Four-in-one multifunctional self-driven photoelectrocatalytic system for water purification: Organics degradation, U(VI) reduction, electricity generation and disinfection against bacteria.

This study addresses the energy-intensive nature of conventional wastewater treatment processes and proposes a solution through the development of a green, low-energy, and multifunctional wastewater treatment technology. The research focuses on a multifunctional self-driven photoelectrocatalytic (PEC) system, exploring its four-in-one applications in eliminating organic pollutants, reducing U(VI), generating electrical energy, and disinfecting pathogenic microorganisms. A TiO2-decorated carbon felt (CF@TiO2) cathode is synthesized to enhance interfacial charge transfer, with TiO2 coating improving surface binding sites (edge TiO and adsorbed -OH) for UO22+ adsorption and reduction. The self-driven PEC system, illuminated solely with simulated sunlight, exhibits remarkable efficiency in removing nearly 100 % of uranium within 0.5 h and simultaneously degrading 99.9 % of sulfamethoxazole (SMX) within 1.5 h, all while generating a maximum power output density (Pmax) of approximately 1065 µW·cm-2. The system demonstrates significant anti-interference properties across a wide pH range and coexisting ions. Moreover, 49.4 % of the fixed uranium on the cathode is reduced into U(IV) species, limiting its migration. The self-driven PEC system also excels in detoxifying various toxic organic compounds, including tetracycline, chlortetracycline, and oxytetracycline, and exhibits exceptional sterilization ability by disinfecting nearly 100 % of Escherichia coli within 0.5 h. This work presents an energy-saving, sustainable, and easily recyclable wastewater purification system with four-in-one capabilities, relying solely on sunlight for operation.

EP300-ZNF384 transactivates IL3RA to promote the progression of B-cell acute lymphoblastic leukemia.

The EP300-ZNF384 fusion gene is an oncogenic driver in B-cell acute lymphoblastic leukemia (B-ALL). In the present study, we demonstrated that EP300-ZNF384 substantially induces the transcription of IL3RA and the expression of IL3Rα (CD123) on B-ALL cell membranes. Interleukin 3 (IL-3) supplementation promotes the proliferation of EP300-ZNF348-positive B-ALL cells by activating STAT5. Conditional knockdown of IL3RA in EP300-ZF384-positive cells inhibited the proliferation in vitro, and induced a significant increase in overall survival of mice, which is attributed to impaired propagation ability of leukemia cells. Mechanistically, the EP300-ZNF384 fusion protein transactivates the promoter activity of IL3RA by binding to an A-rich sequence localized at -222/-234 of IL3RA. Furthermore, forced EP300-ZNF384 expression induces the expression of IL3Rα on cell membranes and the secretion of IL-3 in CD19-positive B precursor cells derived from healthy individuals. Doxorubicin displayed a selective killing of EP300-ZNF384-positive B-ALL cells in vitro and in vivo. Collectively, we identify IL3RA as a direct downstream target of EP300-ZNF384, suggesting CD123 is a potent biomarker for EP300-ZNF384-driven B-ALL. Targeting CD123 may be a novel therapeutic approach to EP300-ZNF384-positive patients, alternative or, more likely, complementary to standard chemotherapy regimen in clinical setting.

Lycocasine A, a Lycopodium Alkaloid from Lycopodiastrum casuarinoides and Its Acid-Sensing Ion Channel 1a Inhibitory Activity.

A novel Lycopodium alkaloid, lycocasine A (1), and seven known Lycopodium alkaloids (2-8), were isolated from Lycopodiastrum casuarinoides. Their structures were determined through NMR, HRESIMS, and X-ray diffraction analysis. Compound 1 features an unprecedented 5/6/6 tricyclic skeleton, highlighted by a 5-aza-tricyclic[6,3,1,02,6]dodecane motif. In bioactivity assays, compound 1 demonstrated weak inhibitory activity against acid-sensing ion channel 1a.

Heteroions Radii Matching Produced Intensely Luminescent Bismuth-Ag2S Nanocrystals for through-Skull NIR-II Imaging of Orthotopic Glioma.

