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Due to its advantages of good toughness, corrosion resistance, low cost and constructability, etc., polyethylene (PE) pipeline is widely used in natural gas transportation. Because of the characteristics of PE pipeline, the material aging becomes a problem while using.The method for effectively and efficiently evaluating the aging performance of PE pipes in service has been highly concerned in the industry. There are differences in its aging condition due to differences in pipe diameter and material. It is found that the antioxidant capacity of PE pipes of the same PE material under the same SDR conditions increases with increasing pipe diameter as influenced by the wall thickness of the pipe. There are obvious differences in the antioxidant performance of PE pipes made from different materials; under the experimental conditions of this paper, the antioxidant performance of PE100 is significantly better than that of PE80.

CO2 geological storage is one of the important means to reduce carbon emission and greenhouse effect, and it is an emerging field of earth science research. The selection of the injection rate has an important impact on the CO2 storage capacity, and it is limited by the injection time and construction conditions, thus the selection of the injection rate is a complex optimization problem. In this paper, the optimal injection site calculated based on dynamic planning is used for injection simulation, based on which the carbon sequestration injection rate optimization problem is transformed into a differential evolution problem, and the problem is optimized by different differential methods. For the Utsira block in the Sleipner project in Norway. On this basis, the effect of injection rate on storage capacity and leakage is researched, and numerical simulations under different injection rates are designed. Thus, it provides theoretical guidance for the selection of injection rate in CO2 geological storage.

The isotropic diffuse γ -ray background (IGRB) serves as a fundamental probe of the evolution of the extreme Universe. Although various astrophysical sources have been proposed as potential contributors to the IGRB, the dominant population is still under debate. γ -ray bursts (GRBs) are among candidate contributors of IGRB, although they are not as frequently discussed as blazars or starburst galaxies. Recent observations of TeV emission from GRB afterglows have provided fresh insights into this subject. This work aims to investigate the potential contribution of GRB afterglows to the IGRB under the standard afterglow model. We carefully examine the influence of each microphysical parameter of the afterglow model on this contribution, with a particular emphasis on the significant role played by the initial kinematic energy. To determine the energy and quantify the contribution of GRB afterglow to IGRBs, we utilize the observed GRB afterglow energy emissions from the Swift X-ray Telescope and Fermi Large Area Telescope instruments. Our calculations, considering the synchrotron self-Compton emission, suggest that GRB afterglows make up less than 10% of the IGRBs. To enhance the precision of our findings, it is crucial to further constrain these parameters by conducting additional ground-based observations of GRB afterglows.

Recently, magnetoelectric (ME) antennas have become a hot topic in the field of antenna miniaturization in the very-low-frequency (VLF) band because their size can be reduced to one-ten-thousandth of the size of conventional electric antennas. However, they still suffer from narrow transmission/reception bandwidth and weak radiation intensity. To address these issues, VLF thin-film ME antennas with a microbridge structure are designed, and the method of array connection is used. Test results show that the detection limit of the ME antenna unit is 636 pT/√Hz at 23 kHz and the radiant magnetic field intensity at 0.12 m is 0.87 nT (input power of 10 mW). By series-connecting three ME antenna units with the same resonance frequency, the output response has been increased to 1.72 times and the EM wave radiation intensity is increased to 1.9 times compared to a single unit. By parallel-connecting two ME antenna units with different resonance frequencies, the output response bandwidth has been expanded to 1.56 times compared to a single unit, and the signal radiation bandwidth has been expanded to 1.47 times. This work provides a valuable reference for the future larger-scale arraying of ME antennas.

BackgroundScintillator-based fast-ion loss detector (FILD) can measure the velocity-space distribution of fast-ion loss and are key in studying the control mechanism of fast-ion loss in nuclear fusion devices.PurposeThis study aims to obtain the velocity-space distribution of fast-ion loss from corresponding FILD data and evaluate the capacity of current FILD probe for the further improvement of diagnostic design.MethodsThe FILDSIM code was employed to establish the linkage between the fast-ion image digitized by FILD and the velocity-space distribution of fast-ion loss. The detection coverage of fast ions on the scintillator was assessed through reverse tracing of the lost fast ions, considering the geometry of the FILD probe as well as the pitch angle and gyroradius of fast ions entering the pinhole of the FILD probe.ResultsThe obtained velocity-space distribution of fast-ion loss under ICRH indicates that the energy of lost fast hydrogen minority ions is above 200 keV. Moreover, analysis shows that the geometry of the probe, particularly the shell behind the scintillator, obstructs the diagnostic detection range, creating a null region on the scintillator.ConclusionsThe acquisition of the velocity-space distribution of fast-ion loss lays the foundation for further evaluation and control of fast-ion loss under ion cyclotron resonance heating. In addition, the investigation of the probe detection range provides a basis for upgrading diagnostic systems.

The shield tunnel is typically simplified as an infinite beam with two free ends in existing analytical models, which are used to calculate the longitudinal deformation of the underlying shield tunnel induced by the excavation of a foundation pit. However, the applicability of those analytical models is limited due to the simplification. The current study is aimed at estimating analytically the longitudinal deformation of the underlying shield tunnel induced by the excavation of a foundation pit adjacent to the station (working shaft). The constraint on the shield tunnel generated by the joint between the station (working shaft) and the tunnel is treated as a rotation spring with the rotation stiffness of K and a vertical rod support. The Winkler foundation–Timoshenko beam model for calculating the longitudinal deformation of the shield tunnel adjacent to the station (working shaft) induced by the foundation pit excavation is proposed. The finite difference solution of the proposed model is strictly derived based on the basic principles of the force method. The reliability and applicability of the proposed analytical model are verified via the comparison with the finite element numerical solution of one-dimensional elastic foundation beam model and the global finite element simulation results of the longitudinal deformation of the underlying tunnel induced by the excavation of a foundation pit adjacent to the station. The parametric studies indicate the following conclusions. (i) The longitudinal deformation and internal forces of the shield tunnel are significantly influenced by the rotation stiffness, K, of the joint between the station (working shaft) and the tunnel. The internal forces and the longitudinal deformation (i.e. rotation angle) at the end of the tunnel increase and decreases nonlinearly with a increasing K, respectively. In addition, when the flexible connection is adopted at the joint between the station (working well) and tunnel, the working performance of the shield tunnel at the joint can be better guaranteed. (ii) The constraint effect of the joint on the end of the tunnel is non-negligible, when the distance from the center of the foundation pit to the station-tunnel joint ranges from 4 to 5 times the width of the pit along the tunnel axis. In this condition, the proposed analytical model should be adopted to evaluate the longitudinal working performance of the tunnel. (iii) The influence of the overlying foundation pit excavation on the underlying tunnel mainly exerts within 2 times the length of the pit perpendicular to the tunnel axis away from the center of the pit.

As a receptor tyrosine kinase with the most family members, erythropoietin-producing hepatocyte kinase (Eph) is closely related to the occurrence and development of malignant tumors and displays a wide range of clinical application value. Animal models have played an important role in exploring the biological functions, molecular mechanisms and screening therapeutic targets of Eph family molecules. In this paper, we reviewed the application and latest research progress of xenotransplantation model, immune-related model, and gene modification model in the study of Eph family's functional research, and summarized the advantages and disadvantages of various models, in order to provide a reference for researchers to select appropriate animal models for Eph related research.

Phage contamination is a persistent problem in industrial biotechnology processes employing bacterial strains. Here, the authors report the construction of E. coli host strains with broad antiphase activities via the genomic integration of the Ssp defense system and mutations of components essential for phage infection cycles.

