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A strategy for the synthesis of iodo-substituted allylic pyrazoles through NIS-mediated regioselective addition of allenamides with pyrazoles is presented. This reaction proceeds rapidly, is scalable up to a gram scale, and tolerates a broad scope of substrates. Moreover, using 1,2,4-triazole as the nucleophile, the corresponding 1,2-addition product was obtained in good yield. Significantly, the products of this reaction, iodo-substituted allylic pyrazoles, could undergo coupling with phenylacetylene under Sonogashira cross-coupling conditions. [ABSTRACT FROM AUTHOR]

Background and Objectives: The Rh blood group system is the most polymorphic human blood group system. Previous studies have investigated variants in the RHD and RHCE promoter. The relevance of these variants to the Chinese Han population is further clarified in this study. Materials and Methods: In total, 317 donors (223 Rh D‐positive [D+], including 20 Del and 94 Rh D‐negative [D−]) were randomly selected. The promoter regions and exon 1 of RHD and RHCE were amplified through polymerase chain reaction (PCR) whose products were directly sequenced using forward and reverse primers. Results: Expected PCR products of the RHD promoter and exon 1 were amplified in 223 D+ individuals, including 20 Del individuals, and were absent in 81 of 94 D− individuals. Expected PCR products of RHCE were observed in all donors. Two single nucleotide variants (SNVs) were observed in the RHD promoter region. Moreover, 11 SNVs were observed in the promoter and exon 1 of RHCE. rs4649082, rs2375313, rs2281179, rs2072933, rs2072932, rs2072931 and rs586178 with strong linkage disequilibria were significantly different between the D+ and D− groups. [A;C] was the most common haplotype in the RHD promoter (NC_000001.11:g.[−1033A>G;−831C>T]). [G;T;T;A;T;A;C;G;A;C;G] was the most predominant haplotype in both total and D− groups. In D+ individuals, [A;C;T;G;C;G;C;G;C;C;C] was the most frequent haplotype in the RHCE promoter (NC_000001.11:g.[−1080A>G;−958C>T;−390T>C;−378G>A;−369C>T;−296G>A;−144C>G;−132G>A;−122C>A;28C>T;48C>G]). Conclusion: We speculate that the SNVs/haplotypes found in this article cannot significantly affect gene expression. The present study findings should help elucidate the molecular basis of the polymorphic expression of RHD and RHCE promoter regions. [ABSTRACT FROM AUTHOR]

Macrophages are highly heterogeneous and exhibit a diversity of functions and phenotypes. They can be divided into pro‐inflammatory macrophages (M1) and anti‐inflammatory macrophages (M2). Diabetic wounds are characterized by a prolonged inflammatory phase and difficulty in healing due to the accumulation of pro‐inflammatory (M1) macrophages in the wound. Therefore, hydrogel dressings with macrophage heterogeneity regulation function hold great promise in promoting diabetic wound healing in clinical applications. However, the precise conversion of pro‐inflammatory M1 to anti‐inflammatory M2 macrophages by simple and biosafe approaches is still a great challenge. Here, an all‐natural hydrogel with the ability to regulate macrophage heterogeneity is developed to promote angiogenesis and diabetic wound healing. The protocatechuic aldehyde hybridized collagen‐based all‐natural hydrogel exhibits good bioadhesive and antibacterial properties as well as reactive oxygen species scavenging ability. More importantly, the hydrogel is able to convert M1 macrophages into M2 macrophages without the need for any additional ingredients or external intervention. This simple and safe immunomodulatory approach shows great application potential for shortening the inflammatory phase of diabetic wound repair and accelerating wound healing. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is a global public health burden. Chronic HCV infection leads to the development of fibrosis, cirrhosis, liver cancer, and liver failure over time. A total of 250 patients with chronic HCV infection and 299 healthy blood donors were recruited. Sixteen candidate single nucleotide polymorphisms (SNPs) in chemokine (C-C motif) ligand 2 (CCL2), CCL5, CCL8, C-C chemokine receptor 2 (CCR2), and CCR5 were genotyped in all participants. The rs1024610 AA genotype was significantly associated with decreased susceptibility to chronic HCV infection. Aspartate aminotransferase (AST) levels, AST/platelet ratio index, and the fibrosis 4 score were significantly lower in the CCL2 rs1024610 T allele and haplotype ATGC carriers. Moreover, expression levels of collagen IV (C–IV) and laminin (LN) were significantly higher in patients with the CCL5 rs2280788 C allele compared to the non-carriers. Similarly, the expression levels of C–IV, LN, and hyaluronic acid were significantly higher in patients with the CCL5 haplotype, TGCT. No significant differences were identified between the SNPs/haplotypes and plasma levels of CCL2, CCL5, CCL8, CCR2, and CCR5 in the healthy controls, and the rs1024610 allele alteration had no effect on CCL2 promoter activity. This is the first study to report an association between CCL2 rs1024610 and the risk of chronic HCV infection in the Chinese Han population. rs1024610 and ATGC haplotype in CCL2 were reasonable candidate markers of liver abnormalities. rs2280788 and TGCT haplotype in CCL5 are likely to play a significant role in liver fibrosis during chronic HCV infection. [ABSTRACT FROM AUTHOR]

