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ASB2 inhibits lipid accumulation to promote ILC1 homeostatic fitness and anti-tumor immunity in the mouse liver
Abstract Type 1 innate lymphoid cells (ILC1) are abundant in the adult liver and are pivotal for immune surveillance and modulation, but the regulation of their maintenance and functionality remains underexplored. Here, we re-analyze published single-cell RNA- sequencing data and find increased expression of Asb2 in ILC1s from adult mouse livers. Conditional ablation of Asb2 in NKp46 + cells, depleting ASB2 in ILC1s and NK cells, in mice impairs ILC1 survival and reduces adult liver ILC1 numbers. Proteomics and bulk RNA-sequencing reveal enriched lipid metabolism pathways in ASB2-deficient ILC1s, concomitant with increased lipid storage. Importantly, pharmacological inhibition of lipid synthesis prevents the apoptosis of ASB2-deficient ILC1s in vitro. In a mouse model of colorectal cancer liver metastasis, we find increased ILC1 lipid storage, and conditional Asb2 deficiency in ILC1 cells exacerbates liver metastasis progression. Conversely, inhibiting lipid accumulation in wild-type colorectal cancer-bearing mice prolongs animal survival, potentially via promoting ILC1-mediated anti-tumor immunity. Thus, our study uncovers ASB2-regulated lipid metabolism as a gatekeeper for ILC1 homeostatic fitness and tumor surveillance, highlighting potential ILC1-based therapeutic strategies against liver tumors.
Engineering Tandem Catalysis for Direct CO <sub>2</sub> ‐Enabled N‐Methylaniline Synthesis With a Fixed‐Bed Flow Reaction Process
ABSTRACT Integrated tandem catalysis within a continuous fixed‐bed reactor represents a promising yet underexplored strategy for process intensification in advanced amine synthesis via CO 2 utilization. Here, we demonstrate the direct conversion of nitrobenzene and CO 2 with H 2 into N‐methylaniline in a continuous fixed‐bed reactor over a CuZnZrO x catalyst, achieving 99% conversion and 95% selectivity with stable operation exceeding 100 h. Mechanistic studies identify Cu‐ZnO interfaces in the form of Cu + ‐O v ‐Zn 2‐δ serve as active sites for CO 2 hydrogenation to key intermediate formaldehyde (CH 2 O*), which couples the CO 2 hydrogenation and methylation of aniline derived from nitrobenzene hydrogenation in kinetics. The tandem configuration provides intrinsic heat‐management benefits, recovering 0.341 kg of steam (1.5 MPa, 201°C) per mole of nitrobenzene—far superior to the methanol consumption characteristic of the conventional three‐step route. This work highlights tandem catalysis as an effective reactor‐level strategy that bridges atomic‐scale active‐site engineering with kinetic synergies, advancing continuous‐flow CO 2 valorization toward higher‐value amines.
Mechanical properties of diatomite modified concrete with different moisture contents after high temperature treatment
A computational framework for designing micron-scale crisscross DNA megastructures
Abstract Crisscross polymerization enables the assembly of hundreds of unique DNA origami ‘slats’ into micron-sized structures with nanoscale precision. To design these megastructures, thousands of handle sequences from a fixed library must be assigned to individual slats to encode the desired binding architecture. This complexity presents two major challenges: handles must be selected to minimize parasitic interactions that compete with desired assembly, and the fabrication of hundreds of unique slats creates a substantial logistical burden. Here, we develop a unified framework that standardizes the design and fabrication of crisscross megastructures. We use an evolutionary algorithm to optimize handle assignment and minimize parasitic binding between slats. Together with an expanded handle library, the algorithm enables the assembly of large, multi-layered megastructures that otherwise would be produced at negligible yields. We have released this framework as #-CAD, an open-source graphical application that integrates these algorithms, streamlines laboratory workflows, and makes crisscross DNA origami more broadly accessible.
