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Abstract Alterations in the reward and cognitive control systems are commonly observed among adolescents with internet dependence (ID), and this impairment is often accompanied by social dysfunctions, such as academic burnout. However, the intercorrelations among ID, reward, cognitive control processing, and learning burnout remain unclear. We recruited 1074 Chinese adolescents to investigate the complex interrelationships among these variables using network analysis. The resulting network revealed patterns that connected ID to the behavioral inhibition/activation system (BIS/BAS), self-control, and learning burnout; these results exhibited reasonable stability and test–retest consistency. Throughout the network, the node of BAS-drive was the critical influencing factor, and the node of self-control was the protection factor. In addition, several symptoms of learning burnout and ID were positively associated with sensitivity to punishment. As revealed by the network comparison test, the network constructed among internet dependent (ID) group differed from the network constructed among internet nondependent (IND) group not only in the edges between BIS and learning burnout but also in terms of the edges associated with learning burnout. In conclusion, this study provides insights into the complex mechanisms underlying ID among adolescents from the perspective of the network relationships between core influencing factors and negative consequences. It validates the dual-system model of risky behavior among adolescents and offers a foundation for early warning and interventions for ID in this context.

Abstract The importance of fuel mixing for the progress of the scramjet engine is indisputable. The present article shows the importance of the non-equal multi-injector system for effective fuel distribution and flame holding inside the combustion segment of a scramjet engine. The supersonic air and fuel jet flow in the non-equal nozzle arrangement is simulated via computational fluid dynamic technique. Two injector types of circular and rectangular nozzle have been analyzed to attain flow characteristics of hydrogen jets at supersonic cross flow. Mach contour is also analyzed for these jet arrangements to show the interface of the jet in the non-equal jet arrangement. Besides, addition of internal air jet is also simulated and evaluated in this research. Our investigation shows that the diffusion height of the fuel jet is higher when a rectangular non-equal nozzle is applied. The circular nozzle is more active in the spreading of the fuel in the combustor and the use of an internal air jet effectively increases fuel in a combustor of the scramjet.

Thymosin beta 10 (TMSB10) overexpression is a general characteristic in human carcinogenesis. It is involved in the malignant process of generating multiple cancers. However, there are only a few reports about TMSB10 in colorectal cancer (CRC) and the mechanism of its carcinogenetic effect is still poorly understood. The present study intends to clarify the biological roles and carcinogenic mechanism of TMSB10 in CRC and to explore the possibility whether TMSB10 might be useful as a non-invasive serum tumor biomarker in detecting CRC. Immunohistochemical results showed that TMSB10 protein expression in CRC tissues was generally higher than that in adjacent tissues, and the TMSB10 contents in serum of CRC patients was significantly elevated compared to that of healthy controls. Knockdown-TMSB10 increased apoptosis and induced S-cell cycle arrest, and finally inhibited cell proliferation in vitro and in vivo. Transcriptome sequencing and western blotting analysis revealed that knockdown-TMSB10 increased phosphorylation of p38 and activated the p38 pathway that blocked cell cycle and promoted apoptosis. Taken together, our study indicated that TMSB10 could serve as a minimally invasive serum tumor marker in detecting CRC. At the same time it demonstrates an effective regulatory capacity of TMSB10 on cell proliferation of CRC, suggesting that TMSB10 and downstream effector molecules regulated by TMSB10 could further be applied as an appealing target in clinical post-surgery chemotherapy.

Abstract This article employs a plate with V-shape ribs inside a tube as turbulator to augment the heat transfer rate. The utilized vortex generators are double-winglets arranged in a V-shape placed on both sides of the plate. The proposed system’s suggested working fluids are water-based hybrid nanofluids, including Al2O3–Cu/water, Cu–CuO/water, and Cu–TiO2/water. This work involves a numerical evaluation of the effects of the type and volume concentration of the examined hybrid nanofluids on the enhancement of heat transfer. The experimental results are used to validate the numerical model. It is worth mentioning that all the obtained numerical results are compared with the simple tube, without any turbulator (vortex generator) and in the presence of water instead of the hybrid nanofluids. Based on the numerical results, it can be concluded that all employed hybrid nanofluids showed improved thermal performance compared to pure water. Furthermore, the differences between the models are more substantial for higher Reynolds numbers than for lower Reynolds numbers. In Re = 30,000, the Cu–TiO2/water exhibits the lowest thermal performance improvement (augmentation of about 0.3%), while the Cu–CuO/water at Re = 50,000 exhibits the largest thermal performance improvement (augmentation of approximately 5.7%), in the case of ∅1 = ∅2 = 0.5%. For ∅1 = ∅2 = 1%, the Cu–TiO2/water at Re = 30,000 has the lowest thermal performance improvement (augmentation of around 1.1%), while the Cu–CuO/water at Re = 50,000 has the most thermal performance improvement (augmentation of roughly 8.7%). According to the augmentation of around 2.8% at Re = 30,000 for Cu–TiO2/water and approximately 10.8% at Re = 50,000 for Cu–CuO/water, the thermal performance increase in the scenario of ∅1 = ∅2 = 1.5% is the lowest. In Conclusion, the Cu–CuO/water hybrid nanofluid with a volume concentration of ∅1 = ∅2 = 1.5% has the greatest thermal performance value of all the hybrid nanofluids studied.

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.

Summary: Border-associated macrophages (BAMs) are tissue-resident macrophages that reside at the border of the central nervous system (CNS). Since BAMs originate from yolk sac progenitors that do not persist after birth, the means by which this population of cells is maintained is not well understood. Using two-photon microscopy and multiple lineage-tracing strategies, we determine that CCR2+ monocytes are significant contributors to BAM populations following disruptions of CNS homeostasis in adult mice. After BAM depletion, while the residual BAMs possess partial self-repopulation capability, the CCR2+ monocytes are a critical source of the repopulated BAMs. In addition, we demonstrate the existence of CCR2+ monocyte-derived long-lived BAMs in a brain compression model and in a sepsis model after the initial disruption of homeostasis. Our study reveals that the short-lived CCR2+ monocytes transform into long-lived BAM-like cells at the CNS border and subsequently contribute to BAM populations.

Objective: Fungiform papillae contain taste buds and play a critical role in mastication and the gustatory system. In this study, we report a series of sequential observations of organogenesis of fungiform papillae in miniature pigs, as well as changes in the expression of BMP2, BMP4, Wnt5a, Sox2, and Notch1 signaling pathway components. Design: In this study, we investigated the spatiotemporal expression patterns of BMP, Wnt, Sox2 and Notch in the fungiform papillae of miniature pigs at the bud stage (E40), cap stage (E50) and bell stage (E60). Pregnant miniature pigs were obtained, and the samples were processed for histological staining. Immunohistochemistry and real-time PCR were used to detect the mRNA and protein expression levels of BMP2, BMP4, Wnt5a, Sox2, and Notch1. Results: At E40, fungiform papillae were present on the anterior two-thirds of the tongue in a specific array and pattern. The fungiform papillae were enlarged and basically developed at E50 and were largest at the earlier stage (E60). Most of the BMP2 was concentrated in the epithelial layer and the connective tissue core of the fungal papilloma and gradually accumulated from E40-E60. BMP-4 was weakly expressed in the fungiform papillae epithelia, but BMP-4-positive cells were also observed in the developing tongue muscle at E50 and E60. Wnt5a-positive cells were observed in the fungiform papillae epithelia and developing tongue muscle at all three time points. Sox2-positive cells were observed only in fungiform papillae epithelial cells, and Notch1-positive cells could not be detected. Conclusions: This study provides primary data regarding the morphogenesis and expression of developmental signals in the fungiform papillae of miniature pigs, establishing a foundation for further research in both this model and humans.

