Recent functionality developments of carboxymethyl chitosan as an active food packaging film material.

In recent years, environmental concerns regarding the persistence of petroleum-based plastic food packaging have increased, prompting the exploration of biopolymer alternatives. Carboxymethyl chitosan (CMCS), a derivative of chitosan, exhibits superior water-soluble film properties, making it an ideal material for degradable food packaging applications. This study comprehensively examines the synthesis methods and properties of CMCS, with a particular emphasis on recent advancements in CMCS-based food packaging films. Various functionalized CMCS-based food packaging films, including coblended, nanoparticle composite, plant extract composite, and cross-linked films, were reviewed. The practical applications of CMCS-based food packaging films and edible coatings in food preservation are also showcased. This study emphasizes that the notable compatibility of CMCC with a range of polymers and additives has facilitated the development of multifunctional packaging films. These innovations, including antibacterial, antioxidant, and smart-indicating variants, have demonstrated remarkable efficacy in preserving fruits, aquatic products, poultry, and other perishable goods.

The first high-quality genome assembly and annotation of Anthocidaris crassispina.

Anthocidaris crassispina is a very popular edible sea urchin distributed along the coast of the South China Sea. In this study, we performed whole-genome sequencing and generated a chromosome-level assembly of this species. The total length of the genomic contig sequence was 891.02 Mb, and contig N50 was 808.15 kb when Hifiasm was used for assembly. The Hi-C library was constructed and sequenced, yielding approximately 68.61 Gb of data. After Hi-C assembly, approximately 886.72 Mb of sequence was able to be mapped onto 21 chromosomes, accounting for 99.52% of the total genome length. Among the sequences located on the chromosomes, those for which the order and direction could be determined accounted for approximately 826.82 Mb, or 93.24% of the total length. These results provide valuable resources for further study of A. crassispina at the genetic level.

Ruthenium Anchored Laser-Induced Graphene as Binder-Free and Free-Standing Electrode for Selective Electrosynthesis of Ammonia from Nitrate.

Developing effective electrocatalysts for the nitrate reduction reaction (NO3RR) is a promising alternative to conventional industrial ammonia (NH3) synthesis. Herein, starting from a flexible laser-induced graphene (LIG) film with hierarchical and interconnected macroporous architecture, a binder-free and free-standing Ru-modified LIG electrode (Ru-LIG) is fabricated for electrocatalytic NO3RR via a facile electrodeposition method. The relationship between the laser-scribing parameters and the NO3RR performance of Ru-LIG electrodes is studied in-depth. At -0.59 VRHE, the Ru-LIG electrode exhibited the optimal and stable NO3RR performance (NH3 yield rate of 655.9 µg cm-2 h-1 with NH3 Faradaic efficiency of up to 93.7%) under a laser defocus setting of +2 mm and an applied laser power of 4.8 W, outperforming most of the reported NO3RR electrodes operated under similar conditions. The optimized laser-scribing parameters promoted the surface properties of LIG with increased graphitization degree and decreased charge-transfer resistance, leading to synergistically improved Ru electrodeposition with more exposed NO3RR active sites. This work not only provides a new insight to enhance the electrocatalytic NO3RR performance of LIG-based electrodes via the coordination with metal electrocatalysts as well as identification of the critical laser-scribing parameters but also will inspire the rational design of future advanced laser-induced electrocatalysts for NO3RR.

Machine Learning-based Framework Develops a Tumor Thrombus Coagulation Signature in Multicenter Cohorts for Renal Cancer.

