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Vegetation greening has long been acknowledged, but recent studies have pointed out that vegetation greening is possibly stalled or even reversed. However, detailed analyses about greening reversal or increased browning of vegetation remain scarce. In this study, we utilized the normalized difference vegetation index (NDVI) as an indicator of vegetation to investigate the trends of vegetation greening and browning (monotonic, interruption, and reversal) through the breaks for the additive season and trend (BFAST) method across China’s drylands from 1982 to 2022. It also reveals the impacts of ecological restoration programs (ERPs) and climate change on these vegetation trends. We find that the vegetation displays an obvious pattern of east-greening and west-browning in China’s drylands. Greening trends mainly exhibits monotonic greening (29.8 %) and greening with setback (36.8 %), whereas browning shows a greening to browning reversal (19.2 %). The increase rate of greening to browning reversal is 0.0342/yr, which is apparently greater than that of greening with setback, 0.0078/yr. This research highlights that, under the background of widespread vegetation greening, vegetation browning is progressively increasing due to the effects of climate change. Furthermore, the ERPs have significantly increased vegetation coverage, with the increase rate in 2000–2022 being twice as much as that of 1982–1999 in revegetation regions. Vegetation browning in southwestern Qingzang Plateau is primarily driven by adverse climatic factors and anthropogenic disturbances, which offset the efforts of ERPs.

Traditionally, virtual inertia is used as the control strategy for wind turbines when participating in frequency regulation. However, it has inherent defects in measurement error amplification due to the frequency differential. Also, when control delay of wind turbines is taken into consideration, virtual inertia is essentially a fast power response, just the same as droop control. Hence, considering the adaptability of droop control, it is valuable to explore a novel droop control method without virtual inertia, as the frequency response model of wind turbines. For this reason, a multi-segment droop control strategy is proposed to provide a reliable frequency regulation model for wind turbines that can be broadly applied to other inverter-based power sources. Firstly, based on the extended system frequency response model, a differential equation including piecewise time-varying coefficients is established, and the analytical expression of the frequency response is obtained using the impulse function balancing principle and the integration by parts algorithm. Subsequently, based on analytical expression, the performance of the presented strategy is theoretically analyzed via comparison with virtual inertia control, and the conclusion that the presented multi-segment droop control has better frequency regulation performance can be got. Furthermore, to achieve optimal frequency regulation performance, a Lagrangian function is established to determine the optimal parameters of the proposed control strategy. Finally, the performance of the proposed strategy was verified in a two-area system model constructed on MATLAB/Simulink. Results show that the proposed multi-segment droop control has better frequency regulation performance.

Summary: Sunitinib, a primary treatment for clear cell renal cell carcinoma (ccRCC), frequently encounters the challenge of resistance development. Metabolic reprogramming, a characteristic change in ccRCC, is likely linked to this resistance. Our research revealed a notable decrease in the expression of the key metabolic gene ABAT in ccRCC, which contributed to diminished sensitivity to sunitinib. Downregulation of ABAT led to an increase in the intracellular level of gamma-aminobutyric acid (GABA), triggering abnormal activation of the G-protein-coupled receptor GABA-B. This activation resulted in increased transactivation of the tyrosine kinase receptors SYK and LYN, thereby reducing the antitumor and antiangiogenic properties of sunitinib. However, the application of SYK and LYN inhibitors successfully inhibited this effect. The transactivation of SYK and LYN caused resistance to the antiangiogenic effects of sunitinib through the upregulation of PGF protein levels. Furthermore, the combined application of an LYN inhibitor with sunitinib has been shown to enhance therapeutic efficacy.

Epidemiological evidence indicates an association between exposure to toxic metals and the occurrence of cardiometabolic diseases (CMDs). However, the impact of exposure to harmful metallic elements, such as lead (Pb), cadmium (Cd), and mercury (Hg), on mortality in individuals with cardiometabolic multimorbidity (CMM) remains uncertain. Therefore, in this study, we analyzed data from 4139 adults diagnosed with CMM from the National Health and Nutrition Examination Survey 1999–2016. CMM was defined as the presence of at least two CMDs (hypertension, diabetes, stroke, and coronary artery disease). Over an average follow-up period of 9.0 years, 1379 deaths from all causes, 515 deaths related to cardiovascular disease (CVD), and 215 deaths attributable to cancer were recorded. After adjusting for potential covariates, serum Pb concentrations were not associated with all-cause, CVD, or cancer mortality. Participants exposed to Cd had an elevated risk of all-cause mortality (hazard ratio [HR], 1.23; 95 % CI, 1.16–1.30), CVD-related mortality (HR, 1.23; 95 % CI, 1.12–1.35), and cancer-related mortality (HR, 1.29; 95 % CI, 1.13–1.47). Participants with serum Hg levels in the highest quantile had lower risks of all-cause (HR, 0.64; 95 % CI, 0.52–0.80) and CVD-related (HR, 0.62; 95 % CI, 0.44–0.88) mortality than did those in the lowest quantile. Stratified analyses revealed significant interactions between serum Cd concentrations and age for CVD-related mortality (P for interaction =0.011), indicating that CMM participants aged < 60 years who were exposed to Cd were at a greater risk of CVD-related mortality. A nonlinear relationship was observed between serum Cd concentrations and all-cause (P for nonlinear relationship = 0.012) and CVD-related (P for nonlinear relationship < 0.001) mortality. Minimizing Cd exposure in patients with CMM may help prevent premature death.

