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Epilepsy is a chronic neurological disorder, and the pathophysiological progression to status epilepticus is closely associated with oxidative stress. Superoxide anions (O 2 •-), as the main, most important precursor of other reactive oxygen species (ROS), play a crucial role in seizure-induced brain damage. However, detecting the actual O 2 •- levels and understanding the physiological roles of O 2 • in epileptic brains remain challenging due to the lack of effective in vivo detection tools. Herein, a new near-infrared fluorescent probe, MB-SO, was prepared for the determination of endogenous O 2 •- in brains experiencing pentylenetetrazole (PTZ)-induced epileptic seizures. MB-SO exhibits high sensitivity (detection limit of 14 nM), good selectivity and a fast response towards O 2 •-. MB-SO was applied in situ to monitor endogenous O 2 •- in living HT-22 cells and living mice. Using this probe, we visualized and quantitatively detected endogenous O 2 •- for the first time in the hippocampi of PTZ-induced epileptic mouse brains. MB-SO also displayed a positive correlation between high O 2 •- levels in epileptic brains and epileptogenesis. These results indicated that the probe MB-SO is an efficient tool for monitoring endogenous O 2 •- in vivo and exploring the pathogenesis of epilepsy. • A novel near-infrared fluorescent probe for highly sensitive detection of O 2 •- was reported. • This probe exhibits high sensitivity (detection limit of 14 nM) and a fast response towards O 2 •-. • MB-SO was utilized to detect endogenous O 2 •- in the hippocampus of PTZ-induced epileptic mouse brains. [ABSTRACT FROM AUTHOR]

Neuroblastoma is the most common malignant tumor in childhood, and metastases occur in more than 30% patients. Recurrent metastasis is the main cause of poor prognosis and high mortality in neuroblastoma. In this regard, there is still a lack of sufficient biomarkers and effective therapies. Therefore, we performed a multi-omics analysis of neuroblastoma patients from Therapeutically Applicable Research To Generate Effective Treatments (TARGET). With clinical relapse site information, tumor samples derived from the primary site were divided into recurrent metastasis and primary tumor groups. The initial gene signature was obtained by comparing RNA-Seq and copy number variation differences. Survival data was used to further filter prognosis-related genes. This 18-gene signature consists of three clusters: tumor suppression, cell proliferation, and immunity. A super enhancer is involved in the enhanced expression of NCAPG in cluster2 together with IRF3. Based on the gene signature expression in primary neuroblastoma, it is possible to predict tumor metastasis before it occurs. According to the anticancer drug dataset of Genomics of Drug Sensitivity in Cancer (GDSC), vinorelbine and docetaxel were predicted to have high sensitivity against recurrent metastatic neuroblastoma. In conclusion, our study offers a novel metastasis biomarker and helps understand the mechanisms of tumor recurrent metastasis. Key messages: We identified a novel eighteen-gene signature of recurrent metastasis neuroblastoma and build risk and classification models. We dissected the regulatory role of NCAPG in signatures. We found immune exhaustion and immunosuppression in recurrent metastasis neuroblastoma. Vinorelbine and docetaxel were predicted to have high sensitivity against recurrent metastatic neuroblastoma. [ABSTRACT FROM AUTHOR]

Sleep problems significantly affect the quality of life of autism spectrum disorder (ASD) children. This study aimed to evaluate the effects of a 12-week ball combination exercise, continuous theta burst stimulation (cTBS) stimulation, and combined intervention on sleep problems in children with ASD. Forty-five ASD children were divided into three intervention groups (ball combination exercise(n = 12), cTBS stimulation(n = 10), combined (n = 12) and a control group (n = 11). The intervention groups underwent intervention, while the control group maintained daily activities. The effects were assessed using the Children’s Sleep Habits Questionnaire (CSHQ) scale. The results revealed that after 12 weeks of intervention, three programs reduced sleep problems in children with ASD. The post-test scores of the cTBS group (p = 0.002) and the combined group (p < 0.001) were significantly lower than the baseline scores on the CSHQ scale. The exercise group (p = 0.002) and the combined group (p < 0.001) showed significant improvement in sleep anxiety, while there was no statistically significant difference in the effectiveness of the three interventions for sleep-onset delay. The combined group outperformed the single intervention groups in the CSHQ score and sleep anxiety sub-dimensions. The combined intervention group showed slightly superior performance in sleep onset latency, however, there was no significant difference. Three interventions alleviated sleep issues in ASD children, with the combined method proving more effective. This study validates non-pharmacologic and combined approaches for ASD sleep problems. Future research should delve deeper into the mechanisms of these interventions in ASD children’s sleep improvement. [ABSTRACT FROM AUTHOR]

Broad learning system (BLS) is an emerging neural network with fast learning capability, which has achieved good performance in various applications. Conventional BLS does not effectively consider the problems of class imbalance. Moreover, parameter tuning in BLS requires much effort. To address the challenges mentioned above, we propose a double-kernelized weighted broad learning system (DKWBLS) to cope with imbalanced data classification. The double-kernel mapping strategy is designed to replace the random mapping mechanism in BLS, resulting in more robust features while avoiding the step of adjusting the number of nodes. Furthermore, DKWBLS considers the imbalance problem and achieves more explicit decision boundaries. Numerous experimental results show the superiority of DKWBLS in tackling imbalance problems over other imbalance learning approaches. [ABSTRACT FROM AUTHOR]

The onset of bipolar disorder (BD) occurs in childhood or adolescence in half of the patients. Early stages of BD usually present depressive episodes, which makes it difficult to be distinguished from major depressive disorder (MDD). Objective biomarkers for discriminating BD from MDD in adolescent patients are limited. We collected basic demographic data and the information of the first blood examination performed after the admission to psychiatry unit of BD and MDD inpatients during 2009–2018. We recruited 261 adolescents (aged from 10 to 18), including 160 MDD and 101 BD. Forward-Stepwise Selection of binary logistic regression was used to construct predictive models for the total sample and subgroups by gender. Independent external validation was made by 255 matched patients from another hospital in China. Regression models of total adolescents, male and female subgroups showed accuracy of 73.3%, 70.6% and 75.2%, with area under curves (AUC) as 0.785, 0.816 and 0.793, respectively. Age, direct bilirubin (DBIL), lactic dehydrogenase (LDH), free triiodothyronine (FT3) and C-reactive protein (CRP) were final factors included into the models. The discrimination was well at external validation (AUC = 0.714). This study offers the evidence that accessible information of common clinical laboratory examination might be valuable in distinguishing BD form MDD in adolescents. With good diagnostic accuracies and external validation, the total regression equation might potentially be applied to individualized clinical inferences on adolescent BD patients. [ABSTRACT FROM AUTHOR]

Thermal compression tests were conducted on Al-1.2Mg-2.4Si-1.2Cu-0.6Mn alloys with process parameters including deformation temperatures ranging from 400°C to 550°C and strain rates ranging from 0.05 s⁻¹ to 1 s⁻¹. The hot working properties of aluminum alloys were evaluated with intrinsic equations and machining diagrams. The results show that the processing safety zones of the alloy are 425–450℃ and 0.05–0.1 s−1, 450–475℃ and 0.1 s−1-0.5 s−1, and 475–500℃ and 0.5 s−1. The microstructure of the aluminum alloy following hot pressing was investigated through the use of optical microscopy (OM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and backscattered electron diffraction (EBSD). When the deformation temperature of the alloy is below 450°C, the alloy organization exhibits a greater prevalence of inhomogeneous defects, which manifest as coarser granular regions in the micro-morphology. Upon reaching a deformation temperature of above 525°C, the deformed alloy organization exhibits an evident thermal cracking phenomenon. At the same temperature, an increase in strain rate is accompanied by a decrease in the Mg 2 Si phase and an increase in the precipitation of the Al(Fe,Mn)Si eutectic phase. Furthermore, the precipitated phase tends to become coarser. The presence of certain Mn-containing nanoparticle dispersions can impede the migration of subgrain grain boundaries, while simultaneously pinning dislocations and accelerating the generation of dislocation entanglement. This also can serve to inhibit the coarsening of the grains to some extent. • Analysis of deformation mechanism by thermal compression behavior of Al-1.2Mg-2.4Si-1.2Cu-0.6Mn alloys. • The alloy is prone to defects in low-temperature deformation and thermal cracking in high-temperature deformation. • A substantial quantity of Mn-containing nanoparticles precipitate within the dislocation aggregation region. [ABSTRACT FROM AUTHOR]