The soil freeze–thaw (FT) cycle is a critical component of the terrestrial cryosphere and plays a significant role in hydrological, ecological, climatic, and biogeochemical processes within permafrost landscapes. The FT states can be monitored with in-situ field measurements, but these procedures are costly and limited to single chosen sites. Remote sensing data provides the opportunity to collect information repeatedly across extensive geographical areas. To explore a more effective way to monitor the FT states in the terrestrial cryosphere, in this study, we used microwave and optical remote sensing data and introduced the Deep Learning approach to simulate the soil FT states in the western part of Nunavik, Canada.Two networks, Multilayer Perceptron (MLP) and Convolutional Neural Network (CNN), were trained and tested with over 35,000 and approximately 54,000 randomly selected data samples, respectively. The trained CNN networks outperformed the MLP networks, achieving the highest testing accuracy of 95.67% and the highest validation accuracy of 87.28% based on ground truth data from 32 measurement stations from all seasons across the year. This study proposed the reference periods concept for convenient labeling in data preparation and tested different combinations of influence variables to achieve better transferability of the method for future studies. Our findings offer a more effective way to monitor FT states in the terrestrial cryosphere, offering valuable insights into the consequences of climate change on permafrost landscapes. Moreover, the suggested deep learning approach can be easily expanded when additional input sources are accessible. This expansion has the potential to further improve the model's performance for the FT retrieval.

During space missions, various waste products are produced. Recyclable waste can be treated by aerobic composting to achieve in situ recycling. Considering the limited logistics supply in the Controlled Ecological Life Support System (CELSS), waste recycling should reduce energy consumption and material carrying pressure, increase recycling efficiency, and improve the quality of the daily life of astronauts. However, current composting technology often has polluting gas emissions in the case of limited oxygen (O2) consumption. Therefore, this review aims to distill available information about aerospace mission waste production and its treatment methods, analyze the influencing factors of composting, and summarize optimal O2 demand of aerobic composting of aerospace biomass waste. It also aims to define optimal O2 demand of each stage of aerobic composting of organic waste in order to achieve a low O2 consumption composting technology for the extraterrestrial planet base. The main recyclable wastes (feces, food residue, and non-edible parts of plants or crops) generated in CELSS are expected to be 0.13 kg, 0.31 kg, and 2.12 kg/person/day, which requires 0.173 to 0.692 kg of O2 for the normal composting process. Due to the change of the degradation rate at different stages, the O2 demand of each stage is different. In detail, the different stages for varying O2 requirements are the heating period: 0.022 to 0.032 L.kg−1. dry matter (DM).min−1, the thermophilic period: 0.027 to 0.05 L.kg−1.DM.min−1, and the cooling period: 0.006 to 0.02 L.kg−1.DM.min−1. The O2 demand of aerospace biomass waste compost could be 0.022 to 0.153 L.kg−1.DM.min−1. Adequate O2 supply according to these requirements could reduce O2 consumption and potential pollutant emission.

Pygopus (Pygo) has been identified as a specific nuclear co-activator of the canonical Wingless (Wg)/Wnt signaling pathway in Drosophila melanogaster. Pygo proteins consist of two conserved domains: an N-terminal homologous domain (NHD) and a C-terminal plant homologous domain (PHD). The PHD’s ability to bind to di- and trimethylated lysine 4 of histone H3 (H3K4me2/3) appears to be independent of Wnt signaling. There is ongoing debate regarding the significance of Pygo’s histone-binding capacity. Drosophila Pygo orthologs have a tryptophan (W) > phenylalanine (F) substitution in their histone pocket-divider compared to vertebrates, leading to reduced histone affinity. In this research, we utilized CRISPR/Cas9 technology to introduce the Pygo-F773W point mutation in Drosophila, successfully establishing a viable homozygous Pygo mutant line for the first time. Adult mutant flies displayed noticeable abnormalities in reproduction, locomotion, heart function, and lifespan. RNA-seq and cluster analysis indicated that the mutation primarily affected pathways related to immunity, metabolism, and posttranslational modification in adult flies rather than the Wnt signaling pathway. Additionally, a reduction in H3K9 acetylation levels during the embryonic stage was observed in the mutant strains. These findings support the notion that Pygo plays a wider role in chromatin remodeling, with its involvement in Wnt signaling representing only a specific aspect of its chromatin-related functions.

Robotic odor source localization (OSL) is a technology that enables mobile robots or autonomous vehicles to find an odor source in unknown environments. An effective navigation algorithm that guides the robot to approach the odor source is the key to successfully locating the odor source. While traditional OSL approaches primarily utilize an olfaction-only strategy, guiding robots to find the odor source by tracing emitted odor plumes, our work introduces a fusion navigation algorithm that combines both vision and olfaction-based techniques. This hybrid approach addresses challenges such as turbulent airflow, which disrupts olfaction sensing, and physical obstacles inside the search area, which may impede vision detection. In this work, we propose a hierarchical control mechanism that dynamically shifts the robot’s search behavior among four strategies: crosswind maneuver, Obstacle-Avoid Navigation, Vision-Based Navigation, and Olfaction-Based Navigation. Our methodology includes a custom-trained deep-learning model for visual target detection and a moth-inspired algorithm for Olfaction-Based Navigation. To assess the effectiveness of our approach, we implemented the proposed algorithm on a mobile robot in a search environment with obstacles. Experimental results demonstrate that our Vision and Olfaction Fusion algorithm significantly outperforms vision-only and olfaction-only methods, reducing average search time by 54% and 30%, respectively.

Abstract Background Cuproptosis, a novel form of programmed cell death, plays an essential role in various cancers. However, studies of the function of cuproptosis lncRNAs (CRLs) in colorectal cancer (CRC) remain limited. Thus, this study aims to identify the cuprotosis-related lncRNAs (CRLs) in CRC and to construct the potential prognostic CRLs signature model in CRC. Methods First, we downloaded RNA-Seq data and clinical information of CRC patients from TCGA database and obtained the prognostic CRLs based on typical expression analysis of cuproptosis-related genes (CRGs) and univariate Cox regression. Then, we constructed a prognostic model using the Least Absolute Shrinkage and Selection Operator algorithm combined with multiple Cox regression methods (Lasso-Cox). Next, we generated Kaplan–Meier survival and receiver operating characteristic curves to estimate the performance of the prognostic model. In addition, we also analysed the relationships between risk signatures and immune infiltration, mutation, and drug sensitivity. Finally, we performed quantitative reverse transcription polymerase chain reaction (qRT -PCR) to verify the prognostic model. Result Lasso-Cox analysis revealed that four CRLs, SNHG16, LENG8-AS1, LINC0225, and RPARP-AS1, were related to CRC prognosis. Receiver operating characteristic (ROC) and Kaplan–Meier analysis curves indicated that this model performs well in prognostic predictions of CRC patients. The DCA results also showed that the model included four gene signatures was better than the traditional model. In addition, GO and KEGG analyses revealed that DE-CRLs are enriched in critical signalling pathway, such as chemical carcinogenesis-DNA adducts and basal cell carcinoma. Immune infiltration analysis revealed significant differences in immune infiltration cells between the high-risk and low-risk groups. Furthermore, significant differences in somatic mutations were noted between the high-risk and low-risk groups. Finally, we also validated the expression of four CRLs in FHCs cell lines and CRC cell lines using qRT-PCR. Conclusion The signature composed of SNHG16, LENG8-AS1, LINC0225, and RPARP-AS1, which has better performance in predicting colorectal cancer prognosis and are promising biomarkers for prognosis prediction of CRC.

Abstract In recent years, the cases of tramadol intoxication have become more frequent in many countries. However, most of the previous studies have been based on cases of tramadol intoxication, and the detailed information on the differences between postmortem distribution and diffusion of tramadol remains unclear. To investigate this issue systematically, we established a postmortem distribution model and two postmortem diffusion models. Then, gas chromatography-mass spectrometry (GC/MS) was used to measure the concentrations of tramadol in various biological specimens of fluids and tissues. In postmortem distribution, the results showed an uneven distribution of tramadol in various biological specimens, and the concentrations of tramadol in urine were significantly higher than those in other fluids. In postmortem diffusion, the results showed a dosage-dependent increase of tramadol concentration in most specimens; at all time points from 0.25 to 6 h after postmortem administration, the concentrations of tramadol in fluids were not significantly different from those in tissues, and the concentrations of tramadol in urine were lower than those in both tissues and other fluids in most time points. We recommend a quantitative examination of the specimens of both fluids and tissues to provide more evidence for the forensic identification, and the realization that there is a correlation between the concentrations of fluids and tissues is important for determining antemortem and postmortem administration of tramadol. This information can serve as ancillary data in inferring the contribution of a drug to death in cases of suspected tramadol poisoning.

