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Abstract Peripheral CD8+ T cell number is tightly controlled but the precise molecular mechanism regulating this process is still not fully understood. In this study, we found that epilepsy patients with loss of function mutation of DEPDC5 had reduced peripheral CD8+ T cells, and DEPDC5 expression positively correlated with tumor-infiltrating CD8+ T cells as well as overall cancer patient survival, indicating that DEPDC5 may control peripheral CD8+ T cell homeostasis. Significantly, mice with T cell-specific Depdc5 deletion also had reduced peripheral CD8+ T cells and impaired anti-tumor immunity. Mechanistically, Depdc5-deficient CD8+ T cells produced high levels of xanthine oxidase and lipid ROS due to hyper-mTORC1-induced expression of ATF4, leading to spontaneous ferroptosis. Together, our study links DEPDC5-mediated mTORC1 signaling with CD8+ T cell protection from ferroptosis, thereby revealing a novel strategy for enhancing anti-tumor immunity via suppression of ferroptosis.

Machine learning is widely recognized as a promising data-driven modeling technique for the model-based control and optimization of building energy systems. However, the generalizability of data-driven models often faces significant challenges, as the available training data from building operations usually only covers a limited range of working conditions. Active learning can proactively test unseen and informative working conditions to enrich the training set by adding new data samples, leading to improved generalization performance of data-driven models. A novel distance and information density-based sample strategy is developed that accounts for the real-time status of building operation and outdoor environment. Based on Mahalanobis distance, this strategy determines the sampling value of an unlabeled sample (unseen working condition) by assessing its similarity to both the training samples and other unlabeled samples. As collecting sufficiently representative samples can be difficult, costly, and time-consuming, a distance-based sampling cost metric is proposed to compare the efficiency of different sampling methods, considering the detrimental effects of the actively sampling process on the normal operation of building energy systems. This paper presents a comprehensive and in-depth comparison of five active learning methods, including one incorporating the distance-based sampling strategy, by conducting data experiments on the data collected from the cooling towers of a real high-rise building. The results show that active learning can effectively identify informative data samples and improve the generalization performance of data-driven models. The research outcomes are valuable for enhancing AI-enabled data-driven modeling of building energy systems with substantial decreases in costs on data sampling.

Compared with lowlander migrants, native Tibetans have a higher reproductive success at high altitude though the underlying mechanism remains unclear. Here, we compared the transcriptome and histology of full-term placentas between native Tibetans and Han migrants. We found that the placental trophoblast shows the largest expression divergence between Tibetans and Han, and Tibetans show decreased immune response and endoplasmic reticulum stress. Remarkably, we detected a sex-biased expression divergence, where the male-infant placentas show a greater between-population difference than the female-infant placentas. The umbilical cord plays a key role in the sex-biased expression divergence, which is associated with the higher birth weight of the male newborns of Tibetans. We also identified adaptive histological changes in the male-infant placentas of Tibetans, including larger umbilical artery wall and umbilical artery intima and media, and fewer syncytial knots. These findings provide valuable insights into the sex-biased adaptation of human populations, with significant implications for medical and genetic studies of human reproduction.

IntroductionThe effectiveness of ultra-high pressure (UHP) technology in retaining the flavor of fresh fruit and vegetable juices has been acknowledged in recent years. Along with previously hypothesized conclusions, the improvement in melon juice flavor may be linked to the reduction of its surface tension through UHP.MethodsIn this paper, the particle size, free-water percentage, and related thermodynamic parameters of melon juice were evaluated in a physical point for a deeper insight.ResultsThe results showed that the UHP treatment of P2-2 (200 MPa for 20 min) raised the free water percentage by 7,000 times than the other treatments and both the melting enthalpy, binding constant and Gibbs free energy of P2-2 were minimized. This significantly increased the volatility of characteristic aromatic compounds in melon juice, resulting in a 1.2-5 times increase in the content of aromatic compounds in the gas phase of the P2-2 group compared to fresh melon juice.

Abstract Targeting tumor-infiltrating regulatory T cells (Tregs) is an efficient way to evoke an anti-tumor immune response. However, how Tregs maintain their fragility and stability remains largely unknown. IFITM3 and STAT1 are interferon-induced genes that play a positive role in the progression of tumors. Here, we showed that IFITM3-deficient Tregs blunted tumor growth by strengthening the tumor-killing response and displayed the Th1-like Treg phenotype with higher secretion of IFNγ. Mechanistically, depletion of IFITM3 enhances the translation and phosphorylation of STAT1. On the contrary, the decreased IFITM3 expression in STAT1-deficient Tregs indicates that STAT1 conversely regulates the expression of IFITM3 to form a feedback loop. Blocking the inflammatory cytokine IFNγ or directly depleting STAT1-IFITM3 axis phenocopies the restored suppressive function of tumor-infiltrating Tregs in the tumor model. Overall, our study demonstrates that the perturbation of tumor-infiltrating Tregs through the IFNγ-IFITM3-STAT1 feedback loop is essential for anti-tumor immunity and constitutes a targetable vulnerability of cancer immunotherapy.

Oil–air lubrication technology is commonly utilized in the lubrication design of traditional components to reduce friction between contact pairs. This study focuses on testing the point-contact friction pairs of two quantitative valves using a self-made oil–air lubrication traction force machine with a G95Cr18 disk and ball as the friction pairs. The test data are analyzed using a four-parameter exponential model. Additionally, a calculation model of the oil–air lubrication flow field is established, defining boundary conditions and conducting flow field simulation analysis. The results of the ball and disk test show that the traction coefficient increases with load and decreases with entrainment speed. Furthermore, when the air-speed is 12 m/s, the traction coefficient is lower for the oil supply of 6 mL/min than for the oil supply of 1.5 mL/min. According to CFD analysis, the volume fraction of the oil phase in the contact area increases with the increase of entrainment speed when the slip–roll ratio is 0.1. The theoretical values from the four-parameter exponential model align well with the experimental results, and the fitting accuracy is higher than 0.95.