Nowadays, the development of human society and daily life are inseparable from the power supply. Therefore, people also put forward higher requirements for the reliability of distribution network, but power companies can only passively deal with distribution network failures, which is a bottleneck for the improvement of distribution network reliability. The Internet of Things (IoT) is the best solution for online equipment status monitoring and basic data sharing for large, widely distributed, relatively fixed, and large numbers of equipment. The construction of the IoT for power distribution equipment faces many important problems, including the selection of networking, equipment selection, and interaction standards. When researching the implementation plan, research on the distribution of IoT market was carried out. Based on the grid, the idea of optimizing the investment selection plan of the power distribution using IoT was discussed, and a result verification model was established. After the completion of the theoretical part, a case study of medium-voltage distribution grid equipment management and medium-voltage distribution network equipment management based on the grid was carried out by taking a real enterprise application situation as an example. Realizing fault diagnosis of distribution network will not only provide decision support for operation and maintenance of distribution network for power companies, but also have great economic and social benefits. Aiming at the shortcomings of single data mining method in distribution network fault diagnosis, hybrid data mining method is proposed. First, rough set theory is used to reduce the original fault data and form a simplified rule set. Because of the non-linearity of distribution network fault and the strong learning ability, adaptability, and robustness of Bayesian network, Bayesian network can be used to classify distribution network faults. Therefore, a simplified fault diagnosis system is established in this paper, and its correctness is confirmed. Then, the learning and training are carried out by using Bayesian network to call the simplest rule set, which has the characteristics of short learning and training time and high diagnostic accuracy.

Nano-modified multimodal and conventional Cr3C2–NiCr coatings were fabricated by high-velocity oxygen-fuel spraying deposited on CuCrZr substrates. Results showed that individual nano-modified multimodal Cr3C2–NiCr particles were composed of nano (25−180 nm), submicron (200 nm to 0.5 μm), and micron (2–4.5 μm) Cr3C2 grains, NiCr binder phases, and a tiny amount of rare earth oxide additives. The nano-modified multimodal Cr3C2–NiCr coatings maintained a unique structure: submicron Cr3C2 grains embedded in the voids formed by micron Cr3C2 grains, NiCr binder phases and nano Cr3C2 grains imbedded in the voids formed by submicron and micron Cr3C2 grains, and nano Cr3C2 grains are dispersed in NiCr metal binder phases. A few discontinuous elongated amorphous and nanocrystalline phases existed in them. The mechanical interlocking was the dominant bonding mechanism accompanied by local metallurgical bonds. Compared to the conventional coating, the multimodal coating was uniform and dense (porosity was 0.3 ± 0.12%) as well as not obvious lamellar structures, the adhesive strength was 75.32 ± 1.21 MPa, exhibiting a 65 pct increase, and the microhardness was increased by about 18%. The lower porosity and higher strength of nano-modified multimodal structure coating were mainly related to dispersion distribution and synergistic coupling effects of Cr3C2 hard grains with different scales.

Abstract We discuss 3d brane webs and effective Chern-Simons levels for 3d N $$ \mathcal{N} $$ = 2 gauge theories. We find that turning on real masses for chiral multiplets leads to various equivalent brane webs that are related by flipping positions of D5-branes. We interpret flips as ST-transformations for chiral multiplets. ST-transformations could turn abelian theories into dual theories with mixed Chern-Simons levels that are interpreted as quiver matrices C ij encoding DT-invariants. We notice that each brane web corresponds to a quiver matrix. ST-transformations of holomorphic blocks are discussed to verify results. We also discuss the movement of flavor D5-branes, which leads to double-layer brane webs and manifests fiber-base duality. In the second part, we compute refined vortex partition functions of nonabelian theories with the gauge group U(N) and find corresponding quiver matrices. The computation shows that on Higgs branch nonabelian groups are broken to abelian groups.

Objective To investigate the clinical effects of microwave ablation (MWA) in addition to open surgery for the treatment of lung cancer‐derived thoracolumbar metastases. Methods This was a single‐institution, retrospective, cohort study. From January 2019 to December 2020, a total of 47 patients with lung cancer‐derived thoracolumbar metastases underwent posterior spinal canal decompression and fixation surgery in our hospital. Two independent surgical teams treated these patients. One group underwent open surgery combined with MWA therapy, while the other had open surgery only (control). The pre‐ and post‐operative visual analog scale (VAS) scores and the overall survival (OS) were compared between the MWA and control groups. The Frankel Grade classification was applied for the evaluation of the post‐surgical spinal cord function. Improvement was defined as an increase of at least one rank from the pre‐operative scores. Each patient was evaluated pre‐ and post‐operatively at 48 h, 1 month, and 3‐month intervals. Data on surgical‐related complications were recorded. Results Thirty men and 17 women were included, with an average age of 57.9 ± 11.4 years (range, 26–81 years). Twenty‐eight patients underwent MWA and were in the MWA group, and 19 patients were included in the control group. Post‐operatively all patients were followed up regularly; the median follow‐up time was 12 months (range, 3–24 months), and their median OS was 14 months. Patients in the MWA group had a lower VAS score than those in the control group at the 48‐h (1.75 ± 1.01 vs 2.47 ± 0.96, P = 0.01) and 1‐month (1.79 ± 0.92 vs 2.53 ± 1.35, P = 0.048) check‐ups. At the 3‐month evaluation, the VAS score differences between the two groups were not significant (P = 0.133). After surgery, spinal cord function improvement was not significantly different between the MWA and control groups (P = 0.515). MWA therapy combined with open surgery was not associated with increased OS compared with the control group (P = 0.492). Conclusion MWA can be an effective and safe pain‐relief method but may not extend the OS of patients with lung cancer.

Abstract. Background:. To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19. Methods:. This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable. Results:. A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%–48.1%; P = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151–3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350–67.410, P 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. Conclusions:. SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events. Trial registration:. Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term=NCT04260594&draw=2&rank=1

Abstract Background Increasing evidence associates air pollution with thyroid dysfunction, whereas the potential relationship between exposure to ozone (O3) and Thyroid Nodules (TNs) is unclear. Methods This retrospective cohort study investigated the association between O3 exposure and TNs in Hunan province, enrolling 191,357 Chinese adults who lived in Hunan province from January 2009 to December 2019 and received voluntary medical examinations. Individual exposure levels to O3 from 2010 to 2019 were measured on account of participants’ residential addresses at the district level. Associations of O3 exposure with the risk of incidental TNs were assessed by restricted cubic splines and surveyed as odds ratios after adjusting for demographic factors. Results In total, 81,900 adults were newly diagnosed with TNs during the study period. Age-standardized TNs detection rate in Hunan province increased from 25.9 to 46.3% between 2010 and 2019, with the greatest annual percent change being 8.1 [95% CI, 7.3–8.8]. A similar trend has been found in all tumor sizes, ages, and both sexes. O3 exposure presented a statistically significant dose-dependent positive correlation (greater than 0.036 ppm) with TNs. Similarly, long-term exposure to high levels of O3 (1-year average O3 concentrations exceeding 0.0417 ppm) was found positively associated with increased TSH levels. Conclusions High-level O3 exposure in the long term was associated with an increase in TSH. Consequently, increased TSH was related to the increased risk of TNs. Being exposed to high-level O3 in the long term was related to the increased detection rates of TNs in Hunan province, which could be mediated by TSH.

