Coronaviruses exploit a host cysteine-aspartic protease for replication.

Highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus 2 (refs. 1,2) (SARS-CoV-2), Middle East respiratory syndrome coronavirus3 (MERS-CoV) and SARS-CoV-1 (ref. 4), vary in their transmissibility and pathogenicity. However, infection by all three viruses results in substantial apoptosis in cell culture5-7 and in patient tissues8-10, suggesting a potential link between apoptosis and pathogenesis of coronaviruses. Here we show that caspase-6, a cysteine-aspartic protease of the apoptosis cascade, serves as an important host factor for efficient coronavirus replication. We demonstrate that caspase-6 cleaves coronavirus nucleocapsid proteins, generating fragments that serve as interferon antagonists, thus facilitating virus replication. Inhibition of caspase-6 substantially attenuates lung pathology and body weight loss in golden Syrian hamsters infected with SARS-CoV-2 and improves the survival of mice expressing human DPP4 that are infected with mouse-adapted MERS-CoV. Our study reveals how coronaviruses exploit a component of the host apoptosis cascade to facilitate virus replication.

Supertough MXene/Sodium Alginate Composite Fiber Felts Integrated with Outstanding Electromagnetic Interference Shielding and Heating Properties.

The development of multifunctional MXene-based fabrics for smart textiles and portable devices has garnered significant attention. However, very limited studies have focused on their structure design and associated mechanical properties. Here, the supertough MXene fiber felts composed of MXene/sodium alginate (SA) fibers were fabricated. The fracture strength and bending stiffness of felts can be up to 97.8 MPa and 1.04 N mm2, respectively. Besides, the fracture toughness of felts was evaluated using the classic Griffith theory, yielding to a critical stress intensity factor of 1.79 MPam. In addition, this kind of felt presents outstanding electrothermal conversion performance (up to 119 °C at a voltage of 2.5 V), high cryogenic and high-temperature tolerance of photothermal conversion performance (-196 to 160 °C), and excellent electromagnetic interference (EMI) shielding effectiveness (54.4 dB in the X-band). This work provides new structural design concepts for high-performance MXene-based textiles, broadening their future applications.

PMS2 amplification contributes brain metastasis from lung cancer.

BACKGROUND: Lung adenocarcinoma metastasizing to the brain results in a notable increase in patient mortality. The high incidence and its impact on survival presents a critical unmet need to develop an improved understanding of its mechanisms. METHODS: To identify genes that drive brain metastasis of tumor cells, we collected cerebrospinal fluid samples and paired plasma samples from 114 lung adenocarcinoma patients with brain metastasis and performed 168 panel-targeted gene sequencing. We examined the biological behavior of PMS2 (PMS1 Homolog 2)-amplified lung cancer cell lines through wound healing assays and migration assays. In vivo imaging techniques are used to detect fluorescent signals that colonize the mouse brain. RNA sequencing was used to compare differentially expressed genes between PMS2 amplification and wild-type lung cancer cell lines. RESULTS: We discovered that PMS2 amplification was a plausible candidate driver of brain metastasis. Via in vivo and in vitro assays, we validated that PMS2 amplified PC-9 and LLC lung cancer cells had strong migration and invasion capabilities. The functional pathway of PMS2 amplification of lung cancer cells is mainly enriched in thiamine, butanoate, glutathione metabolism. CONCLUSION: Tumor cells elevated expression of PMS2 possess the capacity to augment the metastatic potential of lung cancer and establish colonies within the brain through metabolism pathways.

Ultra-Strong Janus Covalent Organic Framework Membrane with Smart Response to Organic Vapor.

Vapor-driven smart Janus materials have made significant advancements in intelligent monitoring, control, and interaction, etc. Nevertheless, the development of ultrafast response single-layer Janus membrane, along with a deep exploration of the smart response mechanisms, remains a long-term endeavor. Here, the successful synthesis of a high-crystallinity single-layer Covalent organic framework (COF) Janus membrane is reported by morphology control. This kind of membrane displays superior mechanical properties and specific surface area, along with excellent responsiveness to CH2Cl2 vapor. The analysis of the underlying mechanisms reveals that the vapor-induced breathing effect of the COF and the stress mismatch of the Janus structure play a crucial role in its smart deformation performance. It is believed that this COF Janus membrane holds promise for complex tasks in various fields.

