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Abstract Background Idiopathic membranous nephropathy (IMN) is a cause of nephrotic syndrome that is increasing in incidence but has unclear pathogenesis. Urinary peptidomics is a promising technology for elucidating molecular mechanisms underlying diseases. Dysregulation of the proteolytic system is implicated in various diseases. Here, we aimed to conduct urinary peptidomics to identify IMN-related proteases. Results Peptide fingerprints indicated differences in naturally produced urinary peptide components among 20 healthy individuals, 22 patients with IMN, and 15 patients with other kidney diseases. In total, 1,080 peptide-matched proteins were identified, 279 proteins differentially expressed in the urine of IMN patients were screened, and 32 proteases were predicted; 55 of the matched proteins were also differentially expressed in the kidney tissues of IMN patients, and these were mainly involved in the regulation of proteasome-, lysosome-, and actin cytoskeleton-related signaling pathways. The 32 predicted proteases showed abnormal expression in the glomeruli of IMN patients based on Gene Expression Omnibus databases. Western blot revealed abnormal expression of calpain, matrix metalloproteinase 14, and cathepsin S in kidney tissues of patients with IMN. Conclusions This work shown the calpain/matrix metalloproteinase/cathepsin axis might be dysregulated in IMN. Our study is the first to systematically explore the role of proteases in IMN by urinary peptidomics, which are expected to facilitate discovery of better biomarkers for IMN.

Abstract Background Accumulating data have established that microRNAs (miRNAs) play significant regulatory roles in the carcinogenesis and progression of ovarian cancer (OC). MiR-425-5p was reported to function in various tumors. However, the roles and underlying mechanism of miR-425-5p involvement in OC development and progression are unclear. Methods A comprehensive strategy of data mining, computational biology, and real-time polymerase chain reaction was employed to identify the involvement of miR-425-5p in OC progression. The effect of miR-425-5p on the proliferation, migration, and invasion of OC cells was determined using Cell Counting Kit-8, wound-healing, and Matrigel invasion assays, respectively. Luciferase assay was performed to evaluate the interactions between miR-425-5p and MAGI2-AS3 or AFF4. Results miR-425-5p was significantly up-regulated in OC tissues and cells. The luciferase reporter assay revealed that miR-425-5p was negatively regulated by MAGI2-AS3. Silencing miR-425-5p inhibited the proliferation, migration, and invasion of OC cells in vitro. Bioinformatics analysis and luciferase reporter assay revealed that AFF4 was the target gene of miR-425-5p. Moreover, AFF4 expression was significantly decreased in OC and was closely related to the good prognosis of patients with OC. AFF4 overexpression inhibited the proliferation, migration, and invasion of OC cells in vitro. By contrast, silencing AFF4 promoted the proliferation, migration, and invasion of OC cells in vitro. Finally, AFF4 suppression rescued the inhibitory effect of silencing miR-425-5p on the proliferation, migration, and invasion of OC cells. Conclusion To the best our knowledge, this is the first study to demonstrate that miR-425-5p overexpression in OC is negatively regulated by MAGI2-AS3. Moreover, miR-425-5p promotes the proliferation, migration, and invasion of OC cells by targeting AFF4, suggesting that miR-425-5p/AFF4 signaling pathway represented a novel therapeutic target for patients with OC.

We estimated the symptomatic, PCR-confirmed secondary attack rate (SAR) for 2,382 close contacts of 476 symptomatic persons with coronavirus disease in Yichang, Hubei Province, China, identified during January 23–February 25, 2020. The SAR among all close contacts was 6.5%; among close contacts who lived with an index case-patient, the SAR was 10.8%; among close-contact spouses of index case-patients, the SAR was 15.9%. The SAR varied by close contact age, from 3.0% for those 60 years of age. Multilevel logistic regression showed that factors significantly associated with increased SAR were living together, being a spouse, and being >60 years of age. Multilevel regression did not support SAR differing significantly by whether the most recent contact occurred before or after the index case-patient’s onset of illness (p = 0.66). The relatively high SAR for coronavirus disease suggests relatively high virus transmissibility.

The flow stress–strain curves appear to be sensitive to deformation conditions. The ratio of critical strain to peak strain εc/εp follows a linear relationship except when the temperature is 1240 °C and the strain rate is 0.001 s−1. During the deformation, the fragmentation and decomposition of γ/α2 lamellae are related to recrystallization of α2 and γ laths in the lamellae and the γ → α2 phase transformation, the former depends on dislocation slip and twinning, and the latter is related to temperature, local stress concentration and diffusion time. As for the recrystallization mechanisms, the γ phase is discontinuous dynamic recrystallization (DDRX) mode, while the α2 phase relies on continuous dynamic recrystallization (CDRX) mode. The β phase has more low-angle grain boundaries (LAGB) during deformation, indicating the continuous coordinated deformation, and this explains the enlarged hot working window of the TiAl alloy (1165–1240 °C/0.001 ~ 1 s−1 and 1120–1165 °C/0.001–0.4 s−1).

