Discovery of -Phenyl-5-propyl-1-pyrazole-3-carboxamide, with Selective Inhibition and Degradation of HDAC6 for the Treatment of Acute Liver Injury.

Acute liver injury is a severe and potentially life-threatening condition. Currently, there are no specific effective treatments available. HDAC6 has been identified as a promising strategy for treating ALI by inhibiting necrosis and inflammation.

Precise Identification of Glioblastoma Micro-Infiltration at Cellular Resolution by Raman Spectroscopy.

Precise identification of glioblastoma (GBM) microinfiltration, which is essential for achieving complete resection, remains an enormous challenge in clinical practice. Here, the study demonstrates that Raman spectroscopy effectively identifies GBM microinfiltration with cellular resolution in clinical specimens. The spectral differences between infiltrative lesions and normal brain tissues are attributed to phospholipids, nucleic acids, amino acids, and unsaturated fatty acids.

Regulation of hepatocyte phospholipid peroxidation signaling by a Chinese patent medicine against psychological stress-induced liver injury.

Background: Psychological stress is associated with various diseases including liver dysfunction, yet effective intervention strategies remain lacking due to the unrevealed pathogenesis mechanism.

Purpose: This study aims to explore the relevance between BMAL1-controlled circadian rhythms and lipoxygenase 15 (ALOX15)-mediated phospholipids peroxidation in psychological stress-induced liver injury, and to investigate whether hepatocyte phospholipid peroxidation signaling is involved in the hepatoprotective effects of a Chinese patent medicine, Pien Tze Huang (PZH).

Methods: Restraint stress models were established to investigate the underlying molecular mechanisms of psychological stress-induced liver injury and the hepatoprotective effects of PZH.

Effect of ZFM4 in -infected C57BL/6 mice: prevention is better than cure.

Objectives: This study was performed to explore the preventive and therapeutic effects of ZFM4 on H. pylori infections of the stomach tissue in C57BL/6 mice.

Methods: In this study, 40 specific-pathogen-free female C57BL/6 mice were randomly divided into five groups, namely, the control, ZFM4 pretreatment) ZFM4 pretreatment before infected), model ( infected), triple therapy ( infected and treated with triple therapy), and ZFM4 treatment groups ( infected and treated with ZFM4).

Rapid visualization of PD-L1 expression level in glioblastoma immune microenvironment via machine learning cascade-based Raman histopathology.

Introduction: Combination immunotherapy holds promise for improving survival in responsive glioblastoma (GBM) patients. Programmed death-ligand 1 (PD-L1) expression in immune microenvironment (IME) is the most important predictive biomarker for immunotherapy. Due to the heterogeneous distribution of PD-L1, post-operative histopathology fails to accurately capture its expression in residual tumors, making intra-operative diagnosis crucial for GBM treatment strategies.

Design and synthesis of 1H-benzo[d]imidazole selective HDAC6 inhibitors with potential therapy for multiple myeloma.

Pan-HDAC inhibitors exhibit significant inhibitory activity against multiple myeloma, however, their clinical applications have been hampered by substantial toxic side effects. In contrast, selective HDAC6 inhibitors have demonstrated effectiveness in treating multiple myeloma. Compounds belonging to the class of 1H-benzo[d]imidazole hydroxamic acids have been identified as novel HDAC6 inhibitors, with the benzimidazole group serving as a specific linker for these inhibitors.

Hosimosines A-E, structurally diverse cytisine derivatives from the seeds of Ormosia hosiei Hemsl. et Wils.

Ormosia hosiei Hemsl. et Wils (Fabaceae family) is an arbor species endemic to China. The seeds of O.

[Using changes of left cardiac functional parameters and CPET evaluated the clinical effectiveness of individualized precise exercise overall program management of chronic disease I --Analysis between groups].

