Evolutionary novelties underlie sound production in baleen whales.

Baleen whales (mysticetes) use vocalizations to mediate their complex social and reproductive behaviours in vast, opaque marine environments1. Adapting to an obligate aquatic lifestyle demanded fundamental physiological changes to efficiently produce sound, including laryngeal specializations2-4. Whereas toothed whales (odontocetes) evolved a nasal vocal organ5, mysticetes have been thought to use the larynx for sound production1,6-8. However, there has been no direct demonstration that the mysticete larynx can phonate, or if it does, how it produces the great diversity of mysticete sounds9. Here we combine experiments on the excised larynx of three mysticete species with detailed anatomy and computational models to show that mysticetes evolved unique laryngeal structures for sound production. These structures allow some of the largest animals that ever lived to efficiently produce frequency-modulated, low-frequency calls. Furthermore, we show that this phonation mechanism is likely to be ancestral to all mysticetes and shares its fundamental physical basis with most terrestrial mammals, including humans10, birds11, and their closest relatives, odontocetes5. However, these laryngeal structures set insurmountable physiological limits to the frequency range and depth of their vocalizations, preventing them from escaping anthropogenic vessel noise12,13 and communicating at great depths14, thereby greatly reducing their active communication range.

Blocking Metal Nanocluster Growth through Ligand Coordination and Subsequent Polymerization: The Case of Ruthenium Nanoclusters as Robust Hydrogen Evolution Electrocatalysts.

Metal nanoclusters providing maximized atomic surface exposure offer outstanding hydrogen evolution activities but their stability is compromised as they are prone to grow and agglomerate. Herein, a possibility of blocking metal ion diffusion at the core of cluster growth and aggregation to produce highly active Ru nanoclusters supported on an N, S co-doped carbon matrix (Ru/NSC) is demonstrated. To stabilize the nanocluster dispersion, Ru species are initially coordinated through multiple Ru─N bonds with N-rich 4'-(4-aminophenyl)-2,2:6',2''-terpyridine (TPY-NH2) ligands that are subsequently polymerized using a Schiff base. After the pyrolysis of the hybrid composite, highly dispersed ultrafine Ru nanoclusters with an average size of 1.55 nm are obtained. The optimized Ru/NSC displays minimal overpotentials and high turnover frequencies, as well as robust durability both in alkaline and acidic electrolytes. Besides, outstanding mass activities of 3.85 A mg-1 Ru at 50 mV, i.e., 16 fold higher than 20 wt.% Pt/C are reached. Density functional theory calculations rationalize the outstanding performance by revealing that the low d-band center of Ru/NSC allows the desorption of *H intermediates, thereby enhancing the alkaline HER activity. Overall, this work provides a feasible approach to engineering cost-effective and robust electrocatalysts based on carbon-supported transition metal nanoclusters for future energy technologies.

Development and Evaluation of Messages for Reducing Overscreening of Breast Cancer in Older Women.

BACKGROUND: Many older women are screened for breast cancer beyond guideline-recommended thresholds. One contributor is pro-screening messaging from health care professionals, media, and family/friends. In this project, we developed and evaluated messages for reducing overscreening in older women. METHODS: We surveyed women ages 65+ who were members of a nationally representative online panel. We constructed 8 messages describing reasons to consider stopping mammograms, including guideline recommendations, false positives, overdiagnosis, and diminishing benefits from screening due to competing risks. Messages varied in their format; some presented statistical evidence, and some described short anecdotes. Each participant was randomized to read 4 of 8 messages. We also randomized participants to one of 3 message sources (clinician, family member, and news story). We assessed whether the message would make participants "want to find out more information" and "think carefully" about mammograms. RESULTS: Participants (N=790) had a mean age of 73.5 years; 25.8% were non-White. Across all messages, 73.0% of the time, participants agreed that the messages would make them seek more information (range among different messages=64.2%-78.2%); 46.5% of the time participants agreed that the messages would make them think carefully about getting mammograms (range =36.7%-50.7%). Top-rated messages mentioned false-positive anecdotes and overdiagnosis evidence. Ratings were similar for messages from clinicians and news sources, but lower from the family member source. CONCLUSIONS: Overall, participants positively evaluated messages designed to reduce breast cancer overscreening regarding perceived effects on information seeking and deliberation. Combining the top-rated messages into messaging interventions may be a novel approach to reduce overscreening.

