Advances in morphology-controlled alumina and its supported Pd catalysts: synthesis and applications.

Alumina materials, as one of the cornerstones of the modern chemical industry, possess physical and chemical properties that include excellent mechanical strength and structure stability, which also make them highly suitable as catalyst supports. Alumina-supported Pd-based catalysts with the advantages of exceptional catalytic performance, flexible regulated surface metal/acid sites, and good regeneration ability have been widely used in many traditional chemical industry fields and have also shown great application prospects in emerging fields. This review aims to provide an overview of the recent advances in alumina and its supported Pd-based catalysts. Specifically, the synthesis strategies, morphology transformation mechanisms, and structural properties of alumina with various morphologies are comprehensively summarized and discussed in-depth. Then, the preparation approaches of Pd/Al2O3 catalysts (impregnation, precipitation, and other emerging methods), as well as the metal-support interactions (MSIs), are revisited. Moreover, Some promising applications have been chosen as representative reactions in fine chemicals, environmental purification, and sustainable development fields to highlight the universal functionality of the alumina-supported Pd-based catalysts. The role of the Pd species, alumina support, promoters, and metal-support interactions in the enhancement of catalytic performance are also discussed. Finally, some challenges and upcoming opportunities in the academic and industrial application of the alumina and its supported Pd-based are presented and put forward.

Colon cancer inhibitory properties of Caulerpa lentillifera polysaccharide and its molecular mechanisms based on three-dimensional cell culture model.

Caulerpa lentillifera is rich in polysaccharides, and its polysaccharides show a significant effect in different biological activities including anti-cancer activity. As an edible algae-derived polysaccharide, exploring the role of colon cancer can better develop the application from a dietary therapy perspective. However, more in-depth studies of C. lentillifera polysaccharide on anti-colon cancer activity and mechanism are needed. In this study, we found that Caulerpa lentillifera polysaccharides (CLP) showed potential anti-colon cancer effect on human colon cancer cell HT29 in monolayer (IC50 = 1.954 mg/mL) and spheroid (IC50 = 0.402 mg/mL). Transcriptomics and metabolomics analyses revealed that CLP had an inhibitory effect on HT29 3D spheroid cells by activating aminoacyl-tRNA biosynthesis as well as arginine and proline metabolism pathways. Furthermore, the anti-colon cancer effects of CLP were confirmed through other human colon cancer cell HCT116 and LoVo in monolayer cells (IC50 = 1.890 mg/mL and 1.437 mg/mL, respectively) and 3D spheroid cells (IC50 = 0.344 mg/mL and 0.975 mg/mL, respectively), and three patient-derived organoids with IC50 values of 6.333-8.780 mg/mL. This study provided basic data for the potential application of CLP in adjuvant therapeutic food for colon cancer on multiple levels, while further investigation of detailed mechanism in vivo was still required.

Long-term outcomes of intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection (IOCCRC): a randomized, multicenter, prospective, phase III trial.

BACKGROUND: We aimed to compare combined intraoperative chemotherapy and surgical resection with curative surgical resection alone in colorectal cancer patients. METHODS: We performed a multicenter, open-label, randomized, phase III trial. All eligible patients were randomized and assigned to intraoperative chemotherapy and curative surgical resection or curative surgical resection alone (1:1). Survival actualization after long-term follow-up was performed in patients analyzed on an intention-to-treat basis. RESULTS: From January 2011 to January 2016, 696 colorectal cancer patients were enrolled and randomly assigned to intraoperative chemotherapy and radical surgical resection (n=341) or curative surgical resection alone (n=344). Intraoperative chemotherapy with surgical resection showed no significant survival benefit over surgical resection alone in colorectal cancer patients (3-year DFS: 91.1% vs. 90.0%, P=0.328; 3-year OS: 94.4% vs. 95.9%, P=0.756). However, colon cancer patients benefitted from intraoperative chemotherapy, with a relative 4% reduction in liver and peritoneal metastasis (HR=0.336, 95% CI: 0.148-0.759, P=0.015) and a 6.5% improvement in 3-year DFS (HR=0.579, 95% CI: 0.353-0.949, P=0.032). Meanwhile, patients with colon cancer and abnormal pretreatment CEA levels achieved significant survival benefits from intraoperative chemotherapy (DFS: HR=0.464, 95% CI: 0.233-0.921, P=0.029 and OS: (HR=0.476, 95% CI: 0.223-1.017, P=0.049). CONCLUSIONS: Intraoperative chemotherapy showed no significant extra prognostic benefit in total colorectal cancer patients who underwent radical surgical resection; however, in colon cancer patients with abnormal pretreatment serum CEA levels (> 5 ng/ml), intraoperative chemotherapy could improve long-term survival.

