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Abstract Magnetic Resonance Imaging (MRI) is increasingly being used in treatment planning due to its superior soft tissue contrast, which is useful for tumor and soft tissue delineation compared to computed tomography (CT). However, MRI cannot directly provide mass density or relative stopping power (RSP) maps, which are required for calculating proton radiotherapy doses. Therefore, the integration of artificial intelligence (AI) into MRI-based treatment planning to estimate mass density and RSP directly from MRI has generated significant interest. A deep learning (DL) based framework was developed to establish a voxel-wise correlation between MR images and mass density as well as RSP. To facilitate the study, five tissue substitute phantoms were created, representing different tissues such as skin, muscle, adipose tissue, 45% hydroxyapatite (HA), and spongiosa bone. The composition of these phantoms was based on information from ICRP reports. Additionally, two animal tissue phantoms, simulating pig brain and liver, were prepared for DL training purposes. The phantom study involved the development of two DL models. The first model utilized clinical T1 and T2 MRI scans as input, while the second model incorporated zero echo time (ZTE) MRI scans. In the patient application study, two more DL models were trained: one using T1 and T2 MRI scans as input, and another model incorporating synthetic dual-energy computed tomography (sDECT) images to provide accurate bone tissue information. The DECT empirical model was used as a reference to evaluate the proposed models in both phantom and patient application studies. The DECT empirical model was selected as the reference for evaluating the proposed models in both phantom and patient application studies. In the phantom study, the DL model based on T1, and T2 MRI scans demonstrated higher accuracy in estimating mass density and RSP for skin, muscle, adipose tissue, brain, and liver. The mean absolute percentage errors (MAPE) were 0.42%, 0.14%, 0.19%, 0.78%, and 0.26% for mass density, and 0.30%, 0.11%, 0.16%, 0.61%, and 0.23% for RSP, respectively. The DL model incorporating ZTE MRI further improved the accuracy of mass density and RSP estimation for 45% HA and spongiosa bone, with MAPE values of 0.23% and 0.09% for mass density, and 0.19% and 0.07% for RSP, respectively. These results demonstrate the feasibility of using an MRI-only approach combined with DL methods for mass density and RSP estimation in proton therapy treatment planning. By employing this approach, it is possible to obtain the necessary information for proton radiotherapy directly from MRI scans, eliminating the need for additional imaging modalities.

Adult survivors of childhood brain tumors often present with cognitive deficits that affect their quality of life. Studying brain structure and function in brain tumor survivors can help understand the underlying mechanisms of their cognitive deficits to improve long-term prognosis of these patients. This study analyzed voxel-based morphometry (VBM) derived from T1-weighted MRI and the amplitude of low-frequency fluctuation (ALFF) from resting-state functional magnetic resonance imaging (rs-fMRI) to examine the structural and functional alterations in 35 brain tumor survivors using 35 matching healthy individuals as controls. Compared with healthy controls, brain tumor survivors had decreased gray matter volumes (GMV) in the thalamus and increased GMV in the superior frontal gyrus. Functionally, brain tumor survivors had lower ALFF values in the inferior temporal gyrus and medial prefrontal area and higher ALFF values in the thalamus. Importantly, we found concurrent but negatively correlated structural and functional alterations in the thalamus based on observed significant differences in GMV and ALFF values. These findings on concurrent brain structural and functional alterations provide new insights towards a better understanding of the cognitive deficits in brain tumor survivors.

Abstract While performing oxygen-related tumour treatments such as chemotherapy and photodynamic therapy, real-time monitoring hypoxia of tumour is of great value and significance. Here, we design a theranostic combination for light-activated ratiometric hypoxia imaging, hypoxia modulating and prodrug activation. This combination consisted of an oxygen-sensitive near-infrared-emitting ratiometric phosphorescence probe and a hypoxia-activated prodrug-loaded covalent organic framework. In this combination, the probe plays two roles, including quantitative monitoring of oxygen concentration by ratiometric imaging and consuming the oxygen of tumour under light excitation by photodynamic therapy. Meanwhile, the enhanced hypoxia microenvironment of tumour can raise the cytotoxicity of prodrug loaded in covalent organic framework, resulting in boosting antitumour therapeutic effects in vivo. This theranostic combination can precisely provide therapeutic regime and screen hypoxia-activated prodrugs based on real-time tumour hypoxia level, offering a strategy to develop hypoxia mediated tumour theranostics with hypoxia targeted prodrugs.

Background: The clinical significance of immune-related antigen CD58 in gliomas remains uncertain. The aim of this study was to examine the clinical importance and possible core related genes of CD58 in gliomas. Methods: Pan-cancer analysis was to observe the association between CD58 and different tumors, glioma RNA sequencing data and clinical sample analyses were used to observe the relationship between CD58 and glioma, shRNA interference models were to observe the impact of CD58 on glioma cell function, and four glioma datasets and two online analysis platforms were used to explore the core related genes affecting the correlation between CD58 and glioma. Results: High CD58 expression was associated with worse prognosis in various tumors and higher malignancy in glioma. Down regulation of CD58 expression was linked to decreased proliferation, increased apoptosis, and reduced metastasis in glioma cells. The pathways involved in CD58-related effects were enriched for immune cell adhesion and immune factor activation, and the core genes were CASP1, CCL2, IL18, MYD88, PTPRC, and TLR2. The signature of CD58 and its core-related genes showed superior predictive power for glioma prognosis. Conclusion: High CD58 expression is correlated with more malignant glioma types, and also an independent risk factor for mortality in glioma. CD58 and its core-related genes may serve as novel biomarkers for diagnosing and treating glioma.

Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells preferentially in the bone marrow. Currently, emerging chemotherapy drugs with improved biosafety profiles, such as immunomodulatory agents and protease inhibitors, have been used in clinics to treat MM in both initial therapy or maintenance therapy post autologous hematopoietic stem cell transplantation (ASCT). We previously discovered that caffeic acid phenethyl ester (CAPE), a water-insoluble natural compound, inhibited the growth of MM cells by inducing oxidative stress. As part of our continuous effort to pursue a less toxic yet more effective therapeutic approach for MM, the objective of this study is to investigate the potential of CAPE for in vivo applications by using magnetic resonance imaging (MRI)-capable superparamagnetic iron oxide nanoparticles (IONP) as carriers. Cyclo (Arg-Gly-Asp-D-Phe-Cys) (RGD) is conjugated to IONP (RGD-IONP/CAPE) to target the overexpressed αvβ3 integrin on MM cells for receptor-mediated internalization and intracellular delivery of CAPE. A stable loading of CAPE on IONP can be achieved with a loading efficiency of 48.7% ± 3.3% (wt%). The drug-release studies indicate RGD-IONP/CAPE is stable at physiological (pH 7.4) and basic pH (pH 9.5) and subject to release of CAPE at acidic pH (pH 5.5) mimicking the tumor and lysosomal condition. RGD-IONP/CAPE causes cytotoxicity specific to human MM RPMI8226, U266, and NCI-H929 cells, but not to normal peripheral blood mononuclear cells (PBMCs), with IC50s of 7.97 ± 1.39, 16.75 ± 1.62, and 24.38 ± 1.71 μM after 72-h treatment, respectively. Apoptosis assays indicate RGD-IONP/CAPE induces apoptosis of RPMI8226 cells through a caspase-9 mediated intrinsic pathway, the same as applying CAPE alone. The apoptogenic effect of RGD-IONP/CAPE was also confirmed on the RPMI8226 cells co-cultured with human bone marrow stromal cells HS-5 in a Transwell model to mimic the MM microenvironment in the bone marrow. In conclusion, we demonstrate that water-insoluble CAPE can be loaded to RGD-IONP to greatly improve the biocompatibility and significantly inhibit the growth of MM cells in vitro through the induction of apoptosis. This study paves the way for investigating the MRI-trackable delivery of CAPE for MM treatment in animal models in the future.

