The signatures and crosstalk of gut microbiome, mycobiome, and metabolites in decompensated cirrhotic patients.

Background: Numerous studies have confirmed that gut microbiota plays a crucial role in the progression of cirrhosis. However, the contribution of gut fungi in cirrhosis is often overlooked due to the relatively low abundance. Methods: We employed 16S ribosomal RNA sequencing, internal transcribed spacer sequencing, and untargeted metabolomics techniques to investigate the composition and interaction of gut bacteria, fungi, and metabolites in cirrhotic patients. Results: Cirrhotic patients exhibited significant differences in the diversity and composition of gut microbiota and their metabolites in cirrhotic patients compared to healthy individuals. Increase in pathogenic microbial genera and a decrease in beneficial microbial genera including bacteria and fungi were observed. Various clinical indexes were closely connected with these increased metabolites, bacteria, fungi. Additionally, endoscopic treatment was found to impact the gut microbiota and metabolites in cirrhotic patients, although it did not significantly alter the gut ecology. Finally, we constructed a cirrhosis diagnostic model based on different features (bacteria, fungi, metabolites, clinical indexes) with an AUC of 0.938. Conclusion: Our findings revealed the characteristics of gut microbial composition and their intricate internal crosstalk in cirrhotic patients, providing cutting-edge explorations of potential roles of gut microbes in cirrhosis.

Angelica sinensis polysaccharide facilitates chondrogenic differentiation of adipose-derived stem cells via MDK-PI3K/AKT signaling cascade.

OBJECT: Adipose-derived mesenchymal stem cells (ADSCs) have received significant attention in the field of cartilage tissue repair. Angelica sinensis polysaccharide (ASP) can enhance both the proliferation and differentiation of mesenchymal stem cells. Therefore, we intend to explore the effect of ASP on chondrogenic differentiation of ADSCs in vitro, and elucidate the underlying mechanisms. METHOD: ADSCs were treated with different concentrations of ASP to determine the optimal concentration. The chondrogenic differentiation of ADSCs was evaluated using Alcian blue staining, qRT-PCR, western blot, and IF staining. Transcriptome sequencing was performed to identify the expression profiles of ADSCs before and after ASP treatment, followed by bioinformatic analyses including differential expression analysis, enrichment analysis, and construction of PPI networks to identify differentially expressed genes (DEGs) associated with ASP and chondrogenic differentiation. RESULT: Surface markers of isolated rat-derived ADSCs were identified by CD44+CD90+CD45-CD106-, and exhibited the capacity for lipogenic, osteogenic, and chondrogenic differentiation. With increasing concentration of ASP treatment, there was an upregulation in the activity and acidic mucosubstance of ADSCs. The levels of Aggrecan, COL2A1, and Sox9 showed an increase in ADSCs after 28 days of 80 µg/ml ASP treatment. Transcriptome sequencing revealed that ASP-associated DEGs regulate extracellular matrix synthesis, immune response, inflammatory response, and cell cycle, and are involved in the NF-κB, AGE-RAGE, and calcium pathways. Moreover, Edn1, Frzb, Mdk, Nog, and Sulf1 are hub genes in DEGs. Notably, ASP upregulated MDK levels in ADSCs, while knockdown of MDK mitigated ASP-induced elevations in acidic mucosubstance, chondrogenic differentiation-related markers (Aggrecan, COL2A1, and Sox9), and the activity of the PI3K/AKT pathway. CONCLUSION: ASP enhances the proliferation and chondrogenic differentiation of ADSCs by activating the MDK-mediated PI3K/AKT pathway.

Influence of suspended particulate matters on P dynamics and eutrophication in the highly turbid estuary: A case study in Hangzhou Bay, China.

