Accelerated Charge Transfer through Interface Chemical Bonds in MoS2/TiO2 for Photocatalytic Conversion of Lignocellulosic Biomass to H2.

Solar photocatalytic H2 production from lignocellulosic biomass has attracted great interest, but it suffers from low photocatalytic efficiency owing to the absence of highly efficient photocatalysts. Herein, we designed and constructed ultrathin MoS2-modified porous TiO2 microspheres (MT) with abundant interface Ti-S bonds as photocatalysts for photocatalytic H2 generation from lignocellulosic biomass. Owing to the accelerated charge transfer related to Ti-S bonds, as well as the abundant active sites for both H2 and ●OH generation, respectively, related to the high exposed edge of MoS2 and the large specific surface area of TiO2, MT photocatalysts demonstrate good performance in the photocatalytic conversion of α-cellulose and lignocellulosic biomass to H2. The highest H2 generation rate of 849 µmol·g-1·h-1 and apparent quantum yield of 4.45% at 380 nm was achieved in α-cellulose aqueous solution for the optimized MT photocatalyst. More importantly, lignocellulosic biomass of corncob, rice hull, bamboo, polar wood chip, and wheat straw were successfully converted to H2 over MT photocatalysts with H2 generation rate of 10, 19, 36, 29, and 8 µmol·g-1·h-1, respectively. This work provides a guiding design approach to develop highly active photocatalysts via interface engineering for solar H2 production from lignocellulosic biomass.

Toll-Like Receptors Mediate Opposing Dendritic Cell Effects on Treg/Th17 Balance in Mice With Intracerebral Hemorrhage.

BACKGROUND: Dendritic cells (DCs) regulate the immune response associated with T lymphocytes, but their role in stroke remains unclear. In this study, we investigated the causal relationship between DCs and T-cell response in intracerebral hemorrhage (ICH) by focusing on TLRs (toll-like receptors) that may modulate the function of DCs. METHODS: We studied the effects of TLR4, TLR2, and TLR9 on DC-mediated T-cell response and the outcomes of ICH using male C57BL/6 and CD11c-DTx (diphtheria toxin) receptor mice. We administered specific agents intraperitoneally or orally and evaluated the results using flow cytometry, real-time polymerase chain reaction, Western blotting, immunofluorescence staining, histopathology, and behavioral tests. RESULTS: TLR4 and TLR2 activation induces DC maturation and reduces the ratio of regulatory T to T-helper 17 cells in the brain and periphery after ICH. When either of these receptors is activated, it can worsen neuroinflammation and exacerbate ICH outcomes. TLR9 also promotes DC maturation, stabilizing the number of DCs, particularly conventional DCs. TLR9 has the opposite effects on regulatory T/T-helper 17 balance, neuroinflammation, and ICH outcomes compared with TLR4 and TLR2. Upon stimulation, TLR4 and TLR9 may achieve these effects through the p38-MAPK (p38-mitogen-activated protein kinase)/MyD88 (myeloid differentiation primary response gene 88) and indoleamine 2,3-dioxygenase 1 (IDO1)/GCN2 (general control nonderepressible 2) signaling pathways, respectively. DCs act as intermediaries for TLR-mediated T-cell response. CONCLUSIONS: TLR-mediated opposing effects of DCs on T-cell response may provide novel strategies to treat ICH.

Interleukin-17A educated hepatic stellate cells promote hepatocellular carcinoma occurrence through fibroblast activation protein expression.

