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This paper proposes a fusion algorithm based on state-tracking collision detection and the simulated annealing potential field (SCD-SAPF) to address the challenges of obstacle avoidance for autonomous underwater vehicles (AUVs) in dynamic environments. Navigating AUVs in complex underwater environments requires robust autonomous obstacle avoidance capabilities. The SCD-SAPF algorithm aims to accurately assess collision risks and efficiently plan avoidance trajectories. The algorithm introduces an SCD model for proactive collision risk assessment, predicting collision risks between AUVs and dynamic obstacles. Additionally, it proposes a simulated annealing (SA) algorithm to optimize trajectory planning in a simulated annealing potential field (SAPF), integrating the SCD model with the SAPF algorithm to guide AUVs in obstacle avoidance by generating optimal heading and velocity outputs. Extensive simulation experiments demonstrate the effectiveness and robustness of the algorithm in various dynamic scenarios, enabling the early avoidance of dynamic obstacles and outperforming traditional methods. This research provides an accurate collision risk assessment and efficient obstacle avoidance trajectory planning, offering an innovative approach to the field of underwater robotics and supporting the enhancement of AUV autonomy and reliability in practical applications.

Two coupled climate models that participated in the CMIP6 project (Coupled Model Intercomparison Project Phase 6), the Earth System Model of Chinese Academy of Sciences version 2 (CAS-ESM2-0), and the Nanjing University of Information Science and Technology Earth System Model version 3 (NESM3) were assessed in terms of the impact of four new sea ice parameterization schemes. These four new schemes are related to air–ice heat flux, radiation penetration and absorption, melt ponds, and ice–ocean flux, respectively. To evaluate the effectiveness of these schemes, key sea ice variables with and without these new schemes, such as sea ice concentration (SIC) and sea ice thickness (SIT), were compared against observation and reanalysis products from 1980 to 2014. The simulations followed the design of historical experiments within the CMIP6 framework. The results revealed that both models demonstrated improvements in simulating Arctic SIC and SIT when the new parameterization schemes were implemented. The model bias of SIC in some marginal sea ice zones of the Arctic was reduced, especially during March. The SIT was increased and the transpolar gradient of SIT was reproduced. The changes in spatial patterns of SIC and SIT after adding new schemes bear similarities between the two coupled models. This suggests that the new schemes have the potential for broad application in climate models for simulation and future climate scenario projection, especially for those with underestimated SIT.

This work investigates the inter-model diversity of the Pacific Decadal Oscillation’s (PDO) impact on tropical cyclone frequency (TCF) over the Western North Pacific (WNP) from the historical simulation of twenty-two Coupled Model Intercomparison Project Phase 6 (CMIP6) models. The impact of the PDO is expressed as the TCF difference between the positive and negative PDO phases. The comparison between the models with high PDO skill and low PDO skill shows that the PDO-related sea surface temperature (SST) gradient between the western and central tropical Pacific plays an important role in changing the large-scale atmospheric dynamic fields for TC genesis and, thus, the TCF over the WNP. This SST gradient also significantly contributes to the inter-model spread of PDO’s impact on TCF across the 22 CMIP6 models. We, therefore, stress that the PDO-related eastward SST gradient between the western and central tropical Pacific triggers the lower troposphere westerly and eastward extending of the monsoon trough over the WNP. The moistening of the atmosphere and enhancing ascending motion in the mid-troposphere promote convection, leading to the easterly wind anomaly over the upper troposphere, which reduces the vertical wind shear. Those favorable dynamic conditions consistently promote the TC formation over the southeastern part of the Western North Pacific. Our results highlight that PDO could impact the WNP TCF through its associated tropical SST gradient.

Additive friction stir deposition (AFSD) is a relatively new additive manufacturing technique to fabricate parts in solid state below the melting temperature. Due to the solid-state nature, AFSD benefits from lower residual stresses as well as significantly lower susceptibility to porosity, hot-cracking, and other defects compared to conventional fusion-based metallic additive manufacturing. These unique features make AFSD a promising alternative to conventional forging for fabricating large structures for aerospace, naval, nuclear, and automotive applications. This review comprehensively summarizes the advances in AFSD, as well as the microstructure and properties of the final part. Given the rapidly growing research in AFSD, we focus on fundamental questions and issues, with a particular emphasis on the underlying relationship between AFSD-based processing, microstructure, and mechanical properties. The implications of the experimental and modeling research in AFSD will be discussed in detail. Unlike the columnar structure in fusion-based additive manufacturing, fully dense material with a fine, fully-equiaxed microstructure can be fabricated in AFSD. The as-wrought structure brings the as-printed parts with comparable properties to wrought parts. The fundamental difference between AFSD and fusion-based metallic additive manufacturing will be summarized. Furthermore, the existing challenges and possible future research directions are explored.

The effects of different test parameters on the creep of axially compressed concrete members were investigated under standard test conditions, considering loading ages of 7, 14 and 28 days and mineral powder admixtures of 0, 15%, 25% and 35%, respectively. The test results show that the creep of concrete decreases with the increase of mineral powder content when the loading age was fixed. When the content of mineral powder was unchanged, the creep of concrete would decrease with the increase of loading age. Based on the CEB-FIP MC 1990 concrete creep calculation model, the creep correction coefficient of mineral powder concrete considering the strength of mineral powder concrete, mineral powder content and loading age was proposed. The formula for the concrete creep correction coefficient which considers the loading age and mineral powder content was established by combining the existing creep test data and the test results of mineral powder concrete strength with the different loading ages and mineral powder contents in this paper. The comparison of the CEB-FIP MC 1978 and experiment values shows that the proposed formula in this paper can predict the development of creep of mineral powder concrete better. Finally, using the creep coefficient formula of mineral powder concrete, the creep coefficient values of concrete under different loading ages and mineral powder contents in CEB-FIP MC 1990 code were modified.

Abstract Immunotherapy is now the main choice of systemic therapy for many cancer patients, while current biomarkers for tumor immunotherapy may be limited by the accessibility of patient tumor tissue or tumor neoplastic content. Rare mutation in the 5’ and 3’-untranslated region (UTR) of CD274 gene (Protein name: PD-L1) has been recently reported in hematologic and solid tumors as a potential biomarker for assessing efficacy during immunotherapy. However, multi-omics analysis for CD274 UTR region, especially circulating tumor DNA (ctDNA), have been little explored in the pan-cancer perspective. We developed a cSMART2.0 technology featured with higher capture efficiency and homogeneity to detect this rare structural variant in 2249 Chinese patients’ cohort with multiple cancers. An incidence of 0.36% was detected in this cohort, consistent with TCGA (The Cancer Genome Atlas), while the prevalence of SV in CD274 UTR region in liver and breast cancer were significantly higher than TCGA. The liquid biopsy result from ctDNA was 100% concordance with gDNA result getting from tumor tissue detection, and further validated by immunohistochemistry (IHC) and multiplex immunofluorescence (mIF) experiments. Patients carrying this SV in CD274 UTR region without driver gene mutation responded to immune checkpoint inhibitors (ICIs). This study proves that rare structural variants in CD274 UTR region exist in various cancer in Chinese population for the first time, which can induce immune escape and be used for prediction of response to ICIs. Liquid biopsy based cSMART 2.0 technology could offer more sensitive and accurate detection to navigate potential ICIs patients and to benefit patients with advanced disease when tissue samples are not available.

