The oxidant-antioxidant imbalance was involved in the pathogenesis of chronic rhinosinusitis with nasal polyps.

Background: Although oxidative stress is involved in the pathophysiological process of chronic rhinosinusitis with nasal polyps (CRSwNP), the specific underlying mechanism is still unclear. Whether antioxidant therapy can treat CRSwNP needs further investigation. Methods: Immunohistochemistry, immunofluorescence, western blotting and quantitative polymerase chain reaction (qPCR) analyses were performed to detect the distribution and expression of oxidants and antioxidants in nasal polyp tissues. qPCR revealed correlations between oxidase, antioxidant enzymes and inflammatory cytokine levels in CRSwNP patients. Human nasal epithelial cells (HNEpCs) and primary macrophages were cultured to track the cellular origin of oxidative stress in nasal polyps(NPs) and to determine whether crocin can reduce cellular inflammation by increasing the cellular antioxidant capacity. Results: The expression of NOS2, NOX1, HO-1 and SOD2 was increased in nasal epithelial cells and macrophages derived from nasal polyp tissue. Oxidase levels were positively correlated with those of inflammatory cytokines (IL-5 and IL-6). Conversely, the levels of antioxidant enzymes were negatively correlated with those of IL-13 and IFN-γ. Crocin inhibited M1 and M2 macrophage polarization as well as the expression of NOS2 and NOX1 and improved the antioxidant capacity of M2 macrophages. Moreover, crocin enhanced the ability of antioxidants to reduce inflammation via the KEAP1/NRF2/HO-1 pathway in HNEpCs treated with SEB or LPS. Additionally, we observed the antioxidant and anti-inflammatory effects of crocin in nasal explants. Conclusion: Oxidative stress plays an important role in the development of CRSwNP by promoting various types of inflammation. The oxidative stress of nasal polyps comes from epithelial cells and macrophages. Antioxidant therapy may be a promising strategy for treating CRSwNP.

Risk factors and early detection of joint damage in patients with psoriasis: a case-control study.

BACKGROUND: Our aim was to target the unsatisfied need for early detection of the at-risk population and determine the subgroup of patients whose psoriasis (PsO) could transform into psoriatic arthritis (PsA). METHODS: A retrospective and longitudinal case-control study was conducted at Beijing Chao-yang Hospital. It included 75 patients who were clinically diagnosed with PsA in the case group and 345 who solely suffered from PsO without PsA in the control group. A variety of baseline covariates were gathered from every patient with PsO. Univariate and multivariate analyses and receiver operating characteristic (ROC) curves were used to identify underlying risk factors and determine whether it was necessary to examine the imaging of PsO patients. RESULTS: In multivariate logistic regression analysis, age ≥40 (odds ratio (OR): 1.04, 95% confidence interval (CI): 1.02-1.06, P < 0.01), nail involvement (OR: 1.17, 95% CI: 1.09-1.32, P < 0.01), erythrocyte sedimentation rate (ESR) (OR: 1.03, 95% CI: 1.01-1.06, P < 0.05) and elevated high-sensitivity C-reactive protein (hs-CRP) (OR: 1.31, 95% CI: 1.13-1.53, P < 0.01) were perceived to be risk factors for the transformation from PsO into clinical PsA. By combining magnetic resonance imaging (MRI)-detected enthesitis with tenosynovitis, combined predictors demonstrated better diagnostic efficacy, with an improvement in specificity (94.3% vs. 69%) and similarities in sensitivity (89% vs. 84.6%). The areas under the ROC curve (AUCs) amounted to 0.925 (95% CI: 0.882-0.967, P < 0.01) and 0.858 (95% CI: 0.814-0.903, P < 0.01). CONCLUSIONS: It was identified that age ≥40, nail involvement, as well as an elevated ESR, and hs-CRP served as independent risk factors for PsO transforming into PsA. Additionally, MRI provides additional value for the early recognition of PsA.

Effect of IL-17 on pulmonary artery smooth muscle cells and connective tissue disease-associated pulmonary arterial hypertension.