Phosphorus (P) is an essential biogenic element in ecosystems; but excessive or insufficient P in coastal waters caused by human activities has led to serious ecological issues. However, the understanding of the dynamic processes of different P forms in high turbidity estuaries/bays, as well as their impact on eutrophication and coastal algal blooms, is still relatively limited. To address this issue, we analyzed P dynamics and their impact on eutrophication in Hangzhou Bay (HZB), which is typical of eutrophic and turbid bay worldwide. The concentration of particulate P (PTP) was 3-5 times higher than that of dissolved inorganic phosphorus (DIP). Seasonal sediment resuspension led to the accumulation of suspended particulate matter (SPM) and PTP with regional variation, both maintaining DIP concentrations above 1 µmol/L within the bay. Furthermore, 3000 tons of bioavailable P were retained in the fine-grained SPM, with the potential for outward transport, fueling subsequent harmful algal blooms. A comparative analysis of global coastal waters highlighted that different turbidity levels significantly affect P cycling. Therefore, understanding the relationship between SPM and P in highly turbid waters is crucial for effective management of eutrophication.

Hydrogen Sulfide Promotes Platelet Autophagy via PDGFR-α/PI3K/Akt Signaling in Cirrhotic Thrombocytopenia.

Background and Aims: The role of platelet autophagy in cirrhotic thrombocytopenia (CTP) remains unclear. This study aimed to investigate the impact of platelet autophagy in CTP and elucidate the regulatory mechanism of hydrogen sulfide (H2S) on platelet autophagy. Methods: Platelets from 56 cirrhotic patients and 56 healthy individuals were isolated for in vitro analyses. Autophagy markers (ATG7, BECN1, LC3, and SQSTM1) were quantified using enzyme-linked immunosorbent assay, while autophagosomes were visualized through electron microscopy. Western blotting was used to assess the autophagy-related proteins and the PDGFR/PI3K/Akt/mTOR pathway following treatment with NaHS (an H2S donor), hydroxocobalamin (an H2S scavenger), or AG 1295 (a selective PDGFR-α inhibitor). A carbon tetrachloride-induced cirrhotic BALB/c mouse model was established. Cirrhotic mice with thrombocytopenia were randomly treated with normal saline, NaHS, or hydroxocobalamin for 15 days. Changes in platelet count and aggregation rate were observed every three days. Results: Cirrhotic patients with thrombocytopenia exhibited significantly decreased platelet autophagy markers and endogenous H2S levels, alongside increased platelet aggregation, compared to healthy controls. In vitro, NaHS treatment of platelets from severe CTP patients elevated LC3-II levels, reduced SQSTM1 levels, and decreased platelet aggregation in a dose-dependent manner. H2S treatment inhibited PDGFR, PI3K, Akt, and mTOR phosphorylation. In vivo, NaHS significantly increased LC3-II and decreased SQSTM1 expressions in platelets of cirrhotic mice, reducing platelet aggregation without affecting the platelet count. Conclusions: Diminished platelet autophagy potentially contributes to thrombocytopenia in cirrhotic patients. H2S modulates platelet autophagy and functions possibly via the PDGFR-α/PI3K/Akt/mTOR signaling pathway.

Fragment correlation mass spectrometry: Determining the structures of biopolymers in a complex mixture without isolating individual components.

Fragment correlation mass spectrometry correlates ion pairs generated from the same fragmentation pathway, achieved by covariance mapping of tandem mass spectra generated with an unmodified linear ion trap without preseparation. We enable the identification of different precursors at different charge states in a complex mixture from a large isolation window, empowering an analytical approach for data-independent acquisition. The method resolves and matches isobaric fragments, internal ions, and disulfide bond fragments. We suggest that this method represents a major advance for analyzing structures of biopolymers in mixtures.

