Electronic medical records imputation by temporal Generative Adversarial Network.

The loss of electronic medical records has seriously affected the practical application of biomedical data. Therefore, it is a meaningful research effort to effectively fill these lost data. Currently, state-of-the-art methods focus on using Generative Adversarial Networks (GANs) to fill the missing values of electronic medical records, achieving breakthrough progress. However, when facing datasets with high missing rates, the imputation accuracy of these methods sharply deceases. This motivates us to explore the uncertainty of GANs and improve the GAN-based imputation methods. In this paper, the GRUD (Gate Recurrent Unit Decay) network and the UGAN (Uncertainty Generative Adversarial Network) are proposed and organically combined, called UGAN-GRUD. In UGAN-GRUD, it highlights using GAN to generate imputation values and then leveraging GRUD to compensate them. We have designed the UGAN and the GRUD network. The former is employed to learn the distribution pattern and uncertainty of data through the Generator and Discriminator, iteratively. The latter is exploited to compensate the former by leveraging the GRUD based on time decay factor, which can learn the specific temporal relations in electronic medical records. Through experimental research on publicly available biomedical datasets, the results show that UGAN-GRUD outperforms the current state-of-the-art methods, with average 13% RMSE (Root Mean Squared Error) and 24.5% MAPE (Mean Absolute Percentage Error) improvements.

Gd(III)-Catalyzed Regio-, Diastereo-, and Enantioselective [4 + 2] Photocycloaddition of Naphthalene Derivatives.

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

Silver(I) Complexes with Mefenamic Acid and Nitrogen Heterocyclic Ligands: Synthesis, Characterization, and Biological Evaluation.

Four Ag(I) complexes with mefenamato and nitrogen heterocyclic ligands, [Ag(2-apy)(mef)]2 (1), [Ag(3-apy)(mef)] (2), [Ag2(tmpyz)(mef)2] (3), and {[Ag(4,4'-bipy)(mef)]2(CH3CN)1.5(H2O)2}n (4), (mef = mefenamato, 2-apy = 2-aminopyridine, 3-apy = 3-aminopyridine, tmpyz = 2,3,5,6-tetramethylpyrazine, 4,4'-bipy = 4,4'-bipyridine), were synthesized and characterized. The interactions of these complexes with BSA were investigated by fluorescence spectroscopy, which indicated that these complexes quench the fluorescence of BSA by a static mechanism. The fluorescence data also indicated that the complexes showed good affinity for BSA, and one binding site on BSA was suitable for the complexes. The in vitro cytotoxicity of the four complexes against human cancer cell lines (MCF-7, HepG-2, A549, and MDA-MB-468) and one normal cell line (HTR-8) was evaluated by the MTT assay. Complex 1 displayed high cytotoxic activity against A549 cells. Further studies revealed that complex 1 could enhance the intracellular levels of ROS (reactive oxygen species) in A549 cells, cause cell cycle arrest in the G0/G1 phase, and induce apoptosis in A549 cells in a dose-dependent manner.

RNAi-mediated knockdown of papilin gene affects the egg hatching in Nilaparvata lugens.

BACKGROUND: The brown planthopper (BPH), Nilaparvata lugens, is one of the most destructive pests of rice. Owing to the rapid adaptation of BPH to many pesticides and resistant varieties, identifying putative gene targets for developing RNA interference (RNAi)-based pest management strategies has received much attention for this pest. The glucoprotein papilin is the most abundant component in the basement membranes of many organisms, and its function is closely linked to development. RESULTS: In this study, we identified a papilin homologous gene in BPH (NlPpn). Quantitative Real-time PCR analysis showed that the transcript of NlPpn was highly accumulated in the egg stage. RNAi of NlPpn in newly emerged BPH females caused nonhatching phenotypes of their eggs, which may be a consequence of the maldevelopment of their embryos. Moreover, the transcriptomic analysis identified 583 differentially expressed genes between eggs from the dsGFP- and dsNlPpn-treated insects. Among them, the 'structural constituent of cuticle' cluster ranked first among the top 15 enriched GO terms. Consistently, ultrastructural analysis unveiled that dsNlPpn-treated eggs displayed a discrete and distorted serosal endocuticle lamellar structure. Furthermore, the hatchability of BPH eggs was also successfully reduced by the topical application of NlPpn-dsRNA-layered double hydroxide nanosheets onto the adults. CONCLUSION: Our findings demonstrate that NlPpn is essential to maintaining the regular structure of the serosal cuticle and the embryonic development in BPH, indicating NlPpn could be a potential target for pest control during the egg stage. © 2024 Society of Chemical Industry.

