The two-step strategy for enhancing the specific activity and thermostability of alginate lyase AlyG2 with mechanism for improved thermostability.

To overcome the trade-off challenge encountered in the engineering of alginate lyase AlyG2 from Seonamhaeicola algicola Gy8T and to expand its potential industrial applications, we devised a two-step strategy encompassing activity enhancement followed by thermal stability engineering. To enhance the specific activity of efficient AlyG2, we strategically substituted residues with bulky steric hindrance proximal to the active pocket with glycine or alanine. This led to the generation of three promising positive mutants, with particular emphasis on the T91S mutant, exhibiting a 1.91-fold specific activity compared to the wild type. To mitigate the poor thermal stability of T91S, mutants with negative ΔΔG values in the thermal flexibility region were screened out. Notably, the S72Y⁎ mutant not only displayed 17.96 % further increase in specific activity but also exhibited improved stability compared to T91S, manifesting as a remarkable 30.97 % increase in relative activity following a 1-hour incubation at 42 °C. Furthermore, enhanced kinetic stability was observed. To gain deeper insights into the mechanism underlying the enhanced thermostability of the S72Y⁎ mutant, we conducted molecular dynamics simulations, principal component analysis (PCA), dynamic cross-correlation map (DCCM), and free energy landscape (FEL) analysis. The results unveiled a reduction in the flexibility of the surface loop, a stronger correlation dynamic and a narrower motion subspace in S72Y⁎ system, along with the formation of more stable hydrogen bonds. Collectively, our findings suggest amino acids substitutions resulting in smaller side chains proximate to the active site can positively impact enzyme activity, while reducing the flexibility of surface loops emerges as a pivotal factor in conferring thermal stability. These insights offer valuable guidance and a framework for the engineering of other enzyme types.

Meta-analysis on the efficacy of allogeneic hematopoietic stem cell transplantation to treat malignant lymphoma.

The goal of the study involved the comparison of clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and autologous hematopoietic stem cell transplantation (auto-HSCT) in the treatment of malignant lymphoma (ML). The effectiveness of allo-HSCT versus auto-HSCT in the treatment of ML was compared by searching EMBASE, PubMed, Web of Science, and the Cochrane Library for relevant studies. The confidence intervals (CI) and odds ratio (OR) of the article's outcomes were described by a forest plot. Finally, 972 patients in seven articles were included. Overall survival (OS) did not differ significantly between allo-HSCT and auto-HSCT groups (OR = 0.87, 95% CI: 0.66-1.14, P = 0.31). Furthermore, there was no significant difference in adverse reactions (AR) between the two groups (OR = 1.35, 95% CI: 0.81-2.24, P = 0.25). We observed a significant difference in progression-free survival (PFS) between the two groups (OR = 4.14, 95% CI: 2.93-5.35, P < 0.01). There was no evidence of publication bias in this meta-analysis. The incidence of OS and AR differ significantly between allo-HSCT and auto-HSCT, but the PFS was longer in ML patients who received allo-HSCT.

Climate-adaptive crop distribution can feed food demand, improve water scarcity, and reduce greenhouse gas emissions.

Optimizing crop distribution stands as a pivotal approach to climate change adaption, enhancing crop production sustainability, and has been recognized for its immense potential in ensuring food security while minimizing environmental impacts. Here, we developed a climate-adaptive framework to optimize the distribution of staple crops (i.e., wheat, maize, and rice), hoping to meet the multi-dimensional needs of crop production in China. The framework considers the feasibility of the multiple cropping systems (harvesting more than once on a cropland a year) and adopts a multi-dimensional approach, incorporating goals related to crop production, water consumption, and greenhouse gas (GHG) emissions. By optimizing, the total irrigated area of three crops would decrease by 7.7 % accompanied by a substantial 69.8 % increase in rain-fed areas compared to the baseline in 2010. This optimized strategy resulted in a notable 10.0 % reduction in total GHG emissions and a 13.1 % decrease in irrigation water consumption while maintaining consistent crop production levels. In 2030, maintaining the existing crop distribution and relying solely on yield growth would lead to a significant maize production shortfall of 27.0 %, highlighting a looming challenge. To address this concern, strategic adjustments were made by reducing irrigated areas for wheat, rice, and maize by 2.3 %, 12.8 %, and 6.1 %, respectively, while simultaneously augmenting rain-fed areas for wheat and maize by 120.2 % and 55.9 %, respectively. These modifications ensure that production demands for all three crops are met, while yielding a 6.9 % reduction in GHG emissions and a 15.1 % reduction in irrigation water consumption. This optimization strategy offers a promising solution to alleviate severe water scarcity issues and secure a sustainable agricultural future, effectively adapting to evolving crop production demands in China.

