Selective Degradation of TEADs by a PROTAC Molecule Exhibited Robust Anticancer Efficacy In Vitro and In Vivo.

Genetic mutations in components of the Hippo pathway frequently lead to the aberrant activation of TEADs, which is often associated with cancer. Consequently, TEADs have been actively pursued as therapeutic targets for diseases driven by TEAD overactivation. In this study, we report two series of TEAD PROTACs based on CRBN binders and VHL binders.

CD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells.

Clinical application of autologous chimeric antigen receptor (CAR)-T cells is complicated by limited targeting of cancer types, as well as the time-consuming and costly manufacturing process. We develop CD70-targeted, induced pluripotent stem cell-derived CAR-natural killer (NK) (70CAR-iNK) cells as an approach for universal immune cell therapy. Besides the CD70-targeted CAR molecule, 70CAR-iNK cells are modified with CD70 gene knockout, a high-affinity non-cleavable CD16 (hnCD16), and an interleukin (IL)-15 receptor α/IL-15 fusion protein (IL15RF).

Hesperidin inhibits colon cancer progression by downregulating SLC5A1 to suppress EGFR phosphorylation.

Hesperidin, an active constituent of traditional Chinese medicine, Chenpi, exhibits anticancer properties across different cancers. This study aimed to clarify the efficacy of Hesperidin against tumors and its mechanisms of action in colon cancer. : We assessed the efficacy of Hesperidin on human colon cancer cells (HCT-116 and DLD-1) and normal colonic epithelial cells (NCM460).

Blinatumomab added to conditioning regimen of allogeneic hematopoietic stem cell transplantation for adult MRDpositive acute lymphoblastic leukemia: a single-center case series.

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) remains the mainstay of treatment for adults with high-risk acute lymphoblastic leukemia (ALL). Due to the crucial role of measurable residual disease (MRD) before Allo-HSCT in predicting relapse and the promising anti-leukemia effect of blinatumomab, we documented a short-course, low-dose conditioning regimen incorporating blinatumomab for Allo-HSCT in three ALL patients with positive MRD. Following the administration of the blinatumomab-containing conditioning regimen, all patients attained complete remission (CR) with negative MRD status, and no severe adverse events were observed.

Development and validation of a risk prediction model related to inflammatory and nutritional indexes for postoperative pulmonary infection after radical colorectal cancer surgery.

Objective: To develop and validate a risk prediction model related to inflammatory and nutritional indexes for postoperative pulmonary infection (POI) after radical colorectal cancer (CRC) surgery.

Design: Cross-sectional study.

Participants: This study analysed 866 CRC patients after radical surgery at a tertiary hospital in China.

A prognostic index for advanced-stage extranodal natural killer/T-cell lymphoma: A multicenter study.

Advanced-stage extranodal natural killer/T-cell lymphoma (ENKTL) is a highly heterogeneous disease with very poor prognosis. All commonly utilized prognostic models incorporated both early-stage and advanced-stage patients in the modeling process. This study aim to design a prognostic model specifically for advanced-stage ENKTL, providing risk stratification in affected patients.

Vulnerable parafoveal microcirculation quadrant in patients with type 2 diabetes mellitus.

Diabetic retinopathy (DR) is a leading cause of vision loss among adults. This study evaluates Optical Coherence Tomography Angiography (OCTA) vessel density (VD) as a marker for DR in diabetes mellitus (DM) patients. An observational study was conducted with 47 type 2 DM patients and 21 healthy controls.

LPS Disrupts Endometrial Receptivity by Inhibiting STAT1 Phosphorylation in Sheep.

Uterine infections reduce ruminant reproductive efficiency. Reproductive dysfunction caused by infusion of Gram-negative bacteria is characterized by the failure of embryo implantation and reduced conception rates. Lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, is highly abortogenic.

Decoding the difference of four species of Cordyceps based on polysaccharides and immunomodulation activity.