Reduced thoracic skeletal muscle size is associated with adverse outcomes in diabetes patients with heart failure and reduced ejection fraction: quantitative analysis of sarcopenia by using cardiac MRI.

BACKGROUND: Sarcopenia is frequently found in patients with heart failure with reduced ejection fraction (HFrEF) and is associated with reduced exercise capacity, poor quality of life and adverse outcomes. Recent evidence suggests that axial thoracic skeletal muscle size could be used as a surrogate to assess sarcopenia in HFrEF. Since diabetes mellitus (DM) is one of the most common comorbidities with HFrEF, we aimed to explore the potential association of axial thoracic skeletal muscle size with left ventricular (LV) remodeling and determine its prognostic significance in this condition. METHODS: A total of 243 diabetes patients with HFrEF were included in this study. Bilateral axial thoracic skeletal muscle size was obtained using cardiac MRI. Patients were stratified by the tertiles of axial thoracic skeletal muscle index (SMI). LV structural and functional indices, as well as amino-terminal pro-B-type natriuretic peptide (NT-proBNP), were measured. The determinants of elevated NT-proBNP were assessed using linear regression analysis. The associations between thoracic SMI and clinical outcomes were assessed using a multivariable Cox proportional hazards model. RESULTS: Patients in the lowest tertile of thoracic SMI displayed a deterioration in LV systolic strain in three components, together with an increase in LV mass and a heavier burden of myocardial fibrosis (all P < 0.05). Moreover, thoracic SMI (ß = -0.25; P < 0.001), rather than body mass index (ß = -0.04; P = 0.55), was independently associated with the level of NT-proBNP. The median follow-up duration was 33.6 months (IQR, 20.4-52.8 months). Patients with adverse outcomes showed a lower thoracic SMI (40.1 [34.3, 47.9] cm2/m2 vs. 45.3 [37.3, 55.0] cm2/m2; P < 0.05) but a similar BMI (P = 0.76) compared with those without adverse outcomes. A higher thoracic SMI indicated a lower risk of adverse outcomes (hazard ratio: 0.96; 95% confidence interval: 0.92-0.99; P = 0.01). CONCLUSIONS: With respect to diabetes patients with HFrEF, thoracic SMI is a novel alternative for evaluating muscle wasting in sarcopenia that can be obtained by a readily available routine cardiac MRI protocol. A reduction in thoracic skeletal muscle size predicts poor outcomes in the context of DM with HFrEF.

Left Atrial Phasic Function Impairment in Subacute and Chronic Pulmonary Embolism Patients With Different Degrees of Obstruction: An MRI Feature Tracking Study.

