Agenesis of the corpus callosum (ACC) is a birth defect in which the corpus callosum is either partially or completely missing. With recent advances in prenatal ultrasound, detection of ACC in ...obstetric practices is becoming more common. Etiologies of ACC include chromosome errors, genetic factors, prenatal infections, and other factors related to the prenatal environment. In an effort to elucidate more about the genetic influence in the pathogenesis of ACC, we identified, through whole-exome sequencing (WES), two gene mutations in two families with complete agenesis of the corpus callosum. These two mutations are located on chromosome X: one is a hemizygous missense mutation c.3746T>C (p. L1249P) in the gene mediator complex subunit 12 (
); the other one is a heterozygous missense mutation c.128+5G>C in gene ephrin B1 (
). Historically, early diagnosis of complete ACC during pregnancy has been difficult; however, WES has provided us with a creative avenue of diagnosis, combining identification of genetic mutations with prenatal imaging.
Abstract
Few study has revealed spatial transmission characteristics of COVID-19 in Wuhan, China. We aimed to analyze the spatiotemporal spread of COVID-19 in Wuhan and its influence factors. ...Information of 32,682 COVID-19 cases reported through March 18 were extracted from the national infectious disease surveillance system. Geographic information system methods were applied to analysis transmission of COVID-19 and its influence factors in different periods. We found decrease in effective reproduction number (
Rt
) and COVID-19 related indicators through taking a series of effective public health measures including restricting traffic, centralized quarantine and strict stay-at home policy. The distribution of COVID-19 cases number in Wuhan showed obvious global aggregation and local aggregation. In addition, the analysis at streets-level suggested population density and the number of hospitals were associated with COVID-19 cases number. The epidemic situation showed obvious global and local spatial aggregations. High population density with larger number of hospitals may account for the aggregations. The epidemic in Wuhan was under control in a short time after strong quarantine measures and restrictions on movement of residents were implanted.
Human breast milk is the primary source of choline and choline-containing compounds for infants at early stages of life. Choline data across lactation in Chinese human milk were limited.
This study ...aimed to quantify the five choline compounds in Chinese human breast milk and explore associated factors.
A total of 540 lactating mothers from the MUAI (Maternal Nutrition and Infant Investigation) study were included. The content of water-soluble choline (free choline, phosphocholine, glycerophosphocholine) and lipid-soluble choline (phosphatidylcholine, sphingomyelin) in 892 human milk samples collected from 0 to 400 days postpartum were examined, and associated factors were explored.
Choline concentrations in human milk varied from postpartum day 0–400 (92.06 ± 65.22 to 171.01 ± 47.84 mg/L). Water-soluble choline was the major component (88.6%–93.8%) in human milk and ranged from 793.03 (659.22) to 1544.43 (443.32) μmol/L. Its trajectory followed that of total choline, increasing from colostrum to transitional milk and then declining in mature milk. In contrast, lipid-soluble choline accounted for 6.2%–11.4% over lactation and had an opposite trajectory. Choline composition varied by delivery mode and parity history.
The concentrations of individual choline and choline-containing compounds during lactation in Chinese human breast milk were described for the first time. Our results address gaps in extant Chinese human milk choline data and support tailored dietary reference intakes for Chinese lactating women and infants. Our data describes the level and profile of choline from 0 to 400 days postpartum in Chinese human breast milk. This is the most updated data on choline and also the first report of water-soluble choline as the predominant type in Chinese human milk. Our results compensate for the deficiencies in data on choline in Chinese human milk.
Clinical Trial Registry number: ChiCTR1800015387. Web link to study on registry: https://www.chictr.org.cn/index.aspx.
