Recycling Fe and improving organic pollutant removal via in situ forming magnetic core-shell Fe3O4@CaFe-LDH in Fe(II)-catalyzed oxidative wastewater treatment.

Due to its high efficiency, Fe(II)-based catalytic oxidation has been one of the most popular types of technology for treating growing organic pollutants. A lot of chemical Fe sludge along with various refractory pollutants was concomitantly produced, which may cause secondary environmental problems without proper disposal. We here innovatively proposed an effective method of achieving zero Fe sludge, reusing Fe resources (Fe recovery = 100%) and advancing organics removal (final TOC removal > 70%) simultaneously, based on the in situ formation of magnetic Ca-Fe layered double hydroxide (Fe3O4@CaFe-LDH) nano-material. Cations (Ca2+ and Fe3+) concentration (≥ 30 mmol/L) and their molar ratio (Ca:Fe ≥ 1.75) were crucial to the success of the method. Extrinsic nano Fe3O4 was designed to be involved in the Fe(II)-catalytic wastewater treatment process, and was modified by oxidation intermediates/products (especially those with COO- structure), which promoted the co-precipitation of Ca2+ (originated from Ca(OH)2 added after oxidation process) and by-produced Fe3+ cations on its surface to in situ generate core-shell Fe3O4@CaFe-LDH. The oxidation products were further removed during Fe3O4@CaFe-LDH material formation via intercalation and adsorption. This method was applicable to many kinds of organic wastewater, such as bisphenol A, methyl orange, humics, and biogas slurry. The prepared magnetic and hierarchical CaFe-LDH nanocomposite material showed comparable application performance to the recently reported CaFe-LDHs. This work provides a new strategy for efficiently enhancing the efficiency and economy of Fe(II)-catalyzed oxidative wastewater treatment by producing high value-added LDHs materials.

Biparatopic anti-PCSK9 antibody enhances the LDL-uptake in HepG2 cells.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce lipids. In 2020, we reported a chimeric camelid-human heavy chain antibody VHH-B11-Fc targeting PCSK9. Recently, it was verified that VHH-B11 binds one linear epitope in the PCSK9 hinge region. To enhance its druggability, we have developed a novel biparatopic B11-H2-Fc Ab herein. Thereinto, surface plasmon resonance (SPR) confirmed the epitope differences in binding-PCSK9 among VHH-B11, VHH-H2 and the approved Repatha. Additionally, SPR revealed the B11-H2-Fc exhibits an avidity of approximately 0.036 nM for PCSK9, representing a considerable increase compared to VHH-B11-Fc (~ 0.69 nM). Moreover, we found the Repatha and B11-H2-Fc exhibited > 95% PCSK9 inhibition efficiency compared to approximately 48% for the VHH-Fc at 7.4 nM (P < 0.0005). Further, we verified its biological activity using the human hepatoma cells G2 model, where the B11-H2-Fc exhibited almost 100% efficiency in PCSK9 inhibition at only 0.75 µM. The immunoblotting results of low-density lipoprotein cholesterol (LDL-c) uptake assay also demonstrated the excellent performance of B11-H2-Fc on recovering the LDL-c receptor (LDLR), as strong as the Repatha (P > 0.05). These findings provide the first evidence of the efficacy of a novel Ab targeting PCSK9 in the field of lipid-lowering drugs.

Novel therapeutic strategies and drugs for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown etiology. Currently, drugs used to treat IPF in clinical practice exhibit severe side effects and limitations. To address these issues, this paper discusses the therapeutic effects of preclinical targeted drugs (such as STAT3 and TGF-ß/Smad pathway inhibitors, chitinase inhibitors, PI3K and phosphodiesterase inhibitors, etc.) and natural products on IPF. Through a summary of current research progress, it is found that natural products possess multitarget effects, stable therapeutic efficacy, low side effects, and nondrug dependence. Furthermore, we discuss the significant prospects of natural product molecules in combating fibrosis by influencing the immune system, expecting that current analytical data will aid in the development of new drugs or the investigation of active ingredients in natural products for potential IPF treatments in the future.

Construction and validation of risk prediction models for pulmonary embolism in hospitalized patients based on different machine learning methods.

