE vs non-CP-CRE infection (P = .049). Carbapenem-containing combinations did not significantly influence in-hospital mortality of CP and non-CP-CRE. The risk factors for 28-day mortality in CRE-cIAI included septic shock, antibiotic exposure during the preceding 30 days, and comorbidities.Conclusions: Klebsiella pneumoniae had the highest prevalence in CRE. Infection with CRE, especially CP-CRE, was associated with increased mortality in cIAI. [ABSTRACT FROM AUTHOR]

In this paper, we propose a general and efficient lattice Boltzmann (LB) model for solving the nonlinear thermistor equations, where the nonlinear diffusion and Poisson equations are solved by two LB equations. Through Chapman–Enskog analysis, the nonlinear thermistor equations can be recovered correctly from the present LB model. We then test the model through some numerical simulations, and find that the numerical results are in good agreement with analytical solutions. Additionally, the numerical results also show that the present LB model has a second-order convergence rate in space. [ABSTRACT FROM AUTHOR]

In this work, a new monometallic metal–organic framework (MOF), namely {[Pb2(L)2(H2O)]·H2O}n (1), was prepared via a N,O-mixed 2-(imidazol-1-yl)terephthalic acid (H2L) ligand and Pb(II) ions. Then, a first new porous d–p heterometallic MOF (HMOF), namely {[PbZn(L)2]·DMA·H2O}n (2), was yielded via Zn(II) ions and MOF 1 as the precursor because of the different coordination affinity of oxygen and nitrogen atoms with various metal ions. MOF 1 is a condensed packing motif, whereas HMOF 2 is a porous three-dimensional (3D) framework with unsaturated Pb(II) and Zn(II) active sites, uncoordinated carboxylate oxygen atoms and two kinds of porous channels due to the introduction of Zn(II) ions into the framework of MOF 1, which thus endowed HMOF 2 with excellent sorption and selectivity for CO2 over CH4. Moreover, HMOF 2 was explored to be an efficient heterogeneous catalyst for the fixation of CO2 with various epoxides because of the existence of the abundant unsaturated bimetallic sites as the Lewis acid. It is hoped that this work may supply an effective strategy to build plenty of d–p HMOF materials with excellent gas adsorption and catalytic properties. [ABSTRACT FROM AUTHOR]

Background: Currently, there are no reliable predictors of risk of development and severity of acute kidney injury (AKI) in septic patients. The surfactant protein D (SP-D) polymorphism rs721917C/T is associated with a greater susceptibility to AKI in the Chinese population. Our aim was to evaluate the value of SP-D polymorphisms rs721917C/T and of plasma SP-D levels to predict the risk of development of AKI (defined with KDIGO criterion) in septic patients. Methods: The study enrolled septic patients admitted to the Critical Care Department of two tertiary care hospitals. SP-D rs721917C/T polymorphisms were determined using the PCR-SSP method. Plasma SP-D and urine NGAL contents were measured using commercially available ELISA kits. Results: 330 septic patients were included. Their SOFA scores were 12 ± 3. Patients with AKI (n = 156) had higher plasma SP-D levels (median: 153 ng/mL, range 111–198 ng/mL) and urinary NGAL levels (median: 575 ng/mL, range 423–727 ng/mL) than those without AKI (SP-D median: 124 ng/mL, range 81–159 ng/mL, P = 0.001; NGAL median: 484 ng/mL, range 429–573 ng/mL). Plasma SP-D levels of AKI patients were correlated with urinary NGAL contents (r = 0.853). In 32 patients receiving continuous renal replacement therapy (CRRT), plasma SP-D levels correlated with duration of CRRT (r = 0.448). The area under the receiver operating characteristic curve for plasma SP-D levels to predict AKI was 0.84. Patients with AKI had a higher rate of rs721917 CC genotype (AKI: 35% vs. non-AKI: 20%; P = 0.012), but a significantly lower rate of TT genotype (AKI: 19% vs. non-AKI: 26%; P = 0.005). SP-D rs721917 CC genotype was an independent predictor of AKI (P = 0.044) and mortality (P = 0.014). Conclusion: Our study showed that increased plasma SP-D level is associated with a higher risk of AKI in patients with sepsis. The SP-D rs721917CC genotype is an independent and significant predictor of AKI development and mortality of septic patients. The SP-D rs721917C/T polymorphisms should be further studied as diagnostic and prognostic biomarkers to facilitate early recognition of AKI. [ABSTRACT FROM AUTHOR]

