Novel microbial fermentation for the preparation of iron-chelating scallop skirts peptides-its profile, identification, and possible binding mode.

Iron chelating peptides have been widely utilized as iron supplements due to their excellent absorption capacity, However, the high cost and cumbersome manufacturing process of these peptides significantly limit their industrial application. In this study, fermentation was used for the first time to prepare iron chelating peptides. Bacillus altitudinis 3*1-3 was selected as the most suitable strain from 50 strains. The hydrolysates of fermented scallop skirts showed excellent iron-chelating capacity (9.39 mg/g). Aspartic acid, glutamic acid, and histidine are crucial for the binding of peptides to ferrous ions. The heptapeptide (FEDPEFE) forms six binding bonds with ferrous irons. Compared with ferrous sulfate, peptide-ferrous chelate showed more stability in salt solution and simulated gastrointestinal juice (p < 0.05). Furthermore, the fermentation method could save >50% of the cost compared with the enzymatic method. The results can provide a theoretical basis for the preparation of ferrous-chelated peptides using the fermentation method.

Lactiplantibacillus plantarum A72, a Strain with Antioxidant Properties, Obtained through ARTP Mutagenesis, Affects Caenorhabditis elegans Anti-Aging.

This research endeavored to elucidate the antioxidant attributes of lactic acid bacteria, specifically their impact on anti-aging and lifespan augmentation in Caenorhabditis elegans. The study focused on Lactiplantibacillus plantarum A72, identified through ARTP mutagenesis for its potent antioxidant properties. In vitro analysis affirmed its free radical neutralizing capacity. In C. elegans, the strain not only extended the lifespan by 25.13% and amplified motility 2.52-fold, but also maintained reproductive capabilities. Remarkably, Lpb. plantarum A72 diminished reactive oxygen species (ROS) and malondialdehyde (MDA) levels in C. elegans by 34.86% and 69.52%, respectively, while concurrently enhancing its antioxidant enzyme activities. The strain also bolstered C. elegans survival rates by 46.33% and 57.78% under high temperature and H2O2 conditions, respectively. Transcriptomic scrutiny revealed that Lpb. plantarum A72 could retard C. elegans aging and extend lifespan by upregulating the sod-5 and hsp-16.1 genes and downregulating the fat-6 and lips-17 genes. These findings propose Lpb. plantarum A72 as a potential antioxidant and anti-aging lactic acid bacteria.

The role of NLRP6 in the development and progression of neurological diseases.

The nervous system possesses the remarkable ability to undergo changes in order to store information; however, it is also susceptible to damage caused by invading pathogens or neurodegenerative processes. As a member of nucleotide-binding oligomerization domain-like receptor (NLR) family, the NLRP6 inflammasome serves as a cytoplasmic innate immune sensor responsible for detecting microbe-associated molecular patterns. Upon activation, NLRP6 can recruit the adapter protein apoptosis-associated speck-like protein (ASC) and the inflammatory factors caspase-1 or caspase-11. Consequently, inflammasomes are formed, facilitating the maturation and secretion of pro-inflammatory cytokines such as inflammatory factors-18 (IL-18) and inflammatory factors-1ß (IL-1ß). Precise regulation of NLRP6 is crucial for maintaining tissue homeostasis, as dysregulated inflammasome activation can contribute to the development of various diseases. Furthermore, NLRP6 may also play a role in the regulation of extraintestinal diseases. In cells of the brain, such as astrocytes and neurons, NLRP6 inflammasome are also present. Here, the assembly and subsequent activation of caspase-1 mediated by NLRP6 contribute to disease progression. This review aims to discuss the structure and function of NLRP6, explain clearly the mechanisms that induce and activate NLRP6, and explore its role within the central and peripheral nervous system.

Severe housing cost burden and premature mortality from cancer.