Quercetin Limits Tumor Immune Escape through PDK1/CD47 Axis in Melanoma.

Quercetin (3,3[Formula: see text],4[Formula: see text],5,7-pentahydroxyflavone) is a bioactive plant-derived flavonoid, abundant in fruits and vegetables, that can effectively inhibit the growth of many types of tumors without toxicity. Nevertheless, the effect of quercetin on melanoma immunology has yet to be determined. This study aimed to investigate the role and mechanism of the antitumor immunity action of quercetin in melanoma through both in vivo and in vitro methods. Our research revealed that quercetin has the ability to boost antitumor immunity by modulating the tumor immune microenvironment through increasing the percentages of M1 macrophages, CD8[Formula: see text] T lymphocytes, and CD4[Formula: see text] T lymphocytes and promoting the secretion of IL-2 and IFN-[Formula: see text] from CD8[Formula: see text] T cells, consequently suppressing the growth of melanoma. Furthermore, we revealed that quercetin can inhibit cell proliferation and migration of B16 cells in a dose-dependent manner. In addition, down-regulating PDK1 can inhibit the mRNA and protein expression levels of CD47. In the rescue experiment, we overexpressed PDK1 and found that the protein and mRNA expression levels of CD47 increased correspondingly, while the addition of quercetin reversed this effect. Moreover, quercetin could stimulate the proliferation and enhance the function of CD8[Formula: see text] T cells. Therefore, our results identified a novel mechanism through which CD47 is regulated by quercetin to promote phagocytosis, and elucidated the regulation of quercetin on macrophages and CD8[Formula: see text] T cells in the tumor immune microenvironment. The use of quercetin as a therapeutic drug holds potential benefits for immunotherapy, enhancing the efficacy of existing treatments for melanoma.

Non-invasive methods for heart rate measurement in fish based on photoplethysmography.

Heart rate is a crucial physiological indicator for fish, but current measurement methods are often invasive or require delicate manipulation. In this study, we introduced two non-invasive and easy-to-operate methods based on photoplethysmography, namely reflectance-type photoplethysmography (PPG) and remote photoplethysmography (rPPG), which we applied to the large yellow croaker (Larimichthys crocea). PPG showed perfect synchronization with electrocardiogram (ECG), with a Pearson's correlation coefficient of 0.99999. For rPPG, the results showed good agreement with ECG. Under active provision of green light, the Pearson's correlation coefficient was 0.966, surpassing the value of 0.947 under natural light. Additionally, the root mean square error was 0.810, which was lower than the value of 1.30 under natural light, indicating not only that the rPPG method had relatively high accuracy but also that green light may have the potential to further improve its accuracy.

Immunomodulation of cuproptosis and ferroptosis in liver cancer.

According to statistics, the incidence of liver cancer is increasing yearly, and effective treatment of liver cancer is imminent. For early liver cancer, resection surgery is currently the most effective treatment. However, resection does not treat the disease in advanced patients, so finding a method with a better prognosis is necessary. In recent years, ferroptosis and cuproptosis have been gradually defined, and related studies have proved that they show excellent results in the therapy of liver cancer. Cuproptosis is a new form of cell death, and the use of cuproptosis combined with ferroptosis to inhibit the production of hepatocellular carcinoma cells has good development prospects and is worthy of in-depth discussion by researchers. In this review, we summarize the research progress on cuproptosis combined with ferroptosis in treating liver cancer, analyze the value of cuproptosis and ferroptosis in the immune of liver cancer, and propose potential pathways in oncotherapy with the combination of cuproptosis and ferroptosis, which can provide background knowledge for subsequent related research.

Spin-orbital angular momentum degeneracy breaking in nanoplasmonic metachain.