Background: Spastic paraplegia type 11 (SPG11) mutations are the most frequent cause of autosomal recessive hereditary spastic paraplegia (ARHSP). We are aiming to identify the causative mutations in SPG11 among families referred to our center with ARHSP in a Chinese population.Methods: Targeted next-generation sequencing was performed on the patients to identify disease-causing mutations. Variants were analyzed according to their predicted pathogenicity and their relevance to the clinical phenotypes. The segregation in the family members was validated by Sanger sequencing.Results: A total of 12 mutations in SPG11 gene from 9 index cases were identified, including 6 frameshift mutations, 3 missense mutations, 1 nonsense mutation, 1 splicing mutation, and 1 intron deletion mutation. In 6 of these patients, the mutations were homozygous, and the other 3 patients carried two compound heterozygous mutations. Six mutations were novel; 2 were classified as pathogenic, 1 were considered as likely pathogenic, and the other 3 were variants of unknown significance. Additionally, 1 missense heterozygous variant we found was also carried by amyotrophic lateral sclerosis (ALS) patient. Clinically and electrophysiologically, some of our ARHSP patients partially shared various features of autosomal-recessive juvenile amyotrophic lateral sclerosis (ARJALS), including combination of both UMN and LMN degeneration.Conclusions: The results contribute to extending of the SPG11 gene mutation spectrum and emphasizing a putative link between ARHSP and ARJALS. [ABSTRACT FROM AUTHOR]

Herein, two new water-stable magnetic frameworks, [Cu1.5(L)(H2O)]·2H2O (1) and [Co4(L)2(CH3CN)(OH)2(H2O)4]·3H2O (2) (H3L = 5-((4-carboxypyridin-2-yl)oxy) isophthalic acid), were synthesized by a solvothermal method in similar reaction systems and characterized by infrared spectroscopy, powder X-ray diffraction and thermogravimetric measurements. Due to their different metal ions, 1 shows a trinodal (4,4,4)-connected three-dimensional (3D) framework that possesses 1D channels based on [Cu2(COO)4] paddle-wheel secondary building units (SBUs), whereas 2 is a 2D layered network based on tetranuclear [Co4(COO)6(μ3-OH)2] SBUs and reveals a (3,6)-connected kgd topological structure. The gas adsorption explorations demonstrated that 1 exhibited commendable selectivity for CO2 over CH4. Moreover, both 1 and 2 showed different degrees of antiferromagnetic exchange action. [ABSTRACT FROM AUTHOR]

• Mind-body and physical exercises can relieve pain symptoms in KOA patients. • Knee pain relief is associated with changes in DLPFC rsFC and serum PD-1 level. • Mind-body and physical exercises can increase gray matter volume in the SMA. • DLPFC-SMA rsFC at baseline can predict the treatment effect of exercises on knee pain. • Significant DLPFC rsFC differences exist among exercise modalities. Knee osteoarthritis (KOA) is a common degenerative joint disease with no satisfactory intervention. Recently, both physical and mindfulness exercises have received considerable attention for their implications in KOA pain management, and the dorsolateral prefrontal cortex (DLPFC) has displayed a critical role in pain modulation. This study aimed to comparatively investigate the modulation effects of different exercises using multidisciplinary measurements. 140 KOA patients were randomized into Tai Chi, Baduanjin, stationary cycling, or health education control groups for 12 weeks. Knee Injury and Osteoarthritis Outcome Score (KOOS), resting state functional magnetic resonance imaging (fMRI), structural MRI, and serum biomarkers were measured at baseline and at the end of the study. We found: 1) increased KOOS pain subscores (pain reduction) and serum programmed cell death protein 1 (PD-1) levels in the three exercise groups compared to the control group; 2) decreased resting state functional connectivity (rsFC) of the DLPFC-supplementary motor area (SMA) and increased rsFC between the DLPFC and anterior cingulate cortex in all exercise groups compared to the control group; 3) significant associations between DLPFC-SMA rsFC with KOOS pain subscores and serum PD-1 levels at baseline; 4) significantly increased grey matter volume in the SMA in the Tai Chi and stationary cycling groups, and a trend toward significant increase in the Baduanjin group compared to the control group; 5) significant DLPFC rsFC differences among different exercise groups; and 6) that baseline DLPFC-SMA rsFC can predict the effect of mind-body exercise on pain improvement in KOA. Our results suggest that different exercises can modulate both common and unique DLPFC (cognitive control) pathways, and altered DLPFC-SMA rsFC is associated with serum biomarker levels. Our findings also highlight the potentials of neuroimaging biomarkers in predicting the therapeutic effect of mind-body exercises on KOA pain. [ABSTRACT FROM AUTHOR]

