Comprehensive analysis of prognostic value and immunotherapy prospect of brain cytoplasmic RNA1 in hepatocellular carcinoma.

BACKGROUND: The expression of brain cytoplasmic RNA1 (BCYRN1) is linked to the clinicopathology and prognosis of several types of cancers, among which hepatocellular carcinoma (HCC) is one of the most frequent types of cancer worldwide. AIM: To explore the prognostic value and immunotherapeutic potential of BCYRN1 in HCC by bioinformatics and meta-analysis. METHODS: Information was obtained from the Cancer Genome Atlas database. First, the correlation between BCYRN1 expression and prognosis and clinicopathologic characteristics of HCC patients was explored. Univariate and multivariate regression analyses were employed to examine the relationship between BCYRN1 and HCC prognosis. Secondly, potential functions and pathways were explored by means of enrichment analysis of differentially-expressed genes. The relationships between BCYRN1 expression and tumor microenvironment, immune cell infiltration, immune checkpoint, drug sensitivity and immunotherapy effect were also investigated. Finally, three major databases were searched and used to conduct a meta-analysis on the relationship between BCYRN1 expression and patient prognosis. RESULTS: BCYRN1 expression was significantly higher in HCC compared to normal tissues and was linked to a poor prognosis and clinicopathological characteristics. Enrichment analysis showed that BCYRN1 regulates the extracellular matrix and transmission of signaling molecules, participates in the metabolism of nutrients, such as proteins, and participates in tumor-related pathways. BCYRN1 expression was linked to the tumor microenvironment, immune cell infiltration, drug sensitivity and the efficacy of immunotherapy. Furthermore, the meta-analysis in this study showed that BCYRN1 overexpression was related to a worse outcome in HCC patients. CONCLUSION: Overexpression of BCYRN1 relates to poor prognosis and may be a potential prognostic factor and immunotherapeutic target in HCC.

Metabolite Signature of Life's Essential 8 and Risk of Coronary Heart Disease among Low-Income Black and White Americans.

Background and Aims: Life's Essential 8 (LE8) is a comprehensive construct of cardiovascular health. Yet, little is known about LE8 score, its metabolic correlates, and their predictive implications among Black Americans and low-income individuals. Methods: In a nested case-control study of coronary heart disease (CHD) among 598 Black and 596 White low-income Americans, we estimated LE8 score, conducted untargeted plasma metabolites profiling, and used elastic net with leave-one-out cross-validation to identify metabolite signature (MetaSig) of LE8. Associations of LE8 score and MetaSig with incident CHD were examined using conditional logistic regression. Mediation effect of MetaSig on the LE8-CHD association was also examined. The external validity of MetaSig was evaluated in another nested CHD case-control study among 598 Chinese adults. Results: Higher LE8 score was associated with lower CHD risk [standardized OR (95% CI)=0.61 (0.53-0.69)]. The identified MetaSig, consisting of 133 metabolites, showed strong correlation with LE8 score ( r =0.61) and inverse association with CHD risk [OR (95% CI)=0.57 (0.49-0.65)], robust to adjustment for LE8 score and across participants with different sociodemographic and health status (ORs: 0.42-0.69; all P <0.05). MetaSig mediated a large portion of the LE8-CHD association: 53% (32%-80%) ( P <0.001). Significant associations of MetaSig with LE8 score and CHD risk were found in validation cohort [ r =0.49; OR (95% CI)=0.57 (0.46-0.69)]. Conclusions: Higher LE8 score and its MetaSig were associated with lower CHD risk among low-income Black and White Americans. Metabolomics may offer an objective and comprehensive measure of LE8 score and its metabolic phenotype relevant to CHD prevention among diverse populations.

Guiqi Baizhu prescription ameliorates cytarabine-induced intestinal mucositis by targeting JAK2 to inhibit M1 macrophage polarization.