Background: Renal cell carcinoma (RCC) is frequently accompanied by tumor thrombus in the venous system with an extremely dismal prognosis. The current Tumor Node Metastasis (TNM) stage and Mayo clinical classification do not appropriately identify preference-sensitive treatment. Therefore, there is an urgent need to develop a better ideal model for precision medicine. Methods: In this study, we developed a coagulation tumor thrombus signature for RCC with 10 machine-learning algorithms (101 combinations) based on a novel computational framework using multiple independent cohorts. Results: The established tumor thrombus coagulation-related risk stratification (TTCRRS) signature comprises 10 prognostic coagulation-related genes (CRGs). This signature could predict survival outcomes in public and in-house protein cohorts and showed high performance compared to 129 published signatures. Additionally, the TTCRRS signature was significantly related to some immune landscapes, immunotherapy response, and chemotherapy. Furthermore, we also screened out hub genes, transcription factors, and small compounds based on the TTCRRS signature. Meanwhile, CYP51A1 can regulate the proliferation and migration properties of RCC. Conclusions: The TTCRRS signature can complement the traditional anatomic TNM staging system and Mayo clinical stratification and provide clinicians with more therapeutic options.

Identification of shared immune infiltration characteristic molecules in dermatomyositis and nasopharyngeal carcinoma using bioinformatics: Traits in dermatomyositis and nasopharyngeal cancer.

BACKGROUND: Dermatomyositis (DM) is a kind of dermatologically associated autoimmune disease that is notably associated with an increased risk of concurrent malignancies, although the underlying mechanisms remain to be fully elucidated. The purpose of this investigation was to examine the immunological parallels between DM and nasopharyngeal carcinoma (NPC), with the aim of identifying pivotal biomarkers that could facilitate a deeper understanding and enhance the predictive capabilities of NPC in DM patients. METHOD: Data for DM and NPC were sourced from the Gene Expression Omnibus (GEO) database. Immune infiltration was analyzed using the "cibersort" R package, differentially expressed genes (DEGs) were identified with the "limma" package, and functional pathways were investigated through Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Characteristic genes were determined by Utilizing Protein-Protein Interaction (PPI) and Least Absolute Shrinkage and Selection Operator (LASSO), and their features were validated using the GSE53819 dataset. RESULTS: In comparison to normal samples, significant infiltration of macrophage M1 was observed in both DM and NPC. The analysis revealed 77 DEGs in DM and 1051 DEGs in NPC, with 22 genes found to be co-DEGs. Following PPI and LASSO analysis, six distinctive genes were retained. Notably, CCL8, IFIH1, CXCL10, and CXCL11 exhibited optimal diagnostic efficacy for NPC and displayed significant correlation with macrophage M1 infiltration within the carcinoma. CONCLUSION: Four characteristic genes, CCL8, IFIH1, CXCL10, and CXCL11 are risk factors for both DM and NPC. They exhibit a robust correlation with the incidence of NPC and offer a commendable diagnostic efficacy. Furthermore, they may serve as prospective predictive biomarkers for the emergence of NPC in DM.

A review of starch/polyvinyl alcohol (PVA) blend film: A potential replacement for traditional plastic-based food packaging film.

In recent years, the development of environmentally friendly packaging materials using biodegradable polymers has emerged as a key challenge for scientists and consumers in response to resource depletion and environmental issues caused by plastic packaging materials. Starch and polyvinyl alcohol (PVA) are being recognized as excellent candidates for producing biodegradable food packaging films. Polymer blending has emerged as a practical approach to overcome the limitations of biopolymer films by developing films with unique properties and enhancing overall performance. This review briefly introduces the molecular structure and properties of starch and PVA, summarizes the common preparation methods and properties of starch/PVA blend films, and focuses on different strategies used to enhance starch/PVA blend films, including nanoparticles, plant extracts, and cross-linking agents. Additionally, this study summarizes the application of starch/PVA blend films as active and smart packaging in food preservation systems. This study demonstrates that starch and PVA blends have potential in manufacturing biodegradable food films with excellent properties due to their excellent compatibility and intermolecular interactions, and can be used as packaging films for a variety of foods to extend their shelf life.

Single-site iron-anchored amyloid hydrogels as catalytic platforms for alcohol detoxification.

