Search

Weijun Wan,1,2,* Yunjing Pan,1,2,* Jinshu Pang,1,2 Xiumei Bai,1,2 Lipeng Li,1,2 Tong Kang,1,2 Jiamin Chen,1,2 Rong Wen,1 Dongyue Wen,1 Hong Yang,1– 3 Yun He1,2 1Department of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 2Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor/Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3Collaborative Innovation Centre of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun He; Hong Yang, Department of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Email heyun@stu.gxmu.edu.cn; yanghong@gxmu.edu.cnPurpose: The explosive progression of residual hepatocellular carcinoma (HCC) following incomplete thermal ablation is challenging, and the underlying mechanisms require further exploration. We investigated the mechanism by which Forkhead box P4 (FOXP4) promotes the malignant transformation of residual HCC cells through N-deacetylase and N-sulfotransferase 2 (NDST2) after incomplete thermal ablation.Methods: The clinical significance of FOXP4 and NDST2 in HCC was evaluated using big data analysis. FOXP4 expression was detected in clinical samples of HCC. The gene expression levels in an in vitro heat-stressed HCC cell model were determined using quantitative real-time PCR (RT-qPCR) and Western blotting. The effects of the genes on heat-stressed HCC cells were investigated using Cell Counting Kit-8 (CCK-8), scratch, Transwell migration, and invasion assays. Additionally, the regulatory relationship between FOXP4 and NDST2 was validated using the Cleavage Under Targets and Tagmentation (CUT&Tag) experiments and phenotypic assays.Results: High FOXP4 expression was correlated with liver cancer occurrence and development. In the heat-stressed HCC cell model, downregulating FOXP4 inhibited cancer cell progression. Besides, there was a positive association between FOXP4 and NDST2 in liver cancer. Suppressing FOXP4 reduced NDST2 expression in the heat-stressed HCC cells. Furthermore, reducing NDST2 expression weakened the biological behavior of heat-stressed HCC cells.Conclusion: FOXP4 and NDST2 are crucial in the incomplete thermal ablation of residual cancer. FOXP4 might regulate the biological progression of residual HCC after incomplete thermal ablation through NDST2.Keywords: ablation therapy, gene expression regulation, cancer inhibition, hepatocellular carcinoma

Weiju Lai,1,* Jiajian Yu,2,* Diguang Wen3 1Central Laboratory, Chongqing FuLing Hospital, School of Medicine, Chongqing University, Chongqing, People’s Republic of China; 2Department of Hepatobiliary, Chongqing Fuling Hospital, School of Medicine, Chongqing University, Chongqing, People’s Republic of China; 3Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Diguang Wen, Email 2018110626@stu.cqmu.edu.cn; 2021140052@stu.cqmu.edu.cnBackground: Liver ischemia-reperfusion is one of the common complications after liver surgery. Uncontrolled liver ischemia-reperfusion will lead to many serious consequences such as surgical failure. It is an urgent clinical problem to search for diagnostic markers and explore its potential pathogenesis.Methods: In this study, we focus on 1411 candidate RNA binding protein. Through several GEO (Gene Expression Omnibus) online datasets, we construct a diagnostic model and perform interactive validation. We evaluate the efficacy of the prognostic model. Using bioinformatics methods, we predicted the relevant signaling pathways of liver ischemia-reperfusion and key genes. We also evaluated the association of RNA binding protein with immune cell infiltration. Single cell sequencing datasets were used to explore the expression profiles of key genes at the single cell level. Machine learning algorithm is used to predict key gene RNA binding domains.Results: ROC (Receiver Operating Characteristic) and DCA (Decision Curve Analysis) curves showed that the above diagnostic model had good and stable diagnostic efficacy and clinical practicability. We identified three key genes (BTG2, CCNL1 and DNAJB1) in liver ischemia-reperfusion. DNAJB1, BTG2 and CCNL1 are mainly expressed in immune cells such as macrophages and T cells, and are closely related to inflammatory pathways such as TNF-α, highlighting their importance in hepatic ischemia reperfusion. We identified RNA-binding domains of the above three genes. We found that the expression of DNAJB1, CCNL1 and BTG2 in the ischemia-reperfusion group were significantly higher than those in the sham operation group.Conclusion: Our study revealed the importance of the candidate RNA binding protein in liver ischemia reperfusion injury and provided new insights into the therapeutic of hepatic ischemia-reperfusion injury.Keywords: RBPs, liver ischemia reperfusion injury, bioinformatics