Sudden Cardiac Death Risk Stratification in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) poses a significant clinical challenge, with sudden cardiac death (SCD) emerging as one of the leading causes of mortality. Despite advancements in cardiovascular medicine, predicting and preventing SCD in HFpEF remains complex due to multifactorial pathophysiological mechanisms and patient heterogeneity. Unlike heart failure with reduced ejection fraction, where impaired contractility and ventricular remodeling predominate, HFpEF pathophysiology involves heavy burden of comorbidities such as hypertension, obesity, and diabetes. Diverse mechanisms, including diastolic dysfunction, microvascular abnormalities, and inflammation, also contribute to distinct disease and SCD risk profiles. Various parameters such as clinical factors and electrocardiogram features have been proposed in SCD risk assessment. Advanced imaging modalities and biomarkers offer promise in risk prediction, yet comprehensive risk stratification models specific to HFpEF ar0e lacking. This review offers recent evidence on SCD risk factors and discusses current therapeutic strategies aimed at reducing SCD risk in HFpEF.

Risk factors and predictive nomograms for bedside emergency endoscopic treatment following endotracheal intubation in cirrhotic patients with esophagogastric variceal bleeding.

Data on emergency endoscopic treatment following endotracheal intubation in patients with esophagogastric variceal bleeding (EGVB) remain limited. This retrospective study aimed to explore the efficacy and risk factors of bedside emergency endoscopic treatment following endotracheal intubation in severe EGVB patients admitted in Intensive Care Unit. A total of 165 EGVB patients were enrolled and allocated to training and validation sets in a randomly stratified manner. Univariate and multivariate logistic regression analyses were used to identify independent risk factors to construct nomograms for predicting the prognosis related to endoscopic hemostasis failure rate and 6-week mortality. In result, white blood cell counts (p = 0.03), Child-Turcotte-Pugh (CTP) score (p = 0.001) and comorbid shock (p = 0.005) were selected as independent clinical predictors of endoscopic hemostasis failure. High CTP score (p = 0.003) and the presence of gastric varices (p = 0.009) were related to early rebleeding after emergency endoscopic treatment. Furthermore, the 6-week mortality was significantly associated with MELD scores (p = 0.002), the presence of hepatic encephalopathy (p = 0.045) and postoperative rebleeding (p < 0.001). Finally, we developed practical nomograms to discern the risk of the emergency endoscopic hemostasis failure and 6-week mortality for EGVB patients. In conclusion, our study may help identify severe EGVB patients with higher hemostasis failure rate or 6-week mortality for earlier implementation of salvage treatments.

Construction of a stable fluorescent sensor based on CsPbBr3/CdS core/shell quantum dots for selective and sensitive detection of tetracycline in ethanol.

The weakly bound organic ligand shells around perovskite quantum dots (QDs) are easily decomposed and cannot provide sufficient stability in polar solvents, which greatly obstructs their applications in sensing. Herein, a fluorescent sensor based on CsPbBr3/CdS core/shell QDs was developed for the detection of tetracycline (TC) in the polar solvent-ethanol. Pristine CsPbBr3 QDs were treated with cadmium diethyldithiocarbamate (Cd(DDTC)2) to form a shell on the surface at 110 °C, while extra oleylammonium bromide (OAmBr) was added to inhibit the phase transformation of CsPbBr3 into a Cs4PbBr6 impurity phase during high-temperature processing. And finally CsPbBr3/CdS core/shell QDs were successfully synthesized. The capping with the CdS inorganic shell remediated surface defects and improved the stability in ethanol without affecting the emission properties of the parent CsPbBr3 QDs. The results showed that the fluorescent sensor detected TC in the range of 0.05-25 µM with a low detection limit of 22.6 nM, whereas it had high selectivity and anti-interference ability for TC. And the fluorescence quenching mechanism of the sensor was mainly photoinduced electron transfer between TC and CsPbBr3/CdS QDs. Our research provides a unique way to improve the stability of perovskite QDs in polar solvents and applications in fluorescence detection.

Optimizing Interplanar Spacing, Oxygen Vacancies and Micromorphology via Lithium-Ion Pre-Insertion into Ammonium Vanadate Nanosheets for Advanced Cathodes in Aqueous Zinc-Ion Batteries.

