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[Display omitted] • Pyroptosis-related genes upregulate in brain cell clusters concurrently after MCAO. • MANF inhibits pyroptosis. • Manf -modified BMSCs play a strong therapeutic role in cerebral infarction. Cerebral infarction is a common disease characterized by high mortality, a narrow therapeutic window, and limited therapeutic options. Recently, cell therapy based on gene modification has brought a glimmer of hope to the treatment of cerebral infarction although the explicit underlying mechanism is beyond being well dissected. In the present study, we constructed an animal model of middle cerebral artery occlusion (MCAO), compared differentially expressed genes (DEGs) between the sham and MCAO groups by single-cell RNA sequencing (scRNA-seq) to explore the potential cell death-related pathways involved in cerebral infarction, and transfected Manf into BMSCs by lentivirus. Subsequently, we injected BMSCs (bone marrow-derived mesenchymal stem cells), Manf -modified BMSCs, or lentivirus encoding Manf into the brain. Their effects on MANF content, apoptosis, pyroptosis, infarct volume in the brain, and neurological function were evaluated after MCAO. We found that the DEGs upregulated in four major cell clusters after MCAO and were enriched with not only apoptosis, ferroptosis, and necroptosis but also with pyroptosis-related pathways. In addition, transfection of Manf into BMSCs significantly increased the expression and secretion of MANF in BMSCs; BMSCs, Manf -modified BMSCs, and Manf treatment all resulted in an increase in Manf content in the brain, a decrease in the expression of apoptosis- and pyroptosis-related molecules, a reduction in infarct volume, and an improvement in neurological function after MCAO. Moreover, Manf -modified BMSCs have the strongest therapeutic effect. Collectively, Manf -modified BMSCs ameliorate ischemic injury after cerebral infarction by repressing apoptosis- and pyroptosis-related molecules, which represents a new cell therapy strategy for cerebral infarction. [ABSTRACT FROM AUTHOR]

Keloid, an aggressive fibroproliferative disease of the skin, is usually caused by infectious skin diseases, burns, and trauma. This study aimed to assess the effect of SPARC on the keloid pathogenesis. In normal skin and keloid scar tissues, changes in SPARC expression were analysed by qRT-PCR, western blotting, and immunohistochemistry. Keloid fibroblasts were isolated from human keloid tissue. GSEA was performed to investigate the signalling pathways related to SPARC. Cell Counting Kit-8, 5-Ethynyl-2′-deoxyuridine, transwell assay, and scratching assays were used to assess fibroblast proliferation and migration. Changes in α-SMA, fibronectin, collagen I, and collagen III levels were examined in fibroblasts by western blotting. SPARC expression was upregulated in keloid scar tissues. In fibroblasts, cell proliferation, migration, collagen production, and extracellular matrix (ECM) synthesis were promoted by SPARC overexpression, whereas SPARC knockdown resulted a converse result. GSEA showed that SPARC regulates the p53 pathway. In keloid scar tissues, there was a negative correlation between SPARC and p53 expression. p53 expression was decreased by SPARC overexpression, whereas SPARC knockdown increased p53 expression. Furthermore, the effects of SPARC on the fibroblast phenotype were reversed by p53 overexpression. Fibroblast proliferation, migration, and ECM synthesis were promoted by SPARC overexpression, which was achieved by regulating the p53 pathway. Our findings provide new therapeutic targets for keloids. • SPARC expression is upregulated in keloid skin tissues. • SPARC promotes the proliferation and migration of keloid fibroblasts. • SPARC promotes the collagen production and ECM synthesis in fibroblasts. • SPARC inhibits the activation of p53 signaling in fibroblasts. [ABSTRACT FROM AUTHOR]

