Single-Cell RNA Sequencing Resolves Spatiotemporal Development of Pre-thymic Lymphoid Progenitors and Thymus Organogenesis in Human Embryos.

Generation of the first T lymphocytes in the human embryo involves the emergence, migration, and thymus seeding of lymphoid progenitors together with concomitant thymus organogenesis, which is the initial step to establish the entire adaptive immune system. However, the cellular and molecular programs regulating this process remain unclear. We constructed a single-cell transcriptional landscape of human early T lymphopoiesis by using cells from multiple hemogenic and hematopoietic sites spanning embryonic and fetal stages. Among heterogenous early thymic progenitors, one subtype shared common features with a subset of lymphoid progenitors in fetal liver that are known as thymus-seeding progenitors. Unbiased bioinformatics analysis identified a distinct type of pre-thymic lymphoid progenitors in the aorta-gonad-mesonephros (AGM) region. In parallel, we investigated thymic epithelial cell development and potential cell-cell interactions during thymus organogenesis. Together, our data provide insights into human early T lymphopoiesis that prospectively direct T lymphocyte regeneration, which might lead to development of clinical applications.

Immunophilin FKB20-2 participates in oligomerization of Photosystem I in Chlamydomonas.

PSI is a sophisticated photosynthesis protein complex that fuels the light reaction of photosynthesis in algae and vascular plants. While the structure and function of PSI have been studied extensively, the dynamic regulation on PSI oligomerization and high light response is less understood. In this work, we characterized a high light-responsive immunophilin gene FKB20-2 (FK506-binding protein 20-2) required for PSI oligomerization and high light tolerance in Chlamydomonas (Chlamydomonas reinhardtii). Biochemical assays and 77-K fluorescence measurement showed that loss of FKB20-2 led to the reduced accumulation of PSI core subunits and abnormal oligomerization of PSI complexes and, particularly, reduced PSI intermediate complexes in fkb20-2. It is noteworthy that the abnormal PSI oligomerization was observed in fkb20-2 even under dark and dim light growth conditions. Coimmunoprecipitation, MS, and yeast 2-hybrid assay revealed that FKB20-2 directly interacted with the low molecular weight PSI subunit PsaG, which might be involved in the dynamic regulation of PSI-light-harvesting complex I supercomplexes. Moreover, abnormal PSI oligomerization caused accelerated photodamage to PSII in fkb20-2 under high light stress. Together, we demonstrated that immunophilin FKB20-2 affects PSI oligomerization probably by interacting with PsaG and plays pivotal roles during Chlamydomonas tolerance to high light.

The Impact of Prone Position Ventilation on the Prognosis of Patients with Pulmonary Infections in Intensive Care Units.

Objective: This retrospective study aimed to analyze the impact of prone position ventilation compared to supine position ventilation on the prognosis of patients with pulmonary infections in the intensive care unit (ICU). Prone position ventilation has been suggested to enhance oxygenation, reduce ventilation-perfusion mismatch, and alleviate lung compression, which may contribute to improved respiratory mechanics and better outcomes in patients with pulmonary infections. By comparing these two ventilation positions, we sought to evaluate their respective effects on patient prognosis and shed light on the potential advantages of prone position ventilation in the ICU setting. Methods: A total of 160 critically ill patients with pulmonary infections were included in the study and divided into two groups: the prone position ventilation group (n=80) and the supine position ventilation group (n=80). Inclusion criteria for patient selection in this study included individuals between the ages of 18 and 75 who were critically ill with pulmonary infections and receiving treatment in the Intensive Care Unit (ICU). Basic vital sign monitoring, airway pathogen examinations, multidrug-resistant bacterial detection rates analysis, and prognosis assessments were conducted. Results: The prone position ventilation group demonstrated several advantages compared to the supine position ventilation group. The positive rate of airway pathogen examinations in the prone position ventilation group was 55%, significantly lower than the 75% in the supine position ventilation group (P = .005). The detection rate of multidrug-resistant bacteria was 20%, significantly lower than the 43.75% in the supine position group (P = .002). Furthermore, the prone position ventilation group showed shorter mechanical ventilation duration, intubation time, and ICU length of stay. Specifically, the duration of mechanical ventilation in the prone position ventilation group was 12.34±3.45 days, compared to 13.89±4.12 days in the supine position ventilation group. The intubation time was 10.56±2.78 days in the prone position group and 11.67±3.01 days in the supine position group. The ICU length of stay was 16.45±4.56 days in the prone position group and 18.67±5.34 days in the supine position group (P < .05). The two groups had no significant differences in total hospital stay and survival rate. Conclusion: Compared to supine position ventilation, prone position ventilation significantly improved airway pathogen examination results and reduced the detection rate of multidrug-resistant bacteria in patients with pulmonary infections in the ICU. Additionally, it decreased the duration of mechanical ventilation and ICU stay, although it did not significantly impact the survival rate. Further validation through larger-scale, multicenter studies is warranted. ICU practices may consider incorporating prone position ventilation as a standard intervention for patients with severe pulmonary infections. This could involve developing guidelines and protocols for the appropriate selection and implementation of prone position ventilation, as well as providing training to healthcare providers on its safe and effective use.

