Myocardial deformation characteristics assessed by cardiovascular magnetic resonance feature tracking in a healthy Chinese population.

Purpose: To explore global/regional myocardial deformation across various layers, vascular distributions, specific levels and distinct walls in healthy individuals using cardiovascular magnetic resonance feature tracking (CMR-FT). Methods: We selected a cohort of 55 healthy participants and CMR cine images were used to obtain the left ventricular (LV) peak longitudinal, circumferential, radial strains (LS, CS, RS). The characteristics of normal LV strain in various layers (endocardium, myocardium, epicardium), territories [left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA)], levels (basal, middle, apical) and walls (anterior, septum, inferior, lateral) were compared. Results: The absolute values of the LV global LS and CS gradually decreased from endocardium to epicardium. The absolute LV global RS (65.7 ± 47.7%) was maximum relative to LS (-22.0 ± 10.8%) and CS (-22.8 ± 7.7%). The absolute values of the LCX territorial strain were the largest compared with the LAD and RCA territorial strains. Regional RS, endo-CS and endo-LS gradually increased from the basal to the apical level. The LV lateral walls had the highest strain values (CS, LS, and RS). Conclusions: Variations in normal LV strain values across various layers, territories, levels, and walls were observed, suggesting the necessity for careful clinical interpretation of these strain values. These findings also partially revealed the complexity of normal cardiac mechanics.

Integrated proteogenomic and metabolomic characterization of papillary thyroid cancer with different recurrence risks.

Although papillary thyroid cancer (PTC) has a good prognosis, its recurrence rate is high and remains a core concern in the clinic. Molecular factors contributing to different recurrence risks (RRs) remain poorly defined. Here, we perform an integrative proteogenomic and metabolomic characterization of 102 Chinese PTC patients with different RRs. Genomic profiling reveals that mutations in MUC16 and TERT promoter as well as multiple gene fusions like NCOA4-RET are enriched by the high RR. Integrative multi-omics analyses further describe the multi-dimensional characteristics of PTC, especially in metabolism pathways, and delineate dominated molecular patterns of different RRs. Moreover, the PTC patients are clustered into four subtypes (CS1: low RR and BRAF-like; CS2: high RR and metabolism type, worst prognosis; CS3: high RR and immune type, better prognosis; CS4: high RR and BRAF-like) based on the omics data. Notably, the subtypes display significant differences considering BRAF and TERT promoter mutations, metabolism and immune pathway profiles, epithelial cell compositions, and various clinical factors (especially RRs and prognosis) as well as druggable targets. This study can provide insights into the complex molecular characteristics of PTC recurrences and help promote early diagnosis and precision treatment of recurrent PTC.

Analysis of morphology, histology characteristics, and circadian clock gene expression of Onychostoma macrolepis at the overwintering period and the breeding period.

Fish typically adapt to their environment through evolutionary traits, and this adaptive strategy plays a critical role in promoting species diversity. Onychostoma macrolepis is a rare and endangered wild species that exhibits a life history of overwintering in caves and breeding in mountain streams. We analyzed the morphological characteristics, histological structure, and expression of circadian clock genes in O. macrolepis to elucidate its adaptive strategies to environmental changes in this study. The results showed that the relative values of O. macrolepis eye diameter, body height, and caudal peduncle height enlarged significantly during the breeding period. The outer layer of the heart was dense; the ventricular myocardial wall was thickened; the fat was accumulated in the liver cells; the red and white pulp structures of the spleen, renal tubules, and glomeruli were increased; and the goblet cells of the intestine were decreased in the breeding period. In addition, the spermatogenic cyst contained mature sperm, and the ovaries were filled with eggs at various stages of development. Throughout the overwintering period, the melano-macrophage center is located between the spleen and kidney, and the melano-macrophage center in the cytoplasm has the ability to synthesize melanin, and is arranged in clusters to form cell clusters or white pulp scattered in it. Circadian clock genes were identified in all organs, exhibiting significant differences between the before/after overwintering period and the breeding period. These findings indicate that the environment plays an important role in shaping the behavior of O. macrolepis, helping the animals to build self-defense mechanisms during cyclical habitat changes. Studying the morphological, histological structure and circadian clock gene expression of O. macrolepis during the overwintering and breeding periods is beneficial for understanding its unique hibernation behavior in caves. Additionally, it provides an excellent biological sample for investigating the environmental adaptability of atypical cavefish species.

