DNA damage response in breast cancer and its significant role in guiding novel precise therapies.

DNA damage response (DDR) deficiency has been one of the emerging targets in treating breast cancer in recent years. On the one hand, DDR coordinates cell cycle and signal transduction, whose dysfunction may lead to cell apoptosis, genomic instability, and tumor development. Conversely, DDR deficiency is an intrinsic feature of tumors that underlies their response to treatments that inflict DNA damage. In this review, we systematically explore various mechanisms of DDR, the rationale and research advances in DDR-targeted drugs in breast cancer, and discuss the challenges in its clinical applications. Notably, poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated favorable efficacy and safety in breast cancer with high homogenous recombination deficiency (HRD) status in a series of clinical trials. Moreover, several studies on novel DDR-related molecules are actively exploring to target tumors that become resistant to PARP inhibition. Before further clinical application of new regimens or drugs, novel and standardized biomarkers are needed to develop for accurately characterizing the benefit population and predicting efficacy. Despite the promising efficacy of DDR-related treatments, challenges of off-target toxicity and drug resistance need to be addressed. Strategies to overcome drug resistance await further exploration on DDR mechanisms, and combined targeted drugs or immunotherapy will hopefully provide more precise or combined strategies and expand potential responsive populations.

Development of a Nomogram Model to Predict the Risk of Stricture Recurrence after Urethroplasty: A Retrospective Study.

OBJECTIVE: A retrospective study was performed to analyse the influencing factors of stricture recurrence after urethroplasty and to establish a predictive nomogram model. METHODS: The clinical data of patients who underwent urethroplasty in our hospital from January 2021 to June 2023 were retrospectively analysed. Depending on whether stenosis occurs six months after surgery, the patients were divided into recurrence and nonrecurrence groups. Logistic regression analysis was performed on the indicators with statistically significant differences between the two groups in single factor analysis to analyse the influencing factors of postoperative recurrence risk of stricture. X64.4.1.3 version R language and external source packages were used to build the nomogram model. The nomogram was internally validated through 10-fold cross-validation, and C-index was calculated. The area under the curve (AUC) of the receiver operating characteristic curve was employed to evaluate the results of the internal validation. RESULTS: Amongst 105 patients who underwent urethroplasty in our hospital, 15 patients with recurrence were included in the recurrence group, and 90 patients without recurrence were included in the nonrecurrence group. The length of stricture segment, history of urethroplasty and smoking history within 3 months before surgery were risk factors for stricture recurrence, with odds ratio (OR) values of 1.874 (95% CI: 1.103-5.725), 1.670 (95% CI: 1.105-2.904) and 1.740 (95% CI: 1.456-5.785), respectively. The constructed nomogram obtained an average AUC of 0.842 and an average C-index of 0.794, calculated after 200 times of 10-fold cross-validation. CONCLUSIONS: From the data of this study, it can be deduced that the influencing factors of stricture recurrence after urethroplasty include the length of stricture segment, history of urethroplasty and smoking history of 3 months before surgery. Using the above factors as a basis to construct a predictive nomogram model is helpful to screen high-risk patients with recurrence of stricture after urethroplasty.

Surface defect detection of steel based on improved YOLOv5 algorithm.

To address the challenge of achieving a balance between efficiency and performance in steel surface defect detection, this paper presents a novel algorithm that enhances the YOLOv5 defect detection model. The enhancement process begins by employing the K-means++ algorithm to fine-tune the location of the prior anchor boxes, improving the matching process. Subsequently, the loss function is transitioned from generalized intersection over union (GIOU) to efficient intersection over union (EIOU) to mitigate the former's degeneration issues. To minimize information loss, Carafe upsampling replaces traditional upsampling techniques. Lastly, the squeeze and excitation networks (SE-Net) module is incorporated to augment the model's sensitivity to channel features. Experimental evaluations conducted on a public defect dataset reveal that the proposed method elevates the mean average precision (mAP) by seven percentage points compared to the original YOLOv5 model, achieving an mAP of 83.3%. Furthermore, our model's size is significantly reduced compared to other advanced algorithms, while maintaining a processing speed of 47 frames per second. This performance demonstrates the effectiveness of the proposed enhancements in improving both accuracy and efficiency in defect detection.

