Developmental Morphology, Physiology, and Molecular Basis of the Pentagram Fruit of Averrhoa carambola.

Averrhoa carambola, a key tropical and subtropical economic tree in the Oxalidaceae family, is distinguished by its unique pentagram-shaped fruit. This study investigates the developmental processes shaping the polarity of A. carambola fruit and their underlying hormonal and genetic mechanisms. By analyzing the Y1, Y2, and Y3 developmental stages-defined by the fruit diameters of 3-4 mm, 4-6 mm, and 6-12 mm, respectively-we observed that both cell number and cell size contribute to fruit development. Our findings suggest that the characteristic pentagram shape is established before flowering and is maintained throughout development. A hormonal analysis revealed that indole-3-acetic acid (IAA) and abscisic acid (ABA) show differential distribution between the convex and concave regions of the fruit across the developmental stages, with IAA playing a crucial role in polar auxin transport and shaping fruit morphology. A transcriptomic analysis identified several key genes, including AcaGH3.8, AcaIAA20, AcaYAB2, AcaXTH6, AcaYAB3, and AcaEXP13, which potentially regulate fruit polarity and growth. This study advances our comprehension of the molecular mechanisms governing fruit shape, offering insights for improving fruit quality through targeted breeding strategies.

Identification of key gene networks controlling organic acid and sugar metabolism during star fruit (Averrhoa carambola) development.

The sugar and organic acid content significantly impacts the flavor quality of star fruit, and it undergoes dynamic changes during development. However, the metabolic network and molecular mechanisms governing the formation of sugar and organic acid in star fruit remain unclear. In this study, 23 of 743 components were detected by metabonomic analysis. The highest metabolites contents were organic acids and derivatives. The highest sugar content in the fruit was fructose and glucose, followed by sucrose, which proved that A. carambola is a hexose accumulation type fruit. Genome identification preliminarily screened 141 genes related to glucose metabolism and 67 genes related to acid metabolism. A total of 7,881 unigenes were found in transcriptome data, 6,124 differentially expressed genes were screened, with more up-regulated than down-regulated genes. Transcriptome and metabolome association analysis screened seven core candidate genes related to glucose metabolism and 17 core genes highly related to organic acid pathway, and eight differentially expressed sugar and acid genes were selected for qRT-PCR verification. In addition, 29 bHLHs and eight bZIPs transcription factors were predicted in the glucose metabolism pathway, and 23 MYBs, nine C2H2s transcription factors and one GRAS transcription factor was predicted in the acid metabolism pathway, and transcription factors have both positive and negative regulatory effects on sugar and acid structure genes. This study increased our understanding of A. carambola fruit flavor and provided basic information for further exploring the ornamental and edible values of star fruit.

Forecasting the trend of tuberculosis incidence in Anhui Province based on machine learning optimization algorithm, 2013-2023.

Tuberculosis has been one of the most common communicable diseases raising global concerns. Accurately predicting the incidence of Tuberculosis remains challenging. Here we constructed a time-series analysis and fusion tool using multi-source data, and aimed to more accurately predict the incidence trend of tuberculosis of Anhui Province from 2013 to 2023. Random forest algorithm (RF), Feature Recursive Elimination (RFE) and Least absolute shrinkage and selection operator (LASSO) were implemented to improve the derivation of features related to infectious diseases and feature work. Based on the characteristics of infectious disease data, a model of RF-RFE-LASSO integrated particle swarm optimization multiple inputs long short term memory recurrent neural network (RRL-PSO-MiLSTM) was created to perform more accurate prediction. Results showed that the PSO-MiLSTM achieved excellent prediction results compared with common single-input and multi-input time-series models (test set MSE:42.3555, MAE: 59.3333, RMSE: 146.7237, MAPE: 2.1133, R2: 0.8634). PSO-MiLSTM enriches and complements the methodological research content of calibrating the time-series predictive analysis of infectious diseases using multi-source data, and can be used as a brand-new benchmark for the analysis of influencing factors and trend prediction of infectious diseases at the public health level in the future, as well as providing a reference for incidence rate prediction of infectious diseases.

