Odoratin balances ROS/NO through EZH2/PPARγ signalling to improve myocardial fibrosis.

Myocardial fibrosis is a critical concern in clinical medicine. This study explores the potential of odoratin as a treatment for myocardial fibrosis and investigates its underlying mechanisms. In vitro experiments involved stimulating primary mouse cardiomyocytes with TGF-ß1, followed by odoratin treatment, to assess levels of reactive oxygen species (ROS) and nitric oxide (NO). In vivo, a mouse model of myocardial fibrosis was established using abdominal aortic constriction (AAC) and treated with odoratin. ROS and NO levels in myocardial tissue were then evaluated. Immunofluorescence and Western blotting analysis showed that odoratin reduced excess ROS, enhanced NO production and decreased fibrosis-related protein expression in vitro. In vivo, odoratin significantly improved cardiac function, reduced ROS, increased NO levels and mitigated fibrosis in AAC-induced mice. Both in vitro and in vivo, odoratin inhibited the expression of NADPH oxidase 4 and EZH2, while promoting the expression of phosphorylated endothelial nitric oxide synthase (p-eNOS) and PPARγ. The anti-fibrotic effects of odoratin were reversed by PPARγ antagonism, and EZH2 overexpression diminished PPARγ activation by odoratin. These findings suggest that odoratin may combat myocardial fibrosis by balancing ROS and NO through PPARγ activation, with EZH2 inhibition likely playing a key regulatory role.

Post myocardial infarction left ventricular intramyocardial dissecting hematoma penetrated right ventricular outflow tract: a rare complication report.

BACKGROUND: Intramyocardial dissecting hematoma (IDH) is a rare mechanical complication following myocardial infarction (MI), and only a few isolated cases have been reported to date. IDH presents with diverse clinical manifestations, often resulting in missed or misdiagnosed cases due to limited physician understanding. The diagnosis and treatment of IDH is a major challenge. CASE PRESENTATIONS: We report a case of acute extensive anterior MI in a 73-year-old woman, who underwent percutaneous coronary intervention (PCI); the left ventricular intramyocardial dissecting hematoma (LVIDH) penetrated the right ventricular outflow tract (RVOT), resulting in thrombus formation and subsequent RVOT obstruction. Clinically insignificant IDH was detected by transthoracic echocardiography (TTE) at 3 days, 43 days, and 75 days post-PCI, with characteristic changes in the left ventricular wall ultrasound images. This unusual case highlights the important role of continuous transthoracic echocardiography in identifying this rare complication of LVIDH. After a detailed discussion with the patient, the choice between conservative or surgical management of IDH depends on factors such as the size of the hematomae, left ventricular systolic function, and the patient's clinical and haemodynamic status. In this particular case, conservative management was chosen by the patient who declined surgery but unfortunately succumbed to cardiogenic shock. CONCLUSIONS: This case describes a rare complication of acute myocardial infarction (AMI) and also focuses on the utility of TTE in the diagnosis of this rare complication. Whether LVIDH is treated conservatively or surgically requires careful evaluation to achieve the best prognosis for the patient.

Isolation of Fluorescent 2π-Aromatic 1,3-Disiladiboretenes.

Herein, we reported the isolation of 2π-aromatic disiladiboretenes (L2Si2B2Ph2) [L = ArC(NtBu)2, Ar = Ph (1), Mes (2)], which have been synthesized from the straightforward reduction of silylene-borane adducts (LSiX → BX2Ph) [X = Cl, Br] with potassium graphite (KC8). X-ray diffraction analysis of 1 and 2 revealed that the Si2B2 units are completely planar, and DFT calculations suggested delocalization of 2π-electrons over the Si2B2 rings. Moreover, their photophysical properties and reactivity toward sulfur were also investigated in detail.

Reactivity of Cyclic (Alkyl)(amino)germylene towards Copper(I) and Gold(I) Complexes.

The reactions of cyclic (alkyl)(amino)germylenes (CAAGe) with copper(I) and gold(I) complexes were investigated. CAAGe (1) reacts with CuBr(SMe2 ) leading to a tetrameric germylene complex [CAAGeCuBr]4 (2), whereas CAAGe (3) undergoes Au-Cl bond insertion with LAuCl (L=phosphine or N-heterocyclic carbene) to afford germanium gold(I) complexes (5 and 6). Chlorine abstraction of 6 gives the cationic germylene gold(I) complex 7.