Abstract In recent years, addressing ill-posed problems by leveraging prior knowledge contained in databases on learning techniques has gained much attention. In this paper, we focus on complete three-dimensional (3D) point cloud reconstruction based on a single red-green-blue (RGB) image, a task that cannot be approached using classical reconstruction techniques. For this purpose, we used an encoder-decoder framework to encode the RGB information in latent space, and to predict the 3D structure of the considered object from different viewpoints. The individual predictions are combined to yield a common representation that is used in a module combining camera pose estimation and rendering, thereby achieving differentiability with respect to imaging process and the camera pose, and optimization of the two-dimensional prediction error of novel viewpoints. Thus, our method allows end-to-end training and does not require supervision based on additional ground-truth (GT) mask annotations or ground-truth camera pose annotations. Our evaluation of synthetic and real-world data demonstrates the robustness of our approach to appearance changes and self-occlusions, through outperformance of current state-of-the-art methods in terms of accuracy, density, and model completeness.

ObjectiveSeveral studies have found that MMP-9, one of the extracellular matrix-degrading proteinases, was involved in EC’s (endometrial cancer) clinical progression and prognosis. However, the results involving the associations of MMP-9 expression with risk, clinical features and prognosis of EC were conflicting. Therefore, we performed a systematic review and meta-analysis to clarify the correlation of MMP-9 expression with EC.MethodsRelative studies involving the associations between MMP-9 expression and EC were retrieved from PubMed, Embase, Web of Science and CNKI (China National Knowledge Infrastructure) electronic databases. OR (odds ratio) with 95% CI (confidence interval) was applied to evaluate the associations of MMP-9 expression with risk and clinical features of EC. Furthermore, we evaluated the role of MMP-9 expression in prognosis of EC using HR and 95% CI. The funnel plots and Begg test were used to assess the publication bias.ResultsA total of 28 eligible studies were acquired from Pubmed, Embase, Web of science and CNKI databases. We found MMP-9 overexpression was significantly associated with the risk of EC (OR = 11.02, 95% CI = 7.51-16.16, P < 0.05). In the meantime, MMP-9 overexpression was significantly associated with the tumor grade, FIGO stage, lymph node metastasis and myometrial invasion (Tumor grade: OR = 1.68, 95% CI = 1.09-2.58, P < 0.05; FIGO stage: OR = 3.25, 95% CI = 1.73-6.08, P < 0.05; Lymph node metastasis: OR = 2.98, 95% CI = 1.27-7.03, P < 0.05; Myometrial invasion: OR = 2.42, 95% CI = 1.42-4.12, P < 0.05) in Asians. In addition, the overall results showed that MMP-9 overexpression predicted a worse prognosis of EC (OR = 1.82, 95% CI = 1.01-2.62, P < 0.05).ConclusionsMMP-9 overexpression might be a potential predictor of poor clinical progression and prognosis of EC.

ABSTRACT Due to the resistance of Streptococcus pneumoniae to β-lactams, macrolides, and tetracyclines, treatment alternatives have become increasingly limited worldwide. We aim to describe the characterization of erythromycin-resistant S. pneumoniae (ERSP) strains in northeastern China over a period of 20 years. A total of 1,240 ERSP strains were collected and classified into five groups based on the ages of the patients. Etest strips and Kirby-Bauer disk diffusion were performed for drug susceptibility testing. The capsule swelling test was used for capsule typing. The phenotype of drug resistance was detected by the erythromycin and clindamycin double-disk method. The ermB, ermTR, mefA, and tetM genes were detected by PCR. Among the 1,240 ERSP strains, 510 were invasive isolates, and 730 were noninvasive isolates. The results of drug susceptibility testing showed that the rates of resistance to penicillin, amoxicillin, cefotaxime, ceftriaxone, meropenem, tetracycline, trimethoprim-sulfamethoxazole, and chloramphenicol varied among the different age groups. 19F, 19A, 23F, 14, and 6B were the serotypes that were commonly found among ERSP strains. Among all strains, 99.03% (1,228/1,240) exhibited an MLSB (macrolide-lincosamide-streptogramin B) resistance phenotype, of which 1,221 strains displayed a constitutive MLSB (cMLSB) phenotype and 7 strains showed an inducible MLSB (iMLSB) phenotype. All of these strains carried the ermB gene. In contrast, only 0.97% of strains of M phenotypes were found to carry the mefA gene. Both the ermB and mefA genes were detected in 704 strains that exhibited multidrug resistance, whereas the ermTR gene was not detected. Furthermore, 1,185 tetracycline-resistant strains were found to carry the tetM gene. Macrolide antimicrobial drugs should be used cautiously for the empirical treatment of S. pneumoniae infections. IMPORTANCE This study presents a retrospective analysis using 1,240 clinical erythromycin-resistant Streptococcus pneumoniae (ERSP) isolates collected in northeastern China between January 2000 and December 2019. The serotype distribution, corresponding vaccine coverage, as well as resistance phenotypes, genes, and mechanisms to macrolide and tetracycline of these isolates were systematically described, analyzed, and discussed. We hope that this study will inform clinicians in their respective regions when selecting antimicrobial agents. We also hope that this study is useful for researchers in related fields. Finally, we emphasize in this study that vaccination is the best preventive measure for S. pneumoniae infection considering its resistance to commonly used antibiotics. The determination of the S. pneumoniae serotype distribution also provides valuable empirical evidence for local health authorities when introducing appropriate vaccines in a specific area.

