Testing for Measurement Invariance (MI): Do the Structures of Microaggression, Discrimination, and Resilience Among Black Women Living with HIV Remain the Same Across Time?

Assessing measurement invariance and the interplay of discrimination, microaggressions, and resilience among Black women living with HIV (BWLWH) across time utilizing latent class and repeated measure analysis may provide novel insights. A total of 151 BWLWH in a southeastern U.S. city completed surveys focused on multiple forms of microaggressions and discrimination (race, gender, sexual orientation, or HIV-related) and resilience factors (social support, self-efficacy, post-traumatic growth) at baseline, 3 months, and 6 months. To capture the psychosocial domains of discrimination, microaggressions, and resilience, three latent factors were developed and measured across three time points. Latent class analysis was also conducted to identify and compare meaningful subgroups based on varying levels of discrimination, microaggressions, and resilience reported. Three latent classes were created. MI testing suggested that measurement invariance was partially met (established metric invariance and scalar invariance), and it is possible to compare factor means of discrimination, microaggressions, and resilience across time. Latent factor mean scores of microaggressions and discrimination decreased after 3 and 6 months and increased for resilience after 6 months and varied over time across the three latent classes identified. The subgroup with the lowest level of discrimination and microaggressions and the highest level of resilience reported at baseline, experienced increases in resilience after months 3 and 6. Clinical interventions, research, and policies aimed at promoting resilience and reducing structural and social barriers linked to racism, sexism, HIV stigma, and classism are needed to improve the health and well-being of BWLWH.

Preventing Cognitive Decline in Older Latino Adults With HIV Through a Culturally Tailored Health Promotion Intervention: Protocol for a Single-Arm Pilot Trial.

BACKGROUND: Older Latino adults with HIV are at increased risk for mild cognitive impairment and earlier onset of aging-related cognitive decline. Improvements in cognitive functioning and cognitive outcomes are possible among people with HIV who adopt health promotion behaviors. However, health promotion interventions for older Latino adults with HIV have not been extensively used or widely recognized as viable treatment options. Happy Older Latinos are Active (HOLA) is a multicomponent, health promotion intervention that is uniquely tailored for older Latino adults with HIV. OBJECTIVE: This study aims to (1) determine the feasibility and acceptability of an adapted version of HOLA aimed at improving cognitive functioning among older Latino adults with HIV; (2) explore whether HOLA will produce changes in cognitive functioning; (3) explore whether HOLA will produce changes in activity, psychosocial functioning, or biomarkers of cognition; and (4) explore whether changes in activity, psychosocial functioning or cognitive biomarkers correlate with changes in cognition, while accounting for genetic risk for dementia. METHODS: A single-arm pilot trial with 30 Latino (aged 50 years and older) men and women with HIV was conducted to assess feasibility, acceptability, and preliminary effects on cognition. Participants were assessed at 2 time points (baseline and postintervention) on measures of neurocognitive and psychosocial functioning. In addition, blood samples were collected to determine biomarkers of cognition at baseline and postintervention. Successful recruitment was defined as meeting 100% of the targeted sample (N=30), with 20% (n=6) or less of eligible participants refusing to participate. Adequate retention was defined as 85% (n=25) or more of participants completing the postintervention assessment and acceptability was defined as 80% (n=38) or more of sessions attended by participants. RESULTS: Participant recruitment began on February 22, 2022, and was completed on August 15, 2022. The last study visit took place on February 20, 2023. Data analysis is currently ongoing. CONCLUSIONS: Encouraging findings from this exploratory study may provide a blueprint for scaling up the HOLA intervention to a larger cohort of older Latino adults with HIV who may be currently experiencing or are at risk for HIV-related cognitive challenges. TRIAL REGISTRATION: ClinicalTrials.gov NCT04791709; https://clinicaltrials.gov/study/NCT04791709. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55507.

TetR family regulator AbrT controls lincomycin production and morphological development in Streptomyces lincolnensis.

