Enhanced Circular Dichroism for Achiral Sensing Based on a DNA-Origami-Empowered Anapole Metasurface.

Circular dichroism (CD) spectroscopy has been extensively utilized for detecting and distinguishing the chirality of diverse substances and structures. However, CD spectroscopy is inherently weak and conventionally associated with chiral sensing, thus constraining its range of applications. Here, we report a DNA-origami-empowered metasurface sensing platform through the collaborative effect of metasurfaces and DNA origami, enabling achiral/slightly chiral sensing with high sensitivity via the enhanced ΔCD. An anapole metasurface, boasting over 60 times the average optical chirality enhancement, was elaborately designed to synergize with reconfigurable DNA origami. We experimentally demonstrated the detection of achiral/slightly chiral DNA linker strands via the enhanced ΔCD of the proposed platform, whose sensitivity was a 10-fold enhancement compared with the platform without metasurfaces. Our work presents a high-sensitivity platform for achiral/slightly chiral sensing through chiral spectroscopy, expanding the capabilities of chiral spectroscopy and inspiring the integration of multifunctional artificial nanostructures across diverse domains.

Real-time synchronized monitoring for the overlap accuracy of the combining beam spot in a wavelength beam combination based on confocal planes.

Beam overlap accuracy in a wavelength beam combination system determines the beam quality and efficiency, so systematic monitoring of overlap accuracy is essential. In this work, a method of performing real-time synchronized monitoring and recording overlap accuracy for a combining beam spot is proposed. Firstly, theoretical calculations for monitoring different wavelength sub-beam positions and angular errors are established. Then, an optical design and grayscale centroid algorithm are developed to analyze and simulate the combination spots. A monitoring device was designed and constructed to meet the requirements of combining system applications, which achieved an accuracy of 8.86 µrad. Finally, the method successfully monitored the system spot fluctuation range within ±22 µrad. This study resolves the issue of distinguishing the different wavelength sub-beams and their response delays in traditional combining beams. It offers precise error data for real-time synchronized calibration of the overlap accuracy in laser beam combining technology.

[Functional and oncologic outcomes of partial nephrectomy for cystic renal cell carcinoma: A single-center retrospective study].

OBJECTIVE: To investigate the postoperative renal function and oncologic outcomes of cystic renal cell carcinoma with partial nephrectomy, and to compared the single-center data on surgical outcomes with the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: This was a retrospective study that included the patients with cystic renal cell carcinoma who underwent partial nephrectomy in the Department of Urology, Peking University Third Hospital (PUTH) from 2010 to 2023. The clinical data and depicting baseline characteristics were collected. Renal dynamic imaging and the Chinese Coefficients for Chronic Kidney Disease Epidemiology Collaboration (C-CKD-EPI) formulae were used to calculate the estimated glomerular filtration rate (eGFR). The renal function curves over time were then plotted, and the patients were followed-up to record their survival status. Cases of cystic renal cell carcinoma in the SEER database between 2000 and 2020 were included, propensity score matching (PSM) was performed to balance the differences between SEER cohort and PUTH cohort, and the cancer-specific survival (CSS) curves for both groups were plotted and statistical differences were calculated by the Kaplan-Meier method. RESULTS: A total of 38 and 385 patients were included in the PUTH cohort and SEER cohort, respectively, and 31 and 72 patients were screened in each cohort after PSM. Of the baseline characteristics, only tumor size (P=0.042) was found to differ statistically between the two groups. There was no statistically significant difference between the two cohorts in terms of CSS after PSM (P=0.556). The median follow-up time in the SEER cohort was 112.5 (65, 152) months and a 10-year survival rate of 97.2%, while the PUTH cohort had a median follow-up of 57.0 (20, 1 172) months and a 10-year survival rate of 100.0%. There was no statistically significant difference between eGFR determined by preoperative renal dynamic imaging and the results of the C-CKD-EPI formulae based on creatinine estimation (P=0.073). There was a statistically significant difference in eGFR among the preoperative, short-term postoperative, and long-term postoperative (P < 0.001), which was characterized by the presence of a decline in renal function in the short-term postoperative period and the recovery of renal function in the long-term period. CONCLUSION: Partial nephrectomy for cystic renal cell carcinoma is safe and feasible with favorable renal function and oncologic outcomes.

