Chiral Phosphoric Acid Catalyzed Asymmetric Mannich Reaction of 2-Aryl-3-indol-3-ones with α-H Diazoacetates.

An asymmetric Mannich reaction between 2-aryl-3-indol-3-ones and α-H diazoacetates catalyzed by chiral phosphoric acid was developed. This strategy achieves the effective synthesis of chiral 2,2-disubstituted indolin-3-ones bearing a quaternary stereocenter and containing a diazo group in the C2 substituent (up to >99% ee and 82% yield). To demonstrate the importance of the synthesized 2,2-disubstituted indolin-3-ones and the diversity of their diazo group reactions, we successfully achieved the relevant transformation reactions with a diazo group (such as hydroxylation, hydrogenation, intramolecular cyclization, etc.

Medium-Chain Fatty Acids Selectively Sensitize Cancer Cells to Ferroptosis by Inducing CD36 and ACSL4.

Background: Inducing ferroptosis in cancer cells is a promising therapeutic strategy. It has been shown that certain types of fatty acids can induce ferroptosis in multiple types of cancer cells.

Methods: Here, we employed crystal violet staining and CCK8 to assess cell viability, a Liperfluo probe and commercial kit to measure lipid peroxides, and western blotting and RNA interference to detect protein levels.

Efficacy and safety of cadonilimab (PD-1/CTLA-4 bispecific) in combination with chemotherapy in anti-PD-1-resistant recurrent or metastatic nasopharyngeal carcinoma: a single-arm, open-label, phase 2 trial.

Background: We aimed to evaluate the efficacy and safety of cadonilimab (anti-PD-1 and CTLA-4 bispecific antibody) plus TPC chemotherapy (NAB-paclitaxel, cisplatin or lobaplatin, and capecitabine) in patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) who failed to PD-1 inhibitor-containing regimens.

Methods: In this single-arm, open-label, phase 2 study, RM-NPC patients who failed to at least one line of systemic chemotherapy and anti-PD-1 immunotherapy were enrolled and received cadonilimab plus TPC chemotherapy every 3 weeks for up to 6 cycles, followed by cadonilimab plus capecitabine every 3 weeks for a maximum of 2 years. The primary endpoint was the objective response rate (ORR).

Analysis of the Sex-Specific Risk Factors for Arterial Stiffness.

Background: To explore the sex-specific risk factors of associated with arterial stiffness.

Methods: A total of 28,291 participants from the Kailuan study cohort were enrolled in this study. A multivariate linear regression analysis and a multivariate logistic regression model were used to analyze the influencing factors of arteriosclerosis (indexed using the brachial-ankle pulse wave velocity, baPWV) between different sexes.

Nomogram for predicting cemented vertebral refracture after percutaneous kyphoplasty in postmenopausal women with osteoporotic vertebral compression fractures.

Objectives: This study aims to develop a nomogram model for predicting cemented vertebral refractures(CVFs) after percutaneous kyphoplasty(PKP) in postmenopausal women, providing guidance for clinical practice to reduce the incidence of such occurrences.

Methods: The hospitalization records and outpatient follow-up data of patients with osteoporotic vertebral compression fractures(OVCFs) who underwent unilateral single-segment PKP at Department of Spine Surgery, Peking University People's Hospital, from April 2015 to July 2022, were collected. We utilized univariate analysis and binary logistic regression to identify the risk factors associated with CVF, and developed a nomogram model.

Instantaneous dose rate as a crucial factor in reducing mortality and normal tissue toxicities in murine total-body irradiation: a comparative study of dose rate combinations.

Purpose: The ultra-high dose rate (UHDR) radiation shows promise in eradicating tumors while reducing normal tissue toxicities. However, the biological outcomes of UHDR are influenced by various factors, particularly the mean dose rate and instantaneous dose rate. Additionally, the UHDR response at large field sizes is lacking.

Dynamic metabolic profiling of sea cucumbers (Apostichopus japonicus) under predation stress.

The present study utilized non-targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate the metabolomic responses of sea cucumber (Apostichopus japonicus) juveniles under predation stress induced by sea stars (Asterina pectinifera) at various time points (3 h, 12 h, 72 h, and 96 h). The findings revealed significant temporal changes in the metabolic profiles of the sea cucumber juveniles under predation stress, with 25, 72, 55, and 53 metabolic products exhibiting significantly different expression levels at each time point (positive ion mode, P < 0.05), respectively.