Factors associated with risk analysis for asymptomatic left ventricular diastolic dysfunction in nondialysis patients with chronic kidney disease.

Heart failure (HF) constitutes a major determinant of outcome in chronic kidney disease (CKD) patients. The main pattern of HF in CKD patients is preserved ejection fraction (HFpEF), and left ventricular diastolic dysfunction (LVDD) is a frequent pathophysiological mechanism and specific preclinical manifestation of HFpEF. Therefore, exploring and intervention of the factors associated with risk for LVDD is of great importance in reducing the morbidity and mortality of cardiovascular disease (CVD) complications in CKD patients. We designed this retrospective cross-sectional study to collect clinical and echocardiographic data from 339 nondialysis CKD patients without obvious symptoms of HF to analyze the proportion of asymptomatic left ventricular diastolic dysfunction (ALVDD) and its related factors associated with risk by multivariate logistic regression analysis. Among the 339 nondialysis CKD patients, 92.04% had ALVDD. With the progression of CKD stage, the proportion of ALVDD gradually increased. The multivariate logistic regression analysis revealed that increased age (OR 1.237; 95% confidence interval (CI) 1.108-1.381, per year), diabetic nephropathy (DN) and hypertensive nephropathy (HTN) (OR 25.000; 95% CI 1.355-48.645, DN and HTN vs chronic interstitial nephritis), progression of CKD stage (OR 2.785; 95% CI 1.228-6.315, per stage), increased mean arterial pressure (OR 1.154; 95% CI 1.051-1.268, per mmHg), increased urinary protein (OR 2.825; 95% CI 1.484-5.405, per g/24 h), and low blood calcium (OR 0.072; 95% CI 0.006-0.859, per mmol/L) were factors associated with risk for ALVDD in nondialysis CKD patients after adjusting for other confounding factors. Therefore, dynamic monitoring of these factors associated with risk, timely diagnosis and treatment of ALVDD can delay the progression to symptomatic HF, which is of great importance for reducing CVD mortality, and improving the prognosis and quality of life in CKD patients.

Single-stage Auricular Reconstruction in Hemifacial Microsomia With Low Hairline by Using Temporoparietal Fascia Flap.

