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UAV swarms have increasingly replaced human labor in various industries. However, controlling a large group of UAVs can be difficult and, if not done correctly, cause significant financial losses and delays. While many methods aim to improve how the group is controlled, little focus is given to optimizing and stabilizing movement trajectories, which limits the emergency response and reliability of UAV swarm in dynamic environments. This paper proposes a new method to control UAVs through Proximal Policy Optimization. This method utilizes two neural networks and incorporates the concept of a game. During training, one neural network generates an action based on the current state, while the other evaluates the output of the first network. With continuous refinement, the performance of both networks can be enhanced, ultimately leading to the optimal decision-making model. Additionally, this research introduces a hierarchical management mechanism to address the issue of complex computations in large bee colonies and to distribute control more evenly. Simulation results demonstrate that this approach can successfully reconstruct formations under various scenarios. Compared to similar algorithms, this method is at the forefront of tackling large-scale problems, with a collision rate close to 0 and a 100% success rate in emergency processing.

Microcirculatory disturbances are complex processes caused by many factors, including abnormal vasomotor responses, decreased blood flow velocity, vascular endothelial cell injury, altered leukocyte and endothelial cell interactions, plasma albumin leakage, microvascular hemorrhage, and thrombosis. These disturbances involve multiple mechanisms and interactions among mechanisms that can include energy metabolism, the mitochondrial respiratory chain, oxidative stress, inflammatory factors, adhesion molecules, the cytoskeleton, vascular endothelial cells, caveolae, cell junctions, the vascular basement membrane, neutrophils, monocytes, and platelets. In clinical practice, aside from drugs that target abnormal vasomotor responses and platelet adhesion, there continues to be a lack of multi-target drugs that can regulate the complex mechanistic links and interactions underlying microcirculatory disturbances. Natural products have demonstrated obvious positive therapeutic effects in treating ischemia/reperfusion (I/R)- and lipopolysaccharide (LPS)-induced microcirculatory disturbances. In recent years, numerous research papers on the improvement of microcirculatory function by natural products have been published in international journals. In 2008 and 2017, the first listed author of this review was invited to publish reviews in the journal of Pharmacology & Therapeutics on the improvement of microcirculatory disturbances and organ injury induced by I/R using Salvia miltiorrhiza ingredients and other natural components of compounded Chinese medicine, respectively. This review systematically summarizes the effects, targets of action, and mechanisms of natural products regarding improving I/R- and LPS-induced microcirculatory disturbances and tissue injury. Based on this summary, scientific proposals are suggested for the discovery of new drugs to improve microcirculatory disturbances in disease.

Abstract Immunotherapy exhibited potential effects for advanced hepatocellular carcinoma, unfortunately, the clinical benefits are often countered by cancer adaptive immune suppressive response. Uncovering the mechanism how cancer cells evade immune surveillance would help to develop new immunotherapy approaches and combination therapy. In this article, by analyzing the transcriptional factors which modulate the differentially expressed genes between T cell infiltration high group and low group, we identified oncoprotein B cell lymphoma 6 (BCL6) suppresses the infiltration and activation of tumor infiltrating T lymphocytes, thus correlated with poorer clinical outcome. By using antibody deletion experiment, we further demonstrated that CD4+T cells but not CD8+T cells are the main lymphocyte population suppressed by Bcl6 to promote HCC development. Mechanistically, BCL6 decreases cancer cell expression of pro-inflammatory cytokines and T lymphocyte chemokines such as IL6, IL1F6, and CCL5. Moreover, BCL6 upregulates Endothelial cell-specific molecule 1 (ESM1) to inhibit T lymphocyte recruitment and activation possibly through ICAM-1/LFA-1 signaling pathway. Our findings uncovered an unappreciated paracrine mechanism how cancer cell-derived BCL6 assists cancer cell immune evasion, and highlighted the role of CD4+T cells in HCC immune surveillance.

Endothelial cell specific-1 (ESM-1), also known as endocan, is a soluble dermatan sulfate proteoglycan that is mainly secreted by endothelial cells. Endocan is associated with tumorigenesis and cancer progression and is also related to cardiovascular disorders, autoimmune diseases, and sepsis. The phenylalanine-rich region and linear polysaccharide of endocan are necessary for the protein to exert its biological functions. Elevated plasma endocan levels reflect endothelial activation and dysfunction. In addition, endocan participates in complex inflammatory responses and proliferative processes. Here, we reviewed current research on endocan, elaborated the protein’s structure and biological functions, and speculated on its possible clinical value in nervous system diseases. We conclude that endocan may be a glycoprotein that plays an important role in neurological disorders.

Objective: Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage damage. In order to find a safer and more effective drug to treat OA, we investigated the role of quercetin-3-O-β-D-glucuronide (Q3GA) in OA. Methods: We used qRT-PCR and western blots to detect the effects of Q3GA on extracellular matrix (ECM) and inflammation related genes and proteins in interleukin-1β (IL-1β) induced chondrocytes. We determined the effect of Q3GA on the NF-κB pathway using western blots and immunofluorescence. Moreover, the effect of Q3GA on the Nrf2 pathway was evaluated through molecular docking, western blots, and immunofluorescence experiments and further validated by transfection with Nrf2 siRNA. Subsequently, we established a rat model of OA and injected Q3GA into the joint cavity for treatment. After 5 weeks of Q3GA administration, samples were obtained for micro-computed tomography scanning and histopathological staining to determine the effects of Q3GA on OA rats. Results: We found that Q3GA reduced the degradation of ECM and the expression of inflammatory related proteins and genes in primary chondrocytes of rats induced by IL-1β, as well as the expression of nitric oxide (NO) and reactive oxygen species (ROS). It inhibited the activation of the NF-κB pathway by increasing the expression of Nrf2 in the nucleus. In addition, Q3GA inhibited cartilage degradation in OA rats and promoted cartilage repair. Conclusion: Q3GA attenuates OA by inhibiting ECM degradation and inflammation via the Nrf2/NF-κB axis. The translational potential of this article: The results of our study demonstrate the promising potential of Q3GA as a candidate drug for the treatment of OA and reveal its key mechanisms.

IntroductionDue to the high-density farming of Larimichthys crocea over the years, diseases caused by pathogens such as bacteria, viruses, and parasites frequently occur in Ningbo, posing a huge threat and challenge to the sustainable and healthy development of the L. crocea’s bay farming industry. In order to understand the diseases occurrence in L. crocea farming in Ningbo area, an epidemiological investigation of L. crocea diseases was carried out through regular sampling in 2023. MethodsFrom April to October 2023, routine sampling of L. crocea was conducted monthly in various farming areas in Ningbo. Each time, live or dying L. crocea with obvious clinical symptoms were sampled, with a total number of 55 L. crocea collected. The samples were preserved in ice bags and transported to the laboratory for pathogen detection(including bacterial isolation and identification,virus identification, and parasites detection).ResultsA total of fifty-five fish dying L. crocea with obvious clinical symptoms were collected in this study, of which 78.18% (43/55) were detected with symptoms caused by pathogenic infection, while 21.82% (12/55) did not have identified pathogens, which were presumed to be breeding abrasions, nutritional metabolic disorders, unconventional pathogens infection or other reasons. A total of twenty-five pathogenic bacteria strains were isolated, which mainly were Pseudomonas plecoglossicida and Vibrio harveyi, accounting for 52% (13/25) and 32% (8/25) of the pathogenic bacteria strains, respectively. Among them, both V. harveyi and Streptococcus. iniae co-infected one fish. Additionally, three other bacterial strains including Nocardia seriolae, Staphylococcus Saprophyticus, and Photobacterium damselae subsp.damselae were isolated. Microscopic examination mainly observed two parasites, Cryptocaryon irritans and Neobenedenia girellae. In virus detection, the red sea bream iridovirus (RSIV) was mainly detected in L. crocea. Statistical analysis showed that among the fish with detected pathogens, 55.81% (24/43) had bacterial infections, 37.21% (16/43) had parasitic infections, and 37.21% (16/43) had RSIV infections. Among them, five fish had mixed infections of bacteria and parasites, three had mixed infections of bacteria and viruses, three had mixed infections of parasites and viruses, and one L. crocea had mixed infections of viruses, bacteria, and parasites. DiscussionThese findings indicate that these three major types of diseases are very common in the L. crocea farming area in Ningbo, implying the complexity of mixed infections of multiple diseases.