Biomarkers and experimental models for cancer immunology investigation.

The rapid advancement of tumor immunotherapies poses challenges for the tools used in cancer immunology research, highlighting the need for highly effective biomarkers and reproducible experimental models. Current immunotherapy biomarkers encompass surface protein markers such as PD-L1, genetic features such as microsatellite instability, tumor-infiltrating lymphocytes, and biomarkers in liquid biopsy such as circulating tumor DNAs. Experimental models, ranging from 3D in vitro cultures (spheroids, submerged models, air-liquid interface models, organ-on-a-chips) to advanced 3D bioprinting techniques, have emerged as valuable platforms for cancer immunology investigations and immunotherapy biomarker research. By preserving native immune components or coculturing with exogenous immune cells, these models replicate the tumor microenvironment in vitro. Animal models like syngeneic models, genetically engineered models, and patient-derived xenografts provide opportunities to study in vivo tumor-immune interactions. Humanized animal models further enable the simulation of the human-specific tumor microenvironment. Here, we provide a comprehensive overview of the advantages, limitations, and prospects of different biomarkers and experimental models, specifically focusing on the role of biomarkers in predicting immunotherapy outcomes and the ability of experimental models to replicate the tumor microenvironment. By integrating cutting-edge biomarkers and experimental models, this review serves as a valuable resource for accessing the forefront of cancer immunology investigation.

Chronic stress induces meiotic arrest failure and ovarian reserve decline via the cAMP signaling pathway.

Chronic stress is suspected to be a causal factor of female subfertility; however, the underlying mechanisms remain unclear. Here, we found that chronic stress inhibited the cyclic adenosine 3',5'-monophosphate (cAMP) signaling pathway, leading to ovarian reserve decline in mice. A chronic stress model was constructed using restraint stress for 8 weeks. An elongated estrous cycle and a significant increase in the number of atretic follicles were observed in the stress group. We identified a significant increase in meiotic arrest failure (MAF) in oocytes in the stress group, characterized by condensed metaphase chromosomes, assembled spindles, or polar bodies in the oocytes. Whole-mount ovarian reserve estimation at the single-oocyte level using the CUBIC method (clear, unobstructed brain/body imaging cocktails and computational analysis) revealed a significant decrease in quiescent oocytes from 2,261/ovary in the control group to 1,373/ovary in the stress group. The number of growing oocytes also significantly decreased from 220/ovary in the control group to 150/ovary in the stress group. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis of the meiotic arrest maintenance pathways revealed significant downregulation of Gpr3, Nppc, and Npr2 in the stress group. These results indicate that blocking cAMP production contributes to MAF and a decline in ovarian reserve. Overall, we present new insights into the mechanisms underlying chronic-stress-induced oocyte loss and potential targets for ovarian reserve preservation.

Single nucleotide polymorphisms associated with female breast cancer susceptibility in Chinese population.

Breast cancer is a complex disease influenced by both external and internal factors, among which genetic factors play a critical role. Single-nucleotide polymorphisms (SNPs) are major contributors to the heritability of breast cancer, and their frequencies vary across ethnic groups. In this study, we aimed to investigate the association between 34 SNPs identified in previous genome-wide association studies (GWAS) and overall breast cancer risk, as well as breast cancer subtypes, in the Chinese female population. To accomplish this, we conducted an extensive association analysis using the high-throughput Sequenom MassARRAY® platform in a case-control study comprising 1848 breast cancer patients and 709 healthy controls. Our analysis, which utilized the SNPassoc package in R based on chi-squared (χ2) test and genetic model analysis, identified significant associations between breast cancer risk and SNP rs12493607 (TGFBR2, risk allele C, OR = 1.28 [1.11-1.47], P = 0.0005), as well as a less conservatively significant association with rs4784227 (CASC16, risk allele T, OR = 1.24 [1.08-1.42], P = 0.0017) and rs2046210 (ESR1, risk allele A, OR = 1.50 [1.16-1.95], P = 0.0016). Furthermore, our stratified analyses revealed that rs12493607 was significantly associated with invasive carcinoma, estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, HER2-negative, and young (aged younger than 45) breast cancer. SNP rs4784227 and rs3803662 (CASC16) were associated with invasive carcinoma and ER-positive breast cancer, while rs2046210 was linked to ductal carcinoma in situ, ER-negative, PR-negative, HER2-positive, and elder (aged more than 45) breast cancers. SNPs rs10484919 (ESR1) and rs1038304 (CCDC170) showed links to HER2-positive breast cancer, and rs616488 (PEX14) with premenopausal breast cancer. In summary, our study shed light on the relationship between SNPs and breast cancer susceptibility within a vast Chinese cohort, supporting the development of polygenetic risk scores for the Chinese population. These findings provide valuable insights into the genetic basis of breast cancer and have important implications for risk prediction, early detection, and personalized treatment of this disease.