Background: The tissue response viewer (TRV) is a multiparametric index that incorporates time, power, tissue pressure, impedance, and wall thickness data during radiofrequency catheter ablation (RFCA) and is used to predict the transmurality of lesions. This study aimed to evaluate the feasibility and accuracy of the TRV in a porcine model. Methods: Twelve pigs underwent preablation high-density voltage and activation mapping of two atria, and both were repeated after linear RFCA. Intentional gaps were kept in the left atrium (LA) and were touched up in the right atrium (RA). Standard and high powers were, respectively, performed in the LA ablation. Six pigs were immediately sacrificed for pathological examination after the mapping and ablation procedure (acute study). Another six pigs were kept for 4 weeks before remapping and pathological examination (chronic study). Results: All animals completed the planned procedure. The TRV function showed a sensitivity of 97.1% and a specificity of 76.9% in the acute study, and a sensitivity of 95.9% and a specificity of 72.5% in the chronic study to predict the transmural lesion. All positive and negative predictive values were over 80%. In addition, the TRV achieved higher sensitivity (92.3% vs. 85.0%) and specificity (88.2% vs. 78.9%) to predict the transmural lesion in LA ablation with high power compared with standard ablation. Conclusions: This study presents the histopathological validation of TRV to predict transmural lesions. The use of TRV may guide a more individual ablation and a more precise touch-up of gaps for atrial arrhythmias.

Background: The vein of Marshall (VOM) ethanol infusion improves rhythm control in atrial fibrillation (AF). The identification and cannulation of the VOM can be technically challenging. This study aimed to assess the angiographic morphology of the VOM and investigate its value in the VOM ethanol infusion. Methods: Patients with AF (n = 162) scheduled for combined catheter ablation and VOM ethanol infusion were enrolled. The VOM morphologic features in the right anterior oblique (RAO), the left anterior oblique (LAO), and the LAO cranial views were analyzed. The impact of morphology on the identification and cannulation of the VOM was investigated. Results: The VOM was identified in 159 (98.1 %) and cannulated in 150 (92.6 %) patients. The VOM identification rate in the RAO and LAO/LAO cranial view was 97.3 % and 89.3 %, respectively. Of 134 patients with VOM identification in the LAO/LAO cranial view, 104 (77.6 %) had a VOM ostium clock location (VOMoClock) of ≤3 and 3–4 o'clock. The VOM cannulation success rate in the ≤3, 3–4, 4–5, and 5–6 o'clock groups was 100 %, 92.6 %, 88.5 %, and 77.8 %, respectively (p = 0.032). The median (interquartile range) cannulation time in the four groups was 10.5 (6.3), 12.0 (9.0), 13.0 (23.0), and 34.0 (30.0) minutes, respectively (p

Superhydrophobic coatings are gaining importance not only in military technology, industrial engineering, power systems and transportation, but also in food science and biomedicine, where they have enormous potential for real-time applications. Many research institutes have recently been working on the development of superhydrophobic blood-repellent tubes to replace clinical heparin-coated tubes during ECMO therapy, but biological toxicity and high blood adhesion have significantly hampered their practical applications. In this study, we created a cardiopulmonary bypass tube with good superhydrophobicity and blood repellency. In terms of biotoxicity, coagulation time, protein and platelet adsorption, the results show that the superhydrophobic-treated tube clotted in 36 min, compared to 21 min for a clinical Bioline heparin-coated tube and 14 min for bare PVC tube. When compared to the bare PVC tube, the clotting time of the superhydrophobic-treated tube was increased by 157% due to the Cassie-Baxter wetting state of the resulting superhydrophobic blood-repellent coating. Meanwhile, the protein and platelet adsorption on the superhydrophobic-treated tube were decreased by 32% and 74%, respectively. It should be noted that we were the first to explain the superhydrophobic anti-platelet adsorption mechanism from the perspective of inhibiting thromboxane-A2 secretion during blood coagulation. Clarification of platelet activation process and activating substances is vital for understanding the anticoagulant properties of superhydrophobic coatings. On the other hand, non-inflammatory response of the organism was confirmed in the vivo experiments and the cell viability after a 48-hour cytotoxicity assay was about 101%, indicating that the superhydrophobic-treated tubes are non-toxic.

Ampelopsis grossedentata is a flavonoid-rich healthy tea, traditionally used as a Chinese herbal medicine, that effectively treats T2DM. In the present study, we investigated the anti-diabetic effect of total flavonoids extracted from Ampelopsis grossedentata (AGT) and the underlying mechanisms using 16S rDNA sequencing and metabolomics. The results indicated that after AGT treatment for 6 weeks, the body weight, liver index, fasting blood glucose (FBG), OGTT-AUC, and serum lipid levels were reduced, and pathological injuries of the liver improved significantly in ZDF rats. Meanwhile, AGT increased the abundance and diversity of gut microbiota, especially BSH-active bacteria, which reduced T-β-MCA and T-α-MCA levels and further activate FXR and FGF15. The activation of FXR-FGF15 axis inhibited excessive bile acid accumulation and liver gluconeogenesis upon AGT treatment. Taken together, our results suggested that AGT ameliorated glycolipid metabolism disorder via the “microbiota-gut-liver” axis, indicating that AGT may be a potential therapeutic strategy for treating T2DM.

Vegetation productivity is controlled by multiple climatic variables such as temperature, precipitation, and radiation, while the driving mechanism remains unclear in Inner Mongolia grasslands. Since climatic factors change geographically and seasonally, we need to know their spatiotemporal patterns and how they impact plant growth. Here, we investigated vegetation responses to climatic changes by analyzing both climatic data and NDVI (Normalized Difference Vegetation Index) for 34 years (1982 to 2015). Our results indicate that water availability dominated the variability of vegetation productivity, regardless of grassland types. The vegetation productivity was more sensitive to variations in water conditions than to variations in temperature, especially in the northern region. The results are of great significance for formulating adaptation and mitigation strategies against climate impacts on grassland productivity in Inner Mongolia and provide an invaluable comparison for grassland studies in other regions.