BACKGROUND: Intestinal mucositis (IM) is characterized by damage to the intestinal mucosa resulting from inhibition of epithelial cell division and loss of renewal capacity following anticancer chemotherapy and radiotherapy. Cytarabine (Ara-C), the main chemotherapy drug for the treatment of leukemia and lymphoma, is a frequent cause of IM. Guiqi Baizhu prescription (GQBZP) is a traditional Chinese medicine with anti-cancer and anti-inflammatory effects. PURPOSE: To determine if GQBZP can ameliorate Ara-C induced IM and identify and characterize the pharmacologic and pharmacodynamic mechanisms. STUDY DESIGN AND METHODS: IM was induced in mice with Ara-C and concurrently treated with orally administered GQBZP. Body weight and food intake was monitored, with HE staining to calculate ileal histomorphometric scoring and villus length/crypt depth. Immunoblotting was used to detect intestinal tissue inflammatory factors. M1 macrophages (M1) were labeled with CD86 by flow cytometry and iNOS + F4/80 by immunofluorescence. Virtual screening was used to find potentially active compounds in GQBZP that targeted JAK2. In vitro, RAW264.7 cells were skewed to M1 macrophage polarization by lipopolysaccharide (LPS) and interferon-γ (INF-γ) and treated orally with GQBZP or potential active compounds. M1 was labeled with CD86 by flow cytometry and iNOS by immunofluorescence. ELISA was used to detect inflammatory factor expression. Active compounds against JAK2, p-JAK2, STAT1 and p-STAT1 were identified by western blotting and HCS fluorescence. Molecular dynamics simulations and pharmacokinetic predictions were carried out on representative active compounds. RESULTS: Experimental results with mice in vivo suggest that GQBZP significantly attenuated Ara-C-induced ileal damage and release of pro-inflammatory factors by inhibiting macrophage polarization to M1. Molecular docking was used to identify potentially active compounds in GQBZP that targeted JAK2, a key factor in macrophage polarization to M1. By examining the main components of each herb and applying Lipinski's rules, ten potentially active compounds were identified. In vitro experimental results suggested that all 10 compounds of GQBZP targeted JAK2 and could inhibit M1 polarization in RAW264.7 cells treated with LPS and INF-γ. Among them, acridine and senkyunolide A down-regulated the expression of JAK2 and STAT1. MD simulations revealed that acridine and senkyunolide A were stable in the active site of JAK2 and exhibited good interactions with the surrounding amino acids. CONCLUSIONS: GQBZP can ameliorate Ara-C-induced IM by reducing macrophage polarization to M1, and acridine and senkyunolide A are representative active compounds in GQBZP that target JAK2 to inhibit M1 polarization. Targeting JAK2 to regulate M1 polarization may be a valuable therapeutic strategy for IM.

SUMO1 modification stabilizes TET3 protein and increases colorectal cancer radiotherapy sensitivity.

OBJECTIVE: To explore more about the role and mechanism of active DNA demethylase in colorectal cancer radiation sensitization, and better understand the function of DNA demethylation in tumor radiosensitization. METHODS: Tested the effect of TET3 overexpression on the sensitivity of colorectal cancer to radiotherapy through G2/M arrest, apoptosis, clonogenic suppression. TET3 knockdown HCT 116 and TET3 knockdown LS 180 cell lines were constructed by siRNA technology, and the effect of exogenous knockdown of TET3 on radiation-induced apoptosis, cell cycle arrest, DNA damage, and clone formation in colorectal cancer cells were detected. The co-localization of TET3 and SUMO1, SUMO2/3 was detected by immunofluorescence and cytoplasmic, nuclear extraction. And the interaction between TET3 and SUMO1, SUMO2/3 was detected by CoIP assay. RESULTS: The malignant phenotype and radiosensitivity of colorectal cancer cell lines were favorably linked with TET3 protein and mRNA expression.TET3 is upregulated in 23 of the 27 tumor types investigated, including colon cancer. TET3 was shown to positively correlate with the colorectal cancer pathological malignancy grade. Overexpression of TET3 in colorectal cancer cell lines increased radiation-induced apoptosis, G2/M phase arrest, DNA damage, and clonal suppression in vitro. The binding region of TET3 and SUMO2/3 was located at 833-1795 AA except for K1012, K1188, K1397, and K1623. SUMOylation of TET3 increased the stability of TET3 protein without changing its nuclear localization. CONCLUSIONS: we elucidated the sensitizing role of TET3 protein in the radiation of CRC cells, depending on SUMO1 modification of TET3 at the lysine sites (K479, K758, K1012, K1188, K1397, K1623), in turn stabilizing TET3 expression in the nucleus and subsequently increasing the sensitivity of colorectal cancer to radiotherapy. Together, this study highlights the potentially critical role of TET3 SUMOylation in radiation regulation, which may contribute to an enhanced understanding of the relationship between DNA demethylation and radiotherapy.