Unaffordable housing has been associated with poor health. We investigated the relationship between severe housing cost burden and premature cancer mortality (death before 65 years of age) overall and by Medicaid expansion status. County-level severe housing cost burden was measured by the percentage of households that spend 50% or more of their income on housing. States were classified on the basis of Medicaid expansion status (expanded, late-expanded, nonexpanded). Mortality-adjusted rate ratios were estimated by cancer type across severe housing cost burden quintiles. Compared with the lowest quintile of severe housing cost burden, counties in the highest quintile had a 5% greater cancer mortality rate (mortality-adjusted rate ratio = 1.05, 95% confidence interval = 1.01 to 1.08). Within each severe housing cost burden quintile, cancer mortality rates were greater in states that did not expand Medicaid, though this association was significant only in the fourth quintile (mortality-adjusted rate ratio = 1.08, 95% confidence interval = 1.03 to 1.13). Our findings demonstrate that counties with greater severe housing cost burden had higher premature cancer death rates, and rates are potentially greater in non-Medicaid-expanded states than Medicaid-expanded states.

Mechanism of thermal oxidation into volatile compounds from (E)-4-decenal: A density functional theory study.

Unsaturated aliphatic aldehyde oxidation plays a significant role in the deep oxidation of fatty acids to produce volatile chemicals. Exposing the oxidation process of unsaturated aliphatic aldehydes is crucial to completely comprehend how food flavor forms. In this study, thermal desorption cryo-trapping in conjunction with gas chromatography-mass spectrometry was used to examine the volatile profile of (E)-4-decenal during heating, and 32 volatile compounds in all were detected and identified. Meanwhile, density functional theory (DFT) calculations were used, and 43 reactions were obtained in the 24 pathways, which were summarized into the peroxide reaction mechanism (ROOH), the peroxyl radical reaction mechanism (ROO·) and the alkoxy radical reaction mechanism (RO·). Moreover, the priority of these three oxidative mechanisms was the RO· mechanism > ROOH mechanism > ROO· mechanism. Furthermore, the DFT results and experimental results agreed well, and the oxidative mechanism of (E)-4-decenal was finally illuminated.

Poor oral health and the risk of esophageal squamous cell carcinoma in Malawi.

Esophageal squamous cell carcinoma (ESCC) is the second most common cancer in Malawi. Risk factors for this cancer in Malawi are poorly understood. Poor oral health has previously been linked to increased ESCC risk in other high-incidence regions, including parts of Eastern and Southern Africa. We assessed the relationship between oral health and ESCC risk in a sex, age and location frequency-matched case-control study based at two hospitals in Lilongwe, Malawi from 2017 to 2020. Trained interviewers used a structured questionnaire and direct observation to collect data on demographics; behaviors; oral hygiene habits; the sum of decayed, missing or filled teeth (DMFT score); oral mucosa status; lip depigmentation and dental fluorosis via a visual scale. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI), adjusted for known and suspected ESCC risk factors. During the study period, 300 cases and 300 controls were enrolled. Subjects in the highest tertile of DMFT score (≥7) had an increased risk of ESCC with an adjusted OR of 1.96 (95% CI: 1.16-3.36) compared to those with a DMFT score of 0. Severe dental fluorosis was associated with a statistically nonsignificant increased risk of ESCC (adjusted OR = 2.24, 95% CI: 0.97-5.49) compared to individuals with no fluorosis. Associations with oral mucosa status, lip depigmentation and toothbrushing method and frequency were mostly null or uncertain. Poor oral health, indicated by a higher DMFT score, was associated with increased ESCC risk in Malawi. Dental fluorosis is another possible risk factor in this population, but further evaluation is necessary to clarify any effects of fluorosis on ESCC risk.

Inoculation of Yarrowia lipolytica promotes the growth of lactic acid bacteria, Debaryomyces udenii and the formation of ethyl esters in sour meat.

Yarrowia lipolytica N12 and A13 with high lipase activity obtained by mutagenesis were inoculated into sour meat, and their effects on physicochemical properties, microbial community succession, free amino acids, and volatile compounds of sour meat were investigated. Inoculation fermentation increased the contents of free amino acids observably, rapidly reduced pH, promoted the accumulation of total acids, decreased 2-thiobarbituric acid reactive substances (TBARS) values. In addition, the addition of Y. lipolytica might contribute to the growth of lactic acid bacteria, Candida spp., and Debaryomyces udenii, which play an important role in production of volatile compounds. It was shown that inoculation promoted the production of esters, aldehydes, and alcohols, especially ethyl esters, giving sour meat a better meat flavor. Besides, it was found that Y. lipolytica A13 had better fermenting property. Sample of A13 group had higher contents of ethyl esters, free amino acids and dominant microorganisms. The results may help to provide new strains for sour meat fermentation.

