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Mesenchymal stem cell (MSC) migration determines the healing capacity of bone and is crucial in promoting bone regeneration. Migration of MSCs is highly dependent on degradation of extracellular matrix by proteolytic enzymes. However, the underlying mechanisms of how enzymolysis paves the way for MSCs to migrate from their niche to the defect area is still not fully understood. Here, this study shows that high-temperature requirement A3 (HtrA3) overcomes the physical barrier and provides anchor points through collagen IV degradation, paving the way for MSC migration. HtrA3 is upregulated in MSCs at the leading edge of bone defect during the early stage of healing. HtrA3 degrades the surrounding collagen IV, which increases the collagen network porosity and increases integrin β1 expression. Subsequently, integrin β1 enhances the mechanotransduction of MSCs, thus remodeling the cytoskeleton, increasing cellular stiffness and nuclear translocation of YAP, eventually promoting the migration and subsequent osteogenic differentiation of MSCs. Local administration of recombinant HtrA3 in rat cranial bone defects significantly increases new bone formation and further validates the enhancement of MSC migration. This study helps to reveal the novel roles of HtrA3, explore potential targets for regenerative medicine, and offer new insights for the development of bioactive materials.

Abstract Background Pulmonary function is very important for the healthy development of children and adolescents. However, fewer studies have been conducted on pulmonary function trends in children and adolescents in remote areas. The aim of this study was to estimate the forced vital capacity (FVC) trend and its relationship with body mass index (BMI) among young people in Xinjiang during 1985–2014 using data from seven successive national surveys. Methods A total of 19,449 Xinjiang children and adolescents aged 7–18 years were extracted from the Chinese National Survey on Students’ Constitution and Health. Height, weight, and FVC were measured repeatedly in each survey. FVC comparisons between adjacent surveys by age and sex were conducted by nonparametric Kruskal-Wallis after Kolmogorov-Smirnov of normality. One-way ANOVA and least significant difference(LSD) method was used to compare differences in FVC levels of Xinjiang children and adolescents with different BMI. The relationship between BMI and FVC was investigated using a nonlinear regression model. Results The FVC levels of Xinjiang children and adolescents peaked in 2000, with overall FVC levels being 8.7% higher in 2000 than in 1985. Since then, a substantial decline occurred, contrasting to 2000, with FVC levels decreasing by 27% in 2014, which was still lower than that in 1985 by 20.73%. The proportion of overnutrition boys increased from 0.2% in 1985 to 22.1% in 2014, and girls from 0.5% in 1985 to 14.5% in 2014. An inverted U-shape association between FVC and BMI values was obtained for Xinjiang children and adolescents. Conclusions Targeted measures should be carried out in schools to control BMI levels to ensure good lung function in children and adolescents in Xinjiang. Future studies should pay more attention to other factors affecting FVC, such as dietary behaviour, physical activity, and racial differences among children and adolescents.

Abstract Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells (BMSCs) and vascular endothelial cells (ECs). However, there are apparent limitations in stem cell-based therapy which hinder its clinic translation. Hence, we investigated the potential of alternative stem cell substitutes for facilitating bone regeneration. In this study, we successfully prepared cell membrane vesicles (CMVs) from BMSCs and ECs. The results showed that BMSC-derived cell membrane vesicles (BMSC-CMVs) possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental cells. EC-derived cell membrane vesicles (EC-CMVs) also contained BMP2 and VEGF derived from their parental cells. BMSC-CMVs enhanced tube formation and migration ability of hUVECs, while EC-CMVs promoted the osteogenic differentiation of hBMSCs in vitro. Using a rat skull defect model, we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in vivo. Therefore, our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.

Highlights Aligned graphene building blocks take full advantages of the outstanding properties of graphene. Comprehensive review of recent advancements in the utilization of highly aligned graphene aerogels for multifunctional applications. By systematically summarizing the controlled assembly, aligned structural attributes, quantitative characterization methods, anisotropic properties, and multifunctional applications of graphene aerogels, this review enhances understanding of the material's potential for diverse applications, offering tailored properties and novel functionalities.