Intermittent versus Continuous Calorie Restriction for Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Randomized Clinical Trial.

BACKGROUND: Calorie restriction has been demonstrated to be effective in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, it has been limited by poor long-term adherence. OBJECTIVE: This study aimed to compare intermittent calorie restriction (ICR) with traditional continuous calorie restriction (CCR) for the treatment of MASLD. METHODS: We conducted a 12-week, parallel-arm, randomized controlled trial that included 60 adults with MASLD and abnormal glucose metabolism. The participants were randomly assigned to either the ICR group (2 successive days of fasting [∼500 kcal/day] and 5 days of recovery per week) or the CCR group. The primary outcome was liver fat content (LFC) measured by 1H-Proton magnetic resonance spectroscopy. The secondary and exploratory outcomes included weight, body composition, glucose, insulin, lipids and liver stiffness. RESULTS: The mean reduction in LFC was -20.5% (95% CI: -25.0, -15.9%) in the ICR group and -15.5% (95% CI: -20.3, -10.8%) in the CCR group. Changes in LFC were not significantly different between the two groups (P = 0.15), and were homogeneous among different liver segments. Analysis of exploratory endpoints provided clues that the ICR was associated with greater reductions in fat mass and glycosylated hemoglobin. There were no significant differences in changes of weight, lean mass, insulin resistance, triglyceride and liver stiffness between the two groups. Participants showed high adherence to both the ICR and CCR schemes. CONCLUSIONS: The ICR and CCR schemes had similar effects on reducing liver fat content, suggesting that the ICR 5:2 diet can be an effective alternative for treating MASLD with high adherence. This trial was registered at clinicaltrials.gov as NCT04283942. CLINICAL TRIALS REGISTRATION: This study is registered at Clinicaltrials.gov (NCT04283942).

Different multicellular trichome types coordinate herbivore mechanosensing and defense in tomato.

Herbivore-induced wounding can elicit a defense response in plants. However, whether plants possess a surveillance system capable of detecting herbivore threats and initiating preparatory defenses before wounding occurs remains unclear. In this study, we reveal that tomato (Solanum lycopersicum) trichomes can detect and respond to the mechanical stimuli generated by herbivores. Mechanical stimuli are preferentially perceived by long trichomes, and this mechanosensation is transduced via intra-trichome communication. This communication presumably involves calcium waves, and the transduced signals activate the jasmonic acid (JA) signaling pathway in short glandular trichomes, resulting in the upregulation of the Woolly (Wo)-SlMYC1 regulatory module for terpene biosynthesis. This induced defense mechanism provides plants with an early warning system against the threat of herbivore invasion. Our findings represent a perspective on the role of multicellular trichomes in plant defense and the underlying intra-trichome communication.

ASH1L in Hepatoma Cells and Hepatic Stellate Cells Promotes Fibrosis-Associated Hepatocellular Carcinoma by Modulating Tumor-Associated Macrophages.

Hepatocellular carcinoma (HCC) often occurs in the context of fibrosis or cirrhosis. Methylation of histone is an important epigenetic mechanism, but it is unclear whether histone methyltransferases are potent targets for fibrosis-associated HCC therapy. ASH1L, an H3K4 methyltransferase, is found at higher levels in activated hepatic stellate cells (HSCs) and hepatoma cells. To determine the role of ASH1L in vivo, transgenic mice with conditional Ash1l depletion in the hepatocyte cell lineage (Ash1lflox/floxAlbcre) or HSCs (Ash1lflox/floxGFAPcreERT2) are generated, and these mice are challenged in a diethylnitrosamine (DEN)/carbon tetrachloride (CCl4)-induced model of liver fibrosis and HCC. Depleting Ash1l in both hepatocytes and HSCs mitigates hepatic fibrosis and HCC development. Multicolor flow cytometry, bulk, and single-cell transcriptomic sequencing reveal that ASH1L creates an immunosuppressive microenvironment. Mechanically, ASH1L-mediated H3K4me3 modification increases the expression of CCL2 and CSF1, which recruites and polarizes M2-like pro-tumorigenic macrophages. The M2-like macrophages further enhance tumor cell proliferation and suppress CD8+ T cell activation. AS-99, a small molecule inhibitor of ASH1L, demonstrates similar anti-fibrosis and tumor-suppressive effects. Of pathophysiological significance, the increased expression levels of mesenchymal ASH1L and M2 marker CD68 are associated with poor prognosis of HCC. The findings reveal ASH1L as a potential small-molecule therapeutic target against fibrosis-related HCC.

