Risk analysis of air pollutants and types of anemia: a UK Biobank prospective cohort study.

Previous studies have suggested that exposure to air pollutants may be associated with specific blood indicators or anemia in certain populations. However, there is insufficient epidemiological data and prospective evidence to evaluate the relationship between environmental air pollution and specific types of anemia. We conducted a large-scale prospective cohort study based on the UK Biobank. Annual average concentrations of NO2, PM2.5, PM2.5-10, and PM10 were obtained from the ESCAPE study using the Land Use Regression (LUR) model. The association between atmospheric pollutants and different types of anemia was investigated using the Cox proportional hazards model. Furthermore, restricted cubic splines were used to explore exposure-response relationships for positive associations, followed by stratification and effect modification analyses by gender and age. After adjusting for demographic characteristics, 3-4 of the four types of air pollution were significantly associated with an increased risk of iron deficiency, vitamin B12 deficiency and folate deficiency anemia, while there was no significant association with other defined types of anemia. After full adjustment, we estimated that the hazard ratios (HRs) of iron deficiency anemia associated with each 10 µg/m3 increase in NO2, PM2.5, and PM10 were 1.04 (95%CI: 1.02, 1.07), 2.00 (95%CI: 1.71, 2.33), and 1.10 (95%CI: 1.02, 1.20) respectively. The HRs of folate deficiency anemia with each 10 µg/m3 increase in NO2, PM2.5, PM2.5-10, and PM10 were 1.25 (95%CI: 1.12, 1.40), 4.61 (95%CI: 2.03, 10.47), 2.81 (95%CI: 1.11, 7.08), and 1.99 (95%CI: 1.25, 3.15) respectively. For vitamin B12 deficiency anemia, no significant association with atmospheric pollution was found. Additionally, we estimated almost linear exposure-response curves between air pollution and anemia, and interaction analyses suggested that gender and age did not modify the association between air pollution and anemia. Our research provided reliable evidence for the association between long-term exposure to PM10, PM2.5, PM2.5-10, NO2, and several types of anemia. NO2, PM2.5, and PM10 significantly increased the risk of iron deficiency anemia and folate deficiency anemia. Additionally, we found that the smaller the PM diameter, the higher the risk, and folate deficiency anemia was more susceptible to air pollution than iron deficiency anemia. No association was observed between the four types of air pollution and hemolytic anemia, aplastic anemia, and other types of anemia. Although the mechanisms are not well understood, we emphasize the need to limit the levels of PM and NO2 in the environment to reduce the potential impact of air pollution on folate and iron deficiency anemia.

Association between pro-inflammatory diet and abdominal pain: Cross-sectional and case-control study from UK biobank and NHANES 2017-2020.

BACKGROUND: There is a close association between diet and abdominal pain, however, relationship between inflammatory diet and characteristics of abdominal pain has not been characterized yet. METHODS: This study analyzed baseline data from the UK Biobank, 3-item DHQ-Abdominal Pain Questionnaire (DHQ-3Q) which including abdominal pain in the past three months, severity of abdominal pain, and frequency of abdominal pain, and data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Energy-adjusted Dietary Inflammatory Index (E-DII), constructed based on 26 or 27 nutrients, was analyzed using continuous or categorical methods. Logistic regression and restricted cubic spline analyses examined the association between E-DII and abdominal pain. RESULTS: In UK Biobank, compared to participants in the lowest quintile of E-DII, the adjusted ORs for the highest quintile were 1.12 (95% CI 1.02-1.24; p = 0.022), 1.05 (95% CI 1.00-1.09; p = 0.030), 1.26 (95% CI 1.17-1.36; p < 0.001), and 1.10 (95% CI 1.00-1.20; p = 0.044) for chronic abdominal pain, abdominal pain in the past three months, severity of abdominal pain, and frequency of abdominal pain, respectively. In NHANES, compared to participants in the lowest quintile of E-DII, the adjusted ORs for the highest quintile were 1.46 (95% CI 1.20-1.77; p < 0.001), 1.75 (95% CI 1.20-2.60; p = 0.005), 1.45 (95% CI 1.14-1.87; p = 0.003), and 1.18 (95% CI 0.82-1.72; p = 0.380) for abdominal pain in the past year, upper left abdominal pain, upper middle abdominal pain, and upper right abdominal pain. Additionally, there was a nonlinear correlation between E-DII score and DHQ-3Q (p nonlinear <0.001). CONCLUSION: Following a pro-inflammatory diet is linked to a higher likelihood of experiencing abdominal pain, as well as increased severity and frequency of such pain. Therefore, further longitudinal studies are necessary to investigate this relationship.

