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Abstract Mitochondrial metabolism-regulated epigenetic modification is a driving force of aging and a promising target for therapeutic intervention. Mitochondrial malate dehydrogenase (MDH2), an enzyme in the TCA cycle, was identified as an anti-aging target through activity-based protein profiling in present study. The expression level of MDH2 was positively correlated with the cellular senescence in Mdh2 knockdown or overexpression fibroblasts. Glibenclamide (Gli), a classic anti-glycemic drug, was found to inhibit the activity of MDH2 and relieve fibroblast senescence in an MDH2-dependent manner. The anti-aging effects of Gli were also further validated in vivo, as it extended the lifespan and reduced the frailty index of naturally aged mice. Liver specific Mdh2 knockdown eliminated Gli’s beneficial effects in naturally aged mice, reducing p16INK4a expression and hepatic fibrosis. Mechanistically, MDH2 inhibition or knockdown disrupted central carbon metabolism, then enhanced the methionine cycle flux, and subsequently promoted histone methylation. Notably, the tri-methylation of H3K27, identified as a crucial methylation site in reversing cellular senescence, was significantly elevated in hepatic tissues of naturally aged mice with Mdh2 knockdown. Taken together, these findings reveal that MDH2 inhibition or knockdown delays the aging process through metabolic-epigenetic regulation. Our research not only identified MDH2 as a potential therapeutic target and Gli as a lead compound for anti-aging drug development, but also shed light on the intricate interplay of metabolism and epigenetic modifications in aging.

Abstract Purpose Uveal melanoma (UM) is adults’ most common primary intraocular malignant tumor. It has been observed that 40% of patients experience distant metastasis during subsequent treatment. While there exist multigene models developed using machine learning methods to assess metastasis and prognosis, the immune microenvironment’s specific mechanisms influencing the tumor microenvironment have not been clarified. Single-cell transcriptome sequencing can accurately identify different types of cells in a tissue for precise analysis. This study aims to develop a model with fewer genes to evaluate metastasis risk in UM patients and provide a theoretical basis for UM immunotherapy. Methods RNA-seq data and clinical information from 79 μm patients from TCGA were used to construct prognostic models. Mechanisms were probed using two single-cell datasets derived from the GEO database. After screening for metastasis-related genes, enrichment analysis was performed using GO and KEGG. Prognostic genes were screened using log-rank test and one-way Cox regression, and prognostic models were established using LASSO regression analysis and multifactor Cox regression analysis. The TCGA-UVM dataset was used as internal validation and dataset GSE22138 as external validation data. A time-dependent subject work characteristic curve (time-ROC) was established to assess the predictive ability of the model. Subsequently, dimensionality reduction, clustering, pseudo-temporal analysis and cellular communication analysis were performed on GSE138665 and GSE139829 to explore the underlying mechanisms involved. Cellular experiments were also used to validate the relevant findings. Results Based on clinical characteristics and RNA-seq transcriptomic data from 79 samples in the TCGA-UVM cohort, 247 metastasis-related genes were identified. Survival models for three genes (SLC25A38, EDNRB, and LURAP1) were then constructed using lasso regression and multifactorial cox regression. Kaplan-Meier survival analysis showed that the high-risk group was associated with poorer overall survival (OS) and metastasis-free survival (MFS) in UM patients. Time-dependent ROC curves demonstrated high predictive performance in 6 m, 18 m, and 30 m prognostic models. Cell scratch assay showed that the 24 h and 48 h migration rates of cells with reduced expression of the three genes were significantly higher than those of the si-NC group. CD8 + T cells may play an important role in tumour metastasis as revealed by immune infiltration analysis. An increase in the percentage of cytotoxic CD8 + T cells in the metastatic high-risk group was found in the exploration of single-cell transcriptome data. The communication intensity of cytotoxic CD8 was significantly enhanced. It was also found that the CD8 + T cells in the two groups were in different states, although the number of CD8 + T cells in the high-risk group increased, they were mostly in the exhausted and undifferentiated state, while in the low-risk group, the CD8 + T cells were mostly in the functional state. Conclusions We developed a precise and stable 3-gene model to predict the metastatic risk and prognosis of patients. CD8 + T cells exhaustion in the tumor microenvironment play a crucial role in UM metastasis.

Abstract Background Patients with spondyloarthritis (SpA)/HLA-B27-associated acute anterior uveitis (AAU) experience recurring acute flares, which pose significant visual and financial challenges. Despite established links between SpA and HLA-B27-associated AAU, the exact mechanism involved remains unclear, and further understanding is needed for effective prevention and treatment. Methods To investigate the acute pathogenesis of SpA/HLA-B27-associated AAU, Mendelian randomization (MR) and single-cell transcriptomic analyses were employed. The MR incorporated publicly available protein quantitative trait locus data from previous studies, along with genome-wide association study data from public databases. Causal relationships between plasma proteins and anterior uveitis were assessed using two-sample MR. Additionally, colocalization analysis was performed using Bayesian colocalization. Single-cell transcriptome analysis utilized the anterior uveitis dataset from the Gene Expression Omnibus (GEO) database. Dimensionality reduction, clustering, transcription factor analysis, pseudotime analysis, and cell communication analysis were subsequently conducted to explore the underlying mechanisms involved. Results Mendelian randomization analysis revealed that circulating levels of AIF1 and VARS were significantly associated with a reduced risk of developing SpA/HLA-B27-associated AAU, with AIF1 showing a robust correlation with anterior uveitis onset. Colocalization analysis supported these findings. Single-cell transcriptome analysis showed predominant AIF1 expression in myeloid cells, which was notably lower in the HLA-B27-positive group. Pseudotime analysis revealed dendritic cell terminal positions in differentiation branches, accompanied by gradual decreases in AIF1 expression. Based on cell communication analysis, CD141+CLEC9A+ classic dendritic cells (cDCs) and the APP pathway play crucial roles in cellular communication in the Spa/HLA-B27 group. Conclusions AIF1 is essential for the pathogenesis of SpA/HLA-B27-associated AAU. Myeloid cell differentiation into DCs and decreased AIF1 levels are also pivotal in this process.

