Epidemiology of multimorbidity associated with atherosclerotic cardiovascular disease in the United States, 1999-2018.

BACKGROUND: The multimorbidity of Atherosclerotic cardiovascular disease (ASCVD) and many other chronic conditions is becoming common. This study aimed to assess multimorbidity distribution in ASCVD among adults in the United States from 1999 to 2018. METHODS: This cross-sectional survey from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 using stratified multistage probability design. Among the 53,083 survey respondents during the study period, 5,729 US adults aged ≥ 20 years with ASCVD. Joinpoint regression was used to assess the statistical significance of prevalence trends in the prevalence of ASCVD stratified by multimorbidity. The Apriori association rule mining algorithm was used to identify common multimorbidity association patterns in ASCVD patients. RESULTS: Overall, 5,729 of 53,083 individuals had ASCVD, and the prevalence showed a slow declining trend (biannual percentage change = -0.81%, p = 0.035, average 7.71%). The prevalence of ASCVD significantly decreased in populations without dyslipidemia, diabetes mellitus (DM), hypertension, asthma, chronic obstructive pulmonary disease (COPD), and arthritis (all groups, p < 0.05). Additionally, 65.6% of ASCVD patients had at least four of the 12 selected chronic conditions, with four and five being the most common numbers of conditions (17.9% and 17.7%, respectively). The five most common chronic conditions were (in order) dyslipidemia, hypertension, arthritis, chronic kidney disease, and DM. The coexistence of hypertension and dyslipidemia had the highest support in association rules (support = 0.63), while the coexistence of dyslipidemia, hypertension, metabolic syndrome, and DM had the highest lift (lift = 1.82). CONCLUSIONS: During the 20-year survey period, there was a significant decrease in the overall prevalence of ASCVD. However, this reduction was primarily observed in individuals without dyslipidemia, DM, hypertension, asthma, COPD, and arthritis. Among populations with any of the evaluated chronic conditions, the prevalence of ASCVD remained unchanged. Most of ASCVD patients had four or more concurrent chronic conditions.

Hydrogen peroxide fluorescent probe-monitored butyric acid inhibition of the ferroptosis process.

Short-chain fatty acids, such as butyrate, play pivotal roles in various physiological processes within the human body. Recent advances in understanding cell death pathways, specifically ferroptosis, have unveiled unique opportunities for therapeutic development. Ferroptosis is linked to iron accumulation and oxidative stress, whereas butyrate has emerged as a cellular protector against oxidative stress, potentially inhibiting ferroptosis. Hydrogen peroxide (H2 O2 ) is a key player in oxidative stress, and its monitoring has gained significance in disease mechanisms. We present an innovative fluorescent probe, HOP, capable of dynamically tracking intracellular H2 O2 levels, enabling spatial and temporal visualization. The probe exhibits high accuracy (limit of detection = 0.14 µM) and sensitivity, paving the way for disease diagnosis and treatment innovations. Importantly, HOP displayed minimal toxicity, making it suitable for cellular applications. Cellular imaging experiments demonstrated its ability to penetrate cells and monitor intracellular H2 O2 levels accurately. The HOP probe confirmed H2 O2 as a critical marker in ferroptosis. Our innovative HOP provides a powerful tool for tracking intracellular H2 O2 levels and offers insights into the modulation of ferroptosis, potentially opening new avenues for disease research and therapeutic interventions.

Vacancy-Modified Porous g-C3N4 Nanosheets Controlled by Physical Activation for Highly Efficient Visible-Light-Driven Hydrogen Evolution and Organics Degradation.