A long transcript mutant of the rubisco activase gene RCA upregulated by the transcription factor Ghd2 enhances drought tolerance in rice.

The transcription factor Ghd2 increases rice yield potential under normal conditions and accelerates leaf senescence under drought stress. However, its mechanism on the regulation of leaf senescence under drought stress remains unclear. In the present study, to unveil the mechanism, one target of Ghd2, the Rubisco activase gene RCA, was identified through the combined analysis of Ghd2-CRISPR transcriptome data and Ghd2-overexpression microarray data. Ghd2 binds to the 'CACA' motif in the RCA promoter by its CCT domain and upregulates RCA expression. RCA has alternative transcripts, RCAS and RCAL, which are predominantly expressed under normal conditions and drought stress, respectively. Similar to Ghd2-overexpressing plants, RCAL-overexpressing plants were more sensitive to drought stress than the wild-type. However, the plants overexpressing RCAS showed a weak drought-sensitive phenotype. Moreover, RCAL knockdown and knockout plants did not show yield loss under normal conditions, but exhibited enhanced drought tolerance and delayed leaf senescence. The chlorophyll content, the free amino acid content and the expression of senescence-related genes in the RCAL mutant were lower than those in the wild-type plants under drought stress. In summary, Ghd2 induces leaf senescence by upregulating RCAL expression under drought stress, and the RCAL mutant has important values in breeding drought-tolerant varieties.

The amino acid residue E96 of Ghd8 is crucial for the formation of the flowering repression complex Ghd7-Ghd8-OsHAP5C in rice.

Ghd7 is an important gene involved in the photoperiod flowering pathway in rice. A Ghd7-involved transcriptional regulatory network has been established, but its translational regulatory pathway is poorly understood. The mutant suppressor of overexpression of Ghd7 (sog7) was identified from EMS-induced mutagenesis on the background of ZH11 overexpressing Ghd7. MutMap analysis revealed that SOG7 is allelic to Ghd8 and delayed flowering under long-day (LD) conditions. Biochemical assays showed that Ghd8 interacts with OsHAP5C and Ghd7 both in vivo and in vitro. Surprisingly, a point mutation E96K in the α2 helix of the Ghd8 histone fold domain (HFD) destroyed its ability to interact with Ghd7. The prediction of the structure shows that mutated amino acid is located in the interaction region of CCT/NF-YB/YC complexes, which alter the structure of α4 of Ghd8. This structural difference prevents the formation of complex NF-YB/YC. The triple complex of Ghd8-OsHAP5C-Ghd7 directly bound to the promotor of Hd3a and downregulated the expression of Ehd1, Hd3a and RFT1, and finally resulted in a delayed heading. These findings are helpful in deeply understanding the Ghd7-involved photoperiod flowering pathway and promote the elucidation of rice heading.

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities.

The acceptorless dehydrogenative coupling (ADC) reaction is an efficient method for synthesizing quinoline and its derivatives. In this paper, various substituted quinolines were synthesized from 2-aminobenzyl alcohols and aryl/heteroaryl/alkyl secondary alcohols in one pot via a cyclometalated iridium-catalyzed ADC reaction. This method has some advantages, such as easy availability of raw materials, mild reaction conditions, wide range of substrates, and environmental friendliness which conforms to the principles of green chemistry. Furthermore, a gram-scale experiment with low catalyst loading offers the potential to access the aryl/heteroaryl quinolones in suitable amounts. In addition, the antibacterial and antifungal activities of the synthesized quinolines were evaluated in vitro, and the experimental results showed that the antibacterial activities of compounds 3ab, 3ad, and 3ah against Gram-positive bacteria and compound 3ck against C. albicans were better than the reference drug norfloxacin.

The transcriptional repressor OsPRR73 links circadian clock and photoperiod pathway to control heading date in rice.

