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Background: As an emerging infectious disease, COVID-19 has garnered great research interest. We aimed to explore the differences between English language and Chinese language Medical/Scientific journals publications, particularly aiming to explore the efficacy/contents of the literature published in English and Chinese in relation to the outcomes of management and characterization of COVID-19 during the early stage of COVID-19 pandemic.Methods: Publications on COVID-19 research were retrieved from both English and Chinese databases. Bibliometric analyses were performed using VOSviewer 1.6.14, and CiteSpace V software. Network maps were generated to evaluate the collaborations between different authors, countries/provinces, and institutions.Results: A total of 143 English and 721 Chinese original research articles and reviews on COVID-19 were included in our study. Most of the authors and institutions of the papers were from China before March 1st, 2020, however, the distribution of authors and institutions were mainly in developed countries or more wealthy areas of China. The range of the keywords in English publications was more extensive than those in Chinese. Traditional Chinese Medicine was seen more frequently in Chinese papers than in English. Of the 143 articles published in English, 54 articles were published by Chinese authors only and 21 articles were published jointly by Chinese and other overseas authors.Conclusions: The publications in English have enabled medical practitioners and scientists to share/exchange information, while on the other hand, the publications in the Chinese language have provided complementary educational approaches for the local medical practitioners to understand the essential and key information to manage COVID-19 in the relatively remote regions of China, for the general population with a general level of education.

Alzheimer disease (AD) has an insidious onset and heterogeneous clinical symptoms. The well-accepted biomarkers for clinical diagnosis of AD include β-amyloid (Aβ) deposition and pathologic tau level within cerebral spinal fluid (CSF) and imaging AD pathology such as positive emission tomography (PET) imaging of the amyloid-binding agent Pittsburgh compound B (PET-PiB). However, the high expense and invasive nature of these methods highly limit their wide usage in clinic practice. Therefore, it is imperious to develop less expensive and invasive methods, and plasma biomarkers are the premium targets. In the current study, we utilized a single-blind comparison method; all the probable AD cases met the core clinical National Institute on Aging and Alzheimer’s Association (NIA-AA) criteria and validated by PET-PiB. We used ultrasensitive immunomagnetic reduction (IMR) assays to measure plasma Aβ42 and total-tau (t-tau) levels, in combination with different variables including Aβ42 × t-tau value, Montreal Cognitive Assessment (MoCA), and Mini Mental State Examination (MMSE). We used logistic regression to analyze the effect of all these variables in the algorism. Our results showed that (1) plasma Aβ42 and t-tau are efficient biomarkers for AD diagnosis using IMR platform, whereas Aβ42 × t-tau value is more efficient for discriminating control and AD; (2) in the control group, Aβ42 level and age demonstrated strong negative correlation; Aβ42 × t-tau value and age demonstrated significant negative correlation; (3) in the AD group, t-tau level and MMSE score demonstrated strong negative correlation; (4) using the model that Aβ42, Aβ42 × t-tau, and MoCA as the variable to generate receiver operating characteristic (ROC) curve, cutoff value = 0.48, sensitivity = 0.973, specificity = 0.982, area under the curve (AUC) = 0.986, offered better categorical efficacy, sensitivity, specificity, and AUC. The multifactor model of plasma Aβ42 and t-tau in combination with MoCA can be a viable model separate health and AD subjects in clinical practice.

Neuroblastoma, a malignant tumor of the sympathetic nervous system, is an aggressive extracranial tumor in childhood. Long noncoding RNAs (lncRNAs) have been discovered to play a key role in the eukaryotic regulatory gene network and be involved in a wide variety of biological processes. We observed that the expression of lncRNA nuclear-enriched abundant transcript-1 (NEAT1) was significantly decreased in human neuroblastoma tissues and cell lines, compared with the normal. We observed cell proliferation, migration, and invasion with Cell Counting Kit-8 assay, colony formation assay, and Transwell assay to investigate the effects of NEAT1, miR-183-5p, or FOXP1 on neuroblastoma cells. And we also used StarBase and luciferase reporter gene assay to predict and confirm the interaction of NEAT1, miR-183-5p, and FOXP1 in neuroblastoma cells. First, overexpression of NEAT1 suppressed cell proliferation and played a key role in cell migration and invasion. In addition, NEAT1 was demonstrated to directly interact with miR-183-5p and exerted its antioncogenic role in neuroblastoma by negatively regulating miR-183-5p expression. miR-183-5p suppressed the expression of FOXP1 and regulated cell proliferation and migration by directly targeting FOXP1 mRNA 3′-untranslated region. Moreover, FOXP1 antagonized the effect of miR-183-5p on the phosphorylation of extracellular-regulated kinase/protein kinase B (ERK/AKT), while FOXP1 siRNA increased the reduced phosphorylation of ERK/AKT caused by miR-183-5p inhibitor in neuroblastoma cells. Taken together, these data showed that NEAT1 negatively regulated cell proliferation and migration of neuroblastoma by the miR-183-5p/FOXP1 axis via suppression of the ERK/AKT pathway. Our findings may provide a new target for the study of pathogenesis and treatment of neuroblastoma.

