Recent Advances in Organic Small-Molecule Fluorescent Probes Based on Dicyanoisophorone Derivatives.

Fluorescent probe technology holds great promise in the fields of environmental monitoring and clinical diagnosis due to its inherent advantages, including easy operation, reliable detection signals, fast analysis speed, and in situ imaging capabilities. In recent years, a wide range of fluorescent probes based on diverse fluorophores have been developed for the analysis and detection of various analytes, yielding significant achievement. Among these fluorophores, the dicyanoisophorone-based fluorophores have garnered significant attention. Dicyanoisoporone exhibits minimal fluorescence, yet possesses a robust electron-withdrawing capability, rendering it suitable for constructing of D-π-A structured fluorophores. Leveraging the intramolecular charge transfer (ICT) effect, such fluorophores exhibit near-infrared (NIR) fluorescence emission with a large Stokes shift, thereby offering remarkable advantages in the design and development of NIR fluorescence probes. This review article primarily focus on small-molecule dicyanoisoporone-based probes from the past two years, elucidating their design strategies, detection performances, and applications. Additionally, we summarize current challenges while predicting future directions to provide valuable references for developing novel and advanced fluorescence probes based on dicyanoisoporone derivatives.

All-Round Passivation Strategy Yield Flexible Perovskite/CuInGaSe2 Tandem Solar Cells with Efficiency Exceeding 26.5.

The perovskite/Cu(InGa)Se2 (CIGS) tandem solar cells (TSCs) presents a compelling technological combination poised for the next generation of flexible and lightweight photovoltaic (PV) tandem devices, featuring a tunable bandgap, high power conversion efficiency (PCE), lightweight flexibility, and enhanced stability and durability. Over the years, the imperative to enhance the performance of wide bandgap (WBG) perovskite solar cells (PSCs) has grown significantly, particularly in the context of a flexible tandem device. In this study, an all-round passivation strategy known as Dual Passivation at Grains and Interfaces (DPGI) is introduced for WBG PSCs in perovskite/CIGS tandem structures. The implementation of DPGI is tailored to improve film crystallinity and passivate defects across the solar cell structure, leading to a substantial performance enhancement for WBG PSCs. Subsequently, both rigid and flexible tandem devices are assembled. Impressively, a fully flexible 4T perovskite/CIGS TSCs is successfully fabricated with a PCE of 26.57%, making it the highest value in this field and highlighting its potential applications in the next generation of flexible lightweight PV tandem devices.

Mitigating bisphenol A-induced apoptosis in KGN cells: the therapeutic role of 1,25-dihydroxyvitamin D3 through upregulation of PGC-1α expression and inhibition of the mitochondrial cytochrome c pathway.

PURPOSE: This study investigated the potential of 1,25-dihydroxyvitamin D3 (1,25(OH)2VD3) to mitigate bisphenol A (BPA)-induced apoptosis in human ovarian granulosa KGN cells with the aim of establishing a theoretical foundation for understanding of how vitamin D improved ovarian function in patients with polycystic ovary syndrome (PCOS). METHODS: The impact of varying concentrations of BPA and 1,25(OH)2VD3 on KGN cell viability was elucidated. It was established that BPA-induced apoptosis in KGN cells. Subsequently, KGN cells underwent pretreatment with 1,25(OH)2VD3, followed by exposure to BPA. The apoptosis rate, reactive oxygen species (ROS) levels, and mitochondrial function of the cells were meticulously assessed, along with the expression levels of genes associated with apoptosis as well as antioxidant and mitochondrial biogenesis. RESULTS: BPA induced a notable increase in apoptosis (P < 0.001) and oxidative stress (P < 0.001) in KGN cells, accompanied by a significant reduction in mitochondrial membrane potential (P < 0.001) and severe impairment of mitochondrial function. Following pretreatment of KGN cells with 1,25(OH)2VD3, there was a significant decrease in the apoptosis rate (P = 0.004), coupled with a reduction in ROS production (P = 0.002). Concomitantly, the upregulation of PGC-1α (P = 0.009) and SOD (P = 0.018) was observed, while mRNA expression of BAX (P = 0.011), Cyt c (P = 0.001), Apaf-1 (P = 0.012), caspase-9 (P < 0.001), and caspase-3 (P = 0.011) was downregulated. Notably, the mitigation of mitochondrial damage was evident through restored mitochondrial membrane potential (P < 0.001), as corroborated by electron microscope results. CONCLUSIONS: 1,25(OH)2VD3 mitigated BPA-induced damage and apoptosis in KGN cells by upregulating the expression of PGC-1α and impeding the mitochondrial cytochrome c (Cyt c) apoptotic pathway. This study established a novel theoretical foundation for utilizing vitamin D in the treatment of PCOS patients.