Selection of Reference Genes of Flower Development in Ludisia discolor.

Background: RT-qPCR is a powerful strategy for recognizing the most appropriate reference genes, which can successfully minimize experimental mistakes through accurate normalization. Ludisia discolor, recognized for its ornamental value, features little, distinctive blossoms with twisted lips and gynostemium showing chiral asymmetry, together with striking blood-red fallen leaves periodically marked with golden blood vessels. Methods and Results: To ensure the accuracy of qRT-PCR, selecting appropriate reference genes for quantifying target gene expression levels is essential. This study aims to identify stable reference genes during the development of L. discolor. In this study, the entire floral buds, including the lips and gynostemium from different development stages, were taken as materials. Based upon the transcriptome information of L. discolor, nine housekeeping genes, ACT, HIS, EF1-α1, EF1-α2, PP2A, UBQ1, UBQ2, UBQ3, and TUB, were selected in this research study as prospect interior referral genes. The expression of these nine genes were found by RT-qPCR and afterwards comprehensively examined by four software options: geNorm, NormFinder, BestKeeper, and ΔCt. The outcomes of the analysis showed that ACT was the most steady gene, which could be the most effective inner referral gene for the expression evaluation of flower advancement in L. discolor. Conclusions: The results of this study will contribute to the molecular biology research of flower development in L. discolor and closely related species.

Combination of transcriptomics and proteomics for analyzing potential biomarker and molecular mechanism underlying skeletal muscle atrophy.

BACKGROUND: The skeletal muscle atrophy is prevalently occurred in numerous chronic disease complications. Despite its important clinical significance, there are currently no therapeutic drugs, so new biomarkers and molecular mechanisms need to be discovered urgently. METHODS: Transcriptome and proteome sequencing data were collected from normal and skeletal muscle atrophic mice. The differentially expressed genes (DEGs) and proteins (DEPs) were analyzed. Applying PPI analysis to obtain overlapping genes and proteins, which were next subjected to GO and KEGG enrichment analysis. Combined analysis of transcriptomics and proteomics was performed to get key genes that were simultaneously found in GO and KEGG enrichment results. Subsequently, RT-qPCR and immunofluorescence were constructed to verify the expression of screened key genes. RESULTS: By combination of transcriptomics, proteomics and RT-qPCR results, we identified 14 key genes (Cav1, Col3a1, Dnaja1, Postn, Ptges3, Cd44, Clec3b, Igfbp6, Lamc1, Alb, Itga6, Mmp2, Timp2 and Cd9) that were markedly different in atrophic mice. Single-gene GSEA and immunofluorescence suggested Cd9 was probably the biomarker for skeletal muscle atrophy. CONCLUSIONS: Our study hinted that Cd9 was potential biomarker and may interfere with skeletal muscle atrophy through process of aerobic respiration, oxidative phosphorylation, and metabolism of amino acids and fatty acids. SIGNIFICANCE: The present study holds the subsequent significance: Frist, we investigated biomarkers for skeletal muscle atrophy using multi-omics approach. A total of 14 genes were markedly different in skeletal muscle atrophic mice. We finally found Cd9 is a potential biomarker for skeletal muscle atrophy. Our work presents novel biomarkers and potential regulatory mechanisms for the early detection and intervention of muscle atrophy.