Background: Clinical responses to EGFR tyrosine kinase inhibitors (TKIs) are restricted to tumors harboring specific activating mutations and even then, not all tyrosine kinase inhibitors provide clinical benefit. All TKIs however, effectively inhibit EGFR phosphorylation regardless of the mutation present. Methods: High-throughput, high-content imaging analysis, western blot, Reversed phase protein arrays, mass spectrometry and RT-qPCR. Findings: We show that the addition of TKIs results in a strong and rapid intracellular accumulation of EGFR. This accumulation mimicked clinical efficacy as it was observed only in the context of the combination of a TKI-sensitive mutation with a clinically effective (type I) TKI. Intracellular accumulation of EGFR was able to predict response to gefitinib in a panel of cell-lines with different EGFR mutations. Our assay also predicted clinical benefit to EGFR TKIs on a cohort of pulmonary adenocarcinoma patients (hazard ratio 0.21, P=0.0004 [Cox proportional hazard model]) and could predict the clinical response in patients harboring rare mutations with unknown TKI-sensitivity. All investigated TKIs, regardless of clinical efficacy, inhibited EGFR phosphorylation and downstream pathway activation, irrespective of the mutation present. Intracellular accumulation of EGFR depended on a continued presence of TKI indicating (type I) TKIs remain associated with the protein even after its dephosphorylation. Accumulation therefore is likely caused by two consecutive conformational changes, induced by both activating mutation and TKI, that combined block EGFR-membrane recycling. Interpretation: We report on an assay that mimics the discrepancy between molecular and clinical activity of EGFR-TKIs, which may allow response prediction in vitro and helps understand the mechanism of effective inhibitors.

Abstract Background Noninvasive prenatal testing (NIPT) is one of the most commonly employed clinical measures for screening of fetal aneuploidy. Fetal Fraction (ff) has been demonstrated to be one of the key factors affecting the performance of NIPT. Accurate quantification of ff plays vital role in NIPT. Methods In this study, we present a new approach, the accurate Quantification of Fetal Fraction with Shallow‐Coverage sequencing of maternal plasma DNA (FF‐QuantSC), for the estimation of ff in NIPT. The method employs neural network model and utilizes differential genomic patterns between fetal and maternal genomes to quantify ff. Results Our results show that the predicted ff by FF‐QuantSC exhibit high correlation with the Y chromosome–based method on male pregnancies, and achieves the highest accuracy compared with other ff estimation approaches. We also demonstrate that the model generates statistically similar results on both male and female pregnancies. Conclusion FF‐QuantSC achieves high accuracy in ff quantification. The method is suitable for application in both male and female pregnancies. Since the method does not require additional information upon NIPT routines, it can be easily incorporated into current NIPT settings without causing extra costs. We believe that FF‐QuantSC shall provide valuable additions to NIPT.

A novel series of dihydrofuro[3,4-d]pyrimidine (DHPY) analogs have recently been recognized as promising HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) with potent antiviral activity. To better understand the pharmacological essentiality of these DHPYs and design novel NNRTI leads, in this work, a systematic in silico study was performed on 52 DHPYs using three-dimensional quantitative structure–activity relationship (3D-QSAR), molecular docking, virtual screening, absorption-distribution-metabolism-excretion (ADME) prediction, and molecular dynamics (MD) methods. The generated 3D-QSAR models exhibited satisfactory parameters of internal validation and well-externally predictive capacity, for instance, the q2, R2, and rpred2 of the optimal comparative molecular similarity indices analysis model were 0.647, 0.970, and 0.751, respectively. The docking results indicated that residues Lys101, Tyr181, Tyr188, Trp229, and Phe227 played important roles for the DHPY binding. Nine lead compounds were obtained by the virtual screening based on the docking and pharmacophore model, and three new compounds with higher docking scores and better ADME properties were subsequently designed based on the screening and 3D-QSAR results. The MD simulation studies further demonstrated that the newly designed compounds could stably bind with the HIV-1 RT. These hit compounds were supposed to be novel potential anti-HIV-1 inhibitors, and these findings could provide significant information for designing and developing novel HIV-1 NNRTIs.