Jiali Liu,1,&ast; Yuanqiang Zhu,1,&ast; Yingjuan Chang,1,&ast; Ziliang Xu,1 Chen Wang,1 Pengpeng Zhang,1 Shuangxin Li,1 Wenxuan Yang,1 Rui An,1,2 Didi Wen,1 Jian Xu,1,2 Minwen Zheng1 1Department of Radiology, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Interventional Surgery Center, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minwen Zheng, Department of Radiology, Xijing Hospital, Air Force Medical University, 127&num; Changle West Road, Xi’an, Shaanxi, 710032, People’s Republic of China, Tel +86-29-84775421, Fax +86-29-84773732, Email zhengmw2007@163.com Jian Xu, Department of Interventional Surgery Center, Xijing Hospital, Air Force Medical University, 127&num; Changle West Road, Xi’an, Shaanxi, 710032, People’s Republic of China, Tel +86-29-84775299, Fax +86-29-84775299, Email xujian771939@163.comPurpose: While prior research has highlighted a significant association between sleep characteristics and angina pectoris (AP) incidence, the link between sleep efficiency (SE) and angina remains unexplored. This study seeks to elucidate the relationship between AP and objectively quantified SE.Patients and Methods: We examined a cohort of 2990 participants (1320 males and 1670 females; mean age 63.69 ± 13.2 years) from the Sleep Heart Health Study. The main exposure variable was SE, as determined by baseline home polysomnography, while the primary outcome was the first incidence of angina pectoris (AP) during the period between the baseline polysomnography and the end of follow-up. A multivariate Cox regression model was utilized, controlling for factors such as age, gender, BMI, smoking and alcohol consumption habits, diabetes, hypertension, sleep duration, triglycerides, cholesterol, high-density lipoprotein, apnea-hypopnea index, nocturnal oxygen saturation, to analyze the relationship between SE and AP.Results: During an average follow-up of 11 years, 284 patients developed AP. The unadjusted Kaplan-Meier analysis identified the 2nd quartile of SE as having the lowest AP risk. The multivariate Cox proportional hazards model demonstrated a higher risk of AP in quartile 1 (HR, 1.679; 95% CI, 1.109– 2.542; P < 0.014) and quartile 3 (HR, 1.503; 95% CI, 1.037– 2.179; P < 0.031), compared to quartile 2 of SE. Upon stratified analysis, this relationship was particularly pronounced in hypertensive individuals.Conclusion: Our results highlight the critical role of optimal sleep efficiency in mitigating the risk of angina pectoris, especially among hypertensive individuals.Keywords: sleep efficiency, angina pectoris, polysomnography, cardiovascular risk, sleep heart health study, hypertension