• Reinforcing the CFRP foam sandwich structure by orthogonal grid. • Testing the impact characteristics of each position at different energies. • Comparing the impact resistance of the sandwich panel at different positions. • Numerical simulation of the impact process for each position. • The proposed structure has the advantage of lightweight and high impact resistance. Orthogonal grid structures, which are widely used in engineering, are incorporated into the foam to form the grid reinforced core. However, the impact resistance of this type of sandwich structure varies with position. In this paper, the low-velocity impact performance of orthogonal grid reinforced CFRP-foam sandwich structure at different positions was investigated. The drop hammer low-velocity impact tests were conducted at 30 J, 50 J and 80 J energy for the intersection, rib, and center positions, respectively, and the impact resistance of the three positions was further compared with the impact data. The test results showed that the intersection and rib exhibited fiber fracture and delamination of CFRP face and grid, as well as foam crushing and cracking. The center position showed face perforation and foam crushing. At the same impact energy, the intersection position had the strongest impact resistance, with an initial stiffness about 18 % higher than that of the rib, and their peak load per unit mass was higher than that of CFRP-foam sandwich panels, and the center was the weakest. In addition, numerical simulations were performed which were in good agreement with the tests, and the damage processes at different stages were discussed. The lightweight, high impact resistant sandwich structure proposed can provide a reference for structural design. [ABSTRACT FROM AUTHOR]

[Display omitted] • S-shaped reinforced cores are designed by flattening hexagonal honeycomb cores. • S-shaped reinforced structures can effectively change the deformation mode of cores. • The peak load of S-shaped reinforced core can be 86.12% greater than plain core. • Theoretical prediction model of S-shaped reinforced honeycomb cores is proposed. • The design capabilities of cores are expanded because of S-shaped structure. Honeycomb structures serve as the core of sandwich structures in various industries, such as aerospace and rail transit. In this study, a novel design was introduced where hexagonal honeycomb cores were flattened in specific areas to form S-shaped reinforced cores. Compression tests were conducted on S-shaped reinforced honeycomb cores with different rotational structures – left-hand, right-hand, and mixed rotation. The deformation process of these cores was thoroughly investigated. Additionally, a theoretical prediction model was proposed to determine the Young's modulus and peak load of S-shaped reinforced honeycomb cores. The experimental data was compared with the theoretical model to validate its accuracy. Moreover, the study examined the effects of changing the relative density and cell wall angle of S-shaped reinforced honeycomb cores on the peak and specific peak loads. The results demonstrated that the use of S-shaped reinforced structures successfully altered the deformation mode of the honeycomb cores. In particular, the peak loads of S-LL and S-LR specimens were 29.14% and 86.12% higher than that of plain honeycomb, respectively. In summary, increasing the relative density of S-shaped reinforced honeycomb cores proved to enhance the peak load and specific peak load, thereby augmenting the design capabilities of these cores. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel DEM-based method to simulate granular flow with dust effectively. • A model of granule equivalent friction coefficient and dust effect is established. • Simulation and experiment results appear equal changes following dust contents. The simulation of dust-bearing granular accumulation flow in the theoretical and practical aspects of the engineering field poses a significant challenge due to the massive computational requirements associated with cross-scale simulations. In this study, a novel approach is proposed to address this issue by developing a model that accounts for the impact of dust on granular flow through changes in the granule friction coefficient. Initially, the theoretical analysis was conducted to examine the effects of dust on granular flow. Subsequently, a method was developed to measure the equivalent friction coefficient of granules by combining theoretical analysis and experimental work. The proposed method was then employed to simulate the stability of a spherical granule pile in a drum influenced by dust content and compared against experimental results. The simulation results demonstrate agreement with the experimental results, indicating the feasibility of modeling the effect of dust on dust-bearing granular flow through the granule equivalent friction coefficient. The dust effect can be considered equivalent to a change in the granule friction coefficient, which facilitates the reduction of the computational load generated by the Discrete Element Method (DEM) method and enables cross-scale simulations. [ABSTRACT FROM AUTHOR]