Abstract. Objective:. Cardiac damage is commonly reported in patients with coronavirus disease 2019 (COVID-19) but its prevalence and impact on the long-term survival of patients remain uncertain. This study aimed to explore the prevalence of myocardial injury and assess its prognostic value in patients with COVID-19. Methods:. A single-center, retrospective cohort study was performed at the Affiliated Hospital of Jianghan University. Data from 766 patients with confirmed COVID-19 who were hospitalized from December 27, 2019 to April 25, 2020 were collected. Demographic, clinical, laboratory, electrocardiogram, treatment data and all-cause mortality during follow-up were collected and analyzed. Results:. Of the 766 patients with moderate to critically ill COVID-19, 86 (11.2%) died after a mean follow-up of 72.8 days. Myocardial injury occurred in 94 (12.3%) patients. The mortality rate was 64.9% (61/94) and 3.7% (25/672) in patients with and without myocardial injury, respectively. Cox regression showed that myocardial injury was an independent risk factor for mortality (hazard ratio: 8.76, 95% confidence interval: 4.76–16.11, P

Abstract Immune checkpoint inhibitors (ICIs) have revolutionized the approach to advanced and locally advanced non‐small‐cell lung cancer (NSCLC). Antibodies blocking inhibitory immune checkpoints, such as programmed death 1 (PD‐1) and its ligand (PD‐L1), have remarkable antitumor efficacy and have been approved as a standard first‐ or second‐line treatment in non‐oncogene‐addicted advanced NSCLC. The successful application of immunotherapy in advanced lung cancer has motivated researchers to further evaluate its clinical role as a neoadjuvant setting for resectable NSCLC and for improved long‐term overall survival and curative rates. In this review, we discuss the efforts that incorporate ICIs into the treatment paradigm for surgically resectable lung cancer. We reviewed the early‐phase results from neoadjuvant clinical trials, the landscape of the majority of ongoing phase III trials, and discuss the prospects of ICIs as a curative therapy for resectable lung cancer. We also summarized the potential biomarkers and beneficiaries involved in the current study, as well as the remaining unresolved challenges for neoadjuvant immunotherapy.

Organoid is an in vitro three-dimensional culture system of stem cells or tissues derived from patients. Both normal gastric organoids and gastric cancer organoids can be established through this culture technique. Organoid possesses high fidelity, it grows with the similar molecular structures, functional characteristics, and genetic information as its tissue-of-origin. According to above, organoid can perform therapeutic targets screen, facilitate drug responses prediction and verification. Meanwhile, it also provides a new idea for precision medicine research of gastric cancer and replacement research of laboratory animals. This paper reviewed the establishment of organoid model of gastric cancer and the development of application of organoid in precision medicine, to provide ideal in vitro models reference for precision medicine research of gastric cancer.

Non-targeted effect is an important complement to the classical target theory of radiation biology which takes nuclear genomic DNA as the core target. The principle of radiation target theory is to assume that an organism or cell has one or more sensitive points or targets, hit and inactivation of which directly by radiation leads to considerable damage and the death event. Recent findings indicate that not only cell nucleus but also other cellular parts can be considered as possible targets. Mitochondrion is considered as a critical organelle where the non-targeted effect is initiated. A series of recent studies have provided substantial evidence and solid data which profoundly facilitate the understanding of radiation-induced non-targeted effects emitted from mitochondrion in the irradiated cells, such the major apparent performances, signaling pathways and biological significance. Mitochondrial genome is more sensitive to genotoxic than nuclear genome. Ionizing radiation can induce mtDNAs double-strand breaks directly or indirectly via increased mitochondrial ROS. Under stress conditions, mitochondrial DNA (mtDNA) fragments are released into the cytoplasm. The cytosol mtDNAs are sensed by cGAS and AIM2 proteins and they activate the corresponding signaling pathways, generating relevant inflammatory and immune responses. These newly developed mitochondrial DNA-initiating pathways may boost the development of targeted therapies for preventing normal tissue toxicity as well as radio-immunotherapy, an emerging trend for cancer therapies. Here we focus and discuss the mechanisms and biological significance of mtDNA-triggering cGAS/AIM2 signaling pathways of immune response from the aspect of non-targeted effect of radiation.

Abstract Background We examined attitudes toward the COVID‐19 vaccine, potential factors underlying these attitudes, and ways to increase vaccination willingness in autoimmune inflammatory rheumatic diseases (AIIRD) patients. Methods A multicenter, web‐based, observational survey using an online questionnaire was conducted among AIIRD patients aged ≥18 years from May 24, 2021, to June 3, 2021. Participants were 3104 AIIRD patients (2921 unvaccinated and 183 vaccinated). Results Of the unvaccinated patients, 32.9% were willing to receive the COVID‐19 vaccine, 45.0% were uncertain, and 14.8% were unwilling. When vaccination was recommended by physicians, patients' willingness increased to 93.8%. Participants' main concerns were that the vaccine may aggravate AIIRD disease (63.0%) and may cause vaccine‐related adverse events (19.9%). Female patients were less likely to be vaccinated. However, patients who had children aged ≤18 years were more willing to be vaccinated. In addition, vaccination willingness was higher in patients with trust in the safety and efficacy of the COVID‐19 vaccine. Notably, 183 (5.9%) patients were vaccinated. The major vaccination side effects were injection reaction, myalgia, and fatigue. At a median follow‐up of 88 (38, 131) days, patients' disease activities were stable. Conclusions The findings show that AIIRD patients were unwilling to receive the COVID‐19 vaccine because of fears of potential disease exacerbation and additional adverse events. Sociodemographic characteristics and concerns about COVID‐19 disease and vaccines had a significant effect on vaccination willingness.

Background: Helicobacter pylori infection is related to the occurrence of various diseases, and its influencing factors have been studied worldwide. Research on the current status of H. pylori infection in underdeveloped rural areas in China is limited. Aim: This research aimed to understand the status of H. pylori infection and its risk factors in rural Yan'an city, Northwest China. Methods: This cross-sectional study was implemented in two villages in Yan'an city in 2018, and 226 individuals underwent the Carbon-14 urea breath test to detect H. pylori infection. Participants' demographic characteristics, socioeconomic status, dietary habits, and lifestyle were collected through structured questionnaires. Results: In this research, the overall infection rate of H. pylori was 32.7% (74/226). Multivariate logistic regression analysis showed that people with a body mass index (BMI)≥24 kg/m2 (OR = 3.03; 95% CI = 1.65–5.57) and people who frequently dined out (OR = 8.87; 95% CI = 1.43–54.97) were more likely to be infected H. pylori. Conversely, the H. pylori infection risk was reduced among people over 60 years of age (OR = 0.32; 95% CI = 0.17–0.62) as well as among those who ate sweet potatoes more than 7 times a week (OR = 0.23; 95% CI = 0.07–0.75). Conclusion: A BMI≥24 kg/m2 and frequent eating out were risk factors for H. pylori infection among the village inhabitants of Yan'an city. The consumption of sweet potatoes was related to a low risk of H. pylori infection.