Abstract Tumor mutational burden (TMB) is an emerging predictive marker of response to immune checkpoint inhibitor therapies. We evaluated the correlation between clinical indicators and high‐throughput sequencing results and TMB in lung adenocarcinoma patients, with the aim of finding simpler and more economical factors as surrogate markers for TMB. The medical records, next‐generation sequencing data, and immunohistochemistry results of 340 lung adenocarcinoma patients who were admitted to the First Affiliated Hospital of Zhengzhou University between 2019 and 2020 were collected. The mutated genes were screened for, and the obtained mutated genes were subjected to functional enrichment analysis using R software. A protein–protein interaction (PPI) network was also constructed, and significant modules in the network were identified. Gene Ontology (GO) analyses were performed for the core genes. Univariate and multivariate correlation analyses were performed to judge the correlation between gene mutations and TMB. Genes with a junction mutation rate >1 were selected to construct PPI network and 13 high‐connection core genes were screened. The results of GO enrichment analysis showed that the biological processes related to mutant core genes mainly included mitotic cell cycle and cell aging. Subsequently, ATM (p = 0.006) and PIK3CA (p = 0.008) mutation positivity were identified by univariate and multivariate correlation analysis, while TP53 (p = 0.003) and EGFR (p = 0.008) mutation negativity were significantly associated with elevated TMB. The results of this study demonstrate that ATM‐ and PIK3CA‐positive and EGFR‐negative mutation status are strongly associated with high levels of TMB and have the potential to be predictive biomarkers of response to immune checkpoint inhibitors in lung adenocarcinoma patients.

Abstract East Asia is undergoing significant climate changes and these changes are likely to grow in the future. It is urgent to characterize both the mechanisms controlling climate and the response of the East Asian climate system at global warming of 1.5 and 2 °C above pre-industrial levels (GW1.5 and GW2 hereafter). This study reviews recent studies on East Asian climate change at GW1.5 and GW2. The intensity and variability of the East Asian summer monsoon are expected to increase modestly, accompanied by an enhancement of water vapor transport. Other expected changes include the intensification of the Western Pacific Subtropical High and an intensified and southward shift of the East Asian jet, while the intensity of the East Asian winter monsoon is projected to reduce with high uncertainty. Meanwhile, the frequency of ENSO may increase in a warming world with great uncertainty. Significant warming and wetting occur in East Asia, with more pronounced intensity, frequency, and duration of climate extremes at GW2 than that at GW1.5. The fine structure of regional climate changes and the presence and location of various warming hotspots, however, show substantial divergence among different model simulations. Furthermore, the Asian climate responses can differ substantially between the transient and stabilized GW1.5 and GW2, which has important implications for emission policies. Thus, to better plan effective mitigation and adaptation activities, further research including an in-depth exploration of the divergent responses in transient versus stabilized scenarios, the quantification of future projection uncertainties, and improvements of the methods to reduce model uncertainties are required.

Objective To investigate the safety, efficiency and cost of total joint arthroplasty (TJA) under the enhanced recovery after surgery (ERAS) program and identify predictors facilitating further decrease in length of stay (LOS). Methods We retrospectively collected the information of patients who underwent primary unilateral TJA by a single surgical team between January 2017 and June 2019. A total of 604 patients with LOS ≤ 3 was enrolled in this study. All patients completed 12‐month or longer follow‐up. Patients received the same ERAS protocol, mainly including preoperative preparation (patient education, preoperative functional exercises, nutritional support), blood management, pain management, sleep management, prevention of infection, prevention of thrombosis and strict discharge criteria. Preoperative characteristics of patients were collected from the medical record system and were compared between the LOS ≤ 2 group and the LOS = 3 group. Factors with significant difference were included in multivariate logistic regression analysis to find independent preoperative predictors for LOS. Joint function at the latest follow‐up, adverse events rate and hospitalization costs were compared between the LOS ≤ 2 group and the LOS = 3 group. Results Of the enrolled 604 patients, 271 patients (44.9%) had a LOS of 2 days or less while 333 patients (55.1%) had a LOS of 3 days. Pittsburgh Sleep Quality Index score (odds ratio [OR] = 1.084, 95% confidence interval [CI] = 1.024–1.147, P = 0.005), preoperative albumin level (OR = 0.945, 95% CI = 0.905–0.988, P = 0.012), digestive diseases (OR = 1.084, 95% CI = 1.024–1.147, P = 0.005) and total hip arthroplasty (THA) (OR = 0.273, 95% CI = 0.170–0.439, P

Abstract The phase-field (PF) method is a physics-based computational approach for simulating interfacial morphology. It has been used to model powder melting, rapid solidification, and grain structure evolution in metal additive manufacturing (AM). However, traditional direct numerical simulation (DNS) of the PF method is computationally expensive due to sufficiently small mesh size. Here, a physics-embedded graph network (PEGN) is proposed to leverage an elegant graph representation of the grain structure and embed the classic PF theory into the graph network. By reformulating the classic PF problem as an unsupervised machine learning task on a graph network, PEGN efficiently solves temperature field, liquid/solid phase fraction, and grain orientation variables to minimize a physics-based loss/energy function. The approach is at least 50 times faster than DNS in both CPU and GPU implementation while still capturing key physical features. Hence, PEGN allows to simulate large-scale multi-layer and multi-track AM build effectively.

One of the critical challenges for the protonic ceramic fuel cell stack is sealing electrolytes and interconnects. However, the traditional AgCuO sealant will aggravate the oxidation along the interconnect surface and result in brittle compound layers at the BaZr0.1Ce0.7Y0.1Yb0.1O3-δ (BZCYYb) electrolyte interface. The present work demonstrates that a silver particle interlayer with high dislocation density can be adopted to join BZCYYb electrolyte to the interconnect (AISI 441 stainless) in air instead of traditional AgCuO sealant. Elevating temperatures result in a sufficient bonding at the Ag/BZCYYb interface, and a defect-free joint is obtained at 950 °C. Atomic bonding at Ag/BZCYYb interface is confirmed by TEM. Also, a dense and thin oxide layer (2–3 μm) is formed along the AISI 441 interface. Ag particles in the interlayer provide the main driving force for the sintering joining. The massive dislocations promote the recovery and recrystallization of the Ag interlayer, as well as the interdiffusion of BZCYYb/Ag. After aging in the wet oxidizing atmosphere at 600 °C for 300 h, joints remain intact and dense, indicating superior oxidation resistance and aging performance. Besides, the joint shear strength (25.3 MPa) is 59 % higher than that of the joint brazed by traditional AgCuO.