Glutathione‐Responsive Acyl‐Modifications for Targeted RNA Decaging and Prolonged Protein Synthesis
ABSTRACT A series of disulfide‐based, self‐immolative acyl conjugates have been designed and tested for reversibly protecting the ribose 2’‐hydroxy position of RNA. These modifications were found to be responsive to endogenous glutathione levels for efficient RNA recovery both in solution and cultured cells. Through this modification strategy, we achieve shielding of the biomolecule from both nuclease enzymes and translational machinery, allowing for a tunable release of RNA with improved cellular stability and minimal innate immune activation. The self‐immolative RNA deprotection includes a cyclization step which exhibits differing kinetic profiles based on ring size and electronic properties. Moreover, we demonstrate sustained target protein production for both green‐fluorescent protein and nanoluciferase in cell models. Both acylated mRNA models resulted in significant increases in protein expression compared to the unmodified mRNA control, with increases in protein expression of up to 600% and sustained higher protein expression of modified mRNA samples observed over 120 h in comparison to unmodified RNA. These exciting results highlight the versatility of our approach in the design of next‐generation RNA‐based prodrugs.
Multi-objective optimization framework for dynamic energy management in hybrid microgrids using NSGA-III
Reforging Mitsunobu reaction via sulfoxides-catalyzed C(sp3)-O bond activation of alkanols
Emissive BN‐Embedded Cumulenes: Synthesis and Bidirectional Photocurrent Modulation
ABSTRACT Embedding boron and nitrogen (BN) units into π‐conjugated frameworks provides an effective strategy to tune electronic structures by introducing intrinsic orbital polarization arising from the vacant p orbital of boron and the lone pair of nitrogen. While BN‐embedding has been extensively explored in C(sp 2 ) polyaromatic hydrocarbons (PAHs), its impact on the optoelectronic properties of C(sp)‐rich systems remains underexplored. Here we report air‐ and moisture‐stable BN‐capped sp‐carbon chains that are isoelectronic to [3]‐ and [5]cumulenes ( [n]BN , n = 3, 5). Structural and spectroscopic analyses reveal that BN‐embedding induces pronounced polarization and localizes the high‐frequency skeletal vibrations. Consequently, [n]BN exhibit excimer‐like solid‐state fluorescence, whereas the all‐carbon counterparts remain weakly or non‐emissive. Leveraging the characteristics of excited‐state charge separation and asymmetric carrier injection, heterojunction optoelectronic devices incorporating [3]BN display unique bidirectional photocurrent modulation, establishing BN‐embedding as an effective strategy to tune the electronic structure and emergent functions of C(sp)‐rich systems.
PI3K gene variants are associated with elevated IL-6 levels and COVID-19 severe outcomes in a multicenter study
Population expansion of early Upper Palaeolithic hunter-gatherers triggered cultural complexity on Paleo-Honshu Island, Japan
A CO <sub>2</sub> ‐Mediated Li‐O <sub>2</sub> Battery With 3.3 V Discharge Voltage
ABSTRACT Lithium‐oxygen (Li‐O 2 ) batteries overcome the ion‐intercalation chemistry in lithium‐ion batteries by employing oxygen conversion reactions beyond the solid cathode framework. However, sluggish kinetic limit practical discharge voltages below 2.85 V, establishing a “high capacity, low power output” dilemma that severely compromises achievable energy and power densities. Herein, a CO 2 ‐mediated Li‐O 2 battery (CLOB) is constructed to redefine the oxygen redox chemistry by strategically optimizing gas composition and catalytic architecture, successfully elevating the discharge voltage to 3.30 V comparable to the LiFePO 4 ‐based lithium‐ion batteries. O 2 and CO 2 are gradually reduced to form the intermediates of Li 2 CO 4 and Li 2 C 2 O 6 , and finally Li 2 CO 3 as the discharge product. It leads to an equilibrium voltage of 3.30 V in a two‐electrode electrochemical cell. Furthermore, iron phthalocyanine (FePc) is introduced as a soluble molecular carrier to mitigate the kinetic constraint. The demonstrated FePc‐based CLOB delivers an exceptional discharge voltage of 3.30 V and the assembled pouch cell exhibits a 1.38 Ah capacity with an ultrahigh energy density of 870.1 Wh kg −1 . This voltage enhancement substantially improves energy output and offers a new paradigm for the commercialization of metal‐gas batteries.