Background Late gadolinium enhancement cardiac magnetic resonance imaging is an effective and reproducible method for characterizing myocardial infarction. However, gadolinium‐based contrast agents are contraindicated in patients with acute and chronic renal insufficiency. In addition, several recent studies have noted tissue deposition of free gadolinium in patients who have undergone serial contrast‐enhanced magnetic resonance imaging. There is a clinical need for alternative forms of magnetic resonance imaging contrast agents that are acceptable in the setting of renal insufficiency. Methods and Results Three days after 80 minutes of ischemia/reperfusion of the left anterior descending coronary artery, cardiac magnetic resonance imaging was performed to assess myocardial lesion burden using both contrast agents. Late gadolinium enhancement cardiac magnetic resonance imaging was examined 10 and 15 minutes after contrast injection. Contrast agents were administered in alternating manner with a 2‐ to 3‐hour washout period between contrast agent injections. Lesion evaluation and image processing were performed using Segment Medviso software. Mean infarct size and transmurality, measured using RVP‐001, were not different compared with those measured using late gadolinium enhancement images. Bland‐Altman analysis demonstrated a nominal bias of 0.13 mL (

Immune checkpoint inhibitors (ICI) therapy based on programmed cell death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) has changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC) and improved the survival expectancy of patients. However, it also leads to immune-related adverse events (iRAEs), which result in multiple organ damage. Among them, the most common one with the highest mortality in NSCLC patients treated with ICI is checkpoint inhibitor pneumonitis (CIP). The respiratory signs of CIP are highly coincident and overlap with those in primary lung cancer, which causes difficulties in detecting, diagnosing, managing, and treating. In clinical management, patients with serious CIP should receive immunosuppressive treatment and even discontinue immunotherapy, which impairs the clinical benefits of ICIs and potentially results in tumor recrudesce. Therefore, accurate diagnosis, detailedly dissecting the pathogenesis, and developing reasonable treatment strategies for CIP are essential to prolong patient survival and expand the application of ICI. Herein, we first summarized the diagnosis strategies of CIP in NSCLC, including the classical radiology examination and the rising serological test, pathology test, and artificial intelligence aids. Then, we dissected the potential pathogenic mechanisms of CIP, including disordered T cell subsets, the increase of autoantibodies, cross-antigens reactivity, and the potential role of other immune cells. Moreover, we explored therapeutic approaches beyond first-line steroid therapy and future direction based on targeted signaling pathways. Finally, we discussed the current impediments, future trends, and challenges in fighting ICI-related pneumonitis.

Doseo depression of Central African Rift System is an important onshore frontier area for oil and gas exploration in Africa, with rift development characterized by the dual control of fault-depression development and strike slip faulting. According to the latest drilling and seismic data in recent years, through the fine seismic interpretation, the calculation of paleo-fault throw and fault growth index and the method of balanced profile cross-section restorations, the fault characteristics and tectonic setting of Doseo depression are analyzed in detail, especially the fault activity, tectonic evolution and genetic mechanism of two large-scale strike slip movements in Doseo depression. The results show that the Doseo depression experienced five main tectonic phases, including two stages of strike slip tectonic movements with different mechanisms. The first stage is characterized by strike slip tectonic movements under tilting extension, which controls the overall structure of the depression. The second stage is characterized by strike slip tectonic movements under transform compression, which play an important role in the formation of some inversion structures and SW-NE trending anticlines and faulted anticlines. The superposition of an early faulted-depression and two later stages of strike slip tectonics led to current pattern of Doseo depression.

The Jurassic Lianggaoshan Formation lacustrine shale oil is the most potential exploration target of unconventional hydrocarbon resource in Southwest China. In this study, nuclear magnetic resonance (NMR), scanning electron microscopy (SEM), low-temperature N2 adsorption (LTNA), and high pressure mercury intrusion mercury injection capillary pressure are intergrated to reveal pore structure and its controlling factors of Lianggaoshan Formation lacustrine shale reservoir. Results indicate that three types of lithology combination are classified in the Jurassic Liangggaoshan lacustrine shale reservoir. Type A comprises pure shale. Type B is characterized by frequent shell limestone interbedding. Type C is characterized by frequent siltstone interbedding. The Type C shale is characterized by relatively high proportion of organic pores, high development and good connectivity of nanopores, and highest pore volume and Surface area. The nanopores of Lianggaoshan lacustrine shales are mainly dominated by mesopores and part of the macropores. Among them, the PV and SA are both mainly dominated by micropores. The enrichment of organic matter has little effect on the development of micropores, and does not affect the mesopore and macropore development. Quartz particles in Lianggaoshan lacustrine shale do not clearly facilitate the development of micropore and mesopore-macropore. Intraparticle pore in feldspar clast is an important component of mesopore and macropore. Clay minerals has no positive effect on the formation of micropore and mesopore-macropore.

Comprehensive surveillance systems are the key to provide accurate data for effective modeling. Traditional symptom-based case surveillance has been joined with recent genomic, serologic, and environment surveillance to provide more integrated disease surveillance systems. A major gap in comprehensive disease surveillance is to accurately monitor potential population behavioral changes in real-time. Population-wide behaviors such as compliance with various interventions and vaccination acceptance significantly influence and drive the overall epidemic dynamics in the society. Original infoveillance utilizes online query data (e.g., Google and Wikipedia search of a specific content topic such as an epidemic) and later focuses on large volumes of online discourse data about the from social media platforms and further augments epidemic modeling. It mainly uses number of posts to approximate public awareness of the disease, and further compares with observed epidemic dynamics for better projection. The current COVID-19 pandemic shows that there is an urgency to further harness the rich, detailed content and sentiment information, which can provide more accurate and granular information on public awareness and perceptions toward multiple aspects of the disease, especially various interventions. In this perspective paper, we describe a novel conceptual analytical framework of content and sentiment infoveillance (CSI) and integration with epidemic modeling. This CSI framework includes data retrieval and pre-processing; information extraction via natural language processing to identify and quantify detailed time, location, content, and sentiment information; and integrating infoveillance with common epidemic modeling techniques of both mechanistic and data-driven methods. CSI complements and significantly enhances current epidemic models for more informed decision by integrating behavioral aspects from detailed, instantaneous infoveillance from massive social media data.

Accurate P-wave first-motion-polarity (FMP) information can contribute to solving earthquake focal mechanisms, especially for small earthquakes, to which waveform-based methods are generally inapplicable due to the computationally expensive high-frequency waveform simulations and inaccurate velocity models. In this paper, we propose a deep-learning-based method for the automatic determination of the FMPs, named “DiTingMotion”. DiTingMotion was trained with the P-wave FMP labels from the “DiTing” and SCSN-FMP datasets, and it achieved ∼97.8% accuracy on both datasets. The model maintains ∼83% accuracy on data labeled as “Emergent”, of which the FMP labels are challenging to identify for seismic analysts. Integrated with HASH, we developed a workflow for automated focal mechanism inversion using the FMPs identified by DiTingMotion and applied it to the 2019 M 6.4 Ridgecrest earthquake sequence for performance evaluation. In this case, DiTingMotion yields comparable focal mechanism results to that using manually determined FMPs by SCSN on the same data. The results proved that the DiTingMotion has a good generalization ability and broad application prospect in rapid earthquake focal mechanism inversion.

