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Abstract The heat shock transcription factor (HSF) family is one of the most widely studied transcription factor families in plants; HSFs can participate in the response to various stressors, such as heat stress, high salt, and drought stress. Based on garlic transcriptome data, we screened and identified 22 garlic HSFs. The HSF proteins of garlic and Arabidopsis can be divided into three (A, B, C) subfamilies. The phylogenetic relationship, chromosome localization, sequence characteristics, conserved motifs, and promoter analysis of the HSF family were analyzed through bioinformatics methods. RT-qPCR analysis showed that the nine selected genes had different degrees of response to heat stress. In addition, we isolated and identified a class B HSF gene, AsHSFB1, from garlic variety ‘Xusuan No.6’. Subsequently, the AsHSFB1 gene was overexpressed in Arabidopsis thaliana. Under heat stress, the germination rate and growth of wild-type plants were better than that of transgenic plants. Moreover, after heat treatment, the contents of peroxidase, catalase, and chlorophyll a and b of transgenic plants were lower, but the contents of malondialdehyde (MDA) and leaf conductivity were higher. Nitroblue tetrazolium (NBT) staining showed that the stained area of transgenic plant leaves was larger than that of the wild type. Further studies showed that AsHSFB1 overexpression inhibited the expression of related reverse resistance genes. These results indicate that AsHSFB1 might play a negative regulatory role in garlic resistance under high stress. Altogether, these findings provide valuable data for revealing the function of HSF genes and lay a foundation for the subsequent selection of heat-resistant garlic varieties.

Abstract Background Lung cancer is one of the major threats to human life worldwide. MiR‐190 has been found to perform essential roles in multiple cancer progression; however, there have been no studies focused on its function and underlying regulatory mechanism in lung cancer. Method The miR‐190 expression was detected by real‐time quantitative polymerase chain reaction (RT‐qPCR). The cell functional experiments, including cell counting kit‐8 (CCK‐8), colony formation and transwell assay were conducted in vitro, as well as animal experiments performed in vivo. The regulation and potential binding sites of CBX4 on miR‐190 were predicted by TCGA data set and JASPAR website and verified by ChIP assay and dual‐luciferase reporter assay. The prospects binding site of miR‐190‐3p on CBX4 3′UTR region was predicted by StarBase and verified by dual‐luciferase reporter assay. Results MiR‐190 was decreased in lung cancer cells. The overexpression of miR‐190 had no effects on cell proliferation, but significantly inhibited cancer metastasis both in vitro and in vivo. Moreover, miR‐190 expression could be transcriptionally inhibited by CBX4, and CBX4 was the direct target of miR‐190‐3p. Conclusion MiR‐190 served as a cancer metastasis inhibitor in lung cancer and formed a regulatory loop with CBX4. These findings provided emerging insights into therapeutic targets and strategies for metastatic lung cancer.

Abstract With global warming, heat stress has become an important factor that seriously affects crop yield and quality. Therefore, understanding plant responses to heat stress is important for agricultural practice, but the molecular mechanism of high-temperature tolerance in garlic remains unclear. In this study, ‘Xusuan No. 6’ was used as the experimental material. After heat stress for 0 (CK), 2 and 24 h, transcriptome sequencing was used to screen metabolic pathways and differentially expressed genes (DEGs) closely related to heat stress and was further verified by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 86,110 unigenes obtained from the raw transcriptome sequencing data were spliced. After 2 h of heat treatment, the expression levels of 8898 genes increased, and 3829 genes were decreased in leaves. After 24 h, the expression levels of 7167 genes were upregulated, and 3176 genes were downregulated. Gene Ontology enrichment analysis showed that DEGs were mainly enriched in seven categories: cellular processes, metabolic processes, binging, catalytic activity, cellular anatomical entity and protein-containing complex response to stimulus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that DEGs are involved in protein processing in the endoplasmic reticulum, plant hormone signal transduction, phenylpropanoid biosynthesis, and photosynthetic antenna proteins. Six genes were selected and further verified by qRT-PCR. In this study, the full-length transcriptome of garlic was constructed, and the regulatory genes related to the heat resistance of garlic were studied. Taken together, these findings can provide a theoretical basis for the cloning of heat resistance genes in garlic and for the analysis of heat resistance mechanisms.

The traditional Chinese medicine (TCM) formulation Shengqiyichang Decoction (SQYCD) has been reported to stimulate host immunity, and it has been administered for the treatment of colorectal cancer (CRC). Here, we applied network and bioinformatics analyses to elucidate the mechanisms by which SQYCD ameliorates CRC and validated its modes of action via in vivo and in vitro experiments. We identified 46 active compounds in SQYCD and selected 237 proteins as potential therapeutic targets in CRC, most notably p38 mitogen-activated protein kinase (p38⍺). Bioinformatics analyses demonstrated differential expression in CRC tissues and prognostic value of the genes encoding TNFα, MAPK14, CASP-3, MAPK1, AKT1, PRKACA, VEGF, IL-6, EGFR and ESR1. We then plotted receiver operating curves (ROC) and time-ROC for the differentially expressed genes (DEGs) ESR1 and AKT1 to predict the progress of CRC. We speculated that the AKT/p38α-MAPK signaling pathway is associated with the clinical prognosis of CRC. In a mouse model, we found that SQYCD inhibits CRC tumor growth by increasing CD4+ and CD8+ T cell abundance and decreasing the ratio of T-regulatory cells (Tregs) in the tumor microenvironment. In cultured mouse CRC cells, SQYCD selectively upregulated levels of the CRC-associated protein lymphocyte antigen 6 family member G6D, while the AKT activator SC-79 reversed this effect. The discoveries made herein suggest that SQYCD exerts a therapeutic effect in CRC by inhibiting Treg recruitment via inhibition of the AKT/p38α/LY6G6D signaling axis.

IntroductionThe serine/threonine kinase 17B (STK17B) is involved in setting the threshold for T cell activation and its absence sensitizes T cells to suboptimal stimuli. Consequently, STK17B represents an attractive potential target for cancer immunotherapy.MethodsTo assess the potential of STK17B as an immuno-oncology target, we developed potent and selective tool compounds from starting points in Blueprint Medicines Corporation's proprietary kinase inhibitor library. To characterize these molecules, enzyme and cellular assays for STK17A and STK17B were established to drive chemistry optimization. Mass spectrometry-based phosphoproteomics profiling with tool inhibitors led to the identification of Ser19 on myosin light chain 2 as STK17B substrate, which is then developed into a flow cytometry-based pharmacodynamic readout of STK17B inhibition both in vitro and in vivo.ResultsIn a mouse T cell activation assay, STK17B inhibitors demonstrated the ability to enhance interleukin-2 (IL-2) production. Similarly, treatment with STK17B inhibitors resulted in stronger cytokine secretion in human T cells activated using a T cell bispecific antibody. Subsequent chemistry optimization led to the identification of a highly selective and orally bioavailable tool compound, BLU7482. In vivo, STK17B inhibition led to dose-dependent modulation of myosin light chain 2 phosphorylation and enhanced priming of naïve T cells, as determined by upregulation of CD69, IL-2 and interferon-γ secretion. In line with increased T cell activation, treatment with STK17B inhibitor enhanced antitumor activity of anti–PD-L1 antibody in the MCA205 model.ConclusionsIn summary, we successfully identified and optimized STK17B kinase inhibitors which led to increased T cell responses in vitro and in vivo. This allowed us to evaluate the potential of STK17B inhibition as an approach for cancer immunotherapy.

