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Abstract Background Bacterial nanocellulose (BNC), a natural polymer material, gained significant popularity among researchers and industry. It has great potential in areas, such as textile manufacturing, fiber-based paper, and packaging products, food industry, biomedical materials, and advanced functional bionanocomposites. The main current fermentation methods for BNC involved static culture, as the agitated culture methods had lower raw material conversion rates and resulted in non-uniform product formation. Currently, studies have shown that the production of BNC can be enhanced by incorporating specific additives into the culture medium. These additives included organic acids or polysaccharides. γ-Polyglutamic acid (γ-PGA), known for its high polymerization, excellent biodegradability, and environmental friendliness, has found extensive application in various industries including daily chemicals, medicine, food, and agriculture. Results In this particular study, 0.15 g/L of γ-PGA was incorporated as a medium additive to cultivate BNC under agitated culture conditions of 120 rpm and 30 ℃. The BNC production increased remarkably by 209% in the medium with 0.15 g/L γ-PGA and initial pH of 5.0 compared to that in the standard medium, and BNC production increased by 7.3% in the medium with 0.06 g/L γ-PGA. The addition of γ-PGA as a medium additive resulted in significant improvements in BNC production. Similarly, at initial pH levels of 4.0 and 6.0, the BNC production also increased by 39.3% and 102.3%, respectively. To assess the characteristics of the BNC products, scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis were used. The average diameter of BNC fibers, which was prepared from the medium adding 0.15 g/L γ-PGA, was twice thicker than that of BNC fibers prepared from the control culture medium. That might be because that polyglutamic acid relieved the BNC synthesis from the shear stress from the agitation. Conclusions This experiment held great significance as it explored the use of a novel medium additive, γ-PGA, to improve the production and the glucose conversion rate in BNC fermentation. And the BNC fibers became thicker, with better thermal stability, higher crystallinity, and higher degree of polymerization (DPv). These findings lay a solid foundation for future large-scale fermentation production of BNC using bioreactors.

Abstract Chemotherapy was the main treatment method for esophageal cancer (EC) patients. However, chemotherapy resistance due to multiple factors is a major barrier to EC treatment. For investigating how small nucleolar RNA host gene 6 (SNHG6) affected the 5-fluorouracil (5-FU) resistance in EC as well as its possible molecular mechanism. This work conducted cell viability assay, clone formation, scratch assays together with cell apoptosis for evaluating the roles of SNHG6 and enhancer of zeste homolog 2 (EZH2, the histone-lysine N-methyltransferase). Relevant molecular mechanism was identified by RT-qPCR analysis together with Western-blot (WB) assays. Our data showed that SNHG6 expression increased in EC cells. SNHG6 promotes colony formation and migration, whereas suppresses EC cell apoptosis. SNHG6 silencing markedly promoted 5-FU-mediated suppression on KYSE150 and KYSE450 cells. Additional mechanism studies showed that SNHG6 modulating STAT3 and H3K27me3 via promoting EZH2 level. Similar to the function of SNHG6, abnormal expression of EZH2 promotes the malignancy of EC and intensifies its resistance to 5-FU. In addition, overexpression of EZH2 abolished the role of SNHG6 silencing in 5-FU sensitivity in EC cells. SNHG6 overexpression promoted malignancy of EC and increased EC cell resistance to 5-FU. Besides, further molecular mechanism studies provided a novel regulatory pathways that SNHG6 knockdown promoted EC cell sensitivity to 5-FU by modulating STAT3 and H3K27me3 via promoting EZH2 expression.

