Decoding the development of the human hippocampus.

The hippocampus is an important part of the limbic system in the human brain that has essential roles in spatial navigation and the consolidation of information from short-term memory to long-term memory1,2. Here we use single-cell RNA sequencing and assay for transposase-accessible chromatin using sequencing (ATAC-seq) analysis to illustrate the cell types, cell linage, molecular features and transcriptional regulation of the developing human hippocampus. Using the transcriptomes of 30,416 cells from the human hippocampus at gestational weeks 16-27, we identify 47 cell subtypes and their developmental trajectories. We also identify the migrating paths and cell lineages of PAX6+ and HOPX+ hippocampal progenitors, and regional markers of CA1, CA3 and dentate gyrus neurons. Multiomic data have uncovered transcriptional regulatory networks of the dentate gyrus marker PROX1. We also illustrate spatially specific gene expression in the developing human prefrontal cortex and hippocampus. The molecular features of the human hippocampus at gestational weeks 16-20 are similar to those of the mouse at postnatal days 0-5 and reveal gene expression differences between the two species. Transient expression of the primate-specific gene NBPF1 leads to a marked increase in PROX1+ cells in the mouse hippocampus. These data provides a blueprint for understanding human hippocampal development and a tool for investigating related diseases.

Bivalent mRNA vaccine effectiveness against SARS-CoV-2 variants of concern.

BACKGROUND: Sequential infections with SARS-CoV-2 variants such as Alpha, Delta, Omicron and its sublineages may cause high morbidity, so it is necessary to develop vaccines that can protect against both wild-type (WT) virus and its variants. Mutations in SARS-CoV-2's spike protein can easily alter viral transmission and vaccination effectiveness. METHODS: In this study, we designed full-length spike mRNAs for WT, Alpha, Delta, and BA.5 variants and integrated each into monovalent or bivalent mRNA-lipid nanoparticle vaccines. A pseudovirus neutralization assay was conducted on immunized mouse sera in order to examine the neutralizing potential of each vaccine. RESULTS: Monovalent mRNA vaccines were only effective against the same type of virus. Interestingly, monovalent BA.5 vaccination could neutralize BF.7 and BQ.1.1. Moreover, WT, Alpha, Delta, BA.5, and BF.7 pseudoviruses were broadly neutralized by bivalent mRNA vaccinations, such as BA.5 + WT, BA.5 + Alpha, and BA.5 + Delta. In particular, BA.5 + WT exhibited high neutralization against most variants of concern (VOCs) in a pseudovirus neutralization assay. CONCLUSIONS: Our results show that combining two mRNA sequences may be an effective way to develop a broadly protective SARS-CoV-2 vaccine against a wide range of variant types. Importantly, we provide the optimal combination regimen and propose a strategy that may prove useful in combating future VOCs.

Post-discharge experiences of patients with extracorporeal membrane oxygenation support: A qualitative study.

PURPOSE: To explore the life experiences of patients who have been discharged after undergoing extracorporeal membrane oxygenation (ECMO) support. DESIGN: A qualitative descriptive approach was used. METHODS: Patients who have undergone ECMO support and have been discharged were recruited. Thirteen participants were involved in this study. The data were collected through a semi-structured interview and analyzed using the Colaizzi method. FINDINGS: Four major themes in life experiences were reported by the participants: changes in physical function, changes in psychological state, active adaptation to daily life, and substantial rehabilitation needs. CONCLUSION: Different, continuous, and convenient post-discharge physical and mental interventions, social support, spiritual support, and rehabilitation services should be provided according to the patient's circumstances. We also call on the government to increase the patient reimbursement rate for ECMO treatment. These measures may help to improve the quality of life of patients.

S-Scheme BiOCl/MoSe2 Heterostructure with Enhanced Photocatalytic Activity for Dyes and Antibiotics Degradation under Sunlight Irradiation.

