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Abstract Background Hepatitis B virus (HBV) infection is a persistent global public health problem, and curing for chronic hepatitis B (CHB) through the application of existing antiviral drugs is beset by numerous challenges. The viral protein HBx is a critical regulatory factor in the life cycle of HBV. Targeting HBx is a promising possibility for the development of novel therapeutic strategies. Methods The Nano-Glo® HiBiT Lysis Detection System was used to screen the herbal monomer compound library for compounds that inhibit HBx expression. Western blotting was used to examine proteins expression. Southern blotting or Northern blotting were used to detect HBV DNA or HBV RNA. ELISA was performed to detect the HBsAg level. The effect of asiatic acid on HBV in vivo was investigated by using recombinant cccDNA mouse model. Results Asiatic acid, an extract of Centella asiatica, significantly reduced the HBx level. Mechanistic studies demonstrated that asiatic acid may promote the degradation of HBx in an autophagy pathway-dependent manner. Subsequently, asiatic acid was found to reduce the amount of HBx bound to covalently closed circular DNA (cccDNA) microchromosomes, and repressive chromatin modifications then occurred, ultimately inhibiting cccDNA transcriptional activity. Moreover, in HBV-infected cells and a mouse model of persistent HBV infection, asiatic acid exhibited potent anti-HBV activity, as evidenced by decreased levels of HBV RNAs, HBV DNA and HBsAg. Conclusions Asiatic acid was identified as a compound that targets HBx, revealing its potential for application as an anti-HBV agent.

Abstract Micro-thermoelectric coolers are emerging as a promising solution for high-density cooling applications in confined spaces. Unlike thin-film micro-thermoelectric coolers with high cooling flux at the expense of cooling temperature difference due to very short thermoelectric legs, thick-film micro-thermoelectric coolers can achieve better comprehensive cooling performance. However, they still face significant challenges in both material preparation and device integration. Herein, we propose a design strategy which combines Bi2Te3-based thick film prepared by powder direct molding with micro-thermoelectric cooler integrated via phase-change batch transfer. Accurate thickness control and relatively high thermoelectric performance can be achieved for the thick film, and the high-density-integrated thick-film micro-thermoelectric cooler exhibits excellent performance with maximum cooling temperature difference of 40.6 K and maximum cooling flux of 56.5 W·cm−2 at room temperature. The micro-thermoelectric cooler also shows high temperature control accuracy (0.01 K) and reliability (over 30000 cooling cycles). Moreover, the device demonstrates remarkable capacity in power generation with normalized power density up to 214.0 μW · cm−2 · K−2. This study provides a general and scalable route for developing high-performance thick-film micro-thermoelectric cooler, benefiting widespread applications in thermal management of microsystems.

Abstract Growth differentiation factor 15 (GDF15) as a stress response cytokine is involved in the development and progression of several diseases associated with metabolic disorders. However, the regulatory role and the underlying mechanisms of GDF15 in sepsis remain poorly defined. Our study analyzed the levels of GDF15 and its correlations with the clinical prognosis of patients with sepsis. In vivo and in vitro models of sepsis were applied to elucidate the role and mechanisms of GDF15 in sepsis-associated lung injury. We observed strong correlations of plasma GDF15 levels with the levels of C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and lactate as well as Sequential Organ Failure Assessment (SOFA) scores in patients with sepsis. In the mouse model of lipopolysaccharide-induced sepsis, recombinant GDF15 inhibited the proinflammatory responses and alleviated lung tissue injury. In addition, GDF15 decreased the levels of cytokines produced by alveolar macrophages (AMs). The anti-inflammatory effect of glycolysis inhibitor 2-DG on AMs during sepsis was mediated by GDF15 via inducing the phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2α) and the expression of activating transcription factor 4 (ATF4). Furthermore, we explored the mechanism underlying the beneficial effects of GDF15 and found that GDF15 inhibited glycolysis and mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) signaling via promoting AMPK phosphorylation. This study demonstrated that GDF15 inhibited glycolysis and NF-κB/MAPKs signaling via activating AMP-activated protein kinase (AMPK), thereby alleviating the inflammatory responses of AMs and sepsis-associated lung injury. Our findings provided new insights into novel therapeutic strategies for treating sepsis.

Sepsis, a life-threatening condition, involves complex interactions among metabolic alterations, inflammatory mediators, and host responses. This study utilized a bidirectional Mendelian randomization approach to investigate the causal relationships between 1400 metabolites and sepsis, and the mediating role of inflammatory factors. We identified 36 metabolites significantly associated with sepsis (p < 0.05), with AXIN1, FGF-19, FGF-23, IL-4, and OSM showing an inverse association, suggesting a protective role, while IL-2 exhibited a positive correlation, indicating a potential risk factor. Among these metabolites, Piperine and 9-Hydroxystearate demonstrated particularly interesting protective effects against sepsis. Piperine’s protective effect was mediated through its interaction with AXIN1, contributing to a 16.296% reduction in sepsis risk. This suggests a potential pathway where Piperine influences sepsis outcomes by modulating AXIN1 levels. 9-Hydroxystearate also exhibited a protective role against sepsis, mediated through its positive association with FGF-19 and negative association with IL-2, contributing 9.436% and 12.565%, respectively, to its protective effect. Experimental validation confirmed significantly elevated IL-2 levels and reduced FGF-19, AXIN1, piperine, and 9-hydroxyoctadecanoic acid levels in sepsis patients compared to healthy controls. Piperine levels positively correlated with AXIN1, while 9-hydroxyoctadecanoic acid levels negatively correlated with IL-2 and positively correlated with FGF-19, supporting the Mendelian randomization findings. Our findings provide insights into the molecular mechanisms of sepsis, highlighting the unique roles and contributions of specific metabolites and their interactions with inflammatory mediators. This study enhances our understanding of sepsis pathophysiology and opens avenues for targeted therapeutic interventions and biomarker development for sepsis management. However, further research is essential to validate these pathways across diverse populations and fully explore the roles of these metabolites in sepsis.

BackgroundSepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infection, yet the potential causal relationship between the immunophenotype and sepsis remains unclear.MethodsGenetic variants associated with the immunophenotype served as instrumental variables (IVs) in Mendelian randomization (MR) to elucidate the causal impact of the immunophenotype on three sepsis outcomes. Additionally, a two-step MR analysis was conducted to identify significant potential mediators between the immunophenotype and three sepsis outcomes.ResultsOur MR analysis demonstrated a significant association between the immunophenotype and sepsis outcome, with 36, 36, and 45 the immunophenotype associated with the susceptibility, severity, and mortality of sepsis, respectively. Specifically, our analysis highlighted the CD14+ CD16+ monocyte phenotype as a significant factor across all three sepsis outcomes, with odds ratios (ORs) and corresponding confidence intervals (CIs) indicating its impact on sepsis (OR = 1.047, CI: 1.001-1.096), sepsis in Critical Care Units (OR = 1.139, CI: 1.014-1.279), and sepsis-related 28-day mortality (OR = 1.218, CI: 1.104-1.334). Mediation analyses identified seven cytokines as significant mediators among 91 potential cytokines, including interleukin-5 (IL-5), S100A12, TNF-related apoptosis-inducing ligand (TRAIL), T-cell surface glycoprotein CD6 isoform, cystatin D, interleukin-18 (IL-18), and urokinase-type plasminogen activator (uPA). Furthermore, reverse MR analysis revealed no causal effect of sepsis outcomes on the immunophenotype.ConclusionOur MR study suggests that the immunophenotype is significantly associated with the susceptibility, severity, and mortality of patient with sepsis, providing, for the first time, robust evidence of significant associations between immune traits and their potential risks. This information is invaluable for clinicians and patients in making informed decisions and merits further attention.

