A ß-Carboline Derivate PAD4 Inhibitor Reshapes Neutrophil Phenotype and Improves the Tumor Immune Microenvironment against Triple-Negative Breast Cancer.

Triple-negative breast cancer is a highly aggressive and heterogeneous breast cancer subtype characterized by early metastasis, poor prognosis, and high recurrence. Targeting histone citrullination-mediated chromatin dysregulation to induce epigenetic alterations shows great promise in TNBC therapy. We report the synthesis, optimization, and evaluation of a novel series of ß-carboline-derived peptidyl arginine deiminase 4 inhibitors that exhibited potent inhibition of TNBC cell proliferation. The most outstanding PAD4 inhibitor, compound 28, hindered the PAD4-H3cit-NET signaling pathway and inhibited the growth of solid tumors and pulmonary metastatic nodules in the 4T1 in situ mouse model. Furthermore, 28 improved the tumor immune microenvironment by reshaping neutrophil phenotype, upregulating the proportions of dendritic cells and M1 macrophages, and reducing the amount of myeloid-derived suppressor cells. In conclusion, our work offered 28 as an efficacious PAD4 inhibitor that exerts a combination of conventional chemotherapy and immune-boosting effects, which represents a potential therapy strategy for TNBC.

A novel histone deacetylase inhibitor Se-SAHA attenuates isoproterenol-induced heart failure via antioxidative stress and autophagy inhibition.

Heart failure is associated with histone deacetylase (HDAC) regulation of gene expression, the inhibition of which is thought to be beneficial for heart failure therapy. Here, we explored the cardioprotective effects and underlying mechanism of a novel selenium-containing HDAC inhibitor, Se-SAHA, on isoproterenol (ISO)-induced heart failure. We found that pretreatment with Se-SAHA attenuated ISO-induced cardiac hypertrophy and fibrosis in neonatal rat ventricular myocytes (NRVMs). Se-SAHA significantly attenuated the generation of ISO-induced reactive oxygen species (ROS) and restored the expression levels of superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) in vitro. Furthermore, Se-SAHA pretreatment prevented the accumulation of autophagosomes. Se-SAHA reversed the high expression of HDAC1 and HDAC6 induced by ISO incubation. However, after the addition of the HDAC agonist, the effect of Se-SAHA on blocking autophagy was inhibited. Using ISO-induced mouse models, cardiac ventricular contractile dysfunction, hypertrophy, and fibrosis was reduced treated by Se-SAHA. In addition, Se-SAHA inhibited HDAC1 and HDAC6 overexpression in ISO-treated mice. Se-SAHA treatment significantly increased the activity of SOD2 and improved the ability to eliminate free radicals. Se-SAHA hindered the excessive levels of the microtubule-associated protein 1 light chain 3 (LC3)-II and Beclin-1 in heart failure mice. Collectively, our results indicate that Se-SAHA exerts cardio-protection against ISO-induced heart failure via antioxidative stress and autophagy inhibition.

A comparative study of the hypolipidemic effects and mechanisms of action of Laminaria japonica- and Ascophyllum nodosum-derived fucoidans in apolipoprotein E-deficient mice.

The structural characteristics of fucoidans exhibit species and regional diversity. Previous studies have demonstrated that Laminaria japonica- and Ascophyllum nodosum-derived fucoidans have type I and type II fucosyl chains, respectively. These chemical differences may contribute to distinct hypolipidemic effects and mechanisms of action. Chemical analysis demonstrated that the percentage contents of sulfate, glucuronic acid, and galactose were higher in L. japonica-derived fucoidans than those of A. nodosum-derived fucoidans. In hyperlipidemic apolipoprotein E-deficient mice, both A. nodosum- and L. japonica-derived fucoidans significantly decreased the plasma and hepatic levels of total cholesterol and triglyceride, leading to the reduction of atherosclerotic plaques. Western blotting experiments demonstrated that these fucoidans significantly enhanced the expression and levels of scavenger receptor B type 1, cholesterol 7 alpha-hydroxylase A1, and peroxisome proliferator-activated receptor (PPAR)-α, contributing to circulating lipoprotein clearance and fatty acid degradation, respectively. Differentially, L. japonica-derived fucoidan significantly increased the LXR/ATP-binding cassette G8 signaling pathway in the small intestine, as revealed by real-time quantitative PCR, which may lead to further cholesterol and other lipid excretion. Collectively, these data are useful for understanding the hypolipidemic mechanisms of action of seaweed-derived fucoidans, and their potential application for the prevention and/or treatment of atherosclerotic cardiovascular diseases.

