Monodispersed Renewable Particles by Cascade and Density Gradient Size Fractionation to Advance Lignin Nanotechnologies.

Control over particle size and shape heterogeneity is highly relevant to the design of photonic coatings and supracolloidal assemblies. Most developments in the area have relied on mineral and petroleum-derived polymers that achieve well-defined chemical and dimensional characteristics. Unfortunately, it is challenging to attain such control when considering renewable nanoparticles. Herein, a pathway toward selectable biobased particle size and physicochemical profiles is proposed. Specifically, lignin is fractionated, a widely available heterogeneous polymer that can be dissolved in aqueous solution, to obtain a variety of monodispersed particle fractions. A two-stage cascade and density gradient centrifugation that relieves the need for solvent pre-extraction or other pretreatments but achieves particle bins of uniform size (~60 to 860 nm and polydispersity, PDI<0.06, dynamic light scattering) along with characteristic surface chemical features is introduced. It is found that the properties and associated colloidal behavior of the particles are suitably classified in distinctive size populations, namely, i) nanoscale (50-100 nm), ii) photonic (100-300 nm) and iii) near-micron (300-1000 nm). The strong correlation that exists between size and physicochemical characteristics (molar mass, surface charge, bonding and functional groups, among others) is introduced as a powerful pathway to identify nanotechnological uses that benefit from the functionality and cost-effectiveness of biogenic particles.

[Network Meta-analysis of Chinese patent medicine in treatment of heart failure with preserved ejection fraction].

This study systematically evaluated the efficacy and safety of different Chinese patent medicines combined with conventional western medicine in the treatment of heart failure with preserved ejection fraction(HFpEF) and ranked for the drug selection. Randomized controlled trial(RCT) on Chinese patent medicines in treatment of HFpEF were obtained from the CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, Web of Science, and other databases from the inception to October 9, 2022. The included RCT was quantitatively analyzed using gemtc and rjags packages of R software for the network Meta-analysis. 74 RCTs were included, with a total of 7 192 patients enrolled, involving 11 different Chinese patent medicines(Shenfu Injection, Shenmai Injection, Qili Qiangxin Capsules, Shexiang Baoxin Pills, Xuezhikang Capsules, Salvia Miltiorrhiza Polyphenols Injection, Tanshinone Ⅱ_A Sulfonate Injection, Xinmailong Injection, Yangxinshi Tablets, Qishen Yiqi Dripping Pills, and Yixinshu Capsules). The results of network Meta-analysis are shown as followed.(1)In terms of improving clinical effective rate, for injection preparations, Xinmailong Injection + conventional western medicine was recommended. while for oral preparations, Shexiang Baoxin Pills + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were preferred.(2)In terms of improving the mitral ratio of peak early to late diastolic filling velocity(E/A), for injection preparations, Shenmai Injection + Salvia Miltiorrhiza Polyphenols Injection + conventional western medicine, Shenmai Injection + conventional western medicine, Shenfu Injection + conventional western medicine were preferred. While for oral preparations, Yixinshu Capsules + conventional western medicine was preferred.(3)In terms of reducing the ratio of early diastolic mitral inflow to early diastolic mitral annular velocity(E/e'), Shenfu Injection + conventional western medicine could be used as injection preparation, and Qili Qiangxin Capsules + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine for oral preparations.(4)In terms of improving 6-minute walking trail(6MWT), the injection preparations such as Shenmai Injection + conventional western medicine, Xinmailong Injection + conventional western medicine were suitable, while oral preparations like Qishen Yiqi Dripping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine were recommended.(5)In terms of reducing N-terminal pro B-type natriuretic peptide(NT-proBNP), Qili Qiangxin Capsules + conventional western medicine were preferred.(6)In terms of reducing B-type natriuretic peptide(BNP), Xinmailong Injection + conventional western medicine could be used for injection preparation and Qili Qiangxin Capsules + conventional western medicine can be used for oral preparation. In terms of adverse drug reactions, there was no significant difference between Chinese patent medicine combined with conventional western conventional and traditional western medicine alone. The results showe that Chinese patent medicine combined with conventional western medicine in treating HFpEF is superior to conventional western medicine alone in reducing clinical symptoms, improving cardiac function, and improving exercise tolerance, which also has good drug safety. However, the existing evidence is still limited by the quality and quantity of included studies, so the above conclusion requires further validation through more prospective RCT.