【Objective】 This study delves into the successional interrelationship between algal communities and environmental factors to uncover the mechanisms behind water bloom outbreaks in Shanzai Reservoir. 【Method】 Utilizing redundancy analysis and correlation analysis, we investigated the temporal variations in water temperature, pH, dissolved oxygen (DO), transparency, and dominant algal species in Shanzai Reservoir from 2020 to 2021. We explored the seasonal succession and vertical distribution of the algal community. A machine learning approach was used to establish the relationship between pertinent environmental factors and chlorophyll a. 【Result】 The average total nitrogen (TN) and total phosphorus (TP) concentrations in Shanzai Reservoir measured in the studied period were (0.675±0.137) mg/L and (0.021±0.006) mg/L, respectively. Water quality in the reservoir was Class III grade. The dominant algal species in the reservoir are diatoms and cyanobacteria. Diatom blooms were prevalent from May to July, particularly under moderate temperature and reduced light conditions. In contrast, cyanobacteria proliferated from July to September, leading to a reduction in pH, DO and water quality. The cyanobacterial outbreaks had a significant positive correlation with water temperature, pH, water turbidity, and TP, with their R2 being 0.71, 0.77, 0.65, and 0.74, respectively. Diatoms were negatively correlated to water temperature, pH, turbidity, and TP, with their R2 ranging from -0.43 to -0.37. Using machine learning algorithms can improve the R2 to 0.852 6. 【Conclusion】 There were differences in outbreak timings between different algae species in Shanzai Reservoir due to the difference in their underlying mechanism. Machine learning model has a good applicability and can be used for accurate analysis of algal blooms in Shanzai Reservoir.

ObjectiveTo establish a rapid detection method for multiple recombinant enzyme polymerase amplification （RPA） of African swine fever virus （ASFV）， Porcine Delta coronavirus （PDCoV）， and Seneca virus type A （SVA）.MethodsRPA detection was carried out using recombinant plasmid as a template， and reaction conditions such as temperature， time， and primer probe ratio were optimized. Multiple RPA detection methods were established， which were applied to the detection of actual samples， and the accuracy of the established method was evaluated by comparing with the results of real-time fluorescence polymerase chain reaction （qPCR）.ResultsSimultaneous detection of the three viruses can be achieved within 20 min with good specificity. Sensitivity to ASFV， PDCoV， and SVA was 940， 770， and 570 copies/μL， respectively. The accuracy rates for actual sample detection were 93.33%， 100.00%， and 100.00%， respectively.ConclusionThe established multiple RPA method is fast and convenient， and it is suitable for on-site preliminary screening of ASFV， PDCoV， and SVA in pork and pork products.

Objective To investigate the application of nurse-led chain management in extended care of children undergoing surgical treatment for Hirschsprung’s disease. Methods Totally 60 children with Hirschsprung’s disease were divided into control group and observation group according to the sequence of hospital admission, with 30 cases in each group. The control group received routine perioperative nursing management, and a nurse-led chain management model was adopted in perioperative nursing management and extended care of children in the observation group. Intervention efficacy was evaluated via incidence of postoperative complications and satisfaction of children’s parents. Results The incidence of postoperative complications in the observation group was lower than that in the control group(P＜0. 05). Parents of children in the observation group were more satisfied with nursing service compared with those in the control group(P＜0. 01). Conclusion The nurse-led chain management in extended care is potentially effective to reduce the risk of postoperative complications and improve the quality of life of children with Hirschsprung’s disease. (目的 探讨以护士为主导的链式管理模式在先天性巨结肠患儿术后延续性护理中的应用效果。方法 将60例先天性巨结肠患儿按照入院时间分为对照组与观察组, 各30例。对照组接受常规先天性巨结肠围手术期管理模式, 观察组采用链式管理协同延续护理模式。干预6个月后评价效果。结果 观察组术后并发症发生率低于对照组, 差异有统计学意义(P＜0. 05)。观察组患儿家属对护理工作的满意度高于对照组, 差异有统计学意义(P＜0. 01)。结论 以护士为主导的链式管理模式有利于减少术后并发症的发生, 对提升先天性巨结肠患儿术后生活质量具有积极意义。)