Heteroions doped Ag2S nanocrystals (NCs) exhibiting enhanced near-infrared-II emission (NIR-II) hold great promise for glioma diagnosis. Nevertheless, current doped Ag2S NCs paradoxically improved properties via toxic dopants, and the blood-brain barrier (BBB) constitutes another challenge for orthotopic glioma imaging. Thus, it is urgent to develop biofriendly high-bright Ag2S NCs with active BBB-penetration for glioma-targeted imaging. Herein, bismuth (Bi) was screened to obtain Bi-Ag2S NCs with high absolute PLQY (∼13.3%) for its matched ionic-radius (1.03 Å) with Ag+. The Bi-Ag2S NCs exhibited a higher luminance and deeper penetration (5-6 mm) than clinical indocyanine green. Upon conjugation with lactoferrin, the NCs acquired BBB-crossing and glioma-targeting abilities. Time-dependent NIR-II-imaging demonstrated their effective accumulation in glioma with skull/scalp intact after intravenous injection. Moreover, the toxic-metal-free NCs exhibited negligible toxicity and great biocompatibility. The success of leveraging the ion-radii comparison may unlock the full potential of doped-Ag2S NCs in bioimaging and inspire the development of various doped NIR-II NCs.

Lycopodium Alkaloids from Huperzia goebelii.

One new fawcettimine-type Lycopodium alkaloid, hupertimine F (1), together with five known (2-6) Lycopodium alkaloids were isolated from Huperzia goebelii. The structure of 1 was elucidated by 1D and 2D NMR spectra, HRESIMS, and X-ray diffraction. Structurally, 1 represents the fourth example of Lycopodium alkaloids characterized by a 5/5/5/5/6 pentacyclic ring system with a 1-aza-7-oxabicyclo[2.2.1]heptane moiety. These known compounds 2, 3, 5, and 6 were isolated from H. goebelii for the first time. Compounds 1-6 were evaluated for acetylcholinesterase, butyrylcholinesterase and monoamine oxidase B inhibitory activities in vitro.

Complementary imaging of nanoclusters interacting with mitochondria via stimulated emission depletion and scanning transmission electron microscopy.

The emerging stress caused by nanomaterials in the environment is of great concern because they can have toxic effects on organisms. However, thorough study of the interactions between cells and diverse nanoparticles (NPs) using a unified approach is challenging. Here, we present a novel approach combining stimulated emission depletion (STED) microscopy and scanning transmission electron microscopy (STEM) for quantitative assessment, real-time tracking, and in situ imaging of the intracellular behavior of gold-silver nanoclusters (AuAgNCs), based on their fluorescence and electron properties. The results revealed an aggregated state of AuAgNCs within the mitochondria and an increase in sulfur content in AuAgNCs, presumably owing to their reaction with thiol-containing molecules inside the mitochondria. Moreover, AuAgNCs (100 µg/mL) induced a 75% decline in mitochondrial membrane potential and a 12-fold increase of mitochondrial reactive oxygen species in comparison to control. This mitochondrial damage may be triggered by the reaction of AuAgNCs with thiol, which provides direct imaging evidence for uncovering the action mechanism of AuAgNCs on the mitochondria. The proposed dual-imaging strategy using STED and STEM is a potential tool to offer valuable insights into cytotoxicity between subcellular structures and diverse NPs, and can serve as a key strategy for nanomaterial biosafety assessment.

LAMC2 mitigates ER stress by enhancing ER-mitochondria interaction via binding to MYH9 and MYH10.

Highly proliferative and metastatic tumors are constantly exposed to both intrinsic and extrinsic factors that induce adaptation to stressful conditions. Chronic adaptation to endoplasmic reticulum (ER) ER stress is common to many different types of cancers, and poses a major challenge for acquired drug resistance. Here we report that LAMC2, an extracellular matrix protein upregulated in many types of cancers, is localized in the ER of lung, breast, and liver cancer cells. Under tunicamycin-induced ER stress, protein level of LAMC2 is upregulated. Transfection of cancer cells with LAMC2 resulted in the attenuation of ER stress phenotype, accompanied by elevation in mitochondrial membrane potential as well as reduction in reactive oxygen species (ROS) levels and apoptosis. In addition, LAMC2 forms protein complexes with MYH9 and MYH10 to promote mitochondrial aggregation and increased ER-mitochondria interaction at the perinuclear region. Moreover, overexpression of LAMC2 counteracts the effects of ER stress and promotes tumor growth in vivo. Taken together, our results revealed that in complex with MYH9 and MYH10, LAMC2 is essential for promoting ER-mitochondria interaction to alleviate ER stress and allow cancer cells to adapt and proliferate under stressful conditions. This study provides new insights and highlights the promising potential of LAMC2 as a therapeutic target for cancer treatment.

