Effect of Auxin on Cadmium Toxicity-Induced Growth Inhibition in Solanum lycopersicum.

Auxins play crucial regulatory roles in plants coping with cadmium (Cd) stress. However, the regulatory mechanism by which auxins alleviate Cd toxicity in tomato seedlings remains unclear. Here, we demonstrate that exposure to Cd stress leads to dynamic changes in the auxin response in tomato roots, characterized by an initial increase followed by a subsequent weakening. Under Cd stress, tomato seedlings show primary root- and hypocotyl-growth inhibition, accompanied by the accumulation of Cd and reactive oxygen species (ROS) in the roots. The exogenous application of 1-naphthylacetic acid (NAA) does not mitigate the inhibitory effect of Cd toxicity on primary root growth, but it does significantly enhance lateral root development under Cd stress. Auxin transport inhibitors, such as 1-N-naphthylphthalamic acid (NPA) and 2,3,5-triiodobenoic acid (TIBA), aggravate the growth inhibition of primary roots caused by Cd stress. Additionally, lateral root development was inhibited by NPA. However, applying auxin synthesis inhibitors L-kynurenine (kyn) and yucasin alleviated the tomato root growth inhibition caused by Cd stress; between them, the effect of yucasin was more pronounced. Yucasin mitigates Cd toxicity in tomato seedlings by reducing Cd2+ absorption and auxin accumulation, strengthening ROS scavenging, and reducing cell death in roots. These observations suggest that yucasin potentially mitigates Cd toxicity and improves the tolerance of tomato seedlings to Cd stress.

Multimodal analysis of cfDNA methylomes for early detecting esophageal squamous cell carcinoma and precancerous lesions.

Detecting early-stage esophageal squamous cell carcinoma (ESCC) and precancerous lesions is critical for improving survival. Here, we conduct whole-genome bisulfite sequencing (WGBS) on 460 cfDNA samples from patients with non-metastatic ESCC or precancerous lesions and matched healthy controls. We develop an expanded multimodal analysis (EMMA) framework to simultaneously identify cfDNA methylation, copy number variants (CNVs), and fragmentation markers in cfDNA WGBS data. cfDNA methylation markers are the earliest and most sensitive, detectable in 70% of ESCCs and 50% of precancerous lesions, and associated with molecular subtypes and tumor microenvironments. CNVs and fragmentation features show high specificity but are linked to late-stage disease. EMMA significantly improves detection rates, increasing AUCs from 0.90 to 0.99, and detects 87% of ESCCs and 62% of precancerous lesions with >95% specificity in validation cohorts. Our findings demonstrate the potential of multimodal analysis of cfDNA methylome for early detection and monitoring of molecular characteristics in ESCC.

Food insecurity and mental health among US adults during the COVID-19 pandemic: Results from National Health Interview Survey, 2020-2021.

OBJECTIVE: To examine socio-demographic disparities in food insecurity during the COVID-19 pandemic and the association between food insecurity and mental health among US adults overall and communities vulnerable to food insecurity. METHODS: A cross-sectional study was conducted using the 2020-2021 National Health Interview Survey of 57,456 US adults. Weighted multivariable logistic regression models were used to estimate the association between food insecurity and anxiety or depression symptoms in overall US adults and subgroups including young adults (18-34 years), females, Hispanic people, non-Hispanic Black people, individuals with prior COVID-19 infection, the unemployed, low-income participants, participants with children, and Supplemental Nutrition Assistance Program (SNAP) participants. RESULTS: Young or middle age, female sex, Hispanic/non-Hispanic Black/other race/ethnicity, lower education level, unmarried/other marital status, unemployment, being below the federal poverty level, and greater number of persons in the household were associated with food insecurity (AOR ranged from 1.35 to 2.70, all p < 0.05). Food insecurity was independently associated with anxiety (AOR = 2.67, 99 % CI: 2.33, 3.06) or depression (AOR = 3.04, 99 % CI: 2.60, 3.55) symptoms in the overall adults. Significant associations between food insecurity and anxiety or depression symptoms were also observed in all subgroups (AOR ranged from 1.95 to 3.28, all p < 0.0001). Compared with overall adults, the magnitude of the association was greater for participants with children, females (for depression only), and non-Hispanic Black people (for depression only). LIMITATIONS: The cross-sectional design prevents inference of causality. CONCLUSIONS: Comprehensive policies are needed to ensure accessible and affordable food resources to reduce disparities in food insecurity and improve mental health, especially for those socioeconomically disadvantaged communities.

