Influence of beeswax-based fish oil oleogels on the mechanism of water and oil retention in Pacific white shrimp (Litopenaeus vannamei) meat emulsion gels: Filling, emulsification and phase transition.

Oleogels have been used in the gelled surimi products to replace animal fats due to its structure characteristics. The effect of structure characteristics in fish oil oleogels on the mechanism of oil/water retention was investigated in meat emulsions. Beeswax assembly improved the oil and water retention. The unsaturation degree of fatty acids lowered the mobility of bound water, immobilized water as well as bound fat in the fish oil oleogel, but enhanced the mobility of free water and protons of unsaturated fatty acids. Beeswax addition and oil phase characteristics could enhance ß-sheets, disulfide bonds and hydrophobic force to improve the viscoelasticity, gel strength and oil/water retention. Beeswax assembly facilitated the tight micro-sol network and filling effect, and high unsaturation degree promoted the emulsification effect, thus reducing phase transition temperature and juice loss. The study could lay the foundation for development of gelled shrimp meat products with EPA and DHA.

Phosphonium Iodide Featuring Blue Thermally Activated Delayed Fluorescence for Highly Efficient X-ray Scintillator.

Organic scintillators are praised for their abundant element reserves, facile preparation procedures, and rich structures. Herein, a new family of highly efficient organic phosphonium halide salts with thermally activated delayed fluorescence (TADF) are designed by innovatively adopting quaternary phosphonium as the electron acceptor, while dimethylamine group and halide anions (I-) serve as the electron donor. The prepared butyl(2-[2-(dimethylamino)phenyl]phenyl)diphenylphosphonium iodide (C4-I) exhibits bright blue emission and an ultra-high photoluminescence quantum yield (PLQY) of 100%. Efficient charge transfer is realized through the unique n-π and anion-π stacking in solid-state C4-I. Photophysical studies of C4-I suggest that the incorporation of I accounts for high intersystem crossing rate (kISC) and reverse intersystem crossing rate (kRISC), suppressing the intrinsic prompt fluorescence and enabling near-pure TADF emission at room temperature. Benefitting from the large Stokes shift, high PLQY, efficient exciton utilization, and remarkable X-ray attenuation ability endowed by I, C4-I delivers an outstanding light yield of 80721 photons/MeV and a low limit of detection (LoD) of 22.79 nGy·s-1. This work would provide a rational design concept and open up an appealing road for developing efficient organic scintillators with tunable emission, strong X-ray attenuation ability, and excellent scintillator performance.

Suppression of MyD88 disturbs gut microbiota and activates the NLR pathway and hence fails to ameliorate DSS-induced colitis.

Background: Myeloid differentiation factor 88 (MyD88) is the core adaptor for Toll-like receptors defending against microbial invasion and initiating a downstream immune response during microbiota-host interaction. However, the role of MyD88 in the pathogenesis of inflammatory bowel disease is controversial. This study aims to investigate the impact of MyD88 on intestinal inflammation and the underlying mechanism. Methods: MyD88 knockout (MyD88-/-) mice and the MyD88 inhibitor (TJ-M2010-5) were used to investigate the impact of MyD88 on acute dextran sodium sulfate (DSS)-induced colitis. Disease activity index, colon length, histological score, and inflammatory cytokines were examined to evaluate the severity of colitis. RNA transcriptome analysis and 16S rDNA sequencing were used to detect the potential mechanism. Results: In an acute DSS-colitis model, the severity of colitis was not alleviated in MyD88-/- mice and TJ-M2010-5-treated mice, despite significantly lower levels of NF-κB activation being exhibited compared to control mice. Meanwhile, 16S rDNA sequencing and RNA transcriptome analysis revealed a higher abundance of intestinal Proteobacteria and an up-regulation of the nucleotide oligomerization domain-like receptors (NLRs) signaling pathway in colitis mice following MyD88 suppression. Further blockade of the NLRs signaling pathway or elimination of gut microbiota with broad-spectrum antibiotics in DSS-induced colitis mice treated with TJ-M2010-5 ameliorated the disease severity, which was not improved solely by MyD88 inhibition. After treatment with broad-spectrum antibiotics, downregulation of the NLR signaling pathway was observed. Conclusion: Our study suggests that the suppression of MyD88 might be associated with unfavorable changes in the composition of gut microbiota, leading to NLR-mediated immune activation and intestinal inflammation.