MTF1 has the potential as a diagnostic and prognostic marker for gastric cancer and is associated with good prognosis.

PURPOSE: Metal Regulatory Transcription Factor 1 (MTF1) can be an essential transcription factor for heavy metal response in cells and can also reduce oxidative and hypoxic stresses in cells. However, the current research on MTF1 in gastric cancer is lacking. METHODS: Bioinformatics techniques were used to perform expression analysis, prognostic analysis, enrichment analysis, tumor microenvironment correlation analysis, immunotherapy Immune cell Proportion Score (IPS) correlation and drug sensitivity correlation analysis of MTF1 in gastric cancer. And qRT-PCR was used to verify MTF1 expression in gastric cancer cells and tissues. RESULTS: MTF1 showed low expression in gastric cancer cells and tissues, and low expression in T3 stage compared with T1 stage. KM prognostic analysis showed that high expression of MTF1 was significantly associated with longer overall survival (OS), FP (first progression) and PPS (post-progression survival) in gastric cancer patients. Cox regression analysis showed that MTF1 was an independent prognostic factor and a protective factor in gastric cancer patients. MTF1 is involved in pathways in cancer, and the high expression of MTF1 is negatively correlated with the half maximal inhibitory concentration (IC50) of common chemotherapeutic drugs. CONCLUSION: MTF1 is relatively lowly expressed in gastric cancer. MTF1 is also an independent prognostic factor for gastric cancer patients and is associated with good prognosis. It has the potential to be a diagnostic and prognostic marker for gastric cancer.

Pilot-scale two-phase anaerobic digestion of deoiled food waste and waste activated sludge: Effects of mixing ratios and functional analysis.

Anaerobic co-digestion of deoiled food waste (dFW) and waste activated sludge (WAS) can address the challenges derived from mono-digestion of FW. In the present study, a pilot-scale methanogenic bioreactor of a two-phase anaerobic digestion system was developed to explore the impact of dFW/WAS volatile solids ratios on the overall performance, microbial community, and metabolic pathways. Besides, the tech-economic of the system was analyzed. The results showed that the degradation efficiency of soluble chemical oxygen demand (SCOD) was more than 84.90% for all the dFW/WAS ratios (v/v) (1:0, 39:1, 29:1, 19:1 and 9:1). Moreover, the dominant genus of bacteria and archaea with different ratios were Lactobacillus (66.84-98.44%) and Methanosaeta (53.66-80.09%), respectively. Co-digestion of dFW and WAS (29: 1 in v/v ratios) obtained the highest yield of methane (0.41 L CH4/Ladded) with approximately 90% of SCOD being removed. In the pilot-scale experiment, the co-digestion of FW and WAS makes positive contribution to reusing solid waste for improving solid management.

Uncovering the special microbiota associated with occurrence and progression of gastric cancer by using RNA-sequencing.

Gastric cancer (GC) has been identified as the third deadly cancer in the world. Accumulating researches suggest a potential role of microorganisms in tumorigenesis. However, the composition of microbiota in GC tissues is not clear and it changes throughout the different stages of GC remain mostly elusive. Our study integrated RNA-Seq data of 727 samples derived from gastric tissues across four datasets and revealed its microbial composition. In order to remove the false positive results, core taxa were defined and characterized. Based on it, we analyzed the influence of biological factors on its composition. The pan-microbiome of gastric tissues was estimated to be over than 1400 genera. Seventeen core genera were identified. Among them, Helicobacter, Lysobacter were significantly enriched in normal tissues, while Pseudomonas was enriched in tumor tissues. Interestingly, Acinetobacter, Pasteurella, Streptomyces, Chlamydia, and Lysobacter, showed a significant increase trend during tumor development and formed strong intra/inter-correlations among them or with other genera. Furthermore, we found that tumor stage played an important role in altering the microbial composition of GC tissues. This study provides support for the in-depth study of tumor microbiome, and the specific microbiome excavated provides a possibility for the subsequent identification of potential biomarkers for GC.

