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Tracing the emergence of the first hematopoietic stem cells (HSCs) in human embryos, particularly the scarce and transient precursors thereof, is so far challenging, largely due to the technical limitations and the material rarity. Here, using single-cell RNA sequencing, we constructed the first genome-scale gene expression landscape covering the entire course of endothelial-to-HSC transition during human embryogenesis. The transcriptomically defined HSC-primed hemogenic endothelial cells (HECs) were captured at Carnegie stage (CS) 12–14 in an unbiased way, showing an unambiguous feature of arterial endothelial cells (ECs) with the up-regulation of RUNX1, MYB and ANGPT1. Importantly, subcategorizing CD34+CD45− ECs into a CD44+ population strikingly enriched HECs by over 10-fold. We further mapped the developmental path from arterial ECs via HSC-primed HECs to hematopoietic stem progenitor cells, and revealed a distinct expression pattern of genes that were transiently over-represented upon the hemogenic fate choice of arterial ECs, including EMCN, PROCR and RUNX1T1. We also uncovered another temporally and molecularly distinct intra-embryonic HEC population, which was detected mainly at earlier CS 10 and lacked the arterial feature. Finally, we revealed the cellular components of the putative aortic niche and potential cellular interactions acting on the HSC-primed HECs. The cellular and molecular programs that underlie the generation of the first HSCs from HECs in human embryos, together with the ability to distinguish the HSC-primed HECs from others, will shed light on the strategies for the production of clinically useful HSCs from pluripotent stem cells.

In Huntington’s disease (HD), expansion of CAG codons in the huntingtin gene (HTT) leads to the aberrant formation of protein aggregates and the differential degeneration of striatal medium spiny neurons (MSNs). Modeling HD using patient-specific MSNs has been challenging, as neurons differentiated from induced pluripotent stem cells are free of aggregates and lack an overt cell death phenotype. Here we generated MSNs from HD patient fibroblasts through microRNA-based direct neuronal conversion, bypassing the induction of pluripotency and retaining age signatures of the original fibroblasts. We found that patient MSNs consistently exhibited mutant HTT (mHTT) aggregates, mHTT-dependent DNA damage, mitochondrial dysfunction and spontaneous degeneration in culture over time. We further provide evidence that erasure of age stored in starting fibroblasts or neuronal conversion of presymptomatic HD patient fibroblasts results in differential manifestation of cellular phenotypes associated with HD, highlighting the importance of age in modeling late-onset neurological disorders.Direct neuronal conversion of skin fibroblasts from individuals with Huntington’s disease (HD) generates a population of medium spiny neurons that recapitulate hallmarks of HD, including aggregation of mutant huntingtin protein, DNA damage and spontaneous cell death.

Context:Momordica charantia L. (Cucurbitaceae) has long been widely used as a traditional remedy for diabetes mellitus in some countries. However, detailed antidiabetic mechanisms are largely unknown.Objectives: This study clarified the ameliorating effects of M. charantia ethanol extracts (MCE) on the insulin resistance in type 2 diabetes mellitus (T2DM) rats.Materials and methods: T2DM rat model was established by high-fat diet and streptozotocin (STZ) injection. Diabetic rats were randomized into five groups: the model control group (n = 8) (common diet), the high-fat diet metformin (50 mg/kg/d), and the three-dose MCE (100, 200, and 400 mg/kg/d) groups (n = 8 each). After 8  weeks, the fasting serum glucose, insulin, TNF-α, and IL-6 were measured, and the relevant factors of glucose and insulin were monitored by glycogen dyeing, RT-PCR, and western blot, respectively.Results: The 8-week treatment of 400 mg/kg MCE significantly lowered body weight (330.1 versus 365.9 g), serum glucose (7.41 versus 16.63 mmol/L), insulin (12.06 versus 15.89 mIU/L), TNF-α (52.72 versus 81.83 ng/L), and IL-6 (104.81 versus 135.74 ng/L) in comparison with those of the diabetic control group (p < 0.05). It was the same for skeletal muscle glucose transporter 4 (GLUT-4) protein, and glycogen level, suppressor of cytokine signaling-3 (SOCS-3), c-Jun N-terminal kinase (JNK), and Akt expression at both protein and mRNA levels in liver (p < 0.05).Conclusions: MCE can ameliorate insulin resistance in T2DM rats. This effect may be related to the regulation of mRNA and protein levels of SOCS-3 and JNK.