BACKGROUND: Liver cancer is typified by a complex inflammatory tumor microenvironment, where an array of cytokines and stromal cells orchestrate a milieu that significantly influences tumorigenesis. Interleukin-17A (IL-17A), a pivotal pro-inflammatory cytokine predominantly secreted by Th17 cells, is known to play a substantial role in the etiology and progression of liver cancer. However, the precise mechanism by which IL-17A engages with hepatic stellate cells (HSCs) to facilitate the development of hepatocellular carcinoma (HCC) remains to be fully elucidated. This investigation seeks to unravel the interplay between IL-17A and HSCs in the context of HCC. METHODS: An HCC model was established in male Sprague-Dawley rats using diethylnitrosamine to explore the roles of IL-17A and HSCs in HCC pathogenesis. In vivo overexpression of Il17a was achieved using adeno-associated virus. A suite of molecular techniques, including RT-qPCR, enzyme-linked immunosorbent assays, Western blotting, cell counting kit-8 assays and colony formation assays, was employed for in vitro analyses. RESULTS: The study findings indicate that IL-17A is a key mediator in HCC promotion, primarily through the activation of hepatic progenitor cells (HPCs). This pro-tumorigenic influence appears to be mediated by HSCs, rather than through a direct effect on HPCs. Notably, IL-17A-induced expression of fibroblast activation protein (FAP) in HSCs emerged as a critical factor in HCC progression. Silencing Fap in IL-17A-stimulated HSCs was observed to reverse the HCC-promoting effects of HSCs. CONCLUSIONS: The collective evidence from this study implicates the IL-17A/FAP signaling axis within HSCs as a contributor to HCC development by enhancing HPC activation. These findings bolster the potential of IL-17A as a diagnostic and preventative target for HCC, offering new avenues for therapeutic intervention.

Cross-species modeling of plant genomes at single nucleotide resolution using a pre-trained DNA language model.

Understanding the function and fitness effects of diverse plant genomes requires transferable models. Language models (LMs) pre-trained on large-scale biological sequences can learn evolutionary conservation, thus expected to offer better cross-species prediction through fine-tuning on limited labeled data compared to supervised deep learning models. We introduce PlantCaduceus, a plant DNA LM based on the Caduceus and Mamba architectures, pre-trained on a carefully curated dataset consisting of 16 diverse Angiosperm genomes. Fine-tuning PlantCaduceus on limited labeled Arabidopsis data for four tasks involving transcription and translation modeling demonstrated high transferability to maize that diverged 160 million years ago, outperforming the best baseline model by 1.45-fold to 7.23-fold. PlantCaduceus also enables genome-wide deleterious mutation identification without multiple sequence alignment (MSA). PlantCaduceus demonstrated a threefold enrichment of rare alleles in prioritized deleterious mutations compared to MSA-based methods and matched state-of-the-art protein LMs. PlantCaduceus is a versatile pre-trained DNA LM expected to accelerate plant genomics and crop breeding applications.

Pan-cancer analysis of the disulfidptosis-related gene RPN1 and its potential biological function and prognostic significance in gliomas.

Background: Numerous studies have shown a strong correlation between disulfidptosis and various cancers. However, the expression and function of RPN1, a crucial gene in disulfidptosis, remain unclear in the context of cancer. Methods: Gene expression and clinical information on lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. RPN1 expression was analyzed using the Timer2.0 and the Human Protein Atlas (HPA) databases. Prognostic significance was assessed using Cox regression analysis and Kaplan-Meier curves. Genetic mutations and methylation levels were examined using the cBioPortal and UALCAN platforms, respectively. The relationship between RPN1 and tumor mutation burden (TMB) and microsatellite instability (MSI) across different cancer types was analyzed using the Spearman correlation coefficient. The relationship between RPN1 and immune cell infiltration was analyzed using the Timer2.0 database, whereas variations in drug sensitivity were explored using the CellMiner database. Receiver operating characteristic curves validated RPN1's diagnostic potential in glioma, and its correlation with immune checkpoint inhibitors (ICIs) was assessed using Spearman's correlation coefficient. Single-sample gene set enrichment analysis elucidated a link between RPN1 and immune cells and pathways. In addition, a nomogram based on RPN1 was developed to predict patient prognosis. The functional impact of RPN1 on glioma cells was confirmed using scratch and Transwell assays. Result: RPN1 was aberrantly expressed in various cancers and affected patient prognosis. The main mutation type of RPN1 in the cancer was amplified. RPN1 exhibited a positive correlation with myeloid-derived suppressor cells, neutrophils, and macrophages, and a negative correlation with CD8+ T cells and hematopoietic stem cells. RPN1 expression was associated with TMB and MSI in various cancers. The expression of RPN1 affected drug sensitivity in cancer cells. RPN1 was positively correlated with multiple ICIs in gliomas. RPN1 also affected immune cell infiltration into the tumor microenvironment. RPN1 was an independent prognostic factor for gliomas, and the nomogram demonstrated excellent predictive performance. Interference with RPN1 expression reduces the migratory and invasive ability of glioma cells. Conclusion: RPN1 exerts multifaceted effects on different stages of cancer, including immune infiltration, prognosis, and treatment outcomes. RPN1 expression affects the prognosis and immune microenvironment infiltration in patients with glioma, making RPN1 a potential target for the treatment of glioma.