Based on proteomics probing into the deterioration mechanism of pork batter gel caused by different cooking temperatures.

The purpose of this experiment was to explore the influence of different cooking temperatures on the deterioration characteristics of pork batter gel by using proteomics, gel electrophoresis, size and chemical bond of aggregates. The results showed that the protein molecules of the pork batter gel was degraded during heating cooking and the protein aggregates were composed of many degraded protein fragments; compared with the control group 75 °C (0 min), the significant degradation of cytoskeleton showed at 110 °C (30 min) and 121 °C (30 min) and the significant degradation of myosin complexonly appeared at 121 °C (30 min). As the heating temperature points increased, compared with the control group 75 °C (0 min), the different temperatures could promote the separation of metal ions with proteins especially at 110 °C (30 min) and 121 °C (30 min), which could ultimately influence quality of pork batter gel by the size of particle. As the increase of heating temperature points, the recombination of aggregates composed of different proteins was not conducive to the retention of capillary water, which reduced the texture of pork batter gel. This research provided theoretical support for improving the process property of the meat products.

Diagnostic and Management Value of Multi-Slice Computed Tomography in Esophageal Jujube Pit Impaction.

Objective: The diagnostic value of multi-slice computed tomography (MSCT) in esophageal jujube pit impaction was explored in this study. Methods: A retrospective analysis was performed on MSCT data obtained from a cohort of 40 patients experiencing esophageal jujube pit impaction. The study period encompassed the interval from December 2018 to November 2019. The analysis involved examining the age distribution of the patients, the location of the jujube pit impaction, its connection to the esophagus, associated complications, and the methods used for treatment. All imaging results were compared with the outcomes of surgical or endoscopic interventions. Results: (1) Out of 40 patients, 30 individuals were 58 years old or above, constituting 75% of the study sample. (2) In 80% of the instances (32 cases), the jujube pit was located in the initial segment of the esophagus, exhibiting a spindle shape with varying levels of central low density. (3) We examined the correlation between the angle of the impacted jujube pit and the esophageal longitudinal axis, categorizing 2 cases as longitudinal impaction, 16 as oblique impaction, and 22 as transverse impaction. Among the 40 cases, 28 displayed only slight thickening of the esophageal wall at the impaction site, while 9 cases exhibited heightened periesophageal fat density, and 3 showed small periesophageal air bubbles. (4) Endoscopic evaluation identified damage to the esophageal mucosa in 35 instances and the formation of esophageal perforation in 5 cases. Among patients with perforation, one or both ends of the jujube pit had penetrated the esophageal wall, accompanied by different levels of surrounding inflammatory encapsulation. Conclusion: MSCT is crucial for pinpointing jujube pit impaction and its relation to the esophageal wall and nearby structures, aiding in preoperative and postoperative complications. It is highly feasible for endoscopic cases but limited in complex ones needing thoracoscopy or open-heart surgery.

[Characteristics and clinical value of intestinal metabolites in children aged 4-6 years with obstructive sleep apnea-hypopnea syndrome]. / 4~6å²é˜»å¡žæ€§ç¡çœ å‘¼å¸æš‚åœä½Žé€šæ°”ç»¼åˆå¾æ‚£å„¿è‚ é“ä»£è°¢äº§ç‰©ç‰¹å¾åŠä¸´åºŠä»·å€¼åˆ†æž.

