Biochemical characterization and antifungal activity of a recombinant ß-1,3-glucanase FlGluA from Flavobacterium sp. NAU1659.

ß-1,3-glucanases can degrade ß-1,3-glucoside bonds in ß-glucan which is the main cell-wall component of most of fungi, and have the crucial application potential in plant protection and food processing. Herein, a ß-1,3-glucanase FlGluA from Flavobacterium sp. NAU1659 composed of 333 amino acids with a predicted molecular mass of 36.6 kDa was expressed in Escherichia coli BL21, purified and characterized. The deduced amino acid sequence of FlGluA showed the high identity with the ß-1,3-glucanase belonging to glycoside hydrolase (GH) family 16. Enzymological characterization indicated FlGluA had the highest activity on zymosan A, with a specific activity of 3.87 U/mg, followed by curdlan (1.16 U/mg) and pachymaran (0.88 U/mg). It exhibited optimal catalytic activity at the pH 5.0 and 40 °C, and was stable when placed at 4 °C for 12 h in the range of pH 3.0-8.0 or at a temperature below 50 °C for 3 h. Its catalytic activity was enhanced by approximately 36 % in the presence of 1 mM Cr3+. The detection of thin-layer chromatography and mass spectrometry showed FlGluA hydrolyzed zymosan A mainly to glucose and disaccharide, and trace amounts of tetrasaccharide and pentasaccharide, however, it had no action on laminaribiose, indicating its endo-ß-1,3-glucanase activity. The mycelium growth of F. oxysporum treated by FlGluA was inhibited, with approximately 37 % of inhibition rate, revealing the potential antifungal activity of the enzyme. These results revealed the hydrolytic properties and biocontrol activity of FlGluA, laying a crucial foundation for its potential application in agriculture and industry.

Quantum Computation of Conical Intersections on a Programmable Superconducting Quantum Processor.

Conical intersections (CIs) are pivotal in many photochemical processes. Traditional quantum chemistry methods, such as the state-average multiconfigurational methods, face computational hurdles in solving the electronic Schrödinger equation within the active space on classical computers. While quantum computing offers a potential solution, its feasibility in studying CIs, particularly on real quantum hardware, remains largely unexplored. Here, we present the first successful realization of a hybrid quantum-classical state-average complete active space self-consistent field method based on the variational quantum eigensolver (VQE-SA-CASSCF) on a superconducting quantum processor. This approach is applied to investigate CIs in two prototypical systems─ethylene (C2H4) and triatomic hydrogen (H3). We illustrate that VQE-SA-CASSCF, coupled with ongoing hardware and algorithmic enhancements, can lead to a correct description of CIs on existing quantum devices. These results lay the groundwork for exploring the potential of quantum computing to study CIs in more complex systems in the future.

Photoluminescence Enhancement of 0D Organic-Inorganic Metal Halides via Aggregation-Induced Emission and Halide Substitution.

0D organic-inorganic metal halides (OIMHs) provide unprecedented versatility in structures and photoluminescence properties. Here, a series of bluish-white emissive 0D OIMHs, (TPE-TPP)2Sb2BrxCl8-x (x = 1.16 to 8), are prepared by assembling the 1-triphenylphosphonium-4-(1,2,2-triphenylethenyl)benzene cation (TPE-TPP)+ with antimony halides anions. Based on experimental characterizations and theoretical calculations, the emission of the 0D OIMHs are attributed to the fluorescence of the organic cations with aggregation-induced emission (AIE) properties. The 0D structure minimized the molecular motion and intermolecular interactions between (TPE-TPP)+ cations, effectively suppressing the non-radiative recombination processes. Consequently, the photoluminescence quantum efficiency (PLQE) of (TPE-TPP)2Sb2Br1.16Cl6.84 is significantly enhanced to 55.4% as compared to the organic salt (TPE-TPP)Br (20.5%). The PLQE of (TPE-TPP)2Sb2BrxCl8-x can also be readily manipulated by halide substitution, due to the competitive processes between non-radiative recombination on the inorganic moiety and the energy transfer from inorganic to organic. In addition, electrically driven light-emitting diodes (LEDs) are fabricated based on (TPE-TPP)2Sb2Br1.16Cl6.84 emitter, which exhibited bluish-white emission with a maximum external quantum efficiency (EQE) of 1.1% and luminance of 335 cd m-2. This is the first report of electrically driven LED based on 0D OIMH with bluish-white emission.

