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Kui Kang,1 Ying Wang,2 Bo Zhang,1 Zhengxing Xie,1 Sheng Qing,1 Yanan Di1 1Department of Gastroenterology, Beijing Aerospace General Hospital, Beijing, People’s Republic of China; 2Department of Endocrinology, Air Force Specialty Medical Center, Beijing, People’s Republic of ChinaCorrespondence: Yanan Di, Department of Gastroenterology, Beijing Aerospace General Hospital, 7 Wanyuan North Road, Fengtai District, Beijing, 100076, People’s Republic of China, Email diyanan4658@sina.comBackground: The biological function and prognostic significance of endothelial cell specific molecule 1 (ESM1) in various cancers have been validated. This study aimed to explore the expression and clinical diagnosis values in patients with stomach adenocarcinoma (STAD) and esophageal carcinoma (ESCA).Methods: Online database Gene Expression Omnibus was used to screen for abnormally expressed genes in STAD and ESCA. Besides, 36 STAD and 36 ESCA patients were enrolled, and their corresponding control groups were also 36 people each. Reverse transcription-quantitative polymerase chain reaction and Western blot were performed to analyze the expression of ESM1. Overall survival (OS) curve and receiver operating characteristics curve (ROC) analysis were used to assess the prognosis, and the sensitivity and specificity of ESM1 for the diagnosis of STAD and ESCA, respectively. Additionally, the effects of ESM1 on cell viability, migration, and invasion were analyzed by cell counting kit-8, transwell migration and invasion assays.Results: The results showed that the poor OS of STAD and ESCA patients was correlated with high ESM1. Besides, ESM1 was increased in ESCA and STAD in in vivo and in vitro studies. ESM1 has a high accuracy [area under the curve (AUC) > 0.79] at stage I and IV of STAD and ESCA. Knockdown of ESM1 suppressed the cell viability, migration, and invasion and increased the apoptosis rate of AGS and TE1 cells.Conclusion: Our study suggested that ESM1 might be used as a new indicator for the diagnosis and prognosis of early and advanced stage digestive tract cancers.Keywords: STAD, ESCA, ESM1, ROC, diagnosis, prognosis

Background: Family caregivers of people with cancer report high levels of psychological distress. Yoga, with well-documented mental health benefits, could be a useful intervention to address distress in this population. However, little is known about yoga practices among cancer caregivers. The present study evaluates their interest in and barriers to yoga practice. Methods: We conducted a cross-sectional survey study of family caregivers of cancer patients at five suburban satellite locations of an academic cancer center. Survey items and statistical analyses focused on yoga usage as well as interest in and barriers to yoga practice. Results: Among 539 participants, most were females (64.8%), white (84.2%), and caring for a spouse or partner (54.7%). Interest in practicing yoga among study participants was 42.3%. Increased interest was independently associated with being females (odds ratio [OR] = 3.30, 95% confidence interval [CI] = 1.98–5.51, P < 0.001) and employed (part-time: OR = 2.58, 95% CI = 1.1–6.18, P = 0.03; full-time: OR = 1.77, 95% CI = 1.1–2.01, P = 0.02). Few participants (6.3%) were currently practicing yoga, although 31% had done so in the past. Sixty-one percent of those who had practiced before their loved one's diagnosis stopped practicing yoga afterward. Commonly cited barriers to yoga practice included time constraints (37.3%) and psychological obstacles (33.6%). About a quarter of those who had never practiced yoga lacked awareness of yoga's benefits (26.6%). Conclusion: Despite the low use of yoga, interest in practicing was moderately high, especially among women and employed caregivers. As caregivers face numerous barriers to yoga practice, strategies are needed to overcome these barriers and help them access yoga's health benefits.

Abstract Background Yoga is a meditative movement therapy focused on mind‐body awareness. The impact of yoga on health‐related quality of life (HRQOL) outcomes in patients with chemotherapy‐induced peripheral neuropathy (CIPN) is unclear. Methods We conducted a pilot randomized wait‐list controlled trial of 8 weeks of yoga (n = 21) versus wait‐list control (n = 20) for CIPN in 41 breast and gynecological cancer survivors with persistent moderate to severe CIPN. HRQOL endpoints were Hospital Anxiety and Depression Scale (HADS), Brief Fatigue Inventory (BFI), and Insomnia Severity Index (ISI). The Treatment Expectancy Scale (TES) was administered at baseline. We estimated mean changes and 95% confidence intervals (CIs) from baseline to weeks 8 and 12 and compared arms using constrained linear mixed models. Results At week 8, HADS anxiety scores decreased −1.61 (−2.75, −0.46) in the yoga arm and −0.32 (−1.38, 0.75) points in the wait‐list control arm (p = 0.099). At week 12, HADS anxiety scores decreased −1.42 (−2.57, −0.28) in yoga compared to an increase of 0.46 (−0.60, 1.53) in wait‐list control (p = 0.017). There were no significant differences in HADS depression, BFI, or ISI scores between yoga and wait‐list control. Baseline TES was significantly higher in yoga than in wait‐list control (14.9 vs. 12.7, p = 0.019). TES was not associated with HADS anxiety reduction and HADS anxiety reduction was not associated with CIPN pain reduction. Conclusions Yoga may reduce anxiety in patients with CIPN. Future studies are needed to confirm these findings. Clinical Trial Registration Number: ClinicalTrials.gov Identifier: NCT03292328.