Semiconductor photocatalysis is considered to be a promising technique to completely eliminate the organic pollutants in wastewater. Recently, S-scheme heterojunction photocatalysts have received much attention due to their high solar efficiency, superior transfer efficiency of charge carriers, and strong redox ability. Herein, we fabricated an S-scheme heterostructure BiOCl/MoSe2 by loading MoSe2 nanosheets on the surface of BiOCl microcrystals, using a solvothermal method. The microstructures, light absorption, and photoelectrochemical performances of the samples were characterized by the means of SEM, TEM, XRD, transient photocurrents, electrochemical impedance, and photoluminescence (PL) spectra. The photocatalytic activities of BiOCl, MoSe2, and the BiOCl/MoSe2 samples with different MoSe2 contents were evaluated by the degradation of methyl orange (MO) and antibiotic sulfadiazine (SD) under simulated sunlight irradiation. It was found that BiOCl/MoSe2 displayed an evidently enhanced photocatalytic activity compared to single BiOCl and MoSe2, and 30 wt.% was an optimal loading amount for obtaining the highest photocatalytic activity. On the basis of radical trapping experiments and energy level analyses, it was deduced that BiOCl/MoSe2 follows an S-scheme charge transfer pathway and •O2-, •OH, and h+ all take part in the degradation of organic pollutants.

Quantitative Proteomic Analysis of Synovial Tissue Reveals That Upregulated OLFM4 Aggravates Inflammation in Rheumatoid Arthritis.

Tandem mass tag (TMT)-coupled liquid chromatography coupled with tandem mass spectrometry is a powerful method to investigate synovial tissue protein profiles in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Protein was isolated from synovial tissue samples of 22 patients and labeled with a TMT kit. Over 500 proteins were identified as the differential expression protein on comparing RA and OA synovial tissue, including 239 upregulated and 271 downregulated proteins. Data are available via ProteomeXchange with identifier PXD027703. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that the majority participated in the developmental processes and protein processing in the endoplasmic reticulum. Olfactomedin 4 (OLFM4), a secreted glycoprotein, in joint inflammation of RA was explored. OLFM4 was upregulated in RA synovial tissue samples. In fibroblast-like synoviocytes (FLS), inflammation cytokines, TNF-α, interleukin (IL)-1ß, and LPS can upregulate OLFM4. After OLFM4 knockdown under TNF-α stimulation, RA FLS proliferation was inhibited and the expression of CXCL9, CXCL11, and MMP-1 was decreased. Overall, the RA synovial tissue protein expression profile by proteomic analysis shows some unique targets in RA pathophysiology, and OLFM4 in FLS plays an important role in RA joint inflammation. OLFM4 can be a promising therapeutic target in RA synovial tissue.

microRNA-106b derived from endothelial cell-secreted extracellular vesicles prevents skin wound healing by inhibiting JMJD3 and RIPK3.

Intriguingly, microRNAs (miRs) transferred as cargo in extracellular vesicles (EVs) can modulate wound healing through their regulation of fibroblast functions. In this study, we investigated the effects of miR-106b transfer via EVs derived from human umbilical vein endothelial cells (HUVECs) on skin wound healing. Dual-luciferase reporter gene assay identified that miR-106b could target and inhibit JMJD3. RT-qPCR analysis showed EVs isolated from HUVECs had enriched expression of miR-106b. LL29 fibroblast cells and HaCaT keratinocytes were co-cultured with HUVEC-derived EVs, in which miR-106b had been up-regulated or down-regulated by its mimic or inhibitor. The co-culture with HUVEC-derived EVs increased miR-106b expression, and reduced the viability and adhesion of LL29 and HaCaT cells, whereas the inhibition of miR-106b in HUVEC-derived EVs enhanced the viability and adhesion of LL29 and HaCaT cells through up-regulation of JMJD3. Next, we showed that JMJD3 overexpression enhanced LL29 and HaCaT cell viability and adhesion through elevating RIPK3, which induced the phosphorylation of AKT during the wound-healing process. We next developed a mouse skin wound model to investigate the actions of miR-106b in vivo after 14 days. The delivery of miR-106b via HUVEC-derived EVs delayed wound healing through suppression of collagen I content and angiogenesis, but had no effects on pro-inflammatory cytokines. In conclusion, miR-106b from HUVEC-derived EVs inhibits JMJD3 and RIPK3, leading to the inhibition of skin wound healing, thus constituting a new therapeutic target.

