Magnetic Induction Heating-Driven Rapid Cold Start of Ammonia Decomposition for Hydrogen Production.

The advantages of ammonia as a hydrogen carrier have led to proposals for on-site hydrogen production through its decomposition. Rapid cold start of ammonia decomposition is crucial for applications such as ammonia-powered vehicles, but conventional heating methods are challenged by the high decomposition temperature of ammonia. In this study, we successfully achieved the rapid cold start of ammonia decomposition using Co nanoparticle catalysts driven by magnetic induction heating, demonstrating excellent catalytic performance and stability. The magnetic induction heating-driven ammonia decomposition system was integrated with a hydrogen fuel cell, proving its ability to achieve the cold start of ammonia decomposition within 10 s, as demonstrated by comparative experiments using 75% H2-25% N2 from a gas cylinder as the control. This study provides a deeper understanding of hysteresis heating catalysis, promoting the practical use of ammonia as a hydrogen carrier for rapid hydrogen production in the energy industry.

dsAMP and dsAMPGAN: Deep Learning Networks for Antimicrobial Peptides Recognition and Generation.

Antibiotic resistance is a growing public health challenge. Antimicrobial peptides (AMPs) effectively target microorganisms through non-specific mechanisms, limiting their ability to develop resistance. Therefore, the prediction and design of new AMPs is crucial. Recently, deep learning has spurred interest in computational approaches to peptide drug discovery. This study presents a novel deep learning framework for AMP classification, function prediction, and generation. We developed discoverAMP (dsAMP), a robust AMP predictor using CNN Attention BiLSTM and transfer learning, which outperforms existing classifiers. In addition, dsAMPGAN, a Generative Adversarial Network (GAN)-based model, generates new AMP candidates. Our results demonstrate the superior performance of dsAMP in terms of sensitivity, specificity, Matthew correlation coefficient, accuracy, precision, F1 score, and area under the ROC curve, achieving >95% classification accuracy with transfer learning on a small dataset. Furthermore, dsAMPGAN successfully synthesizes AMPs similar to natural ones, as confirmed by comparisons of physical and chemical properties. This model serves as a reliable tool for the identification of novel AMPs in clinical settings and supports the development of AMPs to effectively combat antibiotic resistance.

Development of a Bioorthogonal Click-to-Release Reaction for Hydrogen Polysulfide (H2Sn) Detection.

In this study, we present an innovative "click-to-release" strategy for the design of highly specific H2Sn bioorthogonal probes that undergo a specific click reaction with H2Sn and release fluorophores by a following rearrangement. A library of cyclooctyne derivatives was established and successfully demonstrated the availability of the release strategy. Then, a model probe CM-CT was synthesized, which can achieve effective fluorophore release (>80%) in the presence of a H2Sn donor. To further validate the application of this class of probes, a new probe QN-RHO-CT based on Rhodamine 110 was developed. This probe showed good water solubility (>160 µM) and fast release kinetics and can achieve selective H2Sn detection in living cells. We used this probe to study the process of H2S-mediated protein S-persulfidation and demonstrated that excess H2S would directly react with protein persulfides to generate H2S2 and reduce the persulfides to thiols. Additionally, we elucidated the click-to-release mechanism in our design through a detailed mechanistic study, confirming the generation of the key intermediate α, ß-unsaturated cyclooctanethione. This bioorthogonal click-to-release reaction provides a useful tool for investigating the function of H2Sn and paves the way for biological studies on H2Sn.

A Green and Efficient Electrocatalytic Route for the Highly-Selective Oxidation of C-H Bonds in Aromatics over 1D Co3O4-Based Nanoarrays.