The fatigue properties of lithium hydride (LiH) are crucial to its application as neutron shielding and moderating at elevated temperatures. The dynamic fatigue tests of LiH were investigated with the notched 3-point bend (3 PB) specimens over ranges of loading rates at RT up to 400 °C. At RT, the results showed that slow crack growth (SCG) occurred prior to failure as the minor deviation from linearity to nonlinearity in the load-deflection curves. In addition, the fracture strength of LiH decreased with decreasing stress rate and the SCG zone gradually became smaller with higher stress rates, indicating evident dynamic fatigue phenomenon. However, the trends were quite different at 200, 300 and 400 °C due to accumulative creep damage for low stress rates at elevated temperatures. With increasing temperature and decreasing stress rate, there existed a transition of the dominated failure mechanism, from SCG to creep rupture. Evidence of very small SCG zone could also be detected at the notch for the failure dominated by creep rupture. • Lithium hydride (LiH) shows obvious dynamic fatigue phenomenon and the slow crack growth parameter is determined to be 15.787 at room temperature. • A transition in the dominated failure mechanism, from slow crack growth (SCG) to creep rupture, is found with increasing temperature and decreasing stress rate in the dynamic fatigue tests. • Evidence of very small SCG zone could also be detected at the notch for the failure dominated by creep rupture. [ABSTRACT FROM AUTHOR]

3D printed EPS concrete integrates the advantages of 3D printing technology and EPS lightweight concrete, offering the potential to reduce carbon emissions and enhance the environmental sustainability of construction. In this study, we successfully printed EPS concrete with densities ranging from 500 to 1900 kg/m3, using EPS particles to substitute for sand up to 100% volume ratio. The rheology of the mortars was elucidated through the excess paste theory. We introduced a composite aggregate model to calculate excess paste volume when composite aggregates were used. This study revealed that aggregates with distinct properties exhibited different excess paste layer thicknesses under similar rheological states. To address this, the excess paste thickness ratio of different aggregates was measured, enabling precise calculation of excess paste thickness, which aligns with mortar rheological properties. The study further indicates that the relatively high static yield stress of 3D printed concrete mitigates the floating of EPS particles, thereby promoting the uniformity of EPS concrete. • EPS particles are used to fabricate 3D printed low density concrete with densities ranging from 500 to 1900 kg/m3. • A composite aggregate model is developed to enable more precise excess paste volume calculations. • Aggregates with distinct properties exhibit different excess paste layer thicknesses under similar rheological states. • The excess paste layer theory of composite aggregates is optimized. • The high static yield stress of 3D printed concrete ensures a uniform distribution of EPS particles within the concrete. [ABSTRACT FROM AUTHOR]

[Display omitted] Triple negative breast cancer (TNBC) presents a formidable challenge due to its low sensitivity to many chemotherapeutic drugs and a relatively low overall survival rate in clinical practice. Photothermal therapy has recently garnered substantial interest in cancer treatment, owing to its swift therapeutic effectiveness and minimal impact on normal cells. Metal-polyphenol nanostructures have recently garnered significant attention as photothermal transduction agents due to their facile preparation and favorable photothermal properties. In this study, we employed a coordinated approach involving Fe3+ and apigenin, a polyphenol compound, to construct the nanostructure (nFeAPG), with the assistance of β-CD and DSPE-PEG facilitating the formation of the complex nanostructure. In vitro research demonstrated that the formed nFeAPG could induce cell death by elevating intracellular oxidative stress, inhibiting antioxidative system, and promoting apoptosis and ferroptosis, and near infrared spectrum irradiation further strengthen the therapeutic outcome. In 4T1 tumor bearing mice, nFeAPG could effectively accumulate into tumor site and exhibit commendable control over tumor growth. Futher analysis demonstrated that nFeAPG ameliorated the suppressed immune microenvironment by augmenting the response of DC cells and T cells. This study underscores that nFeAPG encompasses a multifaceted capacity to combat TNBC, holding promise as a compelling therapeutic strategy for TNBC treatment. [ABSTRACT FROM AUTHOR]

In this paper, the effect of Si content on the microstructure and mechanical properties of the Al–1.2Mg–xSi–1.2Cu–0.6Mn cast alloy was investigated. The study aimed to explore the optimal addition of Si element to improve the comprehensive properties of alloys. The microstructure, phase composition and fracture morphology of the alloy were determined through OM, SEM, EBSD and XRD analysis. The Si content in the alloy ranged from 0.48 to 2.4 wt.%. With the increase of Si content, the number of strengthening phases increases, which improves the comprehensive properties of the alloy. When the Si content is 0.8 wt.%, the eutectic Mg2Si transforms from rod-shaped to larger block shaped, and the formation of coarse Mg2Si phase limits the elongation of the alloy. When the Si content is 2.4 wt.%, fine Al2Cu phases are present in this alloy and coexist with Al(Fe,Mn)Si phases, while an increase in the Si content appears as partially accompanied by an incipient crystalline Si phase around the Al(Fe,Mn)Si phase. The alloy exhibits a maximum tensile strength, yield strength and elongation of 198.2 MPa, 101.2 MPa and 4.96%, respectively, with a hardness of 80.94 Hv. It consists of five alloy phases, mainly α-Al, Mg2Si, Al(Fe, Mn)Si eutectic phase, Q-AlCuMgSi eutectic phase and the beginning crystalline silicon phase formed due to the increased Si content. The Si content can improve alloy strength, but there is some damage to the toughness of the alloy. Higher silicon alloy content results in the formation of fine Al2Cu eutectic. This result makes it possible to achieve a higher level of strength with a reduced loss of ductility in the alloy. [ABSTRACT FROM AUTHOR]

Chronic diabetic wounds pose a serious threat to human health and safety because of their refractory nature and high recurrence rates. The formation of refractory wounds is associated with wound microenvironmental factors such as increased expression of proinflammatory factors and oxidative stress. Bilirubin is a potent endogenous antioxidant, and morin is a naturally active substance that possesses anti-inflammatory and antioxidant effects. Both hold the potential for diabetic wound treatment by intervening in pathological processes. In this study, we developed bilirubin/morin-based carrier-free nanoparticles (BMn) to treat chronic diabetic wounds. In vitro studies showed that BMn could effectively scavenge overproduced reactive oxygen species and suppress elevated inflammation, thereby exerting a protective effect. BMn was then loaded into a collagen/polyvinyl alcohol gel (BMn@G) for an in vivo study to maintain a moist environment for the skin and convenient biomedical applications. BMn@G exhibits excellent mechanical properties, water retention capabilities, and in vivo safety. In type I diabetic mice, BMn@G elevated the expression of the anti-inflammatory factor IL-10 and concurrently diminished the expression of the proinflammatory factor TNF-α in the tissues surrounding the wounds. Furthermore, BMn@G efficiently mediated macrophage polarization from the M1-type to the M2-type, thereby fostering anti-inflammatory effects. Additionally, BMn@G facilitated the conversion of type III collagen fiber bundles to type I collagen fiber bundles, resulting in a more mature collagen fiber structure. This study provides a promising therapeutic alternative for diabetic wound healing. [ABSTRACT FROM AUTHOR]