Abstract Background Most patients with insufficient bone mass suffer from severe horizontal or vertical bone defects in oral implant surgery. The purpose of this study was to compare the bone regeneration effects of titanium meshes with different porosity in the treatment of bone defects. Methods Nine beagle dogs were equally divided into three groups based on execution time. Three months after the extraction of the first to fourth premolars of the mandible, three bone defects were randomly made in the mandible. Bone particles and three kinds of three-dimensional (3D) printed titanium nets with different porosities (low porosity group (LP), 55%; medium porosity group (MP), 62%; and high porosity group (HP), 68%) were replanted in situ. The beagles were killed 4, 8, and 12 weeks after surgery. Formalin-fixed specimens were embedded in acrylic resin. The specimens were stained with micro-CT, basic fuchsin staining, and toluidine blue staining. Results Micro-CT analysis showed that the trabecular thickness, trabecular number, and bone volume fraction of the HP group were higher than those of the other two groups. Moreover, the trabecular separation of the HP group decreased slightly and was lower than that of the MP and LP groups. Histological staining analysis showed that the trabecular number in the HP group was higher than in the other two groups at 8 and 12 weeks, and the bone volume fraction of the HP was higher than that in the other two groups at 12 weeks. Moreover, the trabecular thickness of the MP was higher than that of the LP group at 12 weeks and the trabecular separation was lower in the HP group at 4 and 8 weeks. The differences were statistically significant (p

With the continuous growth of the global economy, an increasing concern has emerged among individuals with regard to personal digital health. Smart fiber-based sensors meet people’s demands for wearable devices with the advantages of excellent skin-friendliness and breathability, enabling efficient and prompt monitoring of personal digital health signals in daily life. Furthermore, by integrating machine learning and big data analysis techniques, a closed-loop system can be established for personal digital health, covering data collection, data analysis, as well as medical diagnosis and treatment. Herein, we provide a review of the recent research progress on fiber-based wearable sensors for personal digital health. Firstly, a brief introduction is provided to demonstrate the importance of fiber-based wearable sensors in personal digital health. Then, the monitoring of biophysical signals through fiber-based sensors is described, and they are classified based on different sensing principles in biophysical signal monitoring (resistive, capacitive, piezoelectric, triboelectric, magnetoelastic, and thermoelectric). After that, the fiber-based biochemical signal sensors are described through the classification of monitoring targets (biofluids and respiratory gases). Finally, a summary is presented on the application prospects and the prevailing challenges of fiber-based sensors, aiming to implement their future role in constructing personal digital health networks.

Abstract Fiber membranes with high specific surface area can be produced when using electrospinning technology combined with amphiphilic block polymers. Due to the solubility difference between the two segments of amphiphilic block polymers, it is easy to be self‐assembly in solvents, which affects the morphology of the spinning fiber and the surface properties of the membrane. In this work, the relationship between the self‐assembly of the amphiphilic block polymer and the morphology of the spinning fiber and the wetting performance of the spinning membrane was explored. Membrane is produced by electrospinning amphiphilic block copolymer PS‐b‐PHEMA (polystyrene‐block‐poly(2‐hydroxyethyl methacrylate) by using co‐solvent system. PS‐b‐PHEMA with controlled molecular weight (Mw) and polymer dispersity index (PDI) was synthesized via atom transfer radical polymerization (ATRP) and characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The electrospun membrane have both super‐hydrophobic and super‐hydrophilic by adjusting the ratio of mixed solvents, demonstrating that the wetting performance of the fiber membrane mainly depends on the shell structure of the self‐assembly micelles.

Abstract Versatile liquid manipulating surfaces combining patternable and controllable wettability have recently motivated considerable attention owing to their significant advantages in droplet-solid impacting behaviors, microdroplet self-removal, and liquid–liquid interface reaction applications. However, developing a facile and efficient method to fabricate these versatile surfaces remains an enormous challenge. In this paper, a strategy for the fabrication of liquid manipulating surfaces with patternable and controllable wettability on Polyimide (PI) film based on femtosecond laser thermal accumulation engineering is proposed. Because of its controllable micro-/nanostructures and chemical composition through adjusting the local thermal accumulation, the wettability of PI film can be tuned from superhydrophilicity (~ 3.6°) to superhydrophobicity (~ 151.6°). Furthermore, three diverse surfaces with patternable and heterogeneous wettability were constructed and various applications were successfully realized, including water transport, droplet arrays, and liquid wells. This work may provide a facile strategy for achieving patternable and controllable wettability efficiently and developing multifunctional liquid steering surfaces.

BackgroundThe predictive value of biomarkers such as neuron specific enolase (NSE), S100B, neurofilament (NFL), interleukin-6 (IL-6), coagulation factor R, and D-Dimer (DD) after acute Stanford A type aortic dissection (AAAD) with neurological complications has recently gained much attention from the research community. However, results from these studies are conflicting. This meta-analysis is conducted to assess the relationship between the biomarkers and the risk of neurological complications after AAAD.MethodsTwo reviewers performed a systematic literature search across eight databases (CNKI, Wan Fang, VIP, CBM, PubMed, Web of Science, Cochrane Library, and EMBASE). The studies regarding biomarkers in AAAD patients published up to February 2022 were included. These studies were subjected to rigorous scrutiny and data extraction to determine the weighted mean difference (WMD) and the 95% confidence interval (CI), which were analyzed using the RevMan 5.4 and Stata software 14.0.ResultsA total of 12 studies including 360 cases with neurological complications and 766 controls were incorporated into our meta-analysis. WMD analysis showed that there was a higher NSE levels in AAAD patients with postoperative neurological complications compared with controls (WMD = 0.640, 95% CI: 0.205 ~ 1.075, P = 0.004 < 0.005), and the level of S100B was related to the 6 h and 24 h postoperative neurological complications (6 h: WMD = 0.64, 95% CI: 0.27 ~ 1.02, P = 0.0007 < 0.001; 24 h: WMD = 0.281, 95% CI: 0.211 ~ 0.351, P < 0.001). Moreover, S100B levels at 6 hours after operation were significantly higher than that at 24 hours (WMD = 0.260, 95% CI: 0.166 ~ 0.354, P < 0.001).ConclusionNSE and S100B are both candidate biomarkers to predict postoperative neurological complications in patients with AAAD. Other markers are also valuable when used in conjunction with clinical judgement. The findings accentuate the necessity of further research to establish standardized values for these biomarkers in predicting neurological complications.

Introduction: Luscan-Lumish syndrome (LLS) is currently recognized as a rarely-observed condition featured with overgrowth, macrocephaly, obesity, type I Chiari malformation, and linguistic retardation. So far, there have been only a few LLS cases registered worldwide, but with none of them reported from China. To acquire a deeper understanding on the clinical and genetic features of this disease, a Chinese boy with LLS caused by a heterozygous variant in SETD2 gene was investigated in the present study.Methods: The patient was clinically examined and the medical history of his family was collected. Genetic testing was performed to determine the genetic etiology.Results: The proband was a boy aged 5-year-7-month-old, who was referred to our hospital due to “being a slow learner in kindergarten”. The child had a history of delayed motor and language development in comparison to his peers. After admission, physical examination revealed tall stature and macrocephaly as the major manifestation, in addition to a relatively lower rating in intelligence assessment as well as abnormal MRI images showing a slightly shorter corpus callosum accompanied by a mildly thinner corpus callosum body. Whole exome sequencing (WES) revealed a heterozygous c.2514_2516delTAG (p.Ser838del) variant in SETD2 gene, which was subsequently identified as a novel de novo variant. According to the standardized genetic variant classification published by the American College of Medical Genetics and Genomics (ACMG), the variant, with a pathogenicity analysis result indicating PS2 + PM2_Supporting + PM4, was determined to be likely pathogenic. Through literature review, the clinical phenotypes of the 15 LLS cases were summarized, including 8 cases of overgrowth (53%), 13 cases of macrocephaly (87%), 11 cases of developmental delay (73%), 8 cases of autism (53%), and 7 cases of special facial features (47%). Besides, abnormal craniocerebral MRI findings were noticed in 7 cases. Despite that the mutation sites of the 15 patients varied from case to case, they showed a uniformly distributed pattern throughout the whole SETD2 gene, including 5 missense mutations, 5 frameshift mutations and 5 non-sense mutations.Conclusion: LLS, not having been recognized till recent years, is identified as an autosomal dominant syndrome triggered by SETD2 gene mutation. As the first report of LLS in China, the case in our study was proved to be associated with a unique type of SETD2 gene mutation that has never been reported previously, which is believed to enrich the mutation spectrum of SETD2 gene and also, deepening the clinicians’ understanding on the disease.