Electrocatalytic oxidation of C-H bonds in hydrocarbons represents an efficient and sustainable strategy for the synthesis of value-added chemicals. Herein, a highly selective and continuous-flow electrochemical oxidation process of toluene to various oxygenated products (benzyl alcohol, benzaldehyde, and benzyl acetate) is developed with the electrocatalytic membrane electrodes (ECMEs). The selectivity of target products can be manipulated via surface and interface engineering of Co3O4-based electrocatalysts. We achieved a high benzaldehyde selectivity of 90% at a toluene conversion of 47.6% using 1D-Co3O4 nanoneedles (NNs) loaded on a microfiltration (MF) titanium (Ti) membrane, i.e, Co3O4 NNs/Ti. In contrast, the main product shifted to benzyl alcohol with a selectivity of 90.1% at conversion of 32.1% after modifying MnO2 nanosheets (NSs) on Co3O4 NNs/Ti (Co3O4@MnO2/Ti) catalyst. Moreover, benzyl acetate product can be obtained with selectivity of 92% at a conversion of 58.5% at high current density (> 1.5mA cm-2), demonstrating that the pathway of toluene oxidation is readily maneuvered. DFT results reveal that modifying MnO2 on Co3O4 optimizes the electron structure of Co3O4@MnO2/Ti and modulates the adsorption behavior of intermediate species. This work demonstrates a sustainable, and continuous-flow process for precise control over production selectivity of value-added oxygenated derivatives in electrochemical oxidation of aromatic hydrocarbons.

Successful Interventional Therapy for Portal Vein Stenosis after Ex Vivo Liver Resection and Autotransplantation in End-Stage Hepatic Alveolar Echinococcosis with Cavernous Transformation.

BACKGROUND End-stage hepatic alveolar echinococcosis (AE) can result in cavernous transformation of the portal vein (CTPV) due to extensive invasion of the portal vein. Ex vivo liver resection and autotransplantation (ELRA) is a new treatment option for patients with end-stage hepatic AE combined with CTPV. ELRA can achieve radical resection of HAE lesions and vascular reconstruction, and also effectively controls bleeding, particularly in cases involving multiple tortuous PV collaterals. Unfortunately, postoperative complications related to the portal vein can impede liver blood flow, thereby increasing the risk of portal hypertension and eventual failure of the transplanted liver if not promptly treated through appropriate medical interventions. CASE REPORT We report the case of a 31-year-old woman who underwent ELRA for end-stage hepatic AE combined with CTPV, and early postoperative portal vein anastomotic stenosis occurred. Stenting of the portal vein was performed after clarification of the stenotic segment by portal venography, followed by anticoagulation therapy and close ultrasound follow-up. After the operation, the patient's portal vein anastomosis widened and the blood flow into the liver returned to normal, avoiding graft liver failure. At 3-year follow-up, the portal vein stent was patent and no serious portal vein complications such as thrombosis had occurred. CONCLUSIONS ELRA provides a new therapeutic approach for patients with HAE combined with CTPV, and intraoperative portal vein reconstruction is one of the key procedures. For CTPV patients with early postoperative portal vein stenosis, interventional therapy (IVR) offers fresh perspectives and avoids acute liver failure caused by liver hypoperfusion.

The different functions of V-ATPase subunits in adipocyte differentiation and their expression in obese mice.

BACKGROUND: Obesity is a significant global public health issue linked to numerous chronic diseases, including diabetes, cardiovascular conditions, and various cancers. The vacuolar H + ATPase, a multi-subunit enzyme complex involved in maintaining pH balance, has been implicated in various health conditions, including obesity-related diseases. METHOD: This study conducts a comprehensive analysis of V-ATPase subunits' roles in adipogenesis within the context of obesity, using knockdown and RNAseq technologies. RESULT: This study conducts a comprehensive analysis of V-ATPase subunits' roles in adipogenesis, highlighting specific subunits, v0d2 and v1a, which show significant expression alterations. Our findings reveal that v1a plays a crucial role in adipocyte differentiation through pathways related to steroid and cholesterol metabolism. CONCLUSION: This study provides a comprehensive analysis of the roles played by V-ATPase subunits in adipogenesis and finds the critical role of V-ATPase subunits, particularly v1a, in the differentiation of adipocytes and their potential impact on obesity.

Genome-wide identification and characterization of SLEEPER, a transposon-derived gene family and their expression pattern in Brassica napus L.