HCOO- Doping-Induced Multiexciton Emissions in Cs3Cu2I5 Crystals for Efficient X-Ray Scintillation.

Self-trapped exciton (STE) luminescence, typically associated with structural deformation of excited states, has attracted significant attention in metal halide materials recently. However, the mechanism of multiexciton STE emissions in certain metal halide crystals remains largely unexplored. This study investigates dual luminescence emissions in HCOO- doped Cs3Cu2I5 single crystals using transient and steady-state spectroscopy. The dual emissions are attributed to intrinsic STE luminescence originating from the host lattice and extrinsic STE luminescence induced by external dopants, respectively, each of which can be triggered independently at distinct energy levels. Theoretical calculations reveal that multiexciton emission originates from structural distortion of the host and dopant STEs within the 0D lattice in their respective excited states. By meticulously tuning the excitation wavelength and selectively exciting different STEs, the dynamic alteration of color change in Cs3Cu2I5:HCOO- crystals is demonstrated. Ultimately, owing to an extraordinarily high photoluminescence quantum yield (99.01%) and a diminished degree of self-absorption in Cs3Cu2I5:HCOO- crystals, they exhibit remarkable X-ray scintillation characteristics with light yield being improved by 5.4 times as compared to that of pristine Cs3Cu2I5 crystals, opening up exciting avenues for achieving low-dose X-ray detection and imaging.

Spatial-temporal Bayesian accelerated failure time models for survival endpoints with applications to prostate cancer registry data.

Prostate cancer is the most common cancer after non-melanoma skin cancer and the second leading cause of cancer deaths in US men. Its incidence and mortality rates vary substantially across geographical regions and over time, with large disparities by race, geographic regions (i.e., Appalachia), among others. The widely used Cox proportional hazards model is usually not applicable in such scenarios owing to the violation of the proportional hazards assumption. In this paper, we fit Bayesian accelerated failure time models for the analysis of prostate cancer survival and take dependent spatial structures and temporal information into account by incorporating random effects with multivariate conditional autoregressive priors. In particular, we relax the proportional hazards assumption, consider flexible frailty structures in space and time, and also explore strategies for handling the temporal variable. The parameter estimation and inference are based on a Monte Carlo Markov chain technique under a Bayesian framework. The deviance information criterion is used to check goodness of fit and to select the best candidate model. Extensive simulations are performed to examine and compare the performances of models in different contexts. Finally, we illustrate our approach by using the 2004-2014 Pennsylvania Prostate Cancer Registry data to explore spatial-temporal heterogeneity in overall survival and identify significant risk factors.

Inspirations from Field-Reservoir CO2 Flooding with Different Miscible Degrees under Cross-Scale Oil Reservoir Conditions.

In recent years, CO2 flooding has become one of the main enhanced oil recovery (EOR) methods, especially for tight formations in different oilfields around the world. Most of the CO2 flooding projects carried out in the world are based on miscible flooding, however, this technique is less effective in China because of the depth of the reservoirs and the heavy components of the crude oil. Near-miscible flooding and immiscible flooding have also been gradually applied to China's domestic oil fields, and have achieved certain oil increase effects, but there are still some challenges such as gas channeling, corrosion, and solid phase deposition in the process of CO2 flooding. In this paper, through a detailed review of recent domestic and foreign cases of enhanced oil recovery, the effects of development methods of low permeability and ultralow permeability reservoirs under different miscible degrees are analyzed, and the solutions to some of the existing problems in field tests and experience are systematically summarized. According to the results of field tests, both miscible flooding and near-miscible flooding have similar effects and can achieve better recovery increment, with a long effect period and slow gas breakthrough speed. In addition, the problems of gas channeling, corrosion, and solid phase deposition occurring in the process of CO2 flooding are analyzed, and solutions such as a change in injection methods and coatings are put forward, which effectively promote the development of CO2 flooding technology. Those suggestions are of great significance for improving the oil recovery rate of unconventional oil reservoirs, ensuring the national energy supply, and low-carbon emissions reduction in China.

