Rapid identification of the compounds of Bushen Huoxue Prescription based on offline two-dimensional liquid chromatography with high-resolution mass spectrometry and molecular network technology.

The comprehensive and efficient characterization of components in traditional Chinese medicine is crucial for elucidating its active constituents and uncovering its mechanism. Identifying the compounds of the Bushen Huoxue Prescription (BHP) is difficult because of its complex composition and the large difference in concentration among its compounds. In this study, a hydrophilic interaction liquid chromatography coupled with reversed-phase LC (HILIC × RPLC) offline 2D-LC tandem high-resolution mass spectrometry method was established to analyze the total compounds of the BHP. Database screening and molecular networking were performed to identify the compounds. In contrast to conventional 1D chromatography, 2D chromatography increased peak capacity, enriched trace ingredients, and prevented the masking of high-abundance compounds. A total of 165 compounds were identified, and 14 potential compounds needed to be further identified. This study provided an effective method for comprehensively analyzing the complex system of traditional Chinese medicine compounds.

Motion-resistant structured illumination microscopy based on principal component analysis.

Structured illumination microscopy (SIM) has become one of the most significant super-resolution techniques in bioscience for observing live-cell dynamics, thanks to fast full-field imaging and low photodamage. However, artifact-free SIM super-resolution reconstruction requires precise knowledge about variable environment-sensitive illumination parameters. Conventional algorithms typically, under the premise of known and reliable constant phase shifts, compensate for residual parameters, which will be easily broken by motion factors such as environment and medium perturbations, and sample offsets. In this Letter, we propose a robust motion-resistant SIM algorithm based on principal component analysis (mrPCA-SIM), which can efficiently compensate for nonuniform pixel shifts and phase errors in each raw illumination image. Experiments demonstrate that mrPCA-SIM achieves more robust imaging quality in complex, unstable conditions compared with conventional methods, promising a more compatible and flexible imaging tool for live cells.

Association between body fat composition and disease duration, clinical activity, and intravenous corticosteroid-induced response in inflammatory bowel disease.

BACKGROUND: Body fat composition is believed to be associated with the progression, medical response, and prognosis of inflammatory bowel disease (IBD). Hence, we conducted this study to explore if fat metrics were associated with the disease activity of severe IBD and the response to intravenous corticosteroids (IVCS). METHODS: We included 69 patients with ulcerative colitis (UC) and 72 patients with Crohn's disease (CD) who had previously received IVCS during hospitalization. We quantified individual fat distribution using abdominal computed tomography slices. The correlations between fat parameters and disease activity were available with Spearman correlation analysis. The prediction model was developed using independent risk factors derived from multivariable logistic regression analysis. Model discrimination was evaluated leveraging the receiver operating characteristic curve. 1000 bootstrap resamples internally validated the model's prediction performance. RESULTS: Notable differences in age, nutritional status, serum cytomegalovirus replication, stool condition, and extraintestinal involvement between UC and CD patients were observed. UC subjects who responded to IVCS had higher subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), and mesorectal adipose tissue index (MATI) than non-responders. IVCS-responding CD individuals had lower VATI and mesenteric fat index (MFI) than non-responders. CD patients with a prolonged disease duration had a decreased SATI and an elevated MFI. VATI and MATI were reduced as UC clinically progressed, while more prominent clinical activity in CD correlated with increased VATI, MATI, and MFI. A high SATI indicated that patients with UC were more prone to be IVCS responders. For patients with CD, levels of VATI and MFI were negatively associated with effective IVCS treatment. The established models showed a discriminative accuracy of 0.834 [95% confidence interval (CI) 0.740-0.928] in the UC cohort and 0.871 (95% CI 0.793-0.949) in the CD cohort. Repeated samples supported the reliability of the developed models (AUCUC = 0.836, 95% CI 0.735-0.919; AUCCD = 0.876, 95% CI 0.785-0.946). CONCLUSION: Human fat indexes represent novel imaging biomarkers for identifying IBD patients who respond to IVCS, thus building accelerated therapy regimens and avoiding the adverse effects of ineffective IVCS.

Heterosexual Marital Intention: The Influences of Confucianism and Stigma Among Chinese Sexual Minority Women and Men.

