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Nuclear envelope proteins have recently gained traction as novel regulators of endothelial and vascular function. Nuclear pore complexes (NPCs) stand as one of the largest protein complexes found at the nuclear envelope yet the role of component NPC proteins (i.e., nucleoporins) in vascular health remains unclear. In the issue of Aging Cell, Nguyen et al. (2024) identify Nucleoporin93, a major structural protein of the NPC, as an indispensable player in endothelial protection. This discovery raises the possibility that endothelial NPCs are susceptible to risk factors for consequent vascular disease.

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Background: Recently, cold atmospheric plasma (CAP), as well as adipose mesenchymal stem cells derived exosomes (ADMSCs-EX), have been applied separately to wound healing treatment. However, no study has investigated the additive effect on the healing mechanism of these two methods in the same skin lesion treatment model. Aim: We conduct this study to describe the results of using CAP and human ADMSCs-EX on in vitro wound healing. Methods: Exosomes were isolated from donor adipose tissue samples by ultracentrifugation method, characterized by transmission electron microscopy (TEM) and Western blot. Assessment in vitro wound healing on proliferation and migration evaluation experiments on human fibroblasts with culture medium supplemented with 10µg total exosomal proteins/1 mL and irradiated with CAP with an intensity of 30 seconds/cm2. Results: Experimental results to evaluate the ability to stimulate fibroblast migration, showed that cell migration speed in the group supplemented with ADMSCs-EX was equivalent to the group with a combination of CAP and ADMSCs-EX and had the highest rate with 87.8 ± 4.2 % and 84.4 ± 5.3 % while in the control group it was the lowest with 61.9 ± 11.4% (p<0.05). The group supplemented with CAP gave fibroblast proliferation and migration results similar to the control group (p>0.05), showing the safety of CAP with the growth of the cells. Conclusions: Therefore, in animal models, we intend to use a combination of these two therapies by using ADMSCs-EX injection therapy into the dermis at the wound edge to avoid the impact of CAP affecting the cell proliferation.

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Background: The application of fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) in multivessel coronary artery disease (CAD) patients has not been definitively explored. We herein assessed how treatment strategies were decided based on FFR/iFR values in vessels selected clinically. Specifically, we sought to determine whether treatment selection was based on whether the vessel tested was the clinical target stenosis. Methods: 270 consecutive patients with angiographically determined multivessel disease who underwent FFR/iFR testing were included. Patients were classified initially based on their angiographic findings, then re-evaluated from FFR/iFR results (normal or abnormal). Tested lesions were classified into target or non-target lesions based on clinical and non-invasive evaluations. Results: Abnormal FFR/iFR values were demonstrated in 51.9 % of patients, in whom 51.4 % received coronary stenting (PCI) and 44.3 % had bypass surgery (CABG). With two-vessel CAD patients, medical therapy was preferred when the target lesion was normal (72.6 %), while PCI was preferred when it was abnormal (78.4 %). In non-target lesions, PCI was preferred regardless of FFR/iFR results (78.0 %). With three-vessel CAD patients, CABG was preferred when the target lesion was abnormal (68.5 %), and there was no difference in the selected modality when it was normal. Furthermore, the incidence of tested lesions was higher in the left anterior descending (LAD) compared to other coronary arteries, and two-vessel CAD patients with LAD stenoses were more frequently treated by PCI. Conclusion: The use of invasive physiologic testing in multivessel CAD patients may alter the preferred treatment strategy, leading to an overall increase in PCI selection.

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Biochemical covalent modification networks exhibit a remarkable suite of steady state and dynamical properties such as multistationarity, oscillations, ultrasensitivity and absolute concentration robustness. This paper focuses on conditions required for a network of this type to have a species with absolute concentration robustness. We find that the robustness in a substrate is endowed by its interaction with a bifunctional enzyme, which is an enzyme that has different roles when isolated versus when bound as a substrate-enzyme complex. When isolated, the bifunctional enzyme promotes production of more molecules of the robust species while when bound, the same enzyme facilitates degradation of the robust species. These dual actions produce robustness in the large class of covalent modification networks. For each network of this type, we find the network conditions for the presence of robustness, the species that has robustness, and its robustness value. The unified approach of simultaneously analyzing a large class of networks for a single property, i.e. absolute concentration robustness, reveals the underlying mechanism of the action of bifunctional enzyme while simultaneously providing a precise mathematical description of bifunctionality.