Abstract Background Domestication and introduction of dairy animals facilitated the permanent human occupation of the Tibetan Plateau. Yet the history of dairy pastoralism in the Tibetan Plateau remains poorly understood. Little is known how Tibetans adapted to milk and dairy products. Results We integrated archeological evidence and genetic analysis to show the picture that the dairy ruminants, together with dogs, were introduced from West Eurasia into the Tibetan Plateau since ~ 3600 years ago. The genetic admixture between the exotic and indigenous dogs enriched the candidate lactase persistence (LP) allele 10974A > G of West Eurasian origin in Tibetan dogs. In vitro experiments demonstrate that − 13838G > A functions as a LP allele in Tibetans. Unlike multiple LP alleles presenting selective signatures in West Eurasians and South Asians, the de novo origin of Tibetan-specific LP allele − 13838G > A with low frequency (~ 6–7%) and absence of selection corresponds − 13910C > T in pastoralists across eastern Eurasia steppe. Conclusions Results depict a novel scenario of genetic and cultural adaptations to diet and expand current understanding of the establishment of dairy pastoralism in the Tibetan Plateau.

Rolling element bearings are essential components in modern mechanical equipment, providing crucial support for rotating parts. Hybrid ceramic ball bearings, consisting of steel rings and ceramic balls, have gained popularity in high-speed machinery to enhance performance. These bearings offer advantages such as longer fatigue life, improved performance, and higher speeds. Extensive research by scholars has been conducted to promote the wider adoption of hybrid ceramic ball bearings. This paper compiles relevant studies on hybrid ceramic bearings, organizing literature related to their lifetime, arranging literature pertaining to their performance analysis from the perspective of analytical methods, and collating literature on their lubrication techniques from the angle of lubrication methods. This paper covers research on lifetime modeling, fatigue spalling, wear, mechanical and tribological properties, dynamic performance, thermal analysis, temperature considerations, and lubrication techniques of hybrid ceramic ball bearings. The aim is to provide readers and researchers with a comprehensive overview of these innovative bearings.

Abstract Endo-lysosomes transport along microtubules and clustering in the perinuclear area are two necessary steps for microbes to activate specialized phagocyte functions. We report that RUN and FYVE domain-containing protein 3 (RUFY3) exists as two alternative isoforms distinguishable by the presence of a C-terminal FYVE domain and by their affinity for phosphatidylinositol 3-phosphate on endosomal membranes. The FYVE domain-bearing isoform (iRUFY3) is preferentially expressed in primary immune cells and up-regulated upon activation by microbes and Interferons. iRUFY3 is necessary for ARL8b + /LAMP1+ endo-lysosomes positioning in the pericentriolar organelles cloud of LPS-activated macrophages. We show that iRUFY3 controls macrophages migration, MHC II presentation and responses to Interferon-γ, while being important for intracellular Salmonella replication. Specific inactivation of rufy3 in phagocytes leads to aggravated pathologies in mouse upon LPS injection or bacterial pneumonia. This study highlights the role of iRUFY3 in controlling endo-lysosomal dynamics, which contributes to phagocyte activation and immune response regulation.

Opportunistic networks are self-organizing dynamic networks that use the communication opportunities presented by node movement to enable data delivery. Due to the indirect nature of inter-node connections and dynamic topology, opportunistic networks are vulnerable to malicious attacks, which poses a great challenge to their security. In this paper, we first propose a trust-based model for the secure routing of opportunistic networks (TBMOR), which incorporates forwarding positive degree (FP) and node activity degree (NA) into the calculation of trust value, evaluates nodes in the network by a dynamic combination of direct trust and indirect trust, and then optimizes the next node list using trust values and pruning strategies. Secondly, this paper extends the network life cycle by dynamically setting up energy thresholds to reduce network redundancy by dynamically partitioning the number of replicas using trust values.Simulation results show that compared to other routers, TBMOR can effectively resist malicious attacks, has a higher message delivery rate and lower transmission latency than other routers.

Abstract Background Tibetans are genetically adapted to high-altitude environments. Though many studies have been conducted, the genetic basis of the adaptation remains elusive due to the poor reproducibility for detecting selective signatures in the Tibetan genomes. Results Here, we present whole-genome sequencing (WGS) data of 1001 indigenous Tibetans, covering the major populated areas of the Qinghai–Tibetan Plateau in China. We identify 35 million variants, and more than one-third of them are novel variants. Utilizing the large-scale WGS data, we construct a comprehensive map of allele frequency and linkage disequilibrium and provide a population-specific genome reference panel, referred to as 1KTGP. Moreover, with the use of a combined approach, we redefine the signatures of Darwinian-positive selection in the Tibetan genomes, and we characterize a high-confidence list of 4320 variants and 192 genes that have undergone selection in Tibetans. In particular, we discover four new genes, TMEM132C, ATP13A3, SANBR, and KHDRBS2, with strong signals of selection, and they may account for the adaptation of cardio-pulmonary functions in Tibetans. Functional annotation and enrichment analysis indicate that the 192 genes with selective signatures are likely involved in multiple organs and physiological systems, suggesting polygenic and pleiotropic effects. Conclusions Overall, the large-scale Tibetan WGS data and the identified adaptive variants/genes can serve as a valuable resource for future genetic and medical studies of high-altitude populations.

