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During aging, the brain is subject to greater oxidative stress (OS), which is thought to play a critical role in cognitive impairment. Glutathione (GSH), as a major antioxidant in the brain, can be used to combat OS. However, how brain GSH levels vary with age and their associations with cognitive function is unclear. In this study, we combined point-resolved spectroscopy and edited spectroscopy sequences to investigate extended and closed forms GSH levels in the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and occipital cortex (OC) of 276 healthy participants (extended form, 166 females, age range 20–70 years) and 15 healthy participants (closed form, 7 females, age range 26–56 years), and examined their relationships with age and cognitive function. The results revealed decreased extended form GSH levels with age in the PCC among 276 participants. Notably, the timecourse of extended form GSH level changes in the PCC and ACC differed between males and females. Additionally, positive correlations were observed between extended form GSH levels in the PCC and OC and visuospatial memory. Additionally, a decreased trend of closed form GSH levels with age was also observed in the PCC among 15 participants. Taken together, these findings enhance our understanding of the brain both closed and extended form GSH time course during normal aging and associations with sex and memory, which is an essential first step for understanding the neurochemical underpinnings of healthy aging.

Summary: For a long time, myeloid-derived suppressor cells (MDSCs) dilated in circulation system of colorectal cancer (CRC) patients have been puzzling clinicians. Various evidence shows that MDSCs constitute the bulk of immunosuppression in CRC, which is related to tumor growth, adhesion, invasion, metastasis, and immune escape. However, the mechanisms underlying these cells formation remain incompletely understood. In this study, we reported that CRC cell-derived LC3-dependent extracellular vesicles (LDEVs)-mediated M-MDSCs formation via TLR2-MYD88 pathway. Furthermore Hsp60 was the LDEVs surface ligand that triggered these MDSCs induction. In clinical studies, we reported that accumulation of circulating M-MDSCs as well as IL-10 and arginase1 secretion were reliant upon the levels of tumor cell-derived LDEVs in CRC patients. These findings indicated how local tumor cell-derived extracellular vesicles influence distal hematopoiesis and provided novel justification for therapeutic targeting of LDEVs in patients with CRC.

The technology and equipment of speedy drivage with driving and bolting integration of soft surrounding rock is an urgent need for safe and efficient mining and intelligent construction of coal mines. Based on the background of mining roadway engineering with such a swelling soft rock and jointed soft rock , the development status of speedy drivage technology of bolter miner at home and abroad is sorted out, and three problems faced by speedy drivage of bolter miner under soft surrounding rock conditions are analyzed, including: disturbance control of surrounding rock by full width cutting, timely and efficient permanent support of soft surrounding rock, temporary support of lateral wall in speedy drivage of soft surrounding rock. Five key technologies for speedy drivage of soft surrounding rock are proposed, including: ① Low disturbance cutting technology. It mainly includes elliptical full-width cutting drum, pick arrangement optimization, cutting dynamics optimization, etc. ② Timely support technology to reduce the distance between coal face and permanent support for roof or lateral wall. This technology is based on the integrated technology of excavation and anchoring. Through the research of the multi-driller integral sliding platform integrating double cylindrical guidance, multi-link lifting, supporting oil cylinder top and bottom support, and follow-up gangue curtain protection, the distance between coal face and permanent roof support of the bolter miner is reduced from 2.5 m to 1 m, and the empty side distance is reduced from 3.5 m to 1 m. ③ Multi-dimensional collaborative support technology of soft surrounding rock. Considering the space-time synergistic effect between the bolt and anchor cable support parameters and the synergistic effect between the support body and the surrounding rock, the low-density strong bolt support is used to control the roof at the head, and the enhanced permanent support is implemented simultaneously at the rear. ④ Drilling anchor integration technology. It mainly includes bolt structure and mechanical properties, anchoring agent materials and pumping. ⑤ Coal side spraying temporary support technology. It mainly includes fast reaction high elongation spraying material, high proportion precision spraying pumping, irregular coal wall surface adaptive trajectory control, mine explosion-proof high-precision mechanical arm, spraying material matching supply, etc. Based on the above content, a controllable operation empty top distance bolter miner was developed and underground tests were carried out.The test shows that the equipment effectively shortens the empty roof distance and empty side distance, realizes the ' controllable ' empty roof distance, adapts to the speedy drivage of soft surrounding rock roadway, and doubles the excavation efficiency.