Ammonium vanadates, featuring an N─H···O hydrogen bond network structure between NH4 + and V─O layers, have become popular cathode materials for aqueous zinc-ion batteries (AZIBs). Their appeal lies in their multi-electron transfer, high specific capacity, and facile synthesis. However, a major drawback arises as Zn2+ ions tend to form bonds with electronegative oxygen atoms between V─O layers during cycling, leading to irreversible structural collapse. Herein, Li+ pre-insertion into the intermediate layer of NH4V4O10 is proposed to enhance the electrochemical activity of ammonium vanadate cathodes for AZIBs, which extends the interlayer distance of NH4V4O10 to 9.8 Å and offers large interlaminar channels for Zn2+ (de)intercalation. Moreover, Li+ intercalation weakens the crystallinity, transforms the micromorphology from non-nanostructured strips to ultrathin nanosheets, and increases the level of oxygen defects, thus exposing more active sites for ion and electron transport, facilitating electrolyte penetration, and improving electrochemical kinetics of electrode. In addition, the introduction of Li+ significantly reduces the bandgap by 0.18 eV, enhancing electron transfer in redox reactions. Leveraging these unique advantages, the Li+ pre-intercalated NH4V4O10 cathode exhibits a high reversible capacity of 486.1 mAh g-1 at 0.5 A g-1 and an impressive capacity retention rate of 72% after 5,000 cycles at 5 A g-1.

Hollow VO2 microspheres anchored on graphene as advanced cathodes for aqueous zinc-ion batteries.

Vanadium dioxide-based materials have been proved to be promising cathodes for aqueous zinc ion batteries (AZIBs) due to their cost-effectiveness and high theoretical specific capacity; nevertheless, the low electronic conductivity and poor cycle stability restrict their application. Herein, hollow VO2 microspheres anchored on graphene oxide (H-VO2@GO) are synthesized via a facile simple hydrothermal reaction as high-performance cathodes for AZIBs. The hollow micromorphology of the material provides a large specific surface area and effectively alleviates the volume changes during cycling, while the anchoring of VO2 on graphene oxide greatly improves the electronic conductivity and inhibits the agglomeration and pulverization of the material. Resulting from the combination of unique micromorphology and graphene oxide anchoring, the as-prepared H-VO2@GO exhibits the impressive specific capacity of 400.1 mAh/g at 0.5 A/g and excellent cycling performance with 96.1 % of capacity retention after 1500 cycles at 10 A/g. This investigation provides a use reference for designing high-performance cathodes materials for AZIBs by optimizing the microstructure of electrode materials.

The impact of type 2 diabetes mellitus on the clinical profile, myocardial fibrosis, and prognosis in non-ischemic dilated cardiomyopathy: a prospective cohort study.