KBPT: knowledge-based prompt tuning for zero-shot relation triplet extraction.

Knowledge representation is increasingly recognized as an effective method for information extraction. Nevertheless, numerous studies have disregarded its potential applications in the zero-shot setting. In this article, a novel framework, called knowledge-based prompt tuning for zero-shot relation triplet extraction (KBPT), was developed, founded on external ontology knowledge. This framework serves as a catalyst for exploring relation triplet extraction (RTE) methods within low-resource scenarios, warranting further scrutiny. Zero-shot setting RTE aims to extract multiple triplets that consist of head entities, tail entities, and relation labels from an input sentence, where the extracted relation labels are those that do not exist in the training set. To address the data scarcity problem in zero-shot RTE, a technique was introduced to synthesize training samples by prompting language models to generate structured texts. Specifically, this involves integrating language model prompts with structured text methodologies to create a structured prompt template. This template draws upon relation labels and ontology knowledge to generate synthetic training examples. The incorporation of external ontological knowledge enriches the semantic representation within the prompt template, enhancing its effectiveness. Further, a multiple triplets decoding (MTD) algorithm was developed to overcome the challenge of extracting multiple relation triplets from a sentence. To bridge the gap between knowledge and text, a collective training method was established to jointly optimize embedding representations. The proposed model is model-agnostic and can be applied to various PLMs. Exhaustive experiments on four public datasets with zero-shot settings were conducted to demonstrate the effectiveness of the proposed method. Compared to the baseline models, KBPT demonstrated enhancements of up to 14.65% and 24.19% in F1 score on the Wiki-ZSL and TACRED-Revisit datasets, respectively. Moreover, the proposed model achieved better performance compared with the current state-of-the-art (SOTA) model in terms of F1 score, precision-recall (P-R) curves and AUC. The code is available at https://Github.com/Phevos75/KBPT.

Exploring the phosphorus-starch content balance mechanisms in maize grains using GWAS population and transcriptome data.

Examining the connection between P and starch-related signals can help elucidate the balance between nutrients and yield. This study utilized 307 diverse maize inbred lines to conduct multi-year and multi-plot trials, aiming to explore the relationship among P content, starch content, and 100-kernel weight (HKW) of mature grains. A significant negative correlation was found between P content and both starch content and HKW, while starch content showed a positive correlation with HKW. The starch granules in grains with high-P and low-starch content (HPLS) were significantly smaller compared to grains with low-P high-starch content (LPHS). Additionally, mian04185-4 (HPLS) exhibited irregular and loosely packed starch granules. A significant decrease in ZmPHOs genes expression was detected in the HPLS line ZNC442 as compared to the LPHS line SCML0849, while no expression difference was observed in AGPase encoding genes between these two lines. The down-regulated genes in ZNC442 grains were enriched in nucleotide sugar and fatty acid anabolic pathways, while up-regulated genes were enriched in the ABC transporters pathway. An accelerated breakdown of fat as the P content increased was also observed. This implied that HPLS was resulted from elevated lipid decomposition and inadequate carbon sources. The GWAS analysis identified 514 significantly associated genes, out of which 248 were differentially expressed. Zm00001d052392 was found to be significantly associated with P content/HKW, exhibiting high expression in SCML0849 but almost no expression in ZNC442. Overall, these findings suggested new approaches for achieving a P-yield balance through the manipulation of lipid metabolic pathways in grains.