Cycle contrastive adversarial learning with structural consistency for unsupervised high-quality image deraining transformer.

In overcoming the challenges faced in adapting to paired real-world data, recent unsupervised single image deraining (SID) methods have proven capable of accomplishing notably acceptable deraining performance. However, the previous methods usually fail to produce a high quality rain-free image due to neglecting sufficient attention to semantic representation and the image content, which results in the inability to completely separate the content from the rain layer. In this paper, we develop a novel cycle contrastive adversarial framework for unsupervised SID, which mainly consists of cycle contrastive learning (CCL) and location contrastive learning (LCL). Specifically, CCL achieves high-quality image reconstruction and rain-layer stripping by pulling similar features together while pushing dissimilar features further in both semantic and discriminant latent spaces. Meanwhile, LCL implicitly constrains the mutual information of the same location of different exemplars to maintain the content information. In addition, recently inspired by the powerful Segment Anything Model (SAM) that can effectively extract widely applicable semantic structural details, we formulate a structural-consistency regularization to fine-tune our network using SAM. Apart from this, we attempt to introduce vision transformer (VIT) into our network architecture to further improve the performance. In our designed transformer-based GAN, to obtain a stronger representation, we propose a multi-layer channel compression attention module (MCCAM) to extract a richer feature. Equipped with the above techniques, our proposed unsupervised SID algorithm, called CCLformer, can show advantageous image deraining performance. Extensive experiments demonstrate both the superiority of our method and the effectiveness of each module in CCLformer. The code is available at https://github.com/zhihefang/CCLGAN.

Analysis of genetic and clinical characteristics of androgen insensitivity syndrome: a cohort study including 12 families.

CONTEXT: Androgen insensitivity syndrome (AIS) manifests itself as variable symptoms of under-virilization in patients with 46, XY disorders caused by androgen receptor (AR) gene variants. This large-sample study aimed to correlate the genotypes and phenotypes to the fertility of individuals. METHODS: This was a cohort study that analyzed genetic and clinical characteristics of patients with AIS from a single center in China. RESULTS: The 117 patients were divided into 53 with complete AIS (CAIS) and 64 with partial AIS (PAIS). At their first visit the median age was 1.83 years (0.92-4.17) and the EMS was 3.0 (2.0-6.0). At the last follow-up, 92% (49/53) of patients with CAIS maintained their female gender, and 94% (60/64) of patients with PAIS were raised as males. No gender anxiety was observed in this study. Eighty-eight AR variants were identified, with 31 (35%) being unreported. Moreover, 24% (21/88) occurred more than once. The variants that appeared most frequently were located at amino acid 841, including p.R841H(n=5) and p.R841C(n=2). Variants p.N706S, p.R856H, and p.A871V were each observed 4 times. In terms of inheritance, 83% of patients with parental verification inherited variants from their mothers. We also observed that the variants from one case were inherited from his maternal grandfather who had hypospadias. CONCLUSION: Most children with PAIS were raised as males. The abundance of maternally inheritable variants and the presence of case of preserved fertility indicate the fertility potential in patients with AIS. Hence, we recommend a careful evaluation of gonadectomy when fertility preservation is being considered.

Intraoral Acupuncture for Sialorrhea in Stroke Patients: a Study Protocol for a Randomized Controlled Trial.