Unraveling DDIT4 in the VDR-mTOR pathway: a novel target for drug discovery in diabetic kidney disease.

Introduction: Diabetic kidney disease (DKD) necessitates innovative therapeutic strategies. This study delves into the role of DNA damage-inducing transcription factor 4 (DDIT4) within the VDR-mTOR pathway, aiming to identify a novel target for DKD drug discovery. Methods: Transcriptome data from the Gene Expression Omnibus Database were analyzed to assess the expression of mTOR and VDR expression in human renal tissues. Clinical samples from DKD patients and minimal change disease (MCD) controls were examined, and a DKD animal model using 20-week-old db/db mice was established. DDIT4 plasmid transfection was employed to modulate the VDR-mTOR pathway, with its components evaluated using immunohistochemistry, real-time quantitative PCR (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). Results: Changes in the expression of the VDR-mTOR pathway were observed in both DKD patients and the animal model. Overexpression of DDIT4 increased VDR expression and decreased levels of mTOR, p70s6k, and 4E-BP1. Furthermore, DDIT4 treatment regulated autophagy by upregulating LC3I expression and downregulating LC3II expression. Notably, DDIT4 alleviated oxidative stress by reducing the levels of lipid peroxidation product MDA, while simultaneously increasing the levels of superoxide dismutase (SOD) and glutathione (GSH), underscoring the role of DDIT4 in the pathological process of DKD and its potential as a therapeutic target. Conclusion: Unraveling DDIT4's involvement in the VDR-mTOR pathway provides insights for innovative DKD drug discovery, emphasizing its potential as a therapeutic target for future interventions.

Impact of frailty on short-term postoperative outcomes in patients undergoing colorectal cancer surgery: A systematic review and meta-analysis.

BACKGROUND: Colorectal cancer is a major global health challenge that predominantly affects older people. Surgical management, despite advancements, requires careful consideration of preoperative patient status for optimal outcomes. AIM: To summarize existing evidence on the association of frailty with short-term postoperative outcomes in patients undergoing colorectal cancer surgery. METHODS: A literature search was conducted using PubMed, EMBASE and Scopus databases for observational studies in adult patients aged ≥ 18 years undergoing planned or elective colorectal surgery for primary carcinoma and/or secondary metastasis. Only studies that conducted frailty assessment using recognized frailty assessment tools and had a comparator group, comprising nonfrail patients, were included. Pooled effect sizes were reported as weighted mean difference or relative risk (RR) with 95% confidence intervals (CIs). RESULTS: A total of 24 studies were included. Compared with nonfrail patients, frailty was associated with an increased risk of mortality at 30 d (RR: 1.99, 95%CI: 1.47-2.69), at 90 d (RR: 4.76, 95%CI: 1.56-14.6) and at 1 year (RR: 5.73, 95%CI: 2.74-12.0) of follow up. Frail patients had an increased risk of any complications (RR: 1.81, 95%CI: 1.57-2.10) as well as major complications (Clavien-Dindo classification grade ≥ III) (RR: 2.87, 95%CI: 1.65-4.99) compared with the control group. The risk of reoperation (RR: 1.18, 95%CI: 1.07-1.31), readmission (RR: 1.70, 95%CI: 1.36-2.12), need for blood transfusion (RR: 1.67, 95%CI: 1.52-1.85), wound complications (RR: 1.49, 95%CI: 1.11-1.99), delirium (RR: 4.60, 95%CI: 2.31-9.16), risk of prolonged hospitalization (RR: 2.09, 95%CI: 1.22-3.60) and discharge to a skilled nursing facility or rehabilitation center (RR: 3.19, 95%CI: 2.0-5.08) was all higher in frail patients. CONCLUSION: Frailty in colorectal cancer surgery patients was associated with more complications, longer hospital stays, higher reoperation risk, and increased mortality. Integrating frailty assessment appears crucial for tailored surgical management.

