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Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Introduction The COVID-19 pandemic has exacerbated suicide risk factors in Hong Kong, which faces economic shocks and strict travel restrictions due to its unique economic structure and geographical location. However, there is a scarcity of reliable empirical evidence regarding the relationship between the pandemic and suicide mortality. This study examines whether changes in the suicide rate align with COVID-19 situations and anti-COVID-19 policy events in Hong Kong, focusing on vulnerable population groups based on demographic and socioeconomic characteristics.Methods Suicide data spanning 1 January 2019 to 31 December 2022 were sourced from the Hong Kong Suicide Press Database. Case-level data were aggregated monthly by district. Population-weighted Poisson regression with district-level fixed effects was employed to analyse suicide patterns and their association with COVID-19 developments. Robustness checks and demographic-based heterogeneity analysis were conducted, distinguishing suicide risk among different population groups.Results A total of 4061 suicide cases were analysed, encompassing deaths and attempts. The first wave of the pandemic saw a 30% decline in suicide cases compared with the 2019 average, while the second and fifth waves witnessed increases of 33% and 51% in suicide rates, respectively. Older adults and individuals with lower socioeconomic status were particularly susceptible to the adverse effects, as evidenced by a significant rise in suicides during the fifth wave.Conclusions The findings underscore the importance of targeted interventions to address the mental health needs of vulnerable populations during pandemics, highlighting the impact of COVID-19 situations and antipandemic policies on the suicide rate.

Abstract Background and objective Ischemic stroke (IS) is one of the major global health problems. It is not clear whether there is a causal relationship between lactate dehydrogenase (LDH) and the risk of IS attacks. The purpose of this study was to investigate whether LDH has a causal relationship with the development of IS. Methods The genome‐wide association data of LDH and IS were obtained through a Mendelian randomization‐based platform. Single nucleotide polymorphisms (SNP) that were significantly associated with LDH were identified and used as instrumental variables, and a two‐sample Mendelian randomization study was used to examine the causal relationship between LDH and IS. The statistical methods included Inverse‐variance weighted approach, MR‐Egger regression, and weighted median estimator. Results We selected 15 SNPs of genome‐wide significance from Genome‐wide association study database with LDH as instrumental variables. A consistent causal association between LDH and IS was observed by different assessment methods. The results of the inverse‐variance weighted method suggested an inverse association between LDH and higher genetic predictability of IS risk (OR, 0.997; 95%CI 0.995–0.999). The weighted median estimate showed consistent results with the MR‐Egger method (weighted median estimate: OR, 0.995; 95%CI 0.992–0.999; MR‐Egger method: OR, 0.996; 95%CI 0.992–0.999). The inverse‐variance weighted method indicates a causal association between LDH and IS (β = −0.002563, SE = 0.00128, p = .0453). MR‐Egger analysis (β = −0.004498, SE = 0.001877, p = .03) and the weighted median method suggested that LDH and IS also existed causal relationship (β = −0.004861, SE = 0.001801, p = .00695). Conclusions Our Mendelian randomization results suggest that LDH is inversely associated with the risk of developing IS, and are contrary to the results of previous observational studies.

IntroductionPrevious observational studies have established a correlation between Graves’ disease(GD) and systemic lupus erythematosus(SLE). However, whether a causal relationship exists between these two diseases remains unknown.We utilized Mendelian randomization to infer the causal association between GD and SLE.MethodsThis study employed GWAS summary statistics of GD and SLE in individuals of Asian descent. The random effect inverse variance weighted (IVW) method was utilized to aggregate the causal effect estimates of all SNPs. Cochran’s Q values were computed to evaluate the heterogeneity among instrumental variables. Sensitivity analyses such as MR-Egger method, median weighting method, leave-one-out method, and MR-PRESSO method were used to test whether there was horizontal pleiotropy of instrumental variables.ResultsOur study found genetically predicted GD may increase risk of SLE (OR=1.17, 95% CI 0.99-1.40, p=0.069). Additionally, genetically predicted SLE elevated the risk of developing GD by 15% (OR=1.15, 95% CI 1.05-1.27, p= 0.004). After correcting for possible horizontal pleiotropy by excluding outlier SNPs, the results suggested that GD increased the risk of SLE (OR=1.27, 95% CI 1.09-1.48, p =0.018), while SLE also increased the risk of developing GD (OR=1.13, 95% CI 1.05-1.22, p =0.003).ConclusionThe findings of the study indicate that there may be a correlation between GD and SLE, with each potentially increasing the risk of the other. These results have important implications for the screening and treatment of patients with co-morbidities in clinical settings, as well as for further research into the molecular mechanisms underlying the relationship between GD and SLE.