Constructing effective antidotes to reduce global health impacts induced by alcohol prevalence is a challenging topic. Despite the positive effects observed with intravenous applications of natural enzyme complexes, their insufficient activities and complicated usage often result in the accumulation of toxic acetaldehyde, which raises important clinical concerns, highlighting the pressing need for stable oral strategies. Here we present an effective solution for alcohol detoxification by employing a biomimetic-nanozyme amyloid hydrogel as an orally administered catalytic platform. We exploit amyloid fibrils derived from ß-lactoglobulin, a readily accessible milk protein that is rich in coordinable nitrogen atoms, as a nanocarrier to stabilize atomically dispersed iron (ferrous-dominated). By emulating the coordination structure of the horseradish peroxidase enzyme, the single-site iron nanozyme demonstrates the capability to selectively catalyse alcohol oxidation into acetic acid, as opposed to the more toxic acetaldehyde. Administering the gelatinous nanozyme to mice suffering from alcohol intoxication significantly reduced their blood-alcohol levels (decreased by 55.8% 300 min post-alcohol intake) without causing additional acetaldehyde build-up. Our hydrogel further demonstrates a protective effect on the liver, while simultaneously mitigating intestinal damage and dysbiosis associated with chronic alcohol consumption, introducing a promising strategy in effective alcohol detoxification.

DeepSS2GO: protein function prediction from secondary structure.

Predicting protein function is crucial for understanding biological life processes, preventing diseases and developing new drug targets. In recent years, methods based on sequence, structure and biological networks for protein function annotation have been extensively researched. Although obtaining a protein in three-dimensional structure through experimental or computational methods enhances the accuracy of function prediction, the sheer volume of proteins sequenced by high-throughput technologies presents a significant challenge. To address this issue, we introduce a deep neural network model DeepSS2GO (Secondary Structure to Gene Ontology). It is a predictor incorporating secondary structure features along with primary sequence and homology information. The algorithm expertly combines the speed of sequence-based information with the accuracy of structure-based features while streamlining the redundant data in primary sequences and bypassing the time-consuming challenges of tertiary structure analysis. The results show that the prediction performance surpasses state-of-the-art algorithms. It has the ability to predict key functions by effectively utilizing secondary structure information, rather than broadly predicting general Gene Ontology terms. Additionally, DeepSS2GO predicts five times faster than advanced algorithms, making it highly applicable to massive sequencing data. The source code and trained models are available at https://github.com/orca233/DeepSS2GO.

Silicon Hybridization for the Preparation of Room-Temperature Curing and High-Temperature-Resistant Epoxy Resin.

Specialized epoxy resin, capable of achieving room-temperature profound curing and sustaining prolonged exposure to high-temperature environments, stands as a pivotal material in modern high-end manufacturing sectors including aerospace, marine equipment fabrication, machinery production, and the electronics industry. Herein, a silicon-hybridized epoxy resin, amenable to room-temperature curing and designed for high-temperature applications, was synthesized using a sol-gel methodology with silicate esters and silane coupling agents serving as silicon sources. Resin characterization indicates a uniform distribution of silicon elements in the obtained silicon hybrid epoxy resin. In comparison to the non-hybridized epoxy resin, notable improvements are observed in room-temperature curing performance, heat resistance, and mechanical strength.

Curcumin Inhibits the Growth of Hepatocellular Carcinoma via the MARCH1-mediated Modulation of JAK2/STAT3 Signaling.