This study first addresses an extended asynchronous switching control issue resulting from switching delay and false alarm for a family of switched positive systems. Based on a new set of switching signals superior to the average dwell time switching, the state‐feedback controller is designed to guarantee the positivity and global asymptotic stability for the closed‐loop system. In addition, the corresponding sufficient condition formulated in terms of linear programming problem is derived. Different from the previous works, the authors' established results further relax the restriction that all subsystems must be stabilisable in the normal‐running period with matched controller, and allow the increase of the Lyapunov function in the switching delay period, false alarm period, normal‐running period with matched controller and all switching instants. Finally, a numerical example with practical considerations is used to show the effectiveness and potential of the proposed theories. [ABSTRACT FROM AUTHOR]

Background: Knee osteoarthritis is a prevalent disorder with unsatisfactory treatment options. Both physical and mindful exercises may be able to relieve its pain symptoms. We compared the modulatory effects of different exercise modalities on the periaqueductal grey (PAG) and ventral tegmental area (VTA), which play important roles in descending opioidergic pathways and reward/motivation systems in patients with knee osteoarthritis.Methods: We recruited and randomised 140 patients into Tai Chi, Baduanjin, stationary cycling, and health education control groups for 12 weeks. Knee injury and Osteoarthritis Outcome Score (KOOS), functional and structural MRI, and blood biomarkers were measured at the beginning and end of the experiment. We used the PAG and VTA as seeds in resting-state functional connectivity (rsFC) analysis.Results: Compared with the control group: (i) all exercises significantly increased KOOS pain sub-scores (pain reduction) and serum programmed death 1 (PD-1) concentrations; (ii) all exercises decreased right PAG rsFC with the medial orbital prefrontal cortex, and the decreased rsFC was associated with improvements in knee pain; and (iii) grey matter volume in the medial orbital prefrontal cortex was significantly increased in all exercise groups. There was also significantly decreased rsFC between the left VTA and the medial orbital prefrontal cortex in the Tai Chi and Baduanjin groups.Conclusions: Exercise can simultaneously modulate the rsFC of the descending opioidergic pathway and reward/motivation system and blood inflammation markers. Elucidating the shared and unique mechanisms of different exercise modalities may facilitate the development of exercise-based interventions for chronic pain.Clinical Trial Registration: ChiCTR-IOR-16009308. [ABSTRACT FROM AUTHOR]

The migratory locust, Locusta migartoria , is a major agricultural insect pest and its resistance to insecticides is becoming more prevalent. Cytochrome P450 monooxygenases (CYPs) are important enzymes for biotransformations of various endogenous and xenobiotic substances. These enzymes play a major role in developing insecticide resistance in many insect species. In this study, we heterologously co-expressed a CYP enzyme (CYP6FD1) and cytochrome P450 reductase (CPR) from L. migartoria in Sf9 insect cells. The recombinant enzymes were assayed for metabolic activity towards six selected model substrates (luciferin-H, luciferin-Me, luciferin-Be, luciferin-PFBE, luciferin-CEE and 7-ethoxycoumarin), and four selected insecticides (deltamethrin, chlorpyrifos, carbaryl and methoprene). Recombinant CYP6FD1 showed activity towards 7-ethoxycoumarin and luciferin-Me, but no detectable activity towards the other luciferin derivatives. Furthermore, the enzyme efficiently oxidized deltamethrin to hydroxydeltamethrin through an aromatic hydroxylation in a time-dependent manner. However, the enzyme did not show any detectable activity towards the other three insecticides. Our results provide direct evidence that CYP6FD1 is capable of metabolizing deltamethrin. This work is a step towards a more complete characterization of the catalytic capabilities of CYP6FD1 and other xenobiotic metabolizing CYP enzymes in L. migratoria. Unlabelled Image • CYP6FD1 and CPR from Locusta migartoria were co-expressed in Sf9 cells; • CYP6FD1 showed oxidative activity towards 7-ethoxycoumarin and luciferin-Me; • CYP6FD1 showed no detectable activity towards other luciferin derivatives tested; • CYP6FD1 can efficiently oxidize deltamethrin to yield hydroxydeltamethrin; • CYP6FD1 showed no detectable activity towards other three insecticides tested. [ABSTRACT FROM AUTHOR]

