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Abstract Background For youths, abnormalities in ambulatory blood pressure (ABP) patterns are known to be associated with increased cardiovascular disease risk and potential target organ damage. Body composition, including indicators such as lean mass index (LMI), fat mass index (FMI), and visceral fat level (VFL), plays a significant role in blood pressure (BP) regulation. However, little is known about the association between these body composition indicators and ABP. Therefore, the present study examined the association between these body composition indicators and BP among Chinese youths. Methods A total of 477 college students aged 17 to 28 years old (mean ± Standard deviation = 18.96 ± 1.21) from a university in Changsha, Hunan Province, China, were included in this study. Body composition indicators were measured with a bioelectrical impedance body composition analyzer, and 24-hour ambulatory blood pressure monitoring (ABPM) was conducted. Multivariable logistic regression was performed to assess the relationship between body composition indicators and abnormal ABP. Results The prevalence of abnormal BP, including 24-hour BP, daytime BP, nighttime BP, and clinic BP, were 4.8%, 4.2%, 8.6%, and 10.9%, respectively. After adjusting for potential covariates, LMI [abnormal 24-hour BP (OR = 1.85, 95%CI:1.31, 2.62), abnormal daytime BP (OR = 1.76, 95%CI:1.21, 2.58), abnormal nighttime BP (OR = 1.64, 95%CI:1.25, 2.14), abnormal clinic BP (OR = 1.84, 95%CI:1.38, 2.45)], FMI [abnormal 24-hour BP (OR = 1.20, 95%CI:1.02, 1.41), abnormal daytime BP (OR = 1.30, 95%CI:1.07, 1.57), abnormal nighttime BP (OR = 1.24, 95%CI:1.10, 1.39), abnormal clinic BP (OR = 1.42, 95%CI:1.22, 1.65)], and VFL [abnormal 24-hour BP (OR = 1.22, 95%CI:1.06, 1.39), abnormal daytime BP (OR = 1.29, 95%CI:1.10, 1.51), abnormal nighttime BP (OR = 1.24, 95%CI:1.12, 1.39), abnormal clinic BP (OR = 1.38, 95%CI:1.21, 1.57)] are positively linked to abnormal BP. Additionally, there were significant sex differences in the association between body composition and abnormal BP. Conclusions Our findings suggested maintaining an individual’s appropriate muscle mass and fat mass and focusing on the different relations of males’ and females’ body composition is crucial for the achievement of appropriate BP profiles.

Abstract The synthesis of chiral α-azaheteroaryl oxiranes via enantioselective catalysis is a formidable challenge due to the required complex stereoselectivity and diverse N-heterocyclic structures. These compounds play a crucial role in developing bioactive molecules, where precise chirality significantly influences biological activity. Here we show that using chiral phosphoric acid as a catalyst, our method efficiently addresses these challenges. This technique not only achieves high enantio- and diastereoselectivity but also demonstrates superior chemo- and stereocontrol during the epoxidation of alkenyl aza-heteroarenes. Our approach leverages a synergistic blend of electrostatic and hydrogen-bonding interactions, enabling the effective activation of both substrates and hydrogen peroxide. The resulting chiral oxiranes exhibit enhanced diversity and functionality, aiding the construction of complex chiral azaaryl compounds with contiguous stereocenters. Kinetic and density functional theory studies elucidate the mechanism, highlighting chiral phosphoric acid’s pivotal role in this intricate enantioselective process.

Abstract Chironomids are one of the most abundant aquatic insects and are widely distributed in various biological communities. However, the lack of high-quality genomes has hindered our ability to study the evolution and ecology of this group. Here, we used Nanopore long reads and Hi-C data to produce two chromosome-level genomes from mixed genomic data. The genomes of Smittia aterrima (SateA) and Smittia pratorum (SateB) were assembled into three chromosomes, with sizes of 78.45 Mb and 71.56 Mb, scaffold N50 lengths of 25.73 and 23.53 Mb, and BUSCO completeness of 98.5% and 97.8% (n = 1,367), 5.68 Mb (7.24%) and 1.94 Mb (2.72%) of repetitive elements, and predicted 12,330 (97.70% BUSCO completeness) and 11,250 (97.40%) protein-coding genes, respectively. These high-quality genomes will serve as valuable resources for comprehending the evolution and environmental adaptation of chironomids.

