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To investigate the alleviating effect and mechanism of the docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on bisphenol A (BPA)-induced liver injury in mice, the murine liver injury model was established by gavage of BPA (5 mg/kg) or co-administration of BPA and DHA-PS (50 mg/kg or 100 mg/kg) for 6 weeks. The results showed that after administration of 100 mg/kg DHA-PS, the liver index, serum levels of AST, ALT, TC, TG, NEFA, and LDL-C in mice were significantly decreased, while HDL-C was significantly increased. The LPS, IL-6, IL-1β, TNF-α, and MDA levels in liver tissues were effectively down-regulated, and IL-10, SOD, GSH-Px, and CAT levels were effectively up-regulated. The H&E and Oil Red O staining results showed that liver damage was notably repaired and lipid deposition was notably reduced after DHA-PS administration. Furthermore, metabolomics and immunohistochemical studies revealed that DHA-PS mainly regulates glycerophospholipid metabolism and the SIRT1-AMPK pathway to improve metabolic disorders of the liver caused by BPA. Therefore, DHA-PS could potentially alleviate BPA-induced murine liver injury through suppressing inflammation and oxidative stress, and modulating lipid metabolism disorders.

The protective effects of docosahexaenoic acid-enriched phosphatidylserine (DHA-PS, 50 or 100 mg/kg) on bisphenol A (BPA)-induced intestinal damage were assessed. The biochemical indices, pathological examination, non-targeted metabolomics integrated with gut microbiota analysis, and immunofluorescence analysis were used to investigate the protective effects of DHA-PS and its underlying regulatory mechanism. The DHA-PS treatment improved the pathology of intestinal tract and increased the expression levels of Claudin-1, Occludin, and ZO-1. In addition, the DHA-PS treatment also notably decreased the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, and increased the antioxidant enzymes activities. Moreover, DHA-PS treatment increased the relative abundances of Akkermansia, Alistipes, Butyricicoccus, Coriobacteriaceae_UCG-002, Enterorhabdus, and Lachnospiraceae_UCG-006. DHA-PS treatment alleviated BPA-induced intestinal damage by regulating the kynurenine pathway of tryptophan, lipid, and arachidonic acid metabolisms. Overall, this study suggested that DHA-PS could alleviate BPA-induced intestinal damage by enhancing the intestinal barrier integrity, improving gut microbial composition and metabolites, and inhibiting the TLR4/NF-κB pathways.

The intensification of production practices in the aquaculture industry has led to the indiscriminate use of antibiotics to combat diseases and reduce costs, which has resulted in environmental pollution, posing serious threats to aquaculture sustainability and food safety. However, the toxic effect of florfenicol (FF) exposure on the hepatopancreas of crustaceans remains unclear. Herein, by employing Chinese mitten crab (Eriocheir sinensis) as subjects to investigate the toxic effects on histopathology, oxidative stress, apoptosis and microbiota of hepatopancreas under environment-relevant (0.5 and 5 μg/L), and extreme concentrations (50 μg/L) of FF. Our results revealed that the damage of hepatopancreas tissue structure caused by FF exposure in a dose-and time-dependent manner. Combined with the increased expression of apoptosis-related genes (Caspase 3, Caspase 8, p53, Bax and Bcl-2) at mRNA and protein levels, activation of catalase (CAT) and superoxide dismutase (SOD), and malondialdehyde (MDA) accumulation, FF exposure also induced oxidative stress, and apoptosis in hepatopancreas. Interestingly, 7 days exposure triggered more pronounced toxic effect in crabs than 14 days under environment-relevant FF concentration. Integrated biomarker response version 2 (IBRv2) index indicated that 14 days FF exposure under extreme concentration has serious toxicity effect on crabs. Furthermore, 14 days exposure to FF changed the diversity and composition of hepatopancreas microbiota leading remarkable increase of pathogenic microorganism Spirochaetes following exposure to 50 μg/L of FF. Taken together, our study explained potential mechanism of FF toxicity on hepatopancreas of crustaceans, and provided a reference for the concentration of FF to be used in culture of Chinese mitten crab.

More than half of all cancers demonstrate aberrant c-Myc expression, making this arguably the most important human oncogene. Deregulated long non-coding RNAs (lncRNAs) are also commonly implicated in tumorigenesis, and some limited examples have been established where lncRNAs act as biological tuners of c-Myc expression and activity. Here, we demonstrate that the lncRNA denoted c-Myc Enhancing Factor (MEF) enjoys a cooperative relationship with c-Myc, both as a transcriptional target and driver of c-Myc expression. Mechanistically, MEF functions by binding to and stabilizing the expression of hnRNPK in colorectal cancer cells. The MEF-hnRNPK interaction serves to disrupt binding between hnRNPK and the E3 ubiquitin ligase TRIM25, which attenuates TRIM25-dependent hnRNPK ubiquitination and proteasomal destruction. In turn, the stabilization of hnRNPK through MEF enhances c-Myc expression by augmenting the translation c-Myc. Moreover, modulating the expression of MEF in shRNA-mediated knockdown and overexpression studies revealed that MEF expression is essential for colorectal cancer cell proliferation and survival, both in vitro and in vivo. From the clinical perspective, we show that MEF expression is differentially increased in colorectal cancer tissues compared to normal adjacent tissues. Further, correlations exist between MEF, c-Myc, and hnRNPK suggesting the MEF-c-Myc positive feedback loop is active in patients. Together these data demonstrate that MEF is a pivotal partner of the c-Myc network and propose MEF as a valuable therapeutic target for colorectal cancer.