ObjectiveAcute ischemic stroke (AIS) is characterized by high rates of morbidity, disability, mortality, and recurrence, often leaving patients with varying degrees of sequelae. Symptomatic intracranial atherosclerotic stenosis (sICAS) is a significant contributor to AIS pathogenesis and recurrence. The formation and progression of sICAS are influenced by pathways such as lipid metabolism and inflammatory response. Given its high risk of clinical recurrence, timely assessment of intracranial vascular stenosis in AIS is crucial for diagnosing sICAS, treating stroke, and preventing stroke recurrence.MethodsFourteen AIS patients were divided into stenosis and control groups based on the presence or absence of intracranial vessel stenosis. Initially, 4D Label-free proteome quantification technology was employed for mass spectrometry analysis to identify differential proteins between the groups. Subsequently, functional enrichment analysis, including GO classification, KEGG pathway, and Domain, revealed trends related to differential proteins. The STRING (v.11.5) protein interaction network database was used to identify differential protein interactions and target proteins. Finally, parallel reaction monitoring (PRM) validated the selected target proteins.ResultsMass spectrometry identified 1,096 proteins, with 991 being quantitatively comparable. Using a p-value 1.3 for significant up-regulation and

BackgroundGraves’ disease (GD) and drug eruption are closely associated and frequently observed in the clinical setting. However, it remains unclear whether a causal relationship exists between these two conditions. The aim of the study is to investigate whether GD is causal to drug eruptions using two-sample Mendelian randomization.MethodsWe launched a two-sample MR to investigate whether GD is causal to drug eruption using Genome-wide association study (GWAS) summary data from Biobank Japan and FinnGen. Genetic variants were used as instrumental variables to avoid confounding bias. Statistical methods including inverse variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO were conducted to identify the robustness of the causal effect.ResultsGenetically predicted GD may increase the risk of drug eruption by 30.3% (OR=1.303, 95% CI 1.119-1.516, p

Abstract Background and objective Epimedii has long been used as a traditional medicine in Asia for the treatment of various common diseases, including Alzheimer's disease, cancer, erectile dysfunction, and stroke. Studies have reported the ameliorative effects of Icariside II (ICS II), a major metabolite of Epimedii, on acute ischemic stroke (AIS) in animal models. Based on network pharmacology, molecular docking, and molecular dynamics (MD) simulations, we conducted a systematic review to evaluate the effects and neuroprotective mechanisms of ICS II on AIS. Methods First, we have searched 6 databases using studies with ICS II treatment on AIS animal models to explore the efficacy of ICS II on AIS in preclinical studies. The literature retrieval time ended on March 8, 2022 (Systematic Review Registration ID: CRD42022306291). There were no restrictions on the language of the search strategy. Systematic review follows the Patient, Intervention, Comparison and Outcome (PICO) methodology and framework. SYCLE's RoB tool was used to evaluate the the risk of bias. In network pharmacology, AIS-related genes were identified and the target-pathway network was constructed. Then, these targets were used in the enrichments of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO). Molecular docking and MD simulation were finally employed between ICS II and the potential target genes. Results Twelve publications were included describing outcomes of 1993 animals. The literature details, animal strains, induction models, doses administered, duration of administration, and outcome measures were extracted from the 12 included studies. ICS II has a good protective effect against AIS. Most of the studies in this systematic review had the appropriate methodological quality, but some did not clearly state the controlling for bias of potential study. Network pharmacology identified 246 targets with SRC, CTNNB1, HSP90AA1, MAPK1, and RELA as the core target proteins. Besides, 215 potential pathways of ICS II were identified, such as PI3K-Akt, MAPK, and cGMP-PKG signaling pathway. GO enrichment analysis showed that ICS II was significantly enriched in subsequent regulation such as MAPK cascade. Molecular docking and MD simulations showed that ICS II can closely bind with important targets. Conclusions ICS II is a promising drug in the treatment of AIS. However, this systematic review reveals key knowledge gaps (i.e., the protective role of ICS II in women) that ICS II must address before it can be used for the treatment of human AIS. Our study shows that ICS II plays a protective role in AIS through multi-target and multi-pathway characteristics, providing ideas for the development of drugs for the treatment of AIS.