BackgroundThe World Health Organization declared mpox an international public health emergency. Since January 1, 2022, China has been ranked among the top 10 countries most affected by the mpox outbreak globally. However, there is a lack of spatial epidemiological studies on mpox, which are crucial for accurately mapping the spatial distribution and clustering of the disease. ObjectiveThis study aims to provide geographically accurate visual evidence to determine priority areas for mpox prevention and control. MethodsLocally confirmed mpox cases were collected between June and November 2023 from 31 provinces of mainland China excluding Taiwan, Macao, and Hong Kong. Spatiotemporal epidemiological analyses, including spatial autocorrelation and regression analyses, were conducted to identify the spatiotemporal characteristics and clustering patterns of mpox attack rate and its spatial relationship with sociodemographic and socioeconomic factors. ResultsFrom June to November 2023, a total of 1610 locally confirmed mpox cases were reported in 30 provinces in mainland China, resulting in an attack rate of 11.40 per 10 million people. Global spatial autocorrelation analysis showed that in July (Moran I=0.0938; P=.08), August (Moran I=0.1276; P=.08), and September (Moran I=0.0934; P=.07), the attack rates of mpox exhibited a clustered pattern and positive spatial autocorrelation. The Getis-Ord Gi* statistics identified hot spots of mpox attack rates in Beijing, Tianjin, Shanghai, Jiangsu, and Hainan. Beijing and Tianjin were consistent hot spots from June to October. No cold spots with low mpox attack rates were detected by the Getis-Ord Gi* statistics. Local Moran I statistics identified a high-high (HH) clustering of mpox attack rates in Guangdong, Beijing, and Tianjin. Guangdong province consistently exhibited HH clustering from June to November, while Beijing and Tianjin were identified as HH clusters from July to September. Low-low clusters were mainly located in Inner Mongolia, Xinjiang, Xizang, Qinghai, and Gansu. Ordinary least squares regression models showed that the cumulative mpox attack rates were significantly and positively associated with the proportion of the urban population (t0.05/2,1=2.4041 P=.02), per capita gross domestic product (t0.05/2,1=2.6955; P=.01), per capita disposable income (t0.05/2,1=2.8303; P=.008), per capita consumption expenditure (PCCE; t0.05/2,1=2.7452; P=.01), and PCCE for health care (t0.05/2,1=2.5924; P=.01). The geographically weighted regression models indicated a positive association and spatial heterogeneity between cumulative mpox attack rates and the proportion of the urban population, per capita gross domestic product, per capita disposable income, and PCCE, with high R2 values in north and northeast China. ConclusionsHot spots and HH clustering of mpox attack rates identified by local spatial autocorrelation analysis should be considered key areas for precision prevention and control of mpox. Specifically, Guangdong, Beijing, and Tianjin provinces should be prioritized for mpox prevention and control. These findings provide geographically precise and visualized evidence to assist in identifying key areas for targeted prevention and control.

The jet pump is one of the most popular types of fluid machinery in agriculture, industry and environmental engineering and many other fields. However, its internal flow structure is complex, showing obvious unsteady characteristics. The effect of throat diameter size on jet pump performance and energy property was investigated in this study based on numerical calculation and test verification, in order to improve the performance and internal flow field stability of jet pump. Five models with different throat diameters were obtained by adjusting the assembly structure and simulated by the computational fluid dynamics software to solve the Navier–Stokes equations for three-dimensional steady flow. The accuracy of numerical methods was verified by comparison with the experimental results. The compact jet pump performance under different throat diameters was then compared and analysed. The backflow at effuser outlet of different throat diameters causes the changes of vortex structure inside the injector rear chamber. The vortex diffuses downstream to the impeller inlet, making the flow structure of the impeller inlet show obvious circumferential inhomogeneity. This forms different vortex structures at different impeller flow channels, changing the distribution of entropy production within the impeller, ultimately leading to a decrease of pump efficiency. Therefore, this study found that selecting a reasonable throat diameter of the injector can improve the performance of the jet pump impeller, and thus improve the overall efficiency of the system. For the research object in this paper, the recommended range of throat diameter of injector is 16 mm–17 mm. This finding could provide useful insights for the improvement of the hydraulic performance and operational stability of compact jet pumps.

Timely and accurate mapping of rice distribution is crucial to estimate yield, optimize agriculture spatial patterns, and ensure global food security. Feature selection (FS) methods have significantly improved computational efficiency by reducing redundancy in spectral and temporal feature sets, playing a vital role in identifying and mapping paddy rice. However, the optimal feature sets selected by existing methods suffer from issues such as information redundancy or local optimality, limiting their accuracy in rice identification. Moreover, the effects of these FS methods on rice recognition in various machine learning classifiers and regions with different climatic conditions and planting structures is still unclear. To overcome these limitations, we conducted a comprehensive evaluation of the potential applications of major FS methods, including the wrapper method, embedded method, and filter method for rice mapping. A novel hierarchical lustering sequential forward selection (HCSFS) method for precisely extracting the optimal feature set for rice identification is proposed. The accuracy of the HCSFS and other FS methods for rice identification was tested with nine common machine learning classifiers. The results indicated that, among the three FS methods, the wrapper method achieved the best rice mapping performance, followed by the embedded method, and lastly, the filter method. The new HCSFS significantly reduced redundant features compared with eleven typical FS methods, demonstrating higher precision and stability, with user accuracy and producer accuracy exceeding 0.9548 and 0.9487, respectively. Additionally, the spatial distribution of rice maps generated using the optimal feature set selected by HCSFS closely aligned with actual planting patterns, markedly outperforming existing rice products. This research confirms the effectiveness and transferability of the HCSFS method for rice mapping across different climates and cultivation structures, suggesting its enormous potential for classifying other crops using time-series remote sensing images.

The molecular landscape and the intratumor heterogeneity (ITH) architecture of gastric linitis plastica (LP) are poorly understood. We performed whole‐exome sequencing (WES) and T‐cell receptor (TCR) sequencing on 40 tumor regions from four LP patients. The landscape and ITH at the genomic and immunological levels in LP tumors were compared with multiple cancers that have previously been reported. The lymphocyte infiltration was further assessed by immunohistochemistry (IHC) in LP tumors. In total, we identified 6339 non‐silent mutations from multi‐samples, with a median tumor mutation burden (TMB) of 3.30 mutations per Mb, comparable to gastric adenocarcinoma from the Cancer Genome Atlas (TCGA) cohort (P = 0.53). An extremely high level of genomic ITH was observed, with only 12.42%, 5.37%, 5.35%, and 30.67% of mutations detectable across 10 regions within the same tumors of each patient, respectively. TCR sequencing revealed that TCR clonality was substantially lower in LP than in multi‐cancers. IHC using antibodies against CD4, CD8, and PD‐L1 demonstrated scant T‐cell infiltration in the four LP tumors. Furthermore, profound TCR ITH was observed in all LP tumors, with no T‐cell clones shared across tumor regions in any of the patients, while over 94% of T‐cell clones were restricted to individual tumor regions. The Morisita overlap index (MOI) ranged from 0.21 to 0.66 among multi‐regions within the same tumors, significantly lower than that of lung cancer (P = 0.002). Our results show that LP harbored extremely high genomic and TCR ITH and suppressed T‐cell infiltration, suggesting a potential contribution to the frequent recurrence and poor therapeutic response of this adenocarcinoma.