Ferroptosis: A New Mechanism in Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DC) is a pathophysiologic condition caused by diabetes mellitus (DM) in the absence of coronary artery disease, valvular heart disease, and hypertension that can lead to heart failure (HF), manifesting itself in the early stages with left ventricular hypertrophy and diastolic dysfunction, with marked HF and decreased systolic function in the later stages. There is still a lack of direct evidence to prove the exact existence of DC. Ferroptosis is a novel form of cell death characterized by reactive oxygen species (ROS) accumulation and lipid peroxidation. Several cell and animal studies have shown that ferroptosis is closely related to DC progression. This review systematically summarizes the related pathogenic mechanisms of ferroptosis in DC, including the reduction of cardiac RDH10 induced ferroptosis in DC cardiomyocytes which mediated by retinol metabolism disorders; CD36 overexpression caused lipid deposition and decreased GPX4 expression in DC cardiomyocytes, leading to the development of ferroptosis; Nrf2 mediated iron overload and lipid peroxidation in DC cardiomyocytes and promoted ferroptosis; lncRNA-ZFAS1 as a ceRNA, combined with miR-150-5p to inhibit CCND2 expression in DC cardiomyocytes, thereby triggering ferroptosis.

Role of sleep disorders in patients with cardiovascular disease: A systematic review.

In compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we conducted this systemic review on the prevalence, mechanism, and therapy of sleep disorder in patients with cardiovascular disease (CVD). After searching PubMed and Embase, 78 articles were selected for this review. This review discusses the bidirectional relationship between CVD and sleep disorders. Sleep impairment is highly prevalent in patients with CVD and mainly involves insomnia and sleep-breathing disorders. Several valuable biomarkers could be implicated in predicting sleep disorders in CVD patients, such as placental growth factor, vascular endothelial growth factor family, high sensitivity C-reactive protein, endoglin, fms-like tyrosine kinase-1, plasminogen activator inhibitor-1, erythropoietin. Moreover, non-drug therapies, namely physical exercise, cognitive behavioral therapy for insomnia (CBT-I), and continuous positive airway pressure benefit the prognosis of patients with CVD. In conclusion, this study highlights the importance of sleep quality, which is responsible for long- and short-term cardiac outcomes in patients with CVD.

Heterologous expression of taxane genes confers resistance to fall armyworm in Nicotiana benthamiana.

KEY MESSAGE: Taxadiene synthase, taxadiene-5α-hydroxylase, and taxane 13α-hydroxylase genes were introduced into Nicotiana benthamiana, and the improved resistance to lepidoptera pest fall armyworm was reported. Fall armyworm (FAW) is a serious agricultural pest. Genetic engineering techniques have been used to create pest-resistant plant varieties for reducing pest damage. Paclitaxel is a diterpenoid natural metabolite with antineoplastic effects in medicine. However, the effects of taxanes on the growth and development of lepidoptera pests, such as the FAW, are unknown. Here, selected paclitaxel precursor biosynthesis pathway genes, taxadiene synthase, taxane 5α-hydroxylase, and taxane 13α-hydroxylase, were engineered in the heterologous host Nicotiana benthamiana plants. Bioassay experiments showed that the transgenic N. benthamiana plants displayed improved resistance to FAW infestation, with degeneration of gut tissues and induced expression of apoptosis-related genes. Cytotoxicity experiment showed that the paclitaxel precursor, 10-deacetylbaccatin III, is cytotoxic to Sf9 cells, causing cell cycle arrest at the G2/M phase and disorder of the cytoskeleton. Metabolome analysis showed that heterologous expression of taxane genes in N. benthamiana affected the digestive system, steroid hormone and purine metabolism pathways of FAW larvae. In summary, this study provides a candidate approach for FAW control.

