Colletotrichum species (Glomerellales, Glomerellaceae) causing walnut anthracnose in China.

Colletotrichum species can function as plant pathogens, saprobes or endophytes on a wide variety of plant hosts and are considered amongst the ten most significant genera of plant pathogens globally. China contributes almost half the walnut production in the world. However, Colletotrichum species occurring on walnut remain largely unresolved in China. To explore the Colletotrichum species found on walnut in China, 470 walnut fruit or leaf samples with anthracnose were collected from 14 main walnut-producing regions across seven provinces. A total of 165 Colletotrichum strains were isolated from these samples. The Colletotrichum isolates were identified, based on morphological characteristics and sequence analyses of ACT, CHS-1, GAPDH, ITS and TUB2. Twelve species, including 11 known Colletotrichum species (C.boninense, C.citrulli, C.fioriniae, C.fructicola, C.godetiae, C.juglandicola, C.karsti, C.mengyinense, C.pandanicola, C.peakense and C.siamense) and a novel species (C.chinensis sp. nov.) were identified. The species distribution revealed regional prevalence as follows: C.mengyinense was the most dominant species in Gansu, C.mengyinense and C.siamense in Shandong, C.chinensis in Beijing, C.pandanicola in Shaanxi and C.godetiae in Yunnan. Colletotrichumsiamense was the sole species isolated in Sichuan and Xinjiang Provinces. Koch's postulates were fulfilled, demonstrating that all 12 species cause anthracnose on walnut. This is the first report of C.boninense, C.citrulli and C.karsti as pathogens of walnut anthracnose worldwide.

A computational mechanistic study on the formation of aryl sulfonyl fluorides via Bi(III) redox-neutral catalysis and further rational design.

Sulfonyl fluorides hold significant importance as highly valued intermediates in chemical biology due to their optimal balance of biocompatibility with both aqueous stability and protein reactivity. The Cornella group introduced a one-pot strategy for synthesizing aryl sulfonyl fluorides via Bi(III) redox-neutral catalysis, which facilitates the transmetallation and direct insertion of SO2 into the BiC(sp2) bond giving the aryl sulfonyl fluorides. We report herein a comprehensive computational investigation of the redox-neutral Bi(III) catalytic mechanism, disclose the critical role of the Bi(III) catalyst and base (i.e., K3PO4), and uncover the origin of SO2 insertion into the Bi(III)C(sp2) bond. The entire catalysis can be characterized via three stages: (i) transmetallation generating the Bi(III)-phenyl intermediate IM3 facilitated by K3PO4. (ii) SO2 insertion into IM3 leading to the formation of Bi(III)-OSOAr intermediate IM5. (iii) IM5 undergoes S(IV)-oxidation yielding the aryl sulfonyl fluoride product 4 and liberating the Bi(III) catalyst for the next catalytic cycle. Each stage is kinetically and thermodynamically feasible. Moreover, we explored other some small molecules (NO2, CO2, H2O, N2O, etc.) insertion reactions mediated by the Bi(III)-complex, and found that NO2 insertions could be easily achieved due to the low insertion barriers (i.e., 17.5 kcal/mol). Based on the detailed mechanistic study, we further rationally designed additional Bi(III) and Sb(III) catalysts, and found that some of which exhibit promising potential for experimental realization due to their low barriers (<16.4 kcal/mol). In this regard, our study contributes significantly to enhancing current Bi(III)-catalytic systems and paving the way for novel Bi(III)-catalyzed aryl sulfonyl fluoride formation reactions.

Association between ASPECTS region of infarction and clinical outcome in non-acute large vessel occlusion ischaemic stroke after endovascular recanalisation.