This study evaluated the co-production of pigment and bacterial nanocellulose (BNC) from S. salsa biomass. The extraction of the beet red pigment reduced the salts and flavonoids contents by 82.7%–100%, promoting the efficiencies of enzymatic saccharification of the biomass and the fermentation of BNC from the hydrolysate. SEM analysis revealed that the extraction process disrupted the lignocellulosic fiber structure, and the chemical analysis revealed the lessened cellulase inhibitors, consequently facilitating enzymatic saccharification for 10.4 times. BNC producing strains were found to be hyper-sensitive to NaCl stress, produced up to 400.4% more BNC from the hydrolysate after the extraction. The fermentation results of BNC indicated that the LDU-A strain yielded 2.116 g/L and 0.539 g/L in ES-M and NES-M, respectively. In comparison to the control, the yield in ES-M increased by approximately 20.0%, while the enhancement in NES-M was more significant, reaching 292.6%. After conducting a comprehensive characterization of BNC derived from S. salsa through Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), and Thermogravimetric Analysis (TGA), the average fiber diameter distribution of these four BNC materials ranges from 22.23 to 33.03 nanometers, with a crystallinity range of 77%–90%. Additionally, they exhibit a consistent trend during the thermal degradation process, further emphasizing their stability in high-temperature environments and similar thermal properties. Our study found an efficient co-production approach of pigment and BNC from S. salsa biomass. Pigment extraction made biomass more physically and chemically digestible to cellulase, and significantly improved BNC productivity and quality.

ObjectiveWe aimed at summarizing the perceptions and responses to cognitive decline, assessing the disease management, identifying deficiencies and proposing new strategies for improvement in people with diabetes (PWDs).MethodsA comprehensive search was performed in the following nine databases: PubMed, EMBASE, Web of Science, The Cochrane Library, PsycINFO, CINAHL, WanFang, CNKI, and VIP. The Joanna Briggs Institute (JBI) Critical Appraisal Tool for qualitative research was utilized to evaluate the quality of included studies. Descriptive texts and quotations relating to patient experience were extracted from the included studies and thematically analyzed.ResultsEight qualitative studies met the inclusion criteria and 2 overarching themes were identified: (1) self-perception of cognitive decline referred to perceived cognitive symptoms, lack of knowledge and, impaired self-management and coping in multiple methods; (2) reported benefits of cognitive interventions referred to how cognitive interventions improved disease management, attitudes and needs of PWDs.ConclusionPWDs described misconceptions about their cognitive decline and suffered from them during disease management. This study provides a patient-specific reference for cognitive screening and intervention in PWDs, supporting disease management with cognitive decline in clinical practice.

We compared the differential expression of 15 markers in PTCL (Peripheral T-cell lymphoma) subtypes and T-CUS (T-cell clones of uncertain significance), and summarized the specific immunophenotype profiles of each subtype and its impact on prognosis. PD-1 and CD10 are diagnostic markers for AITL (angioimmunoblastic T-cell lymphoma). To avoid confusion with T-CUS of benign clones, it is recommended to define AITL as bounded by PD-1+%>38.01 and/or CD10+%>7.46. T cell-derived ENKTL-N (extranodal NKT cell lymphoma) specifically expresses CD56. ALCL (anaplastic large cell lymphoma) characteristically expresses CD30 and HLA-DR. PTCL-NOS (peripheral T-cell lymphoma unspecified) still lacks a relatively specific phenotype and is prone to loss of basic lineage markers CD3, CD5, and CD7. The determination of T-CUS can be verified by the overall assessment of the bone marrow and a certain period of follow-up. The clustering results showed that the expression of 8 specific markers was significantly different among the 5 groups, suggesting that a combination of related markers can be analyzed in the identification of PTCLs subtypes. The study explores the advantages of TRBC1 combined with CD45RA/CD45RO in detecting T cell clonality, which can efficiently and sensitively analyze multiple target T cell populations at the same time. The sensitivity of PB to replace BM to monitor the tumor burden or MRD (minimal residual disease) of PTCLs is as high as 85.71%, which can relieve the huge pressure of clinical sampling and improve patient compliance. CD7, CD38, and Ki-67 are prognostic indicators for AITL. CD3 and CD8 on PTCL-NOS, and CD56 and HLA-DR on ENKTL-N have prognostic role. This study supports and validates the current classification of PTCL subtypes and establishes an immunophenotypic profile that can be used for precise diagnosis. The important clinical value of PTCLs immunophenotype in routine classification diagnosis, clonality confirmation, prognosis prediction, and treatment target selection was emphasized.

