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In this article, the strength characteristics of the cement mortar with waste glass powder of different size and content at different ages were studied. The mechanism of strength development was analysed from the microstructure of mortar specimens based on scanning electron microscopy (SEM) and electronic dispersive spectroscopy (EDS). The results show that the compressive strength and flexural strength of the mortar specimens increase significantly with a higher age. There is an optimal content of glass powder corresponding to the maximum strength. The glass powder of smaller particle size clearly promotes the development of compressive strength and flexural strength in the mortar specimens. It is found from SEM-EDS that glass cement mortar has a larger amount of internal hydration products and higher density compared with ordinary cement mortar. The density of cement mortar incorporating 15 wt% glass powder increases gradually with the decrease of glass particle size. The hydration products and compactness of the cement mortar adding 200–500 mesh glass powder experience an increase and then a decrease with a rise in the glass content. The strength enhancement with the addition of glass powder are mainly attributed to the microaggregate filling effect and pozzolanic effect of the glass powder, as well as to changes in the interfacial transition zone.

A series of 1,2,3-triazole analogues as novel fat mass and obesity-associated protein (FTO) inhibitors were synthesised in this study. Among all 1,2,3-triazoles, compound C6 exhibited the most robust inhibition of FTO with an IC50 value of 780 nM. It displayed the potent antiproliferative activity against KYSE-150, KYSE-270, TE-1, KYSE-510, and EC109 cell lines with IC50 value of 2.17, 1.35, 0.95, 4.15, and 0.83 μM, respectively. In addition, C6 arrested the cell cycle at G2 phase against TE-1 and EC109 cells in a concentration-dependent manner. Analysis of cellular mechanisms demonstrated that C6 concentration-dependently regulated epithelial mesenchymal transition (EMT) pathway and PI3K/AKT pathway against TE-1 and EC109 cells. Molecular docking studies that C6 formed important hydrogen-bond interaction with Lys107, Asn110, Tyr108, and Leu109 of FTO. These findings suggested that C6 as a novel FTO inhibitor and orally antitumor agent deserves further investigation to treat esophageal cancer.

We previously showed that green tea polyphenols (GTPs) exert antiadipogenic effects on preadipocyte proliferation. Here, we investigated the regulatory effects of GTPs on osteogenesis and adipogenesis during early differentiation of human adipose tissue-derived stem cells (hADSC). Adipogenesis of hADSCs was determined by oil-red-O staining and triglycerides synthesis measurement. Osteoporosis of hADSC was measured using alkaline phosphatase assays and intracellular calcium levels. Immunofluorescence staining and qRT-PCR were used to detect PPARγ-CEBPA regulated adipogenic pathway regulated by PPAR-CEBPA and the osteogenic pathway mediated by RUNX2-BMP2. We found that GTPs treatment significantly decreased lipid accumulation and cellular triglyceride synthesis in mature adipocytes and attenuated pioglitazone-induced adipogenesis in a dose-dependent manner. GTPs downregulated protein and mRNA expression of Pparγ and attenuated pioglitazone-stimulated-Cebpa expression. GTPs treatment significantly enhanced hADSCs differentiation into osteoblasts compared to control and pioglitazone-treated cells. GTPs upregulated RunX2 and Bmp2 proteins and mRNA expression compared to control and significantly attenuated decreased RunX2 and Bmp2 mRNA expression by pioglitazone. In conclusion, our data demonstrates GTPs possesses great ability to facilitate osteogenesis and simultaneously inhibits hADSC differentiation into adipogenic lineage by upregulating the RUNX2-BMP2 mediated osteogenic pathway and suppressing PPARγ-induced signaling of adipogenesis. These findings highlight GTPs’ potential to combat osteoporosis associated with obesity.

Neoadjuvant therapy is recommended for patients with locally advanced breast cancer. Here the authors report the results of a phase 2 clinical trial of oral neoadjuvant therapy with pyrotinib (pan-HER tyrosine kinase inhibitor), letrozole (aromatase inhibitor) and dalpiciclib (CDK4/6 inhibitor) in patients with treatment-naïve and stage II-III triple positive breast cancer.

Abstract Background Riverine ecosystems are one of the most important reservoirs of antibiotic resistance genes (ARGs) in the environment, but the occurrence and controlling factors of ARG distribution in different habitats of riverine ecosystems remain poorly understood. In this study, a metagenomic approach was used to characterize ARG types and their abundance in different habitats (rhizosphere soil, surface bulk soil, bottom bulk soil, and sediment) of riverine ecosystems in eastern China. Sampling sites were located along different rivers of eastern China, which are geographically isolated. Differences in bacterial communities, mobile genetic elements (MGEs), pattern and intensity of human activities, climate, and other environmental factors at the sampling sites and habitats were expected to affect ARG occurrence. Results ARGs were observed with high variations in diversity (44–206 subtypes) and abundance (6.85–105.68 ×/Gb). There were significant south-north differences in ARG occurrence in the same habitat, except for surface bulk soil. And the significant difference was found in ARGs among four southern habitats. South–north differences in ARGs of the same habitat were mainly attributed to the combination of different occurrence frequencies and habitat selections of ARGs. Differences in ARG profiles among the four habitats in the south and the north were both mainly attributed to the different occurrence frequencies of ARGs. Bacterial communities and MGEs (Mobile genetic elements) could account for the observed variance in the resistome of riverine ecosystems across eastern China. The co-occurrences of specific ARGs with bacterial communities and MGEs were more frequent at the northern sampling sites than in the south, and co-occurrence patterns (i.e. ARGs and bacterial communities or ARGs and MGEs) varied between the habitats. Moreover, building land in all habitats, except bulk soils, showed significant positive correlations with ARG abundance. Conclusion This study reveals a high variance in the resistome of riverine ecosystems in eastern China and its controlling factors. We appeal to the importance of assessment of ARGs in the riverine ecosystem and the need for future prevention and intervention of ARG spread.

We present a comprehensive approach to utilize the residues of Chrysanthemum indicum as a source for natural cellulose fibers and carbon for removal of dyes and other pollutants. C. indicum is one of the most common sources for flowers for conventional decoration and also for various chemicals and essential oils. However, flowers form only a part of the plant and the leaves and stems are the major components in terms of weight. The stems and leaves are generally considered as waste and disposed. In this study, we have utilized the stems as a source of natural cellulose fibers. Further, the fibers were carbonized and activated with KOH to improve porosity and pore size. Natural cellulose fibers obtained from the stems were shorter compared to cotton, jute or other common lignocellulosic fibers. However, good strength (121 MPa) and high elongation (14%) make the fibers similar to wool and suitable for developing textiles and composites. The fibers were able to sorb up to 95% of methylene blue within 24 hours under ambient conditions. Carbon obtained from the fibers after activating with 2:1 ratio of KOH has surface area of about 1450 m2/g and a highly porous structure preferable for sorption and energy storage applications. The activated carbon was able to sorb up to 148 mg of dye per gram of activated carbon. Utilizing the C. indicum stems as a source of fibers and carbon will help to further develop sustainable chemicals and materials for commodity applications.