Abstract. Background:. Changes in thyroid hormone levels are commonly recognized characters among the elderly, which were reported to potentially influence incident frailty. Therefore, we examined the cross-sectional associations of thyroid hormones (THs) with frailty as well as the five components characterizing frailty (fatigue, resistance, ambulation, number of illnesses, and loss of weight) among the oldest-old. Methods:. Four hundred and eighty-seven community-dwelling oldest-old from a local community in Haidian District, Beijing, participated in our recruitment campaign between April 2019 and May 2020. The primary outcomes were a definitive diagnosis of frailty according to the FRAIL scale (Fatigue, Resistance, Ambulation, Illnesses, Loss of weight) and a positive score for each frailty subdomain. Demographic information (age, sex, marital status, and educational status), comorbidities, and details on the participants’ lifestyles were recorded. Serum THs including free triiodothyronin (fT3), triiodothyronine (T3), free thyroxine (fT4), and thyroxine (T4) and thyroid stimulating hormone (TSH) levels were also measured at the beginning of our study. Logistic regressions were conducted to screen for potential risk factors for frailty and its subdomains. Results:. Among the total 487 subjects at enrollment, 60 (12.23%) of them were diagnosed with subclinical hypothyroidism and 110 (22.59%) of the total population scored positive for frailty. Logistic regression analyses adjusted for all potential confounders, showed that frailty was significantly associated with the serum TSH concentration (odds ratio [OR]: 1.06), fT3 concentration (OR: 0.54), and subclinical hypothyroidism score (OR: 2.18). The association between fT4 and frailty was absent in our observational study. The fT3/fT4 ratio characterizing peripheral hormone conversion was also tested to be correlated with frailty. Conclusion:. Subclinical hypothyroidism, higher TSH level, lower fT3 level, and decreased fT3/fT4 ratio were all associated with frailty assessed by the FRAIL scale among the community-dwelling oldest-old, suggesting a relevant role of thyroid function in aging. Future longitudinal studies are warranted to determine the casual relationship between thyroid dysfunction and frailty in the oldest-old.

This study reports the occurrence of sustained and intensified microbial CH4 cycling in a giant lake in northwestern China during Early Permian climate warming. Lacustrine CH4 emissions may have contributed to the end of the Late Paleozoic Ice Age.

As 90% of cancer-patient deaths are due to metastasis, novel therapeutics that selectively target and kill metastatic cells are desperately needed. Matrix metalloproteinase-14 (MMP-14), which plays a critical role in digesting the basement membrane and in inducing cancer cell migration, has been found to be expressed at the cell surface of circulating and metastasized tumor cells in various human cancers. We have recently shown that the IVS4 peptide, which mimics the minimal binding motif of the hemopexin-like (PEX) domain of MMP-14, interrupts MMP-14 dimerization and decreases MMP-14-mediated cell invasion. In this study, cancer-homing nanocarriers were assembled by linking IVS4 to polysaccharide-based nanoparticles (NPs), followed by the encapsulation of a pharmaceutical agent. IVS4-NPs efficiently prevented MMP-14-mediated cell migration and conferred an uptake advantage compared to the control peptide in an MMP-14-dependent manner. While the IVS4-NPs alone were not cytotoxic, drug-encapsulated NPs were shown to effectively target MMP-14-expressing cancer cells. This novel nanotherapeutic is capable of inhibiting MMP-14-mediated functions and efficiently killing MMP-14-expressing cancer cells, without affecting the viability of non-cancer cells.

Abstract There is complex air leakage in the mining of shallow buried close distance coal seam group, which affects the generation and migration of CO in the goaf, and easily leads to exceeding safety limits of CO in the return corner of the working face, which threatens the safety of underground production. To examine this problem, taking Lijiahao Coal Mine as an example, this study analyses the generation law of CO gas, the distribution law of overburden fractures, the characteristics of air leakage in the goaf, the sources of CO in the return corner, and the migration and accumulation law of CO in the goaf under multi-source air leakage in the mining of shallow buried close distance coal seam group through experiment tests, numerical simulations, observations and theoretical analyses. The results indicated that there is an exponential growth relationship between the CO generation rate and the coal temperature, and the critical temperature for rapid oxidation of coal samples is between 70 and 80 °C. The 31,115 working face has complicated air leakage from the working face and ground surface and the goaf of this coal seam. The surface air converges to the return corner through the mining fissure of overburden and 2–2 coal goaf, and the air leakage of the working face flows out from the return roadway through the goaf. The gas leakage in the overlying goaf and the oxidation of residual coal are the main sources of CO in the return corner. The CO generated during the coal mining process and the CO generated by the trackless rubber-tired vehicle operation will increase the CO concentration in the return corner to varying degrees. Under the effect of multi-source air leakage, CO from the overlying goaf and the residual coal in the goaf of this coal seam are migrated to the air return side of the goaf, resulting in the accumulation of CO in the return corner, and both of them have a linear positive correlation with the CO concentration in the return corner. The results of the study have scientific guidance for the control of air leakage and the prevention of CO excess in the goaf.

The northwestern Junggar Basin in the southwestern Central Asian Orogenic Belt is a typical petroliferous basin. The widely distributed reservoirs in Jurassic–Cretaceous strata indicate that the region records Yanshanian–Himalayan tectonic activity, which affected the accumulation and distribution of petroleum. The mechanism of this effect, however, has not been fully explored. To fill the knowledge gap, we studied the structural geology and geochemistry of the well-exposed Wuerhe bitumen deposit. Our results indicate that deformation and hydrocarbon accumulation in the northwestern Junggar Basin during the Yanshanian–Himalayan geodynamic transformation involved two main stages. During the Yanshanian orogeny, a high-angle extensional fault system formed in Jurassic–Cretaceous strata at intermediate to shallow depths owing to dextral shear deformation in the orogenic belt. This fault system connected at depth with the Permian–Triassic oil–gas system, resulting in oil ascending to form fault-controlled reservoirs (e.g., a veined bitumen deposit). During the Himalayan orogeny, this fault system was deactivated owing to sinistral shear caused by far-field stress related to uplift of the Tibetan Plateau. This and the reservoir densification caused by cementation formed favorable hydrocarbon preservation and accumulation conditions. Therefore, the secondary oil reservoirs that formed during the Yanshanian–Himalayan tectonic transformation and the primary oil reservoirs that formed during Hercynian–Indosinian orogenies form a total and complex petroleum system comprising conventional and unconventional petroleum reservoirs. This might be a common feature of oil–gas accumulation in the Central Asian Orogenic Belt and highlights the potential for petroleum exploration at intermediate–shallow depths.

BackgroundTraumatic lumbosacral spondyloptosis is a very rare spinal disease caused by high-energy trauma. We report a case of traumatic lumbosacral spondyloptosis with locked L5 inferior articular process.Case presentationA 33-year-old man presented with multisite pain for 6 h following waist trauma and was admitted to the hospital. He suffered multiple injuries from severe impact on the waist after driving an out of control forklift truck. Preoperative imaging examinations revealed that the patient was diagnosed with traumatic lumbosacral spondyloptosis and the L5 inferior articular process was locked into the anterior margin of the S1 vertebra. A posterior instrumentation, decompression of the cauda equina, and interbody fusion procedure was performed. The patient received hyperbaric oxygen and rehabilitation treatment 10 days after the surgery. At the 6-month postoperative follow-up, the muscle strength of the lower limbs was improved, the patient had no numbness of both lower limbs, and the urinary retention symptom was significantly improved. The American Spinal Injury Association grade improved from grade C preoperatively to grade D postoperatively. As far as we know, there have been no relevant reports on traumatic lumbosacral spondyloptosis with locked L5 inferior articular process yet.ConclusionWe believe that the hyperflexion and shear forces were the potential causes of this injury. In addition, the preoperative imaging examinations should be evaluated carefully. If the inferior articular process of L5 were locked, we suggest removing the bilateral inferior articular processes first and then perform reduction.

