DSCI: a database of synthetic biology components for innate immunity and cell engineering decision-making processes.

Although significant progress of clinical strategy has been made in gene editing and cell engineering in immunotherapy, it is now apparent that design and modification in terms of complex signaling pathways and motifs on medical synthetic biology are still full of challenges. Innate immunity, the first line of host defense against pathogens, is critical for anti-pathogens immune response as well as regulating durable and protective T cell-mediated anti-tumor responses. Here, we introduce DSCI (Database of Synthetic Biology Components for Innate Immunity, https://dsci.

High spin-orbit torque efficiency induced by engineering spin absorption for fully electric-driven magnetization switching.

Realizing spin-orbit torque (SOT)-driven magnetization switching offers promising opportunities for the advancement of next-generation spintronics. However, the relatively low charge-spin conversion efficiency accompanied by an ultrahigh critical switching current density () remains a significant obstacle to the further development of SOT-based storage elements. Herein, spin absorption engineering at the ferromagnet/nonmagnet interface is firstly proposed to achieve high SOT efficiency in Pt/Co/Ir trilayers.

Integration of ordered porous materials for targeted three-component gas separation.

Separation of multi-component mixtures in an energy-efficient manner has important practical impact in chemical industry but is highly challenging. Especially, targeted simultaneous removal of multiple impurities to purify the desired product in one-step separation process is an extremely difficult task. We introduced a pore integration strategy of modularizing ordered pore structures with specific functions for on-demand assembly to deal with complex multi-component separation systems, which are unattainable by each individual pore.

CT Multidimensional Radiomics Combined with Inflammatory Immune Score For Preoperative Prediction of Pathological Grade in Esophageal Squamous Cell Carcinoma.

Rationale And Objectives: Inflammation and immune biomarkers can promote angiogenesis and proliferation and metastasis of esophageal squamous cell carcinoma (ESCC). The degree of pathological grade reflects the tumor heterogeneity of ESCC. The purpose is to develop and validate a nomogram based on enhanced CT multidimensional radiomics combined with inflammatory immune score (IIS) for predicting poorly differentiated ESCC.

ETV7 limits the antiviral and antitumor efficacy of CD8 T cells by diverting their fate toward exhaustion.

Terminal exhaustion is a critical barrier to antitumor immunity. By integrating and analyzing single-cell RNA-sequencing and single-cell assay for transposase-accessible chromatin with sequencing data, we found that ETS variant 7 (ETV7) is indispensable for determining CD8 T cell fate in tumors. ETV7 introduction drives T cell differentiation from memory to terminal exhaustion, limiting antiviral and antitumor efficacy in male mice.

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.

An mpox quadrivalent mRNA vaccine elicits sustained and protective immunity in mice against lethal vaccinia virus challenge.

Assessing the long-term efficacy of MPXV vaccine candidates is crucial for the global response to the ongoing mpox epidemic. Built upon our previous study of the mpox quadrivalent mRNA vaccine, herein we reported that MPXV-1103 could elicit sustained humoral and cellular immunity in mice, including the induction of MPXV A35/B6/A29/M1-specific IgG antibodies, VACV neutralizing antibodies and activated cytotoxic CD8T cells, which provides 100% protection against lethal VACV challenge even at 280 days after the first vaccination. Our results provide critical insights for orthopoxvirus vaccine development.

Association of Metabolomics With Incidence of Age-Related Macular Degeneration: The UK Biobank Study.

Purpose: The purpose of this study was to identify serum metabolites associated with age-related macular degeneration (AMD) incidence and investigate whether metabolite profiles enhance AMD risk prediction.

Methods: In a prospective cohort study involving 240,317 UK Biobank participants, we assessed the associations of 168 metabolites with AMD incidence using Cox hazards models. Principal component analysis (PCA) captured 90% of the variance in metabolites.

An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control.

CD73, an ectoenzyme responsible for adenosine production, is often elevated in immuno-suppressive tumor environments. Inhibition of CD73 activity holds great promise as a therapeutic strategy for CD73-expressing cancers. In this study, we have developed a therapeutic anti-human CD73 antibody cocktail, HB0045.

Cardiovascular-Liver-Metabolic Health: Recommendations in Screening, Diagnosis, and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease in Cardiovascular Disease via Modified Delphi Approach.

There is a new awareness of the widespread nature of metabolic dysfunction-associated steatotic liver disease (MASLD) and its connection to cardiovascular disease (CVD). This has catalyzed collaboration between cardiologists, hepatologists, endocrinologists, and the wider multidisciplinary team to address the need for earlier identification of those with MASLD who are at increased risk for CVD. The overlap in the pathophysiologic processes and parallel prevalence of CVD, metabolic syndrome, and MASLD highlight the multisystem consequences of poor cardiovascular-liver-metabolic health.

Cell therapy with human IL-10-producing ILC2s limits xenogeneic graft-versus-host disease by inhibiting pathogenic T cell responses.

Interleukin-10 (IL-10)-producing group 2 innate lymphoid cells (ILC2) regulate inflammatory immune responses, yet their therapeutic potential remains largely unexplored. Here, we demonstrate that cell therapy with human ILC2 inhibits pathogenic T cell responses in humanized mouse models of graft-versus-host disease (GVHD), resulting in reduced GVHD severity and improved overall survival without limiting the graft-versus-leukemia effect. ILC2 conferred superior protection from GVHD than IL-10 ILC2s, and blocking IL-10 and IL-4 abrogated ILC2 protective effects, indicating that these cytokines are important for the protective effects of ILC2.