Subglacial lakes and hydrological systems play crucial roles in Antarctic subglacial hydrology, water balance, subglacial geomorphology, and ice dynamics. Satellite altimetry has revealed that some recurrent water exchange occurs in subglacial lakes. They are referred to as ’active lakes’, which prominently influence a majority of subglacial hydrological processes. Our analysis indicates that active subglacial lakes are more likely to be situated in regions with higher surface ice flow velocities. Nevertheless, the origin of subglacial lakes still remains enigmatic and uncertain. They could have potential associations with geothermal heat, ice sheets melting, and ice flow dynamics. Subglacial lake drilling and water sampling have the potential to provide valuable insights into the origin of subglacial lakes and subglacial hydrological processes. Moreover, they could also offer unique opportunities for the exploration of subglacial microbiology, evolution of the Antarctic ice sheets, and various fundamental scientific inquiries. To date, successful drilling and sampling has been accomplished in Lake Vostok, Lake Mercer, and Lake Whillans. However, the use of drilling fluids caused the water sample contamination in Lake Vostok, and the drilling attempt at Lake Ellsworth failed due to technical issues. To explore more of the conditions of the Antarctic subglacial lakes, the Lake Centro de Estudios Científicos (Lake CECs) and Lake Snow Eagle (LSE) drilling projects are upcoming and in preparation. In this study, we aim to address the following: (1) introduce various aspects of Antarctic subglacial lakes, subglacial hydrological elements, subglacial hydrology, and the interactions between ice sheets and the ocean; and (2) provide an overview and outlook of subglacial lakes drilling projects.

Abstract The emergence of ionic-junction devices has attracted growing interests due to the potential of serving as signal transmission and translation media between electronic devices and biological systems using ions. Among them, fiber-shaped iontronics possesses a great advantage in implantable applications owing to the unique one-dimensional geometry. However, fabricating stable ionic-junction on curved surfaces remains a challenge. Here, we developed a polyelectrolyte based ionic-junction fiber via an integrated opposite charge grafting method capable of large-scale continuous fabrication. The ionic-junction fibers can be integrated into functions such as ionic diodes and ionic bipolar junction transistors, where rectification and switching of input signals are implemented. Moreover, synaptic functionality has also been demonstrated by utilizing the fiber memory capacitance. The connection between the ionic-junction fiber and sciatic nerves of the mouse simulating end-to-side anastomosis is further performed to realize effective nerve signal conduction, verifying the capability for next-generation artificial neural pathways in implantable bioelectronics.

ABSTRACT To explore the functions of Txnip and its mechanism in adipocyte differentiation, the preadipocytes were isolated from subcutaneous adipose tissue of three-day-old piglets and induced into adipogenic differentiation. The expression of Txnip and ChREBP was silenced, and the Txnip overexpression was achieved in the cells with transfection of the recombinant lentivirus strategies. Txnip silencing promoted the differentiation of porcine preadipocytes and PPARγ expression, and a PPARγ inhibitor reduced this facilitation. Instead, Txnip overexpression exerted a suppressive effect on the cell differentiation and PPARγ expression, and the PPARγ agonist offset this inhibition. High glucose stimulated the preadipocyte differentiation and expressions of ChREBP and Txnip. In contrast, Txnip expression was reduced by ChREBP silencing, suggesting glucose-regulated Txnip expression through the mediation of ChREBP. Moreover, the expressions of ChREBP and Glut4 induced by high glucose and glucose uptake of the cells were reduced by Txnip-overexpression, but increased by Txnip silencing, while these changes of Txnip did not alter their expressions under low glucose. Collectively, Txnip could be an inhibitor of porcine preadipocyte differentiation, which attenuated the adipogenesis through the negative feedback regulation on PPARγ. Txnip impaired the induction of glucose on the preadipocyte differentiation through decreasing Glut4 expression and glucose uptake and subsequent decrease of the expression and transcriptional activity of ChREBP.

