Understanding the effects of oxytocin receptor variants on OXT-OXT receptor binding: A mathematical model.

Approximately half of U.S. women giving birth annually receive Pitocin, the synthetic form of oxytocin (OXT), yet its effective dose can vary significantly. This variability presents safety concerns due to unpredictable responses, which may lead to adverse outcomes for both mother and baby. To address the need for improved dosing, we developed a data-driven mathematical model to predict OXT receptor (OXTR) binding. Our study focuses on five prevalent OXTR variants (V45L, P108A, L206V, V281M, and E339K) and their impact on OXT-OXTR binding dynamics in two distinct cell types: human embryonic kidney cells (HEK293T), commonly used in experimental systems, and human myometrial smooth muscle cells, containing endogenous OXTR. We parameterized the model with cell-specific OXTR surface localization measurements. To strengthen the robustness of our study, we conducted a comprehensive meta-analysis of OXT- OXTR binding, enabling parameterization of our model with cell-specific OXT-OXTR binding kinetics (myometrial OXT-OXTR K d = 1.6 nM, kon = 6.8 × 10 5 M -1 min -1 , and koff = 0.0011 min -1 ). Our meta-analysis revealed significant homogeneity in OXT-OXTR affinity across experiments and species with a K d = 0.52 - 9.32 nM and mean K d = 1.48 ± 0.36 nM. Our model achieves several valuable insights into designing dosage strategies. First, we predicted that the OXTR complex reaches maximum occupancy at 10 nM OXT in myometrial cells and at 1 µM in HEK293T cells. This information is pivotal for guiding experimental design and data interpretation when working with these distinct cell types, emphasizing the need to consider effects for specific cell types when choosing OXTR-transfected cell lines. Second, our model recapitulated the significant effects of genetic variants for both experimental and physiologically relevant systems, with V281M and E339K substantially compromising OXT-OXTR binding capacity. These findings suggest the need for personalized oxytocin dosing based on individual genetic profiles to enhance therapeutic efficacy and reduce risks, especially in the context of labor and delivery. Third, we demonstrated the potential for rescuing the attenuated cell response observed in V281M and E339K variants by increasing the OXT dosage at specific, early time points. Cellular responses to OXT, including Ca 2+ release, manifest within minutes. Our model indicates that providing V281M- and E339K-expressing cells with doubled OXT dose during the initial minute of binding can elevate OXT-OXTR complex formation to levels comparable to wild-type OXTR. In summary, our study provides a computational framework for precision oxytocin dosing strategies, paving the way for personalized medicine.

New Alkaloids and Steroids from Hydranth of Goniopora columna Corals and Their Inhibiting Lung Cancer Cell Activities.

A new alkaloids, aplysingoniopora A (1), and new configuration pregnane type steroid compound, 9,17-α-pregn-1,4,20-en-3-one (2), and two known pregnane type steroid compounds (3 and 4) were isolated from hydranth of Goniopora columna corals. The compounds structures and absolute configurations were determined by extensive spectroscopic analysis, MS data, single-crystal X-ray diffraction analysis and quantum chemical calculation. The anticancer effect of the compounds were explored in human non-small-cell lung cancer (NSCLC) A549 cell lines. As the results, the compound 3 and 4 induces toxicity and has proliferation inhibitory effects on A549 cells (IC50=58.99 µM and 58.77 µM, respectively) in vitro.

Clinical features and risk factors for postoperative recurrence in patients with Cushing's syndrome of different etiologies.

