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Copyright of Journal of Zhejiang University: Science B is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Current cancer therapies often fall short in addressing the complexities of malignancies, underscoring the urgent need for innovative treatment strategies. RNA interference technology, which specifically suppresses gene expression, offers a promising new approach in the fight against tumors. Recent studies have identified a novel immunostimulatory small-interfering RNA (siRNA) with a unique sequence (sense strand, 5'-C; antisense strand, 3'-GGG) capable of activating the RIG-I/IRF3 signaling pathway. This activation induces the release of type I and III interferons, leading to an effective antiviral immune response. However, this class of immunostimulatory siRNA has not yet been explored in cancer therapy. Methods: IsiBCL-2, an innovative immunostimulatory siRNA designed to suppress the levels of B-cell lymphoma 2 (BCL-2), contains a distinctive motif (sense strand, 5'-C; antisense strand, 3'-GGG). Glioblastoma cells were subjected to 100 nM isiBCL-2 treatment in vitro for 48 h. Morphological changes, cell viability (CCK-8 assay), proliferation (colony formation assay), migration/invasion (scratch test and Transwell assay), apoptosis rate, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were evaluated. Western blotting and immunofluorescence analyses were performed to assess RIG-I and MHC-I molecule levels, and ELISA was utilized to measure the levels of cytokines (IFN-β and CXCL10). In vivo heterogeneous tumor models were established, and the anti-tumor effect of isiBCL-2 was confirmed through intratumoral injection. Results: IsiBCL-2 exhibited significant inhibitory effects on glioblastoma cell growth and induced apoptosis. BCL-2 mRNA levels were significantly decreased by 67.52%. IsiBCL-2 treatment resulted in an apoptotic rate of approximately 51.96%, accompanied by a 71.76% reduction in MMP and a 41.87% increase in ROS accumulation. Western blotting and immunofluorescence analyses demonstrated increased levels of RIG-I, MAVS, and MHC-I following isiBCL-2 treatment. ELISA tests indicated a significant increase in IFN-β and CXCL10 levels. In vivo studies using nude mice confirmed that isiBCL-2 effectively impeded the growth and progression of glioblastoma tumors. Conclusions: This study introduces an innovative method to induce innate signaling by incorporating an immunostimulatory sequence (sense strand, 5'-C; antisense strand, 3'-GGG) into siRNA, resulting in the formation of RNA dimers through Hoogsteen base-pairing. This activation triggers the RIG-I signaling pathway in tumor cells, causing further damage and inducing a potent immune response. This inventive design and application of immunostimulatory siRNA offer a novel perspective on tumor immunotherapy, holding significant implications for the field. [ABSTRACT FROM AUTHOR]

Objectives: To assess the accuracy of autonomous robotic and fully guided static computer‐assisted implant surgery (sCAIS) performed on models and patients. Materials and Methods: This study was divided into in vitro and in vivo sections. In vitro, 80 operators were assigned to two groups randomly. Forty operators performed forty autonomous robotic implant (ARI group) surgeries and the remaining forty operators carried out forty fully guided sCAIS (FGI group) surgeries on maxillary models, respectively. Each operator placed an implant in one maxillary model. In vivo, 60 patients with 113 implants from 2019 to 2023 (ARI group: 32 patients, 58 implants; FGI group: 28 patients, 55 implants) receiving implant surgeries were incorporated in this retrospective research. The preoperative and postoperative cone beam computer tomographs (CBCTs) were utilized to estimate the linear deviations and angular deviations in two‐dimensional (2D) and three‐dimensional (3D) space. The Pearson's chi‐square test, Shapiro–Wilk test, Student's t test, Mann–Whitney U test and mixed models were applied, and p <0.05 was considered statistically significant. Results: In vitro, a total of 80 implants were enrolled and significant differences were found between the two groups (p < 0.001): The 3D deviation at the platform of ARI and FGI group was 0.58 ± 0.60 mm and 1.50 ± 1.46 mm, respectively, at the apex was 0.58 ± 0.60 mm and 1.78 ± 1.35 mm, respectively, and angle was 1.01 ± 0.87° and 2.93 ± 1.59°, respectively. Also, except for mesiodistal deviation at the implant platform, the rest linear and angular deviations in the ARI group were significantly lower than those in the FGI group in 2D space (p < 0.001). In vivo, a significantly lower mean of angular deviation (0.95 ± 0.50°, p < 0.001) and the linear deviation at both platform (0.45 ± 0.28 mm, p < 0.001) and apex (0.47 ± 0.28 mm, p < 0.001) were observed in ARI group when compared to the FGI group (4.31 ± 2.60°; 1.45 ± 1.27 mm; 1.77 ± 1.14 mm). Conclusions: The use of autonomous robotic technology showed significantly higher accuracy than the fully guided sCAIS. [ABSTRACT FROM AUTHOR]