Mobile Edge Computing (MEC) can support various high-reliability and low-delay applications in Maritime Networks (MNs). However, security risks in computing task offloading exist. In this study, the location privacy leakage risk of Maritime Mobile Terminals (MMTs) is quantified during task offloading and relevant Location Privacy Protection (LPP) schemes of MMT are considered under two kinds of task offloading scenarios. In single-MMT and single-time offloading scenario, a dynamic cache and spatial cloaking-based LPP (DS-CLP) algorithm is proposed; and under the multi-MMTs and multi-time offloading scenario, a pseudonym and alterable silent period-based LPP (PA-SLP) strategy is proposed. Simulation results show that the DS-CLP can save the response time and communication cost compared with traditional algorithms while protecting the MMT location privacy. Meanwhile, extending the alterable silent period, increasing the number of MMTs in the maritime area or improving the pseudonym update probability can enhance the LPP effect of MMTs in PA-SLP. Furthermore, the study results can be effectively applied to MNs with poor communication environments and relatively insufficient computing resources.

In order to improve the corrosion resistance of the anodic oxidation film on magnesium alloy，an anodic oxidation film was fabricated on the surface of magnesium alloy by adding MgO nano - particles into the silicate alkaline electrolyte. The effects of MgO nano - particles on the surface morphology, phase composition and thickness of the anodic oxidation film were analyzed by optical microscopy, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), film thickness meter and X - ray diffraction (XRD). Besides, the effect of MgO nano - particles on the corrosion resistance of the anodic oxidation film was analyzed by dropping test and 3.5% NaCl immersion corrosion test. Results showed that adding MgO nano - particles into the electrolyte could reduce the number of micropores in the film and increase its density, thickness and MgO content, thus improving the corrosion resistance of the film.

Three hundred 21-day-old male Qingjiaoma broilers were randomly assigned to six groups to investigate the effect of dietary stems and leaves of Astragalus mongholicus (AMSLs), Astragalus polysaccharides (APSs), Lactobacillus (Lac) and their combinations on finishing broilers in a 42-day feeding experiment. Supplementary 1% AMSLs, 1 000 mg/kg APSs and 4.5 × 1010 CFU/kg Lac improved significantly growth performance. Dietary AMSLs, APSs and Lac increased the serum concentrations of immunoglobulins IgA, IgG and complements C3 and C4. Furthermore, AMSLs increased glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities and total antioxidation capacity (T-AOC) and decreased the malondialdehyde (MDA) content in both serum and liver tissue. Compared with individual supplementation, the combination of Lac and AMSLs or APSs increased serum IgA, IgG, C3 and C4 concentrations. The combination of AMSLs and Lac increased serum GSH-Px activity and reduced the MDA content in the serum and liver tissue. These results suggested that AMSLs, APSs and Lac are beneficial feed additives, and the applications of combined Lac and AMSLs or APSs could synergistically improve immunity in broilers.

Abstract Cold tolerance at the bud burst stage (CTB) is a key trait for direct-seeded rice. Although quantitative trait loci (QTL) affecting CTB in rice have been mapped using traditional linkage mapping and genome-wide association study (GWAS) methods, the underlying genes remain unknown. In this study, we evaluated the CTB phenotype of 339 cultivars in the Rice Diversity Panel II (RDP II) collection. GWAS identified four QTLs associated with CTB (qCTBs), distributed on chromosomes 1–3. Among them, qCTB-1-1 overlaps with Osa-miR319b, a known cold tolerance micro RNA gene. The other three qCTBs have not been reported. In addition, we characterised the candidate gene OsRab11C1 for qCTB-1-2 that encodes a Rab protein belonging to the small GTP-binding protein family. Overexpression of OsRab11C1 significantly reduced CTB, while gene knockout elevated CTB as well as cold tolerance at the seedling stage, suggesting that OsRab11C1 negatively regulates rice cold tolerance. Molecular analysis revealed that OsRab11C1 modulates cold tolerance by suppressing the abscisic acid signalling pathway and proline biosynthesis. Using RDP II and GWAS, we identified four qCTBs that are involved in CTB and determined the function of the candidate gene OsRab11C1 in cold tolerance. Our results demonstrate that OsRab11C1 is a negative regulator of cold tolerance and knocking out of the gene by genome-editing may provide enhanced cold tolerance in rice.

The receptor-binding domain (RBD) and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) play a crucial role in the entry and replication of viral particles, and co-targeting both of them could be an attractive approach for the treatment of SARS-CoV-2 infection by setting up a “double lock” in the viral lifecycle. However, few dual RBD/Mpro-targeting agents have been reported. Here, four novel RBD/Mpro dual-targeting peptides, termed as MRs 1-4, were discovered by an integrated virtual screening scheme combining molecular docking-based screening and molecular dynamics simulation. All of them possessed nanomolar binding affinities to both RBD and Mpro ranging from 14.4 to 39.2 nM and 22.5–40.4 nM, respectively. Further pseudovirus infection assay revealed that the four selected peptides showed >50% inhibition against SARS-CoV-2 pseudovirus at a concentration of 5 µM without significant cytotoxicity to host cells. This study leads to the identification of a class of dual RBD/Mpro-targeting agents, which may be developed as potential and effective SARS-CoV-2 therapeutics.

