Toward Low-Voltage and High-Sensitivity Direct X-ray Detectors Based on Thick Bulk Heterojunction Organic Device.

Organic semiconducting materials are promising for the fabrication of flexible ionizing radiation detectors for imaging because of their tissue equivalence, simple large-scale processing, and mass production. However, it is challenging to achieve high-sensitivity detection for organic direct detectors prepared by low-cost solution processing because of the compromise between thickness and carrier transport. In this study, high-performance organic direct X-ray detectors were fabricated by building a micrometer-thick bulk heterojunction (BHJ) using poly(3-hexylthiophene-2,5-diyl) (P3HT):(6,6)-phenyl c71 butyric acid methyl ester. A 5 µm BHJ film was fabricated by drop-casting and enhanced crystallization of P3HT using binary solvents and high-boiling-point additives to improve the charge carrier mobility. Furthermore, this organic direct X-ray detector has a sensitivity of >654.26 µC Gyair s-1 and a self-powered response. Because of the architecture of the thick active layer and the energy cascade in this diode detector, it has a very low dark current of 46.26 pA at -2 V. A fast and efficient approach was developed for fabricating thick, highly mobile organic BHJ films for high-performance direct X-ray detectors. It has great potential for application in a new generation of flexible and portable large-area flat-panel detectors.

Multimodal Nature of the Single-cell Primate Brain Atlas: Morphology, Transcriptome, Electrophysiology, and Connectivity.

Primates exhibit complex brain structures that augment cognitive function. The neocortex fulfills high-cognitive functions through billions of connected neurons. These neurons have distinct transcriptomic, morphological, and electrophysiological properties, and their connectivity principles vary. These features endow the primate brain atlas with a multimodal nature. The recent integration of next-generation sequencing with modified patch-clamp techniques is revolutionizing the way to census the primate neocortex, enabling a multimodal neuronal atlas to be established in great detail: (1) single-cell/single-nucleus RNA-seq technology establishes high-throughput transcriptomic references, covering all major transcriptomic cell types; (2) patch-seq links the morphological and electrophysiological features to the transcriptomic reference; (3) multicell patch-clamp delineates the principles of local connectivity. Here, we review the applications of these technologies in the primate neocortex and discuss the current advances and tentative gaps for a comprehensive understanding of the primate neocortex.

Cloning and gene functional analysis study of dynamin-related protein GeDRP1E gene in Gastrodia elata / 药学学报

The gene GeDRP1E encoding dynamin-related protein 1E in Gastrodia elata was cloned by specific primers which were designed based on the transcriptome data of G. elata. Bioinformatics analysis on GeDRP1E gene was carried out by using ExPASy, ClustalW, MEGA, etc. Positive transgenic Arabidopsis plant and potato minituber were obtained with the genetic transformation system of Arabidopsis and potato. The plant height and seed setting rate of transgenic Arabidopsis, and agronomic characters, such as size, weight and starch content of potato minituber of transgenic potato were tested and analyzed. And GeDRP1E gene function was preliminarily investigated. The results showed that the open reading frame of GeDRP1E gene was 1 899 bp in length and 632 amino acids residues were encoded, with a relative molecular weight of 69.90 kDa and a molecular formula of C3079H4973N883O933S19. It was predicted that the theoretical isoelectric point was 7.27, the instability coefficient was 43.34, and the average hydrophilicity index was -0.259, which was indicative of an unstable hydrophilic protein. GeDRP1E has no transmembrane structure and signal peptide, and was localized in the cytoplasm. The phylogenetic tree showed that GeDRP1E was highly homologous with DRP1E proteins of other plant species, among which GeDRP1E had the highest homology with DcDRP1E (XP_020689662.1) in Dendrobium candidum, reaching 90.05%. GeDRP1E plant expression vector pCambia1300-35Spro-GeDRP1E was constructed by double digests, and Arabidopsis complementary mutant and potato overexpression strain of GeDRP1E gene were obtained by Agrobacterium-mediated gene transformation. Compared with the Arabidopsis AtDRP1E mutant, the height and seed setting rate of the GeDRP1E complementation mutant were rescued. The minituber of GeDRP1E overexpression potato had larger size, heavier weight and higher starch content, comparing to wild-type potato. It was preliminarily induced that GeDRP1E was involved in mitochondrial morphology regulation, which related to the growth and development of Arabidopsis plants and potato miniature. The research results laid a foundation for further elucidating the molecular mechanisms underlying the growth and development of G. elata tuber development.