OBJECTIVES: To study the characteristics and clinical value of intestinal metabolites in children aged 4-6 years with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: A total of 31 children aged 4-6 years with OSAHS were prospectively enrolled as the test group, and 24 healthy children aged 4-6 years were included as the control group. Relevant clinical indicators were recorded. Fecal samples were collected, and non-targeted metabolomics analysis using liquid chromatography-mass spectrometry was performed to detect all metabolites. RESULTS: A total of 206 metabolites were detected, mainly amino acids and their derivatives. There was a significant difference in the overall composition of intestinal metabolites between the test and control groups (P<0.05). Eighteen different metabolites were selected, among which six (N-acetylmethionine, L-methionine, L-lysine, DL-phenylalanine, L-tyrosine, and L-isoleucine) had receiver operating characteristic curve areas greater than 0.7 for diagnosing OSAHS. Among them, N-acetylmethionine had the largest area under the curve, which was 0.807, with a sensitivity of 70.83% and a specificity of 80.65%. Correlation analysis between different metabolites and clinical indicators showed that there were positive correlations between the degree of tonsil enlargement and enterolactone, between uric acid and phenylacetaldehyde, between blood glucose and acetylmethionine, and between cholesterol and 9-bromodiphenyl and procaine (P<0.05). There were negative correlations between the degree of tonsil enlargement and N-methyltyramine, aspartate aminotransferase and indolepropionic acid and L-isoleucine, between alanine aminotransferase and DL-phenylalanine, between indolepropionic acid and L-isoleucine, between uric acid and hydroxyquinoline, and between urea nitrogen and N,N-dicyclohexylurea (P<0.05). The metabolic functional pathways affected by differential metabolites mainly included riboflavin metabolism, arginine and proline metabolism, pantothenic acid and coenzyme A biosynthesis, cysteine and methionine metabolism, lysine degradation and glutathione metabolism. CONCLUSIONS: Intestinal metabolites and metabolic functions are altered in children aged 4-6 years with OSAHS, primarily involving amino acid metabolism disorders. The screened differential intestinal metabolites have potential screening and diagnostic value as biomarkers for OSAHS.

[Estimation of soil moisture and organic matter content in saline alkali farmland by using CARS algorithm combined with covariates]. / 利用CARS算法联合协变量估算盐碱农田土壤水分和有机质含量.

Rapid acquisition of the data of soil moisture content (SMC) and soil organic matter (SOM) content is crucial for the improvement and utilization of saline alkali farmland soil. Based on field measurements of hyperspectral reflectance and soil properties of farmland soil in the Hetao Plain, we used a competitive adaptive reweighted sampling algorithm (CARS) to screen sensitive bands after transforming the original spectral reflectance (Ref) into a standard normal variable (SNV). Strategies Ⅰ, Ⅱ, and Ⅲ were used to model the input variables of Ref, Ref SNV, Ref-SNV+ soil covariate (SC), and digital elevation model (DEM). We constructed SMC and SOM estimation models based on random forest (RF) and light gradient boosting machine (LightGBM), and then verified and compared the accuracy of the models. The results showed that after CARS screening, the sensitive bands of SMC and SOM were compressed to below 3.3% of the entire band, which effectively optimized band selection and reduced redundant spectral information. Compared with the LightGBM model, the RF model had higher accuracy in SMC and SOM estimation, and the input variable strategy Ⅲ was better than Ⅱ and Ⅰ. The introduction of auxiliary variables effectively improved the estimation ability of the model. Based on comprehensive analysis, the coefficient of determination (Rp2), root mean square error (RMSE), and relative analysis error (RPD) of the SMC estimation model validation based on strategy Ⅲ-RF were 0.63, 3.16, and 2.01, respectively. The SOM estimation models based on strategy Ⅲ-RF had Rp2, RMSE, and RPD of 0.93, 1.15, and 3.52, respectively. The strategy Ⅲ-RF model was an effective method for estimating SMC and SOM. Our results could provide a new method for the rapid estimation of soil moisture and organic matter content in saline alkali farmland.

m6A demethylation of FOSL1 mRNA protects hepatoma cells against necrosis under glucose deprivation.