Survival After Diagnosis of Esophageal Squamous Cell Carcinoma in Malawi.

PURPOSE: Esophageal cancer (EC) is the second most common cancer in Malawi, with esophageal squamous cell carcinoma (ESCC) representing >90% of all ECs. Despite significant morbidity and mortality, little is known about disease outcomes. In this study, we assess survival after ESCC diagnosis in Malawi. METHODS: We report on ESCC cases enrolled in a case-control study at Kamuzu Central Hospital in Lilongwe from August 2017 to April 2020. Suspected cases completed a questionnaire interview; provided blood, urine, and saliva specimens; and underwent a tumor biopsy for histologic confirmation. Cases were followed up by phone biweekly from enrollment to the study end date (December 31, 2020), date of death, or loss to follow-up. Survival was assessed using Kaplan-Meier analysis with the log-rank test. We also examined associations between treatment and ESCC mortality using Cox regression models. RESULTS: There were 300 patients with ESCC enrolled in this study, of whom 290 (97%) had known vital status at the end of follow-up and 10 (3%) were lost to follow-up. Among the 290 patients, 282 (97%) died during follow-up. The median age at enrollment was 55 years (IQR, 48-66), and the median time to death was 106 days (95% CI, 92 to 127). The 1-year, 2-year, and 3-year survival rates were 11% (95% CI, 8 to 15), 3% (95% CI, 1 to 6), and 0.9% (95% CI, 0.8 to 4), respectively. Palliative chemotherapy significantly improved the overall survival of patients with ESCC (Plog-rank = .038) and was significantly associated with reduced mortality (adjusted hazard ratio, 0.71 [95% CI, 0.51 to 0.99]). No significant association was observed between tobacco use, alcohol consumption, or HIV status and mortality. CONCLUSION: Survival after diagnosis of ESCC was poor in Malawi. Although palliative chemotherapy was associated with improved survival, prevention and earlier detection remain key priorities to improve ESCC mortality at a population level.

CTCF coordinates cell fate specification via orchestrating regulatory hubs with pioneer transcription factors.

CCCTC-binding factor (CTCF), a ubiquitously expressed architectural protein, has emerged as a key regulator of cell identity gene transcription. However, the precise molecular mechanism underlying specialized functions of CTCF remains elusive. Here, we investigate the mechanism through integrative analyses of primary hepatocytes, myocytes, and B cells from mouse and human. We demonstrate that CTCF cooperates with lineage-specific pioneer transcription factors (TFs), including MyoD, FOXA, and PU.1, to control cell identity at 1D and 3D levels. At the 1D level, pioneer TFs facilitate lineage-specific CTCF occupancy via opening chromatin. At the 3D level, CTCF and pioneer TFs form regulatory hubs to govern the expression of cell identity genes. This mechanism is validated using MyoD-null mice, CTCF knockout mice, and CRISPR editing during myogenic differentiation. Collectively, these findings uncover a general mechanism whereby CTCF acts as a cell identity cofactor to control cell identity genes via orchestrating regulatory hubs with pioneer TFs.

Chemical Composition and Flavor Characteristics of Cider Fermented with Saccharomyces cerevisiae and Non-Saccharomyces cerevisiae.