Utilizing iron chloride as a Lewis acid catalyst, we developed a straightforward and mild oxidative cross-coupling reaction between quinoxalinones and indoles, yielding a series of versatile 3-(indol-3-yl)quinoxalin-2-one derivatives. This approach allows for the incorporation of a wide array of functional groups into the final products, demonstrating its synthetic versatility. Notably, the method was successfully scaled up to gram-scale reactions while maintaining high yields. Our mechanistic investigation indicates that iron chloride serves as a catalyst to facilitate the formation of key intermediates which subsequently undergo oxidation to afford the desired products. The merits of this protocol include its cost effectiveness, operational simplicity, and the ease of product isolation via filtration.

BackgroundPain is a common symptom in multiple sclerosis (MS), especially neuropathic pain, which has a significant impact on patients’ mental and physical health and quality of life. However, risk factors that related to neuropathic pain, still remain unclear.ObjectiveThe study aimed to explore the risk factors of neuropathic pain among MS patients.Materials and methodsThis retrospective study examined the consecutive patients diagnosed with MS in the Department of Neurology of Guangdong Provincial Hospital of Chinese Medicine between August 2011 and October 2022. Neuropathic pain was defined as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system”. Demographic and clinical features were obtained from the electronic system of the hospital.ResultsOur cohort revealed that the prevalence of patients with neuropathic pain in MS was 34.1%. The results indicated that the longer the spinal lesions, the greater the neuropathic pain risks (2-4: OR, 13.3(2.1-82), >5: OR, 15.2(2.7-86.8), p for tread: 0.037). Meanwhile, multivariate regression analysis showed that cervical and thoracic lesions (OR 4.276, 95% CI 1.366-13.382, P = 0.013), upper thoracic lesions (T1-T6) (OR 3.047, 95% CI 1.018-9.124, P = 0.046) were positively correlated with neuropathic pain, while basal ganglia lesions (OR 0.188, 95% CI 0.044-0.809, P = 0.025) were negatively correlated with neuropathic pain among MS patients.ConclusionExtended spinal lesions (≥3 spinal lesions), cervical and thoracic lesions, upper thoracic lesions were independent risk factors of neuropathic pain among MS patients. Furthermore, our study found that the longer the spinal lesions, the greater the neuropathic pain risks.

BackgroundAcute respiratory distress syndrome (ARDS) is a severe condition associated with high morbidity, mortality, and healthcare costs. Despite extensive research, treatment options for ARDS are suboptimal.MethodsThis study encompassed patients diagnosed with ARDS from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Pre-intensive care unit (ICU) statin use was assessed as the exposure variable. Kaplan–Meier survival analysis was conducted to evaluate mortality at 30 and 90 days. Adjusted multivariable Cox models were utilized to estimate hazard ratios. Subgroup analyses and propensity score-matching (PSM) were undertaken for further validation.ResultsOur study comprised 10,042 participants diagnosed with ARDS, with an average age of 61.8 ± 15.3 years. Kaplan–Meier survival analysis demonstrated a significantly lower prevalence of mortality at 30 and 90 days in individuals who used statins before ICU admission. Adjusted multivariable Cox models consistently showed a significant decrease in mortality prevalence associated with pre-ICU statin use. After accounting for confounding factors, patients who used statins before ICU admission experienced a 39% reduction in 30-day mortality and 38% reduction in 90-day mortality. We found a significant decrease in ICU stay (0.84 days) for those who used statins before ICU admission. These results were supported by subgroup analyses and PSM.ConclusionThis large cohort study provides evidence supporting the association between pre-ICU statin use, reduced risk of death, and shorter ICU stay in patients with ARDS, thereby suggesting the potential benefits of statin use in critically ill patients.

Nature reserves play a crucial role in providing diverse ecosystem services (ESs) that benefit local residents, but they are also confronted with challenges such as degradation and human-wildlife conflicts. There is limited understanding of the demand for ESs from the public's perspective, although the current nature reserve policy aims to address these issues. Therefore, it is essential to assess the preferences of the public towards ESs in order to ensure sustainable management. In this study, the choice experiment methodology was employed to investigate the preferences of the public for ESs in the Taibai Mountain Nature Reserve (TMNR) in China. Despite its significant benefits to local residents, the TMNR also faces ongoing risks due to unfriendly behavior and conflicting interests among the public. A total of 547 respondents from three counties in the TMNR region were interviewed. Their preferences and marginal willingness to pay (MWTP) for improvements in essential ESs were analyzed using various discrete choice models. The results demonstrate that preference heterogeneity exists in ESs, particularly in habitat and information services. This research demonstrates the policy relevance of attributes related to ESs. It provides valuable empirical evidence that can guide decision-makers in managing nature reserves, enhancing management effectiveness, and promoting local well-being.

Abstract The utilization of chelation reaction between metals and tannins is a common tanning method in leather chemistry. Herein, a novel combination tanning mechanism inspired environmentally benign catalyst (CMBT-Fe0) was synthesized by immobilizing Fe nanoparticles onto bayberry tannin (BT) grafted chitosan microfibers (CM). The obtained catalyst featured a well-defined microfibrous structure, on which Fe0 nanoparticles were highly dispersed to exhibit exceptional catalytic activity for the degradation of tetracycline (TC). The catalytic activity of CMBT-Fe0 was 1.72 times higher than that of the commercial Fe0 nanoparticles without immobilization, with 95.03% of TC degraded within 90.0 min. The CMBT-Fe0 catalysts were recycled 6 times, with the removal rate of TC maintained at 82.56%. Furthermore, a possible mechanism responsible for the catalytic removal of TC was provided by analyzing the catalytic degradation products via liquid chromatography-mass spectrometry. Therefore, our investigation successfully developed efficient catalysts to address the concerned environmental issue of antibiotic pollution. Graphical Abstract

Climate change which is mainly caused by carbon emissions is a global problem affecting the economic development and well-being of human society. Low-carbon agriculture is of particular significance in slowing down global warming and reaching the goal of “carbon peak and carbon neutrality”. Therefore, taking straw incorporation as an example, this paper aims to investigate the impact of risk preferences on farmers’ low-carbon agricultural technology (LCAT) adoption. Based on a two-phase micro-survey data of 1 038 rice farmers in Jiangsu, Jiangxi, and Hunan provinces, this paper uses experimental economics methods to measure farmers’ risk aversion and loss aversion to obtain the real risk preferences information of the farmers. We also explore the data to examine the actual LCAT adoption behavior of farmers. The results revealed that both risk aversion and loss aversion significantly inhibit farmers’ LCAT adoption: more risk-averse or more loss-averse farmers are less likely to adopt LCAT. It is further found that crop insurance, farm scale and governmental regulations can alleviate the negative impact of risk aversion and loss aversion on farmers’ LCAT adoption. Therefore, we propose that local governments need to promote low-carbon agricultural development by propagating the benefits of LCAT, extending crop insurance, promoting appropriate scale operations, and strengthening governmental regulations to promote farmers’ LCAT adoption.

Abstract. Asthma is characterized by chronic airway inflammation and airway hyper-responsiveness. However, the differences in pathophysiology and phenotypic symptomology make a diagnosis of “asthma” too broad hindering individualized treatment. Four asthmatic inflammatory phenotypes have been identified based on inflammatory cell profiles in sputum: eosinophilic, neutrophilic, paucigranulocytic, and mixed-granulocytic. Paucigranulocytic asthma may be one of the most common phenotypes in stable asthmatic patients, yet it remains much less studied than the other inflammatory phenotypes. Understanding of paucigranulocytic asthma in terms of phenotypic discrimination, distribution, stability, surrogate biomarkers, underlying pathophysiology, clinical characteristics, and current therapies is fragmented, which impedes clinical management of patients. This review brings together existing knowledge and ongoing research about asthma phenotypes, with a focus on paucigranulocytic asthma, in order to present a comprehensive picture that may clarify specific inflammatory phenotypes and thus improve clinical diagnoses and disease management.