As a promising photocatalyst material, g-C3N4 has great application potential in energy production and environmental improvement. In this work, surface-modified g-C3N4 nanosheets with excellent stability and high photocatalytic activity were successfully synthesized by physical steam activation. The charge transfer rate of carbon nitride was improved due to the synergistic effect of nitrogen defect and oxygen doping caused by steam activation. Meanwhile, the specific surface area and pore volume of the optimized sample reached 124.3 m2 g-1 and 0.42 cm3 g-1, respectively, which increased the exposed reaction sites of reactants, enhancing the photocatalytic activity of g-C3N4. In addition, this novel g-C3N4 displayed a great H2 evolution rate of 5889.39 µmol h-1 g-1 with a methylene blue degradation rate up to 6.52 × 10-3 min-1, which was 3.7 and 2.1 times of original g-C3N4, respectively. This study provided a simple and economical method to develop a highly efficient g-C3N4 photocatalyst for solar energy conversion.

Positive correlation between snoring and dyslipidemia in adults: results from NHANES.

BACKGROUND: A few studies have shown that snoring, in certain populations, is associated with dyslipidemia. However, there are currently no large-scale national studies available that explore this association. Thus, for further clarification, studies using a large sample of the general population need to be conducted. This study aimed to explore this association using the National Health and Nutrition Examination Survey (NHANES) database. METHODS: A cross-sectional survey was conducted using data from the NHANES database; 2005 to 2008 and 2015 to 2018 datasets were used (weighted to be representative of United States adults aged ≥ 20 years). Information on snoring status, lipid levels, and confounding factors were included. Logistic regression of the generalized linear model was used to analyze the relationship between snoring and dyslipidemia, and hierarchical analysis, interaction analysis, and sensitivity analysis were used to explore the stability of the results. RESULTS: Data from 28,687 participants were analyzed, and 67% of the participants had some degree of snoring. The fully adjusted multivariate logistic regression results demonstrated that snoring frequency was significantly positively associated with dyslipidemia (P < 0.001 for linear trend). Adjusted odds ratios (aORs) of dyslipidemia among those who snored rarely, occasionally, and frequently were 1.1 (95% confidence interval [CI], 1.02-1.18), 1.23 (95% CI, 1.10-1.38), and 1.43 (95% CI, 1.29-1.58), respectively, compared with that among those who never snored. In addition, age and snoring frequency showed a correlation (P = 0.02). Sensitivity analysis demonstrated that frequent snoring was significantly associated with lipid levels (all P ≤ 0.01 for linear trend), including increased low-density lipoprotein cholesterol (LDL-C) (ß = 0.09 mmol/L; 95% CI, 0.02-0.16), triglyceride (TG) (ß = 0.18 mmol/L; 95% CI, 0.10-0.26), total cholesterol (TC) (ß = 0.11 mmol/L; 95% CI, 0.05-0.16), and decreased high-density lipoprotein cholesterol (HDL-C) (ß=-0.04 mmol/L; 95% CI, -0.06--0.03). CONCLUSIONS: A statistically significant positive association was identified between sleep snoring and dyslipidemia. It was suggested that sleep snoring interventions may reduce the risk of dyslipidemia.

MicroRNA-217 ameliorates inflammatory damage of endothelial cells induced by oxidized LDL by targeting EGR1.

Oxidized low-density lipoprotein (ox-LDL) modulates gene transcription and expression and induces the development of endothelium inflammation and endothelial dysfunction, in which microRNAs (miRNAs) play a crucial role. However, the mechanism of ox-LDL in inflammatory damage of endothelial cells still remains elusive. Herein, we focused on the effect of hsa-miR-217-5p (miR-217) on endothelial dysfunction induced by ox-LDL by targeting early growth response protein-1 (EGR1). In the present study, 31 upregulated miRNAs and 59 downregulated miRNAs (Fold Change > 2, P value < 0.05) were identified after 6 h of 80 µg/mL ox-LDL exposure in human aortic endothelial cells (HAECs) by small RNA sequencing, including miR-217 that was significantly decreased (FC = 0.2787, P value = 5.22E-16). MiR-217 knockdown inhibited cell proliferation and increased level of IL-6, IL-1ß, ICAM-1 and TNF-α, while overexpression of miR-217 relieved the growth inhibition induced by ox-LDL and demonstrated anti-inflammatory effect in HAECs. EGR1 was predicted as a potential candidate target gene of miR-217 by TargetScan. The subsequent dual-luciferase reporter assay confirmed the direct binding of miR-217 to 3'UTR of EGR1. And EGR1 expression was negatively correlated with the level of miRNA-217 in HAECs after exposure to ox-LDL. Overexpression of EGR1 recapitulated the effects of miR-217 knockdown on cell proliferation inhibition and inflammation in HAECs, while knockdown EGR1 relieved the proliferative inhibition and demonstrated anti-inflammatory effect in ox-LDL-induced HAECs. The present study confirmed miR-217 ameliorates inflammatory damage of endothelial cells induced by oxidized LDL by targeting EGR1.