BackgroundFew studies have been performed to comprehensively analyze and summarize the immunophenotype and differential diagnosis of mature NK cell tumors, and there is often overlap between tumorigenic and reactive NK cell phenotypes. Furthermore, the impact of different phenotypes on patient prognosis has rarely been reported.MethodsThe degree of expression of extracellular and intracellular markers of NK cells in each group was compared by FCM, and the differences in expression of various markers among different disease groups and their impact on prognosis have been analyzed and summarized.ResultsCompared with normal NK cells, tumor cells of ANKL and ENKTL had characteristics of being more activated and progressive with larger FSC, in contrast to NK-CLPD and RNKL. Differential diagnoses with RNKL, ANKL, and ENKTL have broader FCM clues. In contrast, the phenotypes of NK-CLPD and RNKL are not significantly different, and consistent phenotypic abnormalities require ongoing monitoring to confirm malignant clones. The sensitivity of differentiating malignant NK cells from reactive NK cells by KIRs alone was poor. The clustering results showed that CD5, CD16, CD56, CD57, CD94, CD45RA, CD45RO, HLA-DR, KIRs, Granzyme B, Perforin and Ki-67 were differentially distributed in the expression of three NK cell tumors and reactive NK cell hyperplasia, so a comprehensive judgment using a wide range of antibody combinations is required in disease staging diagnosis. The tumor cell loads in BM and PB were also compared, and there was a clear correlation between the two. Moreover, the sensitivity of PB for monitoring tumor cells was up to 87.10%, suggesting that PB could be used as an alternative to BM for the diagnosis and screening of NK cell tumors. Analysis of the phenotypic impact of ENKTL patients on prognosis showed that those with CD7 and CD45RO expression had a poor prognosis, while those with positive KIRs had a better prognosis.ConclusionThis study systematically characterized the FCM of mature NK cell tumors, emphasizing the importance and clinical value of accurate immunophenotyping in diagnosing, classifying, determining prognosis, and guiding treatment of the disease.

Abstract Rab proteins play crucial roles in membrane trafficking. Some Rab proteins are implicated in cancer development through regulating protein sorting or degradation. In this study, we found that the expression of Rab26 is suppressed in the aggressive breast cancer cells as compared to the levels in non-invasive breast cancer cells. Over-expression of Rab26 inhibits cell migration and invasion, while Rab26 knockdown significantly promotes the migration and invasion of breast cancer cells. Rab26 reduces focal adhesion association of Src kinase and induces endosomal translocation of Src. Further experiments revealed that Rab26 mediates the autophagic degradation of phosphorylated Src through interacting with ATG16L1, consequently, resulting in the suppression of the migration and invasion ability of breast cancer cells.

Abstract Background Moxibustion is a common intervention of Chinese medicine (CM). Systematic reviews (SRs) on moxibustion are increasing. Although the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement provides guidelines for SRs, the quality of moxibustion-related SRs is still not satisfactory. In particular, descriptions of the interventions and the rationale for using moxibustion are insufficient. To address these inadequacies, the working group developed this PRISMA extension for reporting SRs of moxibustion (PRISMA-M 2020). Methods A group of CM clinical professionals, methodologists of SRs, reporting guideline developers, and journal editors developed this PRISMA-M 2020 through a comprehensive process that includes registration, literature review, consensus meetings, Delphi exercises for soliciting comments, and revision, resulting in this final draft. Results Seven of the 27 PRISMA checklist items, namely title (1), rationale (3), eligibility criteria (6), data item (11), additional analyses (16), study characteristics (18), and additional analysis (23), were extended, with specific reference to the application of moxibustion. Illustrative examples and explanations for each item are provided. Conclusion The PRISMA-M 2020 will help improve the reporting quality of SRs with moxibustion. Systematic review registration We have registered it on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network, particularly under the item of PRISMA-TCM: http://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-systematic-reviews/#65 .