Evaluation of left ventricular stiffness with echocardiography.

Half of patients with heart failure are presented with preserved ejection fraction (HFpEF). The pathophysiology of these patients is complex, but increased left ventricular (LV) stiffness has been proven to play a key role. However, the application of this parameter is limited due to the requirement for invasive catheterization for its measurement. With advances in ultrasound technology, significant progress has been made in the noninvasive assessment of LV chamber or myocardial stiffness using echocardiography. Therefore, this review aims to summarize the pathophysiological mechanisms, correlations with invasive LV stiffness constants, applications in different populations, as well as the limitations of echocardiography-derived indices for the assessment of both LV chamber and myocardial stiffness. Indices of LV chamber stiffness, such as the ratio of E/e' divided by left ventricular end-diastolic volume (E/e'/LVEDV), the ratio of E/SRe (early diastolic strain rates)/LVEDV, and diastolic pressure-volume quotient (DPVQ), are derived from the relationship between echocardiographic parameters of LV filling pressure (LVFP) and LV size. However, these methods are surrogate and lumped measurements, relying on E/e' or E/SRe for evaluating LVFP. The limitations of E/e' or E/SRe in the assessment of LVFP may contribute to the moderate correlation between E/e'/LVEDV or E/SRe/LVEDV and LV stiffness constants. Even the most validated measurement (DPVQ) is considered unreliable in individual patients. In comparison to E/e'/LVEDV and E/SRe/LVEDV, indices like time-velocity integral (TVI) measurements of pulmonary venous and transmitral flows may demonstrate better performance in assessing LV chamber stiffness, as evidenced by their higher correlation with LV stiffness constants. However, only one study has been conducted on the exploration and application of TVI in the literature, and the accuracy of assessing LV chamber stiffness remains to be confirmed. Regarding echocardiographic indices for LV myocardial stiffness evaluation, parameters such as epicardial movement index (EMI)/ diastolic wall strain (DWS), intrinsic velocity propagation of myocardial stretch (iVP), and shear wave imaging (SWI) have been proposed. While the alteration of DWS and its predictive value for adverse outcomes in various populations have been widely validated, it has been found that DWS may be better considered as an overall marker of cardiac function performance rather than pure myocardial stiffness. Although the effectiveness of iVP and SWI in assessing left ventricular myocardial stiffness has been demonstrated in animal models and clinical studies, both indices have their limitations. Overall, it seems that currently no echocardiography-derived indices can reliably and accurately assess LV stiffness, despite the development of several parameters. Therefore, a comprehensive evaluation of LV stiffness using all available parameters may be more accurate and enable earlier detection of alterations in LV stiffness.

Clinical and genetic profiles of chinese pediatric patients with catecholaminergic polymorphic ventricular tachycardia.

BACKGROUNDS: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but lethal cardiac ion channelopathy. Delayed diagnosis and misdiagnosis remain a matter of concern due to its rarity and insufficient recognition of this disorder, particularly in developing countries like China. AIMS AND METHODS: We reported six catecholaminergic polymorphic ventricular tachycardia (CPVT) children diagnosed in our center along with a comprehensive review of Chinese pediatric CPVT patients reported in domestic and overseas literature between January 2013 and December 2021 to provide an essential reference for physicians to deepen their understanding of pediatric CPVT. RESULTS: A total of 95 children with CPVT, including our six patients from 21 medical centers were identified. The median age of symptom onset is 8.7 ± 3.0 years. Diagnosis occurred at a median age of 12.9 ± 6.8 years with a delay of 4.3 ± 6.6 years. Selective beta-blockers (Metoprolol and Bisoprolol) were prescribed for 38 patients (56.7%) and 29 (43.3%) patients received non-selective beta-blocker (Propranolol and Nadolol) treatment. Six patients accepted LCSD and seven received ICD implantation at the subsequent therapy. A total of 13 patients died during the disease course. Of the 67 patients with positive gene test results, variants in RYR2 were 47 (70.1%), CASQ2 were 11 (16.4%), and RYR2 accompanied SCN5A were 7 (10.4%). Patients with CASQ2 gene mutations presented with younger symptom onset age, higher positive family history rate and better prognosis than those with RYR2 mutations. CONCLUSION: Chinese pediatric patients with CPVT had a poorer prognosis than other cohorts, probably due to delayed/missed diagnosis, non-standard usage of beta-blockers, unavailability of flecainide, and a lower rate of LCSD and ICD implantation.