The Effectiveness of Artificial Intelligence in Assisting Mothers with Assessing Infant Stool Consistency in a Breastfeeding Cohort Study in China.

Breastfeeding is widely recognized as the gold standard for infant nutrition, benefitting infants' gastrointestinal tracts. Stool analysis helps in understanding pediatric gastrointestinal health, but the effectiveness of automated fecal consistency evaluation by parents of breastfeeding infants has not been investigated. Photographs of one-month-old infants' feces on diapers were taken via a smartphone app and independently categorized by Artificial Intelligence (AI), parents, and researchers. The accuracy of the evaluations of the AI and the parents was assessed and compared. The factors contributing to assessment bias and app user characteristics were also explored. A total of 98 mother-infant pairs contributed 905 fecal images, 94.0% of which were identified as loose feces. AI and standard scores agreed in 95.8% of cases, demonstrating good agreement (intraclass correlation coefficient (ICC) = 0.782, Kendall's coefficient of concordance W (Kendall's W) = 0.840, Kendall's tau = 0.690), whereas only 66.9% of parental scores agreed with standard scores, demonstrating low agreement (ICC = 0.070, Kendall's W = 0.523, Kendall's tau = 0.058). The more often a mother had one or more of the following characteristics, unemployment, education level of junior college or below, cesarean section, and risk for postpartum depression (PPD), the more her appraisal tended to be inaccurate (p < 0.05). Each point increase in the Edinburgh Postnatal Depression Scale (EPDS) score increased the deviation by 0.023 points (p < 0.05), which was significant only in employed or cesarean section mothers (p < 0.05). An AI-based stool evaluation service has the potential to assist mothers in assessing infant stool consistency by providing an accurate, automated, and objective assessment, thereby helping to monitor and ensure the well-being of infants.

Predicting the prognosis of glioma patients with TERT promoter mutations and guiding the specific immune profile of immune checkpoint blockade therapy.

The telomerase reverse transcriptase promoter (TERTp) is frequently mutated in gliomas. This study sought to identify immune biomarkers of gliomas with TERTp mutations. Data from TCGA were used to identify and validate survival-associated gene signatures, and immune and stromal scores were calculated using the ESTIMATE algorithm. High stromal or immune scores in patients with TERTp-mutant gliomas correlated with shorter overall survival compared to cases with low stromal or immune scores. Among TERTp-mutant gliomas with both high immune and high stromal scores, 213 commonly shared DEGs were identified. Among 71 interacting DEGs representing candidate hub genes in a PPI network, HOXC6, WT1, CD70, and OTP showed significant ability in establishing subgroups of high- and low-risk patients. A risk model based on these 4 genes showed strong prognostic potential for gliomas with mutated TERTp, but was inapplicable for TERTp-wild-type gliomas. TERTp-mutant gliomas with high-risk scores displayed a greater percentage of naïve B cells, plasma cells, naïve CD4 T cells, and activated mast cells than low-risk score gliomas. TIDE analysis indicated that immune checkpoint blockade (ICB) therapy may benefit glioma patients with TERTp mutations. The present risk model can help predict prognosis of glioma patients with TERTp mutations and aid ICB treatment options.

Investigation of the Interaction Between Lactones and Ketones in a Cheddar Cheese Matrix Using Feller's Additive Model, σ-τ Plots, U-Models, and Aroma Addition Experiments.

The objective of this study was to examine the sensory interactions between lactones and ketones in a cheddar simulation matrix through perceptual interaction analysis. The olfactory thresholds of 6 key lactones had values ranging from 8.32 to 58.88 µg/kg, whereas those of the 4 key ketones ranged from 6.61 to 660.69 µg/kg. Both Feller's additive model and σ-τ plots demonstrated complex interactions in 24 binary mixtures composed of the 6 lactones and 4 ketones, including synergy, addition, and masking effects. Specifically, we found that 6 binary mixtures exhibited aroma synergistic effects using both methods. Moreover, the σ-τ plot showed a synergistic effect of aroma in 3 ternary mixtures. The U-model further confirmed the synergistic effects of the 6 groups of binary systems and 3 groups of ternary systems on aroma at actual cheese concentrations. In an aroma addition experiment, the combination of δ-octalactone and diacetyl in binary mixtures had the most pronounced impact on enhancing milk flavor. In ternary mixtures, 2 combinations, namely δ-octalactone/δ-dodecalactone/diacetyl and γ-dodecalactone/δ-dodecalactone/acetoin, significantly enhanced the milky and sweet aroma properties of cheese, while also enhancing the overall acceptability of the cheese aroma.