The electrophysiological function of the tongue involves complicated activities in taste sense, producing the perceptions of salty, sweet, bitter, and sour. However, therapies and prevention of taste loss arising from dysfunction in electrophysiological activity require further fundamental research. Optogenetics has revolutionized neuroscience and brought the study of sensory system to a higher level in taste. The year 2022 marks a decade of developments of optogenetics in taste since this technology was adopted from neuroscience and applied to the taste research. This review summarizes a decade of advances that define near‐term translation with optogenetic tools, and newly‐discovered mechanisms with the applications of these tools. The main limitations and opportunities for optogenetics in taste research are also discussed. [ABSTRACT FROM AUTHOR]

Being an important immune stimulant of T lymphocytes and NK cells, the recombinant human interleukin-15 (rhIL-15) has been extensively researched in tumor immunotherapy or as a vaccine adjuvant. However, the rhIL-15 manufacturing level lags far behind its growing clinical demand due to the lack of efficient and exact analysis methodologies to characterize the trace by-products, typically redox and deamidation. In order to improve the production and quality control of rhIL-15, here we developed an expanded resolution reverse-phase high-performance liquid chromatography (ExRP-HPLC) approach to quickly and accurately analyze the oxidation and reduction by-products of rhIL-15, which may appear during the purification processes. Firstly, we developed RP-HPLC methods which can separate rhIL-15 fractions with different levels of oxidization or reduction, respectively, and the redox status of each peak was then determined by measuring the intact mass with a high-resolution mass spectrometer (UPLC-MS). To further clarify the complex pattern of oxidization of specific residues, the peaks with various oxidation levels were digested into pieces for peptide mapping to pinpoint the exact changes of oxygen and hydrogen atoms in the rhIL-15 by-products. In addition, we performed the ExRP-HPLC and UPLC-MS analysis of partially deamidated rhIL-15 to characterize their oxidation and reduction. Our work is the first in-depth characterization of the redox by-products of rhIL-15, even for deamidated impurities. The ExRP-HPLC method we reported can facilitate the rapid and accurate quality analysis of rhIL-15, which is substantially helpful for streamlining the industrial manufacturing of rhIL-15 to better meet the demands of clinical applications. Keypoints: • The oxidization and reduction rhIL-15 by-products were characterized for the first time. • The changes of oxygen and hydrogen atoms in rhIL-15 redox by-products were accurately determined by UPLC-MS. • Oxidation and reduction by-products of deamidated rhIL-15 were further analyzed. [ABSTRACT FROM AUTHOR]

This study aims to provide an accurate finite element (FE) modeling method for structural vibration serviceability evaluation of the suspended floor under human-induced excitation. The fundamental dynamic characteristics and human-induced vibration responses of a typical suspended floor were first measured via a series of field tests. Subsequently, the overall and local equivalent FE models of the suspended floor were respectively established, and their applicability was then verified by comparing the predicted dynamic characteristics and responses of the suspended floor with the corresponding field test results. Finally, passive tuned mass dampers (TMDs) were designed for vibration control of the suspended floor using the local equivalent FE model, and the applicability of the local FE model in assessing the vibration serviceability of the suspended floor with TMDs was further confirmed via pedestrian-induced vibration tests. Results demonstrate that the simplified local equivalent FE model proposed in this study can well replace the complicated overall FE model to evaluate the vibration serviceability of the suspended floor with and without TMDs. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is an increasingly epidemic metabolic disease with complex pathogenesis. Multi-target therapy may be an effective strategy for NAFLD treatment, and traditional Chinese medicine (TCM) characterized by multi-ingredients and multi-targets has unique advantages in long-term clinical practice. Zexie–Baizhu (ZXBZ) decoction is a Chinese classical formula to treat body fluid disorders initially. Although many bioactive monomers from Zexie and Baizhu had been discovered to improve lipid disorders, limited research studies were focused on the aqueous decoction of ZXBZ, the original clinical formulation. In the current study, we identified 94% chemical composition of ZXBZ decoction and first discovered its hepaprotective effect in a gubra-amylin NASH (GAN) diet-induced NAFLD mouse model. Based on metabolomics and transcriptomics analyses, we speculated that lipid and glucose metabolisms might be regulated by ZXBZ decoction, which was further confirmed by improved dyslipidemia and hepatic steatosis in ZXBZ groups. Consistently with cross-omics analysis, we discovered ZXBZ decoction could influence two energy sensors, Sirt1 and AMPK, and subsequently affect related proteins involved in lipid biosynthesis, catabolism, and transport. In conclusion, ZXBZ decoction regulated energy sensors, consequently impeded lipogenesis, and promoted fatty acid oxidation (FAO) to alleviate lipid disorders and protect the liver in NAFLD models, which suggested ZXBZ decoction might be a promising treatment for NAFLD. [ABSTRACT FROM AUTHOR]