BACKGROUND: The TetR family of transcriptional regulators (TFRs), serving as crucial regulators of diverse cellular processes, undergo conformational changes induced by small-molecule ligands, which either inhibit or activate them to modulate target gene expression. Some ligands of TFRs in actinomycetes and their regulatory effects have been identified and studied; however, regulatory mechanisms of the TetR family in the lincomycin-producing Streptomyces lincolnensis remain poorly understood. RESULTS: In this study, we found that AbrT (SLCG_1979), a TetR family regulator, plays a pivotal role in regulating lincomycin production and morphological development in S. lincolnensis. Deletion of abrT gene resulted in increased lincomycin A (Lin-A) production, but delayed mycelium formation and sporulation on solid media. AbrT directly or indirectly repressed the expression of lincomycin biosynthetic (lin) cluster genes and activated that of the morphological developmental genes amfC, whiB, and ftsZ. We demonstrated that AbrT bound to two motifs (5'-CGCGTACTCGTA-3' and 5'-CGTACGATAGCT-3') present in the bidirectional promoter between abrT and SLCG_1980 genes. This consequently repressed abrT itself and its adjacent gene SLCG_1980 that encodes an arabinose efflux permease. D-arabinose, not naturally occurring as L-arabinose, was identified as the effector molecule of AbrT, reducing its binding affinity to abrT-SLCG_1980 intergenic region. Furthermore, based on functional analysis of the AbrT homologue in Saccharopolyspora erythraea, we inferred that the TetR family regulator AbrT may play an important role in regulating secondary metabolism in actinomycetes. CONCLUSIONS: AbrT functions as a regulator for governing lincomycin production and morphological development of S. lincolnensis. Our findings demonstrated that D-arabinose acts as a ligand of AbrT to mediate the regulation of lincomycin biosynthesis in S. lincolnensis. Our findings provide novel insights into ligand-mediated regulation in antibiotic biosynthesis.

Diagnostic Significance of Serum Long Noncoding HOX Antisense Intergenic Ribonucleic Acid in Patients with Hepatitis B Virus Related Hepatocellular Carcinoma.

BACKGROUND/AIMS:  Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and the third leading cause of cancer-related mortality. Extensive literature suggests that long noncoding RNAs play a role in the progression of HCC and hold potential as diagnostic biomarkers for this disease. MATERIALS AND METHODS:  We examined the serum levels of HOX antisense intergenic RNA (HOTAIR) in 49 hepatitis patients, 31 liver cirrhosis (LC), and 37 HCC patients using quantitative real-time polymerase chain reaction. Correlations between serum HOTAIR levels and clinical data were evaluated in HCC patients. The receiver operating characteristic curve was utilized to analyze the diagnostic potency of HOTAIR. RESULTS:  The HOTAIR levels in serum were significantly higher in HCC patients compared to those with hepatitis (P = .003) and LC patients (P = .048). There was a significant association between the serum levels of HOTAIR and positivity of hepatitis B e antigen (HBeAg) (P = .039) as well as portal vein tumor thrombus (P = .040) in HCC patients. The area under the curve (AUC) for HOTAIR for distinguishing HCC from hepatitis and LC was 0.697. The combined AUC for HOTAIR, HBeAg, and alpha-fetoprotein (AFP) was 0.777. CONCLUSION:  Serum HOTAIR functions as a potential diagnostic marker for hepatitis B virus-related HCC. Combining HOTAIR with clinical data and AFP can reinforce the diagnostic precision on HCC.

Adverse Birth Outcomes and Maternal Morbidity Among Afro-Latinas and Their Infants: A Systematic Literature Review.