Motor imagery (MI) is a high-level cognitive process that has been widely applied to clinical rehabilitation and brain-computer interfaces (BCIs). However, the decoding of MI tasks still faces challenges, and the neural mechanisms underlying its application are unclear, which seriously hinders the development of MI-based clinical applications and BCIs. Here, we combined EEG source reconstruction and Bayesian nonnegative matrix factorization (NMF) methods to construct large-scale cortical networks of left-hand and right-hand MI tasks. Compared to right-hand MI, the results showed that the significantly increased functional network connectivities (FNCs) mainly located among the visual network (VN), sensorimotor network (SMN), right temporal network, right central executive network, and right parietal network in the left-hand MI at the $\beta $ (13-30Hz) and all (8-30Hz) frequency bands. For the network properties analysis, we found that the clustering coefficient, global efficiency, and local efficiency were significantly increased and characteristic path length was significantly decreased in left-hand MI compared to right-hand MI at the $\beta $ and all frequency bands. These network pattern differences indicated that the left-hand MI may need more modulation of multiple large-scale networks (i.e., VN and SMN) mainly located in the right hemisphere. Finally, based on the spatial pattern network of FNC and network properties, we propose a classification model. The proposed model achieves a top classification accuracy of 78.2% in cross-subject two-class MI-BCI tasks. Overall, our findings provide new insights into the neural mechanisms of MI and a potential network biomarker to identify MI-BCI tasks.

Abstract Acute Myocardial Infarction (AMI) after Percutaneous Coronary Intervention (PCI) often requires stent implantation leading to cardiovascular injury and cytokine release. Stent implantation induces cytokines production including TNFα, Hs-CRP, IL-1ß, IL2 receptor, IL6, IL8, and IL10, but their co-release is not extensively established. In 311 PCI patients with Drug-Eluting Stent (DES) implantation, we statistically evaluate the correlation of these cytokines release in various clinical conditions, stent numbers, and medications. We observed that TNFα is moderately correlated with IL-1ß (r2 = 0.59, p = 0.001) in diabetic PCI patients. Similarly, in NSTEMI (Non-ST Segment Elevation) patients, TNFα is strongly correlated with both IL-1ß (r2 = 0.97, p = 0.001) and IL8 (r2 = 0.82, p = 0.001). In CAD (Coronary Artery Disease)-diagnosed patients TNFα is highly correlated (r2 = 0.84, p = 0.0001) with IL8 release but not with IL-1ß. In patients with an increased number of stents, Hs-CRP is significantly coupled with IL8 > 5 pg/ml (t-statistic = 4.5, p

Abstract The family Chironomidae is represented by seven subfamilies in China, among which Chironominae and Orthocladiinae are the most diverse. To gain a better understanding of the architecture and evolution of the mitogenomes of Chironomidae, we sequenced mitogenomes of twelve species (including two published species) of the two subfamilies Chironominae and Orthocladiinae, and comparative mitogenomic analyses were performed. Thus, we identified highly conserved genome organization of twelve species with regard to genome content, nucleotide and amino acid composition, codon usage, and gene characteristics. The K a /K s values of most protein-coding genes were far smaller than 1, indicating that these genes were evolving under purifying selection. Phylogenetic relationships between the family Chironomidae were reconstructed using 23 species representing six subfamilies, based on protein-coding genes and rRNAs using Bayesian Inference and Maximum Likelihood. Our results suggested the following relationship within the Chironomidae: (Podonominae + Tanypodinae) + (Diamesinae + (Prodiamesinae + (Orthocladiinae + Chironominae))). This study contributes to the mitogenomic database of Chironomidae, which will be significant for studing the mitogenome evolution of Chironomidae.

