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).

US-Guided Thermal Ablation for Secondary Hyperparathyroidism: A Prospective Multicenter Study.

Background Interest in microwave ablation (MWA) and radiofrequency ablation (RFA) use for treating secondary hyperparathyroidism (SHPT) is rising; however, ablation outcomes in patients with SHPT are not well characterized. Purpose To assess the response of parathyroid hormone (PTH), calcium, phosphorus, and alkaline phosphatase (ALP) levels to US-guided parathyroid MWA and RFA and the safety of these treatments in participants with SHPT. Materials and Methods This prospective multicenter cohort study, conducted from September 2017 to March 2022, included participants with SHPT.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Lysozyme-coated nanoparticles for active uptake and delivery of synthetic RNA and plasmid-encoded genes in plants.

Nanoparticle-mediated delivery of nucleic acids and proteins into intact plants has the potential to modify metabolic pathways and confer desirable traits in crops. Here we show that layered double hydroxide (LDH) nanosheets coated with lysozyme are actively taken up into the root tip, root hairs and lateral root junctions by endocytosis, and translocate via an active membrane trafficking pathway in plants. Lysozyme coating enhanced nanosheet uptake by (1) loosening the plant cell wall and (2) stimulating the expression of endocytosis and other membrane trafficking genes.

Targeted LNPs deliver IL-15 superagonists mRNA for precision cancer therapy.

Interleukin-15 (IL-15) emerges as a promising immunotherapeutic candidate, but the therapeutic utility remains concern due to the unexpected systematic stress. Here, we propose that the mRNA lipid nanoparticle (mRNA-LNP) system can balance the issue through targeted delivery to increase IL-15 concentration in the tumor area and reduce leakage into the circulation. In the established Structure-driven TARgeting (STAR) platform, the LNP and LNP can effectively and selectively deliver optimized IL-15 superagonists mRNAs to local and lungs, respectively, in relevant tumor models.

Optical sectioning methods in three-dimensional bioimaging.

In recent advancements in life sciences, optical microscopy has played a crucial role in acquiring high-quality three-dimensional structural and functional information. However, the quality of 3D images is often compromised due to the intense scattering effect in biological tissues, compounded by several issues such as limited spatiotemporal resolution, low signal-to-noise ratio, inadequate depth of penetration, and high phototoxicity. Although various optical sectioning techniques have been developed to address these challenges, each method adheres to distinct imaging principles for specific applications.

The Benefits of Virtual Reality Travel on Symptom Burden and Mental Health of Hemodialysis Patients.

Context: Hemodialysis (HD) patients often face a heavy symptom burden, low subjective well-being, and high perceived stress. Traditional nonpharmacological interventions have limited effectiveness in improving this situation. Virtual reality (VR) technology, as an emerging approach, has shown significant advantages in alleviating symptom burden and enhancing mental health.

Scalable production of ultraflat and ultraflexible diamond membrane.

Diamond is an exceptional material with great potential across various fields owing to its interesting properties. However, despite extensive efforts over the past decades, producing large quantities of desired ultrathin diamond membranes for widespread use remains challenging. Here we demonstrate that edge-exposed exfoliation using sticky tape is a simple, scalable and reliable method for producing ultrathin and transferable polycrystalline diamond membranes.

Accurate Intramyocardial Hemorrhage Assessment with Fast, Free-running, Cardiac Quantitative Susceptibility Mapping.

Purpose To evaluate the performance of a high-dynamic-range quantitative susceptibility mapping (HDR-QSM) cardiac MRI technique to detect intramyocardial hemorrhage (IMH) and quantify iron content using phantom and canine models. Materials and Methods A free-running whole-heart HDR-QSM technique for IMH assessment was developed and evaluated in calibrated iron phantoms and 14 IMH female canine models. IMH detection and iron content quantification performance of this technique was compared with the conventional iron imaging approaches, R2*(1/T2*) maps, using measurements from ex vivo imaging as the reference standard.

Quantitative Parameters of Intravoxel Incoherent Movement Imaging and Dynamic Contrast Enhancement MRI for the Prediction of HER2-Zero, -Low, and -Positive Breast Cancers.

Rationale And Objectives: To explore the predictive value of quantitative parameters from intravoxel incoherent movement (IVIM) imging and dynamic contrast enhancement MRI (DCE-MRI) for HER2 expression in breast cancer.

Materials And Methods: This retrospective study included 167 women with breast cancer who underwent MRI from December 2019 to December 2023, categorized into 48 HER2-positive, 78 HER2-low and 41 HER2-zero cancers. All patients underwent IVIM imaging and DCE-MRI.

Disruption of PCSK9 Suppresses Inflammation and Attenuates Abdominal Aortic Aneurysm Formation.

Background: Abdominal aortic aneurysm (AAA) is a chronic vascular inflammatory disease without effective medications. PCSK9 (proprotein convertase subtilisin/kexin 9), a serine protease from the proprotein convertase family, has recently been associated with AAA in human genome-wide association studies. However, its role in AAA is unknown.

Dual impacts of serine/glycine-free diet in enhancing antitumor immunity and promoting evasion via PD-L1 lactylation.

