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Bupleurum yinchowense Shan & Yin Li was first described as a new Bupleurum species in 1974, but its classification status has always been disputed. Here, its complete chloroplast genome was provided to resolve this issue. The length of the B. yinchowense chloroplast genome is 155,851 bp and composed of two inverted repeats (IR: 26,307 bp), a large single-copy region (LSC: 85,625 bp), and a small single-copy region (SSC: 17,612 bp). The overall GC content is 37.6%. The chloroplast genome consists of 113 genes, including 79 protein-coding genes, four rRNA genes, and 30 tRNA genes. Phylogenetic analysis suggested that Bupleurum yinchowense holds a distinct phylogenetic position and can be considered as an accepted species.

The root of Bupleurum marginatum var. stenophyllum (H. Wolff) Shan & Yin Li (Apiaceae), a new substitution for the popular Chinese medicinal material, Bupleuri Radix (Chai hu), is not easily distinguishable via traditional methods. The complete chloroplast genome sequence of B. marginatum var. stenophyllum was characterized using next-generation sequencing and the de novo assembly method. The complete genome was 155,576 bp in length and contained two inverted repeat (IR) regions of 26,311 bp, a large single-copy (LSC) region of 85,351 bp, and a small single-copy (SSC) region of 17,603 bp. It encoded 113 unique genes consisting of 79 protein-coding genes (PCGs), 30 transfer RNA genes, and four ribosomal RNA genes. Importantly, three genes (petB, petD and rps16) with small exon, and one trans-splicing gene (rps12) were correctly annotated. The overall GC content of the B. marginatum var. stenophyllum chloroplast genome is 37.7%. The phylogenetic analyses indicated that B. marginatum var. stenophyllum was closely related to B. marginatum. Moreover, many genetic information sites were available for distinguishing B. marginatum var. stenophyllum from the official ‘Chai hu’ plant sources, B. scorzonerifolium Willd. and B. chinense DC.

This research paper investigates the intersection of the maker movement and educational innovation, using the China-U.S. Young Maker Competition as a foundational example. It examines how maker education, fueled by hands-on learning and a curiosity-driven approach, can evolve and influence. The study explores the roles and impacts of Human-Computer Interaction (HCI), Design-Driven Innovation (DDI), and Cross-Cultural Perspectives (CCP) within maker education. It highlights HCI's connection of technology with learning, DDI's focus on user-centered solutions, and the significance of CCP in enhancing cultural collaboration, vital for fostering an innovative and creative future. This paper offers a detailed perspective on the current state and future potential of maker education. It proposes a roadmap for the coming decade, emphasizing collaborative learning and creative endeavors, all set within the engaging environment of the competition.

Abstract Background Systemic nutrition and inflammation status is recognized for its influence on cancer survival, yet its role in perioperative outcomes remains poorly defined. This study aimed to refine the assessment of systemic nutrition and inflammation status in non-small cell lung cancer (NSCLC) patients and to elucidate its impact on perioperative outcomes. Methods All patients underwent video-assisted thoracoscopic lobectomy, with their nutrition and inflammation status assessed based on preoperative blood tests. The development cohort, comprising 1497 NSCLC patients from two centers, evaluated the predictive value of systemic nutrition/inflammation indicators for perioperative endpoints and formulated the systemic nutrition-inflammation index (SNII). The tertiles of SNII were used to classify the nutrition/inflammation risk as high ( 23.1). An external validation cohort of 505 NSCLC patients was utilized to confirm the effectiveness of SNII in guiding perioperative management. Results In the development cohort, the SNII tool, calculated as the product of total cholesterol and total lymphocytes divided by total monocytes, demonstrated a stronger correlation with perioperative outcomes compared to 11 existing nutrition/inflammation indicators. A low SNII score, indicative of high nutrition/inflammation risk, was independently predictive of increased complication incidence and severity, as well as prolonged chest tube duration and hospital stay. These findings were corroborated in the validation cohort. Upon combining the development and validation cohorts, the superiority of the SNII in predicting perioperative outcomes was further confirmed over the existing nutrition/inflammation indicators. Additionally, comprehensive subgroup analyses revealed the moderately variable efficacy of SNII across different patient populations. Conclusions This study developed and validated the SNII as a tool for identifying systemic nutrition and inflammation risk, which can enhance perioperative managements in NSCLC patients. Patients identified with high risk may benefit from prehabilitation and intensive treatments, highlighting the need for further research.