E-cigarette use or dual use of E-cigarette and combustible cigarette and mental health and cognitive impairment: Findings from the National Health Interview Survey, 2020-2021.

BACKGROUND: Studies on the association between e-cigarette use and mental health are mostly among adolescents and young adults, leaving limited evidence of this association among general US adults. Besides, few studies have examined how e-cigarette use or dual use of e-cigarette and combustible cigarette is related to cognitive function. METHODS: Cross-sectional data of 56,734 adults from the 2020-2021 National Health Interview Survey were analyzed. Weighted multivariable logistic regression models were applied to examine the independent association between e-cigarette use or dual use and anxiety symptoms, depression symptoms, serious psychological distress (SPD), and cognitive impairment. RESULTS: Compared with never e-cigarette users, current e-cigarette users had 2.10-fold (95 % CI: 1.84, 2.39), 2.53-fold (95 % CI: 2.13, 3.00), 2.02-fold (95 % CI: 1.47, 2.76), and 2.00-fold (95 % CI: 1.47, 2.72) higher odds of reporting anxiety symptoms, depression symptoms, SPD, and cognitive impairment, respectively. Former e-cigarette use was also associated with all three mental conditions and cognitive impairment (AOR ranged from 1.38 to 2.53, all P < 0.01). Dual users were more likely to report all three mental conditions and cognitive impairment than those who never used combustible cigarette and e-cigarette (AOR ranged from 1.89 to 2.83, all P < 0.01). Dual users also had a greater likelihood of having anxiety or depression symptoms than exclusive combustible cigarette users (AOR ranged from 1.46 to 1.47, all P < 0.01). CONCLUSIONS: E-cigarette use or dual use is associated with poor mental health and cognitive impairment among US adults. Regulations on e-cigarette use are needed to prevent mental illness and improve cognitive function.

Multilayer nanodrug delivery system with spatiotemporal drug release improves tumor microenvironment for synergistic anticancer therapy.

The inflammatory response is one of the general symptoms that accompany tumorigenesis, the pro-inflammatory factors cyclooxygenase-2 (COX-2) and COX-2-derived prostaglandin-2 (PGE-2) in the inflammatory environment surrounding tumors possess promoting tumor development, metastasis and angiogenesis effects. In addition, the hypoxic environment of tumors severely limits the effectiveness of photodynamic therapy (PDT). In this study, a universal extracellular-intracellular 'on-demand' release nanomedicine DOX@PDA-ICG@MnO2@GN-CEL was developed for the combined fight against malignant tumors using a spatiotemporal controlled gelatin coated polydopamine (PDA@GN) as the carrier and loaded with the chemotherapeutic drug doxorubicin (DOX), the photosensitizer indocyanine green (ICG), the PDT enhancer MnO2and the anti-inflammatory drug celecoxib (CEL) individually. Our results showed that DOX@PDA-ICG@MnO2@GN-CEL could release CEL extracellularly by matrix metalloproteinase-2 response and inhibit the COX-2/PGE-2 pathway, reduce chemotherapy resistance and attenuate the concurrent inflammation. After entering the tumor cells, the remaining DOX@PDA-ICG@MnO2released DOX, ICG and MnO2intracellularly through PDA acid response. MnO2promoted the degradation of endogenous H2O2to generate oxygen under acidic conditions to alleviate the tumor hypoxic environment, enhance PDT triggered by ICG. PDA and ICG exhibited photothermal therapy synergistically, and DOX exerted chemotherapy with reduced chemotherapy resistance. The dual responsive drug release switch enabled the chemotherapeutic, photothermal, photodynamic and anti-inflammatory drugs precisely acted on different sites of tumor tissues and realized a promising multimodal combination therapy.

