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In this study, a lytic phage, named PG216, was obtained from seawater collected in Qingdao, using Vibrio parahaemolyticus strain G299 as its host. Transmission electron microscopy revealed that phage PG216 has an icosahedral head with a diameter of 100 ± 6.7 nm and a contractible tail with a length of 126 ± 6.7 nm. The spot assay and EOP assay for host range testing revealed that the phage displayed extensive lytic activity against five Vibrio species: V. alginolyticus , V. parahaemolyticus , V. vulnificus , V. mimicus , and V. harveyi . The one-step growth curve indicated that the phage has a latent period of 25 min, a lysis duration of 115 min, and an average burst size of 135 ± 02 PFU/cell. The genome of PG216 is 244,027 bp in length with a GC content of 42.89%, and itcontains383 ORFs and encodes 28 tRNAs. Phylogenetic analysis suggested that PG216 belongs to the genus Schizotequatrovirus within the family Straboviridae . Phage PG216 was found to be able to eradicate mature biofilms produced by V. parahaemolyticus G299. Phage PG216 demonstrates notable lytic activity while lacking virulence and antibiotic-resistance genes and therefore might be a viable candidate for use in phage therapy of vibriosis.

Quorum sensing (QS) orchestrates many bacterial behaviors, such as virulence and biofilm formation, across bacterial populations. Nevertheless, the underlying mechanism of QS regulating CPS-dependent phage-bacterium interactions remains unclear. In the present study, we report that QS upregulated the expression of CPS-dependent phage receptors, thus increasing phage adsorption and infection rates in V. alginolyticus. We found that QS upregulated the expression of the ugd gene, leading to increased synthesis of Autographiviridae phage receptor capsular polysaccharide (CPS) synthesis in V. alginolyticus. The signal molecule autoinducer-2 (AI-2) released by V. alginolyticus from different sources can potentially enhance CPS-dependent phage infection. Therefore, our data suggest that inhibiting quorum sensing may reduce rather than improve the therapeutic efficacy of CPS-specific phages.

The complexity of tumors and the challenges associated with treatment often stem from the limitations of existing models in accurately replicating authentic tumors. Recently, organoid technology has emerged as an innovative platform for tumor research. This bioengineering approach enables researchers to simulate, in vitro, the interactions between tumors and their microenvironment, thereby enhancing the intricate interplay between tumor cells and their surroundings. Organoids also integrate multidimensional data, providing a novel paradigm for understanding tumor development and progression while facilitating precision therapy. Furthermore, advancements in imaging and genetic editing techniques have significantly augmented the potential of organoids in tumor research. This review explores the application of organoid technology for more precise tumor simulations and its specific contributions to cancer research advancements. Additionally, we discuss the challenges and evolving trends in developing comprehensive tumor models utilizing organoid technology.

Despite the promise of tumor starvation therapies, they are often associated with nonspecific and incomplete energy blockade. Here, a novel paradigm of starvation therapy is proposed to synergize the “Zn2+ interference”‐mediated glycolysis inhibition and Zn2+‐activating GLUT1 (Glucose transporter 1) tumor specific depletion for systematic energy exhaustion. It is discovered that ZIF‐8 (zinc imidazolate metal–organic frameworks ) can induce abrupt intracellular Zn2+ elevation preferentially in melanoma cells, and then achieve effective glycolysis blockade through “Zn2+ interference”‐triggered decrease of NAD+ and inactivation of GAPDH, making it a powerful tumor energy nanoinhibitor. Meanwhile, Zn2+‐activating DNAzymes for specifically cleaving GLUT1 mRNA is designed. This DNAzyme can only be activated under intracellular Zn2+ overloading, and then directionally cut off glucose supply, which further restrains the adaptive up‐regulation of glycolytic flux after glycolysis inhibition in tumors. Afterward, DNAzymes are loaded in ZIF‐8 concurrently tethered by hyaluronic acid (HA), constructing a “nanoenabled energy interrupter ”. Such a rational design presents a preferential accumulation tendency to tumor sites due to the active CD44‐targeting mechanisms, specifically achieves remarkable systematic energy exhaustion in melanoma cells, and affords 80.8% in tumor growth suppression without systemic toxicity in vivo. This work verifies a fascinating therapeutic platform enabling ion interference‐inductive starvation strategy for effective tumor therapy. A “nano‐enabled energy interrupter” with capability of specific Zn(II) homeostasis disrupting in malignant melanoma is designed. The specific Zn(II) overloading in tumor cells can inhibit glycolysis and initiate GLUT1 depletion for energy exhaustion induced tumor therapy, while the “nanoenabled energy interrupter” has negligible impact on Zn(II) homeostasis and energy metabolism in normal cells.