Sijian Chen,1,2 Honghe Li,1 Deliang Wen1 1Institute for International Health Professions Education and Research, China Medical University, Shenyang, People’s Republic of China; 2School of Nursing, China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Deliang Wen, Institute for International Health Professions Education and Research, China Medical University, No. 77 Puhe Road, Shenyang, Liaoning, 110122, People’s Republic of China, Email dlwen@cmu.edu.cnBackground: Sleep problems have become a serious threat to public health worldwide. Daytime sleepiness is an important indicator of many sleep problems, which have a significant impact on academic performance, physical and mental health, and wellbeing among medical students. We aimed to explore the factors associated with daytime sleepiness among medical students.Methods: We conducted a cross-sectional survey of 466 medical students recruited via convenience sampling. Self-rated psychometric scales, including the Social Support Rate Scale, the Epworth Sleepiness Scale, the Chinese version of the UCLA loneliness scale, and the Mobile Phone Addiction Index (MPAI), were utilized to evaluate social support, daytime sleepiness, loneliness, and problematic smartphone use. A sequential mediation model was constructed with daytime sleepiness as the dependent variable, social support as the independent variable, and loneliness and problematic smartphone use as mediating variables. Age, gender, and grade were taken as covariates.Results: Social support among medical students was negatively associated with loneliness, problematic smartphone use, and daytime sleepiness (p < 0.01). A sequential mediation analysis showed that loneliness (the first mediator) and problematic smartphone use (the second mediator) sequentially mediated the path from social support to daytime sleepiness among medical students (β = − 0.008; 95% CI = − 0.016, − 0.002). Moreover, there were also significant mediating roles observed in the relationship between social support and daytime sleepiness via loneliness only (β = − 0.037; 95% CI = − 0.062, − 0.015) and problematic smartphone use only (β = − 0.022; 95% CI = − 0.041, − 0.008).Conclusion: Social support, loneliness, and problematic smartphone use among medical students influenced their daytime sleepiness. Interventions targeting medical student loneliness and problematic smartphone use behaviors might attenuate the effects from low levels of social support and further improve daytime sleepiness.Keywords: social support, daytime sleepiness, loneliness, problematic smartphone use

Sijian Chen,1,2 Honghe Li,1 Lihong Pang,3 Deliang Wen1 1Institute for International Health Professions Education and Research, China Medical University, Shenyang, People’s Republic of China; 2School of Nursing, China Medical University, Shenyang, People’s Republic of China; 3School of Nursing, Qiqihar Medical University, Qiqihar, People’s Republic of ChinaCorrespondence: Deliang Wen, Institute for International Health Professions Education and Research, China Medical University, No. 77 Puhe Road, Shenyang, Liaoning, 110122, People’s Republic of China, Email dlwen@cmu.edu.cnObjective: This study aimed to examine the mediating role of fear of missing out (FoMO) and the moderating role of resilience in the association between social media use and negative emotions among medical college students in China during the COVID-19 pandemic.Participants and Methods: A cross-sectional study design was conducted, medical college students from Qiqihar Medical University, China participated in the study. A total of 470 medical college students were recruited voluntarily to complete questionnaires on social media use, FoMO, resilience, and negative emotions.Results: Social media use was positively associated with FoMO and negative emotions among medical students (p < 0.01). The total effect of social media use on negative emotions was significant (β = 1.101, SE = 0.079, p < 0.001). Social media use had no significant direct effect on negative emotions (β = 0.168, SE = 0.096, p > 0.05), but it had an indirect effect on negative emotions via mediation of FoMO (β = 0.933, SE = 0.106, 95% CI: 0.731 to 1.149). Moreover, resilience had a significant moderating effect on the relationship between FoMO and negative emotions (β = − 0.021, SE = 0.005, 95% CI: − 0.032 to − 0.012). FoMO had a significant positive predictive effect on negative emotions at both levels of resilience (low resilience individuals: β = 1.079, SE = 0.076, p < 0.001; high resilience individuals: β = 0.212, SE = 0.094, p < 0.05).Conclusion: Social media use and FoMO may be risk factors for increased negative emotions, and resilience should be considered in prevention and intervention strategies designed to mitigate negative emotions among medical college students.Keywords: social media use, negative emotions, fear of missing out, resilience, COVID-19