Molecularly Stimuli-Responsive Self-Assembled Peptide Nanoparticles for Targeted Imaging and Therapy.

Self-assembly has emerged as an extensively used method for constructing biomaterials with sizes ranging from nanometers to micrometers. Peptides have been extensively investigated for self-assembly. They are widely applied owing to their desirable biocompatibility, biodegradability, and tunable architecture. The development of peptide-based nanoparticles often requires complex synthetic processes involving chemical modification and supramolecular self-assembly. Stimuli-responsive peptide nanoparticles, also termed "smart" nanoparticles, capable of conformational and chemical changes in response to stimuli, have emerged as a class of promising materials. These smart nanoparticles find a diverse range of biomedical applications, including drug delivery, diagnostics, and biosensors. Stimuli-responsive systems include external stimuli (such as light, temperature, ultrasound, and magnetic fields) and internal stimuli (such as pH, redox environment, salt concentration, and biomarkers), facilitating the generation of a library of self-assembled biomaterials for biomedical imaging and therapy. Thus, in this review, we mainly focus on peptide-based nanoparticles built by self-assembly strategy and systematically discuss their mechanisms in response to various stimuli. Furthermore, we summarize the diverse range of biomedical applications of peptide-based nanomaterials, including diagnosis and therapy, to demonstrate their potential for medical translation.

Pharmacodynamic Material Basis and Potential Mechanism Study of Spatholobi Caulis in Reversing Osteoporosis.

Objective: To elucidate the mechanism of Spatholobi Caulis (SC) in treating osteoporosis (OP) integrated zebrafish model and bioinformatics. Methods: Skeleton staining coupled with image quantification was performed to evaluate the effects of SC on skeleton mineralization area (SSA) and total optical density (TOD). Zebrafish locomotor activity was monitored using the EthoVision XT. Bioactive compounds of SC and their corresponding protein targets were acquired from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Potential therapeutic targets for OP were summarized through retrieving 5 databases, and then, the overlapping genes between SC and OP were acquired. The core genes were selected by CytoHubba. Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) functional analysis of the intersection target genes were carried out by R software. Finally, the molecular docking simulation was manipulated between the ingredients and the hub genes. Results: Compared with the model group, SC significantly increased the SSA and TOD at 10 mg/mL and improved the locomotor activity in a dose-dependent manner (p < 0.001). 33 components of SC were associated with 72 OP-related genes including 10 core genes (MAPK1, VEGFA, MMP9, AKT1, AR, IL6, CALM3, TP53, EGFR, and CAT). Advanced Glycation End Product (AGE) Receptor for AGE (RAGE) signaling pathway was screened out as the principal pathway of SC in anti-OP. The bioactive components (Aloe-emodin, Emodin, Formononetin, Licochalcone A, Luteolin, and Lopac-I-3766) have excellent affinity to core genes (MAPK1, VEGFA, MMP9, AKT1, and IL6). Conclusion: SC had the hierarchical network characteristics of "multicomponents/multitargets/multifunctions/multipathways" in reversing OP, but AGE-RAGE signaling pathway may be the main regulatory mechanism.

Comparison of Efficacy and Safety of Laparoscopic Holmium laser Lithotripsy and Laparoscopic Bile Duct Exploration for Bile Duct Stones: A Systematic Review and Meta-Analysis.