A point prevalence survey and monitoring indicator research on the second batch of national key monitoring and rational use drugs.

Background: With the remarkable effect of controlling the increase in drug costs by the first batch of National Key Monitoring and Rational Use Drugs (first NKMRUDs), the National Health Commission of the People's Republic of China releases the second NKMRUDs to further strengthen the reasonable use of drugs. Unfortunately, the second NKMRUDs include some drugs of National Volume-based Procurement and National Essential Medicines, which challenges the management of pharmaceutical affairs on the three kinds of drugs. Objective: The main objective of this study was to investigate the prevalence of the second NKMRUDs and explore their monitoring indicators. Methods: An adapted WHO methodology for point prevalence surveys was conducted for the second NKMRUDs. For the monitoring indicators, we sought to explore whether the defined daily dose (DDD) and days of therapy (DOT) can be suitable for the second NKMRUDs through comparing differences between DDD and DOT with the prescribed daily dose (PDD). Results: Among the 935 included patients, 29.20% of the patients received at least one of the second NKMRUDs. A total of 273 patients were administered with 487 times of the second NKMRUDs. Among them, 162 , 62 , and 49 patients were receiving one, two, and three or more agents, respectively. The most commonly prescribed second NKMRUDs were compound amino acids, budesonide, and ceftazidime. The total DDDs and DOTs of the second NKMRUDs were 3360.68 and 1819.80, respectively, with the PDDs of 1865.26. The deviations (80.17%) of DDDs from PDDs were significantly greater than those (-2.44%) of DOTs. Conclusion: The prevalence of the second NKMRUDs was obtained by using the adapted PPS methodology at a tertiary university hospital. The DOT indicator is found to more accurately reflect actual consumption than the DDD indicator for second NKMRUDs. It is recommended to use the DOT indicator to monitor second NKMRUDs.

Overcoming challenges in the treatment of massive pulmonary embolism in the elderly: Role of extracorporeal membrane oxygenation.

Population aging represents a paramount medical and socio-demographic challenge globally. As living standards improve and medical technology advances, the elderly population experiences an increasing number of detected and treated pulmonary embolisms (PE). However, rescuing massive pulmonary embolism (MPE) in the elderly remains a difficult task. Conventional thrombolysis or surgical thrombolysis might be contraindicated, leading extracorporeal membrane oxygenation (ECMO) to emerge as a treatment modality for MPE in the elderly. Nevertheless, data are scarce regarding the use of ECMO as a standalone treatment for MPE. In this paper, we present the case of an 85-year-old patient with a prior cerebral infarction, who received a diagnosis of MPE in the main trunks of bilateral pulmonary arteries. Considering the patient's systemic condition, the Pulmonary Embolism Response Team (PERT) opted to administer VA-ECMO as the sole treatment approach. Remarkably, the patient achieved a favorable recovery outcome. Our case report contributes new evidence to the treatment of elderly individuals with MPE and highlights the potential of ECMO-only regimens for addressing such cases.

Human amnion mesenchymal stem cells promote endometrial repair via paracrine, preferentially than transdifferentiation.