Zero-valent iron (ZVI) facilitated in-situ selenium (Se) immobilization and its recovery by magnetic separation: Mechanisms and implications for microbial ecology.

Selenium (Se(VI)) is environmentally toxic. One of the most popular reducing agents for Se(VI) remediation is zero-valent iron (ZVI). However, most ZVI studies were carried out in water matrices, and the recovery of reduced Se has not been investigated. A water-sediment system constructed using natural sediment was employed here to study in-situ Se remediation and recovery. A combined effect of ZVI and unacclimated microorganisms from natural sediment was found in Se(VI) removal in the water phase with a removal efficiency of 92.7 ± 1.1% within 7 d when 10 mg L-1 Se(VI) was present. Soluble Se(VI) was removed from the water and precipitated to the sediment phase (74.8 ± 0.1%), which was enhanced by the addition of ZVI (83.3 ± 0.3%). The recovery proportion of the immobilized Se was 34.2 ± 0.1% and 92.5 ± 0.2% through wet and dry magnetic separation with 1 g L-1 ZVI added, respectively. The 16 s rRNA sequencing revealed the variations in the microbial communities in response to ZVI and Se, which the magnetic separation could potentially mitigate in the long term. This study provides a novel technique to achieve in-situ Se remediation and recovery by combining ZVI reduction and magnetic separation.

Diagnostic Performance of 18F-FDG Positron Emission Tomography/Computed Tomography and Blood Test Parameters for Pulmonary Inflammatory Pseudotumor.

PURPOSE: Pulmonary inflammatory pseudotumor (PIP) is an inflammatory proliferative tumor-like lesion that frequently exhibits hypermetabolism on 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography imaging (PET/CT) and is readily misdiagnosed as a malignant tumor. The purpose of this study was to identify PIP by combining PET/computed tomography metabolic and blood test characteristics with machine learning. PATIENTS AND METHODS: We recruited 27 patients with PIP and 28 patients with lung cancer (LC). The PET metabolic and blood test parameters were collected, and the differences between the groups were evaluated. In addition, we combined the support vector machine (SVM) classifier with the indicators that differed between the groups to classify PIP and LC. RESULTS: For PET metabolic parameters, our findings showed that, as compared with the LC group, maximal standardized uptake value (P< 0.001, t = -4.780), Mean standardized uptake value SUVmean, P< 0.001, t = -4.946), and SD40% (P< 0.001, t = -4.893) were considerably reduced in the PIP group, whereas CV40% (P= 0.004, t = 3.012) was significantly greater. For blood test parameters, the total white blood cell count (P< 0.001, t= 6.457) and absolute neutrophil count (P< 0.001, t= 6.992) were substantially higher in the PIP group than in the LC group. Furthermore, the performance of SVM trained solely on PET metabolic parameters (mean area under the curve [AUC] = 0.84) was comparable to that of SVM trained solely on blood test parameters (mean AUC = 0.86). Surprisingly, utilizing the combined parameters increased SVM performance significantly (mean AUC = 0.98). CONCLUSION: PET metabolic and blood test parameters differed significantly between the PIP and LC groups, and the SVM paradigm using these significantly different features has the potential to be used to classify PIP and LC, which has important clinical implications.

Application of gel based on medical image inspection in total closure resection of oral cancer patients.

Oral cancer is a common malignant tumor, and total closed resection is a common treatment. However, it has always been a challenge to determine the exact extent of excision during surgery. The application of medical image examination in surgery can provide important reference information, but the current methods still have some limitations. This study explored the application of gels based on medical image examination in the total closed resection of oral cancer patients to improve the accuracy of resection range and surgical treatment effect. The study collected medical image data of patients with oral cancer for image enhancement and determination of resection boundaries. By comparing the results of the experimental group and the control group, the application effect of gel in operation was evaluated. Through the application of medical image inspection technology, the determination of surgical resection boundary is more accurate, and the positive incisal margin of patients is effectively avoided. Gel technology improves the success rate and efficacy of surgery, and this method helps to improve the accuracy of surgery and the certainty of the scope of resection, which is of great significance for improving the surgical treatment effect and the survival rate of patients.