BACKGROUND: Laparoscopic holmium laser lithotripsy (LHLL) has been used to treat bile duct stones with unclear outcomes. A meta-analysis was conducted to investigate the LHLL and laparoscopic bile duct exploration (LBDE) efficacy and safety in treating bile duct stones. METHODS: The correlational studies were searched databases, such as PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP, to identify eligible studies from inception to July 2022. The dichotomous and continuous outcomes were evaluated using odds ratio (OR), risk difference (RD) and weighted mean difference (WMD) with 95% confidence intervals (CIs). Stata 15.0 and Review Manager 5.3 software helped in data analyses. RESULTS: A total of 23 studies with 1,890 patients, primarily from China, were included. The results indicated that operation time (WMD = - 26.94; 95% CI:(- 34.30, - 19.58); P < 0.00001), estimated blood loss (WMD = - 17.97; 95% CI: (- 22.94, - 13.00); P = 0.002), rate of residual stone (OR = 0.15, 95%CI: (0.10, 0.23); P < 0.00001), length of hospital stay (WMD = - 2.88; 95% CI:(- 3.80, - 1.96); P < 0.00001) and time to bowel function recovery (WMD = - 0.59; 95% CI: (- 0.76, - 0.41); P < 0.00001) had statistically significant differences between the two groups. In postoperative complications, biliary leakage (RD = -0.03; 95% CI: (- 0.05, -0.00); P = 0.02), infection (RD = - 0.06; 95% CI: (- 0.09,- 0.03); P < 0.00001) and Hepatic injury (RD = - 0.06; 95% CI: (- 0.11, - 0.01); P = 0.02) revealed statistically significant differences. However, no significant differences were observed in biliary damage (RD = - 0.03; 95% CI: (- 0.06, 0.00); P = 0.06) and hemobilia (RD = - 0.03; 95% CI: (- 0.06, 0.00); P = 0.08). CONCLUSION: The current meta-analysis indicated that LHLL could be more effective and safer than LBDC. However, these results should be confirmed with a larger sample size and rigorously designed randomized controlled trials.

Development of Chinese food picture library for inducing food cravings.

Cue-induced food cravings are strong desires directed toward specific foods, usually ones with high caloric content, and can lead to overeating. However, although food cravings vary according to individual preferences for specific high-calorie food subtypes, a structured library of food craving-inducing pictures including multiple categories of high-calorie foods does not yet exist. Here, we developed and validated a picture library of Chinese foods (PLCF) consisting of five subtypes of high-calorie foods (i.e., sweets, starches, salty foods, fatty foods, and sugary drinks) to allow for more nuanced future investigations in food craving research, particularly in Chinese cultural contexts. We collected 100 food images representing these five subtypes, with four food items per subtype depicted in five high-resolution photographs each. We recruited 241 individuals with overweight or obesity to rate the food pictures based on craving, familiarity, valence, and arousal dimensions. Of these participants, 213 reported the severity of problematic eating behaviors as a clinical characteristic. Under the condition of mixing multiple subtypes of high-calorie foods, we did not observe significant differences in craving ratings for high- and low-calorie food images (p tukey > 0.05). Then, we compared each subtype of high-calorie food images to low-calorie ones, and found craving ratings were greater for the images of salty foods and sugary drinks (ps < 0.05). Furthermore, we conducted a subgroup analysis of individuals according to whether they did or did not meet the criteria for food addiction (FA) and found that greater cravings induced by the images of high-calorie food subtypes (i.e., salty foods and sugary drinks) only appeared in the subgroup that met the FA criteria. The results show that the PLCF is practical for investigating food cravings.

Iron accumulation and its impact on osteoporotic fractures in postmenopausal women. / é“è“„ç§¯åŠå ¶å¯¹å¥³æ€§ç»ç»åŽéª¨è´¨ç–æ¾æ€§éª¨æŠ˜çš„å½±å“.

Postmenopausal osteoporosis is a kind of degenerative disease, also described as "invisible killer." Estrogen is generally considered as the key hormone for women to maintain bone mineral content during their lives. Iron accumulation refers to a state of human serum ferritin that is higher than the normal value but less than 1000 µg/L. It has been found that iron accumulation and osteoporosis could occur simultaneously with the decrease in estrogen level after menopause. In recent years, many studies indicated that iron accumulation plays a vital role in postmenopausal osteoporosis, and a significant correlation has been found between iron accumulation and fragility fractures. In this review, we summarize and analyze the relevant literature including randomized controlled trials, systematic reviews, and meta-analyses between January 1996 and July 2022. We investigate the mechanism of the effect of iron accumulation on bone metabolism and discuss the relationship of iron accumulation, osteoporosis, and postmenopausal fragility fractures, as well as the main clinical treatment strategies. We conclude that it is necessary to pay attention to the phenomenon of iron accumulation in postmenopausal women with osteoporosis and explore the in-depth mechanism of abnormal bone metabolism caused by iron accumulation, in order to facilitate the discovery of effective therapeutic targets for postmenopausal osteoporosis.