Background: Little is known how often depressive episodes are accompanied by gastrointestinal symptoms in major depressive disorders (MDD). The authors sought to determine the frequency and clinical correlates of gastrointestinal symptoms during episodes of depressive disorder.Methods: 3,256 MDD patients from the National Survey on Symptomatology of Depression (NSSD), which was designed to investigate the magnitude of symptoms of current major depressive episodes in China, were enrolled and assessed for gastrointestinal symptoms in this study. Illness characteristics were compared in patients with a different frequency of gastrointestinal symptoms. Pearson correlation analysis and multiple linear regression analysis were employed to investigate the associations between gastrointestinal symptoms and psychological characteristics in the patients.Results: More than 70% of the subjects with depressive episodes had concomitant gastrointestinal symptoms. A higher frequency of gastrointestinal symptoms was associated with an increased risk of suicide ideation, suicide attempts, anxious mood, depressed mood, insomnia, feeling a failure, poor concentration, body pain, hopelessness, anger, and irritability. Pearson correlation analysis indicated moderate but significant associations between gastrointestinal symptoms and psychological characteristics (p<0.001). Multiple linear regression analysis showed that suicide ideation (β=0.161, p<0.001), anxiety mood (β=0.166, p = 0.006), insomnia (β =0.262, p<0.001), anger (β=0.144, p<0.001), feeling a failure (β =0.365, p<0.001), and body pain (β=0.581 p<0.001) were independently associated with gastrointestinal symptoms in MDD patients.Conclusion: Gastrointestinal symptoms were one of the most prevalent clinical presentations of MDD. The associations between gastrointestinal symptoms and psychological characteristics may prove useful in expanding our understanding of how gastrointestinal symptoms contributes to MDD. [ABSTRACT FROM AUTHOR]

IR825 is a kind of near-infrared (NIR) small molecule cyanine dye and has distinct near-infrared absorbance and excellent thermal conversion performance. Due to poor stability and insufficient therapy efficacy, various nano-systems have been developed as delivery vehicles for NIR dyes to improve their application in tumor treatment. Herein, we developed an intelligent polymer drug vehicle (Mal-PAH-PEG-DMMA/ poly (ethylene imine) – poly(ε-caprolactone) block polymers, MPPD/PEI-PCL) based on pH-responsive charge-reversal to deliver docetaxel (DTX) and photosensitizer (IR825) for chemo-photothermal combination therapy (MPPD@IR825/DTX NPs). MPPD@IR825/DTX NPs could undergo charge conversion in a slightly acidic microenvironment (pH 6.8), resulted in strong electrostatic repulsion to withdraw the shell of the polymer nanoparticles (MPPD), enhanced cellular uptake and increased drug release. MPPD@IR825/DTX NPs demonstrated nanoscale in size with good mono-dispersity and stability, triggered DTX release in response to acid environment and NIR stimulation, in the same time providing excellent photothermal conversion efficiency. In vitro and In vivo experiments confirmed that charge-reversal polymeric nanoparticles improved antitumor efficiency in 4T1 tumor cell modal than non-charge-reversal polymeric nanoparticles. Furthermore, in comparison with chemotherapy or photothermal therapy in a single treatment mode, chemo-photothermal combination therapy of MPPD@IR825/DTX NPs with laser irradiation showed highly efficient tumor ablation. In addition, the polymeric nanoparticles exhibited good biocompatibility and safety. Therefore, the design of charge-reversal polymeric nanoparticles (MPPD@IR825/DTX NPs) provides a new strategy and promising application for targeting and synergistic chemo-photothermal combination therapy. [Display omitted] • Chemo-photothermal combined therapy enhances the effect of cancer treatment. • IR825 has excellent photothermal conversion efficiency under laser irradiation. • MPPD@IR825/DTX NPs had charge-switchable properties in a slightly acidic environment. • MPPD@IR825/DTX NPs had excellent photothermal conversion properties under laser. • MPPD@IR825/DTX NPs improved antitumor efficiency in 4T1 tumor cell modal. [ABSTRACT FROM AUTHOR]

Current tools for predicting survival outcomes in colon cancer patients predominantly rely on clinical and pathologic characteristics. However, accumulating evidence demonstrates a significant correlation between nutritional status and patient outcomes. This study aimed to establish a new dynamic nomogram for individualized prediction of postoperative overall survival (OS). The clinicopathological and nutritional data of colon cancer patients undergoing radical resection were retrospectively collected and randomly divided into the primary and validation cohorts. Risk factors on OS rates were investigated by Cox analyses and, the nomogram was constructed using significant predictors. Among 1,024 patients, 341 deaths were observed after median follow-up of 54 months. Five independent prognostic factors, including nutritional status assessments, were incorporated into the nomogram. The C-index regarding 1-, 3-, and 5-year OS were 0.830, 0.859, and 0.757 in the primary cohort and 0.843, 0.870, and 0.773 in the validation cohort, respectively. Calibration curves for the probability of OS exhibited an optimal agreement. Decision curve analyses revealed the greater application value of the nomogram than the TNM staging system. Based on the nomogram, patients could be stratified into three scenarios with significant prognostic classification (P < 0.0001). In conclusion, we developed and validated an easy-to-use dynamic nomogram for predicting postoperative OS in colon cancer patients., Competing Interests: Competing interests The authors declare no competing interests or personal relationships that can influence the work reported in this paper., (© 2024. The Author(s).)

Background: Previous studies found that urinary phthalates (PAEs) metabolites may be associated with increased serum uric acid concentration and hyperuricemia risk. However, no population-based study has investigated the underlying biological mechanisms., Methods: This nationwide cross-sectional study analyzed the data from the National Health and Nutrition Examination Survey (NHANES) 2003-2018. Urinary PAEs metabolites were measured and 8 PAEs metabolites (MCPP, MECPP, MEHHP, MEOHP, MBzP, MiBP, MBP, and MEP) were incorporated into the analysis. Serum uric acid was determined and hyperuricemia cases were identified. Multi-variable generalized linear model, exposure-response (E-R) function and weighted quantile sum (WQS) regression were utilized to investigate the relationships of PAEs metabolites with serum uric acid concentration and hyperuricemia risk. Systemic immune inflammation (SII) was assessed using the SII index and its mediation effects were explored using causal mediation effect model., Results: Data from 10,633 US adults in the NHANES 2003-2018 was analyzed. Except for MEP, individual PAEs metabolite and total PAEs metabolites were associated with increased serum uric acid concentration and hyperuricemia risk. E-R function of PAEs metabolites with serum uric acid concentration and the risk of hyperuricemia showed significantly positive associations with most curves in a nearly linear relationship. WQS regression showed that the mixture of PAEs metabolites was related to elevated serum uric acid and hyperuricemia risk, and MBzP was identified as the most contributing PAEs metabolite. The causal mediation effect model found that SII significantly mediated the relationships of PAEs metabolites with serum uric acid and hyperuricemia risk., Conclusion: Individual and mixture of urinary PAEs metabolites were associated with increased serum uric acid concentration and the risk of hyperuricemia. MBzP exhibited the highest contribution to the overall effects. SII alteration may be an important biological mechanism underlining the impact of PAEs metabolites on serum uric acid concentration and hyperuricemia risk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To use an elastography technology and other clinical and radiological data for assessment of liver background and analyze risk factors of complications after thermal ablation in patients with hepatocellular carcinoma., Methods: Demographics, laboratory analyses, and radiological characteristics were collected from all patients. Main elastography-related indicators included F index (fibrosis index), A index (inflammation index), ATT (attenuation coefficient), E (kPa), AREA (area of blue parts), and CORR (correlation). All complications after thermal ablation were collected. Univariate analysis was performed to detect significant variables, which subsequently entered a stepwise logistic regression analysis (conditional forward selection) to identify independent variables., Results: A total of 218 patients from October 2020 to June 2023 with 291 thermal ablation sessions were enrolled. 115 patients (52.8%) developed complications. Fifteen patients (6.9%) developed major complications. Minor complications included postoperative pain (20.6%), fever (19.3%), effusion (22.5%), and hyperammonemia (1.8%). AREA (P = 0.034), tumor size (P = 0.005), and abnormal aspartate aminotransferase (AST) (P = 0.018) were independent predictors for complications. F index (P = 0.021), tumor size (P < 0.001), and abnormal AST (P = 0.047) were independent predictors for effusion. The results of univariate analysis of infection showed that tumor size, CORR, ATT, diabetes, Child-Turcotte-Pugh grade, abnormal AST, total protein, and albumin were significant (all P < 0.05)., Conclusion: Several radiological and combinational elastography indicators related to liver fibrosis, steatosis, or inflammation were significantly correlated with the occurrence of complications. Clinical assessment of the liver background should not be neglected in the management of postablation complications., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by unpredictable progression and limited therapeutic options. Current diagnosis relies on high resolution computed tomography (HRCT), which may not adequately capture early signs of deterioration. The enzyme autotaxin (ATX) emerges as a prominently expressed extracellular secretory enzyme in the lungs of IPF patients. The objective of this study was to evaluate the effectiveness of 18 F-labeled ATX-targeted tracer [ 18 F]ATX-1905, in comparison with [ 18 F]FDG, for early fibrosis diagnosis, disease evolution monitoring, and treatment efficacy assessment in bleomycin-induced pulmonary fibrosis (BPF) models. To assess treatment efficacy, mice were treated with two commonly used drugs for IPF, pirfenidone or nintedanib, from Day 9 to Day 23 postbleomycin administration. Lung tissue assessments encompassed inflammation severity via H&E staining, and Ashcroft scoring via Masson staining, alongside quantification of ATX expression through ELISA. Positron emission tomography (PET) imaging employing [ 18 F]FDG and [ 18 F]ATX-1905 tracked disease progression pre- and post-treatment. The extent of pulmonary fibrosis corresponded to changes in ATX expression levels in the BPF mouse model. Notably, [ 18 F]ATX-1905 exhibited elevated uptake in BPF lungs during the progression of the disease, particularly evident at the early stage (Day 9). This uptake was inhibited by an ATX inhibitor, PF-8380, underscoring the specificity of the radiotracer. Conversely, [ 18 F]FDG uptake, peaking at Day 15, decreased subsequently, likely reflective of diminished inflammation. A 2-week treatment regimen using either pirfenidone or nintedanib resulted in notable reductions of ATX expression levels and fibrosis degrees within lung tissues, based on ELISA and Masson staining, as evidenced by PET imaging with [ 18 F]ATX-1905. [ 18 F]FDG uptake also decreased following the treatment period. Additionally, PET/CT imaging extended to a nonhuman primate (NHP) BPF model. The uptake of [ 18 F]ATX-1905 (SUV max = 2.2) was significantly higher than that of [ 18 F]FDG (SUV max = 0.7) in fibrotic lung tissue. Using our novel ATX-specific radiotracer [ 18 F]ATX-1905 and PET/CT imaging, we demonstrated excellent ability in early fibrosis detection, disease monitoring, and treatment assessment within lungs of the BPF mouse models. [ 18 F]ATX-1905 displayed remarkable specificity for ATX expression and high sensitivity for ATX alterations, suggesting its potential for monitoring varying ATX expression in lungs of IPF patients.