The spin and orbital angular momentum (namely SAM and OAM) mode division provides a promising solution to surmount exhausted available degrees of freedom in conventional optical communications. Nevertheless, SAM and OAM are often subjected to the degeneracy of total angular momentum (AM) because they both have integer variables of quantum eigenstates, which inevitably brings about the shortcomings specific to limited signal channels and multiplexing cross talk. Herein, we present a nanoplasmonic metachain that can discriminatively couple any input SAM and OAM components to an extrinsic orbital AM, corresponding to the chirality and topological charge of incident light. Importantly, the unambiguous measurement has a prominent advantage of detecting the arbitrary AM component rather than the total AM. The miniature metadevice offers the possibility of harnessing AM division on chip or in fiber and holds great promise to delve the spin-orbit interactions for topological photonics and quantum cryptography.

Screening of Transition Metal Supported on Black Phosphorus as Electrocatalysts for CO2 Reduction.

The electrocatalytic CO2 reduction (CO2RR) is an effective and economical strategy to eliminate CO2 through conversion into value-added chemicals and fuels. However, exploring and screening suitable 2D material-based single-atom catalysts (SACs) for CO2 reduction are still a great challenge. In this study, 27 (3d, 4d, and 5d, except Tc and Hg) transition metal (TM) atom-doped black phosphorus (TM@BP) electrocatalysts were systematically investigated for CO2RR by density functional theory calculations. According to the stability of SACs and their effectiveness in activating the CO2 molecule, three promising catalysts, Zr@BP, Nb@BP, and Ru@BP, were successfully screened out, exhibiting outstanding catalytic activity for the production of carbon monoxide (CO), methyl alcohol (CH3OH), and methane (CH4) with limiting potentials of -0.79, -0.49, and -0.60 V, respectively. A catalytic relationship between the d-band centers of SACs and the limiting potential of CO2RR was used to estimate the catalytic activity of catalysts. Furthermore, Nb@BP has high selectivity for CO2RR to CH3OH compared to H2 formation, while the hydrogen evolution reaction significantly impacts the synthesis of CO and CH4 on Zr@BP and Ru@BP. Nitrogen atom doping in BP is beneficial for enhancing the selectivity of CO2RR, but it is detrimental to the activity of CO2RR. This study offers theoretical guidance for synthesizing highly efficient CO2RR electrocatalysts and further enhances structural modulation methods for layered 2D materials.

Ferroptosis: Emerging mechanisms, biological function, and therapeutic potential in cancer and inflammation.

Ferroptosis represents a distinct form of programmed cell death triggered by excessive iron accumulation and lipid peroxidation-induced damage. This mode of cell death differentiates from classical programmed cell death in terms of morphology and biochemistry. Ferroptosis stands out for its exceptional biological characteristics and has garnered extensive research and conversations as a form of programmed cell death. Its dysfunctional activation is closely linked to the onset of diseases, particularly inflammation and cancer, making ferroptosis a promising avenue for combating these conditions. As such, exploring ferroptosis may offer innovative approaches to treating cancer and inflammatory diseases. Our review provides insights into the relevant regulatory mechanisms of ferroptosis, examining the impact of ferroptosis-related factors from both physiological and pathological perspectives. Describing the crosstalk between ferroptosis and tumor- and inflammation-associated signaling pathways and the potential of ferroptosis inducers in overcoming drug-resistant cancers are discussed, aiming to inform further novel therapeutic directions for ferroptosis in relation to inflammatory and cancer diseases.

The temporal association of CapZ with early endosomes regulates endosomal trafficking and viral entry into host cells.

BACKGROUND: Many viruses enter host cells by hijacking endosomal trafficking. CapZ, a canonical actin capping protein, participates in endosomal trafficking, yet its precise role in endocytosis and virus infection remains elusive. RESULTS: Here, we showed that CapZ was transiently associated with early endosomes (EEs) and was subsequently released from the matured EEs after the fusion of two EEs, which was facilitated by PI(3)P to PI(3,5)P2 conversion. Vacuolin-1 (a triazine compound) stabilized CapZ at EEs and thus blocked the transition of EEs to late endosomes (LEs). Likewise, artificially tethering CapZ to EEs via a rapamycin-induced protein-protein interaction system blocked the early-to-late endosome transition. Remarkably, CapZ knockout or artificially tethering CapZ to EEs via rapamycin significantly inhibited flaviviruses, e.g., Zika virus (ZIKV) and dengue virus (DENV), or beta-coronavirus, e.g., murine hepatitis virus (MHV), infection by preventing the escape of RNA genome from endocytic vesicles. CONCLUSIONS: These results indicate that the temporal association of CapZ with EEs facilitates early-to-late endosome transition (physiologically) and the release of the viral genome from endocytic vesicles (pathologically).