LncRNA KIAA0125 promotes the proliferation of Kasumi-1 cells through the miR-4640-5p/KCNQ1 axis with associated changes in the Wnt/β-catenin signaling pathway
High-performance multijunction perovskite LEDs with reduced interconnection loss
Abstract Tandem light-emitting diodes (LEDs) offer advantages in efficiency, brightness and lower the current density for a target brightness, but their implementation in solution-processed perovskite LEDs is limited by interconnection strategies that introduce high voltage penalties and poor robustness. Here we demonstrate a hierarchically structured interconnection layer (ICL) integrating a near-degenerate charge-generation junction with a crystalline-amorphous oxide composite, enabling low-barrier transport and solvent-tolerant stacking with reduced loss. Using this ICL, we realize double-junction perovskite LEDs in which two subunits operate efficiently in series, achieving a peak external quantum efficiency (EQE) of 42.6%, a maximum radiance of 690 W sr −1 m −2 , and low driving voltage. The ICL is compatible with multiple perovskite emitters and supports scalable multijunction integration, yielding multijunction devices with sub-bandgap turn-on voltages and high EQEs exceeding 60%. Our results establish a low-loss interconnection strategy for series-stacked perovskite emitters, providing a practical route toward high-brightness and multi-wavelength perovskite light sources.
A Chemically Fueled Logic Gate With Temporally Programmable Output Delays by Harnessing Transient States of One Molecule in Two Independent Reaction Pathways
ABSTRACT Temporal output delays in logic gates are ubiquitous in biological systems, especially in the nervous system, which sustains the signal transmission with enhanced computational complexity and transmission accuracy. However, temporally programmable output delays in chemically fueled logic gates (CFLGs) have not been achieved in an artificial system. Here, we report a bioinspired CFLG with programmable time delays of the output signal by harnessing transient states of the same molecule in two independent reaction networks. The CFLGs show programmable transient states by regulating reaction networks of urea‐urease and adenosine triphosphate and potato apyrase, respectively. Notably, a transient state with delayed output emerges, mimicking the signal processing in the synaptic delay of biological systems. A self‐destructive information encryption with enhanced coding capacity and safety is achieved in the arrays of CFLGs with spatiotemporally programmable output states. The findings in this work expand the range of non‐equilibrium soft materials and will accelerate the development of innovative materials that can execute exquisite logic functions with enhanced coding capacity and biomimetic time delays.
Evaluation of the performance and temporal variability of large language models in patient education regarding pneumothorax: a seven-day analysis
Reduced melanocortin tone modulates feeding during pregnancy in mice
Andrej Emanuel Cotman
Determination of the most suitable reference gene for transcription analysis of synovial tissue from osteoarthritis patients
Abstract Synovial tissue plays a key role in osteoarthritis (OA) pathogenesis. Gene expression analysis is widely used to investigate underlying pathomechanisms; however, accurate normalization of target mRNA expression depends on the use of stable reference genes. This study evaluated the suitability of common reference genes for determining synovial tissue mRNA expression, considering various factors. In the synovial tissue of 20 patients with end-stage OA, the stability of the expression of 10 reference genes ( GAPDH , RPLP0 , YWHAZ , TBP , PPIA , EEF1A1 , ACTB , HRPT1 , SDHA , and RPL13A ) was evaluated using four different analysis methods (NormFinder, geNorm, the ΔCt method, and Pearson correlation analysis). The most stable genes were identified by means of a subsequent ranking analysis. Both the entire sample pool and various subgroups (sex, age, BMI, and synovitis score) were considered. RPL13A , PPIA , and EEF1A1 were identified as the most stable reference genes overall, with minor variability across subgroups. In contrast, GAPDH proved to be the least suitable reference gene, showing the most variable expression. The stability of the reference gene might be affected by sex, age, and BMI and this should be taken into account.
Renal resistive index-guided mean arterial pressure titration in sepsis: a prospective single-center, single-blind, parallel-group randomized controlled trial
Abstract In sepsis, optimizing mean arterial pressure (MAP) for organ perfusion remains challenging. We conduct a single-center, single-blind, parallel-group randomized controlled trial enrolling 274 sepsis patients to evaluate whether renal resistive index (RRI)-guided MAP titration (MAP titration group, MTG) reduces 28-day all-cause mortality (primary endpoint) compared with conventional treatment (conventional treatment group, CTG). Post-titration, RRI decreases significantly in the MTG versus CTG (0.61 vs. 0.67, P < 0.001). However, 28-day mortality does not differ (25/138 vs. 36/136; RR 0.69, 95% CI 0.44-1.08; P = 0.11). These findings suggest that RRI-guided MAP titration improves renal hemodynamics but does not reduce mortality in this single-center trial; multicenter confirmation is warranted. (Chinese Clinical Trial Registry, ChiCTR2200057136, registered 1 March 2022; https://www.chictr.org.cn/showprojEN.html?proj=153154 ).