BACKGROUND: The alteration of left atrial (LA) phasic function in subacute and chronic pulmonary embolism (PE) patients is unclear. PURPOSE: To investigate LA phasic strain and LA-right ventricular (RV) interaction in subacute and chronic PE patients with different degrees of obstruction by MRI-feature tracking (MRI-FT). STUDY TYPE: Retrospective. POPULATION: One hundred three PE patients (54 subacute [2 weeks to 3 months after initial symptoms], 49 chronic [>3 months after initial symptoms]) and 80 controls. FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady state free precession sequence. ASSESSMENT: Patients were divided into mild (pulmonary artery obstruction index [PAOI] < 30%, N = 57), moderate (30% ≤ PAOI < 50%, N = 27), and severe (50% ≥ PAOI, N = 19) PE subgroups. LA reservoir, conduit, and active pump longitudinal strains (εs, εe, and εa) and strain rates (SRs, SRe, and SRa) and biventricular global strains were measured. Determinants of LA strains were investigated. STATISTICAL TESTS: ANOVA, t-tests, Mann-Whitney U tests, linear regression. P < 0.05 was considered statistically significant. RESULTS: For both subacute and chronic PE patients, LA reservoir, conduit, and active pump strains and strain rates were significantly lower than in controls. However, there were no significant differences in LA strains between patients with subacute and chronic PE (P = 0.933, 0.625, and 0.630 for εs, εe, and εa). The severe PE subgroup had significantly higher εa and SRa than the mild and moderate PE subgroups. LA strains were significantly correlated with RV diameter and biventricular strains, and RV diameter (ß = -6.836, -4.084, and -1.899 for εs, εe, and εa) was independently associated with LA strains after adjustment for other factors (R2 = 0.627, 0.536, and 0.437 for εs, εe, and εa). DATA CONCLUSION: LA phasic function evaluated by MRI-FT was significantly impaired in subacute and chronic PE patients, and LA active pump function in the severe PE subgroup was higher than that in the mild and moderate PE subgroups. The independent association between RV diameter and LA strains demonstrates that RV diameter may be an important indicator for monitoring LA dysfunction in PE patients. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Effect of Metabolic Syndrome on Left Atrial and Left Ventricular Deformation and Atrioventricular Interactions in Patients With Myocardial Infarction.

BACKGROUND: Metabolic syndrome (MetS) is associated with worse prognosis in patients with myocardial infarction (MI). However, it is unclear how MetS in MI patients is associated with left atrial (LA) and left ventricular (LV) deformation. PURPOSE: To determine the effect of MetS on LA and LV deformation and atrioventricular interactions in MI patients. STUDY TYPE: Retrospective. POPULATION: One hundred eighty-one MI patients (73 MetS+ and 108 MetS-), 107 age- and sex-matched controls (49 MetS+ and 58 MetS-). FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession (SSFP)/segmented phase-sensitive inversion recovery SSFP sequence. ASSESSMENT: LA strain and strain rates (reservoir, conduit, and active), left atrioventricular coupling index (LACI), and LV geometry and radial, circumferential and longitudinal global peak strains (PS) were compared among groups. STATISTICAL TESTS: Two-way analysis of variance, Spearman and Pearson's correlation coefficients, and multivariable linear regression analysis. P value <0.05 indicated statistical significance. RESULTS: Compared with controls, the MI patients with or without MetS showed impaired LA function (reservoir, conduit, and active) and LV deformation (radial, circumferential, and longitudinal PS) and higher LACI. The MetS+ group had lower LA reservoir and conduit function and LV deformation than MetS- group. The MetS-MI interaction was not statistically significant. Furthermore, multivariable linear regression showed that MetS was independently associated with LA and LV deformation (ß = -0.181 to -0.209) in MI patients; LA function was independently associated with LV circumferential PS (ß = 0.230 to 0.394) and longitudinal PS (ß = 0.189 to 0.420), and LA passive strain and strain rate were negatively associated with LV mass (ß = -0.178 and -0.298). DATA CONCLUSION: MetS may be associated with the LA and LV dysfunction in MI patients. Impaired LV deformation and LV hypertrophy are independently associated with LA dysfunction in MI patients, and the MI patients have higher LACI than controls, suggesting atrioventricular interaction alterations. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: 3.

Impact of Functional Mitral Regurgitation on Left Ventricular Strain in Nonischemic Dilated Cardiomyopathy Patients with Type 2 Mellitus Diabetes: A Magnetic Resonance Feature Tracking Study.