BACKGROUND: The impact of the coexistence of type 2 diabetes mellitus (T2DM) in patients with non-ischemic dilated cardiomyopathy (DCM) on clinical profiles, myocardial fibrosis, and outcomes remain incompletely understood. METHOD: A total of 1152 patients diagnosed with non-ischemic DCM were prospectively enrolled from June 2012 to October 2021 and categorized into T2DM and non-T2DM groups. Clinical characteristics, cardiac function, and myocardial fibrosis evaluated by CMR were compared between the two groups. The primary endpoint included both all-cause mortality and heart transplantation. Cause of mortality was classified into heart failure death, sudden cardiac death, and non-cardiac death. Cox regression analysis and Kaplan-Meier analysis were performed to identify the association between T2DM and clinical outcomes. Propensity score matching (PSM) cohort including 438 patients was analyzed to reduce the bias from confounding covariates. RESULTS: Among the 1152 included DCM patients, 155 (13%) patients had T2DM. Patients with T2DM were older (55 ± 12 vs. 47 ± 14 years, P < 0.001), had higher New York Heart Association (NYHA) functional class (P = 0.003), higher prevalence of hypertension (37% vs. 21%, P < 0.001), atrial fibrillation (31% vs. 16%, P < 0.001), lower left ventricular (LV) ejection fraction (EF) (23 ± 9% vs. 27 ± 12%, P < 0.001), higher late gadolinium enhancement (LGE) presence (55% vs. 45%, P = 0.02), and significantly elevated native T1 (1323 ± 81ms vs. 1305 ± 73ms, P = 0.01) and extracellular volume fraction (ECV) (32.7 ± 6.3% vs. 31.3 ± 5.9%, P = 0.01) values. After a median follow-up of 38 months (interquartile range: 20-57 months), 239 patients reached primary endpoint. Kaplan-Meier analysis showed that patients with T2DM had worse clinical outcomes compared with those without T2DM in the overall cohort (annual events rate: 10.2% vs. 5.7%, P < 0.001). T2DM was independently associated with an increased risk of primary endpoint in the overall (Hazard ratio [HR]: 1.61, 95% CI: 1.13-2.33, P = 0.01) and PSM (HR: 1.54, 95% CI: 1.05-2.24, P = 0.02) cohorts. Furthermore, T2DM was associated with a higher risk of heart failure death (P = 0.006) and non-cardiac death (P = 0.02), but not sudden cardiac death (P = 0.16). CONCLUSIONS: Patients with T2DM represented a more severe clinical profile and experienced more adverse outcomes compared to those without T2DM in a large DCM cohort. TRIAL REGISTRATION: Trial registration number: ChiCTR1800017058; URL: https://www. CLINICALTRIALS: gov .

Liver T1 Mapping Derived From Cardiac Magnetic Resonance Imaging: A Potential Prognostic Marker in Idiopathic Dilated Cardiomyopathy.

BACKGROUND: Hepatic alterations are common aftereffects of heart failure (HF) and ventricular dysfunction. The prognostic value of liver injury markers derived from cardiac MRI studies in nonischemic dilated cardiomyopathy (DCM) patients is unclear. PURPOSE: Evaluate the prognostic performance of liver injury markers derived from cardiac MRI studies in DCM patients. STUDY TYPE: Prospective. POPULATION: Three hundred fifty-six consecutive DCM patients diagnosed according to ESC guidelines (age 48.7 ± 14.2 years, males 72.6%). FIELD STRENGTH/SEQUENCE: Steady-state free precession, modified Look-Locker inversion recovery T1 mapping and phase sensitive inversion recovery late gadolinium enhancement (LGE) sequences at 3 T. ASSESSMENT: Clinical characteristics, conventional MRI parameters (ventricular volumes, function, mass), native myocardial and liver T1, liver extracellular volume (ECV), and myocardial LGE presence were assessed. Patients were followed up for a median duration of 48.3 months (interquartile range 42.0-69.9 months). Primary endpoints included HF death, sudden cardiac death, heart transplantation, and HF readmission; secondary endpoints included HF death, sudden cardiac death, and heart transplantation. Models were developed to predict endpoints and the incremental value of including liver parameters assessed. STATISTICAL TESTS: Optimal cut-off value was determined using receiver operating characteristic curve and Youden method. Survival analysis was performed using Kaplan-Meier and Cox proportional hazard. Discriminative power of models was compared using net reclassification improvement and integrated discriminatory index. P value <0.05 was considered statistically significant. RESULTS: 47.2% patients reached primary endpoints; 25.8% patients reached secondary endpoints. Patients with elevated liver ECV (cut-off 34.4%) had significantly higher risk reaching primary and secondary endpoints. Cox regression showed liver ECV was an independent prognostic predictor, and showed independent prognostic value for primary endpoints and long-term HF readmission compared to conventional clinical and cardiac MRI parameters. DATA CONCLUSIONS: Liver ECV is an independent prognostic predictor and may serve as an innovative approach for risk stratification for DCM. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Prognostic value of mid-term cardiovascular magnetic resonance follow-up in patients with non-ischemic dilated cardiomyopathy: a prospective cohort study.