BACKGROUND: Auricular reconstruction is one of the most complicated operations in plastic surgery and is more difficult for patients with a low hairline due to limited skin availability. In traditional operations, the skin of the mastoid area was used to cover the front of the ear scaffold, and the retroauricular fascia, combined with a free skin graft, was used to cover the back of the ear framework. This may cause problems such as inadequate skin coverage and affecting the shape of the reconstructed ear when the hairline is low. METHODS: Hemifacial microsomia patients with low hairline have little skin flap to perform the ear reconstruction, and we refined a single-stage ear reconstruction surgery to solve the problem. The temporoparietal fascia is used to cover the entire costal cartilage scaffold, and its surface is covered with a free split-thickness skin taken from the chest wall, thigh, and other parts. RESULTS: From December 2019 to December 2020, 12 patients with hemifacial microsomia underwent single-stage reconstruction with temporoparietal fascia. The duration of patient follow-up was 6 to 24 months. The application of this technique can solve the problem of insufficient available skin flap, complete the ear reconstruction through 1 operation, reduce the treatment cycle, achieve a good shape of the reconstructed ear, and the postoperative effect is satisfactory. CONCLUSION: According to the characteristics of the HFM patients with low hairline, we recommend this new, improved single-stage auricular reconstruction using the temporoparietal fascia for these patients. This method is a suitable choice for HFM patients with low hairline.Level of Evidence: Level-IV, Cases Study.

Nickel-Catalyzed Regio- and Enantioselective Borylative Coupling of Terminal Alkenes with Alkyl Halides Enabled by an Anionic Bisoxazoline Ligand.

Chiral boronic esters are a class of versatile building blocks. We describe herein an asymmetric nickel-catalyzed borylative coupling of terminal alkenes with nonactivated alkyl halides. The success of this asymmetric reaction is ascribed to the application of a chiral anionic bisoxazoline ligand. This study provides a three-component strategy to access α- and ß-stereogenic boronic esters from easily accessible starting materials. This protocol is characterized by mild reaction conditions, wide substrate scope and high regio- and enantioselectivity. We also showcase the value of this method in simplifying the synthesis of several drug molecules. Mechanistic studies suggest that the generation of enantioenriched boronic esters bearing an α-stereogenic center results from a stereoconvergent process, while the enantioselectivity-controlling step in the generation of boronic esters with a ß-stereocenter is switched to the olefin migratory insertion step due to coordination of an ester group.

A highly accumulated secretory protein from cotton bollworm interacts with basic helix-loop-helix transcription factors to dampen plant defense.

Caterpillar oral secretion (OS) contains active molecules that modulate plant defense signaling. We isolated an effector-like protein (Highly Accumulated Secretory Protein 1, HAS1) from cotton bollworm (Helicoverpa armigera) that is the most highly accumulated secretory protein of the nondigestive components in OS and belongs to venom R-like protein. Elimination of HAS1 by plant-mediated RNA interference reduced the suppression of OS on the defense response in plants. Plants expressing HAS1 are more susceptible to insect herbivory accompanied by the reduced expressions of multiple defense genes. HAS1 binds to the basic helix-loop-helix (bHLH) transcription factors, including GoPGF involved in pigmented gland formation and defense compounds biosynthesis in cotton and MYC3/MYC4 the main regulators in jasmonate (JA) signaling in Arabidopsis. The binding activity is required for HAS1 to inhibit the activation of bHLHs on plant defense gene expressions. Together with our previous study that another venom R-like protein HARP1 in cotton bollworm OS blocks JA signaling by interacting with JASMONATE-ZIM-domain repressors, we conclude that the venom R-like proteins in OS interfere with plant defense in a dual suppression manner. Considering the venom proteins in parasitic wasp assault the immune system of its host animal, our investigation reveals their conserved function in carnivorous and herbivorous insects.

GrpE and ComD contribute to the adherence, biofilm formation, and pathogenicity of Streptococcus suis.

Streptococcus suis is a major bacterial pathogen of swine and an emerging zoonotic agent that has to date resulted in substantial economic losses to the swine industry worldwide, and can cause persistent infection by forming biofilms. GrpE and histidine protein kinase ComD are important proteins implicated in the pathogenicity of S. suis, although whether they play roles in adhesion and biofilm formation has yet to be sufficiently clarified. In this study, we constructed grpE and comD deletion strains of S. suis by homologous recombination, and examined their cell adhesion and biofilm formation capacities compared with those of the wild-type strain. The pathogenicity of the grpE and comD deletion strains was evaluated using a mouse infection model, which revealed that compared with the wild-type, these deletion strains induced milder symptoms and lower bacteremia, as well as comparatively minor organ (brain, spleen, liver, and lung) lesions, in the infected mice. Moreover, the deletion of grpE and comD significantly reduced the pro-inflammatory cytokine (IL-6, IL-1ß, and TNF-α) induction capacity of S. suis. Collectively, the findings of this study indicate that the GrpE and ComD proteins of Streptococcus suis play key roles in the adherence to PK-15 cells and the formation of biofilms, thereby contributing to the virulence of this pathogen.