Purpose: Many cancer survivors experience cancer-related cognitive impairment (CRCI). We conducted a randomized controlled pilot trial of 2 types of yoga practice and evaluated their effects on participants’ objective cognitive function. Methods: Sedentary breast or ovarian cancer survivors were randomized to practice either restorative yoga (with more meditative practice and minimal physical exertion) or vigorous yoga (with considerable physical exertion and minimal meditative practice) in 60-minute supervised sessions 3 times a week for 12 weeks, followed by 12 weeks of home practice. We used the NIH Toolbox Cognition Domain to evaluate participants at baseline, week 12, and week 24. Results: We enrolled 35 participants. For women in the restorative yoga group, overall cognitive function was statistically significantly improved at weeks 12 and 24 compared to baseline ( P = .03 and 0.004; Cohen’s D = 0.3 and 0.5). Fluid cognitive function also significantly improved at weeks 12 and 24 ( P = .02 and 0.0007; Cohen’s D = 0.3 and 0.6), whereas improvements in crystallized cognition were not significant. For women in the vigorous yoga group, significant improvement was only seen in tasks of crystallized cognition at week 24 ( P = .03; Cohen’s D = 0.5). Between-group comparisons showed that at week 24, women in the restorative yoga group had significantly higher scores on fluid cognition tasks. Conclusions: Patients who participated in yoga practice demonstrated improvement in objective cognitive function over time. Restorative yoga may be more effective in improving fluid cognitive function at week 24 when compared to vigorous yoga. These promising findings should be confirmed in definitive studies. Trial registration: Clinicaltrials.gov; NCT02305498 (Date Registered: December 2, 2014)

Abstract Background Supportive care is a critical component of the treatment of cancer patients that is underutilized; patient lack of information about these services is an important barrier. Mobile technologies may be useful tools for delivering information, but cancer patient use of and interest in using them to learn about supportive care services have not been described. This study evaluates factors associated with cancer patient use of mobile technologies and interest in smartphone applications for information delivery about supportive care. Methods We conducted a cross‐sectional survey among cancer patients from one urban academic hospital and 11 community hospitals. Patients self‐reported use of mobile technologies and interest in smartphone applications. Multivariate logistic analysis was used to identify determinants of mobile technology use and smartphone interest. Results Among 631 participants, 466 (74%) reported regular use of mobile devices and 242 (39%) expressed an interest in supportive care information via smartphone applications. Patients under 45 were more likely to use a mobile device (Adjusted Odds Ratio [AOR] 6.8, 2.8‐16.9 95% CI, P

Xiaofei Zhu,* Fuqi Li,* Dongchen Shi,* Xiaoping Ju,* Yangsen Cao, Yuxin Shen, Fei Cao, Shuiwang Qing, Fang Fang, Zhen Jia, Huojun Zhang Department of Radiation Oncology, Changhai Hospital Affiliated to Navy Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: To compare the effects of gemcitabine and nab-paclitaxel (GT) plus stereotactic body radiation therapy (SBRT) or gemcitabine and S-1 (GS) plus SBRT on health-related quality of life (HRQOL) of metastatic pancreatic cancer. Methods: Patients with biopsy-proven and radiographically metastatic pancreatic cancer were included. HRQOL was assessed using the Chinese version of Brief Pain Inventory (BPI) and 5-level European quality of life 5-dimensions (EQ-5D-5L). Data were analyzed with Spearman’s rank correlation, ordinal regression, and propensity score-matched analysis. Results: A total of 75 and 89 patients received GT and GS, respectively. The median biological effective dose of GT group and GS group was 59.5 Gy (range 48–85.5 Gy) and 64.4 Gy (range 52.48–85.5 Gy) in 5–8 fractions, respectively. More patients in the GS group had improvement in BPI and EQ-5D-5L compared with those in the GT group (n=38 vs n=15, P