Tea Consumption and Gut Microbiome in Older Chinese Adults.

BACKGROUND: Animal and small-cohort human studies have shown that tea consumption affects the gut microbiome, but evidence from large cohort studies is lacking. OBJECTIVES: We examined associations between tea consumption and gut microbiome composition among older Chinese adults. METHODS: The study included 1179 men and 1078 women from the Shanghai Men's and Women's Health Studies, who reported tea drinking status, type, amount, and duration at baseline and follow-up surveys (1996-2017) and were free of cancer, cardiovascular disease, and diabetes at stool collection (2015-2018). Fecal microbiome was profiled using 16S rRNA sequencing. Associations of tea variables with microbiome diversity and taxa abundance were evaluated using linear or negative binomial hurdle models after adjusting for sociodemographics, lifestyle, and hypertension status. RESULTS: Mean age at stool collection was 67.2 ± 9.0 y in men and 69.6 ± 8.5 y in women. Tea drinking was not associated with microbiome ɑ-diversity in men or women; however, all tea variables were associated with ß-diversity in men (P < 0.001). Significant associations with taxa abundance were also observed mostly in men. Current tea drinking, mainly green tea drinking, was associated with increase in orders Synergistales and RF39 in men (ß = 0.30 to 0.42, all PFDR ≤ 0.10) but not in women (PInteraction-sex = 0.01). Also, increase in families Coriobacteriaceae, Odoribacteraceae, genera Collinsella, Odoribacter, and species Collinsella aerofaciens, Coprococcus catus, and Dorea formicigenerans were observed among men who drank >3.3 cups (781 mL)/d compared to that of nondrinkers (all PFDR <0.10). The increased Coprococcus catus related to tea drinking was more evident among men without hypertension and inversely associated with the prevalence of hypertension (OR: 0.90; 95% CI: 0.84, 0.97; PFDR = 0.03). CONCLUSIONS: Tea consumption may affect gut microbiome ß-diversity and abundance of some bacteria, which may contribute to reduced hypertension risk in Chinese men. Future studies should examine the sex-specific tea-gut microbiome associations and how certain bacteria may mediate the health benefits of tea.

Perturbation of arachidonic acid and glycerolipid metabolism promoted particulate matter-induced inflammatory responses in human bronchial epithelial cells.

Particulate matter (PM) has become the main risk factor for public health, being linked with an increased risk of respiratory diseases. However, the potential mechanisms underlying PM-induced lung injury have not been well elucidated. In this study, we systematically integrated the metabolomics, lipidomics, and transcriptomics data obtained from the human bronchial epithelial cells (HBECs) exposed to PM to reveal metabolic disorders in PM-induced lung injury. We identified 170 differentially expressed metabolites (82 upregulated and 88 downregulated metabolites), 218 differentially expressed lipid metabolites (125 upregulated and 93 downregulated lipid metabolites), and 1417 differentially expressed genes (643 upregulated and 774 downregulated genes). Seven key metabolites (prostaglandin E2, inosinic acid, L-arginine, L-citrulline, L-leucine, adenosine, and adenosine monophosphate), and two main lipid subclasses (triglyceride and phosphatidylcholine) were identified in PM-exposed HBECs. The amino acid metabolism, lipid metabolism, and carbohydrate metabolism were the significantly enriched pathways of identified differentially expressed genes. Then, conjoint analysis of these three omics data and further qRT-PCR validation showed that arachidonic acid metabolism, glycerolipid metabolism, and glutathione metabolism were the key metabolic pathways in PM-exposed HBECs. The knockout of AKR1C3 in arachidonic acid metabolism or GPAT3 in glycerolipid metabolism could significantly inhibit PM-induced inflammatory responses in HBECs. These results revealed the potential metabolic pathways in PM-exposed HBECs and provided a new target to protect from PM-induced airway damage.

