Genetically-encoded targeted protein degradation technology to remove endogenous condensation-prone proteins and improve crop performance.

Effective modulation of gene expression in plants is achievable through tools like CRISPR and RNA interference, yet methods for directly modifying endogenous proteins remain lacking. Here, we identify the E3 ubiquitin ligase E3TCD1 and develope a Targeted Condensation-prone-protein Degradation (TCD) strategy. The X-E3TCD1 fusion protein acts as a genetically engineered degrader, selectively targeting endogenous proteins prone to condensation.

Early Versus Delayed Antihypertensive Treatment After Acute Ischemic Stroke by Hypertension History.

Background: We performed a prespecified subgroup analysis of the CATIS-2 trial (China Antihypertensive Trial in Acute Ischemic Stroke II) to compare the effect of early versus delayed antihypertensive treatment on death and disability in patients with and without medical history of hypertension.

Methods: CATIS-2 is a multicenter randomized clinical trial conducted in 106 hospitals in China. The trial randomized 4810 patients with acute ischemic stroke within 24 to 48 hours of symptom onset and elevated systolic blood pressure between 140 and <220 mm Hg to receive antihypertensive treatment immediately after randomization or to discontinue antihypertensive medications for 7 days and then receive treatment on day 8.

Oral Yeast-Cell Microcapsule-Mediated DNA Vaccines Against Induce Effective Intestinal Immunity and Modulate Gut Microbiota.

is a common opportunistic pathogen that causes gastrointestinal diseases in livestock and poultry. Our preliminary research has demonstrated that administering oral yeast-cell microcapsule (YCM)-mediated DNA vaccines can effectively stimulate mucosal immunity, thereby preventing the occurrence of gastrointestinal diseases. In this study, the α-toxin gene was first cloned and the H126G and C-terminal (C247-370) mutations were created.

A Preclinical Immunogenicity Study of the Recombinant Human Papillomavirus Nine-Valent Virus-like Particle Vaccine.

Background: Cervical cancer is associated with persistent infection of high-risk human papillomaviruses (HPVs). Prophylactic HPV vaccines have been recommended and have significant efficacy in preventing cervical cancer. Multivalent HPV vaccines have a better preventative effect on HPV-related diseases.

Long-term Efficacy of Prostatic Artery Embolization Alone Versus Prostatic Artery Embolization Followed by HoLEP for Large (> 80 cm) Benign Prostatic Hyperplasia.

Rationale And Objectives: To compare the long-term efficacy of prostatic artery embolization (PAE) with PAE followed by holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia (BPH) in patients with large prostatic volume (PV>80 cm), and to identify the appropriate population for PAE+HoLEP.

Methods: From March 2015 to December 2023, 208 consecutive BPH patients were enrolled into two groups: PAE monotherapy (Group A, n=168) and PAE followed by HoLEP (Group B, n=40). Differences in clinical and functional parameters between baseline and each follow-up point were compared.

Age-related decline in CD8 tissue resident memory T cells compromises antitumor immunity.

Aging compromises antitumor immunity, but the underlying mechanisms remain elusive. Here, we report that aging impairs the generation of CD8 tissue resident memory T (T) cells in nonlymphoid tissues in mice, thus compromising the antitumor activity of aged CD8 T cells, which we also observed in human lung adenocarcinoma. We further identified that the apoptosis regulator BFAR was highly enriched in aged CD8 T cells, in which BFAR suppressed cytokine-induced JAK2 signaling by activating JAK2 deubiquitination, thereby limiting downstream STAT1-mediated T reprogramming.

Performance Descriptor of Subsurface Metal-Promoted Boron Catalysts for Low-Temperature Propane Oxidative Dehydrogenation to Propylene.

Boron-based catalysts have exhibited excellent olefin selectivity in the oxidative dehydrogenation of propane (ODHP) reaction. The substrate material should be a potential platform for performance modulation of boron catalysts in this reaction since the introduction of subsurface Ni promoters significantly improves the activity. In this study, we deciphered the substrate effect and identified a performance descriptor to comprehend the roles of subsurface materials in BO/metal/BN ODHP catalysts by evaluating different metal promoters.

Individually addressed entangling gates in a two-dimensional ion crystal.

Two-dimensional (2D) ion crystals may represent a promising path to scale up qubit numbers for ion trap quantum information processing. However, to realize universal quantum computing in this system, individually addressed high-fidelity two-qubit entangling gates still remain challenging due to the inevitable micromotion of ions in a 2D crystal as well as the technical difficulty in 2D addressing. Here we demonstrate two-qubit entangling gates between any ion pairs in a 2D crystal of four ions.

Novel Amorphous Nitride-Halide Solid Electrolytes with Enhanced Performance for All-Solid-State Batteries.

Solid electrolytes (SEs) in all-solid-state batteries (ASSBs) are garnering considerable attention for their potential applications in next-generation energy storage systems. Amorphous SEs with dual-anion hold great promise for achieving favorable performance, such as high ionic conductivity and good compatibility with electrodes within ASSBs. Here, we discover a family of amorphous nitride-halide SEs, LiMClN (M=Ta or La, 1≤3x≤1.

Defect Structure, Oxygen Ion Conduction, and Conducting Mechanism in Ruddlesden-Popper SrZrMO (M = Ga, Y, In).

