A new combination and synonym in Bupleurum (Apiaceae, Apioideae), based on morphological, molecular and cytological evidence.

Specimen examinations and field observations revealed that Bupleurumsmithiivar.parvifolium was distinctly different from B.smithiivar.smithii in umbel, leaf, and fruit morphology, but was very similar to B.commelynoideumvar.flaviflorum. Based on these morphological evidences, the present study re-examined the taxonomic status of these taxa through morphological, cytological, and phylogenetic analyses. The results showed distinguishable features in the width of middle leaves and bracteoles of B.smithiivar.parvifolium compared to B.smithiivar.smithii. Morphological variation between B.smithiivar.parvifolium and B.commelynoideumvar.flaviflorum was continuous and overlapping. Notably, the chromosome number of B.smithiivar.parvifolium was 2n = 14 (x = 7), consistent with B.commelynoideumvar.flaviflorum, whereas B.smithiivar.smithii was 2n = 64 (x = 8). Additionally, phylogenetic analyses revealed B.commelynoideumvar.flaviflorum nested within B.smithiivar.parvifolium, and that both were distant from the B.smithiivar.smithii and B.commelynoideumvar.commelynoideum. Based on the evidence above, the differences between B.smithiivar.parvifolium and B.smithiivar.smithii extend beyond the level of intraspecific variation, and B.commelynoideumvar.flaviflorum is considered to be identical with B.smithiivar.parvifolium. Hence. A new combination and status, B.parvifolium (Shan & Y.Li) Q.R.Liu & L.H.Wang, comb. et stat. nov., is proposed. Furthermore, B.commelynoideumvar.flaviflorum should be treated as a synonym of B.parvifolium.

Clickable X-ray Nanoprobes for Nanoscopic Bioimaging of Cellular Structures.

Synchrotron-based X-ray microscopy (XRM) has garnered widespread attention from researchers due to its high spatial resolution and excellent energy (element) resolution. Existing molecular probes suitable for XRM include immune probes and genetic labeling probes, enabling the precise imaging of various biological targets within cells. However, immune labeling techniques are prone to cross-interference between antigens and antibodies. Genetic labeling technologies have limited systems that allow express markers independently, and moreover, genetically encoded labels based on catalytic polymerization lack a fixed morphology. When applied to cell imaging, this can result in reduced localization accuracy due to the diffusion of labels within the cells. Therefore, both techniques face challenges in simultaneously labeling multiple biotargets within cells and achieving high-precision imaging. In this work, we applied the click reaction and developed a third category of imaging probes suitable for XRM, termed clickable X-ray nanoprobes (Click-XRN). Click-XRN consists of two components: an X-ray-sensitive multicolor imaging module and a particle-size-controllable morphology module. Efficient identification of intra- and extracellular biotargets is achieved through click reactions between the probe and biomolecules. Click-XRN possesses a controllable particle size, and its loading of various metal ions provides distinctive signals for imaging under XRM. Based on this, we optimized the imaging energy of Click-XRN with different particle sizes, enabling single-color and two-color imaging of the cell membrane, cell nucleus, and mitochondria with nanoscale spatial nanometers. Our work provides a potent molecular tool for investigating cellular activities through XRM.

Dynamic Interface-Assisted Rapid Self-Assembly of DNA Origami-Framed Anisotropic Nanoparticles.

The ordered arrangement of nanoparticles can generate unique physicochemical properties, rendering it a pivotal direction in the field of nanotechnology. DNA-based chemical encoding has emerged as an unparalleled strategy for orchestrating precise and controlled nanoparticle assemblies. Nonetheless, it is often time-consuming and has limited assembly efficiency. In this study, we developed a strategy for the rapid and ordered assembly of DNA origami-framed nanoparticles assisted by dynamic interfaces. By assembling Au nanoparticles (AuNPs) onto DNA origami with different sticky ends in various directions, we endowed them with anisotropic specific affinities. After assembling DNA origami-framed AuNPs onto supported lipid bilayers with freely diffusing single-stranded DNA via DNA hybridization, we found that DNA origami-framed AuNPs could form larger ordered assemblies than those in 3D solution within equivalent time frames. Furthermore, we also achieved rapid and ordered assembly of liposome nanoparticles by employing the aforementioned strategy. Our work provides a novel avenue for efficient and rapid assembly of nanoparticles across two-dimensional interfaces, which is expected to promote the application of ordered nanoparticle assemblies in sensor and biomimetic system construction.