Abstract Background Chinese herbal medicines (CHMs) are the major interventions of traditional Chinese medicine (TCM), which are typically administered as either single herbs or formulas. The Cochrane systematic reviews (SRs) of CHMs are essential references for evaluating the efficacy and safety of CHMs interventions; they are expected to be accurate and reliable. This study aimed to assess the reporting quality of these SRs, particularly whether necessary information related to CHM was adequately reported. Methods The Cochrane Database was systematically searched for all SRs of CHM that were published up to 31 December 2017. The primary analysis was to assess their reporting quality based on 27-item of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and 9-item of CHM-related information designed according to TCM theory. Descriptive statistics were additionally used to analyze their baseline characteristics. Results A total of 109 Cochrane SRs of CHM were identified from 1999 to 2017. For 27-item of PRISMA, 26 had the reporting compliances higher than 50%, of which 11 were fully reporting (100%). However, for CHM-related information, 65 (59.6%) SRs did not report the specific name of the CHM in the title, 42 (38.5%) lacked TCM-related rationales in the introduction, 62 (56.9%) did not include CHM-related characteristics in the additional analyses, and 77 (70.6%) did not analyze CHM results in terms of TCM-related theories in the discussion. Of 97 SRs that included clinical trials, 38 (39.2%) did not provide the details of composition and dosage of CHMs, 85 (87.6%) did not report the CHM sources, 13 (13.4%) did not provide the dosage form, 95 (97.9%) lacked CHM quality control information, and 57 (58.8%) did not describe details of the controls. For 62 (72.9%) of 85 SRs that included meta-analysis, it was impossible to assess whether meta-analysis had been properly conducted due to inadequate reporting of CHM interventions. Conclusion Although the Cochrane SRs of CHM showed reporting compliance with PRISMA checklist, their reporting quality needs improvement, especially about full reporting of CHM interventions and of TCM-related rationales. Reporting guideline of “PRISMA extension for CHM interventions” should be developed thus to improve their quality.

Objective: This study aimed to systematically review the status and trends of Chinese clinical practice guidelines (CPGs) during the time period 2010–2020 and explore their methodological characteristics. Then, based on the strengths and weaknesses in development, offer several recommendations for the quality improvement which will serve as a reference for the users and developers of CPG.Introduction: With the development of evidence-based medicine (EBM), the CPGs play an increasingly important role in healthcare decision-making both in China and worldwide.Inclusion criteria: The CPGs that have been used to help the health professionals in the healthcare decision-making were included.Methodology: The China National Knowledge Infrastructure (CNKI) and WanFang databases were searched from 2010 to 2020 for the studies describing the general and methodological characteristics of Chinese CPGs. Comparisons of the methodological characteristics between the groups were conducted using the chi-square test or Fisher's exact test. The M-K test was adopted to identify the monotonically increasing or decreasing trends of methodological characteristics over the timespan.Results: A total of 2,654 CPGs fulfilled the inclusion criteria. The quantity and quality of the guidelines developed in China have improved over the time span. From 2010 to 2020,the guidelines had differing characteristics and covered a wide range of subjects. In total, 2,318(87.34%) guidelines focused on Western Medicine. Eight (0.30%) had been developed for patient versions of guidelines, 10(0.38%) were tentative guidelines, and 16(0.60%) were rapid advice guidelines. Medical specialty societies (including their branches) (71.1%) were the main guideline makers. The most addressed diseases were neoplasms (14.43%). The target population is mainly adults (84.97%). The methodological quality of consensus-based (CB)-CPGs was obviously lower than evidence-based (EB)-CPGs. Except for the item, “recommendations were based on evidence of systematic reviews,” there were statistical differences in all other methodological items between the EB-CPGS and CB-CPGS (P < 0.01). Higher methodological quality has been observed in EB-CPGs. All the data relating to the methodological characteristics indicated that higher methodological quality was present in the guidelines using GRADE (P < 0.01).Conclusion: The quantity and quality of the guidelines developed in China have improved between 2010 and 2020. CB-CPGs have also paid attention to the methodology quality, but obviously, this is lower than that in the EB-CPGs.

Abstract Background Cis- and trans-palmitoleic acids (Cis-POA and trans-POA) are isomers of palmitoleic acid, a monounsaturated fatty acid which affects glucose and lipid metabolism, and reduces insulin resistance. Trans-POA is used as a biomarker for indicating the risk of type II diabetes and coronary heart disease, but no methods of analysis or distinguishing between cis-POA and trans-POA have yet been reported. Method An accurate and precise HPLC method was developed to determine cis- and trans-POA simultaneously, and compared with results from a GC method. Cis- and trans-POA were analyzed by HPLC on a reverse-phase BDS-C18 column, equilibrated and eluted with acetonitrile (A) and water (B). In the established and validated GC method used for comparison, potassium hydroxide ester exchange was chosen to derivatize the cis- and trans-POA, before being determined. Results The calibration curves for cis- and trans-POA were linear over the range 0.05 to 500 μg/mL. The HPLC method exhibited good sensitivity, precision and accuracy. The limits of detection (LOD) for cis- and trans-POA were 0.2 and 0.05 μg/mL, respectively. The method successfully determined cis- and trans-POA in fish oil. For the GC method, the contents of cis-POA quantified were similar to those from the HPLC method, but the contents of trans-POA revealed significant variation between the two methods. Conclusions After a comprehensive consideration of the characteristics of the saponification and methyl esterification methods which have been tested and verified, the HPLC method was found to be suitable for determining cis- and trans-POA contents in fish oil. It was also suggested that in natural fish oil, cis-POA may be in the glyceride state, and trans-POA almost completely in the free acid form. In comparison with the GC method, the HPLC method provided a simpler process and faster analyses for identifying and determining cis- and trans-POA. The study has also provided technical support for studying the pharmacological differences and relationship between structure and activity of cis- and trans-POA. This could help physicians to analyze patients’ samples more quickly in 10 min and therefore provide a more rapid diagnosis of problems relating to the risk of type II diabetes and coronary heart disease.