BACKGROUND: The prognostic value of follow-up cardiovascular magnetic resonance (CMR) in dilated cardiomyopathy (DCM) patients is unclear. We aimed to investigate the prognostic value of cardiac function, structure, and tissue characteristics at mid-term CMR follow-up. METHODS: The study population was a prospectively enrolled cohort of DCM patients who underwent guideline-directed medical therapy with baseline and follow-up CMR, which included measurement of biventricular volume and ejection fraction, late gadolinium enhancement, native T1, native T2, and extracellular volume. During follow-up, major adverse cardiac events (MACE) were defined as a composite endpoint of cardiovascular death, heart transplantation, and heart-failure readmission. RESULTS: Among 235 DCM patients (median CMR interval: 15.3 months; interquartile range: 12.5-19.2 months), 54 (23.0%) experienced MACE during follow-up (median: 31.2 months; interquartile range: 20.8-50.0 months). In multivariable Cox regression, follow-up CMR models showed significantly superior predictive value than baseline CMR models. Stepwise multivariate Cox regression showed that follow-up left ventricular ejection fraction (LVEF; hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.91-0.96; p < 0.001) and native T1 (HR, 1.01; 95% CI, 1.00-1.01; p = 0.030) were independent predictors of MACE. Follow-up LVEF ≥ 40% or stable LVEF < 40% with T1 ≤ 1273 ms indicated low risk (annual event rate < 4%), while stable LVEF < 40% and T1 > 1273 ms or LVEF < 40% with deterioration indicated high risk (annual event rate > 15%). CONCLUSIONS: Follow-up CMR provided better risk stratification than baseline CMR. Improvements in the LVEF and T1 mapping are associated with a lower risk of MACE.

Dual immobilization of porous Si by graphene supported anatase TiO2/carbon for high-performance and safe lithium storage.

Smart surface coatings have been proven to be an effective strategy to significantly enhance the electronic conductivity and cycling stability of silicon-based anode materials. However, the single/conventional coatings face critical challenges, including low initial Coulomb efficiency (ICE), poor cyclability, and kinetics failure, etc. Hence, we proposed a dual immobilization strategy to synthesize graphene supported anatase TiO2/carbon-coated porous silicon composite (denoted as PSi@TiO2@C/Graphene) using industrial-grade ferrosilicon as lithium storage raw materials through the simple etching, combined with sol-gel and hydrothermal coating processes. In this work, the dual immobilization from the "confinement effect" of the inner TiO2 shell and the "synergistic effect" of the outer carbon shell, improves the kinetics of the electrochemical reaction and ensures the integrity of the electrode material structure during lithiation. Furthermore, the introduction of the graphene substrate offers ample space for dispersing and anchoring the Si-based granules, which in turn provides a stable 3D conductive network between the particles. As a result, the PSi@TiO2@C/Graphene electrode delivers high reversible capacity of 1605.4 mAh g-1 with 93.65% retention at 0.5 A g-1 after 100 cycles (vs. 4th discharge), high initial Coulomb efficiency (82.30%), and superior cyclability of 1159.9 mAh g-1 after 250 cycles. The above results suggest that the particle structure has great potential for applications in Si-based anode and may provide some inspiration for the design of other energy storage materials.

Left ventricular underfilling in PAH: A potential indicator for adaptive-to-maladaptive transition.