BACKGROUND: The impact of functional mitral regurgitation and type 2 mellitus diabetes (T2DM) on left ventricular (LV) strain in nonischemic dilated cardiomyopathy (NIDCM) patients remains unclear. PURPOSE: To evaluate the impact of mitral regurgitation severity on LV strain, and explore additive effect of T2DM on LV function across varying mitral regurgitation severity levels in NIDCM patients. STUDY TYPE: Retrospective. POPULATION: 352 NIDCM (T2DM-) patients (49.1 ± 14.6 years, 67% male) (207, 85, and 60 no/mild, moderate, and severe mitral regurgitation) and 96 NIDCM (T2DM+) patients (55.2 ± 12.4 years, 77% male) (47, 30, and 19 no/mild, moderate, and severe mitral regurgitation). FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession sequence. ASSESSMENT: LV geometric parameters and strain were measured and compared among groups. Determinants of LV strain were investigated. STATISTICAL TEST: Student's t-test, Mann-Whitney U test, one-way ANOVA, Kruskal-Wallis test, univariable and multivariable linear regression. P < 0.05 was considered statistically significant. RESULTS: LV GLPS and longitudinal PDSR decreased gradually with increasing mitral regurgitation severity in NIDCM patients with T2DM(GLPS: -5.7% ± 2.1% vs. -4.3% ± 1.6% vs. -2.6% ± 1.3%; longitudinal PDSR:0.5 ± 0.2 sec-1 vs. 0.4 ± 0.2 sec-1 vs. 0.3 ± 0.1 sec-1). NIDCM (T2DM+) demonstrated decreased GCPS and GLPS in the no/mild subgroup, reduced LV GCPS, GLPS, and longitudinal PDSR in the moderate subgroup, and reduced GRPS, GCPS, GLPS, and longitudinal PDSR in the severe subgroup compared with NIDCM (T2DM-) patients. Multivariable regression analysis identified that mitral regurgitation severity (ß = -0.13, 0.15, and 0.25 for GRPS, GCPS, and GLPS) and the presence of T2DM (ß = 0.14 and 0.13 for GCPS and GLPS) were independent determinants of LV strains in NIDCM patients. DATA CONCLUSION: Increased mitral regurgitation severity is associated with reduced LV strains in NIDCM patients with T2DM. The presence of T2DM exacerbated the decline of LV function across various mitral regurgitation levels in NIDCM patients, resulting in reduced LV strains. TECHNICAL EFFICACY: Stage 3.

Atomically Precise Mo2Cu17 Bimetallic Nanocluster: Synergistic Mo2O4-Coupled Copper Alkynyl Cluster for the Improved Hydrogen Evolution Reaction Performance.

Electrolytic hydrogen production via water splitting holds significant promise for the future of the energy revolution. The design of efficient and abundant catalysts, coupled with a comprehensive understanding of the hydrogen evolution reaction (HER) mechanism, is of paramount importance. In this study, we propose a strategy to craft an atomically precise cluster catalyst with superior HER performance by cocoupling a Mo2O4 structural unit and a Cu(I) alkynyl cluster into a structured framework. The resulting bimetallic cluster, Mo2Cu17, encapsulates a distinctive structure [Mo2O4Cu17(TC4A)4(PhC≡C)6], comprising a binuclear Mo2O4 subunit and a {Cu17(TC4A)2(PhC≡C)6} cluster, both shielded by thiacalix[4]arene (TC4A) and phenylacetylene (PhC≡CH). Expanding our exploration, we synthesized two homoleptic CuI alkynyl clusters coprotected by the TC4A and PhC≡C- ligands: Cu13 and Cu22. Remarkably, Mo2Cu17 demonstrates superior HER efficiency compared to its counterparts, achieving a current density of 10 mA cm-2 in alkaline solution with an overpotential as low as 120 mV, significantly outperforming Cu13 (178 mV) and Cu22 (214 mV) nanoclusters. DFT calculations illuminate the catalytic mechanism and indicate that the intrinsically higher activity of Mo2Cu17 may be attributed to the synergistic Mo2O4-Cu(I) coupling.

Investigation of the mutual crosstalk between ER stress and PI3K/AKT/mTOR signaling pathway in iron overload-induced liver injury in chicks.