PURPOSE: This study retrospectively investigated whether infarction in specific Alberta Stroke Program Early CT Score (ASPECTS) regions is associated with clinical outcome in patients with symptomatic non-acute internal carotid or middle cerebral artery occlusion who underwent endovascular recanalisation (ER). METHODS: Preoperative ASPECTS and region of infarction were recorded before recanalisation. Clinical outcome was evaluated 90 days after the procedure using the modified Rankin Scale; a score>2 was defined as poor outcome. Secondary outcomes included postprocedural cerebral oedema, intracranial haemorrhage (ICH) and symptomatic ICH. RESULTS: Among the 86 patients included, 90-day outcome was poor in 30 (34.9%) and 40 experienced cerebral oedema (46.5%). Multivariate logistic regression models showed that lenticular nucleus infarction (OR 19.61-26.00, p<0.05), admission diastolic blood pressure (OR 1.07-1.08, p<0.05), preprocedural National Institutes of Health Stroke Scale (OR 1.96-2.05, p<0.001) and haemorrhagic transformation (OR 14.99-18.81, p<0.05) were independent predictors of poor 90-day outcome. The area under the receiver operating characteristic curve for lenticular nucleus infarction as a predictor of poor outcome was 0.73. M2 region infarction (OR 26.07, p<0.001) and low American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology collateral circulation grade (OR 0.16, p=0.001) were independent predictors of postprocedural cerebral oedema. The area under the receiver operating characteristic curve for M2 region infarction as a predictor of cerebral oedema was 0.64. Region of infarction did not significantly differ between patients with and without postprocedural ICH or symptomatic ICH. CONCLUSIONS: Lenticular nucleus and M2 region infarction were independent predictors of poor 90-day outcome and postprocedural cerebral oedema, respectively, in patients with non-acute anterior circulation large artery occlusion who underwent ER.

Dronedarone inhibits the proliferation of esophageal squamous cell carcinoma through the CDK4/CDK6-RB1 axis in vitro and in vivo.

Treatment options for patients with esophageal squamous cell carcinoma (ESCC) often result in poor prognosis and declining health-related quality of life. Screening FDA-approved drugs for cancer chemoprevention is a promising and cost-efficient strategy. Here, we found that dronedarone, an antiarrhythmic drug, could inhibit the proliferation of ESCC cells. Moreover, we conducted phosphorylomics analysis to investigate the mechanism of dronedarone-treated ESCC cells. Through computational docking models and pull-down assays, we demonstrated that dronedarone could directly bind to CDK4 and CDK6 kinases. We also proved that dronedarone effectively inhibited ESCC proliferation by targeting CDK4/CDK6 and blocking the G0/G1 phase through RB1 phosphorylation inhibition by in vitro kinase assays and cell cycle assays. Subsequently, we found that knocking out CDK4 and CDK6 decreased the susceptibility of ESCC cells to dronedarone. Furthermore, dronedarone suppressed the growth of ESCC in patient-derived tumor xenograft models in vivo. Thus, our study demonstrated that dronedarone could be repurposed as a CDK4/6 inhibitor for ESCC chemoprevention.

Unveiling the spin evolution in van der Waals antiferromagnets via magneto-exciton effects.

Among the fascinating phenomena observed in two-dimensional (2D) magnets, the magneto-exciton effect stands out as a pivotal link between optics and magnetism. Although the excitonic effect has been revealed and exhibits a considerable correlation with the spin structures in certain 2D magnets, the underlying mechanism of the magneto-exciton effect remains underexplored, especially under high magnetic fields. Here we perform a systematic investigation of the spin-exciton coupling in 2D antiferromagnetic NiPS3 under high magnetic fields. When an in-plane magnetic field is applied, the exceptional sharp excitonic emission at ~1.4756 eV exhibits a Zeeman-like splitting with g ≈ 2.0, experimentally identifying the exciton as an excitation of dominant triplet-singlet character. By examining the polarization of excitonic emission and simulating the spin evolution, we further verify the correlation between excitonic emission and Néel vector in NiPS3. Our work elucidates the mechanism behind the spin-exciton coupling in NiPS3 and establishes a strategy for optically probing the spin evolutions in 2D magnets.

Risk benefit analysis to evaluate risk of thromboembolic events after mRNA COVID-19 vaccination and COVID-19.