Introduction: Maintenance hemodialysis is an effective treatment for end-stage renal disease patients. A critical factor contributing to the deterioration and death of maintenance hemodialysis patients is inflammation. Therefore, we focused on two inflammatory markers, serum ferritin and neutrophil-to-lymphocyte ratio, to speculate whether they could predict the prognosis of maintenance hemodialysis patients.Patients and methods: We followed 168 patients with maintenance hemodialysis from July 2019 to July 2022 with the endpoint of all-cause death or follow-up completion. Receiver operating characteristic curves were plotted to assess the values of serum ferritin, neutrophil-to-lymphocyte ratio and serum ferritin combined with neutrophil-to-lymphocyte ratio to predict the outcomes of maintenance hemodialysis patients. Kaplan-Meier survival curves were constructed to compare survival rates over time.Results: Receiver operating characteristic curves demonstrated that the best cut-off value of serum ferritin for predicting the prognosis of maintenance hemodialysis patients was 346.05 μg/L, and that of neutrophil-to-lymphocyte ratio was 3.225. Furthermore, a combination of both had a more excellent predicting value than either index (p < 0.05). Kaplan-Meier survival curve analyses revealed that low serum ferritin levels and low neutrophil-to-lymphocyte ratio had a higher probability of survival than high ferritin levels and high neutrophil-to-lymphocyte ratio, separately.Conclusion: Elevated serum ferritin and neutrophil-to-lymphocyte ratio are closely related to all-cause mortality among maintenance hemodialysis patients, for which they may be predictors of all-cause mortality. Additionally, the combination of the two has a much higher predictor value for the prognosis of maintenance hemodialysis patients.

BackgroundThe prevalence of Tobacco Use Disorder (TUD) represents a significant and pressing global public health concern, with far-reaching and deleterious consequences for individuals, communities, and healthcare systems. The craving caused by smoking cue is an important trigger for relapse, fundamentally hindering the cessation of cigarette smoking. Mindfulness interventions focusing on cue-reactivity was effective for the treatment of related dependence. Brief mindfulness training (BMT) meets the short-term needs for intervention but the effects still need to be examined. The objective of the present study is to investigate the impact of BMT intervention on smoking cue-reactivity among Chinese college students with TUD, to uncover the dynamic models of brain function involved in this process.MethodA randomized control trial (RCT) based on electroencephalography (EEG) was designed. We aim to recruit 90 participants and randomly assign to the BMT and control group (CON) with 1:1 ratio. A brief mindfulness training will be administered to experimental group. After the intervention, data collection will be conducted in the follow-up stage with 5 timepoints of assessments. EEG data will be recorded during the smoking cue-reactivity task and 'STOP' brief mindfulness task. The primary outcomes include subjective reports of smoking craving, changes in EEG indicators, and mindfulness measures. The secondary outcomes will be daily smoking behaviours, affect and impulsivity, as well as indicators reflecting correlation between mindfulness and smoking cue-reactivity. To evaluate the impact of mindfulness training, a series of linear mixed-effects models will be employed. Specifically, within-group effects will be examined by analysing the longitudinal data. Additionally, the effect size for all statistical measurements will be reported, offering a comprehensive view of the observed effects.DiscussionThe current study aims to assess the impact of brief mindfulness-based intervention on smoking cue-reactivity in TUD. It also expected to enhance our understanding of the underlying processes involved in brain function and explore potential EEG biomarkers at multiple time points.Trial registrationTrial registration number: ChiCTR2300069363, registered on 14 March 2023. Protocol Version 1.0., 10 April 2023.

Centrifugal pumps are widely used in various fields and have enormous energy-saving potential. In order to predict efficiency quickly and accurately, firstly, by establishing a hydraulic loss model for centrifugal pump impellers, the functional relationship between impeller hydraulic loss and hydraulic efficiency is constructed to establish the objective function. Secondly, calculate the main dimensions of the impeller using the velocity coefficient method and establish the objective function variables of the number of blades Z and outlet placement angle β2. And the velocity coefficient k0. Then, the method of mathematical statistics, namely response surface analysis, is used to solve the relationship between hydraulic efficiency and dependent variables within the range of variables, which plays the role of predicting hydraulic efficiency. Finally, the accuracy of the predictions is verified by numerical simulation. The results show that the hydraulic efficiency of a high specific speed centrifugal pump reaches its maximum at 1000m3/h operating conditions with a blade number of 3, a speed coefficient of 3.9 and an outlet angle of 30°. The study provides a new direction for the hydraulic design of high specific speed centrifugal pumps to achieve more accurate predictions of high specific speed centrifugal pump efficiency.

Abstract Background A high prevalence of nasopharyngeal carcinoma (NPC) has been found in China, but it rarely occurs with syncope. Studies have demonstrated that syncope due to NPC may be related to carotid sinus syndrome, glossopharyngeal irritation, and parapharyngeal and retropharyngeal space lesions. Such patients require evaluation by nasopharyngoscopy and head magnetic resonance imaging/computed tomography. There is no known single effective treatment for these patients. Various interventions may be considered in an effort to relieve syncope, including vasoconstrictive drugs, cardiac pacemaker implantation, radiotherapy and chemotherapy, and surgical resection. Case presentation This case report describes a 56-year-old man who developed recurrent syncope with atrial fibrillation, a long RR interval, and hypotension. A single chamber pacemaker was fitted, but it failed to relieve the symptom. Cranial magnetic resonance imaging and pathological tests led to a final diagnosis of NPC. After six courses of chemotherapy and 35 sessions of radiotherapy, the patient became asymptomatic. However, he died from a massive uncontrolled hemorrhage in the nasopharynx two years later. Conclusions This case brings attention to the fact that syncope can be a symptom of NPC. Due to the insidiously malignant nature of this cancer, when a patient presents with syncope, clinicians should bear in mind this connection, albeit a rare one. There are at least two ways of treating NPC-associated syncope, but there is disagreement about which is the most effective.

Abstract Background Breast cancer is the major cause of death in females globally. Chemokine-like factor like MARVEL transmembrane domain containing 7 (CMTM7) is reported as a tumor suppressor and is involved in epidermal growth factor receptor degradation and PI3K/AKT signaling in previous studies. However, other molecular mechanisms of CMTM7 remain unclear. Methods The expression level of CMTM7 in breast cancer cells and tissues was detected by qRT-PCR and western blot, and the methylation of CMTM7 promoter was detected by BSP sequencing. The effect of CMTM7 was verified both in vitro and in vivo, including MTT, colony formation, EdU assay, transwell assay and wound healing assay. The interaction between CMTM7 and CTNNA1 was investigated by co-IP assay. The regulation of miR-182-5p on CMTM7 and TCF3 on miR-182-5p was detected by luciferase reporter assay and ChIP analysis. Results This study detected the hypermethylation levels of the CMTM7 promoter region in breast cancer tissues and cell lines. CMTM7 was performed as a tumor suppressor both in vitro and in vivo. Furthermore, CMTM7 was a direct miR-182-5p target. Besides, we found that CMTM7 could interact with Catenin Alpha 1 (CTNNA1) and regulate Wnt/β-catenin signaling. Finally, transcription factor 3 (TCF3) can regulate miR-182-5p. We identified a feedback loop with the composition of miR-182-5p, CMTM7, CTNNA1, CTNNB1 (β-catenin), and TCF3, which play essential roles in breast cancer progression. Conclusion These findings reveal the emerging character of CMTM7 in Wnt/β-catenin signaling and bring new sights of gene interaction. CMTM7 and other elements in the feedback loop may serve as emerging targets for breast cancer therapy.