BACKGROUND: The transposons of the hAT superfamily are the most widespread transposons ever known. SLEEPER genes encode domesticated transposases from the hAT superfamily, which may have lost their transposable functions during long-term evolution and transformed into host proteins that regulate plant growth and development. RESULTS: This study identified 162 members of the SLEEPER gene family from Brassica napus. These members are widely distributed on 19 chromosomes, mainly in the Cn subgenome, and have promoters with various cis-acting elements related to hormone regulation, abiotic stress, and growth and development regulation. Most of the genes in this family contain similar conserved domains and motifs, and the closer the genes are distributed on evolutionary branches, the more similar their structures are. Transcriptome sequencing performed on tissues at different growth stages from B. napus line 3529 indicated that these genes had different expression patterns, and nearly half of the genes were not detectably expressed in all samples. CONCLUSIONS: This study investigated the gene structure, expression patterns, evolutionary features, and gene localization of the SLEEPER family members to confirm the significance of these genes in the growth of B. napus, providing a reference for the study of transposon domestication and outstanding genetic resources for the genetic improvement of B. napus.

Asymmetric synthesis of penostatins A-D from L-ascorbic acid.

The first asymmetric synthesis of (-)-penostatins B and D and the practical synthesis of (+)-penostatins A and C have been accomplished through a flexible strategy. The features of the synthesis are a BF3·OEt2-mediated Diels-Alder reaction of chiral dienophiles and methylcyclopentadienes with high chemo-, regio-, and stereoselectivity, followed by ozonolysis to install the common trisubstituted cyclopentane intermediate, and a hetero-Diels-Alder reaction with easily tunable facial selectivity, followed by sulfonate elimination to construct both enantiomeric tricyclic systems for penostatins A/C and B/D, respectively.

Clinical outcomes of guider-assisted osteotomy compared to conventional pendulum-saw osteotomy in open wedge high tibial osteotomy: a propensity score-matched cohort study.

PURPOSE: We developed a novel guider-assisted osteotomy (GAO) procedure to improve the safety of open wedge high tibial osteotomy (OWHTO) and aimed to compare its efficacy and complications with the conventional pendulum-saw osteotomy (PSO). METHODS: This is a retrospective cohort study of patients undergoing either GAO or PSO procedure in the OWHTO to treat varus knee osteoarthritis, who had a minimum of 2 years of follow-up. Patients were propensity score matched (PSM) in a 1:1 ratio based on demographic and clinical data with a caliper width of 0.02. The outcomes assessed involved the hospital for special surgery (HSS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and the Intraoperative and postoperative complications. RESULTS: 199 patients were included in each group after PSM. The mean duration of follow-up was 38.3 ± 8.9 months. The GAO group had a shorter operation duration (104.5 ± 35.7 vs. 112.1 ± 36.0 min, p = 0.027) and fewer times of intraoperative fluoroscopy (4.2 ± 1.4 vs. 6.0 ± 1.4, p < 0.001). At the last follow-up, clinical scores for knee achieved significant improvements in both GAO and PSO groups: HSS (67.5 ± 10.5 vs. 90.2 ± 7.0, p < 0.001; 69.4 ± 8.2 vs. 91.7 ± 6.8, p < 0.001) and WOMAC (65.7 ± 11.6 vs. 25.2 ± 10.4, p < 0.001; 63.3 ± 12.2 vs. 23.8 ± 9.5, p < 0.001). However, no significant difference was observed between groups for any measures (p > 0.05). In addition, the intraoperative complications (0.5% vs. 3.5%, p = 0.068) and the postoperative bone delayed union and nonunion (1.0% vs. 4.5%, p = 0.032) were marginally or significantly reduced in the GAO versus PSO group. CONCLUSION: GAO demonstrates improvements in intraoperative radiation exposure and complications, with comparable short-term efficacy to PSO, and could be considered a viable alternative in clinical practice.

Aptamer-functionalized triptolide with release controllability as a promising targeted therapy against triple-negative breast cancer.