Abstract Background Testis is the only organ supporting sperm production and with the largest number of proteins and tissue-specific proteins in animals. In our previous studies, we have found that knockdown of ocnus (ocn), a testis-specific gene, resulted in much smaller testis with no germ cells in Drosophila melanogaster. However, the molecular consequences of ocn knockdown in fly testes are unknown. Results In this study, through iTRAQ quantitative proteomics sequencing, 606 proteins were identified from fly abdomens as having a significant and at least a 1.5-fold change in expression after ocn knockdown in fly testes, of which 85 were up-regulated and 521 were down-regulated. Among the differential expressed proteins (DEPs), apart from those proteins involved in spermatogenesis, the others extensively affected biological processes of generation of precursor metabolites and energy, metabolic process, and mitochondrial transport. Protein-protein interaction (PPI) analyses of DEPs showed that several kinases and/or phosphatases interacted with Ocn. Re-analyses of the transcriptome revealed 150 differential expressed genes (DEGs) appeared in the DEPs, and their changing trends in expressions after ocn knockdown were consistent. Many common down-regulated DEGs and DEPs were testis-specific or highly expressed in the testis of D. melanogaster. Quantitative RT-PCR (qRT-PCR) confirmed 12 genes appeared in both DEGs and DEPs were significantly down-regulated after ocn knockdown in fly testes. Furthermore, 153 differentially expressed phosphoproteins (DEPPs), including 72 up-regulated and 94 down-regulated phosphorylated proteins were also identified (13 phosphoproteins appeared in both up- and down-regulated groups due to having multiple phosphorylation sites). In addition to those DEPPs associated with spermatogenesis, the other DEPPs were enriched in actin filament-based process, protein folding, and mesoderm development. Some DEPs and DEPPs were involved in Notch, JAK/STAT, and cell death pathways. Conclusions Given the drastic effect of the ocn knockdown on tissue development and testis cells composition, the differences in protein abundance in the ocn knockdown flies might not necessarily be the direct result of differential gene regulation due to the inactivation of ocn. Nevertheless, our results suggest that the expression of ocn is essential for Drosophila testis development and that its down-regulation disturbs key signaling pathways related to cell survival and differentiation. These DEPs and DEPPs identified may provide significant candidate set for future studies on the mechanism of male reproduction of animals, including humans.

Abstract The purpose of this study was to investigate the association between time restricted feeding (TRF) and different areas of cognitive function in the elderly in Chinese communities. This study consisted of 1353 community-dwelling Chinese older adults aged 60 years and older in Chongming area, Shanghai (563 males; the mean age, 73.38 ± 6.16 years). Mild cognitive impairment (MCI) and six different cognitive domains was assessed by the Chinese-version of Mini Mental State Examination (MMSE). Recording the eating time of each meal through oral inquiry to calculate the time window between the first meal and the last meal of the average day. Participants with an eating time window duration of more than 10 h were then identified, as well as those with eating time restricted to less than 10 h (TRF). Our study found that TRF may be associated with a higher incidence rate of cognitive impairment. TRF only limited the eating time window and did not change the frequency of participants' dietary intake. We used a linear regression model to study the association of TRF with cognitive function. After adjusting for confounding variables, the results showed that TRF was related to MMSE score (P

IntroductionGenetic epilepsy is a large group of clinically and genetically heterogeneous neurological disorders characterized by recurrent seizures, which have a clear association with genetic defects. In this study, we have recruited seven families from China with neurodevelopmental abnormalities in which epilepsy was a predominant manifestation, aiming to elucidate the underlying causes and make a precise diagnosis for the cases.MethodsWhole-exome sequencing (WES) combined with Sanger sequencing was used to identify the causative variants associated with the diseases in addition to essential imaging and biomedical examination.ResultsA gross intragenic deletion detected in MFSD8 was investigated via gap-polymerase chain reaction (PCR), real-time quantitative PCR (qPCR), and mRNA sequence analysis. We identified 11 variants in seven genes (ALDH7A1, CDKL5, PCDH19, QARS1, POLG, GRIN2A, and MFSD8) responsible for genetic epilepsy in the seven families, respectively. A total of six variants (c.1408T>G in ALDH7A1, c.1994_1997del in CDKL5, c.794G>A in QARS1, c.2453C>T in GRIN2A, and c.217dup and c.863+995_998+1480del in MFSD8) have not yet been reported to be associated with diseases and were all evaluated to be pathogenic or likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines.MethodsBased on the molecular findings, we have associated the intragenic deletion in MFSD8 with the mutagenesis mechanism of Alu-mediated genomic rearrangements for the first time and provided genetic counseling, medical suggestions, and prenatal diagnosis for the families. In conclusion, molecular diagnosis is crucial to obtain improved medical outcomes and recurrence risk evaluation for genetic epilepsy.

