Enhanced sensitivity and scalability with a Chip-Tip workflow enables deep single-cell proteomics.

Single-cell proteomics (SCP) promises to revolutionize biomedicine by providing an unparalleled view of the proteome in individual cells. Here, we present a high-sensitivity SCP workflow named Chip-Tip, identifying >5,000 proteins in individual HeLa cells. It also facilitated direct detection of post-translational modifications in single cells, making the need for specific post-translational modification-enrichment unnecessary.

Modulation of the Second-Beyond Coordination Structure in Single-Atom Electrocatalysts for Confirmed Promotion of Ammonia Synthesis.

Although microenvironments surrounding single-atom catalysts (SACs) have been widely demonstrated to have a remarkable effect on their catalytic performances, it remains unclear whether the local structure beyond the secondary coordination shells works as well or not. Herein, we employed a series of metal-organic frameworks (MOFs) with well-defined and tunable second-beyond coordination spheres as model SAC electrocatalysts to discuss the influence of long-distance structure on the ammonia synthesis from nitrate, which were synthesized and denoted as Cu-NDI-X (X = NMe, H, F). It is first experimentally confirmed that the remote substitution of function groups beyond the secondary coordination sphere can remarkably affect the activity of ammonia synthesis.

In Vivo Quantification of Anterior and Posterior Chamber Volumes in Mice: Implications for Aqueous Humor Dynamics.

Purpose: Aqueous humor inflow rate, a key parameter influencing aqueous humor dynamics, is typically measured by fluorophotometry. Analyzing fluorophotometric data depends, inter alia, on the volume of aqueous humor in the anterior chamber but not the posterior chamber. Previous fluorophotometric studies of the aqueous inflow rate in mice have assumed the ratio of anterior:posterior volumes in mice to be similar to those in humans.

Safety and Efficacy of Remote Ischemic Conditioning in Patients With Intravenous Thrombolysis: The SERIC-IVT Trial.

Background: Approximately half of the patients with acute ischemic stroke who receive intravenous thrombolysis (IVT) do not achieve an excellent outcome. Remote ischemic conditioning (RIC) as a promising neuroprotective treatment may improve clinical outcomes in this population. This study aimed to assess the efficacy and safety of RIC in patients with IVT.

The Safety and Immunogenicity of a 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine (CRM197/TT) in Infants: A Double-Blind, Randomized, Phase III Trial.

Objectives: This study aimed to evaluate the immunogenicity and safety of a 13-valent pneumococcal polysaccharide conjugate vaccine (CRM197/TT) (PCV13i) in infants.

Methods: A total of 1200 infants were randomly assigned to either the experimental PCV13i group or the control PCV13 group in a 1:1 ratio. Each group received a three-dose series of the vaccine at 2, 4, and 6 months of age, followed by a booster dose at 12-15 months.

Deficiency of Endothelial Impairs Pulmonary Vascular Angiogenesis and Predisposes Pulmonary Hypertension.

Background: Mechanosensitive Piezo1 channel plays a key role in pulmonary hypertension (PH). However, the role of Piezo2 in PH remains unclear.

Methods: Endothelial cell (EC)-specific knockout (, Tek-Cre; ) rats and primarily cultured pulmonary microvascular ECs were used to determine the role of Piezo2 in PH.

Population Pharmacokinetics of Epcoritamab Following Subcutaneous Administration in Relapsed or Refractory B Cell Non-Hodgkin Lymphoma.

Background And Objectives: Epcoritamab is a CD3xCD20 bispecific antibody approved for the treatment of adults with different types of relapsed or refractory (R/R) B cell non-Hodgkin lymphoma (B-NHL) after ≥ 2 lines of systemic therapy. Here we report the first results from a population pharmacokinetic model-based analysis using data from 2 phase 1/2 clinical trials (EPCORE NHL-1, NCT03625037 and EPCORE NHL-3, NCT04542824) evaluating epcoritamab in patients with R/R B-NHL.

Methods: Plasma concentration-time data included 6819 quantifiable pharmacokinetic samples from 327 patients with R/R B-NHL.

Coordination Regulation Enabling Deep Eutectic Electrolyte for Fast-Charging High-Voltage Lithium Metal Batteries.