Kelp, as a kind of climate-friendly food, animal feed, and bioplastics material, has been gradually cultivated worldwide. In the process of kelp culture, clipping seedling operation is essential to ...guarantee the yield. Traditionally, the clipping seedling operation is conducted by hand with low production efficiency and high labor intensity. In this paper, a novel automatic clipping seedling machine is developed to improve efficiency. The machine consists of an automatic seedling clipping core device, an automatic seedling feeding device, an automatic seedling rope conveyor, and an automatic product storage device. The corresponding structure, mechanism, and control system are introduced and analyzed. The performances of the automatic machine are tested and compared to manual kelp seedling clipping. Compared to manual kelp seedling clipping, the automatic machine can improve efficiency by 35%. Additionally, the quality of kelp seedling clipping is investigated. The attaching force of the kelp seedling clipped by the automatic machine is 2.179 N (224.4 g × 9.8 N/Kg × 10−3). The rate of the clipped kelp seedlings falling off the rope is only 1.3%. These performances prove that the automatic machine Is feasible and can be used to improve clipping efficiency and ensure clipping quality at the same time.
Phosphate (Pi), as the main form of phosphorus that can be absorbed by plants, is one of the most limiting macro-nutrients for plants. However, the mechanism for maintaining Pi homeostasis in rice ...(Oryza sativa) is still not well understood. We identified a Pi-starvation-induced E3 ligase (OsPIE1) in rice. Using an in vitro self-ubiquitination assay, we determined the E3 ligase activities of OsPIE1. Using GUS staining and GFP detection, we analyzed tissue expression patterns of OsPIE1 and the subcellular localization of its encoded protein. The function of OsPIE1 in Pi homeostasis was analyzed using OsPIE1 overexpressors and ospie1 mutants. OsPIE1 was localized to the nucleus, and expressed in epidermis, exodermis and sclerenchyma layers of primary root. Under Pi-sufficient condition, overexpression of OsPIE1 upregulated the expression of OsPT2, OsPT3, OsPT10 and OsPAP21b, resulting in Pi accumulation and acid phosphatases (APases) induction in roots. OsSPX2 was strongly suppressed in OsPIE1 overexpressors. Further comparative transcriptome analysis, tissue expression patterns and genetic interaction analysis indicated that the enhancing of Pi accumulation and APase activities upon overexpression of OsPIE1 was (at least in part) caused by repression of OsSPX2. These results indicate that OsPIE1 plays an important role in maintaining Pi homeostasis in rice.
Immune checkpoint inhibitors (ICIs) shed new light on triple-negative breast cancer (TNBC), but only a minority of patients demonstrate response. Therefore, adaptive immune resistance (AIR) needs to ...be further defined to guide the development of ICI regimens.
Databases, including The Cancer Genome Atlas, Gene Ontology Resource, University of California Santa Cruz Genome Browser, and Pubmed, were used to screen epigenetic modulators, regulators for CD8
T cells, and transcriptional regulators of programmed cell death-ligand 1 (PD-L1). Human peripheral blood mononuclear cell (Hu-PBMC) reconstruction mice were adopted for xenograft transplantation. Tumor specimens from a TNBC cohort and the clinical trial CTR20191353 were retrospectively analyzed. RNA-sequencing, Western blotting, qPCR and immunohistochemistry were used to assess gene expression. Coculture assays were performed to evaluate the regulation of TNBC cells on T cells. Chromatin immunoprecipitation and transposase-accessible chromatin sequencing were used to determine chromatin-binding and accessibility.
The epigenetic modulator AT-rich interaction domain 1A (ARID1A) gene demonstrated the highest expression association with AIR relative to other epigenetic modulators in TNBC patients. Low ARID1A expression in TNBC, causing an immunosuppressive microenvironment, promoted AIR and inhibited CD8
T cell infiltration and activity through upregulating PD-L1. However, ARID1A did not directly regulate PD-L1 expression. We found that ARID1A directly bound the promoter of nucleophosmin 1 (NPM1) and that low ARID1A expression increased NPM1 chromatin accessibility as well as gene expression, further activating PD-L1 transcription. In Hu-PBMC mice, atezolizumab demonstrated the potential to reverse ARID1A deficiency-induced AIR in TNBC by reducing tumor malignancy and activating anti-tumor immunity. In CTR20191353, ARID1A-low patients derived more benefit from pucotenlimab compared to ARID1A-high patients.