Xiaofei Zhu,1,* Fuqi Li,1,* Wenyu Liu,2,* Dongchen Shi,1,* Xiaoping Ju,1 Yangsen Cao,1 Yuxin Shen,1 Fei Cao,1 Shuiwang Qing,1 Fang Fang,1 Zhen Jia,1 Huojun Zhang1 1Departmant of Radiation Oncology, Changhai Hospital affiliated to Navy Medical University, Shanghai, China; 2Departmant of Surgery, Changhai Hospital affiliated to Navy Medical University, Shanghai, China *These authors contributed equally to this article Background: To evaluate and compare the efficacy and safety of stereotactic body radiation therapy (SBRT) plus induction chemotherapy and SBRT plus adjuvant therapy. Methods: Patients with radiographically resectable, biopsy-proven pancreatic cancer were enrolled. Data were prospectively collected from 2012 to 2016. Cox proportional hazards regression was used to identify factors predictive of survival. Propensity score matching analysis was performed to assess the efficacy of SBRT combined with different timing of chemotherapy. Results: One hundred patients were enrolled with 48 receiving induction chemotherapy and 52 undergoing adjuvant chemotherapy. The median overall survival (OS) and progression-free survival (PFS) were 17.5 months (95% CI: 15.8–19.2 months) and 13.7 months (95% CI: 12.3–15.1 months), respectively. Patients with adjuvant chemotherapy (P

Acquiring water is essential for all animals, but doing so is most challenging for desert-living animals. Recently Przewalski's horse has been reintroduced to the desert area in China where the last wild surviving member of the species was seen before it vanished from China in the 1960s. Its reintroduction placed it within the range of a close evolutionary relative, the con-generic Khulan. Determining whether or not these two species experience competition and whether or not such competition was responsible for the extinction of Przewalski's horses in the wild over 50 years ago, requires identifying the fundamental and realized niches of both species. We remotely monitored the presence of both species at a variety of water points during the dry season in Kalamaili Nature Reserve, Xinjiang, China. Przewalski's horses drank twice per day mostly during daylight hours at low salinity water sources while Khulans drank mostly at night usually at high salinity water points or those far from human residences. Spatial and temporal differences in water use enables coexistence, but suggest that Przewalski's horses also restrict the actions of Khulan. Such differences in both the fundamental and realized niches were associated with differences in physiological tolerances for saline water and human activity as well as differences in aggression and dominance.

Here we report the construction of a histidine-tagged T4 RNA ligase expression plasmid (pRHT4). The construct, when overexpressed in BL21 (DE3) cells, allows the preparation of large quantities of T4 RNA ligase in high purity using only a single purification column. The histidine affinity tag does not inhibit enzyme function, and we were able to purify 1–3 mg pure protein/g cell pellet. A simple purification procedure ensures that the enzyme is de-adenylated to levels comparable to those found for many commercial preparations. The purified protein has very low levels of RNase contamination and functioned normally in a variety of activity assays.

Internal ribosome entry sites (IRES) are utilized by a subset of cellular and viral mRNAs to initiate translation during cellular stress and virus infection when canonical cap-dependent translation is compromised. The intergenic region (IGR) IRES of the Dicistroviridae uses a streamlined mechanism in which it can directly recruit the ribosome in the absence of initiation factors and initiates translation using a non-AUG codon. A subset of IGR IRESs including that from the honey bee viruses can also direct translation of an overlapping +1 frame gene. In this study, we systematically examined cellular conditions that lead to IGR IRES-mediated 0 and +1 frame translation in Drosophila S2 cells. Towards this, a novel bicistronic reporter that exploits the 2A "stop-go" peptide was developed to allow the detection of IRES-mediated translation in vivo. Both 0 and +1 frame translation by the IGR IRES are stimulated under a number of cellular stresses and in S2 cells infected by cricket paralysis virus, demonstrating a switch from cap-dependent to IRES-dependent translation. The regulation of the IGR IRES mechanism ensures that both 0 frame viral structural proteins and +1 frame ORFx protein are optimally expressed during virus infection.

The lung's unique extracellular matrix (ECM), while providing structural support for cells, is critical in the regulation of developmental organogenesis, homeostasis and injury-repair responses. The ECM, via biochemical or biomechanical cues, regulates diverse cell functions, fate and phenotype. The composition and function of lung ECM become markedly deranged in pathological tissue remodeling. ECM-based therapeutics and bioengineering approaches represent promising novel strategies for regeneration/repair of the lung and treatment of chronic lung diseases. In this review, we assess the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECM in normal and aberrant lung development, adult lung diseases and autoimmunity; and ECM in the regulation of the stem cell niche. We identify opportunities to advance the field of lung ECM biology and provide a set recommendations for research priorities to advance knowledge that would inform novel approaches to the pathogenesis, diagnosis, and treatment of chronic lung diseases.