The clinical characteristics of Cushing's syndrome (CS) vary with etiology, and few studies have investigated the risk factors affecting CS recurrence after surgery. This retrospective study involved 202 patients diagnosed with CS between December 2012 and December 2022. The patients were divided into three groups according to etiology: Cushing's disease (CD), adrenocortical adenoma (ACA), and ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS). Of the patients with CS, 41.9% had hypokalemia and 15.0% had hypophosphatemia. The cortisol levels were negatively correlated with blood potassium, blood chlorine, and blood phosphorus. Moreover, 22.4% of patients had an abnormal heart structure, 11.2% had centripetal remodeling, 5.6% had centripetal hypertrophy, and 5.6% had centrifugal hypertrophy. The overall recurrence rate of CS caused by pituitary tumors and adrenal adenoma was 25.7%. The recurrence times were longer in the ACA group versus the CD group, in patients < 50 years of age versus in patients ≥ 50 years old group, and in patients with CD with tumors ≥ 1 cm versus tumors < 1 cm. Age, preoperative cortisol level, postoperative cortisol level, and absolute neutrophil value were closely related to postoperative recurrence, and etiology was an independent predictor of tumor recurrence in patients with CS. The results of this study showed that CS caused by different etiologies showed different clinical manifestations, blood electrolyte characteristics, and that CS could affect patient cardiac structure and function. Etiology is an independent predictor of tumor recurrence in patients with CS.

Ferrostatin-1 Blunts Right Ventricular Hypertrophy and Dysfunction in Pulmonary Arterial Hypertension by Suppressing the HMOX1/GSH Signaling.

Ferroptosis plays a critical role in pulmonary arterial hypertension (PAH)-induced right ventricular (RV) dysfunction, but key genes remain largely unclear. We here identified HMOX1 as an essential ferroptosis-related differentially expressed gene in PAH by bioinformatic analysis using FerrDb, GSE119754, and GSE3675 datasets, respectively. Notably, there were marked increases in HMOX1 and iron levels in RV of monocrotaline-induced PAH rats with reduced TAPSE levels. More importantly, treatment with ferrostatin-1 effectively attenuated RV hypertrophy, remodeling, myocardial fibrosis, and dysfunction in PAH rats. In cultured H9C2 cells and primary neonatal rat cardiomyocytes, pretreatment with ferrostatin-1 and knockdown HMOX1 by siRNA strikingly blunted hypoxia-induced promotion of lipid peroxidation, ferroptosis, and cardiomyocyte injury by potentiating glutathione (GSH) and nitric oxide signaling, respectively. In summary, ferrostatin-1 attenuates RV hypertrophy, fibrosis, and dysfunction in PAH by suppressing the HMOX1/GSH signaling. Targeting HMOX1 ferroptosis signaling functions as a potential therapeutic strategy for patients with PAH.

A Novel Polyamino Acid Sulfur Dioxide Prodrug Synergistically Elevates ROS with ß-Lapachone in Cancer Treatment.

Due to the distorted redox balance, cancer cells are considered more vulnerable to excessive reactive oxygen species (ROS). In a variety of oxidative stress-related therapies, gas therapy has emerged as a new therapeutic strategy owing to its efficacy and biosafety. Herein, a newly-discovered gasotransmitter sulfur dioxide (SO2) and a tumor specific ROS generation agent ß-lapachone (Lapa) were firstly combined for anticancer therapy. Firstly, amphiphilic glutathione (GSH) responsive polypeptide SO2 prodrug PEG-b-poly(Lys-DNs) was synthesized by ring opening polymerization of SO2-containing N-carboxyanhydride. Then, Lapa was encapsulated into the polymeric micelles with loading content of 8.6 % and loading efficiency of 51.6 %. The obtained drug-loaded nanoparticles (NPs(Lapa)) exhibited a fast release of Lapa and SO2 in the stimuli of 10 mM GSH in PBS. Subsequently, in vitro experiment showed that NPs(Lapa) exhibited obvious cytotoxicity towards 4 T1 cancer cells at a concentration of 2.0 µg/mL, which may be attributed to the depletion of intracellular GSH and upregulation of ROS level both by SO2 release and by the ROS generation from lapachone transformation. In vivo fluorescence imaging showed that the NPs were gradually enriched in tumor tissues in 24 h, probably due to the enhanced permeability and retention effect of NPs. Finally, NPs(Lapa) showed the best anticancer effect in 4 T1 tumor bearing mice with a tumor inhibiting rate (IRT) of 61 %, whereas IRT for free Lapa group was only 23.6 %. This work may be a new attempt to combine SO2 gas therapy with ROS inducer for anticancer therapy through oxidative stress.

Recent progress on the construction and application of dithienylethene-based photochromic AIEgens.