Zwitterionic polymers have attracted research attention in recent years owing to their unique molecular structures. In the same repeat unit, positive and negative charges are simultaneously located on a pair of cationic and anionic groups; therefore, zwitterionic polymers have a large dipole moment and numerous charged groups. Although the molecular chain of the zwitterionic polymer can be maintained in an electrically neutral state overall, the coexistence of the oppositely charged groups confers extremely high polarity and excellent hydrophilicity to the polymer. At the same time, the electricality of the polymer can be further regulated by the environmental pH and salt ions, which greatly broadens the scope of applications in different fields. This review introduces various structures of zwitterionic polymers and analyzes the reasons why zwitterionic polymers exhibit pH responsiveness, anti-polyelectrolyte effects, and superior electrical conductivity. The application fields are also summarized by generalizing the research status of zwitterionic polymers, including applications in antifouling coatings, drug delivery, wastewater treatment, and sensors, etc.

Abstract Background Diet is a modifiable risk factor for cardiovascular diseases (CVD), but there is still a lack of tools to assess dietary intakes of this high-risk population in Ningxia, China. Objective We aim to evaluate the validity and reliability of the semi-quantitative food frequency questionnaire (SFFQ) in the groups in Ningxia using a 24-hour dietary recall method. Method Two hundred five participants were included in the analysis. The two FFQs were 6 months apart, and during this time two 24-hour dietary recalls (24HDRs) were completed. Statistical methods were compared using inter-class correlation coefficient, unadjusted, energy-adjusted, de-attenuated correlation coefficient, quartile classification, weighted K values, and 95% limits of agreement (LOA). Results The inter-class correlation coefficients between FFQ1 and FFQ2 ranged from 0.25 to 0.73. The number of subjects classified as identical or adjacent was 72.2 to 85.9%. The crude correlation coefficient between FFQs and 24HDRs was 0.30 ~ 0.81, the energy-adjusted correlation coefficient was 0.16 ~ 0.83, and the de-attenuated correlation coefficient was 0.19 ~ 0.98. Weighted k statistics and Bland-Altman plots showed acceptable agreement between FFQs and 24HDRs. Conclusion The FFQ developed for the population at high risk of cardiovascular and cerebrovascular diseases in areas of Ningxia can be used to measure the dietary intake of nutrients and food groups reliably and validly.

Karst wetland is an important regulator of karst ecosystems in southwest China and is of great significance to the sustainable development of the region. Water cycle, as the core factor to maintain the healthy operation of karst wetlands, has become a hot topic in current researches. Based on the field monitoring data of the Shizhiyan underground river system in the Guilin Huixian Wetland from April 15, 2020 to May 30, 2020, hydrological dynamic analysis and water balance are used to study the water cycle of the underground river system. The results show that (1) surface runoff, soil water, surface karst zone water and karst groundwater are sensitive to atmospheric rainfall, but the sensitivity degree is different. The sensitivity of karst groundwater is the highest, the sensitivity of surface runoff and surface karst zone water is weak, and the sensitivity of soil water is greatly affected by depth. (2) The proportion of all kinds of water circulation in the underground river system is different at different grades of rainfall, and the proportion of soil water in the system is the largest in light rain (24 h cumulative rainfall ranges from 4.2 mm to 10 mm), which accounts for about 75.87%. The proportion of soil water and karst groundwater in moderate rain (24 h cumulative rainfall is 17.8 mm) is the largest, which is about 43.38% and 44.12%, respectively. The proportion of karst groundwater in heavy rain (24 h cumulative rainfall is 24 mm) and heavy rainstorm (24 h cumulative rainfall ranges from 110.8 mm to 128.2 mm) is the largest, accounting for about 66.48%. (3) The average coefficient of regulation and storage in the study area is about 0.53, which is significantly higher than that of other karst areas, showing strong regulation and storage capacity. With the increasing rainfall, the coefficient of regulation and storage gradually decreases. (4) The conceptual model of water cycle of underground river system includes the transformation relationship and transformation amount among atmospheric rainfall, surface runoff, soil water, surface karst zone water and karst groundwater. The establishment of the conceptual model can provide a theoretical basis for the development and utilization of water resources and wetland protection of karst wetland.

Abstract Protein tyrosine kinases (PTKs) are a class of proteins with tyrosine kinase activity that phosphorylate tyrosine residues of critical molecules in signaling pathways. Their basal function is essential for maintaining normal cell growth and differentiation. However, aberrant activation of PTKs caused by various factors can deviate cell function from the expected trajectory to an abnormal growth state, leading to carcinogenesis. Inhibiting the aberrant PTK function could inhibit tumor growth. Therefore, tyrosine kinase inhibitors (TKIs), target-specific inhibitors of PTKs, have been used in treating malignant tumors and play a significant role in targeted therapy of cancer. Currently, drug resistance is the main reason for limiting TKIs efficacy of cancer. The increasing studies indicated that tumor microenvironment, cell death resistance, tumor metabolism, epigenetic modification and abnormal metabolism of TKIs were deeply involved in tumor development and TKI resistance, besides the abnormal activation of PTK-related signaling pathways involved in gene mutations. Accordingly, it is of great significance to study the underlying mechanisms of TKIs resistance and find solutions to reverse TKIs resistance for improving TKIs efficacy of cancer. Herein, we reviewed the drug resistance mechanisms of TKIs and the potential approaches to overcome TKI resistance, aiming to provide a theoretical basis for improving the efficacy of TKIs.

Abstract Background Cancer diagnoses and deaths among the elderly (65 +) are expected to increase significantly over the next decade. Immune checkpoint inhibitors specifically target ICI genes and enhance immune system function. However, poor outcomes may be associated with aging. Methods We downloaded the Genomic Data Commons from the Cancer Genome Atlas (TCGA) and collected gene expression data from malignant melanoma (MM) tissues, the third level as the primary site. The CKTTD ICI genes database were applied and validated using the GEO database and lab experiments. Results In 414 patients, 13 ICI genes were obtained as risk gene signature by univariate and multivariate Cox hazard models and were associated with poor survival in the older group. At 1, 3, and 5 years (79%, 76%, and 76%, respectively), we investigate TNFRFS4 gene and age prediction using novel nomogram-associated aging (HR = 1.79, P 0.001, CI = 1.32–2.45) with higher sensitivity testing.TNFRSF4 gene expression was significantly high in younger (15 years interval) MM patients (P

Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC–MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.