Objective: This study aims to apply different machine learning (ML) methods to construct risk prediction models for pulmonary embolism (PE) in hospitalized patients, and to evaluate and compare the predictive efficacy and clinical benefit of each model. Methods: We conducted a retrospective study involving 332 participants (172 PE positive cases and 160 PE negative cases) recruited from Guangdong Medical University. Participants were randomly divided into a training group (70%) and a validation group (30%). Baseline data were analyzed using univariate analysis, and potential independent risk factors associated with PE were further identified through univariate and multivariate logistic regression analysis. Six ML models, namely Logistic Regression (LR), Decision Tree (DT), Random Forest (RF), Naive Bayes (NB), Support Vector Machine (SVM), and AdaBoost were developed. The predictive efficacy of each model was compared using the receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC). Clinical benefit was assessed using decision curve analysis (DCA). Results: Logistic regression analysis identified lower extremity deep venous thrombosis, elevated D-dimer, shortened activated partial prothrombin time, and increased red blood cell distribution width as potential independent risk factors for PE. Among the six ML models, the RF model achieved the highest AUC of 0.778. Additionally, DCA consistently indicated that the RF model offered the greatest clinical benefit. Conclusion: This study developed six ML models, with the RF model exhibiting the highest predictive efficacy and clinical benefit in the identification and prediction of PE occurrence in hospitalized patients.

Cold inducible RNA binding protein-regulated mitochondria associated endoplasmic reticulum membranes-mediated Ca2+ transport play a critical role in hypothermia cerebral resuscitation.

Cardiac arrest is a global health issue causing more deaths than many other diseases. Hypothermia therapy is commonly used to treat secondary brain injury resulting from cardiac arrest. Previous studies have shown that CIRP is induced in specific brain regions during hypothermia and inhibits mitochondrial apoptotic factors. However, the specific mechanisms by which hypothermia-induced CIRP exerts its anti-apoptotic effect are still unknown. This study aims to investigate the role of Cold-inducible RNA-binding protein (CIRP) in mitochondrial-associated endoplasmic reticulum membrane (MAM)-mediated Ca2+ transport during hypothermic brain resuscitation.We constructed a rat model of cardiac arrest and resuscitation and hippocampal neuron oxygen-glucose deprivation/reoxygenation model. We utilized shRNA transfection to interfere the expression of CIRP and observe the effect of CIRP on the structure and function of MAM.Hypothermia induced CIRP can reduce the apoptosis of hippocampal neurons, and improve the survival rate of rats. Hypothermia induced CIRP can reduce the expressions of calcium transporters IP3R and VDAC1 in MAM, reduce the concentration of calcium in mitochondria, decrease the expression of ROS, and stabilize the mitochondrial membrane potential. Immunofluorescence and immunocoprecipitation showed that CIRP could directly interact with IP3R-VDAC1 complex, thereby changing the structure of MAM, inhibiting calcium transportation and improving mitochondrial function in vivo and vitro.Both in vivo and in vitro experiments have confirmed that hypothermia induced CIRP can act on the calcium channel IP3R-VDAC1 in MAM, reduce the calcium overload in mitochondria, improve the energy metabolism of mitochondria, and thus play a role in neuron resuscitation. This study contributes to understanding hypothermia therapy and identifies potential targets for brain injury treatment.

Exceptional Rate Performances of Li-Rich Mn-Based Cathodes Enabled by Boron-Based Additives-Driven Self-Optimized Interface.

Li-rich Mn-based cathode material (LRM), as a promising cathode for high energy density lithium batteries, suffers from severe side reactions in conventional lithium hexafluorophosphate (LiPF6)-based carbonate electrolytes, leading to unstable interfaces and poor rate performances. Herein, a boron-based additives-driven self-optimized interface strategy is presented to dissolve low ionic conductivity LiF nanoparticles at the outer cathode electrolyte interface, leading to the optimized interfacial components, as well as the enhanced Li ion migration rate in electrolytes. Being attributed to these superiorities, the LRM||Li battery delivers a high-capacity retention of 92.19% at 1C after 200 cycles and a low voltage decay of 1.08 mV/cycle. This work provides a new perspective on the rational selection of functional additives with an interfacial self-optimized characteristic to achieve a long lifespan LRM with exceptional rate performances.