Triterpenoids with α-glucosidase inhibitory and cytotoxic activities from the fruits of Schisandra chinensis.

An intensive phytochemical investigation into the fruits of Schisandra chinensis afforded 28 triterpenoids incorporating diverse backbones with methyl-migration, ring-expansion and ring-opening features. Among them, ten compounds (1-10) including three likely extracting artefacts (8-10) were described for the first time. Their structures were fully characterized by comprehensive spectroscopic analyses, with the absolute configurations established via electronic circular dichroism and Mosher's NMR techniques. Preliminary biological evaluations revealed that nine isolates showed inhibitory activity against the hyperglycemic target α-glycosidase and 12 compounds exerted cytotoxicity toward three female tumor cell lines (Hela (cervical), MDA-MB231 and MCF-7 (breast)). Compound 6 exhibited the most promising potency on all the three tested cancer cells, and further assessment demonstrated that it could induce significant cell apoptosis and cycle arrest, as well as suppress cell migration, by regulating relevant proteins in MDA-MB231 cells.

Integrating single-cell RNA-sequencing and bulk RNA-sequencing data to explore the role of mitophagy-related genes in prostate cancer.

Prostate cancer (PCa) is the most common malignancy of the male urinary system. Mitophagy, as a type of autophagy, can remove damaged mitochondria in cells. Mitophagy-related genes (MRGs) have been shown to play critical roles in the development of PCa. To this end, based on the comprehensive analysis of RNA-seq and scRNA-seq data of PCa samples and their controls, this paper identified PCa subtypes and constructed a prognostic model. In this paper, we downloaded scRNA-seq and RNA-seq data from Gene Expression Omnibus (GEO) and TCGA database. Based on the R package "Seurat" to process the scRNA-seq data, a total of five cell types were identified. Each cell population was scored based on the R package "AUCell" and using the intersection genes between MRGs and each cell population. The B cell population was then identified as a high-scoring cell population. Differentially expressed genes in RNA-seq data were identified based on the R package "limma" and intersected with previously intersected genes. Then, based on univariate Cox regression analysis and Lasso-Cox regression analysis, the prognostic genes were screened, and the risk model was constructed (composed of ADH5, CAT, BCAT2, DCXR, OGT, and FUS). The model is validated on internal and external test sets. Independent prognostic analysis identified age, N stage, and risk score as independent prognostic factors. This paper's risk models and prognostic genes can provide a reference for developing novel therapeutic targets for PCa.

The role of RASA2 in predicting radioresistance in lung cancer through regulation of p53.