Promoted off-on recognition of H2O2 based on the fluorescence of silicon quantum dots assembled two-dimensional PEG-MnO2 nanosheets hybrid nanoprobe.

An "off-on" assay system for H2O2 determination was developed based on assembling ultra-bright fluorescent silicon quantum dots (SiQDs) and PEG-MnO2 nanosheets. Among them, SiQDs acted as fluorometric reporter, which can effectively eliminate the interference of plant pigments under excitation of 365 nm. PEG-MnO2 nanosheets played dual function of nanoquencher and H2O2 recognizer. Unlike previous reports, the quenching mechanism of SiQDs by PEG-MnO2 nanosheets is attributed to both the associative effect of inner filter effect and the static quenching effect. Thus, the fluorescence intensity of SiQDs at 445 nm decreased with increasing concentration of PEG-MnO2 nanosheets. After addition of H2O2, PEG-MnO2 nanosheets were reduced to Mn2+, consequently resulting in the recovery of the SiQDs fluorescence. Combined with these properties, an off-on fluorescent method was built for determination of H2O2 in plant leaves with high sensitivity and selectivity. The present method has two linear ranges: from 0.05 to 1 µM with a detection limit of 0.09 µM and from 1 to 80 µM with a detection limit of 4.04 µM. Graphical abstract Schematic representation of the mechanism of SiQD/PEG-MnO2 nanoprobe for determination of H2O2.

Biosynthesis of poly(ß-L-malic acid) from rubberwood enzymatic hydrolysates in co-fermentation by Aureobasidium pullulans.

Co-fermentation of multiple substrates has emerged as the most effective method to improve the yield of bioproducts. Herein, sustainable rubberwood enzymatic hydrolysates (RWH) were co-fermented by Aureobasidium pullulans to produce poly(ß-L-malic acid) (PMA), and RWH + glucose/xylose was also investigated as co-substrates. Owing to low inhibitor concentration and abundant natural nitrogen source content of RWH, a high PMA yield of 0.45 g/g and a productivity of 0.32 g/L/h were obtained by RWH substrate fermentation. After optimization, PMA yields following the fermentation of RWH + glucose and RWH + xylose reached 59.92 g/L and 53.71 g/L, respectively, which were 52 % and 36 % higher than that after the fermentation of RWH. RWH + glucose more significantly affected the correlation between PMA yield and substrate concentration than RWH + xylose. The results demonstrated that the co-fermentation of RWH co-substrate is a promising method for the synthesis of bioproducts.

Tongbian formula alleviates slow transit constipation by increasing intestinal butyric acid to activate the 5-HT signaling.

Slow transit constipation (STC) is a long-lasting and prevalent intestinal condition, marked by hard, dry feces. The primary cause of STC may be attributed to an imbalance in the gut's microbial community and alterations in its metabolic byproducts. Tongbian formula (TB), a traditional Chinese medicinal formula, has been used to treat STC and shows a great effect on relieving constipation. The role of TB in regulating intestinal microbiota has not been fully elucidated. Herein, we investigated the potential effect of TB on gut microbiota and further explored the potential mechanism behind its effects. Our study demonstrated that TB significantly increased fecal water content and intestinal ink propulsion rate in loperamide (Lope)-induced STC rats. 5-HT signaling was suppressed in STC colon tissue, and the abundance of butyric acid (BA) in colonic contents was significantly down-regulated after Lope treatment. Notably, TB administration led to the restoration of microbial dysbiosis and the up-regulation of BA content, subsequently activating 5-HT signaling pathways. When BA was combined with a tryptophan hydroxylase-1 (TPH1) inhibitor, which is crucial for 5-HT synthesis, its therapeutic efficacy for treating STC was compromised. TB alleviates STC by reversing the intestinal microbiota imbalance and activating the 5-HT signaling in the colon through increasing BA levels. These findings suggest that TB is an ideal candidate for STC treatment.