Nucleosides and polysaccharides are the main bioactive ingredients of Cordyceps genus. Nucleosides shows significant differences in different Cordyceps species. However, the differences of polysaccharides have not been decoded.

Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia.

Background: Sequential CD19 and CD22 chimeric antigen receptor (CAR)-T cell therapy offers a promising approach to antigen-loss relapse in relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL); however, research in adults remains limited.

Methods: This study aimed to evaluate the efficacy and safety of sequential CD19 and CD22 CAR-T cell therapy in adult patients with R/R B-ALL between November 2020 and November 2023 (ChiCTR2100053871). Key endpoints included the adverse event incidence, overall survival (OS), and leukemia-free survival (LFS).

Neurotensin-neurotensin receptor 2 signaling in adipocytes suppresses food intake through regulating ceramide metabolism.

Neurotensin (NTS) is a secretory peptide produced by lymphatic endothelial cells. Our previous study revealed that NTS suppressed the activity of brown adipose tissue via interactions with NTSR2. In the current study, we found that the depletion of Ntsr2 in white adipocytes upregulated food intake, while the local treatment of NTS suppressed food intake.

Identification of potential biomarkers and pathways involved in high-altitude pulmonary edema using GC-MS and LC-MS metabolomic methods.

High-altitude pulmonary edema (HAPE) is a life-threatening altitude sickness afflicting certain individuals after rapid ascent to high altitude above 2500 m. In the setting of HAPE, an early diagnosis is critical and currently based on clinical evaluation. The aim of this study was to utilize the metabolomics to identify the altered metabolic patterns and potential biomarkers for HAPE.

A New Perspective for Improving COPD: Ginsenoside Rg3 Links SIRT1 to Inhibit Mitochondrial Autophagy.

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent yet manageable respiratory condition. However, treatments presently used normally have side effects and cannot cure COPD, making it urgent to explore effective medications. The ginsenoside Rg3 (Rg3) has been shown to have anti-inflammatory and anti-tumor properties and can improve COPD.

Risk stratification based on changes in the standard maximal uptake value on PET/CT and the plasma Epstein‒Barr virus (EBV) DNA status after two cycles of chemotherapy for extranodal NK-/T-cell lymphoma.

Although different types of prognostic indices have been applied in extranodal NK-/T-cell lymphoma (ENKTL), they are based mainly on clinical characteristics before treatment. Moreover, these methods lack early assessment and tumor metabolic parameters. It remains unclear whether changes in the plasma Epstein-Barr virus DNA (EBVDNA) status and SUVmax after two cycles of chemotherapy may predict disease prognosis.

Polyketide Synthase Acyltransferase Domain Swapping for Enhanced EPA Recognition and Efficient Coproduction of EPA and DHA in sp.

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are important polyunsaturated fatty acids (PUFAs) used as nutritional supplements. The natural EPA content in sp. is low, and traditional strategies to increase EPA levels often compromise DHA content or lipid accumulation, hindering industrial coproduction.

[Simultaneous determination and toxicokinetic study of six compounds from Zhachong Shisanwei Pills in plasma of chronic cerebral ischemia rats by LC-MS/MS].

A liquid chromatography-tandem mass spectrometry method was established and validated for determining the concentrations of costunolide(CO), piperine(PI), agarotetrol(AG), glycyrrhizic acid(GL), vanillic acid(VA), and glycyrrhetinic acid(GA) in rat plasma. This method was then applied to the toxicokinetic study of these six compounds in rats with chronic cerebral ischemia(CCI) following multiple oral doses of Zhachong Shisanwei Pills. Finally, the effects of continuous multiple-dose administration of Zhachong Shisanwei Pills on the liver of CCI rats were investigated.

Design of a humanized CD40 agonist antibody with specific properties using AlphaFold2 and development of an anti-PD-L1/CD40 bispecific antibody for cancer immunotherapy.