In traditional Confucianist culture in China, marriage and offspring are highly valued, placing sexual minority adults under tremendous pressure to marry an opposite sex partner. This study explored how Confucianism and stigma were associated with the intention to pursue a heterosexual marriage among Chinese sexual minority individuals as well as the moderating mechanisms of gender and age. Cross-sectional data were collected from 747 participants via online social networks from March to June 2020. Items assessed Confucianism values (communalism, filial piety, traditional gender roles); stigma (rejection sensitivity, social discrimination); and heterosexual marital intention (HMI). A total of 1.7% (n = 12) participants had ever been married, 11.6% (n = 87) planned to marry a different-sex partner, 60.4% (n = 451) had no intention to pursue a heterosexual marriage, and 26.4% (n = 197) had no specific marital plan. Bisexual participants scored significantly higher than homosexual individuals in HMI. Sexual minority adults with high levels of Confucianism and stigma were more likely to intend to marry. Importantly, both individual stigma (rejection sensitivity) and interpersonal stigma (social discrimination) partially mediated the relationship between Confucianism and HMI. Confucianism had a stronger impact on HMI for men than women, and age moderated the influence of Confucianism (including communalism and filial piety) on HMI, with a stronger impact for younger than older generations. This study contributes to a better understanding of how Confucianism and stigma may be connected to the intention to pursue a heterosexual marriage, suggesting culture-modified theories of stigma and sexual minority stress are needed to explain the experiences of sexual minority people in contemporary China.

Up-Regulation of SLC26A6 in Hepatocellular Carcinoma and Its Diagnostic and Prognostic Significance.

Hepatocellular carcinoma (HCC), is one of the most common malignancies worldwide, which is globally the third most common cause of cancer-related mortality. This study aims to identify new potential early-stage diagnostic and prognostic biomarker for HCC. The candidate gene SLC26A6 expression was analyzed based on the Oncomine and Tumor Immune Estimation Resource (TIMER) databases and verified forwards with Gene Expression Omnibus (GEO) datasets. The protein expression was retrieved from Human Protein Atlas (HPA) database. We also validated the diagnostic and prognostic value in HCC, and the relationship between SLC26A6 and clinicopathologic parameters were also accessed. The Gene Set Enrichment Analysis (GSEA) and Protein-Protein Interaction (PPI) network were constructed to analyze the SLC26A6-related pathway. These results reveal that SLC26A6 expression was elevated in HCC, and the diagnostic sensitivity of SLC26A6 was higher than α-fetoprotein (AFP). SLC26A6 expression was independent prognostic factor for HCC. SLC26A6 up-regulation was mainly associated with excision repair, DNA replication, etc. SLC26A6-related mR-NAs was enriched in PI3K-AKT signaling pathway, axon guidance, pathways in cancer, and so on. PPI network indicated that SLC26A6 was interacted with solute carrier members, ABC transporters and other ion transport molecule. We further analyzed three positively correlated microRNAs and 10 negatively correlated microRNAs, all of these were reported participating or inhibiting in cancer progression. This is the first study demonstrated that SLC26A6 is up-regulated in HCC and correlated with poor prognosis, which might be served as a diagnostic marker or prognostic biomarker for HCC.

Preparation of magnetic molecularly imprinted polymers for the rapid detection of diethylstilbestrol in milk samples.

BACKGROUND: Diethylstilbestrol (DES) residues are harmful to human health because of their potential carcinogenic properties. Therefore, it is important to develop a fast and efficient pretreatment method to prevent their harmful effects on human health and the environment. RESULTS: In this paper, two types of magnetic molecularly imprinted polymers (MMIPs) of DES were prepared by bulk polymerization and the sol-gel method, respectively. The synthetic materials were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy and thermogravimetric analysis. Adsorption capacities of the bulk and sol-gel MMIPs were investigated. A rapid detection method was developed using the two types of MMIPs as sorbents, coupled to high-performance liquid chromatography, for the determination of DES residues in milk samples. Under optimized conditions, the limit of detection (S/N = 3) of both methods for DES was 2.0 µg L-1 ; and the linear response range to DES was 0.1-500 mg L-1 . The milk samples were analyzed according to this method with good recoveries of 88.3-97.6 and 90.5-103.5% for the two types of MMIPs, respectively. CONCLUSIONS: The method described had high sensitivity and high selectivity, and could prove to be a new method for the rapid determination of DES residues in milk samples. © 2019 Society of Chemical Industry.

Altered brain activation and connectivity during anticipation of uncertain threat in trait anxiety.