We compared the risks and benefits of COVID-19 vaccines using a causal pathway analysis to weigh up possible risk factors of thromboembolic events post-vaccination. The self-controlled case series (SCCS) method examined the association between thromboembolic events and vaccination while a case-control study assessed the association between thromboembolic events and COVID-19, addressing under-reported infection data issues. The net vaccine effect was estimated using results from SCCS and case-control studies. We used electronic health record data from Corewell Health (16,640 subjects in SCCS and 106,143 in case-control). We found increased risks of thromboembolic events post-vaccination (incidence rate ratio: 1.19, 95% CI: [1.08, 1.31] after the first dose; 1.22, 95% CI: [1.11, 1.34] after the second dose). Vaccination attenuated infection-associated thromboembolic risks (odds ratio: 4.65, 95% CI: [4.18, 5.17] in unvaccinated vs 2.77, 95% CI: [2.40, 3.24] in vaccinated). After accounting for vaccine efficacy and protection against infection-associated thromboembolic events, vaccination decreases thromboembolic event risk, especially during high infection rate periods.

Heterogeneity of SARS-CoV-2 immune responses after the nationwide Omicron wave in China.

It remains unclear how previous infections and vaccinations influenced and shaped heterogeneous immune responses against Omicron and its variants in diverse populations in China. After the national wave of Omicron in early 2023, we evaluated serum levels of neutralizing antibodies (nAbs) against Omicron (B.1.1.529) and its variants (BA.5, BF.7, and CH1.1) in 33 COVID-19 convalescents and 40 uninfected vaccinees, using vesicular stomatitis virus-based pseudovirus neutralizing assay. In addition, we followed 34 Delta convalescent patients to compare their immune responses against Omicron before (late 2021) and after the Omicron wave (early 2023). NAbs at the acute phase of the disease were investigated in 50 Omicron inpatients, including 24 vaccinated and 26 unvaccinated patients. Among them, nasal mucosal IgA levels were measured in 42 subjects. Compared to vaccination, breakthrough infections significantly increased the breadth and magnitude of serum nAbs and mucosal IgA levels against Omicron variants. Exposure to Omicron but not Delta elicited stronger pan-Omicron responses. In Omicron inpatients, nAbs continued to rise as vaccination doses increased. However, in both vaccinees and convalescents, a fourth dose vaccination did not elicit higher nAbs against Omicron. Furthermore, nAbs against Omicron variants lasted longer than nAbs against WT SARS-CoV-2. Breakthrough infections of Omicron variants elicited specific immune responses against Omicron compared to vaccination and Delta infection. Although repeated vaccination revealed limited impacts on serum nAbs, populations at high risk of hospitalization may still benefit from continued vaccination.IMPORTANCEThe study described the specific humoral immunity against Omicron and its variants (BA.5, BF.7, and CH1.1) in diverse populations, including Delta-positive convalescent patients, Omicron-infected patients with a previous or current confirmed Delta infection, Omicron-positive patients, and healthy controls. In addition, we followed Delta convalescents for 1 year to evaluate the effect of a booster vaccine, breakthrough infection, and reinfection. Nasal mucosal IgA levels against SARS-CoV-2 were also examined. The findings of this study demonstrated the varied responses of individuals in different states following the outbreak of Omicron, highlighting the potential advantages of ongoing immunization for groups that are more vulnerable and have a greater likelihood of being hospitalized.

The strongest dative bond in main-group compounds. Theoretical study of OAeF- (Ae = Be-Ba).

Quantum chemical calculations of the anions OAeF- (Ae = Be-Ba) have been carried out using ab initio methods at the CCSD(T)/def2-TZVPP level and density functional theory employing BP86 with various basis sets. The equilibrium structures have linear geometries for Ae = Be and Mg but they are strongly bent for Ae = Sr and Ba while the calcium species has a quasi-linear structure with a very low bending potential. The calculated bond dissociation energies suggest a record-high BDE of De = 144.08 kcal mol-1 for OBeF- at the CCSD(T)/def2-TZVPP level, which is the strongest BDE for a dative bond that has been found so far. The BDE of the heavier homologues have a continuously decreasing order for Ae with Be > Mg (113.01 kcal mol-1) > Ca (84.06 kcal mol-1) > Sr (72.06 kcal mol-1) > Ba (60.00 kcal mol-1). The calculation of the charge distribution reveals a significant charge donation OAe ← F- with a declining sequence for the heavier atoms Ae. The oxygen atom in OAeF- carries always a higher partial charge than the fluorine atom, which contradicts the standard electronegativities of the atoms. The surprising partial charges are explained with the bonding situation of the atoms in the actual electronic structure. The bonding analysis of the OAe-F- bonds using the EDA-NOCV method shows that the bonds have much more electrostatic character than the Ae-F- bonds in the diatomic anions. This finding is supported by the results of the LED partitioning approach. The dative interactions have three major and one minor component. The assignment of a quadruple bond for the heavier species with Ae = Ca, Sr, Ba is not reasonable. The driving force for the bent geometries is the accumulation of electronic charge in the lone-pair region at the Ae atoms, which enhances the electrostatic attraction with the other atoms. An adequate description of the bonding situation is given by the formula O--Ae+ ← F-.