Cu(ii)-mediated direct intramolecular cyclopropanation of distal olefinic acetate: access to cyclopropane-fused γ-lactones.

Cyclopropane-fused ring scaffolds represent one of the most appealing structural motifs in organic chemistry due to their wide presence in bioactive molecules and versatility in organic synthesis. These skeletons are typically prepared from olefinic diazo compounds via transition-metal catalysed intramolecular carbenoid insertion, which suffers from prefunctionalization of starting materials and limited substrate scope. Herein, we disclose a practical copper-mediated direct intramolecular cyclopropanation of distal olefinic acetate to synthesize cyclopropane-fused γ-lactones and lactams. This cascade reaction is postulated to proceed through a hydrogen atom transfer event induced radical cyclization and copper-mediated cyclopropanation sequence. The protocol features high atom- and step-economy, excellent diastereoselectivity, broad tolerance of functional groups, and operational simplicity.

Air-Stable Organoradical Boron Reagents.

Both organic radicals and organoboron reagents have been broadly investigated, but the combination of them via direct C-H borylation as organic radical building blocks has never been achieved. Herein, a series of organoradical boron reagents, such as TTM-Bpin and TTM-BOH, were synthesized through the key step of C-H borylation of substrate TTM-H ((2,6-dichlorophenyl) bis(2,4,6-trichlorophenyl)methyl) radical for the first time. They are air stable enough to be stored in the solid state for several months under dark conditions, and fully investigated through single crystal analysis, EPR and DFT calculations. Furthermore, they can smoothly work in the standard Suzuki-Miyaura coupling (SMC) reaction with retention of the carbon radical center. Meanwhile, these radical species bearing different boron units display fluorescent character and are potentially applied for the collective synthesis of luminescent organic radicals, as well as other functionalized open-shell materials.

Multiscale photoacoustic tomography of neural activities with GCaMP calcium indicators.

SIGNIFICANCE: Optical imaging of responses in fluorescently labeled neurons has progressed significantly in recent years. However, there is still a need to monitor neural activities at divergent spatial scales and at depths beyond the optical diffusion limit. AIM: To meet these needs, we aim to develop multiscale photoacoustic tomography (PAT) to image neural activities across spatial scales with a genetically encoded calcium indicator GCaMP. APPROACH: First, using photoacoustic microscopy, we show that depth-resolved GCaMP signals can be monitored in vivo from a fly brain in response to odor stimulation without depth scanning and even with the cuticle intact. In vivo monitoring of GCaMP signals was also demonstrated in mouse brains. Next, using photoacoustic computed tomography, we imaged neural responses of a mouse brain slice at depths beyond the optical diffusion limit. RESULTS: We provide the first unambiguous demonstration that multiscale PAT can be used to record neural activities in transgenic flies and mice with select neurons expressing GCaMP. CONCLUSIONS: Our results indicate that the combination of multiscale PAT and fluorescent neural activity indicators provides a methodology for imaging targeted neurons at various scales.

Genomic architecture of fetal central nervous system anomalies using whole-genome sequencing.

Structural anomalies of the central nervous system (CNS) are one of the most common fetal anomalies found during prenatal imaging. However, the genomic architecture of prenatal imaging phenotypes has not yet been systematically studied in a large cohort. Patients diagnosed with fetal CNS anomalies were identified from medical records and images. Fetal samples were subjected to low-pass and deep whole-genome sequencing (WGS) for aneuploid, copy number variation (CNV), single-nucleotide variant (SNV, including insertions/deletions (indels)), and small CNV identification. The clinical significance of variants was interpreted based on a candidate gene list constructed from ultrasound phenotypes. In total, 162 fetuses with 11 common CNS anomalies were enrolled in this study. Primary diagnosis was achieved in 62 cases, with an overall diagnostic rate of 38.3%. Causative variants included 18 aneuploids, 17 CNVs, three small CNVs, and 24 SNVs. Among the 24 SNVs, 15 were novel mutations not reported previously. Furthermore, 29 key genes of diagnostic variants and critical genes of pathogenic CNVs were identified, including five recurrent genes: i.e., TUBA1A, KAT6B, CC2D2A, PDHA1, and NF1. Diagnostic variants were present in 34 (70.8%) out of 48 fetuses with both CNS and non-CNS malformations, and in 28 (24.6%) out of 114 fetuses with CNS anomalies only. Hypoplasia of the cerebellum (including the cerebellar vermis) and holoprosencephaly had the highest primary diagnosis yields (>70%), while only four (11.8%) out of 34 neural tube defects achieved genetic diagnosis. Compared with the control group, rare singleton loss-of-function variants (SLoFVs) were significantly accumulated in the patient cohort.

ortho-Terphenylene Viologens with Through-Space Conjugation for Enhanced Photocatalytic Oxidative Coupling and Hydrogen Evolution.