This study marks the first occasion that Streptococcus iniae has been isolated, identified, and characterized as the causative pathogen in spotted sea bass (Lateolabrax maculates). Infected fish exhibited a range of external symptoms, including scale loss, bleeding from the jaw, anus, and tail, among other signs, as well as internal manifestations such as congested liver, splenomegaly, branchial anemia, yellow fat syndrome, and intestinal edema. Notably, exophthalmia and meningoencephalitis—typical symptoms associated with previous S. iniae infections—were not observed. A predominant bacterial isolate (designated 10S01) was recovered from the pure culture of spleen of a diseased spotted sea bass in Zhuhai, China. The strain was then subjected to Gram staining, biochemical profiling, and molecular confirmation through 16S rRNA and gyrB gene, corroborating its identity as S. iniae. Pathogenicity was assessed by intraperitoneal injection challenge in spotted sea bass weighing approximately 13 g/fish, revealing a LD50 of 74 cfu/g-fish. The 10S01 strain demonstrated the ability to colonize various organs, including the spleen, liver, kidney, and brain, with a relatively higher affinity for the spleen. Furthermore, antimicrobial susceptibility testing indicated that the 10S01 strain was sensitive to 14 tested antibiotics, particularly chloramphenicol, ciprofloxacin, clarithromycin, florfenicol, ofloxacin, rifampicin, and trimethoprim/sulfamethoxazole, highlighting these as preferred treatments for S. iniae infections in spotted sea bass. These findings contribute significantly to our understanding of S. iniae pathogenesis and inform the prompt and appropriate antibiotic treatment of S. iniae infections.

Abstract The genomic instability (GI) /homologous recombination deficiency (HRD) score, calculated as the sum of the events of loss of heterozygosity (LOH), large-scale state transition (LST) and telomere allele imbalance (TAI), is used to guide the choice of treatment in several cancers, but its relationship with genomic features, clinicopathological characteristics and prognosis in lung cancer is poorly understood, which could lead to population bias in prospective studies. We retrospectively analyzed 1011 lung cancer patients whose tumor samples were successfully profiled by high-throughput sequencing panel including GI/HRD score. Alterations of many cancer suppressor genes were associated with higher GI/HRD scores, biallelic inactivation of TP53 was correlated with a high GI/HRD score. A combination of two gene alterations exhibited a higher GI/HRD scores than single gene alterations. The GI/HRD score was associated with advanced stages in lung adenocarcinoma but not in lung squamous cell carcinoma. Furthermore, patients with higher GI/HRD scores had significantly shorter overall survival and progression-free survival than patients with lower GI/HRD scores. Finally, patients with a combination of a higher GI/HRD scores and TP53 alteration exhibited an extremely poor prognosis compared with patients with a lower GI/HRD scores and wild-type TP53 (overall survival, training cohort, hazard ratio (HR) = 8.56, P

Sonic hedgehog (Shh) is a component of the Hedgehog signaling pathway, playing an important role in regulating cell proliferation, differentiation, apoptosis, and the repair of damaged organisms. To further clarify the expression pattern of Shh gene in the secondary hair follicle growth cycle of cashmere goats and its mechanism of action on secondary hair follicle papilla cells, and improve cashmere quality, in this study, we took Inner Mongolia Albas white cashmere goats as the research objects and collected skin samples at different growth stages to obtain secondary hair follicles, detected Shh and its gene expression by RT-qPCR, Western blot, immunohistochemistry, and other techniques, while we also cultured DPCs in vitro. Shh gene overexpression and interference vectors were constructed, and the effects of Shh gene on the proliferation and apoptosis of DPCs were studied through cell transfection technology. The results showed that there are significant differences in Shh and its gene expression in the secondary hair follicle growth cycle skins of cashmere goats, with the highest expression level in anagen, followed by catagen, and the lowest expression level in telogen. Shh was mainly expressed in the inner root sheath, outer root sheath, and secondary hair follicle papilla. After the overexpression of Shh gene, the proliferation and vitality of the hair papilla cells were enhanced compared to the interference group. After Shh gene interference, the apoptosis rate of the cells increased, indicating that Shh gene can regulate downstream Ptch, Smo, and Gli2 gene expression to promote the proliferation of DPCs, and thus form its expression pattern in the secondary hair follicle growth cycle of cashmere goats.

Xinjiang’s representative asphalt binders, such as Karamay and Tahe asphalt, lack sufficient research on warm-mix additive modification effects. Given their unique microstructure and molecular composition differences, comprehensive investigations are essential for a nuanced understanding of these binders. This study added Sasobit and Evotherm warm mix additives to Karamay 90# asphalt and Tahe 90# asphalt, respectively. The evaluation of diverse warm mix additives’ impact on diverse asphalt binders involved viscosity, softening point, penetration tests, Fourier transform infrared (FTIR) and analysis of saturate, aromatic, resin, and asphaltene (SARA) fractions. Additionally, molecular models of asphalt were constructed using Materials Studio software, based on the SARA test data. Molecular models of Sasobit and Evotherm were also developed, representing organic wax and a cationic quaternary ammonium surfactant, respectively. Conducting molecular dynamics simulations of warm mix additives and two asphalt molecules yielded valuable insights into solubility parameters and the radial distribution function (RDF). This approach enabled a thorough and comparative exploration of the modification mechanisms employed by various warm mix additives on different asphalt types at a molecular scale. The results indicate that, Evotherm excelled in enhancing high-temperature asphalt performance, while Sasobit surpassed it in low-temperature. The viscosity reduction by Sasobit proved more effective for K90, while for T90 asphalt, the trend was reversed with Evotherm exhibiting superior performance. The solubility parameter in MD simulations consistently correlates with asphalt viscosity results. Sasobit showed enhanced compatibility with K90 asphalt, while T90 asphalt demonstrated greater suitability for modification with Evotherm.

Abstract Understanding the variability in the Hadley circulation (HC) changes is crucial for understanding ocean‐atmosphere interactions. In this study, the variability in the boreal winter HC in the last 4 decades is explored using multiple reanalyzes and model simulations. The results show that regime shift occurred in the leading mode of HC variability. The primary mode of the recent HC is dominated by an equatorially symmetrical pattern, which was considered the second mode in previous studies. The regime shift in HC variability is mainly due to the El Niño–Southern Oscillation (ENSO), which explains both the spatiotemporal variation and formation of HC variability. Moreover, the abilities of the models to reproduce HC variability is subject to their ability to simulate ENSO variability, suggesting that the ENSO has become a more important modulator of the HC variability in recent decades, and additional research is warranted to evaluate future climate changes and potential effects on the HC.