Iron is an essential element for the normal functioning of living organisms, but excessive iron deposition can lead to organ damage. This study aims to investigate the interaction between the endoplasmic reticulum stress signaling pathway and the PI3K/AKT/mTOR signaling pathway in liver injury induced by iron overload in chicks. Rspectively, 150 one-day-old broilers were divided into three groups and supplemented with 50 (C), 500 (E1), and 1000 (E2) mg ferrous sulfate monohydrate/kg in the basal diet. Samples were taken after continuous feeding for 14 days. The results showed that iron overload could upregulate the levels of ALT and AST. Histopathological examination revealed bleeding in the central vein of the liver accompanied by inflammatory cell infiltration. Hoechst staining showed that the iron overload group showed significant bright blue fluorescence, and ultrastructural observations showed chromatin condensation as well as mitochondrial swelling and cristae disorganization in the iron overload group. RT-qPCR and Western blot results showed that iron overload upregulated the expression of Bax, Caspase-3, Caspase-9, GRP78, GRP94, P-PERK, ATF4, eIF2α, IRE1, and ATF6, while downregulating the expression of Bcl-2 and the PI3K/AKT/mTOR pathway. XBP-1 splicing experiment showed significant splicing of XBP-1 gene after iron overload. PCA and correlation analysis suggested a potential association between endoplasmic reticulum stress, the PI3K/AKT/mTOR signaling pathway, and liver injury in chicks. In summary, iron overload can induce cell apoptosis and liver injury by affecting endoplasmic reticulum stress and the PI3K/AKT/mTOR signaling pathway.

Effect of exposures to multiple metals on blood pressure and hypertension in the elderly: a community-based study.

A chronic disease, hypertension (HTN) is prevalent among the elderly. Exploring the factors that influence HTN and blood pressure (BP) changes is of great public health significance. However, mixed exposure to multiple serum metals has had less research on the effects on BP and HTN for the elderly. From April to August 2019, 2372 people participated in the community physical examination program for the elderly in Tongling City, Anhui Province. We measured BP and serum levels of 10 metals and collected basic demographic information. We analyzed the relationship between metal levels and changes in BP and HTN by the least absolute shrinkage and selection operator regression, Bayesian kernel machine regression model, and generalized linear model. In multiple models, lead (Pb) and cadmium (Cd) were still significantly associated with HTN occurrence after adjusting for potential confounders (Pb: ORquartile 4 VS quartile 1 = 1.20, 95% CI 1.01-1.43; Cd: ORquartile 4 VS quartile 1 = 1.37, 95% CI 1.16-1.62). In the male subgroup, results were similar to those of the general population. In the female group, Cd was positively correlated with HTN and systolic blood pressure, while Pb was not. According to this study, Pb and Cd were correlated with BP and HTN positively, and there was a certain joint effect. To some extent, our findings provide clues for the prevention of hypertension in the elderly.

A dynamic nomogram predicting symptomatic pneumonia in patients with lung cancer receiving thoracic radiation.

PURPOSE: The most common and potentially fatal side effect of thoracic radiation therapy is radiation pneumonitis (RP). Due to the lack of effective treatments, predicting radiation pneumonitis is crucial. This study aimed to develop a dynamic nomogram to accurately predict symptomatic pneumonitis (RP ≥ 2) following thoracic radiotherapy for lung cancer patients. METHODS: Data from patients with pathologically diagnosed lung cancer at the Zhongshan People's Hospital Department of Radiotherapy for Thoracic Cancer between January 2017 and June 2022 were retrospectively analyzed. Risk factors for radiation pneumonitis were identified through multivariate logistic regression analysis and utilized to construct a dynamic nomogram. The predictive performance of the nomogram was validated using a bootstrapped concordance index and calibration plots. RESULTS: Age, smoking index, chemotherapy, and whole lung V5/MLD were identified as significant factors contributing to the accurate prediction of symptomatic pneumonitis. A dynamic nomogram for symptomatic pneumonitis was developed using these risk factors. The area under the curve was 0.89(95% confidence interval 0.83-0.95). The nomogram demonstrated a concordance index of 0.89(95% confidence interval 0.82-0.95) and was well calibrated. Furthermore, the threshold values for high- risk and low- risk were determined to be 154 using the receiver operating curve. CONCLUSIONS: The developed dynamic nomogram offers an accurate and convenient tool for clinical application in predicting the risk of symptomatic pneumonitis in patients with lung cancer undergoing thoracic radiation.