Abstract A variety of different synthesis methods for the fabrication of solar cell absorbers based on the lead halide perovskite methylammonium lead iodide (MAPbI3, MAPI) have been successfully developed in the past. In this work, we elaborate upon vacuum-based dual source co-evaporation as an industrially attractive processing technology. We present non-stationary processing schemes and concentrate on details of co-evaporation schemes where we intentionally delay the start/end points of one of the two evaporated components (MAI and PbI2). Previously, it was found for solar cells based on a regular n-i-p structure, that the pre-evaporation of PbI $$_2$$ 2 is highly beneficial for absorber growth and solar cell performance. Here, we apply similar non-stationary processing schemes with pre/post-deposition sequences for the growth of MAPI absorbers in an inverted p-i-n solar cell architecture. Solar cell parameters as well as details of the absorber growth are compared for a set of different evaporation schemes. Contrary to our preliminary assumptions, we find the pre-evaporation of PbI2 to be detrimental in the inverted configuration, indicating that the beneficial effect of the seed layers originates from interface properties related to improved charge carrier transport and extraction across this interface rather than being related to an improved absorber growth. This is further evidenced by a performance improvement of inverted solar cell devices with pre-evaporated MAI and post-deposited PbI2 layers. Finally, we provide two hypothetical electronic models that might cause the observed effects.

Purpose: Xiang-Sha-Liu-Jun-Zi-Tang(XSLJZT) is a common formula for the treatment of Gastric Cancer(GC) and is widely used in clinical practice, however, there is a lack of investigation into its mechanism. Methods: We collected and organized drug and disease targets, constructed the “XSLJZT-Active Ingredient-Target” visualization network, and performed GO and KEGG functional enrichment analysis of crossover genes, followed by molecular docking of active ingredients and core targets. The best docked monomers were combined with weighted gene co-expression network analysis(WGCNA) and macroscopically analyzed by GO and KEGG enrichment techniques. The results of cluster gene difference analysis, ROC evaluation, and CIBERSORT immune infiltration analysis were evaluated and finally supported by cellular experiments. Results: The main components of XSLJZT are quercetin, stigmasterol, and naringenin, effectively treat GC by targeting STAT3, TP53 and MAPK3, which are involved in IL-17, TNF and HIF-1 signaling pathways. The results of molecular docking showed that quercetin bound better to the core targets. We performed an in-depth analysis of this monomer and found that quercetin acts on the core targets of TP53, MMP9, TIMP1 and MYC, and is involved in two key signaling pathways, TNF and IL-17, thus effectively treating GC. The experimental results are consistent with our analysis that quercetin inhibits the proliferation of GC cells and promotes apoptosis, and TP53, MYC and TIMP1 are the quercetin targets for the treatment of GC. Conclusion: The present study tentatively suggests that quercetin, the main active ingredient in XSLJZT, can exert a therapeutic effect on GC by targeting TIMP1.

This study models a container routing problem using multimodal transportation to improve its economy, timeliness, and reliability. Pickup and delivery time windows are simultaneously formulated in optimization to provide the shipper and the receiver with time-efficient services, in which early pickup and delayed delivery can be avoided, and nonlinear storage periods at the origin and the destination can be minimized. Furthermore, the capacity uncertainty of the multimodal network is incorporated into the advanced routing to enhance its reliability in practical transportation. The LR triangular fuzzy number is adopted to model the capacity uncertainty, in which its spread ratio is defined to measure the uncertainty level of the fuzzy capacity. Due to the nonlinearity introduced by the time windows and the fuzziness from the network capacity, this study establishes a fuzzy nonlinear optimization model for optimization problem. A chance-constrained linear reformulation equivalent to the proposed model is then generated based on the credibility measure, which makes the global optimum solution attainable by using Lingo software. A numerical case verification demonstrates that the proposed model can effectively solve the problem. The case analysis points out that the formulation of pickup and delivery time windows can improve the timeliness of the entire transportation process and help to achieve on-time transportation. Furthermore, improving the confidence level and the uncertainty level increases the total costs of the optimal route. Therefore, the shipper and the receiver must prepare more transportation budget to improve reliability and address the increasing uncertainty level. Further analysis draws some insights to help the shipper, receiver, and multimodal transport operator to organize a reliable and cost-efficient multimodal transportation under capacity uncertainty through confidence level balance and transportation service and transfer service selection.

Objective: The present study aimed to explore the relationship between insecure attachment (attachment anxiety and avoidance) and depressive symptoms in Chinese young adults as well as the mediating roles of positive and negative self-compassion. Methods: An online survey was administered among college students in mainland China. This involved their completion of questionnaires encompassing socio-demographic details, attachment anxiety, attachment avoidance, self-compassion, and depressive symptoms. Results: Attachment anxiety and avoidance exhibited connections with depressive symptoms through increased negative self-compassion and decreased positive self-compassion. Attachment anxiety was associated with depressive symptoms primarily through the mediating effect of negative self-compassion. Conversely, attachment avoidance was related to depressive symptoms mainly through the mediating role of positive self-compassion. Conclusions: Attachment anxiety exerted a slightly stronger influence on negative self-compassion, whereas attachment avoidance exhibited a more prominent impact on positive self-compassion. Despite these differences, both attachment styles were comparable in their overall influence on depressive symptoms. This revelation provides fresh insights into the relationship between insecure attachment and depressive symptoms among young adults, underscoring the importance for intervention program development.

PurposeProsocial behavior (PSB) plays a critical role in everyday society, especially during the pandemic of COVID-19. Understanding the underlying mechanism will provide insight and advance its implementation. According to the theory of PSB, social interaction, family and individual characters all contribute to its development. The current study aimed to investigate the influencing factor of PSB among Chinese college students during COVID-19 outbreak. This is an attempt to understand the mechanism of PSB and to provide a reference for the formulation of policies aimed at promoting healthy collaborative relationships for college students.MethodThe online questionnaire was administered to 664 college students from 29 provinces of China via Credamo platform. There were 332 medical students and 332 non-medical students aged between 18 and 25 included for final study. The mediating role of positive emotion/affect (PA) and the moderating role of parental care in the association between social support and PSB during the pandemic of COVID-19 was explored by using Social Support Rate Scale (SSRS), Prosocial Tendencies Measurement Scale (PTM), The Positive and Negative Affect (PANAS), as well as Parental Bonding Instrument (PBI). The process macro model of SPSS was adopted for mediating and moderating analysis.ResultsThe results showed that social support positively predicted PSB among Chinese college students, even after adding PA as a mediation variable. PA during COVID-19 mediated the association between social support and PSB. PSB also revealed as a predictor of PA by regression analysis. Moreover, the moderating effect of parental care in the relationship between PA and PSB was detected.ConclusionPA under stress acts as a mediator between social support and PSB. This mediating effect was moderated by PC in childhood. In addition, PSB was observed to predict PA reversely. The promoting factors and path between the variables of PSB are complex and need to be explored extensively. The underlying factors and process should be further investigated for the development of intervention plans.

Abstract Background The efficacy of liraglutide to treat type 2 diabetic nephropathy (T2DN) remains controversial. Thus, we conducted this meta-analysis to systematically evaluate the clinical effect of liraglutide on T2DN patients. Methods Eight databases (PubMed, Web of Science, the Cochrane Library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Wanfang database, China Science and Technology Journal Database, and China Biology Medicine Database (CBM)) were searched for published articles to evaluate the clinical efficacy of liraglutide in subjects with T2DN. The Revman 5.3 and Stata 13 software were used for analyses and plotting. Results A total of 18 randomized controlled trials (RCTs) with 1580 diabetic nephropathy patients were screened. We found that the levels of UACR, Scr, Cysc were lower in the experimental group of T2DN patients treated with liraglutide than in the control group intervened without liraglutide. Liraglutide also reduced the levels of blood glucose (including FBG, PBG, and HbA1c), body mass index (BMI), and anti-inflammatory indicators (TNF–α, IL-6). However, there was no significant difference in BUN and eGFR between the experimental group and the control group. Conclusions Liraglutide reduced the levels of Blood Glucose, BMI, renal outcome indicators, and serum inflammatory factors of patients with T2DN, suggesting the beneficial effects of liraglutide on renal function.