The presumable effects of hydroxychloroquine and its metabolites in the treatment of systemic lupus erythematosus.

OBJECTIVE: Hydroxychloroquine (HCQ) is an essential drug in the treatment of systemic lupus erythematosus (SLE). This study aimed to detect the concentrations of HCQ and its metabolites from peripheral blood of SLE patients and to investigate the relationship between those concentrations and SLE disease activity. METHODS: 176 SLE patients treated with HCQ were enrolled in this study. The concentrations of HCQ and its metabolites in their peripheral blood were measured by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Patients' disease activity was evaluated with the systemic lupus erythematosus disease activity index (SLEDAI). The variables between different concentrations or treatments were statistically analyzed. Linear regression was employed to explore relationships between the concentrations of HCQ and its metabolites with the disease activity. RESULTS: The SLEDAI was lower in patients with higher concentrations of HCQ, desethylhydroxychloroquine (DHCQ), and desethylchloroquine (DCQ) (P = 0.024, P = 0.018, and P = 0.003, respectively). There were no significant differences in SLEDAI and the concentrations of HCQ and its metabolites among groups with different treatments (P > 0.05). After adjusting age, gender, disease duration, HCQ dose adjusted to actual body weight, and glucocorticoid (GC) dose, the SLEDAI was negatively correlated with the concentrations of HCQ, DHCQ, DCQ and bisdesethylchloroquine (BDCQ) (P = 0.007, P = 0.011, P = 0.029, and P = 0.008, respectively). After grouping analysis, in patients treated with HCQ and GC, the SLEDAI was negatively correlated with concentrations of HCQ, DHCQ and BDCQ (P = 0.011, P = 0.035, and P = 0.036, respectively). CONCLUSIONS: The concentrations of HCQ and metabolites were correlated with the SLE disease activity after adjusting possible confounding factors, indicating that HCQ and its metabolites might play certain immunoregulatory roles in SLE treatment. Moreover, GC might have a synergistic effect with HCQ. It is helpful in clinical management and follow-up to monitor the concentrations of HCQ and its metabolites in SLE patients.

The role of immune and inflammatory-related indicators in cognitive dysfunction and disease severity in patients with parkinson's disease.

We aimed to explore the role of immune and inflammatory indicators in cognitive dysfunction and disease severity in patients with Parkinson's disease (PD). A total of 123 patients with Parkinson's disease were enrolled in the PD group and 49 healthy volunteers in the control group. The patients with PD were further divided into 2 subgroups by evaluating cognitive function using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE): the normal cognitive function (PD-NCI) group and the mild cognitive impairment (PD-MCI) group. Moreover, the PD patients were also divided into 2 subgroups using the defined scale of the Hoehn and Yahr (H-Y) stage: the early-stage group and the middle- and late-stage group. Immune and inflammatory indicators, including serum Aß1-42, Tau, CD4+, CD8+, CD3+, B lymphocytes cell, NK cell, Th17 cell, Treg cell, IL-6, IL-17, and TNF-α levels, were evaluated and analyzed to explore the potential correlation with the cognitive dysfunction and disease severity of PD. Among the 123 PD patients, 60 (48.8%) were diagnosed with mild cognitive impairment. Aß1-42, CD4+, CD8+, CD3+, and Treg levels observed in the PD-NCI group were lower than the control group (P < 0.001), while higher than the PD-MCI group (P < 0.001). The levels of Tau, Th17, IL-6, IL-17, and TNF-α observed in the PD-NCI group were higher than the control group (P < 0.001), while lower than in the PD-MCI group (P < 0.01). Using the same method, the results of the early-stage group and the middle- and the late-stage group were the same as above. Logistic regression analysis and ROC curve estimation were performed and indicated that the variation of Tau, CD8+, Treg, TNF-α levels was associated with cognitive decline in PD patients, and may serve as markers of PD onset. Furthermore, the variation of Aß1-42, IL-6, and TNF-α levels was found to correlate with the disease severity of PD. The immune and inflammatory-related indicators may represent an important factor in the pathogenesis of PD, cognitive dysfunction, and disease severity. The variation of Tau protein, CD8+, Treg, and TNF-α levels are associated with the cognitive dysfunction of PD, which may be considered as onset markers. Moreover, the variation of Aß1-42, IL-6, and TNF-α levels can predict the progression of PD.