Genetic architecture of hippocampus subfields volumes in Alzheimer's disease.

BACKGROUND: The hippocampus is a heterogeneous structure, comprising histologically and functionally distinguishable hippocampal subfields. The volume reductions in hippocampal subfields have been demonstrated to be linked with Alzheimer's disease (AD). The aim of our study is to investigate the hippocampal subfields' genetic architecture based on the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set. METHODS: After preprocessing the downloaded genetic variants and imaging data from the ADNI database, a co-sparse reduced rank regression model was applied to analyze the genetic architecture of hippocampal subfields volumes. Homology modeling, docking, molecular dynamics simulations, and Co-IP experiments for protein-protein interactions were used to verify the function of target protein on hippocampal subfields successively. After that, the association analysis between the candidated genes on the hippocampal subfields volume and clinical scales were performed. RESULTS: The results of the association analysis revealed five unique genetic variants (e.g., ubiquitin-specific protease 10 [USP10]) changed in nine hippocampal subfields (e.g., the granule cell and molecular layer of the dentate gyrus [GC-ML-DG]). Among five genetic variants, USP10 had the strongest interaction effect with BACE1, which affected hippocampal subfields verified by MD and Co-IP experiments. The results of association analysis between the candidated genes on the hippocampal subfields volume and clinical scales showed that candidated genes influenced the volume and function of hippocampal subfields. CONCLUSIONS: Current evidence suggests that hippocampal subfields have partly distinct genetic architecture and may improve the sensitivity of the detection of AD.

Androgen Receptor/AP-1 Activates UGT2B15 Transcription to Promote Esophageal Squamous Cell Carcinoma Invasion.

Esophageal squamous cell carcinoma (ESCC) is an aggressive epithelial malignancy with poor prognosis. Interestingly, ESCC is strongly characterized by a male-predominant propensity. Our previous study showed that androgen receptor (AR) orchestrated a transcriptional repression program to promote ESCC growth, but it remains unclear whether AR can also activate oncogenic signaling during ESCC progression. In this study, by analyzing our previous AR cistromes and androgen-regulated transcriptomes, we identified uridine diphosphate glucuronosyltransferase family 2 member B15 (UGT2B15) as a bona fide target gene of AR. Mechanistically, AP-1 cofactors played important and collaborative roles in AR-mediated UGT2B15 upregulation. Functional studies have revealed that UGT2B15 promoted invasiveness in vitro and lymph node metastasis in vivo. UGT2B15 was partially responsible for the AR-induced invasive phenotype in ESCC cells. Importantly, simultaneous blocking of AP-1 and AR resulted in stronger inhibition of cell invasiveness compared to inhibiting AP-1 or AR alone. In conclusion, our study reveals the molecular mechanisms underlying the AR-driven ESCC invasion and suggests that the AR/AP1/UGT2B15 transcriptional axis can be potentially targeted in suppressing metastasis in male ESCC patients.

Protein modified cellulose nanocrystals on reinforcement and self-driven biodegradation of aliphatic polyester.

Due to the highly environment-dependent biodegradation and uncontrolled degradation period, the long-run feasibility and effectiveness of biodegradable polymers are extensively questioned to solve plastics waste accumulation and pollution problems. This work physically incorporated lipase PS from Burkholderia cepacian on cellulose nanocrystals (CNC) and embedded it in polycaprolactone (PCL) to construct stable and controllable interfacial microenvironment between CNC and PCL for the reinforcement and controllable self-driven biodegradation. The physical adsorption of lipase PS on CNC was studied by monitoring the surface charge and particle size. FT-IR spectra confirmed the successful incorporation of lipase PS and CNC. Compared with CNC, protein-modified CNC had a higher maximum thermal decomposition temperature of 345 °C and lower interfacial tension of 11 mN/m with PCL which provided PCL composites with higher nucleation efficiency and tensile elongation of 1086 % at break. In addition, only 0.67 % embedded lipase PS completely hydrolyzed PCL membranes in <140 h. The post-compression molding at 80-100 °C had negligible influence on the lipase activity, which indicated that CNC could protect the lipase from inactivation in polymer extrusion and compression. This work also highlighted protein-modified CNC as a new technology for polymer reinforcement.

