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The discovery of promising cytokines and clarification of their immunological mechanisms in controlling the intracellular fate of Mycobacterium tuberculosis (Mtb) are necessary to identify effective diagnostic biomarkers and therapeutic targets. To escape immune clearance, Mtb can manipulate and inhibit the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. In this study, we found that interleukin 16 (IL-16) is elevated in the serum samples of Tuberculosis (TB) patients and can serve as a specific target for treatment TB. There was a significant difference in IL-16 levels among active TB, latent TB infection (LTBI), and non-TB patients. This study first revealed that macrophages are the major source of IL-16 production in response to Mtb infection, and elucidated that IL-16 can promote Mtb intracellular survival by inhibiting phagosome maturation and suppressing the expression of Rev-erbα which can inhibit IL-10 secretion. The experiments using zebrafish larvae infected with M. marinum and mice challenged with H37Rv demonstrated that reducing IL-16 levels resulted in less severe pathology and improved survival, respectively. In conclusion, this study provided direct evidence that Mtb hijacks the host macrophages-derived interleukin 16 to enhance intracellular growth. It is suggesting the immunosuppressive role of IL-16 during Mtb infection, supporting IL-16 as a promising therapeutic target.

Underground gas storage (UGS) is a crucial method for mitigating seasonal fluctuations in natural gas consumption. However, in China, UGS is primarily achieved through the conversion of abandoned gas reservoirs with limited storage capacity. Radial jet drilling (RJD) is an effective technology for the secondary development of depleted reservoirs. The multiorifice nozzle is a critical component that can efficiently break rock and create radial holes to increase gas production. In this study, we investigate the impact of nozzle structure on energy conversion efficiency through numerical simulations and experiments. Additionally, we design a swirling multiorifice nozzle and verify its effectiveness in field applications. Our findings indicate that the nozzle pressure drop and vorticity are primarily generated at the acute angle of the orifices. The number of forward orifices is directly proportional to energy loss, while the discharge coefficient and hydraulic performance initially increase and then decrease. Swirling multiorifice nozzle have fewer backward orifices, so they have less energy loss and a larger discharge coefficient. It has achieved better rock-breaking results in field applications. In conclusion, this study provides theoretical guidance and technical support for the secondary development of gas storage.

Abstract A contribution to the engineering application of a proposed 500 kV fault current limiter (FCL) is presented. A new type of FCL composed of a highly coupled split reactor (HCSR) and fast switches is proposed. When the circuit breaker (CB) in series with the FCL in the 500 kV power system interrupts the limited fault current, the rate of rise of the recovery voltage (RRRV) reaches a value much higher than the rated value. Based on a simplified equivalent single‐phase circuit, the influence of the new FCL on the interruption procedure of the CB is simulated and discussed. The simulation results show that the high RRRV is caused by high‐frequency resonant oscillations between the HCSR and its parasite capacitance. Analysis indicates that when the reactance of the FCL is close to the short circuit reactance of the system, the RRRV will reach the highest value. To solve this issue, we proposed installing a shunt capacitor with the FCL. Simulation results showed that the RRRV under all fault modes could be restrained to below the rated value by introducing a certain shunt capacitor.

The theoretical research on the percolation mechanism and oil-water relative permeability of low-permeability oil reservoirs is the focus and hotspot of international researchers. Oil-water relative permeability is an important parameter that describes the characteristics of oil-water two-phase flow and is widely used in the dynamic analysis of development and numerical simulation technology in the reservoir. The traditional calculation method of oil-water relative permeability (i.e., the JBN method) is based on the Darcy flow law. When the velocity and the displacement pressure gradient do not follow the linear flow law, there are some errors in the results of oil-water relative permeability calculated by the JBN method. In this paper, the traditional JBN method is improved, and we establish a new processing method of experimental data for oil-water relative permeability considering the effects of nonlinear flow, capillary pressure, and gravity in tight oil reservoirs. The experiments on the flow characteristics of single-phase oil and oil-water relative permeability under nonsteady-state conditions were carried out. The flow velocity and displacement pressure gradient show nonlinear characteristics when single-phase oil is passed through a tight core. At the same time, when the air permeability decreases from 1.92×10−3 μm2 to 0.1×10−3 μm2, the nonlinear characteristics are becoming more and more obvious. Compared with the traditional JBN method, when the nonlinear flow characteristics are considered, the oil phase relative permeability increases, and the water phase relative permeability is slightly lower. If nonlinear flow characteristics are considered, when the water saturation increases from 0.605 to 0.699, the difference of oil phase relative permeability calculated by the JBN method and this method is gradually decreasing and, with the increase of water saturation, decreases from 0.0029 to 0.0001. In addition, the effects of capillary pressure, gravity, and the nonlinear flow coefficient on the oil-water relative permeability in tight oil reservoirs are studied. The capillary pressure also has a great influence on the relative permeability of the oil phase, and the relative permeability of the oil phase increases with the increase in capillary pressure. In the development process of the low-permeability reservoir, the seepage characteristics of each flow area are different, and the oil-water relative permeability is also different. Therefore, the research results play an important role in guiding the understanding of seepage characteristics of low permeability of tight oil reservoirs.