Patch-seq: Advances and Biological Applications.

Multimodal analysis of gene-expression patterns, electrophysiological properties, and morphological phenotypes at the single-cell/single-nucleus level has been arduous because of the diversity and complexity of neurons. The emergence of Patch-sequencing (Patch-seq) directly links transcriptomics, morphology, and electrophysiology, taking neuroscience research to a multimodal era. In this review, we summarized the development of Patch-seq and recent applications in the cortex, hippocampus, and other nervous systems. Through generating multimodal cell type atlases, targeting specific cell populations, and correlating transcriptomic data with phenotypic information, Patch-seq has provided new insight into outstanding questions in neuroscience. We highlight the challenges and opportunities of Patch-seq in neuroscience and hope to shed new light on future neuroscience research.

A primate nigrostriatal atlas of neuronal vulnerability and resilience in a model of Parkinson's disease.

The degenerative process in Parkinson's disease (PD) causes a progressive loss of dopaminergic neurons (DaNs) in the nigrostriatal system. Resolving the differences in neuronal susceptibility warrants an amenable PD model that, in comparison to post-mortem human specimens, controls for environmental and genetic differences in PD pathogenesis. Here we generated high-quality profiles for 250,173 cells from the substantia nigra (SN) and putamen (PT) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian macaques and matched controls. Our primate model of parkinsonism recapitulates important pathologic features in nature PD and provides an unbiased view of the axis of neuronal vulnerability and resistance. We identified seven molecularly defined subtypes of nigral DaNs which manifested a gradient of vulnerability and were confirmed by fluorescence-activated nuclei sorting. Neuronal resilience was associated with a FOXP2-centered regulatory pathway shared between PD-resistant DaNs and glutamatergic excitatory neurons, as well as between humans and nonhuman primates. We also discovered activation of immune response common to glial cells of SN and PT, indicating concurrently activated pathways in the nigrostriatal system. Our study provides a unique resource to understand the mechanistic connections between neuronal susceptibility and PD pathophysiology, and to facilitate future biomarker discovery and targeted cell therapy.

Synthesis and Characterization of Photoswitchable Dithienylethene-Based Chiral Bisoxazoline Compounds with Bidirectional Visible-Light Control.

In this paper, we have successfully synthesized dithienylethene-based chiral bisoxazoline ligands with bidirectional photoswitching capabilities under visible light irradiation and proposed a strategy for adjusting the conjugation system length in sensitizer groups. The detailed experimental procedures and the characterization data are presented in the main text and the Supporting Information. Despite their moderate photoswitching rates, these ligands provide a promising approach towards developing fully visible light-responsive chiral catalysts.

Adult neurogenesis in the primate hippocampus.

Adult hippocampal neurogenesis (AHN) is crucial for learning, memory, and emotion. Deficits of AHN may lead to reduced cognitive abilities and neurodegenerative disorders, such as Alzheimer's disease. Extensive studies on rodent AHN have clarified the developmental and maturation processes of adult neural stem/progenitor cells. However, to what extent these findings apply to primates remains controversial. Recent advances in next-generation sequencing technologies have enabled in-depth investigation of the transcriptome of AHN-related populations at single-cell resolution. Here, we summarize studies of AHN in primates. Results suggest that neurogenesis is largely shared across species, but substantial differences also exist. Marker gene expression patterns in primates differ from those of rodents. Compared with rodents, the primate hippocampus has a higher proportion of immature dentate granule cells and a longer maturation period of newly generated granule cells. Future research on species divergence may deepen our understanding of the mechanisms underlying adult neurogenesis in primates.

Visible-light-induced reactions of methylenecyclopropanes (MCPs).

Diverse, visible-light-induced transformations of methylenecyclopropanes (MCPs) have been reported in recent years, attracting significant attention from synthetic chemists. As readily accessible strained molecules, MCPs have sufficient reactivity to selectively generate different target products, through reactions with various radical species upon visible-light irradiation under regulated reaction conditions. These transformations can be classified into three subcategories of reaction pathway, forming ring-opened products, cyclopropane derivatives, and alkynes. These products include pharmaceutical intermediates and polycyclic/heterocyclic compounds that are challenging to obtain using traditional methods. This review summarizes the recent advancements in this field.