The safety and cycle stability of lithium metal batteries (LMBs) under conditions of high cut-off voltage and fast charging put forward higher requirements for electrolytes. Here, a sulfonate-based deep eutectic electrolyte (DEE) resulting from the eutectic effect between solid sultone and lithium bis(trifluoromethanesulfonyl)imide without any other additives is reported. The intermolecular coordination effect triggers this eutectic phenomenon, as evidenced with nuclear magnetic resonance, and thus the electrochemical behavior of the DEE can be controlled by jointly regulating the coordination effects of F···H and Li···O intermolecular interactions.

Reproducibility of proton density fat fraction assessment of thigh muscle in a multi-site, multi-vendor cohort study at 10 years after anterior cruciate ligament reconstruction.

Background: Dixon-based magnetic resonance imaging (MRI) intramuscular proton density fat fraction (PDFF) is a potentially useful imaging biomarker of muscle quality. However, multi-vendor, multi-site reproducibility of intramuscular PDFF quantification, required for large clinical studies, can be strongly dependent on acquisition and processing. The purpose of this study was (I) to develop a 6-point Dixon MRI-based acquisition and processing technique for reproducible multi-vendor, multi-site quantification of thigh intramuscular PDFF; and (II) to evaluate the ability of the technique to detect differences in thigh muscle status between operated .

Cardiovascular Events Associated with CDK4/6 Inhibitors: A Safety Meta-Analysis of Randomized Controlled Trials and a Pharmacovigilance Study of the FAERS Database.

Background: CDK4/6 inhibitors are highly valued, but the incidence of cardiovascular adverse events (CVAEs) associated with CDK4/6 inhibitors is not clear.

Objective: Our aim was therefore to assess the risk of developing CVAEs associated with CDK4/6 inhibitors, by conducting a systematic review and meta-analysis of randomized controlled trials (RCTs), along with a pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS) database.

Methods: Eligible CVAEs were extracted from the ClinicalTrials.

Consensus Recommendations for Studies of Outflow Facility and Intraocular Pressure Regulation Using Ex Vivo Perfusion Approaches.

Intraocular pressure (IOP) elevation is the primary risk factor and currently the main treatable factor for progression of glaucomatous optic neuropathy. In addition to direct clinical and living animal in vivo studies, ex vivo perfusion of anterior segments and whole eyes is a key technique for studying conventional outflow function as it is responsible for IOP regulation. We present well-tested experimental details, protocols, considerations, advantages, and limitations of several ex vivo model systems for studying IOP regulation.

Exploring the properties of new super-chalcogens based on multiple electron counting rules: a combined DFT and study on [M(BCX)] dianion clusters.

The theoretical exploration of the super-chalcogen properties of multi-charged sandwich structures whose geometry simultaneously satisfyies the octet rule and Hückel's 4+2 rule is reported here a case study of dianion clusters [M(BCX)] (M = Be, Mg or Ca; X = H, F or Cl). The properties of these dianion clusters [M(BCX)] are close to or even superior to those of traditional clusters based on separate electron-counting rules, , the octet rule and Hückel's 4+2 rule. At the theoretical level of combined and DFT methods, these clusters, including halogen-substituents (F, Cl) are super-chalcogens due to their high first vertical electron detachment energy (FVDE), of which the largest value is 1.

Pulsed Field Ablation of Paroxysmal Supraventricular Tachycardia: A Prospective Multicenter Single-Arm Study in China.

Background: Pulsed field ablation (PFA) has gained attention in cardiac electrophysiology, but data on its application to paroxysmal supraventricular tachycardia are limited. This study aimed to assess the feasibility and safety of PFA and its combination with radiofrequency ablation for treating paroxysmal supraventricular tachycardia.

Methods: A prospective, multicenter, single-arm study was conducted across 8 centers in China.

Intestinal NUCB2/nesfatin-1 regulates hepatic glucose production via the MC4R-cAMP-GLP-1 pathway.

Communication of gut hormones with the central nervous system is important to regulate systemic glucose homeostasis, but the precise underlying mechanism involved remain little understood. Nesfatin-1, encoded by nucleobindin-2 (NUCB2), a potent anorexigenic peptide hormone, was found to be released from the gastrointestinal tract, but its specific function in this context remains unclear. Herein, we found that gut nesfatin-1 can sense nutrients such as glucose and lipids and subsequently decreases hepatic glucose production.

Clinical Pharmacology of Asciminib: A Review.