ObjectiveHepatocellular carcinoma (HCC) is the sixth most commonly occurring cancer and ranks third in mortality among all malignant tumors; as a result, HCC represents a major human health issue. Although aberrant glycosylation is clearly implicated in HCC, changes in serum immunoglobulin (Ig)G and IgM glycosylation have not been comprehensively characterized. In this study, we used lectin microarrays to evaluate differences in serum IgG and IgM glycosylation among patients with HCC, hepatitis B cirrhosis (HBC), or chronic hepatitis B (CHB), and healthy normal controls (NC) and aimed to establish a model to improve the diagnostic accuracy of HCC.MethodsIn total, 207 serum samples collected in 2019–2020 were used for lectin microarray analyses, including 97 cases of HCC, 50 cases of HBC, 30 cases of CHB, and 30 cases of NC. Samples were randomly divided into training and validation groups at a 2:1 ratio. Training group data were used to investigate the diagnostic value of the relative signal intensity for the lectin probe combined with alpha-fetoprotein (AFP). The efficacy of models for HCC diagnosis were analyzed by receiver operating characteristic (ROC) curves.ResultsIn terms of IgG, a model combining three lectins and AFP had good diagnostic accuracy for HCC. The area under the ROC curve was 0.96 (P < 0.05), the sensitivity was 82.54%, and the specificity was 100%. In terms of IgM, a model including one lectin combined with AFP had an area under the curve of 0.90 (P < 0.05), sensitivity of 75.41%, and specificity of 100%.ConclusionEstimation of serum IgG and IgM glycosylation could act as complementary techniques to improve diagnosis and shed light on the occurrence and development of the HCC

BackgroundPost-stroke shoulder pain (PSSP) is characterized by shoulder pain on the hemiplegic side, which can limit physical activity in patients with stroke. Acupuncture combined with rehabilitation training (AR) has been widely used in PSSP, but the evidence of its effectiveness is still unclear.ObjectiveThe study aimed to evaluate the effect and safety of AR vs. rehabilitation training (RT) alone on PSSP.MethodsWe searched PubMed, the Cochrane Library, the Chinese Biological Medicine Database (CBM), the Chinese Scientific Journal Database (VIP), China National Knowledge Infrastructure (CNKI), and the WAN FANG database for relevant studies from their inception to February 2022. Only randomized controlled trials (RCTs) comparing the effect of AR with RT alone on PSSP were considered. The primary outcome was shoulder pain. Secondary outcomes included upper limb motor function, activities of daily living (ADL), shoulder range of motion (ROM), and adverse events (AEs). Subgroup analysis and sensitivity analysis were also conducted. Quality assessment was implemented based on Cochrane risk of bias (ROB) criteria, which consist of seven items. When more than four items in a study were judged as low ROB, the overall quality of this study was considered low risk.ResultsA total of 40 studies were included in the qualitative analysis, and 35 (87.5%) studies with 2,554 patients were included in the meta-analysis. Of the 40 studies, 14 (35.0%) were of moderate-to-high quality. The meta-analysis results showed that AR is better than RT alone in reducing shoulder pain (MD −1.32, 95% CI −1.58 to −1.07), improving upper limb motor function (MD 6.81, 95% CI 4.95–8.67), ADL (MD 11.17, 95% CI 9.44–12.91), and shoulder ROM (internal rotation: MD 10.48, 95% CI 8.14–12.83; backward extension: MD 7.82, 95% CI 6.00–9.64; anteflexion: MD 12.88, 95% CI 5.47–20.29; external rotation: MD 11.40, 95% CI 6.17–16.64; abduction: MD 16.96, 95% CI 8.61–25.31) without obvious AEs.ConclusionAR may be better than RT alone for the improvement of shoulder pain, upper limb motor function, ADL, and shoulder ROM, without obvious AEs in patients with PSSP. However, considering the clinical and statistical heterogeneity, our findings need to be interpreted with caution. More rigorous RCTs in this area should be conducted in the future.Systematic review registration[www.crd.york.ac.uk], identifier [CRD42022326763].

Folate is commonly synthesized in natural plants and is an essential water-soluble vitamin of great importance inhuman health. Although the key genes involved in folate biosynthesis and transformation pathways have been identified in plants, the genetic architecture of folate in sweet corn kernels remain largely unclear. In this study, an association panel of 295 inbred lines of sweet corn was constructed. Six folate derivatives were quantified in sweet corn kernels at 20 days after pollination and a total of 95 loci were identified for eight folate traits using a genome-wide association study. A peak GWAS signal revealed that natural variation in ZmFCL, encoding a 5-formyltetrahydrofolate cyclo-ligase, accounted for 30.12% of phenotypic variation in 5-FTHF content. Further analysis revealed that two adjacent SNPs on the second exon resulting in an AA-to-GG in the gene and an Asn-to-Gly change in the protein could be the causative variant influencing 5-FTHF content. Meanwhile, 5-FTHF content was negatively correlated with ZmFCL expression levels in the population. These results extend our knowledge regarding the genetic basis of folate and provide molecular markers for the optimization of folate levels in sweet corn kernels.