Atomic Insight into the Enzymatic Selectivity of Acetyltransferase for Endogenous Polyamines.

The N1-Spermidine/spermine acetyltransferase (SSAT) serves as the rate-limiting enzyme in the polyamine metabolism pathway, specifically catalyzing the acetylation of spermidine, spermine, and other specific polyamines. The source of its enzymatic selectivity remains elusive. Here, we used quantum mechanics and molecular mechanics simulations combined with various technologies to explore the enzymatic mechanism of SSAT for endogenous polyamines from an atomic perspective. The static binding and chemical transformation were considered. The binding affinity was identified to be dependent on the protonated state of polyamine. The order of the binding affinity for Spm, Spd, and Put is consistent with the experimental results, which is also verified by the dynamic separation of polyamine and SSAT. Hydrogen bond interactions and salt bridges contribute most, and the common hot residues were identified. In addition, the transfer of acetyl and proton between polyamine and AcCoA was discovered to follow a concerted mechanism, and thermodynamic properties are responsible for the catalytic efficiency of SSAT. This work may be helpful for the development of polyamine derivatives based on catalysis to regulate polyamine metabolism.

Associations of pyrethroid exposure with bone mineral density and osteopenia in adults.

INTRODUCTION: This study was to investigate the correlations between pyrethroid exposure and bone mineral density (BMD) and osteopenia. MATERIALS AND METHODS: This cross-sectional study included 1389 participants over 50 years of age drawn from the 2007-2010 and 2013-2014 National Health and Nutrition Examination Survey (NHANES). Three pyrethroid metabolites, 3-phenoxybenzoic acid (3-PBA), trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane-1-carboxylic acid (trans-DCCA), and 4-fluoro-3-phenoxybenzoic acid (4-F-3PBA) were used as indicators of pyrethroid exposure. Low BMD was defined as T-score < - 1.0, including osteopenia. Weighted multivariable linear regression analysis or logistic regression analysis was utilized to evaluate the correlation between pyrethroid exposure and BMD and low BMD. Bayesian kernel machine regression (BKMR) model was utilized to analyze the correlation between pyrethroids mixed exposure and low BMD. RESULTS: There were 648 (48.41%) patients with low BMD. In individual pyrethroid metabolite analysis, both tertile 2 and tertile 3 of trans-DCCA were negatively related to total femur, femur neck, and total spine BMD [coefficient (ß) = - 0.041 to - 0.028; all P < 0.05]. Both tertile 2 and tertile 3 of 4-F-3PBA were negatively related to total femur BMD (P < 0.05). Only tertile 2 [odds ratio (OR) = 1.63; 95% CI = 1.07, 2.48] and tertile 3 (OR = 1.65; 95% CI = 1.10, 2.50) of trans-DCCA was correlated with an increased risk of low BMD. The BKMR analysis indicated that there was a positive tendency between mixed pyrethroids exposure and low BMD. CONCLUSION: In conclusion, pyrethroids exposure was negatively correlated with BMD levels, and the associations of pyrethroids with BMD and low BMD varied by specific pyrethroids, pyrethroid concentrations, and bone sites.

Transition-Metal Porphyrin-Based MOFs In Situ-Derived Hybrid Catalysts for Electrocatalytic CO2 Reduction.

Excellent electrocatalytic CO2 reduction reaction activity has been demonstrated by transition metals and nitrogen-codoped carbon (M-N-C) catalysts, especially for transition-metal porphyrin (MTPP)-based catalysts. In this work, we propose to use one-step low-temperature pyrolysis of the isostructural MTPP-based metal-organic frameworks (MOFs) and electrochemical in situ reduction strategies to obtain a series of hybrid catalysts of Co nanoparticles (Co NPs) and MTPP, named Co NPs/MTPP (M = Fe, Co, and Ni). The in situ introduction of Co NPs can efficiently enhance the electrocatalytic ability of MTPP (M = Fe, Co, and Ni) to convert CO2 to CO, particularly for FeTPP. Co NPs/FeTPP endowed a high CO faradaic efficiency (FECOmax = 95.5%) in the H cell, and the FECO > 90.0% is in the broad potential range of -0.72 to -1.22 VRHE. In addition, the Co NPs/FeTPP achieved 145.4 mA cm-2 at a lower potential of -0.70 VRHE with an FECO of 94.7%, and the CO partial currents increased quickly to reach 202.2 mA cm-2 at -0.80 VRHE with an FECO of 91.6% in the flow cell. It is confirmed that Co NPs are necessary for hybrid catalysts to get superior electrocatalytic activity; Co NPs also can accelerate H2O dissociation and boost the proton supply capacity to hasten the proton-coupled electron-transfer process, effectively adjusting the adsorption strength of the reaction intermediates.