Ambient hydrogenation of solid aromatics enabled by a high entropy alloy nanocatalyst.

Hydrogenation is a versatile chemical process with significant applications in various industries, including food production, petrochemical refining, pharmaceuticals, and hydrogen carriers/safety. Traditional hydrogenation of aromatics, hindered by the stable π-conjugated phenyl ring structures, typically requires high temperatures and pressures, making ambient hydrogenation a grand challenge. Herein, we introduce a PdPtRuCuNi high entropy alloy (HEA) nanocatalyst, achieving an exceptional 100% hydrogenation of carbon-carbon unsaturated bonds, including alkynyl and phenyl groups, in solid 1,4-bis(phenylethynyl)benzene (DEB) at 25 °C under ≤1 bar H2 and solventless condition. This results in a threefold higher hydrogen uptake for DEB-contained composites compared to conventional Pd catalysts, which can only hydrogenate the alkynyl groups with a ~ 27% conversion of DEB. Our experimental results, complemented by theoretical calculations, reveal that PdPtRu alloy is highly active and crucial in enabling the hydrogenation of phenyl groups, while all five elements work synergistically to regulate the reaction rate. Remarkably, this newly developed catalyst also achieves nearly 100% reactivity for ambient hydrogenation of a broad range of aromatics, suggesting its universal effectiveness. Our research uncovers a novel material platform and catalyst design principle for efficient and general hydrogenation. The multi-element synergy in HEA also promises unique catalytic behaviors beyond hydrogenation applications.

SRGN promotes macrophage recruitment through CCL3 in osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a degenerative disease that affects synovial joints and leads to significant pain and disability, particularly in older adults. Infiltration of macrophages plays a key role in the progression of OA. However, the mechanisms underlying macrophage recruitment in OA are not fully understood. METHODS: The Serglycin (SRGN) expression pattern was analyzed, along with its association with macrophage infiltration in OA, using bioinformatic methods. SRGN expression in chondrocytes was altered by small interfering RNA (siRNA) and plasmids. Conditioned media (CM) was obtained from transfected chondrocytes to establish a co-culture model of chondrocytes and THP-1 derived macrophages. The impact of SRGN on macrophage recruitment was evaluated using a transwell assay. Furthermore, the regulatory effect of SRGN on CCL3 was validated through qPCR, WB, and ELISA experiments. RESULTS: In OA patients, the upregulation of SRGN positively correlated with K-L grade and macrophage infiltration. It was found that SRGN expression and secretion were up-regulated in OA and that it can promote macrophage migration in vitro. Further investigation showed that SRGN affects macrophage migration by regulating the expression of CCL3. CONCLUSION: SRGN in chondrocytes plays a role in promoting the recruitment of THP-1 derived macrophages in vitro by regulating production of CCL3.

Clinical Study of Carbon Dioxide Laser and Pelvic Floor Function Exercise for Urinary Incontinence Complicated by Genitourinary Syndrome of Menopause.

BACKGROUND: Urinary incontinence is common in patients with genitourinary syndrome of menopause (GSM). A retrospective cohort study was conducted to analyse the clinical efficacy of carbon dioxide laser combined with pelvic floor functional exercise for GSM with urinary incontinence, aiming to provide evidence for its clinical treatment. METHODS: Patients diagnosed with GSM and urinary incontinence and admitted to our hospital from January 2021 to December 2022 were included and allocated to a control group (pelvic floor function exercise) and combined group (carbon dioxide laser combined with pelvic floor function exercise). Confounding factors among the groups were balanced by the propensity score matching method. The clinical efficacy, GSM scale scores, urinary indicators, urinary incontinence quality of life scale (I-QOL) scores and the degree of urinary incontinence of the groups were compared. RESULTS: A total of 192 patients were included in this study, and 36 cases were included in each group after the propensity scores were matched. No statistical difference in baseline data was found between the groups (p > 0.05). The combined group had higher total effective rate and I-QOL scores but lower GSM symptom scale scores than the control group. Urination during daytime and nighttime was less frequent in the combined group than in the control group, which showed a lower degree of urinary incontinence (p < 0.05). CONCLUSIONS: Combining carbon dioxide laser treatment with pelvic floor exercises is potentially effective for patients with GSM and urinary incontinence. This combined approach not only alleviated GSM and urinary incontinence symptoms but also reduced the severity of urinary incontinence, promoted bladder function recovery and enhanced overall quality of life.