From spear to trident: Upgrading arsenal of CAR-T cells in the treatment of multiple myeloma.

Multiple myeloma (MM), marked by abnormal proliferation of plasma cells and production of monoclonal immunoglobulin heavy or light chains in the majority of patients, has traditionally been associated with poor survival, despite improvements achieved in median survival in all age groups since the introduction of novel agents. Survival has significantly improved with the development of new drugs and new treatment options, such as chimeric antigen receptor T-cell therapy (CAR-T), which have shown promise and given new hope in MM therapy. CARs are now classified as first-, second-, and third-generation CARs based on the number of monovalent to trivalent co-stimulatory molecules incorporated into their design. The scope of this review was relatively narrow because it was mainly about a comparison of the literature on the clinical application of CAR-T therapy in MM. Thus, our goal is to provide an overview of the new advances of CAR-T cells in the cure of MM, so in this review we looked at the progress of the clinical use of CAR-T cells in MM to try to provide a reference for their clinical use when managing MM.

Potential rapid intraoperative cancer diagnosis using dynamic full-field optical coherence tomography and deep learning: A prospective cohort study in breast cancer patients.

An intraoperative diagnosis is critical for precise cancer surgery. However, traditional intraoperative assessments based on hematoxylin and eosin (H&E) histology, such as frozen section, are time-, resource-, and labor-intensive, and involve specimen-consuming concerns. Here, we report a near-real-time automated cancer diagnosis workflow for breast cancer that combines dynamic full-field optical coherence tomography (D-FFOCT), a label-free optical imaging method, and deep learning for bedside tumor diagnosis during surgery. To classify the benign and malignant breast tissues, we conducted a prospective cohort trial. In the modeling group (n = 182), D-FFOCT images were captured from April 26 to June 20, 2018, encompassing 48 benign lesions, 114 invasive ductal carcinoma (IDC), 10 invasive lobular carcinoma, 4 ductal carcinoma in situ (DCIS), and 6 rare tumors. Deep learning model was built up and fine-tuned in 10,357 D-FFOCT patches. Subsequently, from June 22 to August 17, 2018, independent tests (n = 42) were conducted on 10 benign lesions, 29 IDC, 1 DCIS, and 2 rare tumors. The model yielded excellent performance, with an accuracy of 97.62%, sensitivity of 96.88% and specificity of 100%; only one IDC was misclassified. Meanwhile, the acquisition of the D-FFOCT images was non-destructive and did not require any tissue preparation or staining procedures. In the simulated intraoperative margin evaluation procedure, the time required for our novel workflow (approximately 3 min) was significantly shorter than that required for traditional procedures (approximately 30 min). These findings indicate that the combination of D-FFOCT and deep learning algorithms can streamline intraoperative cancer diagnosis independently of traditional pathology laboratory procedures.

Cross-Reactive Antibody Responses to Coronaviruses Elicited by SARS-CoV-2 Infection or Vaccination.

BACKGROUND: The newly emerged SARS-CoV-2 possesses shared antigenic epitopes with other human coronaviruses. We investigated if COVID-19 vaccination or SARS-CoV-2 infection may boost cross-reactive antibodies to other human coronaviruses. METHODS: Prevaccination and postvaccination sera from SARS-CoV-2 naïve healthy subjects who received three doses of the mRNA vaccine (BioNTech, BNT) or the inactivated vaccine (CoronaVac, CV) were used to monitor the level of cross-reactive antibodies raised against other human coronaviruses by enzyme-linked immunosorbent assay. In comparison, convalescent sera from COVID-19 patients with or without prior vaccination history were also tested. Pseudoparticle neutralization assay was performed to detect neutralization antibody against MERS-CoV. RESULTS: Among SARS-CoV-2 infection-naïve subjects, BNT or CV significantly increased the anti-S2 antibodies against Betacoronaviruses (OC43 and MERS-CoV) but not Alphacoronaviruses (229E). The prevaccination antibody response to the common cold human coronaviruses did not negatively impact the postvaccination antibody response to SARS-CoV-2. Cross-reactive antibodies that binds to the S2 protein of MERS-CoV were similarly detected from the convalescent sera of COVID-19 patients with or without vaccination history. However, these anti-S2 antibodies do not possess neutralizing activity in MERS-CoV pseudoparticle neutralization tests. CONCLUSIONS: Our results suggest that SARS-CoV-2 infection or vaccination may potentially modulate population immune landscape against previously exposed or novel human coronaviruses. The findings have implications for future sero-epidemiological studies on MERS-CoV.