Accumulating evidence indicates that disruption of the circadian clock contributes to the development of lifestyle-related diseases. We have previously shown that exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, can strongly affect the molecular clocks in the peripheral tissues. This study aimed to investigate the effects of its dosing time and the central nervous system-specific GLP-1 receptor knockdown (GLP1RKD) on the hepatic clock in mice treated with exenatide. Male C57BL/6J and GLP1RKD mice were housed under a 12-h/12-h light/dark cycle, and feeding was restricted to either the light period (L-TRF) or the first 4 h in the dark period (D-TRF). In parallel, exenatide was administered 4-5 times, once daily either at the beginning of the dark (ZT 12) or light period (ZT 0), and we assessed the mRNA expression rhythms of clock genes in the liver thereafter. Exenatide administration at ZT 12 counteracted the phase shift effect of the L-TRF on the hepatic clock of wild-type mice, whereas the dosing at ZT 0 enhanced its effect. However, exenatide did not influence the phase of the hepatic clock under D-TRF regardless of the dosing time. The effect of exenatide in wild-type mice weakened in GLP1RKD mice. These results showed that exenatide dosing time-dependently affects the hepatic circadian clock through the central GLP-1 system. Exenatide administration at the beginning of the active period (i.e., in the morning for humans) might prevent disruption of the peripheral clocks caused by irregular eating habits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background & Aims: Sarcopenia, a prevalent condition, significantly impacts the prognosis of patients with decompensated cirrhosis (DC). Serum fibroblast growth factor 21 (FGF21) levels are significantly higher in DC patients with sarcopenia. Satellite cells (SCs) play a role in aging- and cancer-induced sarcopenia. Here, we investigated the roles of FGF21 and SCs in DC-related sarcopenia as well as the underlying mechanisms., Methods: We developed two DC mouse models and performed in vivo and in vitro experiments. Klotho beta (KLB) knockout mice in SCs were constructed to investigate the role of KLB downstream of FGF21. In addition, biological samples were collected from patients with DC and control patients to validate the results., Results: Muscle wasting and impaired SC myogenesis were observed in the DC mouse model and patients with DC. Elevated circulating levels of liver-derived FGF21 were observed, which were significantly negatively correlated with skeletal muscle mass/skeletal muscle index. Liver-secreted FGF21 induces SC dysfunction, contributing to sarcopenia. Mechanistically, FGF21 in the DC state exhibits enhanced interactions with KLB on SC surfaces, leading to downstream phosphatase and tensin homolog upregulation. This inhibits the protein kinase B (PI3K/Akt) pathway, hampering SC proliferation and differentiation, and blocking new myotube formation to repair atrophy. Neutralizing circulating FGF21 using neutralizing antibodies, knockdown of hepatic FGF21 by adeno-associated virus, or knockout of KLB in SCs effectively improved or reversed DC-related sarcopenia., Conclusions: Hepatocyte-derived FGF21 mediates liver-muscle crosstalk, which impairs muscle regeneration via the inhibition of the PI3K/Akt pathway, thereby demonstrating a novel therapeutic strategy for DC-related sarcopenia., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objective: In a previous study we have shown that, in the presence of interleukin (IL)-33, repeated, per-nasal challenge of murine airways with Streptococcus pneumoniae ( S. pneumoniae ) organisms induces human asthma-like airways inflammation. It is not clear, however, whether this effect is unique or manifest in response to other common respiratory pathogens. Methods: To explore this, airways of BALB/c mice were repeatedly challenged per-nasally with formaldehyde-inactivated bacterial bodies in the presence or absence of murine recombinant IL-33. Serum concentrations of S.pneumoniae , Moraxella catarrhalis ( M.catarrhalis ) and Haemophilus influenzae ( H.influenzae ) lysates-specific IgE were measured in patients with asthma and control subjects. Results: We showed that in the presence of IL-33, repeated, per-nasal airways exposure to the bodies of these bacteria induced airways hyperresponsiveness (AHR) in the experimental mice. This was accompanied by cellular infiltration into bronchoalveolar lavage fluid (BALF), eosinophilic infiltration and mucous hypertrophy of the lung tissue, with elevated local expression of some type 2 cytokines and elevated, specific IgG and IgE in the serum. The precise characteristics of the inflammation evoked by exposure to each bacterial species were distinguishable. Conclusions: These results suggest that in the certain circumstances, inhaled or commensal bacterial body antigens of both Gram-positive ( S. pneumoniae ) and Gram-negative ( M. catarrhalis and H. influenzae ) respiratory tract bacteria may initiate type 2 inflammation typical of asthma in the airways. In addition, we demonstrated that human asthmatic patients manifest elevated serum concentrations of M.catarrhalis- and H.influenzae- specific IgE.

Objectives: Patients with end-stage renal disease (ESRD) on hemodialysis (HD) are at risk for hyperkalemia (HK), associated with cardiac arrhythmia and sudden death. Data on the burden of HK and management techniques among HD patients in China are still scarce. This study assessed the treatment modalities, recurrence, and prevalence of HK in Chinese HD patients., Methods: In this prospective cohort study conducted from May 2021 to July 2022, patients aged ≥18 years who had ESRD and were on HD were enrolled from 15 centers in China (up to 6 months)., Results: Overall, 600 patients were enrolled. At the baseline visit, mean (± standard deviation) urea reduction ratio was 68.0% ± 9.70 and Kt/V was 1.45 ± 0.496. Over 6 months, 453 (75.5%) patients experienced HK, of whom 356 (78.6%) recurred. Within 1, 2, 3, 4, 5, and 6 months, 203 (44.8%), 262 (57.8%), 300 (66.2%), 326 (72.0%), 347 (76.6%), and 356 (78.6%) patients had at least one HK recurrence event, respectively. The proportions of patients with ≥1, 2, 3, 4, 5, or 6 HK recurrence events were 356 (78.6%), 306 (67.5%), 250 (55.2%), 208 (45.9%), 161 (35.5%), and 110 (24.3%), respectively. Among the 453 patients who experienced HK, only 24 (5.3%) were treated with potassium binders: seven (1.5%) with sodium polystyrene sulfonate, 13 (2.9%) with calcium polystyrene sulfonate, and six (1.3%) with sodium zirconium cyclosilicate., Conclusion: Since HK is a chronic illness, long-term care is necessary. Patients on HD should have effective potassium management on non-dialysis days, yet our real-world population rarely used potassium binders., Trial Registration: ClinicalTrials.gov Identifier NCT04799067.