BACKGROUND: Curcumin has been reported to have anti-hepatocellular carcinoma (HCC) effects, but the underlying mechanism is not well known. OBJECTIVES: To investigate whether membrane-associated RING-CH 1 (MARCH1) is involved in the curcumin-induced growth suppression in HCC and its underlying molecular mechanism. A few recent patents for curcumin for cancer are also reviewed in this article. METHODS: The effect of curcumin on growth inhibition of HCC cells was analyzed through in vitro and in vivo experiments, and the expression levels of MARCH1, Bcl-2, VEGF, cyclin B1, cyclin D1, and JAK2/STAT3 signaling molecules were measured in HCC cells and the xenograft tumors in nude mice. Cell transfection with MARCH1 siRNAs or expression plasmid was used to explore the role of MARCH1 in the curcumin-induced growth inhibition of HCC cells. RESULTS: Curcumin inhibited cell proliferation, promoted apoptosis, and arrested the cell cycle at the G2/M phase in HCC cells with the decrease of Bcl-2, VEGF, cyclin B1, and cyclin D1 expression as well as JAK2 and STAT3 phosphorylation, resulting in the growth suppression of HCC cells. MARCH1 is highly expressed in HCC cells, and its expression was downregulated after curcumin treatment in a dose-dependent manner. The knockdown of MARCH1 by siRNA decreased the phosphorylation levels of JAK2 and STAT3 and inhibited the growth of HCC cells. In contrast, opposite results were observed when HCC cells overexpressed MARCH1. A xenograft tumor model in nude mice also showed that curcumin downregulated MARCH1 expression and decelerated the growth of transplanted HCC with the downregulation of JAK2/STAT3 signaling and functional molecules. The ADC value of MRI analysis showed that curcumin slowed down the progression of HCC. CONCLUSION: Our results demonstrated that curcumin may inhibit the activation of JAK2/STAT3 signaling pathway by downregulating MARCH1 expression, resulting in the growth suppression of HCC. MARCH1 may be a novel target of curcumin in HCC treatment.

Observation of Topological Hall Effect in a Chemically Complex Alloy.

The topological Hall effect (THE) is the transport response of chiral spin textures and thus can serve as a powerful probe for detecting and understanding these unconventional magnetic orders. So far, the THE is only observed in either noncentrosymmetric systems where spin chirality is stabilized by Dzyaloshinskii-Moriya interactions, or triangular-lattice magnets with Ruderman-Kittel-Kasuya-Yosida-type interactions. Here, a pronounced THE is observed in a Fe-Co-Ni-Mn chemically complex alloy with a simple face-centered cubic (fcc) structure across a wide range of temperatures and magnetic fields. The alloy is shown to have a strong magnetic frustration owing to the random occupation of magnetic atoms on the close-packed fcc lattice and the direct Heisenberg exchange interaction among atoms, as evidenced by the appearance of a reentrant spin glass state in the low-temperature regime and the first principles calculations. Consequently, THE is attributed to the nonvanishing spin chirality created by strong spin frustration under the external magnetic field, which is distinct from the mechanism responsible for the skyrmion systems, as well as geometrically frustrated magnets.

Emerging two dimensional metastable-phase oxides: insights and prospects in synthesis and catalysis.

Since the discovery of graphene, the development of new two-dimensional (2D) materials has received considerable interest. Recently, as a newly emerging member of the 2D family, 2D metastable-phase oxides that combine the unique advantages of metal oxides, 2D structures, and metastable-phase materials have shown enormous potential in various catalytic reactions. In this review, the potential of various 2D materials to form a metastable-phase is predicted. The advantages of 2D metastable-phase oxides for advanced applications, reliable methods of synthesizing 2D metastable-phase oxides, and the application of these oxides in different catalytic reactions are presented. Finally, the challenges associated with 2D metastable-phase oxides and future perspectives are discussed.

Cortical thickness and white matter microstructure predict freezing of gait development in Parkinson's disease.