Abstract Background Cardiac masses can encompass a variety of conditions, such as tumors, thrombi, vegetations, calcific lesions, and other rare diseases. Treatment and management of these types of cardiac masses differ considerably. Thus, accurately distinguishing among thrombi, benign tumors, and malignant tumors in the heart is of great importance. Contrast echocardiography (CE) has emerged as a promising technology. Although published guidelines suggest that CE can enhance image quality and assist in differentiating between benign and malignant lesions, most studies on CE diagnosis of cardiac masses are limited to case reports or retrospective/small-sample-sized prospective cohorts. This study aims to evaluate the diagnostic accuracy of CE in patients with suspected cardiac masses and address the insufficient evidence for differential diagnosis using CE. Methods Between April 2018 and July 2022, a prospective multicenter study was conducted, which included 145 consecutive patients suspected to have cardiac masses based on transthoracic echocardiography. All patients underwent CE examinations. The echocardiographic diagnosis relied on qualitative factors such as echogenicity, boundary, morphology of the base, mass perfusion, pericardial effusion, and motility as well as quantitative factors such as the area of the masses and the peak intensity ratio of the masses to adjacent myocardium (A1/A2). Results The final confirmed diagnoses were as follows: 2 patients had no cardiac mass, 4 patients had pseudomass, 43 patients had thrombus, 66 patients had benign tumors, and 30 patients had malignant tumors. The receiver operating characteristic (ROC) analysis indicated that an optimal A1/A2 cutoff value of 0.499 distinguished a cardiac tumor from a thrombus, with AUC, sensitivity, specificity, PPV, and NPV of 0.977, 97.9%, 90.7%, 95.9%, and 95.1%, respectively. The optimal A1/A2 cutoff value of 1.583 distinguished a cardiac tumor from a thrombus, with AUC, sensitivity, specificity, PPV, and NPV of 0.950, 93.3%, 93.9%, 87.5%, and 96.9%, respectively. Conclusions Combined with qualitative and quantitative analyses, CE has the potential to accurately differentiate among different types of cardiac masses.

Objective Regular monitoring of serum potassium after a total joint arthroplasty (TJA) is a form of routine examination that can help detect abnormal serum potassium levels and reduce the incidences of adverse events that may occur on account of postoperative hypokalemia. Previous studies rarely discussed hypokalemia after joint replacement. In the present study, our primary goal was to investigate the incidence and possible risk factors of hypokalemia after a total hip and knee replacement procedure was performed. Methods This study included patients who underwent a unilateral total knee or hip arthroplasty in our department between April 2017 and March 2018. Serum potassium levels pre and post operation were collected and retrospectively analyzed. The differences in age, gender, body mass index (BMI), history of diseases, red blood cell (RBC), hemoglobin, hematocrit, glomerular filtration rate, ejection fraction, blood glucose, urine creatinine, urea nitrogen, intraoperative blood loss, operation time, drainage, preoperative potassium, surgery type, were compared between those patients diagnosed with hypokalemia and their non‐hypokalemia at different times post surgery. Thereafter, the risk factors of postoperative hypokalemia patients were analyzed using statistical procedure multiple logistic regression model. Results The risk of hypokalemia after TJA was 53.1%, while, that on the first, third, and fifth day after operation was 12.5%, 40.7%, and 9.6% respectively. The serum potassium level on the first, third, and fifth postoperative days was 3.84 ± 0.32, 3.59 ± 0.34, and 3.80 ± 0.32 mmol/l, respectively. However, the level on the third day appeared to be the lowest (p = 0.015) of them all. The independent risk factors for hypokalemia after a total hip and knee replacement were the level of preoperative serum potassium concentration (p = 0.011), preoperative red blood cells counts (p = 0.027), and history of diabetes (p = 0.007). Conclusion Regular monitoring of serum potassium concentration should be performed post TJA. We need to pay more attention to the patient's preoperative potassium levels along with their red blood cell counts especially in patients diagnosed with type 2 diabetes mellitus.

ObjectiveTo describe clinical and epidemiological characteristics of cases infected with novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant diagnosed during February – May, 2023 in a district of Beijing city for effective containment of coronavirus disease 2019 (COVID-19) epidemic.MethodsThe surveyed cases were 110 laboratory-confirmed novel SARS-CoV-2 variant infections diagnosed in sampling inspection and surveillance at customs departments and medical institutions and reported to health agency of Chaoyang district of Beijing city during February – May, 2023. The collected data were analyzed with descriptive statistics. The novel SARS-CoV-2 variant refers to the SARS-CoV-2 strains not detected previously in the district (except for BA.5.2/ BF.7 and their sub-variants).ResultsThe 110 cases were consisted of 64 males and 46 females, with a median age of 32 years; compared to those in the local cases, significantly higher median age and proportions of COVID19 vaccination and secondary attack were observed in the 72 (65.45% of all the cases) imported cases (P < 0.05 for all). Among all the cases, 100 (90.91%) were identified as having infections of SARS-CoV-2 XBB variant and subvariants based on whole-genome sequencing analysis. The number of symptomatic cases was 100 (90.91% of all cases) and main clinic symptoms were fever (66.00% in proportion), sore throat (53.00%), and cough (52.00%); and 35.00% of the symptomatic cases could be diagnosed as influenza-like illness. Significantly more symptomatic cases were observed in initial infections than in the reinfections (P = 0.004). For all the cases, The duration of negative seroconversion of SARS-CoV-2 nucleic acid or antigen was 5.92 ± 2.95 days and the disease course of was 5.00 (percentile 25∶4.00, percentile 75∶8.75) days. Compared to the cases with initial infection, the cases with reinfection had significant shorter duration (5.08 ± 2.60 days vs. 6.49 ± 3.06 days) of negative seroconversion of SARS-CoV-2 nucleic acid or antigen (P = 0.026). Prevalence of clinical symptoms and the duration of negative seroconversion of SARS-CoV-2 nucleic acid or antigen were not significantly different between the cases with SARS-CoV-2 XBB variant infection and the cases with non-XBB infection (P > 0.05). The epidemiological survey among the 110 cases identified totally 252 intimately close contacts and the secondary attack rate in the close contacts was 12.70%; the secondary attack rate was higher in the contacts of non-XBB variant infections than in the contacts of XBB variant infections.ConclusionDuring February to May 2023 in a district of Beijing, the majority of reported novel SARS-CoV-2 variant cases were imported cases; most of the local cases were initial infections; the proportion of symptomatic cases was higher in initial infections than that in the reinfections but the initial infections had a longer duration of negative seroconversion of SARS-CoV-2 nucleic acid or antigen than the reinfections; the secondary attack rate was higher in the contacts of non-XBB variant infections than in the contacts of XBB variant infections.