Cellulosic bioethanol production generally has a higher operating cost due to relatively expensive pretreatment strategies and low efficiency of enzymatic hydrolysis. The production of other high-value chemicals such as xylitol and phenylacetylcarbinol (PAC) is, thus, necessary to offset the cost and promote economic viability. The optimal conditions of diluted sulfuric acid pretreatment under boiling water at 95°C and subsequent enzymatic hydrolysis steps for sugarcane bagasse (SCB), rice straw (RS), and corn cob (CC) were optimized using the response surface methodology via a central composite design to simplify the process on the large-scale production. The optimal pretreatment conditions (diluted sulfuric acid concentration (% w/v), treatment time (min)) for SCB (3.36, 113), RS (3.77, 109), and CC (3.89, 112) and the optimal enzymatic hydrolysis conditions (pretreated solid concentration (% w/v), hydrolysis time (h)) for SCB (12.1, 93), RS (10.9, 61), and CC (12.0, 90) were achieved. CC xylose-rich and CC glucose-rich hydrolysates obtained from the respective optimal condition of pretreatment and enzymatic hydrolysis steps were used for xylitol and ethanol production. The statistically significant highest (p ≤ 0.05) xylitol and ethanol yields were 65% ± 1% and 86% ± 2% using Candida magnoliae TISTR 5664. C. magnoliae could statistically significantly degrade (p ≤ 0.05) the inhibitors previously formed during the pretreatment step, including up to 97% w/w hydroxymethylfurfural, 76% w/w furfural, and completely degraded acetic acid during the xylitol production. This study was the first report using the mixed whole cells harvested from xylitol and ethanol production as a biocatalyst in PAC biotransformation under a two-phase emulsion system (vegetable oil/1 M phosphate (Pi) buffer). PAC concentration could be improved by 2-fold compared to a single-phase emulsion system using only 1 M Pi buffer.

Paracondylactis sinensis Carlgren, 1934 (Actiniidae, Actiniaria) is an edible sea anemone in China. Their wild population has intensively decreased in recent years due to overharvesting. In this study, the complete mitochondrial genome of this economic species collected in the coast of Zhejiang, China is sequenced and obtained using high throughput methods. The total length of this circular molecule is 20,786 bp. Thirteen protein coding genes, two ribosomal RNA genes, two transfer RNA (tRNATrp, tRNAMet) genes and a putative ORF are annotated in it. Phylogenetic analysis based on the amino acids of mitochondrial genomes indicates that this species belongs to the family of Actiniidae. This result is consistent with the previous work that identified the edible sea anemone as Paracondylactis sinensis although it has always been recognized as Calliactis sinensis (of family Hormathiidae) in most Chinese reports. Overall, the mitochondrial genome produced in this study assists in clarifying the phylogenetic status of this sea anemone and provides a molecular foundation for future protection and breeding work.

Abstract Antiphospholipid syndrome (APS) is typically characterized by increased levels of three classes of antiphospholipid antibodies, namely lupus anticoagulant, anti‐β2‐glycoprotein I (anti‐β2GPI), and anticardiolipin antibodies. β2‐Glycoprotein (β2GPI) is a phospholipid‐binding protein composed of five domains (DI–V) and a major antigen in APS. β2GPI is expressed on the surfaces of several cell types, including endothelial cells, monocytes, trophoblast cells, and platelets. Its binding to the anti‐β2GPI antibody triggers downstream signaling events and ultimately exerts a variety of cellular effects. β2GPI modulates hemostasis and the complement system, as well as playing an important role in APS‐associated vascular injury. Therefore, studying β2GPI will help elucidate the pathogenesis of APS and improve the treatment of patients with this condition. This review will mainly focus on the structure and function of β2GPI, as well as its implication in the pathogenesis of APS.

Abstract Background Clear cell renal cell carcinoma (ccRCC) is an immunologically and histologically diverse tumor. However, how the structural heterogeneity of tumor microenvironment (TME) affects cancer progression and treatment response remains unclear. Hence, we characterized the TME architectures of ccRCC tissues using imaging mass cytometry (IMC) and explored their associations with clinical outcome and therapeutic response. Methods Using IMC, we profiled the TME landscape of ccRCC and paracancerous tissue by measuring 17 markers involved in tissue architecture, immune cell and immune activation. In the ccRCC tissue, we identified distinct immune architectures of ccRCC tissue based on the mix score and performed cellular neighborhood (CN) analysis to subdivide TME phenotypes. Moreover, we assessed the relationship between the different TME phenotypes and ccRCC patient survival, clinical features and treatment response. Results We found that ccRCC tissues had higher levels of CD8+ T cells, CD163− macrophages, Treg cells, endothelial cells, and fibroblasts than paracancerous tissues. Immune infiltrates in ccRCC tissues distinctly showed clustered and scattered patterns. Within the clustered pattern, we identified two subtypes with different clinical outcomes based on CN analysis. The TLS-like phenotype had cell communities resembling tertiary lymphoid structures, characterized by cell–cell interactions of CD8+ T cells-B cells and GZMB+CD8+ T cells-B cells, which exhibited anti-tumor features and favorable outcomes, while the Macrophage/T-clustered phenotype with macrophage- or T cell-dominated cell communities had a poor prognosis. Patients with scattered immune architecture could be further divided into scattered-CN-hot and scattered-CN-cold phenotypes based on the presence or absence of immune CNs, but both had a better prognosis than the macrophage/T-clustered phenotype. We further analyzed the relationship between the TME phenotypes and treatment response in five metastatic ccRCC patients treated with sunitinib, and found that all three responders were scattered-CN-hot phenotype while both non-responders were macrophage/T-clustered phenotype. Conclusion Our study revealed the structural heterogeneity of TME in ccRCC and its impact on clinical outcome and personalized treatment. These findings highlight the potential of IMC and CN analysis for characterizing TME structural units in cancer research.

A sustainable bioeconomy in agricultural and agro-industrial production must inevitably involve the sustainable use of agricultural residues through zero-waste processes. Corn cob is considered crucial agricultural waste as 278 and 293 million tons were produced worldwide in 2022 and 2023, respectively. Corn cob hydrolysates, which are abundant in xylose and glucose, could be efficiently utilized for xylitol and ethanol production through the cultivation of recycling the yeast strain Candida magnoliae TISTR 5664 in the single-stage and sequential-stage co-production of these products. The statistically significant maxima (p ≤ 0.05) ethanol concentrations were improved by 7.8% (49.9–51.7 g/L or 91.3–95.6% of the theoretical) from the single stage of ethanol production employing recycled cells and 9.9% (50.9–54.1 g/L or 77.3–83.9% of the theoretical) from the second step of sequential-stage co-production using recycled cells without xylitol accumulation. Conversely, the single-stage xylitol production utilizing recycled cells under microaerobic conditions resulted in a statistically significant lower (p ≤ 0.05) xylitol concentration by two folds relative to the control, while ethanol concentration was elevated by almost double. The statistically significant maximum (p ≤ 0.05) xylitol was achieved at 25.9 g/L (58.6% of the theoretical) when sequential-stage co-production was initiated in the first step with fresh inoculum only and not recycled cells. The sequential-stage co-production of xylitol and ethanol presented the potential for statistically significant improvement (p ≤ 0.05) of both xylitol and ethanol production processes.