OBJECTIVES: To evaluate and synthesize research findings on adverse birth outcomes and maternal morbidity among Afro-Latinas and their infants. METHODS: A systematic review was conducted within PubMed, Web of Science, and SCOPUS databases. Four thousand five hundred twenty-six published peer-reviewed articles from 1970 to 2023 that reported outcomes related to maternal morbidity and/or birth outcomes were screened. After screening, we assessed 22 for eligibility, and ultimately, seven studies were included for data extraction and analysis. RESULTS: Although limited, the existing studies revealed disparities in abnormal birth weight (LBW & SGA) and higher preterm birth prevalence among Afro-Latinas compared to other racial and ethnic peers. These disparities are also prevalent among U.S.-born Afro-Latinas compared to foreign-born Afro-Latinas. CONCLUSIONS: By critically examining the current empirical evidence, we can gain a deeper understanding of how intersectionality impacts perinatal health outcomes among Afro-Latinas. Understanding the root causes of these outcomes through increased research is critical to preventing and reducing poor maternal and child health among Afro-Latinas, particularly those who are U.S.-born.

The challenge and opportunity of gut microbiota-targeted nanomedicine for colorectal cancer therapy.

The gut microbiota is an integral component of the colorectal cancer (CRC) microenvironment and is intimately associated with CRC initiation, progression, and therapeutic outcomes. We reviewed recent advancements in utilizing nanotechnology for modulating gut microbiota, discussing strategies and the mechanisms underlying their design. For future nanomedicine design, we propose a 5I principle for individualized nanomedicine in CRC management.

Self-Assembled Peptide Hydrogels Loaded with Umbilical Cord-Derived Mesenchymal Stem Cells Repairing Injured Endometrium and Restoring Fertility.

Endometrial injury is a major cause of infertility and recurrent miscarriage. However, no clinically available methods currently exist to effectively repair the damaged endometrium. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for promoting tissue regeneration, yet a biocompatible scaffold capable of delivering MSCs and supporting their growth is needed. Herein, the study reports a peptide hydrogel scaffold, self-assembled from a peptide IVK8-RGD consisting of an ionic complementary peptide sequence IEVEIRVK and a bioactive sequence RGD, to load umbilical cord-derived mesenchymal stem cells (UC-MSCs). This peptide forms a hydrogel under the physiological condition through self-assembly, and the peptide hydrogel exhibits injectability and adhesiveness to uterus, making it suitable for endometrial repair. Importantly, this hydrogel supports the adhesion and proliferation of UC-MSCs in a 3D environment. In vivo experiments using rats with endometrial injury have shown that treatment with IVK8-RGD hydrogel loaded with UC-MSCs effectively restores endometrial thickness, inhibits fibrosis, and facilitates angiogenesis through activating Raf/MEK/ERK pathway, leading to significantly improved fertility and live birth rate. These findings demonstrate the potential of the UC-MSCs-loaded hydrogel in repairing damaged endometrium and may address the unmet clinical needs of treating recurrent miscarriage and infertility induced by endometrial damage.

Metagenomics-Metabolomics Exploration of Three-Way-Crossbreeding Effects on Rumen to Provide Basis for Crossbreeding Improvement of Sheep Microbiome and Metabolome of Sheep.

The objective of this experiment was to explore the effects of three-way hybridization on rumen microbes and metabolites in sheep using rumen metagenomics and metabolomics. Healthy Hu and CAH (Charolais × Australian White × Hu) male lambs of similar birth weight and age were selected for short-term fattening after intensive weaning to collect rumen fluid for sequencing. Rumen metagenomics diversity showed that Hu and CAH sheep were significantly segregated at the species, KEGG-enzyme, and CAZy-family levels. Moreover, the CAH significantly increased the ACE and Chao1 indices. Further, correlation analysis of the abundance of the top 80 revealed that the microorganisms were interrelated at the species, KEGG-enzyme, and CAZy-family levels. Overall, the microbiome significantly affected metabolites of the top five pathways, with the strongest correlation found with succinic acid. Meanwhile, species-level microbial markers significantly affected rumen differential metabolites. In addition, rumen microbial markers in Hu sheep were overall positively correlated with down-regulated metabolites and negatively correlated with up-regulated metabolites. In contrast, rumen microbial markers in CAH lambs were overall negatively correlated with down-regulated metabolites and positively correlated with up-regulated metabolites. These results suggest that three-way crossbreeding significantly affects rumen microbial community and metabolite composition, and that significant interactions exist between rumen microbes and metabolites.

