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Abstract Background Breast cancer (BC) rates have been increasing in young women in the U.S. Alcohol is an established risk factor for breast cancer and has been consistently associated with hormone receptor positive cancers, the type of breast cancer that has been increasing the fastest in young women. Given these trends, we conducted an ecological study to examine whether alcohol consumption, and specifically binge drinking trends, were correlated with female breast cancer diagnosed under 40 years of age using breast cancer data from the Surveillance, Epidemiology, and End Results (SEER) Cancer Registry. We accounted for a latent period before cancer diagnosis by using exposure 10 years before the outcome (lag model); we also conducted a separate cumulative analysis of 10-year aggregate exposure. Findings Moderate (Incidence Rate Ratio (IRR) = 1.05, 95% Confidence Interval (CI) = 1.02–1.07) and heavy (IRR = 1.05, 95% CI = 1.02–1.07)(≥ 1 and ≥ 2 drinks/day, respectively) alcohol consumption were each associated with Luminal A breast cancer but not the other molecular subtypes. Binge drinking was associated with an increased rate of early-onset Luminal A BC in both the 10-year lag model (IRR = 1.06, 95% CI = 1.02 to 1.11) and the cumulative model (IRR = 1.05, 95% CI = 1.02–1.07). Binge drinking was also associated with early-onset Luminal B BC in the cumulative model (IRR = 1.04, 95% CI = 1.01–1.07), but not associated with ERBB2-enriched or triple negative early-onset BC in either model. Conclusion These trends support the hypothesis that one reason for the increase in early-onset breast cancer is from increased alcohol intake including binge drinking.

IntroductionChronic kidney disease (CKD) presents a critical global health challenge, marked by the progressive decline of renal function. This study explores the role of the 3β-hydroxysteroid dehydrogenase type 2 enzyme (HSD3B2) and the steroid hormone biosynthesis pathway in CKD pathogenesis and progression.MethodsUsing an adenine-induced CKD mouse model, we conducted an untargeted metabolomic analysis of plasma samples to identify key metabolite alterations associated with CKD. Immunohistochemistry, Western blotting, and qPCR analyses were performed to confirm HSD3B2 expression in both human and mouse tissues. Additionally, Nephroseq and Human Protein Atlas data were utilized to assess the correlation between HSD3B2 and kidney function. Functional studies were conducted on HK2 cells with HSD3B2 knockdown to evaluate the impact on cell proliferation and apoptosis.ResultsMetabolic characteristics revealed significant shifts in CKD, with 61 metabolites increased and 65 metabolites decreased, highlighting the disruption in steroid hormone biosynthesis pathways influenced by HSD3B2. A detailed examination of seven key metabolites underscored the enzyme's central role. HSD3B2 exhibited a strong correlation with kidney function, supported by data from Nephroseq and the Human Protein Atlas. Immunohistochemistry, Western blotting, and qPCR analyses confirmed a drastic reduction in HSD3B2 expression in CKD-affected kidneys. Suppressed proliferation and increased apoptosis rates in HSD3B2 knocked down HK2 cells further demonstrated the enzyme's significance in regulating renal pathophysiology.DiscussionThese findings underscore the potential of HSD3B2 as a clinical diagnostic and therapeutic target in CKD. While further studies are warranted to fully elucidate the mechanisms, our results provide valuable insights into the intricate interplay between steroid hormone biosynthesis and CKD. This offers a promising avenue for precision medicine approaches and personalized treatment strategies.

Objectives: Recent years have seen increased cases of measles despite widespread vaccination. We examined the potential drivers behind the resurgence of measles. Methods: We analyzed the trends in measles incidence and vaccine coverage from 2010 to 2019 across World Health Organization member countries using country-level linear regression models. We computed the Spearman rank correlation coefficient (ρ) between measles incidence and socioeconomic and vaccination-related variables using published data from the World Health Organization member countries to identify the key factors influencing measles incidence. Results: Between 2010 and 2019, global measles cases fluctuated, with a notable rise in 2019 (measles cases per million in 2019 was about 140% higher than in 2010), alongside a declining vaccination coverage in many countries (59 of 194 countries). Among 10 socioeconomic factors examined, per-capita national gross income, population literacy, urban residences, and political stability were significantly associated with measles incidence (ρ