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As the innermost lining of the vasculature, endothelial cells (ECs) are constantly subjected to systemic inflammation and particularly vulnerable to aging. Endothelial health is hence vital to prevent age-related vascular disease. Healthy ECs rely on the proper localization of transcription factors via nuclear pore complexes (NPCs) to govern cellular behavior. Emerging studies report NPC degradation with natural aging, suggesting impaired nucleocytoplasmic transport in age-associated EC dysfunction. We herein identify nucleoporin93 (Nup93), a crucial structural NPC protein, as an indispensable player in vascular protection. Endothelial Nup93 protein levels are significantly reduced in the vasculature of aged mice, paralleling observations of Nup93 loss when using in vitro models of EC senescence. The loss of Nup93 in human ECs induces cell senescence and promotes the expression of inflammatory adhesion molecules, where restoring Nup93 protein in senescent ECs reverses features of endothelial aging. Mechanistically, we find that both senescence and loss of Nup93 impair endothelial NPC transport, leading to nuclear accumulation of Yap and downstream inflammation. Pharmacological studies indicate Yap hyperactivation as the primary consequence of senescence and Nup93 loss in ECs. Collectively, our findings indicate that the maintenance of endothelial Nup93 is a key determinant of EC health, where aging targets endothelial Nup93 levels to impair NPC function as a novel mechanism of EC senescence and vascular aging.

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Objective: We have previously demonstrated the in vivo importance of the Akt-eNOS substrate-kinase relationship, as defective postnatal angiogenesis characteristic of global Akt1-null mice is rescued when bred to 'gain-of-function' eNOS S1176D mutant mice. While multiple studies support the vascular protective role of endothelial NO generation, the causal role of Akt1-dependent eNOS S1176 phosphorylation during atherosclerotic plaque formation is not yet clear. Approach and results: We herein bred congenic 'loss-of-function' eNOS S1176A and 'gain-of-function' eNOS S1176D mutant mice to the exacerbated atherogenic Akt1-/-; ApoE-/- double knockout mice to definitively test the importance of Akt-mediated eNOS S1176 phosphorylation during atherogenesis. We find that a single amino acid substitution at the eNOS S1176 phosphorylation site yields divergent effects on atherosclerotic plaque formation, as an eNOS phospho-mimic aspartate (D) substitution at S1176 leads to favorable lipid profiles and decreased indices of atherosclerosis, even when on a proatherogenic Akt1 global deletion background. Conversely, mice harboring an unphosphorylatable mutation to alanine (S1176A) result in increased plasma lipids, increased lesion formation and cellular apoptosis, phenocopying the physiological consequence of eNOS deletion and/or impaired enzyme function. Furthermore, gene expression analyses of whole aortas indicate a combinatorial detriment from NO deficiency and Western Diet challenge, as 'loss-of-function' eNOS S1176A mice on a Western Diet present a unique expression pattern indicative of augmented T-cell activity when compared to eNOS S1176D mice. Conclusions: By using genetic epistasis approaches, we conclusively demonstrate that Akt-mediated eNOS S1176 phosphorylation and subsequent eNOS activation remains to be the most physiologically relevant method of NO production to promote athero-protective effects.

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Endothelial cells (ECs) form the innermost lining of the vasculature and serve a pivotal role in preventing age-related vascular disease. Endothelial health relies on the proper nucleocytoplasmic shuttling of transcription factors via nuclear pore complexes (NPCs). Emerging studies report NPC degradation with natural aging, suggesting impaired nucleocytoplasmic transport in age-related EC dysfunction. We herein identify nucleoporin93 (Nup93), a crucial structural NPC protein, as an indispensable player for vascular protection. Endothelial Nup93 protein levels are significantly reduced in the vasculature of aged mice, paralleling observations of Nup93 loss when using in vitro models of endothelial aging. Mechanistically, we find that loss of Nup93 impairs NPC transport, leading to the nuclear accumulation of Yap and downstream inflammation. Collectively, our findings indicate maintenance of endothelial Nup93 as a key determinant of EC health, where aging targets endothelial Nup93 levels to impair NPC function as a novel mechanism for EC senescence and vascular aging.

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Our earlier work in Nguyen et al. (Maximizing metapopulation growth rate and biomass in stream networks. arXiv preprint arXiv:2306.05555 , 2023) shows that concentrating resources on the upstream end tends to maximize the total biomass in a metapopulation model for a stream species. In this paper, we continue our research direction by further considering a Lotka-Volterra competition patch model for two stream species. We show that the species whose resource allocations maximize the total biomass has the competitive advantage.