Background: This study aimed to compare the effects of two 12-week training intervention experimental ball games combined with standard behavioral rehabilitation against a control group solely utilizing standard behavioral rehabilitation on social communication impairments (SCI) in preschool children with Autism Spectrum Disorder (ASD)., Methods: A multi-arm controlled study design was implemented, involving 41 children diagnosed with ASD (mean age: 4.99 ± 0.76 years). 41 participants were randomized assigned to two experimental groups and a control group, The experimental group carried out ball combination training program group (BCTP) and mini-basketball training program group (MBTP) on the basis of routine behavioral rehabilitation, which underwent 12-week training interventions 5 times a week. The control group (n = 14) received only standard behavioral rehabilitation. Evaluations were conducted before and after interventions using the Social Responsiveness Scale, Second Edition (SRS-2)., Results: The results suggest that both 12-week interventions, BCTP, and MBTP, led to significant improvements in social communication impairment among children with ASD (p < 0.05). Despite enhancing the overall scores on the SRS-2, these interventions displayed varying impacts across different sub-dimensions. BCTP primarily exhibited significant enhancements in social awareness and behavior pattern (p < 0.05), whereas MBTP significantly improved social cognition and social communication (p < 0.05). Both interventions showed slight improvements in social motivation., Conclusions: The utilization of recreational ball games has showed to be effective in decreasing the impairment levels of children with ASD, while the control group experienced a worsening of outcomes. This suggests that irrespective of the specific ball game strategy employed, both can be employed on a weekly basis to complement standard behavioral rehabilitation and enhance the ability to improve the quality of life for children diagnosed with ASD., Trial Registration: The trial is retrospectively registered on the Chinese Clinical Trial Registry (ChiCTR1900024973;August 5, 2019)., (© 2024. The Author(s).)

Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cation-exchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK + ) levels >5.0 mmol/L]. This is the first real-world study aimed to assess the effectiveness, safety, and treatment patterns of SZC in Chinese patients with HK. Here we present the results of the first interim analysis. Methods: This multicenter, prospective, cohort study included patients aged ≥18 years with documented HK within 1-year before study enrollment day. These patients were followed up for 6 months from the enrollment day after initiating SZC treatment. The treatment was categorized into correction phase (FAS-P1) and maintenance phase (FAS-P2 new and ongoing users). Subgroup analysis was performed in patients on hemodialysis (FAS-H). The primary objective was evaluation of safety profile of SZC; secondary objectives included assessment of treatment patterns of SZC and its effectiveness. Results: Of 421 screened patients, 193, 354, and 162 patients were enrolled in the FAS-P1, FAS-P2, and FAS-H groups, respectively. sK + levels were reduced significantly from 5.9 mmol/L to 5.0 mmol/L after the correction phase. For the maintenance phase, the mean sK + levels were maintained at 5.2 mmol/L and 5.0 mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3 mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48 h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6 months in the maintenance phase (FAS-P2:44%). SZC was well-tolerated. Conclusion: SZC was effective and safe for the treatment of HK in real-world clinical practice in China., Competing Interests: Author YS was employed by AstraZeneca Investment China Co. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from AstraZeneca Investment China. The funder was involved in the study design, but was not involved in the collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication., (Copyright © 2024 Shen, Zhang, Yang, Lin, Liu, Cai, Cao, Zhu, Luo, Wan, Wu, Ye, Shan, Xie, Wu, Cao, Wang, Yu, Wang, He, Tian, Wu, Jiang, Li, Zuo, Wang, Xing, Yin, Zhao, Ma, Long, Li, Hu, Shi and Lin.)

Objective: Handgrip strength (HGS) and the high-sensitivity modified Glasgow prognostic score (HS-mGPS) are associated with the survival of patients with cancer. However, no studies have investigated the combined effect of HGS and HS-mGPS on the overall survival (OS) of patients with colon cancer., Methods: Prospective follow-up data of colon cancer patients undergoing radical resection from April, 2016 to September, 2019 were retrospectively collected. We combined the HGS and HS-mGPS to create a new composite index, HGS-HS-mGPS. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox regression models to assess the association between variables and OS. Risk factors on OS rates were investigated by Cox analyses and the nomogram was constructed using significant predictors and HGS-HS-mGPS. The predictive performance of the nomogram was evaluated by receiver operating characteristic curve and calibration curve., Results: This study included a total of 811 patients, of which 446 (55.0%) were male. The HGS optimal cut-off values of male and female patients were 28.8 and 19.72 kg, respectively. Multivariate analysis revealed that low HGS and high HS-mGPS were independent risk factors of colon cancer after adjusting confounders (adjusted HR = 3.20; 95% CI: 2.27-4.50; p  < 0.001 and adjusted HR = 1.55; 95% CI: 1.12-2.14; p  = 0.008 respectively). Patients with low HGS and high HS-mGPS had a 10.76-fold higher mortality risk than those with neither (adjusted HR = 10.76; 95% CI: 5.38-21.54; p  < 0.001). A nomogram predicting 1-, 3-, and 5 year OS was constructed based on three clinicopathologic prognostic factors. Importantly, incorporating HGS-HS-mGPS into the nomogram model meaningfully improved the predictive performance. The decision curve analyses demonstrated the application value of the HGS-HS-mGPS nomogram for predicting OS of patients with colon cancer., Conclusion: HGS-HS-mGPS is associated with the survival of patients with colon cancer. These findings indicate the usefulness of HGS and HS-mGPS measurements in clinical practice for improving patient assessment, cancer prognosis, and precise intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shi, Sun, Shen, Yang, Xu and Bao.)

Many current electronic medical record (EMR) sharing schemes that use proxy re-encryption and blockchain do not fully consider the potential threat of malicious node impersonation attacks. This oversight could lead to data leakage as attackers masquerade as legitimate users or proxy nodes during the sharing process. To deal with this problem, we propose an EMR sharing scheme based on proxy re-encryption and blockchain to protect against impersonation attacks. First, we prevent the potential threat of impersonation attacks by generating a shared temporary key and assigning tasks to multiple proxy nodes. Second, we use a random function to ensure that the selection of encrypted proxy nodes is fair. Third, we use a combination of blockchain and the InterPlanetary File System to solve the problem of insufficient storage capacity of shared processes and ensure the storage security of EMRs. Through the security proof, our scheme guarantees anti-impersonation, anti-collusion, and anti-chosen plaintext attack capability in the sharing process of EMRs. Additionally, experiments on the blockchain platform, namely Chain33, show that our scheme significantly increases efficiency.