Trained monocytes and macrophages produce reactive oxygen species (ROS), which trigger antioxidative glutathione (GSH) response to buffer the rising ROS. However, whether and how the trained immunity is shaped by GSH synthesis remains unknown. Here, we report that β-glucan-trained macrophages from mice harboring a myeloid-specific deletion of the catalytic subunit of glutamate-cysteine ligase (Gclc) showed impaired GSH synthesis and decreased proinflammatory cytokine production in response to lipopolysaccharide challenge. Gclc deficiency compromised the activation of mammalian target of rapamycin-1 (mTOR) and expression of c-Myc transcription factors, abrogating the energy utilization and the metabolic reprogramming that allows β-glucan-trained macrophages to switch to glycolysis and glutaminolysis. Furthermore, Gclc deletion repressed effective H3K27me3 demethylation in the promoters of immunometabolic genes, such as Gls, Hk2, and Glut1, in β-glucan-trained macrophages by promoting the methyltransferase enhancer of zeste homolog 2 (EZH2). In vivo, myeloid-specific ablation of Gclc decreased the secretion of proinflammatory cytokines upon rechallenge with Candida albicans and these animals were less protected against the infection, compared with control littermates. Moreover, pharmacological inhibition of EZH2 enhanced the trained immunity response against Candida infection in Gclc-deficient mouse and human peripheral blood mononuclear cells treated with GCLC inhibitor buthionine sulfoximine (BSO). Thus, antioxidative GSH synthesis supports an environment conducive to β-glucan-induced metabolic and epigenetic reprogramming in trained immunity, allowing exploration of its functional consequences in autoimmune or inflammatory disease.

Abstract Background In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high‐level clinical evidence. This study aimed to compare the safety and long‐term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. Methods A prospective, single‐center, open‐label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event‐free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. Results Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1‐3M0 to T2‐3N0‐3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1‐year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1‐year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien‐Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment‐related AEs did not differ between the two groups (12.5% versus 12.4%). Conclusions The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

Abstract Background&Aims Gastrointestinal (GI) cancers, including gastric, liver, esophageal, pancreatic, and colorectal cancers, represent significant global health burdens. Emerging evidence suggests that dietary patterns, particularly their inflammatory and oxidative properties, may influence cancer risk. The Dietary Inflammatory Index (DII) and Dietary Oxidative Balance Score (DOBS) assess the inflammatory and oxidative effects of diets, respectively. This study aims to explore the association between DII, DOBS, and the combined risk of GI cancers, and investigates the potential mediating roles of serum albumin and red cell distribution width (RDW). Methods Data from 26,320 participants in the NHANES 2005–2018 cycles were analyzed. DII was calculated based on 28 dietary components, and DOBS included 17 nutrients (3 pro-oxidants and 14 antioxidants). Logistic regression models assessed the associations between DII, DOBS, and GI cancers. Restricted cubic spline (RCS) models examined dose-response relationships. Mediation analysis evaluated the roles of serum albumin and RDW. Subgroup analyses explored interactions with demographic and health-related factors. Results Higher DII was associated with increased GI cancer risk (OR: 1.26, 95% CI: 1.07–1.49 per unit increase), while higher DOBS was associated with reduced risk (OR: 0.90, 95% CI: 0.76–0.99 per unit increase). RCS analysis indicated a significant nonlinear relationship between DII and GI cancer risk. Serum albumin and RDW partially mediated the associations between DII, DOBS, and GI cancers. Subgroup analyses showed stronger associations for DII among certain demographics, and significant interactions were found between DII and BMI. For DOBS, significant interactions were observed with age and BMI. Conclusion This study reveals significant associations between dietary inflammatory and oxidative balance scores and GI cancer risk. Higher DII is linked to increased risk, while higher DOBS is protective. The mediating roles of serum albumin and RDW provide insights into underlying mechanisms. These findings underscore the potential of dietary modifications in GI cancer prevention and management, emphasizing the importance of anti-inflammatory and antioxidant-rich diets.

Abstract Background Febrile respiratory syndrome (FRS) is often associated with viral infections. The aim of this study was to identify the viral pathogens responsible for FRS in Liaoning Province, China. Methods We tested eight respiratory viruses, namely, influenza virus (IFV), rhinovirus (RV), human adenovirus (HAdV), human bocavirus (HBoV), human parainfluenza virus (HPIV), human coronavirus (HCoV), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV), using reverse transcription-polymerase chain reaction (RT-PCR). Statistical analyses were performed using SPSS version 25.0, and the data were plotted using RStudio 4.2.1 software. Results IFV was the most frequently identified pathogen, followed by RV, HAdV, HBoV, HPIV, HCoV, RSV, and HMPV. RSV/HBoV coinfection occurred most frequently among the mixed cases. The rate of respiratory virus detection was highest in children under one year of age and decreased significantly with age. Seasonal trends showed a peak in virus detection during the winter months. Conclusions IFV is the leading cause of FRS in Liaoning Province, China, with single-virus infections prevailing over coinfections. Observations indicate a differential virus detection rate across age groups and seasons, highlighting the need for focused preventive strategies to mitigate the transmission of respiratory viruses, particularly among susceptible populations in the colder season.

Abstract Lipid nanoparticles (LNPs) have proven themselves as transformative actors in chimeric antigen receptor (CAR) T cell therapy, surpassing traditional methods and addressing challenges like immunogenicity, reduced toxicity, and improved safety. Promising preclinical results signal a shift toward safer and more effective CAR T cell treatments. Ongoing research aims to validate these findings in clinical trials, marking a new era guided by LNPs utility in CAR therapy. Herein, we explore the preference for LNPs over traditional methods, highlighting the versatility of LNPs and their effective delivery of nucleic acids. Additionally, we address key challenges in clinical considerations, heralding a new era in CAR T cell therapy. Graphical Abstract

Numerous factors can contribute to a difficult colonoscopy, potentially leading to an incomplete procedure and overlooked lesions. Alternative strategies for handling difficult and incomplete colonoscopies should be considered. We present the case of an 85-year-old male who underwent a difficult colonoscopy, during which two expert endoscopists spent 1.5 h attempting various techniques but failed to intubate the cecum. Subsequently, colonic transendoscopic enteral tubing (TET) was performed. Abdominal plain film revealed tortuosity of the TET tube in the left abdomen corresponding to the distribution of the descending colon. Retrograde colon imaging was conducted by injecting a mixture of contrast medium and air into the colon via the TET tube. X-ray demonstrated well-developed visualization of the entire colon and terminal ileum. And evident elongation and tortuosity of the descending colon resembled an N-type folding pattern. The final diagnosis was determined as descending colon redundancy. Colonic TET combined with retrograde colon imaging through the TET tube may serve as an effective supplementary approach for identifying causes of difficult colonoscopy and improving diagnostic accuracy for bowel diseases when complete visualization is not achieved.

