Endothelial Activation and Stress Index Serves as a Predictor for Survival in Lymphoma-Associated Hemophagocytic Lymphohistiocytosis: A Retrospective Multicenter Cohort Study of Jiangsu Cooperative Lymphoma Group.

Lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH) is a life-threatening hyperinflammatory syndrome, and hierarchical management based on a prognostic model is important. The endothelial activation and stress index (EASIX) score has demonstrated prognostic utility in recipients of allogeneic stem cell transplantation and chimeric antigen receptor (CAR) T-cell therapy. However, its role in LA-HLH remains unestablished.

-(3-phenylpropiolamido)phenyl (PPAP) glycosides: Harnessing -cyclization-driven glycosylation for strategic flexibility.

We herein report -(3-phenylpropiolamido)phenyl (PPAP) glycosides as a novel class of glycosyl donors with distinct advantages for carbohydrate synthesis. These donors, featured by an intrinsically stable phenolic linkage, undergo glycosylation via a unique -cyclization-mediated activation. Activated with -iodosuccinimide (NIS)/trimethylsilyl trifluoromethanesulfonate (TMSOTf), PPAP donors support both O- and N-glycosylation across a broad range of substrates.

Mechanistic insights into the dual anti-COVID-19 and anti-inflammatory actions of Zhengqi tablets.

Ethnopharmacological Relevance: Zhengqi Tablets (ZQP), derived from the "Huoxiang Zhengqi Powder" in the Song dynasty's "Taiping Huimin Ju Fang", have been endorsed by the Expert Consensus on Traditional Chinese Medcine Diagnosis and Treatment of New Coronavirus Infection in Shanghai (Spring Edition, 2022).

Aim Of The Study: The precise mechanisms underlying the efficacy of ZQP remain incompletely elucidated. To address this gap, we utilized a comprehensive approach integrating computer-aided virtual screening and biological validation to identify the active monomer within ZQP responsible for its anti-coronavirus properties.

Polyphyllin I Inhibits the Metastasis of Cervical Cancer Through the Regulation of the β-Catenin Signaling Pathway.

Cervical cancer ranks as the fourth most prevalent cancer and cause of cancer-related mortality among women globally. It exhibits a recurrence/metastasis rate of approximately 30% and a dismal 5-year survival of only 17% in metastatic cases. Despite significant advancements in surgical techniques, chemoradiotherapy, and targeted therapies, effective treatment options for metastatic cervical cancer remain limited.

Early-life smoking, cardiovascular disease risk, and the mediating role of DNA methylation biomarkers of aging.

Background: Early-life smoking is linked to biological aging and chronic diseases, yet its specific relationship with cardiovascular disease (CVD) risk and the role of DNA methylation biomarkers of aging as potential mediators of that relationship remain underexplored.

Methods: In this study, we analyzed data from 2345 participants in the National Health and Nutrition Examination Survey (NHANES; 1999-2002). Early-life smoking status was assessed on the basis of the age of smoking initiation (ASI) and categorized into three smoking initiation periods (SIPs): childhood (5-14 years), adolescence/adulthood (> 14 years), and never smoked.

Biocatalytic Synthesis of Corticosteroid Derivatives by Toad-Derived Steroid C21-Hydroxylase.

CsCYP21A, a steroid 21-hydroxylase from , exhibits unprecedented sequential oxidations. Optimizing biotransformation conditions enhanced C21-hydroxylation selectivity, converting 14 substrates to 21-hydroxylated products, with 10 conversions of >80% and 4 yields of >80%. Hydrocortisone production reached 1.

Copper-Catalyzed Asymmetric Cloke-Wilson Rearrangement.

Herein we describe the first transition-metal-catalyzed asymmetric Cloke-Wilson rearrangement through unprecedented propargylic alkenoxylation reaction with enol as the -nucleophile. A set of new chiral PPBOX ligands was prepared to guarantee the high enantioselectivity of the transformation. A series of polysubstituted dihydrofuran skeletons bearing an alkyne unit was prepared in good yield and high enantioselectivity under very mild reaction conditions, and various downstream transformations were facilely conducted to access different chiral skeletons.

Discovery of highly potent and novel LSD1 inhibitors for the treatment of acute myeloid leukemia: structure-based virtual screening, molecular dynamics simulation, and biological evaluation.

Acute myeloid leukemia (AML) is a highly aggressive hematological malignancy with a significant unmet clinical need for new therapeutic agents. Lysine-specific demethylase 1 (LSD1), a key regulator of leukemia stem cell self-renewal, has emerged as a promising epigenetic target for AML treatment. Herein, we employed an innovative multi-step integrated screening protocol, encompassing pharmacophore modeling, docking screening, molecular dynamics simulation, and biological evaluation, to identify novel LSD1 inhibitors.

Therapeutic potential and pharmacological mechanisms of Traditional Chinese Medicine in gout treatment.

Gout is a systemic metabolic disorder caused by elevated uric acid (UA) levels, affecting over 1% of the population. The most common complication of gout is gouty arthritis (GA), characterized by swelling, pain or tenderness in peripheral joints or bursae, which can lead to the formation of tophi. At present, western medicines like colchicine, febuxostat and allopurinol are the primary treatment strategy to alleviate pain and prevent flare-ups in patients with GA, but they have significant side effects and increased mortality risks.

Stereoselective P(III)-Glycosylation for the Preparation of Phosphinated Sugars.