Abstract Sample relatedness is a major confounder in genome-wide association studies (GWAS), potentially leading to inflated type I error rates if not appropriately controlled. A common strategy is to incorporate a random effect related to genetic relatedness matrix (GRM) into regression models. However, this approach is challenging for large-scale GWAS of complex traits, such as longitudinal traits. Here we propose a scalable and accurate analysis framework, SPAGRM, which controls for sample relatedness via a precise approximation of the joint distribution of genotypes. SPAGRM can utilize GRM-free models and thus is applicable to various trait types and statistical methods, including linear mixed models and generalized estimation equations for longitudinal traits. A hybrid strategy incorporating saddlepoint approximation greatly increases the accuracy to analyze low-frequency and rare genetic variants, especially in unbalanced phenotypic distributions. We also introduce SPAGRM(CCT) to aggregate the results following different models via Cauchy combination test. Extensive simulations and real data analyses demonstrated that SPAGRM maintains well-controlled type I error rates and SPAGRM(CCT) can serve as a broadly effective method. Applying SPAGRM to 79 longitudinal traits extracted from UK Biobank primary care data, we identified 7,463 genetic loci, making a pioneering attempt to conduct GWAS for these traits as longitudinal traits.

Abstract Esophageal squamous cell carcinoma (ESCC) patients often face a grim prognosis due to lymph node metastasis. However, a comprehensive understanding of the cellular and molecular characteristics of metastatic lymph nodes in ESCC remains elusive. In this study involving 12 metastatic ESCC patients, we employed single-cell sequencing, spatial transcriptomics (ST), and multiplex immunohistochemistry (mIHC) to explore the spatial and molecular attributes of primary tumor samples, adjacent tissues, metastatic and non-metastatic lymph nodes. The analysis of 161,333 cells revealed specific subclusters of epithelial cells that were significantly enriched in metastatic lymph nodes, suggesting pro-metastatic characteristics. Furthermore, stromal cells in the tumor microenvironment, including MMP3+IL24+ fibroblasts, APLN+ endothelial cells, and CXCL12+ pericytes, were implicated in ESCC metastasis through angiogenesis, collagen production, and inflammatory responses. Exhausted CD8+ T cells in a cycling status were notably prevalent in metastatic lymph nodes, indicating their potential role in facilitating metastasis. We identified distinct cell-cell communication networks and specific ligand-receptor pathways. Our findings were validated through a spatial transcriptome map and mIHC. This study enhances our comprehension of the cellular and molecular aspects of metastatic lymph nodes in ESCC patients, offering potential insights into novel therapeutic strategies for these individuals.

Abstract Background Systemic light chain amyloidosis is a rare and debilitating disease, especially for which initially presented with digestive tract involvement. Myocardial amyloidosis is highly aggressive with generally poor prognosis and often resulted in missed diagnosis or misdiagnosis with routine examination tools. Multimodality imaging play an important role in diagnosing the amyloidosis effect on multiple organs. Chemoradiotherapy is the mainstay of treatment. Case presentation This article presents a rare case of systemic light chain amyloidosis, initially with gastrointestinal symptoms, in a 68-year-old male. He was hospitalized with diarrhea for one year and a half, dysphagia for 4 months, but he had no dyspnea. The transthoracic echocardiogram revealed myocardial hypertrophy of the left ventricle, the hypertrophic heart muscle echoed like "ground glass". The left ventricular ejection fraction (LVEF) detected by Simpson method was 51% and global longitudinal strain (GLS) was -9.00%. But cardiac magnetic resonance showed the patient without gadolinium delayed enhancement. The urinary protein series quantification and the serum free light chain levels were all increased. While the ratio of free κ and free λ was decreased. Hence, the abdominal fat biopsy of the patient was amyloidosis by electronic and immunoelectron microscopy. Organs involved include heart, kidneys, gastrointestinal tract and nervous system, stage III of mayo 2012 model. The patient was treated with Dara-BCD chemotherapy. This case underscores the diagnostic complexity, emphasizing the need for early identification given the grim prognosis associated with systemic AL amyloidosis requiring clinical data, detailed imaging, and histopathological insights. After discharge, the patient became better and followed up in the outpatient. Conclusions Systemic light chain amyloidosis can easily be missed diagnosis or misdiagnosis in its early stages, losing the opportunity for initiating earlier treatments to improve potential patient outcomes. Despite advancements in diagnostic biomarkers, this case highlights the potential for missed diagnosis with standard CMR imaging when gadolinium enhancement is negative. The utility of echocardiographic features such as reduced GLS and abnormal ECG findings emerges as critical in early identification of myocardial amyloidosis. The correct diagnosis of this case relied on the comprehensive utilization of multimodal imaging techniques including biopsy.