Abstract Background Although dyslipidaemia may have a crucial impact on cardiovascular health in adults, there is a lack of specific data in transitional-age youth. Therefore, this study attempted to evaluate the association of dyslipidaemia with fat-to-muscle ratio (FMR), and establish FMR thresholds for diagnosing dyslipidaemia in transitional-age youth. Methods One thousand six hundred sixty individuals aged 16 to 24 years from the baseline of a subcohort in the Northwest China Natural Population Cohort: Ningxia Project were analysed. Anthropometric characteristics were gauged by a bioelectrical impedance analyser, and dyslipidaemia components were measured using a Beckman AU480 chemistry analyser. Additionally, this study used logistic regression to estimate the risk of dyslipidaemia based on FMR quintiles, and calculate the gender-specific ideal cut-off values of dyslipidaemia and its components by the receiver operating characteristic (ROC) curve. Results Of the 1660 participants, aged 19.06 ± 1.14 years, 558 males and 1102 females. The prevalence of dyslipidaemia was 13.4% and was significantly associated with FMR quintiles among all participants (P

Abstract Background To evaluate the morphological and positional changes of mandibular condyle after miniscrew-assisted rapid palatal expansion (MARPE) in skeletal Class III malocclusion adult patients with horizontal mandibular deviation (MD). Methods The sample consisted of 15 patients with MD (6 males and 9 females, mean age 21.58 ± 3.12 years). The CBCT scans were taken before and after MARPE immediately. The pre- and post-registered images of the cranial base and mandible were measured, respectively, by Mimics. Results After expansion, the distance between superior condylar point and the Frankfort horizontal plane on the deviated side and the non-deviated side increased by 0.96 ± 0.60 mm (P = 0.011) and 0.70 ± 0.65 mm (P = 0.046); coronal condylar angle of the deviated side increased by 0.39° ± 0.34 (P = 0.028) and 0.06° ± 0.49 (P = 0.917) on the non-deviated side. No statistically significant differences were found when comparing the condylar position on both sides before and after treatment. The degree of mandibular deviation decreased 0.43 mm (P = 0.270). Conclusions This study suggested that for skeletal Class III malocclusion adult patients with horizontal MD, the condyle on the deviated side rotated toward the non-deviated side in the coronal direction; the condylar remodeling occurred mainly on the deviated side after MARPE in the vertical direction.

To improve the accuracy of the evaluation of the equivalent inertia of a power system, a method for evaluating the equivalent inertia level of a power system based on an intelligent optimization algorithm is proposed. The proposed method constructs the objective function based on different degrees of system perturbation, ignores the frequency characteristics of the load, constructs the objective function with the generator swing equation, solves the inertia time constant of each generator using the intelligent optimization algorithm, and then evaluates the equivalent inertia of the whole system, eliminates the influence of inconsistent frequency change rate under perturbation on the system equivalent inertia evaluation, and thus obtains a more accurate system equivalent inertia evaluation, experimental result shows the evaluation accuracy can be improved by 10.79% and 3.48% respectively compared with other two comparison method.

ABSTRACT: Cronobacter sakazakii is a food-borne pathogen that is resistant to a variety of environmental stress conditions. It can survive in harsh environments. We studied the effects of silver nanoparticles (AgNP) on the environmental tolerance and biofilm formation of C. sakazakii. First, we determined the minimum inhibitory concentration (MIC) of AgNP to C. sakazakii and determined the growth curve of C. sakazakii treated with different concentrations of AgNP by using the plate counting method. After determining the sub-inhibition concentrations (SIC) of AgNP on C. sakazakii, we studied the effects of AgNP on the resistance of C. sakazakii to heat, desiccation, osmotic pressure, and acid. The antibiofilm activity of AgNP was also studied. Finally, real-time quantitative PCR was used to analyze the transcription levels of 16 genes related to the environmental tolerance of C. sakazakii. The SIC of AgNP significantly reduced the survival rate of C. sakazakii under various environmental stress conditions. The results showed that AgNP at 0.625 and 1.25 μg/mL significantly inhibited the formation of C. sakazakii biofilms. The expression levels of most genes were significantly downregulated in C. sakazakii cells treated with 0.625 and 1.25 μg/mL AgNP. Therefore, AgNP may reduce the environmental tolerance of C. sakazakii by inhibiting the expression of genes related to stress tolerance. Moreover, AgNP inhibited the production of ATP in C. sakazakii cells and the formation of C. sakazakii biofilms. Our research provides a theoretical basis for the application of AgNP in food packaging, bactericidal coatings, and other fields.

Abstract To reveal the correlation of dynamic serum tumor markers (STMs) and molecular features of epidermal growth factor receptor‐mutated (EGFR‐mutated) lung cancer during targeted therapy, we retrospectively reviewed 303 lung cancer patients who underwent dynamic STM tests [neuron‐specific enolase (NSE), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153), the soluble fragment of cytokeratin 19 (CYFRA21‐1), and squamous cell carcinoma antigen (SCC)] and circulating tumor DNA (ctDNA) testing with a panel covering 168 genes. At baseline, patients with EGFR mutation trended to have abnormal CEA, abnormal CA153, and normal SCC levels. Additionally, patients with Thr790Met (T790M) mutation were more likely to have abnormal CEA levels than patients without T790M mutation. Among patients with secondary resistance to EGFR tyrosine kinase inhibitors (TKI), the dynamic STMs showed a descending trend in the responsive stage and a rising trend in the resistant stage. However, the changing slopes differed between T790M subgroup and the non‐T790M subgroup in individual STMs. Our study demonstrated that the combination of baseline levels and variations of STMs (including the responsive stage and resistant stage) can be suggestive of secondary EGFR‐T790M mutation [area under the curve (AUC) = 0.897] and that changing trends of STMs (within 8 weeks after initiating the TKI therapy) can be potential predictors for the clearance of EGFR ctDNA [AUC = 0.871]. In conclusion, dynamic monitoring STMs can help to predict the molecular features of EGFR‐mutated lung cancer during targeted therapy.

Abstract Background Genetic variants associated with acute side effects of radiotherapy in nasopharyngeal carcinoma (NPC) remain largely unknown. Methods We performed a two-stage genome-wide association analysis including a total of 1084 patients, where 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant variants were then validated in an independent cohort of 765 patients using the MassARRAY system. Gene mapping, linkage disequilibrium, genome-wide association analysis, and polygenic risk score were conducted or calculated using FUMA, LDBlockShow, PLINK, and PRSice software programs, respectively. Results Five SNPs (rs6711678, rs4848597, rs4848598, rs2091255, and rs584547) showed statistical significance after validation. Radiotherapy toxicity was more serious in mutant minor allele carriers of all five SNPs. Stratified analysis further indicated that rs6711678, rs4848597, rs4848598, and rs2091255 correlated with skin toxicity in patients of EBV positive, late stage (III and IV), receiving both concurrent chemoradiotherapy and induction/adjuvant chemotherapy, and with OR values ranging from 1.92 to 2.66. For rs584547, high occurrence of dysphagia was found in A allele carriers in both the discovery (P = 1.27 × 10− 6, OR = 1.55) and validation (P = 0.002, OR = 4.20) cohorts. Furthermore, prediction models integrating both genetic and clinical factors for skin reaction and dysphagia were established. The area under curve (AUC) value of receiver operating characteristic (ROC) curves were 0.657 (skin reaction) and 0.788 (dysphagia). Conclusions Rs6711678, rs4848597, rs4848598, and rs2091255 on chromosome 2q14.2 and rs584547 were found to be novel risk loci for skin toxicity and dysphagia in NPC patients receiving radiotherapy. Trial registration Chinese Clinical Trial Register (registration number: ChiCTR-OPC-14005257 and CTXY-140007-2).

