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Molecular oxygen activation often suffers from high energy consumption and low efficiency. Developing eco-friendly and effective photocatalysts remains a key challenge for advancing green molecular oxygen activation. Herein, graphitic carbon nitride (g-C3N4) with abundant hydroxyl groups (HCN) was synthesized to investigate the relationship between these polar groups and molecular oxygen activation. The advantage of the hydroxyl group modification of g-C3N4 included narrower interlayer distances, a larger specific surface area and improved hydrophilicity. Various photoelectronic measurements revealed that the introduced hydroxyl groups reduced the charge transfer resistance of HCN, resulting in accelerated charge separation and migration kinetics. Therefore, the optimal HCN-90 showed the highest activity for Rhodamine B photodegradation with a reaction time of 30 min and an apparent rate constant of 0.125 min−1, surpassing most other g-C3N4 composites. This enhanced activity was attributed to the adjusted band structure achieved through polar functional group modification. The modification of polar functional groups could alter the energy band structure of photocatalysts, narrow band gap, enhance visible-light absorption, and improve photogenerated carrier separation efficiency. This work highlights the significant potential of polar functional groups in tuning the structure of g-C3N4 to enhance efficient molecular oxygen activation. [ABSTRACT FROM AUTHOR]

Fat storage-inducing transmembrane protein 2 (FITM2) plays an important role in regulating lipid storage and could be regarded as a candidate gene for intramuscular fat deposition in pigs. The aim of this study was to clone the coding domain sequence (CDS) of FITM2 gene, to compare the nucleotide acid and deduced amino acid sequences between breeds and species, to analyze the structure and characteristics of protein and to detect the expression profile of gene. The results exhibited that the CDS of FITM2 gene was 789 bp in length. The mutation of nucleotide acids led to the mutation of deduced amino acids between Banna miniature inbred pigs and other two breeds (Yorkshire × Landrace pigs and Duroc × (Landrace × Yorkshire) pigs). It was indicated that high identities of nucleotide acid and deduced amino acid sequences between Banna miniature inbred pigs and other species. The deduced amino acids were composed of loops and alpha helices in the structure. FITM2 protein may be a 30 kDa hydrophobic protein with 26 phosphorylation sites and one potential N-glycosylated site. FITM2 gene was widely expressed in various tissues, and the highest expression level was in adipose tissue. [ABSTRACT FROM AUTHOR]

In this paper, the effects of partial replacement of cement by metakaolin (MK) and different supplementary cementitious materials (SCMs) were investigated on the compressive strength and elasticity modulus of ultra-high-performance concrete (UHPC) at different ages, and the laws of the effects of MK alone, MK and conventional SCMs on the mechanical properties of UHPC were quantitatively analyzed at the macroscopic level. The results showed that the compressive strength of UHPC reached the maximum value when the MK doping amount reached 10%, and its compressive strength at 7, 28 and 90 days increased by 21%, 28% and 18.2%, respectively. Furthermore, the elasticity modulus of UHPC also showed a similar trend. When MK and Blast furnace slag or Fly ash were compounded, the mechanical properties (compressive strength and elasticity modulus) of UHPC were significantly enhanced in the later stage, showing sound synergistic effects. Based on the experimental test data, a model for predicting the elasticity modulus of UHPC based on the change of time and SCMs was proposed with good reliability. [ABSTRACT FROM AUTHOR]

An eco-friendly and efficient electrochemical method for the synthesis of 5-amine-1,2,4-triazole derivatives has been developed by employing hydrazones or in situ generation of hydrazones with cyanamide using KI as the catalyst and electrolyte. This strategy could be smoothly conducted with simple reaction conditions at room temperature without the addition of a chemical oxidant in an undivided cell, and cyanamide has been proven to be of great value in electrosynthesis. [ABSTRACT FROM AUTHOR]

[Display omitted] • The halogenation of imidazoheterocycles including iodine, bromine and chlorine imidazoheterocycles could perform in very simple and mild conditions. • This transformation features with short reaction time, ambient temperature, facile operation, good functional group tolerance and good yeilds. An efficient and environment-friendly method for the synthesis of 3-haloimidazopyridine derivatives has developed by the halogenation of imidazoheterocycles with Bu 4 NX (X = Cl, Br, and I) using iodobenzene diacetate as oxidant in ethanol. This protocol features with short reaction time for bromination and iodination, ambient temperature, facile operation, good functional group tolerance and good yeilds. [ABSTRACT FROM AUTHOR]

Let L be a Schrödinger operator of the form L=−Δ+V acting on L2(Rn) where the nonnegative potential V belongs to the reverse Hölder class Bq for some q≥n. Let BMOL(Rn) denote the BMO space on Rn associated to the Schrödinger operator L. In this article we will show that a function f∈BMOL(Rn) is the trace of the solution of Lu:=ut+Lu=0,u(x,0)=f(x), where u satisfies a Carleson‐type condition supxB,rBrB−n∫0rB2∫B(xB,rB)t|∂tu(x,t)|2+|∇xu(x,t)|2dxdt≤C<∞.Conversely, this Carleson‐type condition characterizes all the L‐carolic functions whose traces belong to the space BMOL(Rn). [ABSTRACT FROM AUTHOR]

An efficient sulfuration of isoquinolin-1(2H)-ones at the C-4 position is reported by employing ethyl sulfinates, and the corresponding products are obtained in moderate to excellent yields in the presence of iodine. This synthetic strategy provides a range of thioether-isoquinolin-1(2H)-ones while tolerating a number of functional groups on the isoquinoline nitrogen atom and benzene ring. In addition, pyridin-2(1H)-one is also reacted smoothly and afforded the corresponding thioether product in moderate yield. A plausible mechanism is suggested based on the preliminary mechanistic studies. [ABSTRACT FROM AUTHOR]