Background: Social communication impairments (SCI) is a core symptom of autism spectrum disorder (ASD) and is marked by challenges in social interaction. Although physical exercise has been shown to improve SCI, this finding has not been supported by comprehensive scientific evidence. Existing research has established a strong link between the SCI in children with ASD and abnormalities in regional homogeneity (ReHo). Therefore, investigating the effects of physical exercise on SCI and Reho in patients with ASD may help to elucidate the neurological mechanisms involved., Methods: The present study included 30 preschool children diagnosed with ASD, with 15 participants in each group (experimental and control). The experimental group underwent a 12-week mini-basketball training program (MBTP) based on routine behavioral rehabilitation, while the control group only received routine behavioral rehabilitation. The Social Responsiveness Scale-Second Edition (SRS-2) was employed to assess SCI in both groups. Resting-state functional magnetic resonance imaging technology was used to evaluate ReHo in both groups., Results: After 12-week of MBTP, significant group × time interactions were observed between the experimental and control groups in total SRS-2 scores (F = 14.514, p < 0.001, η p 2 = 0.341), as well as in the domains of social cognition (F = 15.620, p < 0.001, η p 2 = 0.358), social communication (F = 12.460, p < 0.01, η p 2 = 0.308), and autistic mannerisms (F = 9.970, p < 0.01, η p 2 = 0.263). No statistical difference was found in the scores for the social awareness subscale and social motivation subscale in the group × time interaction (all p > 0.05). The experimental group exhibited increased ReHo in the right Cerebellum&#95;Crus1 and right parahippocampal gyrus, coupled with decreased ReHo in the left middle frontal gyrus (orbital part), left superior frontal gyrus (dorsolateral), left postcentral gyrus, and right superior parietal gyrus. Furthermore, a decrease in ReHo in the left postcentral gyrus positively correlated with changes in social communication scores in SCI behaviors (p < 0.05)., Conclusions: Our study underscores the effectiveness of a 12-week MBTP in ameliorating SCI and abnormalities in ReHo among preschool children with ASD., Trial Registration: The trial is retrospectively registered on the Chinese Clinical Trial Registry (ChiCTR1900024973; August 5, 2019)., (© 2024. The Author(s).)

This study aimed to explore the relationship between motor skill learning and executive function (EF), with an emphasis on the potential effects of football juggling learning. A randomized controlled trial involving 111 participants aged 17-19 years was conducted. Participants were randomly assigned to either the football juggling learning (FJL) group or a control group. The FJL group underwent 70 sessions of football juggling learning, while the control group engaged in their normal daily activities without any exercise intervention during the same time frame. Both groups were assessed for EF performance and underwent functional magnetic resonance imaging (fMRI) scans before and after the experiment. The executive function test included three tasks, namely, inhibition, working memory, and shifting. The results showed significant improvement in inhibition and shifting in both groups, and the FJL group showed greater improvement in these aspects of EF compared to the control group. Additionally, in comparison to the control group, the FJL group exhibited increased functional connectivity within the frontal, temporal, and cerebellar regions from the pre-test to the post-test. Notably, enhanced functional connectivity between the right superior temporal gyrus (posterior division) and left cerebellum 6 was identified in the FJL group and was associated with improved EF performance induced by football juggling learning. These findings shed light on the potential causal relationship between motor skill learning, EF, and brain plasticity. Importantly, our study provides preliminary evidence supporting the use of motor skill learning, such as football juggling, as a potential avenue for cognitive enhancement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dong, Gui, Klich, Zhu, Chen, Sun, Shi and Chen.)

Consensus clustering can derive a more promising and robust clustering result by integrating multiple partitions strategically. However, there are several limitations in the existing approaches: 1) most of the methods compute the ensemble-information matrix heuristically and lack of sufficient optimization; 2) the information from the original dataset is rarely considered; and 3) the noise in both label space and feature space is ignored. To address these issues, we proposed a novel consensus clustering method with co-association matrix optimization (CC-CMO), which aims at improving the co-association matrix by taking abundant information from both label space and feature space into consideration. In label space, CC-CMO derives a weighted partition matrix capturing the intercluster correlation and further designs a least squares regression (LSR) model to explore the global structure of data. In feature space, CC-CMO minimizes the reconstruction error with doubly stochastic normalization in the projective subspace to eliminate noise features as well as learn the local affinity of data. To improve the co-association matrix by jointly considering the subspace representation, global structure, and local affinity of data, we explicitly propose a unified optimization framework and design an alternating optimization algorithm for the optimal co-association matrix. Extensive experiments on a variety of real-world datasets demonstrate the superior performance of CC-CMO to the state-of-the-art consensus clustering approaches.

African swine fever (ASF) caused by the African swine fever virus (ASFV) is a fatal and highly contagious disease of domestic pigs characterized by rapid disease progression and death within 2 weeks. How the immune cells respond to acute ASFV infection and contribute to the immunopathogenesis of ASFV has not been completely understood. In this study, we examined the activation, apoptosis, and functional changes of distinct immune cells in domestic pigs following acute infection with the ASFV CADC&#95;HN09 strain using multicolor flow cytometry. We found that ASFV infection induced broad apoptosis of DCs, monocytes, neutrophils, and lymphocytes in the peripheral blood of pigs over time. The expression of MHC class II molecule (SLA-DR/DQ) on monocytes and conventional DCs as well as CD21 expression on B cells were downregulated after ASFV infection, implying a potential impairment of antigen presentation and humoral response. Further examination of CD69 and ex vivo expression of IFN-γ on immune cells showed that T cells were transiently activated and expressed IFN-γ as early as 5 days post-infection. However, the capability of T cells to produce cytokines was significantly impaired in the infected pigs when stimulated with mitogen. These results suggest that the adaptive cellular immunity to ASFV might be initiated but later overridden by ASFV-induced immunosuppression. Our study clarified the cell types that were affected by ASFV infection and contributed to lymphopenia, improving our understanding of the immunopathogenesis of ASFV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tian, Wang, He, Cao, Li, Jiang, Shi, Hao, Wei, Wang, Qie, Wang, Li, Hao, Zhu, Wu, Shang and Zhai.)

Objective: Imeglimin is a novel antidiabetic drug structurally related to metformin. Metformin has been shown to modulate the circadian clock in rat fibroblasts. Accordingly, in the present study, we aimed to determine whether imeglimin can impact the circadian oscillator in mouse embryonic fibroblasts (MEFs)., Methods: MEFs carrying a Bmal1-Emerald luciferase (Bmal1-ELuc) reporter were exposed to imeglimin (0.1 or 1 mM), metformin (0.1 or 1 mM), a nicotinamide phosphoribosyltransferase inhibitor FK866, and/or vehicle. Subsequently, Bmal1-ELuc expression and clock gene mRNA expression levels were measured at 10-min intervals for 55 h and 4-h intervals for 32 h, respectively., Results: Imeglimin significantly prolonged the period (from 26.3 to 30.0 h at 0.1 mM) and dose-dependently increased the amplitude (9.6-fold at 1 mM) of the Bmal1-ELuc expression rhythm; however, metformin exhibited minimal effects on these parameters. Moreover, imeglimin notably impacted the rhythmic mRNA expression of clock genes (Bmal1, Per1, and Cry1). The concurrent addition of FK866 partly inhibited the effects of imeglimin on both Bmal1-ELuc expression and clock gene mRNA expression., Conclusion: Collectively, these results reveal that imeglimin profoundly affects the circadian clock in MEFs. Further studies are needed to evaluate whether imeglimin treatment could exert similar effects in vivo., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Background and Aims: Malnutrition is strongly linked to adverse outcomes in patients with Crohn's disease (CD). In this study, our objective was to validate the Global Leadership Initiative on Malnutrition (GLIM) criteria and develop a fast and accurate diagnostic approach for identifying malnutrition in CD patients., Methods: This study assessed 177 CD patients from four general hospitals. The efficacy of the GLIM criteria for the diagnosis of CD malnutrition was compared. By analyzing the independent factors, a nomogram model was derived and internally validated to predict the diagnosis of malnutrition in patients with CD. Model performance was assessed using discrimination and calibration, decision curves, and net benefit analyses., Results: Compared with the SGA criteria, the GLIM criteria was consistent in sensitivity (88.89%) and specificity (78.43%) [AUC = 0.84; 95% Confidence Interval (CI): 0.77-0.89]. The Harvey-Bradshaw index(HBI) score (OR: 1.58; 95% CI: 1.15-2.18), body mass index (OR: 0.41; 95% CI: 0.27-0.64), and mid-upper arm circumference (OR: 0.68; 95% CI: 0.47-0.9) were independent factors associated with malnutrition. The nomogram was developed based on these indicators showing good discrimination in malnutrition diagnosis (AUC = 0.953; 95% CI: 0.922-0.984), with agreement after calibration curve and decision curve analysis., Conclusion: The GLIM criteria are appropriate for diagnosing malnutrition in CD patients. The HBI score may be used to diagnose malnutrition in patients with CD and become a possible selection for the GLIM etiologic criteria of inflammation. The HBM nomogram could be a simple, rapid, and efficient method for diagnosing malnutrition in CD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Niannian, Zhang, Shi, Gao, Zhang, Wu, Dai, Huang, Cao, Zhou, Jiang, Jing, Zhu and Wang.)