Abstract Background Ischemic stroke is one of the most serious global public health problems. However, the performance of current therapeutic regimens is limited due to their poor target specificity, narrow therapeutic time window, and compromised therapeutic effect. To overcome these barriers, we designed an ischemia-homing bioengineered nano-scavenger by camouflaging a catalase (CAT)-loaded self-assembled tannic acid (TA) nanoparticle with a M2-type microglia membrane (TPC@M2 NPs) for ischemic stroke treatment. Results The TPC@M2 NPs can on-demand release TA molecules to chelate excessive Fe2+, while acid-responsively liberating CAT to synergistically scavenge multiple ROS (·OH, ·O2 −, and H2O2). Besides, the M2 microglia membrane not only can be served as bioinspired therapeutic agents to repolarize M1 microglia into M2 phenotype but also endows the nano-scavenger with ischemia-homing and BBB-crossing capabilities. Conclusions The nano-scavenger for specific clearance of multiple pathogenic elements to alleviate inflammation and protect neurons holds great promise for combating ischemic stroke and other inflammation-related diseases.

Abstract Purpose To analyze the mutational landscape of pan-cancer patients with PIK3CA mutations in Chinese population in real-world. Methods We analyzed PIK3CA mutation status in sequencing data of cell-free DNA from plasma and genomic DNA from matched peripheral blood lymphocyte in 11,904 Chinese pan-cancer patients, and compared them with genomic data from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Besides, concomitant genomic aberrations in PIK3CA-mutated samples were detected to investigate cancer driver genes, as well as their enriched pathways. Meanwhile, the mutations of Alpelisib targeting genes were screened and their co-alterations were analyzed according to OncoKB definition to identify the potential actionable ones. Results The proportion of patients with PIK3CA mutations varied among 21 types of cancer, with the top being BRCA, CESC, SCL, and UCEC. The most common PIK3CA mutation hotspots were found to be E545K, E542K and H1047R. The Chinese cohort had significantly lower frequencies of PIK3CA mutations in breast and stomach cancers, but markedly higher PIK3CA mutation frequencies in large intestine, kidney and lung cancers than the COSMIC cohort. Compared with COSMIC cohort, the mutation frequencies of Alpelisib-targeted genes in breast cancer were significantly reduced in the Chinese cohort. All PIK3CA-mutated patients had concomitant genomic aberrations. While the most common concomitant genomic alterations occurred in TP53, EGFR and FAT1, these co-mutated genes were mainly enriched in RTK/RAS pathway, PI3K pathway and P53 pathway. Moreover, 83.6% of patients carrying mutations in Alpelisib-targeted genes had at least one actionable concomitant alteration. Level 1 actionable alteration was identified in LUAD, BRCA, COAD, LUSC, READ, and STAD. Conclusion Compared with the Western cohort, the mutation frequency of PIK3CA in breast cancer was reduced in the Chinese cohort. RTK/RAS pathway, PI3K pathway and P53 pathway were identified as the most common co-mutation pathways, suggesting that they may potentially serve as targets for possible Alpelisib-based combination therapy.

Abstract Background The recent development of quinoline-based radiotracers, which act as fibroblast activation protein inhibitors (FAPIs), has shown promising preclinical and clinical advantages. [68Ga]Ga-FAPI-46 is a new radiotracer for in vivo detection of the fibroblast activation protein by positron emission tomography (PET). Recently, the automated synthesis of [68Ga]Ga-FAPI-46 was reported based on pre-concentration and purification of the generator eluate by using a cation exchange-cartridge. Our aim was to simplify the synthesis and shorten the automated synthesis of [68Ga]Ga-FAPI-46 to make it accessible and thus even more attractive to a broader clinical and scientific community. Results We developed and evaluated the GMP compliant automatic synthesis of [68Ga]Ga-FAPI-46 using two different 68Ge/68Ga generators (an Eckert & Ziegler, GalliaPharm generator, 1.85 GBq/50 mCi and an iThemba generator, 1.85 GBq/50 mCi) Somerset West, South Africa) and three different commercial and customized systems: the EasyOne module from Trasis; the GaSy module from Synthra with a customized synthesis template and a customized single use cassette. Additionally, the automatic synthesis of [68Ga]Ga-FAPI-46 was established on a GallElut synthesis module from Scintomics with fixed tubing. Conclusions Independent of the synthesis modules or the generators employed we were able to complete the synthesis of [68Ga]Ga-FAPI-46 in 12 min including the process of purification and formulation. In all cases, the final products showed more than 99.5% chemical purity and the radiochemical yield reached around 92.5% (decay corrected). All quality control parameters (e.g. sterility, stability and radiochemical purity) were conform to the European Pharmacopoeia.

Nitrene transfer chemistry is an effective strategy for introducing C–N bonds, but inexpensive reaction systems for tunable, intermolecular chemoselective nitrene transfer for late-stage amination of unsaturated natural products remains a challenge. Here, the authors report copper catalysed chemoselective allylic C–H amination and catalyst-free visible-light induced aziridination of alkenes through nitrene transfer.

Abstract Background Systemic Lutetium-177 prostate-specific membrane antigen-617 radioligand therapy (Lu-177-PSMA-617-RLT) is a novel treatment approach in patients suffering from metastasized castration-resistant prostate cancer. Nonetheless, a therapeutic response may fail to appear in a proportion of patients. This study aims to identify routinely obtainable pre- and intratherapeutic parameters to allow a prediction of overall survival in patients receiving Lu-177-PSMA-617 radioligand therapy. Methods Between January 2015 and December 2020 52 patients treated with a total of 146 cycles Lu-177-PSMA-617-RLT were retrospectively analysed in a single-center trial. The median overall survival time (OS) was compared to pre-therapeutic serological parameters, the extend of metastatic spread and previously performed therapies using Kaplan–Meier estimators and multivariate Cox-regression. Bonferroni-Holm correction was performed on all statistical tests. Results The median OS of all patients was 55.6 weeks. Multivariate Cox-regression revealed significant lower survival for decreased pretherapeutic hemoglobin levels (HR 0.698 per g/dl; 95%-CI 0.560–0.872; p = 0.001), increased lactate dehydrogenase (LDH) levels (HR 1.073 per 25 U/l; 95%-CI 1.024–1.125; p = 0.003) and the presence of hepatic metastasis (HR 6.981; 95%-CI 2.583–18.863; p

