The secreted micropeptide C4orf48 enhances renal fibrosis via an RNA-binding mechanism.

Renal interstitial fibrosis is an important mechanism in the progression of chronic kidney disease (CKD) to end-stage kidney disease. However, we lack specific treatments to slow or halt renal fibrosis. Ribosome profiling identified upregulation of a secreted micropeptide, C4orf48 (Cf48), in mouse diabetic nephropathy. Cf48 RNA and protein levels were upregulated in tubular epithelial cells in human and experimental CKD. Serum Cf48 levels were increased in human CKD and correlated with loss of kidney function, increasing CKD stage, and the degree of active interstitial fibrosis. Cf48 overexpression in mice accelerated renal fibrosis, while Cf48 gene deletion or knockdown by antisense oligonucleotides significantly reduced renal fibrosis in CKD models. In vitro, recombinant Cf48 (rCf48) enhanced TGF-ß1-induced fibrotic responses in renal fibroblasts and epithelial cells independent of Smad3 phosphorylation. Cellular uptake of Cf48 and its pro-fibrotic response in fibroblasts operated via the transferrin receptor. RNA immunoprecipitation-sequencing identified Cf48 binding to mRNA of genes involved in the fibrotic response, including Serpine1, Acta2, Ccn2, and Col4a1. rCf48 binds to the 3'-untranslated region of Serpine1 and increases mRNA half-life. We identify the secreted Cf48 micropeptide as a potential enhancer of renal fibrosis which operates as an RNA-binding peptide to promote the production of extracellular matrix.

Work experience of breastfeeding nurses returning to work after maternity leave in Liaoning Province of China: A qualitative study.

AIM: With the implementation of China's three-child policy in 2021, the nurse population faces an increase in the number of breastfeeding nurses returning to work after maternity leave. This study aims to describe the work experience of breastfeeding nurses returning to work after maternity leave. DESIGN: A qualitative descriptive design. METHODS: The data were collected through semi-structured interviews with eight nurses and analysed through Braun and Clarke's thematic analysis. RESULTS: Three themes and nine sub-themes emerged from the analysis of the interviews: changes in nurses (emotional changes, physical changes and changes in work); needs for an improving work environment (needs for a supportive workplace and nurse shortage); support for breastfeeding nurses (support from coworkers, support from the manager, support from the organisation and own need for work). PUBLIC CONTRIBUTION: This study highlighted that breastfeeding nurses need an adjustment period when they return to work after maternity leave. Successful breastfeeding requires support from coworkers, managers and the organisation. In addition, workplace support for breastfeeding and management for nurses needs to be improved.

Exploring Novel Antidepressants Targeting G Protein-Coupled Receptors and Key Membrane Receptors Based on Molecular Structures.

Major Depressive Disorder (MDD) is a complex mental disorder that involves alterations in signal transmission across multiple scales and structural abnormalities. The development of effective antidepressants (ADs) has been hindered by the dominance of monoamine hypothesis, resulting in slow progress. Traditional ADs have undesirable traits like delayed onset of action, limited efficacy, and severe side effects. Recently, two categories of fast-acting antidepressant compounds have surfaced, dissociative anesthetics S-ketamine and its metabolites, as well as psychedelics such as lysergic acid diethylamide (LSD). This has led to structural research and drug development of the receptors that they target. This review provides breakthroughs and achievements in the structure of depression-related receptors and novel ADs based on these. Cryo-electron microscopy (cryo-EM) has enabled researchers to identify the structures of membrane receptors, including the N-methyl-D-aspartate receptor (NMDAR) and the 5-hydroxytryptamine 2A (5-HT2A) receptor. These high-resolution structures can be used for the development of novel ADs using virtual drug screening (VDS). Moreover, the unique antidepressant effects of 5-HT1A receptors in various brain regions, and the pivotal roles of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and tyrosine kinase receptor 2 (TrkB) in regulating synaptic plasticity, emphasize their potential as therapeutic targets. Using structural information, a series of highly selective ADs were designed based on the different role of receptors in MDD. These molecules have the favorable characteristics of rapid onset and low adverse drug reactions. This review offers researchers guidance and a methodological framework for the structure-based design of ADs.

