Precise Identification of Native Peptides with Posttranslational Proline Hydroxylation by Nanopore.

Hydroxylation, an extensive post-translational modification on proline, is critical for the modulation of protein structures, further dominating their functions in life systems. However, current mass spectrometry-based identification, could hardly distinguish hydroxylation from neighboring oxidation due to the same mass shifts, as well as challenges posed by low abundance and exogenous oxidation during sample preparation. To address these, an engineered nanopore was designed, capable of discriminating single hydroxyl group, to achieve the identification of proline hydroxylation on individual native peptides directly in the mixture.

Pyridine Derivatives and Furan Derivatives Identified from the Medicinal Mushroom Irpex lacteus SY1002.

Three new pyridine derivatives, irpelactedines A-C (1-3), and a new furan derivative, irpelactedine D (5), along with two structurally related known compounds, irpexidine A (4) and 5-carboxy-2-furanpropanoic acid (6), were isolated from the medicinal fungus Irpex lacteus SY1002. Their structures were elucidated through NMR and mass spectral analyses, combined with density functional theory calculations of ECD data. Evaluation of angiotensin-converting enzyme (ACE) inhibitory activity revealed that compounds 1 and 3 displayed moderate inhibition, with IC50 values of 31.

FDA-approved drugs featuring macrocycles or medium-sized rings.

Macrocycles or medium-sized rings offer diverse functionality and stereochemical complexity in a well-organized ring structure, allowing them to fulfill various biochemical functions, resulting in high affinity and selectivity for protein targets, while preserving sufficient bioavailability to reach intracellular compartments. These features have made macrocycles attractive candidates in organic synthesis and drug discovery. Since the 20th century, more than three-score macrocyclic drugs, including radiopharmaceuticals, have been approved by the US Food and Drug Administration (FDA) for treating bacterial and viral infections, cancer, obesity, immunosuppression, inflammatory, and neurological disorders, managing cardiovascular diseases, diabetes, and more.

Advances in liver organoids: replicating hepatic complexity for toxicity assessment and disease modeling.

The lack of in vivo accurate human liver models hinders the investigation of liver-related diseases, injuries, and drug-related toxicity, posing challenges for both basic research and clinical applications. Traditional cellular and animal models, while widely used, have significant limitations in replicating the liver's complex responses to various stressors. Liver organoids derived from human pluripotent stem cells, adult stem cells primary cells, or tissues can mimic diverse liver cell types, major physiological functions, and architectural features.

Migrasomes derived from human umbilical cord mesenchymal stem cells: a new therapeutic agent for ovalbumin-induced asthma in mice.

Background: Asthma is a prevalent respiratory disease, and its management remains largely unsatisfactory. Mesenchymal stem cells (MSCs) have been demonstrated to be efficacious in reducing airway inflammation in experimental allergic diseases, representing a potential alternative treatment for asthma. Migrasomes are recently identified extracellular vesicles (EVs) generated in migrating cells and facilitate intercellular communication.

Hybrid technique and total arch replacement combined with frozen elephant trunk in acute aortic dissection involving the aortic arch: a multi-center propensity-matched cohort study.

Background: The aim of this study was to investigate whether the hybrid technique yields superior outcomes in comparison with the total arch replacement combined with frozen elephant trunk (TAR + FET) for acute aortic dissection (AAD) involving the aortic arch.

Methods: This retrospective cohort study using propensity-score matching included patients with AAD involving the aortic arch admitted to Nanjing First Hospital and Shanghai General Hospital from January 2015 to June 2020. The in-hospital and mid-term outcomes were compared between patients who received hybrid treatment (n = 136) and those who received TAR + FET (n = 415).

A dataset of forest regrowth in globally key deforestation regions.

Deforestation-induced forest loss largely affects both the carbon budget and ecosystem services. Subsequent forest regrowth plays a crucial role in ecosystem restoration and carbon replenishment. However, there is an absence of comprehensive datasets explicitly delineating the forest regrowth following deforestation.

Inverse design of promising electrocatalysts for CO reduction via generative models and bird swarm algorithm.

Directly generating material structures with optimal properties is a long-standing goal in material design. Traditional generative models often struggle to efficiently explore the global chemical space, limiting their utility to localized space. Here, we present a framework named Material Generation with Efficient Global Chemical Space Search (MAGECS) that addresses this challenge by integrating the bird swarm algorithm and supervised graph neural networks, enabling effective navigation of generative models in the immense chemical space towards materials with target properties.

Enhancer-driven Shh signaling promotes glia-to-mesenchyme transition during bone repair.

Plp1-lineage Schwann cells (SCs) of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing, and the abnormal plasticity of SCs would jeopardize the bone regeneration. However, how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood. Here, by employing single-cell transcriptional profiling combined with lineage-specific tracing models, we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury.