Alleviation of Salt Stress and Changes in Glycyrrhizic Acid Accumulation by Dark Septate Endophytes in Glycyrrhiza glabra Grown under Salt Stress.

This study aimed to investigate the mechanisms by which dark septate endophytes (DSE) regulate salt tolerance and the accumulation of bioactive constituents in licorice. First, the salt stress tolerance and resynthesis with the plant effect of isolated DSE from wild licorice were tested. Second, the performance of licorice inoculated with DSE, which had the best salt-tolerant and growth-promoting effects, was examined under salt stress. All isolated DSE showed salt tolerance and promoted plant growth, withCurvularia lunata D43 being the most effective. Under salt stress, C. lunata D43 could promote growth, increase antioxidant enzyme activities, enhance glycyrrhizic acid accumulation, improve key enzyme activities in the glycyrrhizic acid synthesis pathway, and induce the expression of the key enzyme gene and salt tolerance gene of licorice. The structural equation model demonstrated that DSE alleviate the negative effects of salt stress through direct and indirect pathways. Variations in key enzyme activities, gene expression, and bioactive constituent concentration can be attributed to the effects of DSE. These results contribute to revealing the value of DSE for cultivating medicinal plants in saline soils.

NRF3 suppresses the metastasis of triple-negative breast cancer cells by inhibiting ERK activation in a ROS-dependent manner.

PURPOSE: Our previous study demonstrated that NRF3 (NFE2L3, Nuclear Factor-erythroid 2-related factor 3) could suppress cell metastasis and proliferation in breast cancer. In this study, we investigated the mechanisms underlying its function in breast cancer. METHODS: In the present study, NRF3 expression and its clinical characteristics in breast cancer were analyzed using public datasets and clinical specimens. After breast cancer cells were overexpressed NRF3, FACS was used to detect the intracellular ROS levels. The migration and invasion activities of NRF3-ectopic expressed breast cancer cells were determined by transwell assay. To validate the role of ROS/ERK axis in the inhibitory effect of NRF3 in cell metastasis, ROS scavenger NAC was also included. RESULTS: We found that NRF3 mRNA was highly expressed, while NRF3 protein was extremely lowly expressed in breast cancer tissues compared with their normal counterparts, and low level NRF3 was associated with poorer prognosis in patients with triple negative breast cancer (TNBC). More interestingly, overexpression of NRF3 protein significantly increased cellular ROS production and dramatically decreased p-ERK level and cell migration in TNBC cells. Mechanistically, NRF3 protein was found to be mutually regulated by valosin-containing protein (VCP). Strikingly, VCP-knockdown dramatically increased NRF3 protein expression, but NRF3-knockin also decreased VCP expression in return. Moreover, antioxidant NAC treatment effectively increased the level of p-ERK and VCP expression, as well as cell migration and invasion abilities of TNBC cells. CONCLUSION: NRF3, a tumor suppressor downregulated by VCP, could attenuate cell metastasis in TNBC cells by increasing cellular ROS accumulation and subsequently inhibiting the ERK phosphorylation.

Defective TiOx overlayers catalyze propane dehydrogenation promoted by base metals.

The industrial catalysts utilized for propane dehydrogenation (PDH) to propylene, an important alternative to petroleum-based cracking processes, either use expensive metals or metal oxides that are environmentally unbenign. We report that a typically less-active oxide, titanium oxide (TiO2), can be combined with earth-abundant metallic nickel (Ni) to form an unconventional Ni@TiOx catalyst for efficient PDH. The catalyst demonstrates a 94% propylene selectivity at 40% propane conversion and superior stability under industrially relevant conditions. Complete encapsulation of Ni nanoparticles was allowed at elevated temperatures (>550°C). A mechanistic study suggested that the defective TiOx overlayer consisting of tetracoordinated Ti sites with oxygen vacancies is catalytically active. Subsurface metallic Ni acts as an electronic promoter to accelerate carbon-hydrogen bond activation and hydrogen (H2) desorption on the TiOx overlayer.