Delineating the cellular composition of tumour boundaries in spatial transcriptomics (ST) data is challenging. Here, the authors develop Cottrazm to integrate ST with histological imaging and single-cell data, identify the malignant and non-malignant tissue boundaries, deconvolute cell-type composition, and reconstruct cell type-specific gene expression profiles.

With the innovation of wireless communication technology and the surge of data in mobile networks, traditional routing strategies need to be improved. Given the shortcomings of existing opportunistic routing strategies in transmission performance and security, this paper proposes a community opportunistic routing decision-making method based on the trust model. This algorithm calculates the node’s trust value through the node’s historical forwarding behavior and then calculates the node’s trust value based on the trust model. Thresholds and trust attenuation divide dynamic security communities. For message forwarding, nodes in the security community are prioritized as next-hop relay nodes, thus ensuring that message delivery is always in a safe and reliable environment. On this basis, better relay nodes are further selected for message forwarding based on the node centrality, remaining cache space, and remaining energy, effectively improving the message forwarding efficiency. Through node trust value and community cooperation, safe and efficient data transmission is achieved, thereby improving the transmission performance and security of the network. Through comparison of simulation and opportunistic network routing algorithms, compared with traditional methods, this strategy has the highest transmission success rate of 81% with slightly increased routing overhead, and this algorithm has the lowest average transmission delay.

In the ultra-low temperature environment, the material properties of the bearing change, which puts forward higher requirements for the dynamic performance of the bearing cage. The bearings operating in ultra-low temperature environments commonly use solid lubricants. This study first focused on measuring the traction coefficients of molybdenum disulfide (MoS2) solid lubricant in a nitrogen atmosphere, and the Gupta fitting model is constructed to derive the traction equation. Subsequently, the dynamic differential equation of angular contact ball bearings was established, and the stability of the bearing cage in a nitrogen environment was simulated and analyzed based on the dynamic model. The accuracy of the simulation model was verified through comparison. The results show that less than 10% of errors exist between the experimental data and the traction curve fitted by the Gupta model, and the stability of the cage is closely related to operating parameters and bearing structure parameters. Cage stability increases with axial load but decreases with radial load. The cage stability is optimal when the radial internal clearance of the bearing is approximately 0.06 mm. When other conditions remain unchanged and the ratio of the cage pocket hole gap to the cage guide surface gap is 0.2, the cage stability is the best. The research results will provide a foundation for the design and application of solid-lubricated angular contact ball bearings in ultra-low temperature environments.

With the advancement of industries such as high-speed railways, new energy vehicles, and wind power, bearings are frequently exposed to various electric field environments, leading to the need for lubricating oil films of bearings to withstand voltage. One of the major issues caused by the breakdown discharge process of the lubricating oil film in bearings is the generation of local instantaneous high temperatures. This temperature rise is a key factor contributing to problems such as high operating temperature of bearings, surface damage in the contact area, and degradation of lubrication performance. This research article focuses on the comprehensive influence of bearing friction and electrical factors. It establishes a heat source calculation model and a temperature field simulation model specifically for current-carrying bearings. This study analyzes both the overall temperature rise of bearings and the local temperature rise resulting from breakdown discharge. Furthermore, the accuracy of the simulation analysis is verified through experiments. The temperature field simulation and experimental results consistently indicate that electrical environmental factors can cause an increase in the overall temperature rise of a bearing. Additionally, the breakdown and discharge of the lubricating oil film generate local instantaneous high temperatures in the contact area of the bearing.

Summary: Tibetans are the ideal population to study genetic adaptation in extreme environments. Here, we performed systematic phenotyping of 11,880 highlanders, covering 133 quantitative traits of 13 organ systems. We provided a comprehensive phenotypic atlas by comparing altitude adaptation and altitude acclimatization. We found the differences between adaptation and acclimatization are quantitative rather than qualitative, with a whole-system “blunted effect” seen in the adapted Tibetans. We characterized twelve different functional changes between adaptation and acclimatization. More importantly, we established a landscape of adaptive phenotypes of indigenous Tibetans, including 45 newly identified Tibetan adaptation-nominated traits, involving specific changes of Tibetans in internal organ state, metabolism, eye morphology, and skin pigmentation. In addition, we observed a sex-biased pattern between altitude acclimatization and adaptation. The generated atlas of phenotypic landscape provides new insights into understanding of human adaptation to high-altitude environments, and it serves as a valuable blueprint for future medical and physiological studies.

Vehicle Ad Hoc Networks (VANETs) can help reduce traffic accidents and improve road safety by broadcasting Emergency Messages (EMs) between vehicles in advance so that the vehicle can take action to avoid accidents. However, its advantages are often compromised by factors such as high mobility, uneven nodes distribution, and signal attenuation, resulting in lower reliability and higher delay in the delivery of EMs. Besides, because of its open and mobility, VANETs are vulnerable to cyber security threats and are prone to multiple malicious attacks in the network. Malicious nodes can join the set of candidate forwarding nodes through collusion and identity forgery, which poses a serious challenge to EMs forwarding. In order to resolve the problems above, this paper proposes a geographic routing strategy to deliver EMs based on trusted nodes, focusing on measuring the reliability of link quality and node quality. The link quality between nodes is evaluated by measuring the actual transmission cost and the link signal-to-noise ratio to minimize the possible link interruption; at the same time, the node trust value is introduced to measure the credibility of the node and filter out the possible malicious nodes in the network. The research results show that the protocol is suitable for dense and sparse traffic conditions, can detect and identify malicious nodes, and has significant performance improvements in message delivery rate, end-to-end delay, and network throughput.