Well-defined asymmetric nitrogen/carbon-coordinated single metal sites for carbon dioxide conversion.

Asymmetric nitrogen/carbon-coordinated single metal sites (M-NxC4-x) outperform symmetric M-N4 sites in carbon dioxide (CO2) electroreduction. However, the challenge of crafting well-defined M-NxC4-x sites complicates the understanding of their structure-catalytic performance relationship. In this study, we employ metallized N-confused tetraphenylporphyrin (M-NCTPP) to investigate CO2 conversion on M-N3C1 sites using both density functional theory and experimental methods. The optimal cobalt (Co)-N3C1 site (Co-NCTPP) achieves a current density of 500 mA cm-2 and a carbon monoxide Faraday efficiency exceeding 90 % at -1.25 V vs. the reversible hydrogen electrode, surpassing the performance of Co-N4 (Co-TPP). This research introduces a novel approach for designing and synthesizing high-activity heteroatom-anchored single metal sites, advancing fundamental understanding in the field.

Impact of additional cytogenetic aberrations at diagnosis on prognosis of adults patients with Philadelphia chromosome positive acute lymphoblastic leukemia undergoing allogeneic hematopoietic cell transplantation: a retrospective analysis.

Additional chromosomal abnormalities(ACAs) at diagnosis are associated with inferior prognosis in chronic myeloid leukemia. However, the prognostic significance of ACAs in adult patients with Philadelphia Chromosome Positive acute lymphoblastic leukemia (Ph + ALL) receiving TKI-targeted drugs and allogeneic hematopoietic stem cell transplantation(HSCT) is unknown. One hundred thirty-six adult patients with Ph + ALL were included in the study and retrospectively analysed, evaluating the effect of ACAs on outcomes of transplantation. ACAs are observed in 60 cases (44%). ACAs detected in more than 5% of cases were defined as major-route and encompass: +der(22), +der(9), + 8, -7 and complex karyotype. The median follow-up was 26.4 months. In the subgroup analyses of major route ACAs, three-year cumulative incidence of relapse (CIR) and progression-free survival(PFS) are statistically significant in + 8[66.7% vs.23.7%, P = 0.024; 77.8% vs. 23.7%, P = 0.0087], -7[53.8% vs. 23.7%, P = 0.035%; 61.5% vs. 32.9%, P = 0.033], and complex karyotypes[42.9% vs. 23.7%, P = 0.027; 47.6% vs. 23.7%] compared with t(9;22) sole. Additionally, the 3-year CIR for Ph + ALL with + der(22) is 44% vs. 23.7% for t(9;22) sole(P = 0.045). The 3-year overall survival (OS) in the - 7 group is 46.5%, which is statistically significant compared with the other groups(P = 0.001). In multivariate analyses, three years CIR and PFS are statistically significant in + der(22), + 8, -7 and complex karyotype compared with t(9;22) sole(P < 0.05). More importantly, Ph + ALL with - 7 was negatively associated with the rate of 3-year OS(P = 0.012). Thus, ACAs at diagnosis appear to have a significant prognostic impact on transplantation outcomes in patients with Ph + ALL.