Natural fractures caused by tectonic stress in shale can not only improve the seepage capacity of shale, but also become the migration and loss channel of free gas. Calcite, quartz and other minerals in shale fracture veins record the fluid evolution information of the shale. Through the analysis of different types of fracture cements in the shale of the Silurian–Ordovician Wufeng–Longmaxi Formations in the southern Sichuan Basin, the effect of different fractures on shale gas construction or destruction was clarified. Geochemical investigations included the diagenetic mineral sequences in the hole–cavity veins, paleo-pressure recovery by Raman quantitative analysis, and the environments of diagenetic fluids traced by rare earth elements (REE) signatures. The density, composition, pressure, and temperature properties of CH4-bearing fluid inclusions were determined by Raman quantitative measurement and thermodynamic simulations to establish the trapping condition of the geo-fluids, and so constrain the periods of gas accumulation. The diagenetic sequences in the fracture veins can be summarized as follows: Cal-I→Qz-II→Cal-III. The Cal-I in the bedding fracture veins crystallized in the late Jurassic (~180 Ma), and originated from hydrothermal origin and diagenetic fluid; the Qz-II veins crystallized in the middle Jurassic (~190 Ma); the Cal-III veins in the high-angle fractures precipitated during the early Eocene (~12 Ma), and derived from atmospheric freshwater leaching. Pore fluid pressure gradually increased. The pressure coefficient of the shale gas reservoir gradually increased to strong overpressure from 160 Ma to 86 Ma. Between 75 Ma and the present day, the pore fluid pressure and the pressure coefficient in the shale reservoirs, having been affected by tectonic activities and strata uplift-erosion, have significantly reduced. Bedding slippage fractures play a constructive role in the enrichment of shale gas, and fracture slip can significantly improve fracture permeability. High-angle shear fractures usually cut through different strata in areas with strong tectonic activity, and destroy the sealing of the shale. The entrapment of primary methane gas inclusions recorded the process of excess reservoir pressure reduction, and indicated the partial loss of shale free gas.

Hypercholesterolemia is a preventable risk factor for atherosclerosis and cardiovascular disease. However, the mechanisms whereby cis-palmitoleic acid (cPOA) and trans-palmitoleic acid (tPOA) promote cholesterol homeostasis and ameliorate hypercholesterolemia remain elusive. To investigate the effects of cPOA and tPOA on cholesterol metabolism and its mechanisms, we induced hypercholesterolemia in mice using a high-fat diet and then intragastrically administered cPOA or tPOA once daily for 4 weeks. tPOA administration reduced serum cholesterol, low-density lipoprotein, high-density lipoprotein, and hepatic free cholesterol and total bile acids (TBAs). Conversely, cPOA had no effect on these parameters except for TBAs. Histological examination of the liver, however, revealed that cPOA ameliorated hepatic steatosis more effectively than tPOA. tPOA significantly reduced the expression of 3-hydroxy-3-methyl glutaryl coenzyme reductase (HMGCR), LXRα, and intestinal Niemann-Pick C1-Like 1 (NPC1L1) and increased cholesterol 7-alpha hydroxylase (CYP7A1) in the liver, whereas cPOA reduced the expression of HMGCR and CYP7A1 in the liver and had no effect on intestinal NPC1L1. In summary, our results suggest that cPOA and tPOA reduce cholesterol synthesis by decreasing HMGCR levels. Furthermore, tPOA, but not cPOA, inhibited intestinal cholesterol absorption by downregulating NPC1L1. Both high-dose tPOA and cPOA may promote the conversion of cholesterol into bile acids by upregulating CYP7A1. tPOA and cPOA prevent hypercholesterolemia via distinct mechanisms.