Background. Infections are an important cause of morbidity and mortality for acute lymphoblastic leukemia (ALL). However, the reports regarding risk factors of induction-related infection are roughly unknown/limited in adult T-ALL during induction chemotherapy. Methods. We performed a retrospective cohort study for the prevalence and risk predictors of induction-related infection among consecutive T-ALL patients (N=97) enrolled in a PDT-ALL-LBL clinical trial. Of 97 patients with T-ALL enrolled in the trial, 46 were early T-cell precursor (ETP) ALL and 51 were non-ETP ALL. Results. When compared with non-ETP, ETP ALL subtype was characterized with lower neutrophil count (1.35×109/L vs. 8.7×109/L, P

Proliferation of vascular smooth muscle cells (VSMCs) plays crucial roles in vascular remodelling and stiffening in hypertension. Vascular adventitial fibroblasts are a key regulator of vascular wall function and structure. This study is designed to investigate the roles of adventitial fibroblasts-derived extracellular vesicles (EVs) in VSMC proliferation and vascular remodelling in normotensive Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR), an animal model of human essential hypertension. EVs were isolated from aortic adventitial fibroblasts of WKY (WKY-EVs) and SHR (SHR-EVs). Compared with WKY-EVs, miR155-5p content was reduced, while angiotensin-converting enzyme (ACE) content was increased in SHR-EVs. WKY-EVs inhibited VSMC proliferation of SHR, which was prevented by miR155-5p inhibitor. SHR-EVs promoted VSMC proliferation of both strains, which was enhanced by miR155-5p inhibitor, but abolished by captopril or losartan. Dual luciferase reporter assay showed that ACE was a target gene of miR155-5p. MiR155-5p mimic or overexpression inhibited VSMC proliferation and ACE upregulation of SHR. WKY-EVs reduced ACE mRNA and protein expressions while SHR-EVs only increased ACE protein level in VSMCs of both strains. However, the SHR-EVs-derived from the ACE knockdown-treated adventitial fibroblasts lost the roles in promoting VSMC proliferation and ACE upregulation. Systemic miR155-5p overexpression reduced vascular ACE, angiotensin II and proliferating cell nuclear antigen levels, and attenuated hypertension and vascular remodelling in SHR. Repetitive intravenous injection of SHR-EVs increased blood pressure and vascular ACE contents, and promoted vascular remodelling in both strains, while WKY-EVs reduced vascular ACE contents and attenuated hypertension and vascular remodelling in SHR. We concluded that WKY-EVs-mediated miR155-5p transfer attenuates VSMC proliferation and vascular remodelling in SHR via suppressing ACE expression, while SHR-EVs-mediated ACE transfer promotes VSMC proliferation and vascular remodelling.

To design Fe-Cu-Sn-Ni metal binders for diamond tools and optimize the performance of binders, Fe-based binders were prepared by hot-press sintering method using Fe powder, Cu powder, Sn powder and Ni powder as the raw materials. The phase constitution, microstructure, mechanical properties and crack formation were evaluated. Results showed that Fe-based matrixes are composed of Cu _3 Sn intermetallic compounds and several solid solutions, such as α -Fe, γ (Fe,Ni), and Cu _13.7 Sn. The relative high Sn content can increase the hardness of the sintered bulk samples and significantly reduce the bending strength. With the increase of Ni content, the hardness increases gradually, while the bending strength increases firstly and then decreases. The cracks initiate from brittle Cu _3 Sn intermetallic phases and quickly propagate in the brittle phases or along the interface between Cu _3 Sn intermetallic compounds and γ (Fe,Ni) phases. The propagation of crack can be impeded by Cu _13.7 Sn solid solution.