The rich and unique energy level structure arising from 4fn inner shell configuration of trivalent lanthanide ions (Ln3+) renders them highly attractive for light‐emitting applications. Currently, research primarily focuses on Ln3+ doping in either traditional garnets or the recently developed perovskite phosphors. However, there have been few reports on stable phosphors crystallized with pure lanthanide elements. Herein, a universal solution‐based route to eight Ln3+‐based metal halides from the organic‐inorganic A4LnX7 family is described, where A+ = 4,4‐difluoropiperidinium (DFPD+), Ln3+ = Nd3+, Eu3+, Ho3+, Sm3+, Tm3+, Tb3+, Yb3+, Er3+, and X− = Cl−, Br−. Visible photoluminescence (PL) is observed from Tb3+‐, Eu3+‐, Ho3+‐, and Sm3+‐based compounds with Tb and Eu compositions exhibiting high PL quantum yields of 90–100%; Nd3+‐, Tm3+‐, Yb3+‐, and Er3+‐based crystals show fascinating near‐infrared emission. Light‐emitting diodes (LEDs) fabricated with (DFPD)4TbCl7 yield characteristic emission of Tb3+, representing the first demonstration of electroluminescence from these organic‐inorganic Ln3+‐based metal halides. Moreover, these materials exhibit distinct excitation wavelength‐dependent emission after alloying with different Ln3+ ions, making them interesting for multicolor display and multilevel information encryption applications. It is foreseen that this study will open up the way to a possible design of robust optoelectronic devices based on lanthanide metal halides.

Abstract To study the evolution rules and behaviors of heat transport in a sandstone geothermal reservoir caused by cooled water reinjection, this research focuses on the quantitative relationship among reinjection parameters and the thermal breakthrough time of production wells. The permeation, tracer, and reinjection tests were conducted in a simulation model using a large sand tank in conjunction with the numerical simulation method based on COMSOL Multiphysics. Subsequently, sensitivity analysis and nonlinear fitting were performed to investigate the effects of fluid viscosity and density on the reinjection process, and to analyze the impact of reinjection parameters on the thermal breakthrough time of production wells, along with their underlying mechanisms and law. The results indicate that the migration velocity of reinjection water is greater in coarse sand layer compared to that in medium sand layer, and the thermal breakthrough time t is linearly correlated with reinjection rate (Q) raised to the power of − 0.85, temperature difference (ΔT) raised to the power of − 0.21, and spacing between the production and reinjection wells (R) raised to the power of 1.4. The correlation equation and analysis show that when the temperature difference between production and reinjection ΔT is more than 30 ℃, the influence of ΔT on the thermal breakthrough time of production well becomes weak, because ΔT exerts an effect on the thermal breakthrough time of production well t by influencing the relative position of the 18.5 ℃ isotherm in the temperature transition region. The error in reinjecting high-temperature fluid into low-temperature fluid may be corrected by introducing a viscosity correction coefficient α μ.

ABSTRACTLimited information on the virome and bacterial community hampers our ability to discern systemic ecological risk factors that cause cattle diarrhea, which has become a pressing issue in the control of disease. A total of 110 viruses, 1,011 bacterial genera, and 322 complete viral genomes were identified from 70 sequencing samples mixed with 1,120 fecal samples from 58 farms in northeast China. For the diarrheic samples, the identified virome and bacterial community varied in terms of composition, abundance, diversity, and geographic distribution in relation to different disease-associated ecological factors; the abundance of identified viruses and bacteria was significantly correlated with the host factors of clinical status, cattle type, and age, and with environmental factors such as aquaculture model and geographical location (P < 0.05); a significant interaction occurred between viruses and viruses, bacteria and bacteria, as well as between bacteria and viruses (P < 0.05). The abundance of SMB53, Butyrivibrio, Facklamia, Trichococcus, and Turicibacter was significantly correlated with the health status of cattle (P < 0.05). The proportion of BRV, BCoV, BKV, BToV, BoNoV, BoNeV, BoAstV, BEV, BoPV, and BVDV in 1,120 fecal samples varied from 1.61% to 12.05%. A series of significant correlations were observed between the prevalence of individual viruses and the disease-associated ecological factors. A genome-based phylogenetic analysis revealed high variability of 10 bovine enteric viruses. The bovine hungarovirus was initially identified in both dairy and beef cattle in China. This study elucidates the fecal virome and bacterial community signatures of cattle affected by diarrhea, and reveals novel disease-associated ecological risk factors, including cattle type, cattle age, aquaculture model, and geographical location.IMPORTANCEThe lack of data on the virome and bacterial community restricts our capability to recognize ecological risk factors for bovine diarrhea disease, thereby hindering our overall comprehension of the disease’s cause. In this study, we found that, for the diarrheal samples, the identified virome and bacterial community varied in terms of composition, abundance, diversity, configuration, and geographic distribution in relation to different disease-associated ecological factors. A series of significant correlations were observed between the prevalence of individual viruses and the disease-associated ecological factors. Our study aims to uncover novel ecological risk factors of bovine diarrheal disease by examining the pathogenic microorganism-host-environment disease ecology, thereby providing a new perspective on the control of bovine diarrheal diseases.