Abstract Background Anesthesiologists need to appreciate the impact of preoperative anxiety in children. The present study aimed to explore whether interactive multimedia-based home-initiated interventions could effectively relieve preoperative anxiety in pediatric patients. Methods In this prospective study, we compared preoperative anxiety between two groups of children aged 4–9 years. Children in the control group received a question-and-answer (Q&A) introduction, and children in the intervention group received multimedia-based home-initiated preoperative education using comic booklets, videos, and coloring game books. Differences in anxiety between the two groups were evaluated by the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF) at four time points: in the ophthalmology outpatient clinic before intervention as the baseline (T0); in the preoperative waiting area (T1); at the time of separating from their parents and moving to the operating room (T2); and at the time of anesthesia induction (T3). Parental anxiety was assessed by the Self-rating Anxiety Scale (SAS) and Visual Analog Scale (VAS) at T0 and T2. Other related information was collected by questionnaire. Results Eighty-four children who underwent pediatric strabismus in our center between November 2020 and July 2021 were included in this study. An intention-to-treat (ITT) analysis was performed on data from 78 enrolled children. Children in the intervention group exhibited lower m-YPAS-SF scores at T1, T2, and T3 than those in the control group (all p 4) was lower (2.6% vs. 17.5%, p = 0.048). The mean parental VAS score at T2 in the intervention group was significantly lower than that in the control group (p = 0.021). Conclusions Interactive multimedia-based home-initiated intervention could reduce preoperative anxiety in children and improve the quality of anesthesia induction based on ICC scores, which may in turn impose a positive impact on parental anxiety.

In this article, we study the following quasilinear Schrödinger equation: −Δu+V(∣x∣)u−κuΔ(u2)+qh2(∣x∣)∣x∣2(1+κu2)u+q∫∣x∣+∞h(s)s(2+κu2(s))u2(s)dsu=(Iα∗∣u∣p)∣u∣p−2u,x∈R2,-\Delta u+V\left(| x| )u-\kappa u\Delta \left({u}^{2})+q\frac{{h}^{2}\left(| x| )}{| x\hspace{-0.25em}{| }^{2}}\left(1+\kappa {u}^{2})u+q\left(\underset{| x| }{\overset{+\infty }{\int }}\frac{h\left(s)}{s}\left(2+\kappa {u}^{2}\left(s)){u}^{2}\left(s)\hspace{0.1em}\text{d}\hspace{0.1em}s\right)u=\left({I}_{\alpha }\ast | u\hspace{-0.25em}{| }^{p})| u\hspace{-0.25em}{| }^{p-2}u,\hspace{1em}x\in {{\mathbb{R}}}^{2}, where κ\kappa , q>0q\gt 0, p>8p\gt 8, Iα{I}_{\alpha } is a Riesz potential, α∈(0,2)\alpha \in \left(0,2) and V∈C(R2,R)V\in {\mathcal{C}}\left({{\mathbb{R}}}^{2},{\mathbb{R}}). By using Jeanjean’s monotone trick, it can be explored that the aforementioned equation has a ground state solution under appropriate assumptions.

Objective Methods Totally 96 children with appendicitis requiring surgical treatment were divided into the two group according to the sequence of hospital admissions: 48 cases with admission date between Jan and Dec, 2020 were included as the control group, receiving routine management after surgery; 48 cases with admission date between Jan and Dec, 2021 were included as the observation group, receiving nursing management using specialist care quality indicators based on doctor-nurse-patient integration model. The primary outcomes included: ambulation distance within 24 hrs after surgery and rate of qualified early ambulation; Time of first exhaust and defecation, postoperative first out-of-bed activity time, first time to food-taking and incidence of symptoms of postoperative discomfort; satisfaction of children’s parents with communication and information support, respect, emotional support and high-quality nursing care. Results ambulation distance within 24 hrs after surgery in the observation group was longer than that in the control group (P＜0. 01). The rate of qualified early ambulation in the observation group (27. 08%) was higher than that in the control group (97. 92% vs. 27. 08%, P＜0. 01). The time of first exhaust and defecation, postoperative first out-of-bed activity time, first time to food-taking in the observation group was shorter than that in the control group(P＜0. 01, respectively). Parents of children in the observation group were more satisfied with communication and information support, respect, emotional support and high-quality nursing care compared with those in the control group(P＜0. 01). Conclusion Application of specialist care quality indicators based on doctor-nurse-patient integration model is potentially effective to improve the children’s compliance with early ambulation, promote the development of standard nursing procedure, improve the parents’ satisfaction and quality of specialist care. The To investigate the effect of specialist care quality indicators based on doctor-nurse-patient integration model in improving compliance with early ambulation in children with appendicitis. (目的 在加速康复外科理念下, 探讨医护患一体化专科护理质量指标管理提高阑尾炎患儿术后早期下床活动中的效果。方法 选取医院小儿外科2020年1月—2021年12月收治的96例阑尾炎的患儿为研究对象。将2020年1月—12月收治的48例患儿作为对照组, 运用常规护理管理落实术后早期下床活动; 将2021年1月—12月收治的48例患儿作为观察组, 运用医护患一体化专科护理质量指标管理落实术后早期下床活动。比较两组患儿术后24 h下床活动距离及达标情况; 术后首次排气排便时间、首次下床活动时间、首次进食时间、术后不适症状(恶心呕吐及腹胀)发生率; 患儿家属在沟通和信息支持、尊重支持、情感支持以及优质护理照护支持四个维度方面的满意度。结果 观察组患儿术后24 h下床活动距离较对照组增加, 差异有统计学意义(P＜0. 01)。观察组术后24 h下床活动达标率(97. 92%)高于对照组(27. 08%), 差异有统计学意义(P＜0. 01)。观察组术后首次下床活动时间、首次排气时间、首次排便时间、首次进食时间均早于对照组, 差异有统计学意义(P＜0. 01), 观察组术后恶心呕吐腹胀发生率低于对照组, 差异有统计学意义(P＜0. 05)。观察组患儿家属在沟通和信息支持、尊重支持、情感支持以及优质护理照护支持四个维度满意度评分高于对照组, 差异有统计学意义(P＜0. 01)。结论 医护患一体化的专科质量指标的实施, 提高了阑尾炎患儿术后早期下床活动的依从性, 促进了标准护理工作的开展, 提高了患儿家属的满意度, 提升了专科护理服务质量水平。)