Generating bulk RNA-Seq gene expression data based on generative deep learning models and utilizing it for data augmentation.

Large-scale high-throughput transcriptome sequencing data holds significant value in biomedical research. However, practical challenges such as difficulty in sample acquisition often limit the availability of large sample sizes, leading to decreased reliability of the analysis results. In practice, generative deep learning models, such as Generative Adversarial Networks (GANs) and Diffusion Models (DMs), have been proven to generate realistic data and may be used to solve this promblem. In this study, we utilized bulk RNA-Seq gene expression data to construct different generative models with two data preprocessing methods: Min-Max-GAN, Z-Score-GAN, Min-Max-DM, and Z-Score-DM. We demonstrated that the generated data from the Min-Max-GAN model exhibited high similarity to real data, surpassing the performance of the other models significantly. Furthermore, we trained the models on the largest dataset available to date, achieving MMD (Maximum Mean Discrepancy) of 0.030 and 0.033 on the training and independent datasets, respectively. Through SHAP (SHapley Additive exPlanations) explanations of our generative model, we also enhanced our model's credibility. Finally, we applied the generated data to data augmentation and observed a significant improvement in the performance of classification models. In summary, this study establishes a GAN-based approach for generating bulk RNA-Seq gene expression data, which contributes to enhancing the performance and reliability of downstream tasks in high-throughput transcriptome analysis.

Ginseng Polysaccharide Enhances the Humoral and Cellular Immune Responses to SARS-CoV-2 RBD Protein Subunit Vaccines.

The COVID-19 pandemic remarkably accelerated vaccine research progress. The role of adjuvants in enhancing vaccine immune intensity and influencing immune types has been considered. Ginseng polysaccharide (GPS) has been demonstrated to have strong immunoregulatory properties. It is important to explore the feasibility of adding GPS to vaccine adjuvant components to improve the immune response effect of RBD vaccines. Here, we prepared a SARS-CoV-2 RBD antigen using the Escherichia coli expression system and determined that subcutaneous administration of GPS at a dose of 40 mg/kg could effectively activate dendritic cells (DCs) and macrophages (MΦ) in mice. Compared with the RBD group, the RBD+GPS triggered stronger and persistent antibody responses. It is also notable that higher levels of RBD-specific IgG and IgA were distributed in the lungs of RBD+GPS-immunized BALB/c mice. In addition, the RBD+GPS also resulted in lower percentages of IFN-γ+ CD4+ T cells and higher percentages of IFN-γ+ CD8+ T cells and CD8+ Tcm cells. These results suggest that GPS could be a promising vaccine immuno-enhancer for SARS-CoV-2 RBD subunit vaccines to establish stronger systemic and pulmonary mucosal protective immunity.

Protein modification regulated autophagy in Bombyx mori and Drosophila melanogaster.

Post-translational modifications refer to the chemical alterations of proteins following their biosynthesis, leading to changes in protein properties. These modifications, which encompass acetylation, phosphorylation, methylation, SUMOylation, ubiquitination, and others, are pivotal in a myriad of cellular functions. Macroautophagy, also known as autophagy, is a major degradation of intracellular components to cope with stress conditions and strictly regulated by nutrient depletion, insulin signaling, and energy production in mammals. Intriguingly, in insects, 20-hydroxyecdysone signaling predominantly stimulates the expression of most autophagy-related genes while concurrently inhibiting mTOR activity, thereby initiating autophagy. In this review, we will outline post-translational modification-regulated autophagy in insects, including Bombyx mori and Drosophila melanogaster, in brief. A more profound understanding of the biological significance of post-translational modifications in autophagy machinery not only unveils novel opportunities for autophagy intervention strategies but also illuminates their potential roles in development, cell differentiation, and the process of learning and memory processes in both insects and mammals.

Identification of mitochondria-related action targets of quercetin in melanoma cells.

