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This work investigated the influence of seven chili varieties in Guizhou on the quality of Zao Chili (ZC), a local traditional fermented chili product. The physical and chemical indicators, volatile components, and product quality of the seven chili varieties and the ZCs were analyzed. Significant differences in physical and chemical properties among the chili varieties substantially affected the quality of ZCs. Chaotian chilies are harder and spicier, have a higher seed/skin ratio and crude fibre content, and lower fruit weight, water content, and reducing sugar content than Erjingtiao chilies. The Erjingtiao chili FQB3 had the highest reducing sugar content (55.296 g/100 g). The ZC produced by FQB3 had the highest comprehensive sensory score (89.7), characterized by high total acid and amino acid nitrogen content and low crude fibre content. There were 181 volatile compounds in the ZCs, including 32 common compounds and 79 differential compounds. More volatile compounds were found in the ZC derived from Erjingtiao chili. The results combined with the OAV analysis indicated that the aroma profile of ZC could be classified into six attributes, comprising 14 key substances, such as β-damascenone and benzaldehyde. In conclusion, the Erjingtiao chili fulfils ZC's processing requirements. These results will serve as a guide in the assessment of ZC quality, the selection of chili processing varieties, and the stabilization of product quality.

Bench blasting is commonly used in open-pit mining. Some design parameters such as positions of hole packing and caving holes have great influences on the blasting effects. In this work, with a hybrid discrete-finite element method, numerical simulations of bench blasting are conducted, capturing the whole continuous-discontinuous processes. Considering two engineering cases, the influences of hole packing and caving holes are evaluated. The numerical results not only lead to some improved designs by relocating the packing positions and caving holes but also indicate the reliability of the adopted numerical tools.

Abstract Background The genomic information available for Pediococcus pentosaceus is primarily derived from fermented fruits and vegetables, with less information available from fermented meat. P. pentosaceus LL-07, a strain isolated from fermented meat, has the capability of producing exopolysaccharides (EPS). To assess the probiotic attributes of P. pentosaceus LL-07, we conducted whole-genome sequencing (WGS) using the PacBio SequelIIe and Illumina MiSeq platforms, followed by in vitro experiments to explore its probiotic potential. Results The genome size of P. pentosaceus LL-07 is 1,782,685 bp, comprising a circular chromosome and a circular plasmid. Our investigation revealed the absence of a CRISPR/Cas system. Sugar fermentation experiments demonstrated the characteristics of carbohydrate metabolism. P. pentosaceus LL-07 contains an EPS synthesis gene cluster consisting of 13 genes, which is different from the currently known gene cluster structure. NO genes associated with hemolysis or toxin synthesis were detected. Additionally, eighty-six genes related to antibiotic resistance were identified but not present in the prophage, transposon or plasmid. In vitro experiments demonstrated that P. pentosaceus LL-07 was comparable to the reference strain P. pentosaceus ATCC25745 in terms of tolerance to artificial digestive juice and bile, autoaggregation and antioxidation, and provided corresponding genomic evidence. Conclusion This study confirmed the safety and probiotic properties of P. pentosaceus LL-07 via complete genome and phenotype analysis, supporting its characterization as a potential probiotic candidate.

Abstract Immediate oral implant placement is a widely accepted technique, known for its efficacy in reducing treatment duration, surgical visits, and overall healing time. One of the primary challenges associated with immediate implant placement is the attainment of initial stability. The inevitable loss of bone and soft tissue after extraction poses a risk to implant osseointegration in both vertical and horizontal dimensions. Guided tissue regeneration/guided bone regeneration (GTR/GBR) is a well‐established method for periodontal regeneration. However, current GTR/GBR membranes lack tissue inherent regeneration properties and necessitate combination with grafts to enhance tissue recovery. In this context, biomaterials have emerged as a promising option due to their good biocompatibility, biodegradability, and bioactive properties. They present a potential alternative to standard autologous/allograft procedures. The field of biomaterials for bone regeneration has rapidly evolved, developing new guiding materials and engineering techniques. These advances have become integral in addressing tissue defects at the immediate implant site. Various materials such as bioceramics, natural polymers, and synthetic polymers have been used for tissue repair. This article undertakes an etiological examination of tissue deficiency associated with immediate implant placement. Additionally, it reviews the advantages and disadvantages of a variety of biomaterials, aiming to provide references for clinical treatment and areas for further investigation.