• Jet fuel conversion utilizes lignin portion of biomass promote the cellulose-bioethanol conversion. • Cellulose content was 83.38% of residuum of Ni catalyzed substrates (Ni-cs for short). • External addition Ru/C inhibited enzymatic hydrolysis from 61% to 47%, but no obvious decrease to fermentation. • External addition Ni have no obvious inhibit effects to enzymatic hydrolysis, but inhibit fermentation process. • Separate hydrolysis fermentation can enhance bioethanol conversion to 70%. As a renewal energy source for bioethanol production, the residuum of apple wood likely offers a major benefit by having the lignin portion transformed into biofuels firstly. In this study, we used the residuum of Raney Ni and Ru/C catalyzed and hydro-deoxygenated (for jet-fuel production) apple wood as the start substrate to produce bio-ethanol. Cellulose content could reach 83.38% for residuum of Ni catalyzed substrates (Ni-cs for short), and the enzymatic hydrolysis rate increased to 88% which is in reasonable high scale. Lignin left in residuum showed more negative effect on cellulose enzymatic hydrolysis than cellulose II. Different catalysts (Ni or Ru/C) concentration influenced the enzymatic hydrolysis and fermentation. Using quasi-simultaneous enzymatic saccharification and combined fermentation (Q-SScombF), the inhibit effect from catalysts was obvious and the ethanol production efficiency were lower than 35%. But for separate hydrolysis and fermentation process (SHF), the ethanol conversion of raw material and catalyzed residuum improved from 33% to 75% (for residuum of Ni-cs) and increased from 25% to 73% for residuum of Ru/C catalyzed substrates (Ru/C-cs). This research provided a good basis for the feasibility of bio-ethanol production from residuum of bio-refined apple wood. [ABSTRACT FROM AUTHOR]

Fusobacterium necrophorum causes bovine hepatic abscess, foot rot, mastitis, and endometritis. The 43 kDa outer membrane protein (43 K OMP) of F. necrophorum is a porin protein that plays an important role in infections by this bacterium, but the biological function and the pathogenesis of this protein are largely unknown. In this study, we investigated the role of the 43 K OMP in bacterial infection of bovine mammary epithelial cells (MAC-T cells) by Tandem Mass Tag proteomic analysis. The RAW264.7 cells were incubated with recombinant 43 K OMP (12.5 μg/mL) for 2 h, 4 h, 6 h, and 12 h, and then the inflammatory related protein and inflammatory cytokine production were measured by Western blot analysis and ELISA, the mRNA expression levels of inflammatory cytokine were measured by Real-Time PCR. Proteomic analysis results demonstrated there were 224 differentially expressed proteins in the MAC-T cells stimulated with the 43 K OMP compared with control, and 118 proteins were upregulated and 106 proteins were downregulated. These differentially expressed proteins were mainly involved in NF-kappa B signaling, bacterial invasion of epithelial cells, cell adhesion, complement and coagulation cascades. The top six differentially expressed proteins were; MMP9, PLAU, STOM, PSMD13, PLAUR, and ITGAV, which were involved in a protein-protein interaction network. Furthermore, TLR/MyD88/NF-κB pathway related proteins and inflammatory cytokines (IL-6, TNF-α, and IL-1β) were assessed by Western blot analysis and ELISA. Results showed the 43 K OMP to enhance the expression of TLR4 protein at 2 h (P < 0.01) and the MyD88 protein at 4 h (P < 0.05) post-stimulation, and to decrease IκBα expression at 4 h, 6 h and 12 h (P < 0.05) post-infection, as well as induce phosphorylation at Ser536 (P < 0.01). Levels of IL-6, IL-1β, and TNF-α in the supernatants of mouse macrophages were increased (P < 0.05), as were mRNA expression levels of IL-6, IL-1β, and TNF-α (P < 0.05), while IL-4 mRNA expression was decreased (P < 0.05). Taken together, these results suggested the important role for 43 K OMP in F. necrophorum infection, promoting the production of pro-inflammatory cytokines (IL-6 and TNF-α) by activation of the TLR/MyD88/NF-κB pathway. These findings provided a theoretical basis for a better understanding of the pathogenesis of F. necrophorum infection. • The 43 K OMP play an important role in F. necrophorum infection. • NF-κB signaling pathway may be involved in 43 K OMP-mediated infection pathway. • 43 K OMP promoting the production of pro-inflammatory cytokines by the NF-κB pathway. [ABSTRACT FROM AUTHOR]