Cardiovascular imaging in conduction system pacing: What does the clinician need?

Permanent pacemakers are used for symptomatic bradycardia and biventricular pacing (BVP)-cardiac resynchronization therapy (BVP-CRT) is established for heart failure (HF) patients traditionally. According to guidelines, patients' selection for CRT is based on QRS duration (QRSd) and morphology by surface electrocardiogram (ECG). Cardiovascular imaging techniques evaluate cardiac structure and function as well as identify pathophysiological substrate changes including the presence of scar. Cardiovascular imaging helps by improving the selection of candidates, guiding left ventricular (LV) lead placement, and optimization devices during the follow-up. Conduction system pacing (CSP) includes His bundle pacing (HBP) and left bundle branch pacing (LBBP) which is screwed into the interventricular septum. CSP maintains and restores ventricular synchrony in patients with native narrow QRSd and left bundle branch block (LBBB), respectively. LBBP is more feasible than HBP due to a wider target area. This review highlights the role of multimodality cardiovascular imaging including fluoroscopy, echocardiography, cardiac magnetic resonance (CMR), myocardial scintigraphy, and computed tomography (CT) in the pre-procedure assessment for CSP, better selection for CSP candidates, the guidance of CSP lead implantation, and the optimization of devices programming after the procedure. We also compare the different characteristics of multimodality imaging and discuss their potential roles in future CSP implantation.

Complications and related risk factors of transradial access cannulation for hemodynamic monitoring in general surgery: a prospective observational study.

PURPOSE: To examine the short-term complications of arterial cannulation for intraoperative monitoring and their related risk factors. METHODS: We included adult inpatients (≥ 18 years old) who underwent an initial transradial access (TRA) cannulation and were scheduled for general surgery between April 8 and November 30, 2020. We used 20G arterial puncture needles for puncturing and manual compression for hemostasis. Demographic, clinical, surgical, anesthetic, and laboratory data were extracted from electronic medical records. Vascular, neurologic, and infectious complications of TRA cannulation were recorded and analyzed. Logistic regression analyses were used to identify risk factors related to TRA cannulation for intraoperative monitoring. RESULTS: Among 509 included patients, 174 developed TRA cannulation-related complications. Puncture site bleeding/hematoma and median nerve injury were observed in 158 (31.0%) and 16 (3.1%) patients, respectively. No patient developed cannula-related infections. Logistic regression analysis revealed increased odds of puncture site bleeding/hematoma in women (odds ratio 4.49, 95% CI 2.73-7.36; P < 0.001) and patients who received intraoperative red blood cell (RBC) suspension transfusion ≥ 4U (odds ratio 5.26, 95% CI 1.41-19.57; P = 0.01). No risk factors for nerve injury were identified. CONCLUSION: Bleeding/hematoma were a common complication of TRA cannulation for intraoperative hemodynamic monitoring during general surgery. Median nerve injury may be an under recognized complication. Female sex and extensive intraoperative RBC transfusion are associated with an increased risk of bleeding/hematoma; however, the risk factors for nerve injury remain unclear. TRIAL REGISTRATION: The study protocol was registered at https://www.chictr.org.cn (ChiCTR1900025140).

Real-world evidence for the use of subcutaneous implantable cardioverter-defibrillators in China: A single-center experience.

