Regioselective Arylation of Amidoaryne Precursors via Ag-Mediated Intramolecular Oxy-Argentation.

An unprecedented silver-mediated intramolecular oxy-argentation of 3-amidoaryne precursors that quickly generates a heteroarylsilver species is developed. AgF acts as both a stoichiometric fluoride source and a reagent for the formation of a benzoxazolylsilver intermediate via aryne generation. Pd-catalyzed coupling reactions of (hetero)aryl iodides with a silver species, generated in situ, allow for the synthesis of various C7-arylated benzoxazoles. As a result, an aryl group is selectively introduced into the meta-position of 3-amidobenzyne precursors. Mechanistic studies have indicated the presence of a benzoxazolylsilver intermediate and revealed that the reaction proceeds via an intramolecular oxy-argentation process, which is initiated by a direct fluoride attack on the silyl group.

Prediction models for post-thrombectomy brain edema in patients with acute ischemic stroke: a systematic review and meta-analysis.

Objective: The objective of this study is to systematically evaluate prediction models for post-thrombectomy brain edema in acute ischemic stroke (AIS) patients. This analysis aims to equip clinicians with evidence-based guidance for the selection of appropriate prediction models, thereby facilitating the early identification of patients at risk of developing brain edema post-surgery. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang, and Vip, aiming to identify studies on prediction models for post-thrombectomy brain edema in AIS patients up to January 2023. Reference lists of relevant articles were also inspected. Two reviewers independently screened the literature and extracted data. The Prediction Model Risk of Bias Assessment Tool (PROBAST) and the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) guidelines were employed to assess study bias and literature quality, respectively. We then used random-effects bivariate meta-analysis models to summarize the studies. Results: The review included five articles, yielding 10 models. These models exhibited a relatively high risk of bias. Random effects model demonstrated that the AUC was 0.858 (95% CI 0.817-0.899). Conclusion: Despite the promising discriminative ability shown by studies on prediction models for post-thrombectomy brain edema in AIS patients, concerns related to a high risk of bias and limited external validation remain. Future research should prioritize the external validation and optimization of these models. There is an urgent need for large-scale, multicenter studies to develop robust, user-friendly models for real-world clinical application. Systematic review registration: https://www.crd.york.ac.uk, unique Identifier: CRD42022382790.

The support dilemma of stroke inpatients and family caregivers under COVID-19 prevention and control: a qualitative study in China.

China has implemented a strict isolation system in hospitals since the COVID-19 pandemic, that adversely affected the psychology of inpatients and their caregivers. Face-to-face, semi-structured interviews with 22 stroke inpatients from two municipal hospitals were conducted to explore the psychological, emotional and related support needs of stroke inpatients and their family caregivers under this environment. Results which showed that external support for stroke inpatients and their family caregivers was insufficient highlight the necessity for developing specific nursing interventions that meet the psychological and emotional needs of inpatients and the caregivers.

Colorectal cancer organoid models uncover oxaliplatin-resistant mechanisms at single cell resolution.

PURPOSE: Oxaliplatin-based chemotherapy is a standard treatment for advanced colorectal cancer (CRC) patients. However, chemoresistance-induced resistance is an essential cause for mortality. Therefore, it is necessary to study the mechanism of drug resistance in CRC. METHODS: Here, we established two strains of patient-derived organoids (PDOs) selected from oxaliplatin-resistant and treatment-naïve CRC patients. To dissect the drug-resistant mechanisms, these CRC-PDOs were subjected to single-cell RNA sequencing (scRNA-Seq). RESULTS: We found that the drug sensitivity test outcome from these organoids subjected to oxaliplatin and 5-FU exposure was consistent with the clinic readout. CRC-PDOs well recapitulated the morphology and histology of their parental biopsies based on HE and IHC staining of pathological biomarkers. The scRNA-Seq data filtered drug-resistant cell populations and related signaling pathways (e.g. oxidative phosphorylation and ATP metabolic process). The data also revealed several putative drug resistant-driven genes (STMN1, VEGFA and NDRG1) and transcription factors (E2F1, BRCA1, MYBL2, CDX2 and CDX1). CONCLUSION: We generated an oxaliplatin-resistant CRC organoid model that was employed to provide potential therapeutic targets for treating CRC patients exhibiting oxaliplatin-resistance.

