Asymmetric catalytic synthesis of chiral covalent organic framework composite (S)-DTP-COF@SiO2 for HPLC enantioseparations by normal-phase and reversed-phase chromatographic modes.

A novel CCOF core-shell composite material (S)-DTP-COF@SiO2 was prepared via asymmetric catalytic and in situ growth strategy. The prepared (S)-DTP-COF@SiO2 was utilized as separation medium for HPLC enantioseparation using normal-phase and reversed-phase chromatographic modes, which displays excellent chiral separation performance for alcohols, esters, ketones, and epoxides, etc. Compared with chiral commercial chromatographic columns (Chiralpak AD-H and Chiralcel OD-H columns) and some previously reported chiral CCOF@SiO2 (CC-MP CCTF@SiO2 and MDI-ß-CD-modified COF@SiO2)-packed columns, there are 4, 3, 13, and 15 tested racemic compounds that could not be resolved on the Chiralpak AD-H column, Chiralcel OD-H column, CC-MP CCTF@SiO2 column, and MDI-ß-CD-modified COF@SiO2 column, respectively, which indicates that the resolution effect of (S)-DTP-COF@SiO2-packed column can be complementary to the other ones. The effects of the analyte mass, column temperature, and mobile phase composition on the enantiomeric separation were investigated. The chiral column exhibits good reproducibility after multiple consecutive injections. The RSDs (n = 5) of the peak area and retention time were less than 1.5% for repetitive separation of 2-methoxy-2-phenylethanol and 1-phenyl-1-pentanol. The chiral core-shell composite (S)-DTP-COF@SiO2 exhibited good enantiomeric separation performance, which not only demonstrates its potential as a novel CSP material in HPLC but also expands the range of applications for chiral COFs.

CD161+CD127+CD8+ T cell subsets can predict the efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer with diabetes mellitus.

The role of CD161+CD127+CD8+ T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function of CD8+ T cell subsets in NSCLC with diabetes. We recruited NSCLC patients (n = 436) treated with anti-PD-1 immunotherapy as first-line treatment. The progression-free survival (PFS), overall survival (OS), T cells infiltration, and peripheral blood immunological characteristics were analyzed in NSCLC patients with or without diabetes. NSCLC patients with diabetes exhibited shorter PFS and OS (p = 0.0069 and p = 0.012, respectively) and significantly lower CD8+ T cells infiltration. Mass cytometry by time-of-flight (CyTOF) showed a higher percentage of CD161+CD127+CD8+ T cells among CD8+T cells in NSCLC with diabetes before anti-PD-1 treatment (p = 0.0071) than that in NSCLC without diabetes and this trend continued after anti-PD-1 treatment (p = 0.0393). Flow cytometry and multiple-immunofluorescence confirmed that NSCLC with diabetes had significantly higher CD161+CD127+CD8+ T cells to CD8+T cells ratios than NSCLC patients without diabetes. The RNA-sequencing analysis revealed immune-cytotoxic genes were reduced in the CD161+CD127+CD8+ T cell subset compared to CD161+CD127-CD8+ T cells in NSCLC with diabetes. CD161+CD127+CD8+ T cells exhibited more T cell-exhausted phenotypes in NSCLC with diabetes. NSCLC patients with diabetes with ≥ 6.3% CD161+CD127+CD8+ T cells to CD8+T cells ratios showed worse PFS. These findings indicate that diabetes is a risk factor for NSCLC patients who undergo anti-PD-1 immunotherapy.CD161+CD127+CD8+ T cells could be a key indicator of a poor prognosis in NSCLC with diabetes. Our findings would help in advancing anti-PD-1 therapy in NSCLC patients with diabetes.

Long-term associations of PM1 versus PM2.5 and PM10 with asthma and asthma-related respiratory symptoms in the middle-aged and elderly population.