BackgroundHepatocellular carcinoma (HCC), the third most prevalent cause of cancer-related death, is a frequent primary liver cancer with a high rate of morbidity and mortality. T-cell depletion (TEX) is a progressive decline in T-cell function due to continuous stimulation of the TCR in the presence of sustained antigen exposure. Numerous studies have shown that TEX plays an essential role in the antitumor immune process and is significantly associated with patient prognosis. Hence, it is important to gain insight into the potential role of T cell depletion in the tumor microenvironment. The purpose of this study was to develop a trustworthy TEX-based signature using single-cell RNA-seq (scRNA-seq) and high-throughput RNA sequencing, opening up new avenues for evaluating the prognosis and immunotherapeutic response of HCC patients.MethodsThe International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases were used to download RNA-seq information for HCC patients. The 10x scRNA-seq. data of HCC were downloaded from GSE166635, and UMAP was used for clustering descending, and subgroup identification. TEX-related genes were identified by gene set variance analysis (GSVA) and weighted gene correlation network analysis (WGCNA). Afterward, we established a prognostic TEX signature using LASSO-Cox analysis. External validation was performed in the ICGC cohort. Immunotherapy response was assessed by the IMvigor210, GSE78220, GSE79671, and GSE91061cohorts. In addition, differences in mutational landscape and chemotherapy sensitivity between different risk groups were investigated. Finally, the differential expression of TEX genes was verified by qRT-PCR.Result11 TEX genes were thought to be highly predictive of the prognosis of HCC and substantially related to HCC prognosis. Patients in the low-risk group had a greater overall survival rate than those in the high-risk group, according to multivariate analysis, which also revealed that the model was an independent predictor of HCC. The predictive efficacy of columnar maps created from clinical features and risk scores was strong.ConclusionTEX signature and column line plots showed good predictive performance, providing a new perspective for assessing pre-immune efficacy, which will be useful for future precision immuno-oncology studies.

IntroductionPorcine anti-human lymphocyte immunoglobulin (pALG) has been used in kidney transplantation, but its impacts on the lymphocyte cell pool remain unclear.MethodsWe retrospectively analyzed 12 kidney transplant recipients receiving pALG, and additional recipients receiving rabbit anti-human thymocyte immunoglobulin (rATG), basiliximab, or no induction therapy as a comparison group.ResultspALG showed high binding affinity to peripheral blood mononuclear cells (PBMCs) after administration, immediately depleting blood lymphocytes; an effect that was weaker than rATG but stronger than basiliximab. Single-cell sequencing analysis showed that pALG mainly influenced T cells and innate immune cells (mononuclear phagocytes and neutrophils). By analyzing immune cell subsets, we found that pALG moderately depleted CD4+T cells, CD8+T cells, regulatory T cells, and NKT cells and mildly inhibited dendritic cells. Serum inflammatory cytokines (IL-2, IL-6) were only moderately increased compared with rATG, which might be beneficial in terms of reducing the risk of untoward immune activation. During 3 months of follow-up, we found that all recipients and transplanted kidneys survived and showed good organ function recovery; there were no cases of rejection and a low rate of complications.DiscussionIn conclusion, pALG acts mainly by moderately depleting T cells and is thus a good candidate for induction therapy for kidney transplant recipients. The immunological features of pALG should be exploited for the development of individually-optimized induction therapies based on the needs of the transplant and the immune status of the patient, which is appropriate for non-high-risk recipients.

Infection, inflammation, tumors, and other illnesses have for a long time posed a major danger to human health and have developed into a global public health issue. However, the existing treatment methods are sometimes not effective, leading to high mortality. Therefore, it is urgent to seek new alternative therapies. Gallium and related derivatives have received a lot of interest recently because of their exceptional biological safety and distinctive pharmacological properties. More crucially, gallium and its compounds have the potential to specifically destroy iron metabolism, called the “Trojan Horse” strategy, which provides unparalleled opportunities in antibacterial, anti-tumor, and bone regeneration. In this review, gallium and its compounds-based biomedical applications in antibacterial, anti-tumor, anti-inflammatory, and bone regeneration are focused upon and the relevant therapeutic mechanisms are discussed. Then, the latest gallium-based drug design and drug delivery system are summarized. Finally, we put forward the limitations of current gallium materials and the development trend of future materials. This review is anticipated to offer new insights into the treatment of gallium and its compounds, and provide new inspiration for application and design in the future.

The lithospheric strength is a key factor in controlling the lithosphere dynamics and deformations. The effective elastic thickness (Te) of the lithosphere can always be used to address the lithospheric strength. Hence, it is a powerful tool for studying the large-scale lithospheric structure. Estimates of Te over both continent and ocean are important for understanding the lithospheric strength with its lateral variations, crustal gravity isostatic state, lithospheric thermal state and rheological structure, and the coupling at the lithosphere-asthenosphere boundary. This article summaries the background of Te estimation and reviews the domestic and overseas research progress on the estimation methods. The main methods for estimating Te include forward modeling of deformations, spectral techniques (i.e., admittance and coherence) based on the cross-spectral analysis of the gravity and topography data, and direct estimations of Te based on the yield strength envelope. The method of deformation forward modeling estimates Te from the optimal lithospheric deflection model, with which the calculated theoretical gravity anomalies best fit the observed ones. The spectral technique calculates Te through analyzing the relationship between observed gravity and topography data in the spatial wavenumber domain, including admittance and coherence methods. The admittance method operates the Te estimation basically based on the spectrum ratio of the gravity to topography signals, while the coherence method works by examining the variation characteristics of the relationship between those two signals in wavenumber domain. Under long-wavelength loading, the lithosphere tends to act as a regional isostatic equilibrium mode. In this model, the lithosphere deflected and the gravity anomaly could be completely related to the topography, i.e., the correlation between those two is close to 1. In contrast, under short-wavelength loading, the lithosphere usually does not deflect due to the lithospheric strength, hence the gravity-topography correlation is close to 0. The gravity-topography correlation decreases from 1 to 0 with the wavenumber. The wavelength around the change point of the correlation with the value of 0.5 representing the state transition of the lithosphere from isostatic equilibrium to disequilibrium, is determined by the lithospheric strength, hence could be used to address Te. The yield strength envelope method estimates Te based on the rock mechanics experiments which usually study how strength varies according to temperature and composition of the crust and mantle lithosphere. Recently, with the development of modern digital signal processing technology, spectral techniques have gradually become the most popular approaches for the Te estimation. Calculating the observed admittance and coherence needs the gravity and topography auto-spectra and the cross-spectrum to be computed first. Those two spectra can be obtained using periodogram, maximum entropy, multitapers and wavelet methods. Periodogram is a direct spectral estimation method used up until the late 1990s，although it is not a very accurate one due to the spectral leakage. While maximum entropy spectral estimation can minimize the spectral leakage to some extent and yield accurate spectra in small-window spectral estimation, multitaper method deals with spectral leakage well circumvent the problem of small window sizes. The wavelet method has also been widely developed for computing spectra during Te estimation, because the wavelet transform can separate closely spaced and high-wavenumber features, whilst the windowed Fourier transform likely to smear the information, either in space or wavenumber depending on the window size. The anisotropy of the lithosphere is an important parameter of the lithospheric mechanical property and can largely affect the calculated Te values. To obtain reliable Te, the anisotropy of Te should be considered during the Te estimation. Moreover, Te anisotropy can affect the crustal stress state, crustal rheological properties, and microfractures developments. Those subjects can provide important clues for the study of breeding environments, occurrence processes, and mechanisms of earthquakes. This review also discusses the principles, advantages, and disadvantages of the estimation methods. Finally, this article provides avenues for future research.