BACKGROUND: Intrauterine adhesion (IUA) is one of the most severe causes of infertility in women of childbearing age with injured endometrium secondary to uterine performance. Stem cell therapy is effective in treating damaged endometrium. The current reports mainly focus on the therapeutic effects of stem cells through paracrine or transdifferentiation, respectively. This study investigates whether paracrine or transdifferentiation occurs preferentially in treating IUA. METHODS: Human amniotic mesenchymal stem cells (hAMSCs) and transformed human endometrial stromal cells (THESCs) induced by transforming growth factor beta (TGF-ß1) were co-cultured in vitro. The mRNA and protein expression levels of Fibronectin (FN), Collagen I, Cytokeratin19 (CK19), E-cadherin (E-cad) and Vimentin were detected by Quantitative real-time polymerase chain reaction (qPCR), Western blotting (WB) and Immunohistochemical staining (IHC). The Sprague-Dawley (SD) rats were used to establish the IUA model. hAMSCs, hAMSCs-conditional medium (hAMSCs-CM), and GFP-labeled hAMSCs were injected into intrauterine, respectively. The fibrotic area of the endometrium was evaluated by Masson staining. The number of endometrium glands was detected by hematoxylin and eosin (H&E). GFP-labeled hAMSCs were traced by immunofluorescence (IF). hAMSCs, combined with PPCNg (hAMSCs/PPCNg), were injected into the vagina, which was compared with intrauterine injection. RESULTS: qPCR and WB revealed that FN and Collagen I levels in IUA-THESCs decreased significantly after co-culturing with hAMSCs. Moreover, CK19, E-cad, and Vimentin expressions in hAMSCs showed no significant difference after co-culture for 2 days. 6 days after co-culture, CK19, E-cad and Vimentin expressions in hAMSCs were significantly changed. Histological assays showed increased endometrial glands and a remarkable decrease in the fibrotic area in the hAMSCs and hAMSCs-CM groups. However, these changes were not statistically different between the two groups. In vivo, fluorescence imaging revealed that GFP-hAMSCs were localized in the endometrial stroma and gradually underwent apoptosis. The effect of hAMSCs by vaginal injection was comparable to that by intrauterine injection assessed by H&E staining, MASSON staining and IHC. CONCLUSIONS: Our data demonstrated that hAMSCs promoted endometrial repair via paracrine, preferentially than transdifferentiation.

IUA is the crucial cause of infertility in women of childbearing age, and no satisfactory treatment measures have been found in the clinic. hAMSCs can effectively treat intrauterine adhesions through paracrine and transdifferentiation mechanisms. This study confirmed in vitro and in vivo that amniotic mesenchymal stem cells preferentially inhibited endometrial fibrosis and promoted epithelial repair through paracrine, thus effectively treating intrauterine adhesions. The level of fibrosis marker proteins in IUA-THESCs decreased significantly after co-culturing with hAMSCs for 2 days in vitro. However, the level of epithelial marker proteins in hAMSCs increased significantly, requiring at least 6 days of co-culture. hAMSCs-CM had the same efficacy as hAMSCs in inhibiting fibrosis and promoting endometrial repair in IUA rats, supporting the idea that hAMSCs promoted endometrial remodeling through paracrine in vivo. In addition, GFP-labeled hAMSCs continuously colonized the endometrial stroma instead of the epithelium and gradually underwent apoptosis. These findings prove that hAMSCs ameliorate endometrial fibrosis of IUA via paracrine, preferentially than transdifferentiation, providing the latest insights into the precision treatment of IUA with hAMSCs and a theoretical basis for promoting the "cell-free therapy" of MSCs.

Polypeptide-PNP2 in Corn Cervi Pantotrichum Ameliorates Cognitive Impairment in Alzheimer's Disease Mice by Inhibiting Microglial Cell Activation.

We isolated a polypeptide PNP2 from Corn Cervi Pantotrichum and investigated its effect and mechanism on cognitive impairment in Alzheimer's disease (AD) mice. Morris water maze was used to assess the degree of cognitive impairment in mice. Histopathological changes were detected by H&E staining; the expressions of inflammatory cytokines were assayed by ELISA. Western blotting was employed to detect the protein expressions. PNP2 could improve cognitive impairment, central inflammatory response, and NLRP3 signaling in AD mice. In vitro experiments revealed that PNP2 could suppress the inflammatory response of microglial cells and reduce the activation of NLRP3 in microglial cells, while MCC950 could antagonize the effects of PNP2. Polypeptide component PNP2 in Corn Cervi Pantotrichum can ameliorate central nervous inflammation and cognitive impairment in AD mice by suppressing NLRP3 signaling.

Depth versus surface: A critical review of subdural and depth electrodes in intracranial electroencephalographic studies.