We explored the effect of microwave heating (MWH) and electric heating (ETH) on the volatile compounds (VCs) of pepper (Capsicum annuum L.). The spectral of the produced melanoidins by baking were used to screen samples with similar baking degrees. Mass spectrometry was used to detect the differences of VCs in samples. The results showed a dose-dependent effect between the intensity of absorption and fluorescence of melanoidins, which can be utilized as indicators for assessment baking degree. MWH samples produced larger variety of VCs than ETH. Changes in the variety and content of VCs infer changes in the flavor of pepper. According to the mechanism of Maillard reaction (MR) and MWH, it was deduced that MWH changes the type of chemical reaction in MR by affecting the distribution of valence electrons in the compounds. Therefore, MWH can be used as a novel method to modify the VCs and flavor of peppers.

Proteogenomic analyses of hepatocellular carcinomas (HCC) have focused on early-stage, HBV-associated tumours and lacked information about the phosphoproteome. Here, the authors present a comprehensive HCC proteogenomics and phosphoproteomics study in patient samples from multiple etiologies and stages.

Abstract Understanding the mechanisms underlying evasive resistance in cancer is an unmet medical need to improve the efficacy of current therapies. In hepatocellular carcinoma (HCC), aberrant expression of hypoxia-inducible factor 1 α (HIF1α) and increased aerobic glycolysis metabolism are drivers of resistance to therapy with the multi-kinase inhibitor Sorafenib. However, it has remained unknown how HIF1α is activated and how its activity and the subsequent induction of aerobic glycolysis promote Sorafenib resistance in HCC. Here, we report the ubiquitin-specific peptidase USP29 as a new regulator of HIF1α and of aerobic glycolysis during the development of Sorafenib resistance in HCC. In particular, we identified USP29 as a critical deubiquitylase (DUB) of HIF1α, which directly deubiquitylates and stabilizes HIF1α and, thus, promotes its transcriptional activity. Among the transcriptional targets of HIF1α is the gene encoding hexokinase 2 (HK2), a key enzyme of the glycolytic pathway. The absence of USP29, and thus of HIF1α transcriptional activity, reduces the levels of aerobic glycolysis and restores sensitivity to Sorafenib in Sorafenib-resistant HCC cells in vitro and in xenograft transplantation mouse models in vivo. Notably, the absence of USP29 and high HK2 expression levels correlate with the response of HCC patients to Sorafenib therapy. Together, the data demonstrate that, as a DUB of HIF1α, USP29 promotes Sorafenib resistance in HCC cells, in parts by upregulating glycolysis, thereby opening new avenues for therapeutically targeting Sorafenib-resistant HCC in patients.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer‐related deaths worldwide. Treatment options for patients with advanced‐stage disease are limited. A major obstacle in drug development is the lack of an in vivo model that accurately reflects the broad spectrum of human HCC. Patient‐derived xenograft (PDX) tumor mouse models could overcome the limitations of cancer cell lines. PDX tumors maintain the genetic and histologic heterogeneity of the originating tumors and are used for preclinical drug development in various cancers. Controversy exists about their genetic and molecular stability through serial passaging in mice. We aimed to establish PDX models from human HCC biopsies and to characterize their histologic and molecular stability during serial passaging. A total of 54 human HCC needle biopsies that were derived from patients with various underlying liver diseases and tumor stages were transplanted subcutaneously into immunodeficient, nonobese, diabetic/severe combined immunodeficiency gamma‐c mice; 11 successfully engrafted. All successfully transplanted HCCs were Edmondson grade III or IV. HCC PDX tumors retained the histopathologic, transcriptomic, and genomic characteristics of the original HCC biopsies over 6 generations of retransplantation. These characteristics included Edmondson grade, expression of tumor markers, tumor gene signature, tumor‐associated mutations, and copy number alterations. Conclusion: PDX mouse models can be established from undifferentiated HCCs, with an overall success rate of approximately 20%. The transplanted tumors represent the entire spectrum of the molecular landscape of HCCs and preserve the characteristics of the originating tumors through serial passaging. HCC PDX models are a promising tool for preclinical personalized drug development.