Head and neck cancer (HNC) ranks as the sixth most prevalent type of cancer globally and accounts for about 4% of all types of cancer. Among all HNC, most are head and neck squamous cell carcinoma (HNSCC) with clinical therapies that include surgery, radiation therapy, chemotherapy, immunotherapy, targeted therapy, and multimodal treatments. In recent years, chimeric antigen receptor (CAR)-T cell immunotherapy has significantly transformed the therapeutic approaches for leukemia and lymphoma and has garnered increased attention as a potential treatment for a wide range of cancers. However, CAR-T immunotherapy in solid tumors, especially HNSCCs, lags significantly behind due to the paucity of tumor-specific antigens, high levels of tumor heterogeneity, immunosuppressive tumor microenvironment, the risk of treatment-related toxicities and off-target adverse events in HNSCCs. The objective of this review is to explore the advancement of CAR-T cell therapy in the treatment of HNSCCs. We aim to outline the targeted antigens in HNSCCs, highlight the challenges and potential solutions, and discuss the relevant combination therapies. Our review presents a comprehensive overview of the recent developments in CAR-T cell therapy for HNSCCs, and provides valuable insights into future research avenues.

BackgroundSpinal cord injury (SCI) is a severe neurological injury for which no effective treatment exists. Granulocyte colony-stimulating factor (G-CSF) is used to treat autologous bone marrow transplantation, chemotherapy-induced granulocytopenia, Acquired Immune Deficiency Syndrome (AIDS), etc. Recent research has revealed the potential application of G-CSF on neuroprotective effectiveness. In central nervous system diseases, G-CSF can be used to alleviate neuronal injury.ObjectiveTo investigate the effects of G-CSF on Basso, Beattie, and Bresnahan (BBB) scale score, inclined plane test, electrophysiologic exam, quantitative analysis of TUNEL-positive cells, and quantitative analysis of glial fibrillary acidic protein (GFAP) immunostaining images in animal models of SCI.MethodsWe searched PubMed, Web of Science, and Embase databases for all articles on G-CSF intervention with animal models of SCI reported before November 2022. A total of 20 studies met the inclusion criteria.ResultsResults revealed that G-CSF intervention could improve the BBB scale score in both groups at 3, 7, 14, 28, and 35 days [at 35 days, weighted mean differences (WMD) = 2.4, 95% CI: 1.92–2.87, p

Corilagin, a polyphenolic tannic acid compound, showed significant anti-inflammatory activity in atherosclerotic mice. The present study aimed to evaluate the effect and mechanism of corilagin in atherosclerosis by in vivo, in vitro and in molecular docking strategies analysis. An atherosclerotic model was established by feeding ApoE−/− mice a high-fat diet. Murine RAW264.7 macrophages were cultured and induced with lipopolysaccharide (LPS). Treatment with corilagin had a marked inhibitory effect on the plaque area and lipid accumulation in atherosclerotic mice. Corilagin decreased the expression of iNOS and promoted the expression of CD206 in aortic plaque, as well as inhibited the production of proinflammatory factors in HFD-fed ApoE−/− mice and LPS-induced RAW264.6 cell. Corilagin also obviously inhibited the expression of TLR4, reduced the phosphorylation of the JNK, the protein expressions of p38 and NF-κB pathway. In addition, corilagin markedly diminished the nuclear translocation of NF-κBp65. Similarly, molecular docking study suggested that hydrogen bonds were detected between the corilagin and the five proteins (TLR4, Myd88, p65, P38, and JNK) with a significant “CDOCKER energy”. These results showed that the antiatherosclerotic effect of corilagin against M1 macrophage polarization and inflammation via suppression the activation of TLR4-NFκB/MAPK signaling pathway. Therefore, corilagin could be a promising lead compound to develop drugs for the treatment of atherosclerosis.

After the public health event of COVID-19, more academics are looking into how to predict combined economic hazards associated with public health incidents. There are currently just a few approaches for detecting aberrant behaviour in aggregated financial risk, and most only work after the economic risk has already been inappropriately aggregated. As a result, we provide a multi-scale convolutional neural network-based model for clustering financial risk anomaly detection (MCNN). First, we use MCNN to train a model for counting economic risks that are used to evaluate aberrant risk aggregating data. Second, we can use the test results to extract the financial risk statistics and economic risk precursor coordinate points. Then, we calculate the economic risk distribution entropy, distance, potential energy and density. To train the three elements of the development state and create the prediction model, we finally use the particle swarm optimization-based extreme learning machine (PSO-ELM). The results of the experiments demonstrate that, in comparison to existing algorithms, our model can efficiently realize early warning and detect abnormal behaviours of aggregated economic risks with high timeliness. Additionally, our method achieves a forecast accuracy of 97.68% and can give additional time to take emergency action.

ABSTRACT To investigate community synergy of lactic acid bacteria (LAB) and cleaner fermentation of oat silage, oat silages were prepared with or without (control) commercial LAB inoculants LI1 (containing Lactiplantibacillus plantarum, Lentilactobacillus buchneri, Lacticaseibacillus paracasei, and Pediococcus acidilactici) and LI2 (containing Lactiplantibacillus plantarum and Lentilactobacillus buchneri). The microbial community, LAB synergy, and cleaner fermentation were analyzed at 1, 3, 6, 15, 35, and 90 days of ensiling. The LAB inoculant improved fermentation quality, with significantly (P

In the context of sustainable economic development, while economic globalization brings new vitality to the company, it also makes the company face an increasingly severe external environment. The managers have to shift their focus to capital market investment. The excessive pursuit of investment benefits can easily lead to decision-making errors, resulting in a financial crisis for the company, and even may be forced to delist in severe cases. This article proposes a financial crisis prediction model based on Artificial Bee Colony—recurrent neural network (ABC-RNN) and bidirectional long short-term memory (Bi-LSTM) company with a characteristic attention mechanism. We combined ABC-RNN with Bi-LSTM to extract more temporal feature vectors from financial data. Then we introduced a feature attention mechanism to extract better depth features from financial data; the ABC algorithm is introduced to optimize the weight and bias of RNN to improve the reasoning speed and accuracy. The experiment shows that the prediction accuracy and recall of the model on the test set have reached 88.94% and 88.23%, respectively, which has good prediction ability. The outcome of this research helps the company to prevent and deal with the financial crisis in time and promote the sustainable development of the market economy.

