Stage IA papillary and chromophobe renal cell carcinoma: effectiveness of cryoablation and partial nephrectomy.

OBJECTIVES: To evaluate the effectiveness of cryoablation compared to partial nephrectomy in patients with stage IA papillary and chromophobe renal cell carcinoma (pRCC; chRCC). MATERIAL AND METHODS: The 2004-2016 National Cancer Database was queried for adult patients with stage IA pRCC or chRCC treated with cryoablation or partial nephrectomy. Patients receiving systemic therapy or radiotherapy, as well as those with bilateral RCC or prior malignant disease were excluded. Overall survival (OS) was assessed using Kaplan-Meier plots and Cox proportional hazard regression models. Nearest neighbor propensity matching (1:1 cryoablation:partial nephrectomy, stratified for pRCC and chRCC) was used to account for potential confounders. RESULTS: A total of 11122 stage IA renal cell carcinoma patients were included (pRCC 8030; chRCC 3092). Cryoablation was performed in 607 (5.5%) patients, and partial nephrectomy in 10515 (94.5%) patients. A higher likelihood of cryoablation treatment was observed in older patients with non-private healthcare insurance, as well as in those with smaller diameter low-grade pRCC treated at non-academic centers in specific US geographic regions. After propensity score matching to account for confounders, there was no statistically significant difference in OS comparing cryoablation vs partial nephrectomy in patients with pRCC (HR = 1.3, 95% CI: 0.96-1.75, p = 0.09) and those with chRCC (HR = 1.38, 95% CI: 0.67-2.82, p = 0.38). CONCLUSION: After accounting for confounders, cryoablation, and partial nephrectomy demonstrated comparable OS in patients with stage IA papillary and chromophobe RCC. Cryoablation is a reasonable treatment alternative to partial nephrectomy for these histological RCC subtypes when radiologically suspected or diagnosed after biopsy. CRITICAL RELEVANCE STATEMENT: Cryoablation might be considered as an upfront treatment alternative to partial nephrectomy in patients with papillary and chromophobe stage IA renal cell carcinoma, as both treatment approaches yield comparable oncological outcomes. KEY POINTS: The utilization of cryoablation for stage IA papillary and chromophobe RCC increases. In the National Cancer Database, we found specific patterns of use of cryoablation. Cryoablation and partial nephrectomy demonstrate comparable outcomes after accounting for confounders.

The effect of gut microbiota-derived carnosine on mucosal integrity and immunity in broiler chickens challenged with Eimeria maxima.

In the first study, an in vitro culture system was developed to investigate the effects of carnosine on macrophage proinflammatory cytokine response using an established chicken macrophage cell line (CMC), gut integrity using a chicken intestinal epithelial cell line (IEC), muscle differentiation in quail muscle cells (QMCs) and primary chicken embryonic muscle cells (PMCs), and direct anti-parasitic effect against Eimeria maxima sporozoites. Cells to be tested were seeded in 24-well plates and treated with carnosine at 4 different concentrations (0.1, 1.0, and 10.0 µg). After 18 h of incubation, cells were harvested to measure gene expression of proinflammatory cytokines in CMC, tight junction (TJ) proteins in IECs, and muscle cell growth markers in QMCs and PMCs. In vivo trials were conducted to investigate the effect of dietary carnosine on disease parameters in broiler chickens challenged with E. maxima. One hundred and twenty male broiler chickens (0-day-old) were allocated into 4 treatment groups: 1) basal diet without infection (NC), 2) basal diet with E. maxima infection (PC), 3) carnosine at 10.0 mg/kg feed with PC (HCS), and 4) carnosine at 1.0 mg/kg feed with PC (LCS). All groups except NC were orally infected with E. maxima on d 14. Jejunal samples were collected for lesion scoring and jejunum gut tissues were used for transcriptomic analysis of cytokines and TJ proteins. In vitro, carnosine treatment significantly decreased IL-1ß gene expression in CMC following LPS stimulation. In vivo feeding studies showed that dietary carnosine increased BW and ADG of chickens in E. maxima-infected groups and reduced the jejunal lesion score and fecal oocyst shedding in HCS group. Jejunal IL-1ß, IL-8, and IFN-γ expression were suppressed in the HCS group compared to PC. The expression levels of claudin-1 and occludin in IECs were also increased in HCS following carnosine treatment. In conclusion, these findings highlight the beneficial effects of dietary carnosine supplementation on intestinal immune responses and gut barrier function in broiler chickens exposed to E. maxima infection.

Differential detection of chicken heterodimeric cytokines, interleukin 12 and 23 using their subunit-specific mouse monoclonal antibodies.