Analysis on the epidemiological and drug resistance characteristics of osteoarticular tuberculosis in South-central China.

Objective: Osteoarticular tuberculosis (OATB) is one of the most common forms of extrapulmonary tuberculosis; however, limited epidemiological data are available on this public health concern worldwide, especially in developing countries. This study aimed to analyze the clinical epidemiology and drug resistance characteristics of OATB cases in Hunan province which located in South-central China. Methods: We retrospectively enrolled OATB patients with Mycobacterium tuberculosis culture positive at Hunan Chest Hospital from January 2013 through March 31, 2022. The multiple demographic, clinical variables and drug susceptibility data of the patients were collected from the hospital's electronic patient records. Descriptive statistical methods, Chi-square test and logistic regression analysis were employed as statistical methods. Results: Of the 269 OATB cases, 197 (73.23%) were males, 206 (76.85%) were farmers; patients' ages ranged from 5 to 85 years, 57 (21.19%) aged at 20-29 years old and 52 (19.33%) aged at 60-69 years old. In terms of the disease, 177 (65.80%) had spinal TB with most occurrence in lumbar vertebrae (26.02%, 70/269), multiple spinal sites (18.96%, 51/269) and thoracic vertebrae (15.24%, 41/269). Outside of the spine, OATB mainly occurred in the lower limb (13.38%, 36/269). In terms of drug resistance, 40 (14.87%) and 72 (26.77%) were resistant to rifampicin (RFP) and isoniazid (INH) respectively; 38 (14.13%) were multi-drug resistant (MDR), and a total of 78 (29.00%) isolates were drug resistant. OATB patients aged 40-49 years old (compared to those aged ≥70 years) and from the west of Hunan province, China (compared to those from the center of Hunan) were at risk for developing RR/MDR (ORs were 5.057 and 4.942, respectively; 95% CIs were 1.009-25.342 and 1.458-16.750, respectively). Conclusion: In South-central China, OATB mainly affected males, farmers and those aged 20-29 and 60-69 years old. Spinal TB is prone to occur in the lumbar and multiple spinal sites. The resistance situation of OATB was serious, and people aged 40-49 years old and patients from the west of Hunan were risk factors of RR/MDR. All these findings will help to improve the prevention, diagnosis and treatment strategies of OATB.

Serum metabolomics profile identifies patients with community-acquired pneumonia infected by bacteria, fungi, and viruses.

PURPOSE: Patients with bacterial, fungal, and viral community-acquired pneumonia (CAP) were studied to determine their metabolic profiles. METHODS: Loop-mediated isothermal amplification technology and nucleic acid sequence-dependent amplification combined with microfluidic chip technology were applied to screen multiple pathogens from respiratory tract samples. Eighteen patients with single bacterial infection (B-CAP), fifteen with single virus infection (V-CAP), twenty with single fungal infection (F-CAP), and twenty controls were enrolled. UHPLC-MS/MS analysis of untargeted serum samples for metabolic profiles. Multiple linear regression and Spearman's rank correlation analysis were used to determine associations between metabolites and clinical parameters. The sensitivity and specificity of the screened metabolites were also examined, along with their area under the curve. RESULTS: The metabolic signatures of patients with CAP infected by bacteria, viruses, and fungi were markedly different from those of controls. The abundances of 45, 56, and 79 metabolites were significantly unbalanced. Among these differential metabolites, 11, 13, and 29 were unique to the B-CAP, V-CAP, and F-CAP groups, respectively. Bacterial infections were the only known causes of disturbances in the pentose and glucuronate and aldarate and ascorbate metabolism interconversions metabolic pathway. CONCLUSIONS: Serum metabolomic techniques based on UHPLC-MS/MS may identify differences between individuals with CAP who have been infected by various pathogens, and they can also build a metabolite signature for early detection of the origin of infection and prompt care.