Ischemic stroke caused by arterial occlusion is the most common type of stroke, which is among the most frequent causes of disability and death worldwide. Current treatment approaches involve achieving rapid reperfusion either pharmacologically or surgically, both of which are time‐sensitive; moreover, blood flow recanalization often causes ischemia/reperfusion injury. However, even though neuroprotective intervention is urgently needed in the event of stroke, the exact mechanisms of neuronal death during ischemic stroke are still unclear, and consequently, the capacity for drug development has remained limited. Multiple cell death pathways are implicated in the pathogenesis of ischemic stroke. Here, we have reviewed these potential neuronal death pathways, including intrinsic and extrinsic apoptosis, necroptosis, autophagy, ferroptosis, parthanatos, phagoptosis, and pyroptosis. We have also reviewed the latest results of pharmacological studies on ischemic stroke and summarized emerging drug targets with a focus on clinical trials. These observations may help to further understand the pathological events in ischemic stroke and bridge the gap between basic and translational research to reveal novel neuroprotective interventions. [ABSTRACT FROM AUTHOR]

We previously reported that interleukin (IL)‐6 in the red nucleus (RN) is involved in the maintenance of neuropathic pain induced by spared nerve injury (SNI), and exerts a facilitatory effect via Janus‐activated kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) and extracellular signal‐regulated kinase (ERK) signal transduction pathways. The present study aimed at investigating the roles of tumor necrosis factor‐α (TNF‐α) and IL‐1β in RN IL‐6‐mediated maintenance of neuropathic pain and related signal transduction pathways. Being similar to the elevation of RN IL‐6 three weeks after SNI, increased protein levels of both TNF‐α and IL‐1β were also observed in the contralateral RN three weeks after the nerve injury. The upregulations of TNF‐α and IL‐1β were closely correlative with IL‐6 and suppressed by intrarubral injection of a neutralizing antibody against IL‐6. Administration of either the JAK2 antagonist AG490 or the ERK antagonist PD98059 to the RN of rats with SNI remarkably increased the paw withdrawal threshold (PWT) and inhibited the up‐regulations of local TNF‐α and IL‐1β. Further experiments indicated that intrarubral injection of exogenous IL‐6 in naive rats apparently lowered the PWT of the contralateral hindpaw and boosted the local expressions of TNF‐α and IL‐1β. Pretreatment with AG490 could block IL‐6‐induced tactile hypersensitivity and suppress the up‐regulations of both TNF‐α and IL‐1β. However, injection of PD98059 in advance only inhibited the upregulation of IL‐1β, but not TNF‐α. These findings indicate that RN IL‐6 mediates the maintenance of neuropathic pain by inducing the productions of TNF‐α and IL‐1β. IL‐6 induces the expression of TNF‐α through the JAK2/STAT3 pathway, and the production of IL‐1β through the JAK2/STAT3 and ERK pathways. [ABSTRACT FROM AUTHOR]