YTHDF2 promotes ATP synthesis and immune evasion in B cell malignancies.

Long-term durable remission in patients with B cell malignancies following chimeric antigen receptor (CAR)-T cell immunotherapy remains unsatisfactory, often due to antigen escape. Malignant B cell transformation and oncogenic growth relies on efficient ATP synthesis, although the underlying mechanisms remain unclear. Here, we report that YTHDF2 facilitates energy supply and antigen escape in B cell malignancies, and its overexpression alone is sufficient to cause B cell transformation and tumorigenesis.

Bed-immersion-ratio variation as an efficient strategy to regulate denitrification efficiency directionally in elemental sulfur packed-bed reactors.

Autotrophic denitrification in sulfur packed-bed reactors (SPBR) has been widely employed for treating municipal secondary effluent. However, the fixed volume of packed sulfur in SPBR restricts the ability to adjust denitrification efficiency in response to fluctuating influent nitrate levels, leading to either effluent standard exceedances or unnecessary sulfur consumption. Here, we proposed a novel method for directionally regulating nitrate removal efficiency (NRE) in SPBR by adjusting the bed-immersion-ratio (BIR).

Targeting viral suppressor of RNAi confers anti-coronaviral activity.

Infections caused by coronaviruses are persistent threats to human health in recent decades, necessitating the development of innovative anti-coronaviral therapies. RNA interference (RNAi) is a conserved cell-intrinsic antiviral mechanism in diverse eukaryotic organisms, including mammals. To counteract, many viruses encode viral suppressors of RNAi (VSRs) to evade antiviral RNAi, implying that targeting VSRs could be a promising strategy to develop antiviral therapies.

Orthostatic and Standing Hypertension and Risk of Cardiovascular Disease.

Background: Orthostatic hypertension is an emerging risk factor for adverse events. Recent consensus statements combine an increase in blood pressure upon standing with standing hypertension, but whether these 2 components have similar risk associations with cardiovascular disease (CVD) is unknown.

Methods: The ARIC study (Atherosclerosis Risk in Communities) measured supine and standing blood pressure during visit 1 (1987-1989).

Simultaneous Development of Antiferromagnetism and Local Symmetry Breaking in a Kagome Magnet (CoFe)Sn.

CoSn and FeSn, two kagome-lattice metals, have recently attracted significant attention as hosts of electronic flat bands and emergent physical properties. However, current understandings of their physical properties are limited to knowledge of the average crystal structure. Here, we report the Fe-doping induced coemergence of the antiferromagentic (AFM) order and local symmetry breaking in (CoFe)Sn.

Effects of Physical Activity and Inactivity on Microvasculature in Children: The Hong Kong Children Eye Study.

Purpose: The purpose of this study was to investigate the effects of physical activity and inactivity on the microvasculature in children, as measured from retinal photographs.

Methods: All participants were from the Hong Kong Children Eye Study, a population-based cross-sectional study of children aged 6 to 8 years. They received comprehensive ophthalmic examinations and retinal photography.

Peli1 Deficiency in Macrophages Attenuates Pulmonary Hypertension by Enhancing Foxp1-Mediated Transcriptional Inhibition of IL-6.

Background: The infiltration of macrophages into the lungs is a common characteristic of perivascular inflammation, contributing to vascular remodeling in pulmonary hypertension (PH). Peli1 (pellino E3 ubiquitin-protein ligase 1) plays a critical role in regulating the production of proinflammatory cytokines and the polarization of macrophages in various diseases. However, the role of Peli1 in PH remains to be investigated.

Circulating tumor-reactive KIRCD8 T cells suppress anti-tumor immunity in patients with melanoma.

Effective anti-tumor immunity is driven by cytotoxic CD8 T cells with specificity for tumor antigens. However, the factors that control successful tumor rejection are not well understood. Here we identify a subpopulation of CD8 T cells that are tumor-antigen-specific and can be identified by KIR expression but paradoxically impair anti-tumor immunity in patients with melanoma.

Genotype-immunophenotype relationships in -mutant AML clonal evolution uncovered by single cell multiomic analysis.

Acute myeloid leukemia (AML) is a multi-clonal disease, existing as a milieu of clones with unique but related genotypes as initiating clones acquire subsequent mutations. However, bulk sequencing cannot fully capture AML clonal architecture or the clonal evolution that occurs as patients undergo therapy. To interrogate clonal evolution, we performed simultaneous single cell molecular profiling and immunophenotyping on 43 samples from 32 -mutant AML patients at different stages of disease.

Spatial multiomic landscape of the human placenta at molecular resolution.

Successful pregnancy relies directly on the placenta's complex, dynamic, gene-regulatory networks. Disruption of this vast collection of intercellular and intracellular programs leads to pregnancy complications and developmental defects. In the present study, we generated a comprehensive, spatially resolved, multimodal cell census elucidating the molecular architecture of the first trimester human placenta.

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.

Nationwide, Couple-Based Genetic Carrier Screening.

Background: Genomic sequencing technology allows for identification of reproductive couples with an increased chance, as compared with that in the general population, of having a child with an autosomal recessive or X-linked genetic condition.

Methods: We investigated the feasibility, acceptability, and outcomes of a nationwide, couple-based genetic carrier screening program in Australia as part of the Mackenzie's Mission project. Health care providers offered screening to persons before pregnancy or early in pregnancy.