Background: One of the most common causes of lung cancer relapse after clinical treatment is radioresistance. However, the mechanism underlying radioresistance remains unclear. In this study, we investigated the role of Ras p21 protein activator (RASA2) in non-small cell lung cancer (NSCLC). Methods: The messenger RNA (mRNA) of RASA2 was tested via reverse-transcription quantitative polymerase chain reaction (RT-qPCR) of cancer tissues from patients with NSCLC. Computed tomography (CT) and bioluminescent imaging (BLI) were used to monitor the tumor growth of patients and orthotopic mice, respectively. Protein-protein interaction was quantified via immunoprecipitation and glutathione S transferase (GST) pulldown assay. Western blotting was used to evaluate the phosphorylation and ubiquitination level of p53. Results: The results indicated a negative correlation between the mRNA expression levels of RASA2 in tumor tissues with patients' response to radiotherapy. Patients with a high expression of RASA2 had a lower objective response rate (ORR) after 1 month of radiotherapy than patients with low expression of RASA2 after 1 month of radiotherapy. In terms of mechanism, we proved that RASA2 can directly bind to p53 to promote the phosphorylation of p53, which inhibits its transcriptional activity and further promotes its degradation through the ubiquitin/proteasome pathway. In this process, the apoptosis of tumor cells is inhibited due to impaired p53 surveillance, which leads to radioresistance. Conclusions: Our results demonstrate that RASA2 negatively regulates p53 in cancer cells and therefore promotes radioresistance, providing a new predictive biomarker and a potential therapeutic target for radioresistance.

Usefulness of KIT mutant transcript levels for monitoring measurable residual disease in t (8;21) acute myeloid leukemia.

In addition to RUNX1::RUNX1T1 transcript levels, measurable residual disease monitoring using KIT mutant (KITmut ) DNA level is reportedly predictive of relapse in t (8; 21) acute myeloid leukemia (AML). However, the usefulness of KITmut transcript levels remains unknown. A total of 202 bone marrow samples collected at diagnosis and during treatment from 52 t (8; 21) AML patients with KITmut (D816V/H/Y or N822K) were tested for KITmut transcript levels using digital polymerase chain reaction. The individual optimal cutoff values of KITmut were identified by performing receiver operating characteristics curve analysis for relapse at each of the following time points: at diagnosis, after achieving complete remission (CR), and after Course 1 and 2 consolidations. The cutoff values were used to divide the patients into the KITmut -high (KIT_H) group and the KITmut -low (KIT_L) group. The KIT_H patients showed significantly lower relapse-free survival (RFS) and overall survival (OS) rates than the KIT_L patients after Course 1 consolidation (p = 0.0040 and 0.021, respectively) and Course 2 consolidation (p = 0.018 and 0.011, respectively) but not at diagnosis and CR. The <3-log reduction in the RUNX1::RUNX1T1 transcript levels after Course 2 consolidation was an independent adverse prognostic factor for RFS and OS. After Course 2 consolidation, the KIT_H patients with >3-log reduction in the RUNX1::RUNX1T1 transcript levels (11/45; 24.4%) had similar RFS as that of patients with <3-log reduction in the RUNX1::RUNX1T1 transcript levels. The combination of KITmut and RUNX1::RUNX1T1 transcript levels after Course 2 consolidation may improve risk stratification in t (8; 21) AML patient with KIT mutation.

Scalable and Multifunctional Polyurethane/MXene/Carbon Nanotube-Based Fabric Sensor toward Baby Healthcare.

Continuous monitoring of physiological health status and effective protection against external hazards is an indispensable aspect of healthcare management for critically vulnerable populations, particularly for infants or babies. So, the exploration of all-in-one devices remains critical to avoiding their injury and illness. The integration of multiple properties such as sensing, electromagnetic protection, warming/cooling, and water/bacterial repellence into a common fabric is no doubt a promising solution to coping with diverse application scenarios. However, achieving simultaneous integration in an effective and durable fashion faces huge challenges. Herein, multifunctional fabric was achieved by sequentially coating MXene, carbon nanotubes (CNTs), and self-healing polyurethane (PU) onto cotton fabric. The outstanding conductivity of MXene and CNTs as well as the self-healing ability of PU synergistically enable a flexible, breathable, protective, and sensing fabric with a good durability. It could detect the body motions like bending of the finger, elbow, wrist, and knee, with a high gauge factor of 8.78 and fast response. Moreover, this sensing fabric could protect the wearers against electromagnetic waves and bacteria, delivering a minimum reflection loss of -57.6 dB at 7.6 GHz and high bacterial inhibition efficiency due to the incorporation of MXene and polyethylenimine. Besides, the electrothermal performance of carbonaceous materials enables them to act as a heater for body warmth. The synergistic design of this multifunctional textile offers a promising strategy for producing advanced smart textiles, holding great promise in infant or baby healthcare.