The combination of high temperature and Vibrio infection worsens summer mortality in the clam Meretrix petechialis by increasing apoptosis and oxidative stress.

The interaction between environmental factors and Vibrio in bivalves is not well understood, despite the widely held belief that pathogen infection and seawater temperature significantly impact summer mortality. In the present study, we conducted simulated experiments to explore the effects of high temperature and Vibrio infection on the clam Meretrix petechialis. The survival curve analysis revealed that the combined challenge of high temperature and Vibrio infection (31°C-vibrio) led to significantly higher clam mortality compared to the groups exposed solely to Vibrio (27°C-vibrio), high temperature (31°C-control), and the control condition (27°C-control). Furthermore, PCoA analysis of 11 immune genes indicated that Vibrio infection predominated during the incubation period, with a gradual equilibrium between these factors emerging during the course of the infection. Additionally, our investigations into apoptosis and autophagy processes exhibited significant induction of mTOR and Bcl2 of the 31°C-vibrio group in the early challenge stage, followed by inhibition in the later stage. Oxidative stress analysis demonstrated a substantial additive effect on malondialdehyde (MDA) and glutathione (GSH) content in the combined challenge group compared to the control group. Comparative transcriptome analysis revealed a significant increase in differentially expressed genes related to immunity, such as complement C1q-like protein, C-type lectin, big defensin, and lysozyme, in the 31°C-vibrio group, suggesting that the synergistic effect of high temperature and Vibrio infection triggers more robust antibacterial immune responses. These findings provide critical insights for understanding the infection process and uncovering the causes of summer mortality.

Bioinformatics and system biology approach to identify the influences among COVID-19, influenza, and HIV on the regulation of gene expression.

Background: Coronavirus disease (COVID-19), caused by SARS-CoV-2, has emerged as a infectious disease, coexisting with widespread seasonal and sporadic influenza epidemics globally. Individuals living with HIV, characterized by compromised immune systems, face an elevated risk of severe outcomes and increased mortality when affected by COVID-19. Despite this connection, the molecular intricacies linking COVID-19, influenza, and HIV remain unclear. Our research endeavors to elucidate the shared pathways and molecular markers in individuals with HIV concurrently infected with COVID-19 and influenza. Furthermore, we aim to identify potential medications that may prove beneficial in managing these three interconnected illnesses. Methods: Sequencing data for COVID-19 (GSE157103), influenza (GSE185576), and HIV (GSE195434) were retrieved from the GEO database. Commonly expressed differentially expressed genes (DEGs) were identified across the three datasets, followed by immune infiltration analysis and diagnostic ROC analysis on the DEGs. Functional enrichment analysis was performed using GO/KEGG and Gene Set Enrichment Analysis (GSEA). Hub genes were screened through a Protein-Protein Interaction networks (PPIs) analysis among DEGs. Analysis of miRNAs, transcription factors, drug chemicals, diseases, and RNA-binding proteins was conducted based on the identified hub genes. Finally, quantitative PCR (qPCR) expression verification was undertaken for selected hub genes. Results: The analysis of the three datasets revealed a total of 22 shared DEGs, with the majority exhibiting an area under the curve value exceeding 0.7. Functional enrichment analysis with GO/KEGG and GSEA primarily highlighted signaling pathways associated with ribosomes and tumors. The ten identified hub genes included IFI44L, IFI44, RSAD2, ISG15, IFIT3, OAS1, EIF2AK2, IFI27, OASL, and EPSTI1. Additionally, five crucial miRNAs (hsa-miR-8060, hsa-miR-6890-5p, hsa-miR-5003-3p, hsa-miR-6893-3p, and hsa-miR-6069), five essential transcription factors (CREB1, CEBPB, EGR1, EP300, and IRF1), and the top ten significant drug chemicals (estradiol, progesterone, tretinoin, calcitriol, fluorouracil, methotrexate, lipopolysaccharide, valproic acid, silicon dioxide, cyclosporine) were identified. Conclusion: This research provides valuable insights into shared molecular targets, signaling pathways, drug chemicals, and potential biomarkers for individuals facing the complex intersection of COVID-19, influenza, and HIV. These findings hold promise for enhancing the precision of diagnosis and treatment for individuals with HIV co-infected with COVID-19 and influenza.