The clinical applications of the association of cortical thickness and white matter fiber with freezing of gait (FoG) are limited in patients with Parkinson's disease (PD). In this retrospective study, using white matter fiber from diffusion-weighted imaging and cortical thickness from structural-weighted imaging of magnetic resonance imaging, we investigated whether a machine learning-based model can help assess the risk of FoG at the individual level in patients with PD. Data from the Parkinson's Disease Progression Marker Initiative database were used as the discovery cohort, whereas those from the Fujian Medical University Union Hospital Parkinson's Disease database were used as the external validation cohort. Clinical variables, white matter fiber, and cortical thickness were selected by random forest regression. The selected features were used to train the support vector machine(SVM) learning models. The median area under the receiver operating characteristic curve (AUC) was calculated. Model performance was validated using the external validation cohort. In the discovery cohort, 25 patients with PD were defined as FoG converters (15 men, mean age 62.1 years), whereas 60 were defined as FoG nonconverters (38 men, mean age 58.5 years). In the external validation cohort, 18 patients with PD were defined as FoG converters (8 men, mean age 66.9 years), whereas 37 were defined as FoG nonconverters (21 men, mean age 65.1 years). In the discovery cohort, the model trained with clinical variables, cortical thickness, and white matter fiber exhibited better performance (AUC, 0.67-0.88). More importantly, SVM-radial kernel models trained using random over-sampling examples, incorporating white matter fiber, cortical thickness, and clinical variables exhibited better performance (AUC, 0.88). This model trained using the above mentioned features was successfully validated in an external validation cohort (AUC, 0.91). Furthermore, the following minimal feature sets that were used: fractional anisotropy value and mean diffusivity value for right thalamic radiation, age at baseline, and cortical thickness for left precentral gyrus and right dorsal posterior cingulate gyrus. Therefore, machine learning-based models using white matter fiber and cortical thickness can help predict the risk of FoG conversion at the individual level in patients with PD, with improved performance when combined with clinical variables.

Core-Shell Design of Metastable Phase Catalyst Enables Highly-Performance Selective Hydrogenation.

Highly selective semihydrogenation of alkynes to alkenes is a highly important reaction for catalytic industry. Developing non-noble metal based catalysts with platinum group metal-like activity and selectivity is extremely crucial yet challenging. Metastable phase catalysts provide a potential candidate to realize high activity, yet the control of selectivity remains an open question. Here, this work first reports a metastable phase core-shell: face-centered cubic (fcc) phase Ag (10 at%) core-metastable hexagonal closest packed (hcp) phase Ni (90 at%) shell catalyst, which represents high conversion rate, high selectivity, and remarkable universality for the semihydrogenation of phenylacetylene and its derivatives. More impressively, a turnover frequency (TOF) value of 8241.8 h-1 is achieved, much higher than those of stable phase catalysts and reported platinum group metal based catalysts. Mechanistic investigation reveals that the surface of hcp Ni becomes more oxidized due to electron transfer from hcp Ni shell to fcc Ag core, which decreases the adsorption capacity of styrene on the metastable phase Ni surface, thus preventing full hydrogenation. This work has gained crucial research significance for the design of high performance metastable phase catalysts.

Association between 2,4-dichlorophenoxyacetic acid and cognitive impairment in older adults: a cross-sectional study from NHANES 2001-2002 and 2011-2014.

BACKGROUND: 2,4-Dichlorophenoxyacetic acid (2,4-D) is reported to be the most widely used herbicide in home and garden environments, rendering it commonly encountered in daily life. Despite being ubiquitous, there is a scarcity of studies that have comprehensively assessed the relationship between 2,4-D exposure and cognition using multiple models. OBJECTIVE: To explore the association between 2,4-D exposure and cognition among older American people. METHODS: This was a cross-sectional study that included 3 cycles of data from the National Health and Nutrition Examination Survey. Generalized linear models (GLMs), restricted cubic spline (RCS) regression, and generalized additive models (GAMs) were used to assess the relationship between exposure to 2,4-D and cognitive performance by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) word learning sub-test, Digit Symbol Substitution Test (DSST), and Animal Fluency Test (AFT). RESULTS: A total of 1364 older U.S. adults (60+ years) were included in the study. The GLMs revealed a negative association between median high levels (0.315-0.566 µg/L) of 2,4-D and cognitive impairment on the DSST and AFT, with multivariate-adjusted ORs of 0.403 (95% CI: 0.208-0.781, P = 0.009) and 0.396 (95% CI: 0.159-0.986, P = 0.047); the RCS regression and GAMs revealed a "U" shaped curve, the left part of which is consistent with the result of the GLMs. IMPACT STATEMENT: There is a U-shaped relationship between human urinary 2,4-D concentrations and cognitive impairment in older U.S. adults, especially in males, so controlling 2,4-D exposure within an appropriate range is particularly important for cognitive function.