The role of excitatory interneurons (EINs) in the cortical has received increasing attention in the discussion of absence seizures. Numerous physiological experiments have confirmed the correlation between EIN and absence seizures. However, the dynamic mechanisms underlying this relationship are not well understood, and there are some challenges in selecting appropriate stimulation strategies for pyramidal clusters. In this study, we incorporated EIN into the previous Taylor model and developed an improved thalamocortical coupled model consisting of ten neuronal populations. Initially, we investigated the excitatory induction effect of EIN to pyramidal clusters and the external input of EIN. Then, four different targeted treatment approaches (deep brain stimulation (DBS), current balanced biphasic pulse (CBBP), 1:0 coordinated resetting stimulation (1:0 CRS), and 3:2 CRS) were applied to the pyramidal clusters. Moreover, we established two quantitative indices to evaluate the stimulation effects. The results showed that modifying the external input of EIN and the coupling strength projected onto the pyramidal clusters can effectively transition the system from an absence seizure state to other normal states. Additionally, inputs from the left compartment were found to reduce the generation of abnormal discharge regions in the right compartment. Furthermore, considering the treatment effects and current consumption, the 3:2 CRS stimulation strategy appeared to be the most suitable treatment approach for the pyramidal clusters. This work introduces a novel coupled model containing EIN, which contributes new theoretical foundations and insights for the future treatment of absence seizures.

Abstract Magnetic core–shell Fe3O4@SiO2 nanoparticles were synthesized by sol–gel method. Based on the characterization and experimental results, the adsorbent was found to have an average particle size of approximately 120 nm, a pore size range of 2–5 nm and superparamagnetic properties. It exhibited electrostatic and hydrogen bonding interactions during adsorption of methyl orange (MO). The adsorption of MO on the magnetic Fe3O4@SiO2 nanoparticles exhibited pseudo-second-order kinetics, the adsorption process is a spontaneous endothermic adsorption process, which conforms to the Langmuir adsorption isotherm model. he maximum amount of MO was adsorbed at pH = 2, T = 45 °C and t = 30 min, and the highest adsorption capacity was 182.503 mg/g; The unit adsorption capacity of the Fe3O4@SiO2 nanoparticles still reached 83% of the original capacity after 5 cycles, so the material was reusable and met the requirements of environmental protection. This study reveals the great potential of magnetic mesoporous nanoparticles for removal of dyes from wastewater.

Abstract Background Progressive hepatitis B virus (HBV) infection can result in cirrhosis, hepatocellular cancer, and chronic hepatitis. While antiviral drugs that are now on the market are efficient in controlling HBV infection, finding a functional cure is still quite difficult. Identifying host factors involved in regulating the HBV life cycle will contribute to the development of new antiviral strategies. Zinc finger proteins have a significant function in HBV replication, according to earlier studies. Zinc finger protein 148 (ZNF148), a zinc finger transcription factor, regulates the expression of various genes by specifically binding to GC-rich sequences within promoter regions. The function of ZNF148 in HBV replication was investigated in this study. Methods HepG2-Na+/taurocholate cotransporting polypeptide (HepG2-NTCP) cells and Huh7 cells were used to evaluate the function of ZNF148 in vitro. Northern blotting and real-time PCR were used to quantify the amount of viral RNA. Southern blotting and real-time PCR were used to quantify the amount of viral DNA. Viral protein levels were elevated, according to the Western blot results. Dual-luciferase reporter assays were used to examine the transcriptional activity of viral promoters. ZNF148’s impact on HBV in vivo was investigated using an established rcccDNA mouse model. Results ZNF148 overexpression significantly decreased the levels of HBV RNAs and HBV core DNA in HBV-infected HepG2-NTCP cells and Huh7 cells expressing prcccDNA. Silencing ZNF148 exhibited the opposite effects in both cell lines. Furthermore, ZNF148 inhibited the activity of HBV ENII/Cp and the transcriptional activity of cccDNA. Mechanistic studies revealed that ZNF148 attenuated retinoid X receptor alpha (RXRα) expression by binding to the RXRα promoter sequence. RXRα binding site mutation or RXRα overexpression abolished the suppressive effect of ZNF148 on HBV replication. The inhibitory effect of ZNF148 was also observed in the rcccDNA mouse model. Conclusions ZNF148 inhibited HBV replication by downregulating RXRα transcription. Our findings reveal that ZNF148 may be a new target for anti-HBV strategies.

Abstract Background Menin is a scaffold protein encoded by the Men1 gene, which interacts with various transcriptional proteins to activate or repress cellular processes and is a key mediator in multiple organs. Both liver-specific and hepatocyte-specific Menin deficiency promotes high-fat diet-induced liver steatosis in mice, as well as insulin resistance and type 2 diabetic phenotype. The potential link between Menin and hepatic metabolism homeostasis may provide new insights into the mechanism of fatty liver disease. Results Disturbance of hepatic Menin expression impacts metabolic pathways associated with non-alcoholic fatty liver disease (NAFLD), including the FoxO signaling pathway, which is similar to that observed in both oleic acid-induced fatty hepatocytes model and biopsied fatty liver tissues, but with elevated hepatic Menin expression and inhibited FABP1. Higher levels of Menin facilitate glucose uptake while restraining fatty acid uptake. Menin targets the expression of FABP3/4/5 and also CD36 or GK, PCK by binding to their promoter regions, while recruiting and deploying the cellular localization of PPARγ and SIRT1 in the nucleus and cytoplasm. Accordingly, Menin binds to PPARγ and/or FoxO1 in hepatocytes, and orchestrates hepatic glucose and fatty acid uptake by recruiting SIRT1. Conclusion Menin plays an orchestration role as a transcriptional activator and/or repressor to target downstream gene expression levels involved in hepatic energy uptake by interacting with the cellular energy sensor SIRT1, PPARγ, and/or FoxO1 and deploying their translocations between the cytoplasm and nucleus, thereby maintaining metabolic homeostasis. These findings provide more evidence suggesting Menin could be targeted for the treatment of hepatic steatosis, NAFLD or metabolic dysfunction-associated fatty liver disease (MAFLD), and even other hepatic diseases. Graphical Abstract

BackgroundAcute pancreatitis (AP) is a severe digestive system disorder with a significant risk of progressing to sepsis, a major cause of mortality. Unraveling the immunological pathways in AP is essential for developing effective treatments, particularly understanding the role of specific immune cell traits in this progression.MethodsEmploying a bidirectional two-sample Mendelian Randomization (MR) approach, this study first examined the causal relationship between AP and 731 immune cell traits to identify those significantly associated with AP. Subsequently, we explored the causal associations between 731 immune cell traits and sepsis. The analysis utilized extensive genome-wide association studies (GWAS) summary datasets, with a focus on identifying common immune cell traits with statistically significant causal associations between AP and sepsis.ResultsOur investigation identified 44 immune cell traits unidirectionally associated with AP and 36 traits unidirectionally associated with sepsis. Among these, CD127 on CD28+ CD45RA- CD8+ T cells emerged as a common mediator, accounting for 5.296% of the increased risk of sepsis in AP patients. This finding highlights the significant role of specific memory CD8+ T cells in the pathophysiology of AP and its progression to sepsis.ConclusionThis study elucidates the critical role of specific immune cell traits, particularly CD127hi memory CD8+ T cells, in the progression of AP to sepsis. Our findings provide a foundation for future research into targeted immune-modulatory therapies, potentially improving patient outcomes in AP-related sepsis and offering new insights into the complex immunological dynamics of this condition.