Mutations highly affect the structural flexibility of two switch domains in M-RAS considered an important target of anticancer drug design. Gaussian accelerated molecular dynamics (GaMD) simulations were applied to probe the effect of mutations P40D, D41E, and P40D/D41E/L51R on the conformational transition of the switch domains from the GTP-bound M-RAS. The analyses of free energy landscapes (FELs) not only reveal that three mutations induce less energetic states than the wild-type (WT) M-RAS but also verify that the switch domains are extremely disordered. Principal component analysis (PCA) and dynamics analysis suggest that three mutations greatly affect collective motions and structural flexibility of the switch domains that mostly overlap with binding regions of M-RAS to its effectors, which in turn disturbs the activity of M-RAS. The analyses of the interaction network between GTP and M-RAS show that the high instability in hydrogen bonding interactions (HBIs) of GTP with residue 41 and Y42 in the switch domain I drives the disordered states of the switch domains. This work is expected to provide a molecular mechanism for deeply understanding the function of M-RAS and future drug design towards the treatment of cancers.

IntroductionLow-grade glioma (LGG) is a prevalent malignant tumor in the intracranial region. Despite the advancements in treatment methods for this malignancy over the past decade, significant challenges still persist in the form of drug resistance and tumor recurrence. The Notch signaling pathway plays essential roles in many physiological processes as well as in cancer development. However, the significance of the pathway and family genes in LGG are poorly understood. MethodsWe conducted gene expression profiling analysis using the TCGA dataset to investigate the gene set associated with the Notch signaling pathway. we have proposed a metric called "NotchScore" that quantifies the strength of the Notch signaling pathway and enables us to assess its significance in predicting prognosis and immune response in LGG. We downregulated JAG1 in low-grade gliomas to assess its influence on the proliferation and migration of these tumors. Ultimately, we determined the impact of the transcription factor VDR on the transcription of PDL1 through chip-seq data analysis.ResultsOur findings indicate that tumors with a higher NotchScore, exhibit poorer prognosis, potentially due to their ability to evade the anti-tumor effects of immune cells by expressing immune checkpoints. Among the genes involved in the Notch signaling pathway, JAG1 has emerged as the most representative in terms of capturing the characteristics of both NotchScore and Notch pathways. The experimental results demonstrate that silencing JAG1 yielded a significant decrease in tumor cell proliferation in LGG cell lines. Our study revealed mechanisms by which tumors evade the immune system through the modulation of PDL1 transcription levels via the PI3K-Akt signaling pathway. Additionally, JAG1 potentially influences PDL1 in LGG by regulating the PI3K-Akt signaling pathway and the expression of the transcription factor VDR.DiscussionThese findings contribute to our understanding of immune evasion by tumors in LGG. The insights gained from this research may have implications for the development of therapeutic interventions for LGG.

Recently, bismuth (Bi)-based photocatalysts have been a well-deserved hotspot in the field of photocatalysis owning to their photoelectrochemical properties driven by the distortion of the Bi 6 s orbital, while their narrow band gap and poor quantum efficiency still restrict their application. With the development of ultrasonic technology, it is expected to become a broom to clear the application obstacles of Bi-based photocatalysts. The special forces and environmental conditions brought by ultrasonic irradiation play beneficial roles in the preparation, modification and performance releasement of Bi-based photocatalysts. In this review, the role and influencing factors of ultrasound in the preparation and modification of Bi-based photocatalysts were introduced. Crucially, the mechanism of the improving the performance for various types of Bi-based photocatalysts by ultrasound in the whole process of photocatalysis was deeply analyzed. Then, the application of ultrasonic synergistic Bi-based photocatalysts in contaminants treatment and energy conversion was briefly introduced. Finally, based on an unambiguous understanding of ultrasonic technology in assisting Bi-based photocatalysts, the future directions and possibilities for ultrasonic synergistic Bi-based photocatalysts are explored.

Abstract Objectives The latest version of the National Comprehensive Cancer Network recommends neoadjuvant therapy followed by surgical treatment or radical chemoradiotherapy for patients with cT3N0M0. Neoadjuvant therapy can improve the prognosis of patients with locally advanced esophageal cancer. Therefore, the evaluation or prediction of T stage is particularly important because the treatment could differently affect the prognosis. Here, we establish a model to predict the T stage of patients with T2‐3N0M0 to help choose the best treatment strategy. Methods From 1637 patents with esophageal cancer, we enrolled 48 patients and performed least absolute shrinkage and selection operator regression to screen for independent factors influencing pathological T stage. We, then, trained the decision tree to obtain the decision tree diagram and divided the T stages obtained by different methods into two categories, T2 and T3, for survival analysis. Results A total of 21 and 27 cases were predicted to be T2 and T3, respectively, under ultrasonic gastroscopy, 19 and 29 under magnetic resonance imaging, and 22 and 26 under pathological examination. Multivariate logistic regression analysis revealed that the muscularis propria thickness (MPT) (p = 0.0097) and the muscularis propria + mucosa thickness (MPMT) in the largest tumor cross‐section (p = 0.0239) were independent influencing factors. We plotted a decision tree diagram with these two factors. MPT in the largest tumor cross‐section >1.3 mm could be judged as pT3; if ≤1.3 mm, MPMT should be considered a thickness ≥1.7 mm could be judged as pT2 (otherwise pT3). Corresponding survival analysis was performed according to the T stage under different examination modalities. Conclusion MPT in the largest tumor cross‐section and MPMT in the largest tumor cross‐section are independent predicting factors of pathological T stage.