Lung adenocarcinoma (LUAD), characterized by a low 5-year survival rate, is the most common and aggressive type of lung cancer. Recent studies have shown that tertiary lymphoid structures (TLS), which resemble lymphoid structures, are closely linked to the immune response and tumor prognosis. The functions of the tertiary lymphoid structure-related genes (TLS-RGs) in the tumor microenvironment (TME) are poorly understood. Based on publicly available data, we conducted a comprehensive study of the function of TLS-RGs in LUAD. Initially, we categorized LUAD patients into two TLS and two gene subtypes. Subsequently, risk scores were calculated, and prognostic models were constructed using seven genes (CIITA, FCRL2, GBP1, BIRC3, SCGB1A1, CLDN18, and S100P). To enhance the clinical application of TLS scores, we have developed a precise nomogram. Furthermore, drug sensitivity, tumor mutational burden (TMB), and the cancer stem cell (CSC) index were found to be substantially correlated with the TLS scores. Single-cell sequencing results reflected the distribution of TLS-RGs in cells. Finally, we took the intersection of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) prognosis-related genes and then further validated the expression of these genes by qRT-PCR. Our in-depth investigation of TLS-RGs in LUAD revealed their possible contributions to the clinicopathological features, prognosis, and characteristics of TME. These findings underscore the potential of TLS-RGs as prognostic biomarkers and therapeutic targets for LUAD, thereby paving the way for personalized treatment strategies.

Background Lung adenocarcinoma (LUAD) is the predominant form of non-small cell lung cancer (NSCLC). Mitochondrial quality-related genes (MQRGs) contribute to the genesis and advancement of tumors. Despite advances in LUAD treatment and detection, early diagnostic biomarkers are still lacking, and the roles of MQRGs in LUAD are not well understood. Methods We extensively examined transcriptome and clinical data from TCGA and GEO databases to discover differentially expressed MQRGs. Utilizing the LASSO algorithm and multivariate COX regression, a predictive risk model was created. Kaplan-Meier study and ROC curves were implemented to predict patient prognosis, resulting in a new Mitochondrial Quality Regulation Gene Signature for accurate prognosis forecasting. R software and packages facilitated statistical, consensus cluster, survival, Cox regression, Lasso regression, and tumor microenvironment analyses. Model-related gene expression was measured using RT-qPCR, immunohistochemistry, single-cell sequencing, HPA data, and UNCAN data. Results We created a concise risk model using four MQRGs ( STRAP , SHCBP1 , PKP2 , and CRTAC1 ) to forecast overall survival in LUAD patients. High-risk patients experienced significantly lower survival rates. Functional analysis linked these MQRGs to alpha-linolenic acid metabolism pathways. Moreover, the tumor immune microenvironment supports previous findings that higher CD8 + T cell infiltration improves LUAD outcomes. Analysis of different risk scores showed increased activated memory T-cell CD4, suggesting its activation is crucial for LUAD prognosis. Nomograms were generated with clinical data and the MQRGscore model. mRNA and IHC analysis manifested significantly upregulated STRAP , SHCBP1 , and PKP2 expression and mitigated CRTAC1 expression in the LUAD contrasted with normal lung tissue. qRT-PCR and immunohistochemistry confirmed these findings, aligning with TCGA data. Conclusions We created a succinct MQRGs risk model to ascertain the LUAD patient’s prognosis, potentially offering a novel method for diagnosing and treating this condition.

Aristolochia contorta Bunge has been widely used as traditional Chinese medicine materials. However, its utility faces a great challenge due to the presence of aristolochic acids (AAs), a class of benzylisoquinoline alkaloid (BIA) derivatives. The first step in BIA skeleton formation is catalysis by norcoclaurine synthase (NCS). To gain knowledge of BIA and AA biosynthesis in A. contorta, genome-wide characterizations of NCS genes were carried out. This resulted in the identification of 15 A. contorta NCSs, namely, AcNCS1–AcNCS15. The AcNCS1–AcNCS8 proteins contained one catalytic domain, whereas the AcNCS9–AcNCS15 proteins had two. Phylogenetic analysis shows that AcNCS proteins can be classified into two clades. Gene expression analysis shows that five AcNCSs, including AcNCS2, AcNCS4, AcNCS5, AcNCS14, and AcNCS15, exhibited relatively high expression in roots and flowers, where norcoclaurine accumulated. An enzyme catalytic activity assay shows that all five of the AcNCSs can catalyze norcoclaurine formation with AcNCS14 and AcNCS15, exhibiting higher catalytic efficiency. Precolumn derivatization analysis shows that the formed norcoclaurine included (S)- and (R)-norcoclaurine, with more (S)-configuration. The results provide useful information for further understanding BIA and AA biosynthesis in A. contorta and for AA elimination and bioactive compound improvement in AA-containing medicinal materials.