Abstract Sepsis involves endothelial cell (EC) dysfunction, which contributes to multiple organ failure. To improve therapeutic prospects, elucidating molecular mechanisms of vascular dysfunction is of the essence. ATP-citrate lyase (ACLY) directs glucose metabolic fluxes to de novo lipogenesis by generating acetyl-Co-enzyme A (acetyl-CoA), which facilitates transcriptional priming via protein acetylation. It is well illustrated that ACLY participates in promoting cancer metastasis and fatty liver diseases. Its biological functions in ECs during sepsis remain unclear. We found that plasma levels of ACLY were increased in septic patients and were positively correlated with interleukin (IL)-6, soluble E-selectin (sE-selectin), soluble vascular cell adhesion molecule 1 (sVCAM-1), and lactate levels. ACLY inhibition significantly ameliorated lipopolysaccharide challenge-induced EC proinflammatory response in vitro and organ injury in vivo. The metabolomic analysis revealed that ACLY blockade fostered ECs a quiescent status by reducing the levels of glycolytic and lipogenic metabolites. Mechanistically, ACLY promoted forkhead box O1 (FoxO1) and histone H3 acetylation, thereby increasing the transcription of c-Myc (MYC) to facilitate the expression of proinflammatory and gluco-lipogenic genes. Our findings revealed that ACLY promoted EC gluco-lipogenic metabolism and proinflammatory response through acetylation-mediated MYC transcription, suggesting ACLY as the potential therapeutic target for treating sepsis-associated EC dysfunction and organ injury.

In this work, steam explosion (SE) was applied to prompt the rapid extraction of ergosterol and polysaccharides from Flammulina velutipes root (FVR) waste. Ultrasound-assisted saponification extraction (UASE) followed by water extraction was used to prepare ergosterol and polysaccharides. The results indicated that SE destroyed the complicated structure of FVR and increased its internal porosity and surface roughness. SE caused the thermal degradation of FVR’s structural components and increased the polysaccharide content 0.97-fold. As a result, the extraction yield and efficiency of ergosterol and polysaccharides were improved. The theoretical maximum extraction concentration (C∞) and diffusion coefficient (D) were increased by 34.10% and 78.04% (ergosterol) and 27.69% and 48.67% (polysaccharides), respectively. The extraction yields obtained within 20–30 min of extraction time exceeded those of untreated samples extracted after several hours. For polysaccharides, SE led to a significant reduction in the average molecular weight, increased the percentage of uronic acids and decreased the neutral sugar percentage. The monosaccharide composition was changed by SE, with an increase in the molar ratio of glucose of 64.06% and some reductions in those of other monosaccharides. This work provides an effective method for the processing of fungi waste and adds to its economic value, supporting its high-value utilization in healthcare products.

The past decade witnessed remarkable success in synthetic molecular nanographenes. Encouraged by the widespread application of chiral nanomaterials, the design, and construction of chiral nanographenes is a hot topic recently. As a classic nanographene unit, hexa-peri-hexabenzocoronene generally serves as the building block for nanographene synthesis. This review summarizes the representative examples of hexa-peri-hexabenzocoronene-based chiral nanographenes.

Abstract Background Delayed neutrophil apoptosis during sepsis may impact neutrophil organ accumulation and tissue immune homeostasis. Elucidating the mechanisms underlying neutrophil apoptosis may help identify potential therapeutic targets. Glycolysis is critical to neutrophil activities during sepsis. However, the precise mechanisms through which glycolysis regulates neutrophil physiology remain under-explored, especially those involving the non-metabolic functions of glycolytic enzymes. In the present study, the impact of programmed death ligand-1 (PD-L1) on neutrophil apoptosis was explored. The regulatory effect of the glycolytic enzyme, pyruvate kinase M2 (PKM2), whose role in septic neutrophils remains unaddressed, on neutrophil PD-L1 expression was also explored. Methods Peripheral blood neutrophils were isolated from patients with sepsis and healthy controls. PD-L1 and PKM2 levels were determined by flow cytometry and Western blotting, respectively. Dimethyl sulfoxide (DMSO)-differentiated HL-60 cells were stimulated with lipopolysaccharide (LPS) as an in vitro simulation of septic neutrophils. Cell apoptosis was assessed by annexin V/propidium iodide (annexin V/PI) staining, as well as determination of protein levels of cleaved caspase-3 and myeloid cell leukemia-1 (Mcl-1) by Western blotting. An in vivo model of sepsis was constructed by intraperitoneal injection of LPS (5 mg/kg) for 16 h. Pulmonary and hepatic neutrophil infiltration was assessed by flow cytometry or immunohistochemistry. Results PD-L1 level was elevated on neutrophils under septic conditions. Administration of neutralizing antibodies against PD-L1 partially reversed the inhibitory effect of LPS on neutrophil apoptosis. Neutrophil infiltration into the lung and liver was also reduced in PD-L1−/− mice 16 h after sepsis induction. PKM2 was upregulated in septic neutrophils and promoted neutrophil PD-L1 expression both in vitro and in vivo. In addition, PKM2 nuclear translocation was increased after LPS stimulation, which promoted PD-L1 expression by directly interacting with and activating signal transducer and activator of transcription 1 (STAT1). Inhibition of PKM2 activity or STAT1 activation also led to increased neutrophil apoptosis. Conclusion In this study, a PKM2/STAT1-mediated upregulation of PD-L1 on neutrophils and the anti-apoptotic effect of upregulated PD-L1 on neutrophils during sepsis were identified, which may result in increased pulmonary and hepatic neutrophil accumulation. These findings suggest that PKM2 and PD-L1 could serve as potential therapeutic targets.