In the research field of anxiety, previous studies generally focus on emotional responses following threat. A recent model of anxiety proposes that altered anticipation prior to uncertain threat is related with the development of anxiety. Behavioral findings have built the relationship between anxiety and distinct anticipatory processes including attention, estimation of threat, and emotional responses. However, few studies have characterized the brain organization underlying anticipation of uncertain threat and its role in anxiety. In the present study, we used an emotional anticipation paradigm with functional magnetic resonance imaging (fMRI) to examine the aforementioned topics by employing brain activation and general psychophysiological interactions (gPPI) analysis. In the activation analysis, we found that high trait anxious individuals showed significantly increased activation in the thalamus, middle temporal gyrus (MTG), and dorsomedial prefrontal cortex (dmPFC), as well as decreased activation in the precuneus, during anticipation of uncertain threat compared to the certain condition. In the gPPI analysis, the key regions including the amygdala, dmPFC, and precuneus showed altered connections with distributed brain areas including the ventromedial prefrontal cortex (vmPFC), dorsolateral prefrontal cortex (dlPFC), inferior parietal sulcus (IPS), insula, para-hippocampus gyrus (PHA), thalamus, and MTG involved in anticipation of uncertain threat in anxious individuals. Taken together, our findings indicate that during the anticipation of uncertain threat, anxious individuals showed altered activations and functional connectivity in widely distributed brain areas, which may be critical for abnormal perception, estimation, and emotion reactions during the anticipation of uncertain threat.

Comparison of inducible versus constitutive expression of plectasin on yields and antimicrobial activities in Pichia pastoris.

BACKGROUND: Plectasin might serve as a substitute for traditional antibiotics, but its yields and antimicrobial activities warrant further investigation. OBJECTIVE: To identify the influence of inducible versus constitutive expression of plectasin on yields and antimicrobial activities. METHODS: Through SOE-PCR, a recombinant plectasin gene was generated and inserted into inducible (pPICZαA) and constitutive (pGAPZαA) vectors in order to create Pichia pastoris GS115 strains. After 120 h of fermentation, supernatants were purified by an AKTA purifier using nickel columns. Minimal inhibitory concentration (MIC) and inhibition zone assays were performed after Tricine-SDS-PAGE. RESULTS: After 120 h of fermentation, the yield of constitutive plectasin (370 µg/ml) was much lower than that from inducible vector (880 µg/ml) (P < 0.05). However, constitutive strain reached its plateau phase faster and keep more consistent yield (P < 0.05). The MICs of inducible plectasin against Methicillin-resistant Staphylococcus aureus (MRSA) 15471118, vancomycin-resistant Enterococcus feces (VREF), and penicillin-resistant Streptococcus pneumonia (PRSP) 31355 were 64, 32, and 64 µg/ml, respectively, while those of constitutive plectasin were 4, 4, and 16 µg/ml. No significant differences were observed in antimicrobial activities between inducible and constitutive plectasin for MRSA 15471118, VREF and PRSP 31355 (all P ï¼ž 0.05). However, constitutive plectasin had a larger inhibition zone than inducible plectasin with the same mass. CONCLUSIONS: Although P. pastoris GS115 (pGAPZαA-Plectasin-GS115) had lower expression than P. pastoris GS115 (pPICZαA-plectasin-GS115), it reached the plateau phase faster, had steadier yields and showed superiority in antimicrobial activities. Therefore, pGAPZαA might be more suitable for expression of plectasin in GS115 compared with pPICZαA.

Development and psychometric testing of the Coronavirus Awareness and Preparedness Scale: A cross-sectional study.

Background and Aims: A comprehensive standardized evaluation tool was needed to assess community awareness and preparedness when the pandemic hit the United States. This study aimed to develop and validate a new Coronavirus Awareness and Preparedness Scale (CAPS) through psychometric testing. Methods: This study unfolded in two phases. Phase 1 (conducted in March and April 2020) focused on the development of the scale. Phase 2 (conducted in June and July 2020) measured the reliability and validity of the scale. Psychometric testing, including exploratory factor analysis and reliability testing, was performed with a convenience sample of 1237 faculty, staff, and students at a southern university in the United States. Results: The final CAPS model consists of four factors with 26 items: threat (seven items), confidence (11 items), individual precautions (three items), and public precautions (five items). The scale demonstrated satisfactory internal consistency (Cronbach's α = 0.75). Strong and statistically significant item correlations were observed within the subscales through item analysis. Conclusion: The CAPS is a reliable and valid comprehensive evaluation instrument designed to gauge community awareness and preparedness during the early stages of the COVID-19 pandemic. Its adaptability makes it suitable for measuring readiness and preparedness concerning any novel airborne disease or future airborne pandemic within a community.

