All-Calixarene-Protected Silver Nanocluster with All Silver Atoms in a Face-Centered Cubic Arrangement.

Tailoring the surface ligands of metal nanoclusters is important for engineering unique configurations of metal nanoclusters. Thiacalix[4]arene has found extensive applications in the construction of metal nanoclusters. In this investigation, we present the synthesis and characterization of the first all-calixarene-protected silver nanoclusters, [Ag(CH3CN)4]2[Ag44(BTCA)6] (Ag44, H4BTCA = p-tert-butylthiacalix[4]arene). Single-crystal X-ray structural analysis reveals that all silver atoms are in a face-centered cubic (fcc) arrangement. The formation of such an fcc structure is attributed to the selectively passivation on {100} facets by BTCA4-. Thiacalixarene substantially facilitates the stability of Ag44 due to its multiple coordination sites and bulkiness. Mass spectrometry and theoretical calculations reveal that Ag44 is a superatomic silver nanocluster with 22 free electrons in the following configuration: 1S21P61D61F22S21D4. This work not only elucidates the impact of macrocyclic ligands on the stabilization of silver clusters but also furnishes an approach for assembling atomically precise fcc nanoclusters.

Interplay of kernel shape and surface structure for NIR luminescence in atomically precise gold nanorods.

It is challenging to attain strong near-infrared (NIR) emissive gold nanoclusters. Here we show a rod-shaped cluster with the composition of [Au28(p-MBT)14(Hdppa)3](SO3CF3)2 (1 for short, Hdppa is N,N-bis(diphenylphosphino)amine, p-MBT is 4-methylbenzenethiolate) has been synthesized. Single crystal X-ray structural analysis reveals that it has a rod-like face-centered cubic (fcc) Au22 kernel built from two interpenetrating bicapped cuboctahedral Au15 units. 1 features NIR luminescence with an emission maximum at 920 nm, and the photoluminescence quantum yield (PLQY) is 12%, which is 30-fold of [Au21(m-MBT)12(Hdppa)2]SO3CF3 (2, m-MBT is 3-methylbenzenethiolate) with a similar composition and 60-fold of Au30S(S­t­Bu)18 with a similar structure. time-dependent DFT(TDDFT)calculations reveal that the luminescence of 1 is associated with the Au22 kernel. The small Stokes shift of 1 indicates that it has a very small excited state structural distortion, leading to high radiative decay rate (kr) probability. The emission of cluster 1 is a mixture of phosphorescence and thermally activated delayed fluorescence(TADF), and the enhancement of the NIR emission is mainly due to the promotion of kr rather than the inhibition of knr. This work demonstrates that the metal kernel and the surface structure are both very important for cluster-based NIR luminescence materials.

Hemolysis attributed to high dose vitamin C: Two case reports.

BACKGROUND: High-dose vitamin C treatment (HVCT) can reduce the adverse effect of chemotherapy and enhance the effect of antitumor therapy, which has been considered one of the safest alternative treatments. However, the severity of its adverse effects may have been underestimated. The most serious adverse effect is hemolysis, which may result in acute kidney injury or death. Although glucose-6-phosphate dehydrogenase (G6PD) deficiency is considered to be the main cause, the probability and pathological mechanism are not completely understood, leading to a lack of effective and standardized treatment methods. CASE SUMMARY: Two patients with colorectal cancer developed hemolytic anemia after using 1 g/kg HVCT. In contrast to previous cases, the lowest hemoglobin level in the two cases was < 50 g/L, which was lower than previously reported. This may be because Case 1 had chronic hepatitis B for many years, which caused abnormal liver reserve function, and Case 2 had grade II bone marrow suppression. Both patients improved and were discharged after blood replacement therapy. Our cases had the most severe degree of hemolysis but the best prognosis, suggesting that our treatment may be helpful for rescue of drug-induced hemolysis. This is the first review of the literature on hemolysis caused by HVCT, and we found that all patients with G6PD deficiency developed hemolysis after HVCT. CONCLUSION: G6PD deficiency should be considered as a contraindication to HVCT, and it is not recommended for patients with bone marrow suppression, moderate-to-severe anemia, hematopoietic abnormalities, or abnormal liver and kidney function. Early blood purification and steroid therapy may avoid acute kidney injury or death caused by HVCT-related hemolytic anemia.