Background: Few studies have compared the associations between long-term exposures to particulate matters (aerodynamic diameter ≤1, ≤2.5 and ≤10 µm: PM1, PM2.5 and PM10, respectively) and asthma and asthma-related respiratory symptoms. The objective of the present study was to compare the strength of the aforementioned associations in middle-aged and elderly adults. Methods: We calculated the mean 722-day personal exposure estimates of PM1, PM2.5 and PM10 at 1 km×1 km spatial resolution between 2013 and 2019 at individual levels from China High Air Pollutants (CHAP) datasets. Using logistic regression models, we presented the associations as odds ratios and 95% confidence intervals, for each interquartile range (IQR) increase in PM1/PM2.5/PM10 concentration. Asthma denoted a self-reported history of physician-diagnosed asthma or wheezing in the preceding 12 months. Results: We included 7371 participants in COPD surveillance from Guangdong, China. Each IQR increase in PM1, PM2.5 and PM10 was associated with a greater odds (OR (95% CI)) of asthma (PM1: 1.22 (1.02-1.45); PM2.5: 1.24 (1.04-1.48); PM10: 1.30 (1.07-1.57)), wheeze (PM1: 1.27 (1.11-1.44); PM2.5: 1.30 (1.14-1.48); PM10: 1.34 (1.17-1.55)), persistent cough (PM1: 1.33 (1.06-1.66); PM2.5: 1.36 (1.09-1.71); PM10: 1.31 (1.02-1.68)) and dyspnoea (PM1: 2.10 (1.84-2.41); PM2.5: 2.17 (1.90-2.48); PM10: 2.29 (1.96-2.66)). Sensitivity analysis results were robust after excluding individuals with a family history of allergy. Associations of PM1, PM2.5 and PM10 with asthma and asthma-related respiratory symptoms were slightly stronger in males. Conclusion: Long-term exposure to PM is associated with increased risks of asthma and asthma-related respiratory symptoms.

Small bowel adenocarcinoma of the jejunum detected by double contrast enhanced ultrasound: a case report of a novel ultrasound modality.

Background: Small Bowel Adenocarcinoma (SBA) is rare, occult and life-threatening malignancy in digestive system. Given low incidence and nonspecific symptoms, SBA is frequently detected in later stages. Double contrast enhanced ultrasound (DCEUS) is an innovative imaging technique applied to visualize the gastrointestinal tract, merging intravenous contrast-enhanced ultrasound with oral contrast-enhanced ultrasound. In this case, DCEUS was utilized and successfully detected an SBA of the jejunum. Case presentation: A Chinese woman, aged 64, sought consultation in the gastroenterology department at our hospital, reporting symptoms of abdominal pain. Three months before entering the hospital, she underwent gastroscopy and colonoscopy which suggested chronic gastritis, and she was treated with oral drugs. However, her symptoms were not relieved, and even worsened. To further investigate, DCEUS was performed. The oral contrast agent dilated the luminal space of the upper gastrointestinal tract, resolving the hindrance caused by gas in the gastrointestinal tract and creating an acoustic window for scanning. Through this acoustic window, oral agent contrast-enhanced ultrasound (OA-CEUS) revealed a localized thickening of jejunal intestinal wall measuring 4x3 cm. Following intravenous injection of ultrasound contrast agent, the jejunal lesion exhibited faster enhancement and heterogeneous hyper-enhancement. Finally, the patient underwent jejunal tumor resection. Pathological examination revealed a jejunal adenocarcinoma. Conclusion: The timely diagnosis of SBA can be challenging. DCEUS may have the potential to contribute to diagnosis and detailed evaluation of SBA, particularly in cases involving jejunum. Further researches are needed to fully explore the benefits of DCEUS in the standard diagnostic approach for small bowel diseases.

Morphological characteristics and phylogenetic analyses revealed four new wood inhabiting fungi (Agaricomycetes, Basidiomycota) in Xizang Autonomous Region, China.