After spinal cord injury, microglia as the first responders to the lesion display both beneficial and detrimental characteristics. Activated microglia phagocyte and eliminate cell debris, release cytokines to recruit peripheral immune cells to the injury site. Excessively activated microglia can aggravate the secondary damage by producing extravagant reactive oxygen species and pro-inflammatory cytokines. Recent studies demonstrated that the voltage-gated proton channel Hv1 is selectively expressed in microglia and regulates microglial activation upon injury. In mouse models of spinal cord injury, Hv1 deficiency ameliorates microglia activation, resulting in alleviated production of reactive oxygen species and pro-inflammatory cytokines. The reduced secondary damage subsequently decreases neuronal loss and correlates with improved locomotor recovery. This review provides a brief historical perspective of advances in investigating voltage-gated proton channel Hv1 and home in on microglial Hv1. We discuss recent studies on the roles of Hv1 activation in pathophysiological activities of microglia, such as production of NOX-dependent reactive oxygen species, microglia polarization, and tissue acidosis, particularly in the context of spinal cord injury. Further, we highlight the rationale for targeting Hv1 for the treatment of spinal cord injury and related disorders.

Introduction: Longxuetongluo Capsule (LTC) is wildly applied to treat ischemic stroke in clinical practice in China. However, the pharmacological mechanism of LTC on ischemic stroke is still unstated. Objective: Our research was designed to study the protective effect of LTC against cerebral ischemia–reperfusion (I/R) injury and reveal the underlying mechanism both in vivo and in vitro. Methods: PC12 cells treated with glucose deprivation/reperfusion (OGD/R) were used to simulate in vitro ischemia/reperfusion (I/R) injury. The cell viability, apoptosis rate, and protein expressions of PC12 cells were evaluated. In vivo validation of the protective effect of LTC was carried out by middle cerebral artery occlusion (MCAO)/reperfusion treatment, and the underlying mechanism of its anti-apoptosis ability was further revealed by immunohistochemistry staining and Western blotting. Results: In the current study, we observed that LTC effectively inhibited oxygen-glucose deprivation/reperfusion (OGD/R) induced apoptosis of PC12 cells through suppressing the cleavage of poly ADP-ribose polymerase (PARP), caspase-3, and caspase-9. Further investigation revealed that OGD/R insult remarkably triggered the endoplasmic reticulum stress responses (ER stress) to induce PC12 cell apoptosis. LTC treatment alleviated OGD/R induced ER stress by inhibiting the activation of protein kinase RNA (PKR)-like ER kinase (PERK)/eukaryotic translation initiation factor 2 (eIF2α) and inositol requiring enzyme 1 (IRE1)/tumor necrosis factor receptor-associated factor 2 (TRAF2) pathways. Additionally, LTC also restrained the OGD/R-induced PC12 cell apoptosis by reversing the activated mitogen-activated protein kinase (MAPK) through IRE1/TRAF2 pathway. Animal studies demonstrated LTC significantly restricted the infarct region induced by middle cerebral artery occlusion (MCAO)/reperfusion, the activation of ER stress and apoptosis of neuronal cells had also been suppressed by LTC in the penumbra region. Conclusion: LTC protects the cerebral neuronal cell against ischemia/reperfusion injury through ER stress and MAPK-mediated mechanisms.

Abstract Background Type II diabetes mellitus (T2DM) is an important risk factor for osseointegration of implants. The aim of this study was to explore key genes of T2DM affecting bone metabolism through bioinformatic analysis of published RNA sequencing data, identify potential biomarkers, and provide a reference for finding the molecular mechanism of abnormal osseointegration caused by T2DM. Methods We identified differentially expressed mRNAs and miRNAs from the Gene Expression Omnibus database using the R package ‘limma’ and analysed the predicted target genes using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene Ontology analysis. At the same time, miRNA–mRNA interactions were explored using miRWalk 2.0. Results We constructed an miRNA-gene regulatory network and a protein–protein interaction network. The enrichment pathways of differentially expressed mRNAs included extracellular matrix receptor interactions, protein digestion and absorption, the PI3K-Akt signalling pathway, cytokine–cytokine receptor interactions, chemokine signalling pathways, and haematopoietic cell lineage functions. We analysed the expression of these differentially expressed mRNAs and miRNAs in T2DM rats and normal rats with bone implants and identified Smpd3, Itga10, and rno-mir-207 as possible key players in osseointegration in T2DM. Conclusion Smpd3, Itga10, and rno-mir-207 are possible biomarkers of osseointegration in T2DM. This study sheds light on the possible molecular mechanism of abnormal osseointegration caused by bone metabolism disorder in T2DM.

Abstract Directional water self‐transport plays a crucial role in diverse applications such as biosensing and water harvesting. Despite extensive progress, current strategies for directional water self‐transport are restricted to a short self‐driving distance, single function, and complicated fabrication methods. Here, a lubricant‐infused heterogeneous superwettability surface (LIHSS) for directional water self‐transport is proposed on polyimide (PI) film through femtosecond laser direct writing and lubricant infusion. By tuning the parameters of the femtosecond laser, the wettability of PI film can be transformed into superhydrophobic or superhydrophilic. After trapping water droplets on the superhydrophilic surface and depositing excess lubricant, the asymmetrical wetting ridge drives water droplets by an attractive capillary force on the LIHSS. Notably, the maximum droplet self‐driving distance can approach ≈3 mm, which is nearly twice as long as the previously reported strategies for direction water self‐transport. Significantly, it is demonstrated that this strategy makes it possible to achieve water self‐transport, anti‐gravity pumping, and chemical microreaction on a tilted LIHSS. This work provides an efficient method to fabricate a promising platform for realizing directional water self‐transport.

Magnification endoscopy with narrow-band imaging (ME-NBI) technology is widely used in the early diagnosis of precancerous lesions and gastric cancer, which is critical to reducing the incidence of gastric cancer and improving the survival rate of gastric cancer patients. The diagnosis based on ME-NBI image is mostly in manual way in clinics. In order to improve its objectivity and efficiency, here we proposed a lightweight attention mechanism deep learning model to automatically classify ME-NBI images for artificial intelligence (AI) diagnosis of early gastric cancer, low-grade intraepithelial neoplasia, and non-neoplasm. We collected 4,098 images from 990 patients for model training and validation and evaluated the performance of our model by comparisons with that of other models, such as the benchmark model. An additional 587 images from 296 patients were collected as an independent test set to further evaluate our method’s performance. The validation set showed that the overall accuracy, recall, precision, F1 score, and the area under the curve of our method were higher than those of other methods. The independent test set showed that our method achieved state-of-the-art classification for low-grade intraepithelial neoplasia (accuracy = 93.9%, sensitivity = 92.6%). Our method displayed the advantages of lightweight and high effectiveness in classifying effectiveness, which is the potential for AI diagnosis of early gastric cancer, low-grade intraepithelial neoplasia, and non-neoplasm.