Photoinduced decarboxylative germylation of α-fluoroacrylic acids: access to germylated monofluoroalkenes.

Herein, a novel strategy is presented for the photoinduced decarboxylative and dehydrogenative cross-coupling of a wide range of α-fluoroacrylic acids with hydrogermanes. This methodology provides an efficient and robust approach for producing various germylated monofluoroalkenes with excellent stereoselectivity within a brief photoirradiation period. The feasibility of this reaction has been demonstrated through gram-scale reaction, conversion of germylated monofluoroalkenes, and modification of complex organic molecules.

Comparison of the protective effects of chitosan oligosaccharides and chitin oligosaccharide on apoptosis, inflammation and oxidative stress.

Chitin degradation products, especially chitosan oligosaccharides (COSs), are highly valued in various industrial fields, such as food, medicine, cosmetics and agriculture, for their rich resources and high cost-effectiveness. However, little is known about the impact of acetylation on COS cellular bioactivity. The present study aimed to compare the differential effects of COS and highly N-acetylated COS (NACOS), known as chitin oligosaccharide, on H2O2-induced cell stress. MTT assay showed that pretreatment with NACOS and COS markedly inhibited H2O2-induced RAW264.7 cell death in a concentration-dependent manner. Flow cytometry indicated that NACOS and COS exerted an anti-apoptosis effect on H2O2-induced oxidative damage in RAW264.7 cells. NACOS and COS treatment ameliorated H2O2-induced RAW264.7 cell cycle arrest. Western blotting revealed that the anti-oxidation effects of NACOS and COS were mediated by suppressing expression of proteins involved in H2O2-induced apoptosis, including Bax, Bcl-2 and cleaved PARP. Furthermore, the antagonist effects of NACOS were greater than those of COS, suggesting that acetylation was essential for the protective effects of COS.

Influence of maximum diameter on fine-needle aspiration biopsy outcomes in ACR TI-RADS 5 thyroid nodules.

Introduction: Fine needle aspiration (FNA) biopsy is a widely accepted method for diagnosing thyroid nodules. However, the influence of maximum diameter (MD) of ACR TIRADS 5 (TR5) thyroid nodules on the FNA outcomes remains debated. This study examined the influence of MD on the FNA outcomes and investigated the optimal MD threshold for FNA in TR5 nodules. Methods: We conducted a retrospective analysis of 280 TR5 thyroid nodules from 226 patients who underwent FNA from January to June 2022 in our department. Probably malignant (PM) group was defined as Bethesda V in cytopathology with confirmed BRAF V600E mutation or Bethesda VI, the other cytopathology outcomes were defined as probably benign (PB) group. We examined factors influencing malignant cytopathology outcomes and determined the optimal MD threshold for FNA in TR5 nodules using logistic regression and restricted cubic spline (RCS) analysis. Results: Among these nodules, 58.2% (163/280) had PM outcomes. The PM group had a significantly larger MD than the PB group [6.5mm (range 5.0-8.4) vs. 5.3mm (range 4.0-7.0), p < 0.001]. In multivariate logistic regression fully adjusted for confounders, MD was significantly associated with PM outcomes [odds ratio 1.16, 95%CI 1.05-1.31; p = 0.042]. The highest quartile of MD had a greater likelihood of PM outcomes compared to the lowest quartile [odds ratio 4.71, 95% CI 1.97-11.69, p = 0.001]. The RCS analysis identified 6.2 mm as the optimal MD threshold for FNA in TR5 nodules. Conclusion: MD significantly affects the probability of malignant outcomes in FNA of TR5 thyroid nodules. A MD threshold of ≥6.2mm is suggested for FNA in these nodules.

Identification of potential therapeutic targets for plaque vulnerability based on an integrated analysis.