Glucagon-like peptide-1 analog liraglutide reduces fat deposition in chicken adipocytes.

Previously, we reported that glucagon-like peptide-1 (GLP-1) and its analog liraglutide could inhibit fat de novo synthesis in the liver and reduce abdominal fat accumulation in broiler chickens. Nevertheless, the impact of GLP-1 on adipocyte fat deposition remains enigmatic. This study aimed to investigate the effects of GLP-1, via its analog liraglutide, on chicken chicken adipocytes in vitro. Chemical assays, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot were employed to assess the proliferation, differentiation, and fat deposition of chicken adipocytes. Our findings indicated that liraglutide significantly suppressed cell proliferation and promoted preadipocyte differentiation in comparison to the control group. This was evidenced by elevated triglyceride (TG) content and upregulated mRNA expression of lipogenesis-related enzymes, such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), as well as regulators including peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element binding protein-1 (SREBP1) and CCAAT/enhancer binding protein α (CEBPα). In mature adipocytes, liraglutide attenuated fat deposition by inhibiting fat de novo synthesis, evidenced by decreased mRNA expression of ACC, FAS, PPARγ, C/EBPα, and SREBP1, and concurrent upregulation of phosphorylated AMP-activated protein kinase (p-AMPK) and phosphorylated ACC (p-ACC). This resulted in reduced accumulation of lipid droplets and TG content in mature adipocytes. Collectively, our findings indicate that liraglutide suppresses the proliferation of preadipocytes, enhances their differentiation, and concurrently inhibits de novo lipogenesis in mature adipocytes. This observation offers profound insights into the mechanisms that underlie liraglutide's anti-adipogenic effects, which could have significant implications for the treatment of obesity in broiler chickens.

The crotonylated and succinylated proteins of jujube involved in phytoplasma-stress responses.

BACKGROUND: Protein posttranslational modifications (PTMs) are fast and early responses to environmental changes, including pathogen infection. Jujube witches' broom (JWB) is a phytoplasma disease causing great economic loss in jujube production. After phytoplasma infection, the transcriptional, translational, and metabolic levels in jujube were activated, enabling it to survive during phytoplasma invasion. However, no study has yet reported on PTMs in jujube. Lysine crotonylation (Kcr) and lysine succinylation (Ksu) have been popular studies in recent years and their function in plant phytoplasma-stress responses remains unclear. RESULTS: Here, 1656 crotonylated and 282 succinylated jujube proteins were first identified under phytoplasma-stress, of which 198 were simultaneously crotonylated and succinylated. Comparative analysis revealed that 656 proteins, 137 crotonylated and 43 succinylated proteins in jujube were regulated by phytoplasma infection, suggesting that Kcr was more universal than Ksu. Kcr differentially expressed proteins (DEPs) were related to ribosomes, photosynthetic and carbon metabolism, while Ksu DEPs were mainly involved in carbon metabolism, the TCA cycle and secondary metabolite biosynthesis. The crosstalk network among proteome, crotonylome and succinylome showed that DEPs related to ribosomal, peroxidases and glutathione redox were enriched. Among them, ZjPOD51 and ZjPHGPX2 significantly increased at the protein and Kcr level under phytoplasma-stress. Notably, 7 Kcr sites were identified in ZjPHGPX2, a unique antioxidant enzyme. After inhibitor nicotinamide (NAM) treatment, GPX enzyme activity in jujube seedlings was reduced. Further, site-directed mutagenesis of key Kcr modification sites K130 and/or K135 in ZjPHGPX2 significantly reduced its activity. CONCLUSIONS: This study firstly provided large-scale datasets of Kcr and Ksu in phytoplasma-infected jujube and revealed that Kcr modification in ZjPHGPX2 positively regulates its activity.