The association between e-cigarette use or dual use of e-cigarette and combustible cigarette and prediabetes, diabetes, or insulin resistance: Findings from the National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: Studies have established associations between combustible cigarette use and diabetes. However, there is limited evidence on the association between e-cigarette use or dual use of e-cigarettes and combustible cigarettes and diabetes. METHOD: With cross-sectional data of 5101 U.S. adults from the National Health and Nutrition Examination Survey, this study examined how e-cigarette use or dual use was related to diabetes, prediabetes, or insulin resistance. The presence of diabetes or prediabetes was determined by fasting glucose level, hemoglobin A1C (HbA1c), or the use of prescribed medications. Insulin resistance was assessed by the homeostatic model (HOMA-IR). The independent association between e-cigarette use or dual use and outcomes was examined using weighted multivariable logistic regression models controlling for potential confounders. RESULTS: Of all participants, 6.3% were current e-cigarette users and 17.1% were former e-cigarette users. In the fully adjusted model, e-cigarette use was not associated with prediabetes or diabetes (P>0.05). However, former e-cigarette users were 22% (95% CI: 1.00, 1.84) more likely to report higher HOMA-IR (Q3 vs Q1) than never e-cigarette users. Among ever combustible cigarette users, current e-cigarette users and former e-cigarette users were 63% (95% CI: 1.00, 2.91) and 64% (95% CI: 1.04, 2.59) more likely to report higher HOMA-IR than never e-cigarette users, respectively. There was no significant association between dual use and diabetes, prediabetes, or insulin resistance (P>0.05). CONCLUSIONS: E-cigarette use may be associated with insulin resistance. Our findings may inform future tobacco control policies and longitudinal studies assessing insulin resistance associated with e-cigarette use.

Trends in unmet health care needs among adults in the U.S., 2019-2021.

To examine recent trends in unmet health care needs among US adults, cross-sectional data of 93,047 adults from 2019 to 2021 National Health Interview Survey were analyzed. The weighted prevalence and changes in prevalence of cost-related or COVID-19-related unmet health care needs were estimated, first overall and then stratified by socio-demographic characteristics. The prevalence of cost-related unmet health care needs was 8.3% (95% CI: 7.8%, 8.8%) in 2019, which significantly decreased to 6.6% (95% CI: 6.2%, 7.0%) in 2020 and 6.1% (95% CI: 5.7%, 6.4%) in 2021. Across most socio-demographic groups, the prevalence of cost-related unmet health care needs significantly decreased between 2019 and 2020 (absolute changes ranged from -7.4% to -1%) and between 2019 and 2021 (absolute changes ranged from -10.5% to -1.2%), with significant reductions among uninsured adults, adults below the federal poverty level, and Hispanics. The prevalence of COVID-19-related unmet health care needs was 15.7% (95% CI: 14.9%, 16.4%) in 2020, which decreased to 11.9% (95% CI: 11.5%, 12.4%) in 2021. The prevalence of COVID-19-related unmet health care needs significantly decreased across most socio-demographic groups between 2020 and 2021 (absolute changes ranged from -4.9% to -2.4%), with significant reductions among the older, the unemployed, non-Hispanic Black adults, and adults with education level ≥ college. Overall, a modest decrease in the prevalence of both cost-related and COVID-19-related unmet health care needs was observed between 2019 and 2021. However, the fact that over 10% of US adults had unmet health care needs because of the COVID-19 pandemic is still concerning, warranting continued surveillance.

Parsimonious clinical prediction model for the diagnosis of complicated appendicitis.