Abstract Angiogenesis is a complex, highly-coordinated and multi-step process of new blood vessel formation from pre-existing blood vessels. When initiated, the sprouting process is spearheaded by the specialized endothelial cells (ECs) known as tip cells, which guide the organization of accompanying stalk cells and determine the function and morphology of the finally-formed blood vessels. Recent studies indicate that the orchestration and coordination of angiogenesis involve dynamic tip cell selection, which is the competitive selection of cells to lead the angiogenic sprouts. Therefore, this review attempt to summarize the underlying mechanisms involved in tip cell specification in a dynamic manner to enable readers to gain a systemic and overall understanding of tip cell formation, involving cooperative interaction of cell rearrangement with Notch and YAP/TAZ signaling. Various mechanical and chemical signaling cues are integrated to ensure the right number of cells at the right place during angiogenesis, thereby precisely orchestrating morphogenic functions that ensure correct patterning of blood vessels. Video Abstract

Coronavirus nonstructural protein 2 (Nsp2) is regarded as a virulence determinant and plays a critical role in virus replication, and innate immunity. Screening and identifying host cell proteins that interact with viral proteins is an effective way to reveal the functions of viral proteins. In this study, the host proteins that interacted with transmissible gastroenteritis virus (TGEV) Nsp2 were identified using immunoprecipitation combined with LC-MS/MS. 77 host cell proteins were identified as putative Nsp2 interaction host cell proteins and a protein-protein interaction (PPI) was constructed. The identified proteins were found to be associated with various subcellular locations and functional categories through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. It is hypothesized that the host cell proteins interacting with TGEV Nsp2 are mainly involved in the formation of the cytoplasmic translation initiation complex, mRNA binding, ribosomes, and proteasomes. Among these, the ATP5B, a core subunit of the mitochondrial ATP synthase was further studied. The Coimmunoprecipitation (Co-IP) and indirect immunofluorescence (IFA) results confirmed that TGEV Nsp2 interacted with ATP5B. Furthermore, the downregulation of ATP5B expression was found to promote TGEV replication, suggesting that ATP5B might function as a negative regulator of TGEV replication. Collectively, our results offer additional insights into the functions of Nsp2 and provide a novel antiviral target against TGEV.

ObjectiveThis sought to explore the association between soybean product consumption and executive function (EF) in Chinese Tibetan adolescents in high-altitude areas.MethodsA total of 1,184 Tibetan children and adolescents were tested on demographic variables, soybean product consumption, and executive function in Lhasa and Nagchu regions of Tibet, China, using stratified whole population sampling. One-way ANOVA, linear regression analysis, and logistic regression analysis were used to analyze the associations existing between soybean product consumption and executive function.ResultsThe proportions of Hardly ever, Occasionally, and Often in Soy Consumption among Tibetan children and adolescents in high altitude areas of Tibet, China were 21.7, 50.3, and 28.0%, respectively. The difference in 2 back reaction time among Tibetan children and adolescents with different soybean product consumption was statistically significant (F = 6.374, p = 0.002). The difference in conversion function reaction time was also statistically significant (F = 8.129, p

BackgroundIn recent years, the addition of immune checkpoint inhibitors (ICI) to chemotherapy (CT) has become a research hotspot in the therapy of metastatic triple-negative breast cancer. Nevertheless, controversial results have been revealed among the published randomized controlled trials. Hence, a meta-analysis was performed to assess the therapeutic effect of this treatment regimen.MethodsFive English databases (PubMed, WOS, CENTRAL, Scopus, and Embase), and four Chinese databases (CBM, CNKI, VIP, and Wanfang), as well as oncological meetings, were systematically searched to identify eligible studies that assessed the addition of ICI to CT versus CT alone in metastatic triple-negative breast cancer. The pooled hazard ratios (HR) of progression-free survival (PFS) and overall survival (OS) were estimated using fixed- or random-effect model. Subgroup analyses were also performed in the intention-to-treat (ITT) and PD-L1-positive individuals.ResultsAll told there are five eligible randomized controlled trials involving 3,000 patients were enrolled in this meta-analysis. Compared with CT alone, the ICI plus CT regimen significantly increased PFS in the ITT (HR = 0.80, 95% CI: 0.73–0.88) and PD-L1-positive (HR = 0.70, 95% CI: 0.62–0.79) populations, as well as OS in the ITT (HR = 0.89, 95% CI: 0.81–0.97) and PD-L1-positive populations (HR = 0.80, 95% CI: 0.71–0.91). Moreover, the PFS of sufferers treated with the combination strategy of ICI with CT increased alongside PD-L1 enrichment. A clinical benefit in terms of objective response rate was also distinctly observed in both populations treated with ICI plus CT. In the subgroup analysis, patients in the no prior CT subgroup experienced a striking increase in PFS in both populations; however, a difference was not observed in other subgroups.ConclusionsThe combination strategy striking improves PFS and OS in both ITT and PD-L1-positive populations, and PFS is prolonged with PD-L1 enrichment. Patients who do not receive CT prior to this treatment are associated with longer PFS in both populations.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42021289817.