Measurement(s) COVID-19 Protocols, Restrictions • Health Behaviors • Personality and Behavioral Change, CTCAE • Emotion • Message Framing • Self-Determination Technology Type(s) Survey • Experiment Design Type Factor Type(s) COVID-19 Protocols, Restrictions • Health Behaviors • Loss-Gain Framing • Cognitive Reappraisal • Self-Determination Messaging Sample Characteristic - Organism Homo Sample Characteristic - Environment Daily Life Sample Characteristic - Location North America • South America • Africa • Australia • Europe • United Kingdom • Asia

The molecular events underlying the lactation curve of dairy animals have long been a biological conundrum for mammary biologists, and a cause of a considerable loss of income for dairy farmers. To better understand the regulatory mechanisms and developmental processes of the mammary gland during the lactation cycle, whole-genome transcriptome profiles of bovine mammary tissues at five different lactation stages were investigated using the RNA-Seq technique. The differentially expressed genes were identified by comparing different lactation stage combinations. Gene expression changes were validated using quantitative reverse-transcription polymerase chain reaction. Some differentially expressed genes were found to locate in the known quantitative trait loci regions that are associated with multiple milk production traits. Proteins of potentially important genes were confirmed to be expressed in the mammary epithelium of dairy cows. An integrated analysis of differential gene expression indicated that internal development regularities underlying the shape of the milk production curve. First, the mammary gland is enriched in similar activities during lactation onset and involution, but in opposite regulatory directions. Second, the lactation stages before and after the milk peak shared similar biological processes that were mainly involved in extracellular matrix remodelling. The discoveries of the study provide information necessary to improve milk production.

Abstract Background We aimed to develop an early warning system for real-time sepsis prediction in the ICU by machine learning methods, with tools for interpretative analysis of the predictions. In particular, we focus on the deployment of the system in a target medical center with small historical samples. Methods Light Gradient Boosting Machine (LightGBM) and multilayer perceptron (MLP) were trained on Medical Information Mart for Intensive Care (MIMIC-III) dataset and then finetuned on the private Historical Database of local Ruijin Hospital (HDRJH) using transfer learning technique. The Shapley Additive Explanations (SHAP) analysis was employed to characterize the feature importance in the prediction inference. Ultimately, the performance of the sepsis prediction system was further evaluated in the real-world study in the ICU of the target Ruijin Hospital. Results The datasets comprised 6891 patients from MIMIC-III, 453 from HDRJH, and 67 from Ruijin real-world data. The area under the receiver operating characteristic curves (AUCs) for LightGBM and MLP models derived from MIMIC-III were 0.98 − 0.98 and 0.95 − 0.96 respectively on MIMIC-III dataset, and, in comparison, 0.82 − 0.86 and 0.84 − 0.87 respectively on HDRJH, from 1 to 5 h preceding. After transfer learning and ensemble learning, the AUCs of the final ensemble model were enhanced to 0.94 − 0.94 on HDRJH and to 0.86 − 0.9 in the real-world study in the ICU of the target Ruijin Hospital. In addition, the SHAP analysis illustrated the importance of age, antibiotics, net balance, and ventilation for sepsis prediction, making the model interpretable. Conclusions Our machine learning model allows accurate real-time prediction of sepsis within 5-h preceding. Transfer learning can effectively improve the feasibility to deploy the prediction model in the target cohort, and ameliorate the model performance for external validation. SHAP analysis indicates that the role of antibiotic usage and fluid management needs further investigation. We argue that our system and methodology have the potential to improve ICU management by helping medical practitioners identify at-sepsis-risk patients and prepare for timely diagnosis and intervention. Trial registration: NCT05088850 (retrospectively registered).

Parkinson’s disease (PD) is the second largest neurodegenerative disorder caused by the decreased number of dopaminergic (DAc) neurons in the substantia nigra pars compacta (SNpc). There is evidence that oxidative stress can contribute degeneration of DAc neurons in SNpc which is mainly caused by apoptotic cell death. Thus, suppressing oxidative stress and apoptosis of DAc neurons is an effective strategy to mitigate the progress of PD. Astaxanthin (AST) is a carotenoid, which mainly exists in marine organisms and is a powerful biological antioxidant. In this study, we aimed to determine the neuroprotective effect of AST on paraquat (PQ) -induced models of PD in vitro and in vivo. Here, we showed that AST significantly enhanced cell survival of SH-SY5Y cells against PQ toxicity by suppressing apoptotic cell death and oxidative stress. Moreover, we found that AST significantly ameliorated PQ-induced behavioral disorders associated with PD in C57BL/6 J mice and the damage to DAc neurons in the SNpc of mice. Lastly, we found that the neuroprotective effects of AST were conducted through inhibiting PQ-induced activation of MAPK signaling. In conclusion, our study indicates that AST had a strong protective effect on PQ-induced oxidative stress and antagonized apoptotic cell death in SH-SY5Y cells and PQ-induced mice PD model, which might provide new insights of AST for PD treatment.

Canine distemper virus (CDV) can cause fatal infections in giant pandas. Vaccination is crucial to prevent CDV infection in giant pandas. In this study, two bacterium-like particle vaccines F3-GEM and H4-GEM displaying the trimeric F protein or tetrameric H protein of CDV were constructed based on the Gram-positive enhanced-matrix protein anchor (GEM-PA) surface display system. Electron microscopy and Western blot results revealed that the F or H protein was successfully anchored on the surface of GEM particles. Furthermore, one more bacterium-like particle vaccine F3 and H4-GEM was also designed, a mixture consisting of F3-GEM and H4-GEM at a ratio of 1:1. To evaluate the effect of the three vaccines, mice were immunized with F3-GEM, H4-GEM or F3 and H4-GEM. It was found that the level of IgG-specific antibodies and neutralizing antibodies in the F3 and H4-GEM group was higher than the other two groups. Additionally, F3 and H4-GEM also increased the secretion of Th1-related and Th2-related cytokines. Moreover, F3 and H4-GEM induce IgG and neutralizing antibodies’ response in dogs. Conclusions: In summary, F3 and H4-GEM can provoke better immune responses to CDV in mice and dogs. The bacterium-like particle vaccine F3 and H4-GEM might be a potential vaccine candidate for giant pandas against CDV infection.

Acute respiratory distress syndrome (ARDS) is associated with high mortality rates in patients admitted to the intensive care unit (ICU) patients with overwhelming inflammation considered to be an internal cause. The authors’ previous study indicated a potential correlation between phenylalanine levels and lung injury. Phenylalanine induces inflammation by enhancing the innate immune response and the release of pro-inflammatory cytokines. Alveolar macrophages (AMs) can respond to stimuli via synthesis and release of inflammatory mediators through pyroptosis, one form of programmed cell death acting through the nucleotide-binging oligomerization domain-like receptors protein 3 (NLRP3) signaling pathway, resulting in the cleavage of caspase-1 and gasdermin D (GSDMD) and the release of interleukin (IL) -1β and IL-18, aggravating lung inflammation and injury in ARDS. In this study, phenylalanine promoted pyroptosis of AMs, which exacerbated lung inflammation and ARDS lethality in mice. Furthermore, phenylalanine initiated the NLRP3 pathway by activating the calcium-sensing receptor (CaSR). These findings uncovered a critical mechanism of action of phenylalanine in the context of ARDS and may be a new treatment target for ARDS.