The source region of the Yellow River (SRYR) is situated on the permafrost boundary in the northeast of the Qinghai-Tibet Plateau (QTP), which is an area highly sensitive to climate change. As a result of increasing global temperatures, the permafrost in this region has undergone significant degradation. In this study, we utilized Sentinel-1 to obtain ground surface deformation data in the SRYR from June 2017 to January 2022. We then analyzed the differences in terrain deformation under various environmental conditions. Our findings indicated an overall subsidence trend in the SRYR, with a long-term deformation velocity of −4.2 mm/a and seasonal deformation of 8.85 mm. Furthermore, the results showed that terrain deformation varied considerably from region to region, and that the Huanghe’ yan sub-basin with the highest permafrost coverage among all sub-basins significantly higher subsidence rates than other regions. Topography strongly influenced ground surface deformation, with flat slopes exhibiting much higher subsidence rates and seasonal deformation. Moreover, the ground temperature and ground ice richness played a certain role in the deformation pattern. This study also analyzed regional deformation details from eight boreholes and one profile line covering different surface conditions, revealing the potential for refining the permafrost boundary. Overall, the results of this study provide valuable insights into the evolution of permafrost in the SRYR region.

Pu-erh tea as a popular post-fermented tea displays a significant effect on improving metabolic syndrome. Puerin III (P3) had already been identified as the characteristic chemical constituent in pu-erh tea. Nevertheless, the activity of P3 on glucose and lipid metabolism disorder is still unclear. In this study, the high-fat high-sucrose diet-induced ApoE−/− mice model was employed to assess the effects of P3 in vivo. Our study found that P3 dose-dependently ameliorated the plasma total cholesterol and fasting blood glucose (FBG) in the hypercholesterolaemic and hyperglycemic ApoE−/− mice. Our investigation in vitro revealed P3 decreased the FBG by inhibiting α-glucosidase. The study on HepG2 cells also confirmed that P3 promoted the clearance of cholesterol by increasing the low-density lipoprotein receptor (LDLR) expression. This research illustrated that P3 might be the active ingredient of Pu-erh tea and a promising therapeutic option to treat glucose and lipid metabolism disorders.

Abstract Background Grocery food taxes represent a stable tax revenue stream for state and municipal government during times of adverse economic shocks such as that observed under the coronavirus disease 2019 (COVID-19) pandemic. Previous research, however, suggests a possible mechanism through which grocery taxes may adversely affect health. Our objectives are to document the spatial and temporal variation in grocery taxes and to empirically examine the statistical relationship between county-level grocery taxes and obesity and diabetes. Methods We collect and assemble a novel national dataset of annual county and state-level grocery taxes from 2009 through 2016. We link this data to three-year, county-level estimates based on data from the Centers for Disease Control and Prevention on rates of obesity and diabetes and provide a nation-wide spatial characterization of grocery taxes and these two health outcomes. Using a county-level fixed effects estimator, we estimate the effect of grocery taxes on obesity and diabetes rates, also controlling for a subset of potential confounders that vary over time. Results We find a 1 percentage point increase in grocery taxes is associated with 0.588 and 0.215 percentage point increases in the county-level obesity and diabetes rates. Conclusion Counties with grocery taxes have increased prevalence of obesity and diabetes. We estimate the economic burden of increased obesity and diabetes rates resulting from grocery taxes to be $5.9 billion. Based on this estimate, the benefit-cost ratio of removing grocery taxes across the United States only considering the effects on obesity and diabetes rates is 1.90.

Abstract This study aimed to compare and verify the osseointegration performance of a novel implant (NI) in vivo, which could provide a useful scientific basis for the further development of NIs. Thirty-two NIs treated with hydrofluoric acid and anodization and sixteen control implants (CIs) were placed in the mandibles of 8 beagles. Micro-CT showed that the trabecular number (Tb.N) significantly increased and trabecular separation (Tb.Sp) significantly decreased in the NIs at 2 weeks. Significant differences were found in the trabecular thickness, Tb.N, Tb.Sp, bone surface/bone volume ratio, and bone volume/total volume ratio between the two groups from the 2nd–4th weeks. However, there were no significant differences between the two groups in the bone volume density at 2, 4, 8, or 12 weeks or bone-implant contact at 2 or 4 weeks, but the BIC in the CIs was higher than that in the NIs at the 8th and 12th weeks. Meanwhile, the histological staining showed a similar osseointegration process between the two groups over time. Overall, the NIs could be used as new potential implants after further improvement.

Objective: To investigate the effect of a pain management core competency education program on surgical nurses’ pain knowledge and pain management nursing practice behaviors. Methods: An 8-h education program focused on pain management core competency was provided twice in two weeks including the multidimensional nature of pain, pain assessment, pharmacological and non-pharmacological management, and knowledge application was developed and implemented for surgical nurses by a multidisciplinary team. Multimodal teaching approaches such as didactic teaching and vignettes of cases for nurses to discuss were used. The Clinical Pain Knowledge Test (CPKT) was completed by 135 and 107 nurses from 17 surgical wards pre and post-program, respectively. Two hundred and three patients’ medical records were randomly sampled according to the number of operations in each ward one week before and in the fifth week after the intervention, respectively. Documentation of patients’ postoperative pain management nursing practice behaviors and pain intensity scores were collected. Results: After the intervention, the CPKT scores of nurses significantly increased from 45.6% ± 12.3% to 54.2% ± 10.2% (t = 5.786, P

Sleep–wake stability is imbalanced with natural aging, and microRNAs (miRNAs) play important roles in cell proliferation, apoptosis, and aging; however, the biological functions of miRNAs in regulating aging-related sleep–wake behavior remain unexplored. This study varied the expression pattern of dmiR-283 in Drosophila and the result showed that the aging decline in sleep–wake behavior was caused by the accumulation of brain dmiR-283 expression, whereas the core clock genes cwo and Notch signaling pathway might be suppressed, which regulate the aging process. In addition, to identify exercise intervention programs of Drosophila that promote healthy aging, mir-283SP/+ and Pdf > mir-283SP flies were driven to perform endurance exercise for a duration of 3 weeks starting at 10 and 30 days, respectively. The results showed that exercise starting in youth leads to an enhanced amplitude of sleep–wake rhythms, stable periods, increased activity frequency upon awakening, and the suppression of aging brain dmiR-283 expression in mir-283SP/+ middle-aged flies. Conversely, exercise performed when the brain dmiR-283 reached a certain accumulation level showed ineffective or negative effects. In conclusion, the accumulation of dmiR-283 expression in the brain induced an age-dependent decline in sleep–wake behavior. Endurance exercise commencing in youth counteracts the increase in dmiR-283 in the aging brain, which ameliorates the deterioration of sleep–wake behavior during aging.

This article presents two new chemical plume tracing (CPT) algorithms for using on autonomous underwater vehicles (AUVs) to locate hydrothermal vents. We aim to design effective CPT navigation algorithms that direct AUVs to trace emitted hydrothermal plumes to the hydrothermal vent. Traditional CPT algorithms can be grouped into two categories, including bio-inspired and engineering-based methods, but they are limited by either search inefficiency in turbulent flow environments or high computational costs. To approach this problem, we design a new CPT algorithm by fusing traditional CPT methods. Specifically, two deep reinforcement learning (RL) algorithms, including double deep Q-network (DDQN) and deep deterministic policy gradient (DDPG), are employed to train a customized deep neural network that dynamically combines two traditional CPT algorithms during the search process. Simulation experiments show that both DDQN- and DDPG-based CPT algorithms achieve a high success rate (>90%) in either laminar or turbulent flow environments. Moreover, compared to traditional moth-inspired method, the averaged search time is improved by 67% for the DDQN- and 44% for the DDPG-based CPT algorithms in turbulent flow environments.