Background: Hyperkalaemia is a known risk factor for cardiac arrhythmia and mortality in patients on haemodialysis. Despite standard adequate haemodialysis, hyperkalaemia is common in patients with end-stage renal disease (ESRD) at interdialytic intervals. Data on hyperkalaemia burden and its effects on dialysis patterns and serum potassium (sK) fluctuations in patients on haemodialysis in China remain limited. The prospective, observational cohort study (PRECEDE-K; NCT04799067) investigated the prevalence, recurrence, and treatment patterns of hyperkalaemia in Chinese patients with ESRD on haemodialysis., Methods: Six hundred adult patients were consecutively enrolled from 15 secondary and tertiary hospitals in China. In this interim analysis, we report the baseline characteristics of the cohort, the prevalence of predialysis hyperkalaemia (sK > 5.0 mmol/L), and the trends in serum-dialysate potassium gradient and intradialytic sK shift at Visit 1 (following a long interdialytic interval [LIDI])., Results: At baseline, most patients (85.6%) received three-times weekly dialysis; mean duration was 4.0 h. Mean urea reduction ratio was 68.0% and Kt/V was 1.45; 60.0% of patients had prior hyperkalaemia (previous 6 months). At Visit 1, mean predialysis sK was 4.83 mmol/L, and 39.6% of patients had hyperkalaemia. Most patients (97.7%) received a dialysate potassium concentration of 2.0 mmol/L. The serum-dialysate potassium gradient was greater than 3 mmol/L for over 40% of the cohort (1- < 2, 2- < 3, 3- < 4, and ≥ 4 mmol/L in 13.6%, 45.1%, 35.7%, and 5.2% of patients, respectively; mean: 2.8 mmol/L). The intradialytic sK reduction was 1- < 3 mmol/L for most patients (0- < 1, 1- < 2, 2- < 3, and ≥ 3 mmol/L in 24.2%, 62.2%, 12.8%, and 0.9% of patients, respectively; mean: 1.4 mmol/L)., Conclusions: Hyperkalaemia after a LIDI was common in this real-world cohort of Chinese patients despite standard adequate haemodialysis, and led to large serum-dialysate potassium gradients and intradialytic sK shifts. Previous studies have shown hyperkalaemia and sK fluctuations are highly correlated with poor prognosis. Effective potassium-lowering treatments should be evaluated for the improvement of long-term prognosis through the control of hyperkalaemia and sK fluctuations., Trial Registration: ClinicalTrials.gov, NCT04799067., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To explore clinical characteristics and symptomatology of major depressive disorder (MDD) with atypical features based on DSM criteria or only reversed vegetative symptoms., Method: A total of 3187 patients who met DSM-IV TR criteria for MDD were enrolled. Demographics and symptomatology covering multiple symptom domains were assessed and compared between three groups of cases: those who met DSM criteria for atypical specifier (the DAD group), those who had at least one reversed vegetative symptoms (hypersomnia or hyperphagia) (the SAD group) without meeting DSM atypical specifier criteria, and those without any reversed vegetative symptoms (the NAD group)., Results: The DAD and SAD group accounted for 4.4% and 14.4% of the participants, respectively. The DAD cases were characterized by a highest proportion of hospitalizations, longest duration of current episode and worst quality of life. The DAD and SAD cases were more likely to adopt unhealthy behaviors (smoking and alcohol drinking). Most depressive symptoms related to higher illness severity and treatment resistance were more frequent in the DAD cases, followed by the SAD cases, and least frequent in the NAD cases., Limitations: A cross-sectional design and a non-validated questionnaire were used., Conclusions: The findings support the role of DSM defined atypical depression as a valid MDD subtype and provide evidence for clinical utility of the simplified approach of defining atypical features based on only reversed vegetative symptoms. This has implications for illness screening, public health, suicide prevention and better treatment planning for depressed individuals with atypical features even below syndromal level., Competing Interests: Conflict of interest All authors have declared no conflict of interest related to this work., (Copyright © 2023. Published by Elsevier B.V.)

Odor pollution caused by brownfield site has attracted increasing attention. However, to date, fewer suitable materials can be used to control the emission of odor pollutant from brownfield site during remediation. This study prepared a kind of combined hydrogel solution based on sodium alginate and carboxymethyl cellulose sodium (CHS-SC) and tested the possibility of its membrane in controlling the emission of three odor pollutants (trichloroethylene, dimethyl disulfide, and p-xylene) from polluted soil. Our results showed that CHS-SC membrane could effectively control the emission of three odor pollutants from polluted soil. Comparatively, CHS-SC membrane had higher control rates for three odor pollutants at high ambient temperature (32 °C), short storage time of CHS-SC (5 days, 25 °C), and low odor pollutant concentration (2 ml/kg soil) than at low ambient temperature (2 °C), long storage time of CHS-SC (10 d, 25 °C), and high odor pollutant concentration (4 ml/kg soil), respectively. CHS-SC membrane was degraded by 79.23% after 150 days in soil and slightly changed soil bacterial community, indicating that it had good biodegradability and environmental friendliness. In addition, CHS-SC cost was the lowest among the products with similar function. This study shows that CHS-SC is effective in short-timely controlling the emission of odor pollutants from brownfield site., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Early distinction of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools are available to estimate the risk of BD. In this study, we aimed to develop and validate a model of oxidative stress injury for predicting BD. Data were collected from 1252 BD and 1359 MDD patients, including 64 MDD patients identified as converting to BD from 2009 through 2018. 30 variables from a randomly-selected subsample of 1827 (70%) patients were used to develop the model, including age, sex, oxidative stress markers (uric acid, bilirubin, albumin, and prealbumin), sex hormones, cytokines, thyroid and liver function, and glycolipid metabolism. Univariate analyses and the Least Absolute Shrinkage and Selection Operator were applied for data dimension reduction and variable selection. Multivariable logistic regression was used to construct a model for predicting bipolar disorder by oxidative stress biomarkers (BIOS) on a nomogram. Internal validation was assessed in the remaining 784 patients (30%), and independent external validation was done with data from 3797 matched patients from five other hospitals in China. 10 predictors, mainly oxidative stress markers, were shown on the nomogram. The BIOS model showed good discrimination in the training sample, with an AUC of 75.1% (95% CI: 72.9%-77.3%), sensitivity of 0.66, and specificity of 0.73. The discrimination was good both in internal validation (AUC 72.1%, 68.6%-75.6%) and external validation (AUC 65.7%, 63.9%-67.5%). In this study, we developed a nomogram centered on oxidative stress injury, which could help in the individualized prediction of BD. For better real-world practice, a set of measurements, especially on oxidative stress markers, should be emphasized using big data in psychiatry., (© 2022. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Type IV collagen is a component of the extracellular matrix in the basement membrane. Abnormal secretion or assembly of type IV collagen may lead to kidney lesions resulting in numerous nephropathy symptoms, e.g., Alport syndrome, thin basement membrane nephropathy, and focal segmental glomerulosclerosis. Treatment for type IV collagen-related nephropathy includes drugs, kidney transplantation, gene and cell therapy. However, drugs are not always effective, and kidney transplantation is hindered by the shortage of donors. Moreover, basement membrane nephritis often occurs after kidney transplantation. Therefore, gene and cell therapy probably is the most promising treatment for type IV collagen related nephropathies.