The Lombok Strait (LS), Ombai Strait (OS), and Timor Passage (TP) are three major outlets of the Indonesian Throughflow to the Indian Ocean. Here, sources and pathways of the LS, OS, and TP outflows are explored by a Lagrangian particle tracking analysis based on a ~3 km regional ocean model simulation. The Makassar Strait transport contributes to ~80%, ~75%, and ~45% of the LS, OS, and TP outflows, respectively. However, ~41% and ~19% of the TP and OS outflows stem from the Lifamatola Passage, which largely feeds the upper and intermediate layers of the outflows. The role of Karimata Strait is quite limited and restricted to the upper layer. It takes 1-2 years and 2-6 years for the Makassar Strait water to reach the OS and TP, respectively, whereas the Lifamatola Passage water passes through the OS (2-6 years) and TP (3-9 years) on a prolonged transit time. In the Banda Sea, the western boundary current is the main pathway toward the OS, while the waters to the TP tend to take a basin interior route.

Abstract While the pivotal role of the Indonesian Throughflow (ITF) in the global ocean circulation and climate has been widely recognized, accurate estimation of its volume transport based on observational data remains challenging. This work provides an updated estimate of the monthly ITF geostrophic transport (ITFG) in the upper 700 m at the IX1 section between Indonesia and Australia. The ITFG estimate is better constrained by improved data correction and new salinity data products. The mean ITFG of 1993–2018 is 8.2 ± 0.2 Sv, in which contributions of the temperature and salinity components (ITFT and ITFS) are 5.5 ± 0.2 and 2.8 ± 0.1 Sv, respectively. The interannual variability (∼4.4 Sv in standard deviation) is dominated by ITFT, as the result of wind‐driven thermocline dynamics, and slightly attenuated in amplitude by ITFS. The strengthening trend of 1.33 Sv decade−1 during 1993–2018 primarily arises from ITFS and secondarily from ITFT.

BackgroundAssociations between body composition and execution function (EF) were currently studied in low altitude (LA) areas. However, the research on the correlation between waist circumference (WC) and EF among adolescents living at high altitude (HA) was limited.ObjectiveWe sought to explore the association between WC and EF in Chinese Tibetan adolescents aged 13–18 years in HA areas.MethodsAfter excluding invalid data and extreme values, 1,228 participants (583 boys and 645 girls) were eventually included. The areas of Lhasa (average elevation of 3650 m), Nagqu (4500 m), Qamdo (3500 m), and Nyingchi (3100 m) in China were chosen as study sites. Participants completed tasks to measure inhibitory control, working memory, and cognitive flexibility. The predictive association between WC and EF was explored by One-way ANOVA, Pearson correlation, and linear regression analysis.ResultsAfter controlling for concomitant variables, the reaction time (RT) of responding to inhibitory control (difference incongruent and congruent), working memory (1-back, 2-back), and cognitive flexibility (heterogeneous, difference in heterogeneous and homogeneous) stimuli in subjects with WC ≥ 85th percentile was longer than that in those with WC of the 15th percentile or below [by 1.785 ms (95% CI: 0.078, 3.491), 208.734 ms (95% CI: 96.886, 320.582), 106.679 ms (95% CI: 16.485, 196.873), 82.307 ms (95% CI: 19.171, 145.442), and 58.397 ms (95% CI: 0.343,116.452), respectively], (P < 0.05).ConclusionAfter adjustment for concomitant variables, WC was significantly positively associated with the RT of inhibitory control, working memory, and cognitive flexibility among Chinese Tibetan adolescents in HA areas.

The southeastern Indian Ocean (SEIO) exhibits prominent decadal variability in sea surface salinity (SSS), showing salinity decreases during 1995-2000 and 2005-2011 and increases during 2000-2005 and after 2011. These salinity changes are linked to the Indo-Pacific climate and have impacts on the regional marine environment. Yet, the underlying mechanism has not been firmly established. In this study, decadal SSS variability of the SEIO is successfully simulated by a high-resolution regional ocean model, and the mechanism is explored through a series of sensitivity experiments. The results suggest that freshwater transport of the Indonesian throughflow (ITF) and local precipitation are two major drivers for the SSS decadal variability. They mutually cause most of the variability, with a generally larger contribution of precipitation. Other processes, such as evaporation and advection driven by local winds, play a minor role. Further analysis shows that the decadal precipitation in the SEIO is mainly associated with the decadal variability of Ningaloo Niño. Ocean dynamic processes significantly modify the relationship between SSS and precipitation, greatly shortening their lag time. The changes in both volume transport and salinity of the ITF water can cause large salinity changes in the SEIO region. Although local wind forcing gives rise to considerable changes in evaporation rate and ocean current advection, its overall contribution to decadal SSS variability is small compared to local precipitation and the ITF.