Water flow is commonly observed in rock fractures, and this flow has considerable significance in many aspects of rock engineering. In this study, seepage-stress coupled tests were performed on fractured rock masses using a computer-controlled direct shear device for rock with seepage control. The flow direction was radial. Eight types of test case were designed, and subgroup tests with varied normal stress, shear velocity, and roughness of fracture surface were conducted. The failure state of the fracture surface after the shear test, changes in shear stress, and fissure width and permeability under the above conditions were analyzed. The results include the following: the grain size of gouge fragments produced in rough fracture decreased with an increase in normal stress during shearing; the grain size of gouge fragments affected the fracture permeability; and the influence of shear velocity on the test results was mainly reflected after the peak strength. Additionally, a new expression describing fluid flow through fracture gouge is proposed.

The subcellular location and cell biological function of small GTPase Rab40c in mammalian cells have not been investigated in detail. In this study, we demonstrated that the exogenously expressed GFP-Rab40c associates with lipid droplets marked by neutral lipid specific dye Oil red or Nile red, but not with the Golgi or endosomal markers. Further examination demonstrated that Rab40c is also associated with ERGIC-53 containing structures, especially under the serum starvation condition. Rab40c is increasingly recruited to the surface of lipid droplets during lipid droplets formation and maturation in HepG2 cells. Rab40c knockdown moderately decreases the size of lipid droplets, suggesting that Rab40c is involved in the biogenesis of lipid droplets. Stimulation for adipocyte differentiation increases the expression of Rab40c in 3T3-L1 cells. Rab40c interacts with TIP47, and is appositionally associated with TIP47-labeled lipid droplets. In addition, over-expression of Rab40c causes the clustering of lipid droplets independent of its GTPase activity, but completely dependent of the intact SOCS box domain of Rab40c. In addition, Rab40c displayed self-interaction as well as interaction with TIP47 and the SOCS box is essential for its ability to induce clustering of lipid droplets. Our results suggest that Rab40c is a novel Rab protein associated with lipid droplets, and is likely involved in modulating the biogenesis of lipid droplets.

A commentary published in Frontiers in Immunology discusses the use of flow cytometry to analyze tumor-infiltrating lymphocytes (TILs) in patients with diffuse large B-cell lymphoma (DLBCL). The study collected data from 102 DLBCL patients and found that TILs have a positive impact on patient survival. The authors suggest that incorporating TIL data into risk prediction models could be beneficial in clinical practice, but more research is needed. The study also highlights the potential of tumor-infiltrating B cells as a favorable prognostic factor in DLBCL and calls for further investigation into their functions and potential therapeutic applications. The study was supported by the Natural Science Foundation of Shandong Province and the authors have no conflicts of interest. The views expressed in the article are solely those of the authors and do not represent their affiliated organizations or the publisher. [Extracted from the article]

Abstract This study investigates the impact of long-term water immersion on the mechanical and hydrochemical properties of cemented calcareous soil, emphasizing the critical role of carbonate content in mechanical performance. Utilizing hydrochemical analysis and triaxial testing, the research revealed that prolonged immersion disrupts the acid-base balance of the solution, resulting in an increased concentration of ions and chemicals. Significant dissolution of carbonates and soluble minerals occurs, which reacts with carbon dioxide to generate bicarbonate ions, thereby elevating the alkalinity of the soaking solution. Additionally, the gradual dissolution of clay minerals compromises the cementitious structure, leading to particle reorientation and interlocking. The study quantitatively assesses the changes in soil properties, demonstrating a substantial reduction in soil cohesion by up to 86.1% and an increase in the internal friction angle by 37.5%. Furthermore, the gradual dissolution of clay minerals compromises the cementitious structure, resulting in particle reorientation and interlocking that contribute to the observed mechanical changes. The findings underscore the importance of understanding the effects of extended immersion on the stability and engineering applicability of cemented calcareous soils.