CSF proteomic profiling with amyloid/tau positivity identifies distinctive sex-different alteration of multiple proteins involved in Alzheimer's disease.

In Alzheimer's disease (AD), the most common cause of dementia, females have higher prevalence and faster progression, but sex-specific molecular findings in AD are limited. Here, we comprehensively examined and validated 7,006 aptamers targeting 6,162 proteins in cerebral spinal fluid (CSF) from 2,077 amyloid/tau positive cases and controls to identify sex-specific proteomic signatures of AD. In discovery (N=1,766), we identified 330 male-specific and 121 female-specific proteomic alternations in CSF (FDR <0.05). These sex-specific proteins strongly predicted amyloid/tau positivity (AUC=0.98 in males; 0.99 in females), significantly higher than those with age, sex, and APOE-ε4 (AUC=0.85). The identified sex-specific proteins were well validated (r≥0.5) in the Stanford study (N=108) and Emory study (N=148). Biological follow-up of these proteins led to sex differences in cell-type specificity, pathways, interaction networks, and drug targets. Male-specific proteins, enriched in astrocytes and oligodendrocytes, were involved in postsynaptic and axon-genesis. The male network exhibited direct connections among 152 proteins and highlighted PTEN, NOTCH1, FYN, and MAPK8 as hubs. Drug target suggested melatonin (used for sleep-wake cycle regulation), nabumetone (used for pain), daunorubicin, and verteporfin for treating AD males. In contrast, female-specific proteins, enriched in neurons, were involved in phosphoserine residue binding including cytokine activities. The female network exhibits strong connections among 51 proteins and highlighted JUN and 14-3-3 proteins (YWHAG and YWHAZ) as hubs. Drug target suggested biperiden (for muscle control of Parkinson's disease), nimodipine (for cerebral vasospasm), quinostatin and ethaverine for treating AD females. Together, our findings provide mechanistic understanding of sex differences for AD risk and insights into clinically translatable interventions.

Effects of Aging Treatment on the Microstructures and Mechanical Properties of a TC18 Alloy.

In the present work, the effects of aging treatment on the microstructures of a TC18 alloy are studied. The influence of aging treatment on the tensile properties and failure mechanisms is systematically analyzed. It is found that the size and morphology of the primary α (αp) phases are insensitive to aging temperature and time. Furthermore, the aging temperature and time dramatically influence the precipitation of the secondary α (αs) phases. Massive αs phases precipitate and gradually coarsen, and finally weave together by increasing the aging temperature or extending the aging time. The variations in αp and αs phases induced by aging parameters also affect the mechanical properties. Both yield strength (YS) and ultimate tensile strength (UTS) first increase and then decrease by increasing the aging temperature and time, while ductility first decreases and then increases. There is an excellent balance between the strengths and ductility. When the aging temperature is changed from 450 to 550 °C, YS varies from 1238.6 to 1381.6 MPa, UTS varies from 1363.2 to 1516.8 MPa, and the moderate elongation ranges from 9.0% to 10.3%. These results reveal that the thickness of αs phases is responsible for material strengths, while the content of α phases can enhance material ductility. The ductile characteristics of the alloy with coarser αs phases are more obvious than those with thinner αs phases. Therefore, the aging treatment is helpful for the precipitation and homogeneous distribution of αs phases, which are essential for balancing the strengths and ductility of the studied Ti alloy.

Visualization of the hepatic and renal cell uptake and trafficking of tetrahedral DNA origami in tumour.

DNA nanostructures, known for their programmability, ease of modification, and favourable biocompatibility, have gained widespread application in the biomedical field. Among them, Tetrahedral DNA Origami (TDOs), as a novel DNA nanostructure, possesses well-defined structures, multiple modification sites, and large cavities, making it a promising drug carrier. However, current understanding of TDOs' interactions with biological systems, particularly with target cells and organs, remains unexplored, limiting its further applications in biomedicine. In this work, we prepared TDOs with an average particle size of 40 nm and labelled them with Cy5 fluorescent molecules. Following intravenous injection in mice, the uptake of TDOs by different types of liver and kidney cells was observed. Results indicated that TDOs accumulate in renal tubules and are metabolized by Kupffer cells, epithelial cells, and hepatocytes in the liver. Additionally, in a tumour-bearing mouse model, TDOs passively targeted tumour tissues and exhibited excellent tumour penetration and retention after rapid metabolism in hepatocytes. Our findings provide crucial insights for the development of TDO-based drug delivery systems.