Defining the ultrastructure of the hematopoietic stem cell niche by correlative light and electron microscopy.

The blood system is supported by hematopoietic stem and progenitor cells (HSPCs) found in a specialized microenvironment called the niche. Many different niche cell types support HSPCs, however how they interact and their ultrastructure has been difficult to define. Here, we show that single endogenous HSPCs can be tracked by light microscopy, then identified by serial block-face scanning electron microscopy (SBEM) at multiscale levels. Using the zebrafish larval kidney marrow (KM) niche as a model, we followed single fluorescently labeled HSPCs by light sheet microscopy, then confirmed their exact location in a 3D SBEM dataset. We found a variety of different configurations of HSPCs and surrounding niche cells, suggesting there could be functional heterogeneity in sites of HSPC lodgement. Our approach also allowed us to identify dopamine beta-hydroxylase (dbh) positive ganglion cells as a previously uncharacterized functional cell type in the HSPC niche. By integrating multiple imaging modalities, we could resolve the ultrastructure of single rare cells deep in live tissue and define all contacts between an HSPC and its surrounding niche cell types.

[Ecosystem structure and function of Sanmen Bay based on Ecopath model.] / 基于Ecopath模型的三门湾生态系统结构与功能.

Ecosystem structure determines material circulation, energy flow, and system function. Based on field investigation data in the Sanmen Bay, East China Sea from 2017 to 2018, ecological channel model was constructed by Ecopath, describing energy flow routes and functional characteristics of the Sanmen Bay ecosystem. Results showed that grazing food chain was the main energy circulation channel, and the trophic level of each functional group ranged from 1 to 3.80. Energy flow of the system was mainly concentrated in the first five levels, with an average energy conversion efficiency of 13.0%. Energy conversion efficiency was 12.8% and 14.5% from primary producers and debris, respectively. Connectance index (CI) and system omnivory index (SOI) were 0.40 and 0.24 respectively. Finn's cycling index (FIC) was 0.40, and Finn's mean path length (MPL) was 2.06. The ratio of total primary productivity to total respiration was 13.59. In conclusion, Sanmen Bay ecosystem was immature in material circulation and energy flow. This work is helpful to understand the structural and functional traits of coastal ecosystems in China.

Integration of a Metal-Organic Framework Film with a Tubular Whispering-Gallery-Mode Microcavity for Effective CO2 Sensing.

Carbon dioxide (CO2) sensing using an optical technique is of great importance in the environment and industrial emission monitoring. However, limited by the poor specific adsorption of gas molecules as well as insufficient coupling efficiency, there is still a long way to go toward realizing a highly sensitive optical CO2 gas sensor. Herein, by combining the advantages of a whispering-gallery-mode microcavity and a metal-organic framework (MOF) film, a porous functional microcavity (PF-MC) was fabricated with the assistance of the atomic layer deposition technique and was applied to CO2 sensing. In this functional composite, the rolled-up microcavity provides the ability to tune the propagation of light waves and the electromagnetic coupling with the surroundings via an evanescent field, while the nanoporous MOF film contributes to the specific adsorption of CO2. The composite demonstrates a high sensitivity of 188 nm RIU-1 (7.4 pm/% with respect to the CO2 concentration) and a low detection limit of ∼5.85 × 10-5 RIU. Furthermore, the PF-MC exhibits great selectivity to CO2 and outstanding reproducibility, which is promising for the next-generation optical gas sensing devices.

Aortic coarctation with cardiac fibroma in a young patient: a case report.