Asciminib is a first-in-class allosteric inhibitor of the kinase activity of BCR::ABL1, specifically targeting the ABL myristoyl pocket (STAMP). This review focuses on the pharmacokinetic (PK) and pharmacodynamic data of asciminib, which is approved at a total daily dose of 80 mg for the treatment of adult patients with chronic myeloid leukemia in chronic phase who are either resistant or intolerant to ≥ 2 tyrosine kinase inhibitors or those harboring the T315I mutation (at a dose of 200 mg twice daily). Asciminib is predicted to be almost completely absorbed from the gut, with an absolute bioavailability (F) of approximately 73%.

Triel Bonds with Methyl Groups as Electron Donors. A Pentacoordinate Carbon Atom.

The triel bond (TrB) formed between Be(CH)/Mg(CH) and TrX (Tr=B, Al, and Ga; X=H, F, Cl, Br, and I) is investigated via the MP2/aug-cc-pVTZ(PP) quantum chemical protocol. The C atoms of the methyl groups in M(CH) are characterized by a negative electrostatic potential and act as an electron donor in a triel bond with the π-hole above the Tr atom of planar TrX. The interaction energy spans a wide range between -2 and -69 kcal/mol.

Discovery of quinazoline-benzothiazole derivatives as novel potent protease-activated receptor 4 antagonists with improved pharmacokinetics and low bleeding liability.

Protease-activated receptor 4 (PAR4) plays a critical role in the development of pathological thrombosis, and targeting PAR4 is considered a promising strategy for improving antiplatelet therapies. Here, we reported the design of a series of quinazoline-benzothiazole-based PAR4 antagonists using a scaffold-hopping strategy. Systematic structure-activity relationship exploration leads to the discovery of compounds 20f and 20g, which displayed optimal activity (h.

Discovery of Novel 5-(Pyridazin-3-yl)pyrimidine-2,4(1,3)-dione Derivatives as Potent and Orally Bioavailable Inhibitors Targeting Ecto-5'-nucleotidase.

Ecto-5-nucleotidase (CD73) is overexpressed in a variety of cancers and associated with the immunosuppressive tumor microenvironment, making it an attractive target for cancer immunotherapy. Herein, we designed and synthesized a series of novel (pyridazine-3-yl)pyrimidine-2,4(1,3)-dione derivatives as CD73 inhibitors. These compounds exhibited remarkable inhibitory activity against CD73 in both enzymatic biochemical and cellular assays.

The H/F substitution strategy can achieve large spontaneous polarization in 1D hybrid perovskite ferroelectrics.

Hybrid organic-inorganic perovskite (HOIP) ferroelectrics exhibit polarization reversibility and have a wide range of applications in the fields of smart switches, memorizers, sensors, However, the inherent limitations of small spontaneous polarization ( ) and large coercive field ( ) in ferroelectrics have impeded their broader utilization in electronics and data storage. Molecular ferroelectrics, as a powerful supplement to inorganic ferroelectrics, have shown great potential in the new generation of flexible wearable electronic devices. The important research responsibility is to greatly improve progressiveness and overcome the above limitations.

High-throughput DNA engineering by mating bacteria.

To reduce the operational friction and scale DNA engineering, we report here an DNA assembly technology platform called SCRIVENER (equential onjugation and ecombination for n ivo longation of ucleotides with low rors). SCRIVENER combines bacterial conjugation, DNA cutting, and homologous recombination to seamlessly stitch blocks of DNA together by mating in large arrays or pools. This workflow is simpler, cheaper, and higher throughput than current DNA assembly approaches that require DNA to be moved in and out of cells at different procedural steps.

Variability in Lipid Profiles During Young Adulthood and the Risk of Coronary Artery Calcium Incidence in Midlife: Insights From the CARDIA Study.

Background: Intraindividual variability in lipid profiles is recognized as a potential predictor of cardiovascular events. However, the influence of early adulthood lipid profile variability along with mean lipid levels on future coronary artery calcium (CAC) incidence remains unclear.

Methods: A total of 2395 participants (41.

Inversion method of NHV based on novel model parameter space acquisition strategy and its application in the Tonghai basin site in Yunnan, China.

The imaging of subsurface soil velocity structures from ambient noise inversion is a difficult problem. Few recording points and a simplified 1-D layered profile lead to important non-uniqueness. From our point of view, improving the reliability of processing methods of the observed data to obtain noise horizontal-to-vertical spectral ratio (NHV) curves and setting a complete model parameter space are important tasks to reduce the non-uniqueness of inversion.

The Protective Efficacy of a SARS-CoV-2 Vaccine Candidate B.1.351V against Several Variant Challenges in K18-hACE2 Mice.

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.