Systematic Optimization of Universal Real-Time Hypersensitive Fast Detection Method for HBsAg in Serum Based on SERS.

Hepatitis B virus (HBV) is a major cause of liver cirrhosis and hepatocellular carcinoma, with HBV surface antigen (HBsAg) being a crucial marker in the clinical detection of HBV. Due to the significant harm and ease of transmission associated with HBV, HBsAg testing has become an essential part of preoperative assessments, particularly for emergency surgeries where healthcare professionals face exposure risks. Therefore, a timely and accurate detection method for HBsAg is urgently needed. In this study, a surface-enhanced Raman scattering (SERS) sensor with a sandwich structure was developed for HBsAg detection. Leveraging the ultrasensitive and rapid detection capabilities of SERS, this sensor enables quick detection results, significantly reducing waiting times. By systematically optimizing critical factors in the detection process, such as the composition and concentration of the incubation solution as well as the modification conditions and amount of probe particles, the sensitivity of the SERS immune assay system was improved. Ultimately, the sensor achieved a sensitivity of 0.00576 IU/mL within 12 min, surpassing the clinical requirement of 0.05 IU/mL by an order of magnitude. In clinical serum assay validation, the issue of false positives was effectively addressed by adding a blocker. The final sensor demonstrated 100% specificity and sensitivity at the threshold of 0.05 IU/mL. Therefore, this study not only designed an ultrasensitive SERS sensor for detecting HBsAg in actual clinical serum samples but also provided theoretical support for similar systems, filling the knowledge gap in existing literature.

Causes and global, regional, and national burdens of traumatic brain injury from 1990 to 2019.

PURPOSE: Traumatic brain injury (TBI), currently a major global public health problem, imposes a significant economic burden on society and families. We aimed to quantify and predict the incidence and severity of TBI by analyzing its incidence, prevalence, and years lived with disability (YLDs). The epidemiological changes in TBI from 1990 to 2019 were described and updated to provide a reference for developing prevention, treatment, and incidence-reducing measures for TBI. METHODS: A secondary analysis was performed on the incidence, prevalence, and YLDs of TBI by sex, age group, and region (n = 21,204 countries and territories) between 1990 and 2019 using the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Proportions in the age-standardized incidence rate due to underlying causes of TBI and proportions of minor and moderate or severe TBI were also reported. RESULTS: In 2019, there were 27.16 million (95% uncertainty intervals (UI): 23.36 - 31.42) new cases of TBI worldwide, with age-standardized incidence and prevalence rates of 346 per 100,000 population (95% UI: 298-401) and 599 per 100,000 population (95% UI: 573-627), respectively. From 1990 to 2019, there were no significant trends in global age-standardized incidence (estimated annual percentage changes: -0.11%, 95% UI: -0.18% - -0.04%) or prevalence (estimated annual percentage changes: 0.01%, 95% UI: -0.04% - 0.06%). TBI caused 7.08 million (95% UI: 5.00 - 9.59) YLDs in 2019, with age-standardized rates of 86.5 per 100,000 population (95% UI: 61.1 - 117.2). In 2019, the countries with higher incidence rates were mainly distributed in Central Europe, Eastern Europe, and Australia. The 2019 global age-standardized incidence rate was higher in males than in females. The 2019 global incidence of moderate and severe TBI was 182.7 per 100,000 population, accounting for 52.8% of all TBI, with falls and road traffic injuries being the main causes in most regions. CONCLUSIONS: The incidence of moderate and severe TBI was slightly higher in 2019, and TBI still accounts for a significant portion of the global injury burden. The likelihood of moderate to severe TBI and the trend of major injury under each injury cause from 1990 to 2019 and the characteristics of injury mechanisms in each age group are presented, providing a basis for further research on injury causes in each age group and the future establishment of corresponding policies and protective measures.

Validity Of A Novel Simulator For Percutaneous Transforaminal Endoscopic Discectomy.