In this study, dielectric barrier discharge (DBD) cold plasma was explored for degrading aflatoxins in naturally contaminated rice. Rice samples were inoculated with strains of toxigenic Aspergillus and incubated to produce various levels of aflatoxins. Cold plasma showed degradation rates of aflatoxin B 1 (AFB 1) and total aflatoxins (AFs) that were related to moisture content, oxygen content, treatment time and voltage. Generally, the treatment reduced 1.08%–55.34% of AFB 1 and 4.23%–56.37% of AFs in rice under different conditions. Relative lower degradation rates can be due to low permeability of the plasma and interference from food matrix. In addition, no significant difference (P > 0.05) was found in moisture, protein, amylose and color of rice before and after treatment. However, cold plasma aggravated the fat oxidation of rice, and made its surface smoother and more porous. The results provided a theoretical basis for aflatoxins degradation from grain system using cold plasma. In this study, dielectric barrier discharge (DBD) cold plasma was applied in the degradation of aflatoxins in naturally contaminated rice, having obvious degradation effect and little quality impact. Cold plasma treatment, as a novel non-thermal processing technology, can reduce mycotoxins in food in order to fully ensure the product safety in various links, including production, storage and so on. Compared with other detoxification methods currently used in the industry, this technology can achieve similar or higher degradation effect in a shorter time. In addition, it is low-cost and will not pollute the environment or damage the sensory properties and nutritional value of products. • Cold plasma reduced 55.34% of aflatoxin B 1 and 56.37% of aflatoxins in rice. • The degradation effects were in accordance with the first-order kinetic model. • Cold plasma had no significant impact on rice quality except for fat oxidation. • The free fatty acid value of rice increased by 275.3% under the voltage of 160 kV. [ABSTRACT FROM AUTHOR]

In the present study, honeycomb cores with periodic tight zones were proposed for carbon-fiber and aluminum-honeycomb sandwich panels by flattening hexagon-shaped cells of honeycomb walls. In-plane compression tests were performed for sandwich panels with three types of local-tight honeycomb cores to evaluate the effects of the local-tight configurations on mechanical properties and failure modes. Experimental results indicated that the mechanical properties of sandwich specimens were effectively increased by using the proposed local-tight honeycomb cores. In particular, the specific energy absorption of sandwich specimens with a local-orthogonal-tight core was increased by 400.46%. In addition, Digital Image Correlation (DIC) technique was employed to further investigate the compressive behaviors of the sandwich specimens with and without local-orthogonal-tight honeycomb cores. The experimental measurements and detailed DIC observations indicated that the local-orthogonal-tight honeycomb core sandwich structures, which provided improved load transferring paths and reduced mismatch between the high-stiffness face sheets and low-stiffness core, exhibited progressive crushing failure modes. [ABSTRACT FROM AUTHOR]

In this study, compression properties of composite honeycomb sandwich panel and tube structures with S-shaped reinforced core was studied. The S-shaped reinforcements was machined from conventional honeycomb core. Quasi-static compression tests showed that the peak force and energy absorption of the proposed sandwich panels were enhanced by up to 85.28% and 31.41% respectively, in comparison to the carbon fiber/aluminum honeycomb sandwich panels. Based on the experimentally validated finite element model, the effects of number of S-shaped reinforcement structures, wall thickness and rotation direction were investigated for mechanical performance of the carbon fiber/aluminum honeycomb sandwich tubes under compression. Numerical results demonstrated that the S-shaped reinforcement structure could change the load transfer path effectively. The mechanical behavior and properties of the honeycomb core with S-shaped reinforcement were significantly influenced by changing the number and distribution of S-shaped reinforcements with different rotating directions. The homodromous structure caused shear damage, while the heterodromous structure showed more stability. • A honeycomb core with S-shaped reinforcements, which could effectively enhanced peak load and energy absorption, was proposed. [ABSTRACT FROM AUTHOR]