Endothelial tip cell outgrowth of blood-vessel sprouts marks the initiation of angiogenesis which is critical in physiological and pathophysiological procedures. However, how mechanical characteristics of extracellular matrix (ECM) modulates tip cell formation has been largely neglected. In this study, we found enhanced CD31 expression in the stiffening outer layer of hepatocellular carcinoma than in surrounding soft tissues. Stiffened matrix promoted sprouting from endothelial cell (EC) spheroids and upregulated expressions of tip cell-enriched genes in vitro. Moreover, tip cells showed increased cellular stiffness, more actin cytoskeleton organization and enhanced YAP nuclear transfer than stalk and phalanx ECs. We further uncovered that substrate stiffness regulates FAK and Paxillin phosphorylation in focal adhesion of ECs promoting Rac1 transition from inactive to active state. YAP is subsequently activated and translocated into nucleus, leading to increased tip cell specification. p-Paxillin can also loosen the intercellular connection which also facilitates tip cell specification. Collectively our present study shows that matrix stiffness modulates tip cell formation through p-PXN-Rac1-YAP signaling axis, shedding light on the role of mechanotransduction in tip cell formation. This is of special significance in biomaterial design and treatment of some pathological situations.

Three-dimensional (3D) printing, alternatively known as additive manufacturing, is a transformative technology enabling precise, customized, and efficient manufacturing of components with complex structures. It revolutionizes traditional processes, allowing rapid prototyping, cost-effective production, and intricate designs. The 3D printed graphene-based materials combine graphene’s exceptional properties with additive manufacturing’s versatility, offering precise control over intricate structures with enhanced functionalities. To gain comprehensive insights into the development of 3D printed graphene and graphene/polymer composites, this review delves into their intricate fabrication methods, unique structural attributes, and multifaceted applications across various domains. Recent advances in printable materials, apparatus characteristics, and printed structures of typical 3D printing techniques for graphene and graphene/polymer composites are addressed, including extrusion methods (direct ink writing and fused deposition modeling), photopolymerization strategies (stereolithography and digital light processing) and powder-based techniques. Multifunctional applications in energy storage, physical sensor, stretchable conductor, electromagnetic interference shielding and wave absorption, as well as bio-applications are highlighted. Despite significant advancements in 3D printed graphene and its polymer composites, innovative studies are still necessary to fully unlock their inherent capabilities.

ObjectivesTo assess the clinical efficacy and toxicity of nimotuzumab in combination with chemoradiotherapy or chemoradiotherapy alone in the treatment of cervical cancer.MethodsThe PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biomedical Medicine, Wanfang, and VIP databases were systematically searched for relevant literature. Ultimately, six randomised controlled trials (n=393) were included in our meta-analysis.ResultsA total of 393 patients were included, of which 197 were in the nimotuzumab combined with chemoradiotherapy group and 196 were in the chemoradiotherapy group. The results of our meta-analysis showed that the complete remission rate (risk ratio [RR] = 1.34, 95% confidence interval [CI]: 1.08-1.65, P = 0.007), objective response rate (RR = 1.30, 95% CI: 1.16-1.44, P < 0.05), and three-year survival rate (RR = 1.27, 95% CI: 1.06-1.51, P = 0.008) in the nimotuzumab combined with chemoradiotherapy group were significantly improved compared with the chemoradiotherapy group. This difference was not statistically significant when comparing the incidence of adverse reactions (such as leukocytopenia, gastrointestinal reaction, radiocystitis, and radioproctitis) between the two groups.ConclusionsNimotuzumab in combination with chemoradiotherapy has some advantages over chemoradiotherapy alone in the treatment of cervical cancer and does not increase toxicity. Therefore, nimotuzumab has the potential to be an effective treatment for cervical cancer; however, further evidence from large-scale randomised controlled trials is needed.

Abstract Background Perioperative neurocognitive disorder (PND) is a long-term postoperative complication in elderly surgical patients. The underlying mechanism of PND is unclear, and no effective therapies are currently available. It is believed that neuroinflammation plays an important role in triggering PND. The secreted glycoprotein myeloid differentiation factor 2 (MD2) functions as an activator of the Toll-like receptor 4 (TLR4) inflammatory pathway, and α5GABAA receptors (α5GABAARs) are known to play a key role in regulating inflammation-induced cognitive deficits. Thus, in this study, we aimed to investigate the role of MD2 in PND and determine whether α5GABAARs are involved in the function of MD2. Methods Eighteen-month-old C57BL/6J mice were subjected to laparotomy under isoflurane anesthesia to induce PND. The Barnes maze was used to assess spatial reference learning and memory, and the expression of hippocampal MD2 was assayed by western blotting. MD2 expression was downregulated by bilateral injection of AAV-shMD2 into the hippocampus or tail vein injection of the synthetic MD2 degrading peptide Tat-CIRP-CMA (TCM) to evaluate the effect of MD2. Primary cultured neurons from brain tissue block containing cortices and hippocampus were treated with Tat-CIRP-CMA to investigate whether downregulating MD2 expression affected the expression of α5GABAARs. Electrophysiology was employed to measure tonic currents. For α5GABAARs intervention experiments, L-655,708 and L-838,417 were used to inhibit or activate α5GABAARs, respectively. Results Surgery under inhaled isoflurane anesthesia induced cognitive impairments and elevated the expression of MD2 in the hippocampus. Downregulation of MD2 expression by AAV-shMD2 or Tat-CIRP-CMA improved the spatial reference learning and memory in animals subjected to anesthesia and surgery. Furthermore, Tat-CIRP-CMA treatment decreased the expression of membrane α5GABAARs and tonic currents in CA1 pyramidal neurons in the hippocampus. Inhibition of α5GABAARs by L-655,708 alleviated cognitive impairments after anesthesia and surgery. More importantly, activation of α5GABAARs by L-838,417 abrogated the protective effects of Tat-CIRP-CMA against anesthesia and surgery-induced spatial reference learning and memory deficits. Conclusions MD2 contributes to the occurrence of PND by regulating α5GABAARs in aged mice, and Tat-CIRP-CMA is a promising neuroprotectant against PND.