Unraveling the molecular mechanisms of lymph node metastasis in ovarian cancer: focus on MEOX1.

BACKGROUND: Lymph node metastasis (LNM) is a major factor contributing to the high mortality rate of ovarian cancer, making the treatment of this disease challenging. However, the molecular mechanism underlying LNM in ovarian cancer is still not well understood, posing a significant obstacle to overcome. RESULTS: Through data mining from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we have identified MEOX1 as a specific gene associated with LNM in ovarian cancer. The expression of MEOX1 was found to be relatively high in serous ovarian adenocarcinoma, and its higher expression were associated with increased tumor grade and poorer clinical prognosis for ovarian cancer patients. Bioinformatics analysis revealed that MEOX1 exhibited the highest mRNA levels among all cancer types in ovarian cancer tissues and cell lines. Furthermore, gene set enrichment analysis (GSEA) and pathway analysis demonstrated that MEOX1 was involved in various LNM-related biological activities, such as lymphangiogenesis, lymphatic vessel formation during metastasis, epithelial-mesenchymal transition (EMT), G2/M checkpoint, degradation of extracellular matrix, and collagen formation. Additionally, the expression of MEOX1 was positively correlated with the expression of numerous prolymphangiogenic factors in ovarian cancer. To validate our findings, we conducted experiments using clinical tissue specimens and cell lines, which confirmed that MEOX1 was highly expressed in high-grade serous ovarian cancer (HGSOC) tissues and various ovarian cancer cell lines (A2780, SKOV3, HO8910, and OVCAR5) compared to normal ovarian tissues and normal ovarian epithelial cell line IOSE-80, respectively. Notably, we observed a higher protein level of MEOX1 in tumor tissues of LNM-positive HGSOC compared to LNM-negative HGSOC. Moreover, our fundamental experiments demonstrated that suppression of MEOX1 led to inhibitory effects on ovarian cancer cell proliferation and EMT, while overexpression of MEOX1 enhanced the proliferation and EMT capacities of ovarian cancer cells. CONCLUSIONS: The results of our study indicate that MEOX1 plays a role in the lymph node metastasis of ovarian cancer by regulating multiple biological activities, including the proliferation and EMT of ovarian cancer, lymphangiogenesis, and ECM remodeling. Our findings suggest that MEOX1 could serve as a potential biomarker for the diagnosis and treatment of ovarian cancer with LNM.

The dynamic recruitment of LAB proteins senses meiotic chromosome axis differentiation in C. elegans.

During meiosis, cohesin and meiosis-specific proteins organize chromatin into an axis-loop architecture, coordinating homologous synapsis, recombination, and ordered chromosome segregation. However, how the meiotic chromosome axis is assembled and differentiated with meiotic progression remains elusive. Here, we explore the dynamic recruitment of two long arms of the bivalent proteins, LAB-1 and LAB-2, in Caenorhabditis elegans. LAB proteins directly interact with the axis core HORMA complexes and weak interactions contribute to their recruitment. LAB proteins phase separate in vitro, and this capacity is promoted by HORMA complexes. During early prophase, synapsis oppositely regulates the axis enrichment of LAB proteins. After the pachytene exit, LAB proteins switch from a reciprocal localization pattern to a colocalization pattern, and the normal dynamic pattern of LAB proteins is altered in meiotic mutants. We propose that LAB recruitment senses axis differentiation, and phase separation of meiotic structures helps subdomain establishment and accurate segregation of the chromosomes.

Targeting the DNA Damage Response for Cancer Therapy.