Anti-CRMP2 antibody induces anxiety-like behavior and increases pyramidal neuron excitability in mice.

BACKGROUND: We have previously identified auto-antibody (Ab) to collapsin response mediator protein 2 (CRMP2) in patients with encephalitis. The present study aims to evaluate the pathogenic effects of anti-CRMP2 Ab. METHODS: Recombinant CRMP2 protein was injected subcutaneously into mice to establish an active immune mouse model with anti-CRMP2 Ab. Behavioral assessments, histopathological staining, and electrophysiological testing were performed to identify any pathogenic changes. RESULTS: The mice exhibited signs of impaired motor coordination four weeks post-immunization of CRMP2 protein. Moreover, CRMP2 immunized mice for eight weeks showed anxiety-like behaviors indicating by tests of open field and the elevated plus maze. After incubating the CA1 region of hippocampal brain section with the sera from CRMP2 immunized mice, the whole-cell path-clamp recordings showed increased excitability of pyramidal neurons. However, no obvious inflammation and infiltration of immune cells were observed by histopathological analysis. Western blot showed that the phosphorylation levels of CRMP2-Thr514 and -Ser522 were not affected. CONCLUSION: In an active immunization model with CRMP2 protein, impaired coordination and anxiety-like behaviors were observed. Also, anti-CRMP2 Abs containing sera heightened the excitability of hippocampal pyramidal neurons in vitro, which imply the pathogenic effects of anti-CRMP2 Ab.

Role of Cancer Side Population Stem Cells in Ovarian Cancer Angiogenesis.

Ovarian cancer is one of the most common gynecologic malignancies. Recurrence and metastasis often occur after treatment, and it has the highest mortality rate of all gynecological tumors. Cancer stem cells (CSCs) are a small population of cells with the ability of self-renewal, multidirectional differentiation, and infinite proliferation. They have been shown to play an important role in tumor growth, metastasis, drug resistance, and angiogenesis. Ovarian cancer side population (SP) cells, a type of CSC, have been shown to play roles in tumor formation, colony formation, xenograft tumor formation, ascites formation, and tumor metastasis. The rapid progression of tumor angiogenesis is necessary for tumor growth; however, many of the mechanisms driving this process are unclear as is the contribution of CSCs. The aim of this review was to document the current state of knowledge of the molecular mechanism of ovarian cancer stem cells (OCSCs) in regulating tumor angiogenesis.

A transcranial multiple waves suppression method for plane wave imaging based on Radon transform.

Transcranial ultrasound imaging presents a significant challenge due to the intricate interplay between ultrasound waves and the heterogeneous human skull. The skull's presence induces distortion, refraction, multiple scattering, and reflection of ultrasound signals, thereby complicating the acquisition of high-quality images. Extracting reflections from the entire waveform is crucial yet exceedingly challenging, as intracranial reflections are often obscured by strong amplitude direct waves and multiple scattering. In this paper, a multiple wave suppression method for ultrasound plane wave imaging is proposed to mitigate the impact of skull interference. Drawing upon prior research, we developed an enhanced high-resolution linear Radon transform using the maximum entropy principle and Bayesian method, facilitating wavefield separation. We detailed the process of wave field separation in the Radon domain through simulation of a model with a high velocity layer. When plane waves emitted at any steering angles, both multiple waves and first arrival waves manifested as distinct energy points. In the brain simulation, we contrasted the characteristic differences between skull reflection and brain-internal signal in Radon domain, and demonstrated that multiples suppression method reduces side and grating lobe levels by approximately 30 dB. Finally, we executed in vitro experiments using a monkey skull to separate weak intracranial reflection signals from strong skull reflections, enhancing the contrast-to-noise ratio by 85 % compared to conventional method using full waveform. This study deeply explores the effect of multiples on effective signal separation, addresses the complexity of wavefield separation, and verifies its efficacy through imaging, thereby significantly advancing ultrasound transcranial imaging techniques.