Measurement of the Earth Tides with a Diamagnetic-Levitated Micro-Oscillator at Room Temperature.

The precise measurement of the gravity of Earth plays a pivotal role in various fundamental research and application fields. Although a few gravimeters have been reported to achieve this goal, miniaturization of high-precision gravimetry remains a challenge. In this work, we have proposed and demonstrated a miniaturized gravimetry operating at room temperature based on a diamagnetic levitated micro-oscillator with a proof mass of only 215 mg. Compared with the latest reported miniaturized gravimeters based on microelectromechanical systems, the performance of our gravimetry has substantial improvements in that an acceleration sensitivity of 15 µGal/sqrt[Hz] and a drift as low as 61 µGal per day have been reached. Based on this diamagnetic levitation gravimetry, we observed Earth tides, and the correlation coefficient between the experimental data and theoretical data reached 0.97. Some moderate foreseeable improvements can develop this diamagnetic levitation gravimetry into a chip size device, making it suitable for mobile platforms such as drones. Our advancement in gravimetry is expected to facilitate a multitude of applications, including underground density surveying and the forecasting of natural hazards.

Dimethyl itaconate inhibits antigen-specific Th17 cell responses and autoimmune inflammation via modulating NRF2/STAT3 signaling.

Pathogenic Th17 cells play a crucial role in autoimmune diseases like uveitis and its animal model, experimental autoimmune uveitis (EAU). Dimethyl itaconate (DMI) possesses potent anti-inflammatory effects. However, there is still a lack of knowledge about the role of DMI in regulating pathogenic Th17 cells and EAU. Here, we reported that intraperitoneal administration of DMI significantly inhibited the severity of EAU via selectively suppressing Th17 cell responses. In vitro antigen stimulation studies revealed that DMI dramatically decreased the frequencies and function of antigen-specific Th17, but not Th1, cells. Moreover, DMI hampered the differentiation of naive CD4+ T cells toward pathogenic Th17 cells. DMI-treated DCs produced less IL-1ß, IL-6, and IL-23, and displayed an impaired ability to stimulate antigen-specific Th17 activation. Mechanistically, DMI activated the NRF2/HO-1 pathway and suppressed STAT3 signaling, which subsequently restrains p-STAT3 nuclear translocation, leading to decreased pathogenic Th17 cell responses. Thus, we have identified an important role for DMI in regulating pathogenic Th17 cells, supporting DMI as a promising therapy in Th17 cell-driven autoimmune diseases including uveitis.

Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Induced Carcinogenesis and Tumorigenesis by Omega-3 Fatty Acids in Mice In Vivo.

Lung cancer is the leading cause of cancer death worldwide. Polycyclic aromatic hydrocarbons (PAHs) are metabolized by the cytochrome P450 (CYP)1A and 1B1 to DNA-reactive metabolites, which could lead to mutations in critical genes, eventually resulting in cancer. Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial against cancers. In this investigation, we elucidated the mechanisms by which omega-3 fatty acids EPA and DHA will attenuate PAH-DNA adducts and lung carcinogenesis and tumorigenesis mediated by the PAHs BP and MC. Adult wild-type (WT) (A/J) mice, Cyp1a1-null, Cyp1a2-null, or Cyp1b1-null mice were exposed to PAHs benzo[a]pyrene (BP) or 3-methylcholanthrene (MC), and the effects of omega-3 fatty acid on PAH-mediated lung carcinogenesis and tumorigenesis were studied. The major findings were as follows: (i) omega-3 fatty acids significantly decreased PAH-DNA adducts in the lungs of each of the genotypes studied; (ii) decreases in PAH-DNA adduct levels by EPA/DHA was in part due to inhibition of CYP1B1; (iii) inhibition of soluble epoxide hydrolase (sEH) enhanced the EPA/DHA-mediated prevention of pulmonary carcinogenesis; and (iv) EPA/DHA attenuated PAH-mediated carcinogenesis in part by epigenetic mechanisms. Taken together, our results suggest that omega-3 fatty acids have the potential to be developed as cancer chemo-preventive agents in people.

Treatment algorithms of relapsing multiple sclerosis: an exploration based on the available disease-modifying therapies in China.