Qirong Lu,1,&ast; Wantong Han,1,&ast; Defeng Wen,1,&ast; Pu Guo,1 Yu Liu,1 Zhongyuan Wu,1 Shulin Fu,1 Chun Ye,1 Xu Wang,2 Yinsheng Qiu1 1Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan, 430023, People’s Republic of China; 2National Reference Laboratory of Veterinary Drug Residues (HZAU) and Ministry of Agriculture Key Laboratory for the Detection of Veterinary Drug Residues in Foods, Huazhong Agricultural University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pu Guo; Yinsheng Qiu, Wuhan Polytechnic University, Wuhan, Hubei, 430023, People’s Republic of China, Email guopu@whpu.edu.cn; qiuyinsheng6405@whpu.edu.cnBackground: At present, the treatment and prevention of Pasteurella multocida infections in pigs mainly rely on antibiotics and vaccines, but inflammatory injury cannot be eliminated. The compound 18β-glycyrrhetinic acid (GA), a pentacyclic triterpenoid extracted from Glycyrrhiza glabra L. root (liquorice) and with a chemical structure similar to that of steroidal hormones, has become a research focus because of its anti-inflammatory, antiulcer, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and neuroprotective effects, but its potential for the treatment of vascular endothelial inflammatory injury by P. multocida infections has not been evaluated. This study aimed to investigate the effects and mechanisms of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections.Materials and Methods: Putative targets of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections were identified using network pharmacological screening and molecular docking simulation. The cell viability of PIEC cells was investigated via the CCK-8 assay. The mechanism of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections were investigated using cell transfection and western blot.Results: Through network pharmacological screening and molecular docking simulation, this study found that PARP1 may be a core target for GA to exert anti-inflammatory effects. Mechanistically, GA alleviates P. multocida-induced vascular endothelial inflammation by PARP1-mediated NF-κB and HMGB1 signalling suppression.Conclusion: These findings, for the first time, demonstrate the potential therapeutic relationship among GA, PARP1 and inflammatory injury, providing a candidate drug, therapeutic targets and explanation for treating vascular endothelial inflammatory injury caused by P. multocida infection.Keywords: network pharmacology, GA, PARP1, inflammatory injury, P. multocida infection

Jie Wang,1,2 Lina Yang,2 Jialing You,2 Dada Wen,2 Bo Yang,2 Canhua Jiang1 1Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, 410078, People’s Republic of China; 2Department of Immunology, Xiangya School of Medicine, Central South University, Changsha, 410078, People’s Republic of ChinaCorrespondence: Canhua JiangDepartment of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410078, Hunan, People’s Republic of ChinaTel/Fax +86-731-89753046Email wj0988@csu.edu.cnObjective: To explore the effect of platelet-derived growth factor (PDGF) on oral mucosal fibroblast autophagy and further elucidate the molecular mechanism by which PDGF-BB regulates the biological behavior of oral mucosal fibroblasts by inducing autophagy.Methods: Primary oral mucosal fibroblasts were isolated and cultured by the tissue block and trypsin methods and identified by indirect immunofluorescence vimentin detection. We detected the autophagy marker Beclin-1 and fibrosis marker Col-I of the primary oral mucosal fibroblasts at different time points after stimulating the fibroblasts with different PDGF-BB concentrations by Western blotting and determined the best experimental concentration and stimulation time of PDGF-BB. Then, indirect immunofluorescence, Western blotting, and quantitative real-time polymerase chain reaction (PCR) were used to detect the effect of PDGF-BB on the expression of autophagy-related and fibrotic proteins before and after 3-methyladenine (3-MA) intervention. Additionally, the effect of 3-MA on the proliferation and migration of primary oral mucosal fibroblasts stimulated by PDGF-BB was detected by the MTT method and a scratch experiment. The effect of PDGF-BB on Beclin-1 and phosphatidylinositol-3 kinase class 3 (PI3KC3) interaction was detected by co-immunoprecipitation.Results: The results demonstrated that PDGF-BB could induce autophagy of the oral mucosal fibroblasts, showing a certain time and dose correlation. It induced cell autophagy through Beclin-1 and PI3KC3 interaction to promote the proliferation, migration, conversion, and collagen synthesis of the fibroblasts. However, 3-MA inhibited the combination of Beclin-1 and PI3KC3 and weakened the fibroblasts’ proliferation, migration, conversion, and collagen synthesis activities.Conclusion: Overall, PDGF-BB induces autophagy through the Beclin-1 pathway to regulate the biological behavior of oral mucosal fibroblasts.Keywords: PDGF-BB, primary oral mucosal fibroblasts, autophagy, 3-MA, biological behavior, signaling pathway