The paucity of medications with novel mechanisms for pain treatment combined with the severe adverse effects of opioid analgesics has led to an imperative pursuit of non-opioid analgesia and a better understanding of pain mechanisms. Here, we identify the putative glutamatergic inputs from the paraventricular thalamic nucleus to the nucleus accumbens (PVTGlut→NAc) as a novel neural circuit for pain sensation and non-opioid analgesia. Our in vivo fiber photometry and in vitro electrophysiology experiments found that PVTGlut→NAc neuronal activity increased in response to acute thermal/mechanical stimuli and persistent inflammatory pain. Direct optogenetic activation of these neurons in the PVT or their terminals in the NAc induced pain-like behaviors. Conversely, inhibition of PVTGlut→NAc neurons or their NAc terminals exhibited a potent analgesic effect in both naïve and pathological pain mice, which could not be prevented by pretreatment of naloxone, an opioid receptor antagonist. Anterograde trans-synaptic optogenetic experiments consistently demonstrated that the PVTGlut→NAc circuit bi-directionally modulates pain behaviors. Furthermore, circuit-specific molecular profiling and pharmacological studies revealed dopamine receptor 3 as a candidate target for pain modulation and non-opioid analgesic development. Taken together, these findings provide a previously unknown neural circuit for pain sensation and non-opioid analgesia and a valuable molecular target for developing future safer medication.

Functional MRI (fMRI) data may be contaminated by artifacts arising from a myriad of sources, including subject head motion, respiration, heartbeat, scanner drift, and thermal noise. These artifacts cause deviations from common distributional assumptions, introduce spatial and temporal outliers, and reduce the signal-to-noise ratio of the data—all of which can have negative consequences for the accuracy and power of downstream statistical analysis. Scrubbing is a technique for excluding fMRI volumes thought to be contaminated by artifacts and generally comes in two flavors. Motion scrubbing based on subject head motion-derived measures is popular but suffers from a number of drawbacks, among them the need to choose a threshold, a lack of generalizability to multiband acquisitions, and high rates of censoring of individual volumes and entire subjects. Alternatively, data-driven scrubbing methods like DVARS are based on observed noise in the processed fMRI timeseries and may avoid some of these issues. Here we propose “projection scrubbing”, a novel data-driven scrubbing method based on a statistical outlier detection framework and strategic dimension reduction, including independent component analysis (ICA), to isolate artifactual variation. We undertake a comprehensive comparison of motion scrubbing with data-driven projection scrubbing and DVARS. We argue that an appropriate metric for the success of scrubbing is maximal data retention subject to reasonable performance on typical benchmarks such as the validity, reliability, and identifiability of functional connectivity. We find that stringent motion scrubbing yields worsened validity, worsened reliability, and produced small improvements to fingerprinting. Meanwhile, data-driven scrubbing methods tend to yield greater improvements to fingerprinting while not generally worsening validity or reliability. Importantly, however, data-driven scrubbing excludes a fraction of the number of volumes or entire sessions compared to motion scrubbing. The ability of data-driven fMRI scrubbing to improve data retention without negatively impacting the quality of downstream analysis has major implications for sample sizes in population neuroscience research.

The foundation for the environmental department to take suitable measures and make a significant contribution towards improving air quality is the precise and dependable prediction of PM2.5 concentration. It is essential to review the development process and hotspots of PM2.5 concentration prediction studies over the past 20 years (2000–2021) comprehensively and quantitatively. This study used detailed bibliometric methods and CiteSpace software to visually analyze the PM2.5 pollution level. The outcomes found that the prediction research phases of PM2.5 can be broadly divided into three phases and enter the rapid growth phase after 2017. Five categories of keywords are clustered, and the forecasting data and forecasting methods are typical cluster representatives. Then, the construction and processing of PM2.5 concentration prediction datasets, the prediction methods and technical processes, and the determination of the prediction spatial-temporal scales are the main content of the analysis. In the future, it is necessary to concentrate on multi-source data fusion for PM2.5 concentration prediction at multiple spatial-temporal scales and focus on technology integration and innovative applications in forecasting models, especially the optimal use of deep machine learning methods to improve prediction accuracy and practical application conversion.

The distribution of antibiotic resistance genes (ARGs) in water sources potentially threatens drinking water safety. However, the sources of antibiotic resistome in groundwater are still under-investigated. Here, we evaluated the profiles of antibiotic resistome in peri-urban groundwater and its associated water sources (river and mountain spring) to characterize the antibiotic resistome from natural water sources on groundwater resistome. A total of 261 antibiotic resistome were detected in groundwater, mountain spring, and river samples. The relative abundances of ARGs and mobile genetic elements (MGEs) were significantly higher in the river samples than in spring water and groundwater samples. The resistome profiles were similar between groundwater and spring water but differed from the river samples. According to source tracking results, the groundwater resistome was likely to be derived from springs (28.0%−50.0%) and rivers (28.6%−48.6%), which share the same trend for the source tracking of bacterial communities. Bacterial α-diversity, bacterial β-diversity, and MGEs directly or indirectly affected the ARGs in groundwater samples. Although the abundance of groundwater resistome was not elevated by river and spring water, groundwater resistomes were diverse and may be derived from both river and spring water. We highlight the importance of groundwater resistome and its association with potential water sources, providing a better understanding and basis for the effective control of the ARG proliferation and dissemination in groundwater from exogenous water bodies in the future.