Limited value of platelet-related markers in diagnosing periprosthetic joint infection.

OBJECTIVE: To evaluate the diagnostic values of serum platelet count (PC), mean platelet volume ratio (MPV), platelet count to mean platelet volume ratio (PVR), platelet to lymphocyte ratio (PLR), platelet to neutrophil ratio (PNR), PC/Albumin-globulin ratio (PC/AGR), and PC/C-reactive protein (PC/ CRP) in the diagnosis of periprosthetic joint infection (PJI). METHODS: The medical records were retrospectively analyzed of the 158 patients who had undergone hip or knee revisions from January 2018 to May 2022. Of them, 79 cases were diagnosed with PJI and 79 with aseptic loosening (AL). PJI was defined using the Musculoskeletal Infection Society criteria. The plasma levels of CRP, the erythrocyte sedimentation rate (ESR), PC, MPV, PVR, PLR, PNR, PC/AGR, and PC/CRP in the 2 groups were recorded and analyzed. In addition, tests were performed according to different joint types. The receiver operating characteristic curve was used to calculate the sensitivity and specificity of each indicator. The diagnostic value for each indicator was calculated according to the area under the curve (AUC). RESULTS: The PC, PVR, PLR and PC/AGR levels in the PJI group were significantly higher than those in the AL group, while PC/CRP levels were significantly lower (P < 0.001). The AUC for PC/CRP, and PC/AGR was 0.804 and 0.802, respectively, which were slightly lower than that of CRP (0.826) and ESR (0.846). ROC analysis for PC/CRP, and PC/AGR revealed a cut-off value of 37.80 and 160.63, respectively, which provided a sensitivity of 73.42% and 84.81% and a specificity of 75.95% and 65.82% for PJI. The area under the curve of PLR and PC was 0.738 and 0.702. The area under the curve values for PVR, PNR, and MPV were 0.672, 0.553, and 0.544, respectively. CONCLUSIONS: The results of this study suggest that PC, PLR, PC/CRP, and PC/AGR values do not offer significant advantages over ESR or CRP values when employed for the diagnosis of PJI. PVR, PNR, and MPV were not reliable in the diagnosis of PJI.

Sumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor function.

BACKGROUND: Fas-associated factor 1 (FAF1) is a multidomain protein that interacts with diverse partners to affect numerous cellular processes. Previously, we discovered two Small Ubiquitin-like Modifier (SUMO)-interacting motifs (SIMs) within FAF1 that are crucial for transcriptional modulation of mineralocorticoid receptor. Recently, we identified Sin3A-associated protein 130 (SAP130), a putative sumoylated protein, as a candidate FAF1 interaction partner by yeast two-hybrid screening. However, it remained unclear whether SAP130 sumoylation might occur and functionally interact with FAF1. RESULTS: In this study, we first show that SAP130 can be modified by SUMO1 at Lys residues 794, 878 and 932 both in vitro and in vivo. Mutation of these three SUMO-accepting Lys residues to Ala had no impact on SAP130 association with Sin3A or its nuclear localization, but the mutations abrogated the association of SAP130 with the FAF1. The mutations also potentiated SAP130 trans-repression activity and attenuated SAP130-mediated promotion of cell growth. Additionally, SUMO1-modified SAP130 was less stable than unmodified SAP130. Transient transfection experiments further revealed that FAF1 mitigated the trans-repression and cell proliferation-promoting functions of SAP130, and promoted SAP130 degradation by enhancing its polyubiquitination in a sumoylation-dependent manner. CONCLUSIONS: Together, these results demonstrate that sumoylation of SAP130 regulates its biological functions and that FAF1 plays a crucial role in controlling the SUMO-dependent regulation of transcriptional activity and protein stability of SAP130.

ZNF384 fusion transcript levels for measurable residual disease monitoring in adult B-cell acute lymphoblastic leukemia.