Abstract Background The association between chronic obstructive pulmonary disease (COPD), lung function and risk of type 2 diabetes mellitus (T2DM) remains controversial. We performed a meta-analysis to clarify this issue. Methods The PubMed and EMBASE databases were searched. Cohort studies on COPD, lung function and risk of T2DM in adults were included. A random effects model was adopted to calculate the summary risk ratio (RR) and 95% confidence interval (CI). Dose-response analysis was conducted where possible. Results A total of 13 eligible cohort studies involving 307,335 incident T2DM cases and 7,683,784 individuals were included. The risk of T2DM was significantly higher in patients with COPD than those without COPD (RR = 1.25, 95% CI 1.16–1.34). Compared to the highest category of percentage forced vital capacity (FVC%), the lowest category of FVC% was associated with a higher risk of T2DM (RR = 1.43, 95% CI 1.33–1.53). Similarly, the summary RR of T2DM for the lowest versus highest category of percentage forced expiratory volume in 1 s (FEV1%) was 1.49 (95% CI 1.39–1.60). Significant linear associations of FVC% and FEV1% with risk of T2DM were found (P non-linearity > 0.05); the RR of T2DM was 0.88 (95% CI 0.82–0.95) and 0.87 (95% CI 0.81–0.94) per 10% increase in FVC% and FEV1%, respectively. There was a non-significant relationship between the FEV1/FVC ratio and the risk of T2DM. Conclusions Both COPD and impaired lung function, especially restricted ventilation dysfunction, could increase the risk of T2DM. However, these findings should be interpreted with caution due to the limited number of studies, and need to be validated by future studies.

(1) Background: There are few diagnostic and therapeutic targets for myocardial remodeling in the salvageable non-infarcted myocardium. (2) Methods: Hub genes were identified through comprehensive bioinformatics analysis (GSE775, GSE19322, and GSE110209 from the gene expression omnibus (GEO) database) and the biological functions of hub genes were examined by gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, the differential expression of hub genes in various cell populations between the acute myocardial infarction (AMI) and sham-operation groups was analyzed by processing scRNA data (E-MTAB-7376 from the ArrayExpress database) and RNA-seq data (GSE183168). (3) Results: Ten strongly interlinked hub genes (Timp1, Sparc, Spp1, Tgfb1, Decr1, Vim, Serpine1, Serpina3n, Thbs2, and Vcan) were identified by the construction of a protein–protein interaction network from 135 differentially expressed genes identified through comprehensive bioinformatics analysis and their reliability was verified using GSE119857. In addition, the 10 hub genes were found to influence the ventricular remodeling of non-infarcted tissue by modulating the extracellular matrix (ECM)-mediated myocardial fibrosis, macrophage-driven inflammation, and fatty acid metabolism. (4) Conclusions: Ten hub genes were identified, which may provide novel potential targets for the improvement and treatment of AMI and its complications.

Soil moisture (SM) products presently available in permafrost regions, especially on the Qinghai–Tibet Plateau (QTP), hardly meet the demands of evaluating and modeling climatic, hydrological, and ecological processes, due to their significant bias and low spatial resolution. This study developed an algorithm to generate high-spatial-resolution SM during the thawing season using Sentinel-1 (S1) and Sentinel-2 (S2) temporal data in the permafrost environment. This algorithm utilizes the seasonal backscatter differences to reduce the effect of surface roughness and uses the normalized difference vegetation index (NDVI) and the normalized difference moisture index (NDMI) to characterize vegetation contribution. Then, the SM map with a grid spacing of 50 m × 50 m in the hinterland of the QTP with an area of 505 km × 246 km was generated. The results were independently validated based on in situ data from active layer monitoring sites. It shows that this algorithm can retrieve SM well in the study area. The coefficient of determination (R2) and root-mean-square error (RMSE) are 0.82 and 0.06 m3/m3, respectively. This study analyzed the SM distribution of different vegetation types: the alpine swamp meadow had the largest SM of 0.26 m3/m3, followed by the alpine meadow (0.23), alpine steppe (0.2), and alpine desert (0.16), taking the Tuotuo River basin as an example. We also found a significantly negative correlation between the coefficient of variation (CV) and SM in the permafrost area, and the variability of SM is higher in drier environments and lower in wetter environments. The comparison with ERA5-Land, GLDAS, and ESA CCI showed that the proposed method can provide more spatial details and achieve better performance in permafrost areas on QTP. The results also indicated that the developed algorithm has the potential to be applied in the entire permafrost regions on the QTP.

Dysregulation and prognostic roles of Karyopherin α2 (KPNA2) were reported in many malignancies including hepatocellular carcinoma (HCC). A multi-omics analysis of KPNA2 is needed to gain a deeper understanding of its multilevel molecular characteristics and provide novel clues for HCC diagnosis, prognosis, and target therapy. Herein multi-omic alterations of KPNA2 were analyzed at genetic, epigenetic, transcript, and protein levels with evaluation of their relevance with clinicopathological features of HCC by integrative analyses. The significant correlations of KPNA2 expression with its gene copy number variation (CNV) and methylation status were shown through Spearman correlation analyses. With Cox regression, Kaplan-Meier survival, and receiver operating characteristic (ROC) analyses, based on the factors of KPNA2 CNV, methylation, expression, and tumor stage, risk models for HCC overall survival (OS) and disease-free survival (DFS) were constructed which could discriminate the 1-year, 3-year, and 5-year OS/DFS status effectively. With Microenvironment Cell Populations-counter (MCP-counter), the immune infiltrations of HCC samples were evaluated and their associations with KPNA2 were shown. KPNA2 expression in liver was found to be influenced by low fat diet and presented significant correlations with fatty acid metabolism and fatty acid synthase activity in HCC. KPNA2 was detected lowered in HCC patient’s plasma by enzyme linked immunosorbent assay (ELISA), consistent with its translocation to nuclei of HCC cells. In conclusion, KPNA2 multilevel dysregulation in HCC and its correlations with immune infiltration and the fatty acid metabolism pathway indicated its multiple roles in HCC. The clinicopathological significance of KPNA2 was highlighted through the in-depth analyses at multilevels.

The freeze–thaw (F-T) cycle of the active layer (AL) causes the “frost heave and thaw settlement” deformation of the terrain surface. Accurately identifying its amplitude and time characteristics is important for climate, hydrology, and ecology research in permafrost regions. We used Sentinel-1 SAR data and small baseline subset-interferometric synthetic aperture radar (SBAS-InSAR) technology to obtain the characteristics of F-T cycles in the Zonag Lake-Yanhu Lake permafrost-affected endorheic basin on the Qinghai-Tibet Plateau from 2017 to 2019. The results show that the seasonal deformation amplitude (SDA) in the study area mainly ranges from 0 to 60 mm, with an average value of 19 mm. The date of maximum frost heave (MFH) occurred between November 27th and March 21st of the following year, averaged in date of the year (DOY) 37. The maximum thaw settlement (MTS) occurred between July 25th and September 21st, averaged in DOY 225. The thawing duration is the thawing process lasting about 193 days. The spatial distribution differences in SDA, the date of MFH, and the date of MTS are relatively significant, but there is no apparent spatial difference in thawing duration. Although the SDA in the study area is mainly affected by the thermal state of permafrost, it still has the most apparent relationship with vegetation cover, the soil water content in AL, and active layer thickness. SDA has an apparent negative and positive correlation with the date of MFH and the date of MTS. In addition, due to the influence of soil texture and seasonal rivers, the seasonal deformation characteristics of the alluvial-diluvial area are different from those of the surrounding areas. This study provides a method for analyzing the F-T cycle of the AL using multi-temporal InSAR technology.

Summary: Although an imbalance between neuronal excitation and inhibition underlies seizures, clinical approaches that target these mechanisms are insufficient in containing seizures in patients with epilepsy, raising the need for alternative approaches. Brain-resident microglia contribute to the development and stability of neuronal structure and functional networks that are perturbed during seizures. However, the extent of microglial contributions in response to seizures in vivo remain to be elucidated. Using two-photon in vivo imaging to visualize microglial dynamics, we show that severe seizures induce formation of microglial process pouches that target but rarely engulf beaded neuronal dendrites. Microglial process pouches are stable for hours, although they often shrink in size. We further find that microglial process pouches are associated with a better structural resolution of beaded dendrites. These findings provide evidence for the structural resolution of injured dendrites by microglia as a form of neuroprotection.