Abstract Background This study aimed to explore the molecular mechanism of estrogen-mediated neuroprotection in the relief of cerebral ischemic injury. The gene expression profiles were downloaded from Gene Expression Omnibus database, and differentially expressed genes (DEGs) were identified using limma package in R software. Further, DEGs were subjected to Gene Ontology (GO) cluster analysis using online Gene Ontology Enrichment Analysis Software Toolkit and to GO functional enrichment analysis using DAVID software. Using the Gene Set Analysis Toolkit V2, enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways was performed. In addition, protein-protein interaction (PPI) network was constructed using STRING database, and submodule analysis of PPI network. Lastly, the significant potential target sites of microRNAs (miRNAs) were predicted using Molecular Signatures Database, and the function analysis of targets of predicted miRNA was also performed using DAVID software. Results In total, 321 DEGs were screened in the estrogen-treated sample. The DEGs were mainly associated with intracellular signaling and metabolic pathways, such as calcium channel, calcineurin complex, insulin secretion, low-density lipoprotein reconstruction, and starch or sugar metabolism. In addition, GO enrichment analysis indicated an altered expression of the genes related to starch and sucrose metabolism, retinol metabolism, anti-apoptosis (eg., BDNF and ADAM17) and response to endogenous stimulus. The constructed PPI network comprised of 243 nodes and 590 interaction pairs, and four submodules were obtained from PPI network. Among the module d, four glutamate receptors as Gria4, Gria3, Grin3a and Grik4 were highlighted. Further, 5 novel potential regulatory miRNAs were also predicted. MIR-338 and MIR520D were closely associated with cell cycle, while the targets of MIR-376A and MIR-376B were only involved in cell soma. Conclusions The DEGs in estrogen-treated samples are closely associated with calcium channel, glutamate induced excitotoxicity and anti-apoptotic activity. In addition, some functionally significant DEGs such as BDNF, ADAM17, Gria4, Gria3, Grin3a, Grik4, Gys2 and Ugtla2, and new miRNAs like MIR-338 and MIR-376A were identified, which may serve as potential therapeutic targets for the effective treatment of cerebral ischemic injury.

Abstract Background Neck circumference (NC), representing upper body subcutaneous adipose tissue, may be correlated with increased risk of overweight/obesity, obstructive sleep apnoea, and metabolic and cardiovascular disease. However, the relationship between NC and the incidence of congestive heart failure (CHF) or mortality due to coronary heart disease (CHD) in a community-based population with and without sleep-disordered breathing (SDB) has not yet been clarified. Methods We performed a prospective study using the Sleep Heart Health Study (SHHS) cohort. Cox proportional hazards regression models were used to estimate the association of different levels of NC with CHF incidence or CHD mortality in 2234 individuals with SDB and 2199 without SDB, respectively. Results After adjusting for age, sex, and body mass index (BMI), NC was significantly associated with CHF when comparing the highest NC quartile group with the lowest (hazard ratio, HR, 2.265, 95% confidence interval, CI, 1.074–4.777) in the non-SDB population. This association diminished after further adjustment for other risk factors, but remained statistically significant, with an adjusted HR of 1.082 (95% CI 1.003–1.166) per unit increase in NC. Additionally, after adjustment for age, sex, and BMI, NC was also shown to be remarkably associated with CHD mortality (HR 1.141, 95% CI 1.014–1.282) per unit increase in NC in the non-SDB population but not in the SDB population. After adjustment for all the covariates, there was a significant association between NC and CHD death in those without SDB, with an adjusted HR of 1.134 (95% CI 1.001–1.284) per unit increase in NC. Conclusions NC may correlate with CHF incidence and CHD mortality in population without SDB. NC measurement may help risk stratification for cardiovascular diseases. Trial registration NCT00005275, January 1994.

The watershed-scale distribution and loss of potentially toxic elements (PTEs) through soil erosion from slope lands to a watershed has not yet been systematically studied, especially in small mountain watersheds with high geological background PTEs in Southwest China. In this study, the spatial distribution, loss intensities and ecological risks of 12 PTEs were investigated in 101 soil samples from four types of land use in a typical watershed, Guizhou Province. Moreover, in order to avoid over- or underestimation of the contamination level in such specific geologies with significant variability in natural PTE distribution, the local background values (local BVs) were calculated by statistical methods. The dry arable land had the highest loss intensity of PTEs and was the largest contributor of PTEs (more than 80%) in the watershed, even though it covers a much smaller area compared to the forest land. The loss of Cd, As, Sb, and Hg from slope arable lands into the watershed leads to a relatively high potential ecological risk. The study suggested that both PTEs content with different types of land-uses and intensities of soil loss are of great importance for PTEs’ risk assessment in the small watershed within a high geological background region. Furthermore, in order to reduce the loss of PTEs in soil, the management of agricultural activities in arable land, especially the slope arable land, is necessary.