A series of novel ortho-terphenylene viologen derivatives (o-TPV2+) with through-space conjugation (TSC) via the combination of ortho-terphenylene skeletons with viologen structure is reported. Their optoelectronic properties can be adjusted by N-arylation or N-alkylation reactions. Compared with other viologen derivatives, o-TPV2+ not only exhibits strong photoluminescence but also retards the charge recombination process and stabilizes the diradical state without forming a quinoid structure due to the special TSC effect. Based on their special redox characteristics, o-TPV2+ was applied to the photocatalytic oxidative coupling of benzylamine with 96% yield. In addition, pTA-o-TPV2+ (tethered with p-toluic acid)-modified g-C3N4 was used for visible-light-driven hydrogen production for the first time, exceeding 15 times the rate over unmodified g-C3N4.

Bacteria-Triggered Solar Hydrogen Production via Platinum(II)-Tethered Chalcogenoviologens.

Multifunctional solar energy conversion offers a feasible strategy to solve energy, environmental and water crises. Herein, a series of platinum(II)-tethered chalcogenoviologens (PtL+ -EV2+ , E=S, Se, Te) is reported, which integrate the functions of photosensitizer, electron mediator and catalyst. PtL+ -EV2+ (particularly for PtL+ -SeV2+ )-based one-component solar H2 production could be triggered not only by EDTA, but also by facultative anaerobic and aerobic bacteria relying on a simplified mechanism, along with efficient antibacterial activities. In addition, by using real pool water, PtL+ -SeV2+ achieved multiple functions, including H2 production, antibacterial action and acid removal, which supplied a new strategy to solve various problems in real life via a single system.

Efficient Photoinduced Electron Transfer from Pyrene-o-Carborane Heterojunction to Selenoviologen for Enhanced Photocatalytic Hydrogen Evolution and Reduction of Alkynes.

A series of pyrene or pyrene-o-carborane-appendant selenoviologens (Py-SeV2+ , Py-Cb-SeV2+ ) for enhanced photocatalytic hydrogen evolution reaction (HER) and reduction of alkynes is reported. The efficient photoinduced electron transfer (PET) from electron-rich pyrene-o-carborane heterojunction (Py-Cb) with intramolecular charge transfer (ICT) characteristic to electron-deficient selenoviologen (SeV2+ ) (kET = 1.2 × 1010 s-1 ) endows the accelerating the generation of selenoviologen radical cation (SeV+• ) compared with Py-SeV2+ and other derivatives. The electrochromic/electrofluorochromic devices' (ECD and EFCD) measurements and supramolecular assembly/disassembly processes of SeV2+ and cucurbit[8]uril (CB[8]) results show that the PET process can be finely tuned by electrochemical and host-guest chemistry methods. By combination with Pt-NPs catalyst, the Py-Cb-SeV2+ -based system shows high-efficiency visible-light-driven HER and highly selective phenylacetylene reduction due to the efficient PET process.

Phosphorescent Bismoviologens for Electrophosphorochromism and Visible Light-Induced Cross-Dehydrogenative Coupling.

A series of novel bismuth-bridged viologen analogues, bismoviologens (BiV2+), synthesized through a combination of a bismuth atom and viologen skeleton is reported. Their optical and electrochemical properties were fine-tuned through the N-arylation or N-alkylation reactions. Bismolviologens not only showed good redox properties but also exhibited phosphorescence under ambient conditions (in air at room temperature). This phenomenon makes BiV2+ the first examples of phosphorescent viologen analogues reported to date. On the basis of the excellent and unique redox and optical properties of BiV2+, their electrophosphorochromic devices were fabricated. Furthermore, BiV2+ was used for the first time as both a photocatalyst and electron mediator in visible light-induced cross-dehydrogenative coupling reactions.

Landscape of immune checkpoint inhibitor-related adverse events in Chinese population.