BACKGROUND: Subcutaneous implantable cardioverter-defibrillators (S-ICDs) have been shown to be non-inferior to transvenous ICDs in the prevention of sudden cardiac death (SCD), but there is still a lack of evidence from clinical trials in China. We investigated whether S­ICD implantation in the Chinese population is safe and feasible and should be promoted in the future. METHODS: Consecutive patients undergoing S­ICD implantation at our center were enrolled in this retrospective study. Data were collected within the median follow-up period of 554 days. Data concerning patient selection, implantation procedures, complications, and episodes of shock were analyzed. RESULTS: In total, 70.2% of all 47 patients (median age = 39 years) were included for secondary prevention of SCD with different etiologies. Vector screening showed that 98% of patients were with > 1 appropriate vector in all postures. An intraoperative defibrillation test was not performed on six patients because of the high risk of disease deterioration, while all episodes of ventricular fibrillation induced post implantation were terminated by one shock. As expected, no severe complications (e.g., infection and device-related complications) were observed, except for one case of delayed healing of the incision. Overall, 15 patients (31.9%) experienced appropriate shocks (AS) with all episodes terminated by one shock. Two patients (4.3%) experienced inappropriate shocks (IAS) due to noise oversensing, resulting in a high Kaplan-Meier IAS-free rate of 95.7%. CONCLUSION: Based on appropriate patient selection and standardized implantation procedures, this real-world study confirmed the safety and efficacy of S­ICD in Chinese patients, indicating that it may help to promote the prevention of SCD in China.

Correlation analysis of structural and functional changes in the carotid artery in patients with H-type hypertension using ultrasound radiofrequency.

OBJECTIVES: To perform a correlation analysis on the structural and functional changes of the carotid artery in patients with H-type hypertension. METHODS: Outpatients and inpatients with hypertension in our hospital between 2017 and 2018 were selected and divided into the H-type hypertension group (primary hypertension + plasma homocysteine ≥ 10 umol/l) (n = 30) and the simple hypertension group (primary hypertension + plasma Hcy < 10 umol/l) (n = 30) based on the plasma homocysteine (Hcy), and 30 healthy people were included in the control group. Thickness and stiffness parameters of the intima of the carotid artery (compliance coefficient [CC], stiffness index [ß], and pulse wave velocity [PWV]) were measured for all study participants using ultrasound radiofrequency signal-based quality intima-media thickness (QIMT) and quantitative arterial stiffness (QAS) for contrast analysis. RESULTS: Indexes such as QIMT, ß, and PWV of the carotid artery were significantly higher, and the CC was significantly lower in the H-type hypertension group and simple hypertension group than the control group (p < .05), and the difference was statistically significant; these indexes were significantly higher in the H-type hypertension group than in the simple hypertension group, and the CC was significantly lower than in the control group (p < .05), and the difference was statistically significant. CONCLUSIONS: Hypertension can accelerate structural and functional changes of the carotid artery intima, with these changes being more significant in H-type hypertension. The ultrasound radiofrequency technique can be used to quantitatively evaluate the structure and function of the carotid artery in patients with H-type hypertension.

High-throughput screening and quantitative analysis of hidden ingredients in plant protection products by GC-MS/MS.

Hidden ingredients in plant protection products (PPPs) threaten public health, food trade, and the environment. In this study, we developed a high-throughput screening method of 639 hidden ingredients in PPPs using GC-MS/MS in multiple reaction monitoring mode. Results showed that the qualitative criteria of retention time (tR) shift and uncertainty of qualifier to quantifier ratio in the commercially available Shimadzu Smart Pesticides Database were set at < 0.17 min and < 30%, respectively, which could be used to tentatively identify compounds without standards. The limits of quantification were 0.01-0.05 mg/kg. A wide linear range of 10-1000 µg/L was observed with R2 ≥ 0.975. Recoveries from three types of PPP formulations were 62.08%- 126.3%, with relative standard deviations < 15.7%. Finally, this method was applied to screen and quantify hidden ingredients in 91 plant protection products (PPPs) samples collected from online sales in China. Only one hidden ingredient, dimethomorph (1.6 g/kg), was detected in the polyoxin formulation (15% wettable powder). The results will be helpful in assessing the potential risks of hidden ingredients in PPPs.