Relationship between 24-h activity behavior and body fat percentage in preschool children: based on compositional data and isotemporal substitution analysis.

OBJECTIVE: This study aims to elucidate the dose‒response relationship between 24-h activity behaviors and body fat percentage (BFP) in Chinese preschool children using a compositional isotemporal substitution model (ISM). METHODS: In a cross-sectional design, 881 children aged 3-6 from urban and rural areas of Jiangxi Province were sampled. Activity behaviors, including sedentary behavior (SB), low-intensity physical activity (LPA), and moderate- to high-intensity physical activity (MVPA), were measured using accelerometers. Sleep patterns were assessed through questionnaires, and BFP was determined by bioelectrical impedance analysis (BIA). The study employed compositional data analysis (CoDA) and ISM to estimate the impact of reallocating durations of different activity behaviors on BFP. RESULTS: Higher BFP was found in urban vs. rural children, decreasing with age. Overweight and obesity rates were 10.6% and 7.6%, respectively, above national averages. MVPA and LPA were negatively correlated with BFP, while SB was positively correlated. A 30-min MVPA reduction significantly increased zBFR, particularly in overweight children. Gender-specific nuances revealed that boys' MVPA negatively influenced zBFP (ß = -0.155), P < 0.05), while girls' SB positively impacted zBFP (ß = 0.636, P < 0.01). Isotemporal simulations emphasized amplified effects in overweight children, with boys' zBFR rising rapidly when MVPA was substituted and girls displaying a notable substitution effect between SB and LPA. CONCLUSION: BFP is closely linked to 24-h activity behaviors, notably in overweight and obese preschoolers. ISM identified MVPA as a critical influencer, with a 30-min reduction substantially increasing BFP. Gender disparities were evident, implicating MVPA in boys and LPA and SB in girls.

Preparation of glucoamylase microcapsule beads and application in solid-state fermentation.

BACKGROUND: Baijiu brewing adopts the solid-state fermentation method, using starchy raw materials, Jiuqu as saccharifying fermenting agent, and distilled spirits made by digestion, saccharification, fermentation and distillation. In the late stages of solid-state fermentation of Baijiu, the reduced activity of glucoamylase leads to higher residual starch content in the Jiupei, which affects the liquor yield. The direct addition of exogenous glucoamylase leads to problems such as the temperature of the fermentation environment rising too quickly, seriously affecting the growth of microorganisms. RESULTS: To solve the problem of reduced activity of glucoamylase in the late stage of solid-state fermentation of Baijiu, microcapsule beads (M-B) based on microcapsule emulsion were prepared and the effect of M-B on solid-state fermentation of Baijiu was investigated. The results showed that the release of M-B before and after drying was 53.27% and 25.77% in the liquid state (120 h) and 29.84% and 22.62% in the solid state (15 days), respectively. Adding M-B improved the alcohol by 0.33 %vol and reducing sugar content by 0.51%, reduced the residual starch content by 1.21% of the Jiupei, and had an insignificant effect on the moisture and acidity of the Jiupei. CONCLUSION: M-B have excellent sustained-release properties. The addition of M-B in solid-state fermentation significantly increased the alcohol content, reduced the residual starch content of Jiupei, ultimately improving the starch utilization rate and liquor yield of Baijiu brewing. The preparation of M-B provides methods and approaches for applying other active substances and microorganisms in the brewing of Baijiu. © 2023 Society of Chemical Industry.

Research progress on natural preservatives of meat and meat products: classifications, mechanisms and applications.

Meat and meat products are highly susceptible to contamination by microorganisms and foodborne pathogens, which cause serious economic losses and health hazards. The large consumption and waste of meat and meat products means that there is a need for safe and effective preservation methods. Furthermore, toxicological aspects of chemical preservation techniques related to major health problems have sparked controversies and have prompted consumers and producers to turn to natural preservatives. Consequently, natural preservatives are being increasingly used to ensure the safety and quality of meat products as a result of customer preferences and biological efficacy. However, information on the current status of these preservatives is scattered and a comprehensive review is lacking. Here, we review current knowledge on the classification, mechanisms of natural preservatives and their applications in the preservation of meat and meat products, and also discuss the potential of natural preservatives to improve the safety of meat and meat products. The current status and the current research gaps in the extraction, application and controlled-release of natural antibacterial agents for meat preservation are also discussed in detail. This review may be useful to the development of efficient food preservation techniques in the meat industry. © 2024 Society of Chemical Industry.