Various offline drought indices have been widely used to project dryness/wetness and drought changes. However, the results derived from these indices often differ from or even contradict observations and direct projections made by coupled climate models. Therefore, it is crucial to investigate this scientific debate thoroughly and identify the potential causes. This study adopts a water demand-side perspective, focusing on potential evapotranspiration (PET), to address such controversy. Employing the Standardized Precipitation-Evapotranspiration Index (SPEI), three PET models including the Food and Agriculture Organization of the United Nations’ report 56 (FAO-56) Penman–Monteith (PM) model, a corrected FAO-56 PM model incorporating CO _2 physiological effect (PM _CO2 ), and a land-atmosphere coupled PET model (PET-LAC) are further compared. Despite projected increases in PET across most land areas, the PM shows the most pronounced increases among these PET models. Compared to PM _CO2 and PET-LAC, the PM model predicts the most significant drying, with the 3-month SPEI decreasing by 0.50 ± 0.23 yr ^−1 . Additionally, it projects the most substantial drought intensification, with increases in areas, intensity, and duration of 28 ± 6.9%, 0.70 ± 0.20 yr ^−1 , and 2.90 ± 0.83 month yr ^−1 , respectively. Meanwhile, these projections correspond to the most extensive area percentages, with 78.5 ± 10% for drying, 94.8 ± 7.2% for drought intensity, and 93.6 ± 7.9% for drought duration. These findings imply that the commonly used PM model overestimates future drought conditions. Differences and contradictions between the drought projections from PM-based offline indices and direct climate model outputs can be partly attributed to the omission of CO _2 physiological effect and land-atmosphere coupling constraints in the PM model. This study highlights the importance of improving PET models by incorporating these constraints, thereby providing valuable insights for enhancing the accuracy of future drought assessments.

The two-dimensional MAX phases with compositional diversity are promising functional materials for electrochemical energy storage. Herein, we report the facile preparation of the Cr2GeC MAX phase from oxides/C precursors by the molten salt electrolysis method at a moderate temperature of 700°C. The electrosynthesis mechanism has been systematically investigated, and the results show that the synthesis of the Cr2GeC MAX phase involves electro-separation and in situ alloying processes. The as-prepared Cr2GeC MAX phase with a typical layered structure shows the uniform morphology of nanoparticles. As a proof of concept, Cr2GeC nanoparticles are investigated as anode materials for lithium-ion batteries, which deliver a good capacity of 177.4 mAh g−1 at 0.2 C and excellent cycling performance. The lithium-storage mechanism of the Cr2GeC MAX phase has been discussed based on density functional theory (DFT) calculations. This study may provide important support and complement to the tailored electrosynthesis of MAX phases toward high-performance energy storage applications.

The half-bridge converter series Y-connection microgrid (HCSY-MG) is a new type of series microgrid. In order to reduce the harmonic content in HCSY-MG grid-connected current and at the same time simplify the parameter design process of the LCL filter, this study proposed an LCL filter parameter design method based on an improved particle swarm optimization-least squares support vector machine (PSO-LSSVM) by analyzing the harmonic characteristics of the HCSY-MG grid-connected current. In addition, to enhance the convergence speed of PSO-LSSVM, the inertia factor during its parameters’ update is made to adjust adaptively according to the direction of two consecutive parameter changes to constitute an improved PSO-LSSVM. Through simulation and comparative analysis, it is demonstrated that the improved PSO-LSSVM can enhance the convergence speed; the proposed filter parameter design method can effectively reduce the harmonic content in the HCSY-MG grid-connected current and is simpler and more comprehensive than the existing design method.

BackgroundPatients with head trauma may develop hydrocephalus after decompressive craniectomy. Many studies have referred one-stage cranioplasty (CP) and ventriculoperitoneal shunt (VPS) was applied to treat cranial defect with post-traumatic hydrocephalus (PTH), but the safety and efficiency of the procedure remain controversial.MethodsThis is a retrospective cohort study including 70 patients of PTH following decompressive craniectomy who underwent simultaneous (50) and separated (20) procedures of cranioplasty and VPS from March 2014 to March 2021 at the authors’ institution with at least 30 days of follow-up. Patient characteristics, clinical findings, and complications were collected and analyzed.ResultsFifty patients with PTH underwent improved simultaneous procedures and 20 patients underwent staged surgeries. Among the cases, the overall complication rate was 22.86%. Complications suffered by patients who underwent one-stage procedure of CP and VPS did not differ significantly, compared with patients in the group of staged procedures (22% vs. 25%, p = 0.763). The significant difference was not observed in the two groups, regarding the complications of subdural/epidural fluid collection (4%/6% vs. 0/2%, p = 1.000/1.000), epidural hemorrhage (6% vs. 4%, p = 0.942), dysfunction of shunting system (0 vs. 2%, p = 0.286), postoperative seizure (8% vs. 4%, p = 1.000), and reoperation case (0 vs. 2%, p = 0.286). No case of subdural hemorrhage, incision/intracranial/abdominal infection, shunting system dysfunction, or reoperation was observed in the group of simultaneous procedure. Complications including subdural/epidural fluid collection, subdural hemorrhage, and incision/intracranial infection were not shown in the case series of the staged procedure group.ConclusionThe improved simultaneous procedure of cranioplasty and VPS is effective and safe to treat cranial defect and post-traumatic hydrocephalus with low risk of complications.