Crumbling Pathogenesis and Biomarkers for Diabetic Peripheral Neuropathy.

: Diabetic sensorimotor polyneuropathy (DSP) is a common chronic diabetic complication. Traditionally, DSP was once considered irreversible with a typical loss of axon. However, the superimpose of acquired demyelination on axonal loss in DSP patients has been observed, implying that DSP may be preventable or reversible, particularly within a subgroup of patients exhibiting early-stage acquired demyelination, underscoring the critical importance of identifying early prognostic markers.

Structural design, accuracy analysis, and mechanical calibration of a small two-component docking mechanism for large loads in space.

Currently, the passive part of the space station platform's docking device has been finalized, emphasizing the need for a docking mechanism that enables the on-orbit assembly of large payloads using in-situ resources. This paper presents the design of a compact, high-precision dual-component docking mechanism for large space loads. First, we propose a parametric design for the active and passive sides, accompanied by the constraint equations for the capture mechanism.

Super-Enhancer Target Gene CBP/p300-Interacting Transactivator With Glu/Asp-Rich C-Terminal Domain, 2 Cooperates With Transcription Factor Forkhead Box J3 to Inhibit Pulmonary Vascular Remodeling.

The function of super-enhancers (SEs) in pulmonary hypertension (PH), especially in the proliferation of pulmonary artery smooth muscle cells (PASMCs), is currently unknown. We identified SEs-targeted genes in PASMCs with chromatin immunoprecipitation (ChIP)-sequence by H3K27ac antibody and proved that CBP/p300-interacting transactivator with Glu/Asp-rich C-terminal domain, 2 (CITED2) is an SEs-targeted gene through bioinformatics prediction, ChIP-PCR, dual-luciferase reporter gene assays and other experimental methods. We also found that the expression of CITED2 and the transcription factor Forkhead Box J3 (FOXJ3) was reduced in hypoxic mouse PASMCs.

The protective effect of amitriptyline on experimental colitis through inhibiting TLR-4/MD-2 signaling pathway.

Amitriptyline, a pleiotropic tricyclic antidepressant, possesses antioxidant and anti-inflammatory properties. Despite its diverse benefits, the specific effects of amitriptyline on inflammatory bowel disease (IBD) are not yet well defined. To explore this, we used a dextran sulfate sodium (DSS)-induced colitis model to examine the anti-inflammatory effects of amitriptyline and the underlying mechanisms by which it operates.

Individual differences in working memory and attentional control continue to predict memory performance despite extensive learning.

Individual differences in working memory predict a wide range of cognitive abilities. However, little research has been done on whether working memory continues to predict task performance after repetitive learning. Here, we tested whether working memory ability continued to predict long-term memory (LTM) performance for picture sequences even after participants showed massive learning.

Dietary Bacillus improves behavior, intestinal health, and growth of juvenile sea cucumbers Apostichopus japonicus at low temperature.

The traditional overwintering process of sea cucumbers (Apostichopus japonicus) requires burning a large amount of coal to raise the water temperature. It is useful but costly and not environmentally friendly. Bacillus is proposed as a cheap and green alternative.

Prediction of Thermodynamic Properties of C-Based Fullerenols Using Machine Learning.

Traditional machine learning methods face significant challenges in predicting the properties of highly symmetric molecules. In this study, we developed a machine learning model based on graph neural networks (GNNs) to accurately and swiftly predict the thermodynamic and photochemical properties of fullerenols, such as C(OH) ( = 1 to 30). First, we established a global method for generating fullerenol isomers through isomer fingerprinting, which can generate all possible isomers or produce diverse structural types on demand.

Ionizable polymeric micelles (IPMs) for efficient siRNA delivery.

Lipid nanoparticles (LNPs) are widely used for nucleic acid delivery but face challenges like limited targeting and accelerated blood clearance (ABC) effect. We design three ionizable oligomers (IOs) that, with polylactide-polyethylene glycol (PLA-PEG), form a potential siRNA delivery system, named Ionizable Polymeric Micelles (IPMs). The siRNA encapsulated IPMs escape from lysosomes upon cellular uptake, and silence the target gene.

Complement C3d enables cell-mediated immunity capable of distinguishing spontaneously transformed from nontransformed cells.