While the original equipment manufacturers are developing engines that can withstand higher PCP, the methodology to maximize the thermal efficiency gain with different PCP limits is still not well-known or documented in the literature. This study aims to provide guidance on how to co-optimize air system parameters, compression ratio, and intake valve closing (IVC) timing of heavy-duty turbocharged diesel engines to enhance thermal efficiency with peak cylinder pressure (PCP) constraints. In this study, a one-dimensional turbocharged engine model is established and validated by experimental data. The effects of turbocharger efficiency, boost pressure, high-pressure exhaust gas recirculation (HP EGR) ratio, compression ratio (CR), and IVC timing on diesel engine efficiency are assessed under PCP constraints through parametric analysis. The results indicate that for enhancing engine thermal efficiency under limited PCP, an increment in boost pressure and CR, and late IVC timing compared to baseline is required. By multiple parameter optimization, the best parameter combination under different PCP constraints is proposed. At a PCP limit of 20 MPa, the combination of a compression ratio of 18.57, boost pressure of 298 kPa, and IVC timing of −95.2 °CA ATDC yields a 1.56% (absolute value) improvement in ITEn over the baseline condition. Raising the PCP limits from 20 MPa to 25 MPa requires increasing the compression ratio to 21.92, boost pressure to 308 kPa, and delaying the intake valve closing timing to −88.7 °CA ATDC, which results in an absolute improvement of 0.86% in ITEn. Baseline engine configuration is updated accordingly to validate the thermal efficiency improvement strategy at a 25 MPa PCP limitation. Experimental results demonstrate a 2.2% (absolute value) improvement in brake thermal efficiency and 1.98% (absolute value) improvement in overall energy efficiency.

Abstract Pregnant women are generally more susceptible to viral infection. Although the impact of SARS-CoV-2 in pregnancy remains to be determined, evidence indicates that the risk factors for severe COVID-19 are similar in pregnancy to the general population. Here we systemically analyzed the clinical characteristics of pregnant and non-pregnant female COVID-19 patients who were hospitalized during the same period and found that pregnant patients developed marked lymphopenia and higher inflammation evident by higher C-reactive protein and IL-6. To elucidate the pathways that might contribute to immunopathology or protective immunity against COVID-19 during pregnancy, we applied single-cell mRNA sequencing to profile peripheral blood mononuclear cells from four pregnant and six non-pregnant female patients after recovery along with four pregnant and three non-pregnant healthy donors. We found normal clonal expansion of T cells in the pregnant patients, heightened activation and chemotaxis in NK, NKT, and MAIT cells, and differential interferon responses in the monocyte compartment. Our data present a unique feature in both innate and adaptive immune responses in pregnant patients recovered from COVID-19.

Abstract. GATA2, a principal member of the GATA family, plays important roles in the generation and maintenance of hematopoietic stem/progenitor cells. Among the three mRNA transcripts, the distal first exon of GATA2 (IS exon) is specific for hematopoietic and neuronal cells. GATA2 mutants with abnormal expression are often present in acute myeloid leukemia-related familial diseases and myelodysplastic syndrome, indicating the crucial significance of GATA2 in the proper maintenance of blood system functions. This article offers an overview of the regulation dynamics and function of GATA2 in the generation, proliferation, and function of hematopoietic stem cells in both mouse and human models. We acknowledge the current progress in the cell fate determination mechanism by dynamic GATA2 expression. The gene modification approaches for inspecting the role of GATA2 in definitive hematopoiesis demonstrate the potential for acquiring hPSC-derived hematopoietic stem cells via manipulated GATA2 regulation.