In this paper, the influence of the silicon (Si) content on microstructure and impact property of submerged arc weld metals (WMs) for weathering bridge steel was clarified. Actual submerged arc welding (SAW) was carried out to produce WMs with 0.18 wt.%, 0.36 wt.%, 0.51 wt.%, and 0.60 wt.% of Si. The low temperature impact property of weld metal was detected, and the weld microstructures were characterized by optical microscopy (OM), scanning and transmission electron microscope (SEM and TEM), and electron backscatter diffraction (EBSD). The results indicate that WMs consist of polygon ferrite (PF), acicular ferrite (AF), granular bainitic ferrite (GBF), and martensite/austenite (M/A) constituents in each Si content. With increasing Si, the proportion of PF increased, while AF and GBF coarsened, the area fraction, fM/A, and the mean size, dM/A, of M/A constituents increased, the number of inclusions decreased, but the size increased. Further, the fraction of high-angle grain boundaries (HAGBs) with the misorientation tolerance angles (MTAs) greater than 15° reduced, while the mean equivalent diameter, MEDMTA≥15°, of ferrite grains with HAGBs increased. Accordingly, the impact toughness of WM was degraded from 108.1 J to 39.4 J with the increase in Si. The increase in M/A constituents and inclusions size reduced the critical fracture stress, thereby formation of larger microcracks and cleavage planes occurred. The reduced HAGBs exhibited a low hindering effect on crack propagation, and, consequently, the impact toughness decreased with increasing Si content.

The development of high-efficiency multi-wire submerged arc welding technology in bridge engineering has been limited due to the high mechanical performance standards required. In this paper, weld metal was obtained by welding at three different high heat inputs with the laboratory-developed high-efficiency submerged arc welding wire for bridges. The effect of changing different high heat inputs on the microstructure and impact toughness of high efficiency submerged arc weld metal was systematically investigated by cutting and Charpy V-notch impact tests at −40 °C, using optical microscopy, scanning electron microscopy, energy-dispersive electron spectroscopy, electron backscatter diffraction, and transmission electron microscopy to characterize and analyze. With the increase in heat input from 50 kJ/cm to 100 kJ/cm, the impact absorption energy decreased significantly from 130 J to 38 J. The number of inclusions in the weld metal significantly decreased and the size increased, which led to a significant decrease in the number of inclusions that effectively promote acicular ferrite nucleation, further leading to a decrease in the proportion of acicular ferrite in the weld metal. At the same time, the microstructure of the weld metal was significantly coarsened, the percentage of high-angle grain boundaries was decreased, and the size of martensite/austenite constituents was significantly increased monotonically. The crack initiation energy was reduced by the coarsened martensite/austenite constituents and inclusions, which produced larger local stress concentrations, and the crack propagation was easier due to the coarsened microstructure and lower critical stress for crack instability propagation. The martensite/austenite constituents and inclusions in large sizes worked together to cause premature cleavage fracture of the impact specimen, which significantly deteriorated the impact toughness. The heat input should not exceed 75 kJ/cm for high-efficiency submerged arc welding wires for bridges.

Abstract In this study we presented a composite standard chronology, spanning 1635–2018 to reconstruct May–July moisture variation in north central China. Our reconstruction revealed four severe dry epochs and five pronounced wet epochs. Additionally, spatial correlation analysis of our reconstruction with the actual self-calibrating Palmer drought severity index showed that our reconstruction was representative of large-scale May–July moisture changes. Both the severe dry and pronounced wet epochs showed one-to-one correspondence with other reconstructions nearby during their common periods, which demonstrated the reliability of our reconstruction backwards in time. Spectral analysis showed that significant spectral peaks were found at 2.1–3.8 years, which fell within the overall bandwidth of the El Niño-Southern Oscillations (ENSO). The spatial correlation patterns between our reconstruction and sea surface temperature (SST) in the equatorial eastern Pacific further confirmed the link between regional moisture and ENSO, with warm-phase ENSO resulting in low moisture and vice-versa. However, this link was time-dependent during the past four centuries, and was modulated by different phases of SST in the tropical Indian Ocean. Additionally, significant peaks at 24.9–46.5 years and spatial correlation patterns indicated that the Pacific Decadal Oscillation and the North Atlantic Oscillation may be the possible forcing factors of regional moisture at lower frequencies.

Abstract Background To compare the postoperative safety, efficacy, predictability, visual quality and biomechanics after implantation of Artisan vs. Artiflex phakic intraocular lenses (PIOLs). Methods Pubmed, Embase, Cochrane Library were conducted up from January 2000 to February 2020. Comparative clinical studies reporting in accordance with the eligibility criteria were included in this meta-analysis. The pooled weighted mean differences (WMDs) and odds ratios (ORs) with corresponding 95% confidence intervals were calculated. Results Comparative trials with myopia patients were selected in this review. The pooled WMD and OR estimates statistical significance in terms of postoperative best corrected visual acuity (BCVA), efficacy, postoperative spherical equivalence (SE), predictability, contrast sensitivity and mean intraocular higher-order aberrations (HOA) (mm) for a 6-mm pupil, manifesting that Artiflex PIOL showed evident beneficial effect for correcting myopia compared to Artisan PIOL. There was no significant difference in the incidence of complications between the two groups. Conclusion Both of two techniques were safe and effective for myopia and compared to Artisan PIOL, Artiflex PIOL had significant improvement in efficacy, predictability, contrast sensitivityand HOA, except safety and complications in the treatment of moderate to high myopia.