ß-sitosterol alleviates high fatty acid-induced lipid accumulation in calf hepatocytes by regulating cholesterol metabolism.

A significant reduction in plasma concentration of cholesterol during early lactation is a common occurrence in high-yielding dairy cows. An insufficient synthesis of cholesterol in the liver has been linked to lipid accumulation caused by high concentrations of fatty acids during negative energy balance (NEB). As ruminant diets do not provide quantitative amounts of cholesterol for absorption, phytosterols such as ß-sitosterol may serve to mitigate the shortfall in cholesterol within the liver during NEB. To gain mechanistic insights, primary hepatocytes were isolated from healthy female 1-day old calves for in vitro studies with or without 1.2 mM fatty acids (FA) to induce metabolic stress. Furthermore, hepatocytes were treated with 50 µM ß-sitosterol with or without FA. Data were analyzed by one-way ANOVA with subsequent Bonferroni correction. Results revealed that calf hepatocytes treated with FA had greater content of non-esterified fatty acids (NEFA) and triacylglycerol (TAG), and greater mRNA and protein abundance of the lipid synthesis-related SREBF1 and FASN. In contrast, mRNA and protein of CPT1A (fatty acid oxidation) and the cholesterol metabolism-related targets SREBF2, HMGCR, ACAT2, APOA1, ABCA1 and ABCG5 was lower. Content of the antioxidant-related glutathione (GSH) and activities of superoxide dismutase (SOD) also was lower. Compared with FA challenge alone, 50 µM ß-sitosterol led to greater mRNA and protein abundance of SREBF2, HMGCR, ACAT2 and ABCG5, and greater content of GSH and activity of SOD. In contrast, compared with the FA group, the mRNA and protein abundance of SREBF1 and ACC1 and the content of TAG and NEFA in the ß-sitosterol + FA group were lower. Overall, ß-sitosterol can promote cholesterol metabolism and reduce oxidative stress while reducing lipid accumulation in hepatocytes challenged with high concentrations of fatty acids.

Interactions between LAMP3+ dendritic cells and T-cell subpopulations promote immune evasion in papillary thyroid carcinoma.

BACKGROUND: The incidence of papillary thyroid cancer (PTC) continues to rise all over the world, 10-15% of the patients have a poor prognosis. Although immunotherapy has been applied in clinical practice, its therapeutic efficacy remains far from satisfactory, necessitating further investigation of the mechanism of PTC immune remodeling and exploration of novel treatment targets. METHODS: This study conducted a single-cell RNA sequencing (scRNA-seq) analysis using 18 surgical tissue specimens procured from 14 patients diagnosed with adjacent tissues, non-progressive PTC or progressive PTC. Key findings were authenticated through spatial transcriptomics RNA sequencing, immunohistochemistry, multiplex immunohistochemistry, and an independent bulk RNA-seq data set containing 502 samples. RESULTS: A total of 151,238 individual cells derived from 18 adjacent tissues, non-progressive PTC and progressive PTC specimens underwent scRNA-seq analysis. We found that progressive PTC exhibits the following characteristics: a significant decrease in overall immune cells, enhanced immune evasion of tumor cells, and disrupted antigen presentation function. Moreover, we identified a subpopulation of lysosomal associated membrane protein 3 (LAMP3+) dendritic cells (DCs) exhibiting heightened infiltration in progressive PTC and associated with advanced T stage and poor prognosis of PTC. LAMP3+ DCs promote CD8+ T cells exhaustion (mediated by NECTIN2-TIGIT) and increase infiltration abundance of regulatory T cells (mediated by chemokine (C-C motif) ligand 17 (CCL17)-chemokine (C-C motif) receptor 4 (CCR4)) establishing an immune-suppressive microenvironment. Ultimately, we unveiled that progressive PTC tumor cells facilitate the retention of LAMP3+ DCs within the tumor microenvironment through NECTIN3-NECTIN2 interactions, thereby rendering tumor cells more susceptible to immune evasion. CONCLUSION: Our findings expound valuable insights into the role of the interaction between LAMP3+ DCs and T-cell subpopulations and offer new and effective ideas and strategies for immunotherapy in patients with progressive PTC.