Four new fungi from Xizang in southwest China, Caloceraramaria, Ceraceomycesrhizomorphus, Leptosporomyceslinzhiensis, and Ramariaxizangensis are described and illustrated based on the morphological and molecular evidence. Caloceraramaria is characterized by the ramal and bright orange basidiomata, a monomitic hyphal system with simple septa generative hyphae, usually 4-septate basidiospores; Ceraceomycesrhizomorphus is characterized by the cream to yellowish basidiomata with rhizomorphs, cylindrical basidiospores; Leptosporomyceslinzhiensis is characterized by white with pink basidiomata, cylindrical to oblong ellipsoid basidiospores; Ramariaxizangensis is characterized by flesh pink basidiomata, branched dichotomously in 4-5 ranks, a monomitic hyphal system with clamped generative hyphae, ellipsoid to cylindrical and densely warted basidiospores.

Twin Boundaries-Induced Centrosymmetric Breaking of Hollow CaTiO3 Nanocuboids for Piezocatalytic Hydrogen Evolution.

Piezocatalysis, a transformative mechanochemical energy conversion technique, has received considerable attention over the past decade for its role in processes such as hydrogen evolution from water. Despite notable progress in the field, challenges remain, particularly in the areas of limited piezocatalysis efficiency and limited availability of materials requiring a non-centrosymmetric structure. Here, a pioneering contribution is presented by elucidating the piezocatalytic properties of hollow CaTiO3 nanocuboids, a centrosymmetric material with a nominally nonpolar state. Remarkably, CaTiO3 nanocuboids exhibit an impressive hydrogen production rate of 3.44 mmol g-1 h-1 under ultrasonic vibrations, surpassing the performance of the well-established piezocatalyst BaTiO3 (2.23 mmol g-1 h-1). In contrast, commercial CaTiO3 nanoparticles do not exhibit piezocatalytic performance. The exceptional performance of hollow CaTiO3 nanocuboids is attributed to the abundance presence of twin boundaries on the {110} facet within its crystal structure, which can impart significant polarization strength to CaTiO3. Extending the investigation to other centrosymmetric materials, such as SrZrO3 and BaZrO3, the experimental results also demonstrate their commendable properties for piezocatalytic hydrogen production from water. This research underscores the significant potential of centrosymmetric materials in piezocatalysis.

miPEP31 alleviates Ang II-induced hypertension in mice by occupying Cebpα binding sites in the pri-miR-31 promoter.

BACKGROUND: Previous studies have shown that peptides encoded by noncoding RNAs (ncRNAs) can be used as peptide drugs to alleviate diseases. We found that microRNA-31 (miR-31) is involved in the regulation of hypertension and that the peptide miPEP31, which is encoded by the primary transcript of miR-31 (pri-miR-31), can inhibit miR-31 expression. However, the role and mechanism of miPEP31 in hypertension have not been elucidated. METHODS: miPEP31 expression was determined by western blot analysis. miPEP31-deficient mice (miPEP31-/-) were used, and synthetic miPEP31 was injected into Ang II-induced hypertensive mice. Blood pressure was monitored through the tail-cuff method. Histological staining was used to evaluate renal damage. Regulatory T (Treg) cells were assessed by flow cytometry. Differentially expressed genes were analysed through RNA sequencing. The transcription factors were predicted by JASPAR. Luciferase reporter and electrophoretic mobility shift assays (EMSAs) were used to determine the effect of pri-miR-31 on the promoter activity of miPEP31. Images were taken to track the entry of miPEP31 into the cell. RESULTS: miPEP31 is endogenously expressed in target organs and cells related to hypertension. miPEP31 deficiency exacerbated but exogenous miPEP31 administration mitigated the Ang II-induced systolic blood pressure (SBP) elevation, renal impairment and Treg cell decreases in the kidney. Moreover, miPEP31 deletion increased the expression of genes related to Ang II-induced renal fibrosis. miPEP31 inhibited the transcription of miR-31 and promoted Treg differentiation by occupying the Cebpα binding site. The minimal functional domain of miPEP31 was identified and shown to regulate miR-31. CONCLUSION: miPEP31 was identified as a potential therapeutic peptide for treating hypertension by promoting Treg cell differentiation in vivo. Mechanistically, we found that miPEP31 acted as a transcriptional repressor to specifically inhibit miR-31 transcription by competitively occupying the Cebpα binding site in the pri-miR-31 promoter. Our study highlights the significant therapeutic effect of miPEP31 on hypertension and provides novel insight into the role and mechanism of miPEPs.