Targeted delivery and precise release of toxins is a prospective strategy for the treatment of triple-negative breast cancer (TNBC), yet the flexibility to incorporate both properties simultaneously remains tremendously challenging in the X-drug conjugate fields. As critical components in conjugates, linkers could flourish in achieving optimal functionalities. Here, we pioneered a pH-hypersensitive tumor-targeting aptamer AS1411-triptolide conjugate (AS-TP) to achieve smart release of the toxin and targeted therapy against TNBC. The multifunctional acetal ester linker in the AS-TP site-specifically blocked triptolide toxicity, quantitatively sustained aptamer targeting, and ensured the circulating stability. Furthermore, the aptamer modification endowed triptolide with favorable water solubility and bioavailability and facilitated endocytosis of conjugated triptolide by TNBC cells in a nucleolin-dependent manner. The integrated superiorities of AS-TP promoted the preferential intra-tumor triptolide accumulation in xenografted TNBC mice and triggered the in-situ triptolide release in the weakly acidic tumor microenvironment, manifesting striking anti-TNBC efficacy and virtually eliminated toxic effects beyond clinical drugs. This study illustrated the therapeutic potential of AS-TP against TNBC and proposed a promising concept for the development of nucleic acid-based targeted anticancer drugs.

Low-density lipoprotein cholesterol-to-lymphocyte count ratio (LLR) is a promising novel predictor of postoperative new-onset deep vein thrombosis following open wedge high tibial osteotomy: a propensity score-matched analysis.

BACKGROUND: The association of low-density lipoprotein cholesterol (LDL-C) and lymphocyte counts with the development of deep vein thrombosis (DVT) has been demonstrated in many fields but remains lacking in open wedge high tibial osteotomy (OWHTO). This study aimed to assess the predictive value of LDL-C to lymphocyte count ratio (LLR) in screening for postoperative new-onset DVT. METHODS: Clinical data were retrospectively collected from patients who underwent OWHTO between June 2018 and May 2023. The limited restricted cubic spline (RCS) was conducted to evaluate the nonlinear relationship between LLR and the risk of postoperative new-onset DVT. The receiver operating characteristic (ROC) curves were plotted and the predictive value of biomarkers was assessed. After adjusting for intergroup confounders by propensity score matching, the univariate logistic regression was applied to assess the association between LLR and DVT. RESULTS: 1293 eligible patients were included. RCS analysis showed a linear positive correlation between LLR and the risk of DVT (P for overall = 0.008). We identified LLR had an area under the curve of 0.607, accuracy of 74.3%, sensitivity of 38.5%, and specificity of 80.7%, and LLR > 1.75 was independently associated with a 1.45-fold risk of DVT (95% CI: 1.01-2.08, P = 0.045). Furthermore, significant heterogeneities were observed in the subgroups of age, BMI, diabetes mellitus, hypertension, Kellgren-Lawrence grade, the American Society of Anesthesiologists (ASA) score, and intraoperative osteotomy correction size. CONCLUSION: LLR is a valuable biomarker for predicting postoperative new-onset DVT in patients with OWHTO, and routine screening is expected to yield positive benefits.

Design and Discovery of New Collagen V-Derived FGF2-Blocking Natural Peptides Inhibiting Lung Squamous Cell Carcinoma In Vitro and In Vivo.

Aberrant FGF2/FGFR signaling is implicated in lung squamous cell carcinoma (LSCC), posing treatment challenges due to the lack of targeted therapeutic options. Designing drugs that block FGF2 signaling presents a promising strategy different from traditional kinase inhibitors. We previously reported a ColVα1-derived fragment, HEPV (127AA), that inhibits FGF2-induced angiogenesis. However, its large size may limit therapeutic application. This study combines rational peptide design, molecular dynamics simulations, knowledge-based prediction, and GUV and FRET assays to identify smaller peptides with FGF2-blocking properties. We synthesized two novel peptides, HBS-P1 (45AA) and HBS-P2 (66AA), that retained the heparin-binding site. Both peptides demonstrated anti-LSCC and antiangiogenesis properties in cell viability and microvessel network induction assays. In two LSCC subcutaneous models, HBS-P1, with its affinity for FGF2 and enhanced penetration ability, demonstrated substantial therapeutic potential without apparent toxicities. Our study provides the first evidence supporting the development of collagen V-derived natural peptides as FGF2-blocking agents for LSCC treatment.

Targeting Ferroptosis as an Advance Strategy in Cancer Therapy.