Permafrost distribution is of great significance for the study of climate, ecology, hydrology, and infrastructure construction in high-cold mountain regions with complex topography. Therefore, updated high-resolution permafrost distribution mapping is necessary and highly demanded in related fields. This case study conducted in a small catchment in the northeast of the Qinghai Tibet Plateau proposes a new method of using ground-penetrating radar (GPR) to detect the stratigraphic structure, interpret the characteristics of frozen ground, and extract the boundaries of permafrost patches in mountain areas. Thus, an empirical–statistical model of mountain frozen ground zonation, along with aspect (ASP) adjustment, is established based on the results of the GPR data interpretation. The spatial mapping of the frozen ground based on this model is compared with a field survey dataset and two existing permafrost distribution maps, and their consistencies are all higher than 80. In addition, the new map provides more details on the distribution of frozen ground. In this case, the influence of ASP on the distribution of permafrost in mountain areas is revealed: the adjustment of ASP on the lower limit of continuous and discontinuous permafrost is 180–200 m, the difference in the annual mean ground temperature between sunny and shady slopes is up to 1.4–1.6 °C, and the altitude-related temperature variation and uneven distribution of solar radiation in different ASPs comprehensively affect the zonation of mountain frozen ground. This work supplements the traditional theory of mountain permafrost zonation, the results of which are of value to relevant scientific studies and instructive to engineering construction in this region.

Background and aims: Internet gaming disorder (IGD) is rapidly becoming a worldwide health concern. The prefrontal-subcortical model of self-regulation emphasizes that an impaired prefrontal cognitive control system and an overwhelming subcortical reward-seeking system are both crucial factors in health problems, including addiction. This study focused on the cognitive control system of IGD, aiming to investigate whether cognitive control is altered and the underlying neural correlates in college students with IGD. Methods: Thirty college students with IGD and twenty-five matched healthy controls were asked to complete a stop-signal task that measures cognitive control while being monitored by functional magnetic resonance imaging (fMRI). Results: Compared to the controls, only the college students with severe IGD, rather than those with mild IGD, had deficient brain activity involved in inhibitory control and response execution (specifically, the inferior frontal gyrus, anterior cingulate cortex and primary motor cortex); this result implies that cognitive control deficits are closely linked to addiction severity in individuals with IGD. Regarding performance monitoring function, college students with IGD exhibited unabated behavioral and brain activity, as did the control group. Conclusions: Combined with our previous finding that the subcortical reward system was enhanced in individuals with IGD, the present findings extend the prefrontal-subcortical model of self-regulation from the perspective of IGD in a college student population and thus provide useful insight for the effective prevention and treatment of IGD.

Converging evidence indicates that addiction involves impairment in reward processing systems. However, the patterns of dysfunction in different stages of reward processing in internet gaming addiction remain unclear. In previous studies, individuals with internet gaming disorder were found to be impulsive and risk taking, but there is no general consensus on the relation between impulsivity and risk-taking tendencies in these individuals. The current study explored behavioral and electrophysiological responses associated with different stages of reward processing among individuals with internet gaming disorders (IGDs) with a delayed discounting task and simple gambling tasks. Compared to the healthy control (HC) group, the IGD group discounted delays more steeply and made more risky choices, irrespective of the outcome. As for the event-related potential (ERP) results, during the reward anticipation stage, IGDs had the same stimulus-preceding negativity (SPN) for both large and small choices, whereas HCs exhibited a higher SPN in large vs. small choices. During the outcome evaluation stage, IGDs exhibited a blunted feedback-related negativity for losses vs. gains. The results indicate impairment across different stages of reward processing among IGDs. Moreover, we found negative correlation between impulsivity indexed by BIS-11 and reward sensitivity indexed by SPN amplitude during anticipation stage only, indicating different neural mechanisms at different stages of reward processing. The current study helps to elucidate the behavioral and neural mechanisms of reward processing in internet gaming addiction.

In the terrestrial cryosphere, freeze/thaw (FT) state transitions play an important and measurable role in climatic, hydrological, ecological, and biogeochemical processes in permafrost landscapes. Active and passive microwave remote sensing has shown a principal capacity to provide effective monitoring of landscape FT dynamics. The study presents a seasonal threshold approach, which examines the timeseries progression of remote sensing measurements relative to signatures acquired during seasonal frozen and thawed reference states. This is used to estimate the FT state from the Sentinel-1 database and applied and evaluated for the region of Eastern Nunavik (Québec, Canada). An optimization process of the threshold is included. In situ measurements from the meteorological station network were used for the validation process. Overall, acceptable estimation accuracy (>70%) was achieved in most tests; on the best-performing sites, an accuracy higher than 90% was reached. The performance of the seasonal threshold approach over the study region was further discussed with consideration of land cover, spatial heterogeneity, and soil depth. This work is dedicated to providing more accurate data to capture the spatiotemporal heterogeneity of freeze/thaw transitions and to improving our understanding of related processes in permafrost landscapes.

In this study, we applied small baseline subset-interferometric synthetic aperture radar (SBAS-InSAR) to monitor the ground surface deformation from 2017 to 2020 in the permafrost region within an ~400 km × 230 km area covering the northern and southern slopes of Mt. Geladandong, Tanggula Mountains on the Tibetan Plateau. During SBAS-InSAR processing, we inverted the network of interferograms into a deformation time series using a weighted least square estimator without a preset deformation model. The deformation curves of various permafrost states in the Tanggula Mountain region were revealed in detail for the first time. The study region undergoes significant subsidence. Over the subsiding terrain, the average subsidence rate was 9.1 mm/a; 68.1% of its area had a subsidence rate between 5 and 20 mm/a, while just 0.7% of its area had a subsidence rate larger than 30 mm/a. The average peak-to-peak seasonal deformation was 19.7 mm. There is a weak positive relationship (~0.3) between seasonal amplitude (water storage in the active layer) and long-term deformation velocity (ground ice melting). By examining the deformation time series of subsiding terrain with different subsidence levels, we also found that thaw subsidence was not restricted to the summer and autumn thawing times but could last until the following winter, and in this circumstance, the winter uplift was greatly weakened. Two import indices for indicating permafrost deformation properties, i.e., long-term deformation trend and seasonal deformation magnitude, were extracted by direct calculation and model approximations of deformation time series and compared with each other. The comparisons showed that the long-term velocity by different calculations was highly consistent, but the intra-annual deformation magnitudes by the model approximations were larger than those of the intra-annual highest-lowest elevation difference. The findings improve the understanding of deformation properties in the degrading permafrost environment.

Bounded rationality is one crucial component in human behaviours. It plays a key role in the typical collective behaviour of evacuation, in which heterogeneous information can lead to deviations from optimal choices. In this study, we propose a framework of deep learning to extract a key dynamical parameter that drives crowd evacuation behaviour in a cellular automaton (CA) model. On simulation data sets of a replica dynamic CA model, trained deep convolution neural networks (CNNs) can accurately predict dynamics from multiple frames of images. The dynamical parameter could be regarded as a factor describing the optimality of path-choosing decisions in evacuation behaviour. In addition, it should be noted that the performance of this method is robust to incomplete images, in which the information loss caused by cutting images does not hinder the feasibility of the method. Moreover, this framework provides us with a platform to quantitatively measure the optimal strategy in evacuation, and this approach can be extended to other well-designed crowd behaviour experiments.

Increasing evidences suggest that angiotensin (Ang) II participates in the pathogenesis of endothelial dysfunction (ED) through multiple signaling pathways, including angiotensin type 1 receptor (AT1R) mediated NADPH oxidase (Nox)/reactive oxygen species (ROS) signal transduction. However, the detailed mechanism is not completely understood. In this study, we reported that AngII/AT1R-mediated activated protein phosphatase 2A (PP2A) downregulated endothelial nitric oxide synthase (eNOS) phosphorylation via Nox/ROS pathway. AngII treatment reduced the levels of phosphorylation of eNOS Ser1177 and nitric oxide (NO) content along with phosphorylation of PP2Ac (PP2A catalytic subunit) Tyr307, meanwhile increased the PP2A activity and ROS production in human umbilical vein endothelial cells (HUVECs). These changes could be impeded by AT1R antagonist candesartan (CAN). The pretreatment of 10−8 M PP2A inhibitor okadaic acid (OA) reversed the levels of eNOS Ser1177 and NO content. Similar effects of AngII on PP2A and eNOS were also observed in the mesenteric arteries of Sprague-Dawley rats subjected to AngII infusion via osmotic minipumps for 2 weeks. We found that the PP2A activity was increased, but the levels of PP2Ac Tyr307 and eNOS Ser1177 as well as NO content were decreased in the mesenteric arteries. The pretreatments of antioxidant N-acetylcysteine (NAC) and apocynin (APO) abolished the drop of the levels of PP2Ac Tyr307 and eNOS Ser1177 induced by AngII in HUVECs. The knockdown of p22phox by small interfering RNA (siRNA) gave rise to decrement of ROS production and increment of the levels of PP2Ac Tyr307 and eNOS Ser1177. These results indicated that AngII/AT1R pathway activated PP2A by downregulating its catalytic subunit Tyr307 phosphorylation, which relies on the Nox activation and ROS production. In summary, our findings indicate that AngII downregulates PP2A catalytic subunit Tyr307 phosphorylation to activate PP2A via AT1R-mediated Nox/ROS signaling pathway. The activated PP2A further decreases levels of eNOS Ser1177 phosphorylation and NO content leading to endothelial dysfunction.