Treatment of diabetic retinopathy with herbs for tonifying kidney and activating blood circulation: A review of pharmacological studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes. Chinese medicine believes that kidney deficiency and blood stasis are significant pathogenesis of DR. A characteristic therapeutic approach for this pathogenesis is the kidney-tonifying and blood-activating method. By literature retrieval from several databases, we methodically summarized the commonly used kidney-tonifying and blood-activating herbs for treating DR, including Lycii Fructus, Rehmanniane Radix Praeparata, and Corni Fructus with the function of nourishing kidney; Salvia Miltiorrhizae Radix et Rhizoma with the function of enhancing blood circulation; Rehmanniae Radix with the function of nourishing kidney yin; and Astragali Radix with the function of tonifying qi. It has been demonstrated that these Chinese herbs described above, by tonifying the kidney and activating blood circulation, significantly improve the course of DR. AIM OF THE STUDY: Through literature research, to gain a thorough comprehension of the pathogenesis of DR. Simultaneously, through the traditional application analysis, modern pharmacology research and network pharmacology analysis of kidney-tonifying and blood-activating herbs, to review the effectiveness and advantages of kidney-tonifying and blood-activating herbs in treating DR comprehensively. MATERIALS AND METHODS: PubMed, the China National Knowledge Infrastructure (CNKI), and Wanfang Data were used to filter the most popular herbs for tonifying kidney and activating blood in the treatment of DR. The search terms were "diabetic retinopathy" and "tonifying kidney and activating blood". Mostly from 2000 to 2023. Network pharmacology was applied to examine the key active components and forecast the mechanisms of kidney-tonifying and blood-activating herbs in the treatment of DR. RESULTS: Kidney deficiency and blood stasis are the pathogenesis of DR, and the pathogenesis is linked to oxidative stress, inflammation, hypoxia, and hyperglycemia. Scientific data and network pharmacology analysis have demonstrated the benefit of tonifying kidney and activating blood herbs in treating DR through several channels, multiple components, and multiple targets. CONCLUSIONS: This review first presents useful information for subsequent research into the material foundation and pharmacodynamics of herbs for tonifying kidney and activating blood, and offers fresh insights into the treatment of DR.

Exploring the mechanism of Bushen Huoxue prescription in the treatment of early diabetic retinal edema from the perspective of inner blood-retinal barrier injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic retinopathy (DR) is one of the most severe complications of diabetes mellitus, diabetes belongs to the category of "emaciation-thirst disease" in traditional Chinese medicine (TCM). Bushen Huoxue Prescription (BHP) is composed of traditional Chinese materia medica, which has therapeutic effects on DR and early diabetic retinal edema (EDRE). However, the therapeutic mechanism is unclear. AIM OF THE STUDY: Exploring the mechanism of BHP against EDRE. METHODS: Feeding Sprague Dawley (SD) rats a high-fat, high-sugar diet as well as providing intraperitoneal injections of streptozotocin (STZ) to promote inner blood-retinal barrier (iBRB) damage that can trigger EDRE, evaluating the therapeutic effect of BHP by the level of expressiveness of TJ proteins (ZO-1,Occludin) of the iBRB and the leakage of rhodamine B isothiocyanate (RITC) in the retina. The combination of network pharmacology and metabolomics was employed to study the mechanism of BHP in preventing of EDRE, then four proteins which were closely to the damage of iBRB were chosen for the validation by employing Western Blot (WB). RESULTS: Research of network pharmacology had shown that BHP had efficacy against EDRE by regulating targets such as AKT1, ALB, TNF, PPARG, etc, its potential pathways mainly involving signaling pathways such as HIF-1. In untargeted metabolomics analysis of serum, 15 differential metabolites were identified, with the metabolic pathways focusing on ketone body metabolism and synthesis, sphingolipid metabolism and phenylalanine metabolism. The conclusions of metabolomics and network pharmacology revealed that BHP can treat EDRE by alleviating hypoxia and oxidative stress and exerting protection of the iBRB. Finally, BHP's protection behavior of the iBRB was validated by WB experiments. CONCLUSION: Through integrating pharmacodynamics, network pharmacology and metabolomics, BHP was discovered to have a crucial function in EDRE therapy by preserving the integrity of iBRB. This comprehensive strategy also provided a reasonable way to reveal the multi-components, multi-targets, multi-pathways mechanism of TCM.