Environmental Evaluation on Toxicity, Toxic Mechanism, and Hydrolysis Behavior of Potential Acethydrazide Fungicide Candidates.

The evaluation of toxicity and environmental behavior of bioactive lead molecules is helpful in providing theoretical support for the development of agrochemicals, in line with the sustainable development of the ecological environment. In previous work, some acethydrazide structures have been demonstrated to exhibit excellent and broad-spectrum fungicidal activity; however, its environmental compatibility needs to be further elucidated if it is to be identified as a potential fungicide. In this project, the toxicity of fungicidal acethydrazide lead compounds F51, F58, F72, and F75 to zebrafish was determined at 10 µg mL-1 and 1 µg mL-1. Subsequently, the toxic mechanism of compound F58 was preliminarily explored by histologic section and TEM observations, which revealed that the gallbladder volume of common carp treated with compound F58 increased, accompanied by a deepened bile color, damaged plasma membrane, and atrophied mitochondria in gallbladder cells. Approximately, F58-treated hepatocytes exhibited cytoplasmic heterogeneity, with partial cellular vacuolation and mitochondrial membrane rupture. Metabolomics analysis further indicated that differential metabolites were enriched in the bile formation-associated steroid biosynthesis, primary bile acid biosynthesis, and taurine and hypotaurine metabolism pathways, as well as in the membrane function-related glycerophospholipid metabolism, linolenic acid metabolism, α-linolenic acid metabolism, and arachidonic acid metabolism pathways, suggesting that the acethydrazide F58 may have acute liver toxicity to common carp. Finally, the hydrolysis dynamics of F58 was investigated, with the obtained half-life of 5.82 days. The above results provide important guiding significance for the development of new green fungicides.

Self-assembly of hyperbranched DNA network structure for signal amplification detection of miRNA.

Catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR) can achieve the high sensitivity and rapid reaction rate in detecting miRNA. However, the amplification efficiency by these methods are limited. Herein, an enzyme-free and label-free hyperbranched DNA network structure (HDNS) was designed, in which localized catalytic hairpin assembly (LCHA) and hybridization chain reaction occurred in the horizontal axis and longitudinal axis, respectively, exhibiting intensive signal dual-amplification. miRNA-122 was selected as the target on behalf of miRNA to design the HDNS sensor. The fluorescence signal change of HDNS showed good linearity for detecting miRNA-122 in the concentration range from 0.1 nM to 60 nM with a limit of detection (LOD) at 37 pM which was lower than those of the sensors based on separate CHA or HCR. Afterwards, the HDNS sensor was applied to detect miRNA-122 in serum samples with the recovery rate in the range of 97.2 %-107 %. The sensor could distinguish different kinds of miRNAs, even the family members with high sequence homology, exhibiting excellent selectivity. This method provided a novel design strategy for improving the sensitivity and selectivity of DNA sensor for miRNA detection.

Corynoline Suppresses Osteoclastogenesis and Attenuates ROS Activities by Regulating NF-κB/MAPKs and Nrf2 Signaling Pathways.