The traffic management system holds immense importance due to its significant impact on human living standards. With the advent of advanced technologies such as natural language processing and autonomous vehicles, this study proposes a novel cooperative traffic management system based on collection auctions at an isolated unsignalized intersection, taking into account the users’ preferences for passing the intersection while being subject to their social credits. Once vehicles enter the vehicle-to-infrastructure communication zone, drivers provide the intersection control center with their bidding information, which reflects their urgency for right-of-way. According to the traffic and biding information, the vehicles’ passing sequence is optimized by the control center, in order to maximize the drivers’ average satisfaction. To demonstrate the effectiveness of the proposed system, a series of simulation experiments were conducted under varying traffic volumes. The simulation results were then compared with several other traffic control systems from the literature. It was shown that the proposed algorithm demonstrates superior performance in terms of computational time, traffic delay, and drivers’ personal satisfaction.

The event camera, a new bio-inspired vision sensor with low latency and high temporal resolution, has brought great potential and demonstrated a promising application in machine vision and artificial intelligence. Corner detection is a key step of object motion estimation and tracking. However, most existing event-based corner detectors, such as G-eHarris and Arc*, lead to a huge number of redundant or wrong corners, and cannot strike a balance between the accuracy and real-time performance, especially in complex scenes with high texture that require higher computational costs. To address these issues, we propose an asynchronous corner detection method: a double threshold filter with Sigmoid eHarris (DTFS-eHarris) and an asynchronous corner tracker. The main contributions are that a double threshold filter is designed to reduce the redundant events and the improved Sigmoid function is utilized to represent the Surface of Active Events (Sigmoid*-SAE). We selected four scenes—shapes, dynamic, poster and boxes—from the public event camera dataset DAVIS240C to compare with the existing state-of-the-art hybrid method; our method has shown more than a 10% reduction in false positive rate and a 5% and 20% improvement in accuracy and throughput, respectively. The evaluations indicate that DTFS-eHarris shows a significant improvement, especially in complex scenes. Thus, it is anticipated to enhance the real-time performance and feature detection accuracy for future robotic applications.

AbstractAlthough many temperature time-series reconstructions, constructed on the basis of tree-ring widths, with lengths of centuries to millennia have been published for many parts of the southeastern Tibetan Plateau (SETP), field reconstruction has been unaddressed to date. Here, we present a tree-ring network comprising 53 chronologies (one δ13C chronology, one regional maximum latewood density chronology, and 51 width chronologies). Using the modified point-by-point reconstruction method, a temperature field consisting of data from 28 meteorological stations in the SETP over the past 200–500 y (the common period was from 1730 to 1998; the longest single period was from 1480 to 2002) was reconstructed. Principal component analysis and rotated principal component analysis results indicated that the reconstructed temperature field may be representative of spatial distribution characteristics. The temperature changes in the SETP were similar. The correlation coefficients between the reconstructed regional average temperature and each observed series were 0.44–0.83 (86% were greater than 0.6, and all the significance tests reported a level of 0.01). Temperature changes were mainly synchronous with those in the middle and low latitudes of the Northern Hemisphere. We then explored the influence of possible climatic forcing and found that the Indian Ocean Basin mode may be a principal factor controlling the interannual variations in the STEP summer temperatures.

BackgroundT-cell lymphoproliferative disease (T-LPD), characterized by primary Epstein–Barr virus (EBV) infection and clonal proliferation of T cells, occurs both in systemic and non-lymphatic organs. However, isolated indolent EBV-positive T-LPD involving the central nervous system has not been reported.Case PresentationA 48-year-old male who complained of headache, blurred vision, and weakness of the left lower limb for 1 month was hospitalized in our department. Neither neurological deficit nor palpable lymphadenopathy had been found. Bone marrow and laboratory tests had shown no abnormality as well. Enhanced MRI demonstrated enhanced cotton-like lesions up to 20 mm in diameter located in the right frontal, temporal, parietal and left parietal, occipital lobes with perifocal edema. Neuronavigation-assisted mini-craniotomy was performed to achieve total excision of the right temporal superficial lesion and identify the diagnosis. Pathological and EBV analysis described the lesion as indolent EBV-positive T-cell lymphoproliferative disease of the central nervous system (CNS). Then, a therapeutic regimen including whole-brain irradiation, chemotherapy, prednisolone, and aciclovir was given. Serial radiological imaging showed no signal of recurrence at 5 months' follow-up.ConclusionPrimary indolent T-LPD in the central nervous system is quite rare, and it needs to be distinguished from aggressive cerebral T-cell lymphoma, metastatic tumors, and other CNS lesions.