Abstract This paper systematically investigates the dynamic mechanical response and fragment characteristics of sandstone with asymmetrical conjugate fissures subjected to preexisting static stress based on the split Hopkinson pressure bar apparatus. The cross-fissured sandstone exhibits significant variations in mechanical behavior when exposed to higher dynamic strain rates under identical static pre-stress. The cross-fissured sandstone with a higher dynamic strain rate is characterized by a greater coupled strength under the same static pre-stress; for a given dynamic load, the highest coupled strength occurs under the static pre-stress of 60% UCS. The failure mode of the cross-fissured sandstone is predominantly governed by the dynamic strain rate, independent of static pre-stress variations considered in this investigation. At lower dynamic strain rates, the specimens typically exhibit a mixed tensile-shear failure mode, characterized by the dominance of larger fragments in the broken specimens. In contrast, under high dynamic impacts, the sandstone tends to fail in a shear-dominated manner, resulting in smaller fragments with a more uniform size distribution. Furthermore, the study explores how varying dynamic strain rates and static pre-stress influence the fragment characteristics of the cross-fissured sandstone. Higher dynamic strain rates and increased static pre-stress generally lead to smaller mean fragment sizes. This phenomenon is quantitatively described by fitting fragment size distributions using the Generalized Extreme Value (GEV) distribution, revealing a decrease in the location parameter (μ) and an increase in fractal dimension. These metrics indicate that higher dynamic strain rates and static pre-stress result in sandstone specimens breaking into smaller fragments with a more homogeneous size distribution. These findings contribute to a deeper understanding of rock dynamics, with potential implications for engineering applications involving similar geological configuration under dynamic loading conditions.

Abstract The Baishi landslide was located in the western part of Beichuan County, Sichuan Province, China. The landslide experienced multiple minor collapses at the front part, accompanying with numerous tensile cracks. To comprehensively grasp the stability conditions and predict the moment of failure of the landslide, deformation monitoring of the landslide has been carried out from the moment that the landslide was reported until it failed. This study analyzed the different phases of landslide deformation and its failure mechanism through the analysis of monitoring data. The result showed that the failure manifests both the retrogressive and advancing features. The landslide was divided into several zones based on the spatial variation of the deformation characteristics. Moreover, the improved tangential angle criterion is applied to categorize the deformation phases of a landslide. Investigating the surface displacement vectors and vector angles of landslides plays a significant role for ascertaining the failure and sliding mechanism. The monitoring results revealed that the front part of the landslide played a key role in the stability of the landslide. Therefore, the monitoring data from this zone were crucial for predicting the moment of complete landslide failure.

Abstract The clinical effects of Schisandra chinensis against human disease are well-documented; however, studies on its application in controlling plant pathogens are limited. Here, we investigated its inhibitory effect on the growth of Alternaria alternata, a fungus which causes significant post-harvest losses on apples, known as black spot disease. S. chinensis fruit extract exhibited strong inhibitory effects on the growth of A. alternata with an EC50 of 1882.00 mg/L. There were 157 compounds identified in the extract by high performance liquid chromatography-mass spectrometry, where benzocaine constituted 14.19% of the extract. Antifungal experiments showed that the inhibitory activity of benzocaine on A. alternata was 43.77-fold higher than the crude extract. The application of benzocaine before and after A. alternata inoculation on apples prevented the pathogen infection and led to mycelial distortion according to scanning electron microscopy. Transcriptome analysis revealed that there were 4226 genes differentially expressed between treated and untreated A. alternata-infected apples with benzocaine. Metabolomics analysis led to the identification of 155 metabolites. Correlation analysis between the transcriptome and metabolome revealed that benzocaine may inhibit A. alternata growth via the beta-alanine metabolic pathway. Overall, S. chinensis extract and benzocaine are environmentally friendly plant-based fungicides with potential to control A. alternata.