Photochromic fluorescent materials have rapidly developed as a new class of intelligent materials, offering a unique combination of traditional photochromic and organic fluorescent materials. These materials possess remarkable photoresponsiveness that can be observed by the naked eye and exhibit fluorescence color change. Consequently, they have found widespread applications in various domains, including molecular switches, logic encryption, medical diagnosis and treatment, and biosensors. Among the multitude of photochromic systems, those based on dithienylethenes (DTEs) have garnered significant attention due to their exceptional photochromic efficiency, commendable reversible photoresponse and fatigue resistance, as well as excellent photostability and thermal stability. Nevertheless, these photochromic fluorescent materials continue to grapple with the issue of aggregation-caused quenching (ACQ), a common problem faced by traditional fluorescent materials. Therefore, the integration of DTE systems with aggregation-induced emission (AIE) systems presents a promising solution to tackle this predicament, enabling an improved quantum yield for photochromic fluorescent materials in their aggregated state and broadening their range of applications. This review comprehensively summarizes and evaluates the construction strategies and application prospects of DTE-based photochromic AIE luminogens (AIEgens) in recent years, while also providing an outlook on their future development.

Drug-coated balloons: A better revascularization strategy in patients with multivessel coronary artery disease undergoing one-stop hybrid coronary revascularization surgery.

BACKGROUND: The optimal revascularization strategy for non-left anterior descending coronary artery (LAD) lesions during one-stop hybrid coronary revascularization (HCR) surgery lacks current evidence. AIMS: This study aimed to compare the outcomes of the drug-coated balloon (DCB) and drug-eluting stent (DES) strategies in patients with non-small non-LAD lesions undergoing one-stop HCR. METHODS: A total of 141 consecutive patients with multivessel coronary artery disease (MVCAD) undergoing one-stop HCR between June 1, 2018 and March 1, 2022 were retrospectively included in this study. In-hospital outcomes and mid-term major adverse cardiovascular and cerebrovascular events (MACCE) were observed. Kaplan-Meier curve analysis was used to evaluate the MACCE-free survival rate. The Cox proportional hazard model was used to identify risk factors of mid-term MACCE. RESULTS: Thirty-eight and 103 patients received only DCB or DES therapy, respectively, in this study. There were no significant differences in demographic characteristics and laboratory parameters between the two groups. The in-hospital MACCE rate in the DES group was numerically higher than that in the DCB group (9.7% vs. 5.3%, respectively), but the difference was not statistically significant (P = 0.4). The incidence of MACCE after patients' discharge was significantly higher in the DES group (22% vs. 5.3%, respectively, P = 0.02) during a median follow-up of 20 months. After multivariable Cox proportional hazard analysis, DCB therapy was independently associated with reduced risk of mid-term MACCE (hazard ratio, 0.21; 95% confidence interval, 0.06-0.91; P = 0.04). CONCLUSION: For patients with MVCAD undergoing one-stop HCR, DCB therapy may be the optimal revascularization strategy for non-small non-LAD coronary artery lesions with a significantly lower rate of mid-term MACCE.

Circulating Exosomal CircRNAs as Diagnostic Biomarkers for Chronic Coronary Syndrome.

Circular RNA (circRNA) has been reported to be involved in the pathogenesis of cardiovascular disease; however, it is unclear whether circRNA carried by exosomes (exos) can be used as biomarkers for chronic coronary syndrome (CCS). High-throughput sequencing was carried out in the plasma exosomal RNA of 15 CCS patients and 15 non-cardiac chest pain patients (NCCP, control group) to screen for differentially expressed circRNAs. Selected differentially expressed exo-circRNAs were further verified by real-time polymerase chain reaction in a small-sample cohort and a large-sample cohort. A total of 276 circRNAs were differentially expressed in the plasma exosomes of CCS patients, with 103 up-regulated and 173 down-regulated. Among the 103 up-regulated circRNAs, 5 circRNAs with high expression levels were selected for validation. Real time quantitative PCR of the first and second validation cohort demonstrated that exo-hsa_circ_0075269 and exo-hsa_circ_0000284 were significantly up-regulated in patients with CCS. Circulating exo-hsa_circ_0075269 and exo-hsa_circ_0000284 yielded the area under the curve values of 0.761 (p < 0.001, 95%CI = 0.669, 0.852) and 0.623 (p = 0.015, 95%CI = 0.522, 0.724) for CCS, respectively, by ROC curve analysis. In conclusion, the expression profile of circRNA in plasma exosomes of patients with CCS was significantly different from that of the control group. Plasma exo-hsa_circ_0075269 and exo-hsa_circ_0000284 have the potential to be new biomarkers for CCS.