Clinical value-oriented research paradigm about inheritance and innovation development of TCM dominant diseases.

Modern medicine has made remarkable achievements in safeguarding people's life and health, however, it is increasingly found that in the face of complex diseases, selective targeting of single target is often difficult to produce a comprehensive rehabilitation effect, and is prone to induce drug resistance, toxic side effects. Traditional Chinese medicine (TCM) has a long history of clinical application, and its clinical value in the treatment of complex diseases such as cardiovascular and cerebrovascular diseases, digestive diseases, skin diseases, rheumatism and immunity diseases, and adjuvant treatment of tumors has been proven to have obvious advantages. However, its modern research is relatively lagging behind, and in the face of the aging society and the characteristics of the modern disease spectrum, the traditional knowledge-driven research paradigm seems to be stuck in a bottleneck and difficult to make greater breakthroughs. Focusing on the key issues of TCM development in the new era, the clinical value-oriented strategy becomes to be a new research paradigm of TCM inheritance and innovation development, and dominant diseases would be the focus of the TCM inheritance and innovation development, which has been highly valued in recent years by the TCM academia and the relevant national management departments. Based on the clinical value, a series of policies are formulated for the selection and evaluation of the TCM dominant diseases (TCMDD), and exploratory researches about the clinical efficacy characteristics, the modern scientific connotation interpretation were carried out. The clinical value-oriented research paradigm of TCMDD inheritance and innovation development has been initially formed, which is characterized by strong policy support as the guarantee, systematic and standardized selection and evaluation methods as the driving force, scientific and effective research on internal mechanisms as the expansion, and effective clinical guidelines and principles as the transformation, which is of great value in promoting the high-quality development of the industries and undertaking of TCM. In this paper, the main policy support, selection and evaluation methods, therapeutic effect characterization, and modern scientific connotation research strategies of TCMDD in recent years have been comprehensively sorted out, with a view to providing the healthy and benign development of the research on TCMDD.

Strategy for economical and enhanced polyhydroxyalkanoate production from synergistic utilization of palm oil and derived wastewater by activated sludge.

The potential of palm oil and derived wastewater pretreated by enzyme as co-substrates to accumulate polyhydroxyalkanoate (PHA) rich in short and medium-chain-length monomers under two feeding strategies was evaluated batchwise through mixed microbial cultures (MMCs) in activated sludge. A terpolymer with the maximum PHA content of 30.5 wt%, volumetric yield of 0.372 g COD/g COD and composition of ca. 84.7 âˆ¼ 97.4/0.5 âˆ¼ 1.6/2.1 âˆ¼ 13.7 (3-hydroxybutyrate/ 3-hydroxyvalerate/ 3-hydroxyoctanoate, %) was achieved as a result of co-substrate incorporation. From the perspective of economic benefits, PHA accumulated via adopting strategy of supplementing carbon source to the same initial concentration per cycle saved 42.7 % of carbon consumption, along with a reduction in culture time (72 h). The above discoveries signify that the combination of palm oil and derived wastewater plus MMCs provides an alternative to the plastics industries for a more sustainable and efficient utilization of biological resources and an economic PHA accumulation approach.

Peripheral origin exosomal microRNAs aggravate glymphatic system dysfunction in diabetic cognitive impairment.