Pulmonary arterial hypertension (PAH) still remains a life-threatening disorder with poor prognosis. The right ventricle (RV) adapts to the increased afterload by a series of prognostically significant morphological and functional changes, the adaptive nature should also be understood in the context of ventricular interdependence. We hypothesized that left ventricle (LV) underfilling could serve as an important imaging marker for identifying maladaptive changes and predicting clinical outcomes in PAH patients. We prospectively enrolled patients with PAH who underwent both cardiac magnetic resonance and right heart catheterization between October 2013 and December 2020. Patients were categorized into four groups based on their LV and RV mass/volume ratio (M/V). LV M/V was stratified using the normal value (0.7 g/mL for males and 0.6 g/mL for females) to identify patients with LV underfilling (M/V ≥ normal value), while RV M/V was stratified based on the median value. The primary endpoint was all-cause mortality, and the composite endpoints included all-cause mortality and heart failure-related readmissions. A total of 190 PAH patients (53 male, mean age 37 years) were included in this study. Patients with LV underfilling exhibited higher NT-proBNP levels, increased RV mass, larger RV but smaller LV, lower right ventricular ejection fraction, and shorter 6-min walking distance. Patients with LV underfilling had a 2.7-fold higher risk of mortality than those without and LV M/V (hazard ratio [per 0.1 g/mL increase]: 1.271, 95% confidence interval: 1.082-1.494, p = 0.004) was also independent predictors of all-cause mortality. Moreover, patients with low LV M/V had a better prognosis regardless of the level of RV M/V. Thus, LV underfilling is an independent predictor of adverse clinical outcomes in patients with PAH, and it could be an important imaging marker for identifying maladaptive changes in these patients.

Pulmonary Transit Time Derived from First-Pass Perfusion Cardiac MR Imaging: A Potential New Marker for Cardiac Involvement and Prognosis in Light-Chain Amyloidosis.

BACKGROUND: First-pass perfusion cardiac MR imaging could reflect pulmonary hemodynamics. However, the clinical value of pulmonary transit time (PTT) derived from first-pass perfusion MRI in light-chain (AL) amyloidosis requires further evaluation. PURPOSE: To assess the clinical and prognostic value of PTT in patients with AL amyloidosis. STUDY TYPE: Prospective observational study. POPULATION: 226 biopsy-proven systemic AL amyloidosis patients (age 58.62 ± 10.10 years, 135 males) and 43 healthy controls (age 42 ± 16.2 years, 20 males). FIELD STRENGTH/SEQUENCE: SSFP cine and phase sensitive inversion recovery late gadolinium enhancement (LGE) sequences, and multislice first-pass myocardial perfusion imaging with a saturation recovery turbo fast low-angle shot (SR-TurboFLASH) pulse sequence at 3.0T. ASSESSMENT: PTT was measured as the time interval between the peaks of right and left ventricular cavity arterial input function curves on first-pass perfusion MR images. STATISTICAL TESTS: Independent-sample t test, Mann-Whitney U test, Chi-square test, Fisher's exact test, analysis of variance, or Kruskal-Wallis test, as appropriate; univariable and multivariable Cox proportional hazards models and Kaplan-Meier curves, area under receiver operating characteristic curve were used to determine statistical significance. RESULTS: PTT could differentiate AL amyloidosis patients with (N = 188) and without (N = 38) cardiac involvement (area under the curve [AUC] = 0.839). During a median follow-up of 35 months, 160 patients (70.8%) demonstrated all-cause mortality. After adjustments for clinical (Hazard ratio [HR] 1.061, confidence interval [CI]: 1.021-1.102), biochemical (HR 1.055, CI: 1.014-1.097), cardiac MRI-derived (HR 1.077, CI: 1.034-1.123), and therapeutic (HR 1.063, CI: 1.024-1.103) factors, PTT predicted mortality independently in patients with AL amyloidosis. Finally, PTT could identify worse outcomes in patients demonstrating New York Heart Association class III, Mayo 2004 stage III, and transmural LGE pattern. DATA CONCLUSION: PTT may serve as a new imaging predictor of cardiac involvement and prognosis in AL amyloidosis. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Ecotoxicological effects of antibiotic adsorption behavior of microplastics and its management measures.