Why is the beautyberry so colourful? Evolution, biogeography, and diversification of fruit colours in Callicarpa (Lamiaceae).

Fruit colour is essential to seed dispersal, speciation, and biological diversity in global ecosystems. The relationship between fruit-colour variation and species diversification has long been of interest in evolutionary biology, but remains poorly understood at the genus level. Here, we used Callicarpa, a typical representative of pantropical angiosperm, to analyse whether fruit colours are correlated with biogeographic distribution, dispersal events, and diversification rate. We estimated a time-calibrated phylogeny for Callicarpa and reconstructed ancestral fruit colour. Utilizing phylogenetic methods, we estimated the major dispersal events across the phylogenetic tree and the most likely fruit colours related to each dispersal event, and tested whether the dispersal frequencies and distances of the four fruit colours between major biogeographical areas were equal. We then tested whether fruit colours are correlated with latitude, elevation, and diversification rate. Biogeographical reconstructions showed that Callicarpa originated in the East Asia and Southeast Asia during the Eocene (∼35.53 Ma) and diverse species diverged mainly in the Miocene and lasted into the Pleistocene. Large-scale dispersal events were significantly associated with violet-fruited lineages. Furthermore, different fruit colours were markedly correlated with different latitudes and elevations (e.g., violet fruits were correlated with higher latitudes and elevations; red fruits and black fruits with lower latitudes; white fruits with higher elevations). Notably, violet fruits were statistically associated with highest diversification rates, driving fruit colour variation among different regions globally. Our results contribute to further understanding why fruit colour is so variable at the genus level of angiosperms in different areas around the world.

Therapeutic challenge for immunotherapy targeting cold colorectal cancer: A narrative review.

Cold colorectal tumors are not likely to trigger a robust immune response and tend to suppress the immune response. There may be three reasons. First, the complex tumor microenvironment of cold colorectal cancer (CRC) leads to tolerance and clearance of immunotherapy. Second, the modification and concealment of tumor-specific targets in cold CRC cause immune escape and immune response interruption. Finally, the difference in number and function of immune cell subsets in patients with cold CRC makes them respond poorly to immunotherapy. Therefore, we can only overcome the challenges in immunotherapy of cold CRC through in-depth research and understanding the changes and mechanisms in the above three aspects of cold CRC.

Comprehensive analysis of the role of ICOS ( CD278 ) in pan-cancer prognosis and immunotherapy.

BACKGROUND: The immunological checkpoint known as Inducible T Cell Costimulatory Factor (ICOS, Cluster of Differentiation, CD278) is activated and expressed on T cells. Both somatic cells and antigen-presenting cells expressed its ligand, ICOSL (including tumor cells in the tumor microenvironment).It is important for immunosuppression. Uncertainty surrounds the function of ICOS in tumor immunity. METHODS: Several bioinformatics techniques were employed by us to thoroughly examine the expression and prognostic value of ICOS in 33 cancers based on data collected from TCGA and GTEx. In addition, ICOS was explored with pathological stage, tumor-infiltrating cells, immune checkpoint genes, mismatch repair (MMR) genes, DNA methyltransferases (DNMTs), microsatellite instability (MSI),and tumor mutation burden (TMB).In addition,To ascertain the level of ICOS expression in various cells, qRT-PCR was employed. RESULTS: The findings revealed that ICOS expression was up regulation in most cancer types. The high expression of ICOS in tumor samples was related to the poor prognosis of UVM and LGG; The positive prognosis was boosted by the strong expression of ICOS in OV, SARC, SKCM, THYM, UCEC, and HNSC. The result is that the expression of malignancy was revealed by the immune cells' invasion.profile of ICOS in different types of cancer. Different ways that ICOS expression is connected to immune cell infiltration account for variations in patient survival. Additionally, the TMB, MSI, MMR, and DNMT genes as well as ICOS expression are linked in many cancer types.The results of PCR showed that it is highly expressed in gastric, breast, liver and renal cell carcinoma cell lines compared with normal cells. CONCLUSION: This study suggests that ICOS may be a potential tumor immunotherapy target and prognostic marker.