Uprighting and protraction of two unilateral mandibular molars using a cantilever arm through a sophisticated biomechanical system with clear aligner: A case report.

Although clear aligner can be efficient and predictable in some tooth movements, mandibular molar protraction is the least predictable owing to biological and biomechanical limitations. This case report presents a 20-year-old female with poor prognosed left mandibular first molar (#36), deviated dental midline and mild crowding. After extraction of #36, clear aligners and an Albert cantilever were used for treatment. Through carefully designed dual mechanical system, we achieved uprighting and protraction of #37 within 27 months, with crown and root movements of 9.9mm and 12.1mm, respectively. The predictability of the crown and root movement was 107.6% and 84.6%. Coincident dental and facial midline, class I molar and canine relationship and good root parallelism were also achieved. Large-distance mandibular molar protraction can be achieved effectively with a combination of Albert cantilever arm and clear aligner.

Molecular and morphological data reveal two new polypores (Polyporales, Basidiomycota) with reddish brown to orange basidiomata from China.

Two taxonomically controversial polypore genera with reddish brown to orange basidiomata that stain reddish with KOH solution, Aurantiporus and Hapalopilus, are revised based on additional sampling, morphological examination, and phylogenetic analysis of a combined dataset of ITS1-5.8S-ITS2-nLSU sequences. Hapalopilus is a monophyletic genus belonging to Phanerochaetaceae, whereas Aurantiporus is a polyphyletic genus belonging to Meruliaceae. Hapalopilus and Aurantiporus s. str. are circumscribed, and two new species - Aurantiporusorientalis and Hapalopilustabuliformis - are described and illustrated from temperate China. In addition, four new combinations, viz. Aurantiporusalboaurantius, A.mutans, A.tropicus and Luteoporiaalbocitrina, are proposed based on morphology and phylogenetic analysis. The relationships between Aurantiporus and Hapalopilus are discussed.

Atomic Layer Deposition of CeO2 Film with a Novel Heteroleptic Ce(III) Complex.

In this paper, four heteroleptic Ce(III) complexes, including Ce(thd)3-phen (thd = 2,2,6,6-tetramethyl-3,5-heptanedione, phen = 1, 10-phenanthroline (1), Ce(thd)3-MEDA (MEDA = N-Methylethylenediamine (2), Ce(thd)3-MOMA (MOMA = N-(2-Methoxyethyl)methylamine (3), and Ce(thd)3-DMDE (DMDE = N,N″-dimethyl ethanol amine (4), were synthesized and characterized with 1H-NMR, elemental analysis, and X-ray single-crystal diffraction. The thermogravimetric analysis and vapor pressure results indicated that the complexing ability of a nitrogen-containing bidentate ligand with a cerium ion was stronger than that of a mixed oxygen-nitrogen-containing bidentate ligand. Complex 2 was selected as an ALD precursor to deposit a CeO2 film on a SiO2/Si (100) wafer. The self-limited deposition results demonstrated that complex 2 was a potential ALD precursor.

Identification, validation and candidate gene analysis of major QTL for Supernumerary spikelets in wheat.