Helicoselective Synthesis of Indolohelicenoids through Organocatalytic Central-to-Helical Chirality Conversion.

We report the helicoselective and convergent construction of indolohelicenoids with excellent efficiency and stereocontrol. This reaction proceeds through a chiral-phosphoric-acid-catalyzed enantioselective cycloaddition and eliminative aromatization sequence, which can be finely controlled by adjusting the reaction temperature. Mechanistic studies reveal that the chiral phosphoric acid cooperatively serves as both a bifunctional and Brønsted acid catalyst, enabling one-pot central-to-helical chirality conversion. Additionally, the optical properties of the synthesized indolohelicenoids were characterized to explore their potential applications in organic photoelectric materials.

First-line immunotherapy with anti-PD-1 antibody for extranodal NK/T-cell lymphoma: A retrospective study.

Anti-PD-1 antibody has shown certain effects in patients with newly diagnosed extranodal NK/T-cell lymphoma (ENKTL). Here, we evaluated the clinical efficacy and safety of first-line anti-PD-1 antibody for the treatment of patients with ENKTL and explored biomarkers for treatment response. The clinical data of 107 patients with newly diagnosed ENKTL were retrospectively analysed. Patients received either first-line anti-PD-1 antibody induction treatment or anti-PD-1 antibody combined with asparaginase-based chemotherapy (immunochemotherapy). We found that immunochemotherapy was an independent prognostic factor for longer PFS (p < 0.001). The overall response rate and complete remission rate of immunochemotherapy group was higher than immunotherapy induction group (86.11% vs. 62.86% and 72.22% vs. 52.29%, respectively, p = 0.013). We also observed pretreatment CD4/CD8 ratio >0.83 was significant associated with better response and longer PFS in ENKTL patients received first-line anti-PD1-antibody. Plasma copy number of EBV decreased more significantly in patients with CD4/CD8 ratio >0.83 after treatment. PD-L1 expression was associated with better response and PFS, while elevated plasma IL-6, IL-10 and IFN-γ were associated with poor prognosis. Anti-PD-1 antibody treatment showed promising results in newly diagnosed ENKTL patients. The assessment of pretreatment CD4/CD8 ratio in ENKTL seems feasible for identifying responders to anti-PD-1 antibody treatment.

Study on Microelectrochemical Inhomogeneity of an SA508-309L/308L Overlay Welded Joint.

The corrosion behavior of the dissimilar metal welded joint (DMWJ) is highly dependent on its heterogeneous microstructures. However, directly measuring the electrochemical properties of microstructures in different heat-affected zones (HAZs) is a formidable challenge, because traditional bulk electrochemistry can only offer an average signal. Herein, the microelectrochemical properties of an SA508-309L/308L DMWJ were measured in 3.5 wt % NaCl solution using lithography and capillary techniques. Specifically, high-throughput microelectrochemical tests, including open circuit potential (OCP), electrochemical impedance spectroscopy (EIS), and potentiodynamic polarization (PDP), were conducted on 168 spots (Φ 12 µm). Results revealed five typical EIS responses and seven varieties of PDP curves (different magnitudes of the current density). The maps of thermodynamic and kinetic metrics, such as polarization resistance derived from EIS, corrosion potentials, and corrosion currents extracted from potentiodynamic polarization curves, demonstrated good consistency. The uniform corrosion tendency of the SA508 HAZ subregions during the immersion tests is basically consistent with its Ecorr_avg order of subcritical HAZ (C5, -371 mV) < intercritical HAZ (C4, -546 mV) < fine-grained HAZ2 (C3, -579 mV) < fine-grained HAZ1 (C2, -593 mV). The random presence of inclusions leads to highly heterogeneous microelectrochemical properties of the DMWJ, thereby causing localized corrosion to occur preferentially. Moreover, the macroscopic corrosion behavior is affected by the corrosion products, which display a protective effect that modifies the local electrochemical activity of the SA508 HAZ. The combination of microelectrochemical properties allows for a more comprehensive understanding of the macroscopic corrosion behavior of metals and the galvanic effect between the heterogeneous microstructures.