Viral communities in a pH>10 serpentinite-like environment: insight into diversity and potential roles in modulating the microbiomes by bioactive vitamin B9 synthesis.

Viral communities exist in a variety of ecosystems and play significant roles in mediating biogeochemical processes, whereas viruses inhabiting strongly alkaline geochemical systems remain underexplored. In this study, the viral diversity, potential functionalities, and virus-host interactions in a strongly alkaline environment (pH = 10.4-12.4) exposed to the leachates derived from the serpentinization-like reactions of smelting slags were investigated. The viral populations (e.g., Herelleviridae, Queuovirinae, and Inoviridae) were closely associated with the dominating prokaryotic hosts (e.g., Meiothermus, Trueperaceae, and Serpentinomonas) in this ultrabasic environment. Auxiliary metabolic genes (AMGs) suggested that viruses may enhance hosts' fitness by facilitating cofactor biosynthesis, hydrogen metabolism, and carbon cycling. To evaluate the activity of synthesis of essential cofactor vitamin B9 by the viruses, a viral folA (vfolA) gene encoding dihydrofolate reductase (DHFR) was introduced into a thymidine-auxotrophic strain Escherichia coli MG1655 ΔfolA mutant, which restored the growth of the latter in the absence of thymidine. Notably, the homologs of the validated vDHFR were globally distributed in the viromes across various ecosystems. The present study sheds new light on the unique viral communities in hyperalkaline ecosystems and their potential beneficial impacts on the coexisting microbial consortia by supplying essential cofactors. IMPORTANCE: This study presents a comprehensive investigation into the diversity, potential functionalities, and virus-microbe interactions in an artificially induced strongly alkaline environment. Functional validation of the detected viral folA genes encoding dihydrofolate reductase substantiated the synthesis of essential cofactors by viruses, which may be ubiquitous, considering the broad distribution of the viral genes associated with folate cycling.

Nuclear alpha-synuclein accelerates cell senescence and neurodegeneration.

BACKGROUND: The progression of Parkinson's disease (PD) is related to ageing. The accumulation of nuclear alpha-synuclein (α-syn) may accelerate the occurrence of neurodegenerative diseases, but its role in PD remains poorly understood. METHODS: In the present study, α-syn expression was specifically targeted to the nucleus by constructing an adeno-associated virus (AAV) vector in which a nuclear localization sequence (NLS) was added to the α-syn coding sequence. Virus-mediated gene transfer, behavioural tests, RNA-Seq, immunohistochemistry, western blotting, and quantitative real-time PCR were then performed. RESULTS: In vivo experiments using a mouse model showed that nuclear α-syn increased the severity of the PD-like phenotype, including the loss of dopaminergic neurons concomitant with motor impairment and the formation of α-syn inclusions. These nuclear inclusions contained α-syn species of high molecular weights and induced strong transcriptional dysregulation, especially induced high expression of p21 and senescence-associated secretory phenotype (SASP)-related genes. In addition, the transcriptional alterations induced by nuclear α-syn were associated with gliosis, inflammation, oxidative and DNA damage, and lysosomal dysfunction, and they eventually accelerated neuronal loss and neurodegeneration. CONCLUSIONS: Our results suggest that nuclear α-syn plays a crucial role in PD pathogenesis.

Race and Ethnicity, Socioeconomic Factors, and Epigenetic Age Acceleration in Survivors of Childhood Cancer.