Objective: Oxidative stress contributes to the development of insulin resistance (IR) and atherosclerosis. Peroxidation of lipids produces reactive dicarbonyls such as Isolevuglandins (IsoLG) and malondialdehyde (MDA) that covalently bind plasma/cellular proteins, phospholipids, and DNA leading to altered function and toxicity. We examined whether scavenging reactive dicarbonyls with 5′-O-pentyl-pyridoxamine (PPM) protects against the development of IR and atherosclerosis in Ldlr−/− mice. Methods: Male or female Ldlr−/− mice were fed a western diet (WD) for 16 weeks and treated with PPM versus vehicle alone. Plaque extent, dicarbonyl-lysyl adducts, efferocytosis, apoptosis, macrophage inflammation, and necrotic area were measured. Plasma MDA-LDL adducts and the in vivo and in vitro effects of PPM on the ability of HDL to reduce macrophage cholesterol were measured. Blood Ly6Chi monocytes and ex vivo 5-ethynyl-2′-deoxyuridine (EdU) incorporation into bone marrow CD11b+ monocytes and CD34+ hematopoietic stem and progenitor cells (HSPC) were also examined. IR was examined by measuring fasting glucose/insulin levels and tolerance to insulin/glucose challenge. Results: PPM reduced the proximal aortic atherosclerosis by 48% and by 46% in female and male Ldlr−/− mice, respectively. PPM also decreased IR and hepatic fat and inflammation in male Ldlr−/− mice. Importantly, PPM decreased plasma MDA-LDL adducts and prevented the accumulation of plaque MDA- and IsoLG-lysyl adducts in Ldlr−/− mice. In addition, PPM increased the net cholesterol efflux capacity of HDL from Ldlr−/− mice and prevented both the in vitro impairment of HDL net cholesterol efflux capacity and apoAI crosslinking by MPO generated hypochlorous acid. Moreover, PPM decreased features of plaque instability including decreased proinflammatory M1-like macrophages, IL-1β expression, myeloperoxidase, apoptosis, and necrotic core. In contrast, PPM increased M2-like macrophages, Tregs, fibrous cap thickness, and efferocytosis. Furthermore, PPM reduced inflammatory monocytosis as evidenced by decreased blood Ly6Chi monocytes and proliferation of bone marrow monocytes and HSPC from Ldlr−/− mice. Conclusions: PPM has pleotropic atheroprotective effects in a murine model of familial hypercholesterolemia, supporting the therapeutic potential of reactive dicarbonyl scavenging in the treatment of IR and atherosclerotic cardiovascular disease.

Osteosarcoma is a highly aggressive cancer common in children and adolescents. There is still a lack of effective treatments for metastatic or recurrent osteosarcoma. The role of long non-coding RNAs (lncRNAs) in osteosarcoma has gradually attracted attention. Here, we identified lncRNAs that were abnormally expressed in metastatic osteosarcoma through analyzing the sequencing data of osteosarcoma tissues and selected upregulated lncRNA MELTF-AS1 for detailed study. The qRT-PCR analysis showed that the expression of MELTF-AS1 was increased in osteosarcoma tissues and cells, and the high expression of MELTF-AS1 indicated a poor prognosis of osteosarcoma patients. The high expression of MELTF-AS1 in osteosarcoma was partly due to the transcriptional activation of RREB1. The results of transwell assays, scratch wound healing assays, and the tail vein injection lung metastasis model demonstrated that knocking down MELTF-AS1 inhibited metastasis ability of osteosarcoma cells. Furthermore, the results of RNA pull-down assays, luciferase reporter assays, and RNA immunoprecipitation (RIP) assays revealed that MELTF-AS1 could regulate MMP14 expression through interaction with miR-485-5p. Our study suggested that MELTF-AS1 functioned as a pro-metastasis gene in osteosarcoma by upregulating MMP14 and that it could be a potential therapeutic and diagnostic target for osteosarcoma.

Brain-wide patterns in resting human brains, as either structured functional connectivity (FC) or recurring brain states, have been widely studied in the neuroimaging literature. In particular, resting-state FCs estimated over windowed timeframe neuroimaging data from sub-minutes to minutes using correlation or blind source separation techniques have reported many brain-wide patterns of significant behavioral and disease correlates. The present pilot study utilized a novel whole-head cap-based high-density diffuse optical tomography (DOT) technology, together with data-driven analysis methods, to investigate recurring transient brain-wide patterns in spontaneous fluctuations of hemodynamic signals at the resolution of single timeframes from thirteen healthy adults in resting conditions. Our results report that a small number, i.e., six, of brain-wide coactivation patterns (CAPs) describe major spatiotemporal dynamics of spontaneous hemodynamic signals recorded by DOT. These CAPs represent recurring brain states, showing spatial topographies of hemispheric symmetry, and exhibit highly anticorrelated pairs. Moreover, a structured transition pattern among the six brain states is identified, where two CAPs with anterior-posterior spatial patterns are significantly involved in transitions among all brain states. Our results further elucidate two brain states of global positive and negative patterns, indicating transient neuronal coactivations and co-deactivations, respectively, over the entire cortex. We demonstrate that these two brain states are responsible for the generation of a subset of peaks and troughs in global signals (GS), supporting the recent reports on neuronal relevance of hemodynamic GS. Collectively, our results suggest that transient neuronal events (i.e., CAPs), global brain activity, and brain-wide structured transitions co-exist in humans and these phenomena are closely related, which extend the observations of similar neuronal events recently reported in animal hemodynamic data. Future studies on the quantitative relationship among these transient events and their relationships to windowed FCs along with larger sample size are needed to understand their changes with behaviors and diseased conditions.