Vacuolar Sugar Transporter TMT2 Plays Crucial Roles in Germination and Seedling Development in Arabidopsis.

Vacuolar sugar transporters transport sugar across the tonoplast, are major players in maintaining sugar homeostasis, and therefore play vital roles in plant growth, development, and biomass yield. In this study, we analyzed the physiological roles of the tonoplast monosaccharide transporter 2 (TMT2) in Arabidopsis. In contrast to the wild type (WT) that produced uniform seedlings, the tmt2 mutant produced three types of offspring: un-germinated seeds (UnG), seedlings that cannot form true leaves (tmt2-S), and seedlings that develop normally (tmt2-L). Sucrose, glucose, and fructose can substantially, but not completely, rescue the abnormal phenotypes of the tmt2 mutant. Abnormal cotyledon development, arrested true leaf development, and abnormal development of shoot apical meristem (SAM) were observed in tmt2-S seedlings. Cotyledons from the WT and tmt2-L seedlings restored the growth of tmt2-S seedlings through micrografting. Moreover, exogenous sugar sustained normal growth of tmt2-S seedlings with cotyledon removed. Finally, we found that the TMT2 deficiency resulted in growth defects, most likely via changing auxin signaling, target of rapamycin (TOR) pathways, and cellular nutrients. This study unveiled the essential functions of TMT2 for seed germination and initial seedling development, ensuring cotyledon function and mobilizing sugars from cotyledons to seedlings. It also expanded the current knowledge on sugar metabolism and signaling. These findings have fundamental implications for enhancing plant biomass production or seed yield in future agriculture.

Supra-Normal Left Ventricular Ejection Fraction as a Prognostic Marker for Long-Term Outcomes in Patients with Acute Coronary Syndrome.

Recently, the supra-normal left ventricular ejection fraction (snLVEF) has been proposed, based on extensive datasets indicating increased all-cause mortality in individuals with an LVEF exceeding 65%. However, the implications of an LVEF > 65% in the context of acute coronary syndrome (ACS) remain underexplored.The aim of the present study was to investigate the correlation between supra-normal left ventricular ejection fraction (snLVEF) and major adverse cardiovascular events (MACE) in patients with ACS.Methods: A total of 874 ACS patients (560 men, mean age 59.5 ± 10.0; 314 women, mean age 61.5 ± 8.9) who underwent their first coronary angiography during the period from March 2013 to October 2015 were divided into 2 groups: normal LVEF (nLVEF) (55% ≤ EF ≤ 65%) and snLVEF (EF > 65%), according to their echocardiography results. The patients were evaluated for MACE after surgery by collecting clinical data and long-term follow-up data. This correlation was further analyzed by Kaplan-Meier analysis and Cox regression analysis.The follow-up data revealed a significantly higher incidence of MACE among snLVEF patients compared to the nLVEF group (15.6% versus 7.4%; P = 0.020). This heightened risk persisted even after adjustment for multiple variables, indicating a strong association between snLVEF and increased MACE risk (HR: 2.346; 95% CI: 1.196-4.602; P = 0.013).SnLVEF was independently associated with poor prognosis after ACS. Enhanced management strategies for snLVEF patients could potentially reduce the incidence of MACE in ACS patients.

Effects of soybean hulls and corn stalk on the performance, colostrum composition and faecal microflora of pregnant sows.