Cider flavor has a very important impact on the quality. Solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) combined with gas chromatography-ion mobility spectrometry (GC-IMS) tested different kinds of non-Saccharomyces yeasts and Saccharomyces cerevisiae (S. cerevisiae) co-inoculated for the fermentation of cider to determine differences in aroma material, and the determination of odor activity value (OAV) is applied less frequently in research. Through Rhodotorula mucilaginosa, Debaryomyces hansenii, Zygosaccharomyces bailii, and Kluyveromyces Marxianus, four different strains of non-Saccharomyces yeast fermented cider, and it was found that, in both the chemical composition and flavor of material things, compared with monoculture-fermented cider using S. cerevisiae, all differences were significant. Co-inoculated fermentation significantly improved the flavor and taste of cider. As in the volatile compounds of OVA > 1, octanoic acid (Sc 633.88 µg/L, co-inoculation fermented group 955.49 µg/L) provides vegetable cheese fragrance and decanoic acid, ethyl ester (Sc 683.19 µg/L, co-inoculation fermented group 694.98 µg/L) a creamy fruity fragrance, etc., and the average content increased after co-inoculated fermentation. Phenylethyl alcohol, which can produce a rose scent, was relatively abundant in cider samples and varied greatly among the groups. Moreover, the contents of ethyl lactate and 1-butanol in the Sc+Rm (ciders fermented by S. cerevisiae and R. mucilaginosa) were the highest of all of the cider samples. Different types of non-Saccharomyces yeast produced cider with different flavor characteristics. This study demonstrates that different species of non-Saccharomyces yeast do have an important impact on the characteristics of cider and that co-inoculation with non-Saccharomyces yeast and S. cerevisiae for cider fermentation may be a strategy to improve the flavor of cider.

Inhibition Mechanism of Lactiplantibacillus plantarum on the Growth and Biogenic Amine Production in Morganella morganii.

Morganella morganii, a spoilage bacterium in fermented foods, produces harmful biogenic amines (BAs). Although Lactiplantibacillus plantarum is widely used to inhibit spoilage bacteria, the inhibition pattern and inhibition mechanism of M. morganii by Lpb. plantarum are not well studied. In this study, we analysed the effects of the addition of Lpb. plantarum cell-free supernatant (CFS) on the growth and BA accumulation of M. morganii and revealed the mechanisms of changes in different BAs by using RNA sequencing transcriptome analysis. The results showed that Lpb. plantarum CFS could significantly inhibit M. morganii BAs in a weak acid environment (pH 6), and the main changes were related to metabolism. Carbohydrate and energy metabolism were significantly down-regulated, indicating that Lpb. plantarum CFS inhibited the growth activity and decreased the BA content of M. morganii. In addition, the change in histamine content is also related to the metabolism of its precursor amino acids, the change in putrescine content may also be related to the decrease in precursor amino acid synthesis and amino acid transporter, and the decrease in cadaverine content may also be related to the decrease in the cadaverine transporter. The results of this study help to inhibit the accumulation of harmful metabolites in fermented foods.

The Screening and Isolation of Ethyl-Carbamate-Degrading Strains from Fermented Grains and Their Application in the Degradation of Ethyl Carbamate in Chinese Baijiu.

Ethyl carbamate (EC), a 2A carcinogen produced during the fermentation of foods and beverages, primarily occurs in distilled spirits. Currently, most studies focus on strategies for EC mitigation. In the present research, we aimed to screen strains that can degrade EC directly. Here, we report two Candida ethanolica strains (J1 and J116), isolated from fermented grains, which can reduce EC concentrations directly. These two yeasts were grown using EC as the sole carbon source, and they grew well on different carbon sources. Notably, after immobilization with chitosan, the two strains degraded EC in Chinese Baijiu by 42.27% and 27.91% in 24 h (from 253.03 ± 9.89 to 146.07 ± 1.67 and 182.42 ± 5.05 µg/L, respectively), which was better than the performance of the non-immobilized strains. Furthermore, the volatile organic compound content, investigated using gas chromatography-mass spectrometry, did not affect the main flavor substances in Chinese Baijiu. Thus, the yeasts J1 and J116 may be potentially used for the treatment and commercialization of Chinese Baijiu.

Trends in Mortality From Poisonings, Firearms, and All Other Injuries by Intent in the US, 1999-2020.