Summary: The role of innate lymphoid cells (ILCs)—including natural killer cells, helper-like ILC1s, ILC2s, ILC3s, and lymphoid tissue inducers—in human cancer is still poorly understood due to the scarcity of cell number. To address this, we present a protocol to analyze or purify ILCs from human blood, adjacent intestine, and colorectal tumor tissue. We describe steps for tissue and blood treatment, density centrifugation, antibody staining, and cell sorting.For complete details on the use and execution of this protocol, please refer to Qi et al. (2021).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Aerospace bearings need to withstand the low-temperature environment of space, which will cause changes in the internal lubrication state of the bearings. This article aims to assess the traction properties of aerospace lubricants under low-temperature micro-oil droplet (hereinafter referred to as ‘micro-oil’) supply conditions, and provide a lubrication theoretical basis for studying the motion characteristics of aerospace bearings in a low-temperature environment. An experimental study on the low-temperature micro-oil traction properties of high-speed bearing lubricants was conducted on a specially designed aerospace bearing lubricant traction characteristic tester. A modified Herschel–Bulkley model (modified H–B model) was presented based on test data analysis, and the fitting results were compared with the Tevaarwerk–Johnson model (T–J model). The findings demonstrated that the traction coefficient of this lubricant decreased at a higher load and entrainment velocity, and decreased with a decreasing inlet oil temperature from 0 °C to −50 °C. The modified H–B model accurately fitted the test data and was suitable for the engineering traction coefficient calculation of lubricants and high viscosities at low temperatures. This paper can provide fundamental information for analyzing aerospace bearing friction torque variation.

Japanese sardine (Sardinops melanostictus) is one of the main species caught in the high seas purse seine fishery in the Northwest Pacific Ocean and its resources gradually recovered in recent years. This paper used the historical yearly catch data of Japanese sardine from 1990 to 2021 and biological data (manily for body length) in April-November 2020–2022 to assess its maximum sustainable yield (MSY) and stock resource status using Catch-MSY and LBB models, respectively. And then based on the evaluation results of Japanese sardine MSY, we analyzed the stock management strategies on this species by the Kobe II Strategy Matrix (K2SM). The results were as follows: (1) the Catch-MSY model assessed its MSY as 170.0 × 104 t with a 95 % confidence interval of 134.1 × 104 t ∼ 211.4 × 104 t; (2) the LBB model assessed the biological parameters for the last three years (2020–2022) with the interval range of Lc/Lc_opt was 0.76–0.95, B/BMSY was 0.79–0.84, and B/B0 was 1.9–2.3, which indicate that Japanese sardine resource is healthy and recovering; (3) the results of these two models and the Kobe Ⅱ management strategy matrix are combined to predict future resource status probability values. The management target range for the medium term (5-10 years) should be set 100 % TAC to MSY values, i.e., 102.0 × 104 t–170.0 × 104 t as TAC, and for the long term (10–20 years) can be set to 120 % TAC to MSY values, i.e., 122.4 × 104 t–170.0 × 104 t. Japanese sardine fishery resource can be sustainably used on a longer time scale.

Tumour microenvironment profiling during colorectal cancer progression may enable the discovery of therapeutic targets. Here, single cell and spatial RNA sequencing of tumour and adjacent normal tissues reveals an interaction between FAP + fibroblasts and SPP1 + macrophages that could be disrupted as an immunotherapy strategy.

Bearings operating in ultra-low-temperature environments are commonly lubricated with solid lubricants. This study first focused on measuring the traction coefficients of molybdenum disulfide (MoS2) solid lubricant under various working conditions. Based on this data, the friction power consumption of the bearings was calculated and analyzed using a dynamic model. Additionally, experimental verification of the bearing friction power consumption in ultra-low temperature environments was conducted. The research findings will serve as a foundation for the application of solid lubrication bearings in ultra-low-temperature environments.

BackgroundPrevious studies showed an increase in HIV prevalence among young men who have sex with men aged 25 years or younger in China. ObjectiveThis study aimed to assess HIV prevalence and associated factors among young men who have sex with men in the Guangxi Zhuang Autonomous Region. MethodsThis study was conducted in 4 cities (Guilin, Liuzhou, Beihai, and Nanning) in the Guangxi Zhuang Autonomous Region between June 2014 and May 2016. Participants were reached through web-based and site recruitment approaches. Laboratory tests were performed to detect HIV and syphilis infections. A self-administered questionnaire was used to collect data from 632 eligible young men who have sex with men. ResultsThe prevalence of HIV and syphilis was 9.3% (59/632) and 11.4% (72/632), respectively. Multivariable logistic analysis showed that ethnic minority (adjusted odds ratio [AOR] for Han Chinese vs other minorities 0.28, 95% CI 0.11-0.71, P=.007), receptive sexual positioning in the past 6 months (AOR 2.94, 95% CI 1.32-6.53, P=.008), current syphilis infection (AOR for individuals without vs those with infection 0.38, 95% CI 0.19-0.75, P=.005), inconsistent condom use in the past 6 months (AOR 1.91, 95% CI 1.06-3.45, P=.03), and psychotropic drug use before last anal intercourse (AOR 16.70, 95% CI 2.34-119.18, P=.005) were independently associated with HIV infection. ConclusionsThere is an urgent need to scale up HIV and syphilis interventions in young men who have sex with men. Some subgroups might need specific attention for HIV prevention, including ethnic minority men, individuals with a history of sexually transmitted infections, and individuals who have been engaging in receptive anal sex.