Declining estrogen production in postmenopausal females causes osteoporosis in which the resorption of bone exceeds the increase in bone formation. Although clinical drugs are currently available for the treatment of osteoporosis, sustained medication use is accompanied by serious side effects. Corydalis bungeana Herba, a famous traditional Chinese herb listed in the Chinese Pharmacopoeia Commission, constitutes various traditional Chinese Medicine prescriptions, which date back to thousands of years. One of the primary active components of C. bungeana Turcz. is Corynoline (Cor), a plant isoquinoline alkaloid derived from the Corydalis species, which possesses bone metabolism disease therapeutic potential. The study aimed at exploring the effects as well as mechanisms of Cor on osteoclast formation and bone resorption. TRAcP staining, F-actin belt formation, and pit formation were employed for assessing the osteoclast function. Western blot, qPCR, network pharmacology, and docking analyses were used for analyzing the expression of osteoclast-associated genes and related signaling pathways. The study focused on investigating how Cor affected OVX-induced trabecular bone loss by using a mouse model. Cor could weaken osteoclast formation and function by affecting the biological receptor activators of NF-κB and its ligand at various concentrations. Mechanistically, Cor inhibited the NF-κB activation, and the MAPKs pathway stimulated by RANKL. Besides, Cor enhanced the protein stability of the Nrf2, which effectively abolished the RANKL-stimulated ROS generation. According to an OVX mouse model, Cor functions in restoring bone mass, improving microarchitecture, and reducing the ROS levels in the distal femurs, which corroborated with its in vitro antiosteoclastogenic effect. The present study indicates that Cor may restrain osteoclast formation and bone loss by modulating NF-κB/MAPKs and Nrf2 signaling pathways. Cor was shown to be a potential drug candidate that can be utilized for the treatment of osteoporosis.

Gasdermins: a dual role in pyroptosis and tumor immunity.

The gasdermin (GSDM) protein family plays a pivotal role in pyroptosis, a process critical to the body's immune response, particularly in combatting bacterial infections, impeding tumor invasion, and contributing to the pathogenesis of various inflammatory diseases. These proteins are adept at activating inflammasome signaling pathways, recruiting immune effector cells, creating an inflammatory immune microenvironment, and initiating pyroptosis. This article serves as an introduction to the GSDM protein-mediated pyroptosis signaling pathways, providing an overview of GSDMs' involvement in tumor immunity. Additionally, we explore the potential applications of GSDMs in both innovative and established antitumor strategies.

A half jaw panoramic stitching method of intraoral endoscopy images based on dental arch arrangement.

To address the challenges of repetitive and low-texture features in intraoral endoscopic images, a novel methodology for stitching panoramic half jaw images of the oral cavity is proposed. Initially, an enhanced self-attention mechanism guided by Time-Weighting concepts is employed to augment the clustering potential of feature points, thereby increasing the number of matched features. Subsequently, a combination of the Sinkhorn algorithm and Random Sample Consensus (RANSAC) is utilized to maximize the count of matched feature pairs, accurately remove outliers and minimize error. Last, to address the unique spatial alignment among intraoral endoscopic images, a wavelet transform and weighted fusion algorithm based on dental arch arrangement in intraoral endoscopic images have been developed, specifically for use in the fusion stage of intraoral endoscopic images. This enables the local oral images to be precisely positioned along the dental arch, and seamless stitching is achieved through wavelet transformation and a gradual weighted fusion technique. Experimental results demonstrate that this method yields promising outcomes in panoramic stitching tasks for intraoral endoscopic images, achieving a matching accuracy of 84.6% and a recall rate of 78.4% in a dataset with an average overlap of 35%. A novel solution for panoramic stitching of intraoral endoscopic images is provided by this method.

Establishment of reference measurement procedure and reference material for Treponema pallidum.

Stem cell preparations, as a new type of biotherapeutic product, should be subject to strict quality control in terms of cell safety. The testing of stem cell donors and blood products used in stem cell cultures, including but not limited to Treponema pallidum, is needed to reduce the risk of transmission of infectious diseases by stem cell medical products. In this study, a reference measurement procedure (RMP) was established based on digital PCR (dPCR). A homogeneous reference material (RM) of TP containing the tpp47 gene has been developed and characterized. Two dPCR assays (A and B) show ideal linearity within five orders of magnitude. The limit of quantification (LoQ) for both assays is 57 copies/reaction; the limits of detection (LoD) are 9.69 and 9.59 copies/reaction, respectively. The quantitative results of the established duplex dPCR assay are in good agreement. The RM of TP containing the tpp47 gene has been developed and characterized. The reference value with its expanded uncertainty is (2.21 ± 0.22) × 106 copies per µL determined by the established dPCR RMP. The developed dPCR was validated by applying a simulated stem cell matrix, and no impact was observed on the accuracy of dPCR. By providing an accurate reference value for the absolute copy number of the target gene, the developed RM can be used to improve the reliability of TP testing in the production of stem cell preparations and clinical diagnostics.