Aim: A total of 241 patients with chronic HCV infection were recruited to investigate the association between liver fibrosis and PLT counts, as well as with MPV, PDW and P-LCR indices. Methods: The determination of PLT indices was carried out using a Sysmex XT-1800i automated hematology analyzer. Serological tests for HA, LN, C-IV and PIIINP were performed in 210 patients. The liver stiffness was measured in 69 patients by transient elastography (FibroScan). Results: The analysis showed that the four serum fibrosis markers were negatively correlated with PLT counts, but positively correlated with the MPV, PDW and P-LCR values. Moreover, a similar pattern was found after analyzing the FibroScan measurements, which were negatively correlated with PLT counts, but positively correlated with MPV, PDW and P-LCR values. We subdivided the HCV-infected patients into mild and advanced fibrosis groups. The PLT counts were significantly decreased and the MPV, PDW and P-LCR values were significantly increased in the advanced fibrosis group when compared with the mild fibrosis group. Conclusions: Our results demonstrate that not only the PLT counts but also the MPV, PDW and P-LCR indices significantly correlate with liver fibrosis in HCV-infected patients. Therefore, these indices may be useful laboratory measures for evaluating liver fibrosis progression. [ABSTRACT FROM AUTHOR]

Background: End-stage renal disease (ESRD), the last stage of chronic renal failure, is a global health problem. The number of ESRD patients worldwide is increasing faster than the number of kidneys available per year for renal transplantation. Most of the ESRD patients are awaiting renal transplantation. The immune response to the transplanted kidney is directed mainly against mismatched human leukocyte antigen (HLA) glycoproteins expressed on donor tissues. Thus, the analysis of HLA allele and haplotype polymorphisms is valuable not only for identifying ESRD susceptibility factors but also to improve graft survival. Methods: In this study, 163 Han ESRD patients were recruited to participate. The blood samples were genotyped by sequence-specific oligonucleotide method. A group of 14,529 healthy Chinese Han individuals registered at the Dalian Blood Center as bone marrow donors, living in the same region and of the same ethnicity, were used as controls. Results: We found that only one allele, HLA-DRB1 12, showed a positive association with ESRD (p = 0.004,pc = 0.028, odds ratio = 1.530, 95% confidence interval = 1.147–2.041); A 02-B 40-DRB1 09, A 02-B 40-DRB1 12, A 24-B 15-DRB1 12, and B 40-DRB1 12 were significantly more frequent in ESRD patients after Bonferroni correction (pc < 0.05). Conclusion: They were potentially valuable predictors for evaluating the risk of ESRD in the Dalian Han population. [ABSTRACT FROM AUTHOR]

Cardioembolic stroke due to atrial fibrillation (AF) and/or rheumatic heart disease (RHD) often involves hemorrhagic transformation (HT), and we examined whether leukoaraiosis (LA) was associated with HT in these cases. We prospectively enrolled 251 patients who were admitted to two hospitals within one month of experiencing cardioembolic stroke due to AF/RHD. LA severity was assessed using three visual rating scales. HT was identified in 99 patients (39.4%) based on baseline computed tomography (CT) and post-admission magnetic resonance imaging or second CT. Univariate analysis identified risk of HT as higher in the presence of frontal LA based on the age-related white matter changes scale and in the presence of anterior LA based on the VSS scale. Multivariate analysis confirmed that moderate to severe LA was independently associated with higher HT risk. Of the various sites affected in LA, frontal LA correlated with highest risk of HT (OR 3.199, 95%CI 1.555–6.580). These results suggest that moderate to severe LA, especially at periventricular and anterior sites, is associated with HT after cardioembolic stroke due to AF/RHD. These findings suggest the need to take LA into account as a HT risk factor when considering the use of anticoagulation and thrombolysis in these patients. [ABSTRACT FROM AUTHOR]