Importance: Although deaths due to external causes are a leading cause of mortality in the US, trends over time by intent and demographic characteristics remain poorly understood. Objective: To examine national trends in mortality rates due to external causes from 1999 to 2020 by intent (homicide, suicide, unintentional, and undetermined) and demographic characteristics. External causes were defined as poisonings (eg, drug overdose), firearms, and all other injuries, including motor vehicle injuries and falls. Given the repercussions of the COVID-19 pandemic, US death rates for 2019 and 2020 were also compared. Design, Setting, and Participants: Serial cross-sectional study using national death certificate data obtained from the National Center for Health Statistics and including all external causes of 3 813 894 deaths among individuals aged 20 years or older from January 1, 1999, to December 31, 2020. Data analysis was conducted from January 20, 2022, to February 5, 2023. Exposures: Age, sex, and race and ethnicity. Main Outcomes and Measures: Trends in age-standardized mortality rates and average annual percentage change (AAPC) in rates calculated by intent (suicide, homicide, unintentional, and undetermined), age, sex, and race and ethnicity for each external cause. Results: Between 1999 and 2020, there were 3 813 894 deaths due to external causes in the US. From 1999 to 2020, poisoning death rates increased annually (AAPC, 7.0%; 95% CI, 5.4%-8.7%). From 2014 to 2020, poisoning death rates increased the most among men (APC, 10.8%; 95% CI, 7.7%-14.0%). During the study period, poisoning death rates increased in all the racial and ethnic groups examined; the most rapid increase was among American Indian and Alaska Native individuals (AAPC, 9.2%; 95% CI, 7.4%-10.9%). During the study period, death rates for unintentional poisoning had the most rapid rate of increase (AAPC, 8.1%; 95% CI, 7.4%-8.9%). From 1999 to 2020, firearm death rates increased (AAPC, 1.1%; 95% CI, 0.7%-1.5%). From 2013 to 2020, firearm mortality increased by an average of 4.7% annually (95% CI, 2.9%-6.5%) among individuals aged 20 to 39 years. From 2014 to 2020, mortality from firearm homicides increased by an average of 6.9% annually (95% CI, 3.5%-10.4%). From 2019 to 2020, mortality rates from external causes accelerated further, largely from increases in unintentional poisoning, and homicide due to firearms and all other injuries. Conclusions and Relevance: Results of this cross-sectional study suggest that from 1999 to 2020, death rates due to poisonings, firearms, and all other injuries increased substantially in the US. The rapid increase in deaths due to unintentional poisonings and firearm homicides is a national emergency that requires urgent public health interventions at the local and national levels.

Multi-omics analysis reveals the mechanism of torularhodin accumulation in the mutant Rhodosporidium toruloides A1-15 under nitrogen-limited conditions.

A carotenoid production strain Rhodosporidium toruloides NP11 and its mutant strain R. toruloides A1-15 were studied under chemostat nitrogen-limited cultivation. Multi-omics analysis (metabolomics, lipidomics and transcriptomics) was used to investigate the different mechanisms of torularhodin accumulation between NP11 and A1-15. The results showed that the carotenoid synthesis pathway was significantly enhanced in A1-15 compared to NP11 under nitrogen limitation, due to the significant increase of torularhodin. Under nitrogen-limited conditions, higher levels of ß-oxidation were present in A1-15 compared to those in NP11, which provided sufficient precursors for carotenoid synthesis. In addition, ROS stress accelerated the intracellular transport of iron ions, promoted the expression of CRTI and CRTY genes, and reduced the transcript levels of FNTB1 and FNTB2 in the bypass pathway, and these factors may be responsible for the regulation of high torularhodin production in A1-15. This study provided insights into the selective production of torularhodin.

Development of 18F-Labeled Acridone Analogue for Tumor Imaging via Stimulator of Interferon Genes Targeting.

The stimulator of interferon genes (STING) is a pivotal protein in the production of STING-dependent type I interferon, which has the potential to enhance tumor rejection. The visualization of STING in the tumor microenvironment is valuable for STING-related treatments, but few STING imaging probes have been reported to date. In this study, we developed a novel 18F-labeled agent ([18F]F-CRI1) with an acridone core structure for the positron emission tomography (PET) imaging of STING in CT26 tumors. The probe was successfully prepared with a nanomolar STING binding affinity of Kd = 40.62 nM. [18F]F-CRI1 accumulated quickly in the tumor sites and its uptake reached a maximum of 3.02 ± 0.42% ID/g after 1 h i.v. injection. The specificity of [18F]F-CRI1 was confirmed both in in vitro cell uptake and in vivo PET imaging by blocking studies. Our findings suggest that [18F]F-CRI1 may be a potential agent for visualizing STING in the tumor microenvironment.

Cancer mortality rates by racial and ethnic groups in the United States, 2018-2020.