Development and validation of a score predicting mortality for older patients with mitral regurgitation / 老年心脏病学杂志（英文版）

OBJECTIVE@#To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score.@*METHODS@#The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion.@*RESULTS@#Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m2, NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m2, albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01).@*CONCLUSIONS@#The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

Paclitaxel drug-coated balloons combined with bare metal stents vs. bare metal stents for the treatment of superficial femoral atherosclerosis obliterans / 中华普通外科杂志

Objective:To compare the efficacy and safety of drug-coated balloons (DCB) combined with bare metal stents (BMS) and BMS only for superficial femoral atherosclerosis obliterans.Methods:The clinical and follow-up data of 80 patients (82 limbs) who received combined treatment or BMS implantation at Cardiovascular Surgery Department of China Japan Friendship Hospital from Jan 2017 to Aug 2022 were retrospectively analyzed.Results:43 patients (43 limbs) were included in combined treatment group. 37 patients (39 limbs) were in BMS only. The average lesion length of combined group was longer than BMS group (19.54±7.04 cm vs. 16.25±6.43 cm, P=0.031). The primary patency rate of combined group at 36 months was not statistically different with BMS only group (56.9% vs. 38.5%, P=0.171). The subgroup analysis of superficial femoral artery TASC C/D (Trans-Atlantic Inter-Society Consensus) and CTO (chronic total occlusion) lesions indicated that efficacy of the combined group was superior to BMS only group. The patency rates of the combined group compared with the BMS group at 36 months were 57.6% vs. 23.8%, P=0.046, 60.2% vs. 31.4%, P=0.028, respectively. There was no significant difference in the FCD-TLR (free from clinical driven target lesion revascularization) between the two groups at 36 months (72.6% vs. 66.5%, P=0.706). There was no significant difference in major adverse events between the two groups ( P>0.05). Conclusion:Paclitaxel drug-coated balloon combined with bare metal stent is a safe and effective treatment for superficial femoral atherosclerosis obliterans, which is superior to bare metal stent, especially in TASC C/D and chronic total occlusive lesions.

Calcium/Calmodulin Mediates Cardiomyocyte Ferroptosis in Myocardial Infarction Through Iron Overload / 中国生物化学与分子生物学报

Myocardial infarction(MI), an acute coronary syndrome that poses a serious risk to human health, involves multiple pathophysiological processes, including calcium overload. Existing therapeutic approaches and preventive measures have limitations and cannot effectively repair myocardial cells with poor regenerative potential. Exploring multiple programmed modes of cardiomyocyte death could help find potential targets for the treatment of myocardial infarction, and the potential role of ferroptosis as a novel mode of cell death in myocardial infarction has attracted great attention. The aim of this study was to investigate whether Ca

Cloning and gene function of dicarboxylate-tricarboxylate carrier protein in Gastrodia elata / 中国中药杂志

The gene GeDTC encoding the dicarboxylate-tricarboxylate carrier protein in Gastrodia elata was cloned by specific primers which were designed based on the transcriptome data of G. elata. Bioinformatics analysis on GeDTC gene was carried out by using ExPASY, ClustalW, MEGA, etc. Positive transgenic plants and potato minituber were obtained by virtue of the potato genetic transformation system. Agronomic characters, such as size, weight, organic acid content, and starch content, of potato minituber were tested and analyzed and GeDTC gene function was preliminarily investigated. The results showed that the open reading frame of GeDTC gene was 981 bp in length and 326 amino acid residues were encoded, with a relative molecular weight of 35.01 kDa. It was predicted that the theoretical isoelectric point of GeDTC protein was 9.83, the instability coefficient was 27.88, and the average index of hydrophilicity was 0.104, which was indicative of a stable hydrophilic protein. GeDTC protein had a transmembrane structure and no signal peptide and was located in the inner membrane of mitochondria. The phylogenetic tree showed that GeDTC was highly homologous with DTC proteins of other plant species, among which GeDTC had the highest homology with DcDTC(XP＿020675804.1) in Dendrobium candidum, reaching 85.89%. GeDTC overexpression vector pCambia1300-35Spro-GeDTC was constructed by double digests, and transgenic potato plants were obtained by Agrobacterium-mediated gene transformation. Compared with the wild-type plants, transgenic potato minituber harvested by transplanting had smaller size, lighter weight, lower organic acid content, and no significant difference in starch content. It is preliminarily induced that GeDTC is the efflux channel of tricarboxylate and related to the tuber development, which lays a foundation for further elucidating the molecular mechanism of G. elata tuber development.