Intracranial electroencephalographic (IEEG) recording, using subdural electrodes (SDEs) and stereoelectroencephalography (SEEG), plays a pivotal role in localizing the epileptogenic zone (EZ). SDEs, employed for superficial cortical seizure foci localization, provide information on two-dimensional seizure onset and propagation. In contrast, SEEG, with its three-dimensional sampling, allows exploration of deep brain structures, sulcal folds, and bihemispheric networks. SEEG offers the advantages of fewer complications, better tolerability, and coverage of sulci. Although both modalities allow electrical stimulation, SDE mapping can tessellate cortical gyri, providing the opportunity for a tailored resection. With SEEG, both superficial gyri and deep sulci can be stimulated, and there is a lower risk of afterdischarges and stimulation-induced seizures. Most systematic reviews and meta-analyses have addressed the comparative effectiveness of SDEs and SEEG in localizing the EZ and achieving seizure freedom, although discrepancies persist in the literature. The combination of SDEs and SEEG could potentially overcome the limitations inherent to each technique individually, better delineating seizure foci. This review describes the strengths and limitations of SDE and SEEG recordings, highlighting their unique indications in seizure localization, as evidenced by recent publications. Addressing controversies in the perceived usefulness of the two techniques offers insights that can aid in selecting the most suitable IEEG in clinical practice.

Global, regional, and national burden of thalassemia, 1990-2021: a systematic analysis for the global burden of disease study 2021.

Background: Anemia is a significant contributor to the global disease burden, of which thalassemia is the most common hereditary anaemic disease. Previous estimates were based on data that were geographically limited and lacked comprehensive global analysis. This study provides the prevalence, incidence, mortality and disability-adjusted life years (DALYs) of thalassemia in 204 countries and regions of thalassemia between 1990 and 2021, focusing on the age structure and time trends of the disease burden. To provide effective information for health policy, allocation of medical resources and optimization of patient management programs. Methods: Using the standardised Global Burden of Disease (GBD) methodologies, we aimed to derive a more precise representation of the health burden posed by thalassemia by considering four distinct types of epidemiological data, namely the incidence at birth, prevalence, mortality and DALYs. The presented data were meticulously estimated and displayed both as numerical counts and as age-standardised rates per 100,000 persons of the population, accompanied by uncertainty interval (UI) to highlight potential statistical variability. The temporal trends spanning the years 1990-2021 were subjected to a rigorous examination utilizing Joinpoint regression analysis. This methodological approach facilitated the computation of the annual percentage change (APC) and the average annual percentage change (AAPC), along with their corresponding 95% confidence intervals (CIs). Findings: Globally, the age-standardized prevalence rates (ASPR), age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and age-standardized DALYs rates for thalassemia in 2021 were 18.28 per 100,000 persons (95% UI 15.29-22.02), 1.93 per 100,000 persons (95% UI 1.51-2.49), 0.15 per 100,000 persons(95% UI 0.11-0.20), and 11.65 per 100,000 persons (95% UI 8.24-14.94), respectively. Compared to 1990, these rates have decreased by 0.18 (95% UI -0.22 to -0.14), 0.25 (95% UI -0.30 to -0.19), 0.48 (95% UI -0.60 to -0.28), and 0.49 (95% UI -0.62 to -0.29) respectively. In 2021, the ASIR of thalassemia was highest in East Asia at 7.35 per 100,000 persons (95% UI 5.37-10.04), and ASMR was highest in Southeast Asia at 0.37 per 100,000 persons (95% UI 0.29-0.45).Gender comparisons showed negligible differences in disease burden, with the highest prevalence noted in children under five, decreasing with age. The global ASPR and ASMR declined from 1990 to 2021 overall, though an increasing trend in prevalence was found among the elderly. Joinpoint analysis revealed that the global ASPR increased between 2018 and 2021 (APC = 9.2%, 95% CI: 4.8%-13.8%, P < 0.001), ASIR decreased (APC = -7.68%, 95% CI: -10.88% to -4.36%, P < 0.001), and there was a significant rise in ASMR from 2019 to 2021 (APC = 4.8%, 95% CI: 0.1%-9.6%, P < 0.05). Trends in ASPR and ASMR varied across regions, with notable changes in South Asia. Interpretation: The global burden of thalassemia, reflected in its prevalence, incidence, mortality, and DALYs, exhibits significant disparities. Geographic and demographic shifts in disease distribution have been observed from 1990 to 2021, with an overall decrease in burden, yet an increase in cases among the elderly population. Analysis of epidemiological trends over time highlights the influence of health policies and significant public health interventions on thalassemia outcomes. There data are crucial for healthcare professionals, policymakers, and researchers to refine and enhance management strategies, aiming to further mitigate thalassemia's global impact. Funding: National Natural Science Foundation of China; Guizhou Province Science and Technology Project; Guizhou Province Science and Technology Foundation of Health Commission.