BACKGROUND: Starting in 2018, national death certificates included a new racial classification system that accounts for multiple-race decedents and separates Native Hawaiian and Pacific Islander (NHPI) individuals from Asian individuals. We estimated cancer death rates across updated racial and ethnic categories, sex, and age. METHODS: Age-standardized US cancer mortality rates and rate ratios from 2018 to 2020 among individuals aged 20 years and older were estimated with national death certificate data by race and ethnicity, sex, age, and cancer site. RESULTS: In 2018, there were approximately 597 000 cancer deaths, 598 000 in 2019, and 601 000 in 2020. Among men, cancer death rates were highest in Black men (298.2 per 100 000; n = 105 632), followed by White (250.8; n = 736 319), American Indian/Alaska Native (AI/AN; 249.2; n = 3376), NHPI (205.6; n = 1080), Latino (177.2; n = 66 167), and Asian (147.9; n = 26 591) men. Among women, Black women had the highest cancer death rates (206.5 per 100 000; n = 104 437), followed by NHPI (192.1; n = 1141), AI/AN (189.9; n = 3239), White (183.0; n = 646 865), Latina (128.4; n = 61 579), and Asian (111.4; n = 26 396) women. The highest death rates by age group occurred among NHPI individuals aged 20-49 years and Black individuals aged 50-69 and 70 years and older. Asian individuals had the lowest cancer death rates across age groups. Compared with Asian individuals, total cancer death rates were 39% higher in NHPI men and 73% higher in NHPI women. CONCLUSIONS: There were striking racial and ethnic disparities in cancer death rates during 2018-2020. Separating NHPI and Asian individuals revealed large differences in cancer mortality between 2 groups that were previously combined in vital statistics data.

p53 inhibits the Urea cycle and represses polyamine biosynthesis in glioma cell lines.

Glioma is the most common malignant tumor of the central nervous system. The urea cycle (UC) is an essential pathway to convert excess nitrogen and ammonia into the less toxic urea in humans. However, less is known about the functional significance of the urea cycle in glioma. p53 functions as a tumor suppressor and modulates several cellular functions and disease processes. In the present study, we aimed to explore whether p53 influences glioma progression by regulating the urea cycle. Here, we demonstrated the inhibitory impact of p53 on the expression of urea cycle enzymes and urea genesis in glioma cells. The level of polyamine, a urea cycle metabolite, was also regulated by p53 in glioma cells. Carbamoyl phosphate synthetase-1 (CPS1) is the first key enzyme involved in the urea cycle. Functionally, we demonstrated that CPS1 knockdown suppressed glioma cell proliferation, migration and invasion. Mechanistically, we demonstrated that the expression of ornithine decarboxylase (ODC), which determines the generation of polyamine, was regulated by CPS1. In addition, the impacts of p53 knockdown on ODC expression, glioma cell growth and aggressive phenotypes were significantly reversed by CPS1 inhibition. In conclusion, these results demonstrated that p53 inhibits polyamine metabolism by suppressing the urea cycle, which inhibits glioma progression.

Combined effects of lipase and Lactiplantibacillus plantarum 1-24-LJ on physicochemical property, microbial succession and volatile compounds formation in fermented fish product.

BACKGROUND: Studies have shown that either the addition of starter culture or enzyme can improve fermentation in fish or other products. However, little research has been carried out on the effects of coupling starter cultures with lipase on the microbial community and product quality. Suanzhayu is a Chinese fermented fish product that mainly relies on spontaneous fermentation, resulting in an unstable flavor and quality. The present study investigated the impact of lipase and Lactiplantibacillus plantarum 1-24-LJ on the quality of Suanzhayu. RESULTS: Inoculation decreased pH and 2-thiobarbituric acid reactive substances (TBARS) values, and also helped the dominance of the strain in the ecosystem, whereas lipase addition raised TBARS values and had little effect on pH, water activity (aw ) and microbiota. The addition of lipase and/or Lpb. plantarum increased the content of alcohols, aldehydes, ketones, esters and umami amino acids. The co-additions with the most significant effect and the total contents of volatile compounds (VCs) and free amino acids (FAAs) were 1801.92 g per 100 g and 21 357.05 mg per 100 g, respectively. Former-Lactobacillus was negatively correlated with pH, aw and Prevotella, but positively with VCs (ethyl ester of heptanoic acid, ethyl ester of octanoic acid) and FAAs (Tyr, Phe). Furthermore, adding Lpb. plantarum 1-24-LJ alone or in combination with lipase shortened the fermentation process. CONCLUSION: The present study provides a recommended Suanzhayu process approach for improving product quality and flavor, as well as shortening fermentation time, by adding Lpb. plantarum 1-24-LJ with or without lipase. © 2023 Society of Chemical Industry.