This study aimed to describe the landscape of Immune checkpoint inhibitors (ICIs)-related adverse events (AEs) in a predominantly Chinese cohort. We searched electronic datasets including PubMed, Web of Science and Embase to identify and recruit relevant trials up to September 2, 2019. Clinical trials focusing on ICIs in Chinese patients or a predominantly Chinese population were included. Incidences of treatment-related AEs (TRAEs) and immune-related AEs (irAEs) were pooled and compared. In total, we recruited 13 trials consisting of 1063 patients, with 922 (86.7%) receiving ICI monotherapy and 141 (13.3%) receiving combination of ICI with chemotherapy or anti-angiogenesis. The pooled incidence of any grade TRAEs, grade 1-2, grade 3-5 TRAEs, any grade irAEs, grade 1-2 irAEs and grade 3-5 irAEs in all 1063 patients were 84.1%, 63.3%, 20.9%, 43.3%, 40.0% and 3.0%, respectively. Moreover, 4.3% (44/1018) of patients experienced treatment discontinuation and only 8 (0.8%) patients experienced treatment-related death. Compared to ICI monotherapy, combination significantly increased grade 3-5 TRAEs (46.1% vs. 17.0%, P < 0.001) and grade 3-5 irAEs (7.1% vs. 2.0%, P = 0.015). By comparing the toxicity profiles between different ICIs, we found some drug-specific AEs such as reactive capillary haemangiomas for camrelizumab (58.6%), hyperglycemia for toripalimab (55.6%) and pyrexia for tislelizumab (54.3%). Additionally, nivolumab has the lowest incidence of any grade (64.1%) and grade 3-5 (11.8%) TRAEs. ICI-related AEs were generally mild and tolerable for a predominantly Chinese cohort. However, we should pay attention to the combination of ICI with chemotherapy as it could increase grade 3-5 TRAEs and irAEs.

Poly(selenoviologen)-Assembled Upconversion Nanoparticles for Low-Power Single-NIR Light-Triggered Synergistic Photodynamic and Photothermal Antibacterial Therapy.

The development of a highly effective photosensitizer (PS) that can be activated with a low-power single light is a pressing issue. Herein, we report a PS for synergistic photodynamic and photothermal therapy constructed through self-assembly of poly(selenoviologen) on the surface of core-shell NaYF4:Yb/Tm@NaYF4 upconversion nanoparticles. The hybrid UCNPs/PSeV PS showed strong ROS generation ability and high photothermal conversion efficiency (∼52.5%) under the mildest reported-to-date irradiation conditions (λ = 980 nm, 150 mW/cm2, 4 min), leading to a high efficiency in killing methicillin-resistant Staphylococcus aureus (MRSA) both in vitro and in vivo. Remarkably, after intravenous injection, the reported PS accumulated preferentially in deep MRSA-infected tissues and achieved an excellent therapeutic index. This PS design realizes a low-power single-NIR light-triggered synergistic phototherapy and provides a simple and versatile strategy to develop safe clinically translatable agents for efficient treatment of deep tissue bacterial inflammations.

Crystalline Boragermenes.

Boragermene 3 featuring a double bond between the Ge and dicoordinate B atoms has been synthesized for the first time by reacting the cyclic (alkyl)(boryl)germylene-PMe3 adduct 1 with Cl2 BN(SiMe3 )2 followed by reductive dehalogenation with KC8 . Addition of a Lewis base (Me NHC) to 3 leads to the formation of the corresponding adduct 4, which shows double bond character between the Ge and tricoordinate B atoms. Compound 3 undergoes hydrogenation with H2 concomitant with a complete scission of the Ge=B bond.

A Cyclic (Alkyl)(boryl)germylene Derived from a Cyclic (Alkyl)(amino)germylene.

A cyclic (alkyl)(amino)germylene undergoes a ring expansion reaction with dibromomesitylborane (MesBBr2 ) to afford a six-membered dibromogermane derivative. In the presence of Lewis bases (PMe3 or Me NHC), reduction of the latter with two equivalents of potassium graphite (KC8 ) gives rise to cyclic (alkyl)(boryl)germylene-Lewis base adducts. Upon heating, the germylene-PMe3 adduct reacts with H2 to yield a germane, probably via a base-free germylene featuring a small HOMO-LUMO gap.

Optical Resolution Photoacoustic Microscopy of Ovary and Fallopian Tube.