BACKGROUND: The number of spikelets per spike is a key trait that affects the yield of bread wheat (Triticum aestivum L.). Identification of the QTL for spikelets per spike and its genetic effects that could be used in molecular assistant breeding in the future. RESULTS: In this study, four recombinant inbred line (RIL) populations were generated and used, having YuPi branching wheat (YP), with Supernumerary Spikelets (SS) phenotype, as a common parent. QTL (QSS.sicau-2 A and QSS.sicau-2D) related to SS trait were mapped on chromosomes 2 A and 2D through bulked segregant exome sequencing (BSE-Seq). Fourteen molecular markers were further developed within the localization interval, and QSS.sicau-2 A was narrowed to 3.0 cM covering 7.6 Mb physical region of the reference genome, explaining 13.7 - 15.9% the phenotypic variance. Similarly, the QSS.sicau-2D was narrowed to 1.8 cM covering 2.4 Mb physical region of the reference genome, and it explained 27.4 - 32.9% the phenotypic variance. These two QTL were validated in three different genetic backgrounds using the linked markers. QSS.sicau-2 A was identified as WFZP-A, and QSS.sicau-2D was identified a novel locus, different to the previously identified WFZP-D. Based on the gene expression patterns, gene annotation and sequence analysis, TraesCS2D03G0260700 was predicted to be a potential candidate gene for QSS.sicau-2D. CONCLUSION: Two significant QTL for SS, namely QSS.sicau-2 A and QSS.sicau-2D were identified in multiple environments were identified and their effect in diverse genetic populations was assessed. QSS.sicau-2D is a novel QTL associated with the SS trait, with TraesCS2D03G0260700 predicted as its candidate gene.

A novel PDGFR inhibitor WQ-C-401 prevents pulmonary vascular remodeling in rats with monocrotaline-induced pulmonary arterial hypertension.

Platelet-derived growth factor (PDGF) is one of the most important cytokines associated with pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). PDGF receptor (PDGFR) inhibition exerted therapeutic effects on PAH in clinical trials, but serious side effects warrant the withdrawal of existing drugs. In this study, a novel highly selective PDGFR inhibitor WQ-C-401 was developed, and its effects on PDGFR signaling pathway and pulmonary vascular remodeling in PAH were investigated. Cell proliferation assays and Western blot analysis of PDGFRα/ß phosphorylation showed that WQ-C-401 inhibited PDGFR-mediated cell proliferation assay and suppressed PDGFR phosphorylation in a concentration-dependent manner. DiscoverX's KinomeScanTM technology confirmed the good kinome selectivity of WQ-C-401 (S score (1) of PDGFR = (0.01)). In monocrotaline (MCT)-induced PAH rats, intragastric administration of WQ-C-401 (25, 50, 100 mg/kg/d) or imatinib (50 mg/kg/d, positive control) significantly decreased right ventricular systolic pressure (RVSP). Histological analysis demonstrated that WQ-C-401 inhibited pulmonary vascular remodeling by reducing muscularization and fibrosis, as well as alleviated right ventricular hypertrophy in MCT-treated rats. In addition, WQ-C-401 suppressed MCT-induced cell hyperproliferation and CD68+ macrophage infiltration around the pulmonary artery. In vitro, WQ-C-401 inhibited PDGF-BB-induced proliferation and migration of human pulmonary arterial smooth muscle cells (PASMCs). Moreover, Western blot analysis showed that WQ-C-401 concertration-dependently inhibited PDGF-BB-induced phosphorylation of ERK1/2 and PDGFRß Y751, decreased collagen Ⅰ synthesis and increased alpha smooth muscle actin (α-SMA) expression in PASMCs. Collectively, our results suggest that WQ-C-401 is a selective and potent PDGFR inhibitor which could be a promising drug for the therapeutics of PAH by preventing pulmonary vascular remodeling.

Colorimetric and ECL dual-mode aptasensor for smartphone-based onsite sensitive detection of aflatoxin B1 in combination with ZnO@MWCNTs/g-C3N4 nanosheets and CuO@CuPt nanocomposites.