Abstract Background Krüppel‐like factors (KLFs) are zinc finger proteins which participate in transcriptional gene regulation. Although increasing evidence indicate that KLFs are involved in carcinogenesis and progression, its clinical significance and biological function in breast cancer are still limited. Methods We investigated all the expression of KLFs (KLF1-18) at transcriptional levels by using Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). The mRNA and protein expression levels of KLFs were also determined by using RT-qPCR and immunohistochemistry, respectively. CBioPortal, GeneMANIA and STRING were used to comprehensive analysis of the molecular characteristics of KLFs. The clinical value of prognostic prediction based on the expression of KLFs was determined by using the KM plotter. The relevant molecular pathways of KLFs were further analyzed by using Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Finally, we investigated the effect of KLF2 and KLF15 on biological behavior of breast cancer cells in vitro. Results The expression of KLF2/4/6/8/9/11/15 was significantly down-regulated in breast cancer. The patients with high KLF2, KLF4 or KLF15 expression had a better outcome, while patients with high KLF8 or KLF11 had a poor prognosis. Furthermore, our results showed that KLF2 or KLF15 can be used as a prognostic factor independent on the other KLFs in patients with breast cancer. Overexpression of KLF2 or KLF15 inhibited cell proliferation and migration, and blocked cell cycle at G0/G1 phase, resulting in cell apoptosis. Conclusions KLF2 and KLF15 function as tumor suppressors in breast cancer and are potential biomarkers for prognostic prediction in patients with breast cancer.

BackgroundEarly identification of response to neoadjuvant chemotherapy (NAC) is instrumental in predicting patients prognosis. However, since a fixed criterion with high accuracy cannot be generalized to molecular subtypes, our study first aimed to redefine grades of clinical response to NAC in invasive breast cancer patients (IBC). And then developed a prognostic model based on clinical features and ultrasound semantics.MethodsA total of 480 IBC patients were enrolled who underwent anthracycline and taxane-based NAC between 2018 and 2020. The decrease rate of the largest diameter was calculated by ultrasound after NAC and their cut-off points were determined among subtypes. Thereafter, a nomogram was constructed based on clinicopathological and ultrasound-related data, and validated using the calibration curve, receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and clinical impact curve (CIC).ResultsThe optimal cut-off points for predicting pCR were 53.23%, 51.56%, 41.89%, and 53.52% in luminal B-like (HER2 negative), luminal B-like (HER2 positive), HER2 positive, and triple-negative, respectively. In addition, time interval, tumor size, molecular subtypes, largest diameter decrease rate, and change of blood perfusion were significantly associated with pCR (all p < 0.05). The prediction model based on the above variables has great predictive power and clinical value.ConclusionTaken together, our data demonstrated that calculated cut-off points of tumor reduction rates could be reliable in predicting pathological response to NAC and developed nomogram predicting prognosis would help tailor systematic regimens with high precision.

Abstract Background Lemierre syndrome (LS) is characterized by multisystemic infection beginning in the oropharynx, local thrombophlebitis (typically, of the internal jugular vein) and peripheral embolism. No evidence-based guidelines exist for the management of this disease, and the use of anticoagulation therapy remains particularly controversial. Case presentation A 61-year-old man presenting with left neck swelling, odynophagia, and dyspnea underwent emergency surgery and received intravenous antibiotics. The primary infection was controlled on hospital day 5, but on day 6 sudden leukocytosis and hypoxemia were observed. CT angiography revealed an intraluminal filling defect in the pulmonary artery on day 8. LS was diagnosed and anticoagulation therapy was initiated. The WBC count, which had maintained its peak values in the previous 2 days, decreased instantly after initiation, and follow-up controls showed thrombus resolution. Conclusions Our case supports the notion that anticoagulation therapy may be a valid supplement to antimicrobial therapy in LS, especially in the presence of a possibly young thrombus as suggested by clinical worsening.

Lamotrigine is an antiepileptic drug that can be used to control many types of seizures as a single-agent or an add-on therapy in patients over 2 years of age. In addition to common adverse reactions, this current case report describes a paediatric male patient with a rare side-effect of persistent penile erectile due to lamotrigine. Previous studies have shown that it can improve sexual function in adult male patients. This patient suffered from refractory epilepsy and pneumonia. He had taken a variety of antiepileptic drugs for a long time and developed priapism after the dosage of lamotrigine had been increased. The priapism improved after drug withdrawal and sedation. Further research is needed to elucidate the mechanism of this rare side-effect.

Vancomycin-associated acute kidney injury (AKI) continues to pose a major challenge to both patients and healthcare providers. The purpose of this study is to construct a machine learning framework for stratified predicting and interpreting vancomycin-associated AKI. Our study is a retrospective analysis of medical records of 724 patients who have received vancomycin therapy from 1 January 2015 through 30 September 2020. The basic clinical information, vancomycin dosage and days, comorbidities and medication, laboratory indicators of the patients were recorded. Machine learning algorithm of XGBoost was used to construct a series risk prediction model for vancomycin-associated AKI in different underlying diseases. The vast majority of sub-model performed best on the corresponding sub-dataset. Additionally, the aim of this study was to explain each model and to explore the influence of clinical variables on prediction. As the results of the analysis showed that in addition to the common indicators (serum creatinine and creatinine clearance rate), some other underappreciated indicators such as serum cystatin and cumulative days of vancomycin administration, weight and age, neutrophils and hemoglobin were the risk factors for cancer, diabetes mellitus, heptic insufficiency respectively. Stratified analysis of the comorbidities in patients with vancomycin-associated AKI further confirmed the necessity for different patient populations to be studied.

BackgroundThe predictive role of sarcopenia in cancer prognosis is an area of increasing concern. However, the influence of sex difference on the predictive role of sarcopenia in cancer prognosis has not been clearly defined. This retrospective cohort study investigated the effect of preoperative sarcopenia on the long-term outcomes of patients with gastric cancer (GC) based on sexual dimorphism.MethodsPreoperative abdominal computed tomography (CT) scans from 379 GC patients who underwent radical gastrectomy were carefully analyzed. The patients were categorized into sarcopenia and non-sarcopenia groups according to the L3 skeletal muscle index (L3 SMI) measured on CT scans. Moreover, other indexes which can be used to evaluate the muscle area or the muscle quality, including skeletal muscle area (SMA), visceral fat area (VFA), subcutaneous fat area (SFA), skeletal muscle radiation attenuation (SM-RA), visceral fat index (VFI), subcutaneous fat index (SFI), and subcutaneous and visceral ratio (SV), were obtained from CT scans.ResultsThere were 254 men and 125 women included in our study. After calculation, we defined sex-specific SMI-related mortality cutoff as 39.73 and 32.97 cm2/m2 for men and women. Univariable analysis showed that pathological tumor-node-metastasis (pTNM), depth of invasion, lymph node metastasis, differentiation degree, preoperative sarcopenia (for men), SMA (for men), L3 SMI, SFA (for women), SFI (for women), SV (for women), and SM-RA (especially for men) were significant independent predictors of overall survival (OS). Multivariable analysis showed that pTNM, depth of invasion, poor differentiation, and SM-RA were significantly associated with 5-year OS in GC patients. However, CT-determined sarcopenia was associated with significantly worse OS only in men, and SFA was significantly associated with 5-year OS only in women.ConclusionSM-RA is a reliable prognostic factor in patients with GC after radical gastrectomy. The impact of indexes mentioned above on survival outcomes is dependent on sex. CT-determined preoperative sarcopenia, a muscle-related indicator, was associated with outcomes in men. Adipose-related indicator (SFA), instead, was associated with outcomes in women.