The paper is concerned with the three-dimensional Boussinesq-Coriolis equations with Caputo time-fractional derivatives. Specifically, by striking new balances between the dispersion effects of the Coriolis force and the smoothing effects of the Laplacian dissipation involving with a time-fractional evolution mechanism, we obtain the global existence of mild solutions to Cauchy problem of three-dimensional time-fractional Boussinesq-Coriolis equations in Besov spaces. [ABSTRACT FROM AUTHOR]

In this paper, we construct a class global large solution to the two-dimensional magnetohydrodynamics equations with damp terms whose initial energy can be arbitrarily large. [ABSTRACT FROM AUTHOR]

Phosphor-converted warm white light-emitting diodes (pc-wLEDs) have played a key role in our daily lighting life, but they are difficult to realize without adding red-emitting phosphors. Conventional Eu 3+ doped red phosphors, however, suffer greatly from the intrinsic shortcomings such as low quantum efficiency, limited absorption of UV LED light and chemical and thermal stability. In this work, we design the Eu 3+ doped Na x Ca 1-2x WO 4 :Eu x 3+ (0 ≤ x ≤ 0.20) phosphors, which can exhibit enhanced Eu 3+ red fluorescence and the tunable color at the same time. Phase purity analysis, which was checked by X-ray powder diffraction (XRD), shows all samples crystallize in a scheelite structure with the space group of I 4 1/a (No.88). Our findings reveal that increasing the Eu 3+ content gives rise to moving the XRD position to low angle direction and, in the meanwhile, decreasing the charge transfer (CT) intensity of samples. Spectral results show that controlling the charge compensation content and energy transfer efficiency from host to Eu 3+ enables us to achieve the enhanced Eu 3+ red fluorescence and simultaneously the tunable color. Unlike the decrease change in the CT band intensity, the Eu 3+ emission upon excitation at 393 nm and 464 nm exhibits a continuous increase in the emission intensity. Due to the inefficiency energy transfer between host and Eu 3+ dopant, controlling the x value enables tuning the relative photoemission intensity between host and Eu 3+ dopant and therefore the color tuning from blue to red. Our time-resolved PL results indicate that the energy transfer between the CaWO 4 host and Eu 3+ dopant begins to occur at t  = 5 μs. A feasible profile, which bases on the energy transfer, has been also established in the work. This work not only demonstrates simultaneous enhanced Eu 3+ fluorescence and color tuning in CaWO 4 matrix through charge compensation method, but also can provide new insight into improving the PL properties in other phosphors for UV converted pc-wLEDs. [ABSTRACT FROM AUTHOR]

In this article, we consider the Cauchy problem to Keller-Segel equations coupled to the incompressible Navier-Stokes equations. Using the Fourier frequency localization and the Bony paraproduct decomposition, let u F:= e tΔ u0; we prove that there exist 2 positive constants σ0 and C0 such that if the gravitational potential [ABSTRACT FROM AUTHOR]

Aims: Methotrexate (MTX) is recognized for its potential to induce hepatotoxicity, commonly manifested by elevated alanine aminotransferase (ALT) levels. However, the quantitative relationship between the pharmacokinetics (PK) of MTX and ALT‐based hepatotoxicity remains unclear. This study aimed to develop a semimechanistic PK/pharmacodynamic (PD) model to characterize the MTX‐induced hepatotoxicity based on ALT in paediatric patients with acute lymphoid leukaemia. Methods: A retrospective study was conducted on paediatric patients who received high‐dose (3–5 g/m2) MTX treatment. MTX concentrations were assessed at 24‐h intervals until the concentration dropped below 0.1 μmol/L. ALT concentrations were measured both before and after MTX administration. A population PK model was initially developed, which was later connected to a semimechanistic hepatotoxicity model. Results: The PK model was developed using 354 MTX concentrations obtained from 51 patients, while the PD model was constructed using 379 ALT concentrations collected from 48 patients. The optimal PK model for MTX consisted of a 2‐compartment structure, where body surface area served as a covariate for clearance and central volume of distribution. An indirect response model coupled to a liver injury signal transduction model was developed to describe the dynamics of ALT after MTX administration. The drug effect was adequately described by a linear model, exhibiting considerable interoccasion variability for each treatment session. No significant covariates were identified to have an impact on the PD parameters. Conclusion: A semimechanistic model was developed to describe ALT‐based hepatotoxicity of MTX, and it has the potential to serve as a valuable tool for characterizing drug‐induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

In this article, we consider Nernst–Planck–Poisson system with generalized dissipation. First, we prove the Gevrey class regularity of local solutions to system with large rough initial data in modulation spaces. Secondly, applying so-called Gevrey estimates, which is motivated by the works of Foias and Temam, we establish Gevrey class regularity of solutions to the system with initial data in a certein critical Fourier–Besov spaces. The results of us particularly imply that the solution is analytic in the spatial variable and obtain temporal decay rates of higher Fourier–Besov norms of solutions. [ABSTRACT FROM PUBLISHER]

In this article, first of all, the global existence and asymptotic stability of solutions to the incompressible nematic liquid crystal flow is investigated when initial data are a small perturbation near the constant steady state (0, δ0); here, δ0 is a constant vector with | δ0|=1. Precisely, we show the existence and asymptotic stability with small initial data [ABSTRACT FROM AUTHOR]

We study global well-posedness for Cauchy problem of the three-dimensional viscous primitive equations of geophysics in the critical functional framework. [ABSTRACT FROM AUTHOR]

In this article, we establish higher-order regularizing rate estimates of solutions to generalized magneto-hydrodynamic equations in Morrey spaces with initial data $(u_{0}, d_{0})$ in Besov-Morrey spaces $\dot {\mathbf{N}}_{r, \lambda,\infty}^{-s}\times\dot{\mathbf{N}}_{r, \lambda , \infty}^{-s}$, where $n\geq2$, $1\leq r<\infty$, $0\leq\lambda< n$, $r>n-\lambda$, $\frac {1}{2}+\frac{n-\lambda}{4r}<\sigma< 1+\frac{n-\lambda}{4r}$, and $s=2\sigma-1-\frac{n-\lambda}{r}$, for which under some smallness condition, the solution of the Cauchy problem is analytic in the spatial variable. Our class of initial data contains strongly singular functions and measures and extends the ones in early work. [ABSTRACT FROM AUTHOR]