Background/Aims: Intrahepatic cholangiocarcinoma (ICC) is a complicated condition, with difficult diagnosis and poor prognosis. The expression and clinical significance of the farnesoid X receptor (FXR), an endogenous receptor of bile acids, in ICC is not well understood. Methods: Western blotting and immunochemical analyses were used to determine the levels of FXR in 4 cholangiocarcinoma cell lines, a human intrahepatic biliary epithelial cell line (HIBEpic) and 322 ICC specimens, respectively, while quantitative reverse transcription polymerase chain reaction was used to detect the mRNA levels of FXR in cholangiocarcinoma cell lines. We evaluated the prognostic value of FXR expression and its association with clinical parameters. We determined the biological significance of FXR in ICC cell lines by agonist-mediated activation and lentivirus-mediated silence. IL-6 expression was tested by an enzyme-linked immunosorbent assay and flow cytometry. In vitro, cell proliferation was examined by Cell Counting Kit-8, migration and invasion were examined by wound healing and transwell assays; in vivo, tumor migration and invasion were explored in NOD-SCID mice. Results: FXR was downregulated in ICC cell lines and clinical ICC specimens. Loss of FXR was markedly correlated with aggressive tumor phenotypes and poor prognosis in patients with ICC. Moreover, FXR expression also had significant prognostic value in carbohydrate antigen 19-9 (CA19-9) negative patients. The expression of FXR was negatively correlated with IL-6 levels in clinical ICC tissues. FXR inhibited the proliferation, migration, invasion and epithelial mesenchymal transition (EMT) of ICC cells via suppression of IL-6 in vitro. Obeticholic acid, an agonist of FXR, inhibited IL-6 production, tumor growth and lung metastasis of ICC in vivo. Conclusions: FXR could be a promising ICC prognostic biomarker, especially in CA19-9 negative patients with ICC. FXR inhibits the tumor growth and metastasis of ICC via IL-6 suppression.

Previous findings have shown that impulsivity and Behavioral Inhibition/Approach System (BIS/BAS) have substantial effects on adolescents’ Internet addiction, but the mechanisms underlying these associations and gender differences in these effects have received little attention. We examined the mediating effects of coping styles from impulsivity, and BIS/BAS to Internet addiction as well as gender differences in these associations. A total of 416 Chinese adolescents were examined using a cross-sectional survey involving Young’s Diagnostic Questionnaire for Internet Addiction, Barratt Impulsiveness Scale, BIS/BAS scales, and Coping Style Scale for Middle School Students. The data were analyzed using the independent sample t-test, chi-square test, Pearson correlation, and structure equation modeling. The results from the multiple-group (by adolescent gender) structural model analysis revealed that both impulsivity (p < 0.001) and BIS (p = 0.001) directly predicted positive Internet addiction in girls, while both impulsivity (p = 0.011) and BAS (p = 0.048) directly predicted positive Internet addiction in boys. Furthermore, emotion-focused coping mediated the relationship between impulsivity and Internet addiction (β = 0.080, 95% CI: 0.023–0.168) and the relationship between BIS and Internet addiction (β = 0.064, 95% CI: 0.013–0.153) in girls, while in boys, problem-focused coping and emotion-focused coping mediated the association between impulsivity and Internet addiction (β = 0.118, 95% CI: 0.031–0.251; β = 0.065, 95% CI: 0.010–0.160, respectively) and problem-focused coping mediated the association between BAS and Internet addiction [β = −0.058, 95% CI: (−0.142)–(−0.003)]. These findings extend our insight into the mechanisms underlying the associations among impulsivity, BIS/BAS, and Internet addiction in adolescents and suggest that gender-sensitive training approaches to decrease adolescents’ Internet addiction are indispensable. These interventions should focus on the different gender predictors of adolescent Internet addiction and on the development of specific coping styles for boys and girls respectively.

We explore the features of the UA(1) and chiral symmetry breaking of the Nambu–Jona-Lasinio model without the Kobayashi–Maskawa–'t Hooft determinant term in the presence of a parallel electromagnetic field. We show that the electromagnetic chiral anomaly can induce both finite neutral pion condensate and isospin-singlet pseudo-scalar η condensate and thus modifies the chiral symmetry breaking pattern. In order to characterize the strength of the UA(1) symmetry breaking, we evaluate the susceptibility associated with the UA(1) charge. The result shows that the susceptibility contributed from the chiral anomaly is consistent with the behavior of the corresponding η condensate. The spectra of the mesonic excitations are also studied.

Neonatal hypoxic-ischemic (HI) injury is a major cause of neonatal death and neurological dysfunction. H2S has been shown to protect against hypoxia-induced injury and apoptosis of neurons. L-Cysteine is catalyzed by cystathionine-β-synthase (CBS) in the brain and sequentially produces endogenous H2S. The present study was designed to investigate whether L-Cysteine could attenuate the acute brain injury and improve neurobehavioral outcomes following HI brain injury in neonatal mice by releasing endogenous H2S. L-Cysteine treatment significantly attenuated brain edema and decreased infarct volume and neuronal cell death, as shown by a decrease in the Bax/Bcl-2 ratio, suppression of caspase-3 activation, and reduced phosphorylation of Akt and ERK at 72 h after HI. Additionally, L-Cysteine substantially up-regulated NF-E2-related factor 2 and heme oxygenase-1 expression. L-Cysteine also decreased endoplasmic reticulum (ER) stress-associated pro-apoptotic protein expression. Furthermore, L-Cysteine had long-term effects by protecting against the loss of ipsilateral brain tissue and improving neurobehavioral outcomes. Importantly, pre-treatment with a CBS inhibitor significantly attenuated the neuroprotection of L-Cysteine on HI insult. Thus, L-Cysteine exerts neuroprotection against HI-induced injury in neonates via the CBS/H2S pathway, mediated in part by anti-apoptotic effects and reduced oxidative stress and ER stress. Thus, L-Cysteine may be a promising treatment for HI.

Spatial information of particle size fractions (PSFs) is primary for understanding the thermal state of permafrost in the Qinghai-Tibet Plateau (QTP) in response to climate change. However, the limitation of field observations and the tremendous spatial heterogeneity hamper the digital mapping of PSF. This study integrated log-ratio transformation approaches, variable searching methods, and machine learning techniques to map the surficial soil PSF distribution of two typical permafrost regions. Results showed that the Boruta technique identified different covariates but retained those covariates of vegetation and land surface temperature in both regions. Variable selection techniques effectively decreased the data redundancy and improved model performance. In addition, the spatial distribution of soil PSFs generated by four log-ratio models presented similar patterns. Isometric log-ratio random forest (ILR-RF) outperformed the other models in both regions (i.e., R2 ranged between 0.36 to 0.56, RMSE ranged between 0.02 and 0.10). Compared with three legacy datasets, our prediction better captured the spatial pattern of PSFs with higher accuracy. Although this study largely improved the accuracy of spatial distribution of soil PSFs, further endeavors should also be made to improve model accuracy and interpretability for a better understanding of the interaction and processes between environmental predictors and soil PSFs at permafrost regions.