Hepatocellular carcinoma (HCC) has become the fourth leading cause of cancer-related deaths worldwide; annually, approximately 830,000 deaths related to liver cancer are diagnosed globally. Since early-stage HCC is clinically asymptomatic, traditional treatment modalities, including surgical ablation, are usually not applicable or result in recurrence. Immunotherapy, particularly immune checkpoint blockade (ICB), provides new hope for cancer therapy; however, immune evasion mechanisms counteract its efficiency. In addition to viral exposure and alcohol addiction, nonalcoholic steatohepatitis (NASH) has become a major cause of HCC. Owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance, NASH-associated HCC patients respond much less efficiently to ICB treatment than do patients with other etiologies. In addition, abnormal inflammation contributes to NASH progression and NASH–HCC transition, as well as to HCC immune evasion. Therefore, uncovering the detailed mechanism governing how NASH-associated immune cells contribute to NASH progression would benefit HCC prevention and improve HCC immunotherapy efficiency. In the following review, we focused our attention on summarizing the current knowledge of the role of CD4+T cells in NASH and HCC progression, and discuss potential therapeutic strategies involving the targeting of CD4+T cells for the treatment of NASH and HCC.

This study focused on the start-up and operating characteristics of the endogenous partial denitrification (EPD) process with different carbon sources. Two sequencing batch reactors (SBRs) with sodium acetate (SBR1#) and glucose (SBR2#) as carbon sources were operated under anaerobic/oxic (A/O) and anaerobic/anoxic/oxic (A/A/O) modes successively for 240 d. The results showed that COD removal efficiency reached 85% and effluent COD concentrations were below 35 mg/L in both SBRs. The difference was that faster absorption and transformation of sodium acetate was achieved compared to glucose (COD removal rate (CRR) was 7.54 > 2.22 mgCOD/(L·min) in SBR1# compared to SBR2#). EPD could be started up with sodium acetate and glucose as carbon sources, respectively, and desirable high nitrite accumulations were both obtained at influent NO3−−N (NO3−-Ninf) increased from 20 to 40 mg/L with nitrate-to-nitrite transformation ratio (NTR) and specific NO3−-N deduction rate (rNa) of 88.4~90% and 2.41~2.38 mgN/(gVSS·h), respectively. However, at NO3−-N of 50~60 mg/L, both the NTR and rNa in SBR1# were higher compared to SBR2# (86.5% > 83.9% and 1.58 > 1.20 mgN/(gVSS·h), respectively). Hereafter, when NO3−-N was increased by 70~90 mg/L, lower NTR and rNa were observed in SBR1# than in SBR2# (72% and 78%, 1.16 and 1.32 mgN/(gVSS·h), respectively). Additionally, similar internal carbon transformations were observed to drive EPD for NO2−−N accumulation, especially for higher and faster carbon transformation with sodium acetate as carbon source compared to glucose. However, precise control of anoxic time as the peak point of nitrite (TNi,max) was still the key to achieve high NO2−−N accumulation.

Abstract Accumulation of inorganic nanoparticles in living organisms can cause an increase in cellular reactive oxygen species (ROS) in a dose-dependent manner. Low doses of nanoparticles have shown possibilities to induce moderate ROS increases and lead to adaptive responses of biological systems, but beneficial effects of such responses on metabolic health remain elusive. Here, we report that repeated oral administrations of various inorganic nanoparticles, including TiO2, Au, and NaYF4 nanoparticles at low doses, can promote lipid degradation and alleviate steatosis in the liver of male mice. We show that low-level uptake of nanoparticles evokes an unusual antioxidant response in hepatocytes by promoting Ces2h expression and consequently enhancing ester hydrolysis. This process can be implemented to treat specific hepatic metabolic disorders, such as fatty liver in both genetic and high-fat-diet obese mice without causing observed adverse effects. Our results demonstrate that low-dose nanoparticle administration may serve as a promising treatment for metabolic regulation.

Pellino1 (Peli1) is a highly conserved E3 Ub ligase that exerts its biological functions by mediating target protein ubiquitination. Extensive evidence has demonstrated the crucial role of Peli1 in regulating inflammation by modulating various receptor signaling pathways, including interleukin-1 receptors, Toll-like receptors, nuclear factor−κB, mitogen-activated protein kinase, and phosphoinositide 3-kinase/AKT pathways. Peli1 has been implicated in the development of several diseases by influencing inflammation, apoptosis, necrosis, pyroptosis, autophagy, DNA damage repair, and glycolysis. Peli1 is a risk factor for most cancers, including breast cancer, lung cancer, and lymphoma. Conversely, Peli1 protects against herpes simplex virus infection, systemic lupus erythematosus, esophageal cancer, and toxic epidermolysis bullosa. Therefore, Peli1 is a potential therapeutic target that warrants further investigation. This comprehensive review summarizes the target proteins of Peli1, delineates their involvement in major signaling pathways and biological processes, explores their role in diseases, and discusses the potential clinical applications of Peli1-targeted therapy, highlighting the therapeutic prospects of Peli1 in various diseases.

Glutamate plays a crucial role in cognitive impairments after ischemic stroke. There is a scarcity of information about how glutamate-induced activation of cAMP-response element binding (CREB) signaling pathway regulates both the negative and positive regulators of synaptic plasticity. Recent studies have demonstrated the involvement of prominent epigenetic repressors, such as MeCP2 and DNMTs, in stroke. Neuroprotective effects of oxytocin against ischemia have been previously reported, while the underlying mechanism is still elusive. In this research, the possible role of CREB-mediated DNA hypermethylation and the potential mechanism of oxytocin in a rat model of permanent middle cerebral artery occlusion (pMCAO) were assessed. Adult male Sprague-Dawley rats were pretreated with intraperitoneal injection of oxytocin at the onset of pMCAO. The effects of oxytocin on spines and the expression levels of synaptic genes were determined. The regulatory effects of oxytocin on glutamate level, N-methyl-D-aspartate receptors (NMDARs), its downstream CREB pathway, and global or gene-specific DNA methylation status were evaluated by immunofluorescence, co-immunoprecipitation, and chromatin immunoprecipitation, respectively. We found that CREB could act as a common transcription factor for MeCP2 and DNMT3B after ischemic stroke. Oxytocin dose-dependently deactivated NR2B-related CaM-CREB pathway and inhibited DNA hypermethylation at the CpG islands of Ngf gene in pMCAO-operated rats. Moreover, oxytocin prevented pMCAO-induced reduction in the number of spines and neural cells. DNA hypermethylation in Ngf gene contributed to the cognitive deficits post-stroke. The neuroprotective effects of oxytocin against ischemia could be attributed to inhibiting glutamate release, providing additional evidence on the mechanism of oxytocin against ischemic stroke.

Abstract Hyperhomocysteinemia (HHcy) is a risk factor for chronic kidney diseases (CKDs) that affects about 85% CKD patients. HHcy stimulates B cells to secrete pathological antibodies, although it is unknown whether this pathway mediates kidney injury. In HHcy-treated 2-kidney, 1-clip (2K1C) hypertensive murine model, HHcy-activated B cells secreted anti-beta 2 glycoprotein I (β2GPI) antibodies that deposited in glomerular endothelial cells (GECs), exacerbating glomerulosclerosis and reducing renal function. Mechanistically, HHcy 2K1C mice increased phosphatidylethanolamine (PE) (18:0/20:4, 18:0/22:6, 16:0/20:4) in kidney tissue, as determined by lipidomics. GECs oxidative lipidomics validated the increase of oxidized phospholipids upon Hcy-activated B cells culture medium (Hcy-B CM) treatment, including PE (18:0/20:4 + 3[O], PE (18:0a/22:4 + 1[O], PE (18:0/22:4 + 2[O] and PE (18:0/22:4 + 3[O]). PE synthases ethanolamine kinase 2 (etnk2) and ethanolamine-phosphate cytidylyltransferase 2 (pcyt2) were increased in the kidney GECs of HHcy 2K1C mice and facilitated polyunsaturated PE synthesis to act as lipid peroxidation substrates. In HHcy 2K1C mice and Hcy-B CM-treated GECs, the oxidative environment induced by iron accumulation and the insufficient clearance of lipid peroxides caused by transferrin receptor (TFR) elevation and down-regulation of SLC7A11/glutathione peroxidase 4 (GPX4) contributed to GECs ferroptosis of the kidneys. In vivo, pharmacological depletion of B cells or inhibition of ferroptosis mitigated the HHcy-aggravated hypertensive renal injury. Consequently, our findings uncovered a novel mechanism by which B cell-derived pathogenic anti-β2GPI IgG generated by HHcy exacerbated hypertensive kidney damage by inducing GECs ferroptosis. Targeting B cells or ferroptosis may be viable therapeutic strategies for ameliorating lipid peroxidative renal injury in HHcy patients with hypertensive nephropathy.