Autophagy is a double-edged sword in tumorigenesis and plays an important role in the resistance of cancer cells to chemotherapy. S100A8 is a member of the S100 calcium-binding protein family and plays an important role in the drug resistance of leukemia cells, with the mechanisms largely unknown. Here we report that S100A8 contributes to drug resistance in leukemia by promoting autophagy. S100A8 level was elevated in drug resistance leukemia cell lines relative to the nondrug resistant cell lines. Adriamycin and vincristine increased S100A8 in human leukemia cells, accompanied with upregulation of autophagy. RNA interference-mediated knockdown of S100A8 restored the chemosensitivity of leukemia cells, while overexpression of S100A8 enhanced drug resistance and increased autophagy. S100A8 physically interacted with the autophagy regulator BECN1 and was required for the formation of the BECN1-PI3KC3 complex. In addition, interaction between S100A8 and BECN1 relied upon the autophagic complex ULK1-mAtg13. Furthermore, we discovered that exogenous S100A8 induced autophagy, and RAGE was involved in exogenous S100A8-regulated autophagy. Our data demonstrated that S100A8 is involved in the development of chemoresistance in leukemia cells by regulating autophagy, and suggest that S100A8 may be a novel target for improving leukemia therapy. [ABSTRACT FROM AUTHOR]

Abstract: Sepsis is caused by an overwhelming immune response to bacterial infection. The discovery of high mobility group box 1 (HMGB1) as a late mediator of lethal sepsis has prompted investigation into the development of new therapeutics which specifically target this protein. Here, we show that chloroquine, an anti-malarial drug, prevents lethality in mice with established endotoxemia or sepsis. This effect is still observed even if administration of chloroquine is delayed. The protective effects of chloroquine were mediated through inhibition of HMGB1 release in macrophages, monocytes, and endothelial cells, thereby preventing its cytokine-like activities. As an inhibitor of autophagy, chloroquine specifically inhibited HMGB1-induced Iκ-B degradation and NF-κB activation. These findings define a novel mechanism for the anti-inflammatory effects of chloroquine and also suggest a new potential clinical use for this drug in the setting of sepsis. [Copyright &y& Elsevier]

Abstract: A quantitative proton nuclear magnetic resonance technique (qHNMR) has been successfully introduced to quantify andrographolide, dehydroandrographolide, deoxyandrographolide and neoandrographolide in Andrographis paniculata, a commonly used important traditional Chinese medicine. Creative use of trifluoroacetic acid-d, which satisfactorily resolved the overlapping signals of these compounds in crowded regions of δ 4.5–5.6ppm in 1H NMR spectrum, made their quantification possible. Optimization of other experimental conditions, including internal standard, NMR pulse sequence, and NMR relaxation delay time, finally established the 1H NMR based quantification approach, which was validated with satisfactory accuracy, precision, repeatability, and recovery. Except for deoxyandrographolide and neoandrographolide in two compound recipes, this method was successfully applied to quantify the four major components in fourteen raw herb materials and five commercial preparations, providing quantification results in good agreement with those determined by HPLC. The inherent advantages of qHNMR, such as its rapidity and simplicity, make itself a feasible alternative to HPLC for the quality control of A. paniculata raw material and herbal preparations. [Copyright &y& Elsevier]

The Suzuki-Miyaura type coupling reaction of aryl halides with triphenylborane-pyridine was described. The reaction can be catalyzed by Pd(OAc)2 (5 mol%) in presence of Cs2CO3 at 50°C or 80°C, and functionalized biaryls were obtained in good to excellent yields. This protocol is general and can tolerate a wide range of functional groups. [ABSTRACT FROM AUTHOR]

There is a scarcity of data on anticoagulation-related nephropathy (ARN) caused by direct-acting oral anticoagulants (DOACs) in recent years. We collected literatures on DOACs-induced ARN to October 1, 2022, without language restrictions for retrospective analysis. Twenty events were included with a median onset time of 28 days among which fourteen were caused by dabigatran. Patients accompanied by chronic kidney disease (85 %) seemed more easily to have an ARN. Clinical symptoms associated with ARN were mostly presented as hematuria and acute decline of renal function (100 %), then abnormal coagulation function (75 %) but only one with an INR over 3. Renal biopsies were performed in 14 patients, with thirteen showing occlusive intratubular red blood cell casts and ten showing acute tubular injury of varying intensity or even tubular necrosis. Extensive changes in interstitial compartment like hemorrhage, fibrosis or inflammation were also presented in eight biopsies. IgA nephropathy as a latent or undiagnosed disease was demonstrated in eight biopsies. Treatments of ARN were mainly supportive with all patients discontinuing DOACs and 35 % initiating dialysis for acute deterioration of renal function. Steroids were used in 9 patients with a severe ARN verified by biopsy. 60 % of patients did not recover baseline renal function and some even deteriorated. In conclusion, DOACs-induced ARN is a rare but serious adverse reaction. A prompt diagnosis of ARN and supportive treatments are necessary for patients receiving DOACs concurrent with an acute renal injury. [ABSTRACT FROM AUTHOR]