This paper presents a novel broadband monopole antenna that was equipped with a bottom semicircle ground structure, a parasitic patch, a T-shaped slot, s transmission line, a parasitic strip, heart-shaped slices and a coplanar waveguide (CPW). The simulation results revealed that the proposed design had a relatively high return loss, a wide bandwidth and high efficiency. A prototype of the proposed antenna with an overall size of 0.94 λ0 × 0.94 λ0 × 0.02 λ0 (λ0 is the free-space wavelength) was fabricated and measured. The measurement results showed that the prototype had a bandwidth of 4.02 GHz (4.69–8.71 GHz) and a relative bandwidth of 60%. Besides, the maximum gain was 3.31 dBi and the maximum efficiency was 91.1% in the range of 5 to 8.5 GHz. Furthermore, it was found that the prototype almost achieved omnidirectional radiation. Its operating frequency band covered those of industrial scientific medical (ISM) (5.725–5.850 GHz), the radio frequency identification (RFID) (5.8 GHz) and the wireless local area network (WLAN) (5.15–5.25 GHz and 5.725–5.825 GHz).

With the growth of metabolomics research, more and more studies are conducted on large numbers of samples. Due to technical limitations of the Liquid Chromatography–Mass Spectrometry (LC/MS) platform, samples often need to be processed in multiple batches. Across different batches, we often observe differences in data characteristics. In this work, we specifically focus on data generated in multiple batches on the same LC/MS machinery. Traditional preprocessing methods treat all samples as a single group. Such practice can result in errors in the alignment of peaks, which cannot be corrected by post hoc application of batch effect correction methods. In this work, we developed a new approach that address the batch effect issue in the preprocessing stage, resulting in better peak detection, alignment and quantification. It can be combined with down-stream batch effect correction methods to further correct for between-batch intensity differences. The method is implemented in the existing workflow of the apLCMS platform. Analyzing data with multiple batches, both generated from standardized quality control (QC) plasma samples and from real biological studies, the new method resulted in feature tables with better consistency, as well as better down-stream analysis results. The method can be a useful addition to the tools available for large studies involving multiple batches. The method is available as part of the apLCMS package. Download link and instructions are at https://mypage.cuhk.edu.cn/academics/yutianwei/apLCMS/ .

Constipation is one of the common gastrointestinal complications after stroke. It not only aggravates the condition of stroke, but also brings huge medical burden to patients, and has a negative impact on the quality of life of patients. Auricular therapy, as a part of Chinese traditional acupuncture and moxibustion, has been found to be effective in the clinical treatment of constipation. However, no systematic review has investigated the efficacy and safety of auricular therapy in the treatment of post-stroke constipation. Therefore, the aim of this systematic review is to assess the effectiveness and safety of auricular therapy for post-stroke constipation. Eight electronic databases including PubMed, Cochrane Library/Cochrane Central Register of Controlled Trials, Web of Science, Embase, China National Knowledge Internet, Chinese Biomedical Literature Database, Wanfang, and VIP databases, will be searched for relevant studies published from inception to February 2023. Two reviewers will independently conduct research selection, data extraction, and evaluation of research quality. Only randomized controlled trials (RCTs) that assess the efficacy and safety of auricular therapy for the treatment of post-stroke constipation will be included in this study. We will use the Cochrane risk of bias assessment tool to evaluate the methodological qualities (including bias risk). If possible, a meta-analysis will be performed after screening. This study may provide high-quality evidence for the efficacy and safety of auricular therapy in treating post-stroke constipation. The conclusions of our study will provide an evidence to judge whether auricular therapy is an effective and safe intervention for patients with post-stroke constipation. Ethical approval is not required, as this study was based on a review of published research. This review will be published in a peer-reviewed journal and disseminated electronically and in print. Registration number: PROSPERO CRD42023402242.

Complementing the genome with an understanding of the human exposome is an important challenge for contemporary science and technology. Tens of thousands of chemicals are used in commerce, yet cost for targeted environmental chemical analysis limits surveillance to a few hundred known hazards. To overcome limitations which prevent scaling to thousands of chemicals, we develop a single-step express liquid extraction and gas chromatography high-resolution mass spectrometry analysis to operationalize the human exposome. We show that the workflow supports quantification of environmental chemicals in human plasma (200 µL) and tissue (≤100 mg) samples. The method also provides high resolution, sensitivity and selectivity for exposome epidemiology of mass spectral features without a priori knowledge of chemical identity. The simplicity of the method can facilitate harmonization of environmental biomonitoring between laboratories and enable population level human exposome research with limited sample volume. Humans are exposed to millions of chemicals but mass spectrometry (MS)-based targeted biomonitoring assays are usually limited to a few hundred known hazards. Here, the authors develop a workflow for MS-based untargeted exposome profiling of known and unidentified environmental chemicals.