The drivers of multidecadal changes in the North Tropical Atlantic−Pacific connection are still not fully understood. Here, the authors show that they are mainly controlled by multidecadal variability associated with the North Atlantic Oscillation.

Emodin, a substance extracted from herbs such as rhubarb, has a protective effect on the central nervous system. However, the potential therapeutic effect of emodin in the context of multiple sclerosis remains unknown. In this study, a rat model of experimental autoimmune encephalomyelitis was established by immune induction to simulate multiple sclerosis, and the rats were intraperitoneally injected with emodin (20 mg/kg/d) from the day of immune induction until they were sacrificed. In this model, the nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and the microglia exacerbated neuroinflammation, playing an important role in the development of multiple sclerosis. In addition, silent information regulator of transcription 1 (SIRT1)/peroxisome proliferator-activated receptor-alpha coactivator (PGC-1α) was found to inhibit activation of the NLRP3 inflammasome, and SIRT1 activation reduced disease severity in experimental autoimmune encephalomyelitis. Furthermore, treatment with emodin decreased body weight loss and neurobehavioral deficits, alleviated inflammatory cell infiltration and demyelination, reduced the expression of inflammatory cytokines, inhibited microglial aggregation and activation, decreased the levels of NLRP3 signaling pathway molecules, and increased the expression of SIRT1 and PGC-1α. These findings suggest that emodin improves the symptoms of experimental autoimmune encephalomyelitis, possibly through regulating the SIRT1/PGC-1α/NLRP3 signaling pathway and inhibiting microglial inflammation. These findings provide experimental evidence for treatment of multiple sclerosis with emodin, enlarging the scope of clinical application for emodin.

LncRNA (long non-coding RNA) H19 is a transcript of the H19 gene that is expressed during embryogenesis. We previously discovered a role for circular lncRNA H19 in the onset and prognosis of cerebral ischemic stroke. In this study, we used serum from patients with ischemic stroke, and mouse and cell culture models to elucidate the roles of plasma and neuronal exosomes in the regulatory effect of lncRNA H19 on insulin-like growth factor-1 and its mechanism in ischemic stroke, using western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assays. Plasma exosomal lncRNA H19 was negatively associated with blood levels of insulin-like growth factor-1 in samples from patients with cerebral ischemic stroke. In a mouse model, levels of exosomal lncRNA H19 were positively correlated with plasma and cerebral lncRNA H19. In a cell co-culture model, we confirmed that lncRNA H19 was transported from neurons to astrocytes by exosomes to induce downregulation of insulin-like growth factor-1 through the H19/let-7a/insulin-like growth factor-1 receptor axis. This study provides the first evidence for the transportation of lncRNA H19 by exosomes and the relationship between lncRNA H19 and insulin-like growth factor-1.

Cerebral ischemia/reperfusion injury impairs learning and memory in patients. Studies have shown that synaptic function is involved in the formation and development of memory, and that DNA methylation plays a key role in the regulation of learning and memory. To investigate the role of DNA hypomethylation in cerebral ischemia/reperfusion injury, in this study, we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery and then treated the rats with intraperitoneal 5-aza-2′-deoxycytidine, an inhibitor of DNA methylation. Our results showed that 5-aza-2′-deoxycytidine markedly improved the neurological function, and cognitive, social and spatial memory abilities, and dose-dependently increased the synaptic density and the expression of SYP and SHANK2 proteins in the hippocampus in a dose-dependent manner in rats with cerebral ischemia/reperfusion injury. The effects of 5-aza-2′-deoxycytidine were closely related to its reduction of genomic DNA methylation and DNA methylation at specific sites of the Syp and Shank2 genes in rats with cerebral ischemia/reperfusion injury. These findings suggest that inhibition of DNA methylation by 5-aza-2′-deoxycytidine promotes the recovery of learning and memory impairment in a rat model of cerebral ischemia/reperfusion injury. These results provide theoretical evidence for stroke treatment using epigenetic methods.

This study examines the comparative atmospheric circulation and tropical sea surface temperature (SST) relationships during the developing and decaying stages of El Niño from a meridional structure standpoint. Results indicate a transition in the variability of the first two modes of the Hadley circulation (HC) during these stages, with the first mode exhibiting a larger explained variance in the decaying stage. The regime change in HC variability corresponds to underlying anomalous SST distributions, as confirmed by sensitive experiments. Quantitative assessment reveals the HC-SST response amplitudes are approximately two times stronger during the decaying stage compared to the developing stage. Employing the Kuo–Eliassen (KE) equation, diabatic heating anomalies during the decaying stage explain the difference in air-sea response intensity between the two stages. Diabatic heating variations are identified as the primary contributor to amplification or reduction of air-sea response intensity during the respective El Niño stages, providing insights into the different air-sea processes throughout the El Niño lifespan.

To date, studies on apoptosis in echinoderms mainly focus on the caspase-dependent extrinsic apoptotic pathway, while knowledges regarding the intrinsic apoptotic pathway is still limited. In this study, 55 genes belong to 7 families of the intrinsic apoptotic pathway, namely, Bcl-2, caspase, AIF, Cyt c, Apaf-1, Smac, HTRA2 and Endo G, were identified by screening of the genomic database of the tropical sea cucumber Holothuria leucospilota. The Bcl-2 family showed significant gene expansion in H. leucospilota but not in other echinoderms, while the pro-apoptotic factor Endo G is generally lost in echinoderms. Transcriptomic data showed that the genes of the intrinsic apoptotic pathway were ubiquitously expressed in all tissues, and all embryonic and larval developmental stages of H. leucospilota. The gene numbers and functional domains of the caspase family and AIF family were further clarified and showed conserved with their counterparts in vertebrates. In primary coelomocytes, the transcript expression of different caspases showed different responses to pathogenic challenges of vibrio and pathogen-associated molecular patterns, and environmental challenges of heave metal and reactive oxygen species. Overall, this study indicates that the intrinsic apoptotic pathway is conserved between vertebrates and echinoderms by using the sea cucumber H. leucospilota as a model. This study may contribute in increasing the knowledge of development and innate immunity in ancestral deuterostomia species.