OBJECTIVE: To explore the role of interleukin (IL)-17 in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) and to investigate its possible mechanism on pulmonary artery smooth muscle cells (PASMCs). METHODS: Enzyme-linked immunosorbent assay (ELISA) were used to compare levels of serum IL-17 in patients with CTD-PAH and healthy controls (HCs). After treatment for 3 months, the serum IL-17 levels were tested in CTD-PAH. ELISA and immunohistochemistry were used to compare levels of serum IL-17 and numbers of pulmonary artery IL-17+ cells, respectively, in a rat model of monocrotaline-induced PAH and untreated rats. Proliferation, migration, and inflammatory factors expression of PASMCs were assessed after stimulation with different concentrations of IL-17 for various time periods. Proteins in the mitogen-activated protein kinase (MAPK) pathway were examined by western blot. RESULTS: Levels of IL-17 were upregulated in patients with CTD-PAH compared to HCs. After 3 months of treatment, serum IL-17 levels were downregulated with pulmonary artery pressure amelioration. Moreover, serum IL-17 levels and numbers of IL-17+ cells infiltrating lung arterioles were increased in PAH model rats. IL-17 could dose- and time-dependently promote proliferation and migration of PASMCs as well as time-dependently induce IL-6 and intercellular cell adhesion molecule-1 (ICAM-1) expression. The levels of MKK6 increased after IL-17 treatment. Inhibition of MAPK decreased proliferation of PASMCs. CONCLUSION: Levels of IL-17 may increase in CTD-PAH, and IL-17 promotes proliferation, migration, and secretion of IL-6 and ICAM in PASMCs, respectively, which likely involves the p-38 MAPK pathway.

[Identification of Cervi Cornu (Cervus elaphus) and its formula granules based on PCR-RFLP].

Cervi Cornu is the ossified antler, or the base antler that falls off in the spring of the following year after the pilose antler is sawn off from Cervus elaphus or C. nippon, as a precious traditional Chinese medicine, has been recognized for its medicinal value and widely used in clinical practice. However, the origins of Cervi Cornu are miscellaneous, and Cervi Cornu is even mixed with adulterants in the market. Currently, there is a shortage of ways to identify Cervi Cornu and no standard to control the quality of Cervi Cornu. So it is valuable to develop a way to effectively identify Cervi Cornu from the adulterants. In this study, the differences in the mitochondrial barcode cytochrome b(Cytb) gene sequences of C. elaphus, C. nippon and their related species were compared and the specific single nucleotide polymorphism(SNP) sites on the Cytb sequences of Cervi Cornu were screened out. According to the screened SNPs, Cervi Cornu-specific primers dishmy-F and dishmy-R were designed. The PCR system was established and optimized, and the tolerance and feasibility of Taq polymerases and PCR systems affecting the repeatability of the PCR method were investigated. The amplification products of C. elaphus and C. nippon were digested using the restriction enzyme MseⅠ. The results showed that after electrophoresis of the product from PCR with the annealing temperature of 56 ℃ and 35 cycles, a single specific band at about 100 bp was observed for C. elaphus samples, and the product of C. elaphus samples was 60 bp shorter than that of C. nippon samples. There was no band for adulterants from other similar species such as Alces alces, Rangifer tarandus, Odocoileus virginianus, O. hemionus, Cap-reolus pygargus, Przewalskium albirostis and negative controls. The polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method established in this study can quickly and accurately identify Cervi Cornu originated from C. elaphus in crude drugs, standard decoctions, and formula granules, and distinguish the origins of Cervi Cornu products, i.e., C. nippon and similar species. This study can be a reference for other studies on the quality standard of other formula granules of traditional Chinese medicines.

SOX6 AU controls myogenesis by cis-modulation of SOX6 in cattle.

Long non-coding RNAs (lncRNAs) have been shown to be involved in the regulation of skeletal muscle development through multiple mechanisms. The present study revealed that the lncRNA SOX6 AU (SRY-box transcription factor 6 antisense upstream) is reverse transcribed from upstream of the bovine sex-determining region Y (SRY)-related high-mobility-group box 6 (SOX6) gene. SOX6 AU was significantly differentially expressed in muscle tissue among different developmental stages in Xianan cattle. Subsequently, knockdown and overexpression experiments discovered that SOX6 AU promoted primary skeletal muscle cells proliferation, apoptosis, and differentiation in bovine. The overexpression of SOX6 AU in bovine primary skeletal muscle cells resulted in 483 differentially expressed genes (DEGs), including 224 upregulated DEGs and 259 downregulated DEGs. GO functional annotation analysis showed that muscle development-related biological processes such as muscle structure development and muscle cell proliferation were significantly enriched. KEGG pathway analysis revealed that the PI3K/AKT and MAPK signaling pathways were important pathways for DEG enrichment. Notably, we found that SOX6 AU inhibited the mRNA and protein expression levels of the SOX6 gene. Moreover, knockdown of the SOX6 gene promoted the proliferation and apoptosis of bovine primary skeletal muscle cells. Finally, we showed that SOX6 AU promoted the proliferation and apoptosis of bovine primary skeletal muscle cells by cis-modulation of SOX6 in cattle. This work illustrates our discovery of the molecular mechanisms underlying the regulation of SOX6 AU in the development of beef.