Over the course of long-term evolution, cells have developed intricate defense mechanisms in response to DNA damage; these mechanisms play a pivotal role in maintaining genomic stability. Defects in the DNA damage response pathways can give rise to various diseases, including cancer. The DNA damage response (DDR) system is instrumental in safeguarding genomic stability. The accumulation of DNA damage and the weakening of DDR function both promote the initiation and progression of tumors. Simultaneously, they offer opportunities and targets for cancer therapeutics. This article primarily elucidates the DNA damage repair pathways and the progress made in targeting key proteins within these pathways for cancer treatment. Among them, poly (ADP-ribose) polymerase 1 (PARP1) plays a crucial role in DDR, and inhibitors targeting PARP1 have garnered extensive attention in anticancer research. By delving into the realms of DNA damage and repair, we aspire to explore more precise and effective strategies for cancer therapy and to seek novel avenues for intervention.

Picroside III Ameliorates Colitis in Mice: A Study Based on Colon Transcriptome and Fecal 16S Amplicon Profiling.

Picroside III (Pic), an iridoid glycoside derived from Picrorhiza scrophulariiflora, exhibits therapeutic potential in mending damage to the intestinal mucosa. This study aimed to explore Pic's regulatory impact on intestinal inflammation and the gut microbiota in mice with dextran sulfate sodium (DSS)-induced colitis. The findings revealed that pretreatment with Pic mitigated the DSS-induced escalation of the disease activity index (DAI), alleviated intestinal damage, and attenuated intestinal inflammation in mice. RNA-seq analysis, complemented by experimental validation, elucidated that Pic significantly hindered Akt phosphorylation in the colon tissues of colitis-afflicted mice. Furthermore, 16S rRNA sequencing demonstrated that Pic pretreatment effectively rectified microbial dysbiosis in colitis mice by elevating the abundance of Lactobacillus murinus and Lactobacillus gasseri. These observations suggest that Pic's efficacy in colitis treatment stems from its inhibition of intestinal inflammation via the suppression of the PI3K-Akt pathway and modulation of gut microbiota. This study contributes novel scientific insights into the potential application of Pic in the management of inflammatory bowel disease (IBD).

Association between frailty and chronic constipation and chronic diarrhea among American older adults: National Health and Nutrition Examination Survey.

BACKGROUND: This study was to explore the relationship between chronic constipation, chronic diarrhea, and frailty in older Americans. METHODS: This cross-sectional study selected a total of 4241 community-dwelling individuals aged 60 years and older from the 2005-2010 National Health and Nutrition Examination Survey. Frailty was measured using a 49-item frailty index, and a frailty index > 0.21 was defined as a frail status. Chronic constipation and chronic diarrhea were defined as the "usual or most common type of stool" by the Bristol Stool Form Scale (BSFS) Types 1 and 2 and BSFS Types 6 and 7, respectively. Weighted logistic regression analysis was used to examine the relationship between gut health and frailty status. Restricted cubic spline (RCS) curves were built to assess the association between frailty index and stool frequency. RESULTS: Frailty status was associated with higher odds of constipation in an unadjusted model; however, after further adjusting for confounding variables, the relationship between frailty status and constipation was not statistically significant. We discovered a positive correlation between the frailty status and diarrhea after adjustment for all variables. The frailty index showed a U-shaped relationship with stool frequency, and the frailty index was the smallest at a frequency of 10 stools/week. CONCLUSION: Negative associations were observed between frailty status and chronic constipation and diarrhea among older adults. Older adults who have a bowel movement frequency of about 10 times per week are the least frail. Future studies are warranted to confirm the causal relationship in this association.

Oral microbiota disorder in GC patients revealed by 2b-RAD-M.

