Galloyl Dialkyl Lipids Drive Encapsulation of Peptides into Lipid Nanoparticles by Hydrogen Bonding.

The intracellular delivery of peptides and proteins is crucial for various biomedical applications. Lipid nanoparticles (LNPs) have emerged as a promising strategy for delivering peptides to phagocytic cells. However, the diverse physicochemical properties of peptides necessitate tailored formulations.

Pan-inhibition of super-enhancer-driven oncogenic transcription by next-generation synthetic ecteinascidins yields potent anti-cancer activity.

The plasticity of cancer cells facilitates their ability to adopt heterogeneous differentiation states, posing a significant challenge to therapeutic interventions. Specific gene expression programs, driven in part by super-enhancers (SEs), underlie cancer cell states. Here we successfully inhibit SE-driven transcription in phenotypically distinct metastatic melanoma cells using next-generation synthetic ecteinascidins.

Design, synthesis, and biological evaluation of a potent and orally bioavailable FGFRs inhibitor for fibrotic treatment.

Organ fibrosis, such as lung fibrosis and liver fibrosis, is a progressive and fatal disease. Fibroblast growth factor receptors (FGFRs) play an important role in the development and progression of fibrosis. Through scaffold hopping, bioisosteric replacement design, and structure-activity relationship optimization, we developed a series of highly potent FGFRs inhibitors, and the indazole-containing candidate compound A16 showed potent kinase activity comparable to that of AZD4547.

Downregulation of the PI3K/AKT/mTOR/MMP-13 pathway for promoting interface healing via lubricating microspheres.

Interface friction impedes tissue healing and stimulates interface cells to produce matrix metalloproteinases (MMPs); however, the precise mechanisms underlying matrix degradation, and the formation of fibrous scars remain unclear. This research involved the development of interface lubricating microspheres that inhibit the PI3K/AKT/mTOR signaling pathway in tenocytes. This inhibition significantly decreased MMP-13 expression and increased COL-1 production, thereby facilitating interface repair and regeneration.

Comparison of blending and bonding of phytic acid arginine salt and cellulose nanofibers on their synergistic flame-retardant effect in poly (butylene succinate).

In this study, cellulose nanofibers (CNFs) were utilized as a synergistic agent, and combined with phytic acid arginine salt (PaArg) via blending and bonding. The effects of these different binding techniques of CNFs and PaArg on the flame retardant and mechanical properties of poly (butylene succinate) (PBS) were explored. The results indicated that both blended and bonded CNFs and PaArg enabled PBS composites to achieve a UL 94 V-0 rating, with the limiting oxygen index (LOI) value of the composite exceeding 28 %.

Engineered MSC-sEVs as a Versatile Nanoplatform for Enhanced Osteoarthritis Treatment via Targeted Elimination of Senescent Chondrocytes and Maintenance of Cartilage Matrix Metabolic Homeostasis.

Chondrocyte senescence is an important pathogenic factor causing osteoarthritis (OA) progression through persistently producing pro-inflammatory factors. Mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) have shown anti-inflammatory effects in OA models, while persistent existence of senescent chondrocytes still promotes cartilage destruction. Therefore, improving the targeted elimination ability on senescent chondrocytes is required to facilitate the translation of MSC-sEVs in OA treatment.

5,7-Dihydroxyflavone acts on eNOS to achieve hypotensive effects in spontaneously hypertensive rats.

Hypertension is one of the most serious chronic diseases. This study will focus on the systemic antihypertensive mechanisms of 5,7-dihydroxyflavone from in silico simulations to in vivo validations. In-silico studies were applied by network pharmacology, molecular docking, and molecular dynamic simulation.

Phasor-FSTM: a new paradigm for multicolor super-resolution imaging of living cells based on fluorescence modulation and lifetime multiplexing.

Multicolor microscopy and super-resolution optical microscopy are two widely used techniques that greatly enhance the ability to distinguish and resolve structures in cellular imaging. These methods have individually transformed cellular imaging by allowing detailed visualization of cellular and subcellular structures, as well as organelle interactions. However, integrating multicolor and super-resolution microscopy into a single method remains challenging due to issues like spectral overlap, crosstalk, photobleaching, phototoxicity, and technical complexity.