Zinc finger protein 384 (ZNF384) rearrangement defined a novel subtype of B-cell acute lymphoblastic leukemia (B-ALL). The prognostic significance of ZNF384 fusion transcript levels represented measurable residual disease remains to be explored. ZNF384 fusions were screened out in 57 adult B-ALL patients at diagnosis by real-time quantitative polymerase chain reaction and their transcript levels were serially monitored during treatment. The reduction of ZNF384 fusion transcript levels at the time of achieving complete remission had no significant impact on survival, whereas its ≥2.5-log reduction were significantly associated with higher relapse free survival (RFS) and overall survival (OS) rates after course 1 consolidation (p = 0.022 and = 0.0083) and course 2 consolidation (p = 0.0025 and = 0.0008). Compared with chemotherapy alone, allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly improved RFS and OS of patients with <2.5-log reduction after course 1 consolidation (p < 0.0001 and = 0.0002) and course 2 consolidation (p = 0.0003 and = 0.019), whereas exerted no significant effects in patients with ≥2.5-log reduction (all p > 0.05). ZNF384 fusion transcript levels after course 1 and course 2 consolidation strongly predict relapse and survival and may guide whether receiving allo-HSCT in adult B-ALL.

Prognostic significance of the frequencies of bone marrow lymphocyte subsets in adult acute myeloid leukemia at diagnosis.

INTRODUCTION: Immune microenvironment plays an important role in the occurrence and development of acute myeloid leukemia (AML). Studies assessing the prognostic significance of bone marrow (BM) lymphocyte subsets' frequencies at diagnosis in patients with AML were limited. METHODS: Fresh BM samples collected from 97 adult AML patients at diagnosis were tested for lymphocyte, T, CD4+ T, CD8+ T, γδT, NK, and B cell frequencies using multi-parameter flow cytometry. RESULTS: Low frequencies of lymphocytes, T, CD4+ T, and CD8+ T cells were associated with significantly lower rates of one-course complete remission (CR) (all p < 0.05). Moreover, the frequency of CD4+ T cells independently predicted one-course CR achievement (p = 0.021). Low frequencies of T and CD8+ T cells were significantly associated with lower relapse-free survival (RFS) rates (p = 0.032; 0.034), respectively, and a low frequency of CD8+ T cells was associated with a significantly lower overall survival (OS) rate (p = 0.028). Combination of frequency of CD8+ T cells and ELN risk stratification showed that patients with ELN-intermediate/adverse risk + high CD8+ T cell frequency had a similar RFS rate to those with ELN-favorable risk + high CD8+ T cell frequency and those with ELN-favorable risk + low CD8+ T cell frequency (p = 0.88; 0.76), respectively. The RFS rate of patients with ELN intermediate/adverse risk + low CD8+ T cell frequency was significantly lower than that of all aforementioned patients (p = 0.021; 0.0007; 0.028), respectively. CONCLUSION: The frequencies of BM lymphocyte subsets at diagnosis predicted clinical outcomes and could help improve risk stratification in AML.

The role of BATF2 deficiency in immune microenvironment rearrangement in cervical cancer - New biomarker benefiting from combination of radiotherapy and immunotherapy.

Despite the significant progress in immunotherapy for certain cancers, including cervical cancer, most patients remain unresponsive or derive limited benefits from combined radiotherapy and chemotherapy. The factors underlying treatment resistance are unknown and there are few reliable predictive biomarkers. BATF2 is a member of the basic leucine zipper transcription factor family and is involved in immune response and immune cell development. However, the role of BATF2 in the immune microenvironment of patients with cervical cancer after radiotherapy remains unclear. In this study, immunohistochemistry and multicolour immunofluorescence analyses of patient tumor samples were used to assess BATF2 expression. We found that cervical cancer patients with high BATF2 expression had higher infiltration levels of CD4+ T cells, CD8+ T cells, and macrophages within the tumor than those with low expression levels. Furthermore, BATF2 expression was positively correlated with the prognosis of patients after concurrent chemoradiotherapy. A wild-type mouse model with BATF2-knockdown U14 cell-derived subcutaneous tumors and a Batf2-/- mouse model with wild-type U14 cell-derived subcutaneous tumors were used to assess CD8+ T cell infiltration and function. As expected, the knockdown of BATF2 in the U14 cell line substantially promoted tumor growth, which was mediated by a reduction in CD8+ T cell infiltration and antitumor function in vivo. Additionally, the Batf2-/- mouse model demonstrated that host BATF2 is also involved in controlling tumor growth. Furthermore, the combination of radiotherapy and anti-PD-1 therapy showed synergistic antitumour effects. These findings collectively suggest that BATF2 may serve as a potent positive regulator of the tumor immune microenvironment of cervical cancer after radiotherapy, and has the potential to be a prognostic biomarker to guide the application of a combination of radiotherapy and immunotherapy.