The phase transition from vegetative to reproductive growth is triggered by internal and external signals that participate in circadian clock in plants. We identified a rice floral inhibitor OsPRR73 encoding a CONSTANS protein. Overexpression of OsPRR73 resulted in late heading under both long-day (LD) and short-day (SD) conditions. Knockout mutants led to early heading under LD conditions but no change under SD. OsPRR73 mRNA accumulated at noon and exhibited a robust oscillation under constant light (LL) and constant darkness (DD) conditions. OsPRR73 overexpression exerted negative feedback on endogenous OsPRR73 expression and altered diurnal expressions of key flowering genes and circadian clock genes. OsPRR73 bound to the promoters of the floral gene Ehd1 and the circadian gene OsLHY, and significantly suppressed their expression at dawn. In LL and DD, the oscillatory patterns of the circadian genes OsLHY, OsTOC1, OsGI and OsELF3 were varied in OsPRR73OX and osprr73 mutants. OsPRR73 expression was decreased in osphyb mutants, and overexpression of OsPRR73 complemented the early heading date phenotype of osphyb, indicating OsPRR73 works downstream of OsPhyB. Therefore, OsPRR73 is involved in a feedback loop of the rice clock and connects the photoperiod flowering pathway by binding to the Ehd1 promoter in rice.

Rectangular multilayer dielectric gratings with broadband high diffraction efficiency and enhanced laser damage resistance.

Broadband multilayer dielectric gratings (MDGs) with rectangular HfO2 grating profile were realized for the first time using a novel fabrication process that combines laser interference lithography, nanoimprint, atomic layer deposition and reactive ion-beam etching. The laser-induced damage initiating at the grating ridge was mitigated for two reasons. First, the rectangular grating profile exhibits the minimum electric-field intensity (EFI) enhancement inside the grating pillar compared to other trapezoidal profiles. Second, our etching process did not create nano-absorbing defects at the edge of the HfO2 grating where the peak EFI locates, which is unavoidable in traditional fabrication process. The fabricated MDGs showed a high laser induced damage threshold of 0.59J/cm2 for a Ti-sapphire laser with pulse width of 40 fs and an excellent broadband diffraction spectrum with 95% efficiency over 150 nm in TE polarization.

Genome-Wide Association Studies Reveal the Genetic Basis of Ionomic Variation in Rice.

Rice (Oryza sativa) is an important dietary source of both essential micronutrients and toxic trace elements for humans. The genetic basis underlying the variations in the mineral composition, the ionome, in rice remains largely unknown. Here, we describe a comprehensive study of the genetic architecture of the variation in the rice ionome performed using genome-wide association studies (GWAS) of the concentrations of 17 mineral elements in rice grain from a diverse panel of 529 accessions, each genotyped at ∼6.4 million single nucleotide polymorphism loci. We identified 72 loci associated with natural ionomic variations, 32 that are common across locations and 40 that are common within a single location. We identified candidate genes for 42 loci and provide evidence for the causal nature of three genes, the sodium transporter gene Os-HKT1;5 for sodium, Os-MOLYBDATE TRANSPORTER1;1 for molybdenum, and Grain number, plant height, and heading date7 for nitrogen. Comparison of GWAS data from rice versus Arabidopsis (Arabidopsis thaliana) also identified well-known as well as new candidates with potential for further characterization. Our study provides crucial insights into the genetic basis of ionomic variations in rice and serves as an important foundation for further studies on the genetic and molecular mechanisms controlling the rice ionome.

Interferon-γ decreases ATP-binding cassette subfamily G member 1-mediated cholesterol efflux through small ubiquitin-like modifier/ubiquitin-dependent liver X receptor-α degradation in macrophages.