Abstract Background The deficiency of serine/threonine protein kinase 11 (STK11), one of the most common tumor suppressor genes in non‐small‐cell lung cancer, is a crucial player in tumor immune microenvironment regulation. This study attempted to unveil how mutated STK11 impact the differentiation of macrophages in lung adenocarcinoma (LUAD). Methods STK11 and CD1E expression levels in different cell models were assessed by quantitative reverse transcription polymerase chain reaction. Western blot was utilized to detect the protein expression levels of STK11, CD1E, apoptosis markers, and AMPK signaling pathway markers after transfection treatment. Cell viability and macrophage differentiation were detected by CCK‐8 and flow cytometry. Immunohistochemistry and immunofluorescence were employed to detect the expression of related genes and macrophage markers, respectively. Results This study found that STK11 mutations promoted the proliferation of LUAD cells and inhibited the differentiation of M1 macrophages, apoptosis, and the AMPK signaling pathway. Mutated STK11 led to CD1E downregulation, which curbed the differentiation of M1 macrophages and hence promoted LUAD progression. It was further validated by the in vivo experimental results that STK11 mutation significantly decreased the immune infiltration of M1 macrophages and promoted LUAD progression. Conclusion It was revealed that STK11 mutation affected CD1E expression to regulate macrophage differentiation in LUAD and then promote tumor progression. In this way, CD1E could be a potential biological target for the therapeutic interventions of STK11‐mutant LUAD patients. These findings also threw new light on a new therapeutic strategy for STK11‐mutant tumor patients that assisted the macrophage polarization pathway.

A differentiating infected from vaccinated animals (DIVA) vaccine is an ideal strategy for viral eradication in poultry. Here, according to the emerging highly pathogenic H7N9 avian influenza virus (AIV), a DIVA vaccine strain, named rGD4HALo-mH3-TX, was successfully developed, based on a substituted 12 peptide of H3 virus located at HA2. In order to meet with the safety requirement of vaccine production, the multi-basic amino acid located at the HA cleavage site was modified. Meanwhile, six inner viral genes from a H9N2 AIV TX strainwere introduced for increasing viral production. The rGD4HALo-mH3-TX strain displayed a similar reproductive ability with rGD4 and low pathogenicity in chickens, suggesting a good productivity and safety. In immuned chickens, rGD4HALo-mH3-TX induced a similar antibody level with rGD4 and provided 100% clinical protection and 90% shedding protection against highly pathogenic virus challenge. rGD4HALo-mH3-TX strain also produced a good cross-protection against low pathogenic AIV JD/17. Moreover, serological DIVA characteristics were evaluated by a successfully established competitive inhibition ELISA based on a 3G10 monoclonal antibody, and the result showed a strong reactivity with antisera of chickens vaccinated with H7 subtype strains but not rGD4HALo-mH3-TX. Collectedly, rGD4HALo-mH3-TX is a promising DIVA vaccine candidate against both high and low pathogenic H7N9 subtype AIV.

Studies in the postfusion structures of the conserved gamete fusogen HAP2 show a trimeric state typical of viral class II fusion proteins. Here, the authors present the crystal structure of a prefusion state of Cyanidioschyzon merolae HAP2 and low resolution structures of intermediates in the pathway to its trimeric postfusion state.

Abstract The impact of El Niño on the Hadley Circulation (HC) has been a topic of previous studies, but the results have been inconclusive. We study how El Niño affects the HC during different stages of its cycle. In development years, the HC anomaly shows an equatorial quasi‐symmetric pattern, while in decay years, it shows an asymmetric pattern. This resolves previous discrepancies among studies about El Niño's impacts on the HC. The differences in tropical sea surface temperature (SST) during different stages of El Niño cause differences in SST meridional gradients, which determine the location of convergence. This explains why the HC anomalies have different spatial structures during El Niño development and decay years. Our results show that the meridional distribution of SST during different El Niño stages has significantly distinct impacts on meridional circulation and clarify the differences in El Niño's effects on climate.

Antibiotic resistance represents a global health crisis for humans, animals, and the environment. However, few studies address the abundance and distribution of the environmental bacterial antibiotic resistance associated with farmed fish during the early breeding stages and their relationship with aquaculture environment. In this study, culture-dependent methods and gene chip technology were respectively used to identify and detect cultivable heterotrophic antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) of water samples from 20 sea bass-rearing ponds in spring in Zhuhai, China. Meanwhile, the relationships among ARGs, ARB, and water nutrients were elucidated. The results showed that bacterial resistance to erythromycin and sulfamethoxazole with trimethoprim was generally high (mean 48.15% and 18.07%, respectively), whereas resistance to rifampicin, florfenicol, ciprofloxacin, and enrofloxacin was generally low (mean 5.46%, 2.16%, 1.43%, and 0.16%, respectively). Acinetobacter sp. (42.31%) and Pseudomonas sp. (25.74%) were the dominant ARB, and most cultivable ARB were opportunistic pathogens. The abundance of sul family genes was higher than that of other tested ARGs. ARGs and ARB were mainly affected by NO3– and PO43–, with PO43– generally positively correlated, whereas NO3– was negatively correlated, with ARGs and ARB. Thus, recommendations for the control of antibiotic resistance risk can be made by understanding the resistance profile of the aquaculture environment.

A study evaluated nine kinetic data and four kinetic parameters related to growth, production of various phytase activities (PEact), and released phosphate ion concentration ([Pi]) from five lactic acid bacteria (LAB) strains cultivated in three types of media: phytate (IP6), milling stage rice bran (MsRB), and whitening stage rice bran (WsRB). Score ranking techniques were used, combining these kinetic data and parameters to select the most suitable LAB strain for each medium across three cultivation time periods (24, 48, and 72 h). In the IP6 medium, Lacticaseibacillus casei TISTR 1500 exhibited statistically significant highest (p ≤ 0.05) normalized summation scores using a 2:1 weighting between kinetic and parameter data sets. This strain also had the statistically highest levels (p ≤ 0.05) of produced phosphate ion concentration ([Pi]) (0.55 g/L) at 72 h and produced extracellular specific phytase activity (ExSp-PEact) (0.278 U/mgprotein) at 48 h. For the MsRB and WsRB media, Lactiplantibacillus plantarum TISTR 877 performed exceptionally well after 72 h of cultivation. It produced ([Pi], ExSp-PEact) pairs of (0.53 g/L, 0.0790 U/mgprotein) in MsRB and (0.85 g/L, 0.0593 U/mgprotein) in WsRB, respectively. Overall, these findings indicate the most promising LAB strains for each medium and cultivation time based on their ability to produce phosphate ions and extracellular specific phytase activity. The selection process utilized a combination of kinetic data and parameter analysis.

Hfq is a global regulator and can be involved in multiple cellular processes by assisting small regulatory RNAs (sRNAs) to target mRNAs. To gain insight into the virulence regulation of Hfq in Vibrio harveyi, the hfq null mutant, ∆hfq, was constructed in V. harveyi strain 345. Compared with the wild-type strain, the mortality of pearl gentian sharply declined from 80% to 0% in ∆hfq when infected with a dose that was 7.5-fold the median lethal dose (LD50). Additionally, ∆hfq led to impairments of bacterial growth, motility, and biofilm formation and resistance to reactive oxygen species, chloramphenicol, and florfenicol. A transcriptome analysis indicated that the expression of 16.39% genes on V. harveyi 345 were significantly changed after the deletion of hfq. Without Hfq, the virulence-related pathways, including flagellar assembly and bacterial chemotaxis, were repressed. Moreover, eleven sRNAs, including sRNA0405, sRNA0078, sRNA0419, sRNA0145, and sRNA0097, which, respectively, are involved in chloramphenicol/florfenicol resistance, outer membrane protein synthesis, electron transport, amino acid metabolism, and biofilm formation, were significantly down-regulated. In general, Hfq contributes to the virulence of V. harveyi 345 probably via positively regulating bacterial motility and biofilm formation. It is involved in flagellar assembly and bacterial chemotaxis by binding sRNAs and regulating the target mRNAs.

PKAN and PD are two distinct diseases with overlapping pathophysiology. Here, authors show that their pathogenic genes PANK2 and PINK1 interact. PANK2 regulates mitophagy via CoA metabolism, while PINK1 supervises PANK2 translation on mitochondria.