Abstract Paeniclostridium sordellii lethal toxin (TcsL) is a potent exotoxin that causes lethal toxic shock syndrome associated with fulminant bacterial infections. TcsL belongs to the large clostridial toxin (LCT) family. Here, we report that TcsL with varied lengths of combined repetitive oligopeptides (CROPs) deleted show increased autoproteolysis as well as higher cytotoxicity. We next present cryo-EM structures of full-length TcsL, at neutral (pH 7.4) and acidic (pH 5.0) conditions. The TcsL at neutral pH exhibits in the open conformation, which resembles reported TcdB structures. Low pH induces the conformational change of partial TcsL to the closed form. Two intracellular interfaces are observed in the closed conformation, which possibly locks the cysteine protease domain and hinders the binding of the host receptor. Our findings provide insights into the structure and function of TcsL and reveal mechanisms for CROPs-mediated modulation of autoproteolysis and cytotoxicity, which could be common across the LCT family.

Abstract Network flow watermark technology is a traffic marking technique that embeds watermark information into the characteristics of network flows to mark and trace attack flows generated by network attackers. However, with the development of network attack techniques, the time and number of packets required for network attacks have decreased. Existing network flow watermark technologies fail to balance watermark robustness and efficiency, resulting in poor practicality. To address this issue, this paper proposes an efficient hexadecimal network flow watermark method. The method introduces an efficient interval watermark algorithm and utilizes an interval synchronization algorithm to self-learn watermark parameters, thereby improving the encoding efficiency of the watermark. The design of watermark start and end markers ensures the practicality of network watermarks, enabling traceability and source attribution of attack flows in real network environments. The proposed method is experimentally tested using real network traffic, and the results demonstrate that even in the presence of a network jitter, the watermark detection success rate of this scheme remains above 95%. Compared to other network flow watermark schemes, the hexadecimal network flow watermark proposed in this paper achieves a 50% improvement in encoding and decoding efficiency while ensuring robustness. It also exhibits excellent resistance to network jitter, packet loss, and false packet insertion.

The [3 + 2] cycloadditions of stabilized azomethine ylides (AMYs) derived from amino esters are well-established. However, the reactions of semi-stabilized AMYs generated from decarboxylative condensation of α-amino acids with arylaldehydes are much less explored. The [3 + 2] adducts of α-amino acids could be used for a second [3 + 2] cycloaddition as well as for other post-condensation modifications. This article highlights our recent work on the development of α-amino acid-based [3 + 2] cycloaddition reactions of N–H-type AMYs in multicomponent, one-pot, and stepwise reactions for the synthesis of diverse heterocycles related to some bioactive compounds and natural products.

The “seesaw relationship” between thermal conductivity and thermal expansion coefficient (CTE) in most high temperature ceramics has become an obstacle to the design of long-life multilayer thermal/environmental barrier coatings (T/EBC). Due to low thermal conductivity and CTE, defect fluorite type high-entropy rare earth (RE) hafnates have drawn a lot of interest for potential application in T/EBC systems. This work designs and synthesizes the (Dy0.2Ho0.2Er0.2Tm0.2Lu0.2)2Hf2O7 with comprehensive thermal performance and investigates the thermophysical mechanism from the phonon scale. In addition to the lattice distortion effect caused by the point defects of multicomponent substitutional atoms in (Dy0.2Ho0.2Er0.2Tm0.2Lu0.2)2Hf2O7, the oxygen vacancies in the defect fluorite lattice also play a critical role in reducing the thermal conductivity. From microscopic thermal expansion behavior, the low-frequency optic phonons originated from the vibration of RE atoms are the key factors in altering CTE for hafnates. And doping smaller RE ions is beneficial for enhancing the RE–O bond strength and further reducing CTE. The results contribute to the understanding of high-entropy strategic design and suggest that (Dy0.2Ho0.2Er0.2Tm0.2Lu0.2)2Hf2O7 is a promising top layer material in the implementation of T/EBC.