Effects of 17ß-Estradiol Pollution on Microbial Communities and Methane Emissions in Aerobic Water Bodies.

17ß-Estradiol (E2) is a widely present trace pollutant in aquatic environments. However, its impact on microbial communities in aerobic lake waters, which are crucial for methane (CH4) production, remains unclear. This study conducted an E2 contamination experiment by constructing laboratory-simulated aerobic microecosystems. Using 16S rRNA high-throughput sequencing, the effects of E2 on bacterial and archaeal communities were systematically examined. Combined with gas chromatography, the patterns and mechanisms of E2's impact on CH4 emissions in aerobic aquatic systems were uncovered for the first time. Generally, E2 contamination increased the randomness of bacterial and archaeal community assemblies and weakened microbial interactions. Furthermore, changes occurred in the composition and ecological functions of bacterial and archaeal communities under E2 pollution. Specifically, two days after exposure to E2, the relative abundance of Proteobacteria in the low-concentration (L) and high-concentration (H) groups decreased by 6.99% and 4.01%, respectively, compared to the control group (C). Conversely, the relative abundance of Planctomycetota was 1.81% and 1.60% higher in the L and H groups, respectively. E2 contamination led to an increase in the relative abundance of the methanogenesis functional group and a decrease in that of the methanotrophy functional group. These changes led to an increase in CH4 emissions. This study comprehensively investigated the ecotoxicological effects of E2 pollution on microbial communities in aerobic water bodies and filled the knowledge gap regarding aerobic methane production under E2 contamination.

Deeply Lithiated Carbonaceous Materials for Great Lithium Metal Protection in All-Solid-State Batteries.

Protection of lithium (Li) metal electrode is a core challenge for all-solid-state Li metal batteries (ASSLMBs). Carbon materials with variant structures have shown great effect of Li protection in liquid electrolytes, however, can accelerate the solid-state electrolyte (SE) decomposition owing to the high electronic conductivity, seriously limiting their application in ASSLMBs. Here, a novel strategy is proposed to tailor the carbon materials for efficient Li protection in ASSLMBs, by in situ forming a rational niobium-based Li-rich disordered rock salt (DRS) shell on the carbon materials, providing a favorable percolating Li+ diffusion network for speeding the carbon lithiation, and enabling simultaneously improved lithiophilicity and reduced electronic conductivity of the carbon structure at deep lithiation state. Using the proposed strategy, different carbon materials, such as graphitic carbon paper and carbon nanotubes, are tailored with great ability to speed the interfacial kinetics, homogenize the Li plating/stripping processes, and suppress the SE decompositions, enabling much improved performances of ASSLMBs under various conditions approaching the practical application. This strategy is expected to create a novel roadmap of Li protection for developing reliable high-energy-density ASSLMBs.

Large Organic Polar Molecules Tailored Electrode Interfaces for Stable Lithium Metal Battery.

Lithium (Li) metal batteries (LMBs) are deemed as ones of the most promising energy storage devices for next electrification applications. However, the uneven Li electroplating process caused by the diffusion-limited Li+ transportation at the Li metal surface inherently promotes the formation of dendritic morphology and instable Li interphase, while the sluggish Li+ transfer kinetic can also cause lithiation-induced stress on the cathode materials suffering from serious structural stability. Herein, a novel electrolyte designing strategy is proposed to accelerate the Li+ transfer by introducing a trace of large organic polar molecules of lithium phytate (LP) without significantly altering the electrolyte structure. The LP molecules can afford a competitive solvent attraction mechanism against the solvated Li+, enhancing both the bulk and interfacial Li+ transfer kinetic, and creating better anode/cathode interfaces to suppress the side reactions, resulting in much improved cycling efficiency of LMBs. Using LP-based electrolyte, the performance of LMB pouch cell with a practical capacity of ~1.5 Ah can be improved greatly. This strategy opens up a novel electrolyte designing route for reliable LMBs.