Assessing the modification impact of vaccination on the relationship of the Discomfort Index with hand, foot, and mouth disease in Guizhou: A multicounty study.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a major public health issue in China while temperature and humidity are well-documented predictors. However, evidence on the combined effect of temperature and humidity is still limited. It also remains unclear whether such an effect could be modified by the enterovirus 71 (EV71) vaccination. METHODS: Based on 320,042 reported HFMD cases during the summer months between 2012 and 2019, we conducted a study utilizing Distributed Lag Non-Linear Models (DLNM) and time-varying DLNM to examine how China's HFMD EV71 vaccine strategy would affect the correlation between meteorological conditions and HFMD risk. RESULTS: The incidence of HFMD changed with the Discomfort Index in an arm-shaped form. The 14-day cumulative risk of HFMD exhibited a statistically significant increase during the period of 2017-2019 (following the implementation of the EV71 vaccine policy) compared to 2012-2016 (prior to the vaccine implementation). For the total population, the range of relative risk (RR) values for HFMD at the 75th, 90th, and 99th percentiles increased from 1.082-1.303 in 2012-2016 to 1.836-2.022 in 2017-2019. In the stratified analyses, Han Chinese areas show stronger relative growth, with RR values at the 75th, 90th, and 99th percentiles increased by 14.3%, 39.1%, and 134.4% post-vaccination, compared to increases of 22.7%, 41.6%, and 38.8% in minority areas. Similarly, boys showed greater increases (24.4%, 47.7%, 121.5%) compared to girls (8.1%, 28.1%, 58.3%). Additionally, the central Guizhou urban agglomeration displayed a tendency for stronger relative growth compared to other counties. CONCLUSIONS: Although the EV71 vaccine policy has been implemented, it hasn't effectively controlled the overall risk of HFMD. There's been a shift in the main viral subtypes, potentially altering population susceptibility and influencing HFMD occurrences. The modulating effects of vaccine intervention may also be influenced by factors such as race, sex, and economic level.

Early evolution of the ecdysozoan body plan.

Extant ecdysozoans (moulting animals) are represented by a great variety of soft-bodied or articulated organisms that may or may not have appendages. However, controversies remain about the vermiform nature (i.e. elongated and tubular) of their ancestral body plan. We describe here Beretella spinosa gen. et sp. nov. a tiny (maximal length 3 mm) ecdysozoan from the lowermost Cambrian, Yanjiahe Formation, South China, characterized by an unusual sack-like appearance, single opening, and spiny ornament. Beretella spinosa gen. et sp. nov has no equivalent among animals, except Saccorhytus coronarius, also from the basal Cambrian. Phylogenetic analyses resolve both fossil species as a sister group (Saccorhytida) to all known Ecdysozoa, thus suggesting that ancestral ecdysozoans may have been non-vermiform animals. Saccorhytids are likely to represent an early off-shot along the stem-line Ecdysozoa. Although it became extinct during the Cambrian, this animal lineage provides precious insight into the early evolution of Ecdysozoa and the nature of the earliest representatives of the group.

Pre-Intercalation of TMA Cations in MoS2 Interlayers for Fast and Stable Zinc Ion Storage.

Applications of aqueous zinc ion batteries (ZIBs) for grid-scale energy storage are hindered by the lacking of stable cathodes with large capacity and fast redox kinetics. Herein, the intercalation of tetramethylammonium (TMA+) cations is reported into MoS2 interlayers to expand its spacing from 0.63 to 1.06 nm. The pre-intercalation of TMA+ induces phase transition of MoS2 from 2H to 1T phase, contributing to an enhanced conductivity and better wettability. Besides, The calculation from density functional theory indicates that those TMA+ can effectively shield the interactions between Zn2+ and MoS2 layers. Consequently, two orders magnitude high Zn2+ ions diffusion coefficient and 11 times enhancement in specific capacity (212.4 vs 18.9 mAh g‒1 at 0.1 A g‒1) are achieved. The electrochemical investigations reveal both Zn2+ and H+ can be reversibly co-inserted into the MoS2-TMA electrode. Moreover, the steady habitat of TMA+ between MoS2 interlayers affords the MoS2-TMA with remarkable cycling stability (90.1% capacity retention after 2000 cycles at 5.0 A g‒1). These performances are superior to most of the recent zinc ion batteries assembled with MoS2 or VS2-based cathodes. This work offers a new avenue to tuning the structure of MoS2 for aqueous ZIBs.

Tumour vasculature at single-cell resolution.