Abstract This study aimed to compare MRI quality between conventional fast spin echo T2 weighted imaging (FSE T2WI) with periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) FSE T2WI for patients with various porcelain fused to metal (PFM) crown and analyze the value of PROPELLER technique in reducing metal artifacts. Conventional FSE T2WI and PROPELLER FSE T2WI sequences for axial imaging of head were applied in participants with different PFM crowns: cobalt-chromium (Co–Cr) alloy, pure titanium (Ti), gold–palladium (Au–Pd) alloy. Two radiologists evaluated overall image quality of section in PFM using a 5-point scale qualitatively and measured the maximum artifact area and artifact signal-to-noise ratio (SNR) quantitatively. Fifty-nine participants were evaluated. The metal crown with the least artifacts and the optimum image quality shown in conventional FSE T2WI and PROPELLER FSE T2WI were in Au–Pd alloy, Ti, and Co–Cr alloy order. PROPELLER FSE T2WI was superior to conventional FSE T2WI in improving image quality and reducing artifact area for Co-Cr alloy (17.0 ± 0.2% smaller artifact area, p

The RNA-binding metabolic enzyme LTA4H is a novel target for cancer chemoprevention and chemotherapy. Recent research shows that the increased expression of LTA4H in laryngeal squamous cell carcinoma (LSCC) promotes tumor proliferation, migration, and metastasis. However, its mechanism remains unclear. To investigate the potential role of LTA4H in LSCC, we employed the improved RNA immunoprecipitation and sequencing (iRIP-Seq) experiment to get the expression profile of LTA4H binding RNA in HeLa model cells, a cancer model cell that is frequently used in molecular mechanism research. We found that LTA4H extensively binds with mRNAs/pre-mRNAs and lncRNAs. In the LTA4H binding peak, the frequency of the AAGG motif reported to interact with TRA2β4 was high in both replicates. More notably, LTA4H-binding genes were significantly enriched in the mitotic cell cycle, DNA repair, RNA splicing-related pathways, and RNA metabolism pathways, which means that LTA4H has tumor-related alternative splicing regulatory functions. QRT-PCR validation confirmed that LTA4H specifically binds to mRNAs of carcinogenesis-associated genes, including LTBP3, ROR2, EGFR, HSP90B1, and lncRNAs represented by NEAT1. These results suggest that LTA4H may combine with genes associated with LSCC as an RNA-binding protein to perform a cancer regulatory function. Our study further sheds light on the molecular mechanism of LTA4H as a clinical therapy target for LSCC.

The variability of the Hadley Circulation (HC) is greatly impacted by the meridional structure of sea surface temperature (SST), which has varied effects depending on its symmetrical or asymmetrical pattern relative to the equator. By using the Coupled Comparison Program International Project Phase 6 (CMIP6) model outputs and reanalysis datasets, this study assesses the capacity of CMIP6 models to simulate the relationship between the HC and tropical SST under different meridional structures, as well as investigates the possible causes for simulation biases. It is shown that the CMIP6 models can successfully reproduce climatological HC, tropical SST, and their spatial patterns of first leading modes under different meridional structures, where the correlation coefficient between simulations and observations reaches 0.8 or above. By comparison, the CMIP6 model outputs exhibit substantial differences in simulating the HC to SST response over the different meridional structures, with obvious inter-model differences. Considering the capability in simulating the HC to tropical SST response, the CMIP6 models are divided into two types, Type I model and Type II model. Models of Type I are those whose simulation results are basically close to the reanalysis data, with the biases being less than 20%. The models of Type II are those whose simulated response ratios are much stronger than those of the reanalysis. It is found that the models of Type II overestimate the intensity of El Niño-Southern Oscillation (ENSO) events, and remarkably underestimate the HC and SST correlation in the equatorial symmetric part, resulting in the inability of the models of Type II to capture the connection of the HC and tropical SST. The results indicate that, the component of the CMIP6 models in reproducing the ENSO events has a considerable impact on the simulation of the HC and tropical SST relationship, which offers recommendations for enhancing the capability of models to simulate large-scale tropical air-sea interactions.

Objectives The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA).Design Our study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III).Setting We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China.Participants 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018.Primary and secondary outcome measures The primary outcome was a new stroke, LDL-C goal (LDL-C

Some of the congenital coronary artery diseases in children have potential life-threatening complications. In addition to anatomical classification, the peadiatricians should pay more attention to the risk of adverse cardiac events classification; and then, they can eventrually make the personalized guidance suggestions and treatment decisions according to different diseases.

Abstract El Niño‐Southern Oscillation (ENSO) triggers variations of the global Hadley circulation (HC), while the latter may potentially feedback to ENSO events. Previous studies mainly investigated the interactions between ENSO and the global zonal‐mean HC. Here, we present a regional perspective of HC variability by introducing zonal variations. Results show that El Niño intensifies the regional HC over the central‐eastern Pacific, while weakening the regional HC over both the Indo‐Pacific warm pool and the tropical Atlantic. The background seasonal cycle modulates the equatorial‐asymmetric component of HC, with an anticlockwise (clockwise) asymmetric circulation over the central equatorial Pacific before (after) El Niño peaks. Remarkably, the asymmetric HC in boreal spring leads ENSO with a lead correlation of up to 0.68, mediated by the wind‐evaporation‐sea surface temperature (SST) feedback and other atmosphere‐ocean dynamics. The antecedent HC anomaly may contribute to ENSO predictability.

Immunoinflammatory mechanisms have been incrementally found to be involved in the pathogenesis of multiple diseases, with chemokines being the main drivers of immune cell infiltration in the inflammatory response. Chemokine-like factor 1 (CKLF1), a novel chemokine, is highly expressed in the human peripheral blood leukocytes and exerts broad-spectrum chemotactic and pro-proliferative effects by activating multiple downstream signaling pathways upon binding to its functional receptors. Furthermore, the relationship between CKLF1 overexpression and various systemic diseases has been demonstrated in both in vivo and in vitro experiments. In this context, it is promising that clarifying the downstream mechanism of CKLF1 and identifying its upstream regulatory sites can yield new strategies for targeted therapeutics of immunoinflammatory diseases.

Conjugation is the most common horizontal gene transfer (HGT) process that can be affected by environmental change and promote bacterial virulence and drug resistance. However, it is unknown whether environmental changes can influence the conjugation ability of the marine fish pathogen Vibrio harveyi, thereby affecting its pathogenicity and drug resistance. This study systematically analyzes the effect of environmental stress on the ability of V. harveyi to obtain shuttle plasmids from Escherichia coli during conjugation. The results indicate that V. harveyi cannot receive shuttle plasmid pMMB207 without exposure to stress. However, certain stress exposure (37–46°C, 4%–16% ethanol, 0.14–0.56 mM SDS, 0.04~0.05 M NaOH, and 0.012–0.024 M HCl for 5–60 minutes) in the log phase of V. harveyi before conjugation successfully induces the fertility of the V. harveyi recipient in intergeneric mating with E. coli. In particular, ethanol and heat stress showed strong induction with up to 2.5 × 105 and 5.3 × 103 transconjugants when exposed to 16% ethanol for 10 minutes and 40°C for 60 minutes, respectively. Additionally, appropriate levels of NaOH (0.05 M, 10 minutes), SDS (0.42 mM, 5 minutes), and HCl (0.024 M, 5 minutes) lead to 2.3 × 103, 4.5 × 102, and 1.8 × 102 transconjugants, respectively. These results will help establish homologous recombination gene knockout technology and greatly advance molecular theoretical research on V. harveyi. They will also support the establishment of disease prevention and control strategies based on the interruption of the HGT process by environmental regulation.