S100A12 is involved in the pathology of osteoarthritis by promoting M1 macrophage polarization via the NF-κB pathway.

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease that affects millions worldwide. Synovitis and macrophage polarization are important factors in the development of OA. However, the specific components of synovial fluid (SF) responsible for promoting macrophage polarization remain unclear. METHODS: Semi-quantitative antibody arrays were used to outline the proteome of SF. Differential expression analysis and GO/KEGG were performed on the obtained data. Immunohistochemistry and ELISA were used to investigate the relationship between SF S100A12 levels and synovitis levels in clinalclinical samples. In vitro cell experiments were conducted to investigate the effect of S100A12 on macrophage polarization. Public databases were utilized to predict and construct an S100A12-centered lncRNA-miRNA-mRNA competing endogenous RNA network, which was preliminarily validated using GEO datasets. RESULTS: The study outlines the protein profile in OA and non-OA SF. The results showed that the S100A12 level was significantly increased in OA SF and inflammatory chondrocytes. The OA synovium had more severe synovitis and higher levels of S100A12 than non-OA synovium. Exogenous S100A12 upregulated the levels of M1 markers and phosphorylated p65 and promoted p65 nuclear translocation, while pretreatment with BAY 11-7082 reversed these changes. It was also discovered that LINC00894 was upregulated in OA and significantly correlated with S100A12, potentially regulating S100A12 expression by acting as a miRNA sponge. CONCLUSIONS: This study demonstrated that S100A12 promotes M1 macrophage polarization through the NF-κB pathway, and found that LINC00894 has the potential to regulate the expression of S100A12 as a therapeutic approach.

Consensus-Agent Deep Reinforcement Learning for Face Aging.

Face aging tasks aim to simulate changes in the appearance of faces over time. However, due to the lack of data on different ages under the same identity, existing models are commonly trained using mapping between age groups. This makes it difficult for most existing aging methods to accurately capture the correspondence between individual identities and aging features, leading to generating faces that do not match the real aging appearance. In this paper, we re-annotate the CACD2000 dataset and propose a consensus-agent deep reinforcement learning method to solve the aforementioned problem. Specifically, we define two agents, the aging process agent and the aging personalization agent, and model the task of matching aging features as a Markov decision process. The aging process agent simulates the aging process of an individual, while the aging personalization agent calculates the difference between the aging appearance of an individual and the average aging appearance. The two agents iteratively adjust the matching degree between the target aging feature and the current identity through a form of synergistic cooperation. Extensive experimental results on four face aging datasets show that our model achieves convincing performance compared to the current state-of-the-art methods.

HeadDiff: Exploring Rotation Uncertainty With Diffusion Models for Head Pose Estimation.

In this paper, we propose a probabilistic regression diffusion model for head pose estimation, dubbed HeadDiff, which typically addresses the rotation uncertainty, especially when faces are captured in wild conditions. Unlike conventional image-to-pose methods which cannot explicitly establish the rotational manifold of head poses, our HeadDiff aims to ensure the pose rotation via the diffusion process and in parallel, refine the mapping process iteratively. Specifically, we initially formulate the head pose estimation problem as a reverse diffusion process, defining a paradigm for progressive denoising on the manifold, which explores the uncertainty by decomposing the large gap into intermediate steps. Moreover, our HeadDiff is equipped with an isotropic Gaussian distribution by encoding the incoherence information in our rotation representation. Finally, we learn the facial relationship of nearest neighbors with a cycle-consistent constraint for robust pose estimation versus diverse shape variations. Experimental results on multiple datasets demonstrate that our proposed method outperforms existing state-of-the-art techniques without auxiliary data.

Synergistic synthesis of gold nanoflowers as upconversion near-infrared nanoprobe energy acceptor and recognition unit for improved hydrogen sulfide sensing.