The Empty-Nest Power User Management Based on Data Mining Technology.

With the aging of the social population structure, the number of empty-nesters is also increasing. Therefore, it is necessary to manage empty-nesters with data mining technology. This paper proposed an empty-nest power user identification and power consumption management method based on data mining. Firstly, an empty-nest user identification algorithm based on weighted random forest was proposed. Compared with similar algorithms, the results indicate that the performance of the algorithm is the best, and the identification accuracy of empty-nest users is 74.2%. Then a method for analyzing the electricity consumption behavior of empty-nest users based on fusion clustering index adaptive cosine K-means was proposed, which can adaptively select the optimal number of clusters. Compared with similar algorithms, the algorithm has the shortest running time, the smallest Sum of the Squared Error (SSE), and the largest mean distance between clusters (MDC), which are 3.4281 s, 31.6591 and 13.9513, respectively. Finally, an anomaly detection model with an Auto-regressive Integrated Moving Average (ARIMA) algorithm and an isolated forest algorithm was established. The case analysis shows that the recognition accuracy of abnormal electricity consumption for empty-nest users was 86%. The results indicate that the model can effectively detect the abnormal behavior of empty-nest power users and help the power department to better serve empty-nest users.

Prospective Cohort Study of Ginseng Consumption in Association with Cancer Risk: Shanghai Women's Health Study.

BACKGROUND: Ginseng has been commonly used in Asian countries to promote longevity and health for >2000 years. Recent in vitro and in vivo studies, coupled with limited epidemiologic studies, have suggested that regular ginseng consumption may be related to lower cancer risk. OBJECTIVES: We evaluated the association of ginseng consumption with risk of total and 15 site-specific cancers in a large cohort study conducted among Chinese women. Given the previous literature on ginseng consumption and cancer risk, we hypothesized that ginseng consumption might be associated with varying risks of cancer. METHODS: This study included 65,732 female participants (mean age: 52.2 years) of the Shanghai Women's Health Study, an ongoing prospective cohort study. Baseline enrollment occurred between 1997 and 2000, and follow-up concluded on 31 December 2016. Ginseng use and covariates were assessed via an in-person interview conducted at the baseline recruitment. The cohort was followed for cancer incidence. Cox proportional hazard models were used to estimate HRs and 95% CIs for ginseng-cancer associations after adjusting for confounders. RESULTS: During a mean 14.7 years of follow-up, 5067 incident cancer cases were identified. Overall, regular ginseng use was mostly not associated with risk of any site-specific cancer, or all cancers combined. Short-term (<3 years) ginseng use was found to be significantly associated with increased risk of liver cancer (HR = 1.71; 95% CI: 1.04, 2.79; P = 0.035), whereas long-term (≥3 years) ginseng use was found to be associated with increased risk of thyroid cancer (HR = 1.40; 95% CI: 1.02, 1.91; P = 0.036). Long-term ginseng use was found to be significantly associated with decreased risk of lymphatic and hematopoietic tissue malignancy (HR = 0.67; 95% CI: 0.46, 0.98; P = 0.039) and non-Hodgkin's lymphoma (HR = 0.57; 95% CI: 0.34, 0.97; P = 0.039). CONCLUSIONS: This study provides suggestive evidence that ginseng consumption may be associated with risk of certain cancers.

Strategies for Synthesizing and Enhancing the Immune Response of Cancer Vaccines Based on MUC1 Glycopeptide Antigens.

Cancer vaccines are based on a vaccinology strategy whereby the patient's immune system is harnessed to induce a specific immune response to kill cancer cells and comprises two categories: prophylactic and therapeutic. Glycoprotein mucin 1 (MUC1), which is overexpressed and poorly glycosylated on cancer cells, is one of the most promising candidates for the development of new cancer vaccines. However, it should be noted that mucin-like glycopeptides are poorly immunogenic and unable to elicit effective and long-lasting immune responses. Therefore, MUC1-derived tumor antigens need to be conjugated with immune activators. This review focuses on the synthesis of MUC1 glycopeptides, provides an overview of recently advanced designs of vaccines based on MUC1, and compares the advantages and disadvantages of the various strategies devised to date.