Enhancing Stability and Performance in Tin-Based Perovskite Field-Effect Transistors Through Hydrogen Bond Suppression of Organic Cation Migration.

Ion migration poses a substantial challenge in perovskite transistors, exerting detrimental effects on hysteresis and operational stability. This study focuses on elucidating the influence of ion migration on the performance of tin-based perovskite field-effect transistors (FETs). It is revealed that the high background carrier density in FASnI3 FETs arises not only from the oxidation of Sn2+ but also from the migration of FA+ ions. The formation of hydrogen bonding between FA+ and F- ions efficiently inhibits ion migration, leading to a reduction in background carrier density and an improvement in the operational stability of the transistors. The strategy of hydrogen bond is extended to fluorine-substituted additives to improve device performance. The incorporation of 4-fluorophenethylammonium iodide additives into FETs significantly minimizes the shift of turn-on voltage during cyclic measurements. Notably, an effective mobility of up to 30 cm2 V-1 s-1 with an Ion/off ratio of 107 is achieved. These findings hold promising potential for advancing tin-based perovskite technology in the field of electronics.

Local delivery of stem cell spheroids with protein/polyphenol self-assembling armor to improve myocardial infarction treatment via immunoprotection and immunoregulation.

Stem cell therapies have shown great potential for treating myocardial infarction (MI) but are limited by low cell survival and compromised functionality due to the harsh microenvironment at the disease site. Here, we presented a Mesenchymal stem cell (MSC) spheroid-based strategy for MI treatment by introducing a protein/polyphenol self-assembling armor coating on the surface of cell spheroids, which showed significantly enhanced therapeutic efficacy by actively manipulating the hostile pathological MI microenvironment and enabling versatile functionality, including protecting the donor cells from host immune clearance, remodeling the ROS microenvironment and stimulating MSC's pro-healing paracrine secretion. The underlying mechanism was elucidated, wherein the armor protected to prolong MSCs residence at MI site, and triggered paracrine stimulation of MSCs towards immunoregulation and angiogenesis through inducing hypoxia to provoke glycolysis in stem cells. Furthermore, local delivery of coated MSC spheroids in MI rat significantly alleviated local inflammation and subsequent fibrosis via mediation macrophage polarization towards pro-healing M2 phenotype and improved cardiac function. In general, this study provided critical insight into the enhanced therapeutic efficacy of stem cell spheroids coated with a multifunctional armor. It potentially opens up a new avenue for designing immunomodulatory treatment for MI via stem cell therapy empowered by functional biomaterials.

New sesquiterpenoids with neuroprotective effects in vitro and in vivo from the Picrasma chinensis.

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1-3), along with nine known ones (4-12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H2O2-induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1, 3-5, and 7 showed a potent neuroprotective effect at 25 or 50 µM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse.

Modified medial gastrocnemius myocutaneous flap with extended anterior, inferior and/or posterior boundaries: Anatomical observation and report of a clinical series of 33 flaps.