Abstract Background Migraine is painful disease in which neurotransmitters related to pain transmission play an important role. Hejie Zhitong prescription (HJZT) has been used in the clinic as an effective prescription for the treatment of migraine for many years. Our team aimed to further explore its antimigraine mechanism based on previous research results and to explore the inhibitory effect of HJZT on the transmission of pain related to nitroglycerine (NTG)-induced migraine as well as the synergistic effect of HJZT with pentobarbital sodium on promoting sleep. Methods Sixty mice were randomly assigned to groups and received the corresponding interventions. Sleep latency and sleep time were recorded to calculate the incidence of sleep. Forty-eight Wistar rats were randomly assigned and administered an intervention corresponding to their group. Calcitonin gene-related peptide (CGRP), serotonin (5-HT), substance P (SP), and cholecystokinin (CCK) levels were measured using ELISAs. Levels of the cannabinoid receptor type 1 (CB1R) and cyclooxygenase-2 (COX-2) protein were assessed using immunohistochemistry. The expression of the CGRP and CCK mRNAs in the midbrain and trigeminal ganglion (TG) were measured using real-time quantitative PCR. Results HJZT promoted the occurrence of sleep in mice. HJZT downregulated COX-2 expression in the midbrain and TG of rats but upregulated the expression of the CB1R, and decreased the plasma level of the CGRP protein and expression of its mRNA in the midbrain and TG. It also downregulated the expression of the CCK mRNA in the midbrain and TG. The high-dose HJZT treatment increased plasma 5-HT levels, but did not induce changes in the plasma levels of the SP or CCK protein. Conclusions HJZT exerts a synergistic effect with pentobarbital sodium on promoting sleep. As for anti-migraine, HJZT can inhibits the expression of nociceptive transmission-associated neurotransmitters, including 5-HT, CGRP and CCK, which may be related to its upregulation of CB1R and downregulation of COX-2.

Studying the variation in the boundary position of the Asian summer monsoon in the Tibetan Plateau (TP) region and its potential drivers is important for understanding the climate in this region. Three sets of mean monthly precipitation data from 1980 to 2019 were sourced from the Global Precipitation Climatology Centre, the Climate Research Unit, and China Meteorological Information Service Centre. Several indicators that represent the Asian summer monsoon boundary (ASMB) were selected to compare their applicability to the TP region and elucidate the changes in the location of the ASMB in the TP over the last four decades. The results showed that the ASMB in the TP region extends in a southwest-northeast direction, with a clear north-south variation. It reaches as far north as the Kunlun Mountains and as far south as the Himalayas. The largest amplitude in spatial fluctuation occurs in the middle of the TP, and the smallest amplitude occurs at both ends of the region. A “small-large-small” fluctuation pattern was observed from west to east. The water vapor mainly originates from the South Asian region. The South Asian summer monsoon can move the ASMB position northward, whereas the westerly wind moves the ASMB position southward. Variation in the ASMB in the TP region is closely associated with the South Asian monsoon and westerly wind.

Monitoring the properties of fluids in microfluidic chips often requires complex open-space optics technology and expensive equipment. In this work, we introduce dual-parameter optical sensors with fiber tips into the microfluidic chip. Multiple sensors were distributed in each channel of the chip, which enabled the real-time monitoring of the concentration and temperature of the microfluidics. The temperature sensitivity and glucose concentration sensitivity could reach 314 pm/°C and −0.678 dB/(g/L), respectively. The hemispherical probe hardly affected the microfluidic flow field. The integrated technology combined the optical fiber sensor with the microfluidic chip and was low cost with high performance. Therefore, we believe that the proposed microfluidic chip integrated with the optical sensor is beneficial for drug discovery, pathological research and material science investigation. The integrated technology has great application potential for micro total analysis systems (μ-TAS).