Importance: Current research in epigenetic age acceleration (EAA) is limited to non-Hispanic White individuals. It is imperative to improve inclusivity by considering racial and ethnic minorities in EAA research. Objective: To compare non-Hispanic Black with non-Hispanic White survivors of childhood cancer by examining the associations of EAA with cancer treatment exposures, potential racial and ethnic disparity in EAA, and mediating roles of social determinants of health (SDOH). Design, Setting, and Participants: In this cross-sectional study, participants were from the St Jude Lifetime Cohort, which was initiated in 2007 with ongoing follow-up. Eligible participants included non-Hispanic Black and non-Hispanic White survivors of childhood cancer treated at St Jude Children's Research Hospital between 1962 and 2012 who had DNA methylation data. Data analysis was conducted from February 2023 to May 2024. Exposure: Three treatment exposures for childhood cancer (chest radiotherapy, alkylating agents, and epipodophyllotoxin). Main Outcomes and Measures: DNA methylation was generated from peripheral blood mononuclear cell-derived DNA. EAA was calculated as residuals from regressing Levine or Horvath epigenetic age on chronological age. SDOH included educational attainment, annual personal income, and the socioeconomic area deprivation index (ADI). General linear models evaluated cross-sectional associations of EAA with race and ethnicity (non-Hispanic Black and non-Hispanic White) and/or SDOH, adjusting for sex, body mass index, smoking, and cancer treatments. Adjusted least square means (ALSM) of EAA were calculated for group comparisons. Mediation analysis treated SDOH as mediators with average causal mediation effect (ACME) calculated for the association of EAA with race and ethnicity. Results: Among a total of 1706 survivors including 230 non-Hispanic Black survivors (median [IQR] age at diagnosis, 9.5 [4.3-14.3] years; 103 male [44.8%] and 127 female [55.2%]) and 1476 non-Hispanic White survivors (median [IQR] age at diagnosis, 9.3 [3.9-14.6] years; 766 male [51.9%] and 710 female [48.1%]), EAA was significantly greater among non-Hispanic Black survivors (ALSM = 1.41; 95% CI, 0.66 to 2.16) than non-Hispanic White survivors (ALSM = 0.47; 95% CI, 0.12 to 0.81). Among non-Hispanic Black survivors, EAA was significantly increased among those exposed to chest radiotherapy (ALSM = 2.82; 95% CI, 1.37 to 4.26) vs those unexposed (ALSM = 0.46; 95% CI, -0.60 to 1.51), among those exposed to alkylating agents (ALSM = 2.33; 95% CI, 1.21 to 3.45) vs those unexposed (ALSM = 0.95; 95% CI, -0.38 to 2.27), and among those exposed to epipodophyllotoxins (ALSM = 2.83; 95% CI, 1.27 to 4.40) vs those unexposed (ALSM = 0.44; 95% CI, -0.52 to 1.40). The association of EAA with epipodophyllotoxins differed by race and ethnicity (ß for non-Hispanic Black survivors, 2.39 years; 95% CI, 0.74 to 4.04 years; ß for non-Hispanic White survivors, 0.68; 95% CI, 0.05 to 1.31 years) and the difference was significant (1.77 years; 95% CI, 0.01 to 3.53 years; P for interaction = .049). Racial and ethnic disparities in EAA were mediated by educational attainment (

N-Phenyl-2-Pyridone-Derived Endoperoxide Suppressing both Lung Cancer and Idiopathic Pulmonary Fibrosis Progression by Three-Pronged Action.

We report an endoperoxide compound (E5) which can deliver three therapeutic components by a thermal cycloreversion, namely, singlet oxygen, triplet oxygen and 3-methyl-N-phenyl-2-pyridone, thus targeting multiple mechanisms for treating non-small cell lung cancer and idiopathic pulmonary fibrosis. In aqueous environment, E5 undergoes clean reaction to afford three therapeutic components with a half-life of 8.3 hours without the generation of other by-products, which not only achieves good cytotoxicity toward lung cancer cells and decreases the levels of HIF-1α protein, but also inhibits the TGF-ß1 induced fibrosis in vitro. In vivo experiments also demonstrated the efficacy of E5 in inhibiting tumor growth and relieving idiopathic pulmonary fibrosis, while exhibiting good biocompatibility. Many lines of evidence reveal the therapeutic efficacy of singlet oxygen and 3-methyl-N-phenyl-2-pyridone, and triplet oxygen could downregulate HIF-1α and relieve tumor hypoxia which is a critical issue in conventional PDT. Unlike other combination therapies, in which multiple therapeutic agents are given in independent formulations, our work demonstrates single molecule endoperoxide prodrugs could be developed as new platforms for treatment of cancers and related diseases.