To explore and study the clinical usefulness of continuous dynamic recording of left cardiac function changes forevaluation the improvement in patients with chronic disease after 3 months of intensive control of individualized precision exercise overall manage program. From 2018 to 2021, 21 patients with chronic cardiovascular and cerebrovascular metabolic diseases mainly controlled by our team were selected to complete the cardiopulmonary exercise test (CPET) and Non-invasive synchronous cardiac function detector (N-ISCFD), electrocardiogram, radial pulse wave, jugular pulse wave and cardiogram data were continuously recorded for 50s.According to the titration results under CPET and continuous functional parameters monitoring, a holistic plan with individualized moderate exercise intensity as the core was developed for 3 months of intensive management, and then N-ISCFD data collection was repeatedafter signing the informed consent.

[Research progress on chemical structures and pharmacological effects of natural cytisine and its derivatives].

Cytisine derivatives are a group of alkaloids containing the structural core of cytisine, which are mainly distributed in Fabaceae plants with a wide range of pharmacological activities, such as resisting inflammation, tumors, and viruses, and affecting the central nervous system. At present, a total of 193 natural cytisine and its derivatives have been reported, all of which are derived from L-lysine. In this study, natural cytisine derivatives were classified into eight types, namely cytisine type, sparteine type, albine type, angustifoline type, camoensidine type, cytisine-like type, tsukushinamine type, and lupanacosmine type.

GPX4 deficiency-dependent phospholipid peroxidation drives motor deficits of ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by oxidative stress that triggers motor neurons loss in the brain and spinal cord. However, the mechanisms underlying the exact role of oxidative stress in ALS-associated neural degeneration are not definitively established. Oxidative stress-generated phospholipid peroxides are known to have extensive physiological and pathological consequences to tissues.

Phospholipid peroxidation inhibits autophagy via stimulating the delipidation of oxidized LC3-PE.

Phospholipid peroxidation of polyunsaturated fatty acids at the bis-allylic position drives ferroptosis. Here we identify a novel role for phospholipid peroxidation in the inhibition of autophagy. Using in vitro and in vivo models, we report that phospholipid peroxidation induced by glutathione peroxidase-4 inhibition and arachidonate 15-lipoxygenase overexpression leads to overload of peroxidized phospholipids and culminate in inhibition of autophagy.

The mutation spectrum of Parkinson-disease-related genes in early-onset Parkinson's disease in ethnic Chinese.

Background And Purpose: Recent genetic progress has shown many causative/risk genes linked to Parkinson's disease (PD), mainly in patients of European ancestry. The study aimed to investigate the PD-related genes and determine the mutational spectrum of early-onset PD in ethnic Chinese.

Methods: In this study, whole-exome sequencing and/or gene dosage analysis were performed in 704 early-onset PD (EOPD) patients (onset age ≤45 years) and 1866 controls.

[Two novel cephalotaxine-type alkaloids from Cephalotaxus sinensis].

Silica gel, octadecyl-silica(ODS), Sephadex LH-20, and semi-preparative high performance liquid chromatography(HPLC) was performed to isolate nine cephalotaxine-type alkaloids from Cephalotaxus sinensis: 8-oxodeoxyharringtonine(1), 8-oxonordeoxyharringtonine(2), cephafortunine A(3), 8-oxocephalotaxine(4), deoxyharringtonine(5), acetylcephalotaxine(6), cephalotaxine(7), epicephalotaxine(8), and cephalotaxinone(9). Compounds 1 and 2 were identified for the first time and their structures were determined by high-resolution-electrospray ionization-mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR), and electronic circular dichroism(ECD). Compounds 1-3 and 5 significantly inhibited the transcription of nuclear factor kappa B(NF-κB), with the half-maximal inhibitory concentration(IC_(50)) of(3.

Comparative Study between ZOOMit and Conventional Intravoxel Incoherent Motion MRI for Assessing Parotid Gland Abnormalities in Patients with Early- or Mid-Stage Sjögren's Syndrome.

Objective: To compare the reproducibility and performance of quantitative metrics between ZOOMit and conventional intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in the diagnosis of early- and mid-stage Sjögren's syndrome (SS).

Materials And Methods: Twenty-two patients (mean age ± standard deviation, 52.0 ± 10.

Abieshanesides A and B, two unique ent-18,19-dinoricetexane diterpenoid glycosides from Abies beshanzuensis M.H. Wu.