Spontaneous neural activity in human as assessed with resting-state functional magnetic resonance imaging (fMRI) exhibits brain-wide coordinated patterns in the frequency of

Recent studies have emphasized the changes in large-scale brain networks related to healthy aging, with the ultimate purpose to aid in differentiating normal neurocognitive aging from neurodegenerative disorders that also arise with age. Emerging evidence from functional Magnetic Resonance Imaging (fMRI) indicates that connectivity patterns within specific brain networks, especially the Default Mode Network (DMN), distinguish those with Alzheimer's disease from healthy individuals. In addition, disruptive alterations in the large-scale brain systems that support high-level cognition are shown to accompany cognitive decline at the behavioral level, which is commonly observed in the aging populations, even in the absence of disease. Although fMRI is useful for assessing functional changes in brain networks, its high costs and limited accessibility discourage studies that need large populations. In this study, we investigated the aging-effect on large-scale networks of the human brain using high-density electroencephalography and electrophysiological source imaging, which is a less costly and more accessible alternative to fMRI. In particular, our study examined a group of healthy subjects in the age range from middle- to older-aged adults, which is an under-studied range in the literature. Employing a high-resolution computation model, our results revealed age associations in the connectivity pattern of DMN in a consistent manner with previous fMRI findings. Particularly, in combination with a standard battery of cognitive tests, our data showed that in the posterior cingulate / precuneus area of DMN higher brain connectivity was associated with lower performance on an episodic memory task. The findings demonstrate the feasibility of using electrophysiological imaging to characterize large-scale brain networks and suggest that changes in network connectivity are associated with normal aging.

Arsenic and antimony are common toxic metalloids found in associated minerals. These metalloids generally cause high-concentration pollution in non-ferrous metal smelting soils; however, few studies have investigated the pollution characteristics of these two metalloids at non-ferrous smelting sites using varying soil particle sizes. In this study, the valency distributions and geochemical fractions were investigated with varying soil particle sizes (≤ 0.05, 0.05–0.25, 0.25–1, and 1–2 mm). Soils were mainly concentrated in ≤ 0.05 and 0.05–0.25 mm with mass percentages of 32.97% and 29.02%, respectively. The highest total As and Sb concentrations in ≤ 0.05 mm were found to be 20,350 and 3655 mg/kg, respectively. In addition, As(Ⅲ), As(Ⅴ), Sb(Ⅲ), and Sb(Ⅴ) concentrations in this soil particle size were found to be 224, 19,813, 1036, and 24 mg/kg, respectively. The geochemical fractions of As and Sb in varying soil particle sizes were mainly residual, accounting for 50% and 90% in the ≤ 0.05 mm. Soil may bind ≤ 0.25 mm due to the disparity found in the geochemical compositions and valency distributions of arsenic and antimony. X-ray diffraction and scanning electron microscopy/energy dispersive system analysis confirmed that arsenolite accumulated in particle sizes of ≤ 0.05 and 0.05–0.25 mm. The results of this study may provide a scientific reference for risk assessment and restoration strategies for non-ferrous metal smelting soils.

Booming aspiration of advanced energy storage equipment elevates lithium-ion batteries vastly. Whereas separator with inferior porous structure and compatibility mismatches battery internal medium and raises ion transference rampart. Herein, fumed SiO2 compound separator is designed via ingenious bidirectional drawing technique to optimize the porous structure and realize fumed SiO2 coating online construction during the pore formation process of β-crystal polypropylene (β-iPP) synchronously. Crystal structure measurement, pore construction diagnosis, and physical properties tests disclose that the fumed SiO2 thins coarse fibril structure and homogenizes porous construction of separator. The de-bonding of fumed SiO2/β-iPP interfaces also remains SiO2 on the top-surface and pore internal wall of separator and thus realizes the SiO2 coating online construction, which eliminate the steps required by coating after fabrication of the separator and greatly reduce the production difficulty and cost. Also, the prepared composite separators present reinforced thermal dimensional stability and electrolyte wettability benefited by the SiO2 coating. Electrochemical impedance spectroscopy and cycle tests further uncover that hydrophilic SiO2 nanoparticles lower lithium-ion migration rampart within separator and enhance compatibility with electrodes, which stifles cell resistances and gives LIBs superior high ratio discharge property and cycling durability.

Background & Aims: Claudin-7 (Cldn7) is a tight junction (TJ) membrane protein located at the apical TJ and basolateral side of intestinal epithelial cells. Deletion of Cldn7 by gene targeting leads to the inflammatory bowel disease–like phenotype in mice, which includes weight loss, diarrhea, mucosa ulceration, and severe intestinal epithelial damage. In this study, we test our hypothesis that Cldn7 plays a critical role in regulating intestinal crypt stem cell functions. Methods: Gene expression microarray, quantitative reverse-transcription polymerase chain reaction, in situ hybridization, histologic examinations, immunoblotting, 3-dimensional organoid culture, and various treatments to rescue Cldn7-deficient organoid defects were conducted using global Cldn7 knockout mice and inducible, conditional Cldn7 knockout mice. Results: Gene deletion of Cldn7 in intestines showed significant alteration of expression profiles with striking down-regulation of intestinal crypt stem cell markers such as Olfm4, dislocated proliferative cells, and disrupted epithelial cell differentiation. In addition, the isolated Cldn7-deficient crypts where the stem cells reside were either unable to survive at all or formed defective spheroids, highlighting the functional impairment of crypt stem cells in the absence of Cldn7. Remarkably, the Cldn7-expressing organoids with buddings underwent rapid cell degeneration within days after turning off Cldn7 expression in the culture. We identified that activation of Wnt/β-catenin signaling rescued the organoid defects caused by Cldn7 deletion. Conclusions: In this study, we show that Cldn7 is indispensable in controlling Wnt/β-catenin signaling–dependent intestinal epithelial stem cell survival, self-renewal, and cell differentiation. This study could open a door to study roles of TJ proteins in stem cell regulations in other tissues and organs.