BACKGROUND: Percutaneous transforaminal endoscopic discectomy (PTED) has steep learning curves and a high incidence of complications, but currently, efficient and economical training methods are lacking. This study aimed to validate a novel simulator for PTED. METHODS: The simulated PTED included puncturing and establishing the working channel (PEWC) and endoscopic discectomy, with the PEWC being the tested module. 11 experts and 21 novices were included and introduced to the simulator and tasks; all participants completed the PEWC. Outcomes included: total operation time, number of fluoroscopy for positioning the working sheath, number of spinal risk region invasion, Global Rating Scale (GRS) and a modified GRS, etc. The Mann-Whitney U test was used to compare two groups. Spearman's correlation coefficient analyzed continuous variables. RESULTS: Experts outperformed novices in total operation time (P = 0.001), requiring fewer number of fluoroscopies for positioning the working sheath (P = 0.003). Additionally, experts had a lower number of spinal risk region invasions (P = 0.016) and higher scores on both the GRS (P < 0.001) and modified GRS (P < 0.001). PTED experience correlated with GRS scores (P = 0.001) and modified GRS (P < 0.001). The overall realism scored a median of 4 (3.75-5), and educational value had a median of 4 (3-5). CONCLUSIONS: This study demonstrates the validity of the novel simulator, revealing significant associations between PTED experience and performance metrics in a simulated PEWC setting. Furthermore, the PEWC module also offers a good realistic design and high education value according to experts.

Serum Interleukin-6 and Serum Ferritin Levels Are the Independent Risk Factors for Pneumonia in Elderly Patients.

Pneumonia is a common infection in elderly patients. We explored the correlations of serum interleukin-6 (IL-6) and serum ferritin (SF) levels with immune function/disease severity in elderly pneumonia patients. Subjects were allocated into the mild pneumonia (MP), severe pneumonia (SP), and normal groups, with their age/sex/body mass index/ disease course and severity/blood pressure/comorbidities/medications/prealbumin (PA)/albumin (ALB)/C-reactive protein (CRP)/procalcitonin (PCT)/smoking status documented. The disease severity was evaluated by pneumonia severity index (PSI). T helper 17 (Th17)/regulatory T (Treg) cell ratios and IL-6/SF/immunoglobulin G (IgG)/Th17 cytokine (IL-21)/Treg cytokine (IL-10)/PA/ALB levels were assessed. The correlations between these indexes/independent risk factors in elderly patients with severe pneumonia were evaluated. There were differences in smoking and CRP/PCT/ALB/PA levels among the three groups, but only CRP/ALB were different between the MP/SP groups. Pneumonia patients exhibited up-regulated Th17 cell ratio and serum IL-6/SF/IL-21/IL-10/IgG levels, down-regulated Treg cell ratio, and greater differences were noted in severe cases. Serum IL-6/SF levels were positively correlated with disease severity, immune function, and IL-21/IL-10/IgG levels. Collectively, serum IL-6 and SF levels in elderly pneumonia patients were conspicuously positively correlated with disease severity and IL-21/IL-10/IgG levels. CRP, ALB, IL-6 and SF levels were independent risk factors for severe pneumonia in elderly patients.

In Situ Probing the Structure Change and Interaction of Interfacial Water and Hydroxyl Intermediates on Ni(OH)2 Surface over Water Splitting.

There is growing acknowledgment that the properties of the electrochemical interfaces play an increasingly pivotal role in improving the performance of the hydrogen evolution reaction (HER). Here, we present, for the first time, direct dynamic spectral evidence illustrating the impact of the interaction between interfacial water molecules and adsorbed hydroxyl species (OHad) on the HER properties of Ni(OH)2 using Au/core-Ni(OH)2/shell nanoparticle-enhanced Raman spectroscopy. Notably, our findings highlight that the interaction between OHad and interfacial water molecules promotes the formation of weakly hydrogen-bonded water, fostering an environment conducive to improving the HER performance. Furthermore, the participation of OHad in the reaction is substantiated by the observed deprotonation step of Au@2 nm Ni(OH)2 during the HER process. This phenomenon is corroborated by the phase transition of Ni(OH)2 to NiO, as verified through Raman and X-ray photoelectron spectroscopy. The significant redshift in the OH-stretching frequency of water molecules during the phase transition confirms that surface OHad disrupts the hydrogen-bond network of interfacial water molecules. Through manipulation of the shell thickness of Au@Ni(OH)2, we additionally validate the interaction between OHad and interfacial water molecules. In summary, our insights emphasize the potential of electrochemical interfacial engineering as a potent approach to enhance electrocatalytic performance.