Tibiofemoral rotation alignment in the normal knee joints among Chinese adults: a CT analysis.

BACKGROUND: Consensus on tibial rotation in total knee arthroplasty (TKA) remains controversial. The present study aimed to investigate the closest anatomical reference to surgical epicondylar axis (SEA) among 10 tibial markers in Chinese adults. METHODS: This study included examination of 122 normal lower extremities. Briefly, 10 axes were drawn on the axial sections: transverse axis of tibia (TAT), axis of medial edge of patellar tendon (MEPT), axis of medial 1/3 of patellar tendon attachment (M1/3), Akagi line, Insall line, axis of medial border of tibial tubercle (MBTT), and axis of anterior border of the tibia 1-4 (ATC1-4). The mean angles between TAT and SEA and that between other axes and the line perpendicular to SEA were measured. Pairwise differences among the 10 tibial axes were examined by applying one-way analysis of variance (ANOVA) and paired t-test. RESULTS: In all the knees, the mean angles of M1/3, Akagi line, Insall line, MBTT, ATC1, ATC2, ATC3, and ATC4 axes were compared to the line perpendicular to the projected SEA and found to be 10.2 ± 5.1°, 1.4 ± 5.0°, 11.9 ± 5.4°, 3.6 ± 4.8°, 12.0 ± 6.9°, 7.2 ± 8.6°, 7.1 ± 10.4°, and 6.6 ± 13.5° external rotation, respectively, and the MEPT axis was 1.6 ± 4.5° internal rotation. The mean angle for TAT was 4.1 ± 5.3° external rotation. The M1/3 and Insall line were significantly more externally rotated than Akagi line, MEPT, MBTT, TAT, ATC2, ATC3, and ATC4 axes. No significant differences were noted between the TAT axis and the MBTT axis and among the ATC2, ATC3, and ATC4 axes. CONCLUSION: The Akagi line, MBTT, and TAT showed good consistency with SEA in the axial femorotibial alignment with knee in extension. The middle segment of the anterior tibial crest also demonstrated good alignment consistency with SEA for the axial femorotibial alignment. Hence, these markers can be used as reliable references for rotational alignment of the tibial component in TKA.

Quercetin inhibited cadmium-induced autophagy in the mouse kidney via inhibition of oxidative stress.

The objective of the current study was to explore the inhibitory effects of quercetin on cadmium-induced autophagy in mouse kidneys. Mice were intraperitoneally injected with cadmium and quercetin once daily for 3 days. The LC3-II/ß-actin ratio was used as the autophagy marker, and autophagy was observed by transmission electron microscopy. Oxidative stress was investigated in terms of reactive oxygen species, total antioxidant capacity, and malondialdehyde. Cadmium significantly induced typical autophagosome formation, increased the LC3-II/ß-actin ratio, reactive oxygen species level, and malondialdehyde content, and decreased total antioxidant capacity. Interestingly, quercetin markedly decreased the cadmium-induced LC3-II/ß-actin ratio, reactive oxygen species levels, and malondialdehyde content, and simultaneously increased total antioxidant capacity. Cadmium can inhibit total antioxidant capacity, produce a large amount of reactive oxygen species, lead to oxidative stress, and promote lipid peroxidation, eventually inducing autophagy in mouse kidneys. Quercetin could inhibit cadmium-induced autophagy via inhibition of oxidative stress. This study may provide a theoretical basis for the treatment of cadmium injury.

[Preliminary study of impact of steroids on expression profile and transcriptome of bone microvascular endothelial cells].