Quantitative Flow Ratio-Derived Index of Microcirculatory Resistance as a Novel Tool to Identify Microcirculatory Function in Patients with Ischemia and No Obstructive Coronary Artery Disease.

BACKGROUND: Coronary microvascular disease (CMVD) is associated with adverse cardiovascular outcomes. However, there is no reliable and noninvasive quantitative diagnostic method available for CMVD. The use of a pressure wire to measure the index of microcirculatory resistance (IMR) is possible, but it has inevitable practical restrictions. We hypothesized that computation of the quantitative flow ratio could be used to predict CMVD with symptoms of ischemia and no obstructive coronary artery disease (INOCA). METHODS: We retrospectively assessed the diagnostic efficiency of the quantitative flow ratio-derived index of microcirculatory resistance (QMR) in 103 vessels from 66 patients and compared it with invasive IMR using the thermodilution technique. RESULTS: Patients were divided into the CMVD group (41/66, 62.1%) and non-CMVD group (25/66, 37.9%). Pressure wire IMR measurements were made in 103 coronary vessels, including 44 left descending arteries, 18 left circumflex arteries, and 41 right coronary arteries. ROC curve analysis showed a good diagnostic performance of QMR for all arteries (area under the curve = 0.820, 95% confidence interval 0.736-0.904, p < 0.001) in predicting microcirculatory function. The optimal cut-off for QMR to predict microcirculatory function was 266 (sensitivity: 82.9%, specificity: 72.6%, and diagnostic accuracy: 76.7%). CONCLUSION: QMR is a promising tool for the assessment of coronary microcirculation. The assessment of the IMR without the use of a pressure wire may enable more rapid, convenient, and cost-effective assessment of coronary microvascular function.

Osimertinib Covalently Binds to CD34 and Eliminates Myeloid Leukemia Stem/Progenitor Cells.

Osimertinib is a third-generation covalent EGFR inhibitor that is used in treating non-small cell lung cancer. First-generation EGFR inhibitors were found to elicit pro-differentiation effect on acute myeloid leukemia (AML) cells in preclinical studies, but clinical trials yielded mostly negative results. Here, we report that osimertinib selectively induced apoptosis of CD34+ leukemia stem/progenitor cells but not CD34- cells in EGFR-negative AML and chronic myeloid leukemia (CML). Covalent binding of osimertinib to CD34 at cysteines 199 and 177 and suppression of Src family kinases (SFK) and downstream STAT3 activation contributed to osimertinib-induced cell death. SFK and STAT3 inhibition induced synthetic lethality with osimertinib in primary CD34+ cells. CD34 expression was elevated in AML cells compared with their normal counterparts. Genomic, transcriptomic, and proteomic profiling identified mutation and gene expression signatures of patients with AML with high CD34 expression, and univariate and multivariate analyses indicated the adverse prognostic significance of high expression of CD34. Osimertinib treatment induced responses in AML patient-derived xenograft models that correlated with CD34 expression while sparing normal CD34+ cells. Clinical responses were observed in two patients with CD34high AML who were treated with osimertinib on a compassionate-use basis. These findings reveal the therapeutic potential of osimertinib for treating CD34high AML and CML and describe an EGFR-independent mechanism of osimertinib-induced cell death in myeloid leukemia. SIGNIFICANCE: Osimertinib binds CD34 and selectively kills CD34+ leukemia cells to induce remission in preclinical models and patients with AML with a high percentage of CD34+ blasts, providing therapeutic options for myeloid leukemia patients.

Casuattimines A-N, fourteen new Lycopodium alkaloids from Lycopodiastrum casuarinoides with Cav3.1 channel inhibitory activity.