Yanshuo Han,1,2 Yanan Ma,1,3 Yang Liu,1 Zhongyi Zhao,1 Shihan Zhen,1 Xuelian Yang,1 Zhiyong Xu,4 Deliang Wen11Institute of Health Science, China Medical University, Shenyang, People’s Republic of China; 2Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 3Public Health Department, China Medical University, Shenyang, People’s Republic of China; 4Educational Research Centre of Huanggu District, Shenyang, People’s Republic of ChinaPurpose: To determine the plasma concentrations of butyrylcholinesterase (BChE), also known as pseudocholinesterase, in different weight categories of adolescents, and to explore the possible association between plasma BChE and overweight (OW), obesity, and metabolic syndrome (MetS) in Chinese adolescents.Patients and methods: This cross-sectional study included 1,236 Chinese adolescents (194 obese [OB], 188 OW, 732 normal weight [NW], and 122 underweight [UW]). The biochemical variables and anthropometric variables of the study participants were evaluated. Plasma BChE level was measured by DGKC method.Results: OB was associated with a higher prevalence of upper strata plasma BChE levels when compared with the BChE levels in UW, NW, and OW group. A logistic regression analysis showed that plasma BChE was positively associated with the OB group when compared with the NW group. Boys in the OW group, but not the OB group, had a significantly higher prevalence of upper stratum of BChE levels. Plasma triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and ApoB levels were positively associated with the upper stratum of BChE levels when compared with lower stratum. MetS and most of its components were more prevalent among subjects with upper stratum rather than lower stratum BChE levels. Receiver operating characteristic curves for plasma BChE in subjects with MetS indicated that the AUC was 0.80 (95%CI:0.70–0.90,P

We prove that if Xi,i=1,2,…, are Banach spaces that are weak* uniformly rotund, then their lp product space (p>1) is weak* uniformly rotund, and for any weak or weak* uniformly rotund Banach space, its quotient space is also weak or weak* uniformly rotund, respectively.

Objective: To investigate the trimester‐specific associations between maternal total physical activity level vs moderate‐to‐vigorous exercise and fetal growth disorders. Methods: We analyzed 2062 mother–neonate pairs participating in the longitudinal China Medical University Birth Cohort Study. The Pregnancy Physical Activity Questionnaire was used to assess the physical activity level of women during the three trimesters. A higher level of total physical activity was defined as meeting or exceeding the cohort‐specific 75th percentile, and a higher level of exercise was defined according to the Physical Activity Guidelines for Americans. Fetal growth disorder was defined as small‐for‐gestational age (SGA) or large‐for‐gestational age (LGA) at birth. Results: Of the neonates included in this study, 7.1% were SGA and 15.5% were LGA. A higher level of total physical activity during the first trimester (adjusted relative risk (aRR), 0.62 (95% CI, 0.42–0.91)) and second trimester (aRR, 0.62 (95% CI, 0.41–0.95)) was associated with a lower risk of SGA, and a higher level of total physical activity during the third trimester was associated with a lower risk of LGA (aRR, 0.73 (95% CI, 0.54–0.97)). When analyzing physical activity by subtype, a higher level of occupational physical activity during the first and second trimesters was associated negatively with SGA risk, and higher levels of occupational and low‐intensity physical activity during the first trimester were associated negatively with LGA risk. No significant association was found between maternal adherence to the Physical Activity Guidelines for Americans and risk of fetal growth disorders. Conclusions: A higher total physical activity level during the first and second trimesters was associated with a decreased risk of SGA, whereas a higher total physical activity level in the third trimester was associated with a decreased risk of LGA. Pregnant women should be advised to increase their total physical activity levels instead of focusing on engaging in only moderate‐to‐vigorous exercise. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Due to their many advantages, such as simple structure, low transmission power, strong penetration capability, high resolution, and high transmission speed, UWB (Ultra-WideBand) radars have been widely used for detecting life information in various scenarios. To effectively detect life information, the key is to use radar echo information-processing technology to extract the breathing and heartbeat signals of the involved person from UWB radar echoes. This technology is crucial for determining life information in different scenarios, such as obtaining location information, monitoring and preventing diseases, and ensuring personnel safety. Therefore, this paper introduces a UWB radar and its classification, electromagnetic scattering mechanisms, and detection principles. It also analyzes the current state of radar echo model construction for breathing and heartbeat signals. The paper then reviews existing methods for extracting breathing and heartbeat signals, including time domain, frequency domain, and time-frequency domain analysis methods. Finally, it summarizes research progress in breathing and heartbeat signal extraction in various scenarios, such as mine rescue, earthquake rescue, medical health, and through-wall detection, as well as the main problems in current research and focus areas for future research.