Ovarian cancer is the leading cause of death among gynecological cancers, but is poorly amenable to preoperative diagnosis. In this study, we investigate the feasibility of "optical biopsy," using high-optical-resolution photoacoustic microscopy (OR-PAM) to quantify the microvasculature of ovarian and fallopian tube tissue. The technique is demonstrated using excised human ovary and fallopian tube specimens imaged immediately after surgery. Quantitative parameters are derived using Amira software. The parameters include three-dimensional vascular segment count, total volume and length, which are associated with tumor angiogenesis. Qualitative results of OR-PAM demonstrate that malignant ovarian tissue has larger and more tortuous blood vessels as well as smaller vessels of different sizes, while benign and normal ovarian tissue has smaller vessels of uniform size. Quantitative analysis shows that malignant ovaries have greater tumor vessel volume, length and number of segments, as compared with benign and normal ovaries. The vascular pattern of benign fallopian tube is different than that of benign ovarian tissue. Our initial results demonstrate the potential of OR-PAM as an imaging tool for fast assessment of ovarian tissue and fallopian tube and could avoid unnecessary surgery if the risk of the examined ovary is extremely low.

Histogram analysis of en face scattering coefficient map predicts malignancy in human ovarian tissue.

Ovarian cancer is a heterogeneous disease at the molecular and histologic level. Optical coherence tomography (OCT) is able to map ovarian tissue optical properties and heterogeneity, which has been proposed as a feature to aid in diagnosis of ovarian cancer. In this manuscript, depth-resolved en face scattering maps of malignant ovaries, benign ovaries, and benign fallopian tubes obtained from 20 patients are provided to visualize the heterogeneity of ovarian tissues. Six features are extracted from histograms of scattering maps. All features are able to statistically distinguish benign from malignant ovaries. Two prediction models were constructed based on these features: a logistic regression model (LR) and a support vector machine (SVM). The optimal set of features is mean scattering coefficient and scattering map entropy. The LR achieved a sensitivity and specificity of 97.0% and 97.8%, and SVM demonstrated a sensitivity and specificity of 99.6% and 96.4%. Our initial results demonstrate the feasibility of using OCT as an "optical biopsy tool" for detecting the microscopic scattering changes associated with neoplasia in human ovarian tissue.

SERS based determination of vanillin and its methyl and ethyl derivatives using flower-like silver nanoparticles on a silicon wafer.

A surface enhanced Raman scattering (SERS) method is described for the determination of vanillin, methyl vanillin and ethyl vanillin at trace levels. Flower-like silver nanoparticles on a silicon wafer are used as the SERS substrate, and the analytes can be specifically and non-destructively recognized by their specific Raman bands. The molecules can be recognized rapidly by identifying the characteristic bands. The SERS spectra of vanillin (C8H8O3) were used as mid-contrast, and specific bands of methyl vanillin and ethyl vanillin (C9H10O3) were acquired at 775 cm-1, 1350 cm-1 and 1282 cm-1, 1382 cm-1, respectively. In addition, by using an improved principal component analysis (PCA) algorithm, the organic molecule can be quantitatively determined. Dissolved in water, vanillin, methyl vanillin and ethyl vanillin still can be detected at a concentration of 10-8 M, at which their characteristic Raman peaks are still visible. The method was successfully applied to the determination of vanillin in milk powder products. Graphical abstract Vanillin can be identified at trace levels by laser irradiation of milk and by using flower-like silver nanoparticles as the surface enhanced Raman scattering (SERS) substrate. Vanillin and its methyl and ethyl derivatives can be quantitatively analyzed by the principal component analysis (PCA) algorithm.

The Angular Spectrum of the Scattering Coefficient Map Reveals Subsurface Colorectal Cancer.

Colorectal cancer diagnosis currently relies on histological detection of endoluminal neoplasia in biopsy specimens. However, clinical visual endoscopy provides no quantitative subsurface cancer information. In this ex vivo study of nine fresh human colon specimens, we report the first use of quantified subsurface scattering coefficient maps acquired by swept-source optical coherence tomography to reveal subsurface abnormities. We generate subsurface scattering coefficient maps with a novel wavelet-based-curve-fitting method that provides significantly improved accuracy. The angular spectra of scattering coefficient maps of normal tissues exhibit a spatial feature distinct from those of abnormal tissues. An angular spectrum index to quantify the differences between the normal and abnormal tissues is derived, and its strength in revealing subsurface cancer in ex vivo samples is statistically analyzed. The study demonstrates that the angular spectrum of the scattering coefficient map can effectively reveal subsurface colorectal cancer and potentially provide a fast and more accurate diagnosis.