Suan Rou (SR), a traditional fermented meat, is widely favored by consumers due to its unique flavor and characteristics. To study the relationship between the core differential micro-organisms and differential volatile organic compounds (VOCs) of SR from six regions of China, high-throughput sequencing (HTS) and gas-chromatography–ion mobility spectrometry (GC-IMS) technologies were used to analyze the correlation between micro-organisms and VOCs in SR from Xiangxi of Hunan, Rongshui of Guangxi, Zunyi of Guizhou, Jinping of Guizhou, Congjiang of Guizhou, and Libo of Guizhou. A total of 13 core micro-organisms were identified at the genus level. Moreover, 95 VOCs were identified in the SR samples by GC-IMS analysis, with alcohols, aldehydes, ketones, and esters comprising the major VOCs among all the samples. The results showed a strong correlation (|r| > 0.8, p < 0.05) between the core differential micro-organisms and differential VOCs, including four bacteria, five fungi, and 12 VOCs. Pediococcus, Debaryomyces, Zygosaccharomyces, and Candida significantly contributed to the unique VOCs of SR.

Concrete subjected to fire loads is susceptible to explosive spalling, which can lead to the exposure of reinforcing steel bars to the fire, substantially jeopardizing the structural safety and stability. The spalling of fire-loaded concrete is closely related to the evolution of pore pressure and temperature. Conventional analytical methods involve the resolution of complex, strongly coupled multifield equations, necessitating significant computational efforts. To rapidly and accurately obtain the distributions of pore-pressure and temperature, the Pix2Pix model is adopted in this work, which is celebrated for its capabilities in image generation. The open-source dataset used herein features RGB images we generated using a sophisticated coupledmodel, while the grayscale images encapsulate the 15 principal variables influencing spalling. After conducting a series of tests with different layers configurations, activation functions and loss functions, the Pix2Pix model suitable for assessing the spalling risk of fire-loaded concrete has been meticulously designed and trained. The applicability and reliability of the Pix2Pix model in concrete parameter prediction are verified by comparing its outcomes with those derived from the strong coupling THC model. Notably, for the practical engineering applications, our findings indicate that utilizing monochrome images as the initial target for analysis yields more dependable results. This work not only offers valuable insights for civil engineers specializing in concrete structures but also establishes a robust methodological approach for researchers seeking to create similar predictive models. [ABSTRACT FROM AUTHOR]

A large amount of data can partly assure good fitting quality for the trained neural networks. When the quantity of experimental or on-site monitoring data is commonly insufficient and the quality is difficult to control in engineering practice, numerical simulations can provide a large amount of controlled high quality data. Once the neural networks are trained by such data, they can be used for predicting the properties/responses of the engineering objects instantly, saving the further computing efforts of simulation tools. Correspondingly, a strategy for efficiently transferring the input and output data used and obtained in numerical simulations to neural networks is desirable for engineers and programmers. In this work, we proposed a simple image representation strategy of numerical simulations, where the input and output data are all represented by images. The temporal and spatial information is kept and the data are greatly compressed. In addition, the results are readable for not only computers but also human resources. Some examples are given, indicating the effectiveness of the proposed strategy. [ABSTRACT FROM AUTHOR]

Cationic polymers as non-viral gene delivery carriers are widely used because of their strong condensing properties and long-term safety, but acute cytotoxicity is a persistent challenge. In this study, two types of polyplexes were prepared by co-formulating plasmid DNA and two cationic diblock copolymers PABOXA5-b-PMOXA33-PA (primary amine) and PABOXA5-b-PMOXA33-TA (tertiary amine) to check their transfection efficacies in HeLa cells and HEK293T cells, respectively. The plasmid DNA/PABOXA5-b-PMOXA33-PA polyplex showed higher transfection efficacy compared to the plasmid DNA/PABOXA5-b-PMOXA33-TA polyplex under an N/P ratio of 40. Both polymers exhibited low toxicity, attributed to the shielding effect of a hydrophilic, noncharged block. Mechanistic insight into differential transfection efficiencies of the polymers were gained by visualization and comparison of the condensates via transmission electron and atomic force microscopy. The results provide information suited for further structure optimization of polymers that are aimed for targeted gene delivery. [ABSTRACT FROM AUTHOR]