This study was conducted to investigate the effects of different supplementation levels of soybean hulls and corn stalk in high-fibre gestation diet on the performance, colostrum composition and faecal microbiota of sows. Forty first-farrowing Danish Landrace sows were randomly assigned to five dietary treatment groups. The control (CON, 3.15% crude fibre) group was fed a normal diet, and the treatment groups were soybean hulls low-fibre (SHL, 6.00% crude fibre) group, soybean hulls high-fibre (SHH, 8.00% crude fibre) group, corn stalk low-fibre (CSL, 6.00% crude fibre) group and corn stalk high-fibre (CSH, 8.00% crude fibre) group. The weaning weight of the litter and the average daily feed intake of the lactating sows in the SHL, SHH and CSH groups were higher than those in the CON group (p < 0.05). The immunoglobulin A and G levels of the colostrum in the SHL, SHH, CSL and CSH groups were higher than those in the CON group (p < 0.05), and the immunoglobulin M levels in the SHL, SHH and CSH groups were higher than those in the CON group (p < 0.05). The abundance of Proteobacteria at the phylum level in the CON group was higher than that in the CSL, CSH and SHH groups (p < 0.05). The abundance of Lactobacillaceae at the family level in the SHH and CSL groups were higher than that in the CON group (p < 0.05). The abundance of Lactobacillus at the genus level in the SHH and CSL groups were higher than that in the CON group (p < 0.05). In conclusion, SHH group had the best effect, and the optimal crude fibre level in the gestation diet of sows is 8%.

Enhancing the Electron Transport, Quantum Yield, and Catalytic Performance of Carbonized Polymer Dots via MnO Bridges.

Carbonized polymer dots (CPDs) have received tremendous attention during the last decade due to their excellent fluorescent properties and catalytic performance. Doping CPDs with transition metal atoms accelerates the local electron flow in CPDs and improves the fluorescent properties and catalytic performance of the CPDs. However, the binding sites and the formation mechanisms of the transition-metal-atom-doped CPDs remain inconclusive. In this work, Mn2+ -ion-doped CPDs (Mn-CPDs) are synthesized by the hydrothermal method. The Mn2+ ions form MnO bonds that bridge the sp2 domains of carbon cores and increases the effective sp2 domains in the Mn-CPDs, which redshifts the fluorescence emission peak of the Mn-CPDs slightly. The Mn2+ ions form covalent bonds in the CPDs and remedy the oxygen vacancies of the CPDs, which cuts off the non-radiative-recombination process of the Mn-CPDs and increases the quantum yield of the Mn-CPDs to 70%. Furthermore, the MnO bonds accelerate the electron flow between adjacent sp2 domains and enhances the electron transport in the Mn-CPDs. Thus, the Mn-CPDs demonstrate excellent catalytic performance to activate hydrogen peroxide (H2 O2 ) and produce hydroxyl radicals (•OH) to degrade methylene blue (MB) and rhodamine B (RhB).

Conduction system pacing following septal myectomy: Insights into site of conduction block.

INTRODUCTION: Septal myectomy for obstructive hypertrophic cardiomyopathy (HCM) is associated with conduction block; however, the electrophysiological characteristics of conduction block have not been well characterized. The aim of study was to assess the feasibility and safety of His bundle pacing (HBP) and left bundle branch area pacing (LBBAP) in patients with septal myectomy-associated conduction block. METHODS AND RESULTS: Patients with HCM and indications for pacing or cardiac resynchronization therapy after septal myectomy were included. Electrophysiological mapping was performed to identify the site of block. The success rates and pacing characteristics of HBP and LBBAP were also recorded. The echocardiographic data and complications were documented and tracked during follow-up. Ten patients with atrioventricular block (AVB) or left bundle branch block (LBBB) post-myectomy were included in the study. The site of block was infranodal in the nine patients with AVB. HBP failed due to the lack of distal His bundle capture (N = 7) or LBBB correction (N = 3). LBBAP was successful in nine patients and failed in one. QRS duration narrowed from 163.3 ± 16.6 ms after surgery to 123.6 ± 15.8 ms during LBBAP (p < .001). The mean depth of the leads was 13.3 ± 4.0 mm (range from 10 to 20 mm). At a mean follow-up of 5.3 ± 3.9 months, pacing parameters and left ventricular ejection fraction remained stable. CONCLUSIONS: Electrophysiological mapping revealed that the site of block was infra-Hisian and not correctable with HBP in patients with HCM post-myectomy. LBBAP appears to be a more feasible physiological strategy for these patients.

Glucose-dependent insulinotropic polypeptide modifies adipose plasticity and promotes beige adipogenesis of human omental adipose-derived stem cells.