Extensive immune adaptations occur during pregnancy to ensure successful delivery. However, these changes can increase the risk of disease in the mother. Here, we conducted single-cell RNA sequencing on peripheral blood mononuclear cells from pregnant women at different stages of pregnancy to elucidate the dynamic transcriptional changes in the maternal immune system. Gradual reduced cytotoxicity phenotype in highly variable cytotoxic T and natural killer cell types were observed during pregnancy. Reduced T- and B-cell response-related MHC-II and CD40 signaling as well as enhanced protolerance inducible costimulator and activin signaling may underlie the pregnancy-related weakening of adaptive immunity. Conversely, pro-inflammatory genes and pathways were upregulated in monocytes, possibly to compensate for the reduced T-cell response. Moreover, the transition from adaptive immune reduction to activation in late pregnancy in dendritic cells and CD4+ T cells was also detected. Notably, we proposed a novel view of the pro-aging effect of pregnancy from the perspective of immunity, and this effect may be restored postpartum. This work expands our knowledge of pregnancy immunity and may provide insights into the altered disease risks during pregnancy.

ObjectiveThe industrial robot industry has put forward higher requirements for RV reducers, and the precision life reflects the ability of the reducer to maintain transmission accuracy, which is one of the most important design criteria and usage indicators. To improve the precision performance of precision reducers, it is crucial to evaluate their reliability. Therefore, the degradation characteristics of precision reducers were analyzed.MethodsTaking the RV80E reducer as an example, a random degradation model based on Gamma process was proposed. Combined with the performance degradation data of the reducer transmission accuracy, the model parameters were estimated based on the matrix method and the maximum likelihood estimation method. A Gaussian process regression model optimized by genetic algorithm was established using vibration characteristic data to optimize the prediction of transmission accuracy.ResultsThe results show that the prediction accuracy based on Gaussian process regression model is significantly better than that of traditional regression model. The posterior distribution parameters of the random degradation model are updated by using the algorithm to predict the results, which can effectively evaluate the reliability of the accuracy life of RV reducer and lay the foundation for further reliability optimization design of accuracy life.