Abstract The role of dairy products in cardiovascular disease (CVD) prevention remains controversial. This study investigates the association between dairy consumption and CVD incidence using data from the China Kadoorie Biobank and the UK Biobank, complemented by an updated meta-analysis. Among Chinese participants, regular dairy consumption (primarily whole milk) is associated with a 9% increased risk of coronary heart disease (CHD) and a 6% reduced risk of stroke compared to non-consumers. Among British participants, total dairy consumption is linked to lower risks of CVD, CHD, and ischemic stroke, with cheese and semi-skimmed/skimmed milk contributing to reduced CVD risk. Meta-analysis reveals that total dairy consumption is associated with a 3.7% reduced risk of CVD and a 6% reduced risk of stroke. Notably, inverse associations with CVD incidence are observed for cheese and low-fat dairy products. Current evidence suggests that dairy consumption, particularly cheese, may have protective effects against CVD and stroke.

By hosting a college students' laboratory skills contest, we provide an interesting activity for students to cultivate good laboratory practices and thereby improve their laboratory skills. The substance of this contest is the detection of the hardness of water, which involves numerous laboratory skills such as solution preparation, weight by difference mass measurements, glassware calibration, pipetting, quantitative transfer, titration, data processing, and cleaning up the laboratory. Initially, due to limited class time, students are unable to master and practice effectively the skills taught in class. Many students wanted to practice these skills at a time after class, and these skills were subsequently redesigned and organized as an extracurricular activity to involve more students. Skills are assigned to students depending on their year: freshmen act as lab assistants to prepare solutions, such as EDTA-2Na, hydrochloric acid, ammonia, and indicators. This is a simple skill that aims to build confidence in mastering chemical experiments, as such experiments are rarely conducted in high school. Sophomores conducted experiments as contestants. Through the contest, students' laboratory skills are improved and evaluated. The task for senior students is to provide guidance to freshmen and sophomores, identify their mistakes, and demonstrate the correct operations. All of the students collaborated to complete this activity.

Abstract Background As a typical medicinal food homology species, Chinese herbal medicine Astragali radix (AR) has been widely used to regulate the human immune system worldwide. However, the human immunomodulation of AR and its corresponding mechanisms remain unclear. Methods First, following a fortnight successive AR administration, the changes in immune cytokines and immune cells from 20 healthy human subjects were used as immune indicators to characterize the immunomodulatory effects of AR. Subsequently, ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) based lipidomics and metabolomics analysis was performed on human serum, urine, and feces samples to investigate the changes in metabolic profiles. Then, 16S rRNA gene sequencing of feces samples was adopted for the changes of human gut microbiota. Finally, correlation analysis was conducted on the gut microbiome, metabolome/lipidome data, and immune indicators. Results AR displayed good safety in clinical use and posed a minor impact on gut microbiota major genera, global metabolic profiles, and immune cells. Meanwhile, AR could significantly up-regulate anti-inflammatory cytokines, down-regulate serum creatinine and pro-inflammatory cytokines, promote the anabolism of arginine, glycerolipid, sphingolipid, and purine, and the catabolism of phenylalanine and glycerophospholipid. Moreover, these AR-induced changes were closely correlated with significantly decreased Granulicatella, slightly higher Bifidobacterium, Ruminococcus, and Subdoligranulum, and slightly lower Blautia. Conclusion The study clearly demonstrated that AR could modulate the human immune, by modifying the metabolism of amino acids, lipids, and purines in a microbiota-related way. Trial registration ChiCTR, ChiCTR2100054765. Registered 26 December 2021-Prospectively registered, https://www.chictr.org.cn/historyversionpub.html?regno=ChiCTR2100054765

Abstract A novel broadband dual‐polarised transmitarray antenna (TA) utilising tightly coupled cross dipole cells is proposed in this work. The transmitarray cell using the tightly coupling wideband principle comprises two radiation patches designed as two orthogonal planar dipoles with four interdigital capacitors, two meandered parallel plate transmission lines, and a ground. Each cell has a square shape and a dimension of approximately 0.28 λc where λc is the wavelength at central frequency 5.5 GHz. The transmitarray cell can achieve 475° phase shift at central frequency and transmission magnitude better than −2.5 dB within the working band. To verify the feasibility of this design, a tightly coupled dual‐polarised transmitarray antenna (TCDPTA) is modelled and manufactured. The transmitarray aperture size is approximately 4.1 λc × 4.1 λc. The simulation and measurement illustrate that the TCDPTA has stable and distortion‐free main beams whose side lobe levels are generally below −10 dB in the band of 3.0–8.0 GHz. The measured gain at central frequency is 16.2 dBi and peak gain is 19 dBi at 7.5 GHz. The working bandwidth is 90.9% and 3 dB gain bandwidth is 66.7%. The measured cross‐polarisation levels are below −15 dB at axial direction. This TA has potential applications for high‐date‐rate communication and high‐revolution radar imaging systems at C‐band.