How the intrinsic functional connectivity patterns of the semantic network support semantic processing.

Semantic processing, a core of language comprehension, involves the activation of brain regions dispersed extensively across the frontal, temporal, and parietal cortices that compose the semantic network. To comprehend the functional structure of this semantic network and how it prepares for semantic processing, we investigated its intrinsic functional connectivity (FC) and the relation between this pattern and semantic processing ability in a large sample from the Human Connectome Project (HCP) dataset. We first defined a well-studied brain network for semantic processing, and then we characterized the within-network connectivity (WNC) and the between-network connectivity (BNC) within this network using a voxel-based global brain connectivity (GBC) method based on resting-state functional magnetic resonance imaging (fMRI). The results showed that 97.73% of the voxels in the semantic network displayed considerably greater WNC than BNC, demonstrating that the semantic network is a fairly encapsulated network. Moreover, multiple connector hubs in the semantic network were identified after applying the criterion of WNC > 1 SD above the mean WNC of the semantic network. More importantly, three of these connector hubs (i.e., the left anterior temporal lobe, angular gyrus, and orbital part of the inferior frontal gyrus) were reliably associated with semantic processing ability. Our findings suggest that the three identified regions use WNC as the central mechanism for supporting semantic processing and that task-independent spontaneous connectivity in the semantic network is essential for semantic processing.

Pluripotency state transition of embryonic stem cells requires the turnover of histone chaperone FACT on chromatin.

The differentiation of embryonic stem cells (ESCs) begins with the transition from the naive to the primed state. The formative state was recently established as a critical intermediate between the two states. Here, we demonstrate the role of the histone chaperone FACT in regulating the naive-to-formative transition. We found that the Q265K mutation in the FACT subunit SSRP1 increased the binding of FACT to histone H3-H4, impaired nucleosome disassembly in vitro, and reduced the turnover of FACT on chromatin in vivo. Strikingly, mouse ESCs harboring this mutation showed elevated naive-to-formative transition. Mechanistically, the SSRP1-Q265K mutation enriched FACT at the enhancers of formative-specific genes to increase targeted gene expression. Together, these findings suggest that the turnover of FACT on chromatin is crucial for regulating the enhancers of formative-specific genes, thereby mediating the naive-to-formative transition. This study highlights the significance of FACT in fine-tuning cell fate transition during early development.

Cloning and functional characterization of a cinnamate 4-hydroxylase gene from the hornwort Anthoceros angustus.

Hornworts, as the sister group to liverworts and mosses, comprise bryophytes, which are critical in understanding the evolution of key land plant traits. Cinnamate 4-hydroxylase (C4H) catalyzes the second step of the phenylpropanoid pathway to synthesize the precursor of numerous phenolic compounds, such as lignin and flavonoids. However, C4H in the hornwort Anthoceros angustus has not yet been cloned and functionally characterized. In this work, we screened the transcriptome database of A. angustus and identified one C4H gene, AnanC4H. AnanC4H maintained conserved cytochrome P450 domains with other typical plant C4Hs. Ultraviolet B irradiation and exogenous application of methyl jasmonate (MeJA) induced the expression of AnanC4H to varying degrees. The coding sequence of AnanC4H was expressed in yeast, and the recombinant proteins were isolated. The recombinant proteins of AnanC4H catalyzed the conversion of trans-cinnamic acid to p-coumaric acid and catalyzed the conversion of 3-hydroxycinnamic acid to caffeic acid. AnanC4H showed higher affinity for trans-cinnamic acid than for 3-hydroxycinnamic acid, but there was no significant difference in the catalytic efficiency of AnanC4H for the two substrates in vitro. Moreover, the expression of AnanC4H in Arabidopsis thaliana led to an increase in both the lignin content and the number of lignified cells in stems. However, there was no significant change in flavonoid content in transgenic Arabidopsis plants.