Effects of predictive nursing interventions on pressure ulcer in older bedridden patients: A meta-analysis.

To evaluate the effect of predictive nursing interventions on pressure ulcers in elderly bedridden patients by meta-analysis. Applied computer searches of PubMed, Embase, Google Scholar, Cochrane Library, China National Knowledge Infrastructure and Wanfang databases for randomised controlled trials (RCTs) on the effect of predictive nursing in preventing pressure ulcers in elderly bedridden patients from the database inception to November 2023. Two researchers independently screened the literature, extracted data and performed quality assessment based on inclusion and exclusion criteria. Stata 17.0 software was utilised for data analysis. Eighteen RCTs involving 6504 patients were finally included. The analysis revealed the implementation of predictive nursing interventions had a significant advantage in reducing the incidence of pressure ulcers in elderly bedridden patients compared with conventional nursing (odds ratio [OR] = 0.20, 95% confidence interval [CI]: 0.15-0.28, p < 0.001), while the patients' satisfaction with nursing care was higher (OR = 3.70, 95% CI: 2.99-4.57, p < 0.001). This study shows that the implementation of a predictive nursing interventions for elderly bedridden patients can effectively reduce the occurrence of pressure ulcers and significantly improve patients' satisfaction with nursing care, which is worthy of clinical promotion and application.

EGFR Oncogenic Mutations in NSCLC Impair Macrophage Phagocytosis and Mediate Innate Immune Evasion Through Up-Regulation of CD47.

INTRODUCTION: EGFR-mutated NSCLC is characterized by an immunosuppressive microenvironment that confers limited clinical effectiveness to anti-PD-1 or PD-L1 antibodies. Despite the discouraging outcomes of immunotherapy, novel immune checkpoints are constantly emerging, among which the specific vulnerability for therapeutic intervention in the context of EGFR-mutated NSCLC remains unresolved. METHODS: Data sets of patient- and cell line-levels were used for screening and mutual validation of association between EGFR mutation and a panel of immune checkpoint-related genes. Regulatory mechanism was elucidated through in vitro manipulation of EGFR signaling pathway and evaluated by immunoblot analysis, quantitative polymerase chain reaction, flow cytometry, immunofluorescence staining, and chromatin immunoprecipitation. In vivo investigation of different therapeutic strategies were conducted using both immunocompetent and immunodeficient mouse models. RESULTS: Among all screened immune checkpoints, CD47 emerged as the candidate most relevant to EGFR activation. Mechanistically, EGFR mutation constitutively activated downstream ERK and AKT pathways to respectively up-regulate the transcriptional factors c-Myc and NF-κB, both of which structurally bound to the promotor region of CD47 and actively transcribed this "don't eat me" signal. Impaired macrophage phagocytosis was observed on introduction of EGFR-sensitizing mutations in NSCLC cell line models, whereas CD47 blockade restored the phagocytic capacity and augmented tumor cell killing in both in vitro and in vivo models. Remarkably, the combination of anti-CD47 antibody with EGFR tyrosine kinase inhibitor revealed an additive antitumor activity compared with monotherapy of either antitumor agent in both immunocompetent and adaptive immunity-deficient mouse models. CONCLUSIONS: EGFR-sensitizing mutation facilitates NSCLC's escape from innate immune attack through up-regulating CD47. Combination therapy incorporating CD47 blockade holds substantial promise for clinical translation in developing more effective therapeutic approaches against EGFR-mutant NSCLC.

Trends of ischemic heart disease mortality attributable to smoking in the five countries with the highest number of smokers during 1990-2019: an age-period-cohort analysis.