Objectives This study aimed to determine the changing prevalence of clustering of cardiovascular disease (CVD) risk factors across socioeconomic spectra in rural southwest China.Design Data were collected from two waves of cross-sectional health interviews and examinations among individuals aged ≥35 years in rural China. Anthropometric measurements, blood pressure and fasting blood sugar levels were recorded for each participant.Setting This study was conducted in rural Yunnan Province of China.Participants 8187 individuals in 2011 and 7572 in 2021 consented to participate in this study.Results From 2011 to 2021, prevalence increased of hypertension (26.1% vs 41.6%), diabetes mellitus (5.9% vs 9.8%), obesity (5.9% vs 12.0%) and central obesity (50.0% vs 58.3%) (p

Manganese (Mn(II)) pollution has recently increased and requires efficient remediation. In this study, Serratia marcescens QZB-1, isolated from acidic red soil, exhibited high tolerance against Mn(II) (up to 364 mM). Strain QZB-1 removed a total of 98.4% of 18 mM Mn(II), with an adsorption rate of 71.4% and oxidation rate of 28.6% after incubation for 48 h. The strain synthesized more protein (PN) to absorb Mn(II) when stimulated with Mn(II). The pH value of the cultural medium continuously increased during the Mn(II) removal process. The product crystal composition (mainly MnO2 and MnCO3), Mn-O functional group, and element-level fluctuations confirmed Mn oxidation. Overall, strain QZB-1 efficiently removed high concentration of Mn(II) mainly via adsorption and showed great potential for manganese wastewater removal.

Introduction Microcurrent therapy (MCT) is a rising conservative treatment for patients with knee osteoarthritis (OA). Considering its potential benefits and convenience, MCT’s application in those individuals with knee OA is capacious. However, no plausible clinical evidence has proved its unequivocal advantages in treating knee OA conservatively. The purpose of this study is to determine whether MCT is helpful in pain management and promoting function of knee OA and is safe in the treatment of knee OA in adult patients.Methods and analysis We will search through MEDLINE, Embase, Cochrane Library, Web of Science and Google Scholar from inception to 15 March 2023. Original studies will include randomised controlled trials of patients treated with MCT. Two authors will independently screen, select studies, extract data and perform risk of bias assessment. Data consistently reported across studies will be pooled using random-effects meta-analysis. Heterogeneity will be evaluated using Cochrane’s Q statistic and quantified using I2 statistics. Graphical and formal statistical tests will be used to assess for publication bias.Ethics and dissemination Ethical approval will not be needed for this study as the data will be extracted from already published studies. The results of this review will be published in a peer-reviewed journal and presented at conferences.PROSPERO registration number CRD42022319828

Instruction: Due to the declining production rate of conventional natural gas reservoir and the rising demand for natural gas resources, conventional natural gas resources cannot satisfy the needs of economic development. Unconventional gas resource is considered to be the most promising energy supplement, therefore it is an inevitable trend to explore and develop unconventional oil and gas resources such as low permeability reservoirs. At present, the carbonate gas reservoirs in the high permeability area of Sichuan Basin have been almost fully developed, while the remaining gas reservoirs in the low permeability area are not well developed. However, the key factors for effectively enhancing gas recovery rate in different types of low permeability reservoirs are not the same. Even gas reservoirs with the same macroscopic geological characteristics will show different development characteristics through the production processes.Method: In order to analyze the factors affecting the effective production rate of low-permeability gas reservoirs, it is necessary to conduct research from the microscopic perspective, to reveal the effective production conditions of natural gas in low-permeability reservoirs. In this study, low-permeability carbonate samples of Sinian Dengying Formation from Sichuan Basin were taken. Micro-CT scanning technology was used to obtain core images for the carbonate rocks, and the digital carbonate core models at microscopic scale were reconstructed. Based on the reconstructed carbonate digital core models, LBM method was applied to obtain the absolute permeability of the core models.Results: The results imply that the porosity, pore area fraction, throat area fraction, mean throat length, shape factor, coordination number and tortuosity are the factors affecting the absolute permeability of carbonate rocks.Discussion: Subsequently, the relationship between different pore structure parameters and absolute permeability was obtained by multi-parameter fitting method, which provided a new research method for directly predicting the absolute permeability of carbonate rocks by using pore structure parameters.

Obesity has become one of the major threats to human health across the globe. The rhizomes of Polygonatum sibiricum have shown promising anti-obesity effect. However, the metabolic and genetic basis mediating this beneficial effect are not fully resolved. It is well known that older rhizomes of P. sibiricum exert stronger pharmacological effects. Here, we performed high-resolution metabolome profiling of P. sibiricum rhizomes at different growth stages, and identified that three candidate anti-obesity metabolites, namely phloretin, linoleic acid and α-linolenic acid, accumulated more in adult rhizomes. To elucidate the genetic basis controlling the accumulation of these metabolites, we performed transcriptome profiling of rhizomes from juvenile and adult P. sibiricum. Through third-generation long-read sequencing, we built a high-quality transcript pool of P. sibiricum, and resolved the genetic pathways involved in the biosynthesis and metabolism of phloretin, linoleic acid and α-linolenic acid. Comparative transcriptome analysis revealed altered expression of the genetic pathways in adult rhizomes, which likely lead to higher accumulation of these candidate metabolites. Overall, we identified several metabolic and genetic signatures related to the anti-obesity effect of P. sibiricum. The metabolic and transcriptional datasets generated in this work could also facilitate future research on other beneficial effects of this medicinal plant.

To investigate the durability of cementitious materials under complex environmental conditions in Xinjiang, this study conducted durability tests on mortar specimens with different fly ash contents under dry/wet sulfate attack conditions, with standard curing and steam curing at 70 °C. The appearance loss and flexural and compressive strength variations in the specimens were analyzed, and an evolution model of the mortar strength under a dry/wet sulfate attack was established. Moreover, XRD and SEM techniques were used to characterize the erosion products and microstructure, and to explore the erosion resistance mechanism of fly ash cementitious materials. The results showed that, after 160 cycles of erosion, the flexural strength of the specimens decreased with the increase in the fly ash content. In the context of steam-cured mortar specimens, throughout the entire erosion period, specimens with a fly ash content of 45% exhibited the highest relative compressive strength. The established strength evolution model had a minimum determination coefficient of 0.879, indicating a good agreement between the model and experimental results. Microscopic research showed that fly ash would undergo a pozzolanic reaction under the action of sulfate and calcium hydroxide, which was beneficial to the improvement of the erosion resistance. As the fly ash content increased, the erosion products of the specimens gradually became dominated by gypsum.

Graphene oxide (GO), as a novel carbon-based nanomaterial (CBN), has been widely applied to every respect of social life due to its unique composite properties. The widespread use of GO inevitably promotes its interaction with heavy metal cadmium (Cd), and influences its functional behavior. However, little information is available on the effects of GO on greening hyperaccumulators under co-occurring Cd. In this study, we chose a typical greening hyperaccumulator (Lonicera japonica Thunb.) to show the effect of GO on Cd accumulation, growth, net photosynthesis rate (Pn), carbon sequestration and oxygen release functions of the plant under Cd stress. The different GO-Cd treatments were set up by (0, 10, 50 and 100 mg L−1) GO and (0, 5 and 25 mg L−1) Cd in solution culture. The maximum rate of Cd accumulation in the roots and shoots of the plant were increased by 10 mg L−1 GO (exposed to 5 mg L−1 Cd), indicating that low-concentration GO (10 mg L−1) combined with low-concentration Cd (5 mg L−1) might stimulate the absorption of Cd by L. japonica. Under GO treatments without Cd, the dry weight of root and shoot biomass, Pn value, carbon sequestration per unit leaf area and oxygen release per unit leaf area all increased in various degrees, especially under 10 mg L−1 GO, were 20.67%, 12.04%, 35% and 28.73% higher than the control. Under GO-Cd treatments, it is observed that the cooperation of low-concentration GO (10 mg L−1) and low-concentration Cd (5 mg L−1) could significantly stimulate Cd accumulation, growth, photosynthesis, carbon sequestration and oxygen release functions of the plant. These results indicated that suitable concentrations of GO could significantly alleviate the effects of Cd on L. japonica, which is helpful for expanding the phytoremediation application of greening hyperaccumulators faced with coexistence with environment of nanomaterials and heavy metals.