Single-cell RNA sequencing indicates cordycepin remodels the tumor immune microenvironment to enhance TIGIT blockade's anti-tumor effect in colon cancer.

Both preclinical and clinical studies have extensively proven the effectiveness of TIGIT inhibitors in tumor immunotherapy. However, it has been discovered that the presence of CD226 on tumor-infiltrating lymphocytes is crucial for the effectiveness of both anti-TIGIT therapy alone and when combined with anti-PD-1 therapy for tumors. In our investigation, we observed that cordycepin therapy significantly augmented the expression of the Cd226 gene. As a result, it was hypothesized that cordycepin therapy could enhance the effectiveness of anti-TIGIT therapy. By employing single-cell RNA sequencing analysis of immune cells in the MC38 tumor model, we discovered that cordycepin combined with anti-TIGIT therapy led to a significant increase in the proportion of NK cells within the tumor immune microenvironment. This increased NK cell activity and decreased the expression of inhibitory receptors and exhaustion marker genes. In the combination therapy group, CD8+ T cells had lower exhaustion state scores and increased cytotoxicity, indicating a better immune response. The combination therapy group increased DCs in the tumor immune microenvironment and promoted cellular interaction with CD4+ T cell and CD8+ T cell populations while decreasing Treg cell interactions. In conclusion, cordycepin with anti-TIGIT therapy in colon cancer could reshape the tumor immune microenvironment and have notable anticancer effects.

Atomic Insights into the Relationship between Molecular Structure and Dispersion Performance of Phenyl Polymer on Graphene Oxide.

The adsorption of organic polymers onto the surface of graphene oxide is known to improve its dispersibility in cement-based materials. However, the mechanism of this improvement at the atomic level is not yet fully understood. In this study, we employ a combination of DFT static calculation and umbrella sampling to explore the reactivity of polymers and investigate the effects of varying amounts of phenyl groups on their adsorption capacity on the surface of graphene oxide. Quantitative analysis is utilized to study the structural reconstruction and charge transfer caused by polymers from multiple perspectives. The interfacial reaction between the polymer and graphene oxide surface is further clarified, indicating that the adsorption process is promoted by hydrogen bond interactions and π-π stacking effects. This study sheds light on the adsorption mechanism of polymer-graphene oxide systems and has important implications for the design of more effective graphene oxide dispersants at the atomic level.

Exploring knowledge, attitude, and intention towards advance care planning, advance directive, and the patient self-determination act among hemodialysis patients.

BACKGROUND: Hemodialysis holds the highest incidence and prevalence rate in Taiwan globally. However, the implementation of advance care planning (ACP), advance directives (AD), and patient self-determination acts (PSDA) remains limited. Our objective was to examine the current status of ACP, AD and PSDA and potential opportunities for enhancement. METHODS: We developed a novel questionnaire to assess individuals' knowledge, attitudes, and intentions regarding ACP, AD, and PSDA. We also collected baseline characteristics and additional inquiries for correlation analysis to identify potential factors. Student's t-test and Analysis of Variance were employed to assess significance. RESULTS: Initially, a cohort of 241 patients was initially considered for inclusion in this study. Subsequently, 135 patients agreed to participate in the questionnaire study, resulting in 129 valid questionnaires. Among these respondents, 76 were male (59.9%), and 53 were female (41.1%). Only 13.2% had signed AD. A significant portion (85.3%) indicated that they had not discussed their dialysis prognosis with healthcare providers. Additionally, a mere 14% engaged in conversations about life-threatening decisions. Ninety percent believed that healthcare providers had not furnished information about ACP, and only 30% had discussed such choices with their families. The findings revealed that the average standardized score for ACP and AD goals was 84.97, while the attitude towards PSDA received a standardized score of 69.94. The intention score stood at 69.52 in standardized terms. Potential candidates for ACP initiation included individuals aged 50 to 64, possessing at least a college education, being unmarried, and having no history of diabetes. CONCLUSION: Patients undergoing hemodialysis exhibited a significant knowledge gap concerning ACP, AD, and the PSDA. Notably, a substantial number of dialytic patients had not received adequate information on these subjects. Nevertheless, they displayed a positive attitude, and a considerable proportion expressed a willingness to sign AD. It is imperative for nephrologists to take an active role in initiating ACP discussions with patients from the very beginning.