Objectives: Long-term use of evidence-based antiplatelet therapy is recommended for management of stable coronary artery disease (SCAD). However, non-adherence to antiplatelet drugs is common in older patients. This study aimed to evaluate the incidence and impact of antiplatelet therapy cessation on clinical outcomes of older patients with SCAD.Methods: A total of 351 consecutive eligible very older patients (≥80 years) with SCAD from the PLA General Hospital were included. Baseline demographics, clinical characteristics, and clinical outcomes were collected during follow-up. Patients were divided into cessation group and standard group based on whether discontinuing of antiplatelet drugs. The primary outcome was major adverse cardiovascular events (MACE) and secondary outcomes were minor bleeding and all-cause mortality.Results: A total of 351 participants, with a mean age of 91.76 ± 5.01 years old (range 80–106 years) were included in statistical analysis. The antiplatelet drug cessation rate was 60.1%. There were 211 patients in cessation group and 140 patients in standard group. During a median follow-up of 98.6 months, the primary outcome of MACE occurred in 155 patients (73.5%) in the cessation group and 84 patients (60.0%) in the standard group (HR = 1.476, 95% CI:1.124-1.938, p = 0.005). Cessation of antiplatelet drugs increased the rates of angina (HR = 1.724, 95% CI:1.211-2.453, p = 0.002) and non-fatal MI (HR = 1.569, 95% CI:1.093-2.251, p = 0.014). The secondary outcomes of minor bleeding and all-cause mortality were similar between the two groups.Conclusion: Among very older patients with SCAD, antiplatelet therapy cessation significantly increased the risk of MACE, and continuous antiplatelet drug therapy didn’t increase the risk of minor bleeding.

Testicular germ cell tumors (TGCTs) commonly occur in males between the ages of 15 and 34, accounting for 98% of testicular malignancies. Long non-coding RNAs (LncRNAs) have been reported to play important roles in TGCT proliferation, invasion, and functioned as prognostic biomarkers. Testis-specific transcript, Y-linked 14 (TTTY14), a long non-coding RNA localized on Chr Y q11.222, has been found to be a potential prognostic biomarker for laryngeal squamous cell carcinoma, gastric cancer, and osteosarcoma. The biological role of TTTY14 in TGCT is not well understood. In this study, we aim to clarify the biological role of TTTY14 in TGCT, as well as its role in TGCT survival prognosis and immunotherapy efficacy prediction through the deep mining of public data combined with the verification of cell biological experiments. We found that high TTTY14 expression was a poor survival prognostic factor in TGCT patients and the expression of TTTY14 might be regulated by copy number variation and DNA methylation. TTTY14 knockdown significantly inhibited the proliferation of TGCT in vitro. TTTY14 expression was positively correlated with immune cell dysfunction, and significantly negatively correlated with B cells, CD8+ T cells, and macrophages, suggesting that TTTY14 may also affect the drug sensitivity by regulating the tumor immune microenvironment. In conclusion, we revealed that lncRNA TTTY14 was a novel oncogene and a biomarker in TGCT. TTTY14 may influence the drugs sensitivity through regulating the tumor immune microenvironment.

The Pacific Decadal Oscillation (PDO) and Pacific Meridional Mode (PMM) are prominent climate modes in the North Pacific with well-established impacts on tropical cyclone (TC) genesis in the western North Pacific (WNP) basin. While previous research has primarily focused on the roles of the PDO and PMM in regulating TC genesis through the modification of large-scale environmental factors, this study investigates the evolving influence of the PDO on WNP TC genesis since the 1950s. Remarkably, our analysis reveals a shift in the PDO-TC genesis relationship, transitioning from a significant negative correlation to a significant positive correlation since the 1990s. This shift is attributed to variations in the specific large-scale factors through which the PDO affects TC genesis. Furthermore, this study suggests that these changes appear to be linked to the PMM strengthening on the interdecadal timescale in recent decades. The linkage of the PMM strengthening to the PDO-related atmospheric circulation is further confirmed by the results of a 500 year pre-industrial numerical experiment, suggesting that the PMM strengthening may result from natural internal variability. The results underscore the non-stationary relationship between PDO and WNP TC genesis, with the PMM intensity probably influencing their relationship.

This paper presents an improved motion controller based on the backstepping method to address nonlinear control challenges in unmanned aerial–aquatic vehicles (UAAVs), enabling them to navigate between two different media. The nonlinear control approach is applied to UAAV motion control, incorporating filters to improve stability. The study designs motion controllers for three UAAV phases: underwater, in the air, and transitioning between media. Fluid simulations of the emergence process of the UAAV for future field experiments were conducted. By fine-tuning the simulations, a comprehensive understanding of the vehicle’s performance is obtained, offering crucial insights for the development of subsequent control systems. Simulation results confirm the controller’s ability to achieve target trajectory tracking with control system responses that meet practical requirements. The controller’s performance in attitude control and trajectory tracking is verified in underwater gliding, transmedia transitions, and airborne phases, demonstrating its effectiveness.

This article explores trajectory-following control for an unmanned aerial–aquatic vehicle (UAAV) navigating complex ocean disturbances and the interplay of air–seawater coupling factors. First, leveraging the backstepping technology, an adaptive algorithm is proposed to tackle the attitude and position following. Additionally, a nonlinear observer is crafted to estimate complex ocean disturbances. The UAAV model, characterized by six degrees of freedom (DOF) and nonlinear properties, experiences significant pose changes when emerging from water, underscoring the critical importance of precise pose control. Finally, stability analysis and numerical simulations are demonstrated to verify the feasibility and validity of the proposed control strategies.

Abstract Background Circular RNAs (circRNA) are important in mediating tumor progression, but their roles in endometrial carcinoma (EC) are not fully understood yet. Many circRNAs are dysregulated and may contribute to EC progression. The functions of circWDR26 in EC remain unknown. Methods The expression of circWDR26 in EC and adjacent normal tissues, and cell lines was determined by qPCR. The proliferation, apoptosis, migration, and invasion of EC cells was examined by CCK-8 assay, flow cytometry, wound healing assay and Transwell assay. The interaction between circWDR26, MSH2 and miR-212-3p was determined by luciferase assay. EC cells were inoculated into nude mice and tumor burden was determined by measuring tumor dimensions, size, and weight. The proliferative marker Ki67 in EC tissue was determined by immunohistochemistry. Results The expression of circWDR26 in EC tissues or cell lines was higher than in the normal tissue or endometrial epithelial cells. Downregulation of circWDR26 resulted in attenuated proliferation, increased apoptosis, reduced migration and invasion of EC cells. Mechanistically, circWDR26 targeted and suppressed the expression of miR-212-3p. We further found that MSH2 was the novel target of miR-212-3p and was upregulated by circWDR26 via inhibiting miR-212-3p. In vivo experiment demonstrated that circWDR26 was essential for EC tumor growth. Conclusion circWDR26 promoted EC progression by regulating miR-212-3p/MSH2 axis and provided novel insights into anti-cancer treatment.

Abstract In additive manufacturing of metal parts, the ability to accurately predict the extremely variable temperature field in detail, and relate it quantitatively to structure and properties, is a key step in predicting part performance and optimizing process design. In this work, a finite element simulation of the directed energy deposition (DED) process is used to predict the space- and time-dependent temperature field during the multi-layer build process for Inconel 718 walls. The thermal model results show good agreement with dynamic infrared images captured in situ during the DED builds. The relationship between predicted cooling rate, microstructural features, and mechanical properties is examined, and cooling rate alone is found to be insufficient in giving quantitative property predictions. Because machine learning offers an efficient way to identify important features from series data, we apply a 1D convolutional neural network data-driven framework to automatically extract the dominant predictive features from simulated temperature history. Very good predictions of material properties, especially ultimate tensile strength, are obtained using simulated thermal history data. To further interpret the convolutional neural network predictions, we visualize the extracted features produced on each convolutional layer and compare the convolutional neural network detected features of thermal histories for high and low ultimate tensile strength cases. A key result is the determination that thermal histories in both high and moderate temperature regimes affect material properties.