Importance: Post-stroke sialorrhea (PSS) refers to excessive saliva flowing out the lip border after a stroke. PSS negatively affects patient self-image and social communication and may lead to depression. Limited evidence supports the link between excessive salivation and PSS. No large-scale, strictly controlled randomized controlled trials have shown the effectiveness of acupuncture in treating PSS patients. Objective: We aim to compare the effects of intraoral and sham acupuncture in PSS patients and explore relationships among salivation and drooling severity and frequency and swallowing function in stroke patients. Design: Clinical study protocol, SPIRIT compliant. Setting: Prospective, single-center, randomized, and sham-controlled trial. Population: We will recruit 106 PSS patients to receive 4-week intraoral or sham acupuncture. Additionally, 53 stroke patients without PSS will undergo a conventional 4-week treatment program to compare salivation between PSS and non-PSS patients. Exposures: Intraoral or sham acupuncture. Main Outcomes and Measures: The main evaluation index will be the 3-minute saliva weight (3MSW), comparing changes in 3MSW from baseline to weeks 4 and 8. Secondary assessment indices will include the "Drooling Severity and Frequency Scale" and "Functional Oral Intake Scale." Results: The results from this study will be published in peer-reviewed journals. Conclusion: Comparing effects of intraoral and sham acupuncture in PSS patients, this study may contribute important evidence for future PSS treatment and provide valuable insights into whether salivation issues in stroke patients are attributed to heightened salivary secretion or dysphagia.

Global, regional, and national cancer burdens of respiratory and digestive tracts in 1990-2044: A cross-sectional and age-period-cohort forecast study.

BACKGROUND: Understanding the current status and future trends of cancer burdens by systems provides important information for specialists, policymakers, and specific risk populations. METHODS: The aim of this study was to compare the current and future cancer burdens of the gastrointestinal (GI) and respiratory tracts in terms of their magnitude and distribution. Data from a total of eight cancers of the digestive and respiratory tracts in the Global Burden of Disease (GBD) database were collected. The age-standardized incidence/death rates (ASIR/ASDRs), disability-adjusted life years (DALYs), and estimated annual percentage changes (EAPCs) were analyzed. Future trends were predicted with Bayesian age-period-cohort (BAPC) and NORDPRED models. RESULTS: In 2019, there was a significant increase in DALY for both digestive and respiratory tract cancers compared to 1990. Meanwhile, ASIR increased slightly and ASDR decreased notably. In 2019, the global cancer burdens of respiratory and digestive tracts were 38568363.53 and 66912328.72 in DALY, 34.28 and 55.32 in ASIR, and 656.82 and 808.22 in ASDR per 100,000 population with changes of +54.63% and +43.93%, +2.92% and +5.65%, and -17.39% and -26.83% compared to those in 1990, respectively. Significant cross-regional differences in the cancer burdens were observed among the regions. Compared to four representative chronic diseases, the burden of cancers showed less remission and greater global inequalities. The burdens of both digestive and respiratory tract cancers were higher in males than in females in terms of the ASIR, ASDR, and DALY. The incidence and mortality rates of respiratory tract cancers were up to 3-4 times higher in males than in females, whereas the difference between male and female rates of digestive tract cancers was relatively smaller. The main risk factor associated with all kinds of digestive and respiratory tract cancers is tobacco, leading to 18.5 in ASDR and 3.38×107 in DALY for respiratory tract cancers; 8.29 in ASDR and 1.60×107 in DALY for digestive tract cancers, in 2019. Additionally, alcohol use contributes to most digestive and respiratory tract cancers (1.23/1.03 in ASDR and 1.60×106/2.57×106 in DALY for respiratory tract cancers; 4.19/3.82 in ASDR and 4.49×106/8.06×106 in DALY for digestive tract cancers), except for stomach cancer and tracheal, bronchus, and lung cancer. The cancer burdens of respiratory and digestive tracts are likely to decrease substantially between 2020 and 2044. For most metrics, except for the ASIR and male-to-female ratios of ASDR and ASDALY in digestive tract cancers, the worldwide variances of burden metrics have been decreasing in the past decades and will possibly maintain stable trends in the future. CONCLUSIONS: The epidemiology of respiratory and GI tract cancers has common features and individual characteristics that are reflected in geography, age characteristics, and risk factors. Current epidemiological status, future trends, and the globalization of these disease burdens are important factors for making scientific planning of resources to minimize the cancer burden metrics and their cross-regional inequalities.

Key residues in the VDAC2-BAK complex can be targeted to modulate apoptosis.