Development of the pulmonary system is essential for terrestrial life. The molecular pathways that regulate this complex process are beginning to be defined, and such knowledge is critical to our understanding of congenital and acquired lung diseases. A recent workshop was convened by the National Heart, Lung, and Blood Institute to discuss the developmental principles that regulate the formation of the pulmonary system. Emerging evidence suggests that key developmental pathways not only regulate proper formation of the pulmonary system but are also reactivated upon postnatal injury and repair and in the pathogenesis of human lung diseases. Molecular understanding of early lung development has also led to new advances in areas such as generation of lung epithelium from pluripotent stem cells. The workshop was organized into four different topics, including early lung cell fate and morphogenesis, mechanisms of lung cell differentiation, tissue interactions in lung development, and environmental impact on early lung development. Critical points were raised, including the importance of epigenetic regulation of lung gene expression, the dearth of knowledge on important mesenchymal lineages within the lung, and the interaction between the developing pulmonary and cardiovascular system. This manuscript describes the summary of the discussion along with general recommendations to overcome the gaps in knowledge in lung developmental biology.

Abstract Background It is important to detect the predictors of prediabetes progressing to diabetes. Although polyols affect glycometabolism, little is known about the association between fasting serum polyol levels of participants with habitual diet and the risk of prediabetes progressing to type 2 diabetes. Methods In this nested case-control study, 180 participants who developed from prediabetes to type 2 diabetes (progressors), and 180 matched controls (non-progressors) with prediabetes during a 3.5-year follow-up were enrolled. The baseline levels of serum polyols in the fasting state were quantified using time-of-flight mass spectrometry. Multivariate conditional logistic regression was performed to assess the effects of the differential polyol levels on the risk of incident diabetes from prediabetes. Results The baseline fasting xylitol levels, but not sorbitol or erythritol levels, were higher in non-progressors than in progressors (P

Abstract Background Conjunctival sporotrichosis is a rare fungal infection, typically presenting as granulomatous lesions. Its manifestations can be atypical, particularly in immunosuppressed patients. Here, we present a rare case of a Mooren’s ulcer patient with bulbar conjunctival Sporotrichosis presenting as a salmon-pink tumor. Case presentation A 61-year-old with a history of Mooren’s ulcer and corneal transplantation was diagnosed with conjunctival Sporotrichosis in the left eye. Slit-lamp examination showed conjunctival congestion and edema with a salmon-pink appearance, accompanied by nodules looking like “bread crumbs” scattered under the conjunctiva. After partial tumor resection, histopathology and immunofluorescence staining suggested fungal infection with squamous epithelial hyperplasia. Microbiological testing (DNA) confirmed Sporothrix schenckii as the pathogen. The conjunctival mass resolved without recurrence after local and systemic anti-fungal medicine treatment. Despite the progression of Mooren’s ulcers, which further dissolved and perforated during treatment, aggressive management helped the patient retain some vision. Conclusion Immunosuppression, such as steroids and tacrolimus eyedrops, may predispose patients to opportunistic infections like sporotrichosis. Oral itraconazole, combined with subconjunctival and topical antifungal therapy, effectively treat severe Sporothrix conjunctivitis. Future studies should explore the balance between antifungal and immunosuppressive therapies to manage coexisting conditions like Mooren’s ulcer while curing fungal infections.

Abstract Digestive and psychiatric disorders tend to co-occur, yet mechanisms remain unclear. Leveraging genetic and transcriptomic data integration, we conduct multi-trait analysis of GWAS (MTAG) and weighted gene co-expression network analysis (WGCNA) to explore shared mechanism between psychiatric and gastrointestinal disorders. Significant genetic correlations were found between these disorders, especially in irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), depression (DEP), and neuroticism (NE). MTAG identify 60 novel pleiotropic loci for IBS and 14 for GERD, predominantly located near genes associated with neurological pathways. Further WGCNA identifies multiple co-expression modules enriched with genes involved in neurological pathways in digestive tissues, with some modules strongly preserved across brain and digestive tissues. Moreover, our network analysis suggests BSN, CELF4, and NRXN1 as central players in the regulation of the gut-brain axis (GBA). This study enhances our understanding of the GBA and underscores BSN, CELF4, and NRXN1 as crucial targets for future research.

Abstract Atherosclerosis is a primary cause of cardiovascular disease, straining healthcare systems. Dendrobium officinale, a widely used food-medicine homology, has demonstrated anti-atherosclerotic (anti-AS) properties, with other species listed in pharmacopoeias exhibiting similar effects. However, their efficacy varies, and the impact of interspecies variations on compounds and mechanisms in Dendrobium’s anti-AS effects remains unclear. This study aimed to explore the anti-AS compounds and mechanisms across various Dendrobium species. The chemical composition of D. fimbriatum, D. officinale, D. devonianum, D. gratiosissimum, and D. catenatum was analyzed using UPLC-Q-Exactive Orbitrap MS. Network pharmacology predicted the pharmacological basis and molecular mechanisms. Molecular docking experiments assessed the binding affinity of the identified compounds with target proteins. A total of 12 different and 65 common components were identified. Key therapeutic targets included SRC, STAT3, and PIK3CA, along with relevant signaling pathways linked to AS prevention. The study provides insights into interspecies differences in Dendrobium’s anti-AS properties.