A novel non-invasive exhaled breath biopsy for the diagnosis and screening of breast cancer.

BACKGROUND: Early detection is critical for improving the survival of breast cancer (BC) patients. Exhaled breath testing as a non-invasive technique might help to improve BC detection. However, the breath test accuracy for BC diagnosis is unclear. METHODS: This multi-center cohort study consecutively recruited 5047 women from four areas of China who underwent BC screening. Breath samples were collected through standardized breath collection procedures. Volatile organic compound (VOC) markers were identified from a high-throughput breathomics analysis by the high-pressure photon ionization-time-of-flight mass spectrometry (HPPI-TOFMS). Diagnostic models were constructed using the random forest algorithm in the discovery cohort and tested in three external validation cohorts. RESULTS: A total of 465 (9.21%) participants were identified with BC. Ten optimal VOC markers were identified to distinguish the breath samples of BC patients from those of non-cancer women. A diagnostic model (BreathBC) consisting of 10 optimal VOC markers showed an area under the curve (AUC) of 0.87 in external validation cohorts. BreathBC-Plus, which combined 10 VOC markers with risk factors, achieved better performance (AUC = 0.94 in the external validation cohorts), superior to that of mammography and ultrasound. Overall, the BreathBC-Plus detection rates were 96.97% for ductal carcinoma in situ, 85.06%, 90.00%, 88.24%, and 100% for stages I, II, III, and IV BC, respectively, with a specificity of 87.70% in the external validation cohorts. CONCLUSIONS: This is the largest study on breath tests to date. Considering the easy-to-perform procedure and high accuracy, these findings exemplify the potential applicability of breath tests in BC screening.

Membrane estrogen receptor α signaling modulates the sensitivity to estradiol treatment in a dose- and tissue- dependent manner.

Estradiol (E2) affects both reproductive and non-reproductive tissues, and the sensitivity to different doses of E2 varies between tissues. Membrane estrogen receptor α (mERα)-initiated signaling plays a tissue-specific role in mediating E2 effects, however, it is unclear if mERα signaling modulates E2 sensitivity. To determine this, we treated ovariectomized C451A females, lacking mERα signaling, and wildtype (WT) littermates with physiological (0.05 µg/mouse/day (low); 0.6 µg/mouse/day (medium)) or supraphysiological (6 µg/mouse/day (high)) doses of E2 (17ß-estradiol-3-benzoate) for three weeks. Low-dose treatment increased uterus weight in WT, but not C451A mice, while non-reproductive tissues (gonadal fat, thymus, trabecular and cortical bone) were unaffected in both genotypes. Medium-dose treatment increased uterus weight and bone mass and decreased thymus and gonadal fat weights in WT mice. Uterus weight was also increased in C451A mice, but the response was significantly attenuated (- 85%) compared to WT mice, and no effects were triggered in non-reproductive tissues. High-dose treatment effects in thymus and trabecular bone were significantly blunted (- 34% and - 64%, respectively) in C451A compared to WT mice, and responses in cortical bone and gonadal fat were similar between genotypes. Interestingly, the high dose effect in uterus was enhanced (+ 26%) in C451A compared to WT mice. In conclusion, loss of mERα signaling reduces the sensitivity to physiological E2 treatment in both non-reproductive tissues and uterus. Furthermore, the E2 effect after high-dose treatment in uterus is enhanced in the absence of mERα, suggesting a protective effect of mERα signaling in this tissue against supraphysiological E2 levels.