Accuracy of liver metastasis detection and characterization: Dual-energy CT versus single-energy CT with deep learning reconstruction.

PURPOSE: To assess whether image quality differences between SECT (single-energy CT) and DECT (dual-energy CT 70 keV) with equivalent radiation doses result in altered detection and characterization accuracy of liver metastases when using deep learning image reconstruction (DLIR), and whether DECT spectral curve usage improves accuracy of indeterminate lesion characterization. METHODS: In this prospective Health Insurance Portability and Accountability Act-compliant study (March through August 2022), adult men and non-pregnant adult women with biopsy-proven colorectal cancer and liver metastases underwent SECT (120 kVp) and a DECT (70 keV) portovenous abdominal CT scan using DLIR in the same breath-hold (Revolution CT ES; GE Healthcare). Participants were excluded if consent could not be obtained, if there were nonequivalent radiation doses between the two scans, or if the examination was cancelled/rescheduled. Three radiologists independently performed lesion detection and characterization during two separate sessions (SECT DLIRmedium and DECT DLIRhigh) as well as reported lesion confidence and overall image quality. Hounsfield units were measured. Spectral HU curves were provided for any lesions rated as indeterminate. McNemar's test was used to test the marginal homogeneity in terms of diagnostic sensitivity, accuracy and lesion detection. A generalized estimating equation method was used for categorical outcomes. RESULTS: 30 participants (mean age, 58 years ± 11, 21 men) were evaluated. Mean CTDIvol was 34 mGy for both scans. 141 lesions (124 metastases, 17 benign) with a mean size of 0.8 cm ± 0.3 cm were identified. High scores for image quality (scores of 4 or 5) were not significantly different between DECT (N = 71 out of 90 total scores from the three readers) and SECT (N = 62) (OR, 2.01; 95% CI:0.89, 4.57; P = 0.093). Equivalent image noise to SECT DLIRmed (HU SD 10 ± 2) was obtained with DECT DLIRhigh (HU SD 10 ± 3) (P = 1). There was no significant difference in lesion detection between DECT and SECT (140/141 lesions) (99.3%; 95% CI:96.1%, 100%).The mean lesion confidence scores by each reader were 4.2 ± 1.3, 3.9 ± 1.0, and 4.8 ± 0.8 for SECT and 4.1 ± 1.4, 4.0 ± 1.0, and 4.7 ± 0.8 for DECT (odds ratio [OR], 0.83; 95% CI: 0.62, 1.11; P = 0.21). Small lesion (≤5mm) characterization accuracy on SECT and DECT was 89.1% (95% CI:76.4%, 96.4%; 41/46) and 84.8% (71.1%, 93.7%; 39/46), respectively (P = 0.41). Use of spectral HU lesion curves resulted in 34 correct changes in characterizations and no mischaracterizations. CONCLUSION: DECT required a higher strength of DLIR to obtain equivalent noise compared to SECT DLIR. At equivalent radiation doses and image noise, there was no significant difference in subjective image quality or observer lesion performance between DECT (70 keV) and SECT. However, DECT spectral HU curves of indeterminate lesions improved characterization.

Comparisons of drug-eluting balloon versus drug-eluting stent for the treatment of cancer patients presenting with acute myocardial infarction.