BACKGROUND AND AIMS: This study aimed to explore potential hub genes and pathways of plaque vulnerability and to investigate possible therapeutic targets for acute coronary syndrome (ACS). METHODS AND RESULTS: Four microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), weighted gene coexpression networks (WGCNA) and immune cell infiltration analysis (IIA) were used to identify the genes for plaque vulnerability. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Disease Ontology, Gene Ontology annotation and protein-protein interaction (PPI) network analyses were performed to explore the hub genes. Random forest and artificial neural networks were constructed for validation. Furthermore, the CMap and Herb databases were employed to explore possible therapeutic targets. A total of 168 DEGs with an adjusted P < 0.05 and approximately 1974 IIA genes were identified in GSE62646. Three modules were detected and associated with CAD-Class, including 891 genes that can be found in GSE90074. After removing duplicates, 114 hub genes were used for functional analysis. GO functions identified 157 items, and 6 pathways were enriched for the KEGG pathway at adjusted P < 0.05 (false discovery rate, FDR set at < 0.05). Random forest and artificial neural network models were built based on the GSE48060 and GSE34822 datasets, respectively, to validate the previous hub genes. Five genes (GZMA, GZMB, KLRB1, KLRD1 and TRPM6) were selected, and only two of them (GZMA and GZMB) were screened as therapeutic targets in the CMap and Herb databases. CONCLUSION: We performed a comprehensive analysis and validated GZMA and GZMB as a target for plaque vulnerability, which provides a therapeutic strategy for the prevention of ACS. However, whether it can be used as a predictor in blood samples requires further experimental verification.

Osteoarthritis and hypertension: observational and Mendelian randomization analyses.

BACKGROUND: The association between osteoarthritis (OA) and hypertension is a subject of ongoing debate in observational research, and the underlying causal relationship between them remains elusive. METHODS: This study retrospectively included 24,871 participants in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2020. Weighted logistic regression was performed to investigate the connection between OA and hypertension. Additionally, Mendelian randomization (MR) analysis was conducted to explore the potential causal relationship between OA and hypertension. RESULTS: In the NHANES data, after adjusting for multiple confounding factors, there was no significant relationship between OA and hypertension (OR 1.30, 95% CI, 0.97-1.73, P = 0.089). However, among males, OA appeared to be associated with a higher risk of hypertension (OR 2.25, 95% CI, 1.17-4.32, P = 0.019). Furthermore, MR results indicate no relationship between multiple OA phenotypes and hypertension: knee OA (IVW, OR 1.024, 95% CI: 0.931-1.126, P = 0.626), hip OA (IVW, OR 0.990, 95% CI: 0.941-1.042, P = 0.704), knee or hip OA (IVW, OR 1.005, 95% CI: 0.915-1.105, P = 0.911), and OA from UK Biobank (IVW, OR 0.796, 95% CI: 0.233-2.714, P = 0.715). Importantly, these findings remained consistent across different genders and in reverse MR. CONCLUSIONS: Our study found that OA patients had a higher risk of hypertension only among males in the observational study. However, MR analysis did not uncover any causal relationship between OA and hypertension.

An Evidence-Based Medical Review on Promoting Gastrointestinal Function Recovery After Colorectal Cancer Surgery.

Objective: The objective of this study was to search for, evaluate, and summarize data related to a faster postoperative recovery in patients with colorectal cancer (CRC) based on literature from China as well as internationally. This will serve as an evidence-based foundation for the clinical implementation of enhanced postoperative recovery of gastrointestinal function in patients with CRC. Methods: Based on the hierarchical "6S" evidence model, we conducted a systematic search of computerized decision-support systems, guideline websites, as well as domestic and international databases for evidence, guidelines, expert consensus statements, clinical decision-making, best practices, evidence summaries, and systematic reviews of interventions focusing on accelerating gastrointestinal function rehabilitation after CRC surgery. The time limit for the search was from the date of creation of the database to January 2023. Two researchers evaluated the quality of the literature that was included, and we extracted data and summarized the evidence from those publications that fulfilled the quality criteria. Results: The review included a total of 21 publications, comprising 6 guidelines, 6 systematic reviews, 3 expert consensus statements, 4 randomized controlled trials, and 2 evidence summaries. We summarized 51 best evidence findings across five areas: organizational management, preoperative risk assessment, education, intraoperative monitoring, and postoperative management. Conclusion: There is a wide variety and wealth of information available on interventions to promote enhanced postoperative recovery of gastrointestinal function in patients with CRC. The use of evidence is discussed, keeping in mind the practical situation in China.