Tunnel fires are generally detected using various sensors, including measuring temperature, CO concentration, and smoke concentration. To address the ambiguity and inconsistency in multi-sensor data, this paper proposes a tunnel fire detection method based on an improved Dempster-Shafer (DS) evidence theory for multi-sensor data fusion. To solve the problem of evidence conflict in the DS theory, a two-level multi-sensor data fusion framework is adopted. The first level of fusion involves feature fusion of the same type of sensor data, removing ambiguous data to obtain characteristic data, and calculating the basic probability assignment (BPA) function through the feature interval. The second-level fusion derives basic probability numbers from the BPA, calculates the degree of evidence conflict, normalizes the BPA to obtain the relative conflict degree, and optimizes the BPA using the trust coefficient. The classical DS evidence theory is then used to integrate and obtain the probability of tunnel fire occurrence. Different heat release rates, tunnel wind speeds, and fire locations are set, forming six fire scenarios. Sensor monitoring data under each simulation condition are extracted and fused using the improved DS evidence theory. The results show that there is a 67.5%, 83.5%, 76.8%, 83%, 79.6%, and 84.1% probability of detecting fire when it occurs, respectively, and identifies fire occurrence in approximately 2.4 s, an improvement from 64.7% to 70% over traditional methods. This demonstrates the feasibility and superiority of the proposed method, highlighting its significant importance in ensuring personnel safety.

This paper details the development and verification tests of an open-source code named hy2LPTFoam intended for solving high-speed non-equilibrium gas-particle flows in OpenFOAM. The solver, based on hy2Foam for high-speed non-equilibrium gas flow, integrates multiple particle force models, heat transfer models, the diffusion-based smoothing method, and the MPPIC method. The verification tests incorporate interactions between shock waves and particle curtains with varying particle volume fractions, a JPL nozzle generating a two-phase gas–particle flow, and a Mars entry body with two particle inflow mass fractions. The tests yield good physical agreement with numerical and experimental data from the literature.

Tetrahedral copper(I) clusters [Cu4(MBIZ)4(PPh3)2] (2), [Cu4(MBOZ)4(PPh3)4] (6) (MBIZ = 2-mercaptobenzimidazole, MBOZ = 2-mercaptobenzoxazole) were prepared by regulation of the copper-thiolate clusters [Cu6(MBIZ)6] (1) and [Cu8(MBOZ)8I]− (5) with PPh3. With the presence of iodide anion, the regulation provided the iodide-containing clusters [CuI4(MBIZ)3(PPh3)3I] (3) and [CuI4(MBOZ)3(PPh3)3I] (7). The cyclic voltammogram of 3 in MeCN (0.1 M nBu4NPF6, 298 K) at a scan rate of 100 mV s−1 shows two oxidation processes at Epa = +0.11 and +0.45 V with return waves observed at Epc = +0.25 V (vs. Fc+/Fc). Complex 3 has a higher capability to lose and gain electrons in the redox processes than complexes 2, 4, 4′, 6, and 7. Its thermal stability was confirmed by thermogravimetric analysis. The catalytic performance of 3 was demonstrated by the catalytic transformation of iodobenzenes to benzonitriles using AIBN as the cyanide source. The nitrile products show potential applications in the preparation of 1,3,5-triazine compounds for organic fluorescence materials.

Abstract Pulmonary thromboembolism caused by thrombi blocking major pulmonary artery and its branches, is a frequently encountered phenomenon and an important cause of high morbidity and mortality in lung diseases and may develop into persistent pulmonary hypertension (PH). Nuclear factor‐κB (NF‐κB) signaling pathway had been reported participated in the formation and development of PH by promoting inflammatory response. The aim of this study was to investigate the effects of NF‐κB activation on the serum levels of tumor necrosis factor α (TNF‐α) and interleukin‐1β (IL‐1β) in acute pulmonary microthromboembolism (APMTE) rats. Rats were randomized into five groups. APMTE group received jugular vein injection of autologous thrombus, while control group rats received normal saline injection. Pulmonary hemodynamic parameters were measured through ECHO‐guided transthoracic puncture. Pulmonary vascular morphological changes were analyzed by HE. The expression changes of NF‐κB and serum TNF‐α、IL‐1β levels were detected by enzyme‐linked immunosorbent assay. Protein expression of the MAPK/NF‐κB signaling pathway including p‐IκBα, p‐p38 MAPK, p‐NF‐κB p65, IκBα, p38 MAPK, and NF‐κB p65 was determined using western blot analysis. Compared with control group, the expression of NF‐κB in lung tissue and the levels of serum TNF‐α and IL‐1β rats were higher, a significant reduction in IκBα and elevation in the phosphorylation of IκBα, p38 MAPK, and NF‐κB p65 were found in APMTE group rats. And UK administration reversed the APMTE‐induced increase in TNF‐α, IL‐1β, p‐IκBα, p‐MAPK, and p‐NF‐κB protein. Furthermore, the levels of NF‐κB, TNF‐α, and IL‐1β were positively correlated with mean pulmonary artery. And the levels of TNF‐α and IL‐1β were positively correlated with NF‐κB. These findings suggest that the activation of MAPK/NF‐κB pathway as a critical driver of increasing TNF‐α and IL‐1β level in APMTE rats and UK exerted protective effects against APMTE‐induced PH may be related to the downregulation of the MAPK/NF‐κB signaling pathway.