A highly sensitive and selective upconversion near-infrared (NIR) fluorescence and colorimetric dual readout hydrogen sulfide (H2S) nanoprobe was constructed based on the excellent NIR fluorescence emission performance of upconversion nanomaterials (UCNPs), the specific recognition effect of synergistically synthesized gold nanoflowers (trypsin-stabled AuNFs (Try-AuNFs)) and the effective NIR fluorescence quenching capability. In this assay, the sensing strategy included three processes. First of all, the synthesized UCNPs can emit 803 nm NIR fluorescence when they were excited by 980 nm excitation light. Secondly, as a result of the principle of fluorescence resonance energy transfer (FRET), Try-AuNFs can effectively quench the NIR fluorescence of UCNPs at 803 nm, which can effectively improve the signal-to-background ratio of nanoprobes, thereby improving the sensitivity of the probes. Thirdly, in the presence of H2S, the Try protective layer on the surface of Try-AuNFs was specifically penetrated, which will subsequently cleave Try-AuNFs via the strong S-Au bond. As such, the NIR fluorescence of UCNPs will be restored, achieving high selectivity and sensitivity detection of H2S. Under optimized conditions, the linear response range of H2S was 0.1-300 µM, and the detection limit was 53 nM. It is worth noting that the Try on the surface of Try-AuNFs via the synergistic effect can increase the steric hindrance of the probe, and this can effectively prevent the interaction between the probe with biothiols (cysteine (Cys), homocysteine (Hcy)) and other natural amino acids (non-thiol-containing) with resultant in the high selectivity regarding the detection of H2S in human serum, which is unlikely to be achieved by AuNFs synthesized by the gold seed method (Se-AuNFs). This work not only provided a new type of UCNPs fluorescence quencher and recognition unit, but also exemplified that the use of the physical properties (steric hindrance) of protein ligands on the surface of nanoflowers can improve the specificity of the probe. This will provide new ideas for the design of other nanoprobes.

Efficacy of respiratory rehabilitation in patients with COVID-19: a retrospective study.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of confirmed cases and deaths globally. The purpose of this study was to investigate the therapeutic effect of airway clearance technology combined with prone ventilation on patients infected with COVID-19. METHODS: 38 patients with COVID-19 (severe) who were treated in the intensive rehabilitation group of Shengli Oilfield Central Hospital. They were randomly divided into a control group and an observation group. The control group received prone position ventilation intervention, and the observation group received airway clearance technology combined with prone position ventilation intervention. The changes of oxygen and index, procalcitonin (PCT), interleukin-6 (IL-6) and chest X-ray image indexes were compared between the two groups. RESULT: There was no significant difference in age, gender and other general data between the control group and the observation group. The results showed that oxygen index, PCT, IL-6 and chest X-ray image index in the observation group were better than that indexes in the control group. CONCLUSION: Airway clearance technology combined with prone ventilation intervention in patients with COVID-19 can improve the total effective rate and oxygenation index, improve the inflammatory indicators and respiratory function of patients. And it may be widely promoted and used in the treatment of patients with COVID-19 (severe).

Physics-Constrained Hardware-Efficient Ansatz on Quantum Computers That Is Universal, Systematically Improvable, and Size-Consistent.

Variational wave function ansätze are at the heart of solving quantum many-body problems in physics and chemistry. Previous designs of hardware-efficient ansatz (HEA) on quantum computers are largely based on heuristics and lack rigorous theoretical foundations. In this work, we introduce a physics-constrained approach for designing HEA with rigorous theoretical guarantees by imposing a few fundamental constraints. Specifically, we require that the target HEA to be universal, systematically improvable, and size-consistent, which is an important concept in quantum many-body theories for scalability but has been overlooked in previous designs of HEA. We extend the notion of size-consistency to HEA and present a concrete realization of HEA that satisfies all these fundamental constraints while only requiring linear qubit connectivity. The developed physics-constrained HEA is superior to other heuristically designed HEA in terms of both accuracy and scalability, as demonstrated numerically for the Heisenberg model and some typical molecules. In particular, we find that restoring size-consistency can significantly reduce the number of layers needed to reach a certain accuracy. In contrast, the failure of other HEA to satisfy these constraints severely limits their scalability to larger systems with more than 10 qubits. Our work highlights the importance of incorporating physical constraints into the design of HEA for efficiently solving many-body problems on quantum computers.

Mage transposon: a novel gene delivery system for mammalian cells.