The evaluation of post-mature source rocks gradually invalidates by traditional organic geochemical parameters due to the decreasing of organic matter abundance. However, the inorganic elements in source rocks are not easily affected by thermal evolution. In order to explore the application of inorganic geochemical methods in the evaluation of post-mature source rocks, this paper takes the Sinian-Cambrian source rocks in the Sichuan Basin as an example to conduct an evaluation based on the inorganic (major, trace and rare earth elements) geochemistry method with three controlling factors of source rock development (paleoproductivity, sedimentary environment and sedimentary rate). The concentration of Ba and Ni, MoEF and UEF and Ce anomaly, and TiO2/Al2O3 ratio could be correlated with paleoproducitvity, sedimentary environment and sedimentary rate, respectively. The results showed that the enrichment of organic matter was mainly controlled by sedimentary environment and paleoproductivity, but are barely effected by sedimentary rate. Source rocks in the Lower Cambrian Qiongzhusi Formation in the central Sichuan and Weiyuan-Ziyang areas have high paleoproductivity and the most reduced environment and thus are one of the best quality source rocks. Therefore, inorganic geochemistry method is an effective way to evaluate postmature source rocks.

The exploration towards cost-effective filler metal for ceramics joining has always been the key issues for ceramics joining. Herein, we reveal that the Al metal prefers to spread on the ZrO2 based ceramic under the air heating condition, due to the geometric limit effects by in-situ formed dense Al2O3 surface. Inspired by this, the joining of ZrO2 based ceramics was realized in air with Al metal as filler, through the diffusion of Al towards ceramic side. The Al element can induce obvious interfacial bonding effect on Al2O3 layer and ZrO2 ceramic, where the hybridization among the Al-p, Zr-d and O-p orbitals plays a key role. The in-situ formed Al2O3 layer on Al filler surface is vital for forming the fine interface (shear strength of ∼36 MPa), which results in the relief of lattice mismatch and peak stress at ceramic-filler metal transition interface.

Abstract Spinal cord injury (SCI) has seriously affected the lives of patients and brought economic and medical burdens to society. Biopharmaceuticals, including transplanted cells, growth factors, enzyme drugs, and microRNA, present multidimensional therapeutic effects in tissue repair and regeneration, and thus are widely utilized for the treatment of SCI. Nevertheless, they still encounter great challenges. The turbulent microenvironment accompanied by various destructive components following SCI has led to poor stability, low local accumulation, and reduced therapeutic efficacy of biopharmaceuticals. To this end, biomaterial‐based defenders (BBDs) that are capable of resisting the destructive components have shown great promise in improving the survival of transplanted cells or retaining the activity of the protein and nucleic acid drugs for the treatment of SCI. In this review, various types of biopharmaceuticals applied in SCI and their limitations are introduced. The destructive components that threaten the activities of biopharmaceuticals in the rigorous microenvironment are then summarized. In particular, the current research progress about BBDs boosting the efficacy of biopharmaceuticals for the treatment of SCI is illustrated with specific examples. The existing challenges and future perspectives are also provided.

Quiescence is a cellular state of reversible growth arrest required to maintain homeostasis and self-renewal. Entering quiescence allows the cells to remain in the non-dividing stage for an extended period of time and enact mechanisms to protect themselves from damage. Due to the extreme nutrient-deficient microenvironment in the intervertebral disc (IVD), the therapeutic effect of cell transplantation is limited. In this study, nucleus pulposus stem cells (NPSCs) were preconditioned into quiescence through serum starvation in vitro and transplanted to repair intervertebral disc degeneration (IDD). In vitro, we investigated apoptosis and survival of quiescent NPSCs in a glucose-free medium without fetal bovine serum. Non-preconditioned proliferating NPSCs served as controls. In vivo, the cells were transplanted into a rat model of IDD induced by acupuncture, and the intervertebral disc height, histological changes, and extracellular matrix synthesis were observed. Finally, to elucidate the mechanisms underlying the quiescent state of NPSCs, the metabolic patterns of the cells were investigated through metabolomics. The results revealed that quiescent NPSCs decreased apoptosis and increased cell survival when compared to proliferating NPSCs both in vitro and in vivo, as well as maintained the disc height and histological structure significantly better than that by proliferating NPSCs. Furthermore, quiescent NPSCs have generally downregulated metabolism and reduced energy requirements in response to a switch to a nutrient-deficient environment. These findings support that quiescence preconditioning maintains the proliferation and biological function potential of NPSCs, increases cell survival under the extreme environment of IVD, and further alleviates IDD via adaptive metabolic patterns.

Background Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degradation. Circular RNAs (circRNAs) are involved in the initiation and development of OA. This study aimed to explore the potential role and mechanism of circRNA protein kinase C eta (circ-PRKCH) in OA. Methods A total of 30 cartilage specimens were collected from OA patients or normal subjects. Human chondrocytes (CHON-001) were stimulated with interleukin-1β (IL-1β) to establish an in vitro OA model. The expression levels of circ-PRKCH, microRNA-502-5p (miR-502-5p) and circ-PRKCH or A disintegrin and metalloproteases metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) in cartilage specimens and IL-1β-treated chondrocytes were detected by quantitative real-time PCR or Western blot, and their correlation in OA cartilage specimens was analysed by Spearman’s correlation coefficient. The targeted relationship between miR-502-5p and circ-PRKCH or ADAMTS5 was verified by dual-luciferase reporter assay and RNA Immunoprecipitation (RIP) assay. Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2′-deoxyuridine (EDU), flow cytometry, wound healing and enzyme-linked immunosorbent assay (ELISA) assays were applied to evaluate cell proliferation, apoptosis, migration and inflammatory response in IL-1β-treated chondrocytes. Exosomes were identified by transmission electron microscope (TEM) and Western blot. Results Circ-PRKCH and ADAMTS5 expression levels were up-regulated, while miR-502-5p expression was down-regulated in OA cartilage tissues and IL-1β-treated chondrocytes. Depletion of circ-PRKCH relieved IL-1β-treated chondrocyte cell phenotypic changes by promoting cell proliferation and migration, as well as inhibiting apoptosis and inflammatory response. Mechanically, circ-PRKCH acted as a sponge for miR-502-5p to regulate ADAMTS5 expression, thereby contributing to IL-1β-treated chondrocyte cell phenotypic changes. Moreover, exosomes derived from IL-1β-treated chondrocytes could transfer circ-PRKCH across cells. Conclusion Circ-PRKCH contributed to IL-1β-treated cell phenotypic changes in chondrocytes via modulating miR-502-5p/ADAMTS5 pathway, which might provide a promising biomarker for OA treatment.

Abstract Shape morphing behavior has applications in many fields such as soft robotics, actuators and sensors, solar cells, tight packaging, flexible electronics, and biomedicine. The most common approach to achieve shape morphing structures is through shape memory alloys or hydrogels. These two materials undergo differential strains which generate a variety of shapes. In this work, we demonstrate the novel concept that 2D knits comprising of yarns from different materials can be morphed into different three-dimensional shapes thereby forming a bridge between traditional knitting and shape changing structures. This concept is referred to as Knitmorphs. Our computational analysis acts as the proof of concept revealing that knitted patterns of varying materials morph into complex shapes, such as saddle, axisymmetric cup, and a plate with waves when subjected to thermal loads. Two-dimensional circular models of plain and rib developed on CAD packages are imported to the finite element analysis software Abaqus, followed by post-processing into wires and assigning fiber material properties of different thermal coefficients of expansion and stiffness. We also propose potential applications for the concept of programmable knits for developing robots based upon jellyfish like locomotion, and complex structures similar to wind turbine blades. This novel concept is meant to introduce a new field for design when considering morphable structures.