Coenzyme A (CoA) functions as a crucial carrier of acyl groups within cells, playing a fundamental role in regulating acyl transfer reactions and participating in cellular metabolic processes. As the principal substrate and cofactor engaged in diverse metabolic reactions, CoA and its derivatives exert central influence over various physiological processes, primarily modulating lipid and ketone metabolism, as well as protein modification. This paper presents a comprehensive review of the molecular mechanisms by which CoA influences the onset and progression of cancer, cardiovascular disease (CVD), neurodegenerative disorders, and other illnesses. The main focal points include the following. (1) In cancer, enzymes such as acetyl-CoA synthetase 2, ATP citrate lyase, and acetyl-CoA carboxylase regulate lipid synthesis and energy metabolism by modulating acetyl-CoA levels. (2) In CVD, the effects of enzymes such as stearoyl-CoA desaturase-1, 3-hydroxy-3-methylglutaryl-CoA (HMGC) synthase 2, and HMGC reductase on the formation and advancement of these diseases are elucidated by their regulation of CoA metabolism across multiple organs. (3) In neurodegenerative disorders, the significance of CoA in maintaining cholesterol homeostasis in the brain and its implications on the development of such disorders are thoroughly discussed. The metabolic processes involving CoA and its derivatives span all physiological aspects within cells, playing a critical role in the onset and progression of various diseases. Elucidating the role of CoA in these conditions yields important insights that can serve as valuable references and guidance for disease diagnosis, treatment, and drug development.

Biomedical imaging, especially molecular imaging, has been a driving force in scientific discovery, technological innovation, and precision medicine in the past two decades. While substantial advances and discoveries in chemical biology have been made to develop molecular imaging probes and tracers, translating these exogenous agents to clinical application in precision medicine is a major challenge. Among the clinically accepted imaging modalities, magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) exemplify the most effective and robust biomedical imaging tools. Both MRI and MRS enable a broad range of chemical, biological and clinical applications from determining molecular structures in biochemical analysis to imaging diagnosis and characterization of many diseases and image-guided interventions. Using chemical, biological, and nuclear magnetic resonance properties of specific endogenous metabolites and native MRI contrast-enhancing biomolecules, label-free molecular and cellular imaging with MRI can be achieved in biomedical research and clinical management of patients with various diseases. This review article outlines the chemical and biological bases of several label-free chemically and molecularly selective MRI and MRS methods that have been applied in imaging biomarker discovery, preclinical investigation, and image-guided clinical management. Examples are provided to demonstrate strategies for using endogenous probes to report the molecular, metabolic, physiological, and functional events and processes in living systems, including patients. Future perspectives on label-free molecular MRI and its challenges as well as potential solutions, including the use of rational design and engineered approaches to develop chemical and biological imaging probes to facilitate or combine with label-free molecular MRI, are discussed.

Abstract Various catalysts are developed to improve the performance of metal oxide semiconductor gas sensors, but achieving high selectivity and response intensity in chemiresistive gas sensors (CGSs) remains a significant challenge. In this study, an in situ‐annealing approach to synthesize Cu catalytic sites on ultrathin WO2.72 nanowires for detecting toluene at ultralow concentrations (Ra/Rg = 1.9 at 10 ppb) with high selectivity is developed. Experimental and molecular dynamic studies reveal that the Cu single atoms (SAs) act as active sites, promoting the oxidation of toluene and increasing the affinity of Cu single‐atom catalysts (SACs)‐containing sensing materials for toluene while weakening the association with carbon dioxide or water vapor. Density functional theory studies show that the selective binding of toluene to Cu SAs is due to the favorable binding sites provided by Cu SAs for toluene molecules over other gaseous species, which aids the adsorption of toluene on WO2.72 nanowires. This study demonstrates the successful atomic‐level interface regulation engineering of WO2.72 nanowire‐supported Cu SAs, providing a potential strategy for the development of highly active and durable CGSs.

Deep wells and ultra-deep wells often encounter cracks, karst caves, and other developed strata, which can lead to leakage during drilling. Conventional bridge slurry plugging technology is prone to leaking due to the poor plugging effect of the plugging agent. The gel plugging agent possesses characteristics of flexible plugging and adaptive matching of formation leakage channels. It can fill cracks or caves and enhance the pressure-bearing capacity of the formation. A controllable crosslinking plugging agent based on low-molecular-weight polyacrylamide was studied. Polyacrylamide with different molecular weights is synthesized from acrylamide and an initiator. A crosslinking time-controllable polymer is synthesized from low-molecular-weight polyacrylamide by adding crosslinking agent and retarder. The low-molecular-weight polyacrylamide plugging agent has low viscosity before gelation and good fluidity in the wellbore. After being configured on the ground, it is transported by pipeline and sent underground to reach the thickening condition. The gel solution rapidly solidifies, and its strength improves after high-temperature crosslinking. The synthesis conditions of the polymer were as follows: a monomer concentration of 9%, initiator 3.5%, synthesis temperature of 65 °C, and hydrogen peroxide initiator. The optimal formula of the gel plugging agent is as follows: a polymer concentration of 6%, a crosslinking agent concentration of 1%, and a retarder concentration of 8%. The generated polymer molecular structure contains amide groups. This crosslinking time-controllable plugging agent based on low-molecular-weight polyacrylamide has stable rheology, and its temperature resistance can reach 150 °C. At 150 °C, the gelation time can be controlled by adjusting the concentration of retarder, and the longest can reach 4 h. The plugging efficiency of the gel plugging agent is more than 95%. With the increase in seam width, the pressure of the gel plugging agent gradually decreases.

With the gradual deepening of the exploration and development of deep and ultra-deep oil and gas resources, the problem of lost circulation in drilling operations is becoming more and more complex. From field experience, conventional plugging materials cannot fully meet the technical requirements of plugging operations in drilling engineering. In this study, a high-temperature- and salt-resistant polymer HDZ−A was synthesized. A high-temperature and delayed crosslinking polymer gel plugging agent can be prepared by adding a certain concentration of a crosslinking agent and a retarder. In this paper, the optimum synthesis conditions of the HDZ−A were determined with orthogonal experiments using viscoelasticity and viscosity as evaluation criteria for newly developed polymers. The molecular structure, temperature resistance, and relative molecular mass of HDZ−A were determined using infrared spectroscopy, nuclear magnetic resonance spectroscopy, and gel permeation chromatography. In addition, the optimal formula of the gel plugging agent was determined using gel strength as the evaluation standard. The results show that the newly developed gel plugging agent has stable performance after high-temperature crosslinking, and can resist high temperatures of 160 °C during formation. Under conditions of 160 °C, the gelation time can reach 4.5 h, and the plugging efficiency can reach more than 97%. Finally, the field test of the newly developed high-temperature-resistant delayed crosslinking polymer gel plugging agent was carried out in the direct exploration well KT-14X in the Ordos Basin. The field test showed that the plugging effect of the HDZ−A gel plugging agent was remarkable.

BackgroundSepsis is a life-threatening condition caused by a dysfunctional response to infection from the host. Septic shock, a subset of sepsis, caused by Talaromyces marneffei infection (talaromycosis) has rarely been reported. Owing to its slow culture and low yield, talaromycosis is typically misdiagnosed in HIV-negative patients as other infections, such as tuberculosis, bacterial pneumonia, and lung cancer, especially in non-endemic regions. Early and accurate diagnosis as well as efficient treatment options are required to improve prognosis.MethodA 30-year-old HIV-negative Chinese woman from a non-endemic area of T. marneffei was initially misdiagnosed with tuberculosis. She had a poor response to anti-tuberculosis treatment. On July 16, 2022, she was admitted to our hospital; the patient developed septic shock on the third day after hospitalization and was ultimately diagnosed with talaromycosis via metagenomic next-generation sequencing (mNGS).ResultThe condition of the patient improved after appropriate treatment with amphotericin B. Furthermore, enzyme-linked immunosorbent assay results confirmed that the patient had a high-titer of anti-interferon gamma (IFN-γ) autoantibodies.ConclusionHIV-negative individuals with anti-IFN-γ autoantibodies typically have relapsing, refractory, and fatal infections, such as talaromycosis, which is typically misdiagnosed in the initial course of the disease. This can lead to septic shock. Clinicians should be aware that they may encounter HIV-negative patients with T. marneffei infection in non-endemic areas. Thus, mNGS is an effective technology for detecting T. marneffei infection. Additionally, the detection of anti-IFN-γ autoantibodies in these patients would aid in knowing their susceptibility to fatal infections.