Development of a nomogram prediction model for early identification of persistent coronary artery aneurysms in kawasaki disease.

BACKGROUND: Coronary artery aneurysms (CAA) persistence prediction is critical in evaluating Kawasaki disease (KD). This study established a nomogram prediction system based on potential risk factors for assessing the risk of CAA persistence in a contemporary cohort of patients with KD. METHODS: This cohort comprised 105 patients with KD who had been diagnosed with CAA during the acute or subacute phase by echocardiography. The follow-up duration was at least 1 year. The clinical and laboratory parameters were compared between the CAA regression and persistence groups. Multivariable logistic regression analysis was used to identify the independent risk factors for CAA persistence, which were subsequently used to build the nomogram predictive model. Decision curve analysis was used to assess the net benefits of different nomogram scores. RESULTS: Of these patients with CAA, 27.6% of patients presented with persistent lesions. The incidences of CAA persistence were 14.1%, 81.3%, and 100.0% in patients with small, medium, and large aneurysms, respectively. The ratio of neutrophils to lymphocytes, γ-GT, and CAA size at diagnosis were considered as the independent risk factors for CAA persistence in patients with KD. The nomogram predictive models yielded a high capability in predicting CAA persistence, based on either univariable or multivariable analyses-identified parameters, compared with using CAA size as a single predictor. CONCLUSION: The initial ratio of neutrophils to lymphocytes, γ-GT, and CAA size were the independent risk factors for CAA persistence in patients with KD. Nomogram scores could help elevate predictive efficacy in detecting CAA persistence.

Modulating the intersystem crossing mechanism of anthracene carboxyimide-based photosensitizers via structural adjustments and application as a potent photodynamic therapeutic reagent.

Herein, a series of compact anthracene carboxyimide (ACI) based donor-acceptor dyads were prepared by substituting bulky aryl moieties with various electron-donating ability to study the triplet-excited state properties. The ISC mechanism and triplet yield of the dyads were successfully tuned via structural manipulation. Efficient ISC (ΦΔ ≈ 99%) and long-lived triplet state (τT ≈ 122 µs) was observed for the orthogonal anthracene-labeled ACI derivative compared to the Ph-ACI and NP-ACI dyads, which showed fast triplet state decay (τT ≈ 7.7 µs). Femtosecond transient absorption study demonstrated the ultrafast charge separation (CS) and efficient charge recombination (CR) in the orthogonal dyads and ISC occurring via spin-orbit charge transfer (SOCT) mechanism (AN-ACI: τCS = 355 fs, τCR = 2.41 ns; PY-ACI: τCS = 321 fs, τCR = 1.61 ns), while in Ph-ACI and NP-ACI dyads triplet populate following the normal ISC channel (nπ* → ππ* transition), no CS was observed. We found that the attachment of suitable aryl donor moiety (AN- or PY-) to the ACI core can ensure the insertion of the intermediate triplet state, resulting in a small energy gap among charge separated state (CSS) and triplet state, which leads to efficient ISC in these derivatives. The SOCT-ISC-based AN-ACI dyad was confirmed to be a potent photodynamic therapeutic reagent; an ultra-low IC50 value (0.27 nM) that was nearly 214 times lower than that of the commercial Rose Bengal photosensitizer (57.8 nM) was observed.