MnO4--Triggered Immediate-Stable Real-Time Fluorescence Immunosensor with High Response Speed and Low Steady-State Error.

Real-time chemical and biological sensing in vitro is important for application in health and environmental monitoring. Thus, a more rapid and stable detection method is urgently needed. Herein, an immediate-stable real-time fluorescent immunosensor with a high response speed (∼100%, <1 s) and approximately zero steady-state error is constructed. The developed sensor is based on the MnO4--triggered in situ immediate-stable fluorogenic reaction between dopamine and orcinol monohydrate to produce azamonardine (DMTM). The obtained DMTM is identified and characterized by high-resolution mass spectrometry, 1H NMR spectroscopy, 13C NMR spectroscopy, and theoretical calculations. The present sensor achieves a highly sensitive detection of dopamine (DA) with a limit of detection (LOD) of 10 nM as well as alkaline phosphates (ALP) with an LOD of 0.1 mU/mL by using orcinol monohydrate phosphate sodium salt as a substrate. As a proof of concept, ALP-triggered fluorescence ELISA using cardiac troponin I (cTnI) as a model antigen target is further constructed. The developed real-time sensor achieves the detection of cTnI with an LOD of 0.05 ng/mL. Moreover, the sensor proposed by us is successfully applied to assess the cTnI level in clinical serum specimens and yields results consistent with those obtained by the commercial ELISA method. The immediate-stable real-time fluorescence immunosensor provides a promising and powerful platform for the trace detection of biomolecules in clinical diagnosis.

Left atrioventricular interaction and impaired left atrial phasic function in type 2 diabetes mellitus patients with or without anemia: a cardiac magnetic resonance study.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) and anemia are related to some cardiovascular diseases and can predict poor outcomes. Both of them can damage the heart in their own ways, but their combined effects have not been well explored. This study aimed to explore the combined effects of T2DM and anemia and the interaction between left atrial (LA) and left ventricular (LV) function by cardiac magnetic resonance (CMR). MATERIALS AND METHODS: A total of 177 T2DM patients without anemia, 68 T2DM patients with anemia and 73 sex-matched controls were retrospectively enrolled in this study from June 2015 to September 2022. Their LA phasic function and LV function parameters were compared to explore the combined effects of T2DM and anemia and the interaction between LA and LV function. Univariate and multivariate linear regression were done to explore the independent factors influencing LA phasic function and LV function. RESULTS: Compared with controls and T2DM patients without anemia, T2DM patients with anemia were older and had higher heart rate, higher creatinine, lower estimated glomerular filtration rate (eGFR) and lower hemoglobin (Hb) (all p < 0.05). LV global longitudinal peak strain (GLPS) significantly declined from T2DM patients with anemia to T2DM patients without anemia to controls (p < 0.001). LA volumetric function and strain were significantly impaired in T2DM patients with anemia compared with the other groups (all p < 0.05). In addition to age, eGFR, Hb and HbA1c, the LV GLPS was independently associated with all LA phasic strains (LA reservoir strain, ß =0.465; LA conduit strain, ß = 0.450; LA pump strain, ß = 0.360, all p < 0.05). LA global conduit strain, total LA ejection fraction (LAEF) and active LAEF were independently associated with LV GLPS and LVEF. CONCLUSION: Both LA and LV function were severely impaired in T2DM patients with anemia, and T2DM and anemia were independently associated with LA phasic function. Deleterious interaction between LA function and LV function would happen in T2DM patients with or without anemia. Timely and effective monitoring and management of both LA and LV function will benefit T2DM patients.