Objective: N4-acetylcytidine (ac4C) acetylation can promote target gene expression through improved mRNA stability. To explore the role of ac4C acetylation in osteosarcoma, U2OS and MG63 cell lines were treated with the N-acetyltransferase 10 (NAT10) inhibitor Remodelin. Reverse transcription–polymerase chain reaction (RT-PCR) and Western blot were used to test the gene and protein expression efficiency. Methods: The proliferation rate of osteosarcoma cells was measured by a cell counting kit-8 (CCK8) assay. The cell cycle and apoptosis were analyzed by flow cytometry. The invasiveness of osteosarcoma cells was detected by a transwell invasion assay. The ac4C acetylation of target genes was screened by acetylated RNA immunoprecipitation and sequencing (acRIP-seq). Results: We found that when osteosarcoma cells were treated with Remodelin at the optimal concentration, their NAT10 expression and the cell proliferation was inhibited, the cells in the G1 phase increased (P

Abstract Background Neuropathic pain is a common complication in neuromyelitis optica spectrum disorder (NMOSD), which seriously affects the quality of life of NMOSD patients, with no satisfactory treatment. And risk factors of neuropathic pain are still uncertain. Objective To investigate the risk factors of neuropathic pain in a NMOSD cohort. Materials and methods Our study was a retrospective case-cohort study, the patients diagnosed with NMOSD in the Department of Neurology from the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2011 to October 2021 were screened. Inclusion criteria were: (1) patients diagnosed as NMOSD according to the International Panel for NMO Diagnosis (IPND) criteria, (2) the aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) test was performed. Patients without AQP4-IgG antibody were excluded. Clinical data, including sex, age of the first onset, symptoms of the first episode including neuropathic pain and attack types, localization of lesions of the first episode on Magnetic Resonance Imaging (MRI), Extended disability status Scale (EDSS) of the first onset, treatment of immunosuppression in the first acute phase, disease modifying therapy (DMT), treatment of neuropathic pain and APQ4-IgG status were collected from the hospital system database. Neuropathic pain was defined according to the International Association for the Study of Pain criteria and was described as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system”. Results One hundred nineteen patients were screened and finally 86 patients fulfilling the inclusion and exclusion criteria were enrolled in our study. The prevalence of neuropathic pain in patients with NMOSD was 43.0%. Univariate analysis showed that the factors associated with neuropathic pain were the age at the onset, the attack type of optic neuritis, the attack type of myelitis, length of spinal cord involvement, localization of thoracic lesion, optic lesion, upper thoracic lesions, lower thoracic lesions, extended spinal cord lesions (≥ 3 spinal lesions), extended thoracic lesions (≥ 4 thoracic lesions), intravenous immunoglobulin and mycophenolate mofetil. Multivariate regression analysis showed that extended thoracic lesions (OR 20.21 [1.18–346.05], P = 0.038) and age (OR 1.35 (1–1.81) P = 0.050) were independently associated with neuropathic pain among NMOSD patients and that gender (OR 12.11 (0.97–151.64) P = 0.053) might be associated with neuropathic pain among NMOSD patients. Conclusion Extended thoracic lesions (≥ 4 thoracic lesions), age and gender might be independent risk factors of neuropathic pain among patients with NMOSD. However, with a small sample size and predominantly female, caution must be applied and these results need validating in further cohorts.

BackgroundLegionella pneumonia, rhabdomyolysis, and acute kidney injury are called the Legionella triad, which is rare and associated with a poor outcome and even death. Early diagnosis and timely treatment are essential for these patients.Case presentationA 63-year-old man with cough, fever, and fatigue was initially misdiagnosed with common bacterial infection and given beta-lactam monotherapy but failed to respond to it. Conventional methods, including the first Legionella antibody test, sputum smear, and culture of sputum, blood, and bronchoalveolar lavage fluid (BALF) were negative. He was ultimately diagnosed with a severe infection of Legionella pneumophila by metagenomics next-generation sequencing (mNGS). This patient, who had multisystem involvement and manifested with the rare triad of Legionella pneumonia, rhabdomyolysis, and acute kidney injury, finally improved after combined treatment with moxifloxacin, continuous renal replacement therapy, and liver protection therapy.ConclusionOur results showed the necessity of early diagnosis of pathogens in severe patients, especially in Legionnaires' disease, who manifested with the triad of Legionella pneumonia, rhabdomyolysis, and acute kidney injury. mNGS may be a useful tool for Legionnaires' disease in limited resource areas where urine antigen tests are not available.

Objectives: To evaluate the effectiveness and safety of pediatric Tui Na for the treatment of cough in children under seven years of age.Design: Systematic review and meta-analysis of randomized controlled trials. Methods: We searched seven major databases and two ongoing trial registers before November 2021 for randomized controlled trials (RCTs) on pediatric Tui Na for cough in children. Main outcome measures were cough related status (such as cough frequency, severity, and duration), use of western medicines, quality of life, medical costs, recurrence rate, adverse events and acceptance. Two reviewers independentlyselected studies and extracted data. Results were presented by RevMan 5.4 as risk ratios (RRs) and mean differences (MDs), both with 95 % confidence intervals (CIs). Risk of bias were assessed using ROB tools and quality of evidence by GRADE. Results: Sixteen RCTs involving 1502 participants were included in this review. Most trials were poor in quality for not reporting allocation concealment, blinding of outcomeassessment or outcome data completeness. The pooled results demonstrated that pediatric Tui Na alone (2 RCTs, 205 participants; MD −2.22, 95 %CI −3.71 to −0.73; P = 0.004; I 2 = 90 %; low certainty) or combined with conventional treatment (7 RCTs, 668 participants; MD −1.66, 95 %CI −2.89 to −0.44; P = 0.008; I 2 = 98 %; low certainty) shortened cough duration. The combined treatment also decreased the recurrence rate of cough (3 RCTs, 135 participants; RR 0.35, 95 %CI 0.21–0.58; P

Gastric cancer (GC) continues to be the most common gastrointestinal malignancy in China, and tumor metastases are a major reason for poor prognosis. Circular RNAs (circRNAs) are an intriguing type of noncoding RNAs with important regulatory roles. However, the roles of circRNAs in GC metastasis have not been fully elucidated. Here, we reported that circ-transportin 3 (TNPO3) was significantly downregulated in 103 pairs of GC tissues compared with matched noncancerous tissues. The level of circ-TNPO3 expression correlated with differentiation of GC, and plasma circ-TNPO3 could serve as a potential diagnostic biomarker. Functionally, circ-TNPO3 inhibited proliferation and migration of GC in vitro and in vivo. We further verified that circ-TNPO3 competitively interacted with insulin-like growth factor 2 binding protein 3 (IGF2BP3) protein; thus, the role of IGF2BP3 in stabilizing MYC mRNA was weakened, which inhibited the expression of MYC and its target SNAIL. Taken together, circ-TNPO3 acts as a protein decoy for IGF2BP3 to regulate the MYC-SNAIL axis, thereby suppressing the proliferation and metastasis of GC. Therefore, circ-TNPO3 has the potential to serve as a therapeutic target for GC.