ObjectivesTo evaluate the clinical curative effects and toxicity of neoadjuvant chemoradiotherapy for resectable gastric cancer compared to those of neoadjuvant chemotherapy.MethodsA systematic review and meta-analysis of the randomized controlled trials (RCTs) of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy were performed in patients with resectable gastric cancer.ResultsSeven RCTs were included (601 patients; 302 in the neoadjuvant chemoradiotherapy group and 299 in the neoadjuvant chemotherapy group). The neoadjuvant chemoradiotherapy group had an increased number of patients with a complete response [odds ratio (OR) = 3.79, 95% confidence interval (CI): 1.68–8.54, p = 0.001] and improved objective response rate (OR = 2.78, 95% CI: 1.69–4.57, p < 0.0001), 1-year (OR = 3.51, 95% CI: 1.40–8.81, p = 0.007) and 3-year (OR = 2.14, 95% CI: 1.30–3.50, p = 0.003) survival rates, R0 resection rate (OR = 2.21, 95% CI: 1.39–3.50, p = 0.0008), and complete pathologic response (OR = 4.39, 95% CI: 1.59–12.14, p = 0.004). Regarding the incidence of adverse effects after neoadjuvant therapy, only the occurrence rate of gastrointestinal reaction in the neoadjuvant chemoradiotherapy group was higher than that in the neoadjuvant chemotherapy group (OR = 1.76, 95% CI: 1.09–2.85, p = 0.02), and there was no significant difference in other adverse effects. There was no difference in the incidence of postoperative complications between the two groups.ConclusionNeoadjuvant chemoradiotherapy for resectable gastric cancer has several advantages in terms of efficacy and safety compared to neoadjuvant chemotherapy. Therefore, neoadjuvant chemoradiotherapy has great potential as an effective therapy for resectable gastric cancers.Systematic Review Registrationhttps://inplasy.com/inplasy-2022-3-0164, registration number INPLASY202230164.

ObjectivesTo compare the survival and complications of neoadjuvant chemoradiation (NCRT) versus neoadjuvant chemotherapy (NCT) for esophageal squamous cell carcinoma (ESCC).MethodsWe conducted a systematic literature search of the PubMed, Web of Science, Cochrane Library, EMBASE, CNKI, Wanfang Data, CBM, and VIP databases from inception to November 2021. Meta-analyses were performed using RevMan (version 5.3) and Stata version 15.0.ResultsA total of 18 studies were included, which involved 3137 patients, The results of the metaanalysis showed that the pathological complete remission rate (odds ratio [OR] = 5.21, 95% confidence interval [CI]: 2.85-9.50, pConclusionThe use of NCRT in the treatment of patients with ESCC patients showed significant advantages in terms of survival and safety relative to the use of NCT.

Background: Previous studies had shown that poor quality of early parental attachment is a risk factor for suicide, but few have focus on the mechanism between suicidal ideation and parental attachment. The aim of this study was to explore how parental attachment, anhedonia, and peer attachment were associated with suicidal ideation in adolescents.Method: Participants were enrolled in middle schools, in Hefei, Anhui, China. All participants completed socio-demographic characteristic and standard assessments on parental attachment, peer attachment, anhedonia, and suicidal ideation by paper surveys. The effect of parental attachment on suicidal ideation mediated by anhedonia and peer attachment was analyzed by a structural equation model (SEM) using SPSS AMOS 23.0.Results: The SEM analysis revealed that the standard total effect of parental attachment on suicidal ideation was −0.137 (Z=−27.00, 95% confidence interval [CI; −0.147, −0.127], p