Background: Methotrexate (MTX) is a key immunosuppressant for children with acute lymphoid leukemia (ALL), and it has a narrow therapeutic window and relatively high pharmacokinetic variability. Several population pharmacokinetic (PopPK) models of MTX in ALL children have been reported, but the validity of these models for model-informed precision dosing in clinical practice is unclear. This study set out to evaluate the predictive performance of published pediatric PopPK models of MTX using an independent patient cohort. Methods: A PubMed literature search was performed to identify suitable models for evaluation. Demographics and measurements of the validation dataset were retrospectively collected from the medical records of ALL children who had received intravenous MTX. Predictive performance for each model was assessed by visual comparison of predictions to observations, median and mean predicted error (PE), and relative root mean squared error (RMSE). Results: Six models were identified for external evaluation, carried out on a dataset containing 354 concentrations from 51 pediatrics. Model performance varied considerably from one model to another. Different models had the median PE for population and individual predictions at −33.23% to 442.04% and −25.20% to 6.52%, mean PE for population and individual predictions at −25.51% to 780.87% and 1.33% to 64.44%, and RMSE for population and individual predictions at 62.88% to 1182.24% and 63.39% to 152.25%. All models showed relatively high RMSE. Conclusions: Some of the published models showed reasonably low levels of bias but had some problems with imprecision, and extensive evaluation is needed before model application in clinical practice. [ABSTRACT FROM AUTHOR]

Background: PDGFRB fusions in acute lymphoblastic leukemia (ALL) is rare. The authors identified 28 pediatric PDGFRB‐positive ALL. They analyzed the features, outcomes, and prognostic factors of this disease. Methods: This multicenter, retrospective study included 6457 pediatric patients with newly diagnosed PDGFRB fusion ALL according to the CCCG‐ALL‐2015 and CCCG‐ALL‐2020 protocols from April 2015 to April 2022 in 20 hospitals in China. Of these patients, 3451 were screened for PDGFRB fusions. Results: Pediatric PDGFRB‐positive ALL accounted for only 0.8% of the 3451 cases tested for PDGFRB. These patients included 21 males and seven females and 24 B‐ALL and 4 T‐ALL; the median age was 10 years; and the median leukocyte count was 29.8 × 109/L at baseline. Only one patient had eosinophilia. Three patients had an IKZF1 deletion, three had chromosome 5q31‐33 abnormalities, and one suffered from a complex karyotype. The 3‐year event‐free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were 33.1%, 65.5%, and 32.1%, respectively, with a median follow‐up of 25.5 months. Twenty patients were treated with chemotherapy plus tyrosine‐kinase inhibitors (TKIs) and eight were treated without TKI. Complete remission (CR) rates of them were 90.0% and 63.6%, respectively, but no differences in EFS, OS, or CIR. Univariate analyses showed patients with IKZF1 deletion or measurable residual disease (MRD) ≥0.01% after induction had inferior outcomes (p <.05). Conclusions: Pediatric PDGFRB‐positive ALL has a poor outcome associated with high‐risk features. Chemotherapy plus TKIs can improve the CR rate, providing an opportunity for lower MRD levels and transplantation. MRD ≥0.01% was a powerful adverse prognostic factor, and stratified treatment based on MRD may improve survival for these patients. Plain Language Summary: Pediatric acute lymphoblastic leukemia patients with PDGFRB fusions are associated with high‐risk clinical features such as older age, high white blood cell count at diagnosis, high measurable residual disease after induction therapy, and increased risk of leukemia relapse.Chemotherapy plus tyrosine‐kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB‐positive acute lymphoblastic leukemia (ALL) patients.The MRD level was also a powerful prognostic factor for pediatric PDGFRB‐positive ALL patients. Pediatric acute lymphoblastic leukemia (ALL) patients with PDGFRB fusions are associated with high‐risk clinical features. Chemotherapy plus tyrosine‐kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB‐positive ALL patients. The MRD level was also a powerful prognostic factor for pediatric PDGFRB‐positive ALL patients. [ABSTRACT FROM AUTHOR]

Purpose: Acute myeloid leukemia (AML) is a refractory hematologic malignancy that poses a serious threat to human health. Exploring alternative therapeutic strategies capable of inducing alternative modes of cell death, such as ferroptosis, holds great promise as a viable and effective intervention. Methods: We analyzed online database data and collected clinical samples to verify the expression and function of BMAL1 in AML. We conducted experiments on AML cell proliferation, cell cycle, ferroptosis, and chemotherapy resistance by overexpressing/knocking down BMAL1 and using assays such as MDA detection and BODIPY 581/591 C11 staining. We validated the transcriptional regulation of HMGB1 by BMAL1 through ChIP assay, luciferase assay, RNA level detection, and western blotting. Finally, we confirmed the results of our cell experiments at the animal level. Results: BMAL1 up-regulation is an observed phenomenon in AML patients. Furthermore, there existed a strong correlation between elevated levels of BMAL1 expression and inferior prognosis in individuals with AML. We found that knocking down BMAL1 inhibited AML cell growth by blocking the cell cycle. Conversely, overexpressing BMAL1 promoted AML cell proliferation. Moreover, our research results revealed that BMAL1 inhibited ferroptosis in AML cells through BMAL1-HMGB1-GPX4 pathway. Finally, knocking down BMAL1 can enhance the efficacy of certain first-line cancer therapeutic drugs, including venetoclax, dasatinib, and sorafenib. Conclusion: Our research results suggest that BMAL1 plays a crucial regulatory role in AML cell proliferation, drug resistance, and ferroptosis. BMAL1 could be a potential important therapeutic target for AML. [ABSTRACT FROM AUTHOR]

In this article, we study the Cauchy problem of the chemotaxis-Navier–Stokes system with the consumption and production of chemosignals with a logistic source. The parameters χ ≠ 0 ,   ξ ≠ 0 ,   λ > 0 and μ > 0 . The system is a model that involves double chemosignals; one is an attractant consumed by the cells themselves, and the other is an attractant or a repellent produced by the cells themselves. We prove the global-in-time existence and uniqueness of the weak solution to the system for a large class of initial data on the whole space R 2 . [ABSTRACT FROM AUTHOR]