A hypothalamic pathway that suppresses aggression toward superior opponents.

Aggression is costly and requires tight regulation. Here we identify the projection from estrogen receptor alpha-expressing cells in the caudal part of the medial preoptic area (cMPOAEsr1) to the ventrolateral part of the ventromedial hypothalamus (VMHvl) as an essential pathway for modulating aggression in male mice. cMPOAEsr1 cells increase activity mainly during male-male interaction, which differs from the female-biased response pattern of rostral MPOAEsr1 (rMPOAEsr1) cells. Notably, cMPOAEsr1 cell responses to male opponents correlated with the opponents' fighting capability, which mice could estimate based on physical traits or learn through physical combats. Inactivating the cMPOAEsr1-VMHvl pathway increased aggression, whereas activating the pathway suppressed natural intermale aggression. Thus, cMPOAEsr1 is a key population for encoding opponents' fighting capability-information that could be used to prevent animals from engaging in disadvantageous conflicts with superior opponents by suppressing the activity of VMHvl cells essential for attack behaviors.

Ideal cardiovascular health and mortality: pooled results of three prospective cohorts in Chinese adults.

BACKGROUND: Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps. METHODS: A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis. RESULTS: During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed. CONCLUSIONS: ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.

Regular Glucosamine Use May Have Different Roles in the Risk of Site-Specific Cancers: Findings from a Large Prospective Cohort.

BACKGROUND: Previous studies indicated that glucosamine supplements may have a general anticancer effect. This study aimed to assess whether the potential effect differs across different types of cancers in a large prospective cohort study. METHODS: All participants from the UK Biobank who were free of cancers and had complete information on glucosamine use at baseline were included and followed up from 2006 until 2021. Cox proportional hazards models were used to assess the associations between regular glucosamine use and different site-specific cancers. Subgroup analyses were performed to explore potential interactions. Several sensitivity analyses were conducted to assess the robustness of the main findings. RESULTS: A total of 450,207 eligible participants (mean age: 56.2 years; females: 53.3%) were included, of whom 84,895 (18.9%) reported regular glucosamine use at baseline. During a median of 12.5 years follow-up, glucosamine use was significantly associated with an increased risk of overall cancer [HR, 1.04; 95% confidence interval (CI), 1.01-1.06], skin cancer (HR, 1.11; 95% CI, 1.07-1.15), and prostate cancer (HR, 1.07; 95% CI, 1.01-1.13), and with a reduced risk of lung cancer (HR, 0.88; 95% CI, 0.79-0.97) after adjusting for potential confounders. Statistical interaction was observed for gender, age, and education for the association of glucosamine use with overall cancer risk (all Pinteraction < 0.027). These results remained unchanged in the sensitivity analyses. CONCLUSIONS: Regular glucosamine use was associated with lower risk of lung cancer but higher risk of skin cancer, prostate cancer, and overall cancer. IMPACT: The roles of glucosamine use potentially differ in the development of different site-specific cancers.

Novel cancer gene discovery using a forward genetic screen in RCAS-PDGFB-driven gliomas.

BACKGROUND: Malignant gliomas, the most common malignant brain tumors in adults, represent a heterogeneous group of diseases with poor prognosis. Retroviruses can cause permanent genetic alterations that modify genes close to the viral integration site. METHODS: Here we describe the use of a high-throughput pipeline coupled to the commonly used tissue-specific retroviral RCAS-TVA mouse tumor model system. Utilizing next-generation sequencing, we show that retroviral integration sites can be reproducibly detected in malignant stem cell lines generated from RCAS-PDGFB-driven glioma biopsies. RESULTS: A large fraction of common integration sites contained genes that have been dysregulated or misexpressed in glioma. Others overlapped with loci identified in previous glioma-related forward genetic screens, but several novel putative cancer-causing genes were also found. Integrating retroviral tagging and clinical data, Ppfibp1 was highlighted as a frequently tagged novel glioma-causing gene. Retroviral integrations into the locus resulted in Ppfibp1 upregulation, and Ppfibp1-tagged cells generated tumors with shorter latency on orthotopic transplantation. In human gliomas, increased PPFIBP1 expression was significantly linked to poor prognosis and PDGF treatment resistance. CONCLUSIONS: Altogether, the current study has demonstrated a novel approach to tagging glioma genes via forward genetics, validating previous results, and identifying PPFIBP1 as a putative oncogene in gliomagenesis.