Two new dimeric Lycopodium alkaloids, casuattimines A and B (1 and 2), along with twelve previously undescribed Lycopodium alkaloids, casuattimines C-N (3-14), and eight known Lycopodium alkaloids, were isolated from Lycopodiastrum casuarinoides. Casuattimines A and B (1 and 2) are the first two ether-linked Lycopodium alkaloid dimers. Casuattimines C and D (3 and 4) are unique Lycopodium alkaloids characterized by a long fatty acid chain. Structural elucidation was achieved through HRESIMS, NMR, and electronic circular dichroism (ECD) calculations. In addition, the absolute configurations of compounds 7, 13, and 14 were determined by single crystal X-ray diffraction. Compounds 1, 2, and 4 demonstrated notable Cav3.1 channel inhibitory activities presenting IC50 values of 10.75 ± 1.02 µM, 9.33 ± 0.79 µM, and 7.14 ± 0.86 µM, respectively. The dynamics of compound 4 against the Cav3.1 channel and preliminary structure-activity relationships of these active Lycopodium alkaloids were also discussed.

Corrigendum: Hydroxychloroquine attenuates autoimmune hepatitis by suppressing the interaction of GRK2 with PI3K in T lymphocytes.

[This corrects the article DOI: 10.3389/fphar.2022.972397.].

Association between Urinary BPA Substitutes and Precocious Puberty among Girls: A Single-Exposure and Mixed Exposure Approach from a Chinese Case-Control Study.

There is an argument that BPA substitutes may have the same or more deleterious health effects as BPA due to their structural similarity. This study explored the association between urinary BPA substitutes and precocious puberty among girls by including 120 girls with precocious puberty (cases) aged 2-10 years enrolled at Nanjing Children's Hospital Department of Endocrinology in China between April 2021 to September 2021 and 145 healthy girls (controls) recruited from a primary school. Logistic regression was used to evaluate the effect of single exposures, and Bayesian kernel machine regression (BKMR) and quantile-based g-computation were used for the mixed effect. In the multivariate logistic regression, BPS (bisphenol S), TBBPA (tetrabromobisphenol A), and BPFL (bisphenol-FL) were significantly associated with increased risk of precocious puberty (odds ratio (OR) = 1.75, 95% confidence interval (CI): 1.13, 2.76, p = 0.014), (OR = 1.46, CI: 1.06, 2.05; p = 0.023), and (OR = 1.47, CI: 1.01, 2.18; p = 0.047), respectively. The BMKR and quantile-based g-computation models revealed consistent associations for single exposures and there was insufficient evidence for the associations of the mixed exposure of bisphenols with precocious puberty. In conclusion, BPA substitutes such as BPS, TBBPA, and BPFL may be associated with an increased risk of precocious puberty in girls.

T Lymphoblastic Lymphoma Hiding in Mature Plasmacytoid Dendritic Cell Proliferation: A Case Report and Literature Review.

To the best of the author's knowledge, studies of mature plasmacytoid dendritic cell proliferation associated with T lymphoblastic lymphoma were extremely rare in the literature. Here, we report a patient who underwent both mature plasmacytoid dendritic cell proliferation and T lymphoblastic lymphoma. With the findings of lymph node biopsy taken from the right cervical and inguinal regions, we identified eye-catching mature plasmacytoid dendritic cells that were considered to be responsible for this lesion at the beginning, until the immunostaining of Ki67 and TDT showed a small group of positive cells hiding in these plasmacytoid dendritic cells. A bone marrow biopsy was also performed on this patient. Microscopically, the hematopoietic tissue was almost completely replaced by lymphoblastoid cells with condensed chromatin, inconspicuous nucleoli and scanty cytoplasm, which were basically the same as those seen in the lymph nodes in morphology. However, there was no sign of plasmacytoid dendritic cells or Langerhans cells in the bone marrow biopsy. With the help of bone marrow biopsy, our final diagnosis of the lymph node was T lymphoblastic lymphoma coexisting with mature plasmacytoid dendritic cell proliferation. Although accumulations of plasmacytoid dendritic cells may occur in some infections or reactive lymphadenopathy, the presence of extensive nodules or infiltration of plasmacytoid dendritic cells strongly reminds the pathologist to carefully evaluate the bone marrow or peripheral blood status of the patient to exclude a hidden myeloid or other neoplasm.