Microfluidic systems represent a key-enabling platform for novel diagnostic tools for use at the point-of-care in clinical contexts as well as for evolving single cell diagnostics. The design of 3D microfluidic systems is an active field of development, but construction of true interconnected 3D microfluidic networks is still a challenge, in particular when the goal is rapid prototyping, accurate design and flexibility. We report a novel approach for the construction of programmable 3D microfluidic systems consisting of modular 3D template casting of interconnected threads to allow user-programmable flow paths and examine its structural characteristics and its modular function. To overcome problems with thread template casting reported in the literature, low-surface-energy polymer threads were used, that allow solvent-free production. Connected circular channels with excellent roundness and low diameter variability were created. Variable channel termination allowed programming a flow path on-the-fly, thus rendering the resulting 3D microfluidic systems highly customizable even after production. Thus, construction of programmable/reprogrammable fully 3D microfluidic systems by template casting of a network of interconnecting threads is feasible, leads to high-quality and highly reproducible, complex 3D geometries. [ABSTRACT FROM AUTHOR]

Recombinant alpha interferon (IFN-α) is used for the treatment of viral hepatitis and some forms of cancer. During these therapies IFN-α is injected once daily or every second day for several months. Recently, the long-acting pegylated IFN-α (pegIFN-α) has replaced standard IFN-α in therapies of chronic hepatitis C because it is more effective, supposedly by inducing a long-lasting activation of IFN signaling pathways. IFN signaling in cultured cells, however, becomes refractory within hours, and little is known about the pharmacodynamic effects of continuously high IFN-α serum concentrations. To investigate the behavior of the IFN system in vivo, we repeatedly injected mice with IFN-α and analyzed its effects in the liver. Within hours after the first injection, IFN-α signaling became refractory to further stimulation. The negative regulator SOCS1 was rapidly upregulated and likely responsible for early termination of IFN-α signaling. For long-lasting refractoriness, neither SOCS1 nor SOCS3 were instrumental. Instead, we identified the inhibitor USP18/UBP43 as the key mediator. Our results indicate that the current therapeutic practice using long-lasting pegIFN-α is not well adapted to the intrinsic properties of the IFN system. Targeting USP18 expression may allow to exploit the full therapeutic potential of recombinant IFN-α. [ABSTRACT FROM AUTHOR]

Vascular endothelial cells (EC) are an exposed tissue with intimate contact with circulating Ag-speciflc CTL. Experimental in vitro and clinical data suggested that endothelial cells present a different repertoire of MHC class I-restricted peptides compared with syngeneic leukocytes or epithelial cells. This endothelial-specific peptide repertoire might protect EC from CTL-mediated cell death. The HLA-A*02-restricted peptide profile of human EC and syngeneic B lymphoblastoid cells was biochemically analyzed and compared. For EC selective peptides, source protein expression, peptide binding affinity, and peptide-HLA-A*02 turnover were measured. The significance of abundant peptide presentation for target cell recognition by immunodominant CTL was tested by small interfering RNA treatment of EC to knock down the source proteins. High amounts of two peptides, PTRF56-64 and CD59106-114, were consistently detected in EC. This predominance of two endothelial peptides was explained by cell type-specific source protein expression that compensated for poor HLA-A*02 binding affinity and short half-live of peptide/HLA-A*02 complexes. Knocking down the source proteins containing the abundant endothelial peptide motifs led to a nearly 100-fold increase of surface expression of SMCY311-319, an immunodominant minor histocompatibility Ag, as detected by cytotoxicity assays using SMCY311-319 specific CTL. We conclude that EC express and present preferentially two distinct HLA-A*02-restricted peptides at extraordinary high levels. These abundant self-peptides may protect EC from CTL-mediated lysis by competing for HLA-A*02 binding sites with immunodominant scarcely expressed antigenic peptides. [ABSTRACT FROM AUTHOR]