The Hadley circulation (HC), as a thermally driven large-scale meridional circulation, acts a significant role in the changes of global climate. The modulation of Indo-Pacific warm pool (IPWP) thermal conditions on the relationship between the HC and different tropical sea surface temperature (SST) meridional structures was investigated. Based on the two components of HC and SST, one equatorially asymmetric component (HEA for HC, SEA for SST) and one equatorially symmetric component (HES for HC, SES for SST), the connections of HC to different SST variations in the warm and cold IPWP are explored. The result demonstrates that the relationship of the HC to tropical SST is suppressed in the cold IPWP conditions, whereas it is equivalent to the climatology in the warm IPWP conditions. The plausible mechanism is that the cold (warm) IPWP events are in concordance with the La Niña (El Niño) decay phase. The La Niña decay phase are associated with significant equatorially asymmetric SST anomalies within the IPWP, generating an anomalous meridional circulation and favoring a strengthened equatorially asymmetric anomalous meridional circulation. By contrast, the SST anomalies associated with El Niño decay phase are insignificant. The role of La Niña decay conditions in determining the suppressed connection between SST and HC is further verified by exploring the result after 1979. A similar suppressed response contrast has been detected. Therefore, the results demonstrate that warm and cold ENSO events have impacts on the interannual thermal conditions of IPWP, whereby it plays considerable role in impacting the relationship between the HC and tropical SST. Particularly, with the rapid warming, the interconnection between ENSO events and thermal conditions of IPWP under different timescales could be altered, the influence of which on the responses of the HC to tropical SST remains uncertain and is worthy further researching.

Ghrelin is a neuropeptide that has various physiological functions and has been demonstrated to be neuroprotective in a number of neurological disease models. However, the underlying mechanisms of ghrelin in Parkinson’s disease remain largely unexplored. The current study aimed to study the effects of ghrelin in a 6-hydroxydopamine (6-OHDA)-induced Parkinson’s disease model and evaluate the potential underlying mechanisms. In the present study, we treated an SH-SY5Y cell model with 6-OHDA, and observed that pretreatment with different concentrations of ghrelin (1, 10, and 100 nM) for 30 minutes relieved the neurotoxic effects of 6-OHDA, as revealed by Cell Counting Kit-8 and Annexin V/propidium iodide (PI) apoptosis assays. Reverse transcription quantitative polymerase chain reaction and western blot assay results demonstrated that 6-OHDA treatment upregulated α-synuclein and lincRNA-p21 and downregulated TG-interacting factor 1 (TGIF1), which was predicted as a potential transcription regulator of the gene encoding α-synuclein (SNCA). Ghrelin pretreatment was able to reverse the trends caused by 6-OHDA. The Annexin V/PI apoptosis assay results revealed that inhibiting either α-synuclein or lincRNA-p21 expression with small interfering RNA (siRNA) relieved 6-OHDA-induced cell apoptosis. Furthermore, inhibiting lincRNA-p21 also partially upregulated TGIF1. By retrieving information from a bioinformatics database and performing both double luciferase and RNA immunoprecipitation assays, we found that lincRNA-p21 and TGIF1 were able to form a double-stranded RNA-binding protein Staufen homolog 1 (STAU1) binding site and further activate the STAU1-mediated mRNA decay pathway. In addition, TGIF1 was able to transcriptionally regulate α-synuclein expression by binding to the promoter of SNCA. The Annexin V/PI apoptosis assay results showed that either knockdown of TGIF1 or overexpression of lincRNA-p21 notably abolished the neuroprotective effects of ghrelin against 6-OHDA-induced neurotoxicity. Collectively, these findings suggest that ghrelin exerts neuroprotective effects against 6-OHDA-induced neurotoxicity via the lincRNA-p21/TGIF1/α-synuclein pathway.

Abstract A quantum interface for two-way entanglement transfer, e.g., between orbital angular momentum degree of freedom in free space and time-energy degree of freedom in optical fibers, provides a way toward establishing entanglement between remote heterogeneous quantum nodes. Here, we experimentally demonstrate this kind of transfer interface by using two interferometric cyclic gates. By using this quantum interface, we perform two-way entanglement transfer for the two degrees of freedom. The results show that the quantum entangled state can be switched back and forth between orbital angular momentum and time-energy degrees of freedom, and the fidelity of the state before and after switching is higher than 90%. Our work demonstrates the feasibility and high performance of our proposed transfer interface, and paves a route toward building a large-scale quantum communication network.

Phenylacetylcarbinol (PAC) is a precursor for the synthesis of several pharmaceuticals, including ephedrine, pseudoephedrine, and norephedrine. PAC is commonly produced through biotransformation using microbial pyruvate decarboxylase (PDC) in the form of frozen–thawed whole cells. However, the lack of microorganisms capable of high PDC activity is the main factor in the production of PAC. In addition, researchers are also looking for ways to utilize agro-industrial residues as an inexpensive carbon source through an integrated biorefinery approach in which sugars can be utilized for bioethanol production and frozen–thawed whole cells for PAC synthesis. In the present study, Candida tropicalis, Saccharomyces cerevisiae, and the co-culture of both strains were compared for their biomass and ethanol concentrations, as well as for their volumetric and specific PDC activities when cultivated in a sugarcane bagasse (SCB) hydrolysate medium (SCBHM). The co-culture that resulted in a higher level of PAC (8.65 ± 0.08 mM) with 26.4 ± 0.9 g L−1 ethanol production was chosen for further experiments. Biomass production was scaled up to 100 L and the kinetic parameters were studied. The biomass harvested from the bioreactor was utilized as frozen–thawed whole cells for the selection of an initial pyruvate (Pyr)-to-benzaldehyde (Bz) concentration ([Pyr]/[Bz]) ratio suitable for the PAC biotransformation in a single-phase emulsion system. The initial [Pyr]/[Bz] at 100/120 mM resulted in higher PAC levels with 10.5 ± 0.2 mM when compared to 200/240 mM (8.60 ± 0.01 mM). A subsequent two-phase emulsion system with Pyr in the aqueous phase, Bz in the organic phase, and frozen–thawed whole cells of the co-culture as the biocatalyst produced a 1.46-fold higher PAC level when compared to a single-phase emulsion system. In addition, the cost analysis strategy indicated preliminary costs of USD 0.82 and 1.01/kg PAC for the single-phase and two-phase emulsion systems, respectively. The results of the present study suggested that the co-culture of C. tropicalis and S. cerevisiae can effectively produce bioethanol and PAC from SCB and would decrease the overall production cost on an industrial scale utilizing the two-phase emulsion system with the proposed multiple-pass strategy.

With the accelerated development of nanotechnology in recent years, nanomaterials have become increasingly prevalent in the medical field. The poly (lactic acid–glycolic acid) copolymer (PLGA) is one of the most commonly used biodegradable polymers. It is biocompatible and can be fabricated into various nanostructures, depending on requirements. Ischemic stroke is a common, disabling, and fatal illness that burdens society. There is a need for further improvement in the diagnosis and treatment of this disease. PLGA-based nanostructures can facilitate therapeutic compounds’ passage through the physicochemical barrier. They further provide both sustained and controlled release of therapeutic compounds when loaded with drugs for the treatment of ischemic stroke. The clinical significance and potential of PLGA-based nanostructures can also be seen in their applications in cell transplantation and imaging diagnostics of ischemic stroke. This paper summarizes the synthesis and properties of PLGA and reviews in detail the recent applications of PLGA-based nanostructures for drug delivery, disease therapy, cell transplantation, and the imaging diagnosis of ischemic stroke.