The major challenges of replacing noble-metal electrocatalysts for hydrogen evolution reaction and oxygen evolution reaction in alkaline electrolytes are stability- and kinetics-related. Here we report the synthesis of MoNi4 electrocatalysts covered by MoO2 nanosheets on carbon cloth. Originating from the high intrinsic catalytic activity of MoNi4 nanoalloy, the 3D porous structure provides many exposed active sites and high conductivity. The sample exhibited high activity with an overpotential of 23 mV and 253 mV, a low Tafel slope of 47 mV dec−1 and 136 mV dec−1 at a current density of 10 mA cm−2 for HER and OER, respectively.

Acupuncture treatment is based on acupoint stimulation; however, the biological basis is not understood. We stimulated one acupoint with catgut embedding for 8 weeks and then used isobaric tags for relative and absolute quantitation to screen proteins with altered expression in adjacent acupoints of Sprague Dawley rats. We found that kininogen expression was significantly upregulated in the stimulated and the nonstimulated adjacent acupoints along the same meridian. The enhanced kininogen expression was meridian dependent and was most apparent among small vessels in the subcutaneous layer. Enhanced signals of nitric oxide synthases, cGMP-dependent protein kinase, and myosin light chain were also observed at the nonstimulated adjacent acupoints along the same meridian. These findings uncover biological changes at acupoints and suggest the critical role of the kininogen–nitric oxide signaling pathway in acupoint activation.

In many industrial applications, parallel connection of power semiconductor switches is widely used to achieve higher power levels and fault-tolerant operation. But there is a current imbalance between parallel connected switches in practical applications. In this research, the impact of unbalanced currents on the junction temperature and the reliability of parallel connected switches are quantified and analyzed. Markov based reliability model is developed for quantitative assessment of reliability for parallel switches under different current sharing. The Mean Time to Failure (MTTF) is calculated for different conditions to be used as reliability metric for comparison of various conditions. A sensitivity analysis is also presented to show the effect of parameter variation on the junction temperatures of devices and reliability of the system. At last, a downscaled setup has been built up and tested. Experimental results verify the theoretical analysis and confirm procedure. Also, junction temperatures of power semiconductor devices are measured using thermal camera.

Lung cancer is the leading cause in all cancer deaths. A low survival rate and high recurrence rate of lung cancer make the endeavor to identify new, more effective therapies a primary goal. MicroRNAs (miRNAs) are regarded as regulators of tumorigenesis and it is known that miR-183-5p is significantly upregulated in non-small cell lung cancer (NSCLC), suggesting it has an oncogenic function in lung cancer. In this study, we found that miR-183-5p could promote lung carcinogenesis by directly targeting phosphatase tensin (PTEN). Further experiments indicated that miR-183-5p could suppress p53 and activate AKT signaling through phosphorylation. Moreover, our data indicated that miR-183-5p promoted tumor metastasis and tumor growth in vivo. Collectively, these results showed that miR-183-5p is required for NSCLC development through the suppressing PTEN, and might be a promising target in the diagnosis and treatment of lung cancer in the future.

Edwardsiella piscicida (E. piscicida) is one of the main pathogens of fish, which could invade the host through the gut. Glucose 6-phosphate (Glu6P) within the gut provides environmental stresses that affect the pathogenicity of bacteria. Here we focus on a novel two-component chemical signal transduction system, named UhpB/UhpA in E. piscicida, including the key component hexose phosphate transport system regulatory protein (UhpA) coded by the uhpA gene. This study will elucidate the functions of the uhpA gene in the pathogenicity of E. piscicida and the immune response in zebrafish when infected with E. piscicida. The results showed that the wild type strain of E. piscicida EIB202 demonstrated significant increases in growth compared to the mutant strain ΔuhpA with or without 20 mM Glu6P (P < 0.05). The LD50 of E. piscicida △uhpA strain (2 × 104 CFU/fish) for zebrafish was significantly lower than the wild-type strain (1 × 105 CFU/fish), which suggested the uhpA gene deletion could increase its virulence. Besides, fish infected with ΔuhpA showed significantly higher (p < 0.05) gene expression of IL-1β and TGF-β in spleen than fish infected with EIB202 at 6 h, 12 h, 24 h, and 48 h after infection, TNF-α in spleen of fish infected with ΔuhpA showed significantly higher (p < 0.05) than fish infected with EIB202 at 24 h, 48 h, and 72 h after infection, and IFN-γ in spleen of fish infected with ΔuhpA showed significantly higher (p < 0.05) than fish infected with EIB202 at 12 h, 24 h and 72 h after infection. In summary, these results suggest that the uhpA gene deletion in E. piscicida affects Glu6P usage; most important, which could enhance the pathogenicity of E. piscicida in zebrafish, particularly increase the induction of the gene expression of IL-1β, TNF-α, IFN-γ and TGF-β in the spleens of zebrafish after infection.

Gastric cancer (GC) is the most prevailing malignant tumor of digestive tract and accounts for a considerable part of cancer-relevant deaths worldwide. An increasing number of literatures highlight the important role of lncRNAs in the occurrence and development of GC. Considering that the function of RHPN1-AS1 in GC remains to be fully inquired, we purposed to investigate the potential and mechanism of RHPN1-AS1 in GC. The expression of RHPN1-AS1 was significantly upregulated in GC samples and cells. High RHPN1-AS1 level was strongly correlated with advanced stages of GC and predicted poor outcomes of GC. Furthermore, depletion of RHPN1-AS1 inhibited cell proliferation and cell cycle whereas promoted cell apoptosis. Subcellular fractionation analysis expounded the main expression of RHPN1-AS1 in GC cell cytoplasm. Herein, we conjectured that RHPN1-AS1 might exert its performance in GC through the ceRNA network. Our findings demonstrated that RHPN1-AS1 enhanced ETS1 expression via sponging miR-1299. More importantly, the transcriptional activation of RHPN1-AS1 was mediated by ETS1. Results of recue assays validated that RHPN1-AS1/miR-1299/ETS1 positive feedback loop aggravated the malignant behaviors of GC, revealing RHPN1-AS1 as a latent effective target for the treatment of GC patients.