County-level geographic disparities in cardiovascular disease mortality among US breast cancer survivors, 2000-2018.

BACKGROUND: Disparities in cardiovascular disease mortality among breast cancer survivors are documented, but geographic factors by county-level socioeconomic status (SES) and rurality are not well described. METHODS: We analyzed 724 518 women diagnosed with localized or regional stage breast cancer between 2000 and 2017 within Surveillance, Epidemiology, and End Results Program-18 with follow-up until 2018. We calculated relative risks (RRs) of cardiovascular disease mortality using Poisson regression, accounting for age- and race-specific rates in the general population, according to county-level quintiles of SES (measured by Yost index), median income, and rurality at breast cancer diagnosis. We also calculated 10-year cumulative mortality risk of cardiovascular disease accounting for competing risks. RESULTS: Cardiovascular disease mortality was 41% higher among breast cancer survivors living in the lowest SES (RR = 1.41, 95% confidence interval [CI] = 1.36 to 1.46, Ptrend < .001) and poorest (RR = 1.41, 95% CI = 1.36 to 1.47, Ptrend < .001) counties compared with the highest SES and wealthiest counties, and 24% higher for most rural relative to most urban counties (RR = 1.24, 95% CI = 1.17 to 1.30, Ptrend < .001). Disparities for the lowest SES relative to highest SES counties were greatest among younger women aged 18-49 years (RR = 2.32, 95% CI = 1.90 to 2.83) and aged 50-59 years (RR = 2.01, 95% CI = 1.77 to 2.28) and within the first 5 years of breast cancer diagnosis (RR = 1.53, 95% CI = 1.44 to 1.64). In absolute terms, however, disparities were widest for women aged 60+ years, with approximately 2% higher 10-year cumulative cardiovascular disease mortality risk in the poorest compared with wealthiest counties. CONCLUSIONS: Geographic factors at breast cancer diagnosis were associated with increased cardiovascular disease mortality risk. Studies with individual- and county-level information are needed to inform public health interventions and reduce disparities among breast cancer survivors.

PuHox52 promotes coordinated uptake of nitrate, phosphate, and iron under nitrogen deficiency in Populus ussuriensis.

It is of great importance to better understand how trees regulate nitrogen (N) uptake under N deficiency conditions which severely challenge afforestation practices, yet the underlying molecular mechanisms have not been well elucidated. Here, we functionally characterized PuHox52, a Populus ussuriensis HD-ZIP transcription factor, whose overexpression greatly enhanced nutrient uptake and plant growth under N deficiency. We first conducted an RNA sequencing experiment to obtain root transcriptome using PuHox52-overexpression lines of P. ussuriensis under low N treatment. We then performed multiple genetic and phenotypic analyses to identify key target genes of PuHox52 and validated how they acted against N deficiency under PuHox52 regulation. PuHox52 was specifically induced in roots by N deficiency, and overexpression of PuHox52 promoted N uptake, plant growth, and root development. We demonstrated that several nitrate-responsive genes (PuNRT1.1, PuNRT2.4, PuCLC-b, PuNIA2, PuNIR1, and PuNLP1), phosphate-responsive genes (PuPHL1A and PuPHL1B), and an iron transporter gene (PuIRT1) were substantiated to be direct targets of PuHox52. Among them, PuNRT1.1, PuPHL1A/B, and PuIRT1 were upregulated to relatively higher levels during PuHox52-mediated responses against N deficiency in PuHox52-overexpression lines compared to WT. Our study revealed a novel regulatory mechanism underlying root adaption to N deficiency where PuHox52 modulated a coordinated uptake of nitrate, phosphate, and iron through 'PuHox52-PuNRT1.1', 'PuHox52-PuPHL1A/PuPHL1B', and 'PuHox52-PuIRT1' regulatory relationships in poplar roots.