Near-unity NIR phosphorescent quantum yield from a room-temperature solvated metal nanocluster.

Metal nanoclusters have emerged as promising near-infrared (NIR)-emissive materials, but their room-temperature photoluminescence quantum yield (PLQY), especially in solution, is often low (<10%). We studied the photophysics of Au22(tBuPhC≡C)18 (Au22) and its alloy counterpart Au16Cu6(tBuPhC≡C)18 (Au16Cu6) (where tBu is tert-butyl and Ph is phenyl) and found that copper (Cu) doping suppressed the nonradiative decay (~60-fold less) and promoted intersystem crossing rate (~300-fold higher). The Au16Cu6 nanocluster exhibited >99% PLQY in deaerated solution at room temperature with an emission maximum at 720 nanometers tailing to 950 nanometers and 61% PLQY in the oxygen-saturated solution. The approach to achieve near-unity PLQY could enable the development of highly emissive metal cluster materials.

Multivariate classification based on large-scale brain networks during early abstinence predicted lapse among male detoxified alcohol-dependent patients.

Identifying biomarkers to predict lapse of alcohol-dependence (AD) is essential for treatment and prevention strategies, but remains remarkably challenging. With an aim to identify neuroimaging features for predicting AD lapse, 66 male AD patients during early-abstinence (baseline) after hospitalized detoxification underwent resting-state functional magnetic resonance imaging and were then followed-up for 6 months. The relevance-vector-machine (RVM) analysis on baseline large-scale brain networks yielded an elegant model for differentiating relapsing patients (n = 38) from abstainers, with the area under the curve of 0.912 and the accuracy by leave-one-out cross-validation of 0.833. This model captured key information about neuro-connectome biomarkers for predicting AD lapse.

EGFR Inhibition Overcomes Resistance to FGFR4 Inhibition and Potentiates FGFR4 Inhibitor Therapy in Hepatocellular Carcinoma.

Aberrant activation of the FGF19-FGFR4 signaling pathway plays an essential role in the tumorigenesis of hepatocellular carcinoma (HCC). As such, FGFR4 inhibition has emerged as a novel therapeutic option for the treatment of HCC and has shown preliminary efficacy in recent clinical trials for patients exhibiting aberrant FGF19 expression. Resistance to kinase inhibitors is common in oncology, presenting a major challenge in the clinical treatment process. Hence, we investigated the potential mechanisms mediating and causing resistance to FGFR4 inhibition in HCC. Upon the successful establishment of a battery of cellular models developing resistance to FGFR4 inhibitors, we have identified the activation of EGFR, MAPK, and AKT signaling as the primary mechanisms mediating the acquired resistance. Combination of inhibitors against EGFR or its downstream components restored sensitivity to FGFR4 inhibitors. In parental HCC cell lines, EGF treatment also resulted in resistance to FGFR4 inhibitors. This resistance was effectively reverted by inhibitors of the EGFR signaling pathway, suggesting that EGFR activation is a potential cause of intrinsic resistance. We further confirmed the above findings in vivo in mouse xenograft tumor models. Genomic analysis of patient samples from The Cancer Genome Atlas confirmed that a segment of patients with HCC harboring FGF19 overexpression indeed exhibited increased activation of EGFR signaling. These findings conclusively indicate that both induced and innate activation of EGFR could mediate resistance to FGFR4 inhibition, suggesting that dual blockade of EGFR and FGFR4 may be a promising future therapeutic strategy for the treatment of FGF19-FGFR4 altered HCC.

[Hippocampal Development Deviation and Its Relationship With Cognition in Major Psychiatric Disorders].