Screening for ferroptosis genes related to endometrial carcinoma and predicting of targeted drugs based on bioinformatics.

Endometrial carcinoma is one of most common malignant tumors in women, and ferroptosis is closely related to the development and treatment of endometrial carcinoma. The aim of this study was to screen ferroptosis-related genes associated with endometrial carcinoma and predict targeted drugs through bioinformatics. 761 differentially expressed genes were obtained by the dataset GSE63678 from the GEO database, and most of the genes were enriched in the KEGG_CELL_CYCLE and KEGG_OOCYTE_MEIOSIS signaling pathways. 22 ferroptosis-differentially expressed genes were obtained by intersection with the FerrDb database. These genes were involved in biological processes including macromolecular complex assembly and others, and involved in signal pathways including glutathione metabolism, p53 signaling pathway and others. CDKN2A, IDH1, NRAS, TFRC and GOT1 were obtained as hub genes by PPI network analysis. GEPIA showed that CDKN2A, IDH1, NRAS and TFRC were significantly expressed in endometrial carcinoma. Immunohistochemical results showed that CDKN2A, NRAS and TFRC were significantly expressed in endometrial carcinoma clinical tissue samples. The ROC constructed by TCGA database showed that CDKN2A, NRAS and TFRC had significant value in the diagnosis of endometrial carcinoma, and all had prognostic efficacy. 136,572-09-3 BOSS and others were identified as potential targeted drugs for endometrial carcinoma targeting ferroptosis. Our study has shown that ferroptosis-related genes CDKN2A, NRAS and TFRC are diagnostic markers of endometrial carcinoma, and 136,572-09-3 BOSS, methyprylon BOSS, daunorubicin CTD 00005752, nitroglycerin BOSS and dUTP BOSS, IRON BOSS, Imatinib mesylate BOSS, 2-Butanone BOSS, water BOSS, and L-thyroxine BOSS may be potential therapeutic drugs.

Comparative Transcriptomic Analysis of WSSV-Challenged Penaeus vannamei with Variable Resistance Levels.

The Pacific white shrimp, Penaeus vannamei, is highly susceptible to white spot syndrome virus (WSSV). Our study explored the transcriptomic responses of P. vannamei from resistant and susceptible families, uncovering distinct expression patterns after WSSV infection. The analysis revealed a higher number of differentially expressed genes (DEGs) in the susceptible family following WSSV infection compared to the resistant family, when both were evaluated against their respective control groups, indicating that the host resistance of the family line influences the transcriptome. The results also showed that subsequent to an identical duration following WSSV infection, there were more DEGs in P. vannamei with a high viral load than in those with a low viral load. To identify common transcriptomic responses, we profiled DEGs across families at 96 and 228 h post-infection (hpi). The analysis yielded 64 up-regulated and 37 down-regulated DEGs at 96 hpi, with 33 up-regulated and 34 down-regulated DEGs at 228 hpi, showcasing the dynamics of the transcriptomic response over time. Real-time RT-PCR assays confirmed significant DEG expression changes post-infection. Our results offer new insights into shrimp's molecular defense mechanisms against WSSV.

Evaluation of ankle brachial index, serum miR-103 and LP-PLA2 in the prognosis of acute ischemic stroke.