The effects of interferon-γ (IFN-γ) on cholesterol accumulation and the development of foam cells are still unclear. In the present study, we found that IFN-γ promoted liver X receptor (LXR)-α degradation through the ubiquitin-proteasome system in macrophages. The process was dependent on its interactions with phosphorylated signal transducer and activator of transcription 1 (p-STAT1) and protein inhibitor of activated STAT 1 (PIAS1) because both fludarabine and PIAS1 shRNA reversed the decrease in LXR-α protein expression induced by IFN-γ. Additionally, IFN-γ enhanced the interactions of ubiquitin-conjugating enzyme 9 (UBC9), small ubiquitin-like modifier (SUMO)-1 and SUMO-2/3 with LXR-α. Moreover, treatment with shRNA specific for them not only reduced LXR-α polyubiquitination but also reversed the IFN-γ-induced decrease in its expression. Two specific sumoylation sites in LXR-α, K22 and K326, were indispensable for its IFN-γ-induced polyubiquitination because the K22R and K326R mutations inhibited the polyubiquitination and degradation of LXR-α in IFN-γ-treated macrophages. In addition, K22R or K326R mutation almost completely restored ATP-binding cassette subfamily G member 1 (ABCG1)-mediated cholesterol efflux in IFN-γ-treated macrophages. Taken together, these findings indicate that IFN-γ promotes LXR-α degradation through a SUMO-ubiquitin-dependent pathway, which may inhibit cholesterol efflux mediated by ABCG1 from macrophages and promote the development of atherosclerosis.

High Concentrations of Atmospheric Isocyanic Acid (HNCO) Produced from Secondary Sources in China.

Isocyanic acid (HNCO) is a potentially toxic atmospheric pollutant, whose atmospheric concentrations are hypothesized to be linked to adverse health effects. An earlier model study estimated that concentrations of isocyanic acid in China are highest around the world. However, measurements of isocyanic acid in ambient air have not been available in China. Two field campaigns were conducted to measure isocyanic acid in ambient air using a high-resolution time-of-flight chemical ionization mass spectrometer (ToF-CIMS) in two different environments in China. The ranges of mixing ratios of isocyanic acid are from below the detection limit (18 pptv) to 2.8 ppbv (5 min average) with the average value of 0.46 ppbv at an urban site of Guangzhou in the Pearl River Delta (PRD) region in fall and from 0.02 to 2.2 ppbv with the average value of 0.37 ppbv at a rural site in the North China Plain (NCP) during wintertime, respectively. These concentrations are significantly higher than previous measurements in North America. The diurnal variations of isocyanic acid are very similar to secondary pollutants (e.g., ozone, formic acid, and nitric acid) in PRD, indicating that isocyanic acid is mainly produced by secondary formation. Both primary emissions and secondary formation account for isocyanic acid in the NCP. The lifetime of isocyanic acid in a lower atmosphere was estimated to be less than 1 day due to the high apparent loss rate caused by deposition at night in PRD. Based on the steady state analysis of isocyanic acid during the daytime, we show that amides are unlikely enough to explain the formation of isocyanic acid in Guangzhou, calling for additional precursors for isocyanic acid. Our measurements of isocyanic acid in two environments of China provide important constraints on the concentrations, sources, and sinks of this pollutant in the atmosphere.

Photonic spin Hall effect based on broadband high-efficiency reflective metasurfaces.

Through the introduction of a broadband (∼1µm) high-efficiency (average above 90%) half-wave plate in the near-infrared (NIR) region, reflective Pancharatnam-Berry metasurfaces that can generate high-intensity (above 90%) left-circular polarization (LCP) and right-circular polarization (RCP) light for broadband (∼900nm) are designed. It provides a method to generate broadband high-efficiency circularly polarized (CP) light, which is a rare complex process in traditional chiroptical spectroscopy. To further show the broadband high-efficiency function of the meta-atom, a broadband high-efficiency reflective vortex beam generator based on metasurfaces is designed for RCP light in the NIR region. Moreover, with the appropriate arrangement, the metasurfaces are able to focus the vortex beam into a point to increase the intensity of the generated vortex beam.

Demonstration of a dual-channel two-dimensional reflection grating filter.