Grid structures have great potential for engineering application, inspired by the leaf texture, the rectangular grid is innovatively added to the honeycomb to form the grid-honeycomb hybrid core. The low-velocity impact response of the composite sandwich structure with grid–honeycomb hybrid core was investigated by experimental and numerical simulation. Low-velocity impact tests with 30 J energy were conducted of the sandwich panel to analyze the mechanical response and damage morphology at typical locations (intersection, rib, and center). The results show that the impact resistance at the intersection was the strongest, the peak load, damage threshold load, and initial stiffness at the intersection were 14.74%, 15.54%, and 16.06% higher, and the maximum displacement and residual displacement were 12.09% and 33.71% lower, respectively than those at the rib, and the center was the weakest. Compared with honeycomb sandwich panel, the impact resistance of unit mass at the intersection and rib was stronger and the internal damage was smaller. In addition, the parametric study of the structural parameters of sandwich panel was conducted. The grid thickness had a significant effect on the impact resistance, while the effects of honeycomb wall thickness and honeycomb unit cell diameter were smaller and had almost no effect on initial stiffness and energy absorption. Finally, the impact resistance efficiency analysis was performed to obtain the optimal design area of structural parameters to provide design guidance. [Display omitted] [ABSTRACT FROM AUTHOR]

Household air pollution prevails in rural residences across China, yet a comprehensive nationwide comprehending of pollution levels and the attributable disease burdens remains lacking. This study conducted a systematic review focusing on elucidating the indoor concentrations of prevalent household air pollutants—specifically, PM2.5, PAHs, CO, SO 2 , and formaldehyde—in rural Chinese households. Subsequently, the premature deaths and economic losses attributable to household air pollution among the rural population of China were quantified through dose-response relationships and the value of statistical life. The findings reveal that rural indoor air pollution levels frequently exceed China's national standards, exhibiting notable spatial disparities. The estimated annual premature mortality attributable to household air pollution in rural China amounts to 966 thousand (95% CI: 714–1226) deaths between 2000 and 2022, representing approximately 22.2% (95% CI: 16.4%−28.1%) of total mortality among rural Chinese residents. Furthermore, the economic toll associated with these premature deaths is estimated at 486 billion CNY (95% CI: 358–616) per annum, constituting 0.92% (95% CI: 0.68%−1.16%) of China's GDP. The findings quantitatively demonstrate the substantial disease burden attributable to household air pollution in rural China, which highlights the pressing imperative for targeted, region-specific interventions to ameliorate this pressing public health concern. [Display omitted] • Indoor air pollution level in rural China was analyzed via a literature review. • Exposure to the pollutant exhibits heterogeneity across different spatial region. • Concerned air pollution attributes to 966 thousand premature deaths annually. • PM2.5 and CVD are key pollutant and disease contributing to health effects. • Targeted regional policies are needed to control rural household air pollution. [ABSTRACT FROM AUTHOR]

[Display omitted] Tumor cells with damaged mitochondria undergo metabolic reprogramming, but gene therapy targeting mitochondria has not been comprehensively reported. In this study, plasmids targeting the normal hepatocyte cell line (L-O2) and hepatocellular carcinoma cell line were generated using three genes SIRT3 , SIRT4 , and SIRT5. These deacetylases play a variety of regulatory roles in cancer and are related to mitochondrial function. Compared with L-O2, SIRT3 and SIRT4 significantly ameliorated mitochondrial damage in HCCLM3, Hep3B and HepG2 cell lines and regulated mitochondrial biogenesis and mitophagy, respectively. We constructed double-gene plasmid for co-express SIRT3 and SIRT4 using the internal ribosome entry site (IRES). The results indicated that the double-gene plasmid effectively expressed SIRT3 and SIRT4, significantly improved mitochondrial quality and function, and reduced mtDNA level and oxidative stress in HCC cells. MitoTracker analysis revealed that the mitochondrial network was restored. The proliferation, migration capabilities of HCC cells were reduced, whereas their differentiation abilities were enhanced. This study demonstrated that the use of IRES-linked SIRT3 and SIRT4 double-gene vectors induced the differentiation of HCC cells and inhibited their development by ameliorating mitochondrial dysfunction. This intervention helped reverse metabolic reprogramming, and may provide a groundbreaking new framework for HCC treatment. [ABSTRACT FROM AUTHOR]