Background Cuproptosis is a novel type of mediated cell death strongly associated with the progression of several cancers and has been implicated as a potential therapeutic target. However, the role of cuproptosis in cholangiocarcinoma for prognostic prediction, subgroup classification, and therapeutic strategies remains largely unknown. Methods A systematic analysis was conducted among 146 cuproptosis-related genes and clinical information based on independent mRNA and protein datasets to elucidate the potential mechanisms and prognostic prediction value of cuproptosis-related genes. A 10-cuproptosis-related gene prediction model was constructed, and its effects on cholangiocarcinoma prognosis were significantly connected to poor patient survival. Additionally, the expression patterns of our model included genes that were validated with several cholangiocarcinoma cancer cell lines and a normal biliary epithelial cell line. Results First, a 10-cuproptosis-related gene signature ( ADAM9, ADAM17, ALB, AQP1, CDK1, MT2A, PAM, SOD3 , STEAP3 , and TMPRSS6 ) displayed excellent predictive performance for the overall survival of cholangiocarcinoma. The low-cuproptosis group had a significantly better prognosis than the high-cuproptosis group with transcriptome and protein cohorts. Second, compared with the high-risk and low-risk groups, the 2 groups displayed distinct tumor microenvironments, reduced proportions of endothelial cells, and increased levels of cancer-associated fibroblasts based on CIBERSORTx and EPIC analyses. Third, patients’ sensitivities to chemotherapeutic drugs and immune checkpoints revealed distinctive differences between the 2 groups. Finally, in replicating the expression patterns of the 10 genes, these results were validated with quantitative real-time polymerase chain reaction results validating the abnormal expression pattern of the target genes in cholangiocarcinoma. Conclusions Collectively, we established and verified an effective prognostic model that could separate cholangiocarcinoma patients into 2 heterogeneous cuproptosis subtypes based on the molecular or protein characteristics of 10 cuproptosis-related genes. These findings may provide potential benefits for unveiling molecular characteristics and defining subgroups could improve the early diagnosis and individualized treatment of cholangiocarcinoma patients.

Osteoporosis is a systemic metabolic disease characterized by disrupted bone formation/resorption and homeostasis. Flavonoids extracted from traditional Chinese medicinal plants regulate bone homeostasis by intervening in differentiating bone marrow mesenchymal stem cells, balancing the bone immune system, inhibiting oxidative stress response, and reversing iron overload. The target molecules and signaling pathways, such as Wnt/β-catenin and OPG/RANKL/RANK, directly affect osteoblast/osteoclast activity, exhibiting significant potential in the treatment of OP. Therefore, this study presents a systematic review of the recent literature to provide comprehensive information on the traditional Chinese medicine flavonoids involved in the regulation of bone homeostasis. Also, the molecular mechanisms and pharmacological uses of these metabolites are summarized, and their clinical translation and development potential are discussed.

Background: Previously, our investigations have underscored the potential of hyperthermia to improve the therapeutic efficacy of gemcitabine (GEM) in pancreatic cancer (PC). Nonetheless, the precise underlying mechanisms remain elusive. Methods: We engineered two GEM-resistant PC cell lines (BxPC-3/GEM and PANC-1/GEM) and treated them with GEM alongside hyperthermia. The impact of hyperthermia on the therapeutic potency of GEM was ascertained through MTT assay, assessment of the concentration of its active metabolite dFdCTP, and evaluation of deoxycytidine kinase (dCK) activity. Lentivirus-mediated dCK silencing was further employed to validate its involvement in mediating the GEM-sensitizing effect of hyperthermia. The mechanism underlying hyperthermia-mediated dCK activation was explored using bioinformatics analyses. The interplay between hyperthermia and the ephrin A4 (EFNA4)/β-catenin/dCK axis was investigated, and their roles in GEM resistance was further explored via the establishment of xenograft tumor models in nude mice. Results: Hyperthermia restored dCK expression in GEM-resistant cell lines, concurrently enhancing GEM sensitivity and fostering DNA damage and cell death. These observed effects were negated by dCK silencing. Regarding the mechanism, hyperthermia activated dCK by downregulating EFNA4 expression and mitigating β-catenin activation. Overexpression of EFNA4 activated the β-catenin while suppressing dCK, thus diminishing cellular GEM sensitivity—a phenomenon remediated by the β-catenin antagonist MSAB. Consistently, in vivo, hyperthermia augmented the therapeutic efficacy of GEM on xenograft tumors through modulation of the ephrin A4/β-catenin/dCK axis. Conclusion: This study delineates the role of hyperthermia in enhancing GEM sensitivity of PC cells, primarily mediated through the suppression of the EFNA4/β-catenin axis and activation of dCK.

BackgroundAtrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a high risk of stroke. This study was designed to investigate the relationship between hemodynamic parameters and left atrial thrombus/spontaneous echo contrast (LAT/SEC) in non-valvular atrial fibrillation (NVAF) patients and establish a predictive nomogram that integrates hemodynamic parameters with clinical predictors to predict the risk of LAT/SEC.MethodsFrom January 2019 to September 2022, a total of 354 consecutive patients with NVAF were enrolled in this cross-sectional study at the First Affiliated Hospital of Guangxi Medical University. To identify the optimal predictive features, we employed least absolute shrinkage and selection operator (LASSO) regression. A multivariate logistic regression model was subsequently constructed, and the results were visualized with a nomogram. We evaluated the model's performance using discrimination, calibration, and the concordance index (C-index).ResultsWe observed a 38.7% incidence of SEC/TH in NVAF patients. Independent influencing factors of LAT/SEC were identified through LASSO and multivariate logistic regression. Finally, four indicators were included, namely, previous stroke/transient ischaemic attack (OR = 4.25, 95% CI = 1.57–12.23, P = 0.006), left atrial volume index (LAVI) (OR = 1.04, 95% CI = 1.01–1.06, P = 0.001), S/D ratio (OR = 0.27, 95% CI = 0.11–0.59, P = 0.002), and left atrial acceleration factor (OR = 4.95, 95% CI = 2.05–12.79, P = 0.001). The nomogram, which incorporated these four influencing factors, demonstrated excellent predictive ability. The training set had a C-index of 0.878, while the validation set had a C-index of 0.872. Additionally, the calibration curve demonstrated great consistency between the predicted probabilities and the observed outcomes, and the decision curve analysis confirmed the important clinical advantage of the model for patients with NVAF.ConclusionOur findings indicate that an enlarged left atrium and abnormal hemodynamic parameters in the left atrial and pulmonary veins are linked to a greater risk of LAT/SEC. Previous stroke/transient ischaemic attack, LAVI, the S/D ratio, and left atrial acceleration factor were independently associated with LAT/SEC in NVAF patients. With the incorporation of these four variables, the developed nomogram effectively predicts the risk of LAT/SEC and outperforms the CHA2DS2-VASc score.

Helicobacter pylori （Hp） is a major human pathogen. Hp infection will cause a series of gastrointestinal diseases， such as chronic gastritis， peptic ulcer and gastric cancer， etc. In recent years， with the increasing incidence of these diseases， their etiology and pathogenesis have attracted more and more attention from many scholars around the world. The pathogenic mechanism of cytotoxin-associated gene A （CagA）， one of the virulence genes of Hp， has captivated widespread attention. EPIYA motif and Hp infection-associated gastropathy have become a hot topic. In this article， the relationship between EPIYA motif and gastropathy related to Hp infection was briefly reviewed.

Aimed at the problem that the accuracy of tool remaining life prediction was reduced due to the abnormal monitoring data in machining process, a data anomaly detection method based on self-paced learning was proposed. First, a multi-layer perceptron model was established to correlate the tool processing monitoring data with the tool remaining life. Next, in the process of updating model weight, the model weight parameters were fixed first, and the loss threshold of abnormal samples was obtained by predicting loss fitting Gaussian distribution. Then, the loss function based on the self-paced learning method was constructed to update model parameters iteratively. At the end of the model training, abnormal samples were divided according to the loss threshold. Finally, the actual processing monitoring data of turbine rotor groove were used to verify the proposed method, and compare with the local anomaly factor algorithm, the density-based clustering algorithm, the K-means algorithm, the isolated forest algorithm, and the one-class support vector machines.