Synoptic systems and microphysical properties associated with a sea fog event are analyzed based on the measurements of visibility, meteorological elements and fog droplet spectrum from a comprehensive field campaign in Xiamen, Fujian province during spring 2013. The influences of meteorological elements on the microstructures of the sea fog are also discussed. The results showed that the wind speed and direction changed suddenly during the intermittent and disperse phases of the sea fog. Liquid water content, number concentration and average diameter varied obviously in the development, mature and disperse phases of the sea fog. The burst re-enforcement of sea fog was accompanied by explosive broadening of fog droplet spectrum; average diameter, number concentration and liquid water content increased sharply; and background meteorological conditions also changed significantly. The microstructures fluctuated intensely due to changes in turbulence, radiation and meteorological conditions at different stages, including nucleation, condensation, coagulation, and evaporation, as well as the discontinuity of spatial distribution of droplets. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to explore factors affecting cardiorespiratory fitness in males and females with different body mass index (BMI). Methods: The National Health and Nutrition Examination Survey 1999–2004 data were used for this retrospective study. Estimated maximal oxygen uptake (VO2max) is surrogate for cardiorespiratory fitness (CRF). Univariate and multivariate linear regression analyses were performed to explore whether study variables were associated with estimated VO2max stratified by gender and BMI categories. Results: A total of 3292 subjects 20–49 years of age were included in the analysis. CRF significantly decreased as BMI increased in both females and males. Ethnic difference was found in normal BMI in both genders and obese females; homocysteine was significantly negatively associated with estimated VO2max, as was total cholesterol. Obese male subjects with diabetes had a lower estimated VO2max than those without diabetes, and C-reactive protein (CRP) level and vitamin B12 level were significantly negatively associated with CRF. Female subjects with diabetes had higher estimated VO2max than those without diabetes. Folate was significantly positively correlated with estimated VO2max, whereas CRP was negatively correlated in obese female. Conclusions: There are different predictors of CRF in males and females, and in individuals with different BMI. Different BMI classes are associated with different predictors of cardiorespiratory fitness. Indicators of cardiorespiratory fitness differ between sexes. [ABSTRACT FROM AUTHOR]

Haze-to-fog transformation during a long lasting, low visibility episode was examined using the observations from a comprehensive field campaign conducted in Nanjing, China during 4-9 December 2013. In this episode, haze was transformed into fog and the fog lasted for dozens of hours. The impacts of meteorological factors such as wind, temperature (T) and relative humidity (RH) on haze, transition and fog during this episode were investigated. Results revealed significant differences between haze and fog days, due to their different formation mechanisms. Comparison was made for boundary-layer conditions during hazy days, haze-to-fog days and foggy days. Distributions of wind speed and wind direction as well as synoptic weather conditions around Nanjing had determinative impacts on the occurrences and characteristics of haze and fog. Weakened southerly wind in southern Nanjing resulted in high concentration of pollutants, and haze events occurred frequently during the study period. The wind speed was less than 1 m s-1 in the haze event, which resulted in a stable atmospheric condition and weak dispersion of the pollutants. The height of the temperature inversion was about 400 m during the period. The inversion intensity was weak and the temperature-difference was 4°C km-1 or less in haze, while the inversion was stronger, and temperature-difference was about 6°C km-1, approaching the inversion layer intensity in the fog event. Haze event is strongly influenced by ambient RH. RH values increased, which resulted in haze days evidently increased, suggesting that an increasing fraction of haze events be caused by hygroscopic growth of aerosols, rather than simply by high aerosol loading. When RH was above 90%, haze aerosols started to be transformed from haze to fog. This study calls for more efforts to control emissions to prevent haze events in the region. [ABSTRACT FROM AUTHOR]

d-glucosamine at concentration of certain range could kill tumor cells without influencing normal cells. There are also some reports on the antitumor activity of d-glucosamine and its derivatives in murine models. It was therefore postulated that d-glucosamine might have the potential to invade tumor cells. We designed and radiosynthesized a glucosamine derivative, N-(2-[F]fluoro-4-nitrobenzoyl)glucosamine ([F]FNBG([F]7)). Evaluations in vitro and in vivo were performed on tumor bearing mice. Excitingly, the radiochemical purity of [F]FNBG([F]7) was 99%, and besides the best radiochemical yield was up to 35%. The best T/Bl (Tumor/Blood) and T/M (Tumor/Muscle) ratios of [F]FNBG([F]7) were 4.40 and 4.84. Although [F]FNBG([F]7) deserved further studies, the results revealed it might become a potential PET imaging agent for detecting tumors. [ABSTRACT FROM AUTHOR]