BACKGROUND: Microbiota alterations are linked with gastric cancer (GC). However, the relationship between the oral microbiota (especially oral fungi) and GC is not known. In this study, we aimed to apply 2b-RAD sequencing for Microbiome (2b-RAD-M) to characterize the oral microbiota in patients with GC. METHODS: We performed 2b-RAD-M analysis on the saliva and tongue coating of GC patients and healthy controls. We carried out diversity, relative abundance, and composition analyses of saliva and tongue coating bacteria and fungi in the two groups. In addition, indicator analysis, the Gini index, and the mean decrease accuracy were used to identify oral fungal indicators of GC. RESULTS: In this study, fungal imbalance in the saliva and tongue coating was observed in the GC group. At the species level, enriched Malassezia globosa (M. globosa) and decreased Saccharomyces cerevisiae (S. cerevisiae) were observed in saliva and tongue coating samples of the GC group. Random forest analysis indicated that M. globosa in saliva and tongue coating samples could serve as biomarkers to diagnose GC. The Gini index and mean decreases in accuracy for M. globosa in saliva and tongue coating samples were the largest. In addition, M. globosa in saliva and tongue coating samples classified GC from the control with areas under the receiver operating curve (AUCs) of 0.976 and 0.846, respectively. Further ecological analysis revealed correlations between oral bacteria and fungi. CONCLUSION: For the first time, our data suggested that changes in oral fungi between GC patients and controls may help deepen our understanding of the complex spectrum of the different microbiotas involved in GC development. Although the cohort size was small, this study is the first to use 2b-RAD-M to reveal that oral M. globosa can be a fungal biomarker for detecting GC.

Aculebiphenyl A-B, new biphenyl derivatives from Ruscus aculeatus.

The investigation of chemical constituents from the rhizomes of Ruscus aculeatus resulted in the isolation of two new biphenyl derivatives, aculebiphenyls A and B (1-2), together with two known analogs (3-4). Their chemical structures were elucidated based on extensive spectroscopic interpretation and HR-ESI-MS analysis. Compounds 3-4 were isolated from the Ruscus genus for the first time. The isolated compounds were tested for anti-inflammatory activities and antibacterial activities. Compound 1 exhibited significant inhibitory effects on LPS-induced NO production and COX-2 with IC50 values of 10.8 µM and 0.4 µM. Compound 1 also significantly down-regulated the levels of inflammatory cytokines IL-1ß, IL-6, and TNF-α. Compound 1 showed moderate antibacterial activities.

Effects of semicore electrons on stopping power in helium-irradiated aluminum nanosheets.

The stopping power of energetic He ions traversing an Al film is studied by combining the time-dependent density-functional theory method with molecular dynamics simulations. We investigated the dependence of the semicore electron excitation of the Al film on the projectile's trajectory and its charge state. Our results show that for the off-channeling trajectories the semicore electrons contribute significantly to the stopping power of the Al film as the He+ ion velocity exceeds 1.0 a.u, and in contrast, it is negligible for the channeling trajectories. Most importantly, we found two unexpected effects of semicore electrons on the stopping power in helium-irradiated aluminum nanosheets, i.e., (1) the semicore electrons can contribute to the energy loss for both high and low energy projectiles under the off-channeling trajectory; (2) as the projectile velocity increases from 0.4 a.u. to 2.0 a.u. although semicore electron excitation (including transition in the target, ionization away from the target and transfer to the projectile ion) of the target atom is gradually inhibited, the influence of semicore electrons on valence electron excitation is gradually enhanced. Our finding allows us to gain new insights into the stopping of ions in metals.

Combining WGCNA and machine learning to construct immune-related EMT patterns to predict HCC prognosis and immune microenvironment.

Hepatocellular carcinoma (HCC) is a malignancy with a very high mortality rate. Because of its high heterogeneity, there is an urgent need to find biomarkers that accurately predict prognosis. Epithelial-mesenchymal transition (EMT) is closely associated with frequent recurrence and high mortality of HCC. Therefore, it is necessary to comprehensively analyze the prognostic value and immunological properties of EMT gene in HCC. In our study, we performed bioinformatics analysis of the TCGA and ICGC liver cancer cohorts and identified the module genes of immune-associated EMTs (iEMT) by Weighted Gene Co-Expression Network Analysis (WGCNA). Further we used machine learning (support vector machines-recursive feature elimination and Lasso) to identify three central iEMT genes (ARMC9, ADAM15 and STC2) and construct iEMT_score. Subsequently, in the training and validation cohorts, it was demonstrated that the overall survival (OS) of patients in the high iEMT_score group was worse than that of patients in the low iEMT_score group. Based on this, we have constructed a nomogram that is easy for clinicians to use. In addition, our study explored differences in pathway enrichment, immunological properties, and sensitivity to common chemotherapy and targeted drugs in different subgroups of iEMT_score. Finally, we showed through in vitro experiments that knockdown of ARMC9 could significantly inhibit the proliferation, migration and invasion of HCC cells BEL7402. Taken together, our findings suggest that iEMT_score is an excellent biomarker for predicting prognosis and provide some new insights for personalized treatment of HCC patients.