Objective: To develop a logistic regression model that combines clinical and radiological parameters for prediction of complicated appendicitis. Methods: 248 patients with histologically proven uncomplicated (n = 214) and complicated (n = 34) acute appendicitis were analyzed retrospectively. All patients had undergone a presurgical abdominal and/or pelvic computed tomography (CT) scan, assessed by two radiologists. A model using univariate and multivariate logistic regression analyses was developed, and the strength of association between independent predictors and complicated acute appendicitis was evaluated by adjusted odds radio. Clinical parameters were gender, age, anorexia, vomiting, duration of symptoms, right lower abdominal quadrant (RLQ) tenderness, rebound tenderness, body temperature, white blood cell (WBC) count, and neutrophil ratio. Radiological parameters were appendix diameter, appendicolith, caecal wall thickening, mesenteric lymphadenopathy, extraluminal air, abscess, fat stranding, and periappendicular fluid. Results: Four features (body temperature＞37.2 °C, vomiting, appendicolith, and periappendiceal fluid) were included in the logistic regression model, and yielded an area under the curve (AUC) of 0.87 (95% confidence interval (CI), 0.80-0.93), sensitive of 88%, and specificity of 74%. Conclusion: The logistic regression model makes an accurate and simple prediction of complicated appendicitis possible.

N-substituting perturbation on the interaction affinity and recognition specificity between rheumatic immune-related Abl SH3 domain and its peptoid ligands.

Abl is a nonreceptor tyrosine kinase involved in a variety of disease pathways such as rheumatic immune. Full-length Abl protein consists of a catalytic tyrosine kinase (TK) domain as well as two regulatory Src homology domains 2 and 3 (SH2 and SH3, respectively); the latter recognizes and binds to those natural proline-rich peptide segments containing a PxxP motif on the protein surface of its interacting partners. However, natural peptides cannot bind effectively to the modular domain in high affinity and strong selectivity due to their small size and broad specificity. Here, a synthetic proline-rich peptide p41 was used as template; its structural diversity was extended by combinationally replacing the Pro0 and Pro+3 residues with a number of N-substituted amino acids. Consequently, peptide affinity change upon the replacement was derived to create a systematic N-substituting perturbation profile, from which we identified several N-substitution combinations at the Pro0 and Pro+3 residues of p41 PxxP motif that may moderately or significantly improve the peptide binding potency to Abl; they represent potent peptoid binders of Abl SH3 domain, with affinity improved considerably relative to p41. More significantly, the designed potent peptoids were also found to exhibit a good SH3-selectivity for their cognate Abl over other noncognate nonreceptor tyrosine kinases, with S = 9.7-fold.

Ultrasensitive electrochemical biosensor for detection of circulating tumor cells based on a highly efficient enzymatic cascade reaction.

There has been great interest in the enzymatic cascade amplification strategy for the electrochemical detection of circulating tumor cells (CTCs). In this work, we designed a highly efficient enzymatic cascade reaction based on a multiwalled carbon nanotubes-chitosan (MWCNTs-CS) composite for detection of CTCs. A high electrochemical effective surface area was obtained for a MWCNTs-CS-modified glassy carbon electrode (GCE) for loading glucose oxidase (GOD), as well as a high loading rate and high electrical activity of the enzyme. As a 'power source', the MWCNTs-CS composites provided a strong driving power for horseradish peroxidase (HRP) on the surface of polystyrene (PS) microspheres, which acted as probes for capturing CTCs and allowed the reaction to proceed with further facilitation of electron transfer. Aptamer, CTCs, and PS microspheres with HRP and anti-epithelial cell adhesion molecule (anti-EpCAM) antibody were assembled on the MWCNTs-CS/GCE to allow for the modulation of enzyme distance at the micrometer level, and thus ultra-long-range signal transmission was made possible. An ultrasensitive response to CTCs was obtained via this proposed sensing strategy, with a linear range from 10 cell mL-1 to 6 × 106 cell mL-1 and a detection limit of 3 cell mL-1. Moreover, this electrochemical sensor possessed the capability to detect CTCs in serum samples with satisfactory accuracy, which indicated great potential for early diagnosis and clinical analysis of cancer.