Conventional upconversion nanoparticles (UCNPs) cannot activate multiple neuron populations independently using optogenetics. Here the authors report trichromatic UCNPs with excitation-specific luminescence to allow activation of three distinct neuronal populations in the brain of awake mice.

Background: Psoriasis is characterized by keratinocyte proliferation and massive inflammatory leukocytes infiltration, affecting 0.14%–1.99% of the world’s population. Our aim was to identify novel potential therapeutic strategies for psoriasis.Methods: Weighted gene co-expression network analysis (WGCNA) was performed to identify gene modules that were closely related to psoriasis based on the GSE30999 dataset, which contained expression data from 85 patients with moderate-to-severe psoriasis. Then, angiopoietin-like 4 (ANGPTL4), one of the most related hub genes, was selected for in vitro and in vivo functional assays. In our experiments, imiquimod (IMQ)-induced psoriasiform dermatitis in mice and human keratinocytes (HaCaT) cells were used to study the potential roles and mechanisms of ANGPTL4 in psoriasis.Results: WGCNA analysis revealed the turquoise module was most correlated with psoriasis, and ANGPTL4 is one of the most related hub genes that significantly upregulated in psoriasis lesions compared with non-lesional skin. Consistent with the bioinformatic analysis, the expression of ANGPTL4 was significantly upregulated in IMQ-induced psoriasiform skin of mice. Exogenous recombinant ANGPLT4 protein treatment could promote the proliferation and induce the expression of inflammatory cytokines in HaCaTs, whereas silencing of ANGPTL4 effectively inhibited these effects. Then we demonstrated that recombinant ANGPTL4 protein exacerbated psoriasiform inflammation and epidermal hyperproliferation in vivo. Mechanismly, extracellular signal-regulated kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3) pathways were involved in ANGPTL4-mediated regulation of proliferation and inflammation.Conclusion: We found ANGPTL4 was significantly increased in IMQ-induced psoriasiform skin of mice. ANGPTL4 could promote keratinocyte proliferation and inflammatory response via ERK1/2 and STAT3 dependent signaling pathways in psoriasis.

PurposeThe prespinal route of contralateral cervical 7 nerve transfer developed by Prof. Wendong Xu helps realize the direct anastomosis of the bilateral cervical 7 nerves. However, 20% of operations still require a nerve graft, which leads to an unfavorable prognosis. This study aims to explore the optimized prespinal route with MRI to further improve the prognosis.MethodsThe current study enrolled 30 patients who suffered from central spastic paralysis of an upper limb and who underwent contralateral cervical 7 nerve transfer via Prof. Xu’s prespinal route through the anterior edge of the contralateral longus colli. MRI images were used to analyze the route length, vertebral artery exposure, and contralateral cervical 7 nerve included angle. Three prespinal routes were virtually designed and analyzed. The selected optimal route was applied to another 50 patients with central spastic paralysis of an upper limb for contralateral cervical 7 nerve transfer.ResultsBy the interventions on the 30 patients, the middle and posterior routes were shorter than the anterior route in length, but with no statistical difference between the two routes. Of 30 contralateral vertebral arteries, 26 were located at the posterior medial edge of the longus colli. The average included angles of the anterior, middle, and posterior routes were 108.02 ± 7.89°, 95.51 ± 6.52°, and 72.48 ± 4.65°, respectively. According to these data, the middle route was optimally applied to 50 patients, in whom the rate of nerve transplantation was only 4%, and no serious complications such as vertebral artery or brachial plexus injury occurred.ConclusionThe low rate of nerve transplantation in 50 patients and the absence of any serious complications in these cases suggests that the middle route is the optimal one.

There is a need for induction filter technology in the field of low-voltage distribution networks. This paper proposes an induction filter distribution transformer with a unique Dd0yn11 three-winding configuration. This approach allows for the control of load side harmonics in low-voltage distribution networks. At present, the induction filter technology proposed in the known literature is mostly used in the high-voltage power system, but there is still no research on the application of induction filter technology to the distribution transformer with Dyn11 under the low-voltage distribution network. In this paper, the wiring scheme of inductive filter distribution transformer and filter system in low-voltage distribution network is established firstly, then the mathematical relationship between the harmonic current generated by the load side and the current on the grid side is derived according to the winding model, and it can be deduced that the induction filter distribution transformer with its filtering system has good filtering performance and reactive power compensation characteristics. Finally, the experiment simulates the three-phase harmonic load, detects the current waveform and other parameters of the actual grid side of the new transformer, verifies the correctness of the theoretical analysis. The induction filter distribution transformer proposed in this paper provides a new solution for harmonic suppression and reactive power compensation in low-voltage distribution network, which fills the vacancy of the application of induction filter technology in low-voltage distribution network, This paper reveals that the inductive filter technique has a good filtering performance when applied to low-voltage distribution network. And it provides a reference for further research on improving power grid efficiency, saving energy cost and improving transformer electromagnetic environment under low-voltage distribution network.