Molecular testing of indeterminate thyroid nodules informs about the presence of point mutations, insertions/deletions, copy number variants, RNA fusions, transcript alterations and miRNA expression. American Thyroid Association (ATA) guidelines suggest molecular testing of indeterminate thyroid nodules may be considered to supplement risk of malignancy (ROM). Although these recommendations have been incorporated in clinical practices in the United States, molecular testing of indeterminate thyroid nodules is not common practice in Asia. Here, we performed molecular testing of 140 indeterminate nodules from Chinese patients using a novel molecular platform composed of RNA and DNA‐RNA classifiers, which is similar to Afirma GEC and ThyroSeq v3. Compared with reports from North America, the new RNA and DNA‐RNA classifiers had a higher positive predictive value (p1 = 0.000 and p2 = 0.020) but a lower negative predictive value (p1 = 0.004 and p2 = 0.098), with no significant differences in sensitivity (p1 = 0.625 and p2 = 0.179) or specificity (p1 = 0.391 and p2 = 0.264). Out of 58 resected nodules, 10 were borderline and 33 malignant, indicating a 74.1% ROM, which was higher than reports in North America (10–40% ROM). Our findings emphasize molecular testing with the newly reported RNA and DNA‐RNA classifiers can be used as a ‘rule‐in’ test when ROM is high.

The development of micro-nano pores and throats in shale oil reservoirs has made it complicated and diversified for the occurrence and state of oil, and is difficult to be studied. A case study was carried out with the Middle Permian Lucaogou Formation in the Jimsar Sag of Junggar Basin by the approaches of Field Emission Scanning Electron Microscopy (FESEM), Nuclear Magnetic Resonance (NMR), Laser Scanning Confocal Microscope (LSCM) and nano-CT. The plane porosities of siltstones and dolomitic siltstones in sweet spots of the study area range from 11.0% to 23.5%, and the dissolved pores and intragranular dissolved pores larger than 2 μm account for more than 49.0%. The distribution of oil and pore water has strong differentiation in micro-nano scale, which is controlled by complex factors such as overpressure migration of hydrocarbon generation, pore surface adsorption and oil quality difference in different stages of continuous shale oil accumulation. In sweet spot reservoirs, intermediate oil and free water occur in the center of pores larger than 2 μm, while heavy oil exists on pore surface as thin film. Pores with the size smaller than 2 μm are mainly filled with heavy oil. Intermediate oil is relatively easier to be explored, while heavy oil is a more realistic and feasible target for enhanced oil recovery in the future.

Despite acral melanoma being the most common melanoma subtype in non-White individuals, its molecular drivers remain unknown. Here, the authors integrate genomic and clinical data from 104 patients and identify late-arising focal amplifications of chr22q11.21 and LZTR1 as a key tumour promoter in this region.

The gradually increasing presence of arsenic, a highly toxic heavy metal, poses a significant threat to both soil environmental safety and human health. Pteris vittata has long been recognized as an efficient hyperaccumulator plant for arsenic pollution. However, the pattern of arsenic accumulation in soil impacts its bioavailability and restricts the extraction efficiency of Pteris vittata. To address this issue, microorganisms have the potential to improve the arsenic accumulation efficiency of Pteris vittata. In this work, we employed anthropogenic enrichment methods to extract functional iron–sulfur-reducing bacteria from soil as a raw material. These bacteria were then utilized to assist Pteris vittata in the phytoremediation of arsenic-contaminated soil. Furthermore, the utilization of organic fertilizer produced from fermented crop straw significantly boosted the remediation effect. This led to an increase in the accumulation efficiency of arsenic by Pteris vittata by 87.56%, while simultaneously reducing the content of available arsenic in the soil by 98.36%. Finally, the experimental phenomena were studied through a soil-microbial batch leaching test and plant potting test. And the mechanism of the microorganism-catalyzed soil iron–sulfur geochemical cycle on arsenic release and transformation in soil as well as the extraction effect of Pteris vittata were systematically investigated using ICP, BCR sequential extraction and XPS analysis. The results demonstrated that using iron–sulfur-reducing microorganisms to enhance the phytoremediation effect is an effective strategy in the field of ecological restoration.

Using a phytoremediation technique for soil remediation usually takes many years, which increases the risk that heavy metals spread into the environment during the project period. Currently, the combined remediation technique (phytoremediation and stabilization) is known as the solution to reduce this risk. In this study, the combined remediation of cadmium–arsenic-contaminated soil via phytoremediation and stabilization was studied. The pot experiment was carried out using modified fly ash (MFA) and solid waste material (steel slag (SS): pyrolusite (PY): ferrous sulfide (FS) = 1:2:8) as stabilization materials and Bidens pilosa as the accumulative plant. The characteristics of B. pilosa, including its water content, biomass, root length, plant height, and heavy metal content, were obtained after harvesting, and the reduction rate of the bioavailability of Cd and As and their physico-chemical properties, including the pH, Eh, and Ec values of the soil, were also measured. The remediation effect was evaluated according to the above indexes, and the mechanism of combined remediation was studied through the FTIR, XRD, and XPS analyses. These experiments have shown that adding an appropriate amount of MFA can enhance the absorption of heavy metals by plants in the soil and reduce the bioavailability of heavy metals in contaminated soil. In addition, the mechanism study revealed that Cd2+/Cd(OH)+ was easily adsorbed on Si-OH and MnOOH, while AsO43− was more easily adsorbed on Fe-OH and Al-OH.

The Cashmere goat is an excellent local goat breed in Gansu Province of China, and it is expected to improve cashmere production and cashmere quality through selection and breeding to enhance its commercial value. Keratin-associated proteins (KAPs) play an important role in maintaining wool structure. The gene encoding the keratin-associated protein 22-2 (KAP22-2) gene has been identified in selected species other than goats, such as humans, mice, and sheep. In this study, the sequence of the sheep KAP22-2 gene (KRTAP22-2) was aligned into the goat genome, and the sequence with the highest homology was assumed to be the goat KRTAP22-2 sequence and used to design primers to amplify the goat gene sequence. A total of 356 Longdong Cashmere goats (Gansu Province, China) were used for screening of genetic variants. Four specific bands were detected by polymerase chain reaction-single-stranded conformational polymorphism (PCR-SSCP) analysis, and they formed a total of six band types individually or in combination. Four alleles were identified by DNA sequencing of PCR amplification products. A total of four single nucleotide polymorphic sites (SNPs) were detected in the four sequenced KRTAP22-2 alleles. Two of them are in the 5’UTR region and the other two are in the coding region, and the variants in the coding region are all non-synonymous mutations. In addition, there was a 6 bp length variation in allele C. The gene was expressed in the cortical layer of primary and secondary hair follicles, the inner root sheath, as well as hair papillae and hair maternal cells in goats. The results of the correlation analysis between genotypes and cashmere traits showed that after excluding genotypes with a gene frequency of less than 5%, the mean fiber diameter (MFD) of cashmere was significantly higher in the AB genotype than in the AA and AC genotypes. That is, the KRTAP22-2 gene variants are associated with mean fiber diameter in cashmere. The above results suggest that the goat KRTAP22-2 variant can be utilized as a molecular marker candidate gene for cashmere traits.