Cognitive dysfunction is one of the common central nervous systems (CNS) complications of diabetes mellitus, which seriously affects the quality of life of patients and results in a huge economic burden. The glymphatic system dysfunction mediated by aquaporin-4 (AQP4) loss or redistribution in perivascular astrocyte endfeet plays a crucial role in diabetes-induced cognitive impairment (DCI). However, the mechanism of AQP4 loss or redistribution in the diabetic states remains unclear. Accumulating evidence suggests that peripheral insulin resistance target tissues and CNS communication affect brain homeostasis and that exosomal miRNAs are key mediators. Glucose and lipid metabolism disorder is an important pathological feature of diabetes mellitus, and skeletal muscle, liver and adipose tissue are the key target insulin resistance organs. In this review, the changes in exosomal miRNAs induced by peripheral metabolism disorders in diabetes mellitus were systematically reviewed. We focused on exosomal miRNAs that could induce low AQP4 expression and redistribution in perivascular astrocyte endfeet, which could provide an interorgan communication pathway to illustrate the pathogenesis of DCI. Furthermore, the mechanisms of exosome secretion from peripheral insulin resistance target tissue and absorption to the CNS were summarized, which will be beneficial for proposing novel and feasible strategies to optimize DCI prevention and/or treatment in diabetic patients.

Tongbian decoction restores intestinal microbiota and activates 5-hydroxytryptamine signaling: implication in slow transit constipation.

Introduction: Slow transit constipation (STC) is a type of functional constipation. The detailed mechanism of STC, for which there is currently no effective treatment, is unknown as of yet. Tongbian decoction (TBD), a traditional Chinese medicinal formula, is commonly used to treat STC in clinical settings. However, the potential impact of TBD on the management of STC via modulation of the gut microbiota remains unclear. Methods: Pseudo-germ-free rats were constructed after 6 days of treatment with bacitracin, neomycin, and streptomycin (abbreviated as ABX forthwith). Based on the successful construction of pseudo-germ-free rats, the STC model (ABX + STC) was induced using loperamide hydrochloride. After successful modeling, based on the different sources of donor rat microbiota, the ABX + STC rats were randomly divided into three groups: Control → ABX + STC, STC → ABX + STC, and STC + TBD → ABX + STC for fecal microbiota transplant (FMT). Body weight, fecal water content, and charcoal power propelling rate of the rats were recorded. Intestinal microbiota was detected by 16S rRNA sequencing, and the 5-hydroxytryptamine (5-HT) signaling pathway was examined by western blots, immunofluorescence, and immunohistochemical analysis. Results: After treatment with fecal bacterial solutions derived from rats treated with Tongbian decoction (TBD), there was an increase in body weight, fecal water content, and the rate of charcoal propulsion in the rats. Additionally, activation of the 5-hydroxytryptamine (5-HT) signaling pathway was observed. The 16S rRNA sequencing results showed that the fecal bacterial solution from TBD-treated rats affected the intestinal microbiota of STC rats by increasing the proliferation of beneficial bacteria and suppressing the expansion of harmful bacteria. Conclusion: Our study showed that TBD alleviated constipation in STC rats by modulating the structure of the intestinal microbiota.

Effects and central mechanism of electroacupuncture and MRI-navigated rTMS for PSD: study protocol for an fMRI-based single-center, randomized, controlled, open-label trial.