Increased plasma AACT level as an indicator of poor prognosis in patients hospitalised with community-acquired pneumonia: a multicentre prospective cohort study.

BACKGROUND AND OBJECTIVE: Community-acquired pneumonia (CAP) is a common respiratory disease that frequently requires hospitalisation, and is a significant cause of death worldwide. This study aimed to evaluate the usefulness of alpha-1-antichymotrypsin (AACT) as a diagnostic and prognostic biomarker of CAP. METHODS: We conducted a multicentre prospective cohort study in patients hospitalised with CAP. Plasma AACT levels were measured using a quantitative enzyme-linked immunosorbent assay. Receiver-operating characteristic (ROC) curves and Cox proportional hazards regression were used to assess the association between plasma AACT levels and CAP diagnosis and prognosis. RESULTS: A total of 274 patients with CAP were enrolled in the study. AACT levels were elevated in patients with CAP, especially those with severe CAP and non-survivors. The area under the curve (AUC) of AACT and CRP for diagnosing CAP was 0.755 and 0.843. Cox regression showed that CURB-65 and AACT levels were independent predictors of 30-day mortality. ROC curves showed that plasma AACT levels had the highest accuracy for predicting acute respiratory distress syndrome (ARDS), with an AUC of 0.862. Combining AACT with Pneumonia Severity Index and CURB-65 significantly improved their predictive accuracy for predicting 30-day mortality. CONCLUSION: Plasma AACT levels are elevated in patients with CAP, but plasma AACT level is inferior to the C-reactive protein level for diagnosing CAP. The AACT level can reliably predict the occurrence of ARDS and 30-day mortality in patients with CAP.

N-acetylcysteine, a small molecule scavenger of reactive oxygen species, alleviates cardiomyocyte damage by regulating OPA1-mediated mitochondrial quality control and apoptosis in response to oxidative stress.

Background: Oxidative stress-induced mitochondrial damage is the major cause of cardiomyocyte dysfunction. Therefore, the maintenance of mitochondrial function, which is regulated by mitochondrial quality control (MQC), is necessary for cardiomyocyte homeostasis. This study aimed to explore the underlying mechanisms of N-acetylcysteine (NAC) function and its relationship with MQC. Methods: A hydrogen peroxide-induced oxidative stress model was established using H9c2 cardiomyocytes treated with or without NAC prior to oxidative stress stimulation. Autophagy with light chain 3 (LC3)-green fluorescent protein (GFP) assay, reactive oxygen species (ROS) with the 2',7'-dichlorodi hydrofluorescein diacetate (DCFH-DA) fluorescent, lactate dehydrogenase (LDH) release assay, adenosine triphosphate (ATP) content assay, and a mitochondrial membrane potential detection were used to evaluate mitochondrial dynamics in H2O2-treated H9c2 cardiomyocytes, with a focus on the involvement of MQC regulated by NAC. Cell apoptosis was analyzed using caspase-3 activity assay and Annexin V-fluorescein isothiocyanate (V-FITC)/propidium iodide (PI) double staining. Results: We observed that NAC improved cell viability, reduced ROS levels, and partially restored optic atrophy 1 (OPA1) protein expression under oxidative stress. Following transfection with a specific OPA1-small interfering RNA, the mitophagy, mitochondrial dynamics, mitochondrial functions, and cardiomyocyte apoptosis were evaluated to further explore the mechanisms of NAC. Our results demonstrated that NAC attenuated cardiomyocyte apoptosis via the ROS/OPA1 axis and protected against oxidative stress-induced mitochondrial damage via the regulation of OPA1-mediated MQC. Conclusions: NAC ameliorated the injury to H9c2 cardiomyocytes caused by H2O2 by promoting the expression of OPA1, consequently improving mitochondrial function and decreasing apoptosis.