Encoding Molecular Docking for Quantum Computers.

Molecular docking is important in drug discovery but is burdensome for classical computers. Here, we introduce Grid Point Matching (GPM) and Feature Atom Matching (FAM) to accelerate pose sampling in molecular docking by encoding the problem into quadratic unconstrained binary optimization (QUBO) models so that it could be solved by quantum computers like the coherent Ising machine (CIM). As a result, GPM shows a sampling power close to that of Glide SP, a method performing an extensive search. Moreover, it is estimated to be 1000 times faster on the CIM than on classical computers. Our methods could boost virtual drug screening of small molecules and peptides in future.

Heterogeneity in tertiary lymphoid structures predicts distinct prognosis and immune microenvironment characterizations of clear cell renal cell carcinoma.

BACKGROUND: Tertiary lymphoid structures (TLS) are organized aggregates of immune cells that develop postnatally in non-lymphoid tissues and are associated with pathological conditions. TLS typically comprise B-cell follicles containing and are encompassed by T- cell zones and dendritic cells. The prognostic and predictive value of TLS in the tumor microenvironment (TME) as potential mediators of antitumor immunity have gained interest. However, the precise relationship between localization and maturation of TLS and the clinical outcome of their presence in clear cell renal cell carcinoma (ccRCC) is yet to be elucidated. METHODS: Immunohistochemistry and multispectral fluorescence were used to evaluate the TLS heterogeneity along with TME cell-infiltrating characterizations. A thorough investigation of the prognostic implications of the TLS heterogeneity in 395 patients with ccRCC from two independent cohorts was conducted. Associations between TLS heterogeneity and immunologic activity were assessed by quantifying the immune cell infiltration. RESULTS: Infiltrated TLS were identified in 34.2% of the ccRCC samples (N=395). These TLS were found to be tumor-proximal, tumor-distal, or both in 37.8%, 74.1%, and 11.9% of the TLS-positive cases, respectively. A higher proportion of early TLS was found in tumor-distal TLS (p=0.016), while tumor-proximal TLS primarily comprised secondary follicle-like structures (p=0.004). In the main study cohort (Fudan University Shanghai Cancer Center, N=290), Kaplan-Meier analyses revealed a significant correlation between the presence of tumor-proximal TLS and improved progression-free survival (PFS, p<0.001) and overall survival (OS, p=0.002). Conversely, the presence of tumor-distal TLS was associated with poor PFS (p=0.02) and OS (p=0.021). These findings were further validated in an external validation set of 105 patients with ccRCC. Notably, the presence of mature TLS (namely secondary follicle-like TLS, with CD23+ germinal center) was significantly associated with better clinical outcomes in patients with ccRCC. Furthermore, novel nomograms incorporating the presence of tumor-proximal TLS demonstrated remarkable predictability for the 8-year outcomes of resected ccRCC (area under the curve >0.80). Additionally, ccRCC samples with tumor-distal TLS enriched with primary follicle-like TLS exhibited higher programmed death-ligand 1 tumor-associated macrophages levels and regulatory T cells infiltration in the tumor-distal region, indicative of a suppressive TME. CONCLUSION: This study for the first time elucidates the impact of TLS localization and maturation heterogeneities on the divergent clinical outcomes of ccRCC. The findings reveal that most TLS in ccRCC are located in the tumor-distal area and are associated with immature, immunosuppressive characterizations. Furthermore, our findings corroborate previous research demonstrating that tumor-proximal TLS were associated with favorable clinical outcomes.

Metastable Hexagonal-Phase Nickel with Ultralow Pt Content for an Efficient Alkaline/Seawater Hydrogen Evolution Reaction.