Immunogenic cell death (ICD) is a type of cell death that is accompanied by the release of damage-associated molecular patterns (DAMPs) and results in a dead-cell antigen-specific immune response. Here, we report that spautin-1, an inhibitor of ubiquitin-specific peptidases, triggers immunogenic cancer cell death in vitro and in vivo. The anticancer activity of spautin-1 occurs independent of autophagy inhibition, but depends on the intrinsic mitochondrial apoptosis pathway. Spautin-1 causes mitochondrial oxidative injury, which results in JUN transcription factor activation in a JNK-dependent manner. Mechanistically, activation of JUN by spautin-1 leads to apoptosis by upregulation of pro-apoptotic BAD expression. Importantly, the release of TFAM, a mitochondrial DAMP, by apoptotic cells may contribute to spautin-1-induced ICD via its action on the receptor AGER. Indeed, cancer cells treated with spautin-1 in vitro were able to elicit an anticancer immune response when inoculated in vivo, in the absence of any adjuvant. This immunogenic effect of spautin-1-treated cancer cells was lost when TFAM or AGER were neutralized by specific antibodies. Altogether, our results suggest that spautin-1 may stimulate an apoptotic pathway that results in ICD, in TFAM- and AGER-dependent fashion. [ABSTRACT FROM AUTHOR]

In this paper, the three-dimensional rotating Boussinesq equations are considered. By striking new balances between the regularizing effects of the Laplacian dissipation and the dispersive effects of the Coriolis force, we obtain the global existence of mild solutions to Cauchy problem of the three-dimensional rotating Boussinesq equations. Particularly, the size of the norm of initial velocity can be arbitrarily large, provided that the speed of rotation is sufficiently high. [ABSTRACT FROM AUTHOR]

Distiller's grains (DGs) are solid mixtures that remain after the production of alcoholic beverages. A large amount of DGs is produced each year during the brewing process. Currently, they are mostly used as a feedstock or substrate in the feed industry. However, the lack of a comprehensive understanding of the chemical composition of DGs is a major constraint on their further development and application for high-value-added usages. Some studies were published on the bioactive constituents of DGs in several different types of journals. Data were therefore collated to provide a comprehensive overview of these natural products. DGs are rich in phenols, phytosterols, and fatty acids, in addition to general lipid and protein constituents. These compounds and their related extracts possess diverse biological activities, including antioxidant, anti-inflammatory, and anti-hyperglycaemic effects. We hope that this review will provide research incentives for the further development and utilisation of DGs to develop high-value-added products. [ABSTRACT FROM AUTHOR]

Ataxia-telangiectasia (A-T) is an infrequent autosomal recessive disorder that involves multiple systems and is characterized by progressive cerebellar ataxia, oculocutaneous telangiectasias, radiosensitivity, immune deficiency with recurrent respiratory infections, and a tendency to develop lymphoid malignancies. A-T is caused by mutations in the ATM gene, with >1,000 mutations reported to date and gradually increasing in number. Patients with A-T have an increased incidence of cancers. The aim of the present study was to retrospectively review the case of a patient who presented at the age of 5 years with cerebellar ataxia without telangiectasia, and was diagnosed with Burkitt leukemia by bone marrow biopsy and molecular testing at the age of 7 years at the Xiangya Hospital of Central South University (Changsha, China). The patient received chemotherapy with the pediatric CCCG-BNHL-2015 regimen (R4 group) and achieved a complete remission after 2 courses. However, recurrent respiratory infections and thrombosis occurred during chemotherapy. The diagnosis of A-T was confirmed by uncovering two variants of the ATM gene, including c.742C>T (p.R248X; rs730881336) in exon 7 and c.6067-c.6068 ins GAGGGAAGAT in exon 41 by whole-exome sequencing. Unfortunately, the patient's parents refused follow-up treatment and he succumbed to recurrent severe infections 4 months after the diagnosis of Burkitt leukemia. The diagnosis of A-T may be challenging, as its phenotype can be incomplete early in the course of the disease. Detailed medical history, characteristic clinical manifestations and increasingly developed exome sequencing techniques may be helpful in diagnosing this rare disease. Management should be based on multidisciplinary guidance and other treatment options must be investigated in the future. [ABSTRACT FROM AUTHOR]

Review: 66 refs. [ABSTRACT FROM AUTHOR]

Background: Contemporary risk‐directed treatment has improved the outcome of patients with acute lymphoblastic leukemia (ALL) and TCF3::PBX1 fusion. In this study, the authors seek to identify prognostic factors that can be used to further improve outcome. Methods: The authors studied 384 patients with this genotype treated on Chinese Children's Cancer Group ALL‐2015 protocol between January 1, 2015 and December 31, 2019. All patients provisionally received intensified chemotherapy in the intermediate‐risk arm without prophylactic cranial irradiation; those with high minimal residual disease (MRD) ≥1% at day 46 (end) of remission induction were candidates for hematopoietic cell transplantation. Results: The overall 5‐year event‐free survival was 84.4% (95% confidence interval [CI], 80.6–88.3) and 5‐year overall survival 88.9% (95% CI, 85.5–92.4). Independent factors associated with lower 5‐year event‐free survival were male sex (80.4%, [95% CI, 74.8–86.4] vs. 88.9%, [95% CI, 84.1–93.9] in female, p =.03) and positive day 46 MRD (≥0.01%) (62.1%, [95% CI, 44.2–87.4] vs. 87.1%, [95% CI, 83.4–90.9] in patients with negative MRD, p <.001). The presence of testicular leukemia at diagnosis (n = 10) was associated with particularly dismal 5‐year event‐free survival (33.3% [95% CI, 11.6–96.1] vs. 83.0% [95% CI, 77.5–88.9] in the other 192 male patients, p <.001) and was an independent risk factor (hazard ratio [HR], 5.7; [95% CI, 2.2–14.5], p <.001). Conclusions: These data suggest that the presence of positive MRD after intensive remission induction and testicular leukemia at diagnosis are indicators for new molecular therapeutics or immunotherapy in patients with TCF3::PBX1 ALL. Minimal residual disease ≥0.01% at the end of remission induction was associated with an inferior event‐free survival in patients with TCF3::PBX1 acute lymphoblastic leukemia despite intensified chemotherapy. The presence of overt testicular leukemia conferred a particularly poor outcome. [ABSTRACT FROM AUTHOR]

Review: ca. 100 refs. [ABSTRACT FROM AUTHOR]