OBJECTIVE: To explore the differential expression profiles and transcriptomes of human bone microvascular endothelial cells via microarray and elucidate the molecular mechanisms underlying steroids-induced osteonecrosis. METHODS: Bone microvascular endothelial cells in cancellous bone of femoral head were harvested by type I collagenase and trypsin digestion and identified by immunofluorescent labeling with primary antibodies specific for vascular endothelial cells' biomarkers such as von Willebrand factor, platelet endothelial cell adhesion molecule 1, vascular endothelial cadherin and vascular cell adhesion molecule 1. Their differential expression profiles and transcriptomes were tested by double-labeled lncRNAs + mRNAs microarrays and single-labeledd microRNAs microarrays. The data were analyzed by bioinformatical software with database checking. The authors spatial correlations and expression relevance were established among lncRNAs, microRNAs and mRNAs. RESULTS: Steroids incurred specific changes in mRNAs, microRNAs and lncRNAs transcribed in human bone microvascular endothelial cells of femoral head in vitro cultured. Thus a model of coexpression network was constructed among transcript modules with bioinformatical tools such as target gene prediction. CONCLUSION: Steroids induced significant changes in transcripts of bone microvascular endothelial cells such as miR-100, miR-222, miR-933, miR-339 and miR-23. They exert considerable influences on osseous tissues and circulatory systems in cancellous bone by targeting cytokines and enzymes such catalase, fibroblast growth factor and nerve growth factor. Through further explorations of these transcripts, we can not only elucidate the underlying pathogenesis, but also discover specific biomarkers and therapeutic targets for corresponding diseases.

[Radiological assessments of proximal femoral geometry and its clinical significance in hip arthroplasty].

OBJECTIVE: To explore the reliability of the relationship between the tip of greater trochanter and the center of femoral head in restoring leg length discrepancy during hip arthroplasty. METHODS: From June 2013 to October 2013, 370 standard anterior-posterior pelvic radiographs were performed. There were 160 males and 210 females with a mean age of 47.6 years. Landmarks were selected by Picture Archiving and Communication Systems (PACS) as follows: the center of femoral head of concentric circles, anatomic axis of proximal femur, the lines perpendicular to anatomic axis of proximal femur through the tip of greater trochanter and the center of femoral head. The distance between two intersected points, i.e. vertical distance between the tip of greater trochanter and the center of femoral head, aka greater trochanter height (GTH), was measured by two orthopedic surgeons respectively. If the tip of greater trochanter was above the center of femoral head, the distance was defined as positive. And the distance was negative if the tip of greater trochanter fell below the center of femoral head. The distance of male and female and that of right and left femurs were compared. RESULTS: Only 6 tips of greater trochanter were below the center of femoral head, 9 at the same level and 725 above the center of femoral head. And 96.89% of tips of the greater trochanter were at 0-15 mm above the center of femoral head. The difference between male and female (P = 0.032) and the difference between right and left sides were statistically significant (P < 0.001). CONCLUSION: The center of femoral head is not at the same level as the tip of greater trochanter. And the distances of right and left tips of greater trochanter to the ipsilateral center of femoral head are not always at the same level. So it should be cautious to employ the relationship between the tip of greater trochanter and the center of femoral head in restoring leg length discrepancy during hip arthroplasty.

Pilomatricoma Located at the Identical Position in the Right Upper Limb of the Twins: A Rare Case Report.

Introduction: Rare studies have reported pilomatricoma in twins, and extremely rare cases showed lesions in the same part of the body position. We reported a case of monozygotic twins with pilomatricoma in the same location on the skin of the right upper extremity. Case Presentation: Seven-year-old monozygotic twins presented to our department with a palpable, painless, and solid mass in the subcutaneous tissue of the right upper limb. A 1.5-cm diameter nodule was seen on the anterolateral aspect of the right upper extremity of the twins. The node was irregular in shape, and upon palpation, the patients reported no noticeable tenderness. Following the administration of local anesthesia, the twins underwent surgical procedure to excise the solid mass. Finally, they were diagnosed with pilomatricoma based on the clinical and histopathological features. Complete surgical resection followed by primary closure was performed. During a follow-up period of three years, there has been no recurrence observed in the twins. Conclusion: We reported a case of monozygotic twins with pilomatricoma in the same location on the skin of the right upper arm. Our findings underscore the requirement of considering genetic factors in the diagnosis and treatment of the rare conditions.

Enhancing the Quality of Low-Salt Silver Carp (Hypophthalmichthys molitrix) Surimi Gel Using Psyllium Husk Powder: An Orthogonal Experimental Approach.