Image reconstruction represents an important technique applied in various fields such as medicine, biology, materials science, nondestructive testing, and so forth. In this paper, we transform the problem of image reconstruction into the problem of solving linear systems with multiple right-hand sides. Based on the idea of K-means clustering, we propose the global randomized block Kaczmarz method, so as to solve the problem of the linear systems with multiple right-hand sides effectively and use this method to image reconstruction. Theoretical analysis proves the convergence of this method, and the simulation results demonstrate the performance of this method in image reconstruction.

Abstract Na+ superionic conductor (NASICON)‐structured Na4VMn(PO4)3 (NVMP) possesses stable cycling performance at 2.5–3.8 V by replacing V with lower cost Mn but suffers rapid capacity decay when further widening the voltage to 2.5–4.2 V, owing to a less stable V4+/V5+ redox couple. Herein, to stabilize the V4+/V5+ couple and improve the reversibility, a series of carbon‐coated NVMP (NVMP@C) with different V/Mn ratios are compared, among which, Na3.25V1.75Mn0.25(PO4)3@C delivers an additional reversible V4+/V5+ capacity of 7 mAh g−1 at the voltage of 3.9–4.2 V. Based on this, to further activate the capacity of V4+/V5+, Al‐doped Na3.25V1.75−yMn0.25Aly(PO4)3 structures are synthesized. When 0.5 Al is doped, 15 mAh g−1 capacity corresponding to V4+/V5+ can be released. In addition, it is found that the activation of V4+/V5+ is not conducive to electrochemical reversibility and C‐rate performance, owing to the shrinkage of the whole framework structure with the oxidization of V4+ to V5+.

At present, most of the fault diagnosis methods with extensive research and good diagnostic effect are based on the premise that the sample distribution is consistent. However, in reality, the sample distribution of rotating machinery is inconsistent due to variable working conditions, and most of the fault diagnosis algorithms have poor diagnostic effects or even invalid. To dispose the above problems, a novel symmetric stacked autoencoder (NSSAE) for adversarial domain adaptation is proposed. Firstly, the symmetric stacked autoencoder network with shared weights is used as the feature extractor to extract features which can better express the original signal. Secondly, adding domain discriminator that constituting adversarial with feature extractor to enhance the ability of feature extractor to extract domain invariant features, thus confusing the domain discriminator and making it unable to correctly distinguish the features of the two domains. Finally, to assist the adversarial training, the maximum mean discrepancy (MMD) is added to the last layer of the feature extractor to align the features of the two domains in the high-dimensional space. The experimental results show that, under the condition of variable speed, the NSSAE model can extract domain invariant features to achieve the transfer between domains, and the transfer diagnosis accuracy is high and the stability is strong.

Concerning the vision of achieving carbon neutral and peak carbon goals, wind energy is extremely important as a renewable and clean energy source. However, existing research ignores the implicit features of the data preprocessing technique and the role of the internal mechanism of the optimization algorithm, making it difficult to achieve high-accuracy prediction. To fill this gap, this study proposes a wind speed forecasting model that combines data denoising techniques, optimization algorithms, and machine learning algorithms. The model discusses the important parameters in the data decomposition technique, determines the best parameter values by comparing the model’s performance, and then decomposes and reconstructs the wind speed time series. In addition, a novel optimization algorithm is used to optimize the parameters of the machine learning algorithm using a waiting strategy and an aggressive strategy to improve the effectiveness of the model. Several control experiments were designed and implemented using 10-min wind speed data from three sites in Penglai, Shandong Province. Based on the numerical comparison results and the discussion of the proposed model, it is concluded that the developed model can obtain high accuracy and reliability of wind speed prediction in the short term relative to other comparative models and can have further applications in wind power plants.

Abstract Background Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors. Method Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data. Results In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as “suspected sHLH positive”. Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P 1922.58 ng/mL), low platelets (2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19. Conclusions HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.

Abstract Background The aim of this study is to assess the prevalence of abnormal urine analysis and kidney dysfunction in COVID-19 patients and to determine the association of acute kidney injury (AKI) with the severity and prognosis of COVID-19 patients. Methods The electronic database of Embase and PubMed were searched for relevant studies. A meta-analysis of eligible studies that reported the prevalence of abnormal urine analysis and kidney dysfunction in COVID-19 was performed. The incidences of AKI were compared between severe versus non-severe patients and survivors versus non-survivors. Results A total of 24 studies involving 4963 confirmed COVID-19 patients were included. The proportions of patients with elevation of sCr and BUN levels were 9.6% (95% CI 5.7–13.5%) and 13.7% (95% CI 5.5–21.9%), respectively. Of all patients, 57.2% (95% CI 40.6–73.8%) had proteinuria, 38.8% (95% CI 26.3–51.3%) had proteinuria +, and 10.6% (95% CI 7.9–13.3%) had proteinuria ++ or +++. The overall incidence of AKI in all COVID-19 patients was 4.5% (95% CI 3.0–6.0%), while the incidence of AKI was 1.3% (95% CI 0.2–2.4%), 2.8% (95% CI 1.4–4.2%), and 36.4% (95% CI 14.6–58.3%) in mild or moderate cases, severe cases, and critical cases, respectively. Meanwhile, the incidence of AKI was 52.9%(95% CI 34.5–71.4%), 0.7% (95% CI − 0.3–1.8%) in non-survivors and survivors, respectively. Continuous renal replacement therapy (CRRT) was required in 5.6% (95% CI 2.6–8.6%) severe patients, 0.1% (95% CI − 0.1–0.2%) non-severe patients and 15.6% (95% CI 10.8–20.5%) non-survivors and 0.4% (95% CI − 0.2–1.0%) survivors, respectively. Conclusion The incidence of abnormal urine analysis and kidney dysfunction in COVID-19 was high and AKI is closely associated with the severity and prognosis of COVID-19 patients. Therefore, it is important to increase awareness of kidney dysfunction in COVID-19 patients.

Abstract Since the 2019 novel coronavirus disease (COVID-19) outbreak originated from Wuhan, Hubei Province, China, at the end of 2019, it has become a clinical threat to the general population worldwide. Among people infected with the novel coronavirus (2019-nCoV), the intensive management of the critically ill patients in intensive care unit (ICU) needs substantial medical resource. In the present article, we have summarized the promising drugs, adjunctive agents, respiratory supportive strategies, as well as circulation management, multiple organ function monitoring and appropriate nutritional strategies for the treatment of COVID-19 in the ICU based on the previous experience of treating other viral infections and influenza. These treatments are referable before the vaccine and specific drugs are available for COVID-19.