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Artificial intelligence methods including deep neural networks (DNN) can provide rapid molecular classification of tumors from routine histology with accuracy that matches or exceeds human pathologists. Discerning how neural networks make their predictions remains a significant challenge, but explainability tools help provide insights into what models have learned when corresponding histologic features are poorly defined. Here, we present a method for improving explainability of DNN models using synthetic histology generated by a conditional generative adversarial network (cGAN). We show that cGANs generate high-quality synthetic histology images that can be leveraged for explaining DNN models trained to classify molecularly-subtyped tumors, exposing histologic features associated with molecular state. Fine-tuning synthetic histology through class and layer blending illustrates nuanced morphologic differences between tumor subtypes. Finally, we demonstrate the use of synthetic histology for augmenting pathologist-in-training education, showing that these intuitive visualizations can reinforce and improve understanding of histologic manifestations of tumor biology.

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Existing predictive models of opioid use disorder (OUD) may change as the rate of opioid prescribing decreases. Using Veterans Administration's EHR data, we developed machine-learning predictive models of new OUD diagnoses and ranked the importance of patient features based on their ability to predict a new OUD diagnosis in 2000-2012 and 2013-2021. Using patient characteristics, the three separate machine learning techniques were comparable in predicting OUD, achieving an accuracy of >80%. Using the random forest classifier, opioid prescription features such as early refills and length of prescription consistently ranked among the top five factors that predict new OUD. Younger age was positively associated with new OUD, and older age inversely associated with new OUD. Age stratification revealed prior substance abuse and alcohol dependency as more impactful in predicting OUD for younger patients. There was no significant difference in the set of factors associated with new OUD in 2000-2012 compared to 2013-2021. Characteristics of opioid prescriptions are the most impactful variables that predict new OUD both before and after the peak in opioid prescribing rates. Predictive models should be tailored to age groups. Further research is warranted to determine if machine learning models perform better when tailored to other patient subgroups.

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Background and Aim: We aimed to evaluate the application of Peptest, a novel technique to detect pepsin in the saliva, and identify its threshold level for the diagnosis of gastroesophageal reflux disease (GERD) with extraesophageal symptoms. Methods: A cross-sectional study was conducted in two groups: patients with extraesophageal GERD symptoms (symptomatic group divided into GERD and non-GERD groups according to 24-h esophageal pH-impedance monitoring [pH-I] results) and healthy controls. For the symptomatic group, endoscopy, pH 24 h, high-resolution manometry (HRM), and salivary Peptest were performed. For the healthy control group, only Peptest was done. The accuracy of Peptest was compared with that of pH-I by the Lyon consensus criteria. Results: Chronic laryngitis was the most frequent extraesophageal symptom. On saliva testing, the GERD group had a higher prevalence of positive samples and pepsin concentration than the control group. Between GERD and non-GERD groups, the optimal threshold level was 31.2 ng/mL, with a sensitivity of 86.7% and specificity of 27.5%. The optimal threshold level was 31.4 ng/mL to differentiate GERD from healthy controls, with a sensitivity of 86.7% and specificity of 66.0%. Age, number of total refluxes, DeMeester score, post-reflux swallow-induced peristaltic wave (PSPW) index, and mean nocturnal baseline impedence (MNBI) were associated with pepsin concentration. Regarding HRM metrics, there was no significant difference of pepsin concentration between low/normal upper esophageal sphincter (UES) resting pressure, low/normal lower esophageal sphincter (LES) resting pressure, low/normal 4-s integrated relaxation pressure (IRP4s), and hypomotility/normal motility. Conclusion: Patients with extraesophageal symptoms had a higher prevalence of positive Peptest. The optimum threshold level of 31.4 ng/mL had high sensitivity and moderate specificity to differentiate between patients with GERD and healthy controls.

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[This corrects the article DOI: 10.1039/D1RA07407E.].

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Background: Hypertension is a major cause of death and disability worldwide. Enhancing health literacy (HL) may help to alleviate the risk of hypertension and its burden. However, evidence on the association between HL and hypertension and potential mechanisms remain to be explored. Objectives: This study examined the association between HL and hypertension; and explored whether body mass index (BMI), body fat percentage (PBF), and visceral fat (VF) were mediators of this association in people who resided in rural and suburban areas in Vietnam. Methods: A cross-sectional survey was conducted from 1st July to 31st December 2019, involving 1655 residents and exploring participants' sociodemographic characteristics, HL, health-related behaviors, comorbidities, body composition, and blood pressure (BP). People with systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg or using antihypertensive medication were classified as having hypertension. Multiple logistic regression and mediation analyses were used to explore associations. Results: The hypertension prevalence was 41.9% (694/1,655). In adjusted models, a higher HL score was associated with a lower hypertension likelihood (OR = 0.96; 95%CI = 0.95-0.97; p < 0.001). Factors associated with a higher odd of hypertension were overweight/obese (OR = 1.69; 95%CI = 1.24-2.29; p = 0.001), high PBF (OR = 2.35; 95%CI = 1.85-2.99; p < 0.001), and high VF (OR = 2.27; 95%CI = 1.63-3.16; p < 0.001). Notably, PBF significantly mediated the association between HL and hypertension (indirect effect, OR = 0.99; 95%CI = 0.98-0.99; p = 0.009; percent mediated = 8.56%). The mediating roles of BMI and VF were not found. Conclusion: The prevalence of hypertension was relatively high. People with better HL were less likely to have hypertension. The association between HL and hypertension was partially explained by PBF. Strategic approaches are required to improve people's HL and body fat which further help to manage hypertension in rural and suburban areas.