Significance: This study innovates by systematically integrating the molecular mechanisms of iron death and its application in cancer therapy. By deeply analyzing the interaction between iron death and the tumor microenvironment, the study provides a new theoretical basis for cancer treatment and directions for developing more effective treatment strategies. In addition, the study points to critical issues and barriers that need to be addressed in future research, providing valuable insights into the use of iron death in clinical translation. Recent Advances: These findings are expected to drive further advances in cancer treatment, bringing patients more treatment options and hope. Through this paper, we see the great potential of iron death in cancer treatment and look forward to more research results being translated into clinical applications in the future to contribute to the fight against cancer. Critical Issues: In today's society, cancer is still one of the major diseases threatening human health. Despite advances in existing treatments, cancer recurrence and drug resistance remain a severe problem. These problems increase the difficulty of treatment and bring a substantial physical and mental burden to patients. Therefore, finding new treatment strategies to overcome these challenges has become significant. Future Directions: The study delved into the molecular basis of iron death in tumor biology. It proposed a conceptual framework to account for the interaction of iron death with the tumor immune microenvironment, guide treatment selection, predict efficacy, explore combination therapies, and identify new therapeutic targets to overcome cancer resistance to standard treatments, peeving a path for future research and clinical translation of ferroptosis as a potential strategy in cancer therapy. Antioxid. Redox Signal. 41, 616-636. [Figure: see text].

Advances in nano-preparations for improving tetrandrine solubility and bioavailability.

Tetrandrine (TET) is a natural bis-benzylisoquinoline alkaloid isolated from Stephania species with a wide range of biological and pharmacologic activities; it mainly serves as an anti-inflammatory agent or antitumor adjuvant in clinical applications. However, limitations such as prominent hydrophobicity, severe off-target toxicity, and low absorption result in suboptimal therapeutic outcomes preventing its widespread adoption. Nanoparticles have proven to be efficient devices for targeted drug delivery since drug-carrying nanoparticles can be passively transported to the tumor site by the enhanced permeability and retention (EPR) effects, thus securing a niche in cancer therapies. Great progress has been made in nanocarrier construction for TET delivery due to their outstanding advantages such as increased water-solubility, improved biodistribution and blood circulation, reduced off-target irritation, and combinational therapy. Herein, we systematically reviewed the latest advancements in TET-loaded nanoparticles and their respective features with the expectation of providing perspective and guidelines for future research and potential applications of TET.

Targeting myeloid-derived suppressor cells promotes antiparasitic T-cell immunity and enhances the efficacy of PD-1 blockade (15 words).

Immune exhaustion corresponds to a loss of effector function of T cells that associates with cancer or chronic infection. Here, our objective was to decipher the mechanisms involved in the immune suppression of myeloid-derived suppressor cells (MDSCs) and to explore the potential to target these cells for immunotherapy to enhance checkpoint blockade efficacy in a chronic parasite infection. We demonstrated that programmed cell-death-1 (PD-1) expression was significantly upregulated and associated with T-cell dysfunction in advanced alveolar echinococcosis (AE) patients and in Echinococcus multilocularis-infected mice. PD-1 blockade ex vivo failed to reverse AE patients' peripheral blood T-cell dysfunction. PD-1/PD-L1 blockade or PD-1 deficiency had no significant effects on metacestode in mouse model. This was due to the inhibitory capacities of immunosuppressive granulocytic MDSCs (G-MDSCs), especially in the liver surrounding the parasite pseudotumor. MDSCs suppressed T-cell function in vitro in an indoleamine 2, 3 dioxygenase 1 (IDO1)-dependent manner. Although depleting MDSCs alone restored T-cell effector functions and led to some limitation of disease progression in E. multilocularis-infected mice, combination with PD-1 blockade was better to induce antiparasitic efficacy. Our findings provide preclinical evidence in support of targeting MDSC or combining such an approach with checkpoint blockade in patients with advanced AE. (200 words).

A simple and economical method for unbiasedly quantifying the alveolar size of entire mouse lung tissue utilizing Hematoxylin and Eosin Staining.