Electrocardiographic features of children with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a clinically common X-linked recessive myopathy, which is caused by mutation of the gene encoding dystrophin on chromosome Xp21. The onset of heart injury in children with DMD is inconspicuous, and the prognosis is poor once it develops to the stage of heart failure. Cardiovascular complications remain an important cause of death in this patient population. At present, population and animal studies have suggested that Electrocardiogram (ECG) changes may be the initial manifestation of cardiac involvement in children with DMD. Relevant clinical studies have also confirmed that significant abnormal ECG changes already exist in DMD patients before cardiomegaly and/or LVEF decrease. With increases in age and decreases in cardiac function, the proportion of ECG abnormalities in DMD patients increase significantly. Some characteristic ECG changes, such as ST-segment changes, T wave inversion, Q wave at the inferolateral leads, LBBB and SDANN, have a certain correlation with the indexes of cardiac remodeling or impaired cardiac function in DMD patients, while VT and LBBB have demonstrated relatively good predictive value for the occurrence of long-term DCM and/or adverse cardiovascular events or even death in DMD patients. The present review discusses the electrocardiographic features in children with DMD.

Mixed Solvents Assisted Post-Treatment Enables High-Efficiency Single-Junction Perovskite and 4T Perovskite/CIGS Tandem Solar Cells.

The interface between the perovskite layer and the hole transport layer (HTL) plays a vital role in hole extraction and electron blocking in perovskite solar cells (PSCs), and it is particularly susceptible to harmful defects. Surface passivation is an effective strategy for addressing the above concerns. However, because of its strong polarity, isopropyl alcohol (IPA) is used as a solvent in all of the surface treatment materials reported thus far, and it frequently damages the surface of perovskite. In this paper, a method is proposed for dissolving the passivation materials, for example, guanidine bromide (GABr), in mixed solvents (1:1) of IPA and toluene (TL), which can efficiently passivate interface and grain boundary defects by minimizing the IPA solubility of the perovskite surface. As a result, all the performance parameters Voc, Jsc, and FF are improved, and the power conversion efficiency (PCE) increased from 20.1 to 22.7%. Moreover, combining the PSCs with GABr post-treatment in mixed solvents with copper indium gallium selenide (CIGS) solar cells, a 4-terminal (4T) perovskite/CIGS tandem device is realized and a PCE of 25.5% is achieved. The mixed solvent passivation strategy demonstrated here, hopefully, will open new avenues for improving PSCs' efficiency and stability.

Efficacy and safety of sitagliptin and insulin for latent autoimmune diabetes in adults: A systematic review and meta-analysis.

AIMS/INTRODUCTION: The optimal therapy for latent autoimmune diabetes in adults (LADA) remains undefined. Increasing evidence has shown that sitagliptin and insulin treatment can benefit patients with LADA, but the efficacy still lacks systematic evaluation. We carried out this systematic review and meta-analysis to summarize the current data on the efficacy and safety of sitagliptin combined with insulin on LADA, providing a reliable reference for the effective therapeutic treatment of LADA patients. MATERIALS AND METHODS: We retrieved the literature in PubMed, Cochrane Library, Embase, Web of Science and CNKI from inception to August 2021. Randomized controlled trials comparing the effects of sitagliptin plus insulin with insulin alone in LADA patients were identified. The outcome measures included parameters of glycemic control, ß-cell function, body mass index and adverse events. The Review Manager 5.2 and Stata 14.0 were utilized for data analysis. RESULTS: Eight randomized controlled trials involving 295 participants were identified. Sitagliptin and insulin treatment lowered hemoglobin A1c (weighted mean difference -0.36, 95% confidence interval -0.61 to -0.10, I2 = 91.6%), increased fasting C-peptide (weighted mean difference 0.08, 95% confidence interval -0.02 to 0.17, I2 = 88.8%) and had fewer adverse events compared with insulin alone. The inter-study heterogeneity, potential publication bias and other factors might interpret asymmetrical presentation of funnel plots. There was no significant association between sitagliptin plus insulin treatment and levels of hemoglobin A1c or fasting C-peptide, regardless of the duration of intervention and sample size. CONCLUSIONS: Sitagliptin combined with insulin can achieve better glycemic control and improve islet ß-cell function with lower incidence of hypoglycemia compared with insulin alone, which provides an effective and tolerated therapeutic regimen for LADA patients. However, further well-designed and rigorous randomized controlled trials are required to validate this benefit due to the limited methodology quality of included trials.