Aluminum alloy adhesive bonding joint widely appears in many industrial products. Improving the mechanical performances of aluminum alloy bonding joints has been attracting much effort. To acquire more excellent bonding strength, this paper focused on the effects of different surface treatments, including laser ablation and milling superposed by phosphoric acid anodizing (PAA). The treated surfaces were characterized by roughness and contact angle, and the effects of the geometric parameters of microstructures on wettability, failure mode, and shear strength were examined. The results indicate that those surfaces where the spacing is smaller than the diameter present a hydrophilic property and the corresponding specimens are mainly subject to cohesive failure, and vice versa. Additionally, laser ablation with a properly designed dimple pattern can greatly improve the bonding strength, and the maximum average shear strength of specimens with a thickness of 50 μm reaches 32.82 MPa, which is an increase of 28.15% compared with the original milling specimen. Moreover, fabricating groove or grid patterns on the surfaces and applying PAA treatment can also significantly enhance the bonding strength, reaching up to 36.28 MPa.

Taking 57 prefecture-level cities in the Yellow River basin as a research area, this study evaluates the coupling coordination level of the water–energy–carbon (WEC) system in the Yellow River basin from 2012 to 2021 and explores the driving factors of coupling coordinated development. The study revealed that: (1) the development level of the three subsystems all showed an upward trend. The development level of the carbon system exhibited the highest level. The development index of the carbon and energy systems rose steadily, whereas the development index of the water system fluctuated considerably during the research period, although the magnitude of the fluctuation gradually slowed down. (2) The coupling coordination degree displayed a distribution characteristic of “high in the east and low in the west, high in the south and low in the north”. While the coupling coordination degree improved year by year, the spatial heterogeneity gradually increased. (3) The coupling coordination degree presented a positive correlation, and the agglomeration level was dominated by “high-high” and “low-low” agglomeration types. The “high-high” agglomeration area had a certain degree of spatial mobility, while the “low-low” agglomeration areas showed a tendency for spreading towards the middle reaches of the Yellow River basin. (4) Technological innovation, and the economic basis, had a significant positive impact on the coupling coordinated development, while the industrial structure bias showed a clear inhibitory effect. The positive role of opening up is not yet significant. Meanwhile, the indirect effect of each driving factor was greater than the direct effect.

Restructuring Particle Swarm Optimization (RPSO) algorithm has been developed as an intelligent approach based on the linear system theory of particle swarm optimization (PSO). It streamlines the flow of the PSO algorithm, specifically targeting continuous optimization problems. In order to adapt RPSO for solving discrete optimization problems, this paper proposes the binary Restructuring Particle Swarm Optimization (BRPSO) algorithm. Unlike other binary metaheuristic algorithms, BRPSO does not utilize the transfer function. The particle updating process in BRPSO relies solely on comparison results between values derived from the position updating formula and a random number. Additionally, a novel perturbation term is incorporated into the position updating formula of BRPSO. Notably, BRPSO requires fewer parameters and exhibits high exploration capability during the early stages. To evaluate the efficacy of BRPSO, comprehensive experiments are conducted by comparing it against four peer algorithms in the context of feature selection problems. The experimental results highlight the competitive nature of BRPSO in terms of both classification accuracy and the number of selected features.

Due to the design or construction defects, the insulation for cathodic protection in the valve chambers of longdistance oil and gas pipelines is prone to failure, which seriously threatens the safe operation of the pipelines. By studying the relevant design documents and referring to the field production experience, the fault detection and elimination process of insulation for cathodic protection in valve chambers was proposed, which could accurately locate the insulation failure and provide the targeted treatment method according to the type of insulation failure. In addition, the solution to the compatibility of cathodic protection insulation and lightning protection grounding was put forward, and the effectiveness of the solution was verified through field practice, which proves that the solution could not only meet the insulation requirements of electrical instrument facilities in the valve chambers, but also effectively guarantee the insulation facilities from lightning damage. Moreover, the research results are of important practical significance for improving the operation and management level of the long-distance oil and gas pipelines.

Abstract To develop a predictive model and a nomogram for predicting postoperative hemorrhage in preoperative patients undergoing laparoscopic pancreaticoduodenectomy (LPD). A total of 409 LPD patients that underwent LPD by the same surgical team between January 2014 and December 2020 were included as the training cohort. The preoperative data of patients were statistically compared and analyzed for exploring factors correlated with postoperative hemorrhage. The predictive model was developed by multivariate logistic regression and stepwise (stepAIC) selection. A nomogram based on the predictive model was developed. The discriminatory ability of the predictive model was validated using the receiver operating characteristic (ROC) curve and leave-one-out method. The statistical analysis was performed using R 3.5.1 ( www.r-project.org ). The predictive model including the risk-associated factors of postoperative hemorrhage was as follows: 2.695843 − 0.63056 × (Jaundice = 1) − 1.08368 × (DM = 1) − 2.10445 × (Hepatitis = 1) + 1.152354 × (Pancreatic tumor = 1) + 1.071354 × (Bile duct tumor = 1) − 0.01185 × CA125 − 0.04929 × TT − 0.08826 × APTT + 26.03383 × INR − 1.9442 × PT + 1.979563 × WBC − 2.26868 × NEU − 2.0789 × LYM − 0.02038 × CREA + 0.00459 × AST. A practical nomogram based on the model was obtained. The internal validation of ROC curve was statistically significant (AUC = 0.7758). The validation by leave-one-out method showed that the accuracy of the model and the F measure was 0.887 and 0.939, respectively. The predictive model and nomogram based on the preoperative data of patients undergoing LPD can be useful for predicting the risk degree of postoperative hemorrhage.