Rice leaf width (RLW) is a crucial determinant of photosynthetic area. Despite the discovery of several genes controlling RLW, the underlying genetic architecture remains unclear. In order to better understand RLW, this study conducted a genome-wide association study (GWAS) on 351 accessions from the rice diversity population II (RDP-II). The results revealed 12 loci associated with leaf width (LALW). In LALW4, we identified one gene, Narrow Leaf 22 (NAL22), whose polymorphisms and expression levels were associated with RLW variation. Knocking out this gene in Zhonghua11, using CRISPR/Cas9 gene editing technology, resulted in a short and narrow leaf phenotype. However, seed width remained unchanged. Additionally, we discovered that the vein width and expression levels of genes associated with cell division were suppressed in nal22 mutants. Gibberellin (GA) was also found to negatively regulate NAL22 expression and impact RLW. In summary, we dissected the genetic architecture of RLW and identified a gene, NAL22, which provides new loci for further RLW studies and a target gene for leaf shape design in modern rice breeding.

Four new wood-inhabiting fungi, Trechispora albofarinosa, T. bisterigmata, T. pileata and T. wenshanensis spp. nov., are proposed based on a combination of morphological features and molecular evidence. Trechispora albofarinosa is characterized by the farinose basidiomata with flocculence hymenial surface, a monomitic hyphal system with clamped generative hyphae, and ellipsoid, warted basidiospores. Trechispora bisterigmata is characterized by the membranous basidiomata with odontioid hymenial surface, rhizomorphic sterile margin, barrelled basidia and subglobose to broad ellipsoid, smooth basidiospores. Trechispora pileata is characterized by the laterally contracted base, solitary or imbricate basidiomata, fan shaped pileus, radially striate-covered surface with appressed scales, odontioid hymenophore surface, and subglobose to broad ellipsoid, thin-walled, smooth basidiospores. Trechispora wenshanensis is characterized by a cottony basidiomata with a smooth hymenial surface, and ellipsoid, thin-walled, warted basidiospores. Sequences of ITS and LSU marker of the studied samples were generated, and phylogenetic analyses were performed with the maximum likelihood, maximum parsimony, and Bayesian inference methods. The phylogenetic tree inferred from the ITS+nLSU sequences highlighted that four new species were grouped into the genus Trechispora. [ABSTRACT FROM AUTHOR]

Using frequency-modulated continuous wave radar data from the 32nd Chinese Antarctic Research Expedition in 2015/16, subsurface profiles were obtained along an East Antarctic inland traverse from Zhongshan station to Dome A, and four distinct regions were selected to analyze the spatiotemporal variability in historical surface mass balance (SMB). Based on depth, density, and age data from ice cores along the traverse, the radar data were calibrated to yield average SMB data. The zone 49–195 km from the coast has the highest SMB (235 kg m−2 a−1). The 780–892 km zone was most affected by the Medieval Warm Period and the Little Ice Age, and the SMB during ad 1454–1836 (71 kg m−2 a−1) was only one-quarter of that in the 20th century. The SMB in the 1080–1157 km zone fluctuates the most, possibly due to erosion or irregular deposition of snow by katabatic winds in low SMB areas with surface elevation fluctuations. Dome A (1157–1236 km) has the lowest SMB (29 kg m−2 a−1) and did not decrease during Little Ice Age. Understanding the spatiotemporal variability of SMB in a larger space can help us understand the complex climate history of Antarctica.

Introduction The pathology of Alzheimer’s disease (AD) includes β-amy�loid (Aβ) (plaques) and neurofibrillary tangles (NFTs). This study aimed to explore the efficacy of Huatuo Zaizao pill (HTZP) in an AD mouse model in�duced by injecting Aβ 1-42 , and the neuroprotective mechanism of HTZP in Material and methods C57BL/6 (B6) mice were randomly divided into 4 groups (n = 10, per group): control group, AD model group, and 2 differ�ent doses of HTZP treated groups. The Morris water maze test was carried out on AD mice to assess the learning ability after treatment with HTZP for 15 day. The levels of inflammatory factors and the nuclear factor-κB (NF-κB) pathway were examined by western blot and real-time polymerase chain reac�tion (PCR). The content of microglia was investigated by immunofluorescence. Results This study revealed that a cognitive disorder could be mitigated when the AD mice were treated with HTZP, which might be associated with the decreased level of pro-inflammatory factors, and the inhibitory activities of microglia. Additionally, phosphorylation of IκB and NF-κB p65 could be reduced by prohibiting the neuroinflammation of NF-κB activation in the hippocampus of AD mice. Conclusions These results showed that HTZP could mitigate a cognitive disorder, diminish the activation of microglia, and inhibit the content of inflammatory factors through the NF-κB pathway in Aβ 1-42 -induced AD mice. HTZP may be an appropriate agent for AD treatment in the future.