Chimeric antigen receptor (CAR) T cell therapy for solid tumors shows promise, but several hurdles remain. Strategies to overcome barriers such as CAR T therapy-related toxicities (CTT), immunosuppression, and immune checkpoints through research and technology are needed to put the last nail to the coffin and offer hope for previously incurable malignancies. Herein we review current literature and infer novel strategies for the mitigation of CTT while impeding immune suppression, stromal barriers, tumor heterogeneity, on-target/off-tumor toxicities, and better transfection strategies with an emphasis on clinical research and prospects.

Since the emergence of blockchain, how to improve its transaction throughput and reduce transaction latency has always been an important issue. Hostuff has introduced a pipeline mechanism and combined it with a chain structure to improve the performance of blockchain networks. HCA has introduced a revoting mechanism on the basis of Hostuff, further reducing transaction latency, but it has also brought some problems. In HCA, if the leader is malicious, it would be possible to continuously call on the replica nodes to revote, which can lead to network congestion. This paper employs the global perfect coin technology to guarantee that every replica can obtain a globally consistent and the freshest candidate proposal during the Revote phase, thereby improving the robustness of the HCA protocol. The performance improvement of RHCA in attack scenarios has been verified through experiments.

The fatigue crack initiation direction of wind turbine gearbox bearings is investigated. Through theoretical research，it is believed that the direction of crack initiation depends on the direction of the maximum shear stress amplitude plane at the local initiation position. After calculation，it is found that the orthogonal shear stress amplitude of the shallow layer inside the bearing raceway is greater than the principal shear stress amplitude，and the principal shear stress amplitude at the deeper layer is greater than the orthogonal shear stress amplitude. Therefore，the crack initiation angle varies with the initiation depth. Aiming at the problem of crack propagation，the method of stress superposition in the polar coordinate of the crack tip in fracture mechanics is used to clarify the influence of Hertz contact stress，residual stress，assembly interference pressure，etc. on the direction of crack propagation. The applicability of the theory is verified by analyzing the failure cases of bearings with different thermal treatment microstructure.

Thin-walled galvanized helical corrugated steel tubes (HCSTs) filled with concrete are promising composite members, consisting of concrete, an anti-corrosion shell, and a multifunctional exterior corrugated steel tube. To investigate the synergistic working mechanism of concrete-filled HCSTs (CFHCSTs), six specimens were designed for axial compression tests, with the inner diameter of the column and the volumetric steel ratios of the longitudinal reinforcement as the variation parameters. The results show that HCSTs can better confine the concrete core and increase its strength. The failure mode of HCSTs is significantly influenced by the column’s diameter, and those with a smaller diameter are prone to slide failure and lock seam tearing. The strains and stresses on HCSTs are discussed in detail to elucidate the confinement effect. This paper proposes a suitable design method to predict the ultimate axial compression load capacity of CFHCST columns based on early studies on steel tube-confined concrete.

Chimeric antigen receptor (CAR) T cell treatment is an emerging subject following its curative response in hematological metastasis. However, solid tumors present a number of obstructions which have been a bull's eye to steer the CARs toward another victory in solid tumor microenvironment (TME). To combat against solid tumors, the construction, transfection and delivery of CARs is obliged to nano-engineering for better results and success in clinical trials. Herein, in this minireview, we discuss some of the potential and novel applications of nanotechnology to engineer better performing CARs to target solid TME. Moreover, we highlight potential gaps and strategies to overcome for future advancements in nano immunoengineering.

Active object recognition (AOR) provides a paradigm where an agent can capture additional evidence by purposefully changing its viewpoint to improve the quality of recognition. One of the most concerned problems in AOR is viewpoint planning (VP) which refers to developing a policy to determine the next viewpoints of the agent. A research trend is to solve the VP problem with reinforcement learning, namely to use the viewpoint transitions explored by the agent to train the VP policy. However, most research discards the trained transitions, which may lead to an inefficient use of the explored transitions. To solve this challenge, we present a novel VP method with transition management based on reinforcement learning, which can reuse the explored viewpoint transitions. To be specific, a learning framework of the VP policy is first established via the deterministic policy gradient theory, which provides an opportunity to reuse the explored transitions. Then, we design a scheme of viewpoint transition management that can store the explored transitions and decide which transitions are used for the policy learning. Finally, within the framework, we develop an algorithm based on twin delayed deep deterministic policy gradient and the designed scheme to train the VP policy. Experiments on the public and challenging dataset GERMS show the effectiveness of our method in comparison with several competing approaches.

Accelerated bridge construction has received widespread attention globally owing to its cost-effectiveness. The integrity of the connections between precast bridge piers and other members of the structure is crucial for developing assembly substructures. This issue was examined in the present study. A novel corrugated steel tube socket connection (CSSC) was developed for column–foundation connections. The CSSC method is a rapid bridge construction method in which a prefabricated corrugated steel tubular concrete column and a corrugated steel pipe in the foundation are connected using concrete or ultra-high-performance concrete. A vertical monotonic static load experiment was performed on six CSSC specimens and one cast-in-place (CIP) specimen to investigate the slip performance, failure modes, and load-transfer mechanism. The side shear performances was compared among specimens with different parameters (connection method, embedment depth, presence of studs, and presence of concrete under the columns). The experimental results indicated that the CSSC specimens had better ductility values and higher axial bearing capacities than the CIP specimen. Increasing the embedment depth, adding studs, and adding concrete under the columns increased the ultimate bearing capacity. To accurately estimate the side shear performance of the CSSC, a reliable finite-element model was developed. An additional parametric analysis was performed to investigate the effects of different parameters on the vertical performance. The CSSC is effective connection type in the prefabricated column-foundation connection and is suitable for bridge high-gravity superstructures. Finally, design recommendations regarding the construction details of the CSSC were presented.