Objective: To investigate hippocampal development deviation and its association with cognition in patients with major psychiatric disorders (MPDs), including schizophrenia, bipolar disorder and major depressive disorder. Methods: The T1-weighted MRI data of 174 first-episode drug-naïve schizophrenia (FES) atients, 169 bipolar disorder (BD) patients, 184 major depressive disorder (MDD) patients, and 321 healthy controls were collected and their hippocampal volume was extracted after preprocessing with Freesurfer 5.3. A normative neurodevelopment model was applied to calculate the hippocampal deviation scores. Data on cognitive functions, including visual memory, attention, spatial working memory, were collected. Comparison by different sexes was made to identify difference between the hippocampal development deviation scores of the control group and those of the disease groups. We also investigated the moderating effect of age on the deviation score and explored the association between the deviation score and cognitive function. Results: The hippocampal development deviation scores of patients with MPDs were significantly lower than those of the healthy controls (false discovery rate [FDR]-P<0.05). Analysis of the moderating effect of age revealed lower deviation scores in young patients (<[25.83-28.56] yr.) and higher deviation scores in old patients (>[35.87-54.35] yr.) in comparison with those of the healthy controls. The right hippocampal deviation scores in male FES patients were positively correlated with the number of errors for tasks concerning spatial working memory ( r=0.32, FDR-P=0.04). Conclusion: Our findings suggest abnormal hippocampal development in MPDs patients and its different distribution in MPDs patients of different age groups. The hippocampal development deviation score may provide a new perspective for further understanding of etiology in MPDs.

Synergism of amlodipine and telmisartan or candesartan on blood pressure reduction by using SynergyFinder 3.0 and probability sum test in vivo.

This study was designed to evaluate the synergism of two couples of antihypertensive drugs (amlodipine + telmisartan and amlodipine + candesartan) on blood pressure reduction in vivo by both SynergyFinder 3.0 and probability sum test. Spontaneously hypertensive rats were treated with intragastric administration of amlodipine (0.5, 1, 2, and 4 mg/kg), telmisartan (4, 8, and 16 mg/kg), candesartan (1, 2, and 4 mg/kg), nine combinations for amlodipine and telmisartan, and nine combinations for amlodipine and candesartan. The control rats were treated by 0.5% carboxymethylcellulose sodium. Blood pressure was recorded continuously up to 6 h after administration. Both SynergyFinder 3.0 and the probability sum test were used to evaluate the synergistic action. The synergisms calculated by SynergyFinder 3.0 are consistent with the probability sum test both in two different combinations. There is an obviously synergistic interaction between amlodipine and telmisartan or candesartan. The combinations of amlodipine and telmisartan (2 + 4 and 1 + 4 mg/kg) and amlodipine and candesartan (0.5 + 4 and 2 + 1 mg/kg) might exert an optimum synergism against hypertension. Compared with the probability sum test, SynergyFinder 3.0 is more stable and reliable to analyze the synergism.

[Karst Hydrogeochemical Characteristics and Controlling Factors of Carlin-type Gold Mining Area Based on Hydrochemistry and Sulfur Isotope].

Mining activities change the groundwater level and flow conditions through pumping and drainage, which enhances the interaction between groundwater and aquifer rocks; mine drainage is discharged into the surface water system, which affects the whole karst water hydrogeochemical process. Based on hydrogeochemistry and the δ34S isotope, the hydrogeochemical processes, characteristics, and main controlling factors for waste water, karst groundwater, and surface water in a typical Carlin gold mining area and its surrounding areas were revealed. The results showed that:chemical compositions of groundwater and surface water unaffected by gold mining activities were mainly controlled by the weathering of limestone and dolomitic limestone; Ca2+, Mg2+, and HCO3- were main ions; and the water chemical types were Ca-HCO3. The mine wastewater and its downstream receiving water were affected by the dissolution of carbonate and silicate minerals, and cation exchange also played a role; the main ions were Ca2+, Mg2+, Na+, and SO42-, and the hydrochemical type gradually evolved from Ca-HCO3 to Ca-SO4. SO42- was the characteristic component in various water bodies affected by mining, and the concentration of SO42- gradually decreased from top to bottom in the well. The values of δ34S for unaffected groundwater and surface water were positive, and SO42- was mainly derived from realgar oxidation. Conversely, mine wastewater and downstream water were negative, SO42- was mainly influenced by the mixing action of realgar oxidation and meteoric precipitation, and pyrite also contributed to a certain extent. At the same time, NO3- came from agricultural fertilizer and rural domestic sewage discharge directly. Principal component analysis (PCA) further demonstrated:sulfide mineral oxidation and mining activities were the main controlling factors for the water chemical composition of mine wastewater and downstream water, whereas unaffected groundwater and surface water were mainly influenced by water-rock (carbonate rock) interactions. Agricultural fertilizer and rural sewage discharge also had a certain influence. Therefore, the study area should strengthen the interception of surface water, control-block-management of sulfide oxidation, rural domestic sewage treatment, and agricultural fertilizer.