Autocatalytic Interfacial Synthesis of Self-Standing Amide-Linked Covalent Organic Framework Membranes.

The synthesis of crystalline covalent organic frameworks (COFs) has in principle relied on reversible dynamic chemistry. A general method to synthesize irreversibly bonded COFs is urgently demanded for driving the COF chemistry to a new era. Here we report a universal two-step method for the straightforward synthesis of irreversibly amide-linked COF (AmCOF) membranes by autocatalytic interfacial polymerization (AIP).

Alarmins and their pivotal role in the pathogenesis of spontaneous abortion: insights for therapeutic intervention.

Alarmins are a class of molecules released when affected cells damaged or undergo apoptosis. They contain various chemotactic and immunomodulatory proteins or peptides. These molecules regulate the immune response by interacting with pattern recognition receptors (PRRs) and play important roles in inflammatory response, tissue repair, infection defense, and cancer treatment.

Development and validation of a nomogram for failure to collect oocytes in POSEIDON Groups 3 and 4 undergoing IVF/ICSI treatment.

This study aimed to develop and validate a predictive model for failure to collect oocytes in the Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) Groups 3 and 4 during their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle. A retrospective analysis was conducted on patients in POSEIDON Groups 3 and 4 who underwent their first IVF/ICSI cycle at our center from January 2016 to December 2023. A total of 2,373 patients were randomly assigned to the training or validation cohort at a ratio of 6:4.

Plant Growth-Promoting Rhizobacteria HL14-3 Inoculation Enhances Drought Tolerance in Cucumber by Triggering Abscisic Acid-Mediated Stomatal Closure.

Drought limits crop growth and yield. Inoculation with plant growth-promoting rhizobacteria (PGPR) emerges as a promising strategy to protect crops against drought. However, the number of drought-tolerant PGPR is limited, and the regulation mechanisms remain elusive.

Involvement of endogenous IAA and ABA in the regulation of arbuscular mycorrhizal fungus on rooting of tea plant (Camellia sinensis L.) cuttings.

Background: Adventitious root (AR) formation is the key step for successful cutting propagation of tea plants (Camellia sinensis L.). Studies showed that arbuscular mycorrhizal fungus (AMF) can promote the rooting ability, and auxin pathway in basal stem of cuttings was involved in this process.

Multiple attention channels aggregated network for multimodal medical image fusion.

Background: In clinical practices, doctors usually need to synthesize several single-modality medical images for diagnosis, which is a time-consuming and costly process. With this background, multimodal medical image fusion (MMIF) techniques have emerged to synthesize medical images of different modalities, providing a comprehensive and objective interpretation of the lesion.

Purpose: Although existing MMIF approaches have shown promising results, they often overlook the importance of multiscale feature diversity and attention interaction, which are essential for superior visual outcomes.

Geographic and socioeconomic disparities in mortality burden attributable to long-term exposure to NO across 231 cities in China from 2015 to 2019.

Research on geographic and socioeconomic disparities of NO attributed mortality burden is limited. This study aims to quantify the geographic and socioeconomic differences in the association between long-term exposure to NO and mortality burden in China. We estimated the all-cause mortality burden of adults over 16 years old attributable to NO exposure above 10 µg/m for 231 Chinese cities from 2015 to 2019, and geographic and socioeconomic differences .

Long-Lasting Protection and Dose Optimization of MPXV Polyvalent Mpox mRNA Vaccines Against Lethal Vaccinia Virus Challenge in Mice.

The outbreak of clade II monkeypox virus (MPXV) and the additional outbreak in Central Africa of clade I virus from 2023 have attracted worldwide attention. The development of a scalable and effective vaccine against the ongoing epidemic of mpox is urgently needed. We previously constructed two bivalent MPXV mRNA vaccines, LBA (B6R-A29L) and LAM (A35R-M1R), and a quadrivalent mRNA vaccine, LBAAM (B6R-A35R-A29L-M1R).

Effects of potassium fertilization on grain yield, taste quality, and starch characteristics of rice (Oryza sativa L.) grain.