ObjectivesTo evaluate the clinical curative effects and toxicity of recombinant human adenovirus-p53 injection (rAd-p53) plus chemotherapy (CT), radiotherapy (RT), or concurrent chemoradiotherapy (CRT) for the treatment of cervical cancer.MethodsWe identified 14 eligible studies in the PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wangfangdate, CBM, and VIP databases from their inception to May 2021 and performed meta-analyses using RevMan version 5.3.ResultsThis analysis included 14 studies involving 737 patients. The results of the meta-analysis results showed significantly improved complete remission (odds ratio [OR] = 2.54, 95% confidence interval [CI]: 1.74–3.70, p < 0.00001), partial remission (OR = 1.56, 95% CI: 1.14–2.14, p = 0.006), and object response (OR = 4.47, 95% CI: 3.02–6.60, p < 0.00001) rates in the rAd-p53 combination therapy group compared to those in the CT/RT/CRT group. The results of subgroup analyses of CT/RT/CRT were consistent with the overall results. Regarding the incidence of adverse reactions, only the occurrence rate of fever (OR = 18.21, 95% CI: 10.54–31.47, p < 0.00001) in the rAd-p53 combination group was higher than that in the CT/RT/CRT group. No other significant differences were observed in other adverse reactions.ConclusionRAd-p53 combined with CT/RT/CRT for the treatment of cervical cancer showed significant advantages in efficacy and safety compared to those in the CT/RT/CRT group. Therefore, rAd-p53 has great potential as an effective therapy for cervical cancer.Systematic Review Registrationhttps://inplasy.com/inplasy-2021-5-0058/.

Soil salinization is an important factor contributing to the deterioration of soil environment and low crop yield in arable land. In this study, the effects of five fulvic acid applications (0 (CK), 150 (T1), 300 (T2), 450 (T3), and 600 (T4) kg·ha−1) on soil physicochemical properties, humus content of each component, and cotton (Xinluzao No. 82) growth were investigated. It was confirmed that fulvic acid improved soil water-stable macroaggregates, moisture distribution, and desalinization. 0–20 cm soil relative desalinization rate was significantly increased by 2–11.75%. The pH value decreased by 0.09–0.21. The soil organic matter content was significantly increased compared to CK (p < 0.05), with 7.5–26.93% increase in organic matter content in 0–20 cm soil layer. Soil humification was increased to different degrees, with the most significant increase in humic carbon content in T3 treatment (p < 0.05). There was a significant increase in leaf area index (LAI), stem diameter, and plant height of cotton (p < 0.05). Cotton yield increased by 3.64–8.36% compared to CK (p < 0.05). Correlation analysis showed that cotton yield was significantly correlated with the soil textures of saline soils. The best improvement was achieved with 450 kg·ha−1 fulvic acid. The results of this study can provide a theoretical basis for the improvement of saline soils in arid zones to enhance crop growth and yield.

In this study, the influence of the relevant parameters of a subsurface pipe layout on soil water and salt transport in a cotton field under mulched drip irrigation is explored. Based on the measured data of the changes in the groundwater level and salt in the field, the DRAINMOD numerical model has been used for simulating the water and salt dynamics of a salinized cotton field under subsurface pipe drainage. The results of the investigation show that the DRAINMOD model can accurately simulate the changes in the hydrological conditions and the salt-leaching process in the study area. The average deviation between the simulated and measured values of the groundwater depth in 2013 and 2014 was −1.72 cm and 2.43 cm, the average absolute deviation was 3.84 cm and 2.43 cm, the root mean square error was 5.14 cm and 3.63 cm, and the correlation coefficient was 0.87 and 0.94, respectively. The average deviation between the simulated and measured values of soil salinity in 2013 and 2014 was −0.68 g/kg and −1.86 g/kg, the average absolute deviation was 1.60 g/kg and 1.99 g/kg, the root mean square error was 1.95 g/kg and 2.99 g/kg, and the correlation coefficient was 0.82 and 0.86, respectively, which are all within the acceptable error range. After validation, the model was used to simulate and analyze the desalination process of a cotton field in the study area for 27 different subsurface pipe layout modes. The projection pursuit classification model has been combined with the accelerated genetic algorithm based on real-number coding. The comprehensive benefits of the subsurface pipe layout were evaluated using the construction cost, average desalination rate, and relative yield of cotton as the evaluation indices. The results show that C11 (buried depth 2.1 m, spacing 30 m) is the optimal layout of the subsurface pipe. The results of this study can provide theoretical support and scientific guidance for the popularization and application of subsurface pipe salt discharge technology and drip irrigation under film in the arid inland areas of northwest China.