Walnut green husk polysaccharides (WGP) are isolated from the walnut green husk with a mean molecular weight of 12.77 kDa. The structural characterization revealed by methylation and NMR analysis indicated that WGP might consist of →4-α-D-Gal p -(1→, α-D-Gal p (1→, and →2)-α-L-Rha p -(1→. Previous studies have been demonstrated that WGP effectively prevented liver injury and modulated gut microbiota in high fructose-treated mice and high fat diet-treated rats. In this study, we found for the first time that WGP presenting outstanding protective effects on liver inflammation and gluconeogenesis dysfunction induced by ochratoxin A (OTA) in mice. Firstly, WGP decreased oxidative stress, down-regulated the expression of inflammatory factors and inhibited the TLR4/p65/IκBα pathway in the liver. Then, WGP reversed OTA-induced lower phosphoenolpyruvate carboxyl kinase (PEPCK), and glucose 6-phosphatase (G6PC) activities in the liver. Furthermore, WGP increased the diversity of gut microbiota and the abundance of beneficial bacteria, especially Lactobacillus and Akkermansia. Importantly, the results of fecal microbiota transplantation (FMT) experiment further confirmed that gut microbiota involved in the protective effects of WGP on liver damage induced by OTA. Our results indicated that the protective effect of WGP on liver inflammation and gluconeogenesis dysfunction caused by OTA may be due to the regulation of gut microbiota. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 Omicron viruses possess a high antigenic shift, and the approved anti-SARS-CoV-2 drugs are extremely limited, which makes the development of new antiviral drugs for the clinical treatment and prevention of SARS-CoV-2 outbreaks imperative. We have previously discovered a new series of markedly potent small-molecule inhibitors of SARS-CoV-2 virus entry, exampled by the hit compound 2. Here, we report a further study of bioisosteric replacement of the eater linker at the C-17 position of 2 with a variety of aromatic amine moieties, followed by a focused structure-activity relationship study, leading to the discovery of a series of novel 3- O - β -chacotriosyl BA amide derivatives as small-molecule Omicron fusion inhibitors with improved potency and selectivity index. Particularly, our medicinal chemistry efforts have resulted in a potent, and efficacious lead compound S-10 with appreciable pharmacokinetic properties, which exhibited broad-spectrum potency against Omicron and other variants with EC 50 values ranging from 0.82 to 5.45 μM. Mutagenesis studies confirmed that inhibition of Omicron viral entry was mediated by the direct interaction with S in the prefusion state. These results reveal that S-10 is suitable for further optimization as Omicron fusion inhibitors, with the potential to be developed as therapeutic agents for the treatment and control of SARS-CoV-2 ant its variants infections. [Display omitted] • A set of 3- O -β-chacotriosyl BA saponins were synthesized and characterized based on the bioisosterism and SBDD strategies. • These title saponins exhibited strong inhibition toward Omicron. • Intensive structure-activity relationships were conducted. • S-10 showed broad-spectrum anti-SARS-CoV-2 activities by blocking membrane fusion. • S-10 displayed promising pharmacokinetic properties in vitro. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic generates a global threat to public health and continuously emerging SARS-CoV-2 variants bring a great challenge to the development of both vaccines and antiviral agents. In this study, we identified UA-18 and its optimized analog UA-30 via the hit-to-lead strategy as novel SARS-CoV-2 fusion inhibitors. The lead compound UA-30 showed potent antiviral activity against infectious SARS-CoV-2 (wuhan-HU-1 variant) in Vero-E6 cells and was also effective against infection of diverse pseudotyped SARS-CoV-2 variants with mutations in the S protein including the Omicron and Delta variants. More importantly, UA-30 might target the cavity between S1 and S2 subunits to stabilize the prefusion state of the SARS-CoV-2 S protein, thus leading to interfering with virus-cell membrane fusion. This study offers a set of novel SARS-CoV-2 fusion inhibitors against SARS-CoV-2 and its variants based on the 3- O -β-chacotriosyl UA skeleton. [Display omitted] • A set of 3-O-β-chacotriosyl UA saponins were synthesized and characterized. • These saponins showed potent inhibition toward diverse pseudotyped SARS-CoV-2 variants with mutations in S. • Intensive structure-activity relationships were conducted. • Lead compound UA-30 displayed improved anti-SARS-CoV-2 activity in vitro and SI. • UA-30 was shown to bind to SARS-CoV-2 S2 protein directly and block the prefusion state of spike protein. [ABSTRACT FROM AUTHOR]