A dual-channel two-dimensional (2D) reflection grating filter operating around the 1.55 µm wavelength region is demonstrated, exhibiting dual-channel reflection peaks at 1.492 µm and 1.647 µm. The sidebands intrinsic to this kind of grating are suppressed by appropriately designed antireflective thin films, and this can be proved by equivalent medium theory. Using the modal analysis method, the excitation modes of the dual-channel reflection peaks are determined to be the TM0 (1.490 µm) and TE0 (1.638 µm) modes. The estimated relative errors in the wavelength determination of these modes are less than 1%. This is found to be in accord with analyses of the reflectivity spectra and electromagnetic fields. The dual-channel reflection peaks are sensitive to the background refractive index and may be useful in biosensing applications.

Combinations of the Ghd7, Ghd8 and Hd1 genes largely define the ecogeographical adaptation and yield potential of cultivated rice.

Rice cultivars have been adapted to favorable ecological regions and cropping seasons. Although several heading date genes have separately made contributions to this adaptation, the roles of gene combinations are still unclear. We employed a map-based cloning approach to isolate a heading date gene, which coordinated the interaction between Ghd7 and Ghd8 to greatly delay rice heading. We resequenced these three genes in a germplasm collection to analyze natural variation. Map-based cloning demonstrated that the gene largely affecting the interaction between Ghd7 and Ghd8 was Hd1. Natural variation analysis showed that a combination of loss-of-function alleles of Ghd7, Ghd8 and Hd1 contributes to the expansion of rice cultivars to higher latitudes; by contrast, a combination of pre-existing strong alleles of Ghd7, Ghd8 and functional Hd1 (referred as SSF) is exclusively found where ancestral Asian cultivars originated. Other combinations have comparatively larger favorable ecological scopes and acceptable grain yield. Our results indicate that the combinations of Ghd7, Ghd8 and Hd1 largely define the ecogeographical adaptation and yield potential in rice cultivars. Breeding varieties with the SSF combination are recommended for tropical regions to fully utilize available energy and light resources and thus produce greater yields.

3D bioprinted tumor model: a prompt and convenient platform for overcoming immunotherapy resistance by recapitulating the tumor microenvironment.

BACKGROUND: Cancer immunotherapy is receiving worldwide attention for its induction of an anti-tumor response. However, it has had limited efficacy in some patients who acquired resistance. The dynamic and sophisticated complexity of the tumor microenvironment (TME) is the leading contributor to this clinical dilemma. Through recapitulating the physiological features of the TME, 3D bioprinting is a promising research tool for cancer immunotherapy, which preserves in vivo malignant aggressiveness, heterogeneity, and the cell-cell/matrix interactions. It has been reported that application of 3D bioprinting holds potential to address the challenges of immunotherapy resistance and facilitate personalized medication. CONCLUSIONS AND PERSPECTIVES: In this review, we briefly summarize the contributions of cellular and noncellular components of the TME in the development of immunotherapy resistance, and introduce recent advances in 3D bioprinted tumor models that served as platforms to study the interactions between tumor cells and the TME. By constructing multicellular 3D bioprinted tumor models, cellular and noncellular crosstalk is reproduced between tumor cells, immune cells, fibroblasts, adipocytes, and the extracellular matrix (ECM) within the TME. In the future, by quickly preparing 3D bioprinted tumor models with patient-derived components, information on tumor immunotherapy resistance can be obtained timely for clinical reference. The combined application with tumoroid or other 3D culture technologies will also help to better simulate the complexity and dynamics of tumor microenvironment in vitro. We aim to provide new perspectives for overcoming cancer immunotherapy resistance and inspire multidisciplinary research to improve the clinical application of 3D bioprinting technology.

Genetically Proxied Autoimmune Diseases and the Risk of Facial Aging.