Parenting style and child mental health at preschool age: evidence from rural China.

BACKGROUND: Mental health problems among children at preschool age are a common issue across the world. As shown in literature, a caregiver's parenting style can play a critical role in child development. This study aims to examine the associations between a caregiver's parenting style and the mental health problems (or not) of their child when he/she is at preschool age in rural China. METHODS: Participants were children, aged 49 to 65 months, and their primary caregivers. The primary caregivers of the sample children completed the Parenting Styles and Dimensions Questionnaire, Short Version, the Strengths and Difficulties Questionnaire, and a questionnaire that elicited their socio-demographic characteristics. The level of cognitive development of each sample child was assessed using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition. Pearson correlation analysis, linear regression analysis, and multivariable regression analysis were used to analyze the data. RESULTS: The prevalence of mental health problems among sample children at preschool age was high (31.6%). If a caregiver practices an authoritative parenting style, it was found to be negatively associated with the mental health problems of their child. In contrast, a caregiver's authoritarian parenting style was positively associated with the mental health problems of their child. Compared to those in a subgroup of primary caregivers that used a combination of low authoritative and low authoritarian parenting style, primary caregivers that used a combination of high authoritarian and low authoritative or a combination of high authoritative and high authoritarian were found to have positive association with child health problems. A number of demographic characteristics were found to be associated with the adoption of different parenting styles. CONCLUSION: Different parenting styles (including authoritative, authoritarian, and combination of authoritative and authoritarian) of the sample caregivers had different associations with the mental health problems of the sample children. Parenting programs that aim to improve the parenting styles (favoring authoritative parenting styles) should be promoted in an effort to improve the status of child mental health in rural China.

Immobilization of Coprinus comatus with magnetic alginate hydrogel microsphere for improving the antioxidant activity of fermentation products.

Coprinus comatus is an edible mushroom and its fermented product possesses antioxidant activity. In this study, to further enhance the antioxidant activity and improve the reusability of the strain, calcium alginate hydrogel was used as the carrier for embedding and immobilizing Coprinus comatus. The effects of CaCl2 concentration, sodium alginate concentration, microsphere diameter, and the amount of magnetic particle on the antioxidant activity of fermented products were investigated. The results showed that the magnetic immobilized microsphere prepared by 2.50% CaCl2, 2.00% sodium alginate and 0.50% Fe3O4 had the best fermentation antioxidant activity (EC50 was 0.43 ± 0.01 mg/mL) when the diameter was 5 mm, which increased by 24.56% compared to the initial activity. Besides, the microsphere showed strong reusability, the antioxidant activity was still better than the free strain after being used five times. This study not only enhanced the antioxidant activity of Coprinus comatus fermented product through immobilization, but also provided an effective method for microbial fermentation.

HBI-8000 improves heart failure with preserved ejection fraction via the TGF-ß1/MAPK signalling pathway.

Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of total heart failure patients and is characterized by peripheral circulation, cardiac remodelling and comorbidities (such as advanced age, obesity, hypertension and diabetes) with limited treatment options. Chidamide (HBI-8000) is a domestically produced benzamide-based histone deacetylase isoform-selective inhibitor used for the treatment of relapsed refractory peripheral T-cell lymphomas. Based on our in vivo studies, we propose that HBI-8000 exerts its therapeutic effects by inhibiting myocardial fibrosis and myocardial hypertrophy in HFpEF patients. At the cellular level, we found that HBI-8000 inhibits AngII-induced proliferation and activation of CFs and downregulates the expression of fibrosis-related factors. In addition, we observed that the HFpEF group and AngII stimulation significantly increased the expression of TGF-ß1 as well as phosphorylated p38MAPK, JNK and ERK, whereas the expression of the above factors was significantly reduced after HBI-8000 treatment. Activation of the TGF-ß1/MAPK pathway promotes the development of fibrotic remodelling, and pretreatment with SB203580 (p38MAPK inhibitor) reverses this pathological change. In conclusion, our data suggest that HBI-8000 inhibits fibrosis by modulating the TGF-ß1/MAPK pathway thereby improving HFpEF. Therefore, HBI-8000 may become a new hope for the treatment of HFpEF patients.