The increase in sedentary behavior in children and adolescents has become a worldwide public health problem. This study aimed to explore the associations between sedentary time (ST) and sedentary patterns (SP) and the cardiorespiratory fitness (CRF) of Chinese children and adolescents. The CRF of 535 participants was determined using a 20-m shuttle run test. ST and SP were measured with accelerometers. Questionnaires were used to investigate the different types of ST. Multiple linear regression models were used to test the associations between ST and SP and CRF. In this study, only some ST and SP indicators were found to be significantly associated with CRF in girls. With each additional 10 min of screen time or passive traffic time, VO2max decreases by 0.06 mL/kg/min (B = −0.006, 95% CI: −0.010~−0.001) and 0.31 mL/kg/min (B = −0.031, 95% CI: −0.061~−0.002), respectively, with MVPA control. With each additional 10 min of breaks in ST or duration of breaks in ST, VO2max increases by 0.41 mL/kg/min (B = 0.041, 95% CI: 0.007~0.076) and 0.21 mL/kg/min (B = 0.021, 95% CI: 0.007~0.035), respectively, with control total ST. Breaks in ST (B = 0.075, 95% CI: 0.027~0.123) and the duration of breaks in ST (B = 0.021, 95% CI: 0.012~0.146) were positively correlated with CRF when controlling for LPA, but these associations were not significant when controlling for MVPA (B = 0.003, 95% CI: −0.042~0.048; B = 0.001, 95% CI: −0.024~0.025). The total ST of children and adolescents was found to not be correlated with CRF, but when ST was divided into different types, the screen time and passive traffic time of girls were negatively correlated with CRF. More breaks in ST and the duration of breaks in ST were positively associated with higher CRF in girls. MVPA performed during breaks in ST may be the key factor affecting CRF. Schools and public health departments should take all feasible means to actively intervene with CRF in children and adolescents.

This paper is to investigate the existence and uniqueness of solutions for an integral boundary value problem of new fractional differential equations with a sign-changed parameter in Banach spaces. The main used approach is a recent fixed point theorem of increasing Ψ−h,r-concave operators defined on ordered sets. In addition, we can present a monotone iterative scheme to approximate the unique solution. In the end, two simple examples are given to illustrate our main results.

With the increase in depth of coal mining, the hydrogeological complexity largely increases and water inrush accidents happen more frequently. For the safety of coal mining, horizontal directional drilling and grouting techniques have been implemented to detect and plug the fractures and conduits that deliver high-pressure groundwater to coal mine. Taking the grouting engineering performed at Xingdong coal mine at 980 m below sea level as an example, we collected the data of grouting quantity, the loss of drilling fluid, gamma value, water temperature, average water absorption, distance between grouting loss points, water pressure on coal seam floor, and aquifuge thickness at 90 boreholes in the mine to conduct grey relational analysis, first. The analysis showed that the grouting quantity was highly correlated with all other factors. Subsequently, grey system evaluation was used to evaluate the risk of water inrush from the coal seam floor. The results of risk analysis illustrated that three water inrushes from Ordovician limestone occurred in mining face 2127, 2125, and 2222 in the study area were all located in the area with a risk score higher than 65. Through grouting, the identified cracks were effectively blocked and waterproof layers beneath the coal seam floors were constructed to reduce the threat of water inrush. By comparing the risk assessment results with three water inrush cases before grouting operation, we found that water inrush areas were consistent with the area of higher risk.

Component factories are experiencing the problems associated with lean production, especially the accuracy of production time prediction and the unnecessary waste in terms of time and resource utilization. In order to solve these problems, a discrete event simulation- (DES-) based lean planning and optimization method for precast component production is proposed by integrating the complexity assessment (CS), discrete event simulation (DES), and lean management (LM). The method includes three submodels: improved production planning, DES, and lean analysis and optimization. In the submodel of improved production planning, a complexity evaluation index system for precast components is established through investigating five component factories, consulting seven domain experts and analysing relevant literature. In the submodel of DES, the DES technique is adopted to simulate and analyse the production activities of precast components. The submodel of lean analysis and optimization provides multidimensional analysis, comparative analysis, and suggestions. Finally, a detailed production case is selected to simulate and test the proposed method. The important findings are as follows: (1) this method can minimize the difference between the processing time of each workstation to avoid bottleneck stations as much as possible; (2) this method can capture the uncertainty during precast component production, and the most likely production time calculated by the method is 12.05 hours instead of the 11.50 hours originally estimated by the component factory; (3) this method can identify some unnecessary waste in the production process of precast components, including less than 50% utilization of workstations and unnecessary equipment purchases; (4) this method also provides some suggestions regarding production optimization. Due to the particularity of precast component production, it further expands the boundary of lean production methodology from the perspective of the construction industry rather than the manufacturing industry. The proposed method assists component factories in planning and optimizing the precast component production when they make detailed production plans.