Oxygen-containing heterocycles are an important class of compounds with diverse biological activities. In recent years, direct α-C-H functionalization of inexpensive and abundant readily available ethers and alcohols by oxidative radical cross-coupling with different nucleophilic partners (C-H, N-H, O-H and S-S), leading to the construction of C-C and C-X (X=C, N, O, S) bonds, has emerged as one of the vital strategies among oxidative cross-coupling reactions. Owing to the features of being atom-economic, environmentally benign, having a simple operation and biologically properties, a series of ether α-C( sp3)-H bond activation reactions have been developed by metal or metal-free systems via the radical oxidative coupling pathway, since the radical oxidative coupling reactions have wide range of applications. This review aims to highlight the recent advances in direct α-C( sp3)-H bond functionalization of ethers and alcohols via radical oxidative process. [ABSTRACT FROM AUTHOR]

Simple Summary: It is urgent to identify new biomarkers for diagnosis, prognostication, and therapeutic targets of acute myeloid leukemia (AML) so as to develop more effective surveillance and treatment programs. Ferroptosis is a crucial, iron-dependent regulated cell death driven by excessive accumulation of lipid hydroperoxides. Accumulating evidence has proven that dysregulated ferroptosis is implicated in tumor progression and is becoming an emerging therapeutic target for the treatment of AML. However, the effect of circRNAs on ferroptosis and the development of AML remain unclear. In this study, we provide the first line of evidence that circZBTB46 is an important oncogenic circRNA as well as a diagnostic or prognostic biomarker for AML. CircZBTB46 exerts a critical role in promoting the expression of SCD to protect AML cells from ferroptotic cell death. Importantly, our findings may offer a potential therapeutic target, circZBTB46, to broaden treatment options for human AML, especially concerning the use of combined treatment with ferroptosis inducers. Circular RNAs (circRNAs) have been shown to be closely linked to the tumorigenesis and treatment response of hematological malignancies. However, the biological functions and clinical implications of circRNAs in acute myeloid leukemia (AML) remain largely unknown. CircRNA microarray datasets were analyzed to screen differentially expressed circRNAs in AML patients. It was found that circZBTB46 was significantly upregulated in AML patients and AML cells. Moreover, the expression of circZBTB46 was associated with the stages of AML patients and showed high sensitivity and specificity for diagnosing AML. Silencing of circZBTB46 inhibited AML cell proliferation and induced cell cycle arrest. Importantly, the depletion of circZBTB46 notably increased ferroptosis and enhanced RSL3-induced ferroptosis in AML cells. Mechanistically, circZBTB46 upregulated the expression of stearoyl-CoA desaturase 1 (SCD) possibly by acting as a miRNA sponge. Finally, the circZBTB46 knockdown repressed the tumor growth of AML in vivo. In conclusion, circZBTB46 protects AML cells from ferroptosis and promotes the proliferation by upregulating SCD, thus suggesting that circZBTB46 may be a potential therapeutic target for AML. [ABSTRACT FROM AUTHOR]

Summary: The effect of prolonged pulse therapy with vincristine and dexamethasone (VD) during maintenance therapy on the outcome of paediatric patients with TCF3‐PBX1 positive acute lymphoblastic leukaemia (ALL) remains uncertain. We conducted non‐inferiority analysis of 263 newly diagnosed TCF3‐PBX1 positive ALL children who were stratified and randomly assigned (1:1) to receive seven additional VD pulses (the control group) or not (the experimental group) in the CCCG‐ALL‐2015 clinical trial from January 2015 to December 2019 (ChiCTR‐IPR‐14005706). There was no significant difference in baseline characteristics between the two groups. With a median follow‐up of 4.2 years, the 5‐year event‐free survival (EFS) and 5‐year overall survival (OS) in the control group were 90.1% (95% confidence interval [CI] 85.1–95.4) and 94.7% (95% CI, 90.9–98.6) comparable to those in the experimental group 89.2% (95% CI 84.1–94.7) and 95.6% (95% CI 91.8–99.6), respectively. Non‐inferiority was established as a one‐sided 95% upper confidence bound for the difference in probability of 5‐year EFS was 0.003, and that for 5‐year OS was 0.01 by as‐treated analysis. Thus, omission of pulse therapy with VD beyond one year of treatment did not affect the outcome of children with TCF3‐PBX1 positive ALL. [ABSTRACT FROM AUTHOR]

Growth performance and meat quality are important traits for pig production. The aim of the present study was to investigate the molecular mechanisms underlying growth performance and meat quality, and to identify novel target molecules for predicting the growth performance and meat quality. The differentially expressed genes (DEGs) in Diannan small ears pigs (DSP) and Landrace pigs (LP) were assessed by RNA-sequencing analyzing technology. A total of 339 DEGs were obtained between DSP and LP. 146 DEGs were upregulated in LP compared with DSP and 193 DEGs were upregulated in DSP compared with LP. The DEGs were significantly enriched in 26 GO and 3 KEGG pathways. The protein–protein interaction (PPI) network with 201 nodes and 382 edges was constructed and 5 modules were extracted from the entire network. The identified upregulated expression of genes involved in glycolysis and myogenesis as well as extracellular matrix may be associated with fast body and muscle deposition rates in LP. Increased expression of genes involved in PPAR signaling pathway and fatty acid metabolism as well as oxidative phosphate processes could be related to the intramuscular fat deposition and meat quality in DSP. The present study may provide an improved understanding of the growth performance and meat quality. [ABSTRACT FROM AUTHOR]