Abstract Background The evolution and development of flowers are biologically essential and of broad interest. Maize and sorghum have similar morphologies and phylogeny while harboring different inflorescence architecture. The difference in flower architecture between these two species is likely due to spatiotemporal gene expression regulation, and they are a good model for researching the evolution of flower development. Results In this study, we generated single nucleus and spatial RNA-seq data for maize ear, tassel, and sorghum inflorescence. By combining single nucleus and spatial transcriptome, we can track the spatial expression of single nucleus cluster marker genes and map single nucleus clusters to spatial positions. This ability provides great power to annotate the single nucleus clusters. Combining the cell cluster resolved transcriptome comparison with genome alignment, our analysis suggested that maize ear and tassel inflorescence diversity is associated with the maize-specific whole genome duplication. Taking sorghum as the outgroup, it is likely that the loss of gene expression profiling contributes to the inflorescence diversity between tassel and ear, resulting in the unisexual flower architecture of maize. The sequence of highly expressed genes in the tassel is more conserved than the highly expressed genes in the ear. Conclusion This study provides a high-resolution atlas of gene activity during inflorescence development and helps to unravel the potential evolution associated with the differentiation of the ear and tassel in maize.

The performance inconsistency in belt cleaning post-discharge presents significant challenges in long-term usage of mine belt conveyors. Issues include material adhesion, dust dispersion, and material spills, posing a direct impact on transportation safety and the effective utilization of energy. Responding to this problem, we propose an effective and environmentally friendly intelligent conveyor system leveraging Digital Twin (DT) technology. In this conceptual model, an Online Sequential Extreme Learning Machine (OS-ELM) is applied within the virtual component to construct a near real-time model predicting sweeping force, using physical feedback data as input parameters. Within the physical counterpart, the sweep force in practice is computed by integrating mechanical models, intellectual and experiential knowledge from the engineering field, as well as operational data. Moreover, forecast values of sweep force at the current moment help formulate the dispatch plan for the cleaning mechanism in the next moment, thus ensuring precise control of the physical model. The Improved Whale Optimization Algorithm (IWOA) is employed to optimize parameters in this blueprint, facilitating real-time scheduling by rapidly converging to the global optimum. In evaluating system performance, we establish key performance indicators: the amount of spillage, wear of crucial components, total power used by the cleaning mechanism, and accuracy in predicting the sweeping force. We compare our system’s performance under various operational scenarios against an array of common optimization algorithms. Simultaneously, we use Sobol’s method and the Fast sensitivity analysis to verify our model’s input reasonability. Results show that the DT-based intelligent conveyor system reduces coal spillage to less than 100 g/min, decreases blade wear rate by 8.99%, cuts actual power consumption by 8.61%, with Mean Absolute Percentage Error (MAPE) and Root Mean Square Error (RMSE) in sweep force prediction being 3.2748% and 0.017 respectively. The innovative solution establishes dynamic informational mapping between the virtual and real worlds. This process helps gain precise real-time readings of sweeping forces in conveyor systems and enables the reasonable dispatch of multiple levels of sweeping mechanisms. Consequently, it significantly lightens maintenance workloads, mitigates environmental pollution, and greatly enhances the safety and stability of conveyor equipment.

Abstract Background Hepatic organoids (HOs), validated through comparative sequencing with human liver tissues, are reliable models for liver research. Comprehensive transcriptomic and proteomic sequencing of HOs throughout their induction period will enhance the platform’s utility, aiding in the elucidation of liver development’s molecular mechanisms. Methods We developed hepatic organoids (HOs) from embryonic stem cells (ESCs) through a de novo induction protocol, mimicking the stages of fetal liver development: ESCs to definitive endoderm (DE), then to foregut (FG), hepatoblasts (HB), and finally to HOs stage 1 (HO1), culminating in self-organizing HOs stage 2 (HO2) via dissociation and re-inoculation. The successful establishment of HOs was validated by immunofluorescence staining and RT-qPCR for specific markers. Comprehensive transcriptomic and proteomic sequencing and analysis were conducted on FG, HB, HO1, and HO2. Results Our data suggest that several transcription factors (TFs) activated during the HB stage share overlapping target genes with the vitamin D receptor (VDR). Calcitriol, a direct activator of VDR, notably facilitated the FG to HB stage transition by activating VDR and enhancing key TFs, thereby promoting hepatic progenitor cell maturation. Furthermore, our findings revealed a significant transition towards glycolytic energy metabolism at the HO2 stage, characterized by increased glycolytic flux and reduced oxidative phosphorylation. Inhibition of glycolysis using 2-deoxy-D-glucose (2-DG) led to suppressed growth and differentiation at the HO2 stage. Analysis of signaling pathways indicated upregulation of the HIF-1 pathway, which is associated with glycolysis activation, as well as the MAPK and PI3K-AKT pathways, which regulate HIF-1α protein translation. Conclusions We elucidated a pivotal role for calcitriol in facilitating the transition from FG to HB by activating VDR and augmenting the expression of critical transcription factors (TFs). Besides, our research underscores a shift in metabolic pathways toward glycolytic energy metabolism in HO2 organoids. Overall, our multiomics approach reveals the intricate molecular regulation during the development of HOs.