Alveolar, the smallest structural and functional units within the respiratory system, play a crucial role in maintaining lung function. Alveolar damage is a typical pathological hallmark of respiratory diseases. Nevertheless, there is currently no simple, rapid, economical, and unbiased method for quantifying alveolar size for entire lung tissue. Here, firstly, we conducted lung sample slicing based on the size, shape, and distribution of airway branches of different lobes. Next, we performed HE staining on different slices. Then, we provided an unbiased quantification of alveolar size using free software ImageJ. Through this protocol, we demonstrated that C57Bl/6 mice exhibit varying alveolar sizes among different lobes. Collectively, we provided a simple and unbiased method for a more comprehensive quantification of alveolar size in mice, which holds promise for a broader range of respiratory research using mouse models.

Efficacy and safety of ultrasound-guided thermal ablation of graves' disease: a retrospective cohort study.

BACKGROUND: Ultrasound-guided thermal ablation (TA) has emerged as a robust therapeutic approach for treating solid tumors in multiple organs, including the thyroid. Yet, its efficacy and safety profile in the management of Graves' Disease (GD) remains to be definitively established. METHODS: A retrospective study was conducted on 50 GD patients treated with TA between October 2017 and December 2021. Key metrics like thyroid volume, volume reduction rate (VRR), thyroid hormones, and basal metabolic rate (BMR) were evaluated using paired Wilcoxon tests. RESULTS: The intervention of ultrasound-guided TA yielded a statistically significant diminution in total thyroid volume across all postoperative follow-up intervals-1, 3, 6, and 12 months-relative to pre-intervention baselines (p < 0.001). The median VRR observed at these time points were 17.5%, 26.5%, 34.4%, and 39.8%, respectively. Euthyroid status was corroborated in 96% of patients at the one-year follow-up milestone. Transient tachycardia and dysphonia were observed in three patients, while a solitary case of skin numbness was noted. Crucially, no instances of enduring injury to the recurrent laryngeal nerve (RLN) were documented. CONCLUSIONS: Our investigation substantiates ultrasound-guided TA as a pragmatic, well-tolerated, and safe therapeutic modality for GD. It effectively improves symptoms of hyperthyroidism, engenders a substantial reduction in thyroid volume, and restores thyroid hormone and BMR to physiological levels. Given its favorable safety profile, enhanced cosmetic outcomes, and minimally invasive nature, ultrasound-guided TA is a compelling alternative to thyroidectomy for GD patients.

Design and synthesis of matrine derivatives for anti myocardial ischemia-reperfusion injury by promoting angiogenesis.

Myocardial ischemia/reperfusion (MI/R) is a common cardiovascular disease that seriously affects the quality of life and prognosis of patients. In recent years, matrine has attracted widespread attention in the treatment of cardiovascular diseases. This study designed, synthesized, and characterized 20 new matrine derivatives and studied their protective effects on ischemia-reperfusion injury through in vivo and in vitro experiments. Based on cellular assays, most newly synthesized derivatives have a certain protective effect on Hypoxia/Reoxygenation (H/R) induced H9C2 cell damage, with compound 22 having the best activity and effectively reducing cell apoptosis and necrosis. In vitro experimental data shows that compound 22 can significantly reduce the infarct size of rat myocardium and improve cardiac function after MI/R injury. In summary, compound 22 is a new potential cardioprotective agent that can promote angiogenesis and enhance antioxidant activity by activating ADCY5, CREB3l4, and VEGFA, thereby protecting myocardial cell apoptosis and necrosis induced by MI/R.

N-heterocyclic carbene catalyzed [2 + 3] annulation reaction for the synthesis of trifluoroethyl 3,2'-spirooxindole γ-lactam.

Asymmetric catalytic processes promoted by N-heterocyclic carbenes (NHCs) hold great potential for the sustainable preparation of chiral molecules. However, catalyzing the reactions by manipulating the reactive intermediates is challenging. We report herein that the known NHC-catalyzed [3 + 2] annulation reaction between ketimine and enal can also be turned into a [2 + 3] annulation reaction for the highly enantioselective direct synthesis of trifluoroethyl 3,2'-spirooxindole γ-lactams (4) through timely catalysis of the intermediates. DFT calculations revealed that this transformation included the key step of the nucleophilic attack of the Breslow intermediate M2 derived from NHC and enal (2) to the unattacked ketimine (1). Our study demonstrates that it is possible to tune the desired selectivities through the dynamic catalysts of the reactive intermediates.