CCL13 and human diseases.

CCL13/MCP-4 belongs to the CC chemokine family, which induces chemotaxis in many immune cells. Despite extensive research into its function in numerous disorders, a thorough analysis of CCL13 is not yet accessible. The role of CCL13 in human disorders and existing CCL13-focused therapies are outlined in this study. The function of CCL13 in rheumatic diseases, skin conditions, and cancer is comparatively well-established, and some studies also suggest that it may be involved in ocular disorders, orthopedic conditions, nasal polyps, and obesity. We also give an overview of research that found very little evidence of CCL13 in HIV, nephritis, and multiple sclerosis. Even though CCL13-mediated inflammation is frequently linked to disease pathogenesis, it's fascinating to note that in some conditions, like primary biliary cholangitis (PBC) and suicide, it might even act as a preventative measure.

Correlation between the number of oocytes and the increase of polyspermy rate in IVF cycles.

Aims: To investigate the association between the number of oocytes and the polyspermy rate following in vitro fertilization (IVF) treatment. Materials and methods: 376 IVF cycles with gonadotropin-releasing hormone (GnRH) antagonist protocol in the reproductive center of our hospital were retrospectively included in the analysis, which were divided into five groups according to the number of oocytes retrieved. Group A (78 cases):1-5 oocytes, group B (118 cases): 6-10 oocytes, group C (94 cases): 11-15 oocytes, group D (55 cases): 16-20 oocytes, group E (31 cases): ≥21 oocytes. According to polyspermy rate, 376 IVF cycles were then divided into two groups. Normal level polyspermy group (170 cases): polyspermy rate<6%, and high level polyspermy group (206 cases): polyspermy rate ≥ 6%. The variables with p < .10 in univariate analysis were incorporated into the multiple logistic regression model to control the confounding, and the effect of the number of oocytes on the increase of polyspermy rate was analyzed. Results: Multiple logistic regression analysis showed that after adjustment for confounding factor, the increase risk of polyspermy rate in group B, C, D and E was 1.763, 3.804, 2.021 and 3.208 times of that in group A respectively (OR = 1.763, p = .085; OR = 3.804, p = .001; OR = 2.021, p = .158; OR = 3.208, p = .068, respectively). Conclusion: This result demonstrated that when the oocyte number is 15 or less, the more the oocyte number, the greater the increase risk of polyspermy rate. While, there appears to be little increase risk of polyspermy rate when the oocyte number is more than 15.

Losartan attenuates acetic acid enema-induced visceral hypersensitivity by inhibiting the ACE1/Ang II/AT1 receptor axis in enteric glial cells.

Enteric glial cells (EGCs) play an important role in visceral hypersensitivity associated with irritable bowel syndrome (IBS). Losartan (Los) is known to reduce pain; however, its function in IBS is unclear. The present study aimed to investigate Los's therapeutic effect on visceral hypersensitivity in IBS rats. Thirty rats were randomly divided into control, acetic acid enema (AA), AA + Los low, medium and high dose groups in vivo. EGCs were treated with lipopolysaccharide (LPS) and Los in vitro. The molecular mechanisms were explored by assessing the expression of EGC activation markers, pain mediators, inflammatory factors and angiotensin-converting enzyme 1(ACE1)/angiotensin II (Ang II)/Ang II type 1 (AT1) receptor axis molecules in colon tissue and EGCs. The results showed that the rats in the AA group showed significantly higher visceral hypersensitivity than the control rats, which was alleviated by different doses of Los. The expression of GFAP, S100ß, substance P (SP), calcitonin gene-related peptide (CGRP), transient receptor potential vanilloid 1 (TRPV1), tumor necrosis factor (TNF), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) was considerably increased in colonic tissues of AA group rats and LPS-treated EGCs compared with control rats and EGCs, and reduced by Los. In addition, Los reversed ACE1/Ang II/AT1 receptor axis upregulation in AA colon tissues and LPS-treated EGCs. These results show that Los inhibits ACE1/Ang II/AT1 receptor axis upregulation by suppressing EGC activation, resulting in reduced expression of pain mediators and inflammatory factors, thereby alleviating visceral hypersensitivity.

Designing narratives and data visuals in comic form for social influence in climate action.