The adipocyte precursors (APs) located in white adipose tissue (WAT) are functionally significant in adipose plasticity and browning. Modifying adipogenesis or WAT browning targeted on APs is a promising mechanism for anti-obesity drug. We herein explored the in vitro actions and mechanisms of glucose-dependent insulinotropic polypeptide (GIP), a gut-derived peptide, in human adipose-derived mesenchymal stem cells (hADSCs) isolated from omentum. The hADSCs were cotreated with 100 nM GIP with or without equimolar concentration of GIP3-42 (a GIP receptor antagonist), and subsequently examined in vitro. CCK-8, EdU incorporation, and flow cytometry assays were used to assess cellular proliferation. Annexin V FTIC/PI double stain, TUNEL staining, and Western blot were applied for apoptosis evaluation. Adipogenesis was reflected by Western blot, real-time PCR, Oil Red O staining, mitochondrial staining, and mitochondrial DNA analysis. Results showed that GIP promoted proliferation and inhibited apoptosis of hADSCs via pleiotropic effects. Besides, GIP facilitated de novo beige adipogenesis, by accelerating mitotic clonal expansion (MCE), upregulating core adipogenic regulators (C/EBPα and PPARγ), augmenting beige-related genes (UCP1, PGC1α, and PRDM16), increasing mitochondrial content and improving beige adipocyte functionalities. Above all, our study expands knowledge on the mechanisms of GIP modifying adipogenesis especially in inducing beige adipogenesis, and thus provides a theoretical support for clinical usage of GIP on obesity treatment.

Cardiac resynchronization therapy via left bundle branch pacing vs. optimized biventricular pacing with adaptive algorithm in heart failure with left bundle branch block: a prospective, multi-centre, observational study.

AIMS: The purpose of our study was to evaluate the feasibility and efficacy of cardiac resynchronization therapy (CRT) via left bundle branch pacing (LBBP-CRT) compared with optimized biventricular pacing (BVP) with adaptive algorithm (BVP-aCRT) in heart failure with reduced left ventricular ejection fraction ≤35% (HFrEF) and left bundle branch block (LBBB). METHODS AND RESULTS: One hundred patients with HFrEF and LBBB undergoing CRT were prospectively enrolled in a non-randomized fashion and divided into two groups (LBBP-CRT, n = 49; BVP-aCRT, n = 51) in four centres. Implant characteristics and echocardiographic parameters were accessed at baseline and during 6-month and 1-year follow-up. The success rate for LBBP-CRT and BVP-aCRT was 98.00% and 91.07%. Fused LBBP had the greatest reduced QRS duration compared to BVP-aCRT (126.54 ± 11.67 vs. 102.61 ± 9.66 ms, P < 0.001). Higher absolute left ventricular ejection fraction (LVEF) and △LVEF was also achieved in LBBP-CRT than BVP-aCRT at 6-month (47.58 ± 12.02% vs. 41.24 ± 10.56%, P = 0.008; 18.52 ± 13.19% vs. 12.89 ± 9.73%, P = 0.020) and 1-year follow-up (49.10 ± 10.43% vs. 43.62 ± 11.33%, P = 0.021; 20.90 ± 11.80% vs. 15.20 ± 9.98%, P = 0.015, P = 0.015). There was no significant difference in response rate between two groups while higher super-response rate was observed in LBBP-CRT as compared to BVP-aCRT at 6 months (53.06% vs. 36.59%, P = 0.016) and 12 months (61.22% vs. 39.22%, P = 0.028) during follow-up. The pacing threshold was lower in LBBP-CRT at implant and during 1-year follow-up (both P < 0.001). Procedure-related complications and adverse clinical outcomes including heart failure hospitalization and mortality were not significantly different in two groups. CONCLUSIONS: The feasibility and efficacy of LBBP-CRT demonstrated better electromechanical resynchronization and higher clinical and echocardiographic response, especially higher super-response than BVP-aCRT in HFrEF with LBBB.