Abstract Background Metastasis is the primary cause of mortality in small cell lung cancer (SCLC), with the liver being a predominant site for distal metastasis. Despite this clinical significance, mechanisms underlying the interaction between SCLC and liver microenvironment, fostering metastasis, remain unclear. Methods SCLC patient tissue array, bioinformatics analysis were performed to demonstrate the role of periostin (POSTN) in SCLC progression, metastasis, and prognosis. Cell migration, invasion and sphere formation assay were performed to determine the oncogenic role of POSTN. RNA sequencing analysis was utilized to identify the key signaling pathway regulated by POSTN. Immunoprecipitation, immunofluorescence and co-culture system were used to clarify the mechanism of POSTN-NOTCH1 axis in tumor cells-hepatic stellate cells (HSCs) crosstalk. Subcutaneous xenograft model and liver metastasis model were established to examine the anti-tumor growth and metastases effect of targeting POSTN-NOTCH1 signaling axis. Results Elevated expression of POSTN in SCLC is correlated with accelerated tumor progression and metastasis. Conditioned medium rich in POSTN derived from SCLC tumors demonstrates the ability to activate HSCs in the liver microenvironment. Mechanistically, POSTN emerges as a binding partner for the membrane receptor NOTCH1 and transducing the extracellular signals to intracellular fibroblasts. Furthermore, targeting the POSTN-NOTCH1 signaling axis proves effective in suppressing SCLC tumor growth and inhibiting liver metastasis. This study elucidates that the SCLC-derived secreted protein POSTN interacts with NOTCH1 on HSCs to promote the activation of HSCs, thereby providing a favorable microenvironment for liver metastasis. Conclusion These findings uncover the intricate communications between primary SCLC cells and HSCs in the tumor microenvironment mediated by the secreted protein POSTN in the context of liver metastasis. Consequently, targeting the POSTN-NOTCH1 signaling axis emerges as a promising therapeutic strategy for metastatic SCLC.

Abstract Structural electromagnetic shielding materials are required to withstand high stress and electromagnetic interference in extreme environments. In this paper, a nano-magnetic Heusler phase with desired structure parameters was successfully obtained in a copper matrix by employing a multi-objective driving design strategy. The resulting copper alloy exhibits a yield strength of up to 1.5 GPa, and the attenuation degree of electromagnetic wave reaches 99.999999999% (110 dB) within the frequency range of 10 kHz to 3 GHz. The research suggests that the Ni2MnSn precipitates with optimized structure parameters (including high number density: 5 × 1023 m−3, small size: 23 nm, large aspect ratio: 4, low mismatch: 2.3%, strong bonding: -0.316 eV/atom, magnetic order: 4.05 μB/f.u.) both reinforce the matrix by strong pinning and enhance electromagnetic shielding properties through magnetic-electric coupling. This design method tailored for multiple performance requirements provides a valuable tool for the development of structure-function integrated materials.

Despite advances in treatment, prostate cancer remains a leading cause of cancer-related deaths among men, highlighting the urgent need for innovative therapeutic strategies. MicroRNAs (miRNAs) have emerged as key regulatory molecules in cancer biology. In this research, we investigated the tumor-suppressive role of miR-5100 in PCa and its underlying molecular mechanism. By using RT-qPCR, we observed lower miR-5100 expression in PCa cell lines than in benign prostate cells. Functional assays demonstrated that miR-5100 overexpression significantly suppressed PCa cell proliferation, migration, and invasion. By using RNA-sequencing, we identified 446 down-regulated and 806 upregulated candidate miR-5100 target genes overrepresenting cell cycle terms. Mechanistically, E2F7 was confirmed as a direct target of miR-5100 using the reporter gene assay and RIP assay. By conducting flow cytometry analysis, cell cycle progression was blocked at the S phase. E2F7 overexpression partially mitigated the suppressive impact of miR-5100 in PCa cells. In conclusion, miR-5100 is a tumor suppressor in PCa by blocking cell cycle and targeting E2F7.

Abstract The PI3K/Akt pathway is overexpressed in nearly 50% of hepatocellular carcinomas and inhibits apoptosis by promoting the expression of antiapoptotic genes. Serine protease inhibitors have been shown to induce apoptosis in hepatoma cells by downregulating SPINK13 in the PI3K/Akt pathway. In this study, SPINK13 was expressed in lentiviral vectors. Changes in signaling pathway adapter proteins, apoptosis regulatory proteins, cell cycle regulatory proteins, and the biological behavior of hepatocellular carcinoma were observed in cell and nude mouse xenograft models. The underlying mechanism of endogenous SPINK13-induced apoptosis in hepatocellular carcinoma cells was explored via transcriptomics. As a result, endogenous SPINK13 might inhibit the activity of Furin protease, downregulate the Notch1/Hes1 pathway in a binding manner, activate the direct effector PTEN, inhibit Akt phosphorylation, inactivate the downstream PI3K/Akt pathway, and ultimately lead to mitochondrial apoptosis and cell cycle arrest in hepatoma cells. Therefore, the Notch1/Hes1/PTEN pathway may act upstream of SPINK13 to downregulate the PI3K/Akt signaling pathway. Our study helps elucidate the underlying mechanism of SPINK13 in anti-hepatocellular carcinoma and lays a theoretical foundation for the development of novel therapeutic serine protease inhibitors.