This study aims to elucidate the appropriate heat input ( E _j ) range for submerged arc welding (SAW) of high-performance weathering steel. Generally, by increasing E _j , the welding efficiency can be improved, but the toughness of the weld metal may be deteriorated. Therefore, SAW was employed to produce the weld microstructure under varying E _j from 20 to 50 kJ cm ^−1 . The Charpy V-notch impact tests were conducted at −40 °C, and the weld microstructures were characterized by optical microscopy (OM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and electron backscatter diffraction (EBSD). The results indicate that the weld microstructures consist of polygonal ferrite (PF), acicular ferrite (AF), granular bainitic ferrite (GBF), and martensite/austenite (M/A) constituents under each E _j . With the increase in E _j , the proportion of PF increases, while AF and GBF are coarsened, and the area fraction ( f _M/A ) and mean size (d _M/A ) of M/A constituents increase monotonically. Further, the fraction ( f _MTA>15° ) of high-angle grain boundaries (HAGBs) with the misorientation tolerance angles (MTAs) greater than 15° is reduced, while the mean equivalent diameter (MED _MTA≥15° ) of ferrite grains with HAGBs increases. Accordingly, with the increase in E _j , the impact toughness of weld degrades from 128.4 to 47.6 J. The higher degree of micro-strain concentration caused by the increase in M/A size and area leads to the formation of larger microcracks under small plastic deformation, while the reduced HAGBs have a lower inhibition effect on crack propagation. Finally, the impact toughness decreases with the increase of E _j . Overall, the findings suggest that the E _j of SAW should not exceed 40 kJ cm ^−1 in the construction of high-performance weathering steel.

One of the most serious and worsening problems in much of the world is traffic congestion, which represents an undoubted menace to the quality of urban life, including wasting of time, and environmental pollution. Therefore, this study proposes a new dynamic cooperative traffic control algorithm based on Vehicle-to-Infrastructure connections to solve this problem. The proposed model contains three parts. First of all, when each vehicle enters the communication zone, it sends its estimated range of arrival time to the control center in the intersection; then the optimal passing sequence is calculated in the control center by dynamically grouping the compatible trajectories with the respect of the related safety constraints; finally, each vehicle optimizes its appropriate speed profile based on the given optimal time and speed to enter the intersection, which is sent by the control center. Several simulation cases are executed for different traffic volumes, whose results prove that vehicles under the proposed algorithm can pass the intersection with less travel time compared with traditional traffic control methods and other algorithms. Therefore, the proposed method can reduce the time delay and improve traffic efficiency.

In the context of global warming, meteorological disasters occur more frequently in various regions which exert increasing influences on human life. Snow disasters are some of the natural disasters that most seriously affect the development of husbandry on the Qinghai–Tibetan Plateau (QTP), so it is necessary to explore their spatio-temporal variations and perform comprehensive risk assessment. Based on the daily snow depth data set in China, obtained by inversion of satellite remote sensing data, the spatio-temporal variation characteristics of snow disasters on the QTP from 1980 to 2019 were studied. The regional difference in the comprehensive risks of snow disasters for the husbandry on the QTP was evaluated from four perspectives, i.e., the risk of hazard factors, sensitivity of hazard-inducing environments, vulnerability of hazard-affected bodies, and disaster prevention and mitigation capacity. The farmer and pastoralist well-being (FPWB) index in five typical regions was constructed to discuss the possible influences of snow disasters on the FPWB since the 21st century. Results show that, in the last 40 years, the frequency, duration, average snow depth, and grade of snow disasters on the QTP all exhibited significant interannual and interdecadal variabilities, and they also displayed a declining long-term trend. The comprehensive risk of snow disasters for the husbandry on the QTP is low in the north while high in the south. The high-risk zone accounts for 1.54% of the total and is mainly located in Kashgar City in the north-western end of the QTP; the sub-high-risk and medium-risk zones are mainly found in the south of the plateau and are distributed in a tripole pattern, separately covering 15.96% and 16.32% of the total area of the plateau; the north of the plateau mainly belongs to low-risk and sub-low-risk zones, which separately account for 43.06% and 23.12% of the total area of the plateau. Since the beginning of the 21st century, the FPWB in five typical regions, namely, Kashgar (I), Shigatse (II), Nagqu (III), Qamdo (IV), and Yushu (V), has been increasing, while the risk of snow disasters has gradually decreased. Every 1% decrease in the risk of snow disasters corresponded to 0.186%, 0.768%, 0.378%, 0.109%, and 0.03% increases in the FPWB index in the five regions. Snow disasters affect FPWB mainly by directly or indirectly damaging material resources (livestock inventories and meat production) and social and financial resources.

Due to the lack of long-term climate records, our understanding of paleoclimatic variability in the Tibetan Plateau (TP) is still limited. In this study, we developed a tree-ring width (TRW) chronology based on tree-ring cores collected from our study site, southeastern TP. This chronology responded well to the mean maximum temperatures of May–June and was thus used to reconstruct early summer (May–June) maximum temperature during the period 1541–2019. The reconstruction explained 33.6% of the climatic variance during the calibration period 1962–2019. There were 34 extremely warm years (7.2% of total years) and 36 extremely cold years (7.5% of total years) during the reconstruction period. The spatial correlation analysis and the comparison with other local temperature reconstructions confirmed the reliability and representativeness of our reconstruction. The results of the ensemble empirical mode decomposition (EEMD) analysis indicated quasi-oscillations of 2.9–4.2 years, 4.5–8.3 years, 11.1–15.4 years, 20–33.3 years, 50.4 years, 159.7 years, and 250 years in this temperature reconstruction which may be associated with ENSO cycles, solar activity, and PDO.