In AIR epigenetics, low ARID1A expression in TNBC contributed to AIR via the ARID1A/NPM1/PD-L1 axis, leading to poor outcome but sensitivity to ICI treatment.
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Transient receptor potential vanilloid1 (TRPV1) channel plays an important role in a wide range of physiological and pathological processes, and a comprehensive understanding of TRPV1 ...gating will create opportunities for therapeutic intervention. Recent incredible advances in cryo-electron microscopy (cryo-EM) have yielded high-resolution structures of all TRPV subtypes (TRPV1–6) and all of them share highly conserved six transmembrane (TM) domains (S1–S6). As revealed by the open structures of TRPV1 in the presence of a bound vanilloid agonist (capsaicin or resiniferatoxin), TM helicesS1 to S4 form a bundle that remains quiescent during channel activation, highlighting differences in the gating mechanism of TRPV1 and voltage-gated ion channels. Here, however, we argue that the structural dynamics rather than quiescence of S1–S4 domains is necessary for capsaicin-mediated activation of TRPV1. Using fluorescent unnatural amino acid (flUAA) incorporation and voltage-clamp fluorometry (VCF) analysis, we directly observed allostery of the S1–S4 bundle upon capsaicin binding. Covalent occupation of VCF-identified sites, single-channel recording, cell apoptosis analysis, and exploration of the role of PSFL828, a novel non-vanilloid agonist we identified, have collectively confirmed the essential role of this coordinated S1–S4 motility in capsaicin-mediated activation of TRPV1. This study concludes that, in contrast to cryo-EM structural studies, vanilloid agonists are also required for S1–S4 movement during TRPV1 activation. Redefining the gating process of vanilloid agonists and the discovery of new non-vanilloid agonists will allow the evaluation of new strategies aimed at the development of TRPV1 modulators.
This article introduces the design and imaging principles of the Advanced Hyperspectral Imager (AHSI) aboard China's GaoFen-5 satellite. The AHSI is a visible and nearinfrared (VNIR)/short-wave ...infrared (SWIR) HSI. It is the first spaceborne hyperspectral sensor that utilizes both a convex-grating spectrophotometry and an improved three-concentric-mirror (Offner) configuration. It has 330 spectral bands, a 60-km swath width, and a 30-m spatial resolution. Various tests have been designed to evaluate its imaging performance, and the results indicate that the AHSI's performance is comparable to other spaceborne HSIs launched recently and those scheduled for launch in the next few years. The AHSI has the capability to detect and identify different ground objects.
Hypertensive renal disease (HRD) contributes to the progression of kidney dysfunction and ultimately leads to end-stage renal disease. Understanding the mechanisms underlying HRD is critical for the ...development of therapeutic strategies. Deubiquitinating enzymes (DUBs) have been recently highlighted in renal pathophysiology. In this study, we investigated the role of a DUB, OTU Domain-Containing Protein 1 (OTUD1), in HRD models. HRD was induced in wild-type or Otud1 knockout mice by chronic infusion of angiotensin II (Ang II, 1 μg/kg per min) through a micro-osmotic pump for 4 weeks. We found that OTUD1 expression levels were significantly elevated in the kidney tissues of Ang II-treated mice. Otud1 knockout significantly ameliorated Ang II-induced HRD, whereas OTUD1 overexpression exacerbated Ang II-induced kidney damage and fibrosis. Similar results were observed in TCMK-1 cells but not in SV40 MES-13 cells following Ang II (1 μM) treatment. In Ang II-challenged TCMK-1 cells, we demonstrated that OTUD1 bound to CDK9 and induced CDK9 deubiquitination: OTUD1 catalyzed K63 deubiquitination on CDK9 with its Cys320 playing a critical role, promoting CDK9 phosphorylation and activation to induce inflammatory responses and fibrosis in kidney epithelial cells. Administration of a CDK9 inhibitor NVP-2 significantly ameliorated Ang II-induced HRD in mice. This study demonstrates that OTUD1 mediates HRD by targeting CDK9 in kidney epithelial cells, suggesting OTUD1 is a potential target in treating this disease.
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