N-Oxide compounds are very important intermediates in synthetic organic chemistry as well as in the chemical industry. Numerous efforts have been devoted to the development of efficient approaches for the CH bond activation and functionalization of N-oxides in recent years, including arylation, alkenylation, alkylation, acyloxylation, amination, amidation and sulfonylation. In this review, recent advances in this area are summarized and their mechanisms are discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] Sepsis is a widespread and life-threatening disease characterised by infection-triggered immune hyperactivation and cytokine storms, culminating in tissue damage and multiple organ dysfunction syndrome. BMAL1 is a pivotal transcription factor in the circadian clock that plays a crucial role in maintaining immune homeostasis. BMAL1 dysregulation has been implicated in inflammatory diseases and immunodeficiency. However, the mechanisms underlying BMAL1 disruption in sepsis-induced acute lung injury (ALI) remain poorly understood. In vitro , we used THP1 and mouse peritoneal macrophages to elucidate the potential mechanism of BMAL1 function in sepsis. In vivo , an endotoxemia model was used to investigate the effect of BMAL1 on sepsis and the therapeutic role of targeting CXCR2. We showed that BMAL1 significantly affected the regulation of innate immunity in sepsis-induced ALI. BMAL1 deficiency in the macrophages exacerbated systemic inflammation and sepsis-induced ALI. Mechanistically, BMAL1 acted as a transcriptional suppressor and regulated the expression of CXCL2. BMAL1 deficiency in macrophages upregulated CXCL2 expression, increasing the recruitment of polymorphonuclear neutrophils and the formation of neutrophil extracellular traps (NETs) by binding to the chemokine receptor CXCR2, thereby intensifying lung injury in a sepsis model. Furthermore, a selective inhibitor of CXCR2, SB225002, exerted promising therapeutic effects by markedly reducing neutrophil infiltration and NETs formation and alleviating lung injury. Importantly, CXCR2 blockade mitigated multiple organ dysfunction. Collectively, these findings suggest that BMAL1 controls the CXCL2/CXCR2 pathway, and the therapeutic efficacy of targeting CXCR2 in sepsis has been validated, presenting BMAL1 as a potential therapeutic target for lethal infections. [ABSTRACT FROM AUTHOR]

Venetoclax is a BCL2-targeted drug employed in treating various cancers, particularly hematologic malignancies. Venetoclax combination therapies are increasingly recognized as promising treatment strategies for acute myeloid leukemia (AML). In this study, we conducted an unbiased drug screen and identified anlotinib, a promising multi-targeted receptor tyrosine kinase inhibitor with oral activity currently utilized in the treatment of solid tumor, as a potent enhancer of venetoclax's anticancer activity in AML. Our investigation encompassed AML cell lines, primary cells, and mouse models, demonstrating effective low-dose combination therapy of anlotinib and venetoclax with minimal cytopenia or organ damage. Proteomic analysis revealed abnormal mitotic signals induced by this combination in AML cells. Mechanistically, anlotinib synergized with venetoclax by suppressing ARPP19 protein, leading to sustained activation of PP2A-B55δ. This inhibited AML cells from entering the mitotic phase, culminating in mitotic catastrophe and apoptosis. Additionally, we identified a specific synthetic lethal vulnerability in AML involving an ARPP19 mutation at S62 phosphorylation. These findings underscore the therapeutic potential of anlotinib and venetoclax combination therapy in AML, warranting further clinical investigation. • The combination of anlotinib and venetoclax induces mitotic catastrophe and subsequent apoptosis in AML. • Low-dose combination of anlotinib and venetoclax for AML shows potent synergistic effects and favorable tolerability. • The combination therapy disrupts mitosis by inhibiting ARPP19 resulting in sustained activation of PP2A-B55δ. [ABSTRACT FROM AUTHOR]

Waterborne polyurethane (WPU) has poor water resistance and low surface hydrophobicity due to the incorporation of hydrophilic chain-extender. The water resistance and the surface hydrophobicity can be improved by incorporation of polydimethylsiloxane (PDMS), which is attributed to the migration of PDMS chain segments toward the surface of WPU film. However, whether the PDMS chain segments can migrate toward the surface of WPU film after UV-curing, resulting in higher hydrophobicity, needs further investigation? We prepared the different WPUA films by changing the molar ratio of aminopropyl-terminated polydimethylsiloxane (APT-PDMS) to hydroxyethyl acrylate (HEA), to deeply understand the migrating phenomenon of PDMS chain segments toward the surface of WPUA films. The migration cause of PDMS chain segments and the influence of chemical cross-linking on the migration were investigated by thermal annealing and solvent immersion of WPUA films. In addition, the migration activation energy and the relaxation time were studied by the migration rate of PDMS chain segments in the thermal annealing and the rheological behavior of WPUA film, aiming to elucidate the migration of PDMS chain segments depending on the chain motion and the fractional free volume. This investigation provides a simple and feasible strategy for improving the hydrophobicity of waterborne polyurethane. • The PDMS chain segments can migrate toward the surface of UV-cured WPU films during thermal annealing or solvent immersing. • Surface energy drives the migration of PDMS chain segments onto the surface of UV-cured WPU films. • Thermal annealing is beneficial to overcome the energy barrier of migration and increases the fractional free volume. • Solvent immersion can also increase the fractional free volume. [ABSTRACT FROM AUTHOR]

An efficient protocol has been developed for the synthesis of pyrazolo[4,3‐c]quinoline derivatives, by reacting (1H‐pyrazol‐5‐yl)anilines and readily available alcohols/amines. A wide range of substrates with diverse functional groups were smoothly converted to the corresponding products in moderate to good yields, under optimal reaction conditions. Furthermore, the strategy also proceeded well with thiol and amino acid to access pyrazolo[4,3‐c]quinoline derivatives. [ABSTRACT FROM AUTHOR]

With environmental and resource issues become increasingly prominent, as well as the requirements of the bioeconomy, the synthesis of polyurethane tends to follow the green chemistry and uses sustainable biological resources as raw materials. As a kind of biomass material, sorbitol has great potential for the bio-based polyurethane industry because of the high performance that sorbitol brings to polyurethane. What,s more, the various extraction technologies for sorbitol have matured. This paper reviews the extraction methods of sorbitol and analyzes the effects of sorbitol as polyols, crosslinkers and chain extenders used in polyurethane. Sorbitol based non-isocyanate polyurethane was also introduced. [ABSTRACT FROM AUTHOR]