BACKGROUND: Treatment for cancer patients presenting with acute myocardial infarction (AMI) remains challenging. The objective of the study was to investigate the safety and efficiency of drug eluting balloon (DEB) versus drug eluting stent (DES) in this high-risk group. METHODS: Between 1st January 2017 and 1st January 2022, cancer patients admitted to Beijing Chaoyang Hospital with AMI were retrospectively enrolled. The primary endpoint was major adverse cardiovascular event (MACE). The secondary endpoints included major bleeding events, heart failure and cardiac complications. RESULTS: A total of 164 cancer patients presenting with AMI were included in the final analysis. Patients treated with DEB had a numerically lower rate of MACE than those treated with DES during a median follow-up of 21.8 months (22.9% vs. 37.1%, p = 0.23). Patients treated with DEB had a trend towards lower rate of major bleeding events than patients treated with DES (6.3% vs. 18.1%, HR 2.96, 95% CI [0.88, 9.92], p = 0.08). There were no significant differences between the two groups with regards to the rate of heart failure (4.2% vs. 9.5%, p = 0.32) and cardiac complications (0.0% vs. 2.6%, p = 0.56). CONCLUSIONS: The present study demonstrated that in cancer patients with AMI, DEB had a trend towards lower rate of major bleeding events and a numerically lower rate of MACE compared with DES.

Two and three-dimensional halogen-bonded frameworks: self-assembly influenced by crystallization solvents.

In this paper, two types of solid phase 2D and 3D XBOFs were selectively constructed from identical building blocks of tetraphenylmethane tetrapyridine derivative and 1,4-diiodotetrafluorobenzene by changing the crystallization solvent. This 3D XBOF is a novel hybrid supramolecular organic framework with the synergistic control of hydrogen and halogen bonds.

Thiol-Responsive Polypeptide Sulfur Dioxide Prodrug Nanoparticles for Effective Tumor Inhibition.

Sulfur dioxide (SO2) based gas therapy has emerged as a novel anticancer therapeutic strategy because of its high therapeutic efficacy and biosafety. To precisely adjust the SO2 content and control gas release, herein, a thiol-responsive polypeptide SO2 prodrug mPEG-block-poly(2-amino-6-(2,4-dinitrophenylsulfonamido)hexanoic acid) (PEG-b-PLys-DNs) was designed and facilely synthesized by polymerization of a novel N-carboxyanhydride SO2-NCA. The anticancer potential of the self-assembled nanoparticles (SO2-NPs) was investigated in detail. First, PEG-b-PLys-DNs were synthesized by ring-opening polymerization of SO2-NCA, which self-assembled into NPs sized 88.4 nm in aqueous. Subsequently, SO2-NPs were endocytosed into 4T1 cells and quickly released SO2 under a high concentration of glutathione in tumor cells. This process depleted cellular glutathione, generated reactive oxygen species, and dramatically increased oxidative stress, which led to cancer cell apoptosis. Finally, the in vivo anticancer efficacy of SO2-NPs was verified in 4T1-tumor-bearing mice. Our results indicated that this novel SO2 polymeric prodrug has great potential in eradicating tumors.

Low pitch significantly reduces helical artifacts in abdominal CT.

PURPOSE: High helical pitch scanning minimizes scan times in CT imaging, and thus also minimizes motion artifact and mis-synchronization with contrast bolus. However, high pitch produces helical artifacts that may adversely affect diagnostic image quality. This study aims to determine the severity and incidence of helical artifacts in abdominal CT imaging and their relation to the helical pitch scan parameter. METHODS: To obtain a dataset with varying pitch values, we used CT exam data both internal and external to our center. A cohort of 59 consecutive adult patients receiving an abdomen CT examination at our center with an accompanying prior examination from an external center was selected for retrospective review. Two expert observers performed a blinded rating of helical artifact in each examination using a five-point Likert scale. The incidence of artifacts with respect to the helical pitch was assessed. A generalized linear mixed-effects regression (GLMER) model, with study arm (Internal or External to our center) and helical pitch as the fixed-effect predictor variables, was fit to the artifact ratings, and significance of the predictor variables was tested. RESULTS: For a pitch of <0.75, the proportion of exams with mild or worse helical artifacts (Likert scores of 1-3) was <1%. The proportion increased to 16% for exams with pitch between 0.75 and 1.2, and further increased to 78% for exams with a pitch greater than 1.2. Pitch was significantly associated with helical artifact in the GLMER model (p = 2.8 × 10-9), while study arm was not a significant factor (p = 0.76). CONCLUSION: The incidence and severity of helical artifact increased with helical pitch. This difference persisted even after accounting for the potential confounding factor of the center where the study was performed.