Melanoma is a complex and genetically heterogeneous malignant tumor with high rates of mortality. Although current therapies provide a short-term clinical benefit, they are unable to cure the majority of patients with metastatic melanoma. Therefore, the investigation of pathological mechanisms and the development of new therapy strategies for melanoma are of great significance. Quercetin can effectively inhibit tumor growth in various tumors. However, the exact action mechanisms of quercetin against melanoma have not been comprehensively clarified, which limits its application. Accumulating evidence has suggested that the dysfunction of mitochondria is closely linked to carcinogenesis, and a better understanding of the regulation of mitochondria-related genes will shed light on providing new therapies for melanoma. In this study, we performed RNA-seq from melanoma B16-F1 cells treated with quercetin versus controls and screened for differentially expressed genes (DEGs). GO and KEGG enrichment analyses were performed, and a protein-protein interaction (PPI) network was constructed. Combining the results of RNA-seq, molecular docking, and bioinformatics analysis, we found six mitochondria-related genes, BTG2, CP, LRIG1, CYP1A1, GBP2, and MBNL1, which might be targets of quercetin in melanoma and provide an available targeting therapy strategy for melanoma.

Development of CRISPR/Cas9-Based Genome Editing Tools for Polyploid Yeast Cyberlindnera jadinii and Its Application in Engineering Heterologous Steroid-Producing Strains.

In this study, a suite of efficient CRISPR/Cas9 tools was developed to overcome the genetic manipulation challenges posed by the polyploid genome of industrial yeast Cyberlindnera jadinii. The developed CRISPR/Cas9 system can achieve a 100% single-gene knockdown efficiency in strain NBRC0988. Moreover, the integration of a single exogenous gene into the target locus using a 50 bp homology arm achieved near-100% efficiency. The efficiency of simultaneous integration of three genes into the chromosome is strongly influenced by the length of the homology arm, with the highest integration efficiency of 62.5% obtained when selecting a homology arm of about 500 bp. By utilizing the CRISPR/Cas system, this study demonstrated the potential of C. jadinii in producing heterologous sterols. Through shake-flask fermentation, the engineered strains produced 92.1 and 81.8 mg/L of campesterol and cholesterol, respectively. Furthermore, the production levels of these two sterols were further enhanced through high-cell-density fed-batch fermentation in a 5 L bioreactor. The highest titer of campesterol reached 807 mg/L [biomass OD600 = 294, productivity of 6.73 mg/(L·h)]. The titer of cholesterol reached 1.52 g/L [biomass OD600 = 380, productivity of 9.06 mg/(L·h)], marking the first gram-scale production of steroidal compounds in C. jadinii.

G-quadruplex forming sequences in the genes coding for cytochrome P450 enzymes and their potential roles in drug metabolism.

The majority of drugs are metabolized by cytochrome P450 (CYP) enzymes, primarily belonging to the CYP1, CYP2 and CYP3 families. Genetic variations are the main cause of inter-individual differences in drug response, which constitutes a major concern in pharmacotherapy. G-quadruplexes (G4s), are non-canonical DNA and RNA secondary structures formed by guanine-rich sequences. G4s have been implicated in cancer and gene regulation. In this study, we investigated putative G4-forming sequences (PQSs) in the CYP genes. Our findings reveal a high density of PQSs in the full genes of CYP family 2. Moreover, we observe an increased density of PQSs in the promoters of CYP family 1 genes compared to non-CYP450 genes. Importantly, stable PQSs were also identified in all studied CYP genes. Subsequently, we assessed the impact of the most frequently reported genetic mutations in the selected genes and the possible effect of these mutations on G4 formation as well as on the thermodynamic stability of predicted G4s. We found that 4 SNPs overlap G4 sequences and lead to mutated DNA and RNA G4 forming sequences in their context. Notably, the mutation in the CYP2C9 gene, which is associated with impaired (S)-warfarin metabolism in patients, alters a G4 sequence. We then demonstrated that at least 10 of the 13 chosen cytochrome P450 G4 candidates form G-quadruplex structures in vitro, using a combination of spectroscopic methods. In conclusion, our findings indicate the potential role of G-quadruplexes in the regulation of cytochrome genes, and emphasize the importance of G-quadruplexes in drug metabolism.