Impact of plaque characteristics on percutaneous coronary intervention-related microvascular dysfunction: insights from angiographic microvascular resistance and intravascular ultrasound.

Background: The correlation between percutaneous coronary intervention (PCI)-related microvascular dysfunction (MVD) and plaque characteristics remains unclear. To investigate this correlation and its prognosis, we assessed changes in MVD by angiographic microvascular resistance (AMR) and intracoronary ultrasound scans after PCI. Methods: We conducted a retrospective study that enrolled 250 patients with coronary artery disease between July 2016 and December 2018. We collected demographic characteristics, laboratory tests, coronary angiography (CAG) and intracoronary ultrasound findings. We calculated quantitative flow ratio (QFR) and AMR by CAG. The endpoint was vessel-oriented composite outcomes (VOCOs). Results: After 47 exclusions, we divided 203 cases into a deteriorated group (n=139) and an improved group (n=64) based on AMR change after PCI. Compared with the improved group, the deteriorated group had smaller lumen area [3.03 (interquartile range, 2.20-3.91) vs. 3.55 mm2 (interquartile range, 2.45-4.57), P=0.033], higher plaque burden [78.92% (interquartile range, 73.95-82.61%) vs. 71.93% (interquartile range, 62.70-77.51%), P<0.001], and higher proportion of lipidic components (13.86%±4.67% vs. 11.78%±4.41%, P=0.024). Of 186 patients who completed 4.81±1.55 years follow-up, 56 developed VOCOs. Receiver-operating characteristic (ROC) curve analysis showed post-PCI AMR and VOCOs correlation (area under the curve: 0.729, P<0.001). Multivariate regression analysis showed post-PCI AMR >285 mmHg·s/m correlated with adverse outcome (hazard ratio =4.350; 95% confidence interval: 1.95-9.703; P<0.001). Conclusions: Intravascular ultrasound (IVUS) imaging and AMR revealed an association of post-PCI MVD with a smaller lumen area, more severe plaque burden, and a higher percentage of lipidic components. Post-PCI MVD was an independent risk factor for poor prognosis.

Adult Laryngeal Pleomorphic Rhabdomyosarcoma: A Rare Entity.

Rhabdomyosarcoma (RMS) is a rare and aggressive cancerous tumor that arises from embryonal mesenchymal cells with skeletal muscle differentiation, and it is exceedingly rare that occurs specifically in the larynx. To date, only 22 instances of laryngeal pleomorphic RMSs have been documented in adults. Consequently, there is limited information available to assist healthcare professionals in effectively handling RMS in the larynx of adult patients. Here, we present an uncommon occurrence involving a 45-year-old man who experienced progressive hoarseness and received a diagnosis of pleomorphic RMS affecting the larynx. Pleomorphic RMS had been pathologically diagnosed after a vertical hemilaryngectomy. Following the surgical intervention, the patient underwent chemotherapy and radiation therapy. As of now, there have been no indications of tumor recurrence.

Regulation of Bimetallic Coordination Centers in MOF Catalyst for Electrochemical CO2 Reduction to Formate.

Electrocatalytic reduction of CO2 to valuable chemicals can alleviate the energy crisis, and solve the greenhouse effect. The key is to develop non-noble metal electrocatalysts with high activity, selectivity, and stability. Herein, bimetallic metal organic frameworks (MOFs) materials (BiZn-MOF, BiSn-MOF, and BiIn-MOF) were constructed by coordinating the metals Zn, In, Sn, and Bi with the organic ligand 3-amino-1H-1,2,4-triazole-5-carboxylic acid (H2atzc) through a rapid microwave synthesis approach. The coordination centers in bimetallic MOF catalyst were regulated to optimize the catalytic performance for electrochemical CO2 reduction reaction (CO2RR). The optimized catalyst BiZn-MOF exhibited higher catalytic activity than those of Bi-MOF, BiSn-MOF, and BiIn-MOF. BiZn-MOF exhibited a higher selectivity for formate production with a Faradic efficiency (FE = 92%) at a potential of -0.9 V (vs. RHE, reversible hydrogen electrode) with a current density of 13 mA cm-2. The current density maintained continuous electrolysis for 13 h. The electrochemical conversion of CO2 to formate mainly follows the *OCHO pathway. The good catalytic performance of BiZn-MOF may be attributed to the Bi-Zn bimetallic coordination centers in the MOF, which can reduce the binding energies of the reaction intermediates by tuning the electronic structure and atomic arrangement. This study provides a feasible strategy for performance optimization of bismuth-based catalysts.