Iron normally exists in the form of ferrous ion (Fe2+) in primary ore deposits of valuable metals. To remove iron from hydrometallurgical leaching solution or suspension by precipitation, ferrous ion should be oxidized to ferric ion (Fe3+) first. Due to the low oxidation rate of Fe2+ by the traditional oxygen oxidation method, industry has to use more agitating barrels, steam, and compressed gas, as well as a larger workshop area, which dramatically increases the equipment investment and operation costs. In this study, a strengthened oxygen oxidation method for Fe2+ using a homemade venturi jet microbubble generator is proposed. Microbubbles of air, oxygen, or oxygen-enriched air can be formed in the leaching solution or suspension, which can greatly improve the dissolved oxygen content in the solution and increase the gas-liquid contact area, thereby accelerating the oxygen oxidation rate of Fe2+ to Fe3+ and realizing the rapid iron removal of the leaching solution or suspension. By measuring the residual concentration of Fe2+ in the solution after oxidation reaction, it was found that the pump power, solution temperature, pH, concentration of Cu2+, and solution flow rate had great effects on the oxidation performance of the produced microbubble. By analyzing the images of the microbubbles and measuring the dissolved oxygen content in the solution, it is confirmed that the accelerated oxidation reaction rate of Fe2+ using the new proposed method was mainly due to the increase of the dissolved oxygen amount in the solution. Moreover, this method can significantly increase the purification depth of iron ion, expand production capacity, and decrease energy consumption.

The economic and health significance of quinoa is steadily growing on a global scale. Nevertheless, the primary obstacle to achieving high yields in quinoa cultivation is pre-harvest sprouting (PHS), which is intricately linked to seed dormancy. However, there exists a dearth of research concerning the regulatory mechanisms governing PHS. The regulation of seed germination by various plant hormones has been extensively studied. Consequently, understanding the mechanisms underlying the role of endogenous hormones in the germination process of quinoa seeds and developing strategies to mitigate PHS in quinoa cultivation are of significant research importance. This study employed the HPLC-ESI-MS/MS internal standard and ELISA method to quantify 8 endogenous hormones. The investigation of gene expression changes before and after germination was conducted using RNA-seq analysis, leading to the discovery of 280 differentially expressed genes associated with the regulatory pathway of endogenous hormones. Additionally, a correlation analysis of 99 genes with significant differences identified 14 potential genes that may act as crucial "transportation hubs" in hormonal interactions. Through the performance of an analysis on the modifications in hormone composition and the expression of associated regulatory genes, we posit a prediction that implies the presence of a negative feedback regulatory mechanism of endogenous hormones during the germination of quinoa seeds. This mechanism is potentially influenced by the unique structure of quinoa seeds. To shed light on the involvement of endogenous hormones in the process of quinoa seed germination, we have established a regulatory network. This study aims to offer innovative perspectives on the breeding of quinoa varieties that exhibit resistance to PHS, as well as strategies for preventing PHS. [ABSTRACT FROM AUTHOR]

Insufficient removal of microplastics (MPs) and nanoplastics (NPs) may exert negative effects on the environment and human health during wastewater reclamation. The fertilizer-driven forward osmosis (FDFO) is an emerging potential technology to generate high-quality water for irrigation of hydroponic systems. In this study, the removal of MPs/NPs by the FDFO process together with their impact on FDFO membrane fouling was investigated, due to FDFO’s low molecular weight cut-off and energy requirement by using fertilizer as draw solution. Plastic particles with two different sizes (100 nm and 1 μm) and extracellular polymers released by real wastewater bacteria were utilized as model compounds for FDFO performance comparison. Results show that FDFO membrane system could generate high-quality irrigation water with only fertilizer, completely removing extracellular polymers, MPs and NPs from wastewater. It was found that the MPs and NPs themselves do not cause a significant membrane fouling. Moreover, it could help to reduce the membrane fouling caused by extracellular substances. That is probably because MPs and NPs helped to form a loose and porous fouling layer. Therefore, the FDFO process could be a long-term stable (low fouling) process for the reclamation of wastewater with high-quality requirements.