The development of dual-mode strategies with superior sensitivity and accuracy have garnered increasing attention for researchers in Aflatoxin B1 (AFB1) analysis. Herein, a colorimetric-electrochemiluminescence (ECL) dual-mode biosensor was constructed for onsite and ultrasensitive determination of AFB1. The multi-wall carbon nanotubes (MWCNTs) were integrated with the ZnO metal organic frameworks (MOFs) to accelerate the electron transfer and boost the ECL intensity of g-C3N4 nanoemitters. Through the aptamer-based DNA sandwich assay, the CuO@CuPt nanocomposites were introduced onto the electrode and acted as the dual functional signal nanoprobes. Due to the good spectrum overlap between the CuO@CuPt nanoprobes and g-C3N4 nanosheets, ECL signal could be efficiently quenched. Additionally, the CuO@CuPt nanoprobes show superior catalytic properties towards the TMB and H2O2 colorimetric reactions, and an obvious color alteration from colorless to blue can be observed using the smartphone. Under optimized conditions, a sensitive and accurate dual-mode analysis of the AFB1 was accomplished with the colorimetric detection limit of 3.26 fg/mL and ECL detection limit of 0.971 fg/mL (S/N = 3). This study combines innovative nanomaterial properties of ZnO@MWCNTs, g-C3N4 and CuO@CuPt for ultrasensitive dual-mode detection, which offers new opportunities for the innovative engineering of the dual-mode sensors and demonstrates significant potential in food safety analysis.

Identification and phylogenetic analysis of Nairobi sheep disease virus from Haemaphysalis longicornis ticks in Shandong Province, China.

Nairobi Sheep Disease (NSD) is a typical tick-borne syndrome characterized by severe hemorrhagic gastroenteritis, spontaneous abortion, and a high case fatality rate in small ruminants. The pathogenic agent, Nairobi sheep disease virus (NSDV), has also been associated with human infections, indicating its possible zoonotic potential. Prior to this study, NSDV has been detected from ticks collected in Jilin, Hubei, and Liaoning provinces in China. In the present study, a total of 343 ticks (Haemaphysalis longicornis) were collected in Shandong province, China in 2020, and pooled into 16 libraries. Analysis of the meta-transcriptomic sequencing data identified NSDV strains SDWL07, SDWL08, and SDWL16 from three pools. The SDWL07 and SDWL16 strains were detected from unfed ticks, while SDWL08 was detected from cattle-feeding ticks. Phylogenetic analyses showed higher sequence identities between the three strains and other Chinese NSDV strains than those from India and Kenya. Phylogenetic analyses also revealed that they clustered together and fell within the China lineage, suggesting no potential genetic reassortment among them. In summary, this is the first report of the identification of NSDV in Shandong province, highlighting the continually expanding endemic regions of this pathogen. Surveillance of NSDV should be intensified in China, especially in areas where H. longicornis is endemic.

Nanomaterial-related hemoglobin-based oxygen carriers, with emphasis on liposome and nano-capsules, for biomedical applications: current status and future perspectives.

Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have been studied and developed as a replacement for red blood cells (RBCs) in oxygen transport due to their similar oxygen-carrying capacities. However, applications of HBOCs are hindered by vasoactivity, oxidative toxicity, and a relatively short circulatory half-life. With advancements in nanotechnology, Hb encapsulation, absorption, bioconjugation, entrapment, and attachment to nanomaterials have been used to prepare nanomaterial-related HBOCs to address these challenges and pend their application in several biomedical and therapeutic contexts. This review focuses on the progress of this class of nanomaterial-related HBOCs in the fields of hemorrhagic shock, ischemic stroke, cancer, and wound healing, and speculates on future research directions. The advancements in nanomaterial-related HBOCs are expected to lead significant breakthroughs in blood substitutes, enabling their widespread use in the treatment of clinical diseases.

Research on "The Belt and Road Initiative" report of think tank based on theme evolution and identification--Taking 2013-2020 as an example.