Abnormal occipital and frontal activity during voluntary convergence in intermittent exotropia: A task-fMRI study.

Intermittent exotropia (IXT) is characterized by intermittently outward deviation of the eye and involved with vergence dysfunction. This study aimed to investigate the brain areas related to voluntary convergence and cortical activation changes between IXT patients and normal subjects. A total of 21 subjects, including 11 IXT patients and 10 age- and sex-matched normal subjects, were recruited for this study. A voluntary convergence task was employed, with changes in brain function measured by functional magnetic resonance imaging (fMRI). Correlations between cortical activation and clinical measurements were conducted by Pearson's correlation analysis. fMRI results showed that during voluntary convergence, the medial frontal gyrus (MFG) and bilateral occipital cortex were activated in the normal group, whereas only activation of the occipital cortex in IXT patients. Compared with the normal, IXT patients showed hypo-activation of both the MFG and cuneus during the task. The activation of MFG was negatively correlated to the duration of IXT. This study demonstrates that both MFG and occipital cortex may participate in voluntary convergence in normal subjects, while IXT patients have an aberrant cortical function of the MFG and cuneus, and the duration of IXT likely influences the severity of MFG. These findings may provide valuable insights for understanding the relationship between convergence and IXT.

Structure-Activity Relationship of PAD4 Inhibitors and Their Role in Tumor Immunotherapy.

Protein arginine deiminase 4 (PAD4) plays an important role in cancer progression by participating in gene regulation, protein modification, and neutrophil extracellular trap (NET) formation. Many reversible and irreversible PAD4 inhibitors have been reported recently. In this review, we summarize the structure-activity relationships of newly investigated PAD4 inhibitors to bring researchers up to speed by guiding and describing new scaffolds as optimization and development leads for new effective, safe, and selective cancer treatments. In addition, some recent reports have shown evidence that PAD4 inhibitors are expected to trigger antitumor immune responses, regulate immune cells and related immune factors, enhance the effects of immune checkpoint inhibitors, and enhance their antitumor efficacy. Therefore, PAD4 inhibitors may potentially change tumor immunotherapy and provide an excellent direction for the development and clinical application of immunotherapy strategies for related diseases.

Highly Conductive Imidazolate Covalent Organic Frameworks with Ether Chains as Solid Electrolytes for Lithium Metal Batteries.

Poly(ethylene oxide) (PEO)-based electrolytes are often used for Li+ conduction as they can dissociate the Li salts efficiently. However, high entanglement of the chains and lack of pathways for rapid ion diffusion limit their applications in advanced batteries. Recent developments in ionic covalent organic frameworks (iCOFs) showed that their highly ordered structures provide efficient pathways for Li+ transport, solving the limitations of traditional PEO-based electrolytes. Here, we present imidazolate COFs, PI-TMEFB-COFs, having methoxyethoxy chains, synthesized by Debus-Radziszewski multicomponent reactions and their ionized form, Li+@PI-TMEFB-COFs, showing a high Li+ conductivity of 8.81 mS cm-1 and a transference number of 0.974. The mechanism for such excellent electrochemical properties is that methoxyethoxy chains dissociate LiClO4, making free Li+, then those Li+ are transported through the imidazolate COFs' pores. The synthesized Li+@PI-TMEFB-COFs formed a stable interface with Li metal. Thus, employing Li+@PI-TMEFB-COFs as the solid electrolyte to assemble LiFePO4 batteries showed an initial discharge capacity of 119.2 mAh g-1 at 0.5 C, and 82.0 % capacity and 99.9 % Coulombic efficiency were maintained after 400 cycles. These results show that iCOFs with ether chains synthesized via multicomponent reactions can create a new chapter for making solid electrolytes for advanced rechargeable batteries.

Azobenzene-Based Linker Strategy for Selective Activation of Antibody-Drug Conjugates.