This article discusses a study on the synthesis of carbon black (CB)/poly(ethylene glycol) (PEG)/poly(methyl methacrylate)(PMMA) composites through polymerization filling to show the role of crystalline polymers (CB) filled amorphous polymer composites and improve the mechanical properties of composite films. The influence of PEG concentration and molecular weight on electrical responses of CB/PEG/PMMA conductive composites against organic vapors is discussed.

The complex configuration, H2 adsorption binding energy, magnetic, and optical properties of FAU zeolites with Ag cations loaded by ion exchange in the vacant dielectric cavities were investigated by employing the first-principles calculations with all-electron-relativistic numerical atom-orbitals scheme and the Metropolis Monte Carlo molecular simulations. The visible absorption spectrum peaked at distinct wavelengths arranging from red or green to blue colors when changing the net charge load, due to the produced various redox states of Ag cations exchanging at multiple Li+-substituted sites. The spin population analyses indicate the ferrimagnetic coupling between Al–O–Si framework and Ag cations originates from the major ferromagnetic spin polarization in Ag cation cluster coordinating with sodalite cages, with the net spins appreciably depending on the Ag content and exchange site. The H2 adsorption capacities and binding energies represent significant dependence on the content, location, and electronic property of Ag cations introduced into the FAU zeolites. The evident decrease of H2 adsorption binding energy with increased loading concentration demonstrates repulsive interaction between H2 molecules and heterogeneous adsorption configuration on Ag cations. The adsorption sites of H2 sorted by the binding energy with different adsorption configurations were correlated with exchange sites of Ag cations under different Ag loading to comprehend the H2 adsorption mechanism. [ABSTRACT FROM AUTHOR]

A simple classification drying method, in which moisture re-adsorption performance is crucial, is proposed to solve the problem of particulate matter emissions during coking coal drying. Coal particles were classified as fine and coarse particles. To maintain the high moisture level of fine particles, lab-scale experiments were used to investigate the influences of the initial moisture of coarse particles before mixing, the mixing time, the mixing temperature, and the drying temperature of the coarse particles. The re-adsorption performance and particle properties were studied using the desiccator method, the FTIR technique and the nitrogen adsorption technique. We concluded that the moisture of fine particles after mixing decreases with the decreasing initial moisture of the coarse particles or with increasing mixing time and that an optimal value would appear at a mixing temperature for coarse particles dried at 205 °C. Additionally, we found that the re-adsorption performance is not only dramatically affected by the water pressure gradient and the properties of the particles but also by the temperature gradient. These factors limit the universality of this technology. Particulate matter emissions decrease because the weight of fine particles increases, and fine particles aggregate slightly at high moisture levels. Unlabelled Image • The re-adsorption performances of thermal particles were distinct at different drying stages. • Temperature gradient of particle would also influence moisture re-adsorption performance. • To some extent, the increase of moisture in fine particles could reduce the particulate matter emissions. [ABSTRACT FROM AUTHOR]

1-Naphthylamine (1NA), which is harmful to human and aquatic animals, has been used widely in the manufacturing of dyes, pesticides, and rubber antioxidants. Nevertheless, little is known about its environmental behavior and no bacteria have been reported to use it as the growth substrate. Herein, we describe a pathway for 1NA degradation in the isolate Pseudomonas sp. strain JS3066, determine the structure and mechanism of the enzyme NpaA1 that catalyzes the initial reaction, and reveal how the pathway evolved. From genetic and enzymatic analysis, a five gene-cluster encoding a dioxygenase system was determined to be responsible for the initial steps in 1NA degradation through glutamylation of 1NA. The γ-glutamylated 1NA was subsequently oxidized to 1,2-dihydroxynaphthalene which was further degraded by the well-established pathway of naphthalene degradation via catechol. A glutamine synthetase-like (GS-like) enzyme (NpaA1) initiates 1NA glutamylation, and this enzyme exhibits a broad substrate selectivity toward a variety of anilines and naphthylamine derivatives. Structural analysis revealed that the aromatic residues in the 1NA entry tunnel and the V201 site in the large substrate-binding pocket significantly influence NpaA1's substrate preferences. The findings enhance understanding of degrading polycyclic aromatic amines, and will also enable the application of bioremediation at naphthylamine contaminated sites., Competing Interests: SZ, SD, TL, MM, DL, JS, NZ No competing interests declared, (© 2024, Zhang, Deng et al.)