Abstract Testosterone deficiency can cause abnormal lipid metabolism in men, leading to hyperlipidemia. We identified the testosterone-degrading bacterium Pseudomonas nitroreducens in the fecal samples of male patients with hyperlipidemia. Gastric administration of P. nitroreducens in mice led to testosterone deficiency and elevated blood lipid levels. Whole-genome sequencing of P. nitroreducens revealed the presence of 3/17β-hydroxysteroid dehydrogenase (3/17β-HSD), a gene responsible for testosterone degradation, which is also associated with hyperlipidemia. Microbiota analysis of fecal samples collected from 158 patients with hyperlipidemia and 151 controls revealed that the relative abundance of P. nitroreducens and 3/17β-HSD in the fecal samples of patients with hyperlipidemia was significantly higher than that in controls. These results suggest that P. nitroreducens and 3/17β-HSD may be related to the onset of testosterone deficiency-induced hyperlipidemia. Therefore, treatments targeted at eradicating testosterone-degrading bacteria are a potential future option for patients with testosterone-induced hyperlipidemia and should thus be studied further.

Metasurfaces have recently gained significant attention due to the strong capacity in light field manipulation. However, most traditional metasurfaces are fabricated on rigid substrates, which fix their functionality after fabrication and limit their applications in dynamic measurement fields. In this work, we designed and fabricated a silver metasurface embedded in a stretchable substrate for sensing applications. This metasurface can generate different point cloud patterns under varying stretch ratios when illuminated by a laser beam. By collecting and analyzing the patterns, we can precisely reconstruct the deformation of the metasurface. Furthermore, the sample exhibits excellent performance under incident light of various wavelengths. These results pave the way for developing microdevices with novel capabilities based on flexible metamaterials.

Abstract Paleogeography is the merger of sediment and volcanic facies, depositional settings, tectonic plate movements, topography, climate patterns and ecosystems through time. The construction of paleogeographic maps on tectonic plate reconstruction models requires a team effort to compile databases, data sharing standards and map projection methods. Two goals of the Paleogeography Working Group of the International Union of Geological Sciences (IUGS) program for Deep‐Time Digital Earth (DDE) are: (1) to interlink online national lexicons for all sedimentary and volcanic formations, and develop online ones for nations that currently lack these; (2) to target specific regions and intervals for testing/showcasing paleogeography output from the merger of these databases. Following those goals, we developed and applied new cloud‐based lexicon data services and interactive visualization techniques to regions in East Asia. This has been a successful collaboration among computer engineers and plate modellers and has involved stratigraphers in India (ONGC), China (Chengdu Univ. Tech., and Chinese Acad. Geol. Sci.), United States (Paleomap Project, and Purdue Univ.), Australia (GPlates visualization team) and Vietnam (Vietnam Nat. Univ.). Independent online lexicons with map‐based and stratigraphy‐based user interfaces have been developed (as of the date of this submission in March 2022) for all Proterozoic to Quaternary formations on the Indian Plate (over 800) and Vietnam (over 200), the majority of the Devonian through Neogene of China (ca. 2000) and partially for Thailand. A multi‐database search system returns all geologic formations of a desired geologic time from these four independent databases. With one click, users can plot the regional extent of one or of all of those regional formations on different plate reconstruction models of that desired age, and these polygons are filled with the lithologic facies pattern.