The metabolic checkpoint of ferroptosis remains obscure. We find that glucose favors system xc− inhibitor-induced ferroptosis by activating pyruvate oxidation, thereby promoting fatty acid synthesis and subsequent lipid peroxidation. In contrast, the upregulation of pyruvate dehydrogenase kinase 4 (PDK4) switches into a ferroptosis-resistant state in pancreatic cancer cells. [ABSTRACT FROM AUTHOR]

Reported herein is a cascade Lewis acid-promoted intramolecular Friedel–Crafts-type imidoylation and Rh(iii)-catalyzed C–H activation/annulation of benzimidoyl chlorides and alkynes, providing a general and concise one-pot approach to 7H-dibenzo[de,h]quinoline analogues. This divergent approach is based on a convergent retrosynthetic disconnection strategy. [ABSTRACT FROM AUTHOR]

Abstract To study the aeroengine containment capability at high temperatures, experimental and numerical investigations have been carried out to determine the ballistic performance and energy absorption characteristics of GH4169 alloy thin plates at temperatures ranging from 25–600 °C. First, experiments were conducted using a gas gun. Target plates were impacted by projectiles with various initial velocities. The effects of the temperature and initial velocity on the deformation, failure pattern and energy absorption of the plate were correspondingly obtained. The experimental results showed that at higher temperature, the deformation of the target plates is greater, the energy absorbed by the target plates is smaller and the ballistic limit velocities are lower. The petal deformation of the target plate caused by bending is severe at the temperature of 600°C. Second, numerical simulations of the impact were conducted by an explicit dynamics FE code (LS-DYNA). The Johnson-Cook constitutive model with parameters obtained from split Hopkinson pressure bar (SHPB) experiments was used to describe the materials properties of the plates at various temperatures and strain rates. It was found that the numerical results are consistent with those obtained by the ballistic experiments. In addition, the results of the numerical simulations also showed that the ballistic limit velocity of the target plate exhibits an approximately linear relationship with the temperature of the target plate. The energy absorbed by the target plate is decreased by 18% and 9% at 600 °C and 300 °C, respectively, compared with that at 25 °C. [ABSTRACT FROM AUTHOR]

La0.8Sr0.2Mn1−xCoxO3 (x = 0, 0.2) polycrystalline samples were prepared by solid-state reaction, and their structural, Griffiths phase, magnetic entropy change, critical behavior, and electrical transport properties were systematically investigated. The results show that all polycrystalline samples are rhombohedral symmetry structures; the Griffiths phase exists above the low-temperature magnetic transition temperature (TC2) of the two samples; the magnetic field is applied to the La0.8Sr0.2Mn1−xCoxO3 (x = 0, 0.2) samples. The maximum magnetic entropy change ΔSmax for 7 T is − 2.28 and − 2.36 J/(kg K), respectively. The doping of Co makes ΔSmax increase, and an obvious negative entropy change occurs at low temperature and low field; the critical behavior of La0.8Sr0.2MnO3 (LSMO) fits best with the mean field model, and the critical behavior of the sample after doping with the 3D Heisenberg model fits best; LSMO is a semiconductor material, and the metal insulator transition appears near the low-temperature magnetic transition temperature (TC2) when the Co element doping amount reaches 0.2. The conductivity of the two samples in the high-temperature region satisfies the small polaron model. [ABSTRACT FROM AUTHOR]

A series of polycrystalline samples of perovskite cobalt oxide Pr(2-x)Tbx CoMnO6 (x =0.00,0.05,0.1 0) were prepared by traditional high-temperature solid-state reaction. The XRD spectra, magnetization curves and variation curve of applied magnetic field (M-T, M-H) with temperature were measured to study the crystal structure and magnetic properties of the sample. The results show that the series of samples Pr(2-x)TbxCoMnO6 (x = 0.00,0.05,0.10) exhibited good single phase. The spatial point group was P21/n. Due to the ferromagnetic super-exchange interaction between Co2 and Mn1 and a small amount of disordered ferromagnetic super-exchange interaction between Co3+ and Mn3+, two ferromagnetic transition points appeared in all the three samples. It is observed that there is a Griffiths-like phase in the series of samples. When temperature T was higher than TG, it showed pure paramagnetic state. When temperature was between TC2-TG, it showed paramagnetic-ferromagnetic coexistence state. At low temperature (T<