Stress-adaptive mechanisms enabling cancer cells to survive under glucose deprivation remain elusive. N6-methyladenosine (m6A) modification plays important roles in determining cancer cell fate and cellular stress response to nutrient deficiency. However, whether m6A modification functions in the regulation of cancer cell survival under glucose deprivation is unknown. Here, we found that glucose deprivation reduced m6A modification levels. Increasing m6A modification resulted in increased hepatoma cell necrosis under glucose deprivation, whereas decreasing m6A modification had an opposite effect. Integrated m6A-seq and RNA-seq revealed potential targets of m6A modification under glucose deprivation, including the transcription factor FOSL1; further, glucose deprivation upregulated FOSL1 by inhibiting FOSL1 mRNA decay in an m6A-YTHDF2-dependent manner through reducing m6A modification in its exon1 and 5'-UTR regions. Functionally, FOSL1 protected hepatoma cells against glucose deprivation-induced necrosis in vitro and in vivo. Mechanistically, FOSL1 transcriptionally repressed ATF3 by binding to its promoter. Meanwhile, ATF3 and MAFF interacted via their leucine zipper domains to form a heterodimer, which competed with NRF2 for binding to antioxidant response elements in the promoters of NRF2 target genes, thereby inhibiting their transcription. Consequently, FOSL1 reduced the formation of the ATF3-MAFF heterodimer, thereby enhancing NRF2 transcriptional activity and the antioxidant capacity of glucose-deprived-hepatoma cells. Thus, FOSL1 alleviated the necrosis-inducing effect of glucose deprivation-induced reactive oxygen species accumulation. Collectively, our study uncovers the protective role of m6A-FOSL1-ATF3 axis in hepatoma cell necrosis under glucose deprivation, and may provide new targets for cancer therapy.

The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio with type 2 diabetes mellitus: recent findings from NHANES 2007-2018.

OBJECTIVE: This study aims to assess the relationship between NHHR (non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio) and Type 2 diabetes mellitus (T2DM) in US adults, using National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2018. METHODS: This study explored the connection between NHHR and T2DM by analyzing a sample reflecting the adult population of the United States (n = 10,420; NHANES 2007-2018). NHHR was characterized as the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol. T2DM was defined based on clinical guidelines. This research used multivariable logistic models to examine the connection between NHHR and T2DM. Additionally, it included subgroup and interaction analyses to assess variations among different groups. Generalized additive models, smooth curve fitting, and threshold effect analysis were also employed to analyze the data further. RESULTS: The study included 10,420 subjects, with 2160 diagnosed with T2DM and 8260 without. The weighted multivariate logistic regression model indicated an 8% higher probability of T2DM for each unit increase in NHHR (OR: 1.08, 95% CI: 1.01-1.15) after accounting for all covariates. Subgroup analysis outcomes were uniform across various categories, demonstrating a significant positive relationship between NHHR and T2DM. Interaction tests showed that the positive link between NHHR and T2DM remained consistent regardless of age, body mass index, smoking status, moderate recreational activities, hypertension, or stroke history, with all interaction P-values exceeding 0.05. However, participants' sex appeared to affect the magnitude of the connection between NHHR and T2DM (interaction P-value < 0.05). Also, a nonlinear association between NHHR and T2DM was discovered, featuring an inflection point at 1.50. CONCLUSIONS: Our study suggests that an increase in NHHR may be correlated with a heightened likelihood of developing T2DM. Consequently, NHHR could potentially serve as a marker for estimating the probability of T2DM development.

The role of small RNAs in resistant melon cultivar against Phelipanche aegyptiaca parasitization.

Bidirectional trans-kingdom RNA silencing, a pivotal factor in plant-pathogen interactions, remains less explored in plant host-parasite dynamics. Here, using small RNA sequencing in melon root systems, we investigated microRNA (miRNA) expression variation in resistant and susceptible cultivars pre-and post-infection by the parasitic plant, broomrape. This approach revealed 979 known miRNAs and 110 novel miRNAs across 110 families. When comparing susceptible (F0) and resistant (R0) melon lines with broomrape infection (F25 and R25), 39 significantly differentially expressed miRNAs were observed in F25 vs. F0, 35 in R25 vs. R0, and 5 in R25 vs. F25. Notably, two miRNAs consistently exhibited differential expression across all comparisons, targeting genes linked to plant disease resistance. This suggests their pivotal role in melon's defense against broomrape. The target genes of these miRNAs were confirmed via degradome sequencing and validated by qRT-PCR, ensuring reliable sequencing outcomes. GO and KEGG analyses shed light on the molecular functions and pathways of these differential miRNAs. Furthermore, our study unveiled four trans-kingdom miRNAs, forming a foundation for exploring melon's resistance to broomrape.

Photoinduced Palladium-Catalyzed Radical Heck-Type Coupling of Cyclobutanone Oxime Esters with Vinyl Arenes.