Objective: To explore the prognostic value of ankle brachial index (ABI), serum microribonucleic acid-103 (miR-103), and lipoprotein associated phospholipase A2 (LP-PLA2) indicators in patients with acute ischemic stroke (AIS). Methods: A retrospective analysis was conducted using the medical records of 202 patients with AIS admitted to the First Affiliated Hospital of Hebei North University from June 2019 to December 2022. Patients were divided into two groups based on their prognosis: the Poor-group (n=72) and the Good-group (n=130). Levels of ABI, serum miR-103, and LP-PLA2 indicators were compared between the two groups. Multivariate logistic regression analysis was used to analyze the independent risk factors for the poor prognosis in patients with AIS, and the receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of ABI, serum miR-103, and LP-PLA2 levels on the prognosis of AIS. Results: Seventy two patients had a poor prognosis (35.6%) and 130 had a good prognosis (64.4%). The Poor-group had a higher proportion of elderly patients, patients with a history of diabetes and hypertension, abnormal ABI, and elevations in serum miR-103 and LP-PLA2 compared to the Good-group (P<0.05). Multivariate logistic regression analysis showed that abnormal ABI, and high levels of serum miR-103 and LP-PLA2 were independent risk factors for the poor prognosis. ROC curve provided a combined AUC of 0.862, which was higher than that of the individual ABI, serum miR-103, and LP-PLA2 curves, with values of 0.625, 0.749, and 0.696, respectively (P<0.05). Conclusions: Abnormal ABI, and high serum miR-103 and LP-PLA2 levels are independent risk factors for poor prognosis in AIS patients. They can be used as important indicators for predicting the prognosis of AIS.

Evolution of Mass Spectrometry Instruments and Techniques for Blood Proteomics.

Mass spectrometry (MS)-based blood proteomics is a crucial research focus in identifying disease biomarkers. Blood serum or plasma is the most commonly used sample for such analysis; however, it presents challenges due to the complexity and dynamic range of protein abundance. Despite these difficulties, the development of high-resolution MS instruments has made comprehensive investigation of blood proteomics possible. The evolution of time-of-flight (TOF) or Orbitrap MS instruments has played a significant role in the field of blood proteomics. These instruments are now among the most prominent techniques for blood proteomics due to their sensitivity, selectivity, fast response, and stability. For optimal results, it is necessary to eliminate high-abundance proteins from the blood sample, to maximize the depth coverage of the blood proteomics analysis. This can be achieved through various methods, including commercial kits, chemically synthesized materials, and MS technologies. This paper reviews recent advancements in MS technology and its remarkable applications in biomarker discovery, particularly in the areas of cancer and COVID-19 studies.

Upgrading the genome of an elite japonica rice variety Kongyu 131 for lodging resistance improvement.

Developing a new rice variety requires tremendous efforts and years of input. To improve the defect traits of the excellent varieties becomes more cost and time efficient than breeding a completely new variety. Kongyu 131 is a high-performing japonica variety with early maturity, high yield, wide adaptability and cold resistance, but the poor-lodging resistance hinders the industrial production of Kongyu 131 in the Northeastern China. In this study, we attempted to improve the lodging resistance of Kongyu 131 from perspectives of both gene and trait. On the one hand, by QTL analysis and fine mapping we discovered the candidate gene loci. The following CRISPR/Cas9 and transgenic complementation study confirmed that Sd1 dominated the lodging resistance and favourable allele was mined for precise introduction and improvement. On the other hand, the Sd1 allelic variant was identified in Kongyu 131 by sequence alignment, then introduced another excellent allelic variation by backcrossing. Then, the two new resulting Kongyu 131 went through the field evaluation under different environments, planting densities and nitrogen fertilizer conditions. The results showed that the plant height of upgraded Kongyu 131 was 17%-26% lower than Kongyu 131 without penalty in yield. This study demonstrated a precise and targeted way to update the rice genome and upgrade the elite rice varieties by improving only a few gene defects from the perspective of breeding.

Trace removal of benzene vapour using double-walled metal-dipyrazolate frameworks.