Temperature seasonality regulates organic carbon burial in lake.

Organic carbon burial (OCB) in lakes, a critical component of the global carbon cycle, surpasses that in oceans, yet its response to global warming and associated feedbacks remains poorly understood. Using a well-dated biomarker sequence from the southern Tibetan Plateau and a comprehensive analysis of Holocene total organic carbon variations in lakes across the region, here we demonstrate that lake OCB significantly declined throughout the Holocene, closely linked to changes in temperature seasonality. Process-based land surface model simulations clarified the key impact of temperature seasonality on OCB in lakes: increased seasonality in the early Holocene saw warmer summers enhancing ecosystem productivity and organic matter deposition, while cooler winters improved organic matter preservation.

Single soliton microcomb combined with optical phased array for parallel FMCW LiDAR.

The frequency-modulated continuous-wave (FMCW) technology combined with optical phased array (OPA) is promising for the all-solid-state light detection and ranging (LiDAR). We propose and experimentally demonstrate a silicon integrated OPA combined with an optical frequency microcomb for parallel LiDAR system. For realizing the parallel wavelengths emission consistent with Rayleigh criterion, the wide waveguide beyond single mode region combined with the bound state in the continuum (BIC) effect is harnessed to obtain an ultra-long optical grating antenna array.

[Effects of long non-coding RNA KLHL7-AS1 on the proliferation and apoptosis of nucleus pulposus cells under the environment of oxidative stress and its mechanism].

To investigate the effects of long non-coding RNA KLHL7-AS1 (LncRNA KLHL7-AS1) on the proliferation and apoptosis of nucleus pulposus cells under oxidative stress and its mechanisms. Human nucleus pulposus cells (HUM-iCell-s012) were divided into 4 groups, and unoxidized nucleus pulposus cells were transfected with an empty pcDNA vector (pcDNA-control) to serve as the blank control group. Based on previous studies on oxidative stress-induced nucleus pulposus cell senescence and preliminary experiments, oxidative stress was induced by treating nucleus pulposus cells with 400 μmol/L HO.

[Effect of SMARCA4 mutations on the outcomes of patients with advanced EGFR mutant lung adenocarcinoma].

To investigate the impact of SMARCA4 mutations on the outcomes of patients with advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations. In the Memorial Sloan Kettering Cancer Center (MSK) MetTropism study, 960 patients with advanced EGFR-mutated lung adenocarcinoma were screened and included in the MSK cohort, composing of 313 males and 647 females, with a median [(, )] age of 64 (56, 72) years. A retrospective analysis was conducted on the data of 178 patients with advanced EGFR-mutated lung adenocarcinoma who received EGFR tyrosine kinase inhibitors (TKIs) treatment in the Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, from January 2018 to December 2022.

[Predictive model for ejection fraction improvement at one year in patients with acute ST-segment elevation myocardial infarction complicated with heart failure with reduced ejection fraction].

To develop a predictive model for improvement of ejection fraction 1 year after heart failure with reduced ejection fraction (HFrEF) following acute ST-segment elevation myocardial infarction (STEMI). This nested case-control study included STEMI patients diagnosed with HFrEF from a prospective multicenter multimodality imaging cohort between August 2014 and March 2021. Based on the improvement of left ventricular ejection fraction (LVEF) at baseline and 1-year follow-up, the patients were classified into the heart failure with improved ejection fraction (HFimpEF) group and the persistent HFrEF group.

Decentralized control of impulsive interconnected switched positive time-delay systems under MDMDT switching.

The paper addresses the issue of decentralized control with positivity constraint for impulsive interconnected switched positive systems (IISPSs) with mixed time-varying delays coexisting in the state term and the interconnection term under mode-dependent minimum dwell time (MDMDT) switching. Firstly, a positivity criterion of IISPSs is given from the aspect of sufficiency and necessity. Next, through adopting a new discretized linear copositive Lyapunov-Krasovskii functional approach, a sufficient stability criterion of IISPSs under MDMDT constraint is presented.

Curcumin encapsulation in self-assembled nanoparticles based on amphiphilic stearic acid-grafted inulin: Preparation, characterization, and functional evaluation.

The clinical application of curcumin (CUR) is restricted by its low solubility, instability, and poor bioavailability. To overcome these limitations, we developed a novel stearic acid-grafted inulin-based nano-delivery system for CUR encapsulation. The structure of stearoyl inulin (SA-IN) was characterized using Fourier-transform infrared spectroscopy, hydrogen nuclear magnetic resonance, thermogravimetric analysis, and contact angle measurements.

N-glycosylation of ephrin B1 modulates its function and confers therapeutic potential in B-cell lymphoma.