Abstract Background Oocytes have a lot of maternal RNAs and proteins, which are used by the early embryo before zygotic genome activation. Transducin‐like enhancer of split 6 (TLE6) is a component of a subcortical maternal complex which plays a critical role in early embryonic development. Methods The patient had been diagnosed with primary infertility for 6 years and had undergone multiple failed in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Genomic DNA samples were extracted from her parents’ peripheral blood as well as hers. Whole‐exome sequencing and Sanger validation were performed to identify candidate variants. Results We identified a novel transducin‐like enhancer of split 6 (TLE6) gene mutations in the female patient with recurrent IVF/ICSI failure. The patient carried a homozygous mutation (NM_001143986.1(TLE6): c.541+1G>A) and had viable but low‐quality embryos. Her parents both had heterozygous mutations at this locus. Conclusion Our study expands the mutational and phenotypic spectrum of TLE6 and suggests the important role of TLE6 during embryonic development. Our findings have implications for the genetic diagnosis of female infertility with recurrent IVF/ICSI failure.

Summary: GATA2 is essential for the endothelial-to-hematopoietic transition (EHT) and generation of hematopoietic stem cells (HSCs). It is poorly understood how GATA2 controls the development of human pluripotent stem cell (hPSC)-derived HS-like cells. Here, using human embryonic stem cells (hESCs) in which GATA2 overexpression was induced by doxycycline (Dox), we elucidated the dual functions of GATA2 in definitive hematopoiesis before and after the emergence of CD34+CD45+CD90+CD38– HS-like cells. Specifically, GATA2 promoted expansion of hemogenic precursors via the EHT and then helped to maintain HS-like cells in a quiescent state by regulating cell cycle. RNA sequencing showed that hPSC-derived HS-like cells were very similar to human fetal liver-derived HSCs. Our findings will help to elucidate the mechanism that controls the early stages of human definitive hematopoiesis and may help to develop a strategy to generate hPSC-derived HSCs. : In this article, Professor Ma and his colleagues at IBT of CAMS & PUMC show that overexpression of GATA2 promoted expansion of hemogenic precursors through EHT, and thereafter enhanced the maintenance of HS-like cells in dormancy by cell-cycle arrest. hESC-derived HS-like cells were highly similar to human fetal liver (FL) HSCs. Keywords: GATA2, hESCs, hematopoietic stem cells, definitive hematopoiesis, cell cycle

Abstract Background Cytoplasmic incompatibility (CI) is the most common phenotype induced by endosymbiont Wolbachia and results in embryonic lethality when Wolbachia-modified sperm fertilize eggs without Wolbachia. However, eggs carrying the same strain of Wolbachia can rescue this embryonic death, thus producing viable Wolbachia-infected offspring. Hence Wolbachia can be transmitted mainly by hosts’ eggs. One of the models explaining CI is “titration-restitution”, which hypothesized that Wolbachia titrated-out some factors from the sperm and the Wolbachia in the egg would restitute the factors after fertilization. However, how infected eggs rescue CI and how hosts’ eggs ensure the proliferation and transmission of Wolbachia are not well understood. Results By RNA-seq analyses, we first compared the transcription profiles of Drosophila melanogaster adult ovaries with and without the wMel Wolbachia and identified 149 differentially expressed genes (DEGs), of which 116 genes were upregulated and 33 were downregulated by Wolbachia infection. To confirm the results obtained from RNA-seq and to screen genes potentially associated with reproduction, 15 DEGs were selected for quantitative RT-PCR (qRT-PCR). Thirteen genes showed the same changing trend as RNA-seq analyses. To test whether these genes are associated with CI, we also detected their expression levels in testes. Nine of them exhibited different changing trends in testes from those in ovaries. To investigate how these DEGs were regulated, sRNA sequencing was performed and identified seven microRNAs (miRNAs) that were all upregulated in fly ovaries by Wolbachia infection. Matching of miRNA and mRNA data showed that these seven miRNAs regulated 15 DEGs. Wolbachia-responsive genes in fly ovaries were involved in biological processes including metabolism, transportation, oxidation-reduction, immunity, and development. Conclusions Comparisons of mRNA and miRNA data from fly ovaries revealed 149 mRNAs and seven miRNAs that exhibit significant changes in expression due to Wolbachia infection. Notably, most of the DEGs showed variation in opposite directions in ovaries versus testes in the presence of Wolbachia, which generally supports the “titration-restitution” model for CI. Furthermore, genes related to metabolism were upregulated, which may benefit maximum proliferation and transmission of Wolbachia. This provides new insights into the molecular mechanisms of Wolbachia-induced CI and Wolbachia dependence on host ovaries.