Objective To evaluate the impacts of equal ratio ventilation (ERV) mode on lung morphology, gastric inflation and laryngeal mask airway ventilation during laparoscopic radical prostatectomy by lung ultrasound（LUS） and gastric ultrasound. Methods A prospective study was performed in 60 patients with prostate cancer undergoing laparoscopy from June 2021 to May 2022 in Nanjing First Hospital. The patients were randomly divided into ERP group (group E) and conventional ventilation group (group C,n=30, each). After induction of routine intravenous anesthesia and mechanical ventilation with laryngeal mask airway, and the ventilation mode was set as follows: the inspiratory-to-expiratory ratio in group E was 1∶1, while that in group C was 1∶2. After anesthesia induction (T0), 30 minutes after surgery begin (T1), 60 minutes after surgery begin (T2) and 10 minutes after surgery (T3), the peak airway pressure (Ppeak), airway plateau pressure(Pplat), mean airway pressure (Pmean),end-expiratory partial pressure of carbon dioxide (PETCO2) and minute ventilation (MV) were observed and compared between two groups. The LUS score, the cross-sectional area of gastric antrum and fundus and the incidence of airway complications were recorded in two groups. Results At T1 and T2, Ppeak in group E was significantly lower than that in group C(P＜0.05), and Pmean was significantly higher than that in group C(P＜0.05). There was no significant difference in PETCO2 and MV between two groups at different time points (P＞0.05). The LUS and the incidence of atelectasis in group E were statistically lower than those in group C (P＜0.05), and there was no significant difference in the cross-sectional area of gastric antrum and fundus（P＞0.05） and the incidence of airway complications（30.0% vs 32.1%，χ2=0.031，P=0.860) between two groups. Conclusion ERV mode during laparoscopic radical prostatectomy can reduce Ppeak, leakage rate of laryngeal mask, atelectasis and LUS scores without increasing the incidence of gastric inflation and laryngeal mask-related adverse complications.

This paper reviewed the clinical data of 5 newborn infants with acute peripheral vascular lesion, and summarized individualized surgical treatment and nursing management. The types of peripheral vascular lesion included mural thrombus at initiation site of left external iliac vein in 2 cases, false aortic aneurysm of posterior tibial of left leg in 1 case, thrombophlebitis of left leg in 1 case, false aortic aneurysm of at left elbow in 1 case. Based on the analysis of cause analysis, implementation of individualized surgical treatment and nursing strategy may achieve good clinical outcomes in the treatment of acute peripheral vascular lesion in neonates. (回顾性分析医院2015年10月—2022年10月收治的5例外周血管病损的新生儿临床护理资料, 分析发病原因, 总结护理经验。5例新生儿外周血管病损类别: 左髂外静脉起始部完全性附壁血栓2例, 左小腿胫后动脉假性动脉瘤1例, 右小腿血栓性静脉炎1例, 左肘部肱动脉假性动脉瘤1例。对于新生儿外周血管病损, 在治疗及护理过程中, 针对不同的病因造成的病损, 应采取个性化治疗护理进行干预, 取得较好的结局。)

Turner syndrome (TS) is a congenital chromosomal abnormality that affects approximately 1 in 2,500 people. Both in China and abroad, few studies exist on the incidence of tumors in patients with TS. Most reported cases are complicated with gonadal germ cell tumors, and extragonadal tumors are rare, with the latter not yet being reported in China. Through chromosome karyotype analysis and surgical exploration, a pediatric patent was diagnosed with TS complicated with gonadoblastoma and adrenal neuroblastoma. The patient was short in stature and had a facial deformity. After admission, adrenal computed tomography was conducted, and a right adrenal mass was identified as a neurogenic tumor. After surgical resection and gonadal exploration, the pathological results revealed left gonadoblastoma, right gonadal stromal cell hyperplasia, and ganglion neuroblastoma (mixed type) in the right adrenal gland. Pediatric patients with TS have an increased likelihood of developing neuroblastoma and adrenal-related tumors, and changes in adrenal hormone levels and clinical manifestations are often not obvious when combined with adrenal-related tumors. To avoid missed diagnosis and delayed treatment, screening for adrenal tumors is therefore recommended for patients with TS before the initiation of growth hormone treatment.

To achieve better mechanical properties and higher scour resistance of yellow mud in Qiang Village, this study investigated how to improve yellow mud by single factors of straw, starch, cement, and epoxy resin. First, the effect of each material on the shear strength of yellow mud was analyzed through the direct shear test, and the effect of the respective material on the scour resistance of yellow mud was examined using a self-made spray device. Subsequently, combined with the results of the two experiments, the improvement effect of the material was comprehensively studied, and the optimal dosage of the respective material was determined. Lastly, an electron microscope was used to observe the microscopic morphology of the samples, and the improvement mechanism of each material was discussed from qualitative and quantitative perspectives. As revealed by the results, straw, starch, cement, and epoxy resin improved the shear strength and scour resistance of yellow mud. Peaks of straw, starch, and epoxy resin were found in their corresponding properties-dosage curves, corresponding to the optimal dosage in the experimental range. The corresponding performance curve of cement showed a unidirectional change, which was found with a significant improvement effect.