Given the pivotal role of the Eph-Ephrin signaling pathway in tumor progression, agonists or antagonists targeting Eph/Ephrin have emerged as promising anticancer strategies. However, the implications of glycosylation modifications within Eph/Ephrin and their targeted protein therapeutics remain elusive. Here, we identify that N-glycosylation within the receptor-binding domain (RBD) of ephrin B1 (EFNB1) is indispensable for its functional repertoire.

Ribes diacanthum Pall modulates bile acid homeostasis and oxidative stress in cholestatic mice by activating the SIRT1/FXR and Keap1/Nrf2 signaling pathways.

Ethnopharmacological Relevance: Cholestatic liver injury (CLI) is a pathophysiological syndrome characterized by the accumulation of bile acids (BAs), which leads to significant hepatic dysfunction. This condition is frequently associated with disturbances in BAs homeostasis and the induction of oxidative stress. Ribes diacanthum Pall (RDP), a conventional folk medicinal plant, has been employed in Mongolia, the Inner Mongolia region of China, and other areas for the remediation of hepatic disorders.

Mitigating LPS-induced stress in Chinese mitten crab (Eriocheir sinensis) with P4' peptide-bearing Bacillus subtilis.

The Chinese mitten crab (Eriocheir sinensis) is an important component in Chinese aquaculture. Due to its lacking adaptive immune system as a crustacean, it exhibits poor tolerance to environmental stresses, particularly the deleterious impact of lipopolysaccharide (LPS) from pathogenic bacteria during E. sinensis culture.

Tumor-derived extracellular vesicle PD-1 promotes tumor immune evasion via disruption of peripheral T cell homeostasis.

The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) axis mediates immune evasion of tumor, and targeting this axis has achieved some clinical benefits. The regulation of PD-1 expression in immune cells has been well studied. However, whether any other potential source of immune cell-expressed PD-1 exists remains unknown.

Isolation, purification and identification of antibacterial peptides from Jinhua ham broth and molecular simulation analyses of their interaction with bacterial porins.

The bioactive peptides in Jinhua ham could be released into the broth during cooking. After comparing peptide antibacterial activity from Jinhua ham broth with varying cooking durations, the cooking-2-h broths were selected for further analysis using cation-exchange and reverse-phase-liquid chromatography. The purified peptide sequences were subsequently synthesized and tested for their antibacterial activity.

Lignin-containing nanofiber-reinforced flexible strain sensors with excellent mechanical properties and ionic conductivity for human motion detection.

A multifunctional hydrogel with outstanding mechanical properties and excellent ionic conductivity holds immense potential for applications in various fields, such as healthcare monitoring, and various devices, such as wearable devices and flexible electronics. However, developing hydrogels that combine high mechanical strength with efficient electrical conductivity remains a considerable challenge. Herein, an ion-conductive hydrogel with excellent mechanical properties and ionic conductivity is successfully created.

A panel of cancer testis antigens in squamous cell carcinoma of the lung, head and neck, and esophagus: implication for biomarkers and therapeutic targets.

This study aims to investigate the expression of seven cancer testis antigens (MAGE-A1, MAGE-A4, MAGE-A10, MAGE-A11, PRAME, NY-ESO-1 and KK-LC-1) in pan squamous cell carcinoma and their prognostic value, thus assessing the potential of these CTAs as immunotherapeutic targets. The protein expression of these CTAs was evaluated by immunohistochemistry in 60 lung squamous cell carcinoma (LUSC), 62 esophageal squamous cell carcinoma (ESCA) and 62 head and neck squamous cell carcinoma (HNSC). The relationship between CTAs expression and progression-free survival (PFS) was assessed.

An involvement of a new zinc finger protein PbrZFP719 into pear self-incompatibility reaction.

This study indicated that the CCHC-type zinc finger protein PbrZFP719 involves into self-incompatibility by affecting the levels of reactive oxygen species and cellulose content at the tips of pollen tubes. S-RNase-based self-incompatibility (SI) facilitates cross-pollination and prevents self-pollination, which in turn increases the costs associated with artificial pollination in fruit crops. Self S-RNase exerts its inhibitory effects on pollen tube growth by altering cell structures and components, including reactive oxygen species (ROS) level and cellulose content.

Development of PFAS-Free Locally Concentrated Ionic Liquid Electrolytes for High-Energy Lithium and Aluminum Metal Batteries.

ConspectusLithium-ion batteries (LIBs) based on graphite anodes are a widely used state-of-the-art battery technology, but their energy density is approaching theoretical limits, prompting interest in lithium-metal batteries (LMBs) that can achieve higher energy density. In addition, the limited availability of lithium reserves raises supply concerns; therefore, research on postlithium metal batteries is underway. A major issue with these metal anodes, including lithium, is dendritic formation and insufficient reversibility, which leads to safety risks due to short circuits and the use of flammable electrolytes.