Abstract Early dissemination refers to the process by which cancer cells spread to distant organs at an early stage of the disease, often before the primary tumor is clinically detectable. Experimental studies have demonstrated that Her2 promotes early dissemination of breast cancer by inhibiting the p38 signaling pathway. However, the precise mechanism by which Her2 suppresses the activation of p38 signaling in early-stage cancer cells (ECCs) remains unclear. Here, we report that MAP3K4, an upstream kinase of p38, is downregulated in Her2 + ductal carcinoma in situ (DCIS) cells and tissues, which is required for Her2-induced early dissemination of DCIS cells by regulating the activation of the p38 signaling cascade. Furthermore, Her2 suppresses the transcription of MAP3K4 by downregulating the expression of HOXB13, a crucial transcription factor contributing to MAP3K4 expression in DCIS cells. Together, these findings unveil a novel downstream regulatory mechanism through which Her2 inhibits the activation of p38 signaling and facilitates early dissemination of breast cancer, offering insights into the development of effective diagnostic methods and targeted therapies for inhibiting the early dissemination of Her2 + breast cancer.

ObjectiveTo investigate the effects of miR-4531/CX3CL1 signaling pathway on the vascular injury in preeclampsia, and to search possible targets for early diagnosis and prevention of preeclampsia. MethodsPlacental tissue samples were obtained from 10 patients with late-onset preeclampsia and 10 normal pregnant women in the Obstetrics and Gynecology Department of Minhang Hospital, Fudan University from October 2021 to December 2022. The levels of miR-4531 and CX3CL1 were evaluated by qRT-PCR. Cell transfection was performed by lipofectamine 2000 in vitro. The binding relationship between miR-4531 and CX3CL1 was determined by luciferase reporter assay. The apoptosis of neutrophils, the migration, repair, colony formation and cell-free DNA (cfDNA) release of human umbilical vein endothelial cells (HUVECs) were detected. ResultsMiR-4531 was significantly downregulated, and CX3CL1 was upregulated in placental tissues of preeclampsia patients (P＜0.05). Luciferase report assay confirmed the direct binding relationship between miR-4531 and CX3CL1. Upregulation of miR-4531significantly promoted the migration, proliferation, repair, and inhibited cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition (P＜0.05). However, downregulation of miR-4531 obviously inhibited the proliferation, migration, repair, and enhanced cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition (P＜0.05). ConclusionsThe miR-4531is downregulated in placental tissues of preeclampsia parients and is a potential therapeutic target for preeclampsia. It might cause endothelial damage and an abnormal hypercoagulable state under hypoxic condition by targeting and regulating the CX3CL1 pathway.

Abstract Background Developing proficiency in ultrasound-guided nerve block (UGNB) demands an intricate understanding of cross-sectional anatomy as well as spatial reasoning, which is a big challenge for beginners. The aim of this pilot study was to evaluate the feasibility of virtual reality (VR)-facilitated anatomy education in the first performance of ultrasound-guided interscalene brachial plexus blockade among novice anesthesiologists. We carried out pilot testing of this hypothesis using a prospective, single blind, randomized controlled trial. Methods Twenty-one anesthesia trainees with no prior ultrasonography or nerve block training were included in this study. All participants underwent a training program encompassing theory and hands-on practice. Trainees were randomized into one of two groups: one received VR-assisted anatomy course while the other did not. Subsequently, both groups completed identical practical modules on ultrasound scanning and needle insertion. The primary end point was defined as the evaluation of trainees’ performance during their initial ultrasound-guided interscalene brachial plexus block, assessed using both the Global Rating Scale (GRS) and a task-specific Checklist. The secondary end point included the improvement in scores for written multiple-choice questions (MCQs). Results In evaluating practical ultrasound-guided nerve block skills, the VR group significantly outperformed the control group on the task-specific Checklist (29.23 ± 3.91 vs. 24.85 ± 5.13; P 0.05). Conclusions Overall, the findings of this pilot study suggest that immersive virtual reality training in anatomy may contribute to improving the proficiency of ultrasound-guided brachial plexus blocks among novice anesthesiologists. Incorporating VR into future anesthesia technique training programs should be considered. Trial registration ClinicalTrials.gov identifier: ChiCTR2300067437. Date of Registration Jan 9, 2023.