Tumours can obtain nutrients and oxygen required to progress and metastasize through the blood supply1. Inducing angiogenesis involves the sprouting of established vessel beds and their maturation into an organized network2,3. Here we generate a comprehensive atlas of tumour vasculature at single-cell resolution, encompassing approximately 200,000 cells from 372 donors representing 31 cancer types. Trajectory inference suggested that tumour angiogenesis was initiated from venous endothelial cells and extended towards arterial endothelial cells. As neovascularization elongates (through angiogenic stages SI, SII and SIII), APLN+ tip cells at the SI stage (APLN+ TipSI) advanced to TipSIII cells with increased Notch signalling. Meanwhile, stalk cells, following tip cells, transitioned from high chemokine expression to elevated TEK (also known as Tie2) expression. Moreover, APLN+ TipSI cells not only were associated with disease progression and poor prognosis but also hold promise for predicting response to anti-VEGF therapy. Lymphatic endothelial cells demonstrated two distinct differentiation lineages: one responsible for lymphangiogenesis and the other involved in antigen presentation. In pericytes, endoplasmic reticulum stress was associated with the proangiogenic BASP1+ matrix-producing pericytes. Furthermore, intercellular communication analysis showed that neovascular endothelial cells could shape an immunosuppressive microenvironment conducive to angiogenesis. This study depicts the complexity of tumour vasculature and has potential clinical significance for anti-angiogenic therapy.

Associations of body mass index, waist circumference and the weight-adjusted waist index with daily living ability impairment in older Chinese people: A cross-sectional study of the Chinese Longitudinal Healthy Longevity Survey.

AIM: To investigate the associations of body mass index (BMI), waist circumference (WC) and the weight-adjusted waist index (WWI) with the impairment of activities of daily living (ADL) in older Chinese people. METHODS: A total of 13 260 participants aged 65 years and older from the 2018 Chinese Longitudinal Healthy Longevity Survey were included in this cross-sectional study. BMI, WC and the WWI were calculated from measurements of height, weight and WC. Binary logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Non-linear correlations were investigated using restricted cubic spline curves. RESULTS: In multivariate logistic regression fully adjusted for confounding variables, our analyses revealed significant associations between WC and WWI and ADL impairment, with adjusted ORs (95% CI) of 1.01 (1.00, 1.01) and 1.08 (1.03, 1.12), respectively. Meanwhile, participants with a high WWI had a higher risk of ADL impairment compared with those with a low WWI, with an adjusted OR (95% CI) of 1.12 (1.02, 1.23). Subgroup analyses showed that only the association between WWI and ADL impairment did not differ in any of the different populations. In addition, we found that BMI, WC and WWI were non-linearly associated with ADL impairment. CONCLUSIONS: There are significant associations between WC and WWI and ADL impairment in older Chinese people. The findings show the ability of the WWI to serve as a comprehensive and effective indicator of obesity in older Chinese people and emphasize the importance of assessing WWI in screening and preventing ADL impairment in older people.

The Diagnostic Efficiency and Safety of Transbronchial Lung Cryobiopsy Using 1.1-mm Cryoprobe in Diagnosing Interstitial Lung Disease.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is increasingly used to diagnose interstitial lung disease (ILD). The 1.1-mm cryoprobe has recently been available in clinical practice. The diagnostic yield and safety of TBLC using a 1.1-mm cryoprobe need to be confirmed. METHODS: A prospective, randomized controlled trial was conducted in patients with suspected ILD and randomly assigned to 1.1-mm and 1.9-mm cryoprobe groups. The primary outcome was the diagnostic yield of multidisciplinary discussion. Secondary outcomes were sample quality and incidence of complications. The tension and stress effects during TBLC onto the target lobe caused by 1.1-mm and 1.9-mm cryoprobes were also evaluated using finite element analysis. RESULTS: A total of 224 patients were enrolled. No significant differences were observed in the diagnostic yield (80.4% vs. 79.5%, p = 0.845) and sample quality scores (5.73 ± 0.64 vs. 5.66 ± 0.77; p = 0.324) between the 1.9-mm cryoprobe group and 1.1-mm cryoprobe group. The average surface areas of samples in 1.1-mm cryoprobe group were smaller, while no difference in sample weights was observed. A decreased incidence of moderate bleeding was found in the 1.1-mm cryoprobe group (17.0% vs. 6.2%, p = 0.027), while there was no difference in the incidence of the pneumothorax, there was a trend to higher rate of pneumothorax in 1.1-mm group. In finite element analysis, the 1.1-mm cryoprobe required the largest tension and produced the largest stress. CONCLUSION: Compared with a 1.9-mm cryoprobe, there was no difference in specimen quality or diagnostic rate but smaller sample size with a 1.1-mm cryoprobe. There was a decreased risk of moderate bleeding, but a trend towards increased risk for pneumothorax with 1.1-mm cryoprobe. TRAIL REGISTRATION: Clinicaltrials.gov identifier NCT04047667; registered August 4, 2019.