Apatinib Inhibits Stem Properties and Malignant Biological Behaviors of Breast Cancer Stem Cells by Blocking Wnt/ß-catenin Signal Pathway through Downregulating LncRNA ROR.

BACKGROUND: Cancer stem cells could influence tumor recurrence and metastasis. OBJECTIVE: To develop a new effective treatment modality targeting breast cancer stem cells (BCSCs) and to explore the role of Apatinib in BCSCs. METHODS: BCSCs were isolated from MDA-MB-231 cells by the immune magnetic beads method. BCSCs were treated with Apatinib, lentiviral plasmids (lncRNA ROR), and iCRT-3 (Wnt pathway inhibitors). Viability, colony numbers, sphere numbers, apoptosis, migration, invasion of BCSCs were detected by MTT, colony formation, tumorsphere, flow cytometry, wound-healing, transwell assays, respectively. The expressions of markers (ABCG2, CD44, CD90, and CD24), epithelial-mesenchymal transition (EMT)-related molecules (Ecadherin, N-cadherin, Vimentin, MMP-2, MMP-9), and Wnt/ß-catenin pathway-related proteins (Wnt3a, Wnt5a, ß-catenin) in breast cancer stem cells were determined by performing Western blot and qRT-PCR analysis. RESULTS: Apatinib decreased the viability and colony numbers of BCSCs in a concentration-dependent manner, and it also reduced sphere numbers, suppressed migration, invasion and lncRNA ROR expression, and induced apoptosis of BCSCs. However, these results were partially reversed by lncRNA ROR overexpression. Apatinib suppressed stem property, EMT process, and Wnt/ß-catenin pathway in BCSCs, which was partially reversed by lncRNA ROR overexpression. Moreover, lncRNA ROR overexpression increased the colony and sphere numbers and promoted the cell viability, apoptosis inhibition, migration, and invasion of BCSCs, but these effects were partially reversed by iCRT-3. LncRNA ROR overexpression increased the stem property, EMT process, and Wnt/ß-catenin pathway, which were partially counteracted by iCRT-3. CONCLUSION: Apatinib inhibited stem property and malignant biological behaviors of BCSCs by blocking the Wnt/ß-catenin signal pathway through down-regulating lncRNA ROR.

The Biogenesis and Functions of circRNAs and Their Roles in Breast Cancer.

Recent statistics show that breast cancer is among the most frequent cancers in clinical practice. It is also the second-leading cause of cancer-related deaths among women worldwide. CircRNAs are a new class of endogenous regulatory RNA molecules whose 5' end and 3' end are connected together to form a covalently closed single-stranded loop by back-splicing. CircRNAs present the advantages of disease-specific expression and excellent expression stability, and they can modulate gene expression at posttranscriptional and transcriptional levels. CircRNAs are abnormally expressed in multiple cancers, such as breast cancer, and drive the initiation and progression of cancer. In this review, we describe current knowledge about the functions of circRNAs and generalize their roles in various aspects of breast cancer, including cell proliferation, cell cycle, apoptosis, invasion and metastasis, autophagy, angiogenesis, drug resistance, and tumor immunity, and their prognostic and diagnostic value. This may add to a better understanding of the functions and roles of circRNAs in breast cancer, which may become new diagnostic and predictive biomarkers of breast cancer.

Combined LC-MS/MS and 16S rDNA analysis on mice under high temperature and humidity and Herb Yinchen protection mechanism.