Comparisons of different new-generation transcatheter aortic valve implantation devices for patients with severe aortic stenosis: a systematic review and network meta-analysis.

BACKGROUND: Whether there are differences among the new-generation transcatheter aortic valve implantation (TAVI) devices for patients with aortic stenosis remains unclear. The aim of the study was to compare the efficiency and safety of different new-generation TAVI devices for patients with aortic stenosis. MATERIALS AND METHODS: A comprehensive search of PubMed, Embase and Web of Science from their inception to 1 February 2022. Randomized clinical trials and observational studies that compared two or more different TAVI devices were enroled. Pairwise meta-analysis and frequentist network meta-analysis were conducted to pool the outcome estimates of interest. RESULTS: A total of 79 studies were finally included. According to the surface under the cumulative ranking, the top two ranked valves for lower rates of events were as follows: direct flow medical (DFM) (4.6%) and Lotus (48.8%) for lower rate of device success; Sapien 3 (16.8%) and DFM (19.7%) for lower mortality; DFM (8.6%) and Sapien 3 (25.5%) for lower rates of stroke; Evolut (27.6%) and DFM (35.8%) for lower rates of major and life-threatening bleeding; Portico (22.6%) and Sapien 3 (41.9%) for lower rates of acute kidney injury; Acurate (8.6%) and DFM (13.2%) for lower rates of permanent pacemaker implantation; Lotus (0.3%) and Sapien 3 (22.7%) for lower rates of paravalvular leak; Evolut (1.4%) and Portico (29.1%) for lower rates of mean aortic valve gradients. CONCLUSIONS: The findings of the present study suggested that the device success rates were comparable among these new-generation valves except for DFM. After excluding DFM, Sapien 3 might be the best effective for decreased mortality and stroke; Lotus might be the best effective for decreased paravalvular leak; Evolut might be the best effective for decreased major and life-threatening bleeding and mean aortic valve gradients; Acurate and Portico might be the best effective for decreased permanent pacemaker implantation and acute kidney injury, respectively.

How Do Cancer-Specific Computed Tomography Protocols Compare With the American College of Radiology Dose Index Registry? An Analysis of Computed Tomography Dose at 2 Cancer Centers.

BACKGROUND: Little guidance exists on how to stratify radiation dose according to diagnostic task. Changing dose for different cancer types is currently not informed by the American College of Radiology Dose Index Registry dose survey. METHODS: A total of 9602 patient examinations were pulled from 2 National Cancer Institute designated cancer centers. Computed tomography dose (CTDI vol ) was extracted, and patient water equivalent diameter was calculated. N-way analysis of variance was used to compare the dose levels between 2 protocols used at site 1, and three protocols used at site 2. RESULTS: Sites 1 and 2 both independently stratified their doses according to cancer indications in similar ways. For example, both sites used lower doses ( P < 0.001) for follow-up of testicular cancer, leukemia, and lymphoma. Median dose at median patient size from lowest to highest dose level for site 1 were 17.9 (17.7-18.0) mGy (mean [95% confidence interval]) and 26.8 (26.2-27.4) mGy. For site 2, they were 12.1 (10.6-13.7) mGy, 25.5 (25.2-25.7) mGy, and 34.2 (33.8-34.5) mGy. Both sites had higher doses ( P < 0.001) between their routine and high-image-quality protocols, with an increase of 48% between these doses for site 1 and 25% for site 2. High-image-quality protocols were largely applied for detection of low-contrast liver lesions or subtle pelvic pathology. CONCLUSIONS: We demonstrated that 2 cancer centers independently choose to stratify their cancer doses in similar ways. Sites 1 and 2 dose data were higher than the American College of Radiology Dose Index Registry dose survey data. We thus propose including a cancer-specific subset for the dose registry.