INTRODUCTION: Reports on medial gastrocnemius myocutaneous (MGM) flaps with extended inferior and posterior boundaries are rare, and information about the MGM flaps with extended anterior boundaries is unavailable. Thus, this study aimed to investigate the vascular anatomical basis and clinical reliability of the modified MGM flap with extended anterior, inferior and/or posterior boundaries. METHODS: Five fresh lower limb specimens from patients with recurrent tumours in the thigh were immediately irrigated and perfused. The stripped integuments were radiographed. The pretibial skin was equally divided into nine zones. The reconstruction outcomes of the modified MGM flaps were documented in 33 patients. RESULTS: True anastomotic connections existed among the branches of the saphenous artery, the perforator from the inferior medial genicular artery and 3-5 (mean, 4.5) perforators from the posterior tibial artery in the upper two-thirds of the leg. A total of 33 modified MGM flaps were applied. The anterior margins of 26 modified flaps with extended anterior boundaries exceeded the medial edge of the tibia by 1.0-4.5 cm (mean, 2.1 cm). Fourteen modified MGM flaps were used to repair the defects involving the lower third leg, whose distal edges were located in the seventh (n = 8) or eighth (n = 6) zone. A 1-169-month (median, 9 months) follow-up was conducted for 33 patients. Of the 33 flaps, 29 (87.9 %) survived completely, partial necrosis occurred in four flaps with extended anterior (n = 2) or inferior (n = 2) boundaries. CONCLUSIONS: Multiple source vessels are the vascular anatomical basis of the modified MGM flap with extended anterior, posterior and/or inferior boundaries. The modification of the MGM flap is feasible and reliable, broadening the applicable scope of the flap. The modified MGM flap can be applied to repair more distal, wider and larger-area defects with a simpler design and procedure.

One-Pot Synthesis of Polycyclic Sultams Enabled by Gold-Catalyzed Hydroamination of o-Alkynylbenzenesulfonamides and Subsequent Iodine(III)-Mediated Counteranion-Assisted Intramolecular Annulation.

Herein we present a facile and efficient one-pot synthetic protocol for the construction of polycyclic sultams. This protocol involves gold-catalyzed intramolecular hydroamination of o-alkynylbenzenesulfonamides followed by HTIB-mediated counteranion-assisted intramolecular annulation. The transformation tolerates a wide range of functional groups, resulting in the formation of highly functionalized and valuable polycyclic sultam skeletons in moderate to excellent yields. These polycyclic sultams are widely used as key building blocks in organic science.

Alteration in gut microbiota is associated with immune imbalance in Graves' disease.

Background: Graves' disease (GD), characterized by immune aberration, is associated with gut dysbiosis. Despite the growing interest, substantial evidence detailing the precise impact of gut microbiota on GD's autoimmune processes remains exceedingly rare. Objective: This study was designed to investigate the influence of gut microbiota on immune dysregulation in GD. Methods: It encompassed 52 GD patients and 45 healthy controls (HCs), employing flow cytometry and enzyme-linked immunosorbent assay to examine lymphocyte and cytokine profiles, alongside lipopolysaccharide (LPS) levels. Gut microbiota profiles and metabolic features were assessed using 16S rRNA gene sequencing and targeted metabolomics. Results: Our observations revealed a disturbed B-cell distribution and elevated LPS and pro-inflammatory cytokines in GD patients compared to HCs. Significant differences in gut microbiota composition and a marked deficit in short-chain fatty acid (SCFA)-producing bacteria, including ASV263(Bacteroides), ASV1451(Dialister), and ASV503(Coprococcus), were observed in GD patients. These specific bacteria and SCFAs showed correlations with thyroid autoantibodies, B-cell subsets, and cytokine levels. In vitro studies further showed that LPS notably caused B-cell subsets imbalance, reducing conventional memory B cells while increasing naïve B cells. Additionally, acetate combined with propionate and butyrate showcased immunoregulatory functions, diminishing cytokine production in LPS-stimulated cells. Conclusion: Overall, our results highlight the role of gut dysbiosis in contributing to immune dysregulation in GD by affecting lymphocyte status and cytokine production.

The association of intraocular efavirenz concentrations and HIV-1 viral load among persons with HIV.