Coronavirus subverts the host cell cycle to create a favorable cellular environment that enhances viral replication in host cells. Previous studies have revealed that nucleocapsid (N) protein of the coronavirus porcine epidemic diarrhea virus (PEDV) interacts with p53 to induce cell cycle arrest in S-phase and promotes viral replication. However, the mechanism by which viral replication is increased in the PEDV N protein-induced S-phase arrested cells remains unknown. In the current study, the protein expression profiles of PEDV N protein-induced S-phase arrested Vero E6 cells and thymidine-induced S-phase arrested Vero E6 cells were characterized by tandem mass tag-labeled quantitative proteomic technology. The effect of differentially expressed proteins (DEPs) on PEDV replication was investigated. The results indicated that a total of 5709 proteins, including 20,560 peptides, were identified, of which 58 and 26 DEPs were identified in the PEDV N group and thymidine group, respectively (P

Guiding technological progress towards clean innovations is crucial to industrial green transformation. This paper explains how clean technology innovation affects industrial green total factor productivity, using Tobit and panel smooth transition regression (PSTR) models to empirically test the relationship between clean technology innovation and industrial green total factor productivity. This research shows that clean technology innovation has a significantly positive effect on industrial green total factor productivity. The magnitude of this effect is different in various regions. When the intensity of environmental regulation reaches a particular threshold value in the central and western regions, clean technology innovation can significantly promote industrial green total factor productivity. In the eastern region, however, strict environmental regulation inhibits the promotion effect of clean technology innovation on industrial green total factor productivity. The corresponding research conclusion provide theoretical support and empirical evidence for exploring the way of industrial green transformation.

Our non-tube no fasting (early oral feeding and no nasogastric tube) fast-track surgery (FTS) was safe and effective to combine with neoadjuvant chemotherapy for McKeown minimally invasive esophagectomy. In addition, the two groups were similar in terms of the recovery time, hospital discharge day, and early resumption of oral feeding.ObjectivesTo evaluate the safety of early oral feeding (EOF) combined with neoadjuvant chemotherapy (NAC) of esophagectomy.Summary Background DataOur non-tube no fasting (early oral feeding and no nasogastric tube) fast-track surgery (FTS) was safe and effective for primary surgery esophageal cancer patients.MethodsWe retrospectively evaluated consecutive patients who underwent non-tube no fasting and McKeown minimally invasive (MIE). They were divided into two groups: one received NAC, and the other received primary surgery. Complications after the operation, postoperative CRG complications, operative time, operative bleeding, and length of stay were evaluated.ResultsBetween 01/2014 and 12/2017, there hundred and eighty two consecutive patients underwent MIE with total two-field lymphadenectomy under the non-tube no fasting fast-track surgery program. A total of 137 patients received NAC, and 245 accepted primary surgery. Propensity score matching was used to compare NAC patients with 62 matched patients from each group. The NAC group had a similar number of total complications as the primary surgery group (32.26% in the primary surgery group vs. 25.81% in the NAC group; p=0.429) and had the same median postoperative hospitalization duration (8 days, p=0.723).ConclusionsAfter McKeown MIE, the patients receiving NAC combined with “non-tube no fasting” FTS had a similar incidence of postoperative complications outcomes as those without NAC. In addition, the two groups were similar in terms of the recovery time, hospital discharge day, and early resumption of oral feeding.

The β2 adrenergic receptor (β2AR), one of important members of the G protein coupled receptors (GPCRs), has been suggested as an important target for cardiac and asthma drugs. Two replicas of Gaussian accelerated molecular dynamics (GaMD) simulations are performed to explore the deactivation mechanism of the active β2AR bound by three different substrates, including the agonist (P0G), antagonist (JTZ) and inverse agonist (JRZ). The simulation results indicate that the Gs protein is needed to stabilize the active state of the β2AR. Without the Gs protein, the receptor could transit from the active state toward the inactive state. During the transition process, helix TM6 moves toward TM3 and TM5 in geometric space and TM5 shrinks upwards. The intermediate state is captured during the transition process of the active β2AR toward the inactive one, moreover the changes in hydrophobic interaction networks between helixes TM3, TM5, and TM6 and the formation of a salt bridge between residues Arg3.50 and Glu6.30 drive the transition process. We expect that this finding can provide energetic basis and molecular mechanism for further understanding the function and target roles of the β2AR.

Immunotherapy has become an important treatment strategy for cancer patients nowadays. Targeting cancer neoantigens presented by major histocompatibility complex (MHC) molecules, which emerge as a result of non-synonymous somatic mutations with high immunogenicity, is one of the most promising cancer immunotherapy strategies. Currently, several therapeutic options based on the personalized or shared neoantigens have been developed, including neoantigen vaccine and adoptive T-cell therapy, both of which are now being tested in clinical trials for various malignancies. The goal of this review is to outline the use of neoantigens as cancer therapy targets, with an emphasis on neoantigen identification, clinical usage of personalized neoantigen-based cancer therapy agents, and the development of off-the-shelf products based on shared neoantigens. In addition, we introduce and discuss the potential impact of the neoantigen–MHC complex on natural killer (NK) cell antitumor function, which could be a novel way to boost immune response-induced cytotoxicity against malignancies.