The Impact of a Diet Rich in Omega-3 Fatty Acids on the Quality of Life of Patients with Squamous Cell Lung Cancer and Comorbid Depression: A Retrospective Study.

BACKGROUND: Lung cancer is a significant health concern, and is often accompanied by comorbid depression, leading to worsened prognosis and decreased quality of life for patients. This study aimed to investigate the potential influence of a diet rich in Omega-3 fatty acids on the quality of life of patients with squamous cell lung cancer and comorbid depression. METHODS: A retroactive analysis of clinical information from patients with squamous cell lung cancer and comorbid depression admitted to Hongqi Hospital Affiliated to Mudanjiang Medical University from June 2022 to June 2023 was conducted. The patients were classified into two groups on the basis of different dietary care approaches: the Routine Dietary Group and the Omega-3 Fatty Acids Group. Baseline characteristics, pulmonary function tests, dietary intake, depression scoring, and quality of life scores were compared between the two groups. RESULTS: 103 patients in total were included, with 51 in the Routine Dietary Group and 52 in the Omega-3 Fatty Acids Group. The Omega-3 Fatty Acids Group exhibited significantly higher ingestion of Omega-3 fatty acids in comparison with the Routine Dietary Group (3.15 ± 0.64 g/day vs. 2.93 ± 0.28 g/day, p = 0.022). Despite similar baseline pulmonary function tests, patients in the Omega-3 Fatty Acids Group showed significantly higher scores in physical (70.17 ± 4.81 vs. 68.18 ± 5.03, p = 0.043) and emotional (71.29 ± 4.58 vs. 69.38 ± 4.25, p = 0.030) functioning, as well as lower scores in insomnia (27.41 ± 4.51 vs. 29.34 ± 4.21, p = 0.027) and constipation (7.34 ± 1.66 vs. 8.43 ± 3.36, p = 0.040). CONCLUSION: The study provided insights into the potential impact of a diet rich in Omega-3 fatty acids on the quality of life of patients with squamous cell lung cancer and complicating depression, suggesting that dietary interventions emphasizing Omega-3 fatty acids may be conducive to improving physical and emotional functioning, as well as symptom management, in this patient population.

The potential role of lung microbiota and lauroylcarnitine in T-cell activation associated with checkpoint inhibitor pneumonitis.

BACKGROUND: Checkpoint inhibitor pneumonitis (CIP) is a potentially fatal adverse event characterized by new pulmonary infiltrates in cancer patients receiving immune checkpoint inhibitor therapy. This study aims to explore the interplay between lung microbiota, dysregulated metabolites, and host immunity in CIP. METHODS: We recruited thirteen hospitalized CIP patients, eleven idiopathic pulmonary fibrosis (IPF) patients, and ten new-onset non-small cell lung cancer patients. Bronchoalveolar lavage fluid samples were collected for 16S rRNA gene sequencing. The percentages of immune cells were determined using manual counting and flow cytometry. Interactions among microbiota, metabolites, and lymphocytes were analyzed using cultured mouse splenocytes and human T cells. FINDINGS: Proteobacteria emerged as the dominant phylum, notably abundant in both the CIP and IPF groups. Vibrio, Halomonas, Mangrovibacter, and Salinivibrio were the predominant microbiota because of their discriminative abundance patterns. Vibrio (r = 0.72, P-adj = 0.007) and Halomonas (r = 0.65, P-adj = 0.023) demonstrated strong correlations with lymphocytes. Vibrio metschnikovii and Mangrovibacter plantisponsors were more abundant in the CIP group than in the IPF group. Lauroylcarnitine, a key intermediary metabolite co-occurring with the predominant microbiota, exhibited a potent effect on cytokine secretion by mouse and human T cells, notably enhancing IFN-γ and TNF-α production from CD4 and CD8 cells in vitro. INTERPRETATION: Lauroylcarnitine, co-occurring with the predominant lung microbiota in CIP, could activate T cells in vitro. These findings suggest potential involvement of lung microbiota and acylcarnitine metabolism dysregulation in the pathogenesis of CIP. FUNDING: This work was supported by Peking University People's Hospital Scientific Research Development Funds (RDJ2022-15) and Provincial Key Clinical Specialty Capacity Building Project 2020 (Department of the Respiratory Medicine).