Uveal melanoma (UM) poses a significant lethality, with approximately 50% of those developing metastases surviving less than one year. In the progression of UM, vasculogenic mimicry (VM) induced by hypoxia plays a pivotal role, which also partially explains the resistance of UM to anti-angiogenic therapies. Nevertheless, the crucial molecular mechanisms underlying VM in the progression of UM remain unclear. We identified ubiquitin conjugating enzyme E2 G2 (UBE2G2) as a critical suppressor through transcriptomic sequencing and metastasis correlation screening. In UM, hypoxia-induced VM and metastasis are markedly exacerbated by UBE2G2 knockdown and significantly alleviated by its overexpression. Mechanistically, UBE2G2 directly binds to galectin 3 binding protein (LGALS3BP) and forms a complex with the E3 ubiquitin ligase tripartite motif containing 38 (TRIM38), facilitating ubiquitination-mediated degradation of LGALS3BP at the K104 residue. Furthermore, UBE2G2 inhibits oncogenic phenotypes by inactivating intracellular PI3K/AKT signaling and reprogramming the tumor microenvironment. Therefore, targeting intercellular and intracellular molecular mechanisms of the hypoxia–UBE2G2–LGALS3BP axis may contribute to developing various therapeutic strategies for UM.

ABSTRACT: Breastfeeding by mothers with gestational diabetes mellitus (GDM) has been shown to reduce maternal insulin demands and diminish the risks of diabetes in infants, leading to improved long-term health outcomes. Milk fat globule membrane (MFGM) proteins play a crucial role in influencing the immunity and cognitive development of infants. Understanding the alterations in MFGM proteins in breast milk from mothers with GDM is essential for enhancing their self-efficacy and increase breastfeeding rates. The objective of this study is to investigate and compare MFGM proteins in milk from mothers with and without GDM based on tandem mass tag (TMT) labeling and liquid chromatography–tandem MS techniques. A total of 5,402 proteins were identified, including 4 upregulated proteins and 24 downregulated proteins. These significantly altered proteins were found to be associated with human diseases, cellular processes, and metabolism pathways. Additionally, the oxidative phosphorylation pathway emerged as the predominant pathway through Gene Set Enrichment Analysis involving all genes.

One of the challenges in the field of multi-photon 3D laser printing lies in further increasing the print speed in terms of voxels/s. Here, we present a setup based on a 7 × 7 focus array (rather than 3 × 3 in our previous work) and using a focus velocity of about 1 m/s (rather than 0.5 m/s in our previous work) at the diffraction limit (40×/NA1.4 microscope objective lens). Combined, this advance leads to a ten times increased print speed of about 108 voxels/s. We demonstrate polymer printing of a chiral metamaterial containing more than 1.7 × 1012 voxels as well as millions of printed microparticles for potential pharmaceutical applications. The critical high-quality micro-optical components of the setup, namely a diffractive optical element generating the 7 × 7 beamlets and a 7 × 7 lens array, are manufactured by using a commercial two-photon grayscale 3D laser printer.

Zeqi ( Euphorbia helioscopia L. ), is a widely distributed plant of the Euphorbiaceae family. Zeqi is a famous Chinese herbal medicine with the effects of inducing diuresis for removing edema, killing pathogens and relieve itching, etc. It can be used to treat edema, dysentery, osteomyelitis, cancer and many other diseases. With the development of processing and extraction technologies, a series of active substances have been extracted from Zeqi, including terpenes, steroids, tannins and flavonoids. Among these components, terpenes are the most abundant. Recent pharmacological studies indicated that Zeqi has multifunction including antitumor activity, antiviral activity, anti-inflammatory activity, anthelmintic activity, antibacterial activity, and antioxidant activity. To provide a more comprehensive analysis of the application of traditional Chinese medicine Zeqi in clinical treatment and modern medicine, we summarize in this review the pharmacological studies on Zeqi in recent years.

Fast and non-destructive analysis of material defect is a crucial demand for semiconductor devices. Herein, we are devoted to exploring a solar-cell defect analysis method based on machine learning of the modulated transient photovoltage (m-TPV) measurement. The perturbation photovoltage generation and decay mechanism of the solar cell is firstly clarified for this study. High-throughput electrical transient simulations are further carried out to establish a database containing millions of m-TPV curves. This database is subsequently used to train an artificial neural network to correlate the m-TPV and defect properties of the perovskite solar cell. A Back Propagation neural network has been screened out and applied to provide a multiple parameter defect analysis of the cell. This analysis reveals that in a practical solar cell, compared to the defect density, the charge capturing cross-section plays a more critical role in influencing the charge recombination properties. We believe this defect analysis approach will play a more important and diverse role for solar cell studies.