Neural network learning defines glioblastoma features to be of neural crest perivascular or radial glia lineages.

Glioblastoma is believed to originate from nervous system cells; however, a putative origin from vessel-associated progenitor cells has not been considered. We deeply single-cell RNA-sequenced glioblastoma progenitor cells of 18 patients and integrated 710 bulk tumors and 73,495 glioma single cells of 100 patients to determine the relation of glioblastoma cells to normal brain cell types. A novel neural network-based projection of the developmental trajectory of normal brain cells uncovered two principal cell-lineage features of glioblastoma, neural crest perivascular and radial glia, carrying defining methylation patterns and survival differences. Consistently, introducing tumorigenic alterations in naïve human brain perivascular cells resulted in brain tumors. Thus, our results suggest that glioblastoma can arise from the brains' vasculature, and patients with such glioblastoma have a significantly poorer outcome.

Relationship Between Serum Concentration of Adrenomedullin and Myocardial Ischemic T Wave Changes in Patients With Lung Cancer.

Background: Patients with lung cancer are at increased risk for the development of cardiovascular diseases. Molecular markers for early diagnosis of cardiac ischemia are of great significance for the early prevention of cardiovascular events in patients with lung cancer. By evaluating the relationship between adrenomedullin (ADM) and myocardial ischemic T wave changes, the clinical value of circulating ADM as a predictor of myocardial ischemia in patients with lung cancer is confirmed. Methods: We enrolled patients with lung cancer and healthy people from 2019 to 2021 and extracted a detailed ECG parameter. After adjustment for potential confounders, logistic regression was used to assess the association of clinical data. We performed analyses on differences in T wave between patients with lung cancer and healthy people, and the relationship between T wave and ADM among patients with lung cancer. Receiver operator characteristic (ROC) curves were drawn to confirm the diagnostic value of biomarkers. Results: After adjusting for potential confounders, the incidence of T wave inversion or flattening in patients with lung cancer was higher than in healthy people (OR: 3.3228, P = 0.02). Also, further analysis of the data of lung cancer patients revealed that the ADM in lung cancer patients with T wave inversion or flat was higher than those with normal T wave (189.8 ± 51.9 vs. 131.9 ± 38.4, p < 0.001). The area under the ROC curve was 0.8137. Conclusion: Among the patients with lung cancer, serum ADM concentration is associated with the incidence of the abnormal T wave. ADM might be a potentially valuable predictor for heart ischemia in patients with lung cancer.

Dietary total antioxidant capacity and mortality outcomes: the Singapore Chinese Health Study.

PURPOSE: To evaluate the relations of dietary total antioxidant capacity (DTAC) with mortality outcomes in a Chinese population. METHODS: The study included 62,063 participants from the Singapore Chinese Health Study. The participants were 45-74 years at baseline (1993-1998) when dietary data were collected with a validated 165-item food frequency questionnaire. The DTAC was derived using two widely adopted scores of integrated dietary consumption of antioxidant nutrients, i.e., the Comprehensive Dietary Antioxidant Index (CDAI) and Vitamin C Equivalent Antioxidant Capacity (VCEAC). We used Cox proportional hazard model to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations with adjustment for potential confounders. RESULTS: During 1,212,318 person-years of follow-up, 23,397 deaths [cardiovascular diseases (CVD): 7523; respiratory diseases: 4696; and cancer: 7713] occurred. In multivariable models, the HR (95% CI) comparing participants in the highest vs. lowest quartile of CDAI was 0.85 (0.82, 0.88) for all-cause mortality, 0.82 (0.76, 0.88) for CVD mortality, 0.76 (0.70, 0.83) for respiratory disease mortality (all P-trend < 0.001), and 0.94 (0.88, 1.00) for cancer mortality (P-trend = 0.16). Similar associations were found with the VCEAC index. Higher intakes of the DTAC components, i.e., vitamin C, vitamin E, carotenoids, and flavonoids, were all associated with lower mortality risk. CONCLUSION: Diet with a higher antioxidant capacity in midlife was associated with a lower risk of all-cause, cardiovascular and respiratory disease mortality in the Singapore Chinese population, supporting the public health recommendation of consuming more plant-based foods that are rich in antioxidant nutrients.