Systems genetics holds the promise to decipher complex traits by interpreting their associated SNPs through gene regulatory networks derived from comprehensive multi-omics data of cell types, tissues, and organs. Here, we propose SpecVar to integrate paired chromatin accessibility and gene expression data into context-specific regulatory network atlas and regulatory categories, conduct heritability enrichment analysis with genome-wide association studies (GWAS) summary statistics, identify relevant tissues, and estimate relevance correlation to depict common genetic factors acting in the shared regulatory networks between traits. Our method improves power upon existing approaches by associating SNPs with context-specific regulatory elements to assess heritability enrichments and by explicitly prioritizing gene regulations underlying relevant tissues. Ablation studies, independent data validation, and comparison experiments with existing methods on GWAS of six phenotypes show that SpecVar can improve heritability enrichment, accurately detect relevant tissues, and reveal causal regulations. Furthermore, SpecVar correlates the relevance patterns for pairs of phenotypes and better reveals shared SNP-associated regulations of phenotypes than existing methods. Studying GWAS of 206 phenotypes in UK Biobank demonstrates that SpecVar leverages the context-specific regulatory network atlas to prioritize phenotypes’ relevant tissues and shared heritability for biological and therapeutic insights. SpecVar provides a powerful way to interpret SNPs via context-specific regulatory networks and is available at https://github.com/AMSSwanglab/SpecVar, copy archived at swh:1:rev:cf27438d3f8245c34c357ec5f077528e6befe829.

The mammalian intestine is an organ that can be spatially defined by two axes: longitudinal and vertical. Such anatomical structure ensures the maintenance of a relatively immuno-quiescent and proliferation-promoting crypt for intestinal stem cell differentiation while actively warding off the invading intestinal microbes at the villus tip during digestion and nutrient absorption. Such behavior is achieved by the fine coordination among intestinal epithelial cells, intestinal mesenchymal stromal cells and tissue-resident immune cells like myeloid cells and lymphocytes. Among these cell types resided in the colon, intestinal mesenchymal stromal cells are considered to be the essential link between epithelium, vasculature, neuronal system, and hematopoietic compartment. Recent advancement of single cell and spatial transcriptomics has enabled us to characterize the spatial and functional heterogeneity of intestinal mesenchymal stromal cells. These studies reveal distinctive intestinal mesenchymal stromal cells localized in different regions of the intestine with diverse functions including but not limited to providing cytokines and growth factors essential for different immune cells and epithelial cells which predict niche formation for immune function from the villus tip to the crypt bottom. In this review, we aim to provide an overall view of the heterogeneity of intestinal mesenchymal stromal cells, the spatial distribution of these cells along with their interaction with immune cells and the potential regulatory cytokine profile of these cell types. Summarization of such information may enrich our current understanding of the immuno-regulatory functions of the newly identified mesenchymal stromal cell subsets beyond their epithelial regulatory function.

Abstract SARS-CoV-2 outbreak has been declared by World Health Organization as a worldwide pandemic. However, there are many unknowns about the antigen-specific T-cell-mediated immune responses to SARS-CoV-2 infection. Here, we present both single-cell TCR-seq and RNA-seq to analyze the dynamics of TCR repertoire and immune metabolic functions of blood T cells collected from recently discharged COVID-19 patients. We found that while the diversity of TCR repertoire was increased in discharged patients, it returned to basal level ~1 week after becoming virus-free. The dynamics of T cell repertoire correlated with a profound shift of gene signatures from antiviral response to metabolism adaptation. We also demonstrated that the top expanded T cell clones (~10% of total T cells) display the key anti-viral features in CD8+ T cells, confirming a critical role of antigen-specific T cells in fighting against SARS-CoV-2. Our work provides a basis for further analysis of adaptive immunity in COVID-19 patients, and also has implications in developing a T-cell-based vaccine for SARS-CoV-2.

Abundant evidence has shown that the integration between urban rail transit system and urban land use planning is of key importance for cities’ sustainable development. For planners and city managers, it is essential to scientifically understand the influencing mechanisms between the functional orientations as well as physical locations of the transit stations and the land use patterns alongside. We established a measurement system for the potential of land parcels. Further, we evaluated the land potential alongside a specific subway line, and conducted interaction analysis for between passenger volumes and station-surrounding land mixing degrees. In the end, we sited the subway stations according to the distance constrains and compared the planning outputs from our methods and the plans proposed by the government section. The result is they basically matched with each other, except for some minor differences that could be explained rationally, and the functional orientations of these stations are similar.

To better develop and protect the pelagic fishery in the northwest Indian Ocean, China’s fishing enterprises have been producing pelagic fisheries in the said area for a long time. Based on the fishing log data of light falling gear in the northwest Indian Ocean from 2016 to 2020, this study analyzed the impact of different time scales on the catch rate and fishing ground center of gravity of light falling gear fishing grounds. We also explored the relationship between different time scales and catch per unit effort (CPUE) by using the fishing ground center of gravity, the Random Forest model (RF), and the generalized additive model (GAM). The results were shown as follows: (1) From 2016 to 2020, 76,576 t were captured, and 16,496 nets were operated; (2) The gravity center of fishing ground in the Northwest Indian Ocean moved to the northeast as a whole, and the monthly fishing ground gravity center changed first to the Southern and then to the northern; (3) RF model (R² = 0.709, RMSE = 0.2034, and prediction accuracy is 55.8%), which is better than the GAM model (R² = 0.632, RMSE = 0.2242, and prediction accuracy is 37.3%). In the RF model, the importance of time variables on CPUE was in the order of week, year, operation time, and lunar phase; in the GAM model, it was week, year, lunar phase, and operation time. On the whole, the importance of the long time scale (year, week) is greater than that of the short time scale (lunar phase and operation time). (4) The RF model and GAM model show that the most critical environmental variables were SST, DO, SSS, and Chla, and the least important were SSH, Δ50, and CV50. SST, Chla, and DO significantly impact pelagic fishing and CPUE and are critical reference indexes for predicting the Northwest Indian Ocean light falling gear fishing ground. (5) The 95% confidence interval showed that the suitable interval of time, space, and environmental variables in the RF model was much smaller than in the GAM model.