Advancing precision medicine in immunoglobulin light-chain amyloidosis: a novel prognostic model incorporating multi-organ indicators.

To develop a more accurate prognostic model that incorporates indicators of multi-organ involvement for immunoglobulin light-chain (AL) Amyloidosis patients. Biopsy-proven AL amyloidosis patients between January 1, 2012, and February 28, 2023, were enrolled and randomly divided into a training set and a test set at a ratio of 7:3. Prognostic indicators that comprehensively cover cardiac, renal, and hepatic involvement were identified in the training set by random survival forest (RSF). Then, RSF and Cox models were established. The Concordance index (C-index) and integrated brier scores (IBS) were applied to evaluate the models' performance in the test set. Besides, the net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated. A total of 173 eligible patients were included. After a median follow-up of 25.9 (9.2, 50.3) months, 48 (27.7%) patients died. Creatine kinase-MB, estimated glomerular filtration rate ≤ 50 mL/min/1.73 m2, interventricular septum ≥ 15 mm, ejection fraction, alanine aminotransferase and Live involved were selected to develop prediction models. The RSF model based on the above indicators achieved C-index and IBS values of 0.834 (95% CI 0.725-0.915) and 0.151 (95% CI 0.1402-0.181), respectively. At last, the NRI and IDI of the RSF model were 0.301 (95% CI 0.048-0.546, P = 0.012) and 0.157 (95% CI 0.041-0.269, P < 0.001) at 5-year by comparing the RSF model with the Cox model which is based on the Mayo 2012 staging system. The RSF model that incorporates indicators of multi-organ involvement had a great performance, which may be helpful for physicians' decision-making and more accurate overall survival prediction.

The anti-non-small cell lung cancer effect of Diosbulbin B: Targeting YY1 induced cell cycle arrest and apoptosis.

BACKGROUND: Toxic components frequently exhibit unique characteristics and activities, offering ample opportunities for the advancement of anti-cancer medications. As the main hepatotoxic component of Dioscorea bulbifera L. (DB), Diosbulbin B (DIOB) has been widely studied for its anti-tumor activity at nontoxic doses. However, the effectiveness and mechanism of DIOB against non-small cell lung cancer (NSCLC) remains unclear. PURPOSE: To evaluate the anti-NSCLC activity of DIOB and to elucidate the specific mechanism of action. METHOD: The effect of DIOB on NSCLCL in vitro was evaluated through CCK8, colony formation, and flow cytometry. The in vivo efficacy and safety of DIOB in treating NSCLC were assessed using various techniques, including HE staining, tunel staining, immunohistochemistry, and biochemical index detection. To understand the underlying mechanism, cell transfection, western blotting, molecular docking, cellular thermal shift assay (CESTA), and surface plasmon resonance (SPR) were employed for investigation. RESULTS: DIOB effectively hindered the progression of NSCLC both in vitro and in vivo settings at a no-observed-adverse-effect concentration (NOAEC) and a safe dosage. Specifically, DIOB induced significant G0/G1 phase arrest and apoptosis in A549, PC-9, and H1299 cells, while also notably inhibiting the growth of subcutaneous tumors in nude mice. Mechanistically, DIOB could directly interact with oncogene Yin Yang 1 (YY1) and inhibit its expression. The reduction in YY1 resulted in the triggering of the tumor suppressor P53, which induced cell cycle arrest and apoptosis in NSCLC cells by inhibiting the expression of Cyclin A2, B2, CDK1, CDK2, CDK4, BCL-2, and inducing the expression of BAX. In NSCLC cells, the induction of G0/G1 phase arrest and apoptosis by DIOB was effectively reversed when YY1 was overexpressed or P53 was knocked down. Importantly, we observed that DIOB exerted the same effect by directly influencing the expression of YY1-regulated c-Myc and BIM, particularly in the absence of P53. CONCLUSION: For the inaugural investigation, this research unveiled the anti-NSCLC impact of DIOB, alongside its fundamental mechanism. DIOB has demonstrated potential as a treatment agent for NSCLC due to its impressive efficacy in countering NSCLC.