To explore the current development and challenges regarding mobile medical applications (mmAPPs), so as to provide reference for application function elevation and quality improvement.

Abstract Background Both massage and topically administered NSAIDs are safe and effective treatments for knee osteoarthritis (KOA); however, different massage technique sects in China caused assessment difficulties for the treatment of KOA. In order to standardize the massage techniques and procedures, we organized multi-disciplinary experts in China to acquire an evidence-based traditional Chinese medicine massage treatment of knee osteoarthritis. The purposes of this study will be to provide clinicians a complementary and alternative therapy for patients and to evaluate the efficacy and safety of evidence-based traditional Chinese medicine massage treatment of KOA compared to External Diclofenac Diethylamine Emulgel. Methods and design A randomized controlled trial in which 300 participants diagnosed with KOA will be recruited and randomly allocated to either the experimental group or the control group in a ratio of 2:1. Two hundred participants will receive evidence-based traditional Chinese medicine massage 2 sessions per week for 10 weeks as the experimental group, and 100 participants will receive External Diclofenac Diethylamine Emulgel 3–4 times per day for 10 weeks as the control group. The patients in the two groups will receive follow-up at two time points at 5 weeks and 10 weeks from the beginning of treatment, respectively. The MRI scans and X-ray will be performed at baseline and at the end of the intervention. The primary outcome will be the changes in the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Secondary outcomes will be measured by the PRO scale for knee osteoarthritis based on the concept of traditional Chinese medicine (Chinese scale for knee osteoarthritis (CSKO)), X-ray evaluation, and MRI scan evaluation. The data of WOMAC and CSKO will be analyzed at the baseline, 5 weeks, and 10 weeks from the beginning of treatment. The data from MRI scans and X-rays will be analyzed at baseline and at the end of the intervention. The significance level sets as 5%. The safety of interventions will be evaluated after each treatment session. Discussion This study will provide clinicians with much-needed knowledge for the treatment of KOA through a controlled trial. Trial registration Chinese Clinical Trial Registry ChiCTR1800014400 . Registered on 10 January 2018

Objective To investigate the potential regualation of the expression of human maternal gene 3(MEG3) by transcription factor Kaiso and the impact on the occurrence and development of breast cancer. Methods The expression of Kaiso and MEG3 in breast cell line MCF-10a and different breast cancer cell lines MCF-7,BT-474,MDA-MB-435,MDA-MB-231 were detected by RT-qPCR. The expression of Kaiso in cells was detected by Western blot.Kaiso expression of 50 samples from cancer and paracancer tissues were examined by Western blot. RT-qPCR was used to detect the effect of Kaiso over-expressed on the transcription of long non-coding RNA(lncRNA) MEG3. Results The transcription of lncRNA MEG3 in MCF-10a was higher than that of Kaiso (P＜0.001). Kaiso was significantly up-regulated in MCF-7, BT-474, MDA-MB-435, and MDA-MB-231 breast cancer cells,while lncRNA MEG3 was significantly down-regulated (P＜0.001). Kaiso expression level was low in MCF-10a, but was high in MDA-MB-231 highly metastatic breast cancer (P＜0.05). Kaiso was low in paracancerous breast tissues (P＜0.001), but highly expressed in cytoplasm and nucleus in cancer tissues. In addition, Kaiso over-expression in MCF-10a significantly down regulated the transcription of lncRNA MEG3(P＜0.01). Conclusions Kaiso regulates the expression of lncRNA MEG3 by breast cancer cells, which may play an important role in the occurrence and development of breast cancer.

More and more attentions were being paid to the study of tumor stem cells. It has been demonstrated that tumor stem cells were present in both differentiated thyroid cancer with a good prognosis as papillary or follicular cancer and undifferentiated ones with poor prognosis. Thyroid cancer stem cells (TCSCs) play a major role in tumor genesis, progression and metastasis, and may even be the root of recurrence and drug resistance in thyroid cancers. Therefore, the study of TCSCs is great importance to thyroid cancer treatment. In this paper, the authors reviewed the latest researches progress on the origin and survival pathways of TCSCs.

More than 2 billion people around the world still use raw earth architecture, in countries like Nepal, India, and Iran. In China, the proportion of people living in earthen structures rose to 36%, some of them in western Sichuan. Minority dwellings in western Sichuan, China, use local stone and yellow mud as building materials and have been used for thousands of years. Because yellow mud is a brittle material with poor mechanical properties, and because the region is prone to earthquakes, the walls are highly susceptible to damage under seismic action. To improve the mechanical properties of yellow mud, the yellow mud of Taoping Qiang Village in western Sichuan was studied and modified. Uniaxial compressive tests were conducted on the modified specimens, and the existing ontogenetic equations of raw soil-based materials were analyzed and optimized. Finally, we developed the constitutive models for yellow clay and modified yellow clay in the western Sichuan area, which can be used for different kinds of modified materials through the variation of parameters. The results show that the compressive strength of yellow clay is improved by adding the modified materials. The optimized constitutive model can better fit the test curves, which can provide a basis for theoretical calculations and seismic mitigation of minority residential structures in western Sichuan or similar structural systems.