Abstract Background Alcohol drinking and gut microbiota are related to hepatocellular carcinoma (HCC), but the specific relationship between them remains unclear. Aims We aimed to establish the alcohol drinking-gut microbiota-liver axis and develop machine learning (ML) models in predicting the occurrence of early-stage HCC. Methods Two hundred sixty-nine patients with early-stage HCC and 278 controls were recruited. Alcohol drinking-gut microbiota-liver axis was established through the mediation/moderation effect analyses. Eight ML algorithms including Classification and Regression Tree (CART), Gradient Boosting Machine (GBM), K-Nearest Neighbor (KNN), Logistic Regression (LR), Neural Network (NN), Random Forest (RF), Support Vector Machine (SVM), and eXtreme Gradient Boosting (XGBoost) were applied. Results A total of 160 pairs of individuals were included for analyses. The mediation effects of Genus_Catenibacterium (P = 0.024), Genus_Tyzzerella_4 (P

Abstract Background Triptans selectively agoniste 5-Hydroxytryptamine(5-HT) receptors and are widely used in the treatment of migraine. Nevertheless, there is a dearth of comprehensive real-world clinical research on the safety of triptans. In light of the growing prevalence of migraine, it is imperative to gain a deeper understanding of the true extent of adverse events (AEs) associated with triptans in the clinical management of migraine. Methods A database query of AEs reported to the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for triptans was performed using the online platform Open Vigil 2.1. The query spanned the period from 1 January 2018 to 31 December 2023 and extracted all AEs for ‘sumatriptan’, ‘zolmitriptan’, ‘rizatriptan’, and ‘naratriptan’ from the 15–49 years old population and retrospective quantitative analyses. A proportional reporting ratio (PRR), reporting odds ratio (ROR), and Bayesian Confidence Propagation Neural Network (BCPNN) methodology were utilized to contrast AEs across the four triptans. Results A total of 1.272 AEs reports for sumatriptan, 114 for zolmitriptan, 162 for rizatriptan, and 15 for naratriptan were identified. The ratio of females to males was approximately three times higher in all cases, with the highest number of reports originating from the Americas. A review of the FAERS database revealed that nervous system disorders were the primary SOC category for four drugs, with all four drugs exhibiting the AE indicative of reversible cerebral vasoconstriction syndrome, also classified as Nervous system disorders. The most frequently reported AE signal for sumatriptan was dyspnea, which is classified as respiratory, thoracic and mediastinal disorders. The most frequently reported AEs signals for the remaining three drugs were nausea, vomiting and terminal ileitis, all of which are classified as gastrointestinal disorders. Conclusion Analyses have demonstrated that AEs are present in a range of systems, including cardiac, nervous, gastrointestinal, and musculoskeletal disorders. It should be noted, however, that the incidence and signal intensity of these AEs vary depending on the specific drug in question. In clinical practice, the selection of an appropriate drug and the monitoring of AEs should be tailored to the individual patient’s and specific characteristics.

Abstract Background Sepsis-associated acute kidney injury (SA-AKI) is common and associated with poor outcomes in critically ill patients. Acetaminophen is often used as an antipyretic and analgesic drug, but the association of acetaminophen use with mortality and recovery of renal function in SA-AKI patients remain unclear. We aimed to investigate the association between acetaminophen use and outcomes in SA-AKI patients. Methods This is a retrospective cohort study based on the MIMIC-IV database. Adult patients with SA-AKI were included in the analysis. The exposure was acetaminophen use within 7 days after the onset of SA-AKI. The primary outcome was 28-day mortality. Secondary outcomes included ICU mortality, in-hospital mortality, 90-day mortality, 1-year mortality, and renal recovery. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) with 95% confidence interval (CI) for mortality. Logistic regression models were used to estimate the odd ratio (OR) with 95% CI for renal recovery. Results 6752 patients with SA-AKI were included, and 3892 (57.6%) patients received acetaminophen. Acetaminophen use was associated with decreased 28-day mortality (HR 0.69, 95% CI 0.63–0.75), ICU mortality (HR 0.56, 95% CI 0.50–0.63), in-hospital mortality (HR 0.62, 95% CI 0.57–0.69), 90-day mortality (HR 0.73, 95% CI 0.68–0.79), and 1-year mortality (HR 0.62, 95% CI 0.57–0.69). Acetaminophen use also was associated with improved renal recovery (OR 1.15, 95% CI 1.04–1.28). Conclusions Acetaminophen use is associated with decreased mortality and improved renal recovery in SA-AKI patients.