OBJECTIVE: Efavirenz (EFV) is commonly used in combination antiretroviral therapy (cART). However, in our previous study, many persons living with human immunodeficiency virus (HIV) exhibited ocular complications despite undergoing effective cART. Here, we aimed to determine the intraocular EFV concentrations in the vitreous and analyze the factors affecting viral load in the vitreous in patients with HIV-associated retinopathies. DESIGN: Observational, retrospective study. METHODS: Fourteen patients receiving EFV in combination with an antiretroviral therapy who underwent pars plana vitrectomy (PPV) were enrolled between January 2019 and August 2022. The patients were divided into two groups based on presence or absence of retinal detachment (RD). Patient characteristics and HIV-1 RNA levels in plasma and vitreous were recorded during PPV. Paired blood plasma and vitreous samples were obtained for EFV concentration analysis using using ultra-high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) . RESULTS: The median age of the enrolled patients was 48 years (interquartile range [IQR], 32.25-53.25), including 12 men and 2 females. Median vitreous and plasma EFV concentrations were 141.5 (IQR, 69.63-323.75) and 2,620 ng/mL (1,680-4,207.5), respectively. Median ratio of vitreous/plasma EFV concentrations in the paired samples among all participants was 0.053 (0.018-0.118). Median vitreous/plasma EFV concentrations significantly differed between the non-RD and RD groups (0,04 vs 0.12, p = 0.042) .ConclusionsThe vitreous EFV concentrations were insufficient to inhibit viral replication in intraocular tissues, which may be due to poor penetration of the blood-retinal barrier. High vitreous EFV concentrations were associated with retinal detachment, indicating a correlation between the EFV concentration and the severity of blood-retinal barrier disruption. It implied that EFV was not a suitable antiviral drug to inhibit the HIV-1 replication in ocular tissues.

Fourier analysis of corneal irregular astigmatism after small-incision lenticule extraction and transepithelial photorefractive keratectomy: A comparative study.

To compare changes in the spherical component, regular astigmatism, and irregular astigmatism of the anterior surface of the cornea after small-incision lenticule extraction (SMILE) and transepithelial photorefractive keratectomy (TransPRK). Fifty-six patients underwent SMILE in 56 eyes, and 68 patients underwet TransPRK in 68 eyes. The right eye was chosen to enter the group. Six months after the procedure, Scheimpflug images were acquired, and Fourier analysis of the anterior surface of patients' corneas was performed using the Pentacam built-in software. Fourier parameters encompass various measurements such as the steepest radius of the curvature and average eccentricity of the spherical components (SphRmin and SphEcc), maximum decentration (MaxDec), central and peripheral regular astigmatism (regular astigmatism at the center [AstC] and regular astigmatism at the periphery [AstP]), and irregularity (Irr). At 6 months postoperatively, SphEcc decreased significantly (P < .001), MaxDec increased significantly (P < .001), and Irr increased insignificantly (P = .254) in the SMILE group. SphEcc decreased significantly (P < .001) and MaxDec and Irr increased significantly (P < .001) in the TransPRK group. TransPRK caused greater changes in SphEcc, MaxDec, and Irr on the anterior corneal surface than SMILE (P < .05). The amount of MaxDec-induced changes in SMILE and TransPRK was significantly correlated with the amount of higher-order aberrations and spherical aberration changes (P < .05). SMILE and TransPRK increase overall irregular astigmatism on the anterior surface of the cornea, more so with TransPRK, where changes in decentration are associated with with increased higher-order aberrations.

SIRT3 and SIRT4 double-genes remodeled the mitochondrial network to induce hepatocellular carcinoma cell line differentiation and suppress malignant phenotypes.

Tumor cells with damaged mitochondria undergo metabolic reprogramming, but gene therapy targeting mitochondria has not been comprehensively reported. In this study, plasmids targeting the normal hepatocyte cell line (L-O2) and hepatocellular carcinoma cell line were generated using three genes SIRT3, SIRT4, and SIRT5. These deacetylases play a variety of regulatory roles in cancer and are related to mitochondrial function. Compared with L-O2, SIRT3 and SIRT4 significantly ameliorated mitochondrial damage in HCCLM3, Hep3B and HepG2 cell lines and regulated mitochondrial biogenesis and mitophagy, respectively. We constructed double-gene plasmid for co-express SIRT3 and SIRT4 using the internal ribosome entry site (IRES). The results indicated that the double-gene plasmid effectively expressed SIRT3 and SIRT4, significantly improved mitochondrial quality and function, and reduced mtDNA level and oxidative stress in HCC cells. MitoTracker analysis revealed that the mitochondrial network was restored. The proliferation, migration capabilities of HCC cells were reduced, whereas their differentiation abilities were enhanced. This study demonstrated that the use of IRES-linked SIRT3 and SIRT4 double-gene vectors induced the differentiation of HCC cells and inhibited their development by ameliorating mitochondrial dysfunction. This intervention helped reverse metabolic reprogramming, and may provide a groundbreaking new framework for HCC treatment.