In principle, porous physisorbents are attractive candidates for the removal of volatile organic compounds such as benzene by virtue of their low energy for the capture and release of this pollutant. Unfortunately, many physisorbents exhibit weak sorbate-sorbent interactions, resulting in poor selectivity and low uptake when volatile organic compounds are present at trace concentrations. Herein, we report that a family of double-walled metal-dipyrazolate frameworks, BUT-53 to BUT-58, exhibit benzene uptakes at 298 K of 2.47-3.28 mmol g-1 at <10 Pa. Breakthrough experiments revealed that BUT-55, a supramolecular isomer of the metal-organic framework Co(BDP) (H2BDP = 1,4-di(1H-pyrazol-4-yl)benzene), captures trace levels of benzene, producing an air stream with benzene content below acceptable limits. Furthermore, BUT-55 can be regenerated with mild heating. Insight into the performance of BUT-55 comes from the crystal structure of the benzene-loaded phase (C6H6@BUT-55) and density functional theory calculations, which reveal that C-H···X interactions drive the tight binding of benzene. Our results demonstrate that BUT-55 is a recyclable physisorbent that exhibits high affinity and adsorption capacity towards benzene, making it a candidate for environmental remediation of benzene-contaminated gas mixtures.

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.

Characterization of Balance Control and Postural Stability in Patients With Alzheimer Disease.

Balance in Alzheimer disease (AD) patients is not rigorously understood. In this study, we characterize balance using qualitative [Berg Balance Scale (BBS)] and quantitative measures (posturography) and assess relationships between qualitative and quantitative balance measures in AD. Patients with mild-moderate AD (n=48) were recruited. BBS scores and posturography metrics, including medial-lateral sway range, anterior-posterior sway range, sway area, and sway velocity, were assessed in eyes-open and eyes-closed conditions. Adjusted linear regressions were used to assess relationships between posturography and BBS score. Mean BBS score was 50.4±5.3. In eyes-open conditions, posturography and BBS score were not significantly associated. In eyes-closed conditions, better BBS score was significantly associated with lower sway area (ß=-0.91; P =0.006). Better scores of BBS items involving turning and reduced base of support were associated with greater eyes-closed sway area. Posturography in the more challenging eyes-closed condition may predict functional balance deficits in AD patients.

Polyamines inhibit abscisic acid-induced stomatal closure by scavenging hydrogen peroxide.

Stomatal closure is regulated by plant hormones and some small molecules to reduce water loss under stress conditions. Both abscisic acid (ABA) and polyamines alone induce stomatal closure; however, whether the physiological functions of ABA and polyamines are synergistic or antagonistic with respect to inducing stomatal closure is still unknown. Here, stomatal movement in response to ABA and/or polyamines was tested in Vicia faba and Arabidopsis thaliana, and the change in the signaling components under stomatal closure was analyzed. We found that both polyamines and ABA could induce stomatal closure through similar signaling components, including the synthesis of hydrogen peroxide (H2 O2 ) and nitric oxide (NO) and the accumulation of Ca2+ . However, polyamines partially inhibited ABA-induced stomatal closure both in epidermal peels and in planta by activating antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), to eliminate the ABA-induced increase in H2 O2 . These results strongly indicate that polyamines inhibit abscisic acid-induced stomatal closure, suggesting that polyamines could be used as potential plant growth regulators to increase photosynthesis under mild drought stress.

Nonenzymatic Electrochemical Sensing Platform Based on 2D Isomorphic Co/Ni-Metal-Organic Frameworks for Glucose Detection.

Two-dimensional metal-organic framework (MOF) crystalline materials possess promising potential in the electrochemical sensing process owing to their tunable structures, high specific surface area, and abundant metal active sites; however, developing MOF-based nonenzymatic glucose (Glu) sensors which combine electrochemical activity and environmental stability remains a challenge. Herein, utilizing the tripodic nitrogen-bridged 1,3,5-tris(1-imidazolyl) benzene (TIB) linker, Co2+ and Ni2+, two 2D isomorphic crystalline materials, including Co/Ni-MOF {[Co (TIB)]·2BF4} (CTGU-31) and {[Ni(TIB)]·2NO3} (CTGU-32), with a binodal (3, 6)-connected kgd topological net were firstly synthesized and fabricated with conducting acetylene black (AB). When modified on a glassy carbon electrode, the optimized AB/CTGU-32 (1:1) electrocatalyst demonstrated a higher sensitivity of 2.198 µA µM-1 cm-2, a wider linear range from 10 to 4000 µM, and a lower detection limit (LOD) value (0.09 µM, S/N = 3) compared to previously MOF-based Glu sensors. Moreover, AB/CTGU-32 (1:1) exhibited desirable stability for at least 2000 s during the electrochemical process. The work indicates that MOF-based electrocatalysts are a promising candidate for monitoring Glu and demonstrate their potential for preliminary screening for diabetes.