The endosymbiotic Wolbachia bacteria frequently cause cytoplasmic incompatibility (CI) in their insect hosts, where Wolbachia-infected males cross with uninfected females, leading to no or fewer progenies, indicating a paternal modification by Wolbachia. Recent studies have identified a Wolbachia protein, CidB, containing a DUB (deubiquitylating enzyme) domain, which can be loaded into host sperm nuclei and involved in CI, though the DUB activity is not necessary for CI in Drosophila melanogaster. To investigate whether and how Wolbachia affect protein ubiquitination in testes of male hosts and are thus involved in male fertility, we compared the protein and ubiquitinated protein expressions in D. melanogaster testes with and without Wolbachia. A total of 643 differentially expressed proteins (DEPs) and 309 differentially expressed ubiquitinated proteins (DEUPs) were identified to have at least a 1.5-fold change with a p-value of Wolbachia. Four genes coding for DEUPs in ubiquitin proteasome pathways were knocked down, respectively, in Wolbachia-free fly testes. Among them, Rpn6 and Rpn7 knockdown caused male sterility, with no mature sperm in seminal vesicles. These results reveal deubiquitylating effects induced by Wolbachia infection, suggesting that Wolbachia can widely deubiquitinate proteins that have crucial functions in male fertility of their hosts, but are not involved in CI. Our data provide new insights into the regulatory mechanisms of endosymbiont/host interactions and male fertility.

Developmental-regulatory networks often include large gene families encoding mechanistically-related proteins like G-protein-coupled receptors, zinc finger transcription factors and solute carrier (SLC) transporters. In principle, a common mechanism may confer expression of multiple members integral to a developmental process, or diverse mechanisms may be deployed. Using genetic complementation and enhancer-mutant systems, we analyzed the 456 member SLC family that establishes the small molecule constitution of cells. This analysis identified SLC gene cohorts regulated by GATA1 and/or GATA2 during erythroid differentiation. As >50 SLC genes shared GATA factor regulation, a common mechanism established multiple members of this family. These genes included Slc29a1 encoding an equilibrative nucleoside transporter (Slc29a1/ENT1) that utilizes adenosine as a preferred substrate. Slc29a1 promoted erythroblast survival and differentiation ex vivo. Targeted ablation of murine Slc29a1 in erythroblasts attenuated erythropoiesis and erythrocyte regeneration in response to acute anemia. Our results reveal a GATA factor-regulated SLC ensemble, with a nucleoside transporter component that promotes erythropoiesis and prevents anemia, and establish a mechanistic link between GATA factor and adenosine mechanisms. We propose that integration of the GATA factor-adenosine circuit with other components of the GATA factor-regulated SLC ensemble establishes the small molecule repertoire required for progenitor cells to efficiently generate erythrocytes.

Osteogenesis imperfecta (OI) is a rare heritable skeletal disorder which is mainly caused by defected type I collagen. Autosomal recessive OI (AR-OI) is caused by mutations of genes that are responsible for type I collagen modification and folding, and is often associated with more severe phenotypes. Due to the limited number of recessive OI patients, it has been difficult to study the mutation spectrum as well as the correlation of genotype and phenotype. This study recruited a Chinese cohort of 74 AR-OI families, aiming to establish the mutation spectrum and to examine the genotypic and phenotypic correlation. We identified 82 variants including 25 novel variants and 57 HGMD reported variants in these AR-OI patients, using whole exome sequencing/panel sequencing combined with Sanger sequencing. Pathogenic mutations were found at WNT1 (n = 30, 40.54%), SERPINF1 (n = 22, 29.73%), FKBP10 (n = 10, 13.51%), CRTAP (n = 3, 4.05%), P3H1 (n = 3, 4.05%), SERPINH1 (n = 2, 2.70%), SEC24D (n = 3, 4.05%), and PLOD2 (n = 1, 1.35%) respectively. Thus, WNT1 represents the most frequent pathogenic gene of AR-OI in Chinese population. The most common clinical manifestations of AR-OI patients include walking problem (72.86%), scoliosis (65.28%) and frequent fractures (fractures ≥2/year) (54.05%). Interestingly, ptosis represents a unique phenotype of patients carrying WNT1 variants, and it was rare in patients harboring other pathogenic genes. Our study expanded the mutation spectrum of AR-OI and enriched the knowledge of genotypic and phenotypic correlation in Chinese cohort with AR-OI.