Multiple sclerosis (MS) was defined as a rare disease in China due to its low prevalence. For a long time, interferon ß was the only approved disease-modifying therapy (DMT). Since the first oral DMT was approved in 2018, DMT approval accelerated, and seven DMTs were approved within 5 years. With an increasing number of DMTs being prescribed in clinical practice, it is necessary to discuss the standardized MS treatment algorithms depending on the disease activity and DMT availability. In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country.

Treatment algorithms of relapsing multiple sclerosis in China In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country: 1) CIS and RRMS account for more than 90% of the MS patients and most of them are mild to moderate; 2) MS patients should initiate DMT treatments as soon as the disease has been diagnosed in order to reduce the risk of disease progression; 3) Patients who have been diagnosed with MS should start treatment with fundamental DMTs unless the disease course has been highly active; 4) MAGNIMS score may be a suitable and simplified assessment tool for measuring treatment response to DMTs; 5) Patients treated with corticosteroids and NSIS should be switched to the standardized DMT treatment during remission in accordance with disease activity.

TOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasma.

Comprehensive expression quantitative trait loci studies have been instrumental for understanding tissue-specific gene regulation and pinpointing functional genes for disease-associated loci in a tissue-specific manner. Compared to gene expressions, proteins more directly affect various biological processes, often dysregulated in disease, and are important drug targets. We previously performed and identified tissue-specific protein quantitative trait loci in brain, cerebrospinal fluid, and plasma. We now enhance this work by analyzing more proteins (1,300 versus 1,079) and an almost twofold increase in high quality imputed genetic variants (8.4 million versus 4.4 million) by using TOPMed reference panel. We identified 38 genomic regions associated with 43 proteins in brain, 150 regions associated with 247 proteins in cerebrospinal fluid, and 95 regions associated with 145 proteins in plasma. Compared to our previous study, this study newly identified 12 loci in brain, 30 loci in cerebrospinal fluid, and 22 loci in plasma. Our improved genomic atlas uncovers the genetic control of protein regulation across multiple tissues. These resources are accessible through the Online Neurodegenerative Trait Integrative Multi-Omics Explorer for use by the scientific community.

Regulation of photosynthetic function and reactive oxygen species metabolism in sugar beet (Beta vulgaris L.) cultivars under waterlogging stress and associated tolerance mechanisms.

Sugar beet (Beta vulgaris L.) is an economically important sugar crop worldwide that is susceptible to sudden waterlogging stress during seedling cultivation, which poses a major threat to sugar beet development and production. Our understanding of the physiological basis of waterlogging tolerance in sugar beet is limited. To investigate the photosynthetic adaptation strategies of sugar beet to waterlogging stress conditions, the tolerant cultivar KUHN1260 (KU) and sensitive cultivar SV1433 (SV) were grown under waterlogging stress, and their photosynthetic function and reactive oxygen species (ROS) metabolism were assessed. Our results showed that waterlogging stress significantly reduced the photosynthetic pigment content, rubisco activity, and expression level of the photosynthetic enzyme genes SvRuBP, SvGAPDH, and SvPRK, gas exchange parameters, and chlorophyll fluorescence parameters, induced damage to the ultrastructure of the chloroplast of the two sugar beet cultivars, inhibited the photosynthetic carbon assimilation capacity of sugar beet leaves, damaged the structural stability of photosystem II (PSII), and disturbed the equilibrium between electrons at the acceptor and donor sides of PSII, which was the result of stomatal and non-stomatal limiting factors. Moreover, the level of ROS, H2O2, and O2▪-, antioxidant enzyme activity, and gene expression levels in the leaves of the two sugar beet cultivars increased over time under waterlogging stress; ROS accumulation was lower and antioxidant enzyme activities and gene expression levels were higher in the waterlogging-tolerant cultivar (KU) than the waterlogging-sensitive cultivar (SV). In sum, these responses in the more tolerant cultivars are associated with their resistance to waterlogging stress. Our findings will aid the breeding of waterlogging-tolerant sugar beet cultivars.

Management and Clinical Outcomes of Membranous Nephropathy, IgA Nephropathy, and Minimal Change Disease Two Years Post-Kidney Biopsy.