Low-salt surimi production is crucial as it addresses health concerns related to sodium intake while maintaining the quality and shelf-life of seafood products. This research focused on optimizing the gelation conditions for silver carp surimi with the addition of psyllium husk powder at low salt concentrations (0.5% and 1%, w/w) to investigate the effects of psyllium husk powder concentration, temperature, and time on gel strength and water-holding capacity. The quality was assessed in terms of gel strength and water-holding capacity. Following a single-factor exploration, a three-level orthogonal experiment was designed to evaluate the influence of these three variables using a combined scoring system. Results indicated that psyllium husk powder levels between 0.1% and 0.3% (w/w) enhanced gel strength and water-holding capacity. The optimal conditions were identified as follows: 1% (w/w) NaCl with 0.2% (w/w) psyllium husk powder for 2.5 h at 35 °C, and 0.5% (w/w) NaCl with 0.3% (w/w) psyllium husk powder for 3 h at 35 °C. Texture profile analysis revealed that psyllium husk powder increased the hardness of the surimi gel, promoting myosin cross-linking and denser gel structure. Compared to traditional surimi gel, which relies on ionic bonds, the optimized gel showed higher levels of disulfide cross-linking and enhanced hydrophobic interactions, resulting in a stronger gel structure. Sensory evaluation suggested that surimi gels with psyllium husk powder were perceived as better than those without psyllium husk powder. The study concludes that selecting the appropriate psyllium husk powder quantity and thermal processing conditions based on salt concentration can significantly improve the quality of low-salt surimi gels. Error analysis using one-way ANOVA was performed on all experimental data and (p < 0.05) indicated the significant difference.

Multivalent mRNA Vaccine Elicits Broad Protection against SARS-CoV-2 Variants of Concern.

SARS-CoV-2 new waves are primarily caused by changes to the spike protein (S), which can substantially decrease the efficacy of vaccines. Therefore, we tested several multivalent mRNA-LNP vaccines, targeting the full-length S proteins of different variants, and identified an optimal combination for protection against VOCs in BALB/c mice. The tested formulations included trivalent (WT + BA.5 + XBB.1.5), pentavalent (WT + BA.5 + XBB.1.5 + BQ.1.1 + CH.1.1), and octavalent (WT + BA.5 + XBB.1.5 + BQ.1.1 + CH.1.1 + Alpha + Delta + BA.2) vaccines. Among these multivalent vaccines, the pentavalent vaccine showed superior protection for almost all tested variants. Despite this, each multivalent vaccine elicited greater broad-spectrum neutralizing antibodies than the previously evaluated bivalent vaccine (WT + BA.5). Subsequently, we redesigned the multivalent vaccine to efficiently generate neutralizing antibodies against recent VOCs, including EG.5.1. Immunization with the redesigned pentavalent vaccine (WT + EG.5.1 + XBB.1.16 + Delta + BA.5) showed moderate levels of protection against recent Omicron VOCs. Results suggest that the neutralization activity of multivalent vaccines is better than those of the tested bivalent vaccines against WT + BA.5 and WT + EG.5.1. Moreover, the pentavalent vaccine we developed may be highly useful for neutralizing new Omicron VOCs.

DLC-1 is a candidate biomarker methylated and down-regulated in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive malignancies in humans, and its prognosis is generally poor even after surgery. Many advances have been made to understand the pathogenesis of PDA; however, the molecular mechanisms that lead to pancreatic carcinogenesis are still not clearly understood. The aims of this study were to investigate the relationship between DLC-1 methylation status and clinicopathological characteristics of PDA patients and evaluate the role of DLC-1 methylation status in PDA. The expression of DLC-1 mRNA in PDA tissues was analyzed by real-time PCR. The methylation status of DLC-1 was analyzed by methylation-specific polymerase chain reaction (MSP). Furthermore, we determined the prognostic importance of DLC-1 methylation status in PDA patients. Our results showed that the expression level of DLC-1 mRNA in PDA tissues was lower than that in non-cancerous tissues. The rate of DLC-1 promoter methylation was significantly higher in PDA tissues than in adjacent non-cancerous tissues (p < 0.001). Downregulation of DLC-1 was strongly correlated with promoter methylation (P = 0.003). The presence of DLC-1 methylation in PDA tissue samples was significantly correlated with clinical stage (P = 0.005), histological differentiation (P = 0.05), and lymph node metastasis (P = 0.006). Kaplan-Meier survival analysis showed that DLC-1 methylation status was inversely correlated with overall survival of the PDA patients. Further, Cox multivariate analysis indicated that DLC-1 methylation status was an independent prognostic factor for the overall survival rate of PDA patients. In conclusion, our data suggest that downregulation of DLC-1 may be explained by DNA methylation; DLC-1 may be a biomarker for PDA.