Background: Post-stroke depression (PSD) is the most common mental complication after stroke and has a serious impact on functional outcomes and quality of life for stroke patients. Antidepressants are the first-line treatment for PSD; however, many reported side effects remain. Clinical research and practice guidelines have shown that electro-acupuncture (EA) or rTMS have a positive effect on PSD. However, there are few clinical studies on EA and MRI-navigated rTMS for PSD that explore the fMRI-based central mechanism in depression. Methods: In this randomized, controlled, open-label trial, 64 patients with PSD will be randomly allocated into the experiment group (n = 32) or control group (n = 32). The experiment group will receive EA and MRI-navigated rTMS and the control group will receive MRI-navigated rTMS treatment, in 12-20 sessions over 4 weeks. In addition, 10 healthy people for fMRI scanning will be recruited as a healthy control group without any intervention. The primary outcome will be the change from baseline in the Hamilton Depression Scale-24 item (HAMD-24) scores at week 4. The primary analysis of the central mechanism will mainly involve cortical morphology, local spontaneous brain activity, and the default mode network (DMN) functional connectivity based on fMRI at 0 and 4 weeks. Secondary outcomes will include the neuro-patho-physiological and quality of life changes in cortical excitability, determined using the motor evoked potential test (MEP), National Institutes of Health Stroke Scale (NIHSS), EuroQol Five Dimensions Questionnaire (EQ-5D) Scale, Modified Barthel Index (MBI) Scale, and Health Scale of Traditional Chinese Medicine (HSTCM). Additional indicators will include the Acceptability Questionnaire and Health Economics Evaluation (cost-effectiveness analysis) to assess the acceptability and economic practicality of the treatment under study. Outcomes will be assessed at baseline and post intervention. Discussion: EA and MRI-navigated rTMS therapy could become an alternative treatment for PSD, and it is expected that this trial will provide reliable clinical evidence and a potential central mechanism for the future use of EA and MRI-navigated rTMS for PSD. Clinical trial registration: NCT05516680, ClinicalTrials.gov (registered in August 2022).

Angiotensinogen gene M235T and T174M polymorphisms and susceptibility of pre-eclampsia: a meta-analysis.

There are controversies in reports on the association of the angiotensinogen (AGT) gene polymorphisms with the risk of developing pre-eclampsia (PE). We performed a meta-analysis to examine the association between the AGT polymorphisms and PE risk: M235T (31 studies involving 2555 patients and 6114 controls) and T174M (six studies involving 681 patients and 2076 controls). For the M235T polymorphism, the TT genotype increased the PE risk as compared to the MM genotype (odds ratio 1.61, 95% confidence intervals 1.22-2.14, P= 0.001). When stratified by ethnicity, the TT genotype remained significantly associated with higher PE risk in Caucasians and Mongolians but not in Africans. Similar results were also obtained under all three genetic models of the M235T polymorphism. For the T174M polymorphism, no significant association was found in the comparisons (MT vs. TT and MM vs. TT) and under any genetic models. The analysis excluding the highly significant Hardy-Weinberg equilibrium-violating studies and sensitivity analysis further strengthened the validity of these associations. No publication bias was observed in this study. This meta-analysis demonstrates that the AGT M235T polymorphism is significantly associated with PE whereas the T174M polymorphism is not.

Achieving polyhydroxyalkanoate production from rubber wood waste using mixed microbial cultures and anaerobic-aerobic feeding regime.

In the past few years, creating value-added products has become the best choice to pretreat biomass waste. For instance, the fermentable sugar obtained after pretreatment bioconversion into valuable bioproducts, biopolymer as a typical representative, has become a potential strategy. In particular, the production of biopolymer polyhydroxyalkanoate (PHA) by mixed microbial cultures in waste activated sludge can be regarded as a promising alternative to traditional petrochemical plastics. In this study, the enzymatic hydrolysate of rubber wood was utilized as substrate to explore the optimal process conditions for the accumulation of PHA under anaerobic-aerobic mode. The results showed that longer operation cycle (24 h), suitable anaerobic duration (3.5 h) and secondary feeding regimen (secondary addition without draining liquid) were more beneficial to PHA production. After accumulation, the highest PHA production, PHA storage yield (YPHA/S) and ratio to cell dry weight (CDW) reached 929.8 mg COD·L-1, 0.24 g COD/g COD and 0.31 g PHA/g CDW, respectively. The YPHA/S values were similar to the previous reported 0.22 âˆ¼ 0.24 g COD/g COD. The results demonstrated that the secondary feeding regimen was an effective approach to improve the production of PHA with rubber wood enzymatic hydrolysate as substrate.

Effects of Different Natural Factors on Rheological Properties of SBS Modified Asphalt.