Sulprostone is a potent prostaglandin E 2 (PGE 2 ) analogue and one of the first identified selective G-protein-coupled receptor 3 (EP 3 ) agonists. It has been investigated as a potential antiulcer agent and frequently used in the research of EP 3 antagonist. To assist pharmacokinetic and pharmacodynamic studies, a rapid and sensitive LC-MS/MS method was developed and qualified for the quantitation of sulprostone in monkey plasma. Using electrospray ionization mass spectrometry, an ammonium adduct in positive mode was chosen for analysis which had seven times of the sensitivity of the depronated ion in negative mode. Latanoprost, a prostaglandin F 2α analogue, was used as the internal standard while good sensitivity and chromatography were obtained on a 2.6 μm core-shell column with pentafluorophenyl stationary phase. An assay dynamic range of 2 to 4000 ng/mL was achieved with a sample volume of 25 μL plasma on a Sciex API4000 instrument with simple protein precipitation. Several esterase inhibitors including sodium fluoride (NaF), phenylmethanesulfonyl fluoride (PMSF), diisopropylfluorophosphate (DFP), paraoxon and dichlorvos as well as wet ice conditions were explored for the stabilization of sulprostone in monkey plasma. The developed method was successfully applied for the evaluation of pharmacokinetics of sulprostone after intravenous administration of 0.5 mg/kg to cynomolgus monkey., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of GDC-0425 concentrations in human plasma has been developed and validated. Supported liquid extraction was used to extract plasma samples (50 μL) and the resulting samples were analyzed using reverse-phase chromatography and mass spectrometry coupled with a turbo-ionspray interface. The mass analysis of GDC-0425 was performed using multiple reaction monitoring transitions in positive ionization mode. The method was validated over the calibration curve range of 1.00-1000 ng/mL using linear regression and 1/x 2 weighting. Within-run relative standard deviation ranged from 0.8 to 5.1%, while between-run RSD varied from 1.9 to 4.7% for QCs. The accuracy ranged from 90.0 to 101.0% of nominal for within-run and from 94.0 to 100.0% of nominal for between-run. Overall extraction recovery was 87.4% for GDC-0425 and 87.9% for GDC-0425-d 9 . Stability of GDC-0425 was established in human plasma for 374 days at -20 and -70 °C and established in reconstituted sample extracts for 88 h when stored at 2-8 °C. Stable-labeled internal standard was used to minimize matrix effects. This assay was used to characterize the pharmacokinetics of GDC-0425 in cancer patients., (Copyright © 2016 John Wiley & Sons, Ltd.)

Objective: To investigate the safety, effectiveness and long-term results of Jinling procedure., Methods: A total of 1 100 patients with refractory constipation were admitted to the Institute of General Surgery between February 2000 and December 2013 and received Jinling procedure. There were 217 male and 883 female patients with an average age of (45±15) years and an average duration of (275±159) months. The Jinling procedure modifies the classic procedure of subtotal colectomy with colorectal anastomosis by adding a new side-to-side cecorectal anastomosis. The general clinical data, postoperative complications, gastrointestinal quality of life index (GIQLI), Wexner constipation score, satisfaction rate, body composition, nutritional status, homeostasis, anal manometry and defecography during follow-up were collected. Statistical analysis was performed by t-test analysis, χ(2) test or Fisher's exact probability., Results: The postoperative follow-up rate were 96.73%, 94.36%, 93.00% and 92.55% at 1, 3, 6, and 12 months. The satisfaction rate were 62.50%, 72.45%, 93.16% and 94.70% respectively during 1, 3, 6 and 12 months follow-up. The postoperative 1 month, GIQLI was lower than that of preoperative (P=0.038), but significantly better at postoperative 3 month than the preoperative (P=0.022), and gradually improve after then. Wexner score was significantly lower at postoperative 1 month than the preoperative (P=0.018), and with the gradually reduce. Compared to the preoperative baseline, all body composition and serum protein parameters decreased significantly at the one-month follow-up and then increased gradually over the remaining follow-up period. Weight and prealbumin were significantly higher than the preoperative at postoperative 12 month. Jinling procedure had no effect on electrolytes. All patients were detected in defecography before surgery, but these abnormal indicators were improved after surgery. Anal function, coordinated movement anorectal function, anorectal reflex and rectal sensation were injured at early postoperative, but as time goes on, these indicators gradually returned to preoperative levels, some indicators better than the preoperative level. Postoperative surgical site infection, anastomotic bleeding , anastomotic leakage, urinary retention, sexual dysfunction, recurrent constipation, bowel obstruction, anastomotic stricture and mortality rates were 4.36%, 5.45%, 6.00%, 6.91%, 0.64%, 0.45%, 8.82%, 4.00% and 0.27% respectively., Conclusions: Jinling procedure is a safe and effective surgical procedure for refractory constipation. It can improve defecation function and quality of life significantly, and has a high follow-up satisfaction rate.

N-acetylneuraminic acid (Neu5Ac or NANA) is the most predominant sialic acid in mammals. As a terminal component in many glycoproteins and glycolipids, sialic acid is believed to be an important biomarker related to various diseases. Its precursor, N-acetylmannosamine (ManNAc), is being investigated as a potential treatment for GNE myopathy. In this work, we developed two highly sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for the quantitation of ManNAc and free Neu5Ac in human plasma. A fit-for-purpose approach was adopted during method validation and sample analysis. To measure the endogenous compounds and overcome the interference from plasma samples, a surrogate matrix that contained 5% bovine serum albumin (BSA) was used for the preparation of calibration standards and certain levels of quality control (QC) samples. QC samples at higher concentrations were prepared in the authentic matrix (human plasma) to best mimic incurred samples. For both methods, an Ostro 96-well phospholipid removal plate was used for sample extraction, which efficiently removed the phospholipids from the plasma samples prior to LC injection, eliminated matrix effect, and improved sensitivity. Chromatographic separation was achieved using hydrophilic interaction chromatography (HILIC) and gradient elution in order to retain the two polar compounds. The lower limit of quantitation (LLOQ) for ManNAc and Neu5Ac was 10.0 and 25.0ng/mL, respectively. The overall accuracy of the two assays was within 100%±8.3% based on three levels of QC samples. Inter- and intra-run precision (coefficient of variation (%CV)) across three analytical runs was less than 6.7% for ManNAc and less than 10.8% for Neu5Ac. These methods have been validated to support clinical studies., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To investigate the mutations of arginine vasopressin receptor 2 (AVPR2) gene in congenital nephrogenic diabetes insipidus (NDI) patients., Methods: Genomic DNA was extracted from the blood samples of 7 congenital NDI patients, all males, and 24 of their family members. The 6 fragments of AVPR2 gene were amplified by PCR. The gene mutations were preliminarily screened by SSCP and further confirmed by DNA sequencing., Results: 5 types of mutation and 8 mutant sites of AVPR2 gene were found in 6 of the 7 patients. Two cases were found to have 2 different sites of mutation in the AVPR2 gene. In 4 cases new mutation sites not reported previously in the literature, i.e., g.469-493del 24, g.541insT, g.462delC and g.935T > C, were identified, resulting in the change of AVPR2 proteins, including A37-L44del (deletion mutation), A61G 190X (insertion frame-shift and nonsense mutation), P34R 36X (deletion frame-shift and nonsense mutation) and C192R (missense mutation). Among the 24 family members examined only one, a mother, was found to have an AVPR2 gene mutation with the same mutation site as the proband., Conclusion: Four novel mutation sites have been identified in the AVPR2 gene among the congenital NDI patients. PCR-SSCP and DNA sequencing can be used to preliminarily screen and diagnose gene mutation among congenital NDI patients.

Objective: To study the value of serum insulin-like growth factor binding protein-3 (IGFBP-3) levels in differential diagnosis of growth hormone deficiency (GHD)., Methods: To measure serum IGFBP-3 levels by RIA in normal children and adolescents, GHD children and short-stature children without GHD., Results: Serum level of IGFBP-3 in 129 children with untreated GHD and with no pubertal development was 1.6 +/- 0.9 mg/L, which was less than that in normal group of the same age, but overlapped with the normal children in Tanner stage I. After six-month treatment with recombinant human growth hormone (rhGH), serum level of IGFBP-3 in 59 GHD significantly increased from 1.3 +/- 0.7 mg/L to 2.7 +/- 0.9 mg/L, accompanied by an increase of body heights, growth velocities and serum level of IGF-1. Serum level of IGFBP-3 in 55 short-stature children without GHD was 3.3 +/- 2.2 mg/L, which was not significantly different from that in normal group., Conclusion: Serum IGFBP-3 level can reflect the status of GH secretion in children with GHD and is a useful marker for differential diagnosis of GHD.