Dbl family RhoGEFs in cancer: different roles and targeting strategies.

Small Ras homologous guanosine triphosphatase (Rho GTPase) family proteins are highly associated with tumorigenesis and development. As intrinsic exchange activity regulators of Rho GTPases, Rho guanine nucleotide exchange factors (RhoGEFs) have been demonstrated to be closely involved in tumor development and received increasing attention. They mainly contain two families: the diffuse B-cell lymphoma (Dbl) family and the dedicator of cytokinesis (Dock) family. More and more emphasis has been paid to the Dbl family members for their abnormally high expression in various cancers and their correlation to poor prognosis. In this review, the common and distinctive structures of Dbl family members are discussed, and their roles in cancer are summarized with a focus on Ect2, Tiam1/2, P-Rex1/2, Vav1/2/3, Trio, KALRN, and LARG. Significantly, the strategies targeting Dbl family RhoGEFs are highlighted as novel therapeutic opportunities for cancer.

Meta-analysis on inflammation and autonomic nervous system of coronary heart disease combined with depression.

OBJECTIVES: This meta-analysis aimed to explore the association between inflammatory factors, heart rate variability (HRV) and the coexistence of coronary heart disease (CHD) and depression. DESIGN: Systematic review and meta-analysis. Complying with the Meta-analysis Of Observational Studies in Epidemiology statement. DATA SOURCES: We searched PubMed, Web of Science and EMBASE for the data from the inception date to 16 March 2023. ELIGIBILITY CRITERIA: We included cross-sectional and cohort studies with inclusion criteria: (1) patients with CHD; (2) depression measurement and (3) including inflammatory factors or cardiac biomarkers or HRV. DATA EXTRACTION AND SYNTHESIS: Two authors searched the databases independently. The effect estimates and heterogeneity were synthesised by Review Manager V.5.3. Sensitivity analysis and publication bias were analysed by STATA software. The quantitative synthesis outcomes were presented by mean difference (MD) or standard MD (SMD) with 95% CI. RESULTS: By searching the databases, we identified a total of 6750 articles. There were 22 articles left after selection, including 6344 participants. This meta-analysis indicated that patients with CHD with depression had higher levels of C reaction protein (CRP) (SMD 0.50, 95% CI (0.19 to 0.81), p=0.001), high-sensitivity C reactive protein (hs-CRP) (SMD 0.28, 95% CI (0.07 to 0.48), p=0.008), IL-6 (SMD 0.49, 95% CI (0.05 to 0.92), p=0.03) and a lower level of the mean RR interval and the SD of all RR intervals (SMD -0.64, 95% CI (-1.11 to -0.17), p=0.008), SD of the 5 min averages of all normal RR intervals (MD -12.77 ms, 95% CI (-21.20 to -4.33), p=0.003), overage of the SD of all normal RR intervals for each 5 min segment (MD -13.83 ms, 95% CI (-15.94 to -11.72), p<0.00001), root mean square of successive differences (MD: -8.02 ms, 95% CI (-13.62 to -2.43), p=0.005), proportion of adjacent cycles differing by >50 ms (pNN50) (SMD -0.86, 95% CI (-1.41 to -0.31), p=0.002), than those without depression. CONCLUSIONS: This study underscores the association between elevated CRP, hs-CRP, IL-6 and lower HRV in patients with CHD with depression. It emphasises the importance of clinicians assessing CRP, hs-CRP, IL-6 and HRV in patients with CHD to potentially identify depressive conditions.