Sociodemographic and geographic disparities in COVID-19 booster vaccination in Nueces County, Texas, USA.

Objective: This paper explores sociodemographic determinants and geographic disparities in COVID-19 booster uptake among fully vaccinated adults in Nueces County, Texas, USA with a population of over 353,000. Methods: A logistic generalized additive model was applied to analyze 184,252 official vaccination records of fully vaccinated adults over the period between December 2020 and August 2022. An individual's odds in receiving a booster shot were estimated with a host of sociodemographic characteristics as predictors. Results: Model estimation results reveal that male (odds ratio 0.836, 95% confidence interval 0.835-0.836, p < 0.001) and Hispanic residents (odds ratio 0.944, 95% confidence interval 0.943-0.945, p < 0.001) in the county were less likely to take a booster shot. Between the ages of 25 and 75, booster uptake increased with age (age 75 vs. 45 odd ratio 3.058, 95% confidence interval 3.052-3.063, p < 0.001). Booster uptake was lower in rural areas (odds ratio 0.804, 95% confidence interval 0.795-0.814, p < 0.001) and communities with high social vulnerability (highest vs. moderate vulnerability odd ratio 0.800, 95% confidence interval 0.767-0.836, p < 0.001). Conclusion: Empirical results confirm that booster uptake varied across individuals and communities of different socioeconomic and demographic characteristics. To advance health equity, a more inclusive vaccine campaign should pay particular attention to those underserved populations.

CircALMS1 Alleviates Pulmonary Microvascular Endothelial Cell Dysfunction in Pulmonary Hypertension.

BACKGROUND: Circular RNAs can serve as regulators influencing the development of pulmonary hypertension (PH). However, their function in pulmonary vascular intimal injury remains undefined. Thus, we aimed to identify specifically expressed circular RNAs in pulmonary microvascular endothelial cells (PMECs) under hypoxia and PH. METHODS AND RESULTS: Deep RNA sequencing and quantitative real-time polymerase chain reaction revealed that circALMS1 (circular RNA Alstrom syndrome protein 1) was reduced in human PMECs under hypoxia (P<0.0001). Molecular biology and histopathology experiments were used to elucidate the roles of circALMS1 in regulating PMEC dysfunction among patients with PH. The circALMS1 expression was decreased in the plasma of patients with PH (P=0.0315). Patients with lower circALMS1 levels had higher risk of death (P=0.0006). Moreover, the circALMS1 overexpression of adeno-associated viruses improved right ventricular function and reduced pulmonary vascular remodeling in monocrotaline-PH and sugen/hypoxia-PH rats (P<0.05). Furthermore, circALMS1 overexpression promoted apoptosis and inhibited PMEC proliferation and migration under hypoxia by directly downregulating miR-17-3p (P<0.05). Dual luciferase assay confirmed the direct binding of circALMS1 to miR-17-3p and miR-17-3p binding to its target gene YT521-B homology domain-containing family protein 2 (YTHDF2) (P<0.05). The YTHDF2 levels were also downregulated in hypoxic PMECs (P<0.01). The small interfering RNA YTHDF2 reversed the effects of miR-17-3p inhibitors on PMEC proliferation, migration, and apoptosis. Finally, the results indicated that, although YTHDF2, as an N(6)-methyladenosine reader protein, contributes to the degradation of many circular RNAs, it could not regulate the circALMS1 levels in PMECs (P=0.9721). CONCLUSIONS: Our study sheds new light on circALMS1-regulated dysfunction of PMECs by the miR-17-3p/YTHDF2 pathway under hypoxia and provides insights into the underlying pathogenesis of PH.

Pharmacological mechanism and clinical study of Qiming granules in treating diabetic retinopathy based on network pharmacology and literature review.