Bispecific antibodies (BsAbs) represent a promising strategy for cancer immunotherapy. Challenges in immunotherapy include inefficient early events in the immune response cycle, such as antigen presentation and T cell priming. Background stimulation of CD40 with agonistic antibodies is a promising strategy to enhance the therapeutic efficacy of immune checkpoint inhibitors (ICIs).

[The effectiveness of CT-MRI image fusion technology in the preoperative assessment of middle ear cholesteatoma].

To evaluate the effectiveness of CT-MRI image fusion technology in the preoperative assessment of middle ear cholesteatoma. The clinical data of patients with middle ear cholesteatoma who underwent surgery at Guangdong Provincial People's Hospital from September 2018 to January 2020 were retrospectively analyzed. Preoperative CT and MRI of the patients were automatically fused using the open-source software 3D Slicer, followed by 3D reconstruction of the fused inner ear structures.

HDACi combination therapy with IDO1i remodels the tumor microenvironment and boosts antitumor efficacy in colorectal cancer with microsatellite stability.

Background: Immunotherapy for colorectal cancer (CRC) with microsatellite stability (MSS) and mismatch repair proficiency (pMMR) has shown limited success in clinical trials. The combination of immunomodulators and immune checkpoint inhibitors (ICIs) is a potential strategy for treating CRC.

Methods: Histone deacetylase (HDAC) and indoleamine 2,3-dioxygenase 1 (IDO1) expression in CRC tissues and adjacent normal tissues was analyzed via database analysis, immunohistochemistry, and western blotting.

Investigating the impact of non-standard positioning on the accuracy of skull tracking algorithms using dual-panel imaging systems.

Objective: This study investigates the impact of non-standard positioning on the accuracy of 6D-skull tracking using dual-panel imaging systems. It explores whether positioning patients' heads at various angles during intracranial lesion treatment affects the accuracy of the CyberKnife 6D-skull tracking system.

Materials And Methods: A heterogeneous density skull phantom was used to simulate various patient skull positioning angles.

No causal association between serum vitamin D levels and bronchiectasis: A Mendelian randomization analysis.

Observational studies have reported an association between Vitamin D deficiency and an increased risk of bronchiectasis. This study aims to investigate the causal relationship between Vitamin D levels and bronchiectasis using a 2-sample Mendelian randomization (MR) analysis. Data from 2 genome-wide association studies (GWAS) based on European ancestry were analyzed: serum vitamin D levels (sample size = 441,291 [UK Biobank]) and bronchiectasis (sample size = 187,830 [cases = 1107, controls = 186,723; FinnGen]).

Impact of the COVID-19 outbreak on the field of hematopoietic cell transplantation in the Asia-Pacific region: APBMT Activity Survey 2020/2021.

COVID-19 became a global pandemic in 2020 and significantly affected the activity of hematopoietic cell transplants (HCT) worldwide. Despite these challenges, a total of 28,793 transplants, including 18,518 allogeneic and 10,275 autologous transplants, were performed in 719 facilities in 2020 in the Asia-Pacific (AP) region. This represented a 5.

Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and gliomagenesis.

Histone lysine lactylation is a physiologically and pathologically relevant epigenetic pathway that can be stimulated by the Warburg effect-associated L-lactate. Nevertheless, the mechanism by which cells use L-lactate to generate lactyl-coenzyme A (CoA) and how this process is regulated remains unknown. Here, we report the identification of guanosine triphosphate (GTP)-specific SCS (GTPSCS) as a lactyl-CoA synthetase in the nucleus.

USP38 exacerbates myocardial injury and malignant ventricular arrhythmias after ischemia/reperfusion by promoting ferroptosis through the P53/SLC7A11 pathway.

Introduction: Myocardial ischemia-reperfusion (I/R) leads to myocardial injury and malignant ventricular arrhythmias (VAs). Ferroptosis is a novel form of cell death that plays a role in myocardial injury after I/R. Ubiquitin-specific protease 38 (USP38), a member of the deubiquitinating enzyme family, is involved in regulating the progression of inflammation and tumors, but its role in myocardial I/R and ferroptosis is unclear.