Expression of NEDD9 in pancreatic ductal adenocarcinoma and its clinical significance.

The aim of this study was to investigate the expression and prognostic significance of NEDD9 in pancreatic ductal adenocarcinoma (PDA). Expressional levels of NEDD9 mRNA and protein in paired pancreatic cancer lesions and adjacent noncancerous tissues were examined by quantitative real-time PCR and western blotting. NEDD9 expression was analyzed by immunohistochemistry in 106 patients with PDA. The correlations between NEDD9 immunostaining levels and clinicopathologic factors, as well as the follow-up data of patients, were analyzed statistically. NEDD9 protein and mRNA levels were elevated in pancreatic carcinoma lesions compared with the paired adjacent noncancerous tissues. A high level of expression of NEDD9 was significantly correlated with clinical staging (P < 0.001), lymph node metastasis (P < 0.001), and histological differentiation (P < 0.001). Patients with a higher NEDD9 expression had a significantly shorter survival time than those patients with lower NEDD9 expression. The multivariate analysis revealed that NEDD9 could serve as an independent factor of poor prognosis. Our finding indicates that NEDD9 could be used as prognostic molecular marker and therapeutic target for PDA.

Bowen's Disease of the Nipple and Areola: Case Report and Literature Review.

Introduction: Bowen's disease (BD) commonly occurs in sites of chronic sunlight exposure such as head, neck and extremities. It rarely distributes on the nipple and areola. Case Presentation: A 59-year-old female presented with crusted plaque on the right breast for over 1 month. Physical examination found an asymptomatic plaque (5 cm × 5 cm) with irregular shape on the right breast. Histopathological examination suggested irregularly acanthotic epidermis and atypical epidermal cells. Dermis showed inflammatory cell infiltration. Immunohistochemical staining showed negative staining for cytokeratin 7 and cytokeratin 20, and positive staining for Ki67 (60%). The mass was excised and no recurrence occurred in the follow-up. Additionally, we reviewed the literature about BD of the breast and summarized the clinical manifestations, histological features, and treatment options. Conclusion: We reported a rare BD case involving nipple and areola. Wide local excision and complete nipple excision are effective for patients with BD of the nipple and areola.

Single-cell epigenomics and spatiotemporal transcriptomics reveal human cerebellar development.

Human cerebellar development is orchestrated by molecular regulatory networks to achieve cytoarchitecture and coordinate motor and cognitive functions. Here, we combined single-cell transcriptomics, spatial transcriptomics and single cell chromatin accessibility states to systematically depict an integrative spatiotemporal landscape of human fetal cerebellar development. We revealed that combinations of transcription factors and cis-regulatory elements (CREs) play roles in governing progenitor differentiation and cell fate determination along trajectories in a hierarchical manner, providing a gene expression regulatory map of cell fate and spatial information for these cells. We also illustrated that granule cells located in different regions of the cerebellar cortex showed distinct molecular signatures regulated by different signals during development. Finally, we mapped single-nucleotide polymorphisms (SNPs) of disorders related to cerebellar dysfunction and discovered that several disorder-associated genes showed spatiotemporal and cell type-specific expression patterns only in humans, indicating the cellular basis and possible mechanisms of the pathogenesis of neuropsychiatric disorders.

Ferrodifferentiation regulates neurodevelopment via ROS generation.