Associations between e-cigarette use or dual use of e-cigarette and combustible cigarette and metabolic syndrome: results from the National Health and Nutrition Examination Survey (NHANES).

PURPOSE: Examine associations between e-cigarette use or dual use of e-cigarette and combustible cigarette and metabolic syndrome (MetS). METHODS: Cross-sectional data of 5121 U.S. adults from the National Health and Nutrition Examination Survey were analyzed. Weighted multivariable Poisson regression models were used to examine associations between e-cigarette use or dual use and MetS and its components. Prevalence ratios (PRs) with 95% confidence intervals (95% CI) were estimated. RESULTS: Current and former e-cigarette users were 30% (95% CI: 1.13, 1.50) and 15% (95% CI: 1.03, 1.28) more likely to have MetS than never e-cigarette users. Current or former e-cigarette use was also associated with elevated triglycerides, reduced high-density lipoprotein (HDL) cholesterol, and elevated blood pressure (AOR ranged from 1.15 to 1.42, all P < 0.05). The prevalence of MetS for dual users was 1.35-fold (95% CI: 1.15, 1.58) higher than that for never smokers and 1.21-fold (95% CI: 1.00, 1.46) higher than that for combustible cigarette-only users. Dual users were also more likely to report elevated triglycerides and reduced HDL cholesterol than never smokers or combustible cigarette-only users (all P < 0.05). CONCLUSIONS: E-cigarette use or dual use is associated with MetS. Our findings may inform tobacco control policies regarding regulations of e-cigarette use.

Sarcopenia is an independent risk factor for all-cause mortality rate in patients with diabetic foot ulcers.

Objective: This study aimed to determine whether sarcopenia affects the all-cause mortality rate of patients with diabetic foot ulcers (DFUs). Research design and methods: The clinic-based observational study included 217 patients treated at the Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University during a 4-year period. All subjects underwent dual-energy X-ray absorptiometry to determine their body composition during hospitalization. Diagnosis of sarcopenia was based on the Baumgartner diagnostic criteria. Patients were followed up regularly by phone calls until April 1, 2019, and their survival status was recorded.Univariate and multivariate Cox risk ratio regression models were used to analyze factors influencing the all-cause mortality rate of patients with DFUs. Results: Of the 217 patients, 158 people survived (82.7%), 33 died (17.3%), and 26 were lost to follow-up. The median follow-up time was 23 (Range 11-34) months. The majority of patients were male (68.6%), with a mean age of 67.29 ± 11.14 years. The 5-year survival rate was 68.3% and 45.9% for all study patients (n = 217) and sarcopenia patients (n = 81), respectively. Multivariate Cox risk regression model showed that age (HR 1.042[95%CI:1.006, 1.078], P = 0.021), sarcopenia (HR 5.051[95%CI:1.968, 12.961], P = 0.001), and serum creatinine (HR 1.007[95%CI: 1.003, 1.010], P < 0.001) were independent risk factors for all-cause mortality rate of patients with DFUs. Kaplan-Meier survival curve indicated that the survival rate of patients with sarcopenia was significantly lower than non-sarcopenia patients (P < 0.001). Conclusions: Sarcopenia is an independent risk factor for all-cause mortality of patients with DFUs and hence an important prognostic factor for patients with DFUs. Active prevention and improvement of sarcopenia can potentially improve the survival outcomes of this patient population.

Food Insecurity and COVID-19 Infection: Findings From the 2020-2021 National Health Interview Survey.