Abstract The goal of global carbon peak and neutrality gives an impetus to the utilization of clean energy (e.g., fuel cell) and carbon dioxide (CO2) at a large scale, where the oxygen reduction reaction (ORR) and CO2 reduction reaction (CO2RR) are the key reactions via the sustainable system, respectively. As a main precursor for fabricating affordable carbon‐based electrocatalysts with uniformly dispersed active centers and tailorable performances for ORR and CO2RR, metal organic frameworks (MOFs) have captured a surge of interest in recent years. Despite the facilitated development of MOF‐derived carbon‐based electrocatalysts by many investigations, it is still plagued by high overpotential and unsatisfied life span, which are greatly determined by the efficient and alterable confinement effect on synthesis and performance. In this review, firstly, the confined synthetic strategies (doping engineering, defect engineering, geometric engineering, etc.) of MOF‐derived carbon‐based electrocatalysts with multi‐sized active centers (atom, atomic clusters and nanoparticles (NPs)) are systematically summarized; secondly, the confinement effect on the interaction of ORR and CO2RR intermediates, as well as the catalytic durability and activity, was discussed from chemical and physical aspects. In the end, the review discusses the remaining challenges and emerging research topics in the future, including support upgradation and catalyst innovation, high selectivity and effective confinement synthesis, in situ and operando characterization techniques, theoretical investigation, and artificial intelligence (AI) assistant. The new understanding and insights into these aspects will guide the rational confinement concept of MOF‐derived carbon‐based electrocatalysts for ORR and CO2RR with optimized performances in terms of confinement engineering and are believed to be helpful for filling the existing gaps between scientific communities and practical use.

Summary: Background: A previous randomized controlled trial showed contralateral seventh cervical nerve (CC7) cross transfer to be safe and effective in restoring the arm function of spastic arm paralysis patients in a specified population. Guidance on indications, safety and expected long-term improvements of the surgery are needed for clinical practice. Methods: This is a retrospective, multicenter, propensity score-matched cohort study. All patients registered between 2013 and 2019 with unilateral spastic arm paralysis over 1 year who were registered at one of five centers in China and South Korea were included. Patients received CC7 cross transfer or rehabilitation treatment in each center. Primary outcome was the change in the upper-extremity Fugl–Meyer (UEFM) score from baseline to 2-year follow-up; larger increase indicated better functional improvements. Findings: The analysis included 425 eligible patients. After propensity score matching, 336 patients who were 1:1 matched into surgery and rehabilitation groups. Compared to previous trial, patient population was expanded on age ( 45 years old), duration of disease (

Burkholderia pseudomallei is an important infectious disease pathogen that can cause melioidosis. Melioidosis is mainly prevalent in Thailand, northern Australia and southern China and has become a global public health problem. Early identification of B. pseudomallei is of great significance for the diagnosis and prognosis of melioidosis. In this study, a simple and visual device combined with lateral flow strip-based recombinase polymerase amplification (LF-RPA) was developed, and the utility of the LF-RPA assay for identifying B. pseudomallei was evaluated. In order to screen out the optimal primer probe, a total of 16 pairs of specific primers targeting the orf2 gene of B. pseudomallei type III secretion system (T3SS) cluster genes were designed for screening, and F1/R3 was selected as an optimal set of primers for the identification of B. pseudomallei, and parameters for LF-RPA were optimized. The LF-RPA can be amplified at 30-45°C and complete the entire reaction in 5-30 min. This reaction does not cross-amplify the DNA of other non-B. pseudomallei species. The limit of detection (LOD) of this assay for B. pseudomallei genomic DNA was as low as 30 femtograms (fg), which was comparable to the results of real-time PCR. Moreover, 21 clinical B. pseudomallei isolates identified by 16S rRNA gene sequencing were retrospectively confirmed by the newly developed LF-RPA system. Our results showed that the newly developed LF-RPA system has a simple and short time of operation and has good application prospect in the identification of B. pseudomallei.