G-quadruplexes have drawn widespread attention for serving as a potential anti-cancer target and their application in material science. Molecular dynamics (MD) simulation is the key theoretical tool in the study of GQ’s structure-function relationship. In this article, we systematically benchmarked the five force fields of parmbsc0, parmbsc1, OL15, AMOEBA, and Drude2017 on the MD simulation of G-quadruplex from four aspects: structural stability, central ion channel stability, description of Hoogsteen hydrogen bond network, and description of the main chain dihedral angle. The results show that the overall performance of the Drude force field is the best. Although there may be a certain over-polarization effect, it is still the best choice for the MD simulation of G-quadruplexes.

Soil moisture (SM) plays a significant part in regional hydrological and meteorological systems throughout Earth. It is considered an indispensable state variable in earth science. The high sensitivity of microwave remote sensing to soil moisture, and its ability to function under all weather conditions at all hours of the day, has led to its wide application in SM retrieval. The aim of this study is to evaluate the ability of ALOS-2 data to estimate SM in areas with high vegetation coverage. Through the water cloud model (WCM), the article simulates the scene coupling between active microwave images and optical data. Subsequently, we use a genetic algorithm to optimize back propagation (GA-BP) neural network technology to retrieve SM. The vegetation descriptors of the WCM, derived from optical images, were the normalized difference vegetation index (NDVI), the normalized difference water index (NDWI), and the normalized multi-band drought index (NMDI). In the vegetation-covered area, 240 field soil samples were collected simultaneously with the ALOS-2 SAR overpass. Soil samples at two depths (0–10 cm, 20–30 cm) were collected at each sampling site. The backscattering of the ALOS-2 with the copolarization was found to be more sensitive to SM than the crosspolarization. In addition, the sensitivity of the soil backscattering coefficient to SM at a depth of 0–10 cm was higher than at a depth of 20–30 cm. At a 0–10 cm depth, the best results were the mean square error (MAE) of 2.248 vol%, the root mean square error (RMSE) of 3.146 vol%, and the mean absolute percentage error (MAPE) of 0.056 vol%, when the vegetation is described as by the NDVI. At a 20–30 cm depth, the best results were an MAE of 2.333 vol%, an RMSE of 2.882 vol%, a MAPE of 0.067 vol%, with the NMDI as the vegetation description. The use of the GA-BP NNs method for SM inversion presented in this paper is novel. Moreover, the results revealed that ALOS-2 data is a valuable source for SM estimation, and ALOS-2 L-band data was sensitive to SM even under vegetation cover.

We introduce a thermodynamically consistent, minimal stochastic model for complementary logic gates built with field-effect transistors. We characterize the performance of such gates with tools from information theory and study the interplay between accuracy, speed, and dissipation of computations. With a few universal building blocks, such as the not and nand gates, we are able to model arbitrary combinatorial and sequential logic circuits, which are modularized to implement computing tasks. We find generically that high accuracy can be achieved provided sufficient energy consumption and time to perform the computation. However, for low-energy computing, accuracy and speed are coupled in a way that depends on the device architecture and task. Our work bridges the gap between the engineering of low dissipation digital devices and theoretical developments in stochastic thermodynamics, and provides a platform to study design principles for low dissipation digital devices.

Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease characterized by extracellular senile plaques including amyloid-β peptides and intracellular neurofibrillary tangles consisting of abnormal Tau. Depression is one of the most common neuropsychiatric symptoms in AD, and clinical evidence demonstrates that depressive symptoms accelerate the cognitive deficit of AD patients. However, the underlying molecular mechanisms of depressive symptoms present in the process of AD remain unclear. Methods: Depressive-like behaviors and cognitive decline in hTau mice were induced by chronic restraint stress (CRS). Computational prediction and molecular experiments supported that an asparagine endopeptidase (AEP)- derived Tau fragment, Tau N368 interacts with peroxisome proliferator-activated receptor delta (PPAR-δ). Further behavioral studies investigated the role of Tau N368-PPAR-δ interaction in depressive-like behaviors and cognitive declines of AD models exposed to CRS. Results: We found that mitochondrial dysfunction was positively associated with depressive-like behaviors and cognitive deficits in hTau mice. Chronic stress increased Tau N368 and promoted the interaction of Tau N368 with PPAR-δ, repressing PPAR-δ-mediated transactivation in the hippocampus of mice. Then we predicted and identified the binding sites of PPAR-δ. Finally, inhibition of AEP, clearance of Tau N368 and pharmacological activation of PPAR-δ effectively alleviated CRS-induced depressive-like behaviors and cognitive decline in mice. Conclusion: These results demonstrate that Tau N368 in the hippocampus impairs mitochondrial function by suppressing PPAR-δ, facilitating the occurrence of depressive-like behaviors and cognitive decline. Therefore, our findings may provide new mechanistic insight in the pathophysiology of depression-like phenotype in mouse models of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Object: To investigate the efficacy and safety of tyrosine kinase inhibitors (TKIs: sorafenib and lenvatinib) plus PD-1 inhibitor (camrelizumab) versus TKIs alone in transarterial chemoembolization-refractory (TACE-refractory) hepatocellular carcinoma (HCC). Materials and methods: Data of TACE-refractory HCC patients treated with TACE+TKIs+PD-1 inhibitor (TACE+TKIs+PD-1group) (n=57) or TACE+TKIs (TACE +TKIs group) (n=50) from January 2019 to January 2022 were retrospectively collected and analyzed. The differences in overall survival (OS), progression-free survival (PFS), tumor responses (based on modified Response Evaluation Criteria in Solid Tumors) and adverse events (AEs) were compared between the two groups. Potential factors affecting OS and PFS were evaluated by univariate and multivariate analyses. Results: Compared with the TKIs group, both PFS and OS were prolonged in the TACE+TKIs+PD-1 group (median PFS: 7 months vs. 5 months, P=0.007; median OS: 17 months vs. 11 months, P=0.002). In multivariate analysis, tumor size and treatment were independent prognostic factors for PFS and OS. The incidence and severity of AEs related to the treatment between the two groups showed no significant difference. Conclusion: The treatment of TACE combined with TKIs plus camrelizumab demonstrated promising efficacy and safety in TACE-refractory HCC. [ABSTRACT FROM AUTHOR]

The intermetallic FeRh system has displayed tremendous fascination to investigators due to its remarkable physical properties and potential applications. Here we synthesized near-equiatomic FeRh films on MgO (001) substrate by magnetron co-sputtering of Fe and Rh, and our results revealed a magnetic glass (MG) state existing after field cooling to low temperature. The MG state is nonequilibrium with a configuration of metastable supercooled ferromagnetic (FM) and equilibrium antiferromagnetic (AFM) phases, and arises from a kinetic arrest of the first-order FM–AFM phase transition. Our finding is beneficial to a better understanding of the underlying mechanism of the FeRh phase transition.

This paper documents that the principal mode of Pan-Asian monsoon summer precipitation experienced a prominent interdecadal shift around 1992/1993 in terms of spatial pattern and major driving factors. During 1979‒1992 (Period 1, P1), Pan-Asian monsoon summer precipitation anomalies mainly display a meridional dipole pattern from north to south, whereas in the period 1993‒2016 (Period 2, P2), it shows a meridional tripole pattern instead. The summer precipitation in P1 is primarily associated with a combination of the developing phase (central-eastern Pacific type) and decaying phase (eastern Pacific type) of El Niño–Southern Oscillation (ENSO); while in P2, it is mainly associated with the decaying phase of central-eastern-Pacific-type ENSO.

In recent years, haze pollution events in Beijing have increased sharply, and the haze pollution of Beijing in October 2016 reached a new high. Meteorological conditions are thought to have influences on the haze occurrence, yet the associated atmospheric circulation of haze in October and why the most severe haze pollution occurred in 2016 is still unclear. Here, the authors show through daily observation and reanalysis data that key regions of North Atlantic and North Pacific sea surface temperature (SST) anomalies may be the main factors for this most severe haze event. Since 2013, the SSTs of these two key regions have increased dramatically and reached a peak, which could have induced the severe haze pollution by affecting the Eurasia teleconnection (EU) and the North Pacific Oscillation, with these factors then providing favorable dynamic and thermodynamic conditions for haze development.