Iron is important for life, and iron deficiency impairs development, but whether the iron level regulates neural differentiation remains elusive. In this study, with iron-regulatory proteins (IRPs) knockout embryonic stem cells (ESCs) that showed severe iron deficiency, we found that the Pax6- and Sox2-positive neuronal precursor cells and Tuj1 fibers in IRP1-/-IRP2-/- ESCs were significantly decreased after inducing neural differentiation. Consistently, in vivo study showed that the knockdown of IRP1 in IRP2-/- fetal mice remarkably affected the differentiation of neuronal precursors and the migration of neurons. These findings suggest that low intracellular iron status significantly inhibits neurodifferentiation. When supplementing IRP1-/-IRP2-/- ESCs with iron, these ESCs could differentiate normally. Further investigations revealed that the underlying mechanism was associated with an increase in reactive oxygen species (ROS) production caused by the substantially low level of iron and the down-regulation of iron-sulfur cluster protein ISCU, which, in turn, affected the proliferation and differentiation of stem cells. Thus, the appropriate amount of iron is crucial for maintaining normal neural differentiation that is termed ferrodifferentiation.

The single-cell and spatial transcriptional landscape of human gastrulation and early brain development.

The emergence of the three germ layers and the lineage-specific precursor cells orchestrating organogenesis represent fundamental milestones during early embryonic development. We analyzed the transcriptional profiles of over 400,000 cells from 14 human samples collected from post-conceptional weeks (PCW) 3 to 12 to delineate the dynamic molecular and cellular landscape of early gastrulation and nervous system development. We described the diversification of cell types, the spatial patterning of neural tube cells, and the signaling pathways likely involved in transforming epiblast cells into neuroepithelial cells and then into radial glia. We resolved 24 clusters of radial glial cells along the neural tube and outlined differentiation trajectories for the main classes of neurons. Lastly, we identified conserved and distinctive features across species by comparing early embryonic single-cell transcriptomic profiles between humans and mice. This comprehensive atlas sheds light on the molecular mechanisms underlying gastrulation and early human brain development.

Polymorphic variations in manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPX1), and catalase (CAT) contribute to elevated plasma triglyceride levels in Chinese patients with type 2 diabetes or diabetic cardiovascular disease.

Manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPX1), and catalase (CAT) provide the primary antioxidant defense system. Impaired antioxidant defense increases oxidative stress and contributes to the development of type 2 diabetes and diabetic cardiovascular disease (CVD). We preformed a case-control study in Chinese type 2 diabetes patients, to determine if the MnSOD Val16Ala (T→C), GPX1 Pro198Leu (C→T), and CAT -262C/T (C→T) functional polymorphisms contribute to the development of type 2 diabetes or diabetic CVD. Patients with type 2 diabetes (n = 168) were divided into the non-CVD group (n = 83, >10 year since diagnosis) and CVD group (n = 85, history of ischemic CVD). Genotyping was performed using PCR-restriction fragment length polymorphism (PCR-RFLP) or PCR-based direct sequencing. The genotypic distribution in the non-CVD- and CVD-group and the clinical parameters in genotypic groups were not significantly different in the three polymorphic sites, respectively. Among eight genotypic combinations, the most common TT+CC+CC genotype (59.5%) was associated with higher triglyceride levels than the TT+CT+CC genotype, the second frequent one (14.9%; 1.77 ± 0.12 vs. 1.21 ± 0.11 mmol/l, P = 0.001), and all non-TT+CC+CC genotypes (40.5%; 1.77 ± 0.12 vs. 1.43 ± 0.12 mmol/l, P = 0.048). In the CVD group, significantly elevated triglyceride levels were also observed in patients with TT+CC+CC compared to patients with TT+CT+CC (2.00 ± 0.18 vs. 1.37 ± 0.16 mmol/l, P = 0.018) or non-TT+CC+CC genotypes (2.00 ± 0.18 vs. 1.65 ± 0.19 mmol/l, P = 0.070). The common MnSOD, GPX1, and CAT TT+CC+CC genotype may contribute to hypertriglyceridemia in Chinese patients with type 2 diabetes or diabetic CVD.