Microplastics adsorb heavy metals and organic pollutants to produce combined pollution. Recently, the adsorption behavior of antibiotics on microplastics has received increasing attention. Exploring the sorption behavior of pollutants on microplastics is an important reference in understanding their ecological and environmental risk studies. In this paper, by reviewing the academic literature in recent years, we clarified the current status of research on the adsorption behavior of antibiotics on microplastics, discussed its potential hazards to ecological environment and human health, and summarized the influence of factors on the adsorption mechanisms. The results show that the adsorption behavior of antibiotics on microplastics is controlled by the physical and chemical properties of antibiotics, microplastics, and water environment. Antibiotics are adsorbed on microplastics through physical and chemical interactions, which include hydrophobic interaction, partitioning, electrostatic interaction, and other non-covalent interactions. Intensity of adsorption between them is mainly determined by their physicochemical properties. The basic physicochemical properties of the aqueous environment (e.g., pH, salinity, ionic strength, soluble organic matter content, and temperature) will affect the physicochemical properties of microplastics and antibiotics (e.g., particle size, state of dispersibility, and morphology), leading to differences in the type and strength of their interactions. This paper work is expected to provide a meaningful perspective for better understanding the potential impacts of antibiotic adsorption behavior of microplastics on aquatic ecology and human health. In the meantime, some indications for future related research are provided.

Characterization of Rab32- and Rab38-positive lysosome-related organelles in osteoclasts and macrophages.

Both the biogenesis and functions of osteoclasts and macrophages involves dynamic membrane traffic. We screened transcript levels for Rab family small GTPases related to osteoclasts and identified Rab38. Rab38 expression is upregulated during osteoclast differentiation and maturation. In osteoclasts, both Rab38 and its paralog, Rab32, colocalize to lysosome-related organelles (LROs). In macrophages, Rab32 is also found in LROs. LROs are part of the endocytic pathway but are distinct from lysosomes. After receptor activator of NF-κB ligand stimulation, LROs contain cathepsin K and tartrate-resistant acid phosphatase inside and help both proteins to accumulate around bone resorption pits. After osteoclast maturation, these enzymes are hardly found within LROs. In macrophages derived from Rab32 and Rab38 double knockout mice, both acidification and V-ATPase a3 localization were severely compromised. Both the double knockout macrophage and bafilomycin-treated wildtype macrophage show an increase in Lamp1-positive organelles, implying that biogenesis of lysosomes and LROs are related. These results indicate that Rab32 and Rab38 both play a crucial role in LRO biogenesis in macrophages and in osteoclasts.

Silica particles convert thiol-containing molecules to disulfides.

Synthetic amorphous silica is a common food additive and a popular cosmetic ingredient. Mesoporous silica particles are also widely studied for their potential use in drug delivery and imaging applications because of their unique properties, such as tunable pore sizes, large surfaces areas, and assumed biocompatibility. Such a nanomaterial, when consisting of pure silicon dioxide, is generally considered to be chemically inert, but in this study, we showed that oxidation yields for different compounds were facilitated by simply incubating aqueous solutions with pure silica particles. Three thiol-containing molecules, L-cysteine, glutathione, and D-penicillamine, were studied separately, and it was found that more than 95% of oxidation happened after incubating any of these compounds with mesoporous silica particles in the dark for a day at room temperature. Oxidation increased over incubation time, and more oxidation was found for particles having larger surface areas. For nonporous silica particles at submicron ranges, yields of oxidation were different based on the structures of molecules, correlating with steric hindrance while accessing surfaces. We propose that the silyloxy radical (SiO•) on silica surfaces is what facilitates oxidation. Density functional theory calculations were conducted for total energy changes for reactions between different aqueous species and silicon dioxide surfaces. These calculations identified two most plausible pathways of the lowest energy to generate SiO• radicals from water radical cations H2O•+ and hydroxyl radicals •OH, previously known to exist at water interfaces.