BACKGROUND: Cardiac fibroma and aortic coarctation are rarely observed concomitantly in the same patient. We report a case of cardiac fibroma with aortic coarctation treated with a hybrid surgical procedure. To the best of our knowledge, this is the first case of these two abnormalities existing in one patient. CASE SUMMARY: A 22-year-old female patient visited the clinic with a 10-year history of hypertension. Physical examination revealed blood pressure of the upper extremities 50 mmHg higher than that of the lower extremities. Computed tomography angiography revealed a post-ductal-type aortic coarctation at the beginning segment of the descending aorta along with a 7.7 cm × 5.1 cm left ventricular mass. Transthoracic echocardiogram showed a mass at the middle segments of the lateral wall and apex and posterior wall of the left ventricle. Cardiac magnetic resonance imaging also showed the mass with hypointense signal on T1, hyperintense signal on T2, and intense signal on late gadolinium enhancement. No evidences of metastatic lesions were observed on 18F-fluorodeoxyglucose positron emission tomography. The patient underwent a hybrid surgery involving aortic stent implantation and complete left ventricular mass removal. The gradient between stenosis returned to <10 mmHg after the procedure. Pathologic findings revealed cardiac fibroma. DISCUSSION: It is rare to encounter a patient suffering from both cardiac fibroma and aortic coarctation. No evidences indicated a single cause or syndrome resulting in the coexistence of these two abnormalities. A hybrid surgery involving aortic stent implantation and complete cardiac mass resection could optimize the treatment in such cases.

Flying Squirrel-Inspired Motion Control of a Light-Deformed Pt-PAzoMA Micromotor through Drag Force Manipulation.

Micromotors require stable and precise motion control for complex tasks such as microsurgery, drug delivery in vivo, or environmental monitoring ex vivo. However, a continuous control signal is needed for micromotors to achieve motion control during their whole journey, which hinders their application in areas where external control stimuli are limited or unavailable. Fortunately, nature suggests an excellent solution that flying squirrel exhibits motion tuning capability by deforming itself when jumping off a tall tree. Inspired by this, we propose a Pt-PAzoMA Janus micromotor that precisely changes its shape (from a spherical shape to an elliptical shape) under a brief light signal (450 nm) and maintains this deformation until next signal reception. The deformed elliptical micromotor performs relatively low-speed motion compared to the spherical one, which is further confirmed by massive simulation results. In addition, by investigating motion behavior experimentally and theoretically, it is proved that the motion modulation is caused by the drag force changing brought from the deformation. This method represents a different route to regulate the motion of micromotors without a continuous signal, which is useful in application scenarios where the environmental control signal is inaccessible/limited or long-time operation with minimum energy input is required to maintain motion manipulation. With further function modification, this kind of shape-changing micromotor has potential in optimizing drug diffusion efficiency by speed altering and long-term monitoring at the diseased area by confining the active range of the micromotor in the targeted area through deformation.

Distal Remodeling After Operations for Extensive Acute Aortic Dissection.

BACKGROUND: The clinical predictors of distal aortic remodeling (DAR) after various procedures for extensive acute aortic dissection are not fully understood. METHODS: From 2008 to 2018, a total of 122 candidates with extensive acute type A and B aortic dissections survived operations of total arch replacement plus frozen elephant trunk (n = 36), ascending aortic replacement plus supraaortic debranching plus retrograde stenting (hybrid procedure; n = 25), and total endovascular repair (n = 61). We assessed DAR at 4 thoracoabdominal aortic levels based on true lumen expansion, false lumen patency, maximal aortic area, and the blood supply of major branches. Univariate and multivariate logistic and mixed-effect models were performed to delineate patterns and risks for DAR at midterm follow-up. RESULTS: At 3.9 years, 13 aorta-related adverse events (10.7%; including 3 aortic-related deaths [2.5%]) and 8 aortic reinterventions (6.6%) occurred. Follow-up computed tomography angiography was performed in all patients at 3.3 years (interquartile range, 2.7-4.4 years). The degree of DAR, which was relatively independent among aortic levels, was maximal at the pulmonary bifurcation level (90.2% complete false lumen thrombosis) and decreased along the distal aorta. Analyses of longitudinal data indicated that baseline overall false lumen patency was the only available factor to predict DAR at all 4 aortic levels. Dissection type, surgical technique, implant size, and medication did not sufficiently influence DAR at midterm follow-up. CONCLUSIONS: After distinct operations for extensive acute aortic dissection, DAR beyond the stent graft coverage is a local anatomical behavior independent of dissection type or proximal management.