Ultrafast Response in Nonenzymatic Electrochemical Glucose Sensing with Ni(II)-MOFs by Dimensional Manipulation.

Metal-organic frameworks (MOFs) are emerging as promising candidates for electrochemical glucose sensing owing to their ordered channels, tunable chemistry, and atom-precision metal sites. Herein, the efficient nonenzymatic electrochemical glucose sensing is achieved by taking advantage of Ni(II)-based metal-organic frameworks (Ni(II)-MOFs) and acquiring the ever-reported fastest response time. Three Ni(II)-MOFs ({[Ni6L2(H2O)26]4H2O}n (CTGU-33), {Ni(bib)1/2(H2L)1/2(H2O)3}n (CTGU-34), {Ni(phen)(H2L)1/2(H2O)2}n (CTGU-35)) have been synthesized for the first time, which use benzene-1,2,3,4,5,6-hexacarboxylic acid (H6L) as an organic ligand and introduce 1,4-bis(1-imidazoly)benzene (bib) or 1,10-phenanthroline (phen) as spatially auxiliary ligands. Bib and phen convert the coordination mode of CTGU-33, affording structural dimensions from 2D of CTGU-33 to 3D of CTGU-34 or 1D of CTGU-35. By tuning the dimension of the skeleton, CTGU-34 with 3D interconnected channels exhibits an ultrafast response of less than 0.4 s, which is superior to the existing nonenzymatic electrochemical sensors. Additionally, a low detection limit of 0.12 µM (S/N = 3) and a high sensitivity of 1705 µA mM-1 cm-2 are simultaneously achieved. CTGU-34 further showcases desirable anti-interference and cycling stability, which demonstrates a promising application prospect in the real-time detection of glucose.

Correlation between nonalcoholic fatty liver disease and left ventricular diastolic dysfunction in non-obese adults: a cross-sectional study.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with a greater risk of developing cardiovascular disease and have adverse impacts on the cardiac structure and function. Little is known about the effect of non-obese NAFLD upon cardiac function. We aimed to compare the echocardiographic parameters of left ventricle (LV) between non-obese NAFLD group and control group, and explore the correlation of non-obese NAFLD with LV diastolic dysfunction. METHODS AND RESULTS: In this cross-sectional study, 316 non-obese inpatients were enrolled, including 72 participants with NAFLD (non-obese NAFLD group) and 244 participants without NAFLD (control group). LV structural and functional indices of two groups were comparatively analyzed. LV diastolic disfunction was diagnosed and graded using the ratio of the peak velocity of the early filling (E) wave to the atrial contraction (A) wave and E value. Compared with control group, the non-obese NAFLD group had the lower E/A〔(0.80 ± 0.22) vs (0.88 ± 0.35), t = 2.528, p = 0.012〕and the smaller LV end-diastolic diameter〔(4.51 ± 0.42)cm vs (4.64 ± 0.43)cm, t = 2.182, p = 0.030〕. And the non-obese NAFLD group had a higher prevalence of E/A < 1 than control group (83.3% vs 68.9%, X2 = 5.802, p = 0.016) while two groups had similar proportions of LV diastolic dysfunction (58.3% vs 53.7%, X2 = 0.484, p = 0.487). Multivariate logistic regression analysis showed that non-obese NAFLD was associated with an increase in E/A < 1 (OR = 6.562, 95%CI 2.014, 21.373, p = 0.002). CONCLUSIONS: Non-obese NAFLD was associated with decrease of E/A, while more research will be necessary to evaluate risk of non-obese NAFLD for LV diastolic dysfunction in future.

Alleviating the hypoxic tumor microenvironment with MnO2-coated CeO2 nanoplatform for magnetic resonance imaging guided radiotherapy.