The natural transition in a gas–liquid two-phase boundary layer over an underwater flat plate is studied, taking into account the interphase slip between gas and liquid. An interphase slip model is proposed to determine the dynamic viscosity of the two-phase flow based on the physical origins of fluid viscosity. The model is then applied to laminar flow calculation, instability analysis, transition prediction, and prediction of the spectrum of wall fluctuating pressure in the laminar region. Numerical calculations are conducted for boundary layers for different void fractions, including liquid single-phase flow at a zero void fraction. The results reveal the differences between two-phase and single-phase flows and show that these differences become more obvious as the void fraction increases: (i) the thickness of the two-phase laminar boundary layer becomes less; (ii) the unstable zone becomes larger; (iii) the transition location moves upstream, and the transition advance distance caused by the microbubbles becomes longer and is proportional to the void fraction; (iv) the dangerous frequency becomes higher, and the frequency bandwidth becomes wider; and (v) the wall fluctuating pressure in the laminar region becomes stronger, and its peak frequency becomes slightly higher. As the oncoming flow velocity increases, the transition advance coefficient becomes smaller, and the dangerous frequency becomes higher. The comparison of the results of the interphase slip model and those of the conventional homogeneous flow model implies that the above differences between two-phase and single-phase flows are caused by the interphase slip between gas and liquid.

The tumor microenvironment (TME) plays an important role in the development, progression, and metastasis of cancer, and the extremely crucial feature is hypoxic and acidic. Cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), mesenchymal cells, blood vessels, and interstitial fluid are widely recognized as fundamentally crucial hallmarks for TME. As nanotechnology briskly boomed, the nanoscale drug delivery and imaging platform (NDDIP) emerged and has attracted intensive attention. Based on main characteristics of TME, NDDIP can be classified into pH-sensitive delivery and imaging platforms, enzyme-sensitive delivery and imaging platforms, thermo-sensitive delivery and imaging platforms, redox-sensitive delivery and imaging platforms, and light-sensitive delivery and imaging platforms. Furthermore, imageology is one of the significant procedures for disease detection, image-guided drug delivery, and efficacy assessment, including magnetic resonance imaging (MRI), computed tomography (CT), ultrasound (US), and fluorescence imaging. Therefore, the stimuli-responsive NDDIP will be a versatile and practicable tumor disease diagnostic procedure and efficacy evaluation tool. In this review article, we mainly introduce the characteristics of TME and summarize the progress of multitudinous NDDIP as well as their applications.

This study aims to investigate the effect of heterogeneous environmental regulation on the green transformation of the manufacturing sector in the Yellow River Basin by using the SBM-GML. Spatial econometrics and threshold regression models were utilized to examine the effect of heterogeneous environmental regulation on the green transformation of the manufacturing sector in the Yellow River Basin and the regulatory function of green technology innovation. The results demonstrated that the green total factor productivity (GTFP) of the manufacturing sector in the Yellow River Basin increased with fluctuations from 2010 to 2019. The analysis revealed a U-shaped relationship between command-and-control type environmental regulation and the green transformation. It also signifies that market-incentive type environmental regulation had a negligible effect on the green transformation. The relationship between public-participation type environmental regulation and the green transformation of the manufacturing sector in the Yellow River Basin was “U”-shaped but inverted. Innovations in green technology are a significant variable that influences the heterogeneous environmental regulations that affect the green transformation.

Disturbance of the internal environment in the spinal cord after spinal cord injury (SCI) is an important cause of the massive death of neurons in the injury area and one of the major problems that lead to the difficult recovery of motor function in patients. Rehmannia glutinosa, a famous traditional Chinese medicine, is commonly used in neurodegenerative diseases, whereas an iridoid glycoside extract of catalpol (CAT), with antioxidant, antiapoptotic, and neuroprotective pharmacological effects. However, the neuroprotective and anti-apoptosis mechanism of CAT in SCI remains unclear. In our study, we found that CAT has a restorative effect on the lower limb motor function of rats with SCI by establishing a rat model of SCI and treating CAT gavage for 30 days. Our study further found that CAT has the effect of inhibiting apoptosis and protecting neurons, and the action pathway may reduce endoplasmic reticulum (ER) stress by inhibiting CHOP and GRP78 expression and then reduce apoptosis and protect neurons through the Caspase3/Bax/Bcl-2 pathway. In conclusion, we demonstrated that CAT can treat SCI by inhibiting ER stress-mediated neuronal apoptosis and has the potential to be a clinical drug for the treatment of SCI.