Introduction: Smoking increases the risk of various cardiovascular diseases, including ischemic heart disease (IHD). This study aimed to assess the impact of age, period, and cohort on long-term trends in IHD mortality in China, India, Indonesia, the United States, and Russia, the five countries with the highest number of smokers, from 1990 to 2019. Material and methods: The data were obtained from the Global Burden of Disease (GBD) Study 2019, and the age-standardized mortality rate (ASMR) was calculated. Joinpoint regression analysis was used to assess the magnitude and direction of trends in smoking-attributable mortality from IHD. Age-period-cohort (APC) studies were used to estimate net drift (estimated annual percentage change (EAPC)s), local drift (age-specific EAPCs), and independent trends in age, period, and cohort effects. Results: The analysis revealed a significant downward trend in ASMRs attributable to IHD as a result of smoking in the United States, India, and Russia. Indonesia and China showed an upward trend. Age effects were increasing for both country and sex, with China showing the most significant increase in the older age group; period effects were decreasing in all countries except Indonesia, and cohort effects were increasing only in Indonesia and China. Conclusions: From 1990 to 2019, mortality from IHD caused by smoking showed a downward trend in these five countries. However, the pattern of increased mortality from IHD in women caused by smoking warrants further study.

Choice of refractive surgery types for myopia assisted by machine learning based on doctors' surgical selection data.

In recent years, corneal refractive surgery has been widely used in clinics as an effective means to restore vision and improve the quality of life. When choosing myopia-refractive surgery, it is necessary to comprehensively consider the differences in equipment and technology as well as the specificity of individual patients, which heavily depend on the experience of ophthalmologists. In our study, we took advantage of machine learning to learn about the experience of ophthalmologists in decision-making and assist them in the choice of corneal refractive surgery in a new case. Our study was based on the clinical data of 7,081 patients who underwent corneal refractive surgery between 2000 and 2017 at the Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences. Due to the long data period, there were data losses and errors in this dataset. First, we cleaned the data and deleted the samples of key data loss. Then, patients were divided into three groups according to the type of surgery, after which we used SMOTE technology to eliminate imbalance between groups. Six statistical machine learning models, including NBM, RF, AdaBoost, XGBoost, BP neural network, and DBN were selected, and a ten-fold cross-validation and grid search were used to determine the optimal hyperparameters for better performance. When tested on the dataset, the multi-class RF model showed the best performance, with agreement with ophthalmologist decisions as high as 0.8775 and Macro F1 as high as 0.8019. Furthermore, the results of the feature importance analysis based on the SHAP technique were consistent with an ophthalmologist's practical experience. Our research will assist ophthalmologists in choosing appropriate types of refractive surgery and will have beneficial clinical effects.

The Osmolality and Hemolysis of High-Concentration Monoclonal Antibody Formulations.

PURPOSES: Highly concentrated monoclonal antibody (mAb) formulations for subcutaneous administration are becoming increasingly preferred within the biopharmaceutical industry for ease of use and improved patient compliance. A common phenomenon observed in the industry is that osmolality detected via freezing-point depression (FPD) in high-concentration mAb formulations is much higher than the theoretical concentrations, yet the occurrence of this phenomenon and its possible safety issues have been rarely reported. METHODS: The current study summarized theoretical osmolality of U.S. Food and Drug Administration approved high-concentration mAb formulations and evaluated effects of high osmolality on safety using hemolysis experiments for the first time. Two mAbs formulated at 150 mg/mL were used as models and configured into two isotonic solutions: a, a theoretically calculated molarity in the isotonic range (H) and b, an osmolality value measured via the FPD in the isotonic range (I). The H and I formulations of each mAb were individually subjected to hemolysis experiments, and the hemolysis rates of the two formulations of the same mAb were compared. Besides, the effect of mAb concentration on osmolality detected by FPD was explored as well. RESULTS: The results indicated that the hemolysis rates were similar between the H and I formulations of mAbs at the same sample addition volume, and the osmolality values increased approximately linearly with the increase in mAb concentration. CONCLUSIONS: High osmolality for high-concentration mAb formulations would not affect product safety and the excipients could be added at relatively high levels to maintain product stability, especially for labile products.

Single-cell profiling of the microenvironment in human bone metastatic renal cell carcinoma.