Introduction This study evaluated the phenotypic and pathology characteristics of patients undergoing kidney biopsy at a single center, while also determining the frequency and factors associated with clinical outcomes. Methods The incidence and distribution of biopsy-proven kidney diseases in 2000-2019 were surveyed. Consecutive individuals diagnosed with membranous nephropathy (MN), immunoglobulin A nephropathy (IgAN), and minimal change disease (MCD) between August 2015 and December 2019 were enrolled in the prospective two-year follow-up study. Outcomes included remission of proteinuria and kidney disease progression events. Multivariable adjusted Cox proportional hazards model was applied. Results 4,550 kidney biopsies were performed in 2000-2019, showing a noticeable increase in the proportion of MN. 426 patients were enrolled in follow-up cohort. 346 (81.2%) achieved remission of proteinuria, 39 (9.2%) suffered kidney disease progression and 51.3% of them were diagnosed with IgAN. Kidney pathological diagnosis (MN vs. MCD: hazard ratio [HR], 0.42; 95% confidence interval [95% CI], 0.31-0.57; IgAN vs. MCD: 0.58; 0.39-0.85), levels of 24-h urine protein at biopsy (1.04; 1.00-1.08) and presence of nodular mesangial sclerosis (0.70; 0.49-0.99) were significantly correlated with remission of proteinuria after adjusting for baseline variables. 24-h urine protein levels at biopsy (1.14; 1.04-1.25) and the presence of crescents (2.30; 1.06-4.95) were the independent risk factors for kidney disease progression events after adjusting for baseline variables. Conclusion The increasing frequency of MN was affirmed over the past two decades. The therapeutic status, clinical outcomes, and factors influencing these outcomes were presented in this single-center study for the three primary glomerular diseases. Number of China Clinical Trial Registry: ChiCTR2100043001.

DNA Framework-Programmed Nanoscale Enzyme Assemblies.

Multienzyme assemblies mediated by multivalent interaction play a crucial role in cellular processes. However, the three-dimensional (3D) programming of an enzyme complex with defined enzyme activity in vitro remains unexplored, primarily owing to limitations in precisely controlling the spatial topological configuration. Herein, we introduce a nanoscale 3D enzyme assembly using a tetrahedral DNA framework (TDF), enabling the replication of spatial topological configuration and maintenance of an identical edge-to-edge distance akin to natural enzymes. Our results demonstrate that 3D nanoscale enzyme assemblies in both two-enzyme systems (glucose oxidase (GOx)/horseradish peroxidase (HRP)) and three-enzyme systems (amylglucosidase (AGO)/GOx/HRP) lead to enhanced cascade catalytic activity compared to the low-dimensional structure, resulting in ∼5.9- and ∼7.7-fold enhancements over homogeneous diffusional mixtures of free enzymes, respectively. Furthermore, we demonstrate the enzyme assemblies for the detection of the metabolism biomarkers creatinine and creatine, achieving a low limit of detection, high sensitivity, and broad detection range.

Construction of ceRNA network mediated by circRNAs screening from microarray and identification of novel biomarkers for myasthenia gravis.

BACKGROUND: Recent studies have revealed that circRNA can serve as ceRNA to participate in multiple autoimmune diseases. Our study aims to explore the key circRNA as ceRNA and biomarker for MG. METHODS: We used circRNA microarray to explore differentially expressed circRNAs (DECs) from MG and compare with control. Then, we predicted the target miRNA associated with DECs and screened miRNAs by the algorithm of random walk with restart (RWR). Next, we constructed the circRNA-miRNA-mRNA ceRNA regulated network (CMMC) to identify the hub objects. Following, we detected the expression of hub-circRNAs by RT-PCR. We verify has_circ_0004183 (circFRMD4) sponging miR-145-5p regulate cells proliferation using luciferase assay and CCK-8. RESULTS: We found that the expression level of circFRMD4 and has_circ_0035381 (circPIGB) were upregulated and has_circ_0089153(circ NUP214) had the lowest expression level in MG. Finally, we proved circFRMD4 sponging miR-145-5p regulate Jurkat cells proliferation. CircFRMD4 take part in the genesis and development of MG via circFRMD4/miR145-5p axis. CONCLUSIONS: We found that circFRMD4, circPIGB and circNUP214 can be considered as valuable potential novel biomarkers for AchR + MG. CircFRMD4 participate in the development of AchR + MG via targeting binding with miR-145-5p.

miR-30a-5p mediates ferroptosis of hippocampal neurons in chronic cerebral hypoperfusion-induced cognitive dysfunction by modulating the SIRT1/NRF2 pathway.