Human milk fat substitutes rich in 1,3-dioleoyl-2-palmitoylglycerol and 1-oleoyl-2-palmitoyl-3-linoleoylglycerol simultaneously: Preparation strategy and simulated infant in vitro digestion.

In this study, fractionated palm stearin, oleic acid, and linoleic acid were selected as the base materials to prepare human milk fat substitutes (HMFS) rich in OPO and OPL by enzymatic acidolysis combined with physical blending. Under optimum conditions, contents of OPO, OPL, and sn-2 palmitic acid in the OPO and OPL-rich triacylglycerols (TAGs) were higher than that in commercial OPO-rich TAGs, with values of 37.25%, 28.12%, and 79.44%, respectively. Physical blending the OPO and OPL-rich TAGs (47%), bovine milk fat (18%), sunflower oil (13%), coconut oil (13%), corn oil (8%), and palm oil (1%) can obtain HMFS with a fat composition that like HMF. The fatty acid, sn-2 saturated fatty acid, and TAG contents of HMFS were within the lower and upper limit of HMF. The lipolysis degree of infant formula (IF) with HMFS as fat source is 9.0% higher than that of commercial plant oil-based infant formula (PIF), and 3.4% lower than that of human milk. IF with HMFS as fat source released less saturated free fatty acids and more saturated monoacylglycerols during digestion than that of PIF, which would help improve the IF fat utilization by infants.

An Efficient Graph Learning System for Emotion Recognition Inspired by the Cognitive Prior Graph of EEG Brain Network.

Benefiting from the high-temporal resolution of electroencephalogram (EEG), EEG-based emotion recognition has become one of the hotspots of affective computing. For EEG-based emotion recognition systems, it is crucial to utilize state-of-the-art learning strategies to automatically learn emotion-related brain cognitive patterns from emotional EEG signals, and the learned stable cognitive patterns effectively ensure the robustness of the emotion recognition system. In this work, to realize the efficient decoding of emotional EEG, we propose a graph learning system Graph Convolutional Network framework with Brain network initial inspiration and Fused attention mechanism (BF-GCN) inspired by the brain cognitive mechanism to automatically learn graph patterns from emotional EEG and improve the performance of EEG emotion recognition. In the proposed BF-GCN, three graph branches, i.e., cognition-inspired functional graph branch, data-driven graph branch, and fused common graph branch, are first elaborately designed to automatically learn emotional cognitive graph patterns from emotional EEG signals. And then, the attention mechanism is adopted to further capture the brain activation graph patterns that are related to emotion cognition to achieve an efficient representation of emotional EEG signals. Essentially, the proposed BF-CGN model is a cognition-inspired graph learning neural network model, which utilizes the spectral graph filtering theory in the automatic learning and extracting of emotional EEG graph patterns. To evaluate the performance of the BF-GCN graph learning system, we conducted subject-dependent and subject-independent experiments on two public datasets, i.e., SEED and SEED-IV. The proposed BF-GCN graph learning system has achieved 97.44% (SEED) and 89.55% (SEED-IV) in subject-dependent experiments, and the results in subject-independent experiments have achieved 92.72% (SEED) and 82.03% (SEED-IV), respectively. The state-of-the-art performance indicates that the proposed BF-GCN graph learning system has a robust performance in EEG-based emotion recognition, which provides a promising direction for affective computing.