Abstract The impact of common environmental exposures in combinations with socioeconomic and lifestyle factors on cancer development, particularly for young adults, remains understudied. Here, we leveraged environmental and cancer incidence data collected in New York State at the county level to examine the association between 31 exposures and 10 common cancers (i.e., lung and bronchus, thyroid, colorectal, kidney and renal pelvis, melanoma, non-Hodgkin lymphoma, and leukemia for both sexes; corpus uteri and female breast cancer; prostate cancer), for three age groups (25–49, 50–69, and 70–84 year-olds). For each cancer, we stratified by age group and sex, and applied regression models to examine the associations with multiple exposures simultaneously. The models included 642,013 incident cancer cases during 2010–2018 and found risk factors consistent with previous reports (e.g., smoking and physical inactivity). Models also found positive associations between ambient air pollutants (ozone and PM2.5) and prostate cancer, female breast cancer, and melanoma of the skin across multiple population strata. Additionally, the models were able to better explain the variation in cancer incidence data among 25–49 year-olds than the two older age groups. These findings support the impact of common environmental exposures on cancer development, particularly for younger age groups.

Summary: Inflammatory bowel disease (IBD) has high prevalence in Western counties. The high fat content in Western diets is one of the leading causes for this prevalence; however, the underlying mechanisms have not been fully defined. Here, we find that high-fat diet (HFD) induces ferroptosis of intestinal regulatory T (Treg) cells, which might be the key initiating step for the disruption of immunotolerance and the development of colitis. Compared with effector T cells, Treg cells favor lipid metabolism and prefer polyunsaturated fatty acids (PUFAs) for the synthesis of membrane phospholipids. Therefore, consumption of HFD, which has high content of PUFAs such as arachidonic acid, cultivates vulnerable Tregs that are fragile to lipid peroxidation and ferroptosis. Treg-cell-specific deficiency of GPX4, the key enzyme in maintaining cellular redox homeostasis and preventing ferroptosis, dramatically aggravates the pathogenesis of HFD-induced IBD. Taken together, these studies expand our understanding of IBD etiology.

Diglyphus wani (Hymenoptera: Eulophidae) is a dominant parasitoid that attacks agromyzid leafminers. Two reproductive types occur in D. wani: arrhenotoky (in which virgin females produce only male offspring; and virgin females mate with males to produce bisexual offspring) and thelytoky (in which virgin females produce female offspring). As a potential biological control agent, exploring the differences in the relevant biological parameters of both strains is necessary. In this study, comparisons between the two strains of D. wani were performed by evaluating the life table and host-killing rate. The thelytokous strain exhibited significantly better life table parameters than its arrhenotokous counterpart. Higher values for the intrinsic rate of increase, finite rate of increase, net reproductive rate, and fecundity were found in the thelytokous strain. The thelytokous strain also performed better than the arrhenotokous strain in terms of net parasitism, host-feeding, host-stinging, and total host-killing rates. Thus, populations of the thelytokous strain could grow fast and kill more hosts. In conclusion, the thelytokous strain of D. wani may be the more promising biological agent against agromyzid leafminers compared to its arrhenotokous counterpart. Also, since the thelytokous strain of D. wani is only known to produce females, it should be given priority in future biocontrol applications owing to the cost savings of breeding only females.

Abstract Drug-resistant bacterial biofilm infections (BBIs) are refractory to elimination. Near-infrared-II photothermal therapy (NIR-II PTT) and chemodynamic therapy (CDT) are emerging antibiofilm approaches because of the heavy damage they inflict upon bacterial membrane structures and minimal drug-resistance. Hence, synergistic NIR-II PTT and CDT hold great promise for enhancing the therapeutic efficacy of BBIs. Herein, we propose a biofilm microenvironment (BME)-responsive nanoplatform, BTFB@Fe@Van, for use in the synergistic NIR-II PTT/CDT/antibiotic treatment of BBIs. BTFB@Fe@Van was prepared through the self-assembly of phenylboronic acid (PBA)-modified small-molecule BTFB, vancomycin, and the CDT catalyst Fe2+ ions in DSPE-PEG2000. Vancomycin was conjugated with BTFB through a pH-sensitive PBA-diol interaction, while the Fe2+ ions were bonded to the sulfur and nitrogen atoms of BTFB. The PBA-diol bonds decomposed in the acidic BME, simultaneously freeing the vancomycin and Fe2+ irons. Subsequently, the catalytic product hydroxyl radical was generated by the Fe2+ ions in the oxidative BME overexpressed with H2O2. Moreover, under 1064 nm laser, BTFB@Fe@Van exhibited outstanding hyperthermia and accelerated the release rate of vancomycin and the efficacy of CDT. Furthermore, the BTFB@Fe@Van nanoplatform enabled the precise NIR-II imaging of the infected sites. Both in-vitro and in-vivo experiments demonstrated that BTFB@Fe@Van possesses a synergistic NIR-II PTT/CDT/antibiotic mechanism against BBIs.