This study aimed to explore the impact of environmental factors such as latitude, altitude, family socioeconomic status (SES), and level of urbanization on overweight and obesity (ow/ob) in children and adolescents. The participants comprised 26,120 children and adolescents aged 10–18 from 16 provinces in China. Differences in the prevalence of ow/ob under different environmental conditions were evaluated by the chi-square test. The influence of various environmental factors on ow/ob was obtained by logistic regression analysis. We found that (1) the prevalence of ow/ob fell between from 19.2% to 11.9% at 10 years old and from 13.8% to 6% at 18 years old; (2) latitude, family SES, income, and urbanization level are positively correlated with the prevalence of ow/ob; and (3) altitude has a negative correlation with the prevalence of ow/ob. The prevalence of ow/ob decreased with age in children and adolescents aged 10–18, and the risk of ow/ob showed significant differences in latitude, altitude, family SES level, gross domestic product (GDP), and level of urbanization.

ATP-binding cassette (ABC) transporter proteins are a gene super-family in plants and play vital roles in growth, development, and response to abiotic and biotic stresses. The ABC transporters have been identified in crop plants such as rice and buckwheat, but little is known about them in soybean. Soybean is an important oil crop and is one of the five major crops in the world. In this study, 255 ABC genes that putatively encode ABC transporters were identified from soybean through bioinformatics and then categorized into eight subfamilies, including 7 ABCAs, 52 ABCBs, 48 ABCCs, 5 ABCDs, 1 ABCEs, 10 ABCFs, 111 ABCGs, and 21 ABCIs. Their phylogenetic relationships, gene structure, and gene expression profiles were characterized. Segmental duplication was the main reason for the expansion of the GmABC genes. Ka/Ks analysis suggested that intense purifying selection was accompanied by the evolution of GmABC genes. The genome-wide collinearity of soybean with other species showed that GmABCs were relatively conserved and that collinear ABCs between species may have originated from the same ancestor. Gene expression analysis of GmABCs revealed the distinct expression pattern in different tissues and diverse developmental stages. The candidate genes GmABCB23, GmABCB25, GmABCB48, GmABCB52, GmABCI1, GmABCI5, and GmABCI13 were responsive to Al toxicity. This work on the GmABC gene family provides useful information for future studies on ABC transporters in soybean and potential targets for the cultivation of new germplasm resources of aluminum-tolerant soybean.

MYB transcription factors have been demonstrated to play key regulatory roles in plant growth, development and abiotic stress response. However, knowledge concerning the involvement of rice MYB genes in salinity and drought stress resistance are largely unknown. In the present study, we cloned and characterized the OsMYB6 gene, which was induced by drought and salinity stress. Subcellular localization of OsMYB6-YFP fusion protein in protoplast cells indicated that OsMYB6 was localized in the nucleus. Overexpression of OsMYB6 in rice did not suggest a negative effect on the growth and development of transgenic plants, but OsMYB6-overexpressing plants showed increased tolerance to drought and salt stress compared with wild-type plants, as are evaluated by higher proline content, higher CAT and SOD activities, lower REL and MDA content in transgenic plants under drought and salt stress conditions. In addition, the expression of abiotic stress-responsive genes were significantly higher in OsMYB6 transgenic plants than that in wild-type plants under drought and salt stress conditions. These results indicate that OsMYB6 gene functions as a stress-responsive transcription factor which plays a positive regulatory role in response to drought and salt stress resistance, and may be used as a candidate gene for molecular breeding of salt-tolerant and drought-tolerant crop varieties.

Karst aquifers are prominent sources of water worldwide; they store large amounts of water and are known for their beautiful springs. However, extensive groundwater development and climate variation has resulted in a decline in the flow of most karst springs; some have even dried up. In order to obtain a better understanding of the factors contributing to this development, this study introduced grey system models, which quantified spring flow, taking Jinci Springs (China), which dried up in May 1994, as an example. Based on the characteristics of Jinci Springs, spring flow was divided into two stages: first (1954–1960), when the spring flow was affected only by climate variation; and second (1961–1994), when the flow was impacted by both climate variation and anthropogenic activities. The results showed that Jinci Springs flow had a strong relationship with precipitation occurring one year and three years earlier in the first stage. Subsequently, a grey system GM (1,3) model with one-year and three-year lags was set up for the first stage. By using the GM (1,3) model, we simulated the spring flow in the second stage under effects of climate variation only. By subtracting the observed spring flow from the simulated flow, we obtained the contribution of anthropogenic activities to Jinci Springs’ cessation. The contribution of anthropogenic activities and climate variation to the decline was 1.46 m3/s and 0.62 m3/s, respectively. Finally, each human activity that caused the decline was estimated. The methods devised herein can be used to describe karst hydrological processes that are under the effects of anthropogenic activities and climate variation.