ETHNOPHARMACOLOGY RELEVANCE: Diabetic retinopathy (DR) is a general complication of diabetes, which has become a serious threat to human health worldwide. However, the best treatment is still under development. Qiming (QM) granules are mainly composed of Astragalus membranaceus, Pueraria lobata, Rehmannia Glutinosa, Lycium barbarum, Cassiae Semen, Fructus Leonuri, Pollen Typhae, and Leech, which are beneficial to qi, nourish liver and kidney, and clear collaterals and eyes. The treatment of DR is a comprehensive application based on the above traditional Chinese medicine. In recent years, satisfactory results have been achieved for DR. AIM OF THE STUDY: Through the traditional application analysis, network pharmacology analysis and clinical research summary of QM granules, to review the effectiveness and advantages of QM granules in the treatment of DR comprehensively. MATERIALS AND METHODS: Analysis of main active components of QM granules by network pharmacology and prediction of mechanism of action of QM granules on DR. Further, PubMed, Web of Science, and China National Knowledge Infrastructure were used to search literature, using the keywords of "Qiming granules", "diabetic retinopathy", "clinical research" and their combinations, mainly from 1999 to 2022. RESULTS: Traditional pharmacological analysis, Network pharmacological analysis, animal experiments, and clinical studies have confirmed that QM granules plays a role in the treatment of DR through multiple components, multiple targets, and multiple channels. CONCLUSIONS: This systematic review for the first time provides meaningful information for the further study of the pharmacodynamic material basis and pharmacological mechanism of QM granules, and also provides a basis for further study of quality markers and quality control of QM granules.

Improving Mechanical and Barrier Properties of Antibacterial Poly(Phenylene Sulfide) Nanocomposites Reinforced with Nano Zinc Oxide-Decorated Graphene.

Nano zinc oxide-decorated graphene (G-ZnO) was blended with polyphenylene sulfide (PPS) to improve its tensile, thermal, crystalline, and barrier properties. The properties of neat PPS and PPS/G-ZnO nanocomposites were characterized and compared using various tests, including tensile tests, scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, evaluation of Escherichia coli inhibition, and barrier performance. The results demonstrated that G-ZnO played a crucial role in heterogeneous nucleation and reinforcement. When the concentration of G-ZnO was 0.3%, the tensile strength, elongation at break, thermostability, crystallinity, and water vapor permeability coefficients (WVPC) approached their maximum values, and the microscopic morphology changed from the original brittle fracture to a relatively tough fracture. In addition, when G-ZnO was added to PPS at a ratio of 0.3%, the tensile strength, elongation at break, and WVPC of PPS were increased by 129%, 150%, and 283%, respectively, compared to pure PPS. G-ZnO endowed the nanocomposites with antibacterial properties. The improvement in barrier performance can be attributed to three reasons: (1) the presence of G-ZnO extended the penetration path of molecules; (2) the coordination and hydrogen bonds between PPS polymer matrix and G-ZnO nanofiller narrowed the H2O transmission path; and (3) due to its more hydrophobic surface, water molecules were less likely to enter the interior of PPS/G-ZnO nanocomposites. This study provides valuable insights for developing high-performance PPS-based nanocomposites for various applications.

Exploring the quality markers and mechanism of Bushen Huoxue Prescription in prevention and treatment of diabetic retinopathy based on Chinmedomics strategy.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicines have complex chemical composition; therefore, revealing the effective substances of Chinese herbal medicine becomes a prerequisite for scientific elucidation of the mechanism of action of Bushen Huoxue Prescription (BHP) against diabetic retinopathy (DR) and the development of new drugs. AIM OF THE STUDY: The Chinmedomics technique was used to evaluate the pharmacodynamic ingredients and mechanism of action of BHP against DR rats. MATERIALS AND METHODS: The overall physiological condition of the rats, including body weight, blood glucose, inflammatory factor levels, histological staining, and urine metabolic profile were examined to evaluate the model and its effects. The chemical composition of BHP in vivo and ex vivo was fully analyzed utilizing UPLC-Q-Exactive Orbitrap MS in conjunction with TCM serum pharmacochemistry. Finally, correlation analysis between biomarkers, and serum migration components was used to identify Quality markers (Q-markers) that were significantly associated with effectiveness. RESULTS: The UPLC-Q-Exactive Orbitrap MS platform was used to identify a total of 29 chemicals in serum, 17 of which were highly linked with effectiveness and can be potentially employed as pharmacodynamic substances for BHP against DR. In addition, 14 biomarkers related to galactose metabolism, starch and sucrose metabolism, pantothenate and CoA biosynthesis, glycine, serine, and threonine metabolism were identified. These pathways reveal that DR may be inextricably linked to levels of oxidative stress and inflammation in the organism. Finally, five active ingredients were identified as potential Q-markers of BHP against DR, namely ajugol, protocatechuic acid, tanshinone IIA, panaxatriol and puerarin. CONCLUSION: This study successfully clarified the efficacy and Q-markers of BHP through the Chinmedomics strategy, which is of great significance in determining the quality standards of BHP.