A palladium-catalyzed radical Heck-type coupling reaction of cyclobutanone oxime esters with olefins under visible-light irradiation has been developed. The cyanoalkyl/Pd(I) hybrid species generated by selected ring-opening C-C bond cleavage of imino/Pd(I) species reacted smoothly with vinyl arenes, delivering the cyanoalkylation olefins under mild conditions. This elegant strategy has a broad scope and functional group tolerance. Subsequently, late-stage functionalization of bioactive molecules and synthetic transformations of the product further confirm the practicality.

Correlation between the dynamic changes of γδT cells, Th17 cells, CD4+CD25+ regulatory T cells in peripheral blood and pharmacological interventions against bleomycin-induced pulmonary fibrosis progression in mice.

The involvement of γδT cells, Th17 cells, and CD4+CD25+ regulatory T cells (Tregs) is crucial in the progression of pulmonary fibrosis (PF), particularly in maintaining immune tolerance and homeostasis. However, the dynamics of these cells in relation to PF progression, especially under pharmacological interventions, remains poorly understood. This study aims to unravel the interplay between the dynamic changes of these cells and the effect of pharmacological agents in a mouse model of PF induced by intratracheal instillation of bleomycin. We analyzed changes in lung histology, lung index, hydroxyproline levels, and the proportions of γδT cells, Th17 cells, and Tregs on the 3rd, 14th, and 28th days following treatment with Neferine, Isoliensinine, Pirfenidone, and Prednisolone. Our results demonstrate that these drugs can partially or dynamically reverse weight loss, decrease lung index and hydroxyproline levels, and ameliorate lung histopathological damage. Additionally, they significantly modulated the abnormal changes in γδT, Th17, and Treg cell proportions. Notably, on day 3, the proportion of γδT cells increased in the Neferine and Prednisolone groups but decreased in the Isoliensinine and Pirfenidone groups, while the proportion of Th17 cells decreased across all treated groups. On day 14, the Neferine group showed an increase in all three cell types, whereas the Pirfenidone group exhibited a decrease. In the Isoliensinine group, γδT and Th17 cells increased, and in the Prednisolone group, only Tregs increased. By day 28, an increase in Th17 cell proportion was observed in all treatment groups, with a decrease in γδT cells noted in the Neferine group. These shifts in cell proportions are consistent with the pathogenesis changes induced by these anti-PF drugs, suggesting a correlation between cellular dynamics and pharmacological interventions in PF progression. Our findings imply potential strategies for assessing the efficacy and timing of anti-PF treatments based on these cellular changes.

Oridonin attenuates liver ischemia-reperfusion injury by suppressing PKM2/NLRP3-mediated macrophage pyroptosis.

BACKGROUND: The NOD-like receptor protein 3 (NLRP3) mediated pyroptosis of macrophages is closely associated with liver ischemia reperfusion injury (IRI). As a covalent inhibitor of NLRP3, Oridonin (Ori), has strong anti-inflammasome effect, but its effect and mechanisms for liver IRI are still unknown. METHODS: Mice and liver macrophages were treated with Ori, respectively. Co-IP and LC-MS/MS analysis of the interaction between PKM2 and NLRP3 in macrophages. Liver damage was detected using H&E staining. Pyroptosis was detected by WB, TEM, and ELISA. RESULTS: Ori ameliorated liver macrophage pyroptosis and liver IRI. Mechanistically, Ori inhibited the interaction between pyruvate kinase M2 isoform (PKM2) and NLRP3 in hypoxia/reoxygenation（H/R）-induced macrophages, while the inhibition of PKM2/NLRP3 reduced liver macrophage pyroptosis and liver IRI. CONCLUSION: Ori exerted protective effects on liver IRI via suppressing PKM2/NLRP3-mediated liver macrophage pyroptosis, which might become a potential therapeutic target in the clinic.

Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

BACKGROUND: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention. METHODS: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P<0.05 was considered statistically significant. RESULTS: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P=0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P=0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P=0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours. CONCLUSIONS: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723.

Shared genetic basis and causality between schizophrenia and inflammatory bowel disease: evidence from a comprehensive genetic analysis.