Ensuring food security in China is the primary task in solving the problems of ‘agriculture, countryside, and farmers’. Based on Chinese provincial panel data from 2009 to 2018, this paper evaluates the impact of a water rights trading pilot policy (WRTPP) on food security and examines its underlying mechanism. To overcome the estimation bias existing in previous studies, we use the difference-in-differences method, which can separate time effects from policy treatment effects and is an effective tool to compare the effect before and after policy implementation. We, therefore, use this method to evaluate the net effect of the WRTPP on food security. It is found that the WRTPP can help ensure food security. This effect reaches its maximum in the fourth year after the policy's implementation. It is further found that the WRTPP can improve the adoption of agricultural water-saving irrigation technology to increase the grain yield. Our conclusions complement existing evidence on the factors influencing food security. From the perspective of improving farmers’ water-saving irrigation technology, we confirm that the mechanism of the water rights trading pilot policy helps ensure food security. HIGHLIGHTS Water rights trading pilot policy can help guarantee food security.; The policy help guarantee food security by improving the adoption of water-saving irrigation technology.; This effect reaches its maximum in the fourth year after the implementation of the policy.; The policy will have a long-term effect on helping guaranteeing food security.; The research does not violate the parallel trend assumption of the difference-in-differences method.;

Objectives Optimal periprocedural blood pressure (BP) management during mechanical thrombectomy (MT) for acute ischaemic stroke is still controversial. The aim of this study was to investigate the association between intraprocedural BP variability (BPV) and outcomes in patients with large vessel occlusion (LVO) following MT with general anaesthesia.Design A prospective observational cohort study.Setting This study was conducted in a single tertiary hospital of Hangzhou in Zhejiang province.Participants A total of 141 patients with LVO treated with MT were finally included between January 2018 and September 2020.Main outcome measures Intraprocedural BP was recorded every 5 min throughout the procedure. BPV was measured as SD, coefficient of variation (CV), max-min (RANGE) and successive variation. Haemorrhagic transformation was assessed on 24-hour CT images according to European Cooperative Acute Stroke Study III trial. Poor functional outcome was defined as 90-day modified Rankin Scale score 3–6. Binary logistic regression analysis was used to investigate the association of BPV parameters with the incidence of parenchymal haemorrhage (PH) and poor functional outcome.Results After controlling for age, female, history of smoking, hypertension and atrial fibrillation, baseline National Institutes of Health Stroke Scale, baseline systolic BP (SBP), baseline Alberta Stroke Program Early CT Score, bridging thrombolysis and times of retrieval attempts, the results demonstrated that intraprocedural SBPRANGE (OR 1.029; 95% CI 1.003 to 1.055; p=0.027), SBPSD (OR 1.135; 95% CI 1.023 to 1.259; p=0.017) and SBPCV (OR 1.189; 95% CI 1.053 to 1.342; p=0.005) were independently associated with poor functional outcome. However, the independent association between intraprocedural BPV and PH at 24 hours has not been established in this study.Conclusions Increased intraprocedural BPV was more likely to have poor functional outcome in patients with LVO following MT with general anaesthesia. This finding indicates that special precautions should be taken to minimise BP fluctuation during procedure.

Previous studies have suggested that Hestia criteria could effectively identifying patients with acute pulmonary embolism (PE) who were at low risk of mortality for outpatient treatment or early discharge. But the performance of Hestia criteria in stratifying patients at different risk class is still unknown. We sought to comprehensively evaluate the prognostic impact of Hestia criteria for PE. The literatures search was conducted in PubMed, Web of Science and EMBASE from 1 August 2011 to 31 October 2021. Finally, Eight studies with 4110 patients were included in our meta-analysis. Overall, the pool percentage of patients classified as low-risk group and high-risk group were 41.4%% and 58.6% respectively, and the all-course mortality rates of each group were 2.3% and 10.6%, respectively. The pooled rate of PE-related composite adverse outcomes in high-risk group was increasingly higher than in low-risk group (15.7% vs 4.4%). High risk group was also markedly associated with overall mortality (OR: 7.21, 95%CI: 4.96-10.46, p

AimsTo evaluate the clinical efficiency of on-table extubation (OTE) versus delayed extubation in patients aged over 60 years that underwent minimally invasive mitral or aortic valve replacement surgery and evaluate the factors associated with successful OTE implementation.MaterialsPatients over 60 years with mitral or aortic valve disease who received minimally invasive mitral or aortic valve replacement surgery from October 2020 to October 2021 were selected retrospectively. We divided patients into the on-table extubated (OTE) group (n = 71) and the delayed extubation (DE) group (n = 22). Preoperative, intraoperative, and postoperative clinical variables were compared between the two groups.ResultsPatients in the DE group underwent longer surgery time, longer aortic occlusion clamping time and longer cardiopulmonary bypass time than those in the OTE group(217.48 ± 27.83 vs 275.91 ± 77.22, p = 0.002; 76.49 ± 16.00 vs 126.55 ± 54.85, p = 0.001; 112.87 ± 18.91 vs 160.77 ± 52.17, p = 0.001). Patients in the OTE group had shorter postoperative mechanical ventilation time (min), shorter ICU time, shorter postoperative hospital length of stay and lower total cost and medication cost (p

Mitochondria are key targets for photothermal and photodynamic treatment for cancer but delivery of therapeutics to these organelles remains a challenge. In this study, authors develop a mitochondrial targeted liposomal delivery platform using a dendritic peptide moiety as a mitochondria targeting moiety and demonstrate its targeting and antitumour efficacy in a mouse model of breast cancer.

Abstract Background Glioblastoma (GBM) is a universally lethal tumor with frequently overexpressed or mutated epidermal growth factor receptor (EGFR). NADPH quinone oxidoreductase 1 (NQO1) and glutathione-S-transferase Pi 1 (GSTP1) are commonly upregulated in GBM. NQO1 and GSTP1 decrease the formation of reactive oxygen species (ROS), which mediates the oxidative stress and promotes GBM cell proliferation. Methods High-throughput screen was used for agents selectively active against GBM cells with EGFRvIII mutations. Co-crystal structures were revealed molecular details of target recognition. Pharmacological and gene knockdown/overexpression approaches were used to investigate the oxidative stress in vitro and in vivo. Results We identified a small molecular inhibitor, “MNPC,” that binds to both NQO1 and GSTP1 with high affinity and selectivity. MNPC inhibits NQO1 and GSTP1 enzymes and induces apoptosis in GBM, specifically inhibiting the growth of cell lines and primary GBM bearing the EGFRvIII mutation. Co-crystal structures between MNPC and NQO1, and molecular docking of MNPC with GSTP1 reveal that it binds the active sites and acts as a potent dual inhibitor. Inactivation of both NQO1 and GSTP1 with siRNA or MNPC results in imbalanced redox homeostasis, leading to apoptosis and mitigated cancer proliferation in vitro and in vivo. Conclusions Thus, MNPC, a dual inhibitor for both NQO1 and GSTP1, provides a novel lead compound for treating GBM via the exploitation of specific vulnerabilities created by mutant EGFR.

The creatine transporter (CrT) maintains brain creatine (Cr) levels, but the effects of its deficiency on energetics adaptation under stress remain unclear. There are also no effective treatments for CrT deficiency, the second most common cause of X-linked intellectual disabilities. Herein, we examined the consequences of CrT deficiency in brain energetics and stress-adaptation responses plus the effects of intranasal Cr supplementation. We found that CrT-deficient (CrT–/y) mice harbored dendritic spine and synaptic dysgenesis. Nurtured newborn CrT–/y mice maintained baseline brain ATP levels, with a trend toward signaling imbalance between the p-AMPK/autophagy and mTOR pathways. Starvation elevated the signaling imbalance and reduced brain ATP levels in P3 CrT–/y mice. Similarly, CrT–/y neurons and P10 CrT–/y mice showed an imbalance between autophagy and mTOR signaling pathways and greater susceptibility to cerebral hypoxia-ischemia and ischemic insults. Notably, intranasal administration of Cr after cerebral ischemia increased the brain Cr/N-acetylaspartate ratio, partially averted the signaling imbalance, and reduced infarct size more potently than intraperitoneal Cr injection. These findings suggest important functions for CrT and Cr in preserving the homeostasis of brain energetics in stress conditions. Moreover, intranasal Cr supplementation may be an effective treatment for congenital CrT deficiency and acute brain injury.