Monosymmetric Fe-N4 sites enabling durable proton exchange membrane fuel cell cathode by chemical vapor modification.

The limited durability of metal-nitrogen-carbon electrocatalysts severely restricts their applicability for the oxygen reduction reaction in proton exchange membrane fuel cells. In this study, we employ the chemical vapor modification method to alter the configuration of active sites from FeN4 to the stable monosymmetric FeN2+N'2, along with enhancing the degree of graphitization in the carbon substrate. This improvement effectively addresses the challenges associated with Fe active center leaching caused by N-group protonation and free radicals attack due to the 2-electron oxygen reduction reaction. The electrocatalyst with neoteric active site exhibited excellent durability. During accelerated aging test, the electrocatalyst exhibited negligible decline in its half-wave potential even after undergoing 200,000 potential cycles. Furthermore, when subjected to operational conditions representative of fuel cell systems, the electrocatalyst displayed remarkable durability, sustaining stable performance for a duration exceeding 248 h. The significant improvement in durability provides highly valuable insights for the practical application of metal-nitrogen-carbon electrocatalysts.

Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men : A Randomized Controlled Trial.

BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.

Structure-based characterization and compound identification of the wild-type THF class-II riboswitch.

Riboswitches are conserved regulatory RNA elements participating in various metabolic pathways. Recently, a novel RNA motif known as the folE RNA motif was discovered upstream of folE genes. It specifically senses tetrahydrofolate (THF) and is therefore termed THF-II riboswitch. To unravel the ligand recognition mechanism of this newly discovered riboswitch and decipher the underlying principles governing its tertiary folding, we determined both the free-form and bound-form THF-II riboswitch in the wild-type sequences. Combining structural information and isothermal titration calorimetry (ITC) binding assays on structure-based mutants, we successfully elucidated the significant long-range interactions governing the function of THF-II riboswitch and identified additional compounds, including alternative natural metabolites and potential lead compounds for drug discovery, that interact with THF-II riboswitch. Our structural research on the ligand recognition mechanism of the THF-II riboswitch not only paves the way for identification of compounds targeting riboswitches, but also facilitates the exploration of THF analogs in diverse biological contexts or for therapeutic applications.

Engineering High-Performance Li Metal Batteries through Dual-Gradient Porous Cu-CuZn Host.

Porous copper (Cu) current collectors show promise in stabilizing Li metal anodes (LMAs). However, insufficient lithiophilicity of pure Cu and limited porosity in three-dimensional (3D) porous Cu structures led to an inefficient Li-Cu composite preparation and poor electrochemical performance of Li-Cu composite anodes. Herein, we propose a porous Cu-CuZn (DG-CCZ) host for Li composite anodes to tackle these issues. This architecture features a pore size distribution and lithiophilic-lithiophobic characteristics designed in a gradient distribution from the inside to the outside of the anode structure. This dual-gradient porous Cu-CuZn exhibits exceptional capillary wettability to molten Li and provides a high porosity of up to 66.05%. This design promotes preferential Li deposition in the interior of the porous structure during battery operation, effectively inhibiting Li dendrite formation. Consequently, all cell systems achieve significantly improved cycling stability, including Li half-cells, Li-Li symmetric cells, and Li-LFP full cells. When paired synergistically with the double-coated LiFePO4 cathode, the pouch cell configured with multiple electrodes demonstrates an impressive discharge capacity of 159.3 mAh g-1 at 1C. We believe this study can inspire the design of future 3D Li anodes with enhanced Li utilization efficiency and facilitate the development of future high-energy Li metal batteries.