This Special Issue of the journal Axioms pays tribute to Professor Feng Qi’s significant contributions and provides some important recent advances in mathematics [...]

Estimation of continuous motion of human joints using surface electromyography (sEMG) signals has a critical part to play in intelligent rehabilitation. Traditional methods always use sEMG signals as inputs to build regression or biomechanical models to estimate continuous joint motion variables. However, it is challenging to accurately estimate continuous joint motion in new subjects due to the non-stationarity and individual differences in sEMG signals, which greatly limits the generalisability of the method. In this paper, a continuous motion estimation model for the human knee joint with a parameter self-updating mechanism based on the fusion of particle swarm optimization (PSO) and deep belief network (DBN) is proposed. According to the original sEMG signals of different subjects, the method adaptively optimized the parameters of the DBN model and completed the optimal reconstruction of signal feature structure in high-dimensional space to achieve the optimal estimation of continuous joint motion. Extensive experiments were conducted on knee joint motions. The results suggested that the average root mean square errors (RMSEs) of the proposed method were 9.42° and 7.36°, respectively, which was better than the results obtained by common neural networks. This finding lays a foundation for the human–robot interaction (HRI) of the exoskeleton robots based on the sEMG signals.

Analysis of the biomarkers of saturated hydrocarbon and related compound specific carbon isotopes of crude oils were carried out for the research of origin of oils and controlling factors of oil properties in the Mosuowan area of the Junggar Basin, and mixed-source oil simulation was also carried out to reveal hydrocarbon accumulation in the study area. The carbon isotope of crude oil in the Pen 5 well block is relatively heavy, the Pr/Ph value is higher, between 1.4 and 1.9, and the index of adamantane isomerization is greater, indicating that the oil maturity of the Pen 5 well block is higher than that of the Pencan 2 well and had a more oxidative sedimental environment. The C7 light hydrocarbons of oil of the Mosuowan area are dominated by methylcyclohexane, with a content over 40%, and the distributions of regular steranes are dominated by C29 homologues with a content over 40%. Crude oils in the study area are thus indicated to be generated from terrestrial partial humus source rocks. The carbon isotope compositions and distribution of n-alkanes in the Pen 5 and Pencan 2 well blocks are similar, indicating that they were from the comparable sources, and they are generally similar to the source rocks in the Lower Wuerhe Formation. But the carbon isotope values of n-alkanes with different carbon numbers in the source rocks of the Lower Wuerhe Formation have a large span, reaching 4.6‰, while the carbon isotope values of n-alkanes with different carbon numbers of crude oil in the Mosuowan area have a smaller span, between 2.2‰ and 3.0‰. It is mainly caused by the different mixing ratio of crude oil. The quantitative calculation results of biomarkers in mixed-source oil showed that crude oil in the Mosuowan area was mainly derived from the late high-maturity source rocks in the Lower Wuerhe Formation, mixed with those from the early mature source rocks in the Fengcheng Formation. Among them, the high-maturity source rocks in the Lower Wuerhe Formation have a relatively greater contribution to crude oil in the Pen 5 well block, around 80%, and contribute about 60% to crude oil in the Pencan 2 well block. As a result, it is concluded that different proportions of mixed sources are the main reason which caused differences in the geochemical characteristics of crude oil in the Mosuowan area.

This paper introduces the usage and performance of the R package tlrmvnmvt, aimed at computing high-dimensional multivariate normal and Student-t probabilities. The package implements the tile-low-rank methods with block reordering and the separationof-variable methods with univariate reordering. The performance is compared with two other state-of-the-art R packages, namely the mvtnorm and the TruncatedNormal packages. Our package has the best scalability and is likely to be the only option in thousands of dimensions. However, for applications with high accuracy requirements, the TruncatedNormal package is more suitable. As an application example, we show that the excursion sets of a latent Gaussian random field can be computed with the tlrmvnmvt package without any model approximation and hence, the accuracy of the produced excursion sets is improved.

With an upsurge of biodegradable metal implants, the research and application of Mg alloys in the gastrointestinal environment of the digestive tract have been of great interest. Digestive enzymes, mainly pepsin in the stomach and pancreatin in the small intestine, are widespread in the gastrointestinal tract, but their effect on the degradation of Mg alloys has not been well understood. In this study, we investigated the impacts of pepsin and pancreatin on the degradation of Mg-2Zn alloy wires. The results showed that the pepsin and pancreatin had completely different even the opposite effects on the degradation of Mg, although they both affected the degradation product layer. The degradation rate of Mg wire declined with the addition of pepsin in simulated gastric fluid (SGF) but rose with the addition of pancreatin in simulated intestinal fluid (SIF). The opposite trends in degradation rate also resulted in completely different degradation morphologies in wires surface, where the pitting corrosion in SGF was inhibited because of the physical barrier effect of pepsin adsorption. In contrast, the adsorption of pancreatin affected the integrity of magnesium hydrogen phosphate film, causing a relatively uneven degraded surface. These results may help us to understand the role of different digestive enzymes in the degradation of magnesium and facilitate the development and clinical application of magnesium alloy implanted devices for the digestive tract.

In this work, the Mn–Co spinel coating is successfully employed to control adverse reactions at the Crofer 22 APU interconnect/Ag–CuO braze interface through blocking their direct contact. The Mn–Co spinel coating is fabricated on the Crofer 22 APU before reactive air brazing (RAB). Wetting of Ag–CuO braze on the Mn–Co spinel coated Crofer 22 APU is studied. Ag-8mol%CuO braze is used to successfully braze the Mn–Co spinel coated Crofer 22 APU and YSZ at 1050 °C for 30 min in air. The Crofer 22 APU is protected well by the Mn–Co spinel coating during RAB, avoiding its oxidation and the outward diffusion of Fe and Cr. The long-term stability of joints is also evaluated in air at 800 °C for 200 h. The Mn–Co spinel coating effectively mitigates further degradation of the joint caused by oxidation at the interconnect/braze interface.

Background: The association between serum bilirubin level and heart failure (HF) was controversial in previous observational studies and the causal effects of bilirubin on HF have not been investigated. Here, we conducted a Mendelian randomization (MR) study to investigate the associations between genetically determined bilirubin level and HF.Methods: Summary data on the association of single nucleotide polymorphisms (SNPs) with serum bilirubin levels were obtained from genome-wide association study (GWAS) for individuals of European descent and East Asian descent separately. Statistical data for gene-HF associations were extracted from three databases: the HERMES Consortium (47,309 cases and 930,014 controls), FinnGen study (30,098 cases and 229,612 controls) for European population and Biobank Japan (2,820 HF cases and 192,383 controls) for East Asian population. We applied a two-sample Mendelian randomization framework to investigate the causal association between serum bilirubin and HF.Results: Findings from our MR analyses showed that genetically determined serum bilirubin levels were not causally associated with HF risk in either European or East Asian population (odds ratio [OR] = 1.01 and 95% confidence interval [CI] = .97–1.05 for HERMES Consortium; OR = 1.01 and 95% CI = .98–1.04 for FinnGen Study; OR = .82, 95% CI: .61–1.10 for Biobank Japan). These results remained unchanged using different Mendelian randomization methods and in sensitivity analyses.Conclusion: Our study did not find any evidence to support a causal association between serum bilirubin and HF.