Abstract: The enantioselective ring-opening reaction of meso-epoxides with aryl thiols catalyzed by a chiral heterobimetallic Ti–Ga–Salen complex was realized, and the 1,2-mercapto alcohols were obtained in good yields and moderate to high enantioselectivities (up to 92% ee). A strong synergistic cooperation between different Lewis acids in the system was exhibited in the catalytic process. [Copyright &y& Elsevier]

Abstract: The addition of organogallium to aldehydes was realized with titanium tetrachloride as a Lewis acid catalyst. For the first time, the catalytic asymmetric addition of organogallium to aldehydes was investigated with chiral titanium complexes, which were formed from titanium tetrachloride and salan ligands, with mediocre to good chemical yields and enantioselectivities. [Copyright &y& Elsevier]

Background: Vincristine plus dexamethasone pulses are generally used throughout maintenance treatment for childhood acute lymphoblastic leukaemia. However, previous studies remain inconclusive about the benefit of this maintenance therapy and the absence of randomised, controlled trials in patients with low-risk or high-risk acute lymphoblastic leukaemia provides uncertainty. We therefore aimed to determine if this therapy could be safely omitted beyond 1 year of treatment without leading to an inferior outcome in any risk subgroup of childhood acute lymphoblastic leukaemia.Methods: This open-label, multicentre, randomised, phase 3, non-inferiority trial involved 20 major medical centres across China. We enrolled patients who were aged 0-18 years with newly diagnosed acute lymphoblastic leukaemia that was subsequently in continuous remission for 1 year after initial treatment. Patients with secondary malignancy or primary immunodeficiency were excluded. Eligible patients were classified as having low-risk, intermediate-risk, or high-risk acute lymphoblastic leukaemia based on minimal residual disease and immunophenotypic and genetic features of leukaemic cells. Randomisation and analyses were done separately for the low-risk and intermediate-to-high-risk cohorts. Randomisation was generated by the study biostatistician with a block size of six. Stratification factors included participating centre, sex, and age at diagnosis; the low-risk cohort was additionally stratified for ETV6-RUNX1 status, and the intermediate-to-high-risk cohort for cell lineage. Patients in each risk cohort were randomly assigned (1:1) to either receive (ie, the control group) or not receive (ie, the experimental group) seven pulses of intravenous vincristine (1·5 mg/m2) plus oral dexamethasone (6 mg/m2 per day for 7 days) during the second year of treatment. The primary endpoint was difference in 5-year event-free survival between the experimental group and the control group for both the low-risk and intermediate-to-high-risk cohorts, with a non-inferiority margin of 0·05 (5%). The analysis was by intention to treat. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-14005706.Findings: Between Jan 1, 2015, and Feb 20, 2020, 6141 paediatric patients with newly diagnosed acute lymphoblastic leukaemia were registered to this study. Approximately 1 year after diagnosis and treatment, 5054 patients in continuous remission were randomly assigned, including 2923 (1442 in the control group and 1481 in the experimental group) with low-risk acute lymphoblastic leukaemia and 2131 (1071 control, 1060 experimental) with intermediate-to-high risk acute lymphoblastic leukaemia. Median follow-up for patients who were alive at the time of analysis was 3·7 years (IQR 2·8-4·7). Among patients with low-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (90·3% [95% CI 88·4-92·2] vs 90·2% [88·2-92·2]; p=0·90). The one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·024, establishing non-inferiority. Among patients with intermediate-to-high-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (82·8% [95% CI 80·0-85·7] vs 80·8% [77·7-84·0]; p=0·90), but the one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·055, giving a borderline inferior result for those in the experimental group. In the low-risk cohort, we found no differences in the rates of infections, symptomatic osteonecrosis, or other complications during the second year of maintenance treatment between patients in the control and experimental groups. Patients with intermediate-to-high-risk acute lymphoblastic leukaemia in the control group were more likely to develop grade 3-4 pneumonia (26 [2·4%] of 1071 vs ten [0·9%] of 1060) and vincristine-related peripheral neuropathy (17 [1·6%] vs six [0·6%]) compared with the experimental group. Incidence of grade 5 fatal infection was similar between the control group and the experimental group in both the low-risk cohort (two [0·1%] of 1442 vs five [0·3%] of 1481) and intermediate-to-high risk cohort (six [0·6%] of 1071 vs five [0·5%] of 1060).Interpretation: Vincristine plus dexamethasone pulses might be omitted beyond 1 year of treatment for children with low-risk acute lymphoblastic leukaemia. Additional studies are needed for intermediate-to-high-risk acute lymphoblastic leukaemia.Funding: VIVA China Children's Cancer Foundation, the National Natural Science Foundation of China, the China fourth round of Three-Year Public Health Action Plan (2015-2017), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities.Translation: For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Venetoclax is a highly selective BCL2 inhibitor widely used in the treatment of leukemia, especially chronic lymphocytic leukemia and acute myeloid leukemia (AML). However, long-term use of venetoclax may lead to secondary drug resistance, which constitutes an important obstacle to prolonging the duration of the therapeutic response. Here, we show that the acquired resistance to venetoclax in human AML cell lines depends on NF-κB activation rather than on the upregulation of anti-apoptotic BCL2L1 expression. Moreover, alkaliptosis induced by the small molecular compound JTC801, but not necroptosis and ferroptosis, inhibits the growth of venetoclax-resistant AML cells in vitro and in xenograft mouse models. Mechanistically, NF-κB–mediated CA9 downregulation is required for intracellular pH upregulation, thereby inducing alkaliptosis in venetoclax-resistant cells. These findings provide a new strategy to selectively remove venetoclax-resistant AML cells. • BCL2L1 is not required for acquired resistance to venetoclax. • NF-κB is required for acquired resistance to venetoclax. • NF-κB–dependent alkaliptosis inhibits the growth of venetoclax-resistant cells. • JTC801 inhibits the growth of venetoclax-resistant cells in vivo. [ABSTRACT FROM AUTHOR]