Abstract Pulsing cellular dynamics in genetic circuits have been shown to provide critical capabilities to cells in stress response, signaling and development. Despite the fascinating discoveries made in the past few years, the mechanisms and functional capabilities of most pulsing systems remain unclear, and one of the critical challenges is the lack of a technology that allows pulsatile regulation of transgene expression both in vitro and in vivo. Here, we describe the development of a synthetic BRET-based transgene expression (LuminON) system based on a luminescent transcription factor, termed luminGAVPO, by fusing NanoLuc luciferase to the light-switchable transcription factor GAVPO. luminGAVPO allows pulsatile and quantitative activation of transgene expression via both chemogenetic and optogenetic approaches in mammalian cells and mice. Both the pulse amplitude and duration of transgene expression are highly tunable via adjustment of the amount of furimazine. We further demonstrated LuminON-mediated blood-glucose homeostasis in type 1 diabetic mice. We believe that the BRET-based LuminON system with the pulsatile dynamics of transgene expression provides a highly sensitive tool for precise manipulation in biological systems that has strong potential for application in diverse basic biological studies and gene- and cell-based precision therapies in the future.

Abstract Background and objectives The diagnostic performance of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in the differential diagnosis of pulmonary tumors remained debatable among published studies. This study aimed to pool and summary the relevant results to provide more robust evidence in this issue using a meta-analysis method. Materials and methods The researches regarding the differential diagnosis of lung lesions using IVIM-DWI were systemically searched in Pubmed, Embase, Web of science and Wangfang database without time limitation. Review Manager 5.3 was used to calculate the standardized mean difference (SMD) and 95% confidence intervals of apparent diffusion coefficient (ADC), tissue diffusivity (D), pseudo-diffusivity (D*), and perfusion fraction (f). Stata 12.0 was used to pool the sensitivity, specificity, and area under the curve (AUC), as well as publication bias and heterogeneity. Fagan’s nomogram was used to predict the post-test probabilities. Results Eleven studies with 481 malignant and 258 benign lung lesions were included. Most include studies showed a low to unclear risk of bias and low concerns regarding applicability. Lung cancer demonstrated a significant lower ADC (SMD = -1.17, P

The longitudinal distribution of upper atmospheric density has been broadly studied. However, the studies mostly focused on 24 h averaged distribution. This study presents the longitudinal distribution of thermospheric density at dawn and dusk, using observations collected by the atmospheric density detector onboard the Chinese satellite APOD (Atmospheric Density Detection and Precise Orbit Determination) during low solar activity. The APOD observations show a significant relative longitudinal variation of thermospheric density with global maxima (Δρrmax) near the geomagnetic pole, especially in the winter hemisphere. The annual maximum of Δρrmax appears in the Southern Hemisphere around the June solstices and reaches 26.3% and 39.6% at dawn and dusk, respectively. The auroral heating and meridional wind might play a significant role in the longitudinal variation of thermospheric density. We further compare the APOD observations with the semi-empirical atmospheric model MSIS (Mass Spectrometer Incoherent Scatter Radar) 2.0 predictions under low solar activity conditions. The MSIS 2.0 model reproduces similar longitudinal variations to the observations, with hemispheric asymmetry. The longitudinal variation of thermospheric density from APOD should be related to the distribution of the atmospheric average molecular weight from the model. More observational data are needed to verify the results of this study further.

To investigate the attitude and knowledge score of the elderly in different majors.

Abstract China's lunar exploration program has developed and progressed for more than 13 years. Over this time, Precise Orbit Determination (POD) has guaranteed successful execution of the Chang’e missions, and is the basis for further scientific investigations using radio science data; for example, recovering the lunar gravity field to explore the inner structure and detect craters to study the evolutionary history of the moon. This study briefly reviews the Chang’e series mission orbit and radio tracking measurements. We reprocessed the tracking data and comprehensively summarized the evolution of the POD accuracy and the tracking system precision from the Chang’e 1 to Chang’e 4 missions using in‐house software. Our results show a progression of the tracking station, as the first Chang’e 1 mission only reached several millimeters per second level accuracy in the Doppler measurements and several meters level accuracy for the two‐way range measurements. Later on the accuracy of Chang’e 5T1 Doppler measurements reached about 0.35 mm/s and the accuracy of the Chang’e 3 two‐way range measurements below 0.7 m. Moreover, the newest Chang’e 4 relay satellite achieved POD residuals Root Mean Square for the two‐way range less than a meter and orbital accuracy at 200 m level, in contrast to meters level residual and the half‐kilometer level accuracy achieved during the Chang’e 1 mission. We can clearly see that the POD performance of the Chang’e spacecraft continuously improved. This research study is a reference for future Chinese Lunar exploration missions, as well as Chinese Mars and asteroid explorations.

The radio-occultation technique can provide vertical profiles of planetary ionospheric and atmospheric parameters, which merit the planetary-climate and space-weather scientific research so far. The Tianwen-1 one-way single-frequency radio-occultation technique was developed to retrieve Mars ionospheric and atmospheric parameters. The first radio-occultation event observation experiment was conducted on 5 August 2021. The retrieved excess Doppler frequency, bending angle, refractivity, electron density, neutral mass density, pressure and temperature profiles are presented. The Mars ionosphere M1 (M2) layer peak height is at 140 km (105 km) with a peak density of about 3.7 × 1010 el/m3 (5.3 × 1010 el/m3) in the retrieved electron-density profile. A planetary boundary layer (−2.35 km~5 km), a troposphere (temperature decreases with height) and a stratosphere (24 km–40 km) clearly appear in the retrieved temperature profile below 50 km. Results show that Tianwen-1 radio occultation data are scientifically reliable and useful for further Mars climate and space-weather studies.