Abstract Adult patients with relapsed or refractory T‐cell acute lymphoblastic leukemia (R/R‐T‐ALL) have extremely poor prognosis, representing an urgent unmet medical need. Finding an optimal salvage regimen to bridge transplantation is a priority. The CAG (cytarabine, aclarubicin, and G‐CSF) regimen was initially used by one group in China, showing unexpectedly promising results in 11 R/R‐T‐ALL patients. Here, we report the multicenter results of 41 patients who received the CAG regimen as salvage therapy. After one cycle of the CAG regimen, complete remission and partial remission were achieved in 33 (80.5%) and two (4.9%) patients, respectively. Failure to respond was observed in six patients (14.6%). Early T‐cell precursor (ETP) (n = 26) and non‐ETP (n = 15) patients had a similar CR rate (80.8% vs 80.0%, P = .95). Among 41 patients, allo‐HSCT was successfully performed in 27 (66%) patients (22 in CR and 5 in non‐CR). With a median follow‐up time of 12 months, the estimated 2‐year overall survival and event‐free survival were 68.8% (95% CI, 47.3%‐83.0%) and 56.5% (95% CI, 37.1%‐71.9%), respectively. The CAG regimen was well‐tolerated, and no early death occurred. Our multicenter results show that the CAG regimen is highly effective and safe, representing a novel choice for adult patients with R/R‐T‐ALL and providing a better bridge to transplantation.

Abstract Background Cushing’s syndrome has been described as a complex endocrine disorder characterized with high cortisol concentration. Correct and early diagnosis of Cushing’s syndrome is challenging. According to the latest guideline, bilateral inferior petrosal sinus sampling (BIPSS) is considered to be the gold standard for the differential diagnosis. However, in some unusual cases, this method may be false positive. Here, we presented a rare case of orbital neuroendocrine tumor secreting adrenocorticotrophic hormone with false positive inferior petrosal sinus sampling. Case presentation A 48-year-old woman was admitted to West China Hospital of Sichuan University, presenting with fatigue, whole body edema for 1 year, alopecia and skin pigmentation for 5 months. Hormonal profiles including plasma cortisol and adrenocorticotrophic hormone (ACTH) measurements and low-dose dexamethasone inhibition test suggested that the patient had Cushing’s syndrome. However, during tumor location phase, the results of high-dose dexamethasone inhibition test (HDDST) contradicted desmopressin (DDAVP) stimulation test. Thus, BIPSS was employed, and its results indicated a pituitary origin. Interestingly, MRI of sellar region showed an innocent pituitary but caught a serendipitous lesion in the lateral rectus muscle of left eye, which was later proved to be an orbital neuroendocrine tumor secreting ACTH by pathological and immunohistochemical results. ACTH level of the patients was

Abstract Background Circular RNA (circRNA) is highly expressed in the brain tissue, but its molecular mechanism in cerebral ischemia–reperfusion remains unclear. Here, we explored the role and underlying mechanisms of circRNA antisense non-coding RNA in the INK4 locus (circ_ANRIL) in oxygen–glucose deprivation and reoxygenation (OGD/R)-induced cell injury. Results The expression of circ_ANRIL in OGD/R-induced human brain microvascular endothelial cells (HBMECs) was significantly up-regulated, while that of miR-622 was significantly down-regulated. Overexpression of circ_ANRIL significantly inhibited the proliferation of OGD/R-induced HBMECs and aggravated OGD/R-induced cell apoptosis. Moreover, circ_ANRIL overexpression further increased the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in OGD/R-treated HBMECs. The results of bioinformatics analysis and luciferase reporter assay indicated that circ_ANRIL served as an miR-622 sponge to negatively regulate the expression of miR-622 in OGD/R-treated HBMECs. Additionally, circ_ANRIL silencing exerted anti-apoptotic and anti-inflammatory effects by positively regulating the expression of miR-622. Furthermore, inhibition of OGD/R-induced activation of the nuclear factor (NF)-κB pathway by circ_ANRIL silencing was significantly reversed by treatment with miR-622 inhibitor. Conclusions Knockdown of circ_ANRIL improved OGD/R-induced cell damage, apoptosis, and inflammatory responses by inhibiting the NF-κB pathway through sponging miR-622.

Objective To investigate the effect of down-regulation of Notch1 expression mediated by lentivirus on the activation of caspase-9 and mitochondrial membrane potential of fibroblast from pathological scars(PSF). Methods PSFs were isolated and cultured and then infected by Notch1 siRNA lentivirus and negative control lentivirus respectively.The level of Notch1 mRNA and protein was detected by real-time PCR and Western blot,respectively.MTT assay was used to detect cell proliferation; PI monochrome staining was used to detect cell cycle changes. Annexin V-FITC/PI assay was used to detect apoptotic changes; Western blot was used to detect the level of cyclin D1, CDK4, c-caspase-3, c-caspase-9 and cytochrome C protein levels in cytoplasm and mitochondria; JC-1 method was used to detect the mitochondrial membrane potential. Results The expression of Notch1 in PSFs transfected with Notch1 siRNA lentivirus was significantly lower than that in the negative control lentiviruses and the non-transfected PSFs(P＜0.05).The proliferation of PSFs decreased after Notch1 was down-regulated (P＜0.05);the percen-tage of G0/G1 phase increased(P＜0.05); the apoptotic rate increased(P＜0.05); the expression of c-caspase-3 and c-caspase-9 protein increased(P＜0.05); the mitochondrial membrane potential of the cells decreased significantly(P＜0.05); the level of cyclin D1 and CDK4 protein in cells decreased(P＜0.05); cytochrome C protein increased in cytoplasm and decreased in mitochondria(P＜0.05). Conclusions Down-regulation of Notch1 inhibits proliferation and induces apoptosis of PSF.