Taking the mechanism of glucose catabolism disorder in depression as an example to explore the research ideas and strategies of stable isotope tracer metabolomics / 药学学报

Stable isotope tracer metabolomics tracks and analyzes the whole metabolic process of the body through the tracer atoms, which belongs to the frontier technology in the field of biomedicine. This technology is of great significance and value for explaining the pathogenesis of diseases, finding biomarkers of diseases and drug action targets. Taking the mechanism of glucose catabolism disorder in depression as an example, this paper systematically expounds the stable isotope tracer metabolomics technology and its application. The research idea of stable isotope tracer metabolomics based on unmarked metabolomics was put forward, and the research strategy of biological significance interpretation from four dimensions of metabolite isotope abundance, key metabolic enzymes, metabolic flow direction and metabolite flow was given, which broke through the bottleneck of stable isotope tracer metabolomics research technology based on overall animal experiment, and provided scientific basis for the promotion and application of this technology.

Identification of visual cortex cell types and species differences using single-cell RNA sequencing.

The primate neocortex exerts high cognitive ability and strong information processing capacity. Here, we establish a single-cell RNA sequencing dataset of 133,454 macaque visual cortical cells. It covers major cortical cell classes including 25 excitatory neuron types, 37 inhibitory neuron types and all glial cell types. We identified layer-specific markers including HPCAL1 and NXPH4, and also identified two cell types, an NPY-expressing excitatory neuron type that expresses the dopamine receptor D3 gene; and a primate specific activity-dependent OSTN + sensory neuron type. Comparisons of our dataset with humans and mice show that the gene expression profiles differ between species in relation to genes that are implicated in the synaptic plasticity and neuromodulation of excitatory neurons. The comparisons also revealed that glutamatergic neurons may be more diverse across species than GABAergic neurons and non-neuronal cells. These findings pave the way for understanding how the primary cortex fulfills the high-cognitive functions.

Deciphering the core seed endo-bacteriome of the highland barley in Tibet plateau.

Highland barley (Hordeum vulgare var. nudum (L.) Hook.f., qingke) has unique physical and chemical properties and good potential for industrial applications. As the only crop that can be grown at high altitudes of 4200-4500 m, qingke is well adapted to extreme habitats at high altitudes. In this study, we analysed the seed bacterial community of 58 genotypes of qingke grown in different regions of Tibet, including qingke landraces, modern cultivars, and winter barley varieties, and characterised endophytic bacterial communities in seeds from different sources and the core endo-bacteriome of qingke. This study aim to provide a reference for the application of seed endophytes as biological inoculants for sustainable agricultural production and for considering microbe-plant interactions in breeding strategies. A total of 174 qingke seed samples from five main agricultural regions in Tibet were collected and subjected to investigation of endophytic endo-bacteriome using high-throughput sequencing and bioinformatics approaches. The phyla of endophytic bacteria in qingke seeds from different sources were similar; however, the relative proportions of each phylum were different. Different environmental conditions, growth strategies, and modern breeding processes have significantly changed the community structure of endophytic bacteria in seeds, among which the growth strategy has a greater impact on the diversity of endophytic bacteria in seeds. Seeds from different sources have conserved beneficial core endo-bacteriome. The core endo-bacteriome of qingke seeds dominated by Enterobacteriaceae may maintain qingke growth by promoting plant growth and assisting plants in resisting pests and diseases. This study reveals the core endo-bacteriome of qingke seeds and provides a basis for exploiting the endophytic endo-bacteriome of qingke seeds.

Linking transcriptomes with morphological and functional phenotypes in mammalian retinal ganglion cells.