The paper mainly studied the temperature rise characteristics of under-race lubricated high-speed angular contact ball bearings under operational conditions from the perspective of dynamics. The steady-state calculation model of the bearing was established using a thermal network method in consideration of the influence factor of friction power consumption in bearing components based on a dynamic model. Following this, the steady-state change characteristics of the bearing were obtained by solving a thermal balance equation. Through this process, the influence laws of bearing rotation speed, oil supply, and environmental temperature on the friction temperature rise of the bearing were analyzed. Finally, the finite element analysis software ANSYS was employed to provide comparative verification. The results showed that the bearing temperature nonlinearly increased with the increase in inner ring rotation speed, and when it approached a certain critical value, the outer ring temperature exceeded the inner ring temperature. It had an obvious effect on controlling the temperature rise of the bearing inner ring by way of increasing the quantity and reducing the temperature of the lubricating oil supply. Comparative verification showed that the speed–temperature variation tendency from the dynamics-based thermal analysis well agrees with that of the finite element analysis.

Memory T cells are particularly reliant on fatty acid oxidation as a source of energy. Here the authors show this reliance is controlled by AMPK sensing of glucose deprivation that triggers SENP1-Sirt3 signalling, driving fatty acid oxidation and memory differentiation in T cells via deacetylation of YME1L1 to induce mitochondrial fusion.

Abstract. The battle between pathogens and hosts is an ongoing phenomenon that has been studied for centuries. Although multicellular organisms have developed sophisticated immune systems to defend against pathogens, pathogens are often able to successfully infect their hosts. To enhance their chance of survival, pathogens can hijack the host's metabolism, which serves as a critical control point that can potentially impact infections. Mammalian target of rapamycin (mTOR) is the nutrient sensor and central regulator of metabolism in innate and adaptive immune cells. Rapamycin, a drug targeting the mTOR pathway, has been widely used in clinical practice for decades and is relatively safe. However, some unexpected infections occur after long-term administration of rapamycin, indicating the presence of a close relationship between mTOR signaling and the infection process. In this manuscript, we briefly review the mTOR pathway and the current clinical use of rapamycin; we also summarize the role of the mTOR pathway in immune cell death, including apoptosis, necroptosis, pyroptosis, and ferroptosis, and its impact on anti-infection immunity. Finally, potential application of mTOR inhibitor in coronavirus disease 2019 clinical therapy is discussed.

Objectives: This study intended to investigate the dynamics of anti-spike (S) IgG and IgM antibodies in COVID-19 patients. Methods: Anti-S IgG/IgM was determined by a semi-quantitative fluorescence immunoassay in the plasma of COVID-19 patients at the manifestation and rehabilitation stages. The immunoreactivity to full-length S proteins, C-terminal domain (CTD), and N-terminal domain (NTD) of S1 fragments were determined by an ELISA assay. Clinical properties at admission and discharge were collected simultaneously. Results: The positive rates of anti-S IgG/IgM in COVID-19 patients were elevated after rehabilitation compared to the in-patients. Anti-S IgG and IgM were not apparent until day 14 and day ten, respectively, according to Simple Moving Average analysis with five days’ slide window deduction. More than 90% of the rehabilitation patients exhibited IgG and IgM responses targeting CTD-S1 fragments. Decreased total peripheral lymphocytes, CD4+ and CD8+ T cell counts were seen in COVID-19 patients at admission and recovered after the rehabilitation. Conclusions: Anti-S IgG and IgM do not appear at the onset with the decrease in T cells, making early serological screening less significant. However, the presence of high IgG and IgM to S1-CTD in the recovered patients highlights humoral responses after SARS-CoV-2 infection, which might be associated with efficient immune protection in COVID-19 patients.

Abstract Background Liquidambaris Fructus is the infructescences of Liquidambar formosana Hance and it has been used to treat some breast disease in Traditional Chinese Medicine. In the previous study we found the anti-breast cancer effect of triterpenoid in Liquidambaris Fructus. This study is a further investigation of the triterpenoids in Liquidambaris Fructus and aims to identify their anti-breast cancer targets, meanwhile, to estimate the rationality of the traditional applications of Liquidambaris Fructus. Methods Triterpenoids in Liquidambaris Fructus were isolated and their structures were identified by NMR spectrums. Potential targets of these triterpenoids were predicted using a reverse pharmacophore mapping strategy. Associations between these targets and the therapeutic targets of breast cancer were analyzed by constructing protein-protein interaction network, and targets played important roles in the network were identified using Molecular Complex Detection method. Binding affinity between the targets and triterpenoids was studied using molecular docking method. Gene ontology enrichment analysis was conducted to reveal the biological process and signaling pathways that the identified targets were involved in. Results Thirteen triterpenoids were identified and 6 of them were the first time isolated from Liquidambaris Fructus. Predicted ADME properties revealed a good druggability of these triterpenoids. We identified 18 protein targets which were closely related to breast cancer progression, especially triple-negative, basal-like or advanced stage breast cancers. The triterpenoids could bind with these targets as their inhibitors: hydrophobic skeleton is a favorable factor for them to stabilize at binding site and polar C17- or C3- substituent was necessary for binding. GO enrichment analysis indicated that inhibition of protein tyrosine kinases autophosphorylation might be the primary mechanism for the anti-breast cancer effect of the triterpenoids, and ErbB4 and EGFR were the most relevant targets. Conclusions The study revealed that triterpenoids from Liquidambaris Fructus might exert anti-breast cancer effect by directly inhibit multiple protein targets and signaling pathways, especially ErbB4 and EGFR and related pathways. This study also brings up another hint that the traditional applications of Liquidambaris Fructus on hypogalactia should be reassessed systematically because it might suppress rather than promote lactation by inhibiting the activity of ErbB4.