BAK and BAX execute intrinsic apoptosis by permeabilising the mitochondrial outer membrane. Their activity is regulated through interactions with pro-survival BCL-2 family proteins and with non-BCL-2 proteins including the mitochondrial channel protein VDAC2. VDAC2 is important for bringing both BAK and BAX to mitochondria where they execute their apoptotic function. Despite this important function in apoptosis, while interactions with pro-survival family members are well characterised and have culminated in the development of drugs that target these interfaces to induce cancer cell apoptosis, the interaction between BAK and VDAC2 remains largely undefined. Deep scanning mutagenesis coupled with cysteine linkage identified key residues in the interaction between BAK and VDAC2. Obstructive labelling of specific residues in the BH3 domain or hydrophobic groove of BAK disrupted this interaction. Conversely, mutating specific residues in a cytosol-exposed region of VDAC2 stabilised the interaction with BAK and inhibited BAK apoptotic activity. Thus, this VDAC2-BAK interaction site can potentially be targeted to either inhibit BAK-mediated apoptosis in scenarios where excessive apoptosis contributes to disease or to promote BAK-mediated apoptosis for cancer therapy.

[Effects of plumbagin on proliferation and apoptosis of human hepatocellular carcinoma cells based on CKB/p53 signaling pathway].

To investigate the effects of plumbagin on the proliferation and apoptosis of human hepatoma Huh-7 cells and its mechanism based on the creatine kinase B(CKB)/p53 signaling pathway. Huh-7 cells were treated with plumbagin from 1 to 12 µmol·L~(-1) for cell counting kit-8(CCK-8) assay, and 1, 3, and 6 µmol·L~(-1) were determined as low, medium, and high concentrations of plumbagin for subsequent experiments. CKB gene was knocked out in Huh-7 cells by clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated proteins(Cas)-9 gene editing technology. CKB overexpression lentivirus was transfected into Huh-7 cells to up-regulate the expression of CKB. Cell proliferation and apoptosis were detected by plate cloning assay and flow cytometry. The mRNA expression of CKB was detected by quantitative real-time PCR(qRT-PCR). CKB, p53, mouse double minute 2 homolog(MDM2), B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), and caspase-3 protein were detected by Western blot(WB). The results showed that plumbagin significantly inhibited the proliferation of Huh-7 cells and induced cell apoptosis. Compared with the control group, the apoptosis level was significantly increased in the plumbagin group, while the apoptosis level was significantly decreased in the plumbagin combined with the apoptosis inhibitor group. Plumbagin significantly down-regulated the protein expression levels of CKB, Bcl-2, and MDM2 and up-regulated the protein expression levels of p53, Bax, and caspase-3. Knockdown of the CKB gene decreased the proliferative ability of Huh-7 cells, increased the apoptotic rate, decreased the expression levels of Bcl-2 and MDM2 proteins, and increased the expression levels of p53, Bax, and caspase-3 proteins. After up-regulation of CKB expression, the proliferation ability of Huh-7 cells was enhanced, and the protein expression levels of Bcl-2 and MDM2 were elevated. The protein expression levels of p53, Bax, and caspase-3 were decreased. In addition, plumbagin reversed the effect of overexpression of CKB on the proliferation and apoptosis of Huh-7 cells. In conclusion, plumbagin significantly inhibited the proliferative ability of Huh-7 cells, and the mechanism may be related to the inhibition of CKB expression, activation of the p53 signaling pathway, and regulation of the expression of mitochondrial-associated apoptotic proteins, ultimately inducing cell apoptosis.

[Determination of nine components of fried Ziziphi Spinosae Semen extract in beagle dog plasma by UPLC-MS/MS and its application in pharmacokinetic research].