BACKGROUND: The comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared genetic components and the causality relationship between them remains unclear. METHODS: By leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), and Crohn's disease (CD), we conducted a comprehensive genetic pleiotropic analysis to uncover shared loci, genes, or biological processes between SCZ and each of IBD, UC, and CD, independently. Univariable and multivariable Mendelian randomization (MR) analyses were applied to assess the causality across these two disorders. RESULTS: SCZ genetically correlated with IBD (rg = 0.14, p = 3.65 × 10−9), UC (rg = 0.15, p = 4.88 × 10−8), and CD (rg = 0.12, p = 2.27 × 10−6), all surpassed the Bonferroni correction. Cross-trait meta-analysis identified 64, 52, and 66 significantly independent loci associated with SCZ and IBD, UC, and CD, respectively. Follow-up gene-based analysis found 11 novel pleiotropic genes (KAT5, RABEP1, ELP5, CSNK1G1, etc) in all joint phenotypes. Co-expression and pathway enrichment analysis illustrated those novel genes were mainly involved in core immune-related signal transduction and cerebral disorder-related pathways. In univariable MR, genetic predisposition to SCZ was associated with an increased risk of IBD (OR 1.11, 95% CI 1.07­1.15, p = 1.85 × 10−6). Multivariable MR indicated a causal effect of genetic liability to SCZ on IBD risk independent of Actinobacteria (OR 1.11, 95% CI 1.06­1.16, p = 1.34 × 10−6) or BMI (OR 1.11, 95% CI 1.04­1.18, p = 1.84 × 10−3). CONCLUSIONS: We confirmed a shared genetic basis, pleiotropic loci/genes, and causal relationship between SCZ and IBD, providing novel insights into the biological mechanism and therapeutic targets underlying these two disorders.

Palladium-catalyzed alkynylation of allylic gem-difluorides.

Herein, a palladium-catalyzed regioselective alkynylation, esterification, and amination of allylic gem-difluorides via C-F bond activation/transmetallation/ß-C elimination or nucleophilic attack has been achieved. This innovative protocol showcases an extensive substrate range and operates efficiently under mild reaction conditions, resulting in high product yields and Z-selectivity. Particularly noteworthy is its exceptional tolerance towards a wide array of functional groups. This developed methodology provides effective and convenient routes to access a diverse array of essential fluorinated enynes, esters and amines.

[Element relationship and extension path of clinical evidence knowledge map with Chinese patent medicine].

This study aims to construct the element relationship and extension path of clinical evidence knowledge map with Chinese patent medicine, providing basic technical support for the formation and transformation of the evidence chain of Chinese patent medicine and providing collection, induction, and summary schemes for massive and disorganized clinical data. Based on the elements of evidence-based PICOS, the conventional construction methods of knowledge graph were collected and summarized. Firstly, the data entities related to Chinese patent medicine were classified, and entity linking was performed(disambiguation). Secondly, the study associated and classified the attribute information of the data entity. Finally, the logical relationship between entities was constructed, and then the element relationship and extension path of the knowledge map conforming to the characteristics of clinical evidence of Chinese patent medicine were summarized. The construction of the clinical evidence knowledge map of Chinese patent medicine was mainly based on process design and logical structure, and the element relationship of the knowledge map was expressed according to the PICOS principle and evidence level. The extension path crossed three levels(model layer, data layer application, and new evidence application), and the study gradually explored the path from disease, core evaluation indicators, Chinese patent medicine, core prescriptions, syndrome and treatment rules, and medical case comparison(evolution law) to new drug research and development. In this study, the top-level design of the construction of the clinical evidence knowledge map of Chinese patent medicine has been clarified, but it still needs the joint efforts of interdisciplinary disciplines. With the continuous improvement of the map construction technology in line with the characteristics of TCM, the study can provide necessary basic technical support and reference for the development of the TCM discipline.

[Guidelines for post-marketing research on clinical effectiveness of Chinese patent medicines].