Pickering emulsion stabilized by palm-pressed fiber cellulose nanocrystal extracted by acid hydrolysis-assisted high pressure homogenization.

Palm pressed fibre (PPF) is a lignocellulose biomass generated from palm oil mill that is rich in cellulose. The present work aimed to combine acid hydrolysis followed by high-pressure homogenisation (HPH) to produce nanocrystal cellulose (CNC) with enhanced physicochemical properties from PPF. PPF was alkaline treated, bleached, acid hydrolysed and homogenised under high pressure condition to prepare CNC. The effects of homogenisation pressure (10, 30, 50, 70 MPa) and cycles (1, 3, 5, 7) on the particle size, zeta potential and rheological properties of CNC produced were investigated. HPH was capable of producing CNC with better stability. Results revealed that utilizing 1 cycle of homogenisation at a pressure of 50 MPa resulted in CNC with the smallest dimension, highest aspect ratio, moderate viscosity and exceptionally high zeta potential. Subsequently, 0.15% (CNC 0.15 -PE) and 0.30% (CNC 0.30 -PE) of CNC was used to stabilise oil-in-water emulsions and their stability was evaluated against different pH, temperature and ionic strength. All the CNC-stabilised emulsions demonstrated good thermal stability. CNC 0.30 -PE exhibited larger droplets but higher stability than CNC 0.15 -PE. In short, CNC with gel like structure has a promising potential to serve as a natural Pickering emulsifier to stabilise oil-in-water emulsion in various food applications.

Site-specific doping of silver atoms into a Au25 nanocluster as directed by ligand binding preferences.

For the first time site-specific doping of silver into a spherical Au25 nanocluster has been achieved in [Au19Ag6(MeOPhS)17(PPh3)6] (BF4)2 (Au19Ag6) through a dual-ligand coordination strategy. Single crystal X-ray structural analysis shows that the cluster has a distorted centered icosahedral Au@Au6Ag6 core of D 3 symmetry, in contrast to the I h Au@Au12 kernel in the well-known [Au25(SR)18]- (R = CH2CH2Ph). An interesting feature is the coexistence of [Au2(SPhOMe)3] dimeric staples and [P-Au-SPhOMe] semi-staples in the title cluster, due to the incorporation of PPh3. The observation of only one double-charged peak in ESI-TOF-MS confirms the ordered doping of silver atoms. Au19Ag6 is a 6e system showing a distinct absorption spectrum from [Au25(SR)18]-, that is, the HOMO-LUMO transition of Au19Ag6 is optically forbidden due to the P character of the superatomic frontier orbitals.

The Epidemiological, Clinical Features and Outcomes of Imported Chinese COVID-19 Patients Following Inactivated Vaccines Injection.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination had been demonstrated as an effective way to reduce the risk of coronavirus disease 2019 (COVID-19), and only a few vaccines suffered from SARS-CoV-2 infection. However, limited data concerning the clinical features of these vaccines infected with SARS-CoV-2 can be identified. Methods: We retrospectively collected and analyzed epidemiological and clinical characteristics data of the imported COVID-19 cases who received Chinese inactivated vaccines abroad. Data were extracted from electronic medical records from a designated hospital in the Shaanxi Province of China between March 22 and May 17, 2021. Results: Totally, 46 confirmed SARS-CoV-2 infection patients were enrolled. The mean age was 40.5 years (range 20-61), 41 (89.1%) are male. Eighteen (39.1%) patients were from Pakistan. Fourteen (30.4%) patients had at least one comorbidity. Forty (87.0%) and 6 cases were fully vaccinated and partly vaccinated. The time interval between vaccination and infection was 88 days (IQR, 33-123), 31 (67.4%) and 15 (32.6%) were asymptomatic and symptomatic cases, respectively. Fever (3/46, 6.5%) was the most common symptom; however, none had a body temperature higher than 38.0°C, and no severe case was observed. Notably, the rate of SARS-CoV-2 shedding discontinuation at 7 days after hospitalization in asymptomatic cases was higher than symptomatic one (93.5% vs 40%, P < 0.0001). Conclusion: Individuals who received Chinese inactivated vaccines abroad remain to have the probability of being infected with SARS-CoV-2, but all the vaccines infected with SARS-CoV-2 were asymptomatic or had mild symptoms with favorable clinical outcomes.