This study explores a road–rail intermodal routing problem. To improve the carbon efficiency of transportation, reducing CO2 emissions is considered by the routing. Soft time windows are incorporated into the routing to optimize the timeliness of the first-mile pickup and last-mile delivery services in intermodal transportation. The routing is further modeled in a time-dependent and fuzzy environment where the average truck speeds of the road depend on the truck departure times and are simultaneously considered fuzzy along with rail capacities. The fuzzy truck speed leads to the fuzziness of three aspects, including speed-dependent CO2 emissions of the road, a timetable-constrained transfer process from road to rail, and delivery time window violation. This study formulates the routing problem under the above considerations and carbon tax regulation as a combination of transportation path planning problem and truck departure time and speed matching problem. A fuzzy nonlinear optimization model is then established for the proposed routing problem. Furthermore, chance-constrained programming with general fuzzy measure is used to conduct the defuzzification of the model to make the problem solvable, and linearization techniques are adopted to linearize the model to enhance the efficiency of problem-solving. Finally, this study presents an empirical case to demonstrate the effectiveness of the designed approach. This case study evaluates the performance of carbon tax regulation by comparing it with multi-objective optimization. It also focuses on sensitivity analysis to discuss the influence of the optimistic–pessimistic parameter and confidence level on the optimization results. Several managerial insights are revealed based on the case study.

Long non-coding RNAs (lncRNAs) can influence the proliferation, autophagy, and apoptosis of non-small cell lung cancer (NSCLC). LncRNAs also emerge as valuable prognostic factors for NSCLC patients. Consequently, we set out to discover more autophagy-associated lncRNAs. We acquired autophagy-associated genes and information on lncRNAs from The Cancer Genome Atlas database (TCGA), and the Human Autophagy Database (HADb). Then, the prognostic prediction signature was constructed through using co-expression and Cox regression analysis. The signature was constructed including 7 autophagy-associated lncRNAs (ABALON, NKILA, LINC00941, AL161431.1, AL691432.2, AC020765.2, MMP2-AS1). After that, we used univariate and multivariate Cox regression analysis to calculate the risk score. The survival analysis and ROC curve analysis confirmed good performances of the signature. GSEA indicated that the high-risk group was principally enriched in the adherens junction pathway. In addition, biological experiments showed that ABALON promoted the proliferation, metastasis and autophagy levels of NSCLC cells. These findings demonstrate that the risk signature consisting of 7 autophagy-associated lncRNAs accurately predicts the prognosis of NSCLC patients and should be investigated for potential therapeutic targets in clinic.

WRKY transcription factors (TFs) are primarily involved in regulating the response of plants to different types of abiotic stress and related physiological processes. WRKY genes have yet to be characterized in garlic (Allium sativum L.), which is in the family Alliaceae. Here, 78 WRKY TFs were identified based on the garlic transcriptome and genome. They were divided into seven subfamilies based on Arabidopsis thaliana WRKY domains. Cis-element analysis revealed that the WRKY family members have ABRE and MBS cis-response elements that respond to salt stress, gibberellins, and drought stress. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis revealed that the expression of nine WRKY genes was induced under heat and salt stress.

Summary: The Wiskott-Aldrich syndrome protein and SCAR homolog (WASH), an actin nucleation-promoting factor, is present in the nucleus where it regulates gene transcription and maintains nuclear organization. Here, we show that WASH interacts with core non-homologous end-joining (NHEJ) factors including Ku70/Ku80 and DNA-PKcs, and Ku70/Ku80 is involved in the recruitment of WASH to the sites of DNA double-stranded break (DSB). WASH depletion leads to increased cell sensitivity and impaired DNA repair capacity in response to etoposide-induced DSBs and reduces NHEJ efficiency. Mechanistically, we show that loss of WASH inhibits the phosphorylation of DNA-PKcs, H2AX, and KAP1 after DSB induction and reduces chromatin relaxation and the recruitment of several downstream NHEJ factors to DSBs. Moreover, WASH role in DSB repair depends on its conserved C-terminal VCA domain and Arp2/3 activation. Our findings reveal a function and mechanistic insight for WASH in DNA DSB repair by the NHEJ pathway.

As compared with a conventional centrifugal pump, a high-specific-speed centrifugal pump mostly operates under large flow conditions. In this paper, a typical high-specific-speed centrifugal pump is examined, and the effect of the blade number on the internal flow condition is investigated numerically. The numerical predictions have been verified through measurement. It was found that the predictions and the measurements are in good agreement of discrepancy. Serious cavitation could be observed within the pump when the flow rate reached 1300 m3/h. Meanwhile, the effect of the blade number on the cavitation intensity was extremely obvious. The cavitation area at the inlet edge of the blades significantly reduced when the blade number increased from three to six. In addition, the turbulent kinetic energy within the pump was more uniformly distributed. This demonstrates that the blade number can be reasonably chosen to improve the internal flow pattern within the pump, which could provide a theoretical basis for the practical application of high-specific-speed centrifugal pumps

Breast cancer is the most common malignant tumor and the main cause of cancer-associated mortality in females worldwide. Long non-coding RNAs (lncRNAs) have been reported to play vital roles in breast cancer development and progression; however, our understanding of most lncRNAs in breast cancer is still limited. In this study, we demonstrated that small nucleolar RNA host gene 5 (SNHG5) promotes breast cancer cell proliferation both in vitro and in vivo, and depletion of SNHG5 significantly led to cell-cycle arrest at G1 phase. Accumulating evidence has shown that many lncRNA transcripts could function as competing endogenous RNAs (ceRNAs) by competitively binding common microRNAs (miRNAs). We found that SNHG5 acts as a sponge for miR-154-5p, reducing its ability to repress proliferating cell nuclear antigen (PCNA). SNHG5 promoted breast cancer proliferation and cell-cycle progression by upregulation of PCNA expression. Clinically, we observed an increased SNHG5 expression in breast cancer, whereas miR-154-5p was decreased in breast cancer tissues compared with the adjacent normal breast tissues. Furthermore, the SNHG5 expression was significantly negatively correlated with miR-154-5p expression. Taken together, our data uncover the SNHG5-miR-154-5p-PCNA axis and provide a novel mechanism to explain breast cancer proliferation. Keywords: breast cancer, proliferation, cell cycle, SNHG5, miR-154-5p, PCNA

Abstract Background Breast cancer is the most common cancer among women worldwide, and approximately 70% of breast cancers are hormone receptor-positive and express estrogen receptor-α (ERα) or/and progesterone receptor. ERα has been identified to promote the growth of primary breast cancer, however, it can also antagonize signaling pathways that lead to epithelial-mesenchymal transition (EMT), including transforming growth factor-β (TGF-β) signaling. miRNA alteration or dysfunction is involved in cancer development and progression. Although miR-1271 has identified as a tumor suppressor in various cancers, the role of miR-1271 in breast cancer is still limited. Methods The effect of miR-1271 on breast cancer progression was investigated both in vitro and in vivo. The EMT-related protein expression levels and localization were analyzed by western blotting and immunofluorescence, respectively. Chromatin immunoprecipitation and dual-luciferase reporter assays were used to validate the regulation of ERα-miR-1271-SNAI2 feedback loop. Results miR-1271 suppresses breast cancer progression and EMT phenotype both in vitro and in vivo by targeting SNAI2. Estrogen reverses TGF-β-induced EMT in a miR-1271 dependent manner. Furthermore, ERα transactivates the miR-1271 expression and is also transcriptionally repressed by SNAI2. Conclusions Our data uncover the ERα-miR-1271-SNAI2 feedback loop and provide a mechanism to explain the TGF-β network in breast cancer progression.