China's "the Belt and Road Initiative" (BRI) is a top-level cooperation initiative among countries proposed by China, which has promoted China's cooperation with relevant countries in various aspects and fields. Research reports from think tanks and experts on the evaluation, analysis, and research conclusions of the BRI can reflect the stance, opinions, and demands of various countries abroad regarding the initiative. This paper takes the BRI reports of important think tanks in the " Global Go To Think Tank Index Report 2020" as the subject of its research, and analyzes the key points and development trends of foreign think tank research on the BRI by using text mining, topic evolution, and social network analysis. It provides reasonable suggestions and ideas for promoting the construction of the BRI and deepening related cooperation in China. Research shows that the thematic distribution of research reports on the BRI by think tanks is mainly focused on the fields of politics, economy, and military. The research areas are relatively stable, and there is not a strong trend of thematic evolution. The evolution paths are also mainly distributed in the fields of politics, economy, and military. There are not many expansions in the thematic evolution directions over the years, and there is a strong inheritance of themes. The connection between research themes and the main purpose of the BRI is somewhat inadequate, indicating a certain limitation in the understanding of the BRI.

Feature-Based Molecular Network-Assisted Cannabinoid and Flavonoid Profiling of Cannabis sativa Leaves and Their Antioxidant Properties.

Cannabis sativa (C. sativa) leaves are rich in cannabinoids and flavonoids, which play important antioxidant roles. Since the environmental factors may influence the accumulation of antioxidants in herbal medicines, which affects their activity, this study aimed to investigate the correlation between the chemical composition of C. sativa leaves and their geographical origin and antioxidant activity. Firstly, a high-resolution mass spectrometry method assisted by semi-quantitative feature-based molecular networking (SQFBMN) was established for the characterization and quantitative analysis of C. sativa leaves from various regions. Subsequently, antioxidant activity analysis was conducted on 73 batches of C. sativa leaves, and a partial least squares regression (PLS) model was employed to assess the correlation between the content of cannabinoids and flavonoids in the leaves and their antioxidant activity. A total of 16 cannabinoids and 57 flavonoids were annotated from C. sativa, showing a significant regular geographical distribution. The content of flavonoid-C glycosides in Sichuan leaves is relatively high, and their antioxidant activity is also correspondingly high. However, the leaves in Shaanxi and Xinjiang were primarily composed of flavonoid-O glycosides, and exhibited slightly lower antioxidant activity. A significant positive correlation (p < 0.001) was found between the total flavonoids and cannabinoids and the antioxidant activity of the leaves, and two flavonoids and one cannabinoid were identified as significant contributors.

Predicting Bloodstream Infection in High-risk Groups of Liver Failure Patients with Artificial Liver Support System.

Background: Liver failure is a rare, life-threatening disease that has a high mortality rate and affects many organ systems. Bloodstream bacterial infection has played a key role in liver failure patients with plasma exchange-centered artificial liver support systems, but the predicted risk factors of infection have not been fully understood. Objective: We aimed to predict bloodstream bacterial infection in high-risk groups of liver failure patients during a plasma exchange-centered artificial liver support system. Design: This was a prospective cohort study. Setting: This study was performed in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School. Participants: 118 liver failure patients with plasma exchange-centered artificial liver support system therapy from Nanjing Drum Tower Hospital from November 2019 to November 2020 were selected. Interventions: We used a stepwise binary logistic regression model to select the optimal risk factors of infection with minimum Akaike information criterion, and the Nomogram prognostic model for bloodstream infection was constructed for visualization. Primary Outcome Measures: Risk factors of bloodstream infection (2) predictive accuracy of the constructed nomogram model. Results: Among the 118 liver failure patients, 22 (18.64%) were diagnosed with bloodstream bacterial infection. The univariable and multivariate logistic regression analyses suggested that culture level, glucocorticoids use, number of punctures, blood platelet counts, white blood cell counts, and indwelling catheter time were the sex predictors of bloodstream infection for liver failure patients during plasma exchange-centered artificial liver support system (P = .042, P = .013, P = .025, P = .003, P = .024 and P = .026). The nomogram predictive model was established with high prediction accuracy, of which the area under the curve was 0.935 (95% confidence interval: 0.884-0.986), the sensitivity was 0.955, and the specificity was 0.854. Conclusion: The constructed nomogram prognostic model can recognize the risk factors and accurately predict bloodstream infection for liver failure patients during plasma exchange-centered artificial liver support system.