Purpose: Previous studies have suggested a relationship between autoimmune diseases and the risk of facial skin aging. However, evidence from population-based studies on this topic is limited, leaving the causal association between these factors unknown. This study aimed to systematically evaluate the causal effects of 18 autoimmune diseases on the risk of facial skin aging, aim of providing strategies to mitigate early facial aging in patients with autoimmune diseases. Patients and Methods: We conducted univariate Mendelian randomization (UVMR) analyses to examine the causal relationship between 18 autoimmune diseases and facial aging using publicly available summary data from genome-wide association studies (GWASs). We also conducted multivariate Mendelian randomization (MVMR) analyses to adjust for confounding factors, including smoking, alcohol consumption, and body mass index (BMI). Results: The main inverse variance weighted (IVW) method revealed that genetically proxied ankylosing spondylitis (AS) (OR 1.017; 95% CI: 1.003-1.031; P=0.018), sicca syndrome (SS) (OR 1.008; 95% CI: 1.005-1.011; P= 2.66×10-6), systemic lupus erythematosus (SLE) (OR 1.006; 95% 1.001-1.011; P=0.014), multiple sclerosis (MS) (OR 1.004; 95% CI: 1.001-1.007; P=0.021), primary sclerosing cholangitis (PSC) (OR 1.002; 95% CI: 1.000-1.004; P=0.023), and celiac disease (CeD) (OR 1.002; 95% CI: 1.001-1.004; P=0.009) were significantly associated with higher risk of facial aging. After adjusting for potential confounding factors, the association persisted between AS, SLE, and CeD. Conclusion: These findings indicated that autoimmune diseases play a causal role in facial skin aging. Therefore, patients with autoimmune diseases should take appropriate measures to prevent early facial aging.

Exploring the roles and potential therapeutic strategies of inflammation and metabolism in the pathogenesis of vitiligo: a mendelian randomization and bioinformatics-based investigation.

Introduction: Vitiligo, a common autoimmune acquired pigmentary skin disorder, poses challenges due to its unclear pathogenesis. Evidence suggests inflammation and metabolism's pivotal roles in its onset and progression. This study aims to elucidate the causal relationships between vitiligo and inflammatory proteins, immune cells, and metabolites, exploring bidirectional associations and potential drug targets. Methods: Mendelian Randomization (MR) analysis encompassed 4,907 plasma proteins, 91 inflammatory proteins, 731 immune cell features, and 1400 metabolites. Bioinformatics analysis included Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Subnetwork discovery and hub protein identification utilized the Molecular Complex Detection (MCODE) plugin. Colocalization analysis and drug target exploration, including molecular docking validation, were performed. Results: MR analysis identified 49 proteins, 39 immune cell features, and 59 metabolites causally related to vitiligo. Bioinformatics analysis revealed significant involvement in PPI, GO enrichment, and KEGG pathways. Subnetwork analysis identified six central proteins, with Interferon Regulatory Factor 3 (IRF3) exhibiting strong colocalization evidence. Molecular docking validated Piceatannol's binding to IRF3, indicating a stable interaction. Conclusion: This study comprehensively elucidates inflammation, immune response, and metabolism's intricate involvement in vitiligo pathogenesis. Identified proteins and pathways offer potential therapeutic targets, with IRF3 emerging as a promising candidate. These findings deepen our understanding of vitiligo's etiology, informing future research and drug development endeavors.

The Predictive Values of White Blood Cell Indices (Lymphocyte and Eosinophilic Granulocyte) for Heart Failure in Acute Coronary Syndrome Patients Following Percutaneous Coronary Intervention: A Prospective Cohort Study.

Background: White blood cell (WBC) indices are strongly associated with cardiovascular disease, but data on the prognostic values of these parameters in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI) are sparse. The current study aimed to investigate the relationship between baseline WBC indices levels and the incidence of heart failure (HF) in ACS patients after PCI and explore the predictive values over a 2-year follow-up period. Methods: A total of 416 consecutive ACS patients treated with PCI were enrolled and received a median of 27.7 months follow-up. Univariate and multivariate Cox regression analyses and the receiver operating characteristic (ROC) curves were performed. Results: Baseline lymphocyte (LYMPH) count, eosinophil (EO) count and eosinophil percentage (EO %) were higher in patients who experienced HF over a 2-year follow-up. In multivariate Cox proportional hazards analysis, LYMPH count, EO count and EO % were independently associated with the occurrence of HF (hazard ratio [HR] = 12.876, P = 0.025; HR = 16.625, P = 0.004; HR = 1.196, P = 0.031, respectively). The area under the ROC curve of baseline EO count predicting the occurrence of HF in ACS patients following PCI was 0.625 (P = 0.037). For patients aged 60 years and above, who had PCI or history of coronary artery bypass grafting, the higher EO count, the higher the risk of HF. Conclusion: Elevated baseline LYMPH count, EO count and EO % were independently associated with the incidence of HF in ACS patients following PCI, suggesting that WBC indices might be available, simple, and cost-efficient biomarkers with predictive value, especially for patients aged more than 60 years.