Abstract Background Breast cancer is the most common cancer among women worldwide, and approximately 70% of breast cancers are hormone receptor-positive and express estrogen receptor-α (ERα) or/and progesterone receptor. Therapies targeting ERα have been successfully used in patients with ERα+ breast cancer. However, intrinsic or acquired resistance to anti-estrogen therapy presents a major challenge. The Wnt/β-catenin signaling pathway regulates various processes that are important for cancer progression, and emerging evidences have shown a close interaction between Wnt/β-catenin and ERα signaling. miR-190 is also involved in ER signaling and our previous study indicated that miR-190 suppresses breast cancer metastasis. Methods The effect of miR-190 on breast cancer anti-estrogen sensitivity was investigated both in vitro and in vivo. The protein expression levels and localization were analyzed by western blotting and immunofluorescence, respectively. Chromatin immunoprecipitation and dual-luciferase reporter assays were used to validate the regulation of the zinc-finger E-box binding homeobox 1/ ERα-miR-190-SRY-related high mobility group box 9 (ZEB1/ERα-miR-190-SOX9) axis. Results miR-190 increased the anti-estrogen sensitivity of breast cancer cells both in vitro and in vivo. miR-190 inhibited Wnt/β-catenin signaling by targeting SOX9, and its expression inversely correlated with that of SOX9 in breast cancer samples. Furthermore, ERα and ZEB1 competitively regulated miR-190 expression. Conclusions Our data uncover the ZEB1/ERα-miR-190-SOX9 axis and suggest a mechanism by which the Wnt/β-catenin signaling pathway is involved in breast cancer anti-estrogen therapy.

The horizontal submerged jet (HSJ), as a special form of jet, is widely used in aerospace, food and drug, water engineering, and other industries. In order to further understand the mechanism of the HSJ, the Wray–Agarwal turbulence model was used to predict the HSJ with different incidence heights H/D and Reynolds number (Re) conditions in this paper. The results show that the jet horizontal height H/D has a large influence on the flow field structure. The unsteady flow within the flow field is dominated by vortexes. In addition, their distribution is relatively independent of H/D. Under different H/D conditions, the axial velocity distribution of the jet has very high similarity, all of them have an obvious velocity inflection point at x = 10D. When H/D is small, the wall attachment effect of the jet and the boundary layer effect generated at the bottom of the fluid domain have a certain role in maintaining the velocity of the jet near the wall, resulting in a significantly higher axial velocity than other H/D conditions, up to 1.29 times. In this paper, we thoroughly investigated the structure of the internal flow field and velocity distribution of the submerged horizontal jet. The results have a guiding significance for engineering practice and academic research.

Objective: Both rhino-orbital-cerebral mycosis and lethal midline granuloma (LMG) may result in midline destruction. LMG has now been generally considered as a natural killer/T cell lymphoma, nasal type (ENKTL-NT) with an association of EBV. Fungi have been detected from the diseased tissues now and then but are often considered as lymphoma-associated infections. We previously reported an ENKTL-NT case with Mucor irregularis, which played a causal role in the disease and was involved in the overexpression of Ki67 and CD56 in the mouse experiment. The present study describes a chronic Rhizopus arrhizus infection with immunological parameters that are closely similar to LMG. We aim to explore the relationship of another Mucorales fungus, R. arrhizus, and LMG in a patient and in mice.Methods: Case study and mouse infection modules were designed for our observation. A 35-year-old man with midline face ulcers which was clinically suspected as LMG was selected. Biopsy specimens were sent for lymphoma diagnosis and microbiological detection. The isolated fungus was tested in an ICR mouse model for mycological and histological analyses.Results: Five tissue samples yielded Rhizopus arrhizus. In the pathology, characteristic inflammation, necrosis, and granulation with thin-walled hyphae are observed. Immunohistochemistry showed NK/T cell infiltration (CD3+, CD8+, TIA1+, GZMB+, PRF+, individual CD56+) with hyperplasia (Ki67+) and angioinvasion. The patient recovered completely with amphotericin B. In the murine experiment, R. arrhizus caused angioinvasion with NK/T cell infiltration (CD3+, CD56+, TIA1+, GZMB +, PRF+) with proliferation (Ki67+) and was re-isolated from the infected host.Conclusions: We here describe a mid-face destruction patient, which was diagnosed by the top pathologists in China according to the current criteria of NK/T cell lymphoma, with a negative result for EBV and positive result for R. arrhizus. With a then developed mouse experiment, the R. arrhizus in the diseased lesions was responsible for the NK/T cell infiltration (CD3+, CD8+, CD56+, TIA1+, GZMB+, PRF+), proliferation (Ki67+), and angioinvasion, suggesting another fungal etiological agent for LMG, which could be eradicated with amphotericin B.Limitations: The sample size is not sufficient for statistical analysis. However, our findings are suggestive for the role fungus plays in LMG.

Background: 5-fluorouracil (5-FU) is basically used in the field of postoperative chemotherapy of gastric cancer (GC), the goal of this study was to evaluate improvement of long-term survival rate among GC patients after the 5-FU implants treatment.Methods: The study included 145 patients with gastric cancer who received postoperative chemotherapy with 5-FU implants and had complete follow-up information. According to the sex, age and clinical stage of 5-FU implants group, 74 patients were matched as the control group at the same time. In the study, we compared the 5-year overall survival rate with progression-free survival rate in the two groups, and the drug safety for both groups during the treatment was also compared.Results: The median follow-up time was 85 months (range 60–116 months). 31 patients (21.38%) died of tumor recurrence in 5-FU implants group and 21 (28.38%) in control group. In the control group, metastatic lesions were found in the small intestine, left adrenal gland and peritoneum in three patients. The 5-year progression-free survival (PFS) rate was 79.71% in 5-FU group and 67.12% in control (p = 0.0045). The 5-year overall survival (OS) rate was 77.68% in 5-FU implants group and 64.87% in control (p = 0.0159). Both the 5-years OS and PFS rates in 5-FU group were better than control group without significant side effect.Conclusions: 5-FU implants may improve 5-years OS and PFS rates after surgery in gastric cancer patients, while good safety profile suggests it could be reliable.

Objectives This study aimed to investigate the knowledge–attitude–practice (KAP) of Chinese college students regarding COVID-19 and evaluate their psychological status against the background of the COVID-19 outbreak.Design This was a cross-sectional study.Setting This study covered 31 provinces, municipalities and autonomous regions of mainland China.Participants The participants, who were college students with ordinary full-time status, were surveyed anonymously on their KAP regarding COVID-19 by using self-made questionnaires. In addition, the Self-Rating Anxiety Scale was used to assess the psychological status of the students.Methods The online cross-sectional study among Chinese college students was conducted in February 2020. Logistic regression analysis was used to analyse the predictors of anxiety symptoms.Primary outcome measures The level of KAP and anxiety symptoms.Results A total of 740 college students from 31 provinces, municipalities and autonomous regions in China were recruited in the survey. Among them, 139 (18.78%) revealed having anxiety. Multivariable logistic regression analysis revealed that female gender was the risk factor for anxiety symptoms with an increased 2.164-fold risk than male gender (OR=2.164, 95% CI=1.279 to 3.662). The knowledge (OR=0.825, 95% CI=0.779 to 0.873) and attitude (OR=0.822, 95% CI=0.762 to 0.887) regarding COVID-19 were protective factors against anxiety symptoms.Conclusions The level of KAP regarding COVID-19 was significantly negatively correlated with anxiety symptoms. Thus, understanding the level of KAP among college students during the early stages of major public health emergencies, such as a pandemic, is important. Such understanding plays an important role in adopting targeted health education strategies and reducing the psychological damage caused by these emergencies.