Neurofibromatosis type I (NF1) is characterized by prominent skeletal abnormalities mediated in part by aberrant ERK pathway activation due to NF1 loss-of-function. Here, the authors report the MEKK2 is a key mediator of this aberrant ERK activation and that MEKK2 inhibitors, including ponatinib, ameliorate skeletal defects in a mouse model of NF1.

Abstract Objective To evaluate the application value of different‐duration electrocardiograms (ECGs) in paroxysmal atrial fibrillation (AF) diagnosis. Methods A total of 220 patients with paroxysmal atrial fibrillation diagnosed by 24‐h dynamic electrocardiogram in our hospital from January 2019 to December 2020 were selected as the study subjects. The patients were monitored for 10 s, 5 min, and 24 hr, respectively. The results of the three different‐duration ECGs were compared and analyzed in order to evaluate their paroxysmal AF diagnosis value. Results Paroxysmal AF was detected in 18 patients (8.2%) with the 10‐s ECG; in 89 patients (40.5%) with the 5‐min ECG; and in 199 patients (90.5%) with the 24‐h dynamic ECG. Conclusion In patients with paroxysmal AF, ECGs with longer detection times had higher detection rates.

Tibetan adaptation to the high-altitude environment represents a case of natural selection during recent human evolution. Here the authors investigated the chromatin and transcriptional landscape of umbilical endothelial cells from Tibetan and Han Chinese donors and provide genome-wide characterization of the hypoxia regulatory network associated high-altitude adaptation.

As a consequence of expedited urban construction, large quantities of wastes are shipped every day. Because of the excessive pursuit of economic benefits by muck truck drivers and unreasonable transportation route choices, the accident rates of these drivers continue to increase. It is very important to optimize the safe transportation routing of muck trucks. In this paper, a safe transportation routing model was established to minimizes path safety risks and single driving time as the bi-objective, and two different situations for the optimal path of the model were analyzed. For the situation in which there are several short paths in the network, one of which is the path with the least safety risks, an exact algorithm, A*, was designed, and time complexity was analyzed. For the situation in which there is a single path or several shortest paths in the network but the path with the minimal path safety risks is not included in the set of shortest paths, an approximation algorithm, GA*, was designed, and time complexity and the approximation ratio were analyzed. Our experimental results demonstrated the validity of our developed model and approaches. Moreover, a case study is carried out on a real-case application related to the network in the Xi'an International Port District.

In vehicular ad hoc networks, opportunistic routing can effectively improve the reliability and throughput. However, opportunistic routing also has security issues. For example, malicious nodes can easily mix into node candidate sets, which can interfere with network performance. In this paper, a trust model based on node behavior is proposed for solving the problem of malicious nodes in the opportunistic routing and forwarding candidate set. The proposed trust model uses pruning and filtering mechanisms to remove malicious suggestions,and uses dynamic weight calculation methods to combine direct trust and indirect trust when calculating the comprehensive trust value, which can screen and filter low-trust nodes in the network. Then, combining the ETX (Expected Transmission Count) value and the node trust value, an opportunity routing algorithm based on trust model (BTOR) is proposed. Extensive simulation results represent that the algorithm can significantly improve the network performance and reduce the interference of malicious nodes to the network system.

Currently, a significant focus has been established on the privacy protection of multi-dimensional data publishing in various application scenarios, such as scientific research and policy-making. The K-anonymity mechanism based on clustering is the main method of shared-data desensitization, but it will cause problems of inconsistent clustering results and low clustering accuracy. It also cannot defend against several common attacks, such as skewness and similarity attacks at the same time. To defend against these attacks, we propose a K-anonymity privacy protection algorithm for multi-dimensional data against skewness and similarity attacks (KAPP) combined with t-closeness. Firstly, we propose a multi-dimensional sensitive data clustering algorithm based on improved African vultures optimization. More specifically, we improve the initialization, fitness calculation, and solution update strategy of the clustering center. The improved African vultures optimization can provide the optimal solution with various dimensions and achieve highly accurate clustering of the multi-dimensional dataset based on multiple sensitive attributes. It ensures that multi-dimensional data of different clusters are different in sensitive data. After the dataset anonymization, similar sensitive data of the same equivalence class will become less, and it eventually does not satisfy the premise of being theft by skewness and similarity attacks. We also propose an equivalence class partition method based on the sensitive data distribution difference value measurement and t-closeness. Namely, we calculate the sensitive data distribution’s difference value of each equivalence class and then combine the equivalence classes with larger difference values. Each equivalence class satisfies t-closeness. This method can ensure that multi-dimensional data of the same equivalence class are different in multiple sensitive attributes, and thus can effectively defend against skewness and similarity attacks. Moreover, we generalize sensitive attributes with significant weight and all quasi-identifier attributes to achieve anonymous protection of the dataset. The experimental results show that KAPP improves clustering accuracy, diversity, and anonymity compared to other similar methods under skewness and similarity attacks.

The off-target effects and on-target mutations of CRISPR editing in higher non-human primates are complex. Here the authors perform whole genome trio sequencing of rhesus monkeys and see no unexpected mutations.