TRIM47 inhibits cisplatin chemosensitivity and endoplasmic reticulum stress-induced apoptosis of ovarian cancer cells.

Ovarian cancer (OC) is the fifth most common cause of death in women worldwide. Chemoresistance is a key reason for treatment failure, causing high mortality. As a member of the tripartite motif-containing (TRIM) protein family, tripartite motif 47 (TRIM47) plays a vital role in the carcinogenesis and drug resistance of various cancers. This study investigated the impact and mechanisms of TRIM47 on cisplatin (DDP) chemosensitivity and apoptosis in OC. OC cell viability was assessed with a cell counting kit-8 assay and OC cell apoptosis was assessed using flow cytometry, caspase-3 and caspase-9 activity, and Bax and Bcl-2 expression assays while gene and protein expression were assessed using qRT-PCR and Western blot assays. The expression of TRIM47 was significantly increased in both DDP-resistant tissues from patients with OC tissues and in cancer cell lines compared with that in normal tissue or parental cell lines. The increased level of TRIM47 correlated with poor prognosis in patients with OC. Functional assays demonstrated that TRIM47 promoted DDP resistance both in vitro and in vivo. The increased viability and reduced apoptosis of OC cells induced by TRIM47 can be rescued by the endoplasmic reticulum (ER) stress-inducer tunicamycin, suggesting that TRIM47 inhibits OC cell apoptosis by suppressing ER stress. Therefore, TRIM47 may be targeted as a therapeutic strategy for DDP resistance in OC.

Preparation, characterization, and mechanism of DPP-IV inhibitory peptides derived from Bactrian camel milk.

In this study, double enzyme hydrolysis significantly enhanced the DPP-IV inhibition rate compared to single enzyme. The α + K enzymes exhibited the highest inhibition rate. Ultrasonic pretreatment for 30 min improved the hydrolysis efficiency and DPP-IV inhibition rate, potentially due to the structural changes in hydrolysates, such as the increased surface hydrophobicity, and reduced particle size, α-helix and ß-turn. Six peptides were screened and verified in vitro. QPY, WPEYL, and YPPQVM displayed competitive inhibition, while LPAAP and IPAPSFPRL displayed mixed competitive/non-competitive inhibition. The interactions between these six peptides and DPP-IV primarily occurred through hydrogen bonds, electrostatic and hydrophobic interactions. Network pharmacological analysis indicated that LPAAP might inhibit DPP-IV activity trough interactions with diabetes-related targets such as CASP3, HSP90AA1, MMP9, and MMP9. These results uncover the potential mechanism of regulating blood glucose by camel milk hydrolysates, establishing camel milk peptide as a source of DPP-IV inhibitory peptide.

Circ_0006476 modulates macrophage apoptosis through the miR-3074-5p/DLL4 axis: implications for Notch signalling pathway regulation in cardiovascular disease.

As the population ages, the prevalence of atherosclerosis (AS), a significant cause of cardiovascular disease (CVD), continues to increase. Apoptosis is an independent risk factor for atherosclerosis. Macrophages are the primary immune cell group in AS lesions, and their apoptosis plays a crucial role in the occurrence and development of AS. There is a common mechanism of action for circular RNAs (circRNAs) that involves the sponging of microRNAs (miRNAs) by binding to the miRNA response element (MRE), thereby increasing the transcription of their target messenger RNAs (mRNAs). Most diseases are profoundly reliant on circRNAs. However, the underlying mechanism of circRNAs in apoptosis is yet to be elucidated. All differentially expressed genes (DEGs) and their expression levels were analysed by whole-transcriptome sequencing of samples from the control and nicotine groups of THP-1 macrophages. GO and KEGG analyses revealed that nicotine affects macrophage physiological processes and related pathways. GSEA focused on gene sets to better understand the potential pathways and biological functions of all mRNAs. A competitive endogenous RNA (ceRNA) regulatory network was constructed and validated through molecular biology experiments. The Notch signalling pathway was activated in nicotine-treated macrophages, and the expression of DLL4 in this pathway was increased. Circ_0006476 is involved in apoptosis via miR-3074-5p/DLL4, regulating pathogenic processes related to the Notch signalling pathway. The better we understand the pathways involved in macrophage apoptosis, the more likely we are to find other novel therapeutic targets that can help treat, prevent, and reduce the mortality associated with AS.