Existing antibody-drug conjugate (ADC) linkers, whether cleavable or non-cleavable, are designed to release highly toxic payloads or payload derivatives upon internalisation of the ADCs into cells. However, clinical studies have shown that only <1 % of the dosed ADCs accumulate in tumour cells. The remaining >99 % of ADCs are nonspecifically distributed in healthy tissue cells, thus inevitably leading to off-target toxicity. Herein, we describe an intelligent tumour-specific linker strategy to address these limitations. A tumour-specific linker is constructed by introducing a hypoxia-activated azobenzene group as a toxicity controller. We show that this azobenzene-based linker is non-cleavable in healthy tissues (O2 >10 %), and the corresponding payload derivative, cysteine-appended azobenzene-linker-monomethyl auristatin E (MMAE), can serve as a safe prodrug to mask the toxicity of MMAE (switched off). Upon exposure to the hypoxic tumour microenvironment (O2<1 %), this linker is cleaved to release MMAE and fully restores the high cytotoxicity of the ADC (switched on). Notably, the azobenzene linker-containing ADC exhibits satisfactory antitumour efficacy in vivo and a larger therapeutic window compared with ADCs containing traditional cleavable or non-cleavable linkers. Thus, our azobenzene-based linker sheds new light on the development of next-generation ADC linkers.

Durable cross-protective neutralizing antibody responses elicited by lipid nanoparticle-formulated SARS-CoV-2 mRNA vaccines.

The advent of SARS-CoV-2 variants with defined mutations that augment pathogenicity and/or increase immune evasiveness continues to stimulate global efforts to improve vaccine formulation and efficacy. The extraordinary advantages of lipid nanoparticles (LNPs), including versatile design, scalability, and reproducibility, make them ideal candidates for developing next-generation mRNA vaccines against circulating SARS-CoV-2 variants. Here, we assess the efficacy of LNP-encapsulated mRNA booster vaccines encoding the spike protein of SARS-CoV-2 for variants of concern (Delta, Omicron) and using a predecessor (YN2016C isolated from bats) strain spike protein to elicit durable cross-protective neutralizing antibody responses. The mRNA-LNP vaccines have desirable physicochemical characteristics, such as small size (~78 nm), low polydispersity index (<0.13), and high encapsulation efficiency (>90%). We employ in vivo bioluminescence imaging to illustrate the capacity of our LNPs to induce robust mRNA expression in secondary lymphoid organs. In a BALB/c mouse model, a three-dose subcutaneous immunization of mRNA-LNPs vaccines achieved remarkably high levels of cross-neutralization against the Omicron B1.1.529 and BA.2 variants for extended periods of time (28 weeks) with good safety profiles for all constructs when used in a booster regime, including the YN2016C bat virus sequences. These findings have important implications for the design of mRNA-LNP vaccines that aim to trigger durable cross-protective immunity against the current and newly emerging variants.

Screening of natural inhibitors against peptidyl arginine deiminase 4 from herbal extracts by a high-performance liquid chromatography ultraviolet-visible based method.

Peptidyl arginine deiminase 4 (PAD4) is an important biocatalytic enzymes involved in the conversion of protein arginine to citrulline, its dysregulation has a great impact on many physiological processes. Recently, PAD4 has emerged as a potential therapeutic target for the treatment of various diseases including rheumatoid arthritis (RA). Traditional Chinese Medicines (TCMs), also known as herbal plants, have gained great attention by the scientific community due to their good therapeutic performance and far fewer side effects observed in the clinical treatment. However, limited researches have been reported to screen natural PAD4 inhibitors from herbal plants. The color developing reagent (COLDER) or fluorescence based methods have been widely used in PAD4 activity assay and inhibitor screening. However, both methods measure the overall absorbance or fluorescence in the reaction solution, which are easy to be affected by the background interference due to colorful extracts from herbal plants. In this study, a simple, and robust high-performance liquid chromatography ultraviolet-visible (HPLC-UV) based method was developed to determine PAD4 activity. The proposed strategy was established based on COLDER principle, while used hydrophilic l-arginine instead of hydrophobic N-benzoyl-l-arginine ethyl ester (BAEE) as a new substrate to determine PAD4 inhibition activity of herbal extracts. The herbal extracts and PAD4 generated hydrophobic l-citrulline were successfully separated by the HPLC, and the developed method was optimized and validated with a known PAD4 inhibitor (GSK484) in comparison with COLDER assay. The IC50 value of GSK484 measured by HPLC-UV method was 153 nM, and the detection limit of the citrulline was 0.5 nmol, respectively, with a linear range of 0.5 nmol to 20 nmol. The IC50 value of the HPLC-UV method was improved by nearly three times compared with COLDER assay (527 nM), and the results indicated the reliability of PAD4 inhibition via HPLC-UV method. The inhibitory effect against PAD4 were fast and accurately screened for the twenty-four extracts from eight herbs. Among them, Ephedra Herba extracts showed significant inhibitory activity against the PAD4 with the IC50 values of three extracts (ethanol, ethyl acetate and water) ranging from 29.11 µg/mL to 41.36 µg/mL, which may help researchers to discover novel natural compounds holding high PAD4 inhibition activity.