Fucosylated chondroitin sulfate (FCS) from the sea cucumber Acaudina molpadioides (FCSAm) is the first one that was reported to be branched by disaccharide GalNAc-(α1,2)-Fuc3S4S (15%) and sulfated Fuc (85%). Here, four size-homogenous fractions, and seven oligosaccharides, were separated from its β-eliminative depolymerized products. Detailed NMR spectroscopic and MS analyses revealed the oligomers as hexa-, hepta-, octa-, and nonasaccharide, which further confirmed the precise structure of native FCSAm: it was composed of the CS-E-like backbone with a full content of sulfation at O-4 and O-6 of GalNAc in the disaccharide repeating unit, and the branches consisting of sulfated fucose (Fuc4S and Fuc2S4S) and heterodisaccharide [GalNAc-(α1,2)-Fuc3S4S]. Pharmacologically, FCSAm and its depolymerized derivatives, including fractions and oligosaccharides, showed potent neurite outgrowth-promoting activity in a chain length-dependent manner. A comparison of analyses among oligosaccharides revealed that the sulfate pattern of the Fuc branches, instead of the heterodisaccharide, could affect the promotion intensity. Fuc2S4S and the saccharide length endowed the neurite outgrowth stimulation activity most.

Background: More and more trials have been conducted. We aimed to assess the efficacy and safety of different JAKinibs in RA. Methods: A systematic search of randomized controlled trials (RCTs) with JAKinib treatment in RA published in the Medline, Embase, and Cochrane databases up to May 2021 was performed. Results: 37 trials involving 15,174 patients were identified. Pooled analysis revealed that JAKinibs were associated with significant therapeutic improvement in RA patients as determined by ACR20 (RR = 2.03, 95% CI: 1.85 to 2.28) and HAQ-DI (MD = −0.31, 95% CI: −0.33 to −0.28) over placebo. Compared to placebo, JAKinib treatment was also associated with more adverse events (RR = 1.10, p < 0.001; RR = 1.29, p < 0.001; RR = 1.59, p = 0.02). Baricitinib and upadacitinib were related to more frequent adverse events (RR = 1.10; 95% CI: 1.01, 1.21; RR = 1.19; 95% CI: 1.11, 1.28) and infection (RR = 1.22; 95% CI: 1.09, 1.37; RR = 1.38; 95% CI: 1.22, 1.56), whereas only baricitinib was associated with more herpes zoster (RR = 3.15; 95% CI: 1.19, 8.33). Conclusions: JAKinibs were superior to placebo for improving signs, symptoms, and health-related quality of life in RA patients at short term, whereas the overall risk of adverse events and infections were greater with baricitinib and upadacitinib, and a higher risk of herpes zoster was only associated with baricitinib. More trials are needed to investigate the long-term safety.

Background: Up to 80% of pancreatic cancer patients suffer from cachexia. White adipose tissue (WAT) browning caused by the tumorigenicity and progression aggravates the cancer-associated cachexia (CAC). Cancer-initiated changes in the protein-38 mitogen-activated protein kinases (p38 MAPK) pathway are likely involved in the development of CAC. Methods: p38 MAPK inhibitors, VCP979 or SB203580, were used in the in vitro and in vivo models of pancreatic cancer cachexia. Expression of uncoupling protein 1 (UCP1) in the p38 MARK pathway and the properties and level of white adipocytes were analyzed and correlated to browning, followed by immunohistochemistry and Western blotting validations. Changes in the volume and fat fraction of WAT in animals were monitored by magnetic resonance imaging (MRI). Results: The size of white adipocytes was increased after being treated with the p38 MAPK inhibitors, along with increase in the MRI-measured volume and fat fraction of WAT. Comparing two p38 MAPK inhibitors, the p38α subunit-specific inhibitor VCP979 had a better therapeutic effect than SB203580, which targets both p38α and β subunits. Conclusions: Blockade of p38 MAPK reduced the WAT browning that contributes to CAC. Thus, p38 MARK inhibitors can potentially be used as a therapy for treating CAC. Non-invasive MRI can also be applied to assess the progression and treatment responses of CAC.

Background and Purpose: Optimal periprocedural management of blood pressure during mechanical thrombectomy (MT) remains controversial. This study aimed to investigate the relationship between the duration of blood pressure drops during general anesthesia and the outcomes in large vessel occlusion (LVO) patients treated with MT.Methods: We retrospectively reviewed our prospectively collected data for LVO patients treated with MT between January 2018 and July 2020. Intraprocedural mean arterial pressure (MAP) was recorded every 5 min throughout the procedure. Baseline MAP minus each MAP value recorded during general anesthesia was defined ΔMAP. Cumulated time (in min) and longest continuous episode (in min) with ΔMAP more than 10, 15, 20, 25, and 30 mmHg were calculated, respectively. Poor outcome was defined as 90-day modified Rankin score (mRS) 3–6. Associations between cumulated time of different ΔMAP thresholds and poor outcome were determined using binary logistic regression models.Results: A total of 131 patients were finally included in the study. After controlling for age, atrial fibrillation, baseline NIHSS, baseline ASPECTS, procedure duration of MT, and times of retrieval attempts, the results indicated that cumulated time of MAP drop more than 10 mmHg (OR 1.013; 95% CI 1.004–1.023; P = 0.007) and 15 mmHg (OR 1.011; 95% CI 1.002–1.020; P = 0.017) were independently associated with poor outcomes.Conclusion: Prolonged episodes of intraprocedural MAP lowering were more likely to have poor outcomes in LVO patients following MT with general anesthesia, which might be helpful in guiding intraprocedural hemodynamic management of patients under general anesthesia.

Objective: To evaluate the utility of magnetic resonance imaging (MRI) with an advanced motion correction technique in characterizing lung tissue changes and lesions induced by pulmonary tuberculosis (TB). Methods: Sixty-three subjects with computed tomography (CT) features of pulmonary TB underwent lung MRI. All subjects with pulmonary TB were confirmed by acid-fast bacillus (AFB) testing or the detection of Mycobacterium tuberculosis. T2-weighted turbo spin echo (TSE) sequence MRI with the MultiVane motion correction technique was used to image the lungs. Routine lung CT images were obtained as reference. MRI and CT images were reviewed by multiple readers independently. The performance of MRI in depicting abnormalities induced by pulmonary TB and their morphological changes were evaluated and compared with the performance of CT. Results: Lung MRI found pulmonary abnormalities in all 63 TB subjects, with satisfactory quality. With the implementation of MultiVane for T2-weighted TSE sequences to reduce the motion correction effect, MRI showed excellent agreement with CT in detecting abnormal imaging features of pulmonary TB (κ = 0.88, p 10 mm, respectively. However, MRI was less effective in identifying lesions with calcification. Conclusions: The clinical implementation of an optimized MRI protocol with the MultiVane motion correction technique for imaging pulmonary TB is feasible. Lung MRI without ionizing radiation is a promising alternative to the clinical standard CT, especially for pregnant women, children, adolescents, and patients requiring short-term and repeated follow-up observations. Keywords: Magnetic resonance imaging, Lung, Computed tomography, Pulmonary tuberculosis, Motion correction

Filtration loss control under high-temperature conditions is a worldwide issue among water-based drilling fluids (WBDFs). A core–shell high-temperature filter reducer (PAASM-CaCO3) that combines organic macromolecules with inorganic nanomaterials was developed by combining acrylamide (AM), 2-acrylamide-2-methylpropane sulfonic acid (AMPS), styrene (St), and maleic anhydride (MA) as monomers and nano-calcium carbonate (NCC). The molecular structure of PAASM-CaCO3 was characterized. The average molecular weight of the organic part was 6.98 × 105 and the thermal decomposition temperature was about 300 °C. PAASM-CaCO3 had a better high-temperature resistance. The rheological properties and filtration performance of drilling fluids treated with PAASM-CaCO3 were stable before and after aging at 200 °C/16 h, and the effect of filtration control was better than that of commonly used filter reducers. PAASM-CaCO3 improved colloidal stability and mud cake quality at high temperatures.