Abstract Background Silicosis is an important occupational disease caused by inhalation of free silica and is characterized by persistent pulmonary inflammation, subsequent fibrosis and lung dysfunction. Until now, there has been no effective treatment for the disease due to the complexity of pathogenesis. Fermented cordyceps powder (FCP) has a similar effect to natural cordyceps in tonifying the lung and kidney. It has started to be used in the adjuvant treatment of silicosis. This work aimed to verify the protective effects of FCP against silicosis, and to explore the related mechanism. Methods Wistar rats were randomly divided into four groups including the saline-instilled group, the silica-exposed group, the silica + FCP (300 mg/kg) group and the silica + FCP (600 mg/kg) group. Silicosis rat models were constructed by intratracheal instillation of silica (50 mg). Rats in the FCP intervention groups received the corresponding dose of FCP daily by intragastric gavage. Rats were sacrificed on days 7, 28 and 56 after treatment, then samples were collected for further analysis. Results FCP intervention reduced the infiltration of inflammatory cells and the concentration of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) at days 7, 28, 56, and decreased the expression of collagen, α-smooth muscle actin (α-SMA) and fibronectin (FN) at days 28 and 56 in the lung of silicosis rats. FCP also decreased the immune response of Th1 and Th17 at days 7, 28, 56 and inhibited the enhancement of the Th2 response at day 56. Conclusions FCP intervention could alleviate silica-induced pulmonary inflammation and fibrosis, the protective effect may be achieved by reducing Th1 and Th17 immune responses and inhibiting the enhancement of the Th2 response.

Thermal-sprayed coatings are expected to have a relatively smooth surface when used under certain service conditions, such as to improve their erosion resistance or decrease the adhesion of CMAS sands. In this study, a new method for grinding ceramic coatings was proposed that uses an industrial robot, a floating spindle, a rubber binder grinding head, and diamond plaster to automatically grind ceramic coatings on basis of free abrasive grinding. Typical 8YSZ thermal barrier coatings (TBCs) were created on nickel-based superalloy plates using atmospheric plasma spraying (APS) in order to explore the impact of such grinding on their morphology and comprehensive performance. Following the grinding with the proposed process, the coating's surface roughness, removal weight and thickness, as well as 3D surface morphology were all measured. The microstructure, wetting angle, infrared emittance, microhardness, bonding strength, particulate erosion resistance, and thermal cycling life of the as-sprayed and ground 8YSZ coatings were comparatively studied using the corresponding characterization instrument. The results show that the coating's surface roughness can be decreased to roughly 1 μm, and its removal thickness ranges between 45 and 90 μm. Besides from the wettability of the droplet on the coating's surface rises, the coating's infrared emittance, mechanical properties, thermal cycling life, and erosion resistance are not noticeably different after grinding, demonstrating that such novel grinding technique won't weaken the microstructure or shorten the coating life. It could offer guidance for the urgently required development of grinding processes for ceramic coatings with complex surfaces.

Abstract Epigenetic modifications play important roles during the pathogenesis of multiple myeloma (MM). Herein, we found that protein arginine methyltransferase 1 (PRMT1) was highly expressed in MM patients, which was positively correlated with MM stages. High PRMT1 expression was correlated with adverse prognosis in MM patients. We further showed that silencing PRMT1 inhibited MM proliferation and tumorigenesis in vitro and in vivo. Mechanistically, we revealed that the knockdown of PRMT1 reduced the oxidative phosphorylation (OXPHOS) of MM cells through NDUFS6 downregulation. Meanwhile, we identified that WTAP, a key component of the m6A methyltransferase complex, was methylated by PRMT1, and NDUFS6 was identified as a bona fide m6A target of WTAP. Finally, we found that the combination of PRMT1 inhibitor and bortezomib synergistically inhibited MM progression. Collectively, our results demonstrate that PRMT1 plays a crucial role during MM tumorigenesis and suggeste that PRMT1 could be a potential therapeutic target in MM.

Improving ferro-piezoelectric properties of niobate-based perovskites is highly desirable for developing eco-friendly high-performance sensors and actuators. Although electro-strain coupling is usually obtained by constructing multiphase boundaries via complex chemical compositions, defect engineering can also create opportunities for novel property and functionality advancements. In this work, a representative tetragonal niobate-based perovskite, i.e., KNbO3, is studied by using first-principles calculations. Two intrinsic types of Nb antisite defect complexes are selected to mimic alkali-deficiency induced excess Nb antisites in experiments. The formation energy, electronic profiles, polarization, and piezoelectric constants are systematically analyzed. It is shown that the structural distortion and chemical heterogeneity around the energetically favorable antisite pair defects, i.e., (NbK4·+KNb4′), lower the crystal symmetry of KNbO3 from tetragonal to triclinic phase, and facilitate polarization emergence and reorientation to substantially enhance intrinsic ferro-piezoelectricity (i.e., spontaneous polarization Ps of 68.2 μC/cm2 and piezoelectric strain constant d33 of 228.3 pC/N) without complicated doping and alloying.