Summary: Inflammatory bowel disease (IBD) is multi-factorial chronic intestinal inflammation driven by pathogenic T cells, among which a large portion of patients are resistant to current anti-inflammatory regimes. The mechanisms underlying colitis pathogenicity and drug resistance are not fully understood. Here, we demonstrate that RORα is highly expressed in active UC patients, particularly in those non-responsive to anti-TNF treatment. Rorα deficiency in CD4+ T cells greatly reduced colitis development. Mechanistically, RORα regulated T cell infiltration in colon and inhibited T cell apoptosis. Meanwhile, genome-wide occupancy and transcriptome analysis revealed that RORα promoted mTORC1 activation. mTORC1 signaling, also hyperactivated in active UC patients, is necessary for T cell-mediated colitis. Our results thus demonstrate a crucial role of the RORα-mTORC1 axis in CD4+ T cells in promoting IBD, which may be targeted in human patients.

We report here that RUFY4, a newly characterized member of the ‘RUN and FYVE domain-containing’ family of proteins previously associated with autophagy enhancement, is highly expressed in alveolar macrophages (AM). We show that RUFY4 interacts with mitochondria upon stimulation by microbial-associated molecular patterns of AM and dendritic cells. RUFY4 interaction with mitochondria and other organelles is dependent on a previously uncharacterized OmpH domain located immediately upstream of its C-terminal FYVE domain. Further, we demonstrate that rufy4 messenger RNA can be translated from an alternative translation initiation codon, giving rise to a N-terminally truncated form of the molecule lacking most of its RUN domain and with enhanced potential for its interaction with mitochondria. Our observations point towards a role of RUFY4 in selective mitochondria clearance in activated phagocytes.

Comparative genomic analysis of human and primate relatives can reveal important biological and evolutionary insights. Here, the authors present a long-read assembly of the Chinese rhesus macaque genome and identify ape-specific structural variants.

There are currently few AAV vectors that can effectively target the diverse cell types of the inner ear. Here the authors design AAV-ie for gene delivery to the mouse cochlea, targeting cochlear supporting cells.

Abstract Background Brucellosis is a worldwide zoonotic infectious disease that is transmitted in various ways and causes great harm to humans and animals. The brucellosis pathogen is Brucella, which mainly resides in macrophage cells and survives and replicates in host cells. However, the mechanisms underlying Brucella survival in macrophage cells have not been thoroughly elucidated to date. Peroxiredoxin 6 (Prdx6) is a bifunctional protein that shows not only GSH peroxidase activity but also phospholipase A2 activity and plays important roles in combating oxidative damage and regulating apoptosis. Results Recombinant mouse (Mus musculus) Prdx6 (MmPrdx6) was expressed and purified, and monoclonal antibodies against MmPrdx6 were prepared. Using the Brucella suis S2 strain to infect RAW264.7 murine macrophages, the level of intracellular Prdx6 expression first decreased and later increased following infection. Overexpressing Prdx6 in macrophages resulted in an increase in B. suis S2 strain levels in RAW264.7 cells, while knocking down Prdx6 reduced the S2 levels in cells. Conclusions Host Prdx6 can increase the intracellular survival of B. suis S2 strain and plays a role in Brucella infection.

This study aimed to test the friction coefficient of cryogenic bearing lubrication materials. A ball-on-disc type friction tester was developed in our lab using air bearings that could simulate the movement of cryogenic bearings under sliding-rolling contact. The tester is equipped with a temperature-controlled chamber to provide a minimum −175 °C low-temperature environment. Using air bearings is an important technique to reduce the base friction of the tester measurement system and ensure the accuracy of the friction coefficient measurement. The friction coefficients of the Ag coating and the PTFE coating were measured at different sliding-rolling velocities on this tester, and the results showed that the friction coefficient curves agreed well with the Gupta sliding model. The developed tester will provide important data for the dynamic analysis and life evaluation of the cryogenic bearings.

Based on a dynamic analysis of rolling bearings, the equations for rocker arm full-type needle bearings were established by considering the traction coefficients of FVA-M reference lubricating oil, and then they were solved by the GSTIFF (Gear Stiff) integer algorithm with variable steps. The influence of working conditions on friction power consumption and the lubricant’s convective coefficients were investigated. Then, on the basis of the heat generation and heat transfer mechanisms, the frictional power consumption was used as the boundary condition of the bearings’ simulation model. Finally, temperature fields were calculated by the finite element method. The results showed that the overall value of frictional power consumption increased gradually with the increase in either the radial load or the rotation speed. The presence or absence of lubricating oil film in the contact area affected the heat conduction of the bearing, resulting in a temperature difference. Compared with the temperature of the radial load exerted on the bearing, the maximum temperature was more sensitive to the variations in the rotation speed. When running under the conditions of a fatigue life test, the steady-state temperature value of the bearing gradually decreased from the outer raceway to the needle roller and the outer ring surface, and then to the central shaft. The maximum temperature rise was 25.9 °C relative to the ambient temperature.

LncRNA H19 has been shown to be aberrantly expressed in different cancers. Here, the authors show that H19 lncRNA is downregulated in pituitary adenomas and H19 is able to impede pituitary tumorigenesis via disruption of 4E-BPB1 and Raptor interaction to inhibit the phosphorylation of 4E-BP1.

Aimed at the problem of occasional congestion control, the cusp catastrophe theory is used to establish the catastrophe model of the urban road system under occasional congestion, finding breakpoints and analyzing stability after urban road system catastrophes by constructing the energetic function; based on the catastrophe characteristics of the urban road system, the feasibility method of congestion control is discussed. The results show that the control method of traffic flow based on catastrophe characteristics of the urban road system can effectively improve the efficiency of the road system in theory. Finally, the applicability of the control method based on catastrophe characteristics is analyzed by examples under different occasional congestion situations.