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BACKGROUND: Little is known about the trends in colorectal cancer (CRC) in Vietnam. We aimed to investigate the trends in epidemiology and anatomical subsites of CRC in Ho Chi Minh City, Vietnam. METHODS: Based on the Ho Chi Minh City Cancer Registry data during 1996-2015, we calculated the average annual percent changes (AAPCs) of the age-standardized incidence rates (ASRs) by sex, age groups, and anatomical subsites, using joinpoint regressions analysis. We further performed age-period-cohort (APC) analysis using the United States National Cancer Institute's web-based statistical tool to explore the underlying reason for the incidence trend. RESULTS: Over 20 years the overall ASR of CRC increased from 10.5 to 17.9 per 100,000, a 1.7-fold increase. CRC incidence elevated more rapidly in men (AAPC 4.7, 95%CI 2.2-7.3) than in women (AAPC 2.6, 95%CI 0.6-4.8). The highest and lowest increasing rates of ASRs were observed in the 50-64-year-old age group (AAPC 5.3, 95%CI 2.8-7.9) and < 50-year-old age group (AAPC 1.1, 95%CI -0.7 to 2.9), respectively. Regarding subsites, rectal cancer had the highest rate of increase (AAPC 3.3, 95%CI 1.0-5.7). Furthermore, the APC analysis indicated significant increases in CRC incidence in birth cohorts after 1975 in both genders. CONCLUSIONS: The CRC incidence in Ho Chi Minh City increased, with the more prominent rates being among men and older populations, in rectal subsites, and in people born after 1975. The upward trend of CRC incidence in Ho Chi Minh City may be due to the adoption of a westernized lifestyle.

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BACKGROUND: The burden and trend of thyroid cancer in Vietnam have not been well documented. This study aimed to investigate the trends in incidence and histological pattern of thyroid cancer in Ho Chi Minh City from 1996 to 2015. METHODS: A population-based study retrieved data from the Ho Chi Minh City Cancer Registry during 1996-2015. Trends in the incidence of thyroid cancer were investigated based on age, gender, and histology for each 5-year period. Annual percentage change (APC) in incidence rates was estimated using Joinpoint regression analysis. RESULTS: In the study period, there were 5953 thyroid cancer cases (men-to-women ratio 1:4.5) newly diagnosed in Ho Chi Minh City with the mean age of 42.9 years (±14.9 years). The age-standardized incidence rate of thyroid cancer increased from 2.4 per 100,000 during 1996-2000 (95% confidence interval [95% CI]: 2.2-2.6) to 7.5 per 100,000 during 2011-2015 (95% CI: 7.3-7.9), corresponded to an overall APC of 8.7 (95% CI 7.6-9.9). The APC in men and women was 6.2 (95% CI: 4.2-8.2) and 9.2 (95% CI: 8.0-10.4), respectively. The incidence rate in the < 45 years age group was the highest diagnosed overall and increased significantly in both men (APC 11.0) and women (APC 10.1). Both genders shared similar distribution of subtype incidences, with papillary thyroid cancer constituted the most diagnosed (73.3% in men and 85.2% in women). The papillary thyroid cancer observed a markedly increase overall (APC of 10.7 (95% CI 9.3-12.0)). CONCLUSIONS: There were appreciable increases in the age-standardized incidence rate of thyroid cancer in both genders, mainly contributed by the papillary subtype. The age of patients at diagnosis decreased gradually. The widespread utilization of advanced diagnostic techniques and healthcare accessibility improvement might play a potential role in these trends. Further investigations are needed to comprehend the risk factors and trends fully.