Rationale and Objectives: Diffusion kurtosis imaging (DKI) is a promising imaging technique, but the results regarding the diagnostic performance of DKI in the characterization and classification of breast tumors are inconsistent among published studies. This study aimed to pool all published results to provide more robust evidence of the differential diagnosis between malignant and benign breast tumors using DKI.Methods: Studies on the differential diagnosis of breast tumors using DKI-derived parameters were systemically retrieved from PubMed, Embase, and Web of Science without a time limit. Review Manager 5.3 was used to calculate the standardized mean differences (SMDs) and 95% confidence intervals of the mean kurtosis (MK), mean diffusivity (MD), and apparent diffusion coefficient (ADC). Stata 12.0 was used to pool the sensitivity, specificity, and diagnostic odds ratio (DOR) as well as the publication bias and heterogeneity of each parameter. Fagan's nomograms were plotted to predict the post-test probabilities.Results: Thirteen studies including 867 malignant and 460 benign breast lesions were analyzed. Most of the included studies showed a low to unclear risk of bias and low concerns regarding applicability. Breast cancer showed a higher MK (SMD = 1.23, P < 0.001) but a lower MD (SMD = −1.29, P < 0.001) and ADC (SMD = −1.21, P < 0.001) than benign tumors. The MK (SMD = −1.36, P = 0.006) rather than the MD (SMD = 0.29, P = 0.20) or ADC (SMD = 0.26, P = 0.24) can further differentiate invasive ductal carcinoma from ductal carcinoma in situ. The DKI-derived MK (sensitivity = 90%, specificity = 88%, DOR = 66) and MD (sensitivity = 86% and specificity = 88%, DOR = 46) demonstrated superior diagnostic performance and post-test probability (65, 64, and 56% for MK, MD, and ADC) in differentiating malignant from benign breast lesions, with a higher sensitivity and specificity than the DWI-derived ADC (sensitivity = 85% and specificity = 83%, DOR = 29).Conclusion: The DKI-derived MK and MD demonstrate a comparable diagnostic performance in the discrimination of breast tumors based on their microstructures and non-Gaussian characteristics. The MK can further differentiate invasive ductal carcinoma from ductal carcinoma in situ.

Objectives: Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is a promising non-invasive imaging technique to detect and grade prostate cancer (PCa). However, the results regarding the diagnostic performance of IVIM-DWI in the characterization and classification of PCa have been inconsistent among published studies. This meta-analysis was performed to summarize the diagnostic performance of IVIM-DWI in the differential diagnosis of PCa from non-cancerous tissues and to stratify the tumor Gleason grades in PCa.Materials and Methods: Studies concerning the differential diagnosis of prostate lesions using IVIM-DWI were systemically searched in PubMed, Embase, and Web of Science without time limitation. Review Manager 5.3 was used to calculate the standardized mean difference (SMD) and 95% confidence intervals of the apparent diffusion coefficient (ADC), tissue diffusivity (D), pseudodiffusivity (D*), and perfusion fraction (f). Stata 12.0 was used to pool the sensitivity, specificity, and area under the curve (AUC), as well as publication bias and heterogeneity. Fagan's nomogram was used to predict the post-test probabilities.Results: Twenty studies with 854 patients confirmed with PCa were included. Most of the included studies showed a low to unclear risk of bias and low concerns regarding applicability. PCa showed a significantly lower ADC (SMD = −2.34; P < 0.001) and D values (SMD = −1.86; P < 0.001) and a higher D* value (SMD = 0.29; P = 0.01) than non-cancerous tissues, but no difference was noted with the f value (SMD = −0.16; P = 0.50). Low-grade PCa showed higher ADC (SMD = 0.63; P < 0.001) and D values (SMD = 0.80; P < 0.001) than the high-grade lesions. ADC showed comparable diagnostic performance (sensitivity = 86%; specificity = 86%; AUC = 0.87) but higher post-test probabilities (60, 53, 36, and 36% for ADC, D, D*, and f values, respectively) compared with the D (sensitivity = 82%; specificity = 82%; AUC = 0.85), D* (sensitivity = 70%; specificity = 70%; AUC = 0.75), and f values (sensitivity = 73%; specificity = 68%; AUC = 0.76).Conclusion: IVIM parameters are adequate to differentiate PCa from non-cancerous tissues with good diagnostic performance but are not superior to the ADC value. Diffusion coefficients can further stratify the tumor Gleason grades in PCa.