Sodium Ferulate Inhibits Rat Cardiomyocyte Hypertrophy Induced by Angiotensin II Through Enhancement of Endothelial Nitric Oxide Synthase/Nitric Oxide/Cyclic Guanosine Monophosphate Signaling Pathway.

ABSTRACT: Sodium ferulate (SF) is the sodium salt of ferulic acid, which is one of the effective components of Angelica sinensis and Lignsticum chuanxiong , and plays an important role in protecting the cardiovascular system. In this study, myocardial hypertrophy was induced by angiotensin II 0.1 µmol/L in neonatal Sprague-Dawley rat ventricular myocytes. Nine groups were designed, that is, normal, normal administration, model, L-arginine (L-arg 1000 µmol/L), SF (50, 100, 200 µmol/L) group, and N G -nitro-L-arg-methyl ester 1500 µmol/L combined with SF 200 µmol/L or L-arg 1000 µmol/L group, respectively. Cardiomyocyte hypertrophy was confirmed by observing histological changes and measurements of cell diameter, protein content and atrial natriuretic factor, and ß-myosin heavy chain levels of the cells. Notably, SF could inhibit significantly myocardial hypertrophy of neonatal rat cardiomyocytes in a concentration-dependent manner without producing cytotoxicity, and the levels of nitric oxide, NO synthase (NOS), endothelial NOS, and cyclic guanosine monophosphate were increased, but the level of cyclic adenosine monophosphate was decreased in cardiomyocytes. Simultaneously, levels of protein kinase C beta, Raf-1, and extracellular regulated protein kinase 1/2 (ERK1/2) were downregulated, whereas levels of mitogen-activated protein kinase phosphatase-1 were significantly upregulated. All the beneficial effects of SF were blunted by N G -nitro-L-arg-methyl ester. Overall, these findings reveal that SF can inhibit angiotensin II-induced myocardial hypertrophy of neonatal rat cardiomyocytes, which is closely related to activation of endothelial NOS/NO/cyclic guanosine monophosphate, and inhibition of protein kinase C and mitogen-activated protein kinase signaling pathways.

Iodine-125 induced cholangiocarcinoma cell death is enhanced by inhibition of endoplasmic reticulum stress-mediated protective autophagy.

Cholangiocarcinoma (CCA) is the second most common primary liver malignancy, however, it is difficult to diagnose and treat, and only a few patients with CCA are suitable for surgery. Iodine-125 (I-125) is an effective treatment for cancer, but the molecular mechanisms underlying the effects of I-125 differ among different cancers. This study aimed to explore the effects of I-125 on CCA cell activity and determine the possible mechanisms of action of I-125 in this type of cancer. CCA cell proliferation, cycling, apoptosis, autophagy, and endoplasmic reticulum (ER) stress were determined after irradiation of CCA cells with I-125 seeds. The effects of I-125 on autophagy and ER stress in three CCA cell lines were evaluated using western blotting, while the effects of I-125 on apoptosis and autophagy in QBC939 cells treated with si-Beclin1 or si-PERK, respectively, were assessed using flow cytometry. I-125 suppressed cell viability and induced cell cycle G2/M-phase arrest in three CCA cell lines (QBC939, TFK-1, HuCCT1). I-125 induced apoptosis, autophagy, and ER stress by altering the expression levels of some related proteins in each of the three CCA cell lines. Furthermore, autophagy inhibition (treatment with si-Beclin1) increased expression of apoptosis-related proteins (cleaved-PARP and cleaved-caspase-3, Bax/Bcl2) in QBC939 cells irradiated with I-125 seeds, while ER stress inhibition (with si-PERK) suppressed the expression of autophagy-related proteins (LC3-I, LC3-II, p62). Therefore, I-125 induces ER stress, thereby activating protective autophagy in CCA cells through the PERK signaling pathway. Combined inhibition of ER stress and autophagy signaling may increase the killing effect of I-125 on cancer cells and serve as a new auxiliary method in I-125 radiotherapy.