Brain frailty associated with stroke events in anterior circulation large artery occlusion.

OBJECTIVE: To investigate the factors associated with brain frailty and the effect of brain frailty in patients with anterior circulation large artery occlusion (AC-LAO). METHODS: 1100 patients with AC-LVO consecutively admitted to the Second Hospital of Hebei Medical University, North China between June 2016 and April 2018 were retrospectively analyzed. The variables associated with brain frailty and stroke outcome were analyzed by ANOVA analysis, the Mann-Whitney U test and multiple linear regression. Based on previous research. Brain frailty score comprises 1 point each for white matter hyperintensity (WMH), old infarction lesions, and cerebral atrophy among 983 participants with baseline brain magnetic resonance imaging or computed tomography. RESULTS: Among AC-LAO participants, baseline brain frailty score ≥ 1 was common (750/983, 76.3%). Duration of hypertension > 5 years (mean difference [MD] 0.236, 95% CI 0.077, 0.395, p = 0.004), multiple vessel occlusion (MD 0.339, 95% CI 0.068, 0.611, p = 0.014) and basal ganglia infarction (MD -0.308, 95% CI -0.456, -0.160, p < 0.001) were independently associated with brain frailty score. Brain frailty score was independently associated with stroke events, and higher brain frailty scores were associated with higher rates of stroke events (p < 0.001). However, brain frailty has no independent effect on short-term outcome of ACI in AC-LAO patients. CONCLUSIONS: In AC-LAO patients, older age, duration of hypertension > 5 years, and multiple vessel occlusion influenced the brain frailty score. Brain frailty score was independently associated with the occurrence of stroke events in AC-LAO patients.

DAE-CFR: detecting microRNA-disease associations using deep autoencoder and combined feature representation.

BACKGROUND: MicroRNA (miRNA) has been shown to play a key role in the occurrence and progression of diseases, making uncovering miRNA-disease associations vital for disease prevention and therapy. However, traditional laboratory methods for detecting these associations are slow, strenuous, expensive, and uncertain. Although numerous advanced algorithms have emerged, it is still a challenge to develop more effective methods to explore underlying miRNA-disease associations. RESULTS: In the study, we designed a novel approach on the basis of deep autoencoder and combined feature representation (DAE-CFR) to predict possible miRNA-disease associations. We began by creating integrated similarity matrices of miRNAs and diseases, performing a logistic function transformation, balancing positive and negative samples with k-means clustering, and constructing training samples. Then, deep autoencoder was used to extract low-dimensional feature from two kinds of feature representations for miRNAs and diseases, namely, original association information-based and similarity information-based. Next, we combined the resulting features for each miRNA-disease pair and used a logistic regression (LR) classifier to infer all unknown miRNA-disease interactions. Under five and tenfold cross-validation (CV) frameworks, DAE-CFR not only outperformed six popular algorithms and nine classifiers, but also demonstrated superior performance on an additional dataset. Furthermore, case studies on three diseases (myocardial infarction, hypertension and stroke) confirmed the validity of DAE-CFR in practice. CONCLUSIONS: DAE-CFR achieved outstanding performance in predicting miRNA-disease associations and can provide evidence to inform biological experiments and clinical therapy.

Biomimetic tri-layered artificial skin comprising silica gel-collagen membrane-collagen porous scaffold for enhanced full-thickness wound healing.