Copyright of Modern Food Science & Technology is the property of Editorial Office of Modern Food Science & Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We systematically investigated the modulation effects of substrates on the ferromagnetism properties of Fe3GeTe2 experimentally and theoretically. The polar refractive magnetic circular dichroism results demonstrate that the ferromagnetism could be modulated significantly by selecting different substrates. We explain this phenomenon using the first-principles calculation, revealing that it was induced by the lattice distortion and charge redistribution between the interfaces. Our work is useful to understand the fundamental mechanism of tunable ferromagnetism and paves the way for exploring interface physics and practical spintronic applications of two-dimensional ferromagnetic van der Waals crystals. [ABSTRACT FROM AUTHOR]

The liquid biopsy is being integrated into cancer diagnostics and surveillance. However, critical questions still remain, such as how to precisely evaluate cancer mutation burden and interpret the corresponding clinical implications. Herein, we evaluated the role of peripheral blood cell‐free DNA (cfDNA) in characterizing the dynamic mutation alterations of 48 cancer driver genes from cervical cancer patients. We performed targeted deep sequencing on 93 plasma cfDNA from 57 cervical cancer patients and from this developed an algorithm, allele fraction deviation (AFD), to monitor in an unbiased manner the dynamic changes of genomic aberrations. Differing treatments, including chemotherapy (n = 22), radiotherapy (n = 14) and surgery (n = 15), led to a significant decrease in AFD values (Wilcoxon, p = 0.029). The decrease of cfDNA AFD values was accompanied by shrinkage in the size of the tumor in most patients. However, in a subgroup of patients where cfDNA AFD values did not reflect a reduction in tumor size, there was a detection of progressive disease (metastasis). Furthermore, a low AFD value at diagnosis followed a later increase of AFD value also successfully predicted relapse. These results show that plasma cfDNA, together with targeted deep sequencing, may help predict treatment response and disease development in cervical cancer. What's new? Liquid biopsy is increasingly being integrated into cancer diagnostics and surveillance. However, critical questions still remain, such as how to precisely evaluate cancer mutation burden and infer clinical implications. Here, the authors develop a new algorithm that evaluates in an unbiased manner the mutation deviation of every single site in the target regions covered by a cancer panel, including the sites that usually fail to pass the single nucleotide variations (SNV)‐calling criteria of most algorithms. By analyzing 93 cervical cancer samples, they demonstrate that this algorithm is able to efficiently monitor patient response to treatment and prognosticate tumor progression. [ABSTRACT FROM AUTHOR]

Natural products are some of the most important sources of lead compounds for drug discovery. It is an effective way to isolate some lead compounds from complex multiconstituent extracts by combining some advanced isolation techniques with therapeutically relevant bioassays. Smilax china L. exhibits important pharmacological property of anti-chronic pelvic inflammation disease (CPID). With the bioassay guiding in induced CPID rats, high-speed counter-current chromatography (HSCCC) was applied to separate and purify some bioactive compounds from the effective solvent extract of the Smilax china L. with the optimized solvent system of n-hexane-ethyl acetate-methanol-water(1:10:1:10, v/v/v/v). 4 mg epicatechin and 10 mg catechin-[8,7-e]-4 β-(3,4-dihydroxyphenyl)-dihydro-2(3H)-pyranone were successfully obtained from 300 mg of crude sample with purity of 98.5 and 95.6 %, respectively. The anti-inflammation of the separated compounds was also studied by MTT assay. The results showed that HSCCC method was successful for the separation of the flavanols from Smilax china L. and suggested catechin-[8,7-e]-4β-(3,4-dihydroxyphenyl)-dihydro-2(3H)-pyranone be one potential compound for the anti-inflammation. [ABSTRACT FROM AUTHOR]

Flavonoids are the main chemical constituents ofSmilax chinaL. and thought to be responsible for the anti-inflammatory activity ofSmilax chinaL. In this study, a suitable HSCCC method was developed to separate the three main flavonoids in a one-separation from the anti-chronic pelvic inflammation disease (CPID) effective fraction ofSmilax chinaL. with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (1:10:1:10, v/v/v/v). 42 milligrams of astilbin, 10 mg neoisoastilbin, and 6 mg quercetin-3-O-α-L-rhamnoside were separated from 200 mg of the anti-CPID effective fraction ofSmilax chinaL. with purity of 98.3%, 98.7%, 98.5%, respectively, by HPLC analysis. Orthogonal test L9(34) was also applied to investigate the optimum extracting conditions of the three flavonoids. HSCCC was successfully used for the isolation and purification of the three flavonoids from the anti-CPID effective fraction ofSmilax chinaL. and the neoisoastilbin was first separated fromSmilax chinaL. [ABSTRACT FROM AUTHOR]

We investigated the fiber Bragg grating (FBG) thermal response in space vacuum thermal environment. The FBGs were packaged with 6061-T6 aluminum. The liquid nitrogen immersion experiment results show that its wavelength shift standard deviation is 0.76 pm for 217 h. The combination effect of vacuum and cryogenic temperature was studied by thermal cycling process in space environment simulator. The FBG sensors show accuracy better than 2% full scale, and the hysteresis errors are below 1%. It proves that these metal packaged FBG sensors can survive and meet the requirement of space measurement. [ABSTRACT FROM AUTHOR]