Diamond-like carbon (DLC) films with excellent anti-friction and wear resistance, can effectively reduce the energy loss of tribosystems and the wear failure of parts, but the high residual stress limits their application and service life. Researchers found that doping heterogeneous elements in the carbon matrix can alleviate the defects in the microstructure and properties of DLC films (reduce the residual stress; enhance adhesion strength; improve tribological, corrosion resistance, hydrophobic, biocompatibility, and optical properties), and doping elements with different properties will have different effects on the structure and properties of DLC films. In addition, the comprehensive properties of DLC films can be coordinated by controlling the doping elements and their contents. In this paper, the effects of single element and co-doping of carbide-forming elements (Nb, W, Mo, Cr, Ti, Si) and non-carbide-forming elements (Cu, Al, Ag, Ni) on the properties of microstructure, mechanical, tribological, optical, hydrophobic, corrosion resistance, etc. of DLC films are reviewed. The mechanisms of the effects of doping elements on the different properties of DLC films are summarized and analyzed.

AbstractThere are 1,000 geothermal wells with depths of 1500–2000 m drilled into the upper Tertiary sandstone geothermal reservoir in the Guantao Formation in the North Shandong Plain, which support about 61 million square meters of domestic space heating. Concerning the large-scale exploitation of the Guantao Formation geothermal reservoir and its important role in clean space heating, it is essential to fully understand the characteristics of the geotemperature, geothermal water flow, and hydrochemical features, especially the heat accumulation and geothermal water enrichment mechanism. Based on the data from pumping tests, temperature logging, water level measurements, and hydrochemistry and isotope sampling and analysis, in this study, the heat sources and accumulation, water sources, and enrichment mechanism of the sandstone geothermal reservoir in the Guantao Formation were explored. The geothermal gradient of the cap rocks and the reservoir’s temperature revealed that the geothermal temperature fields are controlled by fault structures, and the relative high temperature zones are distributed in the area where the uplifts and deep heat-controlled faults converge. The geothermal water-rich area is located in the ancient river channel zone. The closer the water-rich area is to the ancient river channel belt, the deeper and coarser the buried conglomerate aquifer is, and the better the water-rich condition is. The best water-rich areas are found in the alluvial fan of the ancient channel belt.

Previous studies have shown that on the surface, Jiaobei uplift and Weihai uplift have higher heat flow values than Jiaolai depression. However, the mechanism by which the deep heat flow migrates and the exposure of geothermal resources are still unclear. In this study, the geothermal field distribution, thermal conductivity, temperature logging data, and chemical composition of the geothermal fluid in the Jiaodong Peninsula were analyzed. Regarding the thermal field’s characteristics and their controlling factors, a conceptual model of heat flow diversion-accumulation between the uplift and basin areas in the Jiaodong Peninsula is proposed. The lithology of the uplift area is mainly composed of intrusive rocks and metamorphic rocks with high thermal conductivities. The lithology of the basin mainly consists of sandstone with a low thermal conductivity. The bottom of the basin, which has a low thermal conductivity and low permeability, serves as a heat insulation and water insulation roof, which causes the heat flow and the heat-carrying fluids and gases from the deep crust to be refracted and redistributed at the bottom of the basin area. As a result, the bottom of the uplift areas has a higher heat flow. In particular, the axial position in the uplift area has the highest heat flow. In addition, the geothermal resources in the Jiaodong Peninsula are mainly distributed in the V-shaped area where the upper block of the NE- and NW-trending faults intersect, and the scope of the exposure of the geothermal resources is very limited.

The addition of supplemental light (SL) is an effective way to offset insufficient lighting. Although it is commonly believed that SL increases leaf photosynthesis and therefore improves yield and fruit flavor, the mechanism underlying the effects of SL on the photosystem II (PSII) apparatus remains unclear, and SL leads to high energy consumption. In order to save energy, we investigated the physiological status of the PSII apparatus, plant growth parameters and fruit parameters under two types of overhead SL with a low daily energy consumption of 0.0918 kWh m-2. The results showed that SL significantly increased the leaf chlorophyll content from full unfolding to yellowing. However, a remarkable increase in the absorption flux per cross-section (ABS/CS), the quantum yield of electron transport (φEo) and the performance index (PIabs) was observed only in a relatively short period of the leaf life cycle. SL also enhanced the fruit yield and quality. The obviously increased ΔVK and ΔVJ components of the chlorophyll fluorescence induction kinetic (OJIP) curve, along with the significantly decreased PIabs from days 40-60 after unfolding in the SL-treated groups, resulted in more rapid leaf aging and earlier fruit ripening compared with the control plants (CK). Therefore, an energy-friendly SL strategy can alter the physiological status of the PSII apparatus, affecting yield and fruit quality and maturity.

Objective. To assess whether professional endoscopists need additional training on inflammatory bowel disease (IBD) diagnosis. Methods. This retrospective study was conducted in patients with IBD, including Crohn’s disease (CD) and ulcerative colitis (UC), which were diagnosed and treated for the first time in our hospital between January 2005 and December 2020. Doctors including gastroenterologists (group G) and professional endoscopists (group E) participated in the study. The data divided into CD or UC and group G or group E were compared. Results. Patients with CD exhibited higher rates of terminal ileal lesions, reexamined colonoscopy within 6 months, and intestinal stenosis than patients with UC (P