Exposure to proton pump inhibitors and risk of diabetes: A systematic review and meta-analysis.

BACKGROUND: Exposure to proton pump inhibitors (PPIs) has been reported to have a potential role in the development of diabetes. AIM: To determine the association between PPIs and diabetes. METHODS: This meta-analysis is registered on PROSPERO (CRD42022352704). In August 2022, eligible studies were identified through a comprehensive literature search. In this study, odds ratios were combined with 95% confidence intervals using a random-effects model. The source of heterogeneity was assessed using sensitivity analysis and subgroup analysis. The publication bias was evaluated using Egger's test and Begg's test. RESULTS: The meta-analysis included 9 studies with a total of 867185 participants. Results showed that the use of PPIs increased the risk of diabetes (odds ratio = 1.23, 95% confidence interval: 1.05-1.43, n = 9, I2 = 96.3%). Subgroup analysis showed that geographic location and study type had significant effects on the overall results. Both Egger's and Begg's tests showed no publication bias (P > 0.05). Sensitivity analysis also confirmed the stability of the results. CONCLUSION: The results of this study indicated that the use of PPIs was related to an increased risk of diabetes. However, more well-designed studies are needed to verify these results in the future.

An epipolythiodioxopiperazine alkaloid and diversified aromatic polyketides with cytotoxicity from the Beibu Gulf coral-derived fungus Emericella nidulans GXIMD 02509. / 北部湾珊瑚来源构巢裸胞壳菌GXIMD 02509ä¸­å ·æœ‰ç»†èƒžæ¯’æ€§çš„ä¸€ä¸ªå¤šç¡«ä»£äºŒé ®å“Œå—ªç”Ÿç‰©ç¢±å’Œç»“æž„å¤šæ ·çš„èŠ³é¦™èšé ®ç±»åŒ–åˆç‰©.

Marine microorganisms, especially marine fungi, have historically proven their value as a prolific source for structurally novel and pharmacologically active secondary metabolites (Deshmukh et al., 2018; Carroll et al., 2022). The corals constitute a dominant part of reefs with the highest biodiversity, and harbor highly diverse and abundant microbial symbionts in their tissue, skeleton, and mucus layer, with species-specific core members that are spatially partitioned across coral microhabitats (Wang WQ et al., 2022). The coral-associated fungi were very recently found to be vital producers of structurally diverse compounds, terpenes, alkaloids, peptides, aromatics, lactones, and steroids. They demonstrate a wide range of bioactivity such as anticancer, antimicrobial, and antifouling activity (Chen et al., 2022). The genetically powerful genus Emericella (Ascomycota), which has marine and terrestrial sources, includes over 30 species and is distributed worldwide. It is considered a rich source of diverse secondary metabolites with antimicrobial activity or cytotoxicity (Alburae et al., 2020). Notably, Emericella nidulans, the sexual state of a classic biosynthetic strain Aspergillus nidulans, was recently reported as an important source of highly methylated polyketides (Li et al., 2019) and isoindolone-containing meroterpenoids (Zhou et al., 2016) with unusual skeletons.

Association between heavy metal mercury in body fluids and tissues and diabetes mellitus: a systematic review and meta-analysis.