Abstract Background Osteochondral lesion of the talus (OLT) is one of the most common ankle injuries, which will lead to biomechanical changes in the ankle joint and ultimately affect ankle function. Finite element analysis (FEA) is used to clarify the effect of talus osteochondral defects on the stability of the ankle joint at different depths. However, no research has been conducted on talus osteochondral defect areas that require prompt intervention. In this research, FEA was used to simulate the effect of the area size of talus osteochondral defect on the stress and stability of the ankle joint under a specific depth defect. Methods Different area sizes (normal, 2 mm* 2 mm, 4 mm* 4 mm, 6 mm* 6 mm, 8 mm* 8 mm, 10 mm* 10 mm, and 12 mm* 12 mm) of the three-dimensional finite element model of osteochondral defects were established. The model was used to simulate and calculate joint stress and displacement of the articular surface of the distal tibia and the proximal talus when the ankle joint was in the heel-strike, midstance, and push-off phases. Results When OLT occurred, the contact pressure of the articular surface, the equivalent stress of the proximal talus, the tibial cartilage, and the talus cartilage did not change significantly with an increase in the size of the osteochondral defect area when the heel-strike phase was below 6 mm * 6 mm. Gradual increases started at 6 mm * 6 mm in the midstance and push-off phases. Maximum changes were reached when the defect area size was 12 mm * 12 mm. The same patterns were observed in the talus displacement. Conclusions The effect of the defect area of the ankle talus cartilage on the ankle biomechanics is evident in the midstance and push-off phases. When the size of the defect reaches 6 mm * 6 mm, the most apparent change in the stability of the ankle joint occurs, and the effect does not increase linearly with the increase in the size of the defect.

Abstract There was very limited evidence linking high-sensitivity C-reactive protein (HS-CRP) and total bone mineral density (BMD) in adolescents. The aim of this population-based study was to investigate the relationship between HS-CRP and total BMD in adolescents aged 10–20 years. A cross-sectional study was performed in the normal U.S. population from the data of the National Health and Nutrition Examination Survey (NHANES). The correlation between HS-CRP and total BMD was evaluated by using weighted multivariate linear regression models. And further subgroup analysis was conducted. There were 1747 participants in this study, 47.1% were female, 29.4% were white, 19.5% were black, and 22.3% were Mexican–American. In the multi-regression model that after the potential confounders had been adjusted, HS-CRP was negatively associated with total BMD. The negative association was also observed in the subgroup analyses stratified by gender and age. Our results demonstrated that higher HS-CRP was negatively correlated with total BMD in 10–20 years old adolescents.

Abstract Background Chemoresistance of pancreatic cancer is the main reason for the poor treatment effect of pancreatic cancer patients. Exploring chemotherapy resistance-related genes has been a difficult and hot topic of oncology. Numerous studies implicate the key roles of circular RNAs (circRNAs) in the development of pancreatic cancer. However, the regulation of circRNAs in the process of pancreatic ductal adenocarcinoma (PDAC) chemotherapy resistance is not yet fully clear. Methods Based on the cross-analysis of the Gene Expression Omnibus (GEO) database and the data of our center, we explored a new molecule, hsa_circ_0078297 (circ-MTHFD1L), related to chemotherapy resistance. QRT-PCR was used to detect the expression of circRNAs, miRNAs, and mRNAs in human PDAC tissues and their matched normal tissues. The interaction between circ-MTHFD1L and miR-615-3p/RPN6 signal axis was confirmed by a series of experiments such as Dual-luciferase reporter assay, fluorescence in situ hybridization (FISH) RNA immunoprecipitation (RIP) assays. Results Circ-MTHFD1L was significantly increased in PDAC tissues and cells. And in PDAC patients, the higher the expression level of circ-MTHFD1L, the worse the prognosis. Mechanism analysis showed that circ-MTHFD1L, as an endogenous miR-615-3p sponge, upregulates the expression of RPN6, thereby promoting DNA damage repair and exerting its effect on enhancing gemcitabine chemotherapy resistance. More importantly, we also found that Silencing circ-MTHFD1L combined with olaparib can increase the sensitivity of pancreatic cancer to gemcitabine. Conclusion Circ-MTHFD1L maintains PDAC gemcitabine resistance through the miR-615-3p/RPN6 signal axis. Circ-MTHFD1L may be a molecular marker for the effective treatment of PDAC.

The infection countermeasure, in which the main idea is to prevent adversaries from exploiting faulty ciphertexts to break the key by spreading the induced fault, is a very effective countermeasure against fault attacks. However, most existing infection countermeasures struggle to defend against double-fault attacks effectively due to the single-fault assumption. By analyzing the principle of infection mechanism and adding different random Boolean masks in the two encryption paths, this paper proposes a measure called a random mask infection countermeasure to defend against double-fault attacks. In addition, the multiplication mask is used to randomize the fault diffusion to further resist single-byte fault attacks. The experimental results indicate that the random mask infection countermeasure proposed can perform fault diffusion effectively when the cryptographic circuit suffers double-fault attacks, and the fault diffusion shows randomness, and can effectively defend against these fault attacks.

Parental phubbing behavior is a significant predictor of adolescent smartphone dependence. However, previous research has mainly focused on the child and adolescent’s perspective, overlooking potential differences in how parents and their children perceive parental phubbing. Therefore, this study investigates whether disparities exist in how parents and adolescents perceive parental phubbing and how these perceptual differences impact adolescent smartphone dependence. We also explore the role of the parent–child relationship in this context. In this study, 728 families from a middle school in Wuhan were selected and surveys were administered to both children and parents. The findings are as follows: (1) Significant perceptual differences were found between parents and adolescents regarding parental phubbing. (2) These perceptual discrepancies positively predict adolescent smartphone dependence and negatively impact parent–child relationships. Additionally, parent–child relationships have a negative influence on adolescent smartphone dependence. (3) The parent–child relationship serves as a mediator between perceptual differences in parental phubbing behavior and adolescent smartphone dependence. In summary, this research highlights the importance of considering both parent and adolescent perspectives on parental phubbing and emphasizes the role of the parent–child relationship in influencing adolescent smartphone dependence.

Urban forests by the riverside are important habitats for various animals and contribute various soundscapes for citizens. Unfortunately, urban forests are exposed to the influence of riverside traffic noises from freeways. This study aims to explore the spatial and temporal variation of soundscape, conduct soundscape optimization for multiple parameters, and find a balance and its interval of soundscape elements through optimizing a soundscape map. Questionnaires and measuring equipment were used to gather soundscape information in an urban forested area in Fuzhou, China. Diurnal variations and soundscape mapping were used to analyze spatial and psychophysical relationships between soundscape drivers. We then conducted optimization for a soundscape map, which included normalization, critical value determination, target interval of optimal SPL determination, and modification of SPL and mapping. Our findings suggest that biological activities and natural phenomena are potential drivers for diurnal variation of soundscapes, especially tidal phenomena contributing water and shipping soundscapes. Our results also suggest that all the high values of perceived soundscapes were found at the southwest corner of the study area, which includes both riverside and urban forest elements. Furthermore, we suggest combining both optimal soundscape and SPL correction maps to aid in sustainable design in urban forests. This can contribute to the understanding and methodology of soundscape map optimization in urban forests when proposing suitable design plans and conservation of territorial sound.