Background: Postoperative urinary retention (POUR) is a common and disruptive complication following total joint arthroplasty (TJA). The aim of this study is to investigate whether doxazosin can decrease the incidence of POUR and promote recovery under the setting of modern enhanced recovery after TJA.Methods: In this randomized placebo-controlled trial, patients over 35 years of age undergoing primary unilateral TJA were recruited. Patients received doxazosin (4 mg once) or placebo 2 h before surgery. The primary outcome of interest was the development of POUR, which was diagnosed when patients with a urine volume over 400 ml or overflow incontinence. Postoperative recovery was assessed in terms of hospital length of stay after surgery, daily ambulation distance, visual analogue scale (VAS) pain score and opioid consumption.Results: A total of 170 male patients were equally randomized into Doxazosin group (mean age 54.2 ± 13.7 years, range 36–88 years) and Placebo group (mean age 54.6 ± 13.9 years, range 38–81 years). The POUR rate was significant lower in Doxazosin group (17.6%) than in Placebo group (36.5%) (p = .006). The mean LOS in the Doxazosin group was 3.1 ± 1.1 days compared to 3.6 ± 1.7 days in the Placebo group (p = .030). Doxazosin group had a longer daily mobilization distance than Placebo group on postoperative day 1 (26.8 ± 11.1 vs. 22.8 ± 9.7; p = .015). Postoperative pain assessed by VAS score and opioid usage was comparable between two groups.Conclusion: Our results support the routine use of prophylactic doxazosin in male patients to decrease POUR rate and promote postoperative recovery under the setting of modern enhanced recovery after TJA.

BackgroundWhether cementless fixation on femoral and tibial components increases blood loss during total knee arthroplasty (TKA) is unclear. The purpose of this randomized controlled trial was to compare blood loss and early functional recovery between patients who underwent cementless or cemented TKA.MethodsBetween November 2021 and April 2022, sixty-one eligible patients at our medical center were randomized to cementless and cemented group. The primary outcome was total blood loss (TBL). Secondary outcomes were drainage, knee swelling, anemia, transfusion, hematological indicators, early functional recovery, and postoperative complications. The early functional recovery included range of motion (ROM), Hospital for Special Surgery (HSS) score, walking distance.ResultsA total of 61 patients were analyzed, of whom 30 underwent cementless fixation. On postoperative day 1, the mean TBL was 394.39 ml (SD 182.97 ml) in the cementless group and 382.41 ml (SD 208.67 ml) in the cemented group (P = 0.863). By postoperative day 3, the corresponding mean TBL was higher at 593.48 ml (SD 230.04 ml) and 603.80 ml (SD 213.16 ml) (P = 0.751). The two groups did not differ significantly in drainage, knee swelling, anemia, levels of hemoglobin or hematocrit or platelets, ROM, HSS score, walking distance, or rates of transfusion or postoperative complications.ConclusionsCementless fixation on femoral and tibial components during TKA does not increase blood loss or impede early functional recovery, which suggests that clinicians need not worry about blood loss and early functional recovery when deciding what type of fixation to perform during TKA.Trial registrationNumber: ChiCTR2100052857; Date: November 6, 2021.

DNA sensing through the cGAS-STING pathway plays an important role in cancer immunosurveillance. Pharmaceutical activation of STING in the tumor environment is considered an attractive approach to induce anti-tumor immunity, but had limited efficacy in the clinic. Several studies have found that STING is epigenetically silenced in many tumors, including colon cancer. This suggests that STING silencing in tumor cells contributes to immune escape and may limit the application of STING agonists. We previously found that inhibition of the KDM5 family histone demethylases restored STING expression in human breast cancer cells and activated the cGAS-STING pathway. In this study, we used MC38 and CT26 syngeneic mouse colorectal cancer models to show that loss of STING in tumor cells accelerates tumor growth. KDM5 inhibitors activate STING expression in mouse colorectal cancer cells and suppress colon cancer growth in immune competent mice in a STING-dependent manner. This study highlights KDM5 inhibitors as novel immune modulators in cancer therapies.

Abstract Background The most critical concern for the management of childhood intussusception is bowel resection due to intestinal ischemia and necrosis. The early prediction of this problem is of great importance. We investigated the value of various combinations of inflammatory factors to predict intestinal necrosis and resection. Methods We retrospectively reviewed the medical records of pediatric patients with intussusception who underwent surgical management. During the research period, 47 patients who underwent intestinal resection due to intestinal necrosis and 68 patients who did not undergo intestinal resection were enrolled. We evaluated the diagnostic value of various combinations of inflammatory markers from preoperative laboratory analyses using the receiver operating characteristic (ROC) method. Results In the current cohort, 115 patients underwent operations for intussusception; among them, 47 patients (40.9%) underwent intestinal resections. In the patients with intestinal resection, the neutrophil count(p = 0.013), CRP level(p = 0.002), platelet–lymphocyte ratio (PLR, p = 0.008), NLR (neutrophil–lymphocyte ratio, p = 0.026), and LCR (lymphocyte–CRP ratio, p

To discover the values of Fourier Transform Infrared Spectroscopy (FTIR) in the research of organic geochemistry, hydrocarbon generation features of source rocks of Lower Permian Fengcheng, Junggar Basin were studied by the means of FTIR analysis on the extracts. Seven FTIR functional groups appeared to have indicative significance, based on which three new index were proposed, including A index (A2 920/A3 600), B index (A2 920/A1 460), and C index (A1 140/A1 600). Specifically, A index unraveled a higher hydrocarbon generation potential of the source rocks located in saline areas, B index indicated that the possible hydrothermal fluid injection have caused the abnormal thermal evolution of organic matter in saline source rocks, and C index showed that an increasing salinity from marginal zone to saline zones has affected to the organic molecular polymerization in the Fengcheng Formation source rocks. Based on that, the saline zone located at the center of Fengcheng Formation deposition has great potential for oil-gas exploration, particularly for light oils in the deep reservoirs. These understandings provided new references for the regional oil-gas exploration and pointed out that FTIR can supplement traditional organic geochemistry, displaying a broad application potential.

Introduction: As an important advanced functional material, the memory effect of nitinol shape memory alloy (SMA) is the focus of research. According to the current research, the memory function of the alloy decreases after welding, and there is no sufficient explanation for the phenomenon. Objectives: For the problem, this research is to explore the underlying causes of the decrease of shape memory function after welding by analyzing the microstructure and micro defects. Methods: The vacuum electron beam welding tests of 1 mm thick Ni50Ti50 alloy plate was carried out to determine the appropriate welding process parameter. And the shape memory function of the welded joint was compared with that of the base metal to analyze the change of memory function. Results: It was found that the shape memory function of the welded joint decreased significantly under different strain variables. And the phase transition temperature also changed. Conclusions: This was due to the micro stress field produced by non-equilibrium solidification in molten pool promoted the formation and propagation of dislocations, increasing the dislocation density in the martensite. Dislocations entangled with each other in the martensite, showing a grid-like distribution, which destroyed the integrity of martensite substructure. At the same time, the twin substructure of martensite was often accompanied by vacancies, dislocations, stacking faults, and a consequently large stress field formed between twin planes due to lattice distortion. Secondary twin was identified inside martensite under micro shear stress, where the martensite showed the bending state. The habitual relationship between martensite phase and parent phase was destroyed, resulting in the decrease of shape memory function.