[Mechanisms of NLRP3 inflammasome-mediated pyroptosis in chronic heart failure and research progress in traditional Chinese medicine].

Chronic heart failure(CHF) is a severe cardiovascular disease characterized by a complex pathogenesis involving myocardial structural and functional abnormalities and the activation of inflammatory responses. The NOD-like receptor thermal protein domain-associated protein 3(NLRP3) inflammasome, acting as a sensor for inflammatory cells, plays a pivotal role in the development of CHF. Research indicates that the activation of the NLRP3 inflammasome can induce inflammatory responses, leading to cardiac inflammation and impairing myocardial function, and it is correlated with the severity of CHF. Traditional Chinese medicine(TCM) has garnered increasing attention as a traditional therapeutic approach in recent years. Various TCM drugs and treatment methods have exhibited potential efficacy in suppressing inflammatory responses, alleviating myocardial cell pyroptosis, improving myocardial structure and function, and inhibiting myocardial fibrosis. Several TCM drugs and their extracts have been utilized in CHF treatment, with mechanisms potentially involving the inhibition of NLRP3 inflammasomes and the mitigation of inflammatory responses. The article provided an overview of the composition, structural characteristics, initiation, and activation modes of the NLRP3 inflammasome, its mechanisms in CHF, and the research progress of TCM in CHF treatment. It aims to offer references and foundations for a deeper understanding of CHF pathogenesis and subsequent development of new therapeutic strategies.

First Report of Globisporangium ultimum Causing Pythium Damping-off and Root Rot on Pepper in Guizhou, China.

Pepper (Capsicum annuum L.) is a popular vegetable and condiment consumed around the world. In the Guizhou Province of China, peppers are the most commonly grown crop on 300,000 planted hectares. A variety of diseases routinely occur on peppers in this province, resulting in yield losses (Liu et al., 2022). Root rot is one of the most common symptoms and produces poor root growth and wilting of pepper. In April 2023, symptomatic pepper plants displaying stunting, dwarfism, wilting, and root browning were collected from five fields in Guizhou, with disease incidence ranging from 10% to 20%. The collected rotten roots were cleaned with sterilize distilled water and placed in selective V8 juice agar (V8A) medium (15% clarified V8 juice with 2.5 g/L CaCO3 and 2% agar) containing nystatin, ampicillin, rifampicin, and miconazole, and incubated at 25℃ for 1 to 2 days (Morita and Tojo, 2007). Eight isolates with similar colony morphology were transferred to V8A medium via hyphal tipping, and incubated at 25℃ in the dark. Colony and sexual structures were observed using a microscope. Mycelium was aseptate and formed white cottony colonies. Globose, intercalary, or terminal hyphal swellings were observed with a diameter of 20.5 to 25 µm (average: 22 µm), and aplerotic oospores had a diameter of 15 to 20 µm (average: 17.5 µm) with a wall thickness of approximately 2 µm. Three representative isolates HSLJ-3, LJG-1, and LJY-2 were chosen for further molecular identification. Sequences of the internal transcribed spacer (ITS) and mitochondrial cytochrome c oxidase subunit 1 (cox1) genes were identified using primer sets ITS4/ITS5 (White et al., 1990) and OomCoxI-Levup/OomCoxI-Levlo (Robideau et al., 2011), respectively. All sequences were deposited in GenBank (accession nos. OR554005, PP083310, and PP083420 for ITS, and OR529247, PP093821 and PP093822 for cox1). BLAST analysis revealed all ITS and cox1 sequences exhibited 100% identity with Globisporangium ultimum (Pythium ultimum) isolate BR850 (GenBank accession nos. HQ643892.1 and HQ708933.1 for ITS and cox1, respectively). Phylogenetic analysis was performed by the maximum-likelihood method on the CIPRES web portal (https://www.phylo.org/portal2/login!input.action, accessed on 9 January 2024). For pathogenicity tests, each isolate was cultured in V8A medium containing 50 autoclaved wheat seeds at 25℃ for 7 days. Budding pepper seedling (cv. Huaxi) was transplanted into a 0.4 L pot containing sterilized commercial potting mix (Seedling Cultivation Substrate, Hunan Xianghui Agricultural E-commerce Co., Ltd.) which was saturated with deionized water. Eight infected and non-infected wheat seeds were placed near the roots of five pepper seedlings, respectively. Plants were placed in an artificial climate chamber, with a 14 h photoperiod and approximately 75% relative humidity at 25℃. After 14 days, inoculated seedlings showed symptoms of stunting, wilting, and rotting roots similar to those observed in the field. No disease was observed on the non-inoculated control plants. The pathogen was isolated from infected pepper roots and confirmed as G. ultimum by morphological and molecular analyses as previously described. This is the first report of G. ultimum causing root rot on pepper in Guizhou, China. This finding is critical to the discover of treatment options for this pathogen, thereby improving management practices to reduce yield losses in pepper.