Fibrosis is an inevitable stage in the development of chronic liver disease and has an irreplaceable role in characterizing the degree of progression of chronic liver disease. Histopathological diagnosis is the gold standard for the interpretation of fibrosis parameters. Conventional hematoxylin-eosin (H&E) staining can only reflect the gross structure of the tissue and the distribution of hepatocytes, while Masson trichrome can highlight specific types of collagen fiber structure, thus providing the necessary structural information for fibrosis scoring. However, the expensive costs of time, economy, and patient specimens as well as the non-uniform preparation and staining process make the conversion of existing H&E staining into virtual Masson trichrome staining a solution for fibrosis evaluation. Existing translation approaches fail to extract fiber features accurately enough, and the decoder of staining is unable to converge due to the inconsistent color of physical staining. In this work, we propose a prior-guided generative adversarial network, based on unpaired data for effective Masson trichrome stained image generation from the corresponding H&E stained image. Conducted on a small training set, our method takes full advantage of prior knowledge to set up better constraints on both the encoder and the decoder. Experiments indicate the superior performance of our method that surpasses the previous approaches. For various liver diseases, our results demonstrate a high correlation between the staging of real and virtual stains (ρ = 0. 82 ; 95% CI: 0.73-0.89). In addition, our finetuning strategy is able to standardize the staining color and release the memory and computational burden, which can be employed in clinical assessment. [ABSTRACT FROM AUTHOR]

• The capillary water absorption properties of recycled concrete after freeze–thaw under different substitution rates were studied. • The relationship between the relative peak stress of recycled concrete and the number of freeze–thaw cycles and different aggregate replacement rates was studied. • Establishing the recycled concrete freeze–thaw damage constitutive model. In order to study the capillary water absorption and damage characteristics of recycled aggregate concrete (RAC) after freeze–thaw cycles, the capillary water absorption and the stress–strain curve under uniaxial compression of recycled coarse aggregate replacement rates of 0%, 30% and 50% RAC were tested. The effects of recycled coarse aggregate replacement rate and freeze–thaw cycles on the mass loss, compressive strength, relative dynamic elastic modulus and capillary water absorption of recycled concrete were analyzed. According to the basic theory of damage mechanics, the damage constitutive model of recycled concrete was established based on the double factors of replacement rate and freeze–thaw cycles. The results show that with the increase of freeze–thaw cycles, the mass, compressive strength and relative dynamic elastic modulus of RAC with different substitution rates decrease, and the water absorption rate increases first and then tends to be stable. After freezing and thawing, the peak stress of each substitution rate RAC decreased in varying degrees, and the peak strain increased slightly. The test results are compared with the calculation results of the constitutive model, and the two are in good agreement, which has certain reference significance for the promotion and application of recycled concrete in cold regions. [ABSTRACT FROM AUTHOR]