Immune surveillance depends in part on the recognition of peptide variants by T cell antigen receptors. Given that both normal B cells and malignant B cells accumulate mutations we chose a murine model of multiple myeloma to test conditions to induce cell-mediated immunity targeting malignant plasma cell (PC) clones but sparing of normal PCs. Revealing a previously unknown function for intracellular C3d, we found that C3d engaged T cell responses against malignant PC in the bone marrow of mice that had developed multiple myeloma spontaneously.

Development of Conductive Antibacterial Coatings on Cotton Fabrics via Polyphenol-Mediated Silver Mirror Reaction.

Herein, this study reports the development of a multifunctional conductive antibacterial cotton fabric through the utilization of the natural polyphenol-mediated silver mirror reaction. The experimental results demonstrate that polyphenols can effectively facilitate the deposition of silver nanoparticles (AgNPs), resulting in a uniform and durable hybrid nanocoating on the cotton fabric. The effects of polyphenol's molecular weights on the coating structures and stabilities have been revealed via two distinct approaches: washing resistance and electrochemical testing systems.

A preprocessing toolbox for 2-photon subcellular calcium imaging.

Recording the spiking activity from subcellular compartments of neurons such as axons and dendrites during behavior with 2-photon calcium imaging is increasingly common yet remains challenging due to low signal-to-noise, inaccurate region-of-interest (ROI) identification, movement artifacts, and difficulty in grouping ROIs from the same neuron. To address these issues, we present a computationally efficient pre-processing pipeline for subcellular signal detection, movement artifact identification, and ROI grouping. For subcellular signal detection, we capture the frequency profile of calcium transient dynamics by applying Fast Fourier Transform (FFT) on smoothed time-series calcium traces collected from axon ROIs.

Latent Profile Analysis of Acute Stress Disorder Symptoms and Their Links to Individual Characteristics and Mental Health Among College Students During the Early COVID-19 Pandemic.

Objectives: acute stress disorder (ASD) became prevalent among various populations during the COVID-19 pandemic, yet little research has examined the heterogeneity of ASD symptoms among college students. The purpose of this research was to explore subgroups of ASD symptoms using latent profile analysis (LPA) and to explore the predictors and mental health outcomes associated with these profiles.

Methods: Using the person-centered method, we recruited 1198 college students (71.

Regression equation analysis enhances detection of conduction slowing beyond axonal loss in diabetic neuropathy.

Objectives: To evaluate the utility of regression analysis in the assessment of conduction slowing in diabetic distal symmetrical polyneuropathy (DSP) and in identifying superimposed demyelination beyond fiber loss.

Background: Causes of conduction slowing beyond pure axonal loss has been attributed to an additional demyelinating component. We therefore evaluated the utility of regression analysis in the assessment of conduction slowing in diabetic DSP and in identifying superimposed demyelination beyond fiber loss.

Design of dinuclear osmium complex doped antifouling cellulose nanoparticles for targeting and dual photodynamic/photothermal therapy under near infrared irradiation.

Transition metal complexes has been explored in the treatment of tumors in photodynamic theray (PDT) or photothermal therapy (PTT) and Osmium complex attracts attentration due to its lower toxicity and longer absorption wavelength. However, there was no report about binuclear Os complex for combined therapy of PDT and PTT which could have a synergistic effect and improve the effectiveness. Herein, we synthesis of mono/dinuclear Os complexes (OsY1, OsY2) with dual PDT/PTT capabilities under a single near-infrared (NIR) excitation wavelength.

Risk factors of level Ib lymph node metastasis and clinical outcome of its selectively prophylactic irradiation in nasopharyngeal carcinoma: A real-world study.

Purpose: To evaluate the risk factor of level Ib lymph node metastasis (LNM) and the clinical outcome of its selectively prophylactic irradiation (pRT) in nasopharyngeal carcinoma (NPC) patients treated with IMRT.

Methods: 518 NPC patients receiving radical IMRT were collected. The structures of primary tumor invasions and neck LNM levels were analyzed bilaterally to estimate the risk factors of level Ib LNM.

Evaluation of dose and anatomy variability for nasopharyngeal carcinoma radiotherapy with a new fully integrated CT-linac.

The goal of this study was to investigate the variability of target volume and parotid gland dose distribution for nasopharyngeal carcinoma (NPC), and to explore the shifting patterns of parotid gland centroid and neck radius during radiotherapy. Twenty patients with NPC were enrolled. The target volume dose difference between planning dose and recalculated dose on weekly CT was analyzed.