[Trophic structure of pelagic fishery organism assemblage in the central and western South China Sea in spring revealed by carbon and nitrogen stable isotope analysis]. / åŸºäºŽç¢³æ°®ç¨³å®šåŒä½ç´ çš„å—æµ·ä¸­è¥¿éƒ¨æµ·åŸŸæ˜¥å­£ä¸­ä¸Šå±‚æ¸”ä¸šç”Ÿç‰©ç¾¤è½è¥å »ç»“æž„.

Carbon and nitrogen stable isotope analysis was carried out on pelagic fishery organisms caught in light traps and falling nets in the central and western South China Sea in the spring of 2018. The stable isotope values of the sampled individuals were used to elucidate the isotopic variations for the pelagic fishery organisms, to classify species into trophic functional groups, and to compare the differences of trophic structure among the classified trophic functional groups. The results showed that among 23 fishery species the mean δ13C value of Coryphaena hippurus was the lowest (-17.58‰±0.21‰), and that of Grammistes sexlineatus was the highest (-19.86‰±0.33‰). The mean δ15N values ranged from 8.31‰ in Psenes cyanophrys to (12.46±0.74)‰ in Chirocentrus dorab. The continuous trophic spectrum indicated that the trophic level (TL) for the sampled pela-gic fishery organisms ranged from 3.01 to 4.23, of which 19 species (83% of the total) fell between TL 3.0 and 4.0. The 23 species of fishery organisms were classified into three trophic functional groups, i.e., plankton feeding functional group (PFFG), nekton feeding functional group (NFFG), and mixed feeding functional group (MFFG). The analysis of standard ellipse area (SEA) showed that the PFFG occupied the largest trophic niche width (SEA=1.56‰2), followed by the MFFG (SEA=0.99‰2) and NFFG (SEA=0.31‰2). The MFFG overlapped with PFFG and NFFG in the trophic niche, with a relative percentage of 17% and 26%, respectively. There was no overlap between PFFG and NFFG.

Acute Commissural Rupture in a Giant Aortic Root Aneurysm.

Idiopathic rupture of aortic valve commissure is an extremely rare cause of acute aortic regurgitation. Here, we report a case of commissural rupture with giant root aneurysm and history of chronic aortic regurgitation, emphasizing the diagnostic value of high-quality three-dimensional reconstructions of multimodality imaging in assessing the cause of abruptly deteriorating valve regurgitation.

Mesenchymal stem cells rejuvenate cardiac muscle through regulating macrophage polarization.

We have shown that the effects of transplantation of CD146+ mesenchymal stem cells (MSCs) on myocardial regeneration after myocardial infarction (MI) exceeds the effects of transplantation of MSCs, likely resulting from reduction of aging-associated cellular reactive oxygen species in injured cardiac muscle cells (CMCs). Since the role of macrophages in the MSC-mediated recovery of heart function after MI remains unclear, this question was thus addressed in the current study. We found that transplantation of MSCs did not alter the total number of the macrophages in the injured heart, but induced their polarization towards a M2-phenotype. Moreover, administration of tumor necrosis factor alpha (TNFα) into MSC-transplanted mice, which prevented M2-polarization of macrophages, abolished the effects of MSCs on recovery of heart function and on the reduction of infarcted cardiac tissue. Thus, our data suggest that MSCs may rejuvenate CMCs after ischemic injury at least partially through induction of M2-polarization of macrophages.

Hypoxic Macrophage-Derived VEGF Promotes Proliferation and Invasion of Gastric Cancer Cells.