Bone metastasis is of common occurrence in renal cell carcinoma with poor prognosis, but no optimal treatment approach has been established for bone metastatic renal cell carcinoma. To explore the potential therapeutic targets for bone metastatic renal cell carcinoma, we profile single cell transcriptomes of 6 primary renal cell carcinoma and 9 bone metastatic renal cell carcinoma. We also include scRNA-seq data of early-stage renal cell carcinoma, late-stage renal cell carcinoma, normal kidneys and healthy bone marrow samples in the study to better understand the bone metastasis niche. The molecular properties and dynamic changes of major cell lineages in bone metastatic environment of renal cell carcinoma are characterized. Bone metastatic renal cell carcinoma is associated with multifaceted immune deficiency together with cancer-associated fibroblasts, specifically appearance of macrophages exhibiting malignant and pro-angiogenic features. We also reveal the dominance of immune inhibitory T cells in the bone metastatic renal cell carcinoma which can be partially restored by the treatment. Trajectory analysis showes that myeloid-derived suppressor cells are progenitors of macrophages in the bone metastatic renal cell carcinoma while monocytes are their progenitors in primary tumors and healthy bone marrows. Additionally, the infiltration of immune inhibitory CD47+ T cells is observed in bone metastatic tumors, which may be a result of reduced phagocytosis by SIRPA-expressing macrophages in the bone microenvironment. Together, our results provide a systematic view of various cell types in bone metastatic renal cell carcinoma and suggest avenues for therapeutic solutions.

An investigation into the HIF-dependent intestinal barrier protective mechanism of Qingchang Wenzhong decoction in ulcerative colitis management.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic, non-specific inflammatory disease affecting the colon and rectum with an etiology that remains elusive. Traditional Chinese medicine (TCM) has been widely used on long-term UC treatment to better maintain the efficacy than traditional aminosalicylic acid or glucocorticosteroids and to ease financial burden of patients. Qingchang Wenzhong Decoction (QCWZD) is a modern TCM decoction with established clinical efficacy but the mechanism of its protection on intestinal barrier function remains unclear. AIM OF THE STUDY: Current findings highlight that the activation of the hypoxia inducible factor (HIF) pathway can facilitate the repair of intestinal epithelium barrier. This study is to investigate the protective effects of QCWZD and its HIF-targeted ingredients on hypoxia-dependent intestinal barrier. METHODS: The mice model of UC was induced by dextran sulfate sodium (DSS). Disease activity index (DAI) and histopathology scores and colon length were used to measure the severity of colitis. The DAO activity in serum and protein expression of tight junction (TJ) proteins were detected to explore the function of intestinal barrier. The protein levels of HIF-1α and its downstream gene heme oxygenase-1 (HO-1) were measured as well. HIF-targeted active ingredients in QCWZD were selected by network pharmacology and molecular docking. Protective effects of six constituents on HIF-related anti-oxidative and barrier protective pathway were evaluated by lipopolysaccharide (LPS)-induced HT29 and RAW264.7 cells, through the measurement of the production of ROS and mRNA level of pro-inflammatory cytokines. HIF-1α knockdown was carried out to explore the correlation of protection effects with HIF-related pathway of the active ingredients. RESULTS: QCWZD effectively alleviated colitis induced by DSS and demonstrated a protective effect on intestinal barrier function by upregulating HIF-related pathways. Six specific ingredients in QCWZD, targeting HIF, successfully reduced the production of cellular ROS and proinflammatory cytokines in LPS-induced cells. It is noteworthy that the barrier protection provided by these molecules is intricately linked with the HIF-related pathway. CONCLUSIONS: This study elucidates the HIF-related molecular mechanism of QCWZD in protecting the function of the epithelial barrier. Six compounds targeting the activation of the HIF-dependent pathway were demonstrated to unveil a novel therapeutic approach for managing UC.

Zebrafish spop promotes ubiquitination and degradation of mavs to suppress antiviral response via the lysosomal pathway.

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) signaling pathways are required to be tightly controlled to initiate host innate immune responses. Fish mitochondrial antiviral signaling (mavs) is a key determinant in the RLR pathway, and its ubiquitination is associated with mavs activation. Here, we identified the zebrafish E3 ubiquitin ligase Speckle-type BTB-POZ protein (spop) negatively regulates mavs-mediated the type I interferon (IFN) responses. Consistently, overexpression of zebrafish spop repressed the activity of IFN promoter and reduced host ifn transcription, whereas knockdown spop by small interfering RNA (siRNA) transfection had the opposite effects. Accordingly, overexpression of spop dampened the cellular antiviral responses triggered by spring viremia of carp virus (SVCV). A functional domain assay revealed that the N-terminal substrate-binding MATH domain regions of spop were necessary for IFN suppression. Further assays indicated that spop interacts with mavs through the C-terminal transmembrane (TM) domain of mavs. Moreover, zebrafish spop selectively promotes K48-linked polyubiquitination and degradation of mavs through the lysosomal pathway to suppress IFN expression. Our findings unearth a post-translational mechanism by which mavs is regulated and reveal a role for spop in inhibiting antiviral innate responses.