This study established a convenient, rapid, and sensitive ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of magnoflorine,(R)-coclaurine, vicenin Ⅱ, isospinosin, spinosin, swertisin, N-nornuciferine, 6-feruloylspinosin, and jujuboside B in beagle dog plasma after oral administration of fried Ziziphi Spinosae Semen(FZSS) extract. The Waters HSS-T3 C_(18) column(2.1 mm×100 mm, 1.8 µm) was used. The methanol-aqueous solution(containing 0.01% formic acid) was adopted as the mobile phase for gradient elution. The nine components and two internal standards were completely separated within 8 min. The mass spectrometry detection was performed in multiple reaction monitoring(MRM) mode by positive and negative ion switching of electrospray ionization. The analytical method was validated in terms of specificity, selectivity, linear range, accuracy, precision, recovery, matrix effect, and stability. It could meet the requirement of pharmacokinetic research after oral administration of FZSS extract to beagle dogs. The results showed that the time to reach the peak concentration(T_(max)) of magnoflorine,(R)-coclaurine, vicenin Ⅱ, isospinosin, spinosin, 6-feruloylspinosin, and jujuboside B was 2.40-3.20 h, and the elimination halflife(t_(1/2)) was 2.08-6.79 h after a single-dose oral administration of FZSS to beagle dogs. The exposure of magnoflorine and spinosin was high, with a peak concentration(C_(max)) of 76.7 and 31.5 ng·mL~(-1) and an area under the curve(AUC_(0-∞)) of 581 and 315 ng·h·mL~(-1), respectively. The exposure of the remaining five compounds was lower, with a C_(max) of 0.81-13.0 ng·mL~(-1) and an AUC_(0-∞) of 6.00-106 ng·h·mL~(-1). This study provides a reference for the follow-up research of FZSS.

A bionic mimosa soft robot based on a multi-responsive PNIPAM-PEGDA hydrogel composition.

Deformation plays a vital role in the survival of natural organisms. One example is that plants deform themselves to face the sun for sufficient sunlight exposure, which allows them to produce nutrients through photosynthesis. Drawing inspiration from nature, researchers have been exploring the development of 3D deformable materials. However, the traditional approach to manufacturing deformable hydrogels relies on complex technology, which limits their potential applications. In this study, we simulate the stress variations observed in the plant tissue to create a 3D structure from a 2D material. Using UV curing technology, we create a single-layer poly(N-isopropylacrylamide) hydrogel sheet with microchannels that exhibit distinct swelling rates when subjected to stimulation. After a two-step curing process, we produce a poly(N-isopropylacrylamide)-polyethylene glycol diacrylatedouble-layer structure that can be manipulated to change its shape by controlling the light and solvent content. Based on the double-layer structure, we fabricate a dual-response driven bionic mimosa robot that can perform a variety of functions. This soft robot can not only reversibly change its shape but also maintain a specific shape without continuous stimulation. Its capacity for reversible deformation, resulting from internal stress, presents promising application prospects in the biomedical and soft robotics domain. This study delivers an insightful framework for the development of programmable soft materials.

YANK2 activated by Fyn promotes glioma tumorigenesis via the mTOR-independent p70S6K activation pathway.

Glioma, particularly glioblastomas (GBM), is incurable brain tumor. The most targeted receptor tyrosine kinase (RTKs) drugs did not bring benefit to GBM patients. The mechanism of glioma growth continues to be explored to find more effective treatment. Here, we reported that Ser/Thr protein kinase YANK2 (yet another kinase 2) is upregulated in glioma tissues and promotes the growth and proliferation of glioma in vitro and in vivo. Further, we confirmed that oncogene Fyn directly activated YANK2 through phosphorylation its Y110, and Fyn-mediated YANK2 phosphorylation at Y110 site promotes glioma growth by increasing its stability. Finally, YANK2 was proved to be a novel upstream kinase of p70S6K and promotes glioma growth by directly phosphorylating p70S6K at T389. Taken together, we found a new mTOR-independent p70S6K activation pathway, Fyn-YANK2-p70S6K, which promotes glioma growth, and YANK2 is a potential oncogene and serves as a novel therapeutic target for glioma.

Longitudinal manipulation of local nonseparability in vector beams.

The inherent nonseparability of vector beams presents a unique opportunity to explore novel optical functionalities, expanding new degrees of freedom for optical information processing. In this Letter, we introduce a novel, to the best of our knowledge, method for tailoring the local nonseparability along the propagation axis of vector beams. Employing higher-order Bessel vector beams, the longitudinal control over the local nonseparability is achieved through targeted amplitude modulation of constituent orthogonal polarization components within the main ring region. Experimental demonstrations of diverse longitudinal nonseparability profiles corroborate the efficacy and versatility of our approach, opening avenues for further exploration of the nonseparability manipulation in vector beams.