PurposeThe present study sets out to evaluate the feasibility, safety, and effectiveness of conversion surgery following induction immunochemotherapy for patients with initially unresectable locally advanced esophageal squamous cell carcinoma (ESCC) in a real-world scenario.Materials and MethodsIn this multi-center, real-world study (NCT04822103), patients who had unresectable ESCC disease were enrolled across eight medical centers in China. All patients received programmed death receptor-1 (PD-1) inhibitor plus chemotherapy every 3 weeks for at least two cycles. Patients with significant relief of cancer-related clinical symptoms and radiological responsive disease were deemed surgical candidates. Feasibility and safety profile of immunochemotherapy plus conversion surgery, radiological and pathological tumor responses, as well as short-term survival outcomes were evaluated. Moreover, data of an independent ESCC cohort receiving induction chemotherapy (iC) were compared.ResultsOne hundred and fifty-five patients were enrolled in the final analysis. Esophagectomy was offered to 116 patients, yielding a conversion rate of 74.8%. R0 resection rate was 94%. Among the 155 patients, 107 (69.0%) patients experienced at least one treatment-related adverse event (TRAE) and 45 (29.0%) patients reported grade 3 and above TRAEs. Significant differences in responsive disease rate were observed between iC cohort and induction immunochemotherapy (iIC) cohort [objective response rate: iIC: 63.2% vs. iC: 47.7%, p = 0.004; pathological complete response: iIC: 22.4% vs. iC: 6.7%, p = 0.001). Higher anastomosis fistula rate was observed in the iC group (19.2%) compared with the iIC group (4%). Furthermore, Significantly higher event-free survival was observed in those who underwent conversion surgery.ConclusionOur results supported that conversion surgery following immunochemotherapy is feasible and safe for patients with initially unresectable locally advanced ESCC. Both radiological and pathological response rates were significantly higher in the iIC cohort compared with those in the traditional iC cohort.

Abstract Background Depression and chronic musculoskeletal pain (CMSP) are the leading causes of years lived with disabling diseases worldwide. Moreover, they often commonly coexist, which makes diagnosis and treatment difficult. A safe and effective treatment is urgently needed. Previous studies have shown that acupuncture is a cost-effective treatment for simple depression or CMSP. However, there is limited evidence that acupuncture is effective for depression comorbid with CMSP. Methods This is a randomized, sham acupuncture-controlled trial with three arms: real acupuncture (RA), sham acupuncture (SA), and healthy control (HC). Forty-eight depression combined CMSP participants and 12 healthy people will be recruited from GDTCM hospital and randomized 2:2:1 to the RA, SA, and HC groups. The patients will receive RA or SA intervention for 8 weeks, and HC will not receive any intervention. Upon completion of the intervention, there will be a 4-week follow-up. The primary outcome measures will be the severity of depression and pain, which will be assessed by the Hamilton Depression Rating Scale (HAMD-17) and Brief Pain Inventory (BPI), respectively. The secondary outcome measures will be cognitive function and quality of life, which will be measured by the Montreal Cognitive Assessment (MoCA), P300, and World Health Organization Quality of Life (WHOQOL-BREF). In addition, the correlation between brain-derived neurotrophic factor (BDNF) and symptoms will also be determined. Discussion The aim of this study is to evaluate the clinical efficacy and underlying mechanism of acupuncture in depression comorbid with CMSP. This study could provide evidence for a convenient and cost-effective means of future prevention and treatment of combined depression and CMSP. Trial registration Chinese Clinical Trial Registry ChiCTR1800014754 . Preregistered on 2 February 2018. The study is currently recruiting.

Abstract Current studies on cable harness layouts have mainly focused on cable harness route planning. However, the topological structure of a cable harness is also extremely complex, and the branch structure of the cable harness can affect the route of the cable harness layout. The topological structure design of the cable harness is a key to such a layout. In this paper, a novel multi-branch cable harness layout design method is presented, which unites the probabilistic roadmap method (PRM) and the genetic algorithm. First, the engineering constraints of the cable harness layout are presented. An obstacle-based PRM used to construct non-interference and near to the surface roadmap is then described. In addition, a new genetic algorithm is proposed, and the algorithm structure of which is redesigned. In addition, the operation probability formula related to fitness is proposed to promote the efficiency of the branch structure design of the cable harness. A prototype system of a cable harness layout design was developed based on the method described in this study, and the method is applied to two scenarios to verify that a quality cable harness layout can be efficiently obtained using the proposed method. In summary, the cable harness layout design method described in this study can be used to quickly design a reasonable topological structure of a cable harness and to search for the corresponding routes of such a harness.

In order to achieve China’s carbon peaking and carbon neutrality (double carbon) targets and to advance ecological conservation and high-quality development in the Yellow River Basin, it is essential that China reduces its energy intensity and increases its energy efficiency. This research developed an evaluation index system for energy efficiency and green development in the Yellow River Basin based on panel data collected from 64 of its prefecture-level cities and covering the period from 2011 to 2020. Each city’s energy efficiency and green development level index was calculated, and was analyzed together with the characteristics of its spatial pattern progression. The STIRPAT model was then used to investigate the influence mechanism of energy efficiency on green development. The final step in the analysis was to assess the process by which technical innovation influences the rise in energy efficiency from a green development point of view. The findings of this study indicate that: (1) There was a marked improvement in energy efficiency and green development levels across the Yellow River Basin over the study period of 2011 to 2020, but there are notable disparities among prefecture-level cities, with higher levels found in capital cities and cities in the lower reaches of the basin. (2) The improvement in energy efficiency has had a positive impact on the transition to green development, with factors such as human capital, urbanization levels, and the upgrading of industrial structures contributing significantly, while the level of foreign direct investment has had a limited impact. (3) Technological innovation plays a partial role in mediating the relationship between energy efficiency and green development in the Yellow River Basin, and passes the single-threshold test. When technological innovation surpasses the threshold value, the effect of energy efficiency on green development is significantly strengthened. This study indicates that improving energy efficiency, stimulating emerging industries, and enhancing technological innovation capabilities can significantly promote transformative green and high quality development in the Yellow River Basin of China.