Invasive alien ants (IAAs) are among the most aggressive, competitive, and widespread invasive alien species (IAS) worldwide. Wasmannia auropunctata, the greatest IAAs threat in the Pacific region and listed in “100 of the world’s worst IAS”, has established itself in many countries and on islands worldwide. Wild populations of W. auropunctata were recently reported in southeastern China, representing a tremendous potential threat to China’s agricultural, economic, environmental, public health, and social well-being. Estimating the potential geographical distribution (PGD) of W. auropunctata in China can illustrate areas that may potentially face invasion risk. Therefore, based on the global distribution records of W. auropunctata and bioclimatic variables, we predicted the geographical distribution pattern of W. auropunctata in China under the effects of climate change using an ensemble model (EM). Our findings showed that artificial neural network (ANN), flexible discriminant analysis (FDA), gradient boosting model (GBM), Random Forest (RF) were more accurate than categorical regression tree analysis (CTA), generalized linear model (GLM), maximum entropy model (MaxEnt) and surface distance envelope (SRE). The mean TSS values of ANN, FDA, GBM, and RF were 0.820, 0.810, 0.843, and 0.857, respectively, and the mean AUC values were 0.946, 0.954, 0.968, and 0.979, respectively. The mean TSS and AUC values of EM were 0.882 and 0.972, respectively, indicating that the prediction results with EM were more reliable than those with the single model. The PGD of W. auropunctata in China is mainly located in southern China under current and future climate change. Under climate change, the PGD of W. auropunctata in China will expand to higher-latitude areas. The annual temperature range (bio7) and mean temperature of the warmest quarter (bio10) were the most significant variables affecting the PGD of W. auropunctata in China. The PGD of W. auropunctata in China was mainly attributed to temperature variables, such as the annual temperature range (bio7) and the mean temperature of the warmest quarter (bio10). The populations of W. auropunctata in southern China have broad potential invasion areas. Developing strategies for the early warning, monitoring, prevention, and control of W. auropunctata in southern China requires more attention.

Abstract Background Residing in a nursing home (NH) may increase emergency department (ED) utilization in patients with dementia; however, evidence regarding the status of and predictors for ED utilization of NH residents with dementia remains unclear, especially in Asia. This study aimed to assess the incidence density of ED visits and associated factors for the risk of ED utilization among NH residents with dementia. Methods This one-year cohort study followed 6595 NH residents with dementia aged ≧ 40 years from Taiwan’s National Health Insurance Research Database between 2012 and 2014. The Andersen-Gill extension of Cox regression analysis with death as a competing risk was applied to investigate the association of the risk of all causes and the most common causes of ED utilization with the predisposing, enabling, and need factors as defined by the Andersen model. Results All participants encountered 9254 emergency visits in the 5371.49 person-years observed, representing incidence densities of ED visits of 1722.80 per 1000 person-years. Among them, respiratory disease was the most common cause of ED visits. The significant predictors for the risk of all-cause and respiratory-cause ED visits included: (1) predisposing factors (i.e., age and gender); (2) enabling factors (i.e., regional variables); and (3) need factors (i.e., prolonged ventilator dependence and comorbidity status). Conclusions Predisposing, enabling, and need factors could influence ED visits among studies patients. NH providers should consider these factors to develop strategies for reducing ED utilization.