Abstract Background Systemic reactivation of Epstein–Barr virus (EBV) may occur in novel coronavirus disease 2019 (COVID‐19) caused by the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). However, the clinical consequences of EBV reactivation remain uncertain. Methods In this retrospective study, we screened 1314 patients with confirmed COVID‐19 who died or were discharged between January 1, 2020 and March 12, 2020, in Wuhan Infectious Disease Hospital, Wuhan, China. Patients who had complete data for EBV serology and cytomegalovirus (CMV) serology were eligible. Serum levels of viral capsid antigen (VCA)‐immunoglobulin G (IgG), Epstein–Barr nuclear antigen‐IgG, VCA‐IgM, early antigen (EA)‐IgG, CMV‐IgG, and CMV‐IgM were compared between survivors and nonsurvivors. Dynamic changes of laboratory tests and outcomes were compared in patients with and without ganciclovir treatment. We used 1:1 matching based on age, gender, and illness severity to balance baseline characteristics. Results EBV reactivation was present in 55 of 217 patients. EBV reactivation was associated with age (57.91 [13.19] vs. 50.28 [12.66] years, p

The converter transformer is the core equipment of HVDC transmission system, the valve-side winding of which needs to withstand DC voltage. Partial discharge is one of the main threats to the safe operation of converter transformer, yet the characteristics of partial discharge development of the oil-pressboard insulations under constant DC voltage are insufficiently understood. In order to better understand the partial discharge characteristics of the oil-pressboard insulation under DC voltage and provide deeper theoretical support for insulation diagnosis of converter transformers, development characteristics including the time-varying tendency of discharge magnitude and repetition rate of partial discharge in oil-pressboard insulation under constant positive and negative DC voltage were studied. The results indicate that the development of partial discharge in a needle-plane oil-pressboard insulation model under constant DC voltage has three stages: the intensive discharging stage, the silent-burst stage, and the breakdown stage. Throughout all stages, the partial discharge magnitude and repetition rate first decrease and increase afterwards. At the silent-burst stage, the partial discharge appears in the form of a “cluster” with very large magnitude and repetition rate. Each cluster exists for tens of seconds but with at a very long interval with each other. Further analysis shows that the repeated accumulation and dissipation of free charges on the surface of the pressboard cause the above phenomena. Negative charges are easy to accumulate and difficult to dissipate under the same voltage amplitude compared to positive charges, leading to a weaker actual electric field at the needle tip and thus partial discharges under negative DC voltage with a lower magnitude and longer interval.

The study investigated the extrusion modification of wheat bran and its effects on structural and rheological properties of wheat flour dough. Extruded bran showed better solubility of dietary fiber and structural porosity, leading to higher hydration and swelling power. Addition of extruded bran to dough caused water redistribution as an intensive aggregation of bound water to gluten matrix with reduced mobility. The bran–gluten interaction influenced by water sequestering caused partial gluten dehydration and conversion of β-turn into β-sheet, which demonstrated the formation of a more polymerized and stable gluten network. Farinographic data confirmed the promotion of dough stability with extruded bran addition at lower gluten content, while viscoelastic data suggested improved dough elasticity at all gluten contents by increasing elastic moduli and decreasing loss tangent. This study would be useful for interpreting the modification effect and mechanism of extrusion on cereal brans and provide valuable guidance for applying it as an effective modification technology on the commercial production of cereal bran and its flour products.

External ophthalmoplegia with rib and vertebral anomalies (EORVA) is characterized by congenital nonprogressive external ophthalmoplegia, ptosis, scoliosis, torticollis, vertebral, and rib anomalies, caused by homozygous mutations in the myogenic factor 5 gene (MYF5) located on chromosome 12q21.31. Uniparental disomy (UPD) is a rare inheritance of a pair of chromosomes originating from only one parent. This study describes a case of an 8-year-old boy with ptosis, scoliosis, and dysmorphic hypoplastic ribs with fusion anomalies. Trio-based exome sequencing (trio-ES) identified a novel homozygous mutation c.191delC (p.Ala64Valfs*33) in MYF5 in the proband, with the father being heterozygous and the mother wild-type, as verified by Sanger sequencing. UPD identified from trio-ES variant call format data suggested the possibility of paternal UPD of chromosome 12 (UPD12pat) in the proband, further confirmed to be a complete isodisomy type of UPD by genome-wide single nucleotide polymorphism array. MYF5 was significantly downregulated by 69.14% (**p < 0.01) in HeLa cells transfected with mutant MYF5 containing c.191delC compared to those transfected with the wild-type MYF5, resulting in a truncated protein with a size of ∼20 kDa. In conclusion, this study identified a novel homozygous mutation in MYF5, broadening the genetic spectrum of EORVA and further deepening the understanding of this rare disease.

Duchenne muscular dystrophy (DMD), one of the most common progressive and severely disabling neuromuscular diseases in children, can be largely attributed to the loss of function of the DMD gene on chromosome Xp21.2-p21.1. This paper describes the case of a 10-year-old boy diagnosed with DMD. Whole exome sequencing confirmed the hypothesized large partial exonic deletion of c.7310-11543_7359del (chrX:g.31792260_31803852del) spanning exon 51 and intron 50 in DMD. This large deletion was verified to be de novo by PCR, and the two breakpoints were further confirmed by Sanger sequencing and long-read whole-genome sequencing. Notably, this partial exonic deletion was the only complex variation in the deep intron regions or intron–exon junction regions in DMD. In addition, the case study demonstrates the clinical importance of using multiple molecular genetic testing methods for the diagnosis of rare diseases.

This study aimed to examine first-born children's sibling jealousy and explore the relationships among first-born children's sibling jealousy, temperament, and emotion regulation in China during COVID-19 pandemic. The research hypotheses of this study are empirically examined through online and offline surveys. A sample of 304 two-child families from China participated in the study; the first-born children were aged between 1.17 and 7 years. The results indicated the following: (1) the older the first-born children and the greater the age difference between siblings, the lower the sibling jealousy. (2) Difficult temperament of first-born children could predict sibling jealousy significantly and positively, and emotion regulation could predict sibling jealousy negatively. (3) There was a partially mediating effect of emotion regulation between temperament and sibling jealousy. Compared with intermediate temperament, first-born children with difficult temperament had weaker emotion regulation and higher sibling jealousy. Overall, findings have important implications for psychological interventions for families of first-born children with difficult temperament.

Severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) strongly hampered the broad clinical applicability of chimeric antigen receptor T cell (CAR-T) therapy. Vascular endothelial activation has been suggested to contribute to the development of CRS and ICANS after CAR-T therapy. However, therapeutic strategies targeting endothelial dysfunction during CAR-T therapy have not been well studied yet. Here, we found that tumor necrosis factor α (TNFα) produced by CAR-T cells upon tumor recognition and interleukin 1β (IL1β) secreted by activated myeloid cells were the main cytokines in inducing endothelial activation. Therefore, we investigated the potential effectiveness of TNFα and IL1β signaling blockade on endothelial activation in CAR-T therapy. The blockade of TNFα and IL1β with adalimumab and anti-IL1β antibody respectively, as well as the application of focal adhesion kinase (FAK) inhibitor, effectively ameliorated endothelial activation induced by CAR-T, tumor cells, and myeloid cells. Moreover, adalimumab and anti-IL1β antibody exerted synergistic effect on the prevention of endothelial activation induced by CAR-T, tumor cells, and myeloid cells. Our results indicate that TNFα and IL1β blockade might have therapeutic potential for the treatment of CAR-T therapy-associated CRS and neurotoxicity.