In order to analyze the pump shaft stability of multistage centrifugal pump during the closed-valve start-up process, the transient internal fluid field and structural field during the closed-valve start-up process of the TDM 35-140 × 13 segmental multistage centrifugal pump are solved by transient fluid-solid coupling. The transient deformation and vibration velocity of the pump shaft are analyzed. It is found that the maximum deformation amount of the third stage impeller and the pump shaft cylindrical contact surface (N = 7 node area) during the whole closed-valve transition start-up process is the largest. The maximum deformation in the region where the nodes 1 ≤ N ≤ 10 are significantly greater than that in other regions. In the 11 ≤ N ≤ 19 node, with the node position coordinate value N increasing, the maximum deformation amount is continuously decreasing. During the entire closed-valve transition start-up process, the vibration speed of the pump shaft fluctuates drastically. In the node of 1 ≤ N ≤ 19, with the node position coordinate value N increasing, the maximum vibration velocity first increases and then decreases. The maximum vibration speed at N = 11 nodes is higher than that of all other nodes.

To study the influence of impinging height H/D on the flow field characteristics of oblique submerged impinging jets, the numerical calculation of an oblique submerged impinging jet was carried out based on Wray–Agarwal (W–A) turbulence model. The jet flow field structure and pressure distribution under various impinging heights (1 ≤ H/D ≤ 8) when the impinging angle was θ = 45° were analyzed. The results show that with the increase in the impinging height, the diffusion degree of the jet gradually increased and the velocity decreased when the jet reached the impingement region, and the distance between the stagnation point (SP) and the geometric center (GC) gradually increased, the flow angle φ along the jet centerline remained constant in the free-jet region and rapidly decreased in the impingement region. The impingement plate pressure distribution at various heights was similar, and the impinging pressure concentration on the upstream side of the maximum pressure point was higher.

The impinging jet is a classical flow model with relatively simple geometric boundary conditions, and it is widely used in marine engineering. In recent years, scholars have conducted more and more fundamental studies on impact jets, but most of the classical turbulence models are used in numerical simulations, and the accuracy of their calculation results is still a problem in regions with large changes in velocity gradients such as the impact zone. In order to study the complex flow characteristics of the water flow under the condition of a submerged jet impacting a stationary wall, the Wray–Agarwal turbulence model was chosen for the Computational Fluid Dynamics (CFD) numerical simulation study of the impacting jet. Continuous jets with different Reynolds numbers and different impact heights H/D were used to impact the stationary wall, and the results show that the jet flow structure depends on the impact height and is relatively independent of the Reynolds number. With the increase in the impact height, the diffusion of the jet reaching the impact area gradually increases, and its velocity gradually decreases. As the impact height increases, the maximum pressure coefficient decreases and the rate of decrease increases gradually, and the dimensionless pressure distribution is almost constant. In this paper, the flow field structure and pressure characteristics of a continuous submerged jet impacting a stationary wall are explored in depth, which is of great guidance to engineering practice.

Summary: Electrodeposition (ED) technology is a low-cost industrial candidate for solar cell fabrication. However, the practical aspects of controlling deposit morphology and composition have not been significantly addressed because of the complex co-plating variables that still need to be understood for multinary alloy ED. This work addresses these practical aspects on how to control composition and deposit morphology using co-electrodeposited kesterite alloy precursors as a case study. The alloy precursors co-plated under the optimized conditions from a mixed thiosulfate-sulfite electrolyte bath show uniform, smooth, and compact film morphology as well as uniform distribution of composition, well suited for efficient kesterite absorbers, finally delivering a Cu2ZnSnS4 (CZTS) thin-film solar cell with 7.4% efficiency based on a configuration Mo/CZTS/CdS/ZnO/aluminum-doped ZnO. This work underscores that alloy ED, with the advantage of controllable composition and morphology, holds promise for low-cost industrial manufacture of thin-film solar cells. : Energy Materials; Energy Sustainability; Materials Chemistry Subject Areas: Energy Materials, Energy Sustainability, Materials Chemistry

Abstract Background Breast cancer is the most common cancer among women worldwide and metastasis is the leading cause of death among patients with breast cancer. The transforming growth factor-β (TGF-β) pathway plays critical roles during breast cancer epithelial–mesenchymal transition (EMT) and metastasis. SMAD2, a positive regulator of TGF-β signaling, promotes breast cancer metastasis through induction of EMT. Methods The expression of miR-190 and SMAD2 in breast cancer tissues, adjacent normal breast tissues and cell lines were determined by RT-qPCR. The protein expression levels and localization were analyzed by western blotting and immunofluorescence. ChIP and dual-luciferase report assays were used to validate the regulation of ZEB1-miR-190-SMAD2 axis. The effect of miR-190 on breast cancer progression was investigated both in vitro and in vivo. Results miR-190 down-regulation is required for TGF-β-induced EMT. miR-190 suppresses breast cancer metastasis both in vitro and in vivo by targeting SMAD2. miR-190 expression is down-regulated and inversely correlates with SMAD2 in breast cancer samples, and its expression level was associated with outcome in patients with breast cancer. Furthermore, miR-190 is transcriptionally regulated by ZEB1. Conclusions Our data uncover the ZEB1-miR-190-SMAD2 axis and provide a mechanism to explain the TGF-β network in breast cancer metastasis.

The COVID-19 vaccination behavior of people living with HIV (PLWH) was examined via a cross-sectional web-based survey of PLWH aged 18 years and older. The survey was conducted from l May to 20 June 2021. The survey included social demographic information; vaccination behavior (B); and questions related to perceived usefulness (PU), perceived risk (PR), subjective norms (SNs), perceived behavior control (PBC), and behavior intention (BI). The associations between the questionnaire variables and COVID-19 vaccination behavior were assessed by calculating the descriptive data, correlation analysis, and structural equation modeling. In total, 43.71% of the 350 eligible respondents had received a COVID-19 vaccine. The differences in COVID-19 vaccination behavior according to age, gender, religious belief, marital status, income, education level, and occupation were not obvious (p > 0.05). PU had a significantly negative effect on PR (p < 0.05). PR had a significantly negative effect on BI (p < 0.05). SNs had a significantly positive effect on BI (p < 0.05). BI had a significantly positive effect on B (p < 0.05). PR fully mediated the effects of PU on BI, BI fully mediated the effects of PR on B, and BI fully mediated the effects of SNs on B (p < 0.05). Health policymakers and medical workers should provide more information about the risks of vaccine application to improve the vaccination behavior of PLWH.

Abstract Background EphA2 is a crucial oncogene in gastric cancer (GC) development and metastasis, this study aims to identify microRNAs that target it and serve as key regulators of gastric carcinogenesis. Methods We identified several potential microRNAs targeting EphA2 by bioinformatics websites and then analyzed the role of miR-302b in modulating EphA2 in vitro and in vivo of GC, and it’s mechanism. Results Our analysis identified miR-302b, a novel regulator of EphA2, as one of the most significantly downregulated microRNA (miRNA) in GC tissues. Overexpression of miR-302b impaired GC cell migratory and invasive properties robustly and suppressed cell proliferation by arresting cells at G0–G1 phase in vitro. miR-302b exhibited anti-tumor activity by reversing EphA2 regulation, which relayed a signaling transduction cascade that attenuated the functions of N-cadherin, β-catenin, and Snail (markers of Wnt/β-catenin and epithelial-mesenchymal transition, EMT). This modulation of EphA2 also had distinct effects on cell proliferation and migration in GC in vivo. Conclusions miR-302b serves as a critical suppressor of GC cell tumorigenesis and metastasis by targeting the EphA2/Wnt/β-catenin/EMT pathway.