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The burden of breast cancer in Vietnam has not been documented. This study sought to estimate the incidence of breast cancer in Ho Chi Minh City, the largest economic center of Vietnam, from 1996 to 2015. This was a population-based study using the Ho Chi Minh City Cancer Registry as a source of data (coverage period: 1996-2015). The Registry adopted the International Classification of Diseases for Oncology, 3rd Edition for the classification of primary sites and morphology, and guidelines from the International Agency for Research on Cancer and the International Association of Cancer Registries. Using the population statistics from census data of Ho Chi Minh City, the point incidence of breast cancer for 5-year period was estimated. Based on the national population, we calculated the age-standardized rate (ASR) of breast cancer between 1996 and 2015. Overall 14,222 new cases of breast cancer (13,948 women, or 98%) had been registered during the 1996-2015 period; among whom, just over half (52%) were in the 2nd stage and 26% in the 3rd and 4th stages. In women, the median age at diagnosis was 50 years and there was a slight increase over time. The ASR of breast cancer during the 2011-2015 period was 107.4 cases per 100,000 women, representing an increase of 70% compared to the rate during the 1996-2000 period. In men, there was also a significant increase in the ASR: from 1.13 during the 1996-2001 period to 2.32 per 100,000 men during the 2011-2015 period. These very first data from Vietnam suggest that although the incidence of breast cancer in Vietnam remains relatively low, it has increased over time.

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BACKGROUND AND AIMS: Although cancer is common in Ho Chi Minh city, Vietnam, the community awareness is still unknown. The primary objective of this study was to examine and compare the knowledge and risk perceptions of cancer possessed by cancer patients - relatives and healthy adults in Ho Chi Minh City, Vietnam. METHODS: A cross-sectional study was conducted from June to August 2019. Cancer patients and their relatives were drawn from those who were hospitalized in the Oncology Hospital, Ho Chi Minh City. Healthy individuals were those without a known diagnosis of cancer, and they were drawn from the participants of the Vietnam Osteoporosis Study. A total of 533 participants including 249 patients and relatives (cancerous group) and 284 healthy individuals (healthy group), were asked to respond to a structured questionnaire that was comprised of items concerning cancer knowledge, risk factor perception, and general attitude towards cancer, using Yes, No, or Likert Scale for response. RESULTS: The findings showed that patients hold poorer knowledge of pathology, signs, symptoms, prevention, and treatment and lower awareness of risk factors but more positive attitude towards cancer as compared to their healthy counterparts. Overall, both groups varied in their cancer knowledge, with many areas remain to be improved. CONCLUSIONS: Knowledge about cancer and its risk factors should be improved among the general population as well as among those with direct experiences with cancer.  Practical implications: The findings provided by this study has major implications for the design of an educational program for cancer patients in clinical settings and awareness programs for the general public as a primary preventive measure for mitigating the cancer burden. Future studies with larger and more diverse samples or qualitative studies exploring the personal narratives of people living with cancer could take advantage from the preliminary data provided by this study. 
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Cobalt doped magnetite nanoparticles (Co x Fe3-x O4 NPs) are investigated extensively because of their potential hyperthermia application. However, the complex interrelation among chemical compositions and particle size means their correlation with the magnetic and heating properties is not trivial to predict. Here, we prepared Co x Fe3-x O4 NPs (0 ≤ x ≤ 1) to investigate the effects of cobalt content and particle size on their magnetic and heating properties. A detailed analysis of the structural features indicated the similarity between the crystallite and particle sizes as well as their non-monotonic change with the increase of Co content. Magnetic measurements for the Co x Fe3-x O4 NPs (0 ≤ x ≤ 1) showed that the blocking temperature, the saturation magnetization, the coercivity, and the anisotropy constant followed a similar trend with a maximum at x = 0.7. Moreover, 57Fe Mössbauer spectroscopy adequately explained the magnetic behaviour, the anisotropy constant, and saturation magnetization of low Co content samples. Finally, our study shows that the relaxation loss is a primary contributor to the SAR in Co x Fe3-x O4 NPs with low Co contents as well as their potential application in magnetic hyperthermia.

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For more than a half-century, lists of words have served as the memoranda of choice in studies of human memory. To better understand why some words and lists are easier to recall than others, we estimated multivariate models of word and list recall. In each of the 23 sessions, subjects (N = 98) studied and recalled the same set of 576 words, presented in 24 study-test lists. Fitting a statistical model to these data revealed positive effects of animacy, contextual diversity, valence, arousal, concreteness, and semantic structure on recall of individual words. We next asked whether a similar approach would allow us to account for list-level variability in recall performance. Here we hypothesized that semantically coherent lists would be most memorable. Consistent with this prediction, we found that semantic similarity, weighted by temporal distance, was a strong positive predictor of list-level recall. Additionally, we found significant effects of average contextual diversity, valence, animacy, and concreteness on list-level recall. Our findings extend previous models of item-level recall and show that aggregate measures of item recallability also account for variability in list-level performance. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

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