BackgroundType 2 diabetes mellitus (T2DM) known as non-insulin-dependent diabetes mellitus, which is increasingly acknowledged as being associated with an increased risk for a series of cancers. Pancreatic cancer is currently the fourth most common cause of cancer-related mortality, which has been proved to be worsened by internal diabetic condition. However, the underlying molecular mechanisms are less addressed. Furthermore, current knowledge revealed that therapeutic strategy by anti-diabetes for pancreatic cancer under diabetes condition have no satisfactory efficacy, and nor by chemotherapy in our study.MethodsTo clarify these mysteries and widen our knowledge, both obesity-associated and non-obese-associated T2DM mouse models were generated by chemical induction with streptozotocin (STZ) and leptin receptor knockout (db/db) in mice. Then, the process of tumor progression was researched, and the gene expression profiling of pancreatic cancer in mice was performed using RNA-seq.ResultsOur results showed that pancreatic cancer malignancy was increased with notable proliferation and metastatic potential in two diabetic mice model. Totally, 136 and 64 significantly differentially expressed genes (DEGs) were identified in STZ and db/db mice by transcriptomic analysis. The results also suggested that different carcinogenesis-related genes and potential molecular mechanisms contribute to the malignancy of pancreatic cancer in obesity-associated and non-obesity-associated T2DM. In obesity-associated db/db mice, the GO subcategories associated with most of the genes with downregulated expression are involved in the immune response. However, in non-obesity-associated STZ mice, in addition to the immune response category, the enriched subcategories also included angiogenesis and the extracellular matrix. While, two genes respectively encoding MMP-2 and MMP-9 were simultaneously abnormal up-regulated in pancreatic cancer tissue from diabetic mice of both STZ and db/db, that could act as potential therapeutic targets for significantly suppressing the malignant progression. Furthermore, an optimizing therapeutic strategy was further proposed that combining MMP-2/9 inhibitor with gemcitabine significantly enhanced anti-tumor effects on pancreatic cancer under diabetic condition, providing a theoretical basis for clinical applications.ConclusionsGenerally, this study provides a comprehensive insight into diabetes as a risk factor for pancreatic cancer and has the potential to guide the development of enhanced treatment strategies.

Poly(ionic liquid)s nanofiber (PIL NF) membrane was derived from polyacrylonitrile by converting its cyano groups to imidazoline moieties via cyclization with ethylenediamine, followed by quaternization with 1-bromobutane. The novel PIL NF is further decorated with photocatalyst phosphotungstic acid PW12 via anion exchanging to give PW-PIL. The degradation rate of the novel supported photocatalyst towards methyl orange irradiated under visible light was found to be 98%. In addition, the nanofiber membrane morphology is beneficial for easy recycling, and 98% of original degradation rate was maintained after 5 cycles of photocatalysis degradation. This robust, efficient, and recyclable material offers a new approach for serving as catalyst supporter. The photocatalyst PW-PIL is reported for the first time. The inexpensive functional membrane is used to exploit the sun as a cheap and clean source of light.

High-throughput and high-accuracy nanofabrication methods are required for the ever-increasing demand for nanoelectronics, high-density data storage devices, nanophotonics, quantum computing, molecular circuitry, and scaffolds in bioengineering used for cell proliferation applications. The scanning probe lithography (SPL) nanofabrication technique is a critical nanofabrication method with great potential to evolve into a disruptive atomic-scale fabrication technology to meet these demands. Through this timely review, we aspire to provide an overview of the SPL fabrication mechanism and the state-the-art research in this area, and detail the applications and characteristics of this technique, including the effects of thermal aspects and chemical aspects, and the influence of electric and magnetic fields in governing the mechanics of the functionalized tip interacting with the substrate during SPL. Alongside this, the review also sheds light on comparing various fabrication capabilities, throughput, and attainable resolution. Finally, the paper alludes to the fact that a majority of the reported literature suggests that SPL has yet to achieve its full commercial potential and is currently largely a laboratory-based nanofabrication technique used for prototyping of nanostructures and nanodevices.

Background: The use of magnetic resonance imaging (MRI) in diagnosis of neonatal acute bilirubin encephalopathy (ABE) in newborns has been limited by its difficulty in differentiating confounding image contrast changes associated with normal myelination. This study aims to demonstrate the feasibility of building a machine learning prediction model based on radiomics features derived from MRI to better characterize and distinguish ABE from normal myelination.Methods: In this retrospective study, we included 32 neonates with clinically confirmed ABE and 29 age-matched controls with normal myelination. Radiomics features were extracted from the manually segmented region of interest (ROI) on T1-weighted spin echo images, followed by the feature selection using two-sample independent t-test, least absolute shrinkage and selection operator (Lasso) regression, and Pearson's correlation matrix. Additional feature quantifying the relative mean intensity of ROI was defined and calculated. A prediction model based on the selected features was built to classify ABE and normal myelination using multiple machine learning classifiers and a leave-one-out cross-validation scheme. Receiver operating characteristics (ROC) analysis was used to evaluate the prediction performance with the area under the curve (AUC) and feature importance ranked based on the Fisher score.Results: Among 1319 radiomics features, one radiologist-defined intensity-based feature and 12 texture features were selected as the most discriminative features. Based on these features, decision trees had the best classification performance with the largest AUC of 0.946, followed by support vector machine (SVM), tree-bagger, logistic regression, Naïve Bayes, discriminant analysis, and k-nearest neighborhood (KNN), which have an AUC of 0.931, 0.925, 0.905, 0.891, 0.883, and 0.817, respectively. The relative mean intensity outperformed other 12 texture features in differentiating ABE from controls.Conclusions: The results from this study demonstrated a new strategy of characterizing ABE-induced intensity and morphological changes in MRI, which are difficult to be recognized, interpreted, or quantified by the routine experience and visual-based reading strategy. With more quantitative and objective measurements, the reported machine learning assisted radiomics features-based approach can improve the diagnosis and support clinical decision-making.

Microfluidic platforms are an attractive setup for performing clinical tests but integrated liquid mixing and bioseparation is difficult at small scales. Here Xiong et al. propose magnetic nanochains which can stir the solution and capture agents and thus enable liquid analysis in a short amount of time.

Adult survivors of pediatric brain tumors exhibit deficits in executive functioning. Given that brain tumors and medical treatments for brain tumors result in disruptions to white matter, a network analysis was used to explore the topological properties of white matter networks. This study used diffusion tensor imaging and deterministic tractography in 38 adult survivors of pediatric brain tumors (mean age in years = 23.11 (SD = 4.96), 54% female, mean years post diagnosis = 14.09 (SD = 6.19)) and 38 healthy peers matched by age, gender, handedness, and socioeconomic status. Nodes were defined using the Automated Anatomical Labeling (AAL) parcellation scheme, and edges were defined as the mean fractional anisotropy of streamlines that connected each node pair. Global efficiency and average clustering coefficient were reduced in survivors compared to healthy peers with preferential impact to hub regions. Global efficiency mediated differences in cognitive flexibility between survivors and healthy peers, as well as the relationship between cumulative neurological risk and cognitive flexibility. These results suggest that adult survivors of pediatric brain tumors, on average one and a half decades post brain tumor diagnosis and treatment, exhibit altered white matter topology in the form of suboptimal integration and segregation of large scale networks, and that disrupted topology may underlie executive functioning impairments. Network based studies provided important topographic insights on network organization in long-term survivors of pediatric brain tumor. Keywords: Brain tumor survivorship, Graph theory, Executive functioning, Long-term outcomes, Cognitive flexibility, Diffusion MRI

The removal of organic pollutants using green environmental photocatalytic degradation techniques urgently need high-performance catalysts. In this work, a facile one-step hydrothermal technique has been successfully applied to synthesize a Nb2O5 photocatalyst with uniform micro-flower structure for the degradation of methyl orange (MO) under UV irradiation. These nanocatalysts are characterized by transmission and scanning electron microscopies (TEM and SEM), X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET) method, and UV-Vis diffuse reflectance spectroscopy (DRS). It is found that the prepared Nb2O5 micro-flowers presents a good crystal phases and consist of 3D hierarchical nanosheets with 400–500 nm in diameter. The surface area is as large as 48.6 m2 g−1. Importantly, the Nb2O5 micro-flowers exhibit superior catalytic activity up to 99.9% for the photodegradation of MO within 20 mins, which is about 60-fold and 4-fold larger than that of without catalysts (W/O) and commercial TiO2 (P25) sample, respectively. This excellent performance may be attributed to 3D porous structure with abundant catalytic active sites.