Dietary Total Antioxidant Capacity and Late-Life Cognitive Impairment: The Singapore Chinese Health Study.

BACKGROUND: With the dramatically rapid rate of aging worldwide, the maintenance of cognitive function in old age is a major public health priority. The association between total antioxidant capacity (TAC) of midlife diet and cognitive function in late life is still unclear. METHOD: The study included 16 703 participants from a prospective cohort study in Singapore. Dietary intakes and selected supplementary use were assessed with a validated 165-item food frequency questionnaire at baseline (1993-1998). Two dietary TACs were calculated from the intake of antioxidant nutrients: the Comprehensive Dietary Antioxidant Index (CDAI) and the Vitamin C Equivalent Antioxidant Capacity (VCEAC). Cognitive function was assessed 20.2 years later using a Singapore-modified version of the Mini-Mental State Examination when subjects were 61-96 years old. Cognitive impairment was defined using education-specific cutoffs. Multivariable logistic regression models were utilized to estimate the associations between dietary TACs, component nutrients, and cognitive impairment. RESULTS: A total of 2 392 participants (14.3%) were defined to have cognitive impairment. Both CDAI and VCEAC scores were inversely associated with odds of cognitive impairment in a dose-dependent manner. The odds ratio (95% confidence interval; p-trend) comparing the highest with the lowest quartile was 0.84 (0.73, 0.96; p-trend = .003) for the CDAI and 0.75 (0.66, 0.86; p-trend < .001) for the VCEAC. Higher intakes of vitamin C, vitamin E, carotenoids, and flavonoids were all inversely associated with cognitive impairment. CONCLUSIONS: Higher dietary TAC was associated with lower odds of cognitive impairment in later life in a Chinese population in Singapore.

Dietary Intake and Circulating Concentrations of Carotenoids and Risk of Type 2 Diabetes: A Dose-Response Meta-Analysis of Prospective Observational Studies.

Previous meta-analysis studies have indicated inverse associations between some carotenoids and risks of metabolic syndrome, cardiovascular disease, cancer, and all-cause mortality. However, the results for associations between carotenoids and type 2 diabetes (T2D) remain inconsistent and no systematic assessment has been done on this topic. We conducted a systematic review and meta-analysis to examine the associations of dietary intakes and circulating concentrations of carotenoids with risk of T2D. We searched PubMed and Ovid Embase from database inception to July 2020. Prospective observational studies of carotenoids and T2D risk were included. Random-effects models were used to summarize the RRs and 95% CIs. Thirteen publications were included. Dietary intake of ß-carotene was inversely associated with the risk of T2D, and the pooled RR comparing the highest with the lowest categories was 0.78 (95% CI: 0.70, 0.87; I2 = 13.7%; n = 6); inverse associations were also found for total carotenoids (n = 2), α-carotene (n = 4), and lutein/zeaxanthin (n = 4), with pooled RRs ranging from 0.80 to 0.91, whereas no significant associations were observed for ß-cryptoxanthin and lycopene. Circulating concentration of ß-carotene was associated with a lower risk of T2D, and the pooled RR comparing extreme categories was 0.60 (95% CI: 0.46, 0.78; I2 = 56.2%; n = 7); inverse associations were also found for total carotenoids (n = 3), lycopene (n = 4), and lutein (n = 2), with pooled RRs ranging from 0.63 to 0.85, whereas no significant association was found for circulating concentrations of α-carotene and zeaxanthin when comparing extreme categories. Dose-response analysis indicated that nonlinear relations were observed for circulating concentrations of α-carotene, ß-carotene, lutein, and total carotenoids (all P-nonlinearity < 0.05), but not for other carotenoids or dietary exposures. In conclusion, higher dietary intakes and circulating concentrations of total carotenoids, especially ß-carotene, were associated with a lower risk of T2D. More studies are needed to confirm the causality and explore the role of foods rich in carotenoids in prevention of T2D. This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42020196616.