APAAACI clinical pathway on direct provocation testing for penicillin allergy delabeling.

Background: Allergy to penicillin is commonly reported in many countries and is an overwhelming global public health concern. Penicillin allergy labels can lead to the use of less effective antibiotics and can be associated with antimicrobial resistance. Appropriate assessment of suspected penicillin allergy (often including skin testing, followed by drug provocation testing [DPT] performed by allergists) can prevent the unnecessary restriction of penicillin or delabelling. Many countries in the Asia Pacific (AP) have very limited access to allergy services, and there are significant disparities in the methods of evaluating penicillin allergy. Therefore, a clinical pathway for the management of penicillin allergy is essential. Objectives: To develop a risk-stratified clinical pathway for delabeling penicillin allergy, taking into account the distinct epidemiology, patient/sensitization profiles, and disparities of allergy services or facilities within the AP. Methods: A risk-stratified penicillin allergy delabeling clinical pathway was formulated by the Drug Allergy Committee of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. and members of the Penicillin Allergy Disparities survey in AP each representing one country/region of the AP. The clinical pathway was tested based on a database of anonymized patients who were sequentially referred for and completed penicillin allergy evaluation in Hong Kong. Results: The clinical pathway was piloted employing a "hub-and-spoke" approach to foster multidisciplinary collaboration between allergists and nonallergists. A simulation run of the algorithm on a retrospective Hong Kong cohort of 439 patients was performed. Overall, 367 (84%) of patients were suitable for direct DPT and reduced the need for skin testing or specialist's care for 357 (97%) skin test-negative individuals. Out of the skin test-negative patients, 345 (94%) patients had a negative DPT. Conclusions: This risk-stratification strategy for direct oral DPT can reduce the need for unnecessary skin testing in patients with low-risk penicillin allergy histories. The hub and spoke model of care may be considered for further piloting and validation in other AP populations that lack adequately trained allergists.

Electrocatalytic Lignin Valorization into Aromatic Products via Oxidative Cleavage of Cα-Cß Bonds.

Lignin is the most promising candidate for producing aromatic compounds from biomass. However, the challenge lies in the cleavage of C-C bonds between lignin monomers under mild conditions, as these bonds have high dissociation energy. Electrochemical oxidation, which allows for mild cleavage of C-C bonds, is considered an attractive solution. To achieve low-energy consumption in the valorization of lignin, the use of highly efficient electrocatalysts is essential. In this study, a meticulously designed catalyst consisting of cobalt-doped nickel (oxy)hydroxide on molybdenum disulfide heterojunction was developed. The presence of molybdenum in a high valence state promoted the adsorption of tert-butyl hydroperoxide, leading to the formation of critical radical intermediates. In addition, the incorporation of cobalt doping regulated the electronic structure of nickel, resulting in a lower energy barrier. As a result, the heterojunction catalyst demonstrated a selectivity of 85.36% for cleaving the Cα-Cß bond in lignin model compound, achieving a substrate conversion of 93.69% under ambient conditions. In addition, the electrocatalyst depolymerized 49.82 wt% of soluble fractions from organosolv lignin (OL), resulting in a yield of up to 13 wt% of aromatic monomers. Significantly, the effectiveness of the prepared electrocatalyst was also demonstrated using industrial Kraft lignin (KL). Therefore, this research offers a practical approach for implementing electrocatalytic oxidation in lignin refining.

H/F Substitution Achieved Enantiomeric Organic Inorganic Hybrid Perovskites and Trigonal Structure [DMFP]3(CdBr3)(CdBr4).