Introduction: The purpose of this study was to examine the sociodemographic and health-related factors associated with food insecurity and the association between food insecurity and COVID-19 infection using a nationally representative sample in the U.S. Methods: Cross-sectional data of 61,050 adults (aged ≥18 years) from the 2020 and 2021 National Health Interview Survey were analyzed. Food insecurity was measured by the 10-item U.S. Department of Agriculture Food Security Survey Module. Weighted multivariable logistic regression models were used to estimate associations with food insecurity. Results: A total of 6.8% of the National Health Interview Survey participants lived in food-insecure households, and 18.9% tested positive for COVID-19 infection. Young (aged 18-34 years) or middle (aged 35-64 years) age, female sex, minor race/ethnicity (Hispanic/non-Hispanic Black/non-Hispanic Asian/others), education level less than high school, unmarried status, unemployment, poverty (below the federal poverty level), having no health insurance, a larger number of adults and children in the household, poorer self-reported health status, and the presence of chronic conditions were significantly associated with food insecurity (AOR ranged from 1.20 to 3.15, all p<0.0001). Food insecurity was independently associated with positive COVID-19 infection (AOR=1.25, 95% CI=1.11, 1.40), controlling for sociodemographic and health-related factors. The greatest magnitude of the association was observed for the non-Hispanic Black participants (AOR=1.47, 95% CI=1.15, 1.88), female participants (AOR=1.44, 95% CI=1.20, 1.71), and those below the federal poverty level (AOR=1.39, 95% CI=1.12, 1.73) across all the subgroups. Conclusions: Food insecurity disproportionately affected vulnerable subgroups such as young adults, female individuals, minority race/ethnicity groups, and those with lower socioeconomic status, and was associated with positive COVID-19 infection. Policies addressing food insecurity may help to reduce the likelihood of COVID-19 infection, especially for those vulnerable subgroups.

The association between genetic variations and morphology-based brain networks changes in Alzheimer's disease.

Alzheimer's disease (AD) is a highly heritable disease. The morphological changes of cortical cortex (such as, cortical thickness and surface area) in AD always accompany by the change of the functional connectivity to other brain regions and influence the short- and long-range brain network connections, causing functional deficits of AD. In this study, the first hypothesis is that genetic variations might affect morphology-based brain networks, leading to functional deficits; the second hypothesis is that protein-protein interaction (PPI) between the candidate proteins and known interacting proteins to AD might exist and influence AD. 600 470 variants and structural magnetic resonance imaging scans from 175 AD patients and 214 healthy controls were obtained from the Alzheimer's Disease Neuroimaging Initiative-1 database. A co-sparse reduced-rank regression model was fit to study the relationship between non-synonymous mutations and morphology-based brain networks. After that, PPIs between selected genes and BACE1, an enzyme that was known to be related to AD, are explored by using molecular dynamics (MD) simulation and co-immunoprecipitation (Co-IP) experiments. Eight genes affecting morphology-based brain networks were identified. The results of MD simulation showed that the PPI between TGM4 and BACE1 was the strongest among them and its interaction was verified by Co-IP. Hence, gene variations influence morphology-based brain networks in AD, leading to functional deficits. This finding, validated by MD simulation and Co-IP, suggests that the effect is robust.

The association between food insecurity and cognitive impairment among the US adults: The mediation role of anxiety or depression.

BACKGROUND: Using a nationally representative sample, this study aimed to examine (1) socio-demographic and health-related disparities in cognitive impairment, (2) the association between food insecurity and cognitive impairment, and (3) the mediation role of anxiety or depression in the pathway between food insecurity and cognitive impairment. METHODS: Cross-sectional data of 28,508 adults from the 2020 National Health Interview Survey were analyzed. Multivariable logistic regression models were used to estimate associations with cognitive impairment. Mediation analyses were conducted using the four-way decomposition method under a counterfactual framework. RESULTS: Disparities in cognitive impairment were observed across socio-demographic and health-related characteristics (all p < 0.0001). Food insecurity was significantly associated with cognitive impairment in the overall population and the magnitude of the association was greater for the young or middle-aged, females and non-Hispanic Blacks than the general population (AOR ranged from 1.19 to 2.54, all p < 0.01). With anxiety as a mediator, 28.66 % of the total effect of food insecurity on cognitive impairment was attributable to mediation only, and 22.39 % was attributable to interaction (between food insecurity and anxiety) and mediation. With depression as a mediator, 22.33 % of the total effect was attributable to mediation only, and 16.00 % was attributable to interaction (between food insecurity and depression) and mediation. LIMITATIONS: The cross-sectional design prevents inference of causality. CONCLUSIONS: Ensuring available and adequate food resources is important to prevent adverse cognitive outcomes. Clinical interventions or treatments for anxiety or depression may help improve cognitive function.