OBJECTIVE: Chronic cerebral hypoperfusion (CCH) is a common cause of brain dysfunction. As a microRNA (also known as miRNAs or miRs), miR-30a-5p participates in neuronal damage and relates to ferroptosis. We explored the in vivo and in vitro effects and functional mechanism of miR-30a-5p in CCH-triggered cognitive impairment through the silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway. METHODS: After 1 month of CCH modeling through bilateral common carotid artery stenosis, mice were injected with 2 µL antagomir (also known as anti-miRNAs) miR-30a-5p, with cognitive function evaluated by Morris water maze and novel object recognition tests. In vitro HT-22 cell oxygen glucose deprivation (OGD) model was established, followed by miR-30a-5p inhibitor and/or si-SIRT1 transfections, with Fe2+ concentration, malonaldehyde (MDA) and glutathione (GSH) contents, reactive oxygen species (ROS), miR-30a-5p and SIRT1 and glutathione peroxidase 4 (GPX4) protein levels, NRF2 nuclear translocation, and miR-30a-5p-SIRT1 targeting relationship assessed. RESULTS: CCH-induced mice showed obvious cognitive impairment, up-regulated miR-30a-5p, and down-regulated SIRT1. Ferroptosis occurred in hippocampal neurons, manifested by elevated Fe2+ concentration and ROS and MDA levels, mitochondrial atrophy, and diminished GSH content. Antagomir miR-30a-5p or miR-30a-5p inhibitor promoted SIRT1 expression and NRF2 nuclear translocation, increased GPX4, cell viability and GSH content, and reduced Fe2+ concentration and ROS and MDA levels. miR-30a-5p negatively regulated SIRT1. In vitro, miR-30a-5p knockout increased NRF2 nuclear translocation by up-regulating SIRT1, inhibiting OGD-induced ferroptosis in HT-22 cells. CONCLUSION: miR-30a-5p induces hippocampal neuronal ferroptosis and exacerbates post-CCH cognitive dysfunction by targeting SIRT1 and reducing NRF2 nuclear translocation.

The development of the neurocritical care specialty in China based on the analysis of neurocritical care unit volume and quality.

PURPOSE: Through three neurocritical care unit (NCCU) surveys in China, we tried to understand the development status of neurocritical care and clarify its future development. METHODS: Using a cross-sectional survey method and self-report questionnaires, the number and quality of NCCUs were investigated through three steps: administering the questionnaire, sorting the survey data, and analyzing the survey data. RESULTS: At the second and third surveys, the number of NCCUs (76/112/206) increased by 47% and 84%, respectively. The NCCUs were located in tertiary grade A hospitals or teaching hospitals (65/100/181) in most provinces (24/28/29). The numbers of full-time doctors (359/668/1337) and full-time nurses (904/1623/207) in the NCCUs increased, but the doctor-bed ratio and nurse-bed ratio were still insufficient (0.4:1 and 1.3:1). CONCLUSION: In the past 20 years, the growth rate of NCCUs in China has accelerated, while the allocation of medical staff has been insufficient. Although most NCCU hospital bed facilities and instruments and equipment tend to be adequate, there are obvious defects in some aspects of NCCUs.

Genome-wide association study of plant color in Sorghum bicolor.

Introduction: Sorghum plant color is the leaf sheath/leaf color and is associated with seed color, tannin and phenol content, head blight disease incidence, and phytoalexin production. Results: In this study, we evaluated plant color of the sorghum mini core collection by scoring leaf sheath/leaf color at maturity as tan, red, or purple across three testing environments and performed genome-wide association mapping (GWAS) with 6,094,317 SNPs markers. Results and Discussion: Eight loci, one each on chromosomes 1, 2, 4, and 6 and two on chromosomes 5 and 9, were mapped. All loci contained one to three candidate genes. In qPC5-1, Sobic.005G165632 and Sobic.005G165700 were located in the same linkage disequilibrium (LD) block. In qPC6, Sobic.006G149650 and Sobic.006G149700 were located in the different LD block. The single peak in qPC6 covered one gene, Sobic.006G149700, which was a senescence regulator. We found a loose correlation between the degree of linkage and tissue/organ expression of the underlying genes possibly related to the plant color phenotype. Allele analysis indicated that none of the linked SNPs can differentiate between red and purple accessions whereas all linked SNPs can differentiate tan from red/purple accessions. The candidate genes and SNP markers may facilitate the elucidation of plant color development as well as molecular plant breeding.

Discovery and validation of molecular patterns and immune characteristics in the peripheral blood of ischemic stroke patients.