Identified as the pathogenic genes of Alzheimer's disease (AD), APP, PSEN1, and PSEN2 mainly lead to early-onset AD, whose course is more aggressive, and atypical symptoms are more common than sporadic AD. Here, a novel missense mutation, APP E674Q (also named “Shanghai APP”), was detected in a Chinese index patient with typical late-onset AD (LOAD) who developed memory decline in his mid-70s. The results from neuroimaging were consistent with AD, where widespread amyloid β deposition was demonstrated in 18F-florbetapir Positron Emission Tomography (PET). APP E674Q is close to the β-secretase cleavage site and the well-studied Swedish APP mutation (KM670/671NL), which was predicted to be pathogenic in silico. Molecular dynamics simulation indicated that the E674Q mutation resulted in a rearrangement of the interaction mode between APP and BACE1 and that the E674Q mutation was more prone to cleavage by BACE1. The in vitro results suggested that the E674Q mutation was pathogenic by facilitating the BACE1-mediated processing of APP and the production of Aβ. Furthermore, we applied an adeno-associated virus (AAV)-mediated transfer of the human E674Q mutant APP gene to the hippocampi of two-month-old C57Bl/6 J mice. AAV-E674Q-injected mice exhibited impaired learning behavior and increased pathological burden in the brain, implying that the E674Q mutation had a pathogenicity that bore a comparison with the classical Swedish mutation. Collectively, we report a strong amyloidogenic effect of the E674Q substitution in AD. To our knowledge, E674Q is the only pathogenic mutation within the amyloid processing sequence causing LOAD.

Abstract Background The relationship between periodontitis and Alzheimer’s disease (AD) has attracted more attention recently, whereas profiles of subgingival microbiomes and gingival crevicular fluid (GCF) metabolic signatures in AD patients have rarely been characterized; thus, little evidence exists to support the oral-brain axis hypothesis. Therefore, our study aimed to characterize both the microbial community of subgingival plaque and the metabolomic profiles of GCF in patients with AD and amnestic mild cognitive impairment (aMCI) for the first time. Methods This was a cross-sectional study. Clinical examinations were performed on all participants. The microbial community of subgingival plaque and the metabolomic profiles of GCF were characterized using the 16S ribosomal RNA (rRNA) gene high-throughput sequencing and liquid chromatography linked to tandem mass spectrometry (LC–MS/MS) analysis, respectively. Results Thirty-two patients with AD, 32 patients with aMCI, and 32 cognitively normal people were enrolled. The severity of periodontitis was significantly increased in AD patients compared with aMCI patients and cognitively normal people. The 16S rRNA gene sequencing results showed that the relative abundances of 16 species in subgingival plaque were significantly correlated with cognitive function, and LC–MS/MS analysis identified a total of 165 differentially abundant metabolites in GCF. Moreover, multiomics Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) analysis revealed that 19 differentially abundant metabolites were significantly correlated with Veillonella parvula, Dialister pneumosintes, Leptotrichia buccalis, Pseudoleptotrichia goodfellowii, and Actinomyces massiliensis, in which galactinol, sn-glycerol 3-phosphoethanolamine, D-mannitol, 1 h-indole-1-pentanoic acid, 3-(1-naphthalenylcarbonyl)- and L-iditol yielded satisfactory accuracy for the predictive diagnosis of AD progression. Conclusions This is the first combined subgingival microbiome and GCF metabolome study in patients with AD and aMCI, which revealed that periodontal microbial dysbiosis and metabolic disorders may be involved in the etiology and progression of AD, and the differential abundance of the microbiota and metabolites may be useful as potential markers for AD in the future.

On 1 September 2022, a landslide in Hongya Village, Weiyuan Town, Huzhu Tu Autonomous County, Qinghai Province, caused significant casualties and economic losses. To mitigate such risks, InSAR technology is employed due to its wide coverage, all-weather operation, and cost-effectiveness in detecting landslides. In this study, focusing on the landslide in Hongya Village, SBAS-InSAR and Sentinel-1A satellite data from July 2021 to September/October 2022 were used to accurately identify the areas of active landslides and to analyze the landslide deformation trends, in combination with the geological characteristics of the landslides and rainfall data. The results showed that strong deformation was detected in the middle and back of the landslide in Hongya Village, with a maximum deformation rate of approximately -13 mm/year. The surface of the landslide consisted of mainly Upper Pleistocene wind-deposited loess, which is extremely sensitive to water. The deformation of the landslide was closely related to the rainfall, and the deformation of the landslide increased with the increase in rainfall. The research results prove that the combination of ascending and descending orbit data based on SBAS-InSAR technology is highly feasible in the field of landslide deformation monitoring and is of great practical significance for landslide disaster prevention and mitigation.