The effect of the serine/glycine-free diet (-SG diet) on colorectal cancer (CRC) remains unclear; meanwhile, programmed death-1 (PD-1) inhibitors are less effective for most CRC patients. Here, we demonstrate that the -SG diet inhibits CRC growth and promotes the accumulation of cytotoxic T cells to enhance antitumor immunity. Additionally, we also identified the lactylation of programmed death-ligand 1 (PD-L1) in tumor cells as a mechanism of immune evasion during cytotoxic T cell-mediated antitumor responses, and blocking the PD-1/PD-L1 signaling pathway is able to rejuvenate the function of CD8+ T cells recruited by the -SG diet, indicating the potential of combining the -SG diet with immunotherapy.

Middle Meningeal Artery Embolization for Nonacute Subdural Hematoma.

Background: The effect of embolization of the middle meningeal artery in patients with subacute or chronic subdural hematoma is uncertain.

Methods: We performed a multicenter, open-label, randomized trial in China, involving patients with symptomatic nonacute subdural hematoma with mass effect. Patients were assigned to undergo burr-hole drainage or receive nonsurgical treatment at the surgeon's discretion, and patients in each group were then randomly assigned, in a 1:1 ratio, to undergo middle meningeal artery embolization with liquid embolic material or to receive usual care.

Sodium oligomannate disrupts the adherence of Rib bacteria to gut epithelia to block SAA-triggered Th1 inflammation in 5XFAD transgenic mice.

Sodium oligomannate (GV-971), an oligosaccharide drug approved in China for treating mild-to-moderate Alzheimer's disease (AD), was previously found to recondition the gut microbiota and limit altered peripheral Th1 immunity in AD transgenic mice. As a follow-up study, we here made advances by pinpointing a Lactobacillus murinus (L.m.

One-Stage Orbital Decompression Combined With Intraoperative Muscle Relaxation for TAO: A Randomized Controlled Trial.

Purpose: To gauge the efficacy and safety of performing a one-stage endoscopic orbital decompression procedure combined with the intraoperative relaxed medial rectus muscle (MR) positioning technique as a means of treating esotropia associated with thyroid-associated ophthalmopathy (TAO).

Design: Prospective, single-blind, randomized controlled trial.

Setting: Eye Hospital of Wenzhou Medical University.

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.

Belimumab safety in adult and paediatric Chinese patients with systemic lupus erythematosus: A Phase 4, multicentre, observational study.

Objective: Although belimumab has been widely used in patients with systemic lupus erythematosus (SLE) globally, real-world safety data among Chinese patients are limited, particularly for children. This study assessed the safety and tolerability of belimumab in adult and paediatric patients with SLE in China in real-world clinical practice.

Methods: This Phase 4, multicentre, prospective, observational study enrolled patients prescribed intravenous belimumab by their physicians in tertiary hospitals, independent of a clinical study, during routine clinical visits between May 2021 and May 2022.

Utilizing artificial intelligence to determine bone mineral density using spectral CT.

Background: Dual-energy computed tomography (DECT) has demonstrated the feasibility of using HAP-water to respond to BMD changes without requiring dedicated software or calibration. Artificial intelligence (AI) has been utilized for diagnosising osteoporosis in routine CT scans but has rarely been used in DECT. This study investigated the diagnostic performance of an AI system for osteoporosis screening using DECT images with reference quantitative CT (QCT).

Spermidine mediates acetylhypusination of RIPK1 to suppress diabetes onset and progression.

It has been established that N-acetyltransferase (murine NAT1 (mNAT1) and human NAT2 (hNAT2)) mediates insulin sensitivity in type 2 diabetes. Here we show that mNAT1 deficiency leads to a decrease in cellular spermidine-a natural polyamine exhibiting health-protective and anti-ageing effects-but understanding of its mechanism is limited. We identify that mNAT1 and hNAT2 modulate a type of post-translational modification involving acetylated spermidine, which we name acetylhypusination, on receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-a key regulator of inflammation and cell death.

Efficacy and safety of JMT103 in patients with unresectable or surgically-challenging giant cell tumor of bone: a multicenter, phase Ib/II study.

This was a multicenter, single-arm, open-label, phase Ib/II study (NCT04255576), aimed to evaluate the efficacy and safety of JMT103 in patients with unresectable or surgically-challenging giant cell tumor of bone (GCTB). JMT103 (2 mg/kg) was administered subcutaneously every four weeks, with loading doses on days 8 and 15. The primary endpoint was the objective tumor response rate (OTR) based on best response, defined as the proportion of patients who achieved elimination of at least 90% of the giant cells or radiologic complete or partial response per the modified Inverse Choi density/size (mICDS) or modified European Organization for Research and Treatment of Cancer (mEORTC) within 12 weeks.

Autoinhibition of dimeric NINJ1 prevents plasma membrane rupture.

Lytic cell death culminates in plasma membrane rupture, which releases large intracellular molecules to augment the inflammatory response. Plasma membrane rupture is mediated by the effector membrane protein ninjurin-1 (NINJ1), which polymerizes and ruptures the membrane via its hydrophilic face. How NINJ1 is restrained under steady-state conditions to ensure cell survival remains unknown.

Microwave versus Radiofrequency Ablation in Treating Predominantly Solid Benign Thyroid Nodules: A Randomized Controlled Trial.

Background Current guidelines recommend radiofrequency ablation (RFA) as the first-line treatment for benign thyroid nodules. Purpose To compare the efficacy and safety of microwave ablation (MWA) and RFA for the treatment of predominantly solid benign thyroid nodules. Materials and Methods This prospective, randomized, open-label, multicenter study was conducted from August 2019 to February 2023.