Enhanced osteogenic and ROS-scavenging MXene nanosheets incorporated gelatin-based nanocomposite hydrogels for critical-sized calvarial defect repair.

The healing of critical-sized bone defects is a major challenge in the field of bone tissue engineering. Gelatin-related hydrogels have emerged as a potential solution due to their desirable properties. However, their limited osteogenic, mechanical, and reactive oxygen species (ROS)-scavenging capabilities have hindered their clinical application. To overcome this issue, we developed a biofunctional gelatin-Mxene nanocomposite hydrogel. Firstly, we prepared two-dimensional (2D) Ti3C2 MXene nanosheets using a layer delamination method. Secondly, these nanosheets were incorporated into a transglutaminase (TG) enzyme-containing gallic acid-imbedded gelatin (GGA) pre-gel solution to create an injectable GGA-MXene (GM) nanocomposite hydrogel. The GM hydrogels exhibited superior compressive strength (44-75.6 kPa) and modulus (24-44.5 kPa) compared to the GGA hydrogels. Additionally, the GM hydrogel demonstrated the ability to scavenge reactive oxygen species (OH- and DPPH radicals), protecting MC3T3-E1 cells from oxidative stress. GM hydrogels were non-toxic to MC3T3-E1 cells, increased alkaline phosphatase secretion, calcium nodule formation, and upregulated osteogenic gene expressions (ALP, OCN, and RUNX2). The GM400 hydrogel was implanted in critical-sized calvarial defects in rats. Remarkably, it exhibited significant potential for promoting new bone formation. These findings indicated that GM hydrogel could be a viable candidate for future clinical applications in the treatment of critical-sized bone defects.

In Vitro Bioactivities and Characterization of Mycelial Extracts from Different Strains of Phellinus igniarius (Agaricomycetes).

To fully utilize Phellinus igniarius fermentation mycelia, the present study investigated the in vitro antioxidant and α-amylase inhibitory properties of four Ph. igniarius strains. Organic solvents were used to extract fatty acids, phenolics, and flavonoids from the selected mushrooms. The composition and bioactivity of the extracts were evaluated. The lipid yield obtained using petroleum ether (7.1%) was higher than that obtained using 1:1 n-hex-ane+methanol (5.5%) or 2:1 dichloromethane+methanol (3.3%). The composition and relative content of saturated and unsaturated fatty acids in the petroleum ether extract were higher than those in other solvent extracts. Furthermore, ethyl acetate extracts had higher flavonoid and phenolic content and better antioxidant activity than other extracts; however, the 70% ethanol extracts had the best α-amylase inhibitory activity. The supernatant from the ethanol precipitation of aqueous and 1% (NH4)2C2O4 extracts could also be biocompound sources. This comparative study is the first highlighting the in vitro antioxidant and α-amylase inhibitory properties of the four strains of Ph. igniarius extracts prepared using different organic solvents, which makes the investigated species and extracts promising for biological application.