Constipation is one of the common gastrointestinal complications after stroke. It not only aggravates the condition of stroke, but also brings huge medical burden to patients, and has a negative impact on the quality of life of patients. Auricular therapy, as a part of Chinese traditional acupuncture and moxibustion, has been found to be effective in the clinical treatment of constipation. However, no systematic review has investigated the efficacy and safety of auricular therapy in the treatment of post-stroke constipation. Therefore, the aim of this systematic review is to assess the effectiveness and safety of auricular therapy for post-stroke constipation. Eight electronic databases including PubMed, Cochrane Library/Cochrane Central Register of Controlled Trials, Web of Science, Embase, China National Knowledge Internet, Chinese Biomedical Literature Database, Wanfang, and VIP databases, will be searched for relevant studies published from inception to February 2023. Two reviewers will independently conduct research selection, data extraction, and evaluation of research quality. Only randomized controlled trials (RCTs) that assess the efficacy and safety of auricular therapy for the treatment of post-stroke constipation will be included in this study. We will use the Cochrane risk of bias assessment tool to evaluate the methodological qualities (including bias risk). If possible, a meta-analysis will be performed after screening. This study may provide high-quality evidence for the efficacy and safety of auricular therapy in treating post-stroke constipation. The conclusions of our study will provide an evidence to judge whether auricular therapy is an effective and safe intervention for patients with post-stroke constipation.

The attine ant–fungus agricultural symbiosis evolved over tens of millions of years, producing complex societies with industrial-scale farming analogous to that of humans. Here we document reciprocal shifts in the genomes and transcriptomes of seven fungus-farming ant species and their fungal cultivars. We show that ant subsistence farming probably originated in the early Tertiary (55–60 MYA), followed by further transitions to the farming of fully domesticated cultivars and leaf-cutting, both arising earlier than previously estimated. Evolutionary modifications in the ants include unprecedented rates of genome-wide structural rearrangement, early loss of arginine biosynthesis and positive selection on chitinase pathways. Modifications of fungal cultivars include loss of a key ligninase domain, changes in chitin synthesis and a reduction in carbohydrate-degrading enzymes as the ants gradually transitioned to functional herbivory. In contrast to human farming, increasing dependence on a single cultivar lineage appears to have been essential to the origin of industrial-scale ant agriculture. Attine ants, including the leaf-cutting ants, cultivate fungi as their sole source of food. Here, Nygaard et al . use whole genome and transcriptome sequences from seven ant species and their fungal cultivars to reconstruct the reciprocal genetic changes underlying the evolution of the ant-fungus mutualism.

The existing fertilizer spreader has suboptimal performance in terms of fertilizer uniformity, lack of controllability of fertilizer spreading width, low utilization rate, and inability to meet the requirements of hills, mountains, and other complex terrains. In response to these shortcomings, we have developed a rotary tube fertilizer spreader for mountainous terrain. This device uses a fertilizer trajectory based on the drop distribution of overlapping prolate cycloids, which enables uniform fertilizer application in both the transversal and longitudinal directions. Based on an analysis of the structure and operating principles of the device, Table L 9 (3 4 ) was selected for orthogonal array testing, and the results showed that the transversal fertilizer distribution uniformity ( Y 1 ) and the longitudinal fertilizer distribution uniformity ( Y 2 ) were 14.24% and 12.75%, respectively, when the number of rotating tubes was Z  = 3, the angle θ of the rotating tubes with respect to the vertical was 50°, and the length of the rotating tubes was L  = 100. The results of the simulation experiments were validated through bench experiments, and the relative errors of the coefficients of variation of traversal and longitudinal fertilizer distribution uniformity in the bench verification experiments were 11.45% and 2.8%, respectively. This demonstrated that the results of the simulation experiments were reliable. A mathematical model was constructed through bench experiments, in which the width of transversal fertilizer spreading ( y ) was regulated by operating parameters such as the rotational speed of the rotary tube ( n ) and the height of the tube mouth from the ground ( h ). The fitting results showed a corrected coefficient of determination of 0.9906. The experimental results were in agreement with the fitted results, thus adapting to crops with 40 cm to 160 cm spacing between rows. This study offers a theoretical foundation for the design of a rotary tube strip fertilizer spreader.