Genome-Wide Identification and Expression Pattern Analysis of TIFY Family Genes Reveal Their Potential Roles in Phalaenopsis aphrodite Flower Opening.

The TIFY gene family (formerly known as the zinc finger proteins expressed in inflorescence meristem (ZIM) family) not only functions in plant defense responses but also are widely involved in regulating plant growth and development. However, the identification and functional analysis of TIFY proteins remain unexplored in Orchidaceae. Here, we identified 19 putative TIFY genes in the Phalaenopsis aphrodite genome. The phylogenetic tree classified them into four subfamilies: 14 members from JAZ, 3 members from ZML, and 1 each from PPD and TIFY. Sequence analysis revealed that all Phalaenopsis TIFY proteins contained a TIFY domain. Exon-intron analysis showed that the intron number and length of Phalaenopsis TIFY genes varied, whereas the same subfamily and subgroup genes had similar exon or intron numbers and distributions. The most abundant cis-elements in the promoter regions of the 19 TIFY genes were associated with light responsiveness, followed by MeJA and ABA, indicating their potential regulation by light and phytohormones. The 13 candidate TIFY genes screened from the transcriptome data exhibited two types of expression trends, suggesting their different roles in cell proliferation and cell expansion of floral organ growth during Phalaenopsis flower opening. Overall, this study serves as a background for investigating the underlying roles of TIFY genes in floral organ growth in Phalaenopsis.

Identifying the association between depression and constipation: An observational study and Mendelian randomization analysis.

BACKGROUND: Both depression and constipation are universal disorders that seriously affect quality of life. But the phenotypic relationship and causality between depression and constipation are still unclear. METHODS: We first assessed phenotypic relationships by logistic regression analysis using large-scale data extracted from the National Health and Nutrition Examination Survey (N = 11,585). We then evaluated causality by bidirectional two-sample mendelian randomization (MR) analysis using Genome-wide association study (GWAS) data (depression: N = 807,553; constipation: N = 377,277). To investigate whether depression severity affects the causal relationship between depression and constipation, we conducted a further MR study on GWAS data of major depression (N = 480,359). RESULTS: About 11.31 % of the participants in the constipation group suffered from depression, which was significantly higher than the normal bowel group (6.09 %). The observational study showed a positive correlation between depression and constipation (OR = 1.968, 95%CI = 1.530-2.532). Besides, the risk of constipation was higher in participants with severe depression (OR = 2.294, 95%CI = 1.538-3.422) than in participants with mild depression (OR = 1.549, 95%CI = 1.242-1.932). Bidirectional MR analysis revealed an obviously causal effect of depression on constipation, but no causal effect of constipation on depression. In addition, the MR analysis also revealed a causal relationship between major depression and constipation. LIMITATION: The exact mechanism by which depression affects constipation is still unclear. CONCLUSION: This study reveals a positive correlation between depression and constipation and the causal effect of depression on constipation. Clinicians should keep the risk of constipation in mind when treating patients with depression.

[Mechanism of astragaloside â £ combined with Panax notoginseng saponins in regulating angiogenesis to treat cerebral ischemia based on network pharmacology and experimental verification].