Typical climatic environments such as UV radiation, high temperature and strong wind in cold and arid regions have a significant effect on asphalt aging. The intent of this work is to reveal the evolution law of natural aging of SBS-modified asphalt under the complex adverse climate environment in cold and arid regions. Furthermore, the contribution rate of various environmental factors of natural aging of asphalt in cold and arid regions was analyzed. Based on rheological parameters, this paper characterized the influence of natural aging on the viscoelastic properties, rutting resistance at a high temperature, fatigue resistance and cracking resistance at a low temperature of SBS-modified asphalt. The evolution law of natural aging performance of SBS-modified asphalt was revealed. A quantitative evaluation index (CIi) of natural aging contribution rate of asphalt was put forward and the contribution rate of various environmental factors to asphalt natural aging was analyzed. The results showed that the effects of simulated aging and natural aging on asphalt properties were similar. After aging, the viscoelastic properties of asphalt were deteriorated, and the risk of fatigue cracking and low temperature cracking was increased. It also enhanced the deformation resistance of asphalt and increased the rutting resistance at high temperature. The aging contribution index CIi obtained based on rheological parameters such as complex modulus and rutting factor could directly reflect the influence of different natural factors on the performance of asphalt during aging. Among them, the effect of thermal oxygen was more obvious on the natural aging of SBS-modified asphalt.

Storax Inhibits Caveolae-Mediated Transcytosis at Blood-Brain Barrier After Ischemic Stroke in Rats.

Background and Purpose: Blood-brain barrier (BBB) disruption following ischemic stroke (IS) contributes to hemorrhagic transformation, brain edema, increased neural dysfunction, secondary injury, and mortality. The prevailing view attributes the destruction of tight junction proteins (TJs) to the resulting BBB damage following IS. However, recent studies define a stepwise impairment of the transcellular barrier followed by the paracellular barrier which accounts for the BBB leakage in IS. The increased endothelial transcytosis that has been proven to be caveolae-mediated, preceding and independent of TJs disintegration. Emerging experimental investigations suggested Storax attenuates BBB damage after stroke. This study aimed to test our hypothesis that Storax inhibits caveolae-mediated transcytosis at BBB after ischemic stroke in rats. Methods: Male Wistar rats (250-300 g) were subjected to transient middle cerebral artery occlusion (t-MCAO). Brain water content and the cerebral infarction size were assessed by brain tissue drying-wet method and 2,3,5-triphenyltetrazolium chloride (TTC) staining. BBB permeability was detected by the leakage of Evans blue and Albumin-Alexa594. The ultrastructure of BBB was examined by transmission electron microscopy (TEM). Cav-1 and Mfsd2a were quantified by western blotting and immunofluorescence staining, AQP4, PDGFR-ß, ZO-1 and Occludin were quantified by western blotting. Results: Storax treatment of 0.1 g/kg had no significant effects on brain lesions. Storax treatment of 0.2, 0.4, and 0.8 g/kg led to a significant decrease in infarction size, and the Storax 0.4, 0.8 g/kg groups displayed a significant reduction in brain water content. Storax treatment of 0.8 g/kg showed mild toxic reactions. Thus, 0.4 g/kg Storax was selected as the optimal dose for subsequent studies. Storax significantly inhibited the fluorescent albumin intensity in the brain parenchyma and the number of caveolae in ECs, alongside attenuating the ultrastructural disruption of BBB at 6 h after stroke. Meanwhile, Storax significantly increased the expression of Mfsd2a and PDGFR-ß, and decrease the expression of Cav-1 and AQP4, corresponding to the significantly decreased Cav-1 positive cells and increased Mfsd2a positive cells. However, Storax has no significant effects on Evan blue leakage or the expression ZO-1, Occludin. Conclusion: Our experimental findings demonstrate Storax treatment inhibits caveolae-mediated transcytosis at BBB in the focal stroke model of rats. We also speculate that regulation of Cav-1, Mfsd2a, AQP4, and PDGFR-ß expressions might be associated with its beneficial pharmacological effect, but remain to define and elucidate in future investigation.