Full-thickness wounds are severe cutaneous damages with destroyed self-healing function, which need efficient clinical interventions. Inspired by the hierarchical structure of natural skin, we have for the first time developed a biomimetic tri-layered artificial skin (TLAS) comprising silica gel-collagen membrane-collagen porous scaffold for enhanced full-thickness wound healing. The TLAS with the thickness of 3-7 mm displays a hierarchical nanostructure consisting of the top homogeneous silica gel film, the middle compact collagen membrane, and the bottom porous collagen scaffold, exquisitely mimicking the epidermis, basement membrane and dermis of natural skin, respectively. The 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide/N-Hydroxysuccinimide-dehydrothermal (EDC/NHS-DHT) dual-crosslinked collagen composite bilayer, with a crosslinking degree of 79.5 %, displays remarkable biocompatibility, bioactivity, and biosafety with no risk of hemolysis and pyrogen reactions. Notably, the extra collagen membrane layer provides a robust barrier to block the penetration of silica gel into the collagen porous scaffold, leading to the TLAS with enhanced biocompatibility and bioactivity. The full-thickness wound rat model studies have indicated the TLAS significantly facilitates the regeneration of full-thickness defects by accelerating re-epithelization, collagen deposition and migration of skin appendages. The highly biocompatible and bioactive tri-layered artificial skin provides an improved treatment for full-thickness wounds, which has great potential in tissue engineering.

Copper-Catalyzed Site-Selective Electrophilic Aromatic Alkylation of Monosubstituted Simple Arenes.

A copper-catalyzed highly para-selective electrophilic aromatic alkylation of monosubstituted simple arenes has been accomplished. This method provides a practical platform for the transformation from simple commercial arenes to well-defined di- and multisubstituted aromatics with high added value. Control experiments and DFT calculations reveal that the achievement of the excellent site-selectivity is ascribed to the controlled deprotonation of the Wheland intermediates. Remarkably, the type of alkylating regent has been shown to have a significant impact on site-selectivity.

Potential Function of 3,5-Dihydroxy-4-Methoxybenzyl Alcohol from Pacific Oyster (Crassostrea gigas) in Brain of Old Mice.

SCOPE: 3,5-Dihydroxy-4-methoxybenzyl alcohol (DHMBA) is found in oyster extracts in recent years and is reported to have antioxidant activity. Although it has been reported to be protective in various models of oxidative stress, the therapeutic effect of DHMBA on neurological damage caused by aging remains to be demonstrated. METHODS AND RESULTS: The present study investigates the potential functions of DHMBA in brain of old C57BL/6J mice and aging cell model. Administration of DHMBA improves working memory, reduces anxiety behavior, decreases the expression levels of cell cycle proteins, cycin-dependent kinase inhibitor 1(P21) and peptidase inhibitor 16(P16)  and inhibits neuronal loss in old mice. The data obtained from the aging cell model are consistent with those from the old mice. The interaction between DHMBA and Kelch-like ECH-associated protein 1 (Keap1) is predicted by molecular docking assay, and then it is verified by co-immunopricipitation (CoIP) that factor red lineage 2-related factor 2 (Nrf2)-Keap1 protein-protein interaction is inhibited by DHMBA. Protein levels of Nrf2 and its target genes, such as glutathione peroxidase 4(GPX4) and heme oxygenase 1 (HO-1), are detected in old mice and aging cell model. CONCLUSION: This study provides new evidence that explores the antioxidant mechanism of DHMBA and implies a potential role of DHMBA on antiaging in brain.

Autokinesis Reveals a Threshold for Perception of Visual Motion.

In natural viewing conditions, the brain can optimally integrate retinal and extraretinal signals to maintain a stable visual perception. These mechanisms, however, may fail in circumstances where extraction of a motion signal is less viable such as impoverished visual scenes. This can result in a phenomenon known as autokinesis in which one may experience apparent motion of a small visual stimulus in an otherwise completely dark environment. In this study, we examined the effect of autokinesis on visual perception of motion in human observers. We used a novel method with optical tracking in which the visual motion was reported manually by the observer. Experiment results show at lower speeds of motion, the perceived direction of motion was more aligned with the effect of autokinesis, whereas in the light or at higher speeds in the dark, it was more aligned with the actual direction of motion. These findings have important implications for understanding how the stability of visual representation in the brain can affect accurate perception of motion signals.