Network pharmacology and animal and cell experiments were employed to explore the mechanism of astragaloside Ⅳ(AST Ⅳ) combined with Panax notoginseng saponins(PNS) in regulating angiogenesis to treat cerebral ischemia. The method of network pharmacology was used to predict the possible mechanisms of AST Ⅳ and PNS in treating cerebral ischemia by mediating angiogenesis. In vivo experiment: SD rats were randomized into sham, model, and AST Ⅳ(10 mg·kg~(-1)) + PNS(25 mg·kg~(-1)) groups, and the model of cerebral ischemia was established with middle cerebral artery occlusion(MCAO) method. AST Ⅳ and PNS were administered by gavage twice a day. the Longa method was employed to measure the neurological deficits. The brain tissue was stained with hematoxylin-eosin(HE) to reveal the pathological damage. Immunohistochemical assay was employed to measure the expression of von Willebrand factor(vWF), and immunofluorescence assay to measure the expression of vascular endothelial growth factor A(VEGFA). Western blot was employed to determine the protein levels of vascular endothelial growth factor receptor 2(VEGFR2), VEGFA, phosphorylated phosphatidylinositol 3-kinase(p-PI3K), and phosphorylated protein kinase B(p-AKT) in the brain tissue. In vitro experiment: the primary generation of rat brain microvascular endothelial cells(rBEMCs) was cultured and identified. The third-generation rBMECs were assigned into control, model, AST Ⅳ(50 µmol·L~(-1)) + PNS(30 µmol·L~(-1)), LY294002(PI3K/AKT signaling pathway inhibitor), 740Y-P(PI3K/AKT signaling pathway agonist), AST Ⅳ + PNS + LY294002, and AST Ⅳ + PNS + 740Y-P groups. Oxygen glucose deprivation/re-oxygenation(OGD/R) was employed to establish the cell model of cerebral ischemia-reperfusion injury. The cell counting kit-8(CCK-8) and scratch assay were employed to examine the survival and migration of rBEMCs, respectively. Matrigel was used to evaluate the tube formation from rBEMCs. The Transwell assay was employed to examine endothelial cell permeability. Western blot was employed to determine the expression of VEGFR2, VEGFA, p-PI3K, and p-AKT in rBEMCs. The results of network pharmacology analysis showed that AST Ⅳ and PNS regulated 21 targets including VEGFA and AKT1 of angiogenesis in cerebral infarction. Most of these 21 targets were involved in the PI3K/AKT signaling pathway. The in vivo experiments showed that compared with the model group, AST Ⅳ + PNS reduced the neurological deficit score(P<0.05) and the cell damage rate in the brain tissue(P<0.05), promoted the expression of vWF and VEGFA(P<0.01) and angiogenesis, and up-regulated the expression of proteins in the PI3K/AKT pathway(P<0.05, P<0.01). The in vitro experiments showed that compared with the model group, the AST Ⅳ + PNS, 740Y-P, AST Ⅳ + PNS + LY294002, and AST Ⅳ + PNS + 740Y-P improved the survival of rBEMCs after OGD/R, enhanced the migration of rBEMCs, increased the tubes formed by rBEMCs, up-regulated the expression of proteins in the PI3K/AKT pathway, and reduced endothelial cell permeability(P<0.05, P<0.01). Compared with the LY294002 group, the AST Ⅳ + PNS + LY294002 group showed increased survival rate, migration rate, and number of tubes, up-regulated expression of proteins in the PI3K/AKT pathway, and decreased endothelial cell permeability(P<0.05,P<0.01). Compared with the AST Ⅳ + PNS and 740Y-P groups, the AST Ⅳ + PNS + 740Y-P group presented increased survival rate, migration rate, and number of tubes and up-regulated expression of proteins in the PI3K/AKT pathway, and reduced endothelial cell permeability(P<0.01). This study indicates that AST Ⅳ and PNS can promote angiogenesis after cerebral ischemia by activating the PI3K/AKT signaling pathway.