Long-term survival after stereotactic body radiotherapy combined with immunotherapy plus anti-angiogenesis therapy in patients with advanced non-small cell lung cancer and EGFR exon 20 insertion mutation: a report of two cases.

Background: Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutation is the third most common EGFR-mutant form, accounting for 10-12% of all EGFR mutations in non-small cell lung cancer (NSCLC). Chemotherapy was the first-line treatment for patients with EGFR ex20ins mutation in the era when EGFR ex20ins tyrosine kinase inhibitors (EGFR ex20ins-TKIs) were inaccessible. Although EGFR ex20ins-TKIs have since then demonstrated certain efficacy, the population benefit rate is not high due to the high cost of the drug and limited benefit to the population. Therefore, the choice of treatment modality when a patient does not have access to EGFR ex20ins-TKIs or are resistant to them remains an avenue worth exploring. Case Description: In this report, we present two cases of patients with lung adenocarcinoma and EGFR ex20ins mutation. The two patients were middle-aged Asian women with no smoking history, and both had one or more metastatic lesions. Both achieved long-term clinical benefit (progression-free survival ≥12 months) after receiving combined treatment, suggesting that this is a promising treatment modality. Conclusions: To the best of our knowledge, this is the first report supporting the combination of stereotactic body radiotherapy and apatinib and camrelizumab as an effective treatment strategy in patients with advanced EGFR ex20ins-positive NSCLC who have been previously treated with chemotherapy. The therapy described in this report might serve as a potential alternative approach for clinical oncologists.

Protein kinase CK2: An emerging regulator of cellular metabolism.

The protein kinase casein kinase 2 (CK2) exerts its influence on the metabolism of three major cellular substances by phosphorylating essential protein molecules involved in various cellular metabolic pathways. These substances include hormones, especially insulin, rate-limiting enzymes, transcription factors of key genes, and cytokines. This regulatory role of CK2 is closely tied to important cellular processes such as cell proliferation and apoptosis. Additionally, tumor cells undergo metabolic reprogramming characterized by aerobic glycolysis, accelerated lipid ß-oxidation, and abnormally active glutamine metabolism. In this context, CK2, which is overexpressed in various tumors, also plays a pivotal role. Hence, this review aims to summarize the regulatory mechanisms of CK2 in diverse metabolic pathways and tumor development, providing novel insights for the diagnosis, treatment, and prognosis of metabolism-related diseases and cancers.

Pan-cancer Analysis of the Disulfidptosis-related Gene NCKAP1 and Its Prognostic Value for Lung Adenocarcinoma.