The aim of this study was to examine the effects of habitual iron supplementation on the risk of CKD in individuals with different hypertensive statuses and antihypertension treatment statuses. We included a total of 427,939 participants in the UK Biobank study, who were free of CKD and with complete data on blood pressure at baseline. Cox proportional hazards regression models were used to examine the adjusted hazard ratios of habitual iron supplementation for CKD risk. After multivariable adjustment, habitual iron supplementation was found to be associated with a significantly higher risk of incident CKD in hypertensive participants (HR 1.12, 95% CI 1.02 to 1.22), particularly in those using antihypertensive medication (HR 1.21, 95% CI 1.08 to 1.35). In contrast, there was no significant association either in normotensive participants (HR 1.06, 95% CI 0.94 to 1.20) or in hypertensive participants without antihypertensive medication (HR 1.02, 95% CI 0.90 to 1.17). Consistently, significant multiplicative and additive interactions were observed between habitual iron supplementation and antihypertensive medication on the risk of incident CKD (p all interaction < 0.05). In conclusion, habitual iron supplementation was related to a higher risk of incident CKD among hypertensive patients, the association might be driven by the use of antihypertensive medication.

Bamboo is composed of thick-walled fibrous tissue and thin-walled parenchymal tissue. To compare the energy consumption of preparing lignocellulose nanofibrils (LCNF) from these bamboo tissues, the crystallinity, sol. viscosity, morphology and mechanical properties of LCNF at different preparation stages were characterized in detail. It required at least nine homogenization cycles for dissociating the fibrous tissue, but only six cycles for the parenchymal tissue. The average diameter of LCNF isolated from fibrous and parenchymal tissues was 45.1 nm and 36.2 nm, respectively. The tensile strength of the LCNF film prepared from parenchymal tissue reached 142.46 MPa, whereas the film from fibrous tissue reached only 122.82 MPa. Additionally, a metal organic framework (MOF) was used to produce MOF-LCNF film with enhanced UV protection and antibacterial properties. The results indicated that the energy consumption for preparing LCNF from parenchymal tissue is significantly lower than that for preparing LCNF from fibrous tissue. This study offers a low-cost and eco-friendly method for preparing LCNF, promoting the precise utilization of different tissues from bamboo based on their unique characteristics.

Self-made agglomerated nanometer CeO2-Y2O3-ZrO2 (CYSZ) powders for plasma spray–physical vapor deposition (PS-PVD) were prepared by spray-drying, followed by calcination treatment at four different temperatures (600 °C, 700 °C, 800 °C, 900 °C). The physical properties, microstructure, and phase composition of the calcined powders were investigated using a laser particle size analyzer, scanning electron microscopy (SEM), and X-ray diffraction (XRD). The results showed that compared to the agglomerated powders obtained through spray-drying, the particle size of the agglomerated powders changed with increasing calcination temperature, accompanied by an increase in the self-bonding force of the agglomerated powder particles. The proper calcination temperature improved the sprayability of the powders. Additionally, with the increase in the calcination temperature, a transformation from the m-phase to the t-phase occurred in the powder, with Ce4+ partially entering the Zr lattice to form the t-Zr0.84Ce0.16O2 phase, which facilitated the suppression of the m-phase and improved the high-temperature phase stability. It was also found that the PS-PVD coatings prepared using the aforementioned powders exhibited coarser columnar structures with increasing powder calcination temperature.

Collision detection is very important for robot motion planning. The existing accurate collision detection algorithms regard the evaluation of each node as a discrete event, ignoring the correlation between nodes, resulting in low efficiency. In this paper, we propose a novel approach that transforms collision detection into a binary classification problem. In particular, the proposed method searches the k-nearest neighbor (KNN) of the new node and estimates its collision probability by the prior node. We perform the hierarchical navigable small world (HNSW) method to query the nearest neighbor data and store the detected nodes to build the database incrementally. In addition, this research develops a KNN query technique tailored for linear data, incorporating threshold segmentation to facilitate collision detection along continuous paths. Moreover, it refines the distance function of the collision classifier to enhance the precision of probability estimations. Simulation results demonstrate the effectiveness of the proposed method.

Network traffic classification is crucial for identifying network applications and defending against network threats. Traditional traffic classification approaches struggle to extract structural features and suffer from poor interpretability of feature representations. The high symmetry between network traffic classification and its interpretable feature representation is vital for network traffic analysis. To address these issues, this paper proposes a traffic classification and feature representation model named the attention mechanism autoencoder (AMAE). The AMAE model extracts the global spatial structural features of network traffic through attention mechanisms and employs an autoencoder to extract local structural features and perform dimensionality reduction. This process maps different network traffic features into one-dimensional coordinate systems in the form of spectra, termed FlowSpectrum. The spectra of different network traffic represent different intervals in the coordinate system. This paper tests the interpretability and classification performance of network traffic features of the AMAE model using the ISCX-VPN2016 dataset. Experimental results demonstrate that by analyzing the overall distribution of attention weights and local weight values of network traffic, the model effectively explains the differences in the spectral representation intervals of different types of network traffic. Furthermore, our approach achieves the highest classification accuracy of up to 100% for non-VPN-encrypted traffic and 99.69% for VPN-encrypted traffic, surpassing existing traffic classification schemes.