Organic-inorganic hybrid perovskites (OIHPs) have been emerging as a hot research topic due to their potential applications in energy storage, semiconductors, and electronic devices. Herein, we systematically investigated the synthesis and phase transition behaviors of the enantiomeric OIHPs, (R) and (S)-N,N-dimethyl-3-fluoropyrrolidinium cadmium bromide ([DMFP][CdBr3]), and the hybrid trigonal structure [DMFP]3 (CdBr3)(CdBr4). The enantiomers have a mirror-symmetric structure and enhanced solid-state phase transition points of 417 and 443 K, in contrast to the nonfluorinated parent compound, N,N-dimethyl-pyrrolidinium cadmium bromide ([DMP][CdBr3], 385 K). Moreover, racemic H/F substitution on the pyrrolidinium cations leads to the formation of a trigonal compound, showing above-room-temperature structural phase transition and dominant ferroelasticity. This work discovers chiral enantiomeric OIHPs through H/F substitution, demonstrating a useful chemical synthesis strategy for exploring novel phase transition materials.

P25/CDK5-mediated Tau Hyperphosphorylation in Both Ipsilateral and Contralateral Cerebra Contributes to Cognitive Deficits in Post-stroke Mice.

OBJECTIVE: Post-stroke cognitive impairment (PSCI) develops in approximately one-third of stroke survivors and is associated with ingravescence. Nonetheless, the biochemical mechanisms underlying PSCI remain unclear. The study aimed to establish an ischemic mouse model by means of transient unilateral middle cerebral artery occlusions (MCAOs) and to explore the biochemical mechanisms of p25/cyclin-dependent kinase 5 (CDK5)-mediated tau hyperphosphorylation on the PSCI behavior. METHODS: Cognitive behavior was investigated, followed by the detection of tau hyperphosphorylation, mobilization, activation of kinases and/or inhibition of phosphatases in the lateral and contralateral cerebrum of mice following ischemia in MACO mice. Finally, we treated HEK293/tau cells with oxygen-glucose deprivation (OGD) and a CDK5 inhibitor (Roscovitine) or a GSK3ß inhibitor (LiCl) to the roles of CDK5 and GSK3ß in mediating ischemia-reperfusion-induced tau phosphorylation. RESULTS: Ischemia induced cognitive impairments within 2 months, as well as causing tau hyperphosphorylation and its localization to neuronal somata in both ipsilateral and contralateral cerebra. Furthermore, p25 that promotes CDK5 hyperactivation had significantly higher expression in the mice with MCAO than in the shamoperation (control) group, while the expression levels of protein phosphatase 2 (PP2A) and the phosphorylation level at Tyr307 were comparable between the two groups. In addition, the CDK5 inhibitor rescued tau from hyperphosphorylation induced by OGD. CONCLUSION: These findings demonstrate that upregulation of CDK5 mediates tau hyperphosphorylation and localization in both ipsilateral and contralateral cerebra, contributing to the pathogenesis of PSCI.

A new isoflavone from the stems of Derris eriocarpa How.

A preliminary screening test was performed to discover new antihyperlipidaemic active compounds from the leguminous plant Derris eriocarpa How. A new compound, derris-isoflavone F (1), and derrubone dimethyl ether (6), a known synthetic compound of natural origin, were isolated from the stems of D. eriocarpa alongside eight recognised compounds. To our knowledge, this is the first instance of documenting the identification of compounds 1-10 from this plant. The new compound were evaluated for their antihyperlipidemic and antiproliferative properties. Compound 1 evidently reduced the triglyceride (TG) content in oleic acid-treated HepG2 cells, which validated its efficacy as a potential TG-lowering agent.

Delayed-type allergic reaction to furazolidone: A case report and review of the literature.

BACKGROUND: Furazolidone is a nitrofuran antimicrobial agent used in the treatment of bacterial and protozoal infections. Hypersensitivity to furazolidone is rarely reported and only eight cases have been documented in English since 1967. OBJECTIVES: To report a 24-year-old man who developed exanthematous drug eruptions in general and swelling sensation of the hands after first dose of oral administration of medicines for Helicobacter pylori infection 7 h later, who was finally confirmed with delayed-type IV allergic reaction to furazolidone by provocation tests. And to review the existing literature. METHODS: Thorough clinical examination, prick, intradermal, and patch tests, drug provocation tests were performed in the patient. RESULTS: Skin tests of all used drugs were negative. Drug provocation tests to furazolidone resulted to be positive. CONCLUSIONS: Clinicians should be aware that furazolidone may induce delayed-type allergic reactions; diagnostic approaches should be taken to identify the responsible drug when multiple medications were used concurrently.