BACKGROUND: Gastric cancer (GC) is one of the most common causes of cancer death. Hypoxia is an important property of the tumor microenvironment of GC. Increasing evidence demonstrates that tumor-associated macrophages are related to the metastasis of GC, while the precise mechanism of how hypoxic macrophages affect tumor progression is still not fully understood. AIMS: To examine whether the mediators released from hypoxic macrophages contribute to the invasion and proliferation of GC cells. METHODS: Cell Counting Kit-8 was utilized to determine the proliferation of SGC7901 and MKN45 cells. The invasion of SGC7901 and MKN45 cells was measured by transwell invasion assay. Expression of VEGF mRNA in THP-1-derived macrophages was determined by RT-PCR, and protein level of VEGF in the culture medium was detected by ELISA. RESULTS: The proliferation and invasion of SGC7901 and MKN45 cells were dramatically increased after treatment with conditioned medium (CM) collected from THP-1-derived macrophages under hypoxia (H-CM), and the phosphorylation of Akt and p38 in SGC7901 and MKN45 cells was also up-regulated by H-CM stimulation. Notably, blockage of PI3K-Akt or p38 MAP kinase abolished the effects of H-CM on the proliferation and invasion of SGC7901 and MKN45 cells. Furthermore, VEGF was increased in macrophages after hypoxia and administration with nintedanib, an inhibitor of VEGFR, significantly decreases the phosphorylation of Akt and p38, as well as the proliferation and invasion of SGC7901 and MKN45 cells in response to H-CM. CONCLUSIONS: Our findings suggest that hypoxia-injured macrophages contribute to the proliferation and invasion of GC cells through the release of mediators such as VEGF.

Patient-prosthesis mismatch in mitral annuloplasty for degenerative mitral regurgitation: an ignored issue.

OBJECTIVES: Elevated postoperative transmitral gradient (TMG), partially induced by a small annuloplasty ring, is associated with late atrial fibrillation (AF) after mitral valve repair. Here, we aimed to provide the optimal cut-off of prosthetic ring size to reduce patient-prosthesis mismatch (PPM) after mitral annuloplasty. METHODS: From 2006 to 2017, 262 patients who underwent mitral valve repair for degenerative pathologies were retrospectively studied. The relationships of body surface area (BSA)-indexed prosthetic orifice area (POAi)-postoperative TMG and POAi-late AF were tested using regression curves and receiver operating characteristic curves, respectively. The optimal cut-off of POAi predictive of late AF was used to define PPM. Baseline and follow-up data of patients with and without PPM were compared in propensity score-matched cohorts. RESULTS: In-hospital mortality was 0. Late AF was observed in 9.2% (24/262) patients during a median follow-up of 3.8 years. An exponential model was best fitted based on the POAi-postoperative TMG relationship (P < 0.001). Using late AF as the dependent variable, the optimal cut-off for PPM was POAi ≤2.28 cm2/m2 (c-statistic 0.71; sensitivity 0.61; specificity 0.80; P < 0.001). PPM was identified in 113 (43.1%) patients. After propensity score matching, the estimated 5-year rate of late AF was significantly higher in PPM patients than in non-PPM patients (24% vs 5%; P < 0.001). CONCLUSIONS: Postoperative TMG increases significantly with a small POAi for full ring annuloplasty. A patient's BSA should be considered in addition to valvular dimensions during the selection of a proper ring size to reduce PPM-related AF.

Rivaroxaban, Aspirin, or Both to Prevent Early Coronary Bypass Graft Occlusion: The COMPASS-CABG Study.

BACKGROUND: Patients with recent coronary artery bypass graft (CABG) surgery are at risk for early graft failure, which is associated with a risk of myocardial infarction and death. In the COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) trial, rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced the primary major adverse cardiovascular events (MACE) outcome of cardiovascular death, stroke, or myocardial infarction. Rivaroxaban 5 mg twice daily alone did not significantly reduce MACE. OBJECTIVES: This pre-planned substudy sought to determine whether the COMPASS treatments are more effective than aspirin alone for preventing graft failure and MACE after CABG surgery. METHODS: The substudy randomized 1,448 COMPASS trial patients 4 to 14 days after CABG surgery to receive the combination of rivaroxaban plus aspirin, rivaroxaban alone, or aspirin alone. The primary outcome was graft failure, diagnosed by computed tomography angiogram 1 year after surgery. RESULTS: The combination of rivaroxaban and aspirin and the regimen of rivaroxaban alone did not reduce the graft failure rates compared with aspirin alone (combination vs. aspirin: 113 [9.1%] vs. 91 [8.0%] failed grafts; odds ratio [OR]: 1.13; 95% confidence interval [CI]: 0.82 to 1.57; p = 0.45; rivaroxaban alone vs. aspirin: 92 [7.8%] vs. 92 [8.0%] failed grafts; OR: 0.95; 95% CI: 0.67 to 1.33; p = 0.75). Compared with aspirin, the combination was associated with fewer MACE (12 [2.4%] vs. 16 [3.5%]; hazard ratio [HR]: 0.69; 95% CI: 0.33 to 1.47; p = 0.34), whereas rivaroxaban alone was not (16 [3.3%] vs. 16 [3.5%]; HR: 0.99, CI: 0.50 to 1.99; p = 0.98). There was no fatal bleeding or tamponade within 30 days of randomization. CONCLUSIONS: The combination of rivaroxaban 2.5 mg twice daily plus aspirin or rivaroxaban 5 mg twice daily alone compared with aspirin alone did not reduce graft failure in patients with recent CABG surgery, but the combination of rivaroxaban 2.5 mg twice daily plus aspirin was associated with similar reductions in MACE, as observed in the larger COMPASS trial. (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS [COMPASS]; NCT01776424).