Retinal ganglion cells (RGCs) are the brain's gateway to the visual world. They can be classified into different types on the basis of their electrophysiological, transcriptomic, or morphological characteristics. Here, we characterize the transcriptomic, morphological, and functional features of 472 high-quality RGCs using Patch sequencing (Patch-seq), providing functional and morphological annotation of many transcriptomic-defined cell types of a previously established RGC atlas. We show a convergence of different modalities in defining the RGC identity and reveal the degree of correspondence for well-characterized cell types across multimodal data. Moreover, we complement some RGC types with detailed morphological and functional properties. We also identify differentially expressed genes among ON, OFF, and ON-OFF RGCs such as Vat1l, Slitrk6, and Lmo7, providing candidate marker genes for functional studies. Our research suggests that the molecularly distinct clusters may also differ in their roles of encoding visual information.

1,1-Dimethylhydrazine adsorption on intrinsic, vacancy, and N-doped graphene: a first-principle study.

Graphene and its derivatives have been widely used in the area of high-sensitivity sensing materials for small-molecule gases. Based on first-principle calculations, the present study systematically investigated the adsorption of 1,1-dimethylhydrazine on intrinsic graphene, graphene with vacancy defects, and nitrogen-doped graphene. The adsorption effects, when 1,1-dimethylhydrazine takes on different orientations, were determined separately, and the specific adsorption energy and charge transfer were calculated accordingly. The results reveal that the 1,1-dimethylhydrazine adsorption on intrinsic graphene, graphene with vacancy defects, and nitrogen-doped graphene falls into physical adsorption. Besides, both vacancy defect and nitrogen doping help enhance the adsorption but the effect of vacancy defect is superior to that of nitrogen doping.

Routes and rates of bacterial dispersal impact surface soil microbiome composition and functioning.

Recent evidence suggests that, similar to larger organisms, dispersal is a key driver of microbiome assembly; however, our understanding of the rates and taxonomic composition of microbial dispersal in natural environments is limited. Here, we characterized the rate and composition of bacteria dispersing into surface soil via three dispersal routes (from the air above the vegetation, from nearby vegetation and leaf litter near the soil surface, and from the bulk soil and litter below the top layer). We then quantified the impact of those routes on microbial community composition and functioning in the topmost litter layer. The bacterial dispersal rate onto the surface layer was low (7900 cells/cm2/day) relative to the abundance of the resident community. While bacteria dispersed through all three routes at the same rate, only dispersal from above and near the soil surface impacted microbiome composition, suggesting that the composition, not rate, of dispersal influenced community assembly. Dispersal also impacted microbiome functioning. When exposed to dispersal, leaf litter decomposed faster than when dispersal was excluded, although neither decomposition rate nor litter chemistry differed by route. Overall, we conclude that the dispersal routes transport distinct bacterial communities that differentially influence the composition of the surface soil microbiome.

Identification of TPBG-Expressing Amacrine Cells in DAT-tdTomato Mouse.

Purpose: Neurons are the bricks of the neuronal system and experimental access to certain neuron subtypes will be of great help to decipher neuronal circuits. Here, we identified trophoblast glycoprotein (TPBG)-expressing GABAergic amacrine cells (ACs) that were selectively labeled in DAT-tdTomato transgenic mice. Methods: Retina and brain sections were prepared for immunostaining with antibodies against various biomarkers. Patch-sequencing was performed to obtain the transcriptomes of tdTomato-positive cells in DAT-tdTomato mice. Whole-cell recordings were conducted to identify responses to light stimulation. Results: Tyrosine hydroxylase immunoreactive cells were colocalized with tdTomato-positive cells in substantia nigra pars compacta, but not in the retina. Transcriptomes collected from tdTomato-positive cells in retinas via Patch-sequencing exhibited the expression of marker genes of ACs (Pax6 and Slc32a1) and marker genes of GABAergic neurons (Gad1, Gad2, and Slc6a1). Immunostaining with antibodies against relevant proteins (GAD67, GAD65, and GABA) also confirmed transcriptomic results. Furthermore, tdTomato-positive cells in retinas selectively expressed Tpbg, a marker gene for distinct clusters molecularly defined, which was proved with TPBG immunoreactivity in fluorescently labeled cells. Finally, tdTomato-positive cells recorded showed ON-OFF responses to light stimulation. Conclusions: Ectopic expression occurs in the retina but not in the substantia nigra pars compacta in the DAT-tdTomato mouse, and fluorescently labeled cells in the retina are TPBG-expressing GABAergic ACs. This type of transgenic mice has been proved as an ideal tool to achieve efficient labeling of a distinct subset of ACs that selectively express Tpbg.