Background: There is limited information on the effect of potassium (K) on the taste quality of rice. Field experiments with five K fertilizer application rates (0, 60, 120, 180, and 240 kg KO ha) were conducted in 2019 and 2020 using two cultivars (Xiadao No. 1 and Shenliangyou 5814) to study the effects of K fertilization on grain yield, taste quality, starch components, and protein components in grains.

Case report: A novel third-generation anti-CD19/CD22 CAR T-cells combined with auto-HSCT for relapsed Burkitt lymphoma.

This study explores a novel therapeutic strategy for relapsed/refractory (R/R) Burkitt lymphoma (BL) by integrating autologous hematopoietic stem cell transplantation (ASCT) with tandem anti-CD19/CD22 chimeric antigen receptor (CAR) T cell therapy. A 20-year-old Asian male with refractory BL, whose lymphoma had not responded to multiple chemoimmunotherapy regimens, received myeloablative ASCT followed three days later by infusion of a novel third-generation CAR T cells engineered with CD28 and CD3ζ signaling domains, along with a TLR2 costimulatory domain. This resulted in sustained complete remission at the 306-day follow-up, without experiencing any severe complications.

Nanogel imprinting improving affinity and selectivity of domain-limited ssDNA aptamer to Pb: Interaction mechanisms revealed by molecular dynamics simulation.

Aptamer conformations are susceptible to environmental conditions, which makes it difficult to achieve stable targets detection in complex environments with aptasensors. Imprinting strategy was proposed to immobilize the specific conformation of aptamers, aiming to enhance their recognition anti-interference. However, it is mechanistically unclear how the imprinted polymers affect aptamers' recognition, which limits application of the strategy.

An Orientation-Enhanced Interlayer Enables Efficient Sn-Pb Binary Perovskite Solar Cells and All-Perovskite Tandem Solar Cells with High Fill Factors.

The performance of narrow-bandgap (NBG) perovskite solar cells (PSCs) is limited by the severe nonradiative recombination and carrier transport barrier at the electron selective interface. Here, we reveal the importance of the molecular orientation for effective defect passivation and protection for Sn at the perovskite/C interface. We constructed an internally self-anchored dual-passivation (ISADP) layer, where the orientation of PCBM can be significantly enhanced by the interaction between ammonium and carbonyl groups.

Decoding the regulatory role of ATP synthase inhibitory factor 1 (ATPIF1) in Wallerian degeneration and peripheral nerve regeneration.

ATP synthase inhibitory factor 1 (ATPIF1), a key modulator of ATP synthase complex activity, has been implicated in various physiological and pathological processes. While its role is established in conditions such as hypoxia, ischemia-reperfusion injury, apoptosis, and cancer, its involvement remains elusive in peripheral nerve regeneration. Leveraging ATPIF1 knockout transgenic mice, this study reveals that the absence of ATPIF1 impedes neural structural reconstruction, leading to delayed sensory and functional recovery.

Per- and polyfluoroalkyl substances exacerbate the prevalence of plasmid-borne antibiotic resistance genes by enhancing natural transformation,in vivo stability, and expression in bacteria.

Per- and polyfluoroalkyl substances (PFAS) as emerging pollutants are ubiquitous and disrupt biological processes across water boundaries. Their coexistence with antibiotic resistance genes (ARGs) in water matrix is associated with the spread of ARGs via conjugative transfer, posing a threat to public health. However, their role in natural transformation-where microorganisms actively take up extracellular ARGs (eARGs)-and the subsequent persistence and expression of ARGs after transformation remains poorly understood.

Dual-signal, one-step simultaneous monitoring of genetic mutation in multiple gene regions using FeO@Au and MOF.

Genetic testing plays a crucial role in guiding individualized medication, however, detecting fine structural mutations in genes continues to present significant challenges. This study introduces a dual-signal fluorescence system, termed FeO@Au@PEG@P1+MOF@P, that integrates magnetic separation of FeO@Au with NH-MIL-88 (MOF) catalysis. Initially, the specimen (T1/T2) facilitated the formation of a specific complex (FeO@Au@PEG@P1+T1/T2) with FeO@Au@PEG@P1.