By Maker Fringe (MF) method, all of the nonlinear optical (NLO) coefficients including d11, d12, d13, d31, d32 and d33 of TmCa4O(BO3)3 (TmCOB) crystals were measured to be 0.19, 0.26, −0.61, −0.30, 1.66 and −1.25 pm/V, respectively. Based on which, the second-harmonic-generation (SHG) phase-matching (PM) characteristics of TmCOB crystals in two-dimensional principal planes and three-dimensional non-principal planes (space) were theoretically calculated, such as PM tuning curves, distribution of effective NLO coefficient (deff), beam walk-off angle, and angular acceptance bandwidth. At the fundamental waves of 1064 nm, the type-II optimal PM angles with largest deff for principal planes and space were decided to be (52.8°, 90.0°) (deff = 0.24 pm/V) and (118.0°, 77.2°) (deff = 0.35 pm/V), respectively. The type-II SHG of TmCOB crystals was found to present large acceptance angle bandwidth (~2–12 times of type-I values) and small beam walk-off angle (~0.2–0.4 times of type-I values). At a high input energy of 6.89 mJ (35 ps, 10 Hz, 1064 nm), the SHG transformation efficiency for an uncoated TmCOB crystal sample cut along type-II optimal angle (118.0°, 77.2°) with 12 mm in length was measured to be 55.9%, which achieved the same conversion efficiency grade as type-I optimal PM.

Imbalance in redox homeostasis is a major cause of age-related cognitive impairment. The endocannabinoid system (ECS) is a key player in regulating synaptic transmission, plasticity and memory. Increasing evidence indicates an important interplay between the two systems. However, how excessive oxidative stress could alter ECS and that, in turn, impairs its modulatory role in synaptic plasticity and cognitive function remains elusive. In the present study, we examined this causal link in D-galactose-induced oxidative rats. First, the reactive oxygen species generating enzymes, especially nitric oxide synthase (NOS), indeed show an elevated expression in D-galactose-treated rats, and this was correlated to an impaired hippocampal long-term potentiation (LTP) and spatial memory loss in animal behavioral tests. Second, the cannabinoid receptor type I (CB1)-mediated signaling is known to regulate synaptic plasticity. We show that a decrease in CB1 and increase in degradation enzymes for CB1 ligand endocannabinoid anandamide all occurred to D-galactose-treated rats. Surprisingly, application of low-dose anandamide, known to reduce LTP under physiological condition, now acted to enhance LTP in D-galactose-treated rats, most likely resulted from the inhibition of GABAergic synapses. Furthermore, this reversal behavior of CB1-signaling could be fully simulated by a NOS inhibitor, diphenyleneiodonium. These observations suggest that interaction between redox dysfunction and ECS should contribute significantly to the impaired synaptic plasticity and memory loss in D-galactose-treated rats. Therefore, therapies focusing on the balance of these two systems may shed lights on the treatment of age-related cognitive impairment in the future.

Memristors store information through a history dependent resistance, which could be used in future computing technologies as a resistive random access memory or to mimic synaptic behaviors with all electronic components. Realizing memristive behavior in the emerging two-dimensional (2D) materials will add new applications to this group of interesting materials. In this study, we successfully fabricate memristors based on a layered 2D material GeSe. Few-layer GeSe flakes are used as the ionic and electronic conductor, and silver is deposited as the active electrode. Reproducible resistance switching is realized in this type of device with the ratio of high resistance to low resistance reaching 104. Thanks to the planar device structure, the conductive path responsible for the resistance state switching is directly imaged with a conductive atomic force microscope. An in situ observation shows that the conductive path is reconfigurable by the polarity of the voltage between the silver and GeSe electrodes. These results demonstrate a facile method for fabricating memristors with 2D materials and provide insights into the resistance switching mechanism.

A genome-wide association study (GWAS) was conducted on 23 serum biochemical traits in Chinese Holstein cattle. The experimental population consisted of 399 cattle, each genotyped by a commercial bovine 50K SNP chip, which had 49,663 SNPs. After data cleaning, 41,092 SNPs from 361 Holstein cattle were retained for GWAS. The phenotypes were measured values of serum measurements of these animals that were taken at 11 days after parturition. Two statistical models, a fixed-effect linear regression model (FLM) and a mixed-effect linear model (MLM), were used to estimate the association effects of SNPs. Genome-wide significant and suggestive thresholds were set up to be 1.22E−06 and 2.43E−06, respectively. In the Chinese Holstein population, FLM identified 81 genome-wide significant (0.05/41,092 = 1.22E−06) SNPs associated with 11 serum traits. Among these SNPs, five SNPs (BovineHD0100005950, ARS-BFGL-NGS-115158, BovineHD1500021175, BovineHD0800028900, and BTB-00442438) were also identified by the MLM to have genome-wide suggestive effects on CHE, DBIL, and LDL. Both statistical models pinpointed two SNPs that had significant effects on the Holstein population. The SNP BovineHD0800028900 (located near the gene LOC101903458 on chromosome 8) was identified to be significantly associated with serum high- and low-density lipoprotein (HDL and LDL), whereas BovineHD1500021175 (located in 73.4Mb on chromosome 15) was an SNP significantly associated with total bilirubin and direct bilirubin (TBIL and DBIL). Further analyses are needed to identify the causal mutations affecting serum traits and to investigate the correlation of effects for loci associated with fatty liver disease in dairy cattle.

A purified polysaccharide, designated as SE-WGPI, was isolated from wheat germ modified by steam explosion. The primary structure characteristics were determined by HPGPC, GC, periodate oxidation-Smith degradation, methylation analysis, FT-IR, NMR and Congo red test. The results showed that SE-WGPI was a homogeneous hetero-polysaccharide with the average molecular weight of 5.6 × 103 Da. The monosaccharide composition mainly consisted of glucose, arabinose and xylose with a molar ratio of 59.51: 20.71: 19.77. The main backbone of SE-WGPI consisted of →4,6)-α-D-Glcp(1→6)-α-D-Glcp(1→3)-β-D-Xylp(1→5)-α-L-Araf(1→ and the side chain was α-D-Glcp(1→ linked at the C4-position of →4,6)-α-D-Glcp(1→. SE-WGPI likely has a complex netted structure with triple helix conformation and good thermal stability. In addition, SE-WGPI had valid in vitro radical scavenging activities on DPPH and hydroxyl radicals. This study may provide structural information of SE-WGPI for its promising application in the fields of functional foods or medicines.

Although some traditional autoencoders and their extensions have been widely used in the research of intelligent fault diagnosis of rotating parts, their feature extraction capabilities are limited without label information. In response to this problem, this research proposes a hierarchical sparse discriminant autoencoder (HSDAE) method for fault diagnosis of rotating components, which is a new semi-supervised autoencoder structure. By considering the sparsity of autoencoders, a hierarchical sparsity strategy was proposed to improve the stacked sparsity autoencoders, and the particle swarm optimization algorithm was used to obtain the optimal sparsity parameters to improve network performance. In order to enhance the classification of the autoencoder, a class aggregation and class separability strategy was used, which is an additional discriminative distance that was added as a penalty term in the loss function to enhance the feature extraction ability of the network. Finally, the reliability of the proposed method was verified on the bearing data set of Case Western Reserve University and the bearing data set of the laboratory test platform. The results of comparison with other methods show that the HSDAE method can enhance the feature extraction ability of the network and has reliability and stability for different data sets.