Protein S-palmitoylation is a reversible post-translational modification that plays a significant role in tumor progression. However, the impact of palmitoylation metabolism on the prognosis and tumor microenvironment characteristics of lung adenocarcinoma (LUAD) remains unclear. Clinical and mRNA data from LUAD patients were collected from public databases. A palmitoylation-related gene cluster was constructed using consensus clustering. A prognostic model based on palmitoylation-related genes was developed using univariate Cox regression and Lasso regression analysis, and the contribution of each gene was assessed using shapley additive explanations (SHAP) analysis. The role of the key gene ZDHHC5 in LUAD was experimentally validated. Cluster analysis divided patients into two groups, with group B exhibiting a better prognosis. Group A had a higher frequency of TP53 mutations, and significant differences in immune cell infiltration were observed between the two groups. A prognostic risk model, based on five key genes (ZDHHC5, ZDHHC12, ZDHHC21, LYPLA1, and PPT2), revealed significant survival differences between the high-risk and low-risk groups. Immune infiltration analysis showed differences in immune cell lineages and functional activities between risk groups. Drug sensitivity analysis indicated varying patient responses to different chemotherapy drugs across risk strata. Further analysis of ZDHHC5 expression across 33 cancers demonstrated its upregulation in multiple cancers, including LUAD. Experimental results suggest that ZDHHC5 may promote LUAD cell proliferation and metastasis both and via the PI3K/AKT pathway. A prognostic model based on palmitoylation-related genes offers a valuable tool for survival prediction and the development of personalized treatment strategies in LUAD. ZDHHC5, a key gene related to palmitoylation, demonstrates potential as both a therapeutic target and a prognostic marker for LUAD and other cancers.

We provide a method to regulate intramolecular charge transfer (ICT) through distorting fragment dipole moments based on molecular planarity and intuitively investigate the physical mechanisms of one-photon absorption (OPA), two-photon absorption (TPA), and electron circular dichroism (ECD) properties of the multichain 1,3,5 triazine derivatives o-Br-TRZ, m-Br-TRZ, and p-Br-TRZ containing three bromobiphenyl units. As the position of the C–Br bond on the branch chain becomes farther away, the molecular planarity is weakened, with the position of charge transfer (CT) on the branch chain of bromobiphenyl changing. The excitation energy of the excited states decreases, which leads to the redshift of the OPA spectrum of 1,3,5-triazine derivatives. The decrease in molecular plane results in a change in the magnitude and direction of the molecular dipole moment on the bromobiphenyl branch chain, which weakens the intramolecular electrostatic interaction of bromobiphenyl branch chain 1,3,5-triazine derivatives and weakens the charge transfer excitation of the second step transition in TPA, leading to an increase in the enhanced absorption cross-section. Furthermore, molecular planarity can also induce and regulate chiral optical activity through changing the direction of the transition magnetic dipole moment. Our visualization method helps to reveal the physical mechanism of TPA cross-sections generated via third-order nonlinear optical materials in photoinduced CT, which is of great significance for the design of large TPA molecules.

Phytopathogen Dickeya oryzae is a causal agent of rice foot rot disease and the pathogen has an array of virulence factors, such as phytotoxin zeamines, plant cell wall degrading enzymes, cell motility, and biofilms, collectively contributing to the bacterial pathogenesis. In this study, through deletion analysis of predicted regulatory genes in D. oryzae EC1, we identified a two-component system associated with the regulation of bacterial virulence. The two-component system contains a histidine kinase ArcB and a response regulator ArcA, and deletion of their coding genes resulted in changed phenotypes in cell motility, biofilm formation, and bacterial virulence. Electrophoretic mobility shift assay revealed that ArcA bound to the promoters of the bcs operon and bssS , which respectively encode enzymes for the synthesis of celluloses and a biofilm formation regulatory protein. ArcA could also bind to the promoters of three virulence associated transcriptional regulatory genes, i.e., fis , slyA and ohrR . Surprisingly, although these three regulators were shown to modulate the production of cell wall degrading enzymes and zeamines, deletion of arcB and arcA did not seem to affect these phenotypes. Taken together, the findings from this study unveiled a new two-component system associated with the bacterial pathogenesis, which contributes to the virulence of D. oryzae mainly through its action on bacterial motility and biofilm formation.