The role of prolactin/vasoinhibins in cardiovascular diseases.

Prolactin (PRL) is a polypeptide hormone that is mainly synthesized and secreted by the lactotroph cells of the pituitary. There are two main isoforms of PRL: 23-kDa PRL (named full-length PRL) and vasoinhibins (including 5.6-18 kDa fragments). Both act as circulating hormones and cytokines to stimulate or inhibit vascular formation at different stages and neovascularization, including endothelial cell proliferation and migration, protease production, and apoptosis. However, their effects on vascular function and cardiovascular diseases are different or even contrary. In addition to the structure, secretion regulation, and signal transduction of PRL/vasoinhibins, this review focuses on the pathological mechanism and clinical significance of PRL/vasoinhibins in cardiovascular diseases.

Impact of reduced apolipoprotein A-I levels on pulmonary arterial hypertension.

OBJECTIVE: The significance of apolipoprotein A-I (ApoA-I) is the anti-inflammatory functional component of high-density lipoprotein, which needs to be further studied in relation to pulmonary arterial hypertension (PAH). This study aimed to identify the predictive value of ApoA-1 on the risk and prognosis of PAH, as well as the underlying anti-inflammatory mechanism. METHODS: Proteomic analysis was conducted on lung tissue from 6 PAH patients and 4 lung donors. Prediction of risk and mortality risk factors associated with PAH in 343 patients used logistic analysis and Cox regression analysis, respectively. The protective function of ApoA-I was assessed in human pulmonary arterial endothelial cells (HPAEC), while its anti-inflammatory function was evaluated in THP-1 macrophages. RESULTS: In the lung tissues of patients with PAH, 168 differentially expressed proteins were associated with lipid metabolism according to GO and KEGG enrichment analysis. A protein-protein interaction network identified ApoA-I as a key protein associated with PAH. Lower ApoA-I levels were independent risk factors for PAH and displayed a stronger predictive value for PAH mortality. Plasma interleukin 6 (IL-6) levels were positively correlated with risk stratification and were higher in PAH patients with lower ApoA-I levels. ApoA-I was downregulated in the lung tissues of monocrotaline (MCT) -induced rats. ApoA-I could reduce the IL-6-induced pro-proliferative and pro-migratory abilities of HPAEC and inhibit the secretion of IL-6 from macrophages, which is compromised under hypoxic conditions. CONCLUSION: Our study identified the significance of ApoA-I as a biomarker for predicting the survival outcome of PAH patients, which might relate to its altered anti-inflammatory properties.

Biology and function of pericytes in the vascular microcirculation.

Pericytes are the main cellular components of tiny arteries and capillaries. Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines, thus affecting the contraction and relaxation of microvessels and playing an essential role in regulating vascular microcirculation. Moreover, due to the characteristics of stem cells, pericytes can differentiate into a variety of inflammatory cell phenotypes, which then affect the immune function. Additionally, pericytes can also participate in angiogenesis and wound healing by interacting with endothelial cells in vascular microcirculation disorders. Here we review the origin, biological phenotype and function of pericytes, and discuss the potential mechanisms of pericytes in vascular microcirculation disorders, especially in pulmonary hypertension, so as to provide a sound basis and direction for the prevention and treatment of vascular microcirculation diseases.

COVID-19 Vaccine Hesitancy: The Role of Socioeconomic Factors and Spatial Effects.

This paper investigates the spatial dimension of socioeconomic and demographic factors behind COVID-19 vaccine hesitancy. With a focus on a county with considerable sociodemographic diversity in the state of Texas, USA, we apply regression models to census-tract-level data of the unvaccinated population. In addition to disparities in accessing the vaccination service, particularly for residents in rural areas, empirical results confirm under-vaccination among lower socioeconomic neighborhoods and communities with signs of distrust in government. The spatial model regressions further underscore the impact that vaccine hesitancy among residents in one community spread to its nearby communities. This observed spatial spillover effect is attributable to the geographic interactions of similar socioeconomic groups.