The formation mechanism and evolution of plastic damage in billet during reduction pretreatment were investigated using laboratory experiments and simulations. The microstructure and damage distribution were observed using reduction pretreatment experiments. Isothermal tension tests were designed to study the mechanism of damage under different deformation temperatures and strain rates. A plastic damage model based on tension tests was established to further analyze damage evolution during reduction pretreatment. Experimental results showed that the distribution of the damage was characterized by microvoids near the surface and microcracks along the grain boundary at the center. With the increase in strain rate, plastic damage above 1050 °C was transformed from grain boundary damage caused by grain boundary slip to inclusion damage caused by dislocation movement. The simulation results showed that the established plastic damage model was reliable and could be used to describe the plastic damage evolution during reduction pretreatment.

Waxy corn kernels with different colors have high phenolic content and good application potential in medicine and food healthcare. In our work, the content changes of phenolic and anthocyanins profiles were related to genes in the anthocyanin biosynthesis pathway, and the antioxidant activities of three different colors of waxy corn kernels (black, white, and yellow) were determined during kernel development. Results showed that growing temperature and light intensity could affect the accumulation of phytochemicals and antioxidant activities in waxy corns during maturation. Phenolic and antioxidant activities decreased over kernel maturation, and spring had higher nutrition levels during the best harvest time (20 and 25 days after pollination in the spring and autumn, respectively) for waxy corns. Cyanidin-3-O-glucoside and pelargonidin-3-O-glucoside were the main anthocyanins detected in the black waxy corns. The contents of cyanidin are higher than pelargonidin followed by peonidin in the autumn, while on the other hand, pelargonidin had a slightly higher content compared to cyanidin in the spring. DFR, CF1, and ANS were the key genes affecting anthocyanin accumulation. This work provided information on the best harvest time for the pigment of waxy corn in order to achieve relatively high phenolic profiles and antioxidant activities. It also illustrated the possible relationship between weather conditions, gene expression levels, and phenolic content during kernel development.

At present, polarization imaging detection experiments of underwater objects mainly focus on the degree of polarization but lack of Stokes vector imaging effect of each element. Based on the principle that the polarization characteristics of different materials are different, the experiment of underwater target detection by laser pulse polarization is carried out in this paper, and the influence of different depths of an underwater object and material factors on polarization imaging detection is studied. The results show that in air, the average degree of polarization of iron sheet is 0.56, that of ceramic tile is 1.00, and that of plastic is 0.48. In water, the average degree of polarization of iron sheet is 0.3625 at 7.5 m, the average degree of polarization of ceramic tile at 7.5 m is 0.359, and that of plastic at 7.5 m is 0.3805. The medium will change the degree of polarization of the measured object. The targets made of different materials have different polarization characteristics, and the polarization information is of great value in improving the detection performance of man-made targets. Polarization detection can obtain better information about underwater objects than traditional radiation intensity detection and can effectively suppress the absorption and scattering of light by water.

To investigate the dynamic recrystallization (DRX) behavior of as-cast Fe-20Cr-5.5Al-0.64La stainless steel, a series of compression tests were carried out on a Gleeble-3500 thermal simulator in the temperature range of 1000~1150 °C and the strain rate range of 0.001~1 s−1. The true stress-true strain curves were obtained and their characteristics were analyzed. Using regression analysis, the apparent activation energy for the Fe-20Cr-5.5Al-0.64La stainless steel was estimated to be 300.19 kJ/mol, and the constitutive equation was developed successfully with a hyperbolic sine equation as: ε˙=e21.91sinh0.035σ3.18exp−300190RT. The critical strain, the peak strain and the strain for the maximum softening rate were identified based on the work hardening rate curves and expressed as a function of the Zener−Hollomon parameter. The kinetic model of DRX was established using the stress−strain data. According to the analysis of the kinetics model and microstructure evolution, the evolution of DRX volume could be described as follows: the volume fraction of DRX grains increased with an increase in strain; at a fixed deformation temperature, the DRX volume fraction was larger at a lower strain rate for the same strain; and the size of DRX grains increased with an increase in temperature or a decrease in strain rate.

Carbon capture, utilization, and storage (CCUS) technology is considered an effective way to reduce greenhouse gases, such as carbon dioxide (CO2), which is significant for achieving carbon neutrality. Based on Derwent patent data, this paper explored the technology topics in CCUS patents by using the latent Dirichlet allocation (LDA) topic model to analyze technology’s hot topics and content evolution. Furthermore, the logistic model was used to fit the patent volume of the key CCUS technologies and predict the maturity and development trends of the key CCUS technologies to provide a reference for the future development of CCUS technology. We found that CCUS technology patents are gradually transforming to the application level, with increases in emerging fields, such as computer science. The main R&D institutes in the United States, Europe, Japan, Korea, and other countries are enterprises, while in China they are universities and research institutes. Hydride production, biological carbon sequestration, dynamic monitoring, geological utilization, geological storage, and CO2 mineralization are the six key technologies of CCUS. In addition, technologies such as hydride production, biological carbon sequestration, and dynamic monitoring have good development prospects, such as CCUS being coupled with hydrogen production to regenerate synthetic methane and CCUS being coupled with biomass to build a dynamic monitoring and safety system.