To investigate the mechanism of melatonin (MT)-mediated glutathione (GSH) in promoting glucoraphanin (GRA) and sulforaphane (SF) synthesis, the gene expression pattern and protein content of hairy broccoli roots under MT treatment were analyzed by a combination of RNA-seq and tandem mass spectrometry tagging (TMT) techniques in this study. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that both proteins and mRNAs with the same expression trend were enriched in the “Glutathione metabolism (ko00480)” and “Proteasome (ko03050)” pathways, and most of the differentially expressed genes (DEGs) and differentially abundant proteins (DAPs) regulating the two pathways were downregulated. The results showed that endogenous GSH concentration and GR activity were increased in hairy roots after MT treatment. Exogenous GSH could promote the biosynthesis of GRA and SF, and both exogenous MT and GSH could upregulate the expression of the GSTF11 gene related to the sulfur transport gene, thus promoting the biosynthesis of GRA. Taken together, this study provides a new perspective to explore the complex molecular mechanisms of improving GRA and SF synthesis levels by MT and GSH regulation.

Minerals of the apatite group commonly occur in granite pegmatites, and their ability to incorporate a wide range of trace elements makes them a good indicator of magma composition and magmatic–hydrothermal processes. Gem-quality purple apatite crystals from the Dara-e-Pech pegmatite field in Afghanistan have rarely been reported. Here, we investigated apatite crystals originated from this locality, using gemological testing, chemical analysis, and in situ U–Pb dating, with the purpose of identifying their origin, the constraints on the magma source in which the apatite crystals were formed, and the timing of the magmatic–hydrothermal activity. Our findings demonstrate that the purple apatite crystals were impure fluorapatite, characterized by heavy rare-earth element (HREE) enrichment, intermediate Eu anomalies, and non-CHARAC Y/Ho ratios. The results showed that these apatite crystals yielded a lower intercept age of 135.8 ± 6.9 Ma. We proposed that the pegmatitic apatite samples formed in a transitional magmatic–hydrothermal pegmatitic system with moderate fO2 in the Early Cretaceous (~135 Ma). Our study helps to constrain the magmatic–hydrothermal activities of the little-known Dara-e-Pech pegmatite field.

The cleanliness of charging power determines whether electric vehicles can fully utilize their low-carbon properties. This paper, taking into account the impact of temperature on the energy consumption of electric vehicle air conditioning, uses the Monte Carlo algorithm to calculate the typical daily charging load of electric vehicle clusters in different seasons. Secondly, based on the Shapley value carbon responsibility allocation method, a reasonable range of carbon emission responsibilities for different electric vehicle agents is calculated, and a tiered carbon pricing method is proposed accordingly. Then, using carbon emission flow theory, we calculate the carbon emissions generated by the different agents’ charging amounts and corresponding carbon emission costs. Finally, a low-carbon incentive guidance model is constructed with the signal of tiered carbon prices and the goal of minimizing operating costs to re-optimize the charging load distribution of electric vehicles. Case studies showcase that the proposed method is effective in reducing power system carbon emissions and electric vehicle charging costs.

The rhizosphere harbors abundant plant growth-promoting rhizobacteria (PGPR) that are vital for plant health. In this study, we screened growth-promoting bacteria from tomato rhizosphere soil, verified their functions, and constructed the optimal combination of growth-promoting bacteria for promoting tomato growth. Furthermore, the effects of these bacteria on various physiological and biochemical parameters of tomato plants were evaluated. A total of 36 strains of rhizobacteria were isolated from tomato rhizosphere soil and their abilities to produce indole-3-acetic acid (IAA), solubilize phosphate and iron carriers were assessed. The bacterial strains with the highest capacities for IAA production (R62, R317), phosphate solubilization (R41, R219), and siderophore production (R25, R325) were selected to form three bacterial combinations: R62 + R219 + R317 + R325 (T1), R62 + R325 (T5), and R317 + R325 (T8). Fifteen days after inoculation, all three combinations showed a stimulatory effect on seedling growth compared to the un-inoculated control. Inoculation with T1, T5 and T8 increased the seedling vigor index by 173.7%, 204.1%, and 168.7%, respectively. Compared to the un-inoculated control, the T1 combination increased the activities of polyphenol oxidase, peroxidase, and the net photosynthetic rate by 132.7%, 18.7%, 58.5%, and upregulated the relative expression levels of the photosynthetic assimilation-related genes RbcL, RbcS, FBPase and FDA by 22.2-, 6.6-, 1.95-, and 2.0-fold, respectively. Our findings provide a potential for constructing rhizobacterial combinations of different functional groups for improving crop growth.

Managing soil salinity has always been a difficult problem for agriculture. Balancing water and salt while maintaining crop quality and yield is a key issue for agricultural sustainability. The Hetao lrrigation District in China has a complex mix of cultivated and uncultivated land which plays a crucial role in soil salinization processes. To investigate the dynamic properties of soil moisture and salinity, soil ions and groundwater, cultivated and fallow soils in the Hetao lrrigation District were analyzed, side by side, using a combination of field and laboratory tests, with data processed using univariate and multivariate statistical approaches. The results showed that soil moisture increased with increasing soil depth in both cultivated and fallow soils. Salinity showed an increasing trend in 2022 and 2023 from April to September. The soil ions were mainly sulfate in the cultivated soils and chloride in the fallow soils. The characteristic factors affecting salt accumulation in cultivated soils are Na++K+, Cl−, SSC, SO42−, HCO3−, and pH, and the characteristic factors affecting salt accumulation in fallow soils are Na++K+, Cl−, SSC, HCO3−, and pH. Water table depth varied with irrigation and precipitation and was strongly influenced by external environmental factors. Groundwater salinity remained stable throughout the study period. This study provides a theoretical basis for the prevention and control of soil salinization in arid and semiarid areas through the “dry drainage salt” measure.