Influence of Electrospinning Parameters on the Morphology of Electrospun Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Fibrous Membranes and Their Application as Potential Air Filtration Materials.

A large number of non-degradable materials have severely damaged the ecological environment. Now, people are increasingly pursuing the use of environmentally friendly materials to replace traditional chemical materials. Polyhydroxyalkonates (PHAs) are receiving increasing attention because of the unique biodegradability and biocompatibility they offer. However, the applications of PHAs are still limited due to high production costs and insufficient study. This project examines the optimal electrospinning parameters for the production of PHA-based fibrous membranes for air filtration. A common biodegradable polyester, Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), was electrospun into a nanofibrous membrane with a well-controlled surface microstructure. In order to produce smooth, bead-free fibers with micron-scale diameters, the effect of the process parameters (applied electric field, solution flow rate, inner diameter of hollow needle, and polymer concentration) on the electrospun fiber microstructure was optimized. The well-defined fibrous structure was optimized at an applied electric field of 20 kV, flow rate of 0.5 mL/h, solution concentration of 12 wt.%, and needle inner diameter of 0.21 mm. The morphology of the electrospun PHBV fibrous membrane was observed by scanning electron microscopy (SEM). Fourier transform infrared (FTIR) and Raman spectroscopy were used to explore the chemical signatures and phases of the electrospun PHBV nanofiber. The ball burst strength (BBS) was measured to assess the mechanical strength of the membrane. The small pore size of the nanofiber membranes ensured they had good application prospects in the field of air filtration. The particle filtration efficiency (PFE) of the optimized electrospun PHBV fibrous membrane was above 98% at standard atmospheric pressure.

Injectable Hydrogels Prepared Using Novel Synthetic Short Peptides with Defined Structure and Gelatin as Scaffolds to Support Cell and Tissue Growth.

Animal-derived basement-membrane matrices such as Geltrex are used to grow cells and tissues. Particularly, these are commonly applied to support tumor growth in animals for cancer research. However, a material derived from an animal source has an undefined composition, and may thus have unavoidable batch-to-batch variation in properties. To overcome these issues, a series of synthetic short peptides to form hydrogels is designed in combination with gelatin to promote cell adhesion and growth. The peptides have sequences of (X1Y1X2Y2)2 , where X1 and X2 are hydrophobic residues, while Y1 and Y2 are hydrophilic residues. The peptides spontaneously fold and self-assemble into a ß-sheet secondary structure upon contact with salts, and then aggregate to form hydrophilic networks of hydrogels. Hybrid hydrogels formed by mixing the peptide IEVEIRVK (IVK8) with gelatin are injectable and enzymatically degradable. The hybrid hydrogels at optimal compositions support SW480 and HepG2 tumor spheroid growth in vitro as effectively as Geltrex. More importantly, the peptide/gelatin hydrogels support tumor growth in a SW480 human colorectal adenocarcinoma xenograft mouse model. Altogether, the results illustrate that the synthetic peptide/gelatin hybrid hydrogel is a promising scaffold that can be used to support cell and tissue growth both in vitro and in vivo.

Rumen-protected lysine supplementation improved amino acid balance, nitrogen utilization and altered hindgut microbiota of dairy cows.