Abstract Background Distal arthrogryposis (DA) is a group of clinically and genetically heterogeneous disorders that involve multiple congenital limb contractures and comprise at least 10 clinical subtypes. Here, we describe our findings in two Chinese families: Family 1 with DA2B (MIM 601680) and Family 2 with mild DA. Methods To map the disease locus, two-point linkage analysis was performed with microsatellite markers closed to TPM2, TNNI2/TNNT3 and TNNC2. In Family 1, a positive LOD (logarithm of odds) score was only obtained at the microsatellite marker close to TPM2 and mutation screening was performed using direct sequencing of TPM2 in the proband. In Family 2, for the LOD score that did not favor linkage to any markers, whole-exome sequencing (WES) was performed on the proband. PCR–restriction fragment length polymorphism (RFLP) and bioinformatics analysis were then applied to identify the pathogenic mutations in two families. In order to correlate genotype with phenotype in DA, retrospective analyses of phenotypic features according to the TPM2 and PIEZO2 mutation spectrums were carried out. Results A heterozygous missense mutation c.308A > G (p.Q103R) in TPM2 in Family 1, and a novel variation c.8153G > A (p.R2718Q) in PIEZO2 in Family 2 were identified. Each of the two novel variants was co-segregated with the DA manifestations in the corresponding family. Bioinformatics analysis from several tools supported the pathogenicity of the mutations. Furthermore, our study suggests that there is no relation between the types or locations of TPM2 mutations and the clinical characteristics, and that different inheritance modes and mutation types concerning PIEZO2 cause distinct clinical manifestations. Conclusions We report two novel mutations within TPM2 and PIEZO2 responsible for DA2B and mild DA in two Chinese families, respectively. Our study expands the spectrum of causal mutations in the TPM2 and PIEZO2 genes.

Abstract Background Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder caused by a heterozygous germline mutation in the tumor suppressor gene NF1. Because of the existence of highly homologous pseudogenes, the large size of the gene, and the heterogeneity of mutation types and positions, the detection of variations in NF1 is more difficult than that for an ordinary gene. Methods In this study, we collected samples from 23 patients among 46 study participants from 12 unrelated Chinese families with NF1. We used a combination of Sanger sequencing, targeted next-generation sequencing, and multiplex ligation-dependent probe amplification to identify potential mutations of different types. Results Seven recurrent mutations and four novel mutations were identified with the aforementioned methods, which were subsequently confirmed by either restriction fragment length polymorphism analysis or Sanger sequencing. Truncating mutations accounted for 73% (8/11) of all mutations identified. We also exhaustively investigated the clinical manifestations of NF1 in patients via acquired pathography, photographs and follow-up. However, no clear genotype–phenotype correlation has been found to date. Conclusion In conclusion, the novel mutations identified broaden the spectrum of NF1 mutations in Chinese; however, obvious correlations between genotype and phenotype were not observed in this study.

Osteogenesis Imperfecta (OI) is a rare inherited bone dysplasia, which is mainly caused by mutations in genes encoding type I collagen including COL1A1 and COL1A2. It has been well established to identify the classical variants as well as consensus splicing-site-variants in these genes in our previous studies. However, how atypical variants affect splicing in OI patients remains unclear. From a cohort of 867 OI patients, we collected blood samples from 34 probands which contain 29 variants that are located close to splice donor/acceptor sites in either COL1A1 or COL1A2. By conducting minigene assay and sequencing analysis, we found that 17 out of 29 variants led to aberrant splicing effects, while no remarkable aberrant splicing effect was observed in the remaining 12 variants. Among the 17 variants that affect splicing, 14 variants led to single splicing influence: 9 led to exon skipping, 2 resulted in truncated exon, and 3 caused intron retention. There were three complicated cases showing more than one mutant transcript caused by recognition of several different splice sites. This functional study expands our knowledge of atypical splicing variants, and emphasizes the importance of clarifying the splicing effect for variants near exon/intron boundaries in OI.