Abstract In this study, the effects of apple pomace (AP) addition (0%, 5%, 10%, and 20% on a dry weight basis, named as control, AP1, AP2, and AP3) and citric acid (CA) addition on nitrogen conservation were investigated during aerobic composting of pig manure. Gaseous emissions of NH3 and N2O were inhibited by AP and CA addition, with AP’s effect greater. The inhibition improved with increasing AP addition. The AP3 treatment was the most effective on NH3 adsorption and transformation to $${{\bf{NH}}}_{{\bf{4}}}^{{\boldsymbol{+}}}$$ NH 4 + -N, improved with subsequent transformation to $${{\bf{NO}}}_{{\bf{3}}}^{{\boldsymbol{-}}}$$ NO 3 − -N, and inhibition of N2O and $${{\bf{NO}}}_{{\bf{2}}}^{{\boldsymbol{-}}}$$ NO 2 − production. Compared with control, AP3 showed the highest inhibition of accumulated NH3 and N2O emission, by 57% and 24%, respectively, and with a 19% increase of total Kjeldahl nitrogen in the compost. The further pot experiment proved the application of the AP amendment compost could improve the yield and trace element nutrient accumulation in Chinese cabbage when planted in a typical Zn-deficient soil. This study illustrates that AP application benefits both compost nitrogen conservation and fertilizer quality.

Objective: Asthma and chronic obstructive pulmonary disease (COPD) are representative chronic inflammatory airway diseases responsible for a considerable burden of disease. In this article, we reviewed the relationship between neutrophil extracellular traps (NETs) and chronic inflammatory airway diseases. Data Sources: Articles published up to January 1, 2017, were selected from the PubMed, Ovid Medline, Embase databases, with the keywords of “asthma” or “pulmonary disease, chronic obstructive”, “neutrophils” and “extracellular traps.” Study Selection: Articles were obtained and reviewed to analyze the role of NETs in asthma and COPD. Results: NETs are composed of extracellular DNA, histones, and granular proteins, which are released from activated neutrophils. Multiple studies have indicated that there are a large amount of NETs in the airways of asthmatics and COPD patients. NETs can engulf and kill invading pathogens in the host. However, disordered regulation of NET formation has shown to be involved in the development of asthma and COPD. An overabundance of NETs in the airways or lung tissue could cause varying degrees of damage to lung tissues by inducing the death of human epithelial and endothelial cells, and thus resulting in impairing pulmonary function and accelerating the progress of the disease. Conclusions: Excessive NETs accumulate in the airways of asthmatics and COPD patients. Although NETs play an essential role in the innate immune system against infection, excessive components of NETs can cause lung tissue damage and accelerate disease progression in asthmatics and COPD patients. These findings suggest that administration of NETs could be a novel approach to treat asthma and COPD. Mechanism studies, clinical practice, and strategies to regulate neutrophil activation or directly interrupt NET function in asthmatics and COPD patients are desperately needed.

The biological roles of nucleic acid methylation, other than at the C5-position of cytosines in CpG dinucleotides, are still not well understood. Here, we report genetic evidence for a critical role for the putative DNA demethylase NMAD-1 in regulating meiosis in C. elegans. nmad-1 mutants have reduced fertility. They show defects in prophase I of meiosis, which leads to reduced embryo production and an increased incidence of males due to defective chromosomal segregation. In nmad-1 mutant worms, nuclear staging beginning at the leptotene and zygotene stages is disorganized, the cohesin complex is mislocalized at the diplotene and diakinesis stages, and chromosomes are improperly condensed, fused, or lost by the end of diakinesis. RNA sequencing of the nmad-1 germline revealed reduced induction of DNA replication and DNA damage response genes during meiosis, which was coupled with delayed DNA replication, impaired DNA repair and increased apoptosis of maturing oocytes. To begin to understand how NMAD-1 regulates DNA replication and repair, we used immunoprecipitation and mass spectrometry to identify NMAD-1 binding proteins. NMAD-1 binds to multiple proteins that regulate DNA repair and replication, including topoisomerase TOP-2 and co-localizes with TOP-2 on chromatin. Moreover, the majority of TOP-2 binding to chromatin depends on NMAD-1. These results suggest that NMAD-1 functions at DNA replication sites to regulate DNA replication and repair during meiosis.

To study the seismic performance of the box-plate steel structure system, two three-storey single box-plate steel structure space stress-bearing unit test pieces have been designed and fabricated according to the 1 : 3 reduced scale. In addition, the quasi-static loading test has been performed on the test pieces where the destruction process, destroy mode, bearing capacity, hysteretic behavior, etc., have been studied and the impact of reinforcing measures with a corner or not on the seismic performance of test pieces has been mainly analyzed. The test results show that the destruction of the box-plate steel structure modular unit under the low cyclic loading effect starts with corner buckling and ends with corner wallboard tear. The test piece has excellent bearing capacity and energy dissipation; the corner reinforcing structure measure also has enhanced the seismic performance of the modular unit. Based on the test, we have taken finite element numerical simulation to the test pieces, compared the analysis result of the test with the finite element, and verified the effectiveness of the finite element analysis method. This paper designs four groups of 64 finite element model test pieces and discusses the influence law of the height-thickness ratio of the wallboard, flexibility coefficient of corner reinforcing structure rib, and axial compression ratio to the seismic performance of the modular unit. The results show that the bearing capacity of the test piece is decreased with the increase of axial compression ratio under the premise that the wallboard height-thickness ratio and flexibility coefficient of the corner reinforcing structure rib are certain. Based on the above analysis results, we have put forward the lateral force resistance calculation model of the reinforcing structure modular unit with or without corner.

Dynamic susceptibility contrast enhanced magnetic resonance imaging (DSC MRI) is widely used for studying blood perfusion in brain tumors. While the time-dependent change of MRI signals related to the concentration of the tracer is used to derive the hemodynamic parameters such as regional blood volume and flow into tumors, the tissue-specific information associated with variations in profiles of signal time course is often overlooked. We report a new approach of combining model free independent component analysis (ICA) identification of specific signal profiles of DSC MRI time course data and extraction of the features from those time course profiles to interrogate time course data followed by calculating the region specific blood volume based on selected individual time courses. Based on the retrospective analysis of DSC MRI data from 38 patients with pathology confirmed low (n = 18) and high (n = 20) grade gliomas, the results reveal the spatially defined intra-tumoral hemodynamic heterogeneity of brain tumors based on features of time course profiles. The hemodynamic heterogeneity as measured by the number of independent components of time course data is associated with the tumor grade. Using 8 selected signal profile features, machine-learning trained algorithm, e.g., logistic regression, was able to differentiate pathology confirmed low intra-tumoral and high grade gliomas with an accuracy of 86.7%. Furthermore, the new method can potentially extract more tumor physiological information from DSC MRI comparing to the traditional model-based analysis and morphological analysis of tumor heterogeneity, thus may improve the characterizations of gliomas for better diagnosis and treatment decisions. Keywords: Magnetic resonance imaging, Dynamic susceptibility contrast, Brain tumor, Cerebral blood volume, Feature extraction, Signal time course