This study was conducted to evaluate the effects of dietary crude protein (CP) and rumen-protected lysine (RPL) supplementation on lactation performance, amino acid (AA) balance, nitrogen (N) utilization and hindgut microbiota in dairy cows. Treatments were in a 2 × 2 factorial arrangement, and the main effects were CP concentration (16% vs. 18%) and RPL supplementation (with or without RPL at 40 g/cow per day). Forty cows were randomly allocated to 4 groups: low-CP diet (LP), low-CP diet plus RPL (LPL), high-CP diet (HP), high-CP diet plus RPL (HPL). The experiment was conducted for 8 weeks. Results showed that RPL increased the dry matter intake (P < 0.01), milk protein yield (P = 0.04) and energy corrected milk (P = 0.04), and tended to increase milk fat yield (P = 0.06) and fat corrected milk (P = 0.05). Cows in the HP group tended to have higher milk urea N (P = 0.07). Plasma concentrations of Arg, Ile, Lys, Met, Pro, total essential AA and total nonessential AA were increased by RPL (P < 0.05). The total essential AA, total nonessential AA and most AA (except Ile, Phe, Gly and Pro) were increased in the HP group (P < 0.05). N excretion was increased in the HP group through an increase in urea N excretion (P < 0.01) and an upward trend in plasma urea N (P = 0.07). In addition, RPL tended to increase milk protein N secretion (P = 0.08), milk N (P = 0.07) and microbial protein synthesis (P = 0.06), and decreased plasma urea N (P < 0.001). In the hindgut, the bacterial community were different between the LP and LPL groups (P < 0.01). The probiotic abundances of Christensenellaceae_R-7_group and Acinetobacter were increased by RPL (P = 0.03 and 0.03, respectively). The pathogenic abundances of Clostridium_sensu_stricto_1 (P < 0.001) and Turicibacter (P < 0.01) were decreased by RPL. In conclusion, supplementing RPL with low dietary CP could balance AA supply and increase milk protein yield, resulting in an improvement in N utilization efficiency, and altered the composition of the hindgut microbiota to favor the lactation performance of dairy cows.

Lightweight Extendable Stacking Framework for Structure Classification in Atomistic Simulations.

Identifying an atom's local crystal structure is one crucial step in many atomistic simulation analyses. However, many traditional methods are available to only a few limited types of structures, and their performance often relies on manually determined parameters, which may lead to poor classification results in complex material systems. Machine learning models can enhance accuracy and generalizability, but they typically require large amounts of data and computation. This issue could be more severe for deep-learning-based frameworks, especially when confronted with unfamiliar crystal structures. To address this challenge, we propose a lightweight and extendable stacked structure (LESS) classifier, which adopts bond orientational order parameters as features and assembles several efficient machine learning methods as based models. The LESS classifier can recognize a variety of crystal structures, e.g., amorphous, mono, and binary structures, with over 98.8% accuracy on our validation data set, outperforming many current methods even including some deep-learning methods. Our model can also conduct probabilistic classification that aids in the interpretation of atomic structures in complicated environments such as heterogeneous interfaces. Furthermore, when exposed to a completely unknown crystal structure, the LESS framework can efficiently incorporate this new knowledge with generative sampled data from the current model. Overall, our model exhibits great potential as an accurate and flexible atomic structure identification tool featuring high efficiency in both learning and retraining.

Anthraquinone-Based Silicate Covalent Organic Frameworks as Solid Electrolyte Interphase for High-Performance Lithium-Metal Batteries.

Lithium (Li)-metal batteries (LMBs) possess the highest theoretical energy density among current battery designs and thus have enormous potential for use in energy storage. However, the development of LMBs has been severely hindered by safety concerns arising from dendrite growth and unstable interphases on the Li anode. Covalent organic frameworks (COFs) incorporating either redox-active or anionic moieties on their backbones have high Li-ion (Li+) conductivities and mechanical/chemical stabilities, so are promising for solid electrolyte interphases (SEIs) in LMBs. Here, we synthesized anthraquinone-based silicate COFs (AQ-Si-COFs) that contained both redox-active and anionic sites via condensation of tetrahydroxyanthraquinone with silicon dioxide. The nine Li+-mediated charge/discharge processes enabled the AQ-Si-COF to demonstrate an ionic conductivity of 9.8 mS cm-1 at room temperature and a single-ion-conductive transference number of 0.92. Computational studies also supported the nine Li+ mechanism. We used AQ-Si-COF as the solid electrolyte interphase on the Li anode. The LMB cells with a LiCoO2 cathode attained a maximum reversible capacity of 188 mAh g-1 at 0.25 C during high-voltage operation. Moreover, this LMB cell demonstrated suppressed dendrite growth and stable cyclability, with its capacity decreasing by less than 3% up to 100 cycles. These findings demonstrate the effectiveness of our redox-active and anionic COFs and their practical utility as SEI in LMB.

Reverse Micellar Dyeing of Cotton Fabric with Reactive Dye Using Biodegradable Non-Ionic Surfactant as Nanoscale Carrier: An Optimisation Study by One-Factor-at-One-Time Approach.