The impact of recreational cannabis legalization on ED visit rates for acute cannabis intoxication.

BACKGROUND: In December 2018 the Michigan Regulation and Taxation of Marihuana Act legalized the recreational use of cannabis in Michigan. There are now high potency forms of cannabis readily available in the state, which could result in increased emergency department (ED) visit rates due to intoxication in adults and children. Although cannabis related visits account for a small percentage of all adult and pediatric ED visits, they impose a significant burden on the health care system's resources. This study aimed to assess the impact of the legalization of recreational marijuana on the rate of ED visits for acute cannabis intoxication. METHODS AND DESIGN: We utilized the legalization of marijuana in the state of Michigan to conduct a natural experiment utilizing a retrospective observational cohort design of ED visits for acute intoxication before and after legalization. The study was conducted at a health system composed of eight hospitals in southeast Michigan, including both academic and community hospitals serving a diverse patient population. We estimated monthly cannabis-related ED visits based on cannabis-related ICD-10 discharge codes and total ED visits using electronic health record data from 2016 to 2022. A negative-binomial (NB) regression model was used to estimate the immediate and cumulative changes in cannabis-related ED visit rate after legalization. RESULTS: There were a total of 2177 ED visits from 2066 patients for cannabis intoxication in our study cohort. Of the 2177 visits, 671 were before and 1506 were after legalization. In the univariate analysis, recreational cannabis legalization was associated with an increase in the average cannabis-related ED visit rate (Rate Ratio [RR]:1.70, 95% CI: (1.49, 1.94), p-value <0.001). In the multivariate analysis adjusting for age, results remain significant (RR 1.47, 95% CI (1.29, 1.70), p-value <0.001). The increased visit rate occurred in the first month after legalization; however, the slope of the increasing rate of ED visits were similar before and after cannabis legalization (RR, 1.28, 95% CI (1.07, 1.54), p-value <0.001). CONCLUSIONS: The legalization of recreational cannabis in Michigan was associated with an immediate increase in ED visit rates for acute cannabis intoxications across all ages, especially among middle-aged adults, in the context of an stably increasing ED visit rate.

Retrospective Analysis of Risk Factors for Urinary Tract Infection after Ureteral Calculi Surgery.

BACKGROUND: Ureteral calculi are a common diagnosis in the field of urology worldwide, and they represent a prevalent subtype of urolithiasis. Ureteroscopic stone surgery is the cornerstone treatment, but postoperative urinary tract infection (UTI) remains a clinical concern. Our study aims to analyse specific risk factors associated with postoperative UTIs following ureteroscopic stone surgery. METHODS: We conducted a case-control study and collected clinical data from 145 patients who underwent ureteroscopic lithotripsy at our hospital from January 2021 to January 2023. Binary logistic regression analysis was used to investigate risk factors for postoperative UTI. Receiver operating characteristic curves were plotted, and area under the curve (AUC) was calculated to evaluate the predictive value of each factor. RESULTS: Forty patients developed UTI after ureteroscopic stone surgery. Compared with the control group, the case group showed significant differences in stone size, history of diabetes mellitus and preoperative urine culture results (p < 0.05). Multivariable binary logistic regression analysis revealed that stone size (Odds Ratio (OR) = 1.952, p = 0.010), history of diabetes mellitus (OR = 2.438, p = 0.038) and preoperative urine culture (OR = 2.914, p = 0.009) were independent risk factors for postoperative UTI. The AUC values of stone size, history of diabetes mellitus and preoperative urine culture were 0.680, 0.627 and 0.630, respectively. The AUC of the combined prediction was 0.756. CONCLUSIONS: This study identified risk factors for postoperative UTI following ureteroscopic stone surgery and emphasised the importance of stone size, history of diabetes mellitus and preoperative urine culture in the diagnosis.