Hydrogen has been hailed as the core of the world's future energy architecture. It is imperative to develop catalysts with an efficient and sustained hydrogen evolution reaction (HER) to scale up alkaline/seawater electrolysis, yet significant difficulties and challenges, such as the high usage of precious metals, still remain. In this paper, a metastable-phase hexagonal close-packed (hcp) Ni-based catalyst with ultralow Pt content (3.1 at %) was designed, which has excellent catalytic performance in the alkaline/seawater HER. The optimal catalyst offers low overpotentials of 21 and 137 mV at 10 mA cm-2 and remains stable during operation for 100 and 300 h at this current density in 1.0 M KOH and real seawater, respectively. A mechanistic study shows that the metastable-phase Ni acts as an anchor site for OH-, which promotes the dissociation of water and greatly improves the formation rate of H2.

Protein Arginine Methyltransferases Refine the Classification of Clear Cell Renal Cell Carcinoma with Distinct Prognosis and Tumor Microenvironment Characteristics.

Background: Clear cell renal cell carcinoma (ccRCC) is an aggressive urological cancer that originates from the proximal tubular epithelium. As one of the most common post-translational modification, protein arginine methylation plays a pivotal role in various cancer-associated biological functions, especially in cancer immunity. Therefore, constructing a protein arginine methylation-related prognostic signature would be beneficial in guiding better personalized clinical management for patients with ccRCC. Methods: Based on the multi-omics profiling of the expression levels of eight protein arginine methyltransferases (PRMTs) in 763 ccRCC samples (from TCGA, CPTAC, EMBL, and ICGC databases), we established a scoring system with machine-learning algorithms to quantify the modification patterns on clinical and immunological characterizations of individual ccRCC patient, which was termed as PRMTScore. Moreover, we utilized two external clinical cohorts receiving immunotherapy (n=302) to validate the reliability of the PRMTScore system. Multiplex immunohistochemistry (mIHC) was performed to characterize the cellular composition of 30 paired ccRCC samples. The proteomic profiling of 232 ccRCC samples obtained from Fudan University Shanghai Cancer Center (FUSCC) was analyzed to validate the protein expression of PRMT5 in ccRCC. Finally, CCK-8, transwell, and wound healing assays were conducted to elucidate the role of PRMT5 in ccRCC in vitro. Results: A total of 763 ccRCC patients with available multi-omics profiling were stratified into two clusters (PRMTCluster A and B) with distinctive prognosis, genomic alterations, tumor microenvironment (TME) characteristics, and fundamental biological mechanisms. Subsequently, protein arginine methylation-related prognostic signature (PRMTScore) was constructed and consisted of SLC16A12, HRH2, F2RL3, and SAA1. The PRMTScore showed remarkable differences in outcomes, immune and stromal fractions, expressions of immune checkpoints, the abundance of immune cells, and immunotherapy response in ccRCC patients. Additionally, preliminary insights unveiled the tumor-suppressive role of PRMT5 in ccRCC, and the signal of PRMT5low significantly predicted aggressive prognosis and the high abundance of PD1+ CD8+ cells in ccRCC. Conclusion: We constructed a PRMTScore system, which showed the potent ability to assess the prognosis, TME characteristics, and immunotherapy response for patients with ccRCC. Moreover, this is the first study to propose that PRMT5 acts as a cancer suppressor in ccRCC.

Plasma proteomic profiling discovers molecular features associated with upper tract urothelial carcinoma.

Upper tract urothelial carcinoma (UTUC) is often diagnosed late and exhibits poor prognosis. Limited data are available on potential non-invasive biomarkers for disease monitoring. Here, we investigate the proteomic profile of plasma in 362 UTUC patients and 239 healthy controls. We present an integrated tissue-plasma proteomic approach to infer the signature proteins for identifying patients with muscle-invasive UTUC. We discover a protein panel that reflects lymph node metastasis, which is of interest in identifying UTUC patients with high risk and poor prognosis. We also identify a ten-protein classifier and establish a progression clock predicting progression-free survival of UTUC patients. Finally, we further validate the signature proteins by parallel reaction monitoring assay in an independent cohort. Collectively, this study portrays the plasma proteomic landscape of a UTUC cohort and provides a valuable resource for further biological and diagnostic research in UTUC.