Abstract Background This study investigated the clinicopathological features, immunophenotypic characteristics and differential diagnosis of primary breast carcinomas with signet ring cell differentiation, as well as differences in the traits of signet ring-like cell mucin. Methods A total of five cases of primary breast cancer diagnosed with signet ring cell differentiation and treated at The First People’s Hospital of Jingmen from January 2016 to December 2021 were collected. HE, immunohistochemical staining, and AB-PAS staining were used for the analysis. Results Although we strictly selected all the primary breast cancer cases with signet ring cell differentiation, there were differences in the arrangement of the cells and the grading of nuclei. Our immunohistochemical results showed that the ER was consistently strongly positive, and the PR expression was not consistent, while all the cases of HER2 were negative. CK7 was negative in one case, and CK20 and CK5/6 were not expressed in all the cases. The mucin MUC1 was positive and showed two patterns. MUC2 was strongly positive in all the cases. All the cases were negative for CDX2, SATB2, PAX8, TTF-1, and Napsin A, while the positive expression of COX2, Villin, and WT-1 was not constant. One case expressed neuroendocrine markers. The expression level of Ki67 was between 10 and 30%. AB (pH 2.5)-PAS staining revealed that the intracellular mucus contained more cells with neutral mucus, while the extracellular mucus was mainly acidic. Conclusion We found that histological morphology, cell morphology, and nuclear grading differentiate among different cases. The immunohistochemical characteristics of primary breast cancers diagnosed with signet ring cell differentiation are helpful for identification. The differences in the expression patterns of mucins may be related to unfavorable clinicopathological factors, but their usefulness as a prognostic marker remains to be further understood. The heterogeneity of cell mucus, the differentiation of tumor cells, and the phenotypic changes of tumors also need further study.

Summary: Prenatal stress has been extensively documented as a contributing factor to adverse cardiac development and function in fetuses and infants. The release of glucocorticoids (GCs), identified as a significant stressor, may be a potential factor inducing cardiac hypertrophy. However, the underlying mechanism remains largely unknown. Herein, we discovered that corticosterone (CORT) overload induced cardiac hypertrophy in embryonic chicks and fetal mice in vivo, as well as enlarged cardiomyocytes in vitro. The impaired mitochondria dynamics were observed in CORT-exposed cardiomyocytes, accompanied by dysfunction in oxidative phosphorylation and ATP production. This phenomenon was found to be linked to decreased mitochondrial fusion protein mitofusin 2 (MFN2). Subsequently, we found that CORT facilitated the ubiquitin-proteasome-system-dependent degradation of MFN2 with an enhanced binding of appoptosin to MFN2, serving as the underlying cause. Collectively, our findings provide a comprehensive understanding of the mechanisms by which exposure to stress hormones induces cardiac hypertrophy in fetuses.

Abstract Determining whether SARS-CoV-2 exhibits seasonality like other respiratory viruses is critical for public health planning. We evaluated whether COVID-19 rates follow a seasonal pattern using time series models. We used time series decomposition to extract the annual seasonal component of COVID-19 case, hospitalization, and mortality rates from March 2020 through December 2022 for the United States and Europe. Models were adjusted for a country-specific stringency index to account for confounding by various interventions. Despite year-round disease activity, we identified seasonal spikes in COVID-19 from approximately November through April for all outcomes and in all countries. Our results support employing annual preventative measures against SARS-CoV-2, such as administering seasonal booster vaccines in a similar timeframe as those in place for influenza. Whether certain high-risk individuals may need more than one COVID-19 vaccine booster dose each year will depend on factors like vaccine durability against severe illness and levels of year-round disease activity.

Hydroperoxy-eicosatetraenoyl-phosphatidylethanolamine (HpETE-PE) is a ferroptotic cell death signal. HpETE-PE is produced by the 15-Lipoxygenase (15LOX)/Phosphatidylethanolamine Binding Protein-1 (PEBP1) complex or via an Fe-catalyzed non-enzymatic radical reaction. Ferrostatin-1 (Fer-1), a common ferroptosis inhibitor, is a lipophilic radical scavenger but a poor 15LOX inhibitor arguing against 15LOX having a role in ferroptosis. In the current work, we demonstrate that Fer-1 does not affect 15LOX alone, however, it effectively inhibits HpETE-PE production by the 15LOX/PEBP1 complex. Computational molecular modeling shows that Fer-1 binds to the 15LOX/PEBP1 complex at three sites and could disrupt the catalytically required allosteric motions of the 15LOX/PEBP1 complex. Using nine ferroptosis cell/tissue models, we show that HpETE-PE is produced by the 15LOX/PEBP1 complex and resolve the long-existing Fer-1 anti-ferroptotic paradox.

GNASis a complex locus characterized by multiple transcripts and an imprinting effect. It orchestrates a variety of physiological processes via numerous signaling pathways. Human diseases associated with the GNAS gene encompass fibrous dysplasia (FD), Albright’s Hereditary Osteodystrophy (AHO), parathyroid hormone(PTH) resistance, and Progressive Osseous Heteroplasia (POH), among others. To facilitate the study of the GNAS locus and its associated diseases, researchers have developed a range of mouse models. In this review, we will systematically explore the GNAS locus, its related signaling pathways, the bone diseases associated with it, and the mouse models pertinent to these bone diseases.