Cancer testis antigen subfamilies: Attractive targets for therapeutic vaccine (Review).

Cancer­testis antigen (CTA) is a well­accepted optimal target library for cancer diagnosis and treatment. Most CTAs are located on the X chromosome and aggregate into large gene families, such as the melanoma antigen, synovial sarcoma X and G antigen families. Members of the CTA subfamily are usually co­expressed in tumor tissues and share similar structural characteristics and biological functions. As cancer vaccines are recommended to induce specific antitumor responses, CTAs, particularly CTA subfamilies, are widely used in the design of cancer vaccines. To date, DNA, mRNA and peptide vaccines have been commonly used to generate tumor­specific CTAs in vivo and induce anticancer effects. Despite promising results in preclinical studies, the antitumor efficacy of CTA­based vaccines is limited in clinical trials, which may be partially attributed to weak immunogenicity, low efficacy of antigen delivery and presentation processes, as well as a suppressive immune microenvironment. Recently, the development of nanomaterials has enhanced the cancer vaccination cascade, improved the antitumor performance and reduced off­target effects. The present study provided an in­depth review of the structural characteristics and biofunctions of the CTA subfamilies, summarised the design and utilisation of CTA­based vaccine platforms and provided recommendations for developing nanomaterial­derived CTA­targeted vaccines.

TPM2 attenuates progression of prostate cancer by blocking PDLIM7-mediated nuclear translocation of YAP1.

BACKGROUND: Prostate cancer (PCa) is a common malignant tumor of the genitourinary system. Clinical intervention in advanced PCa remains challenging. Tropomyosins 2 (TPM2) are actin-binding proteins and have been found as a biomarker candidate for certain cancers. However, no studies have explored the role of TPM2 in PCa and its regulatory mechanism. METHODS: TPM2 expression was assessed in Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) PCa patient dataset. The effect of TPM2 on PCa progression was assessed in vitro and in vivo by quantifying proliferation, migration, invasion and tumor growth assays, and the mechanism of TPM2 in PCa progression was gradually revealed by Western blotting, immunoprecipitation, and immunofluorescence staining arrays. RESULTS: TPM2 was found to be severely downregulated in tumor tissues of PCa patients compared with tumor-adjacent normal tissues. In vitro experiments revealed that TPM2 overexpression inhibited PCa cell proliferation, invasion and androgen-independent proliferation. Moreover, TPM2 overexpression inhibited the growth of subcutaneous xenograft tumors in vivo. Mechanistically, this effect was noted to be dependent on PDZ-binding motif of TPM2. TPM2 competed with YAP1 for binding to PDLIM7 through the PDZ-binding motif. The binding of TPM2 to PDLIM7 subsequently inhibited the nuclear transport function of PDLIM7 for YAP1. YAP1 sequestered in the cytoplasm phosphorylated at S127, resulting in its inactivation or degradation which in turn inhibited the expression of YAP1 downstream target genes. CONCLUSIONS: This study investigated the role of TPM2, PDLIM7, and YAP1 in PCa progression and castration resistance. TPM2 attenuates progression of PCa by blocking PDLIM7-mediated nuclear translocation of YAP1. Accordingly, targeting the expression or functional modulation of TPM2, PDLIM7, or YAP1 has the potential to be an effective therapeutic approach to reduce PCa proliferation and prevent the progression of castration-resistant prostate cancer (CRPC).