BackgroundNuclear science and technology are closely related to the lives of people. However, nuclear radiation may harm the health of the general public; hence, nuclear radiation monitoring must be strengthened. A wired nuclear radiation monitoring system has the characteristics of complex wiring, a long construction period, high cost, poor mobility, and more difficult troubleshooting.PurposeThis study aims to address the demand for convenient measurement and monitoring of gamma radiation fields.MethodsBased on the LoRa wireless communication technology, a γ radiation monitoring system using silicon photomultiplier (SiPM) tube-scintillator detector was designed. The main functions of the system included data collection from the detector, data processing and transmission using a STM32 single-core processor. The collected data packaging and transmission were processed in STM32 microcontroller using the LoRa wireless communication module. Considering the possible channel congestion in the monitoring system and the frequent data transmission, a dynamic optimal path communication algorithm was designed to find the optimal reconnection path and realize the priority allocation of data transmission.Results & ConclusionsThe test results show that the data transmission stability of γ radiation monitoring system based on LoRa is higher than 99.57%, and has the advantages of flexible networking, a further distance of transmission, low cost, and substantial expansion, hence has a broad reference prospect.

Abstract The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.

In view of the fatigue failure of the transmission shaft in advance, the study of the stress state and life is carried out. Through the analysis of the actual measured load, the cause of the fatigue failure of the drive shaft in advance is the inconsistent output load of the left and right splines. The finite element model of the transmission shaft is established by using finite element software, and the maximum stress at the root of the right tooth of the transmission shaft is obtained, which is the weak part of the transmission shaft. The response surface method and genetic algorithm are used to optimize the structural parameters of the transmission shaft（tooth root fillet, spline transition arc, and arc groove depth）. After optimization, the stress of the weak part of the transmission shaft tooth root is reduced by 28.3%. The fatigue life of the transmission shaft is increased by five times, and the reliability is higher. Finally, the fatigue test is carried out on the scaled down sample. The test result shows that the life of the drive shaft is doubled. The effectiveness of the optimization method is verified through experiments, and the method has certain reference significance for the optimization of shaft parts in the future.

Compare with the airborne and satellite-borne gravity measurements, terrestrial gravity measurements (TGMs) are closer to the sources of mass change and have relatively higher accuracy. The static anomalies and dynamic changes derived from TGMs have been widely used to study various geodynamic problems. Many high-precision gravity products using TGMs have become available since 21 century because of the development of modern observation techniques (especially those in absolute gravimetry) and the terrestrial network. Much of the progress of geodesy and geophysics has come from these products. In this paper, we briefly summarize the recent progress in geodesy and geophysics using high-precision TGMs during the last decade or so. The first group of applications adopts the gravity anomalies from TGMs, which includes constructing gravity field and geoid models, establishing crustal models, computing Moho undulations, and estimating the effective elastic thickness of the lithosphere. The second group of applications adopts the time-varying gravity changes from TGMs, which includes constructing time-varying gravity field models, detecting weak dynamic signals, estimating crustal tectonic deformation rates, and analyzing possible correlations with volcanic and seismic processes. We also discuss the next opportunities for ground gravimetry. Our findings could benefit the construction and development of the gravity observation system in the Chinese Mainland.

With the acceleration of urbanization and industrialization, the migration of rural labor force has led to the decline of rural industries and communities. As one important way to adjust the rural industrial structure and revitalize rural culture, rural tourism has developed through the rural revitalization strategy and the leisure tourism transformation. In this context, with the use of idle housing resources, homestay inns are meeting consumers' increasing demand for leisure, while also improving facility capability regarding rural tourism, maintaining local landscape, and becoming an important industry for rural tourism. Thus, we took southern Jiangsu and northern Zhejiang, which have strong economic power and close regional cooperation, as examples, and used the location retrieval service in the Baidu Map API to obtain information on homestay inns. Then, we analyzed the spatial distribution characteristics of homestay inns with the help of ArcGIS, and Geodetector was used to further analyze the influencing factors leading to the spatial differentiation of homestay inns. The main conclusions are summarized as follows: (1) Homestay inns in southern Jiangsu and northern Zhejiang are both clustered in terms of spatial distribution, and tend to be distributed in areas with low terrain and water systems around tourism resources and traffic roads. (2) Homestay inns in southern Jiangsu have differences in the degree of agglomeration among cities, showing "a lumpy distribution of four core and secondary centers," while the spatial agglomeration of homestay inns in northern Zhejiang is balanced and has a wide range of contiguous areas, with a gradient distribution in the west, east, and middle. (3) Consumption level, market conditions, and traffic capacity are important common factors affecting the distribution of homestay inns. Interactions between any two factors enhances the explanatory power of the spatial differentiation, which proves that the unique distribution phenomenon of homestay inns is formed under the interaction of multiple influencing factors. (4) Homestay inns in northern Zhejiang are weakly affected by objective factors. In addition, the spatial distribution of homestay inns along a lake or river is a distinguishing characteristic between southern Jiangsu and northern Zhejiang. Homestay inns in southern Jiangsu are usually close to scenic spots, while homestay inns in northern Zhejiang are less dependent on tourism resources. Overall, the study aims to provide a reference for factors suitable for homestay inn operation and those to be improved, and to promote the transformation and rational layout of the homestay industry. The study is of practical significance to the distribution planning of homestay inns in areas with higher economic development, and it also summarizes the distribution characteristics of typical clusters of homestay inns.

Rocket Force is an important strategic branch of our army, but rocket force medicine, as an independent new discipline of military medicine, is still in its infancy. This paper briefly introduces the establishment background, discipline connotation, construction achievements and development prospect of the new discipline of rocket force medicine.

Abstract Background Systematic review is an indispensable tool for optimal evidence collection and evaluation in evidence-based medicine. However, the explosive increase of the original literatures makes it difficult to accomplish critical appraisal and regular update. Artificial intelligence (AI) algorithms have been applied to automate the literature screening procedure in medical systematic reviews. In these studies, different algorithms were used and results with great variance were reported. It is therefore imperative to systematically review and analyse the developed automatic methods for literature screening and their effectiveness reported in current studies. Methods An electronic search will be conducted using PubMed, Embase, ACM Digital Library, and IEEE Xplore Digital Library databases, as well as literatures found through supplementary search in Google scholar, on automatic methods for literature screening in systematic reviews. Two reviewers will independently conduct the primary screening of the articles and data extraction, in which nonconformities will be solved by discussion with a methodologist. Data will be extracted from eligible studies, including the basic characteristics of study, the information of training set and validation set, and the function and performance of AI algorithms, and summarised in a table. The risk of bias and applicability of the eligible studies will be assessed by the two reviewers independently based on Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Quantitative analyses, if appropriate, will also be performed. Discussion Automating systematic review process is of great help in reducing workload in evidence-based practice. Results from this systematic review will provide essential summary of the current development of AI algorithms for automatic literature screening in medical evidence synthesis and help to inspire further studies in this field. Systematic review registration PROSPERO CRD42020170815 (28 April 2020).

Obesity is a main risk factor for diabetes and cardiovascular disorders and is closely linked to preadipocyte differentiation or adipogenesis. Peroxisome proliferator-activated receptor γ (PPARγ) is an indispensable transcription factor in adipogenesis. A newly identified long noncoding RNA, Acart, exerts a protective effect against cardiomyocyte injury by transactivating PPARγ signaling. However, the function of Acart in preadipocyte differentiation is unclear. To investigate the function of Acart in adipogenesis, a well-established preadipocyte, the 3T3-L1 cell line, was induced to differentiate, and Acart level was assessed during differentiation using quantitative real-time PCR. The biological role of Acart in adipogenesis was analyzed by assessing lipid droplet accumulation, PPARγ and CCAAT/enhancer-binding protein α (C/EBPα) expression, and 3T3-L1 cell proliferation and apoptosis after Acart silencing. We found that Acart level was promptly increased during preadipocyte differentiation in vitro. Acart was also significantly upregulated in obese mouse-derived subcutaneous, perirenal, and epididymal fat tissues compared with nonobese mouse-derived adipose tissues. Functionally, Acart depletion inhibited preadipocyte differentiation, as evidenced by a significant decrease in lipid accumulation and PPARγ and C/EBPα expression levels. Acart silencing also inhibited 3T3-L1 cell proliferation, whereas Acart overexpression accelerated 3T3-L1 cell proliferation and decreased cell apoptosis. Taken together, the current results reveal a novel function of Acart in regulating preadipocyte proliferation and differentiation.