Due to the lack of specialized guidance, the post-marketing research on clinical effectiveness of Chinese patent medicines demonstrates varied quality and lacks high-quality evidence, failing to meet the demands of policy-making, clinical decision-making, and industrial decision-making. To address this issue, this project gathered experts in clinical medicine, clinical pharmacy, evidence-based medicine, drug epidemiology, medical ethics, and policy and regulation in China. They referred to the model of international post-marketing research on medicines and developed Guidelines for post-marketing research on clinical effectiveness of Chinese patent medicines under the framework of relevant laws and regulations and technical guidance documents in China. The guidelines were developed with consideration to the characteristics of Chinese patent medicines, China's national conditions, and all the stakeholders including marketing authorization holders, clinical researchers, drug administration, and users. The development of the guidelines followed the requirements for developing group standards set by the China Association of Chinese Medicine. The guidelines fully implement the concept of full life-cycle research, emphasizing the combination of traditional Chinese medicine(TCM) theory, human use experience, and clinical trials and pay attention to the compliance, scientificity, and ethics of research. The guidelines clarify the topic selection and decision-making path of the post-marketing research on effectiveness of Chinese patent medicines through six steps: determining research purpose, analyzing drug characteristics, evaluating research basis, proposing clinical orientation, clarifying research purpose, and implementing classified research. The general principles of research design and implementation were clarified from eight aspects: research type, research objects, sample size, efficacy indicators, bias, missing data, evidence level, and practicality. It focuses on the research on the TCM syndrome-based efficacy evaluation, clinical value-oriented mechanism of action, and the effectiveness of Chinese patent medicines with different routes of administration. The guidelines provide a universal methodological basis for the post-marketing research on clinical effectiveness of Chinese patent medicines.

Icariin accelerates bone regeneration by inducing osteogenesis-angiogenesis coupling in rats with type 1 diabetes mellitus.

BACKGROUND: Icariin (ICA), a natural flavonoid compound monomer, has multiple pharmacological activities. However, its effect on bone defect in the context of type 1 diabetes mellitus (T1DM) has not yet been examined. AIM: To explore the role and potential mechanism of ICA on bone defect in the context of T1DM. METHODS: The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining, alizarin red S staining, quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence. Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis. A bone defect model was established in T1DM rats. The model rats were then treated with ICA or placebo and micron-scale computed tomography, histomorphometry, histology, and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area. RESULTS: ICA promoted bone marrow mesenchymal stem cell (BMSC) proliferation and osteogenic differentiation. The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers (alkaline phosphatase and osteocalcin) and angiogenesis-related markers (vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1) compared to the untreated group. ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs. In the bone defect model T1DM rats, ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation. Lastly, ICA effectively accelerated the rate of bone formation in the defect area. CONCLUSION: ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.

Analysis of the expression level and predictive value of CLEC16A|miR-654-5p|RARA regulatory axis in the peripheral blood of patients with ischemic stroke based on biosignature analysis.

Introduction: Ischemic stroke (IS) is a cerebrovascular disease that can be disabling and fatal, and there are limitations in the clinical treatment and prognosis of IS. It has been reported that changes in the expression profile of circRNAs have been found during injury in ischemic stroke, and circRNAs play an important role in the IS cascade response. However, the specific mechanisms involved in the pathogenesis of IS are not yet fully understood, and thus in-depth studies are needed. Methods: In this study, one circRNA dataset (GSE161913), one miRNA dataset (GSE60319) and one mRNA dataset (GSE180470) were retrieved from the Gene Expression Omnibus (GEO) database and included, and the datasets were differentially expressed analyzed by GEO2R and easyGEO to get the DEcircRNA, DEmiRNA and DEmRNA, and DEmRNA was enriched using ImageGP, binding sites were predicted in the ENCORI database, respectively, and the competitive endogenous RNA (ceRNA) regulatory network was visualized by the cytoscape software, and then selected by MCC scoring in the cytoHubba plugin Hub genes. In addition, this study conducted a case-control study in which blood samples were collected from stroke patients and healthy medical examiners to validate the core network of ceRNAs constructed by biosignature analysis by real-time fluorescence quantitative qRT-PCR experiments. Results: A total of 233 DEcircRNAs, 132 DEmiRNAs and 72 DEmRNAs were screened by bioinformatics analysis. circRNA-mediated ceRNA regulatory network was constructed, including 148 circRNAs, 43 miRNAs and 44 mRNAs. Finally, CLEC16A|miR-654-5p|RARA competitive endogenous regulatory axis was selected for validation by qRT-PCR, and the validation results were consistent with the bioinformatics analysis. Discussion: In conclusion, the present study establishes a new axis of regulation associated with IS, providing new insights into the pathogenesis of IS.