The morphological evolution and pore formation mechanism of different kinds of β-iPP spherulites during biaxial stretching were analyzed. The smaller radial-growth spherulite deforms heterogeneous, causing a faster reduction in β-crystal content and higher orientation degree during longitudinal stretching, while the bigger spherulite derived from the hedrites deformed more homogeneous due to the more violent lamellae separation, causing a slower β-crystal content decline and lower orientation degree. However, plentiful coarse fibrils form within β-spherulite derived from the hedrites during longitudinal stretching due to abundant lamellae paralleled to the loading direction, with more connections between the coarse fibrils, which delayed the micropores formation and caused the inferior pore size distribution in following transverse stretching. While the radial-growth β-spherulite generates more refined microfibrils and the higher orientation means lesser connection between finer fibrils, making abundant micropores at the beginning of transverse stretching and superior pore size distribution throughout the whole transverse stretching ultimately. Keywords: β-iPP spherulite, Pore formation mechanism, Pore size distribution

Summary: Somatic mutations in DNMT3A are recurrent events across a range of blood cancers. Dnmt3a loss of function in hematopoietic stem cells (HSCs) skews divisions toward self-renewal at the expense of differentiation. Moreover, DNMT3A mutations can be detected in the blood of aging individuals, indicating that mutant cells outcompete normal HSCs over time. It is important to understand how these mutations provide a competitive advantage to HSCs. Here we show that Dnmt3a-null HSCs can regenerate over at least 12 transplant generations in mice, far exceeding the lifespan of normal HSCs. Molecular characterization reveals that this in vivo immortalization is associated with gradual and focal losses of DNA methylation at key regulatory regions associated with self-renewal genes, producing a highly stereotypical HSC phenotype in which epigenetic features are further buttressed. These findings lend insight into the preponderance of DNMT3A mutations in clonal hematopoiesis and the persistence of mutant clones after chemotherapy. : Jeong et al. show that a single genetic manipulation, conditional inactivation of the DNA methyltransferase enzyme Dnmt3a, removes all inherent hematopoietic stem cell (HSC) self-renewal limits and replicative lifespan. Deletion of Dnmt3a allows HSCs to be propagated indefinitely in vivo. Keywords: DNMT3A, DNA methylation, HSC, self-renewal, leukemia

Carthamus tinctorius L. is widely used in traditional Chinese medicines for the treatment of cardiovascular disease. However, our current understanding of the molecular mechanisms supporting its clinical application still lags behind. In this study, a systems pharmacology approach integrating drug-likeness evaluation, oral bioavailability prediction, target exploration, GO enrichment analysis, KEGG pathway performance and network construction was adopted to explore its therapeutic mechanism. A total of 21 active ingredients contained in Carthamus tinctorius L. and 113 major proteins were screened out as effective players in the treatment of cardiovascular disease through some related pathways. And the association among the active ingredients, major hubs and main pathways was investigated, implying the potential biological progression of Carthamus tinctorius L. acting on cardiovascular disease. Importantly, the majority of hubs and pathways were found to be highly related with platelet activation process. Core genes that can be regulated by Carthamus tinctorius L. in platelet activation pathway were PRKACA, PIK3R1, MAPK1, PPP1CC, PIK3CA and SYK, and they may play a central role in suppressing platelet aggregation. The systems pharmacology approach used in this study may provide a feasible tool to clarify the mechanism of traditional Chinese medicines and further develop their therapeutic potentials.

Macrophage apoptosis and efferocytosis are key determinants of atherosclerotic plaque inflammation and necrosis. Bone marrow transplantation studies in ApoE- and LDLR-deficient mice revealed that hematopoietic scavenger receptor class B type I (SR-BI) deficiency results in severely defective efferocytosis in mouse atherosclerotic lesions, resulting in a 17-fold higher ratio of free to macrophage-associated dead cells in lesions containing SR-BI−/− cells, 5-fold more necrosis, 65.2% less lesional collagen content, nearly 7-fold higher dead cell accumulation, and 2-fold larger lesion area. Hematopoietic SR-BI deletion elicited a maladaptive inflammatory response [higher interleukin (IL)-1β, IL-6, and TNF-α lower IL-10 and transforming growth factor β]. Efferocytosis of apoptotic thymocytes was reduced by 64% in SR-BI−/− versus WT macrophages, both in vitro and in vivo. In response to apoptotic cells, macrophage SR-BI bound with phosphatidylserine and induced Src phosphorylation and cell membrane recruitment, which led to downstream activation of phosphoinositide 3-kinase (PI3K) and Ras-related C3 botulinum toxin substrate 1 (Rac1) for engulfment and clearance of apoptotic cells, as inhibition of Src decreased PI3K, Rac1-GTP, and efferocytosis in WT cells. Pharmacological inhibition of Rac1 reduced macrophage efferocytosis in a SR-BI-dependent fashion, and activation of Rac1 corrected the defective efferocytosis in SR-BI−/− macrophages. Thus, deficiency of macrophage SR-BI promotes defective efferocytosis signaling via the Src/PI3K/Rac1 pathway, resulting in increased plaque size, necrosis, and inflammation.