BackgroundClopidogrel is a cornerstone antiplatelet drug used in cardiovascular, cerebrovascular, and peripheral artery diseases. The sulfhydryl group of clopidogrel metabolite could induce insulin autoimmune syndrome (IAS) with hypoglycemia as the major symptom. Discontinuing clopidogrel and substituting it with ticagrelor has been revealed as an effective treatment in previous studies. Since hypoglycemia serves as a risk factor for cardiovascular and cerebrovascular events, we aimed to determine the association between hypoglycemia/IAS and clopidogrel and to investigate whether clopidogrel is a modifiable and causal risk factor of hypoglycemia/IAS.MethodsMEDLINE, Embase, Cochrane databases, and clinical trial registries were searched for randomized controlled trials (RCTs) of clopidogrel from inception to 28 February 2022. RCTs comparing clopidogrel with placebo or other antiplatelet drugs were eligible if meeting the inclusion criteria: 1) clopidogrel was administrated 75 mg qd orally as a long-term antiplatelet prescription at least for months, and 2) hypoglycemia-inducible drugs were not used in the control arm. One investigator abstracted articles and performed a quality assessment. Uncertainties were resolved by discussions with two investigators independently. Odds ratio (OR) and risk difference (RD) were calculated and performed with subgroup analyses. The pre-specified protocol was registered in PROSPERO (CRD42022299622).ResultsSix trials with 61,399 participants in total fulfilled the criteria and were included in the meta-analysis. Clopidogrel might not be associated with higher hypoglycemia odds (OR 0.95, 95% CI 0.65 to 1.40). However, Asian participants (p = 0.0437) seemed more likely to develop clopidogrel-associated hypoglycemia. Clopidogrel-associated hypoglycemia occurred at the highest rate of 0.03% (RD −0.00023, 95% CI −0.00077 to 0.00031), and this increased to 0.91% (RD 0.00210, 95% CI −0.00494 to 0.00914) in an aging population and to 0.18% (RD 0.00040, 95% CI −0.00096 to 0.00177) when Asian ratio of the population was elevated.ConclusionsWe raise the concern that clopidogrel might be a modifiable and causal risk factor of hypoglycemia. The Asian population might be more vulnerable and need additional care.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022299622.

Abstract Objective Asthma is a chronic respiratory disease with an increasing incidence every year. microRNAs (miRNAs) have been demonstrated to have implications for asthma. However, limited information is available regarding the effect of miR‐124‐3p on this disease. Therefore, this study aimed to explore the possible effects of miR‐124‐3p and S100A4 on inflammation and epithelial–mesenchymal transition (EMT) in asthma using mouse models. Method Ovalbumin was used to induce asthmatic mouse models. Lung injury in mouse models was assessed, and the bronchoalveolar lavage fluid of mice was collected to determine the number of eosinophilic granulocytes and assess inflammation. The expression levels of miR‐124‐3p, S100A4, E‐cadherin, N‐cadherin, Snail1, vimentin, and TGF‐β1/Smad2 signaling pathway‐related proteins were measured using reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) and western blot analysis. In vitro experiments, cells were transfected with miR‐124‐3p mimics or inhibitors to test the expression of S100A4 by RT‐qPCR and western blot analysis, and the mutual binding of miR‐124‐3p and S100A4 was validated by dual‐luciferase reporter gene assay. Results Overexpression of miR‐124‐3p or inhibition of S100A4 expression attenuated bronchial mucus secretion and collagenous fibers and suppressed inflammatory cell infiltration. Additionally, upon miR‐124‐3p overexpression or S100A4 suppression, eosinophilic granulocytes were decreased, interleukin‐4 (IL‐4) and IL‐13 expression levels were reduced in the bronchoalveolar lavage fluid, serum total IgE level was reduced, and the TGF‐β1/Smad2 signaling pathway was suppressed. Mechanically, a dual‐luciferase reporter gene assay verified the binding relationship between miR‐124‐3p and S100A4. Conclusion miR‐124‐3p can negatively target S100A4 to attenuate inflammation in asthmatic mouse models by suppressing the EMT process and the TGF‐β/smad2 signaling pathway.

Epicenter locations are generally adjacent to active faults and past seismicity regions. Past earthquake catalogs and the geometry of the active faults can provide key prior knowledge concerning earthquake forecasts. In this study, we first introduce two straightforward dedicated models, the proximity-to-past-earthquakes (PPE) and proximity-to-mapped-faults (PMF) models, to fit the seismicity in the Sichuan-Yunnan region, China. The hybrid proximity-to-known-sources (PKS) model with the optimized model parameters is then used to estimate the probability of earthquake occurrence. Second, to compare the PKS forecast efficiency to those of different models, retrospective tests are applied to a dataset located in the Sichuan-Yunnan region. The results show that the probability maps derived from PPE, PMF, and PKS have non-uniform Poisson distribution features and that there is forecasting significance for past cases of moderate earthquakes in the test region. Finally, using Molchan error diagram tests, we find that the hybrid PKS model performs better than the other models in the testing region. The unsatisfactory performance of the PMF model for earthquake forecasting may lie both in the incompleteness of the fault database and the lack of consideration of co-seismic ruptures. Therefore, one of the three models can be used as a base model for comparing and evaluating earthquake forecast strategies.

ABSTRACT Bacterial defense barriers, such as DNA methylation-associated restriction-modification (R-M) and the CRISPR-Cas system, play an important role in bacterial antimicrobial resistance (AMR). Recently, a novel R-M system based on DNA phosphorothioate (PT) modification has been shown to be widespread in the kingdom of Bacteria as well as Archaea. However, the potential role of the PT R-M system in bacterial AMR remains unclear. In this study, we explored the role of PT R-Ms in AMR with a series of common clinical pathogenic bacteria. By analyzing the distribution of AMR genes related to mobile genetic elements (MGEs), it was shown that the presence of PT R-M effectively reduced the distribution of horizontal gene transfer (HGT)-derived AMR genes in the genome, even in the bacteria that did not tend to acquire AMR genes by HGT. In addition, unique gene variation analysis based on pangenome analysis and MGE prediction revealed that the presence of PT R-M could suppress HGT frequency. Thus, this is the first report showing that the PT R-M system has the potential to repress HGT-derived AMR gene acquisition by reducing the HGT frequency. IMPORTANCE In this study, we demonstrated the effect of DNA PT modification-based R-M systems on horizontal gene transfer of AMR genes in pathogenic bacteria. We show that there is no apparent association between the genetic background of the strains harboring PT R-Ms and the number of AMR genes or the kinds of gene families. The strains equipped with PT R-M harbor fewer plasmid-derived, prophage-derived, or integrating mobile genetic element (iMGE)-related AMR genes and have a lower HGT frequency, but the degree of inhibition varies among different bacteria. In addition, compared with Salmonella enterica and Escherichia coli, Klebsiella pneumoniae prefers to acquire MGE-derived AMR genes, and there is no coevolution between PT R-M clusters and bacterial core genes.