Background: Covid-19 is an infectious disease caused by an invasion of the alveolar epithelial cells by coronavirus 19. The most severe outcome of the disease is the Acute Respiratory Distress Syndrome (ARDS) combined with hypoxemia and cardiovascular damage. ARDS and co-morbidities are associated with inflammatory cytokine storms, sympathetic hyperactivity, and respiratory dysfunction.Hypothesis: In the present paper, we present and justify a novel potential treatment for Covid19-originated ARDS and associated co-morbidities, based on the non-invasive stimulation of the auricular branch of the vagus nerve.Methods: Auricular vagus nerve stimulation activates the parasympathetic system including anti-inflammatory pathways (the cholinergic anti-inflammatory pathway and the hypothalamic pituitary adrenal axis) while regulating the abnormal sympatho-vagal balance and improving respiratory control.Results: Along the paper (1) we expose the role of the parasympathetic system and the vagus nerve in the control of inflammatory processes (2) we formulate our physiological and methodological hypotheses (3) we provide a large body of clinical and preclinical data that support the favorable effects of auricular vagus nerve stimulation in inflammation, sympatho-vagal balance as well as in respiratory and cardiac ailments, and (4) we list the (few) possible collateral effects of the treatment. Finally, we discuss auricular vagus nerve stimulation protective potential, especially in the elderly and co-morbid population with already reduced parasympathetic response.Conclusions: Auricular vagus nerve stimulation is a safe clinical procedure and it could be either an effective treatment for ARDS originated by Covid-19 and similar viruses or a supplementary treatment to actual ARDS therapeutic approaches.

Summary: In addition to acting as building blocks for biosynthesis, amino acids might serve as signaling regulators in various physiological and pathological processes. However, it remains unknown whether amino acid levels affect the activities of hematopoietic stem cells (HSCs). By using a genetically encoded fluorescent sensor of the intracellular levels of branched-chain amino acids (BCAAs), we could monitor the dynamics of BCAA metabolism in HSCs. A mitochondrial-targeted 2C-type Ser/Thr protein phosphatase (PPM1K) promotes the catabolism of BCAAs to maintain MEIS1 and p21 levels by decreasing the ubiquitination-mediated degradation controlled by the E3 ubiquitin ligase CDC20. PPM1K deficiency led to a notable decrease in MEIS1/p21 signaling to reduce the glycolysis and quiescence of HSCs, followed by a severe impairment in repopulation activities. Moreover, the deletion of Ppm1k dramatically extended survival in a murine leukemia model. These findings will enhance the current understanding of nutrient signaling in metabolism and function of stem cells. : Liu et al. show that the dynamics of BCAA metabolism in hematopoietic stem cells (HSCs) and leukemia-initiating cells (LICs) can be monitored by a genetically encoded fluorescent sensor. PPM1K promotes BCAA catabolism and maintains the glycolysis and quiescence of HSCs/LICs through the downregulation of CDC20-mediated ubiquitination of MEIS1 and p21. Keywords: branched-chain amino acids, PPM1K, ubiquitination, CDC20, MEIS1/p21, hematopoietic stem cells, leukemia-initiating cells

With the development of information technology, it is of great practical significance to construct an intelligent teaching platform for business English to supplement the traditional business English teaching. Through the analysis of the current situation of Business English teaching, we can see that the emphasis on theory teaching has neglected the cultivation of students' Business English practical skills. Facing the new business English application environment, by highlighting the characteristics of professionalism and innovation, giving full play to the advantages of information technology application, and building an intelligent teaching platform for business English, promoting business English teaching in an all-round way and realizing real reform.

Abstract Background Dieulafoy’s lesion (DL) is one of the rare causes of upper gastrointestional bleeding. This disease is characterized by small sub-mucosal arteriole that eroded the stomach mucosa and cause severe upper GI bleeding without obvious ulceration. The most common location is fundus area of stomach and usually affects patients over 50 years of age with multiple comorbidities. Case presentation We report a case of life-threatening bleeding from DL during late pregnancy 31 weeks. Hemoclips were used twice through upper endoscopy with successful hemostasis. Unfortunately, she developed HELLP syndrome diagnosed 5 days after the GI bleeding was stopped. Her pregnancy had to be terminated with delivery of a premature infant. She recovered from her illness and discharged from hospital uneventfully. There is no current report in literature of DL in pregnant woman subsequently suffered HELLP syndrome. Conclusion Endoscopic hemoclip application is an effective technique in the treatment of upper GI bleeding from DL. For this patient, laparoscopic surgery or combination therapy before pregnancy may have been a suitable treatment on preventing rebleeding.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death globally, and early detection of high-risk individuals is essential for initiating timely interventions. The authors aimed to develop and validate a deep learning (DL) model to predict an individuals elevated 10-year ASCVD risk score based on retinal images and limited demographic data. METHODS: The study used 89,894 retinal fundus images from 44,176 UK Biobank participants (96% non-Hispanic White, 5% diabetic) to train and test the DL model. The DL model was developed using retinal images plus age, race/ethnicity, and sex at birth to predict an individuals 10-year ASCVD risk score using the pooled cohort equation (PCE) as the ground truth. This model was then tested on the US EyePACS 10K dataset (5.8% non-Hispanic White, 99.9% diabetic), composed of 18,900 images from 8969 diabetic individuals. Elevated ASCVD risk was defined as a PCE score of ≥7.5%. RESULTS: In the UK Biobank internal validation dataset, the DL model achieved an area under the receiver operating characteristic curve of 0.89, sensitivity 84%, and specificity 90%, for detecting individuals with elevated ASCVD risk scores. In the EyePACS 10K and with the addition of a regression-derived diabetes modifier, it achieved sensitivity 94%, specificity 72%, mean error -0.2%, and mean absolute error 3.1%. CONCLUSION: This study demonstrates that DL models using retinal images can provide an additional approach to estimating ASCVD risk, as well as the value of applying DL models to different external datasets and opportunities about ASCVD risk assessment in patients living with diabetes.