Chimeric antigen receptors (CARs) are fusion proteins with an extracellular antigen recognition domain and numerous intracellular signaling domains that have been genetically modified. CAR-engineered T lymphocyte-based therapies have shown great success against blood cancers; however, potential fatal toxicity, such as in cytokine release syndrome, and high costs are some shortcomings that limit the clinical application of CAR-engineered T lymphocytes and remain to overcome. Natural killer (NK) cells are the focal point of current immunological research owing to their receptors that prove to be promising immunotherapeutic candidates for treating cancer. However, to date, manipulation of NK cells to treat malignancies has been moderately successful. Recent progress in the biology of NK cell receptors has greatly transformed our understanding of how NK cells recognize and kill tumor and infected cells. CAR-NK cells may serve as an alternative candidate for retargeting cancer because of their unique recognition mechanisms, powerful cytotoxic effects especially on cancer cells in both CAR-dependent and CAR-independent manners and clinical safety. Moreover, NK cells can serve as an ‘off-the-shelf product’ because NK cells from allogeneic sources can also be used in immunotherapies owing to their reduced risk of alloreactivity. Although ongoing fundamental research is in the beginning stages, this review provides an overview of recent developments implemented to design CAR constructs to stimulate NK activation and manipulate NK receptors for improving the efficiency of immunotherapy against cancer, summarizes the preclinical and clinical advances of CAR-NK cells against both hematological malignancies and solid tumors and confronts current challenges and obstacles of their applications. In addition, this review provides insights into prospective novel approaches that further enhance the efficiency of CAR-NK therapies and highlights potential questions that require to be addressed in the future.

As medical technology continues to improve, many patients diagnosed with brain injury survive after treatments but are still in a coma. Further, multiple clinical studies have demonstrated recovery of consciousness after transcranial direct current stimulation. To identify possible neurophysiological mechanisms underlying disorders of consciousness (DOCs) improvement, we examined the changes in multiple resting-state EEG microstate parameters after high-definition transcranial direct current stimulation (HD-tDCS). Because the left dorsolateral prefrontal cortex is closely related to consciousness, it is often chosen as a stimulation target for tDCS treatment of DOCs. A total of 21 patients diagnosed with prolonged DOCs were included in this study, and EEG microstate analysis of resting state EEG datasets was performed on all patients before and after interventions. Each of them underwent 10 anodal tDCS sessions of the left dorsolateral prefrontal cortex over 5 consecutive working days. According to whether the clinical manifestations improved, DOCs patients were divided into the responsive (RE) group and the non-responsive (N-RE) group. The dynamic changes of resting state EEG microstate parameters were also analyzed. After multiple HD-tDCS interventions, the duration and coverage of class C microstates in the RE group were significantly increased. This study also found that the transition between microstates A and C increased, while the transition between microstates B and D decreased in the responsive group. However, these changes in EEG microstate parameters in the N-RE group have not been reported. Our findings suggest that EEG neural signatures have the potential to assess consciousness states and that improvement in the dynamics of brain activity was associated with the recovery of DOCs. This study extends our understanding of the neural mechanism of DOCs patients in consciousness recovery.

Using systemic, periodic surveys from 2015 to 2019, population distribution, speculated age and habitat preference were analyzed to assess the living status for the Silver Carp (Hypophthalmichthys molitrix) in the lower Yangtze River. Small Silver Carps became more temporarily abundant in spring and autumn, and the catch per unit effort (CPUE) fluctuated yearly. Spatially, going from Anqing (AQ) to Changshu (CS), Silver Carps in the 200 mm standard length(SL) group became less abundant, whereas those in the 400–600 mm and >600 mm SL groups steadily increased. According to the Von Bertalanffy growth equation, the Silver Carp exhibits isometric growth, and the inflection point of SL and body weight (BW) were 564.01mm and 2948.31g, respectively, with a growth characteristic index (φ) of 5.0655. The fish dominant age range was 0+ to 5 years, reflecting the young age composition of the fish. Furthermore, the habitat survey findings revealed that the Silver Carp has the different preference on habitat selection in different life history. Juvenile Silver Carps were comparatively staying in the lower Yangtze River, where there exists a relatively stable bifurcated river. Adult fishes were mostly found in the CS and Nantong(NT) section where the river is wide and the food is rich. When compared with the historical survey data, it was found that the Silver Carp live in the AQ through NT section. The living status and perspective of the Silver Carp in the lower reach of the Yangtze River were clarified, and future work should be more concerned with the strengthening of conservation and the restoration of adequate habitat.

View planning (VP) is a technique that guides the adjustment of the sensor’s postures in multi-view perception tasks. It converts the perception process into active perception, which improves the intelligence and reduces the resource consumption of the robot. We propose a generic VP system for multiple kinds of visual perception. The VP system is built on the basis of the formal description of the visual task, and the next best view is calculated by the system. When dealing with a given visual task, we can simply update its description as the input of the VP system, and obtain the defined best view in real time. Formal description of the perception task includes the task’s status, the objects’ prior information library, the visual representation status and the optimization goal. The task’s status and the visual representation status are updated when data are received at a new view. If the task’s status has not reached its goal, candidate views are sorted based on the updated visual representation status, and the next best view that can minimize the entropy of the model space is chosen as the output of the VP system. Experiments of view planning for 3D recognition and reconstruction tasks are conducted, and the result shows that our algorithm has good performance on different tasks.

Active object recognition (AOR) aims at collecting additional information to improve recognition performance by purposefully adjusting the viewpoint of an agent. How to determine the next best viewpoint of the agent, i.e., viewpoint planning (VP), is a research focus. Most existing VP methods perform viewpoint exploration in the discrete viewpoint space, which have to sample viewpoint space and may bring in significant quantization error. To address this challenge, a continuous VP approach for AOR based on reinforcement learning is proposed. Specifically, we use two separate neural networks to model the VP policy as a parameterized Gaussian distribution and resort the proximal policy optimization framework to learn the policy. Furthermore, an adaptive entropy regularization based dynamic exploration scheme is presented to automatically adjust the viewpoint exploration ability in the learning process. To the end, experimental results on the public dataset GERMS well demonstrate the superiority of our proposed VP method.