Spatial transcriptomics reveals gene interactions and signaling pathway dynamics in rat embryos with anorectal malformation.

Anorectal malformation (ARM) is a prevalent early pregnancy digestive tract anomaly. The intricate anatomy of the embryonic cloaca region makes it challenging for traditional high-throughput sequencing methods to capture location-specific information. Spatial transcriptomics was used to sequence libraries of frozen sections from embryonic rats at gestational days (GD) 14 to 16, covering both normal and ARM cases. Bioinformatics analyses and predictions were performed using methods such as WGCNA, GSEA, and PROGENy. Immunofluorescence staining was used to verify gene expression levels. Gene expression data was obtained with anatomical annotations of clusters, focusing on the cloaca region's location-specific traits. WGCNA revealed gene modules linked to normal and ARM cloacal anatomy development, with cooperation between modules on GD14 and GD15. Differential gene expression profiles and functional enrichment were presented. Notably, protein levels of Pcsk9, Hmgb2, and Sod1 were found to be downregulated in the GD15 ARM hindgut. The PROGENy algorithm predicted the activity and interplay of common signaling pathways in embryonic sections, highlighting their synergistic and complementary effects. A competing endogenous RNA (ceRNA) regulatory network was constructed from whole transcriptome data. Spatial transcriptomics provided location-specific cloaca region gene expression. Diverse bioinformatics analyses deepened our understanding of ARM's molecular interactions, guiding future research and providing insights into gene regulation in ARM development.

Examining the Mechanism of Treatment for Primary Dysmenorrhea with Wenjing Huoxue Decoction Based on Transcriptomics, Metabolomics, and Network Pharmacology.

BACKGROUND: Wenjing Huoxue Decoction (WJHXD) is a traditional treatment for primary dysmenorrhea (PD) that can quickly relieve various symptoms caused by PD. Previous clinical studies have shown that WJHXD has better long-term efficacy than ibuprofen in the treatment of PD and can reverse the disorder of T cell subsets. OBJECTIVE: To investigate the effect of WJHXD on serum-related factors in the treatment of PD, including the identification of key targets, pathways, and active ingredients. METHODS: In order to study the effects of the WJHXD intervention in Parkinson's Disease (PD) rats, we used transcriptomics and metabolomics methods to examine the differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs). We also utilized network pharmacology to predict the target and effective route of WJHXD in treating PD. Finally, we employed molecular docking (MD) technology to confirm the placement of important targets and metabolites. RESULTS: WJHXD has been found to be effective in prolonging the onset time and decreasing the number of writhing episodes in PD rats after oxytocin injection. It has also been observed to reduce the levels of PGF2, COX-2, AVP, and PGE2 in the serum of PD rats to different degrees. Transcriptomics analysis has revealed that the core targets of WJHXD include KRT1, KRT16, CCL5, F2, NOS2, RAC2, and others, while the core pathways are Calcium signaling and cAMP signaling. The Estrogen signaling pathway was found to be downregulated in PD rats compared to normal uterine tissue, but WJHXD was able to up-regulate the pathway. A combined transcriptomics and metabolomics analysis suggested that WJHXD may be involved in eight metabolism-related pathways, with the most reliable ones being mucin-type O-glycan biosynthesis and glycolysis or gluconeogenesis. MD has shown that Hydroxyisocaproic acid may bind to important targets such as SLC6A4, PTGER3, IGFBP3, and IGF2. CONCLUSION: In WJHXD, the most targeted herbs were Corydalis rhizoma, licorice, and Myrrha. The most targeted active ingredients include quercetin, 3'-Hydroxy-4'-O-methylglabridin, shinpterocarpin, and isorhamnetin. Potential targets include PTGS2, NOS2, AR, SCN5A, and GAS6. Analysis revealed 72 highly reliable relationships between group A and B DEGs and DEMs, with 23 positive correlations and 49 negative correlations among them. A combined analysis of transcriptomics, metabolomics, and network pharmacology was used to identify possible targets, pathways, and active ingredients of WJHXD in PD treatment, and the correlation between DEGs and DEMs was investigated. However, further research is required to confirm the relationship between active ingredients, targets, and metabolites.