Ruddlesden-Popper (RP)-structured materials based on transition metals with a variable valence, such as Fe, Mn, Ni, and so on, have been well documented for their potential of being used as electrodes in solid-oxide fuel cells. However, RP materials with pure or dominant ionic conduction are rare. Here, a series of Zr-based RP materials SrZrMO (M = Ga, Y, In) with electrical conductivity as high as 3.

Enhancing lithium storage performance with silicon-based anodes: a theoretical study on transition metal-integrated SiO/M@C (M = Fe, Co, Ni) heterostructures.

In lithium-ion batteries, infusible metals with lithium, such as Mg, Fe, Co, Ni, and Cu are often utilized. However, current research predominantly focuses on the experimental aspects of the (de)lithiation process, with limited exploration from a theoretical calculation perspective. The extensive use of experimental methods to study the many electrochemically inert metals is time-consuming and costly.

Crotonylation of NAE1 Modulates Cardiac Hypertrophy via Gelsolin Neddylation.

Background: Cardiac hypertrophy and its associated remodeling are among the leading causes of heart failure. Lysine crotonylation is a recently discovered posttranslational modification whose role in cardiac hypertrophy remains largely unknown. NAE1 (NEDD8 [neural precursor cell expressed developmentally downregulated protein 8]-activating enzyme E1 regulatory subunit) is mainly involved in the neddylation modification of protein targets.

Three SARS-CoV-2 spike protein variants delivered intranasally by measles and mumps vaccines are broadly protective.

As the new SARS-CoV-2 Omicron variants and subvariants emerge, there is an urgency to develop intranasal, broadly protective vaccines. Here, we developed highly efficacious, intranasal trivalent SARS-CoV-2 vaccine candidates (TVC) based on three components of the MMR vaccine: measles virus (MeV), mumps virus (MuV) Jeryl Lynn (JL1) strain, and MuV JL2 strain. Specifically, MeV, MuV-JL1, and MuV-JL2 vaccine strains, each expressing prefusion spike (preS-6P) from a different variant of concern (VoC), were combined to generate TVCs.

Effect of Activated Charcoal on Mavacamten Pharmacokinetics in Healthy Participants.

Objective: To assess the effect of activated charcoal on the single-dose pharmacokinetics of mavacamten when administered 2 h or 6 h after mavacamten dosing.

Methods: In this open-label, randomized, parallel-group study, healthy adults were randomized into three groups to receive mavacamten 15 mg alone or mavacamten 15 mg plus activated charcoal 50 g administered either 2 h or 6 h after mavacamten dosing. Pharmacokinetic parameters were derived from plasma concentration-time data using noncompartmental methods.

Dual Antiplatelet Therapy After Embolic Stroke of Undetermined Source: A Subgroup Analysis of the CHANCE-2 Trial.

Background: The atherosclerotic sources of embolism are a significant contributor to embolic stroke of undetermined source (ESUS). However, there is limited evidence for the efficacy of intensive dual antiplatelet therapy for ESUS. We conducted an investigation to determine whether gene-directed dual antiplatelet therapy could reduce the risk of recurrent stroke in patients with ESUS.

Adjuvant treatment strategy evolution and risk stratification for hormone receptor-positive, human epidermal growth factor receptor-2 negative early breast cancer in China.

Background: Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) early breast cancer (EBC) with high-risk clinicopathological features face an increased risk of recurrence. This study explored the evolving treatment landscape and clinical outcomes in patients with EBC using a nationwide database.

Patients And Methods: The study cohort comprised HR+/HER2-, stages 1-3, patients with EBC who underwent surgery and received adjuvant endocrine therapy (AET) from January 2013 to March 2021.

Hsc70 promotes anti-tumor immunity by targeting PD-L1 for lysosomal degradation.

Immune checkpoint inhibition targeting the PD-1/PD-L1 pathway has become a powerful clinical strategy for treating cancer, but its efficacy is complicated by various resistance mechanisms. One of the reasons for the resistance is the internalization and recycling of PD-L1 itself upon antibody binding. The inhibition of lysosome-mediated degradation of PD-L1 is critical for preserving the amount of PD-L1 recycling back to the cell membrane.

Weakening Mn-O Bond Strength in Mn-Based Perovskite Catalysts to Enhance Propane Catalytic Combustion.

Exploring highly efficient and robust non-noble metal catalysts for VOC abatement is crucial but challenging. Mn-based perovskites are a class of redox catalysts with good thermal stability, but their activity in the catalytic combustion of light alkanes is insufficient. In this work, we modulated the Mn-O bond strength in a Mn-based perovskite via defect engineering, over which the catalytic activity of propane combustion was significantly enhanced.

Efforts to promote osteogenesis-angiogenesis coupling for bone tissue engineering.

Repair of bone defects exceeding a critical size has been always a big challenge in clinical practice. Tissue engineering has exhibited great potential to effectively repair the defects with less adverse effect than traditional bone grafts, during which how to induce vascularized bone formation has been recognized as a critical issue. Therefore, recently many studies have been launched to attempt to promote osteogenesis-angiogenesis coupling.

Associations of Intrapancreatic Fat Deposition With Incident Diseases of the Exocrine and Endocrine Pancreas: A UK Biobank Prospective Cohort Study.

Introduction: To investigate whether increased intrapancreatic fat deposition (IPFD) heightens the risk of diseases of the exocrine and endocrine pancreas.

Methods: A prospective cohort study was conducted using data from the UK Biobank. IPFD was quantified using MRI and a deep learning-based framework called nnUNet.