BACKGROUND: The nck-associated protein 1 (NCKAP1) of the disulfidptosis-related gene is essential in programmed cell death. However, a comprehensive analysis of the biological significance of NCKAP1 in pan-cancer is lacking. METHODS: Gene expression matrices and clinical expression information of cancers were obtained from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEX) databases. A comprehensive analysis of NCKAP1 expression, biological function, gene mutation, immune cell infiltration, DNA methylation, and drug sensitivity profiles in pan-cancer was performed using the Timer2.0, HPA, GEPIA, STRING, cBioPortal, UALCAN and CellMiner databases. The prognostic value of NCKAP1 was investigated based on COX regression analysis and the Kaplan-Meier(K-M) curves. A nomogram was established to verify the clinical value of NCKAP1 for LUAD. The correlation between NCKAP1 and immune cells and signaling pathways were investigated by single-sample gene set enrichment analysis(ssGSEA). Validation was performed using PCR, Western Blot (WB), and Transwell assays. RESULT: Significant differences in expression levels, mutation levels, and methylation levels of NCKAP1 between tumor and normal samples. NCKAP1 affects the prognosis of various cancers. NCKAP1 is strongly associated with microsatellite instability (MSI) and tumor mutational burden (TMB). The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicate that NCKAP1 is strongly associated with cell death and tumor immunity. The expression of NCKAP1 affects the sensitivity to various drugs. Moreover, NCKAP1 is an independent predictor of prognosis in LUAD patients. The results of ssGSEA showed that elevated NCKAP1 expression was positively correlated with multiple immune-related signaling pathways. PCR analysis showed that the expression of NCKAP1 was increased in LUAD cells. Transwell invasion assay showed that overexpression of NCKAP1 resulted in enhanced invasion of LUAD cells. CONCLUSIONS: We comprehensively analyzed the relationship between NCKAP1 and pan-cancer and its potential clinical value. NCKAP1 could be a potential immune marker for various cancers (especially LUAD), providing new insights and insights for cancer therapy.

Small Plasma Membrane-Targeted Fluorescent Dye for Long-Time Imaging and Protein Degradation Analyses.

Plasma membrane (PM)-targeted fluorescent dyes have become an important tool to visualize morphological and dynamic changes in the cell membrane. However, most of these PM dyes are either too large and thus might potentially perturb the membrane and affect its functions or exhibit a short retention time on the cell membrane. The rapid internalization problem is particularly severe for PM dyes based on cationic and neutral hydrophobic fluorescent dyes, which can be easily transported into the cells by transmembrane potential and passive diffusion mechanisms. In this paper, we report a small but highly specific PM fluorescent dye, PM-1, which exhibits a very long retention time on the plasma membrane with a half-life of approximately 15 h. For biological applications, we demonstrated that PM-1 can be used in combination with protein labeling probes to study ectodomain shedding and endocytosis processes of cell surface proteins and successfully demonstrated that native transmembrane human carbonic anhydrase IX (hCAIX) is degraded via the ectodomain shedding mechanism. In contrast, hCAIX undergoes endocytic degradation in the presence of sheddase inhibitors. We believe that PM-1 can be a versatile tool to provide detailed insights into the dynamic processes of the cell surface proteins.

Tuning electronic structure for enhanced photocatalytic performance: theoretical and experimental investigation of CuM1-xM'xO2 (M, M' = B, Al, Ga, In) solid solutions.

This study introduces robust screening methodology for the efficient design of delafossite CuM1-xM'xO2 solid-solution photocatalysts using band-structure engineering. The investigation not only reveals the formation rules for various CuM1-xM'xO2 solid solutions but also highlights the dependence on both lattice compatibility and thermodynamic stability. Moreover, the study uncovers the nonlinear relationship between composition and band gaps in these solid solutions, with the bowing coefficient determined by the substitution constituents. By optimizing the constituent elements of the conduction band edge and adjusting solubility, the band structure of CuM1-xM'xO2 samples can be fine-tuned to the visible light region. Among the examined photocatalysts, CuAl0.5Ga0.5O2 exhibits the highest H2 evolution rate by striking a balance between visible-light absorption and sufficient reduction potential, showing improvements of 28.8 and 6.9 times those of CuAlO2 and CuGaO2, respectively. Additionally, CuGa0.9In0.1O2 demonstrates enhanced electron migration and surpasses CuGaO2 in H2 evolution due to a reduction in the effective mass of photogenerated electrons. These findings emphasize the pivotal role of theoretical predictions in synthesizing CuM1-xM'xO2 solid solutions and underscore the importance of rational substitution constituents in optimizing light absorption, reduction potentials, and effective mass for efficient hydrogen production.