OsMADS6-OsMADS32 and REP1 control palea cellular heterogeneity and morphogenesis in rice.

Precise regulation of cell proliferation and differentiation is vital for organ morphology. Rice palea, serving as sepal, comprises two distinct regions: the marginal region (MRP) and body of palea (BOP), housing heterogeneous cell populations, which makes it an ideal system for studying organ morphogenesis. We report that the transcription factor (TF) REP1 promotes epidermal cell proliferation and differentiation in the BOP, resulting in hard silicified protrusion cells, by regulating the cyclin-dependent kinase gene, OsCDKB1;1. Conversely, TFs OsMADS6 and OsMADS32 are expressed exclusively in the MRP, where they limit cell division rates by inhibiting OsCDKB2;1 expression and promote endoreduplication, yielding elongated epidermal cells. Furthermore, reciprocal inhibition between the OsMADS6-OsMADS32 complex and REP1 fine-tunes the balance between cell division and differentiation during palea morphogenesis. We further show the functional conservation of these organ identity genes in heterogeneous cell growth in Arabidopsis, emphasizing a critical framework for controlling cellular heterogeneity in organ morphogenesis.

The characteristic and prognostic role of blood inflammatory markers in patients with Huntington's disease from China.

Objectives: This study aims to elucidate the role of peripheral inflammation in Huntington's disease (HD) by examining the correlation of peripheral inflammatory markers with clinical manifestations and disease prognosis. Methods: This investigation involved 92 HD patients and 92 matched healthy controls (HCs). We quantified various peripheral inflammatory markers and calculated their derived metrics including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). Clinical assessments spanning cognitive, motor, and disease severity were administered. Comparative analysis of inflammatory markers and clinical correlations between HD and controls was performed. Kaplan-Meier survival analysis and Cox regression model were used to assess the effect of inflammatory markers on survival. Results: The study revealed that HD patients had significantly reduced lymphocyte counts, and LMR. Conversely, NLR, PLR, and SII were elevated compared to HCs. Lymphocyte levels inversely correlated with the age of onset and monocyte levels inversely correlated with the UHDRS-total functional capacity (TFC) scores. After adjusting for age, sex, and CAG repeat length, lymphocyte count, NLR, PLR, and SII were significantly correlated with the progression rate of TFC scores. Elevated levels of white blood cells and monocytes were associated with an increased risk of disability and mortality in the HD cohort. Conclusion: Our findings indicate that HD patients display a distinct peripheral inflammatory profile with increased NLR, PLR, and SII levels compared to HCs. The peripheral inflammation appears to be linked with accelerated disease progression and decreased survival in HD.

Cross-talk between BCKDK-mediated phosphorylation and STUB1-dependent ubiquitination degradation of BCAT1 promotes GBM progression.

Branched-chain amino acid transferase 1 (BCAT1) is highly expressed in multiple cancers and is associated with poor prognosis, particularly in glioblastoma (GBM). However, the post-translational modification (PTM) mechanism of BCAT1 is unknown. Here, we investigated the cross-talk mechanisms between phosphorylation and ubiquitination modifications in regulating BCAT1 activity and stability. We found that BCAT1 is phosphorylated by branched chain ketoacid dehydrogenase kinase (BCKDK) at S5, S9, and T312, which increases its catalytic and antioxidant activity and stability. STUB1 (STIP1 homology U-box-containing protein 1), the first we found and reported E3 ubiquitin ligase of BCAT1, can also be phosphorylated by BCKDK at the S19 site, which disrupts the interaction with BCAT1 and inhibits its degradation. In addition, we demonstrate through in vivo and in vitro experiments that BCAT1 phosphorylation inhibiting its ubiquitination at multiple sites is associated with GBM proliferation and that inhibition of the BCKDK-BCAT1 axis enhances the sensitivity to temozolomide (TMZ). Overall, we identified novel mechanisms for the regulation of BCAT1 modification and elucidated the importance of the BCKDK-STUB1-BCAT1 axis in GBM progression.