Macrophages play crucial roles in the formation of atherosclerotic lesions. Akt, a serine/threonine protein kinase B, is vital for cell proliferation, migration, and survival. Macrophages express three Akt isoforms, Akt1, Akt2, and Akt3, but the roles of Akt1 and Akt2 in atherosclerosis in vivo remain unclear. To dissect the impact of macrophage Akt1 and Akt2 on early atherosclerosis, we generated mice with hematopoietic deficiency of Akt1 or Akt2. After 8 weeks on Western diet, Ldlr−/− mice reconstituted with Akt1−/− fetal liver cells (Akt1−/−→Ldlr−/−) had similar atherosclerotic lesion areas compared with control mice transplanted with WT cells (WT→Ldlr−/−). In contrast, Akt2−/−→Ldlr−/− mice had dramatically reduced atherosclerotic lesions compared with WT→Ldlr−/− mice of both genders. Similarly, in the setting of advanced atherosclerotic lesions, Akt2−/−→Ldlr−/− mice had smaller aortic lesions compared with WT→Ldlr−/− and Akt1−/−→Ldlr−/− mice. Importantly, Akt2−/−→Ldlr−/− mice had reduced numbers of proinflammatory blood monocytes expressing Ly-6Chi and chemokine C-C motif receptor 2. Peritoneal macrophages isolated from Akt2−/− mice were skewed toward an M2 phenotype and showed decreased expression of proinflammatory genes and reduced cell migration. Our data demonstrate that loss of Akt2 suppresses the ability of macrophages to undergo M1 polarization reducing both early and advanced atherosclerosis.

Objective: To report the vascular anatomic characteristics and surgical outcomes of hemifacial spasm (HFS) caused by an anterior inferior cerebellar artery (AICA) segment passing between cranial nerve VII (CN VII) and cranial nerve VIII (CN VIII)., Patients and Methods: This case series study retrospectively reviewed records of 1040 consecutive patients treated with MVD for HFS in our hospital in 10 years. 25 patients had the culprit vessel recorded as an AICA segment passing between CN VII and CN VIII. Vascular anatomic characteristics were reviewed from intraoperative microscopic videos. The clinical outcomes were followed up at 3-month and 1-year time points., Results: The culprit AICA segments feature 3 discrete anatomic patterns. The patterns denoted as pattern A, B, and C were identified in 19(76%), 3(12%), and 3 (12%) of the 25 patients respectively. Postoperative spasm relief were achieved in 19(76%), 22(88%), and 23 (92%) of the patients at immediately after surgery, 3-month, and 1-year follow-up respectively. 3(12%) of them have permanent postoperative cranial nerve deficits, including one patient with hearing loss and 2 patients with vocal cord palsy., Conclusions: Though an AICA segment passing between CN VII and CN VIII is common, very rarely it was deemed the culprit for HFS in our patients. We used fREZ centered definition and operation. We found the culprit AICA segments feature 3 discrete anatomic patterns. We observed good spasm relief outcome and relatively fewer complications with CN VII and CN VIII. Identifying the 3 anatomic patterns may help with a smooth decision-making when vascular compression by an AICA segment passing between CN VII and CN VIII is suspected., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To explore the structural and functional reorganization of contralateral hippocampus in patients with unilateral mesial temporal lobe epilepsy (mTLE) who achieved seizure-freedom after anterior temporal lobectomy (ATL)., Methods: We obtained high-resolution structural MRI and resting-state functional MRI data in 28 unilateral mTLE patients and 29 healthy controls. Patients were scanned before and three and 24 months after surgery while controls were scanned only once. Hippocampal gray matter volume (GMV) and functional connectivity (FC) were assessed., Results: No obvious GMV changes were observed in contralateral hippocampus before and after successful surgery. Before surgery, ipsilateral hippocampus showed increased FC with ipsilateral insula (INS) and temporoparietal junction (TPJ), but decreased FC with widespread bilateral regions, as well as contralateral hippocampus. After successful ATL, contralateral hippocampus showed: (1) decreased FC with ipsilateral INS at three months follow-up, without further changes; (2) decreased FC with ipsilateral TPJ, postcentral gyrus and rolandic operculum at three months, with an obvious increase at 24 months follow-up; (3) increased FC with bilateral medial prefrontal cortex (MPFC) and superior frontal gyrus (SFG) at three months follow-up, without further changes., Conclusions: Successful ATL may not lead to an obvious structural reorganization in contralateral hippocampus. Surgical manipulation may lead to a transient FC reduction of contralateral hippocampus. Increased FC between contralateral hippocampus and bilateral MPFC and SFG may be related to postoperative functional remodeling., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the potential risk factors associated with seizure recurrence in different periods after epilepsy surgery., Methods: A total of 303 patients with refractory epilepsy after epilepsy surgery were included. The Kaplan-Meier method with log-rank test and univariate and multivariate Cox proportional hazards model were performed to calculate the comparison of survival curves between groups and identify the risk factors associated with seizure recurrence in different periods after surgery., Results: The significant predictors of seizure recurrence were determined, including duration of epilepsy (P = 0.018), seizure types (P = 0.009), magnetic resonance imaging findings (P = 0.007), intracranial electroencephalographic recordings (P = 0.002), sides of epileptogenic zone (P = 0.025), and types of surgery (P = 0.002). Moreover, the significant predictors of seizure recurrence within 12 months after surgery were also included, such as gender (P = 0.007), duration of epilepsy (P = 0.013), intracranial electroencephalographic recordings (P = 0.003), and types of surgery (P < 0.001). Our results indicated that the variables of magnetic resonance imaging findings (P = 0.015), sides of epileptogenic zone (P = 0.004), and seizure relapse within 12 months after surgery (P < 0.001) were significantly associated with seizure recurrence in 12-36 months after surgery. Seizure relapse within 12 months after surgery (P < 0.001) was also associated with seizure recurrence >36 months after surgery., Conclusions: We reconfirmed the well-known risk factors associated with seizure recurrence and also identified the controversial variables. In addition, we found that the risk factors associated with seizure recurrence were different in different periods after epilepsy surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)