The development of human erythroid cells has been mostly examined in models of adult hematopoiesis, while their early derivation during embryonic and fetal stages is largely unknown. We observed the development and maturation of erythroblasts derived from human pluripotent stem cells (hPSCs) by an efficient co-culture system. These hPSC-derived early erythroblasts initially showed definitive characteristics with a glycophorin A+ (GPA+) CD34lowCD36− phenotype and were distinct from adult CD34+ cell-derived ones. After losing CD34 expression, early GPA+CD36− erythroblasts matured into GPA+CD36low/+ stage as the latter expressed higher levels of β-globin along with a gradual loss of mesodermal and endothelial properties, and terminally suppressed CD36. We establish a unique in vitro model to trace the early development of hPSC-derived erythroblasts by serial expression of CD34, GPA, and CD36. Our findings may provide insight into the understanding of human early erythropoiesis and, ultimately, therapeutic potential.

Quick capacity loss due to the polysulfide shuttle effects is a critical challenge for high-performance lithium–sulfur (Li–S) batteries. Herein, a novel 2D/1D V2O5 nanoplates anchored carbon nanofiber (V-CF) interlayer coated on standard polypropylene (PP) separator is constructed, and a stabilization mechanism derived from a quasi-confined cushion space (QCCS) that can flexibly accommodate the polysulfide utilization is demonstrated. The incorporation of the V-CF interlayer ensures stable electron and ion pathway, and significantly enhanced long-term cycling performances are obtained. A Li–S battery assembled with the V-CF membrane exhibited a high initial capacity of 1140.8 mAh·g−1 and a reversed capacitance of 1110.2 mAh·g−1 after 100 cycles at 0.2 C. A high reversible capacity of 887.2 mAh·g−1 is also maintained after 500 cycles at 1 C, reaching an ultra-low decay rate of 0.0093% per cycle. The excellent electrochemical properties, especially the long-term cycling stability, can offer a promising designer protocol for developing highly stable Li–S batteries by introducing well-designed fine architectures to the separator.

The relationship between scenic beauty grade and measured tree indicators was studied through evaluation of 427 photos of individual Pinus tabulaeformis trees by using the scenic beauty estimation (SBE) method. Thirteen indices to reflect trunk, crown and stem-to-canopy ratios of individual trees were evaluated by invited students. Results showed that students preferred large diameters at breast height, full canopies and straight stems or some trees with minor crook stems. Tree height had a minor contribution to individual tree quality. Correlation analysis and factor analysis were employed to select indices and to integrate them into a comprehensive index. The stepwise method of nonlinear model incorporation of four comprehensive indices—tree crown form, stem-crown coordination, tree growth and stem for—were proven valuable in order to evaluate the scenic beauty of individual trees.

Cytisine-pterocarpan derived compounds were biomimetically synthesized with (-)-cytisine and (-)-maackiain via a N,N-4-dimethyl-4-aminopyridine (DMAP)-mediated synthetic strategy in a mild manner. In the present study, tonkinensine B (4) was elaborated in good and high yields with the optimized reaction conditions. The in vitro cytotoxicity of compound 4 was evaluated against breast cancer cell lines and showed that 4 had a better cytotoxicity against MDA-MB-231 cells (IC50 = 19.2 μM). Depending on the research on cytotoxicities of 4 against RAW 264.7 and BV2 cells, it was suggested that 4 produced low cytotoxic effects on the central nervous system. Further study indicated that 4 demonstrated cytotoxic activity against MDA-MB-231 cells and the cytotoxic activity was induced by apoptosis. The results implied that the apoptosis might be induced by mitochondrion-mediated apoptosis via regulating the ratio of Bax/Bcl-2 and promoting the release of cytochrome c from the mitochondrion to the cytoplasm in MDA-MB-231 cells.