Amyloid beta (Aβ)-induced neurotoxicity and oxidative stress plays an important role in the pathogenesis of Alzheimer’s disease (AD). ZL006 is shown to reduce over-produced nitric oxide and oxidative stress in ischemic stroke by interrupting the interaction of neuronal nitric oxide synthase and postsynaptic density protein 95. However, few studies are reported on the role of ZL006 in AD. To investigate whether ZL006 exerted neuroprotective effects in AD, we used Aβ1–42 to treat primary cortical neurons and N2a neuroblastoma cells as an in vitro model of AD. Cortical neurons were incubated with ZL006 or dimethyl sulfoxide for 2 hours and treated with Aβ1–42 or NH3•H2O for another 24 hours. The results of cell counting Kit-8 (CCK-8) assay and calcein-acetoxymethylester/propidium iodide staining showed that ZL006 pretreatment rescued the neuronal death induced by Aβ1–42. Fluorescence and western blot assay were used to detect oxidative stress and apoptosis-related proteins in each group of cells. Results showed that ZL006 pretreatment decreased neuronal apoptosis and oxidative stress induced by Aβ1–42. The results of CCK8 assay showed that inhibition of Akt or NF-E2-related factor 2 (Nrf2) in cortical neurons abolished the protective effects of ZL006. Moreover, similar results were also observed in N2a neuroblastoma cells. ZL006 inhibited N2a cell death and oxidative stress induced by Aβ1–42, while inhibition of Akt or Nrf2 abolished the protective effect of ZL006. These results demonstrated that ZL006 reduced Aβ1–42-induced neuronal damage and oxidative stress, and the mechanisms might be associated with the activation of Akt/Nrf2/heme oxygenase-1 signaling pathways.

Perchlorate (ClO4−) is harmful to human health, and knowledge on the levels and sources of natural ClO4− in different environments remains rather limited. Here, we investigate ClO4− in aerosol samples collected along a cross-hemisphere ship cruise between China and Antarctica and on a traverse between coastal East Antarctica and the ice sheet summit (Dome Argus). Perchlorate concentrations range from a few to a few hundred pg m−3. A clear latitudinal trend is found, with elevated ClO4− concentrations near populated areas and in the southern mid-high latitudes. Spatial patterns of atmospheric ClO4− over oceans near the landmasses support that terrestrial ClO4− is not transported efficiently over long distances. In the southern mid-latitudes, higher ClO4− concentrations in March than in November-December may be caused by significant stratospheric inputs in March. Perchlorate concentrations appear to be higher in the warm half than in the cold half of the year in the southern high latitudes, suggesting seasonal difference in main atmospheric sources. ClO4− may be formed in the reactions between chlorine free radical (Cl·) and ozone (O3) in the stratosphere when Antarctic ozone hole occurs during September-October. And the stratosphere-produced ClO4− is moved to the boundary layer in several months and may be responsible for the high ClO4− concentrations in the warm half of the year. Perchlorate produced by photochemical reactions between O3 and Cl· in the Antarctic stratosphere is likely responsible for the higher ClO4− concentrations in Antarctica than in Arctic.

Data-space inversion (DSI) is a data assimilation procedure that directly generates posterior flow predictions, for time series of interest, without calibrating model parameters. No forward flow simulation is performed in the data assimilation process. DSI instead uses the prior data generated by performing O(1000) simulations on prior geomodel realizations. Data parameterization is useful in the DSI framework as it enables representation of the correlated time-series data quantities in terms of low-dimensional latent-space variables. In this work, a recently developed parameterization based on a recurrent autoencoder (RAE) is applied with DSI for a real naturally fractured reservoir. The parameterization, involving the use of a recurrent neural network and an autoencoder, is able to capture important correlations in the time-series data. RAE training is accomplished using flow simulation results for 1,350 prior model realizations. An ensemble smoother with multiple data assimilation (ESMDA) is applied to provide posterior DSI data samples. The modeling in this work is much more complex than that considered in previous DSI studies as it includes multiple 3D discrete fracture realizations, three-phase flow, tracer injection and production, and complicated field-management logic leading to frequent well shut-in and reopening. Results for the reconstruction of new simulation data (not seen in training), using both the RAE-based parameterization and a simpler approach based on principal component analysis (PCA) with histogram transformation, are presented. The RAE-based procedure is shown to provide better accuracy for these data reconstructions. Detailed posterior DSI results are then presented for a particular “true” model (which is outside the prior ensemble), and summary results are provided for five additional “true” models that are consistent with the prior ensemble. These results again demonstrate the advantages of DSI with RAE-based parameterization for this challenging fractured reservoir case.