Most of the reported work focus on the development of O-, N-, C- and S-glycosylation methods. However, no study explores P(III)-glycosylation reaction. Herein we describe a convenient protocol to realize P(III)-glycosylation process.

The impact of behavioral risks on cardiovascular disease mortality in China between 1990 and 2019.

Aims: Behavioral risks including tobacco use, alcohol use, low physical activity and dietary risks had been proven to contribute to the pathological process in cardiovascular diseases (CVD). Herein the lethal effects attributable to behavioral risks on CVD in China were investigated.

Methods: Data were obtained from the Global Burden of Disease Study 2019.

Deciphering substrate promiscuity and specificity of indolethylamine N-methyltransferase family enzymes from amphibian toads.

N-methylation is a crucial post-modification process in natural product biosynthesis and also contributes to the metabolism of various physiological substances, such as neurotransmitter, hormone, and trace elements. In this study, we identified seven indolethylamine N-methyltransferase (INMT) family enzymes from the amphibian toad Bufo gargarizan with distinct catalytic properties. Among these enzymes, BNMT 1, BNMT 5, BNMT 6 and BNMT 7 exhibited notable promiscuity, demonstrating the ability to methylate multiple derivatives of indolethylamine, phenylethylamine, phenylethanolamine, and nicotinamide.

Bufotalin Induces Oxidative Stress-Mediated Apoptosis by Blocking the ITGB4/FAK/ERK Pathway in Glioblastoma.

Bufotalin (BT), a major active constituent of Chansu, has been found to possess multiple pharmacological activities. Although previous studies have shown that BT could inhibit the growth of glioblastoma (GBM), the safety of BT in vivo and the potential mechanism are still unclear. We conducted a systematic assessment to investigate the impact of BT on GBM cell viability, migration, invasion, and colony formation.

Adenanthin exhibits anti-inflammatory effects by covalently targeting the p65 subunit in the NF-κB signaling pathway.

Adenanthin is a structurally unique ent-kaurane diterpenoid isolated from Rabdosia adenantha, a traditional Chinese medicinal plant with potent anti-cancer and anti-inflammatory activities. However, its anti-inflammatory molecular mechanism remains largely elusive to date. Here, we developed an affinity-based label-free protein profiling (ALFPP) to identify potential covalent targets of electrophilic natural products with ketone or aldehyde groups.

Clinicopathological characteristics, prognostic factors, and outcomes of elderly patients with lymphoma-associated hemophagocytic lymphohistiocytosis: A multicenter analysis.

Background: Lymphoma is the most common secondary cause of hemophagocytic lymphohistiocytosis (HLH) in adults. Lymphoma-associated HLH (LA-HLH) in the elderly population is not rare, however, little has been reported regarding clinicopathological characteristics, prognostic factors, and outcomes of LA-HLH in the elderly population.

Methods: We retrospectively analyzed a multicenter cohort of elderly patients with LA-HLH.

The protective role of vagus nerve stimulation in ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) encompasses the damage resulting from the restoration of blood supply following tissue ischemia. This phenomenon commonly occurs in clinical scenarios such as hemorrhagic shock, severe trauma, organ transplantation, and thrombolytic therapy. Despite its prevalence, existing treatments exhibit limited efficacy against IRI.

Combination of venetoclax and azacitidine in relapsed/refractory acute B-cell lymphoblastic leukemia: a case series from a single center.

Objectives: Relapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) often responds poorly to induction chemotherapy. However, recent research has shown a novel and effective drug treatment for R/R B-ALL.

Methods: A total of eight patients with R/R B-ALL were enrolled in the study from November 2021 to August 2022.

Identification of benzo[b]thiophene-1,1-dioxide derivatives as novel PHGDH covalent inhibitors.

The increased de novo serine biosynthesis confers many advantages for tumorigenesis and metastasis. Phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in serine biogenesis, exhibits hyperactivity across multiple tumors and emerges as a promising target for cancer treatment. Through screening our in-house compound library, we identified compound Stattic as a potent PHGDH inhibitor (IC = 1.

Asymmetric copper-catalyzed alkynylallylic monofluoroalkylations with fluorinated malonates.

The unprecedented copper-catalyzed asymmetric alkynylallylic monofluoroalkylation reaction is described the use of 1,3-enynes and fluorinated malonates. A series of 1,4-enynes bearing a monofluoroalkyl unit are achieved in high yields, excellent regio- and enantioselectivity and high selectivity. The asymmetric propargylic monofluoroalkylation is also developed.

Discovery of natural catechol derivatives as covalent SARS-CoV-2 3CL inhibitors.

The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a threat to public health, and extensive research by scientists worldwide has also prompted the development of antiviral therapies. The 3C-like protease (3CL) is critical for SARS-CoV-2 replication and acts as an effective target for drug development. To date, numerous of natural products have been reported to exhibit inhibitory effects on 3CL, which encourages us to identify other novel inhibitors and elucidate their mechanism of action.

The clinical significance and prognostic value of serum beta-2 microglobulin in adult lymphoma-associated hemophagocytic lymphohistiocytosis: a multicenter analysis of 326 patients.

To investigate the prognostic impact of serum beta-2 microglobulin (B2M) in adult lymphoma-associated hemophagocytic lymphohistiocytosis (HLH). The clinical and laboratory characteristics of 326 adult patients in a multicenter cohort with lymphoma-associated HLH with available baseline serum B2M levels were retrospectively analyzed. A total of 326 cases were included in this study, and the median serum B2M level was 5.