Association of Consumption of Sugar-Sweetened Beverages or Artificially Sweetened Beverages with Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

Sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) intakes have been reported to be associated with mortality; however, conclusions have been inconsistent. This review synthesized the evidence on the associations of SSB and ASB intakes with mortality from all causes, cardiovascular disease (CVD), and cancer among all populations (including general, diseased, or occupational populations, etc.). PubMed, EMBASE, Web of Science, Cochrane Library, ProQuest, ClinicalTrials.gov, and the International Clinical Trials Registry Platform were searched up to March 2020. Fifteen studies including 17 cohorts were included in meta-analyses. Each serving (12 fluid ounces or 355 mL) increase in daily SSB consumption was associated with higher risks of all-cause (HR: 1.08; 95% CI: 1.04, 1.12; 11 cohorts with 965,851 participants) and CVD (HR: 1.08; 95% CI: 1.04, 1.12; 13 cohorts with 898,005 participants) mortality. The associations of ASB intakes with all-cause and CVD mortality were J-shaped, and HRs (95% CI) across different doses (0, 1, 1.5, 2, and 2.5 servings/d) were 1.00, 1.01 (0.99, 1.03), 1.04 (1.02, 1.07), 1.08 (1.05, 1.11), and 1.13 (1.09, 1.18) for all-cause mortality and 1.00, 1.01 (0.96, 1.07), 1.07 (1.01, 1.13), 1.15 (1.08, 1.23), and 1.25 (1.14, 1.37) for CVD mortality. No significant association was found for cancer mortality. According to the NutriGrade scoring system, the quality of evidence on the associations of SSB intakes with all-cause and CVD mortality was high, and the quality of evidence on other associations was low to moderate. In summary, higher SSB and ASB intakes were associated with higher risks of all-cause mortality and CVD mortality. Given the limited evidence, future studies should further investigate the association between ASB intakes and cause-specific mortality.

Association of sugar-sweetened beverage and artificially sweetened beverage intakes with mortality: an analysis of US National Health and Nutrition Examination Survey.

PURPOSE: Current evidence on the associations between sugar-sweetened beverage (SSB) intakes and mortality is inconsistent, whereas the evidence on artificially sweetened beverages (ASBs) was sparse. We aimed to investigate the associations of SSB and ASB intakes with mortality in a nationally representative sample of US adults. METHODS: Participants from the National Health and Nutrition Examination Survey (NHANES, 1999-2014; n = 31,402) were linked to the US mortality registry by the end of 2015. SSB and ASB intakes were collected using 24-h dietary recalls. Cox proportional hazard regression models were used to assess the associations of intakes of SSBs, ASBs, and added sugar from SSBs with mortality with adjustment for demographic, lifestyle, comorbidity, and dietary factors. RESULTS: After a mean follow-up of 7.9 years, 3878 deaths were identified. The multivariate-adjusted hazard ratios (95% confidence intervals) associated with each additional serving/d of SSB were 1.05 (1.01-1.09) for all-cause mortality and 1.11 (1.03-1.21) for heart disease mortality. Hazard ratios (95% confidence intervals) comparing the extreme quintiles of added sugar intakes from SSBs were 1.22 (1.05-1.42) for all-cause mortality and 1.45 (1.06-1.97) for heart disease mortality. No significant relationship was found between SSB intakes and cancer mortality or between high ASB intakes and mortality. Substituting one serving/d of SSB by an equivalent amount of ASBs, unsweetened coffees and teas, and plain water was associated with a 4-7% lower risk of all-cause mortality. CONCLUSION: Higher SSB intakes were associated with higher risks of all-cause mortality and heart disease mortality. High ASB intakes were not significantly associated with mortality. ASBs, unsweetened coffees and teas, and plain water might be optional alternatives for reducing SSB intakes.