Construction of a Matrix Cancer-Associated Fibroblast Signature Gene-Based Risk Prognostic Signature for Directing Immunotherapy in Patients with Breast Cancer Using Single-Cell Analysis and Machine Learning.

Cancer-associated fibroblasts (CAFs) are heterogeneous constituents of the tumor microenvironment involved in the tumorigenesis, progression, and therapeutic responses of tumors. This study identified four distinct CAF subtypes of breast cancer (BRCA) using single-cell RNA sequencing (RNA-seq) data. Of these, matrix CAFs (mCAFs) were significantly associated with tumor matrix remodeling and strongly correlated with the transforming growth factor (TGF)-ß signaling pathway. Consensus clustering of The Cancer Genome Atlas (TCGA) BRCA dataset using mCAF single-cell characteristic gene signatures segregated samples into high-fibrotic and low-fibrotic groups. Patients in the high-fibrotic group exhibited a significantly poor prognosis. A weighted gene co-expression network analysis and univariate Cox analysis of bulk RNA-seq data revealed 17 differential genes with prognostic values. The mCAF risk prognosis signature (mRPS) was developed using 10 machine learning algorithms. The clinical outcome predictive accuracy of the mRPS was higher than that of the conventional TNM staging system. mRPS was correlated with the infiltration level of anti-tumor effector immune cells. Based on consensus prognostic genes, BRCA samples were classified into the following two subtypes using six machine learning algorithms (accuracy > 90%): interferon (IFN)-γ-dominant (immune C2) and TGF-ß-dominant (immune C6) subtypes. Patients with mRPS downregulation were associated with improved prognosis, suggesting that they can potentially benefit from immunotherapy. Thus, the mRPS model can stably predict BRCA prognosis, reflect the local immune status of the tumor, and aid clinical decisions on tumor immunotherapy.

Delineating highly transcribed noncoding elements landscape in breast cancer.

Highly transcribed noncoding elements (HTNEs) are critical noncoding elements with high levels of transcriptional capacity in particular cohorts involved in multiple cellular biological processes. Investigation of HTNEs with persistent aberrant expression in abnormal tissues could be of benefit in exploring their roles in disease occurrence and progression. Breast cancer is a highly heterogeneous disease for which early screening and prognosis are exceedingly crucial. In this study, we developed a HTNE identification framework to systematically investigate HTNE landscapes in breast cancer patients and identified over ten thousand HTNEs. The robustness and rationality of our framework were demonstrated via public datasets. We revealed that HTNEs had significant chromatin characteristics of enhancers and long noncoding RNAs (lncRNAs) and were significantly enriched with RNA-binding proteins as well as targeted by miRNAs. Further, HTNE-associated genes were significantly overexpressed and exhibited strong correlations with breast cancer. Ultimately, we explored the subtype-specific transcriptional processes associated with HTNEs and uncovered the HTNE signatures that could classify breast cancer subtypes based on the properties of hormone receptors. Our results highlight that the identified HTNEs as well as their associated genes play crucial roles in breast cancer progression and correlate with subtype-specific transcriptional processes of breast cancer.

A conserved N protein nano-vaccine of COVID-19 exerts potent and cross-reactive humoral and cellular immune responses in mice.

As severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mutates continually, the current vaccines are unable to provide sufficient protection. It is important to develop a broad-spectrum vaccine with conserved antigens to prevent variant infection. Here we fused the SARS-CoV-2 N protein with Helicobacter pylori nonheme ferritin to construct a SARS-CoV-2 N-Ferritin nanoparticle vaccine. Compared with the monomer N protein, the N-Ferritin nanoparticles induced more lymph node dendritic cells in mice to trigger adoptive immunity. Following this, the N-Ferritin elicited more robust and long-lasting antibody responses, which had better cross-reactivity with the SARS-CoV N protein. It is also worth noting that higher levels of N-specific IgG and IgA were distributed in the lungs of N-Ferritin-immunized mice. Furthermore, the N-Ferritin nanoparticles also resulted higher proportion of interferon-γ+ CD8+ T cells, CD8+ Tcm cells, and T cells with cross-reactivity in SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome-related coronavirus. The conserved N-based nanoparticles could provide a promising vaccine developing strategy against SARS-CoV-2 variants and other coronaviruses.