Efficient and economical production of polyhydroxyalkanoate from sustainable rubber wood hydrolysate and xylose as co-substrate by mixed microbial cultures.

Using co-substrate to accumulate polyhydroxyalkanoate (PHA) is an efficient approach to reduce production cost and improve yield of PHA. In the study, PHA was biosynthesized under full aerobic mode by using rubber wood hydrolysate and xylose co-substrate as the carbon source. The effects of co-substrate on PHA production, microbial community and carbon conversion were explored. The results showed that proper addition of xylose was beneficial for the synthesis of PHA and monomer 3-hydroxyvalerate (3HV). Higher conversion yield of substrate-to-PHA (YPHA/S) of 0.933 g COD PHA/g COD S and PHA content of 43.6 g PHA/100 g VSS were gained at co-substrate ratio of 1:1. Likewise, under this condition, PHA production also reached the highest value of 1849 mg COD/L (1088 mg/L). Moreover, the addition of xylose created a favorable screening of PHA dominant strains, improved the conversion of carbon source, and saved 72.3% of feedstock consumption.

Deep learning and machine intelligence: New computational modeling techniques for discovery of the combination rules and pharmacodynamic characteristics of Traditional Chinese Medicine.

It has been increasingly accepted that Multi-Ingredient-Based interventions provide advantages over single-target therapy for complex diseases. With the growing development of Traditional Chinese Medicine (TCM) and continually being refined of a holistic view, "multi-target" and "multi-pathway" integration characteristics of which are being accepted. However, its effector substances, efficacy targets, especially the combination rules and mechanisms remain unclear, and more powerful strategies to interpret the synergy are urgently needed. Artificial intelligence (AI) and computer vision lead to a rapidly expanding in many fields, including diagnosis and treatment of TCM. AI technology significantly improves the reliability and accuracy of diagnostics, target screening, and new drug research. While all AI techniques are capable of matching models to biological big data, the specific methods are complex and varied. Retrieves literature by the keywords such as "artificial intelligence", "machine learning", "deep learning", "traditional Chinese medicine" and "Chinese medicine". Search the application of computer algorithms of TCM between 2000 and 2021 in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Elsevier and Springer. This review concentrates on the application of computational in herb quality evaluation, drug target discovery, optimized compatibility and medical diagnoses of TCM. We describe the characteristics of biological data for which different AI techniques are applicable, and discuss some of the best data mining methods and the problems faced by deep learning and machine learning methods applied to Chinese medicine.

Zwitterionic ionic liquids modulating two-dimensional hierarchically porous zeolitic imidazolate framework composites.

HYPOTHESIS: Two-dimensional hierarchically porous zeolitic imidazolate frameworks (H-ZIFs) show great promising applications in catalysis, gas separation, energy storage and sensing. Herein, a facile ionic-liquid-modulation approach is proposed for constructing H-ZIFs nanosheets with tunable thickness. EXPERIMENTS: Sulfo-functionalized zwitterionic ionic liquids (SFIL) have been designed as monodentate ligands to direct the formation of microporous nanosheets (ZIF-SFIL) in aqueous solution. Anions of SFIL have been tuned to modulate the coordination environment, enabling the control of the structure, thickness and pores of the nanosheets. FINDINGS: SFIL is demonstrated to pre-coordinate with Zn(II) to induce micropores with high specific surface areas (up to 1176 m2·g-1) and accelerate the nucleation of crystals. The BF4- anion serves as a competitive ligand to partially replace SFIL to cause structural defects, thus yielding hierarchically porous ZIF-SFIL nanosheets with high specific surface areas (270-466 m2·g-1) and variable thicknesses (from ca. 58 nm to ca. 455 nm). Benefiting from the versatile designability and multifunctionality of ionic liquids, the strategy in this work offers a facile approach for designing and constructing multifunctional materials with hierarchical pores.