The extensive accumulation of polyethylene terephthalate (PET) has become a critical environmental issue. PET hydrolases can break down PET into its building blocks. Recently, we identified a glacial PET hydrolase GlacPETase sharing less than 31% amino acid identity with any known PET hydrolases. In this study, the crystal structure of GlacPETase was determined at 1.8 Å resolution, revealing unique structural features including a distinctive N-terminal disulfide bond and a specific salt bridge network. Site-directed mutagenesis demonstrated that the disruption of the N-terminal disulfide bond did not reduce GlacPETase's thermostability or its catalytic activity on PET. However, mutations in the salt bridges resulted in changes in melting temperature ranging from -8°C to +2°C and the activity on PET ranging from 17.5% to 145.5% compared to the wild type. Molecular dynamics simulations revealed that these salt bridges stabilized the GlacPETase's structure by maintaining their surrounding structure. Phylogenetic analysis indicated that GlacPETase represented a distinct branch within PET hydrolases-like proteins, with the salt bridges and disulfide bonds in this branch being relatively conserved. This research contributed to the improvement of our comprehension of the structural mechanisms that dictate the thermostability of PET hydrolases, highlighting the diverse characteristics and adaptability observed within PET hydrolases.IMPORTANCEThe pervasive problem of polyethylene terephthalate (PET) pollution in various terrestrial and marine environments is widely acknowledged and continues to escalate. PET hydrolases, such as GlacPETase in this study, offered a solution for breaking down PET. Its unique origin and less than 31% identity with any known PET hydrolases have driven us to resolve its structure. Here, we report the correlation between its unique structure and biochemical properties, focusing on an N-terminal disulfide bond and specific salt bridges. Through site-directed mutagenesis experiments and molecular dynamics simulations, the roles of the N-terminal disulfide bond and salt bridges were elucidated in GlacPETase. This research enhanced our understanding of the role of salt bridges in the thermostability of PET hydrolases, providing a valuable reference for the future engineering of PET hydrolases., Competing Interests: The authors declare no conflict of interest.