A series of industrial trials of argon injection into ladle shroud (AIILS) with different argon-blowing rates were conducted in this study. Firstly, bubbles in actual liquid steel of the tundish were captured by the method of “cold steel plate dipping” and characterized by microscope examination. A detailed investigation on the three-dimension morphology of bubbles was carried out by using industrial computerized tomography (ICT). Then, the two-phase flow of liquid steel and argon gas in the tundish was numerically simulated to further investigate the motion behaviors of bubbles in liquid steel of the tundish. The simulated results showed that bubbles in the size range of this investigation had a large enough filtration rate to demonstrate a good performance on inclusion removal. Finally, the effect of AIILS on inclusion removal was analyzed by detecting the variations of inclusions as well as total oxygen content in steels taken from the ladle, tundish, and casting billet. The method of AIILS was more effective at improving the removal of inclusions in the range of 5 to 10 μm and obviously increased the removal rate of total oxygen content.

Abstract Background Behcet’s disease (BD) is a relapsing systemic vascular autoimmune/inflammatory disease. Despite much effort to investigate BD, there are virtually no unique laboratory markers identified to help in the diagnosis of BD, and the pathogenesis is largely unknown. The aim of this work is to explore interactions between different clinical variables by correlation analysis to determine associations between the functional linkages of different paired variables and potential diagnostic biomarkers of BD. Methods We measured the immunoglobulin proteome (IgG, IgG1–4, IgA, IgA1–2) and 29 clinical variables in 66 healthy controls and 63 patients with BD. We performed a comprehensive clinical variable linkage analysis and defined the physiological, pathological and pharmacological linkages based on the correlations of all variables in healthy controls and BD patients without and with immunomodulatory therapy. We further calculated relative changes between variables derived from comprehensive linkage analysis for better indications in the clinic. The potential indicators were validated in a validation set with 76 patients with BD, 30 healthy controls, 18 patients with Takayasu arteritis and 18 patients with ANCA-associated vasculitis. Results In this study, the variables identified were found to act in synergy rather than alone in BD patients under physiological, pathological and pharmacological conditions. Immunity and inflammation can be suppressed by corticosteroids and immunosuppressants, and integrative analysis of granulocytes, platelets and related variables is likely to provide a more comprehensive understanding of disease activity, thrombotic potential and ultimately potential tissue damage. We determined that total protein/mean corpuscular hemoglobin and total protein/mean corpuscular hemoglobin levels, total protein/mean corpuscular volume, and plateletcrit/monocyte counts were significantly increased in BD compared with controls (P

The influences of the micron bondline thickness, temperature, and loading rate on the tensile strength of adhesive joints were studied for the precision adhesive structures, and the fractured surfaces were analyzed by the infrared imaging and SEM methods. The testing results show that the tensile strength increases and then linearly decreases with the increase of bondline thickness; the peak tensile strength is always acquired at the bondline thickness of around 30 μm; the maximum tensile strength increases up to 28.6% as the thickness increases from 10 to 30 μm at the loading rate of 1 mm/min; the strength decreases by more than 33% and finally reaches a closed value at different bondline thicknesses as the temperature rises from −30 to 110 °C. The results indicate that reducing the bondline thickness, less than about 10 μm, could result in a weak bonding interface; the tensile strength increases with the increase of the loading rate, exhibiting the strain-rate hardening effect below the Tg; the plastic-damage characteristic appears and becomes clearer on the fractured surface as the temperature increases. Under the tested conditions, the temperature shows the most significant effect on the tensile strength, then the bondline thickness followed by the loading rate.

It has been recognized that colistin resistance is a growing problem that seriously impairs the clinical efficacy of colistin against bacterial infections. One strategy that has been proven to have therapeutic effect is to overcome the widespread emergence of antibiotic-resistant pathogens by combining existing antibiotics with promising non-antibiotic agents. In this work, antibiotic susceptibility testing, checkerboard assays and time-kill curves were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of the combination. The molecular mechanisms of tetrandrine in combination with colistin were analyzed using fluorometric assay and Real-time PCR. To predict possible interactions between tetrandrine and MCR-1, molecular docking assay was taken. Finally, we evaluated the in vivo efficacy of tetrandrine in combination with colistin against MCR-positive Salmonella. Overall, the combination of tetrandrine and colistin showed significant synergistic activity. In-depth mechanistic analysis showed that the combination of tetrandrine with colistin enhances the membrane-damaging ability of colistin, undermines the functions of proton motive force (PMF) and efflux pumps in MCR-positive bacteria. The results of molecular docking and RT-PCR analyses showed that tetrandrine not only affects the expression of mcr-1 but is also an effective MCR-1 inhibitor. Compared with colistin monotherapy, the combination of tetrandrine with colistin significantly reduced the bacterial load in vivo. Our findings demonstrated that tetrandrine serves as a potential colistin adjuvant against MCR-positive Salmonella.