Cytophagic Histiocytic Panniculitis Presenting as Subcutaneous Nodules and Generalized Edema - A Case Report.

Background: Cytophagic histiocytic panniculitis (CHP) is a rare form of nodular panniculitis characterized by clinical manifestations such as skin erythema, nodules, fever, pancytopenia, liver failure, plasmacytosis, and hepatosplenomegaly. We report a case of CHP that was initially misdiagnosed as subcutaneous panniculitis-like T-cell lymphoma (SPTCL) but achieved complete remission with a favorable prognosis. Methods: A 38-year-old female presented to the dermatology department with a 15-day history of subcutaneous nodules, generalized edema, and continuous fever. Results: The patient was diagnosed as CHP combined with hemophagocytic syndrome by typical clinical manifestations, low value of SUVmax in positron emission tomography/computed tomography (PET/CT), benign differentiated T cells, negative TCR gene rearrangement, pancytopenia, abnormal coagulation, hypertriglyceridemia, decreased NK cell count, impaired liver function, and the presence of hemophagocytic cells observed in bone biopsy smears. Conclusion: In our case, the patient presented with hemophagocytic syndrome with hemodynamic instability, indicating an intensive treatment is needed. The diagnosis of SPTCL necessitates a meticulous process of differential diagnosis, along with the cautious administration of an aggressive chemotherapy regimen. Extended follow-up is imperative to ascertain the long-term outcomes.

Prevalence of and factors associated with symptoms consistent with a diagnosis of irritable bowel syndrome among resident physicians in standardised training in China: a cross-sectional study.

OBJECTIVES: This study aims to investigate the incidence of and factors associated with irritable bowel syndrome (IBS) among resident physicians in standardised training at eight traditional Chinese medicine (TCM) hospitals in China. DESIGN: A cross-sectional survey was administered to resident physicians in their first to third years of standardised training at eight TCM hospitals. PARTICIPANTS AND SETTING: A total of 514 resident physicians in standardised training were included. MEASURES: The questionnaire consisted of two sections, namely: section A collected basic information, and section B included the four-item Perceived Stress Scale (PSS-4), the Patient Health Questionnaire-4 (PHQ-4), the Pittsburgh Sleep Quality Index (PSQI) and the Rome IV criteria for IBS. Univariate and multivariate logistic regression models were constructed to assess the associations of age, sex, body mass index, stress, depression, anxiety, sleep quality and IBS. RESULTS: Of the included resident doctors, 77.2% were female, 20.4% were obese or underweight and 8.6% had symptoms consistent with a diagnosis of IBS. There were no statistically significant differences in lifestyle factors (night shift work, overtime work or working efficiency during the COVID-19 pandemic) between patients with IBS and participants without IBS (hereafter, non-IBS participants) (p=0.429, p=0.572 or p=0.464, respectively). Notably, compared with non-IBS participants, patients with IBS had significantly higher mean scores on the PSS-4 and PHQ-4 (p=0.028 and p=0.012, respectively); however, there was not a significant difference in PSQI scores between these two groups (p=0.079). Depression symptoms were significantly associated with IBS (unadjusted OR 0.498, 95% CI 0.265 to 0.935, p=0.030). CONCLUSION: These findings suggest that IBS is common among resident physicians in standardised training. Future studies should investigate emotional distress, especially stress and depression, in the development of prevention or treatment of IBS.