A Novel Approach for the Detection and Severity Grading of Chronic Obstructive Pulmonary Disease Based on Transformed Volumetric Capnography.

Chronic Obstructive Pulmonary Disease (COPD), as the third leading cause of death worldwide, is a major global health issue. The early detection and grading of COPD are pivotal for effective treatment. Traditional spirometry tests, requiring considerable physical effort and strict adherence to quality standards, pose challenges in COPD diagnosis. Volumetric capnography (VCap), which can be performed during natural breathing without requiring additional compliance, presents a promising alternative tool. In this study, the dataset comprised 279 subjects with normal pulmonary function and 148 patients diagnosed with COPD. We introduced a novel quantitative analysis method for VCap. Volumetric capnograms were converted into two-dimensional grayscale images through the application of Gramian Angular Field (GAF) transformation. Subsequently, a multi-scale convolutional neural network, CapnoNet, was conducted to extract features and facilitate classification. To improve CapnoNet's performance, two data augmentation techniques were implemented. The proposed model exhibited a detection accuracy for COPD of 95.83%, with precision, recall, and F1 measures of 95.21%, 95.70%, and 95.45%, respectively. In the task of grading the severity of COPD, the model attained an accuracy of 96.36%, complemented by precision, recall, and F1 scores of 88.49%, 89.99%, and 89.15%, respectively. This work provides a new perspective for the quantitative analysis of volumetric capnography and demonstrates the strong performance of the proposed CapnoNet in the diagnosis and grading of COPD. It offers direction and an effective solution for the clinical application of capnography.

In vitro inhibitory effects of selumetinib on activity of human UDP-glucuronosyltransferases and prediction of in vivo drug-drug interactions.

Selumetinib is an oral, effective, and selective tyrosine kinase inhibitor targeting mitogen-activated protein kinase 1 and 2 (MEK1/2), which is clinically active in multiple tumor types, such as neurofibromatosis type 1 (NF1), melanoma, gliomas and non-small cell lung cancer (NSCLC). The purpose of this article was to assess the effects of selumetinib on the activities of twelve human UDP-glucosyltransferases (UGTs) including UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B15, and 2B17, and its potential for inducing clinical drug-drug interactions (DDIs). The results demonstrated that selumetinib potently inhibited the activity of UGT2B7 through the mechanism of mixed inhibition with the inhibition constant value of 5.79 ± 0.65 µM. Furthermore, the plasma concentration of UGT2B7 substrate as the co-administered drug was predicted to be increased by at least 84 % when patients took selumetinib 75 mg twice daily, suggesting a high potential to induce clinical DDIs. Selumetinib exhibited weak inhibitory effects on other human UGTs and was unlikely to trigger off UGTs-mediated DDIs except for UGT2B7. Therefore, the combination of selumetinib with the substrate drug of UGT2B7 requires additional attention to avoid adverse events in clinical treatment.

High-Fidelity Spatiotemporal Recognition of Golgi ALP through an Initial-Accumulation and Postactivation Strategy.

Various signal molecules mediate complex physiological processes collectively in the Golgi. However, most currently accessible probes are questionable in illuminating the functions of these reactive species in Golgi because of the inability to irradiate these probes only at the desired Golgi location, which compromises specificity and accuracy. In this study, we rationally designed the first photocontrollable and Golgi-targeted fluorescent probe to in situ visualize the Golgi alkaline phosphatase (ALP). The designed probe with natural yellow fluorescence can provide access into Golgi and monitor the exact timing of accumulation in Golgi. On-demand photoactivation at only the desired Golgi location affords a significant emission response to ALP with illuminating red fluorescence at 710 nm. Through the photocontrollable fluorescence responsiveness to ALP, precise spatiotemporal recognition of Golgi ALP fluctuations is successfully performed. With this probe, for the first time, we revealed the Golgi ALP levels during cisplatin-induced acute kidney injury (AKI), which will further facilitate and complement the comprehensive exploration of ALP kinetics during physiological and pathological processes.