A full analysis of 3-month Standardized Precipitation-Evapotranspiration index (SPEI-3) changes and attribution analyses are of significance for deeply understanding dryness/wetness evolutions and thus formulating specific measures to sustain regional development. In this study, we analyze monthly and annual SPEI-3 changes over Southwest China (SWC; including Sichuan (SC), Chongqing (CQ), Guizhou (GZ), Yunnan (YN), and west Guangxi (wGX)) during 1961–2012, using the SPEI model and routine meteorological measurements at 269 weather sites. For SWC and each subregion (excluding wGX), annual SPEI-3 during 1961–2012 tends to decrease, and drying is at most of months in January and September–December, but wetting is in February–August (excluding March for wGX). Additionally, more than 50% of sites show declined and increased SPEI-3 in January, April, June, and August–December and the remaining months, respectively. Except for wGX with dominant of ET0, annual SPEI-3 changes in SWC and other four subregions have dominant of precipitation. Spatially, annual SPEI-3 changes at 59% of sites are because of precipitation, generally located in southeast SC, south YN, CQ, GZ, and south and northeast wGX. Nevertheless, dominants at regional and site scales vary among months, e.g., SWC, SC, CQ, and GZ, having dominant of precipitation (ET0) during September–December (most of months during January–August), YN always with dominant of precipitation, and wGX with dominant of precipitation (ET0) in February–April and July–December (January, May, and June). Importantly, this study provides a reference for quantitatively evaluating spatiotemporal dryness/wetness variations with climate change, especially for regions with significant drying/wetting.

Phosphodiesterase 2 (PDE2) has been regarded as a novel target for the treatment of Alzheimer’s disease (AD). In this study, we obtained (R)-LZ77 as a hit compound with moderate PDE2 inhibitory activity (IC50 = 261.3 nM) using a high-throughput virtual screening method based on molecular dynamics. Then, we designed and synthesized 28 dihydropyranopyrazole derivatives as PDE2 inhibitors. Among them, compound (+)-11h was the most potent PDE2 inhibitor, with an IC50 value of 41.5 nM. The molecular docking of PDE2-(+)-11h reveals that the 4-(trifluoromethyl)benzyl)oxyl side chain of the compound enters the H-pocket and forms strong hydrophobic interactions with L770/L809/F862, which improves inhibitory activity. The above results may provide insight for further structural optimization of highly potent PDE2 inhibitors and may lay the foundation for their use in the treatment of AD.

Hong Kong is an area of complex topography, with mixtures of urban and greenbelt spaces. Local bioaerosol concentrations are multifaceted, depending on seasonal variations of meteorological conditions and emission sources. This study is the first known attempt at both quantitatively measuring and identifying airborne bioaerosol contributions, by utilising multiple single particle ultraviolet light-induced fluorescence spectrometers. Based in the Hong Kong University of Science and Technology’s super-site, a WIBS-NEO and PLAIR Rapid-E were operated from June to November, 2018. The purpose of this long-term campaign was to observe the shift in wind patterns and meteorological conditions as the seasons changed, and to investigate how, or if, this impacted on the dispersion and concentrations of bioaerosols in the area. Bioaerosol concentrations based on the particle auto-fluorescence spectra remained low through the summer and autumn months, averaging 4.2 L−1 between June and October. Concentrations were greatest in October, peaking up to 23 L−1. We argued that these concentrations were dominated by dry-weather fungal spores, as evidenced by their spectral profile and relationship with meteorological variables. We discuss potential bioaerosol source regions based on wind-sector cluster analysis and believe that this study paints a picture of bioaerosol emissions in an important region of the world.

The problem of reducing traffic delays and decreasing fuel consumption simultaneously in a network of intersections without traffic lights is solved by a cooperative traffic control algorithm, where the cooperation is executed based on the connection of Vehicle-to-Infrastructure (V2I). This resolution of the problem contains two main steps. The first step concerns the itinerary of which intersections are chosen by vehicles to arrive at their destination from their starting point. Based on the principle of minimal travel distance, each vehicle chooses its itinerary dynamically based on the traffic loads in the adjacent intersections. The second step is related to the following proposed cooperative procedures to allow vehicles to pass through each intersection rapidly and economically: on one hand, according to the real-time information sent by vehicles via V2I in the edge of the communication zone, each intersection applies Dynamic Programming (DP) to cooperatively optimize the vehicle passing sequence with minimal traffic delays so that the vehicles may rapidly pass the intersection under the relevant safety constraints; on the other hand, after receiving this sequence, each vehicle finds the optimal speed profiles with the minimal fuel consumption by an exhaustive search. The simulation results reveal that the proposed algorithm can significantly reduce both travel delays and fuel consumption compared with other papers under different traffic volumes.