Two unprecedented ent-18,19-dinoricetexane diterpenoid glycosides, named abieshanesides A (1) and B (2), together with seven known compounds, have been isolated from the dead trunks and branches of Abies beshanzuensis M.H. Wu.

Site-Selective Itaconation of Complex Peptides by Photoredox Catalysis.

Site-selective peptide functionalization provides a straightforward and cost-effective access to diversify peptides for biological studies. Among many existing non-invasive peptide conjugations methodologies, photoredox catalysis has emerged as one of the powerful approaches for site-specific manipulation on native peptides. Herein, we report a highly N-termini-specific method to rapidly access itaconated peptides and their derivatives through a combination of transamination and photoredox conditions.

Discovery of new genetic loci for male sexual orientation in Han population.

Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, P = 8.

[Clinical observation and research on the use of precise electromagnetic power meter (arm dynamometer) for upper limbs to evaluate the holistic function of cardiopulmonary metabolism].

Subjects used upper limb (arm dynamometer) and lower limb precision electromagnetic power meter (cycle ergometer) to perform symptom-restricted limit cardiopulmonary exercise testing (CPET). Then we analyzed the clinical value of arm ergometer CPET. The upper limb and lower limb precision electromagnetic power meters were used to complete the CPET in two different days for 6 normal people and 9 chronic patients.

[Individualization analysis of pulse wave shape characteristics before and after single precise power exercise in young healthy subjects].

To observe and study the resting radial artery pulse wave and the pulse wave changes after a single individualized exercise in young healthy normal subjects. We selected 16 young healthy graduate students, advanced training doctors, and visiting scholars from Fuwai Hospital without any disease diagnosis and low daily exercise. They first completed the symptom-restricted limit cardiopulmonary exercise testing (CPET).

[The preliminary report of investigation: Using mask for cardiopulmonary exercise testing in Chinese children may result misinterpretation and misdiagnosis].

Observe the increased anatomical dead space of the mask, summarize the law of exercise induced oscillatory breathing (EIOB) in the results of CPET's new 9 figure, and analyze its incidence and age groups that are prone to oscillatory breathing. After signed the informed consent form by guardian, 501 children from pre-school to middle-school, aged 3~14 year, performed Harbor-UCLA standard protocol CPET with strict quality control in the CPET laboratory of Liaocheng Children's Hospital since 2014. CPET data was interpreted second by second from the breath by breath collection, averaged by 10s and then display by 9 plots.

[The new theory CPET guides the overall plan of individualized precision exercise to effectively improve the overall functional status of "frailty"].

Under the guidance of the new theory of holistic integrated physiology and medicine, the effect of individualized accurate exercise program on the overall functional state was studied according to cardiopulmonary exercise testing (CPET). Li xx, female, 31 years old, has a fast heart rate since childhood (90~100 bpm), usually feel cold, especially in autumn and winter, and general health good. CPET was performed after signing the informed consent form at Fuwai Hospital in September 2019.

[Individualized analysis of pulse wave shape before and after a single accurate power exercise in patients with long-term chronic diseases].

To observe and study the resting radial artery pulse wave and changes after a single individualized exercise in patients with long-term chronic diseases. We selected 16 patients with chronic disease (disease duration ≥5 years) who have been clearly diagnosed as hypertension and/or diabetes and/or hyperlipemia, and first completed the symptom-restricted limit cardiopulmonary exercise testing (CPET). Then a single individualized exercise with Δ50% power as the exercise intensity was completed within one week after CPET.

[A clinical research report on the pathophysiological characteristics of exercise in patients with mitral regurgitation].

Cardiopulmonary exercise testing (CPET) was used to investigate the exercise pathophysiology of mitral regurgitation. 26 patients with moderate and severe mitral regurgitation who completed standardized extreme exercise CPET under strict quality control after signing informed consent since 2016, and 11 normal subjects in the same period as the control group. The core indexes of CPET were analyzed and calculated according to the standard method and compared with normal subjects for intergroup statistical independent sample t-test.