Background: Spiritual wellbeing emphasizes optimistic and positive attitudes while self-regulating negative emotions when coping with stress. However, there have only been a few small studies of spiritual wellbeing of pancreatic ductal adenocarcinoma (PDAC) patients undergoing chemotherapy. The core factors influencing spiritual wellbeing in this clinical population are still unclear., Aim: To identify factors influencing spiritual wellbeing among patients with PDAC receiving chemotherapy., Methods: A total of 143 PDAC patients receiving chemotherapy were enrolled from January to December 2022. Patients completed general information questionnaires including: Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12 Item Scale (FACIT-Sp-12), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and Zung's Self-rating Anxiety Scale (SAS). Independent sample t -test, one-way analysis of variance, Pearson's correlation analysis, and multiple linear regression analysis were adopted for statistical analyses. P < 0.05 (two-tailed) was considered statistically significant for all tests., Results: Total spiritual wellbeing (FACIT-Sp-12) score was 32.16 ± 10.06 points, while dimension sub-scores were 10.85 ± 3.76 for faith, 10.55 ± 3.42 for meaning, and 10.76 ± 4.00 for peace. Total spiritual wellbeing score was negatively correlated with SAS score for anxiety and with the symptom domain of EORTC QLC-C30. Conversely, spiritual wellbeing score was positively correlated with global health status and EORTC QLQ-C30 role functioning domain score. Multivariate regression analysis identified educational level, health insurance category, symptom domain, functional role domain, and global health status as significant independent factors influencing spiritual wellbeing among PDAC patients undergoing chemotherapy ( R 2 = 0.502, P < 0.05)., Conclusion: Individualized spiritual support is needed for PDAC patients. Health, daily functioning, emotional, cognitive, and social function status should be taken into account to promote implementation of spirituality in nursing practice., Competing Interests: Conflict-of-interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Context: Shen-Shi-Jiang-Zhuo formula (SSJZF) exhibits a definite curative effect in the clinical treatment of non-alcoholic fatty liver disease (NAFLD)., Objective: To explore the therapeutic effect and mechanism of SSJZF on NAFLD., Materials and Methods: Sprague Dawley rats were randomly divided into control, NAFLD, positive drug (12 mg/kg/day), SSJZF high-dose (200 mg/kg/day), SSJZF middle-dose (100 mg/kg/day), and SSJZF low-dose (50 mg/kg/day) groups. After daily intragastric administration of NAFLD rats for 8 weeks, lipid metabolism and hepatic fibrosis were evaluated by biochemical indices and histopathology. Then we uncovered the main active compounds and mechanism of SSJZF against NAFLD by integrating RNA-sequencing and network pharmacology, and PI3K/AKT pathway activity was verified by western blot., Results: High dose SSJZF had the best inhibitory effect on hepatic lipid accumulation and fibrosis in rats with NAFLD, which significantly down-regulated t otal triglycerides (58%), cholesterol (62%), aspartate aminotransferase (57%), alanine aminotransferase (41%) andγ-glutamyl transpeptidase (36%), as well as the expression of ACC (5.3-fold), FAS (12.1-fold), SREBP1C (2.3-fold), and CD36 (4.4-fold), and significantly reduced collagen deposition (67%). Then we identified 23 compounds of SSJZF that acted on 25 key therapeutic targets of NAFLD by integrating RNA-sequencing and network pharmacology. Finally, we also confirmed that high dose SSJZF increased p-PI3K/PI3K (1.6-fold) and p-AKT/AKT (1.6-fold) in NAFLD rats., Discussion and Conclusion: We found for first time that SSJZF improved NAFLD in rats by activating the PI3K/Akt pathway. These findings provide scientific support for SSJZF in the clinical treatment of NAFLD and contribute to the development of new NAFLD drugs.

Background: Single subcortical infarction (SSI) is caused by two main etiological subtypes, which are branch atheromatous disease (BAD) and cerebral small vessel disease (CSVD)-related SSI. We applied the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ), the Shape Trail Test (STT), and the Stroop Color and Word Test (SCWT) to investigate the differences in cognitive performance between these two subtypes of SSI., Methods: Patients with acute SSIs were prospectively enrolled. The differences of MoCA-BJ, STT, and SCWT between the BAD group and CSVD-related SSI group were analyzed. A generalized linear model was used to analyze the associations between SSI patients with different etiological mechanisms and cognitive function. We investigated the correlations between MoCA-BJ, STT, and SCWT using Spearman's correlation analysis and established cut-off scores for Shape Trail Test A (STT-A) and STT-B to identify cognitive impairment in patients with SSI., Results: This study enrolled a total of 106 patients, including 49 and 57 patients with BAD and CSVD-related SSI, respectively. The BAD group performances were worse than those of the CSVD-related SSI group for STT-A (83 [60.5-120.0] vs. 68 [49.0-86.5], P = 0.01), STT-B (204 [151.5-294.5] vs. 153 [126.5-212.5], P = 0.015), and the number of correct answers on Stroop-C (46 [41-49] vs. 49 [45-50], P = 0.035). After adjusting for age, years of education, National Institutes of Health Stroke Scale and lesion location, the performance of SSI patients with different etiological mechanisms still differed significantly for STT-A and STT-B., Conclusions: BAD patients were more likely to perform worse than CSVD-related SSI patients in the domains of language, attention, executive function, and memory. The mechanism of cognitive impairment after BAD remains unclear., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)