This study investigates the feasibility of using biodegradable secondary alcohol ethoxylate (SAE) non-ionic surfactant as a building block for the formation of reverse micelles, functioning as reactive dye carriers for the dyeing of cotton fabric in non-aqueous octane medium. Ten dyeing parameters were optimised, by a one-factor-at-a-time approach, namely: (i) effect of colour fixation agent; (ii) surfactant-to-water mole ratio; (iii) surfactant-to-co-surfactant mole ratio; (iv) volume of soda ash; (v) volume of dye; (vi) solvent-to-cotton ratio; (vii) dyeing temperature; (viii) dyeing time; (ix) fixation time; (x) soda-ash-to-cotton ratio. The colour properties, fastness properties and physical properties of SAE-dyed samples were experimentally compared with the conventional water-dyed samples. The optimised condition was found when SAE samples were dyed as follows: (a) 1:20 surfactant-to-water ratio; (b) 1:8 surfactant-to-co-surfactant ratio; (c) 10:1 solvent ratio; (d) 40 min dyeing time; (e) 60 min fixation time; and (f) 70 °C dyeing and fixation temperature. The results showed that SAE-dyed samples have better colour strength, lower reflectance percentage and comparable levelness, fastness and physical properties than that of water-dyed samples. SEM images revealed that the dyed cotton fibres had no severe surface damage caused by an SAE-based reverse micellar dyeing system. The TEM image depicts that the reverse micelle was of nanoscale, spherical-shaped and had a core-shell structure, validating the presence of reverse micelle as a reactive dye carrier and the potential of an SAE-based reverse micellar system for dyeing of cotton fabrics.

Activation of endoplasmic reticulum stress by harmine suppresses the growth of esophageal squamous cell carcinoma.

The worldwide overall 5-year survival rate of esophageal squamous cell carcinoma (ESCC) patients is less than 20%, and novel therapeutic strategies for these patients are urgently needed. Harmine is a natural ß-carboline alkaloid, which received great interest in cancer research because of its biological and anti-tumor activities. The aim of this study is to examine the effects of harmine on ESCC and its mechanism. We investigated the effects of harmine on proliferation, cell cycle, apoptosis, and tumor growth in vivo. RNA sequencing (RNA-seq), real-time PCR, and western blotting were used to detect the mechanism. Harmine inhibited ESCC cell growth in vitro and tumor growth in vivo. Differentially expressed genes in harmine-treated ESCC cells were mainly involved in protein processing in the endoplasmic reticulum (ER). Real-time PCR and western blotting confirmed harmine-induced cellular ER stress. CRISPR-Cas9 knockout of C/EBP homologous protein (CHOP) abolished harmine-induced expression of death receptor 5 and apoptosis. Harmine also induced the expression of CHOP-mediated sestrin-2, which in turn contributes to autophagosome formation via suppressing the AMP-activated protein kinase-protein kinase B-mammalian target of rapamycin signaling pathway. In conclusion, our results demonstrate that harmine inhibits the growth of ESCC through its regulation of ER stress, suggesting that it is a promising candidate for ESCC treatment.

Experimental Study on the Effect of CO2 Injection Pressure on the Migration Characteristics and Extraction Effects of Replacement CH4.

To study the effect of CO2 injection pressure on gas migration characteristics and coalbed methane (CBM) extraction, a platform for the experimental replacement of CH4 with CO2 was used to conduct experiments on the replacement of CH4 under different CO2 injection pressures and analyze the gas transport characteristics and CH4 extraction during the experiment. The results reveal that the rate of gas migration out of the coal seam accelerates with increasing gas injection pressure, as determined by comparisons of the migration rates between adjacent monitoring points. The change trend of the CH4 desorption rate under different gas injection pressures is divided into slow decline, sharp decline, and stability stages, and the maximum value of the effective diffusion coefficient increases from 2.3 × 10-5 to 3.4 × 10-5 and 4.6 × 10-5 cm2/s as the gas injection pressure increases from 0.6 to 0.8 and 1.0 MPa. Similarly, the change pattern of coal seam permeability can be divided into slow decline, sharp decline, and stability stages. After the gas injection pressure was increased from 0.6 to 0.8 and 1.0 MPa, the CH4 desorption volume increased from 90.2 to 94.1 and 97.8 L, whereas the coal seam CO2 sequestration volume increased from 269.2 to 274.2 and 322.8 L, respectively. In contrast, the CH4 extraction efficiency increased from 76.9 to 80.2 and 82.9%, respectively. The research results have important reference value and practical significance for optimizing the CO2 injection pressure and improving the CBM extraction.