Colchicine efficacy comparison at varying time points in the peri-operative period for coronary artery disease: a systematic review and meta-analysis of randomized controlled trials.

Objectives: Over the years, it has been found that colchicine offers substantial benefits in secondary prevention in patients with coronary artery disease (CAD). We studied the effects of colchicine timing because there are no guidelines about when to provide it during the perioperative period for patients with CAD. Methods: Up to January 1, 2023, seven electronic literature databases were screened (including three English databases and four Chinese databases). Randomized controlled trials included only treatment with colchicine in the perioperative period of CAD. The Cochrane Evaluation Tool was used to judge the risk of bias in research. Statistical analysis was performed by Stata 16.0 software. Results: We evaluated twelve studies that found colchicine to be effective in decreasing the occurrence of major adverse cardiac events (MACEs) (p < 0.00001), but it also raised the rate of adverse events (p = 0.001). Subgroup analysis showed the same benefit in lowering the incidence of MACE with continuous administration of a total daily dose of 0.5 mg postoperatively while minimizing drug-related side effects in the patients (p = 0.03). When it comes to preventing surgical stroke occurrences, postoperative administration is more effective (p = 0.006). While the effect of simultaneous preoperative and postoperative administration was marginally greater than other periods in reducing postoperative hs-CRP levels (p = 0.02). Conclusion: Colchicine, a traditional anti-inflammatory drug, also reduces the risk of MACE by reducing inflammation after PCI. Administration at different periods had no significant effect on decreasing the occurrence of MACE, but when administered postoperatively, we advise continuous administration with a total daily dose of 0.5 mg to obtain the same benefit while minimizing the drug's side effects. Postoperative administration is the better measure to prevent postoperative stroke events. Due to the effective anti-inflammatory effect of colchicine, we recommend its use as early as possible in the perioperative period and its continued use at low doses in the postoperative period. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=316751, identifier CRD42022316751.

[Correlation of mitochondrial tRNA variants with coronary heart disease in a Chinese pedigree].

OBJECTIVE: To explore the correlation of mitochondrial DNA (mtDNA) variants and coronary heart disease (CHD) in a Chinese pedigree and the possible molecular mechanisms. METHODS: A Chinese pedigree featuring matrilineal inheritance of CHD who visited Hangzhou First People's Hospital in May 2022 was selected as the study subject. Clinical data of the proband and her affected relatives was collected. By sequencing the mtDNA of the proband and her pedigree members, candidate variants were identified through comparison with wild type mitochondrial genes. Conservative analysis among various species was conducted, and bioinformatics software was used to predict the impact of variants on the secondary structure of tRNA. Real-time PCR was carried out to determine the copy number of mtDNA, and a transmitochondrial cell line was established for analyzing the mitochondrial functions, including membrane potential and ATP level. RESULTS: This pedigree had contained thirty-two members from four generations. Among ten maternal members, four had CHD, which yielded a penetrance rate of 40%. Sequence analysis of proband and her matrilineal relatives revealed the presence of a novel m.4420A>T variant and a m.10463T>C variant, both of which were highly conserved among various species. Structurally, the m.4420A>T variant had occurred at position 22 in the D-arm of tRNAMet, which disrupted the 13T-22A base-pairing, while the m.10463T>C variant was located at position 67 in the acceptor arm of tRNAArg, a position critical for steady-state level of the tRNA. Functional analysis revealed that patients with the m.4420A>T and m.10463T>C variants exhibited much fewer copy number of mtDNA and lower mitochondrial membrane potential (MMP) and ATP contents (P < 0.05), which were decreased by approximately 50.47%, 39.6% and 47.4%, respectively. CONCLUSION: Mitochondrial tRNAMet 4420A>T and tRNAArg 10463T>C variants may underlay the maternally transmitted CHD in this pedigree, which had shown variation in mtDNA homogeneity, age of onset, clinical phenotype and other differences, suggesting that nuclear genes, environmental factors and mitochondrial genetic background have certain influence on the pathogenesis of CHD.