Sandstones are enriched in deep energy reservoirs and also exist as outcrop rocks, where the pore characteristics of sandstone are influenced by hydration absorption and thermal effects. To study the influence of the initial temperature on the hydration absorption characteristics of outcrop porous sandstone in the Mogao Grottoes, China, an intelligent experimental device for rock hydration was used. The hydration absorption characteristics and temperature effects of sandstone were analyzed by using infrared thermography techniques to monitor the infrared radiation characteristics of the sandstone’s surface during hydration absorption. The experimental results show that the higher the initial temperature of the rock samples, the shorter the time it takes for the sandstone to absorb enough water to reach saturation. The temperature variation of sandstone with different initial temperatures was also determined; the variation in the hydration absorption of sandstone conforms to certain rules, which can be expressed by formulae containing certain parameters. The changing trend of hydration absorption in outcrop porous sandstone shows that the hydration absorption increases rapidly at first, and then the rate of increase slows down until the hydration absorption remains unchanged after saturation. The experimental technique and method provide feasible means and techniques to evaluate the hydration absorption and thermal effects of outcrop porous sandstone, for further detecting the weathering degree of rock grottoes and revealing the damage mechanisms.

With the use of Li-ion batteries, Li-ion batteries will experience unavoidable aging, which can cause battery safety issues, performance degradation, and inaccurate SOC estimation, so it is necessary to predict the state of health (SOH) of Li-ion batteries. Existing methods for Li-ion battery state of health assessment mainly focus on parameters such as constant voltage charging time, constant current charging time, and discharging time, with little consideration of the impact of changes in Li-ion battery temperature on the state of health of Li-ion batteries. In this paper, a new prediction method for Li-ion battery health state based on the surface difference temperature (DT), incremental capacity analysis (ICA), and differential voltage analysis (DVA) is proposed. Five health factors are extracted from each of the three curves as input features to the model, respectively, and the weights, thresholds, and number of hidden layers of the Elman neural network are optimized using the Whale of a Whale Algorithm (WOA), which results in an average decrease of 43%, 49%, and 46% in MAE, RMSE, and MAPE compared to the Elman neural network. For the problem where the three predictions depend on different sources, the features of the three curves are fused using the weighted average method and predicted using the WOA–Elman neural network, whose MAE, RMSE, and MAPE are 0.00054, 0.0007897, and 0.06547% on average. The results show that the proposed method has an overall error of less than 2% in SOH prediction, improves the accuracy and robustness of the overall SOH estimation, and reduces the computational burden to some extent.

As a dietary supplement or functional food additive, vitamin D (VD) deficiency may impact extra-skeletal functions associated with metabolic syndrome (MetS) risk factors. However, the precise effects and mechanisms of VD supplementation on dyslipidemia and insulin resistance in MetS subjects remain controversial. Here, we investigate potential therapeutic targets, pathways and mechanisms of VD against MetS through a comprehensive strategy including meta-analysis, network pharmacology analysis, molecular docking, dynamics simulations, and quantum chemical calculations. Our results reveal that VD supplementation significantly reduces triglyceride levels, fasting glucose, and insulin concentrations in subjects, thereby improving insulin homeostasis to some extent. We theoretically identify 14 core MetS-associated targets. Notably, VD exhibits substantial interactions with three targets (PPARγ, FABP4, and HMGCR) in the PPAR signaling pathway, indicating that VD can modulate this pathway. Van der Waals forces predominantly stabilize the complexes formed between VD and the three targets. Nonetheless, to provide valuable insights for personalized MetS management, further research is necessary to confirm our findings, emphasizing the importance of exploring genetic variability in VD response. In conclusion, our study contributes insights into the mechanisms of VD in preventing and treating MetS through dietary supplementation, promoting the development of VD-based functional foods or nutritious diets.

Dendrobium officinale polysaccharide (DOP) has shown various biological activities. However, the ability of DOP to participate in immune regulation during anti-gastric cancer treatment has remained unclear. In this study, the in vitro results showed that DOP has the potential to polarize THP-1 macrophages from the M2 to the M1 phenotype, downregulate the STAT6/PPAR-r signaling pathway and the protein expression of their down-targeted ARG1 and TGM2, and further decrease the main protein and mRNA expression in the JAGGED1/NOTCH1 signaling pathway. DOP suppressed the migration of gastric cancer cells by decreasing the protein expression of N-cadherin and Vimentin and increasing E-cadherin. In addition, CM-DOP promoted the apoptosis of gastric cancer cells by upregulating Caspase-3 and increasing the ratio of Bax/Bcl-2. In vivo, DOP effectively inhibited the growth of tumors and the expression of Ki-67. In summary, these findings demonstrated that DOP converted the polarization of M2 subtype macrophages into M1 subtypes via the STAT6/PPAR-r and JAGGED1/NOTCH1 signaling pathways in order to reduce apoptosis and prevent migration, thus indicating the potential of DOP as an adjuvant tumor therapy in preclinical and clinical trials.

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important pathogens in the global swine industry over the past three decades. There is no licensed antiviral medication that can effectively control this infection. In the present study, the structure of SP-1 isolated and purified from Sargassum weizhouense was analyzed, and its antioxidant capacity and antiviral effect in MARC-145 cells against PRRSV were investigated. The results showed that SP-1 is a novel polysaccharide which mainly is composed of →4)-β-D-ManpA-(1→, →4)-α-L-GulpA-(1→ and a small amount of →4)-β-D-GalpA-(1→. PRRSV adsorption, replication, and release were all suppressed by SP-1. SP-1 therapy down-regulated mRNA expression of the CD163 receptor while increasing the antioxidant gene expression of Nrf2, TXNIP, and HO-1; increasing the protein expression of NQO1 and HO-1; and drastically reducing the protein expression of p-p65. The findings indicated that SP-1 reduces PRRSV adsorption, replication, and release through blocking the expression of the crucial CD163 receptor during infection. Meanwhile, SP-1 exerts antioxidant effects in PRRSV-infected cells through the activation of the Nrf2-HO1 signaling pathway.

MicroRNAs (miRNAs) are important regulators in gene expression. The dysregulation of miRNA expression is widely reported in the transformation from physiological to pathological states of cells. A large number of differentially expressed miRNAs (DEMs) have been identified in various human cancers by using high-throughput technologies, such as microarray and miRNA-seq. Through mining of published studies with high-throughput experiment information, the database of DEMs in human cancers (dbDEMC) was constructed with the aim of providing a systematic resource for the storage and query of the DEMs. Here we report an update of the dbDEMC to version 3.0, which contains two-fold more data entries than the second version and now includes also data from mice and rats. The dbDEMC 3.0 contains 3268 unique DEMs in 40 different cancer types. The current datasets for differential expression analysis have expanded to 9 generalized categories. Moreover, the current release integrates functional annotations of DEMs obtained by using experimentally validated targets. The annotations can be of great benefit to the intensive analysis of the roles of DEMs in cancer. In summary, dbDEMC 3.0 provides a valuable resource for characterizing molecular functions and regulatory mechanisms of DEMs in human cancers. The dbDEMC 3.0 is freely accessible at https://www.biosino.org/dbDEMC.