Background: Stroke is a disease with high morbidity, disability, and mortality. Immune factors play a crucial role in the occurrence of ischemic stroke (IS), but their exact mechanism is not clear. This study aims to identify possible immunological mechanisms by recognizing immune-related biomarkers and evaluating the infiltration pattern of immune cells. Methods: We downloaded datasets of IS patients from GEO, applied R language to discover differentially expressed genes, and elucidated their biological functions using GO, KEGG analysis, and GSEA analysis. The hub genes were then obtained using two machine learning algorithms (least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE)) and the immune cell infiltration pattern was revealed by CIBERSORT. Gene-drug target networks and mRNA-miRNA-lncRNA regulatory networks were constructed using Cytoscape. Finally, we used RT-qPCR to validate the hub genes and applied logistic regression methods to build diagnostic models validated with ROC curves. Results: We screened 188 differentially expressed genes whose functional analysis was enriched to multiple immune-related pathways. Six hub genes (ANTXR2, BAZ2B, C5AR1, PDK4, PPIH, and STK3) were identified using LASSO and SVM-RFE. ANTXR2, BAZ2B, C5AR1, PDK4, and STK3 were positively correlated with neutrophils and gamma delta T cells, and negatively correlated with T follicular helper cells and CD8, while PPIH showed the exact opposite trend. Immune infiltration indicated increased activity of monocytes, macrophages M0, neutrophils, and mast cells, and decreased infiltration of T follicular helper cells and CD8 in the IS group. The ceRNA network consisted of 306 miRNA-mRNA interacting pairs and 285 miRNA-lncRNA interacting pairs. RT-qPCR results indicated that the expression levels of BAZ2B, C5AR1, PDK4, and STK3 were significantly increased in patients with IS. Finally, we developed a diagnostic model based on these four genes. The AUC value of the model was verified to be 0.999 in the training set and 0.940 in the validation set. Conclusion: Our research explored the immune-related gene expression modules and provided a specific basis for further study of immunomodulatory therapy of IS.

Associations between Geriatric Nutrition Risk Index, bone mineral density and body composition in type 2 diabetes patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM), a fast-growing issue in public health, is one of the most common chronic metabolic disorders in older individuals. Osteoporosis and sarcopenia are highly prevalent in T2DM patients and may result in fractures and disabilities. In people with T2DM, the association between nutrition, sarcopenia, and osteoporosis has rarely been explored. AIM: To evaluate the connections among nutrition, bone mineral density (BMD) and body composition in patients with T2DM. METHODS: We enrolled 689 patients with T2DM for this cross-sectional study. All patients underwent dual energy X-ray absorptiometry (DXA) examination and were categorized according to baseline Geriatric Nutritional Risk Index (GNRI) values calculated from serum albumin levels and body weight. The GNRI was used to evaluate nutritional status, and DXA was used to investigate BMD and body composition. Multivariate forward linear regression analysis was used to identify the factors associated with BMD and skeletal muscle mass index. RESULTS: Of the total patients, 394 were men and 295 were women. Compared with patients in tertile 1, those in tertile 3 who had a high GNRI tended to be younger and had lower HbA1c, higher BMD at all bone sites, and higher appendicular skeletal muscle index (ASMI). These important trends persisted even when the patients were divided into younger and older subgroups. The GNRI was positively related to ASMI (men: r = 0.644, P < 0.001; women: r = 0.649, P < 0.001), total body fat (men: r = 0.453, P < 0.001; women: r = 0.557, P < 0.001), BMD at all bone sites, lumbar spine (L1-L4) BMD (men: r = 0.110, P = 0.029; women: r = 0.256, P < 0.001), FN-BMD (men: r = 0.293, P < 0.001; women: r = 0.273, P < 0.001), and hip BMD (men: r = 0.358, P < 0.001; women: r = 0.377, P < 0.001). After adjustment for other clinical parameters, the GNRI was still significantly associated with BMD at the lumbar spine and femoral neck. Additionally, a low lean mass index and higher ß-collagen special sequence were associated with low BMD at all bone sites. Age was negatively correlated with ASMI, whereas weight was positively correlated with ASMI. CONCLUSION: Poor nutrition, as indicated by a low GNRI, was associated with low levels of ASMI and BMD at all bone sites in T2DM patients. Using the GNRI to evaluate nutritional status and using DXA to investigate body composition in patients with T2DM is of value in assessing bone health and physical performance.