Due to the mechanical equipment working under variable speed and load for a long time, the distribution of samples is different (domain shift). The general intelligent fault diagnosis method has a good diagnostic effect only on samples with the same sample distribution, but cannot correctly predict the faults of samples with domain shift in a real situation. To settle this problem, a new intelligent fault diagnosis method, domain adaptation network with double adversarial mechanism (DAN-DAM), is proposed. The DAN-DAM model is mainly composed of a feature extractor, two label classifiers and a domain discriminator. The feature extractor and the two label classifiers form the first adversarial mechanism to achieve class-level alignment. Moreover, the discrepancy between the two classifiers is measured by Wasserstein distance. Meanwhile, the feature extractor and the domain discriminator form the second adversarial mechanism to realize domain-level alignment. In addition, maximum mean discrepancy (MMD) is used to reduce the distance between the extracted features of two domains. The DAN-DAM model is verified by multiple transfer experiments on some datasets. According to the transfer experiment results, the DAN-DAM model has a good diagnosis effect for the domain shift samples. Moreover, the diagnostic accuracy is generally higher than other mainstream diagnostic methods.

The angular non-critical phase-matching (A-NCPM) second-harmonic-generation (SHG) properties of RE1xRE21−xCOB (RE1, RE2 = Y, Gd, La, Tm, Sm, and Nd) type mixed crystals including NCPM wavelength and conversion efficiency were detailedly investigated. Theoretical calculations manifest that the A-NCPM SHG scope of these crystals is 0.72~1.42 µm, and in experiments, the A-NCPM SHG waveband of 0.72~1.25 µm has been realized, by changing the ratio of the rare-earth elements RE1 and RE2 in RE1xRE21−xCOB crystals. Comparing to the temperature-dependent A-NCPM SHG of 0.95~1.34 µm in LiB3O5 (LBO) crystal, the composition-dependent A-NCPM SHG of 0.72~0.95 µm in RE1xRE21−xCOB type crystals is unique and has special significance for the frequency conversion of Ti:Sapphire lasers. Relationships between the birefringence and radius of rare-earth ion RE3+ in RE1xRE21−xCOB mixed crystals were discussed. Aiming for the A-NCPM SHG of 0.72~1.42 µm, we supply a clear, completed, and optimized solution on how to select the compositions of RE1xRE21−xCOB mixed crystals. Under focusing light beam conditions, high efficient A-NCPM SHG for both OPO and Ti:sapphire lasers were realized experimentally by using long Y- and Z-cut RE1xRE21−xCOB crystal samples.

In this paper, the partial eigenvalue assignment problem of gyroscopic second-order systems with time delay is considered. We propose a multi-step method for solving this problem in which the undesired eigenvalues are moved to desired values and the remaining eigenvalues are required to remain unchanged. Using the matrix vectorization and Hadamard product, we transform this problem into a linear systems of lower order, and analysis the computational costs of our method. Numerical results exhibit the efficiency of our method.

Summary: Retroactive interference (RI) occurs when new incoming information impairs an existing memory, which is one of the primary sources of forgetting. Although long-term potentiation (LTP) reversal shows promise as the underlying neural correlate, the key molecules that control the sensitivity of memory circuits to RI are unknown, and the developmental trajectory of RI effects is unclear. Here we found that depotentiation in the hippocampal dentate gyrus (DG) depends on GluN2A-containing NMDA receptors (NMDARs). The susceptibility of LTP to disruption progressively increases with the rise in the GluN2A/GluN2B ratio during development. The vulnerability of hippocampus-dependent memory to interference from post-learning novelty exploration is subject to similar developmental regulation by NMDARs. Both GluN2A overexpression and GluN2B downregulation in the DG promote RI-induced forgetting. Altogether, our results suggest that a switch in GluN2 subunit predominance may confer age-related differences to depotentiation and underlie the developmental decline in memory resistance to RI. : Ge et al. report that the NMDA receptor GluN2A/GluN2B subunit ratio determines the sensitivity of strengthened neuronal connections to depotentiation. As the ratio rises during development, memories become more vulnerable to disruption by post-learning interference. These findings help to illuminate the mechanism by which forgetting rates may vary with age. Keywords: forgetting, retroactive interference, depotentiation, NMDA receptor

Frequently occurring fatty liver disease in dairy cows during the perinatal period, a typical type of non-alcoholic fatty liver disease (NAFLD), results in worldwide high culling rates of dairy cows (averagely about 25%) after calving. This has been developing into a critical industrial problem throughout the world, because the metabolic disease severely affects the welfare and economic value of dairy cows. Findings about the molecular mechanisms how the fatty liver disease develops would help scientists to discover novel therapeutic targets for NAFLD. Studies have shown that PPARγ participates or regulates the fat deposition in liver by affecting the biological processes of hepatic lipid metabolism, insulin resistance, gluconeogenesis, oxidative stress, endoplasmic reticulum stress and inflammation, which all contribute to fatty liver. This review mainly focuses on crucial regulatory mechanisms of PPARγ regulating lipid deposition in the liver via direct and/or indirect pathways, suggesting that PPARγ might be a potential critical therapeutic target for fatty liver disease, however, it would be of our significant interest to reveal the pathology and pathogenesis of NAFLD by using dairy cows with fatty liver as an animal model. This review will provide a molecular mechanism basis for understanding the pathogenesis of NAFLD.

Antipsychotic-induced weight gain is one of the most common adverse effects of antipsychotic treatment. However, there are no well-established interventions for the weight gain yet. In this study, we pooled the data from two clinical trials, which were originally examining the efficacy of betahistine and the efficacy of metformin in treating antipsychotic-induced weight gain and insulin resistance. A total of 67 people with schizophrenia or bipolar disorder treated with antipsychotics were assigned to 36 mg day−1 betahistine (n = 13) or 1,000 mg day−1 metformin (n = 25) or placebo (n = 29) treatment for 12 weeks, with evaluation at baseline and week 12. The primary outcome was the body mass index (BMI). After treatment, metformin group had a mean decrease in BMI of 1.46 ± 0.14 (p < 0.001) and insulin resistance index (IRI) of 4.30 ± 2.02 (p < 0.001). The betahistine group had no significant alteration in BMI or IRI. However, placebo group had a mean increase in BMI of 1.27 ± 0.77 (p < 0.001) and IRI of 0.45 ± 0.86 (p < 0.001). Between the two treatment groups, metformin significantly decreased weight, BMI, fasting glucose, insulin level, and IRI but not waist circumference when compared with betahistine. Moreover, metformin significantly decreased weight, BMI, waist circumference, fasting glucose, insulin level, and IRI when compared with placebo, whereas betahistine significantly decreased body weight, waist circumference, BMI, insulin level, and IRI but not fasting glucose when compared with placebo. In this study, we found that both metformin treatment and betahistine treatment were efficacious in improving antipsychotic-induced weight gain and insulin resistance, and metformin was more efficacious in preventing and revising the weight gain induced by antipsychotics.Clinical Trial Registration:www.ClinicalTrials.gov, NCT00451399(Study 1), NCT00709202(Study 2)