Transposons, as non-viral integration vectors, provide a secure and efficient method for stable gene delivery. In this study, we have discovered Mage (MG), a novel member of the piggyBac(PB) family, which exhibits strong transposability in a variety of mammalian cells and primary T cells. The wild-type MG showed a weaker insertion preference for near genes, transcription start sites (TSS), CpG islands, and DNaseI hypersensitive sites in comparison to PB, approaching the random insertion pattern. Utilizing in silico virtual screening and feasible combinatorial mutagenesis in vitro, we effectively produced the hyperactive MG transposase (hyMagease). This variant boasts a transposition rate 60% greater than its native counterpart without significantly altering its insertion pattern. Furthermore, we applied the hyMagease to efficiently deliver chimeric antigen receptor (CAR) into T cells, leading to stable high-level expression and inducing significant anti-tumor effects both in vitro and in xenograft mice models. These findings provide a compelling tool for gene transfer research, emphasizing its potential and prospects in the domains of genetic engineering and gene therapy.

Superior Strength, Toughness, and Damage-Tolerance Observed in Microlattices of Aperiodic Unit Cells.

Characterized by periodic cellular unit cells, microlattices offer exceptional potential as lightweight and robust materials. However, their inherent periodicity poses the risk of catastrophic global failure. To address this limitation, a novel approach, that is to introduce microlattices composed of aperiodic unit cells inspired by Einstein's tile, where the orientation of cells never repeats in the same orientation is proposed. Experiments and simulations are conducted to validate the concept by comparing compressive responses of the aperiodic microlattices with those of common periodic microlattices. Indeed, the microlattices exhibit stable and progressive compressive deformation, contrasting with catastrophic fracture of periodic structures. At the same relative density, the microlattices outperform the periodic ones, exhibiting fracture strain, energy absorption, crushing stress efficiency, and smoothness coefficients at least 830%, 300%, 130%, and 160% higher, respectively. These improvements can be attributed to aperiodicity, where diverse failure thresholds exist locally due to varying strut angles and contact modes during compression. This effectively prevents both global fracture and abrupt stress drops. Furthermore, the aperiodic microlattice exhibits good damage tolerance with excellent deformation recoverability, retaining 76% ultimate stress post-recovery at 30% compressive strain. Overall, a novel concept of adopting aperiodic cell arrangements to achieve damage-tolerant microlattice metamaterials is presented.

Coated sodium butyrate and vitamin D3 supplementation improve gut health through influencing intestinal immunity, barrier, and microflora in early-stage broilers.

BACKGROUND: Intestinal development and function are critical to maintaining sustained broiler growth. The present study aimed to evaluate the effects of coated sodium butyrate (CSB) and vitamin D3 (VD3) on the intestinal immunity, barrier, oxidative stress and microflora in early-stage broilers. In total, 192 one-day-old broilers were assigned to a 2 × 2 factorial design including two dietary supplements at two different levels, in which the main effects were VD3 (3000 or 5000 IU kg-1) and CSB (0 or 1 g kg-1). RESULTS: The results showed that CSB supplementation increased ileal goblet cells (GCs) numbers, villus height and decreased crypt depth in broilers. CSB increased ileal proliferating cell nuclear antigen expression and high-level VD3 decreased cluster of differentiation 3 expression. CSB reduced serum d-lactate, endotoxin (ET), adrenocorticotropic hormone, corticosterone and malondialdehyde (MDA) concentrations and increased total antioxidant capacity (T-AOC) level. Meanwhile, high-level VD3 decreased serum ET concentration. Furthermore, CSB increased ileal T-AOC, lysozyme (LYZ) and transforming growth factor (TGF)-ß and decreased MDA, whereas high-level VD3 decreased ileal MDA and increased secretory immunoglobulin A. CSB up-regulated ileal claudin1, superoxide dismutase 1, TGF-ß and LYZ mRNA expression and down-regulated interleukin-1ß mRNA expression. CSB combined with high-level VD3 increased ileal Faecalibaculum abundance. Spearman correlation analysis showed that Faecalibaculum was related to the immune and barrier function. CONCLUSION: Dietary supplementation with CSB and high-level VD3 improved early gut health in broilers by promoting intestinal development, enhancing antioxidant capacity, strengthening barrier function and enhancing the favorable composition of the gut bacterial flora. © 2024 Society of Chemical Industry.