Comparison of the safety profiles for pirfenidone and nintedanib: a disproportionality analysis of the US food and drug administration adverse event reporting system.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown etiology. Pirfenidone (PFD) and nintedanib (NDN) were both conditionally recommended in the clinical practice guideline published in 2015. Safety and tolerability are related to the risk of treatment discontinuation. Therefore, this study evaluated and compared the adverse events (AEs) of PFD and NDN in a large real-world population by analyzing data from the FDA Adverse Event Reporting System (FAERS) to provide a reference for their rational and safe use. Methods: The AEs of PFD and NDN were extracted from the FAERS database. The pharmacovigilance online analysis tool OpenVigil 2.1 was used to retrieve data from the FAERS database from the first quarter of 2012 to the second quarter of 2022. The reporting odds ratio (ROR) and proportional reporting ratio were used to detect the risk signals. Results: The database included 26,728 and 11,720 reports for PFD and NDN, respectively. The most frequent AEs of PFD and NDN were gastrointestinal disorders. The RORs for these drugs were 5.874 and 5.899, respectively. "Cardiac disorders" was the most statistically significant system order class for NDN with an ROR of 9.382 (95% confidence interval = 8.308-10.594). Furthermore, the numbers of designated medical events of PFD and NDN were 552 and 656, respectively. Notably, liver injury was reported more frequently for NDN (11.096%) than for PFD (6.076%). Conclusion: This study revealed differences in the reporting of AEs between PFD and NDN. The findings provide reference for physicians in clinical practice. Attention should be paid to the risks of cardiac disorders and liver injury associated with NDN.

Rational Design of Dual-Functionalized Gd@C82 Nanoparticles to Relieve Neuronal Cytotoxicity in Alzheimer's Disease via Inhibition of Aß Aggregation.

The accumulation of amyloid-ß (Aß) peptides is a major hallmark of Alzheimer's disease (AD) and plays a crucial role in its pathogenesis. Particularly, the structured oligomeric species rich in ß-sheet formations were implicated in neuronal organelle damage. Addressing this formidable challenge requires identifying candidates capable of inhibiting peptide aggregation or disaggregating preformed oligomers for effective antiaggregation-based AD therapy. Here, we present a dual-functional nanoinhibitor meticulously designed to target the aggregation driving force and amyloid fibril spatial structure. Leveraging the exceptional structural stability and facile tailoring capability of endohedral metallofullerene Gd@C82, we introduce desired hydrogen-binding sites and charged groups, which are abundant on its surface for specific designs. Impressively, these designs endow the resultant functionalized-Gd@C82 nanoparticles (f-Gd@C82 NPs) with high capability of redirecting peptide self-assembly toward disordered, off-pathway species, obstructing the early growth of protofibrils, and disaggregating the preformed well-ordered protofibrils or even mature Aß fibrils. This results in considerable alleviation of Aß peptide-induced neuronal cytotoxicity, rescuing neuronal death and synaptic loss in primary neuron models. Notably, these modifications significantly improved the dispersibility of f-Gd@C82 NPs, thus substantially enhancing its bioavailability. Moreover, f-Gd@C82 NPs demonstrate excellent cytocompatibility with various cell lines and possess the ability to penetrate the blood-brain barrier in mice. Large-scale molecular dynamics simulations illuminate the inhibition and disaggregation mechanisms. Our design successfully overcomes the limitations of other nanocandidates, which often overly rely on hydrophobic interactions or photothermal conversion properties, and offers a viable direction for developing anti-AD agents through the inhibition and even reversal of Aß aggregation.