Background: Recent studies have shown that the relationship between mercury exposure and diabetes is controversial. The aim of this study is to determine the relationship between mercury exposure and diabetes using a systematic review and meta-analysis approach. Methods: We systematically searched PubMed, Web of Science, Cochrane, and Embase databases for cross-sectional, case-control, or cohort studies assessing the correlation between mercury exposure and diabetes in any population. Details of each included study were extracted using a pre-designed Excel spreadsheet. Quality assessment of cohort and case-control studies used the Newcastle-Ottawa Scale (NOS), whereas cross-sectional studies were assessed by the Agency for Healthcare Research and Quality (AHRQ) scale. Meta-analyses were performed using random-effects models to calculate the pooled odds ratio (OR), standardized mean difference (SMD), and their 95% confidence intervals (CIs). Subgroup and sensitivity analyses were employed to assess heterogeneity sources. Begg's and Egger's tests were used to evaluate publication bias. Results: Our meta-analysis included 8 eligible articles, comprising a total of 40,891 subjects, reporting mercury OR and/or concentrations. Among the included studies, one was a case control, one was a cohort study, and the rest were cross-sectional studies. Two studies were rated as high quality and six as medium quality. The results revealed no link between mercury exposure and diabetes (OR: 1.11, 95% CI: 0.80, 1.55, n=6, I2=73.7%; and SMD: 0.41, 95% CI: -0.32, 1.14, n=3, I2=88.7%). In the stratified male and female subgroups, the pooled OR was 0.71 (95% CI: 0.57, 0.90, n=3, I2=0.0%), 1.11 (95% CI: 0.69, 1.79, n=3, I2=67.7%). The Begg's test results revealed no significant publication bias (P=0.06), but the Egger's test results did (P=0.013). The sensitivity analysis confirmed the stability of our results. Conclusions: No significant relationship was observed between mercury and diabetes mellitus. However, more well-designed studies on mercury exposure and diabetes risk are still needed, particularly on the type of mercury (i.e., elemental, inorganic, and organic), exposure time and dose, type of biological specimen, and the population's sex and age.

Comparisons of Drug-Eluting Balloon versus Drug-Eluting Stent in the Treatment of Young Patients with Acute Myocardial Infarction.

BACKGROUND: The incidence of acute myocardial infarction (AMI) in the younger population has been increasing gradually in recent years. The objective of the present study is to investigate the safety and effectiveness of drug-eluting balloons (DEBs) in young patients with AMI. METHODS: All consecutive patients with AMI aged ≤ 45 years were retrospectively enrolled. The primary endpoint was a device-oriented composite endpoint (DOCE) of cardiac death, target vessel myocardial infarction (MI), or target lesion revascularization (TLR). The secondary study endpoints included heart failure and major bleeding events. RESULTS: A total of 276 young patients presenting with AMI were finally included. The median follow-up period was 1155 days. Patients treated with DEBs had a trend toward a lower incidence of DOCEs (3.0% vs. 11.0%, p = 0.12) mainly driven by the need for TLR (3.0% vs. 9.1%, p = 0.19) than those treated with DESs. No significant differences between the two groups were detected in the occurrence of cardiac death (0.0% vs. 0.5%, p = 0.69), MI (0.0% vs. 1.4%, p = 0.40), heart failure (0.0% vs. 1.9%, p = 0.39), or major bleeding events (1.5% vs 4.8%, p = 0.30). Multivariate regression analysis showed that DEBs were associated with a trend toward a lower risk of DOCEs (HR 0.13, 95% CI [0.02, 1.05], p = 0.06). CONCLUSIONS: The findings of the present study suggested that DEBs might be a potential treatment option in young patients with AMI. A larger scale, randomized, multicenter study is required to investigate the safety and effectiveness of DEBs in this setting.

Integrative taxonomy of the subfamily Orbioninae (Crustacea: Isopoda) based on mitochondrial and nuclear data with evidence that supports Epicaridea as a suborder.

Epicaridea is a group of isopods with high morphological diversity, reduction and loss of characters, and strong sexual dimorphism due to their parasitic lifestyles but their systematics is not well understood. Despite the use of nuclear and mitochondrial genes to test the phylogeny of many invertebrate groups, few molecular data from epicarideans are known, especially from the subfamily Orbioninae. Species in this group are obligate penaeoid shrimp parasites and the lack molecular data has hampered studies on the phylogeny of Orbioninae. To rectify this, mitochondrial and nuclear genes of 9 orbionine species are sequenced here. Compared to the isopod ground pattern, the sequences of orbionines seem to be more plastic near the control region and major translocations are located between rrns and cob. A phylogenetic analysis based on three data sets showed strong support for a monophyletic Orbioninae and that Epicaridea should be accepted at the rank of a suborder within Isopoda. The monophyly of Parapenaeon and Orbione is in doubt based on morphological and molecular data. The genus Parapenaeon is revised and a new genus Aparapenaeon is erected for Parapenaeon japonica and three closely related species.