Mesenchymal stem cells rejuvenate cardiac muscle after ischemic injury.

Previous studies have shown that transplantation of mesenchymal stem cells (MSCs) enhances myocardial regeneration after myocardial infarction (MI), primarily resulting from the production and release of trophic growth factors and cytokines by MSCs. However, effects of MSCs or a subtype of MSCs on the ageing of injured cardiac muscle cells (CMCs) are limitedly known. Here, we addressed this question. CD146+ MSCs were isolated from total MSCs (tMSCs), and their effects on injured CMCs were assessed. In vivo, transplantation of isogenic CD146+ MSCs into MI-mice increased the proliferation of CMCs and reduced apoptosis of CMCs in a significantly higher degree than transplantation of tMSCs, resulting in significant improvement of the heart function. In vitro, CMCs were co-cultured under hypoxia condition with CD146+MSCs or tMSCs. We found that CD146+MSCs increased the proliferation of CMCs and reduced apoptosis of CMCs in a significantly higher degree, compared to tMSCs, likely resulting from reduction of aging-associated cellular reactive oxygen species in CMCs. Together, these data suggest that MSCs rejuvenate CMCs after ischemic injury and a subtype of MSCs, CD146+ MSCs, appears to have higher potential in coordinating this process.

Elevated gradient after mitral valve repair: The effect of surgical technique and relevance of postoperative atrial fibrillation.

OBJECTIVES: We sought to investigate the effect of surgical technique in mitral valve repair on postoperative transmitral gradient (PTMG) and the relationship between PTMG and postoperative atrial fibrillation (AF). METHODS: In this retrospective study, 390 patients who underwent mitral valve repair for degenerative mitral regurgitation without AF were included. PTMG was measured using transthoracic echocardiography before patient discharge. At follow-up, occurrences of AF within 6 months of surgery (early AF) and 6 months after surgery (late AF), as well as clinical and echocardiographic data were documented and investigated. RESULTS: The in-hospital mortality was 0, and the mean gradient was 3.1 ± 1.2 mm Hg before patient discharge. The risks for higher PTMG included cleft closure, edge-to-edge technique, full ring annuloplasty, and smaller indexed prosthetic size (P < .05 for all). After a median follow-up of 46 months, stable sinus rhythm was maintained in 73.1% of the overall cohort and early AF occurred in 22.7% of patients. A total of 32 patients (8.5%) had late AF, which was significantly associated with PTMG (odds ratio, 3.93; P = .004). The minimum P value approach identified a mean gradient of ≥4.5 mm Hg as the best threshold for predicting late AF (χ2 = 40.704; P < .001). CONCLUSIONS: Patients who undergo mitral valve repair for degenerative mitral insufficiency might benefit from modification of the existing leaflet repair and annuloplasty techniques to achieve a lower PTMG level, which is associated with a decreased incidence of late AF during midterm follow-up.

Three-Dimensional Printed Models-Guided Surgical Repair for Recurrent Coronary Artery Fistula.

Recurrent coronary artery fistula is rare and can be difficult for surgical treatment because of anatomic complexity. Here, we reported a case of successful re-repair of a recurrent coronary artery fistula, with added evidence of the three-dimensional printed models guiding surgical correction of complex intracardiac abnormalities.