Trap Characterization Techniques for GaN-Based HEMTs: A Critical Review.

Gallium nitride (GaN) high-electron-mobility transistors (HEMTs) have been considered promising candidates for power devices due to their superior advantages of high current density, high breakdown voltage, high power density, and high-frequency operations. However, the development of GaN HEMTs has been constrained by stability and reliability issues related to traps. In this article, the locations and energy levels of traps in GaN HEMTs are summarized. Moreover, the characterization techniques for bulk traps and interface traps, whose characteristics and scopes are included as well, are reviewed and highlighted. Finally, the challenges in trap characterization techniques for GaN-based HEMTs are discussed to provide insights into the reliability assessment of GaN-based HEMTs.

The evolution of hot Jupiters revealed by the age distribution of their host stars.

The unexpected discovery of hot Jupiters challenged the classical theory of planet formation inspired by our solar system. Until now, the origin and evolution of hot Jupiters are still uncertain. Determining their age distribution and temporal evolution can provide more clues into the mechanism of their formation and subsequent evolution. Using a sample of 383 giant planets around Sun-like stars collected from the kinematic catalogs of the Planets Across Space and Time project, we find that hot Jupiters are preferentially hosted by relatively younger stars in the Galactic thin disk. We subsequently find that the frequency of hot Jupiters declines with age as [Formula: see text]. In contrast, the frequency of warm/cold Jupiters shows no significant dependence on age. Such a trend is expected from the tidal evolution of hot Jupiters' orbits, and our result offers supporting evidence using a large sample. We also perform a joint analysis on the planet frequencies in the stellar age-metallicity plane. The result suggests that the frequencies of hot Jupiters and warm/cold Jupiters, after removing the age dependence are both correlated with stellar metallicities as [Formula: see text] and [Formula: see text], respectively. Moreover, we show that the above correlations can explain the bulk of the discrepancy in hot Jupiter frequencies inferred from the transit and radial velocity (RV) surveys, given that RV targets tend to be more metal-rich and younger than transits.

Inflammatory response-based prognostication and personalized therapy decisions in clear cell renal cell cancer to aid precision oncology.

OBJECTIVE: The impact of inflammatory response on tumor development and therapeutic response is of significant importance in clear cell renal cell carcinoma (ccRCC). The customization of specialized prognostication approaches and the exploration of supplementary treatment options hold critical clinical implications in relation to the inflammatory response. METHODS: In the present study, unsupervised clustering was implemented on TCGA-KIRC tumors using transcriptome profiles of inflammatory response genes, which was then validated in two ccRCC datasets (E-MATB-1980 and ICGC) and two immunotherapy datasets (IMvigor210 and Liu et al.) via SubMap and NTP algorithms. Combining co-expression and LASSO analyses, inflammatory response-based scoring system was defined, which was evaluated in pan-cancer. RESULTS: Three reproducible inflammatory response subtypes (named IR1, IR2 and IR3) were determined and independently verified, each exhibiting distinct molecular, clinical, and immunological characteristics. Among these subtypes, IR2 had the best OS outcomes, followed by IR3 and IR1. In terms of anti-angiogenic agents, sunitinib may be appropriate for IR1 patients, while axitinib and pazopanib may be suitable for IR2 patients, and sorafenib for IR3 patients. Additionally, IR1 patients might benefit from anti-CTLA4 therapy. A scoring system called IRscore was defined for individual ccRCC patients. Patients with high IRscore presented a lower response rate to anti-PD-L1 therapy and worse prognostic outcomes. Pan-cancer analysis demonstrated the immunological features and prognostic relevance of the IRscore. CONCLUSION: Altogether, characterization of inflammatory response subtypes and IRscore provides a roadmap for patient risk stratification and personalized treatment decisions, not only in ccRCC, but also in pan-cancer.