Abstract Chronic ischemia in moyamoya disease (MMD) impaired white matter microstructure and neural functional network. However, the coupling between cerebral blood flow (CBF) and functional connectivity and the association between structural and functional network are largely unknown. 38 MMD patients and 20 sex/age-matched healthy controls (HC) were included for T1-weighted imaging, arterial spin labeling imaging, resting-state functional MRI and diffusion tensor imaging. All patients had preoperative and postoperative digital subtraction angiography. Upon constructing the structural connectivity (SC) and functional connectivity (FC) networks, the SC-FC coupling was calculated. After obtaining the graph theoretical parameters, neurovascular coupling represented the spatial correlation between node degree centrality (DC) of functional networks and CBF. The CBF-DC coupling and SC-FC coupling were compared between MMD and HC groups. We further analyzed the correlation between coupling indexes and cognitive scores, as well as postoperative collateral formation. Compared with HC, CBF-DC coupling was decreased in MMD (p = 0.021), especially in the parietal lobe (p = 0.047). SC-FC coupling in MMD decreased in frontal, occipital, and subcortical regions. Cognitive scores were correlated with the CBF-DC coupling in frontal lobes (r = 0.394, p = 0.029) and SC-FC coupling (r = 0.397, p = 0.027). The CBF-DC coupling of patients with good postoperative collateral formation was higher (p = 0.041). Overall, neurovascular decoupling and structure-functional decoupling at the cortical level may be the underlying neuropathological mechanisms of MMD.

Abstract Mesenchymal stem cells (MSCs) have been widely used in the treatment of various inflammatory diseases. The inadequate understanding of MSCs and their heterogeneity can impact the immune environment, which may be the cause of the good outcomes of MSCs-based therapy that cannot always be achieved. Recently, stem cells from human exfoliated deciduous teeth (SHED) showed great potential in inflammatory and autoimmune diseases due to their immature properties compared with MSCs. In our study, single-cell RNA sequencing (scRNA-seq) revealed that SHED in a low differentiation state (S7) exhibited the powerful ability to recruit multiple immune cells. In contrast, SHED in a relatively high differentiation state (S1) may hold a solid ability to secret many factors with paracrine signaling capacity. The analysis result shows that SHED has more robust immunomodulatory properties than human bone marrow-derived mesenchymal stem cells (hBMSCs) or human umbilical cord-derived mesenchymal stem cells (hUCMSCs). When co-cultured with PBMCs, SHED can enhance the proliferation of Treg and down-regulate TNF-α in vitro. SHED may have some advantages in the treatment of inflammatory and autoimmune diseases.

Abstract Background Oocyte maturation defect (OMD) and early embryonic arrest result in female infertility. Previous studies have linked biallelic mutations in the PATL2 gene to OMD, yet the underlying mechanism remains largely unknown. Results This study uncovers three novel mutations (c.1201G > T, c.1284delA and c.1613 + 2_1613 + 3insGT) and three reported mutations (c.1204 C > T, c.1271T > C, c.223 − 14_223-2delCCCTCCTGTTCCA) in the PATL2 gene across five unrelated individuals exhibiting OMD, oocyte death, and early embryonic arrest. RNA sequencing revealed that PATL2 mutations decreased mRNA storage in human germinal vesicle (GV) oocytes and impeded mRNA decay during maturation and in early embryos. We demonstrate that PATL2 interacts with CPEB1 and TUT7 in human oocytes to maintain mRNA homeostasis. Additionally, we observed a reduction in CCNB1 and CCNE1 mRNA levels in PATL2-mutant GV oocytes, which may be linked to GV arrest. Employing both wild-type and mutated PATL2V401F/R402W variants, we characterized the protein interactome of PATL2, identifying disruptions of PATL2V401F/R402W variants predominantly affecting cell cycle-related proteins, including CDC23, APC1 and MAD2L1. PATL2’s interaction with and stabilization of CDC23 in oocytes may elucidate the mechanisms behind the mutation-induced MI arrest. PALT2 is required for the efficient mRNA translation and it maintains the protein level of CDC23, APC1 and MAD2L1 in mouse GV oocyte. Conclusion PATL2 plays a critical role in regulating mRNA accumulation and decay in human oocytes, potentially through interactions with CPEB1 and TUT7, respectively. Mutations in PATL2 lead to oocyte meiosis defects by affecting the mRNA accumulation, mRNA translation, and direct binding to and stabilizing proteins related to cell cycle regulation, such as CCNB1 and CDC23. This study expands the mutational spectrum of PATL2 and provides new insights into the molecular mechanisms underlying PATL2 mutation-associated oocyte maturation disorders.