The association between chronic conditions, COVID-19 infection, and food insecurity among the older US adults: findings from the 2020-2021 National Health Interview Survey.

BACKGROUND: This study aims to examine how the presence of chronic conditions or positive COVID-19 infection (as exposures) is related to food insecurity (as an outcome) in the older population and whether there is a dose-response relationship between the number of chronic conditions and the severity of food insecurity. METHODS: Cross-sectional data of 17,977 older adults (≥ 65 years) from the 2020-2021 National Health Interview Survey were analyzed. Chronic conditions included physical health conditions (i.e., arthritis, coronary heart diseases, hypertension, stroke, prediabetes, diabetes, asthma, chronic obstructive pulmonary disease, and disability) and mental health conditions (i.e., anxiety and depression disorder). COVID-19 infection status was determined by a self-reported diagnosis of COVID-19. Household food insecurity was measured using the 10-item US Department of Agriculture (USDA) Food Security Survey Module with a 30-day look-back window. Multinomial logistic regression models were used to examine the association between health conditions and food insecurity controlling for socio-demographic factors. RESULTS: Our results indicated that 4.0% of the older adults lived in food-insecure households. The presence of chronic conditions was significantly associated with higher odds of being food insecure independent of socio-demographic factors (AOR ranged from 1.17 to 3.58, all p < 0.0001). Compared with participants with 0-1 chronic condition, the odds of being (low or very low) food insecure was 1.09 to 4.07 times higher for those with 2, or ≥ 3 chronic conditions (all p < 0.0001). The severity of food insecurity significantly increased as the number of chronic conditions increased (p for trend < 0.0001). Besides, COVID-infected participants were 82% more likely to be very low food secure than the non-infected participants (AOR = 1.82, 95% CI: 1.80, 1.84). CONCLUSIONS: The presence of chronic conditions or positive COVID-infection is independently associated with household food insecurity. Clinical health professionals may help identify and assist individuals at risk of food insecurity. Management and improvement of health conditions may help reduce the prevalence and severity of food insecurity in the older population.

The value of chest computed tomography in evaluating lung cancer in a lobe affected by stable pulmonary tuberculosis in middle-aged and elderly patients: A preliminary study.

Introduction: Lung cancer can be masked by coexisting stable tuberculosis lesions, which may result in delayed lung cancer diagnosis and treatment. Information about pulmonary tuberculosis patients who are at high-risk of developing lung cancer is scarce. We aimed to examine the value of chest computed tomography (CT) in evaluating lung cancer in a lobe affected by stable pulmonary tuberculosis in middle-aged and elderly patients. Methods: In this single-centered, retrospective, observational study, we enrolled 41 middle-aged and elderly patients with pulmonary tuberculosis who developed lung cancer in the same lobe from January 30, 2011 to December 30, 2020. Comparisons of the clinical and chest CT data were made with age-matched and sex-matched control groups of patients with stable pulmonary tuberculosis but no lung cancer diagnosis (n = 38). Results: Seventeen patients in the lung cancer group (41%) were initially misdiagnosed. Compared to lesions in the control group, lesions in the lung cancer group were significantly more likely to demonstrate the following CT features: large size, vessel convergence, lobulation, spiculation, spinous protuberance, bronchial obstruction or stenosis, vacuolation, ground-glass opacification, heterogeneous or homogeneous enhancement, and gradual increase in size. Nodular enlargement showed the best diagnostic performance in the diagnosis of lung cancer in a lobe affected by tuberculosis (area under the receiver operating characteristic curve = 0.974; P <0.001; accuracy = 98.2%; sensitivity =94.7%; specificity = 100%). Conclusion: Chest CT might play an important role in early diagnosis of lung cancer in a lobe affected by tuberculosis. Regular CT re-examination is necessary in continuous controls monitoring of patients with stable pulmonary tuberculosis. The study indicates necessity of prospective study in this field.