Climate change is difficult to connect with personally, because people only regard the phenomenon as important if it becomes a perceived threat to themselves. Arguments like statistics and policy debates are extrinsic motivators, which do not necessarily align people's own intrinsic motives with those of climate action. Instead, narratives and visual communication can influence viewers implicitly by the way they show and reinforce actions and thoughts that align with climate action. In this design study, we used comics created for human-level climate change influence to promote ideas like future-based thinking, sharing of responsibility, and caring for each other. We also created data visuals that illustrate future consequences of climate change for the purpose of averting negative alternative realities. To see whether our design can affect audience perception of climate change on the human level of goals and desires, we showed the comics to readers unfamiliar with the themes of the stories, presenting them as manga about characters and situations. The survey showed that data stories can affect the way naive readers interpret narratives to align with pro-climate attitudes such as sharing and future-vision, and that readers are focused on the human-level of the data and story as opposed to the physical resource level. Speculative fiction and data visuals provide a potentially effective way to influence individuals' climate change attitudes by showing alternative realities and attributes of collective responsibility and planning-for-the-future as data stories.

The PDGF Family Is Associated with Activated Tumor Stroma and Poor Prognosis in Ovarian Cancer.

The initiation and progression of cancer depend on the genetic alterations inherent in cancer cells, coupled with the mutual interplay of cancer cells with the surrounding tumor stroma. The platelet-derived growth factor (PDGF) family, as a mesenchymal growth factor, was involved in tumor progression by affecting the surrounding tumor stroma in some cancer types. However, the association of the PDGF family with the ovarian cancer stroma remains elusive. In our study, we first explored the expression pattern of the PDGF family using RNA expression profiles from public databases. We found that the PDGF family was highly expressed in tumor stroma compared with the corresponding epithelial components of ovarian cancer. In particular, PDGF receptors were weakly expressed in ovarian cancer tissues compared with the respective normal tissues; even in tumor mass, PDGF receptors were predominantly expressed by tumor stroma rather than ovarian cancer cells. Importantly, functional enrichment analyses and correlation analyses revealed that the PDGF family was strongly associated with activated stromal scores in ovarian cancer, including higher stromal scores, enriched pathways related to the extracellular matrix (ECM) organization and remodeling, elevated cancer-associated fibroblasts (CAFs) infiltration, and increased tumor-associated macrophages (TAMs) infiltration, especially macrophage M2. Besides, the positive correlations of the PDGF family with CAFs infiltration and macrophage M2 infiltration were observed in other various cancer types. Of note, the PDGF family was also involved in tumor progression-related pathways, such as transforming growth factor ß (TGF-ß) signaling, epithelial-mesenchymal transition (EMT), angiogenesis, and phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling. Higher expressions of PDGF receptors were also observed in ovarian cancer patients with venous or lymphatic invasion. Furthermore, we uncovered the prognostic prediction of the PDGF family in ovarian cancer and constructed a PDGF family-based risk prognosis model with a hazard ratio of 1.932 (95%confidence interval (CI) = 1.27-2.95) and P value < 0.01 (AUC = 0.782, 0.752 for 1 year and 2 years, respectively). Taken together, we demonstrated that ovarian cancers with high PDGF family expression biologically exhibit malignant progression behaviors as well as poor clinical survival, which is attributed to the activated tumor stroma in ovarian cancer.

A durable response to programmed cell death 1 blockade in a multidrug-resistant recurrent ovarian cancer patient with HLA-B44 supertype: A case report.

Relapsed/refractory ovarian cancer, especially platinum resistance recurrence, remains a major therapeutic challenge. Here, we present the case of a patient with recurrent ovarian clear cell carcinoma (OCCC) who failed to respond to multiline chemotherapy and target therapy but achieved an immune complete response (iCR) with programmed cell death 1 (PD-1) inhibitor treatment. The overall survival (OS) was 59 months, and the recurrence-free survival (RFS) was 34 months after immunotherapy, which was counting. Meantime, molecular testing results revealed that traditional biomarkers for immunotherapy, including PD-L1 expression, microsatellite instability (MSI), and tumor mutational burden (TMB), were negative. HLA-B44 (B*18:01) supertype was confirmed by sequence-based HLA typing. This case raises the possibility that ovarian cancer patients with multidrug resistance may still benefit from PD-1 inhibitor therapy, even if PD-L1 pathology is negative.