BACKGROUND: Radiotherapy is a commonly used tool in clinical practice to treat solid tumors. However, due to the unique microenvironment inside the tumor, such as high levels of GSH, overexpressed H2O2 and hypoxia, these factors can seriously affect the effectiveness of radiotherapy. RESULTS: Therefore, to further improve the efficiency of radiotherapy, a core-shell nanocomposite CeO2-MnO2 is designed as a novel radiosensitizer that can modulate the tumor microenvironment (TME) and thus improve the efficacy of radiation therapy. CeO2-MnO2 can act as a radiosensitizer to enhance X-ray absorption at the tumor site while triggering the response behavior associated with the tumor microenvironment. According to in vivo and in vitro experiments, the nanoparticles aggravate the killing effect on tumor cells by generating large amounts of ROS and disrupting the redox balance. In this process, the outer layer of MnO2 reacts with GSH and H2O2 in the tumor microenvironment to generate ROS and release oxygen, thus alleviating the hypoxic condition in the tumor area. Meanwhile, the manganese ions produced by degradation can enhance T1-weighted magnetic resonance imaging (MRI). In addition, CeO2-MnO2, due to its high atomic number oxide CeO2, releases a large number of electrons under the effect of radiotherapy, which further reacts with intracellular molecules to produce reactive oxygen species and enhances the killing effect on tumor cells, thus having the effect of radiotherapy sensitization. In conclusion, the nanomaterial CeO2-MnO2, as a novel radiosensitizer, greatly improves the efficiency of cancer radiation therapy by improving the lack of oxygen in tumor and responding to the tumor microenvironment, providing an effective strategy for the construction of nanosystem with radiosensitizing function. CONCLUSION: In conclusion, the nanomaterial CeO2-MnO2, as a novel radiosensitizer, greatly improves the efficiency of cancer radiation therapy by improving the lack of oxygen in tumor and responding to the tumor microenvironment, providing an effective strategy for the construction of nanosystems with radiosensitizing function.

Interseason waning of vaccine-induced hemagglutination inhibition antibody titers and contributing factors to pre-existing humoral immunity against influenza in community-dwelling older adults 75 years and older.

BACKGROUND: Seasonal influenza causes significant morbidity and mortality with a disproportionately high disease burden in older adults. Strain-specific hemagglutination-inhibition (HAI) antibody titer is a well-established measure of humoral immunity against influenza and pre-vaccination HAI titer is a valuable indicator of pre-existing humoral immunity at the beginning of each influenza season in highly vaccinated older adults. While vaccine-induced HAI antibody titers are known to wane over time, accurate assessment of their interseason waning has been challenging. This is because pre-vaccination HAI titers are routinely measured using current season vaccine strain antigens instead of the prior season vaccines with which individuals were immunized; as such, they do not accurately represent residual antibody titers from prior season vaccination. This study took advantage of available pre-vaccination HAI titers measured using both current and prior season vaccine strain antigens in a longitudinal influenza immunization study with participants enrolled for multiple consecutive influenza seasons from 2014 through 2017. Influenza A virus (IAV) H3N2 and influenza B virus (IBV) strains in the vaccine formula changed in 2015 and again in 2016 season. IAV H1N1 vaccine strain remained the same from 2014 through 2016 seasons, but changed in 2017. We also investigated factors contributing to pre-existing humoral immunity. RESULTS: Interseason waning of HAI titers was evident, but rates of waning varied among vaccine strains and study seasons, from 18% (p = .43) to 61% (p < .01). Rates of waning were noticeably greater when pre-vaccination HAI titers were measured by the routine approach, i.e., using current season vaccine strain antigens, from 33% (p = .12) to 83% (p < .01), adjusting for age at prior study season, sex, race, and education. This was largely because the routinely measured pre-vaccination HAI titers underrepresented residual HAI titers from prior season vaccinations. Moreover, interseason antibody waning and prior season post-vaccination HAI titers had significant and independent associations with pre-vaccination HAI titers. CONCLUSIONS: The routinely measured pre-vaccination HAI titer overestimates interseason HAI antibody waning as it underestimates residual antibody titers from prior season vaccination when virus strains in the vaccine formula change. Moreover, interseason antibody waning and prior season post-vaccination HAI titers independently contribute to pre-existing humoral immunity in this highly vaccinated, community-dwelling older adult population.