With increased global warming, the impact of high temperature and humidity (HTH) on human health is increasing. Traditional Chinese medicine describes the Herb Yinchen as a remedy for reducing heat and eliminating dampness. This study focused on the impact of HTH conditions on mice and the potential protective effect of Herb Yinchen. Five male Balb/c mouse groups included two normal control groups, two HTH-exposed groups, and one Yinchen-treated group. For either three or ten days, normal and HTH-exposed mice were housed under normal or HTH (33 ± 2 °C,85% relative humidity) conditions, respectively. Yinchen-treated mice, housed under HTH conditions, received the Herb Yinchen decoction for three days. Metabolite profiles of plasma and liver samples from each group were analyzed using LC-MS/MS. Fecal DNA was extracted for 16S rDNA analysis to evaluate the intestinal microbiome. Spearman correlation analysis was performed on metabolites, bacteria, and bile acids that differed between the groups. We found that HTH altered the host metabolite profiles and reduced microbial diversity, causing intestinal microbiome imbalance. Interestingly, Herb Yinchen treatment improved HTH-mediated changes of the metabolite profiles and the intestinal microbiome, restoring them to values observed in normal controls. In conclusion, our study reveals that HTH causes intestinal bacterial disturbances and metabolic disorders in normal mice, while Herb Yinchen could afford protection against such changes.

Juniperus indica Bertol. extract synergized with cisplatin against melanoma cells via the suppression of AKT/mTOR and MAPK signaling and induction of cell apoptosis.

Juniperus indica Bertol. is an herbal plant that belongs to the genus Juniperus, which is commonly used in traditional medicine to refresh the mind and for diuretic use. However, few studies have reported the function of J. indica Bertol. Hence, this study aimed to investigate the anti-tumor and synergistic potential of J. indica Bertol. extract (JIB extract) for melanoma cells. Our results indicated the anti-melanoma activity of JIB extract. JIB extract induced cell cycle arrest at the G0/G1 phase and decreased cyclin and cdk protein expressions. In addition, AKT/mTOR signaling and MAPK signaling were inhibited by JIB extract to suppress melanoma cell growth and proliferation. Additionally, JIB extract induced B16/F10 cell apoptosis via the caspase cascade. According to the JIB extract's anti-melanoma capacity, to assess the synergistic effects of cisplatin and JIB extract. The results demonstrated that JIB extract combined with cisplatin enhanced the inhibition of cell growth, proliferation, and survival through the obstruction of cell cycle progression and AKT/mTOR and MAPK signaling as well as the induction of cell apoptosis. Collectively, our results indicate that JIB extract showed anti-tumor effects and synergized with cisplatin against B16/F10 cells, indicating the possibility of JIB extract to be developed as adjuvant therapy for melanoma.

Diallyl trisulfide regulates cell apoptosis and invasion in human osteosarcoma U2OS cells through regulating PI3K/AKT/GSK3ß signaling pathway.

AIMS: To investigate the effects and the mechanisms of action of Diallyl trisulfide (DATS) on the proliferation and metastasis of human osteosarcoma (OS) U2OS. METHODS: U2OS cells were treated by different concentrations of DATS at different time points. Cell proliferations were measured by MTT assay. DATS induced cell cycle distribution and apoptosis were evaluated by flow cytometry (FCM) with Annexin-V. Cell migration and invasion were detected by wound healing assay and transwell assay. The effects of DATS in U2OS cell growth and metastasis were also detected in a mouse OS xenograft model. RESULTS: A time- and concentration-dependent cytotoxic effect of DATS was observed in U2OS cells. FCM with PI staining and Annexin-V -FITC indicated that DATS induces apoptosis and a G0/G1 cell cycle arrest of U2OS cells at all concentrations from 25 µmol/l to 100 µmol/l. DATS also inhibits the migration and invasion of U2OS cells. Western blot showed that the expression levels of p-AKT, p-GSK3ß, Bcl-2, Vimentin and ß-catenin were decreased, while the expression levels of Bad, Bax and E-cadherin were significantly increased in DATS treated U2OS cells. Analysis using a mouse xenograft model indicated that xenografts of DATS treatment group had a significant decrease in tumor volume and weight compared to the control group. Lung metastasis models in mice demonstrated that treatment of DATS inhibits lung metastasis of OS in vivo. CONCLUSIONS: These data suggested that DATS inhibits OS development and progression through the regulation of PI3K/AKT/GSK3ß signaling pathways, accompanied by downregulation of Bcl-2, Vimentin and ß-catenin, as well as upregulation of Bad, Bax and E-cadherin. Therefore, our data demonstrated that DATS exerted its anticancer effects by inhibiting cell proliferation, migration and invasion in vitro and in vivo. These results provide evidence for the use of the natural product DATS either alone or in combination with standard therapy for OS.