Interleukin-23 (IL-23) is a recently identified member of the IL-12 family of heterodimeric cytokines that play a critical role in regulating T helper cell function. IL-12 and IL-23 share a common p40 subunit, but differ in their p35 and p19 subunits, respectively. This difference in subunit composition results in distinct signaling pathways and biological functions for IL-12 and IL-23. Here, we report the functional characterization and immunomodulatory properties of chicken IL-12 and IL-23 using the panels of newly developed mouse anti-IL-12p40, IL-12p35-α and IL-23p19 monoclonal antibodies (mAbs). Western blot and indirect ELISA analysis demonstrated that the anti-chicken IL-12p40 mAbs (chIL-12p40; #10G10F4 and #10D8G2) bound to both recombinant proteins (IL-12 and IL-23), the anti-chicken IL-12p35 mAb (chIL-12p35; #2F1) specifically recognized recombinant IL-12, and the anti-chicken IL-23p19 mAb (chIL-23p19; #15A3) exhibited specificity for recombinant IL-23, without any cross-reactivity. Two ELISAs detecting specific chicken IL-12 (#10G10F4 and #2F1) or IL-23 (#10D8G2 and #15A3) were developed using newly developed mAb combinations, #10G10F4/ #2F1 and #10D8G2/#15A3 for IL-12 and IL-23, respectively, identified through a pairing assay. The levels of IL-12 and IL-23 in Resiquimod-848 stimulated-HD11 chicken macrophage cells were monitored over time using antigen-capture sandwich ELISA developed in this study. Furthermore, the levels of chicken IL-12 and IL-23 in the circulation of Eimeria maxima (E. maxima) and Eimeria tenella (E. tenella)-infected chickens were determined. Notably, the anti-chIL-12p40 mAbs (#10G10F4 and #10D8G2) neutralized the function of both chIL-12 and chIL-23 proteins, which share the p40 subunit, while the anti-chIL-23p19 mAb (#15A3) specifically neutralized chIL-23 protein in HD11 cells in vitro. The anti-chIL-12p35 mAb (#2F1), which is specific to the p35 subunit of IL-12, showed a partial neutralizing effect on chIL-12 protein. Collectively, our study validates the specificity and significance of 2 newly developed antigen-capture immunoassays for chIL-12 and chIL-23 which will expand our understanding of the functional characteristics of IL-12 and IL-23 and their association in normal and diseased chickens. These mAbs for each subunit, anti-chIL-12p35, anti-chIL-12p40 and anti-chIL-23p19, will serve as valuable immune reagents to elucidate host immune responses against disease pathogenesis in both fundamental and applied studies of avian species.

In vitro and genomic mining studies of anti-Clostridium perfringens Compounds Derived from Bacillus amyloliquefaciens.

Clostridium perfringens is an important opportunistic microorganism in commercial poultry production that is implicated in necrotic enteritis (NE) outbreaks. This disease poses a severe financial burden on the global poultry industry, causing estimated annual losses of $6 billion globally. The ban on in-feed antibiotic growth promoters has spurred investigations into approaches of alternatives to antibiotics, among which Bacillus probiotics have demonstrated varying degrees of effectiveness against NE. However, the precise mechanisms underlying Bacillus-mediated beneficial effects on host responses in NE remain to be further elucidated. In this manuscript, we conducted in vitro and genomic mining analysis to investigate anti-C. perfringens activity observed in the supernatants derived from 2 Bacillus amyloliquefaciens strains (FS1092 and BaD747). Both strains demonstrated potent anti-C. perfringens activities in in vitro studies. An analysis of genomes from 15 B. amyloliquefaciens, 11 B. velezensis, and 2 B. subtilis strains has revealed an intriguing clustering pattern among strains known to possess anti-C. perfringens activities. Furthermore, our investigation has identified 7 potential antimicrobial compounds, predicted as secondary metabolites through antiSMASH genomic mining within the published genomes of B. amyloliquefaciens species. Based on in vitro analysis, BaD747 may have the potential as a probiotic in the control of NE. These findings not only enhance our understanding of B. amyloliquefaciens's action against C. perfringens but also provide a scientific rationale for the development of novel antimicrobial therapeutic agents against NE.

Electrofluorochromic Hydrogels by Oligothiophene-Based Color-Tunable Fluorescent Dye Doping.

Soft electronic materials hold great promise for advancing flexible functional devices. Among the various soft materials available, hydrogels are particularly attractive for soft electronic device development due to their inherent properties, including transparency, shape adaptability through swelling/deswelling, and self-healing capabilities. Transparent hydrogels contribute to the creation of advanced smart devices such as sensors, smart windows, and anticounterfeiting technologies. Poly(vinyl alcohol) hydrogels are used as a platform for creating electrofluorochromic (EFC) devices in combination with oligothiophene-conjugated benzothiazole derivatives (OCBs) as fluorescent emitters. OCBs demonstrated excited-state intramolecular proton transfer (ESIPT) behavior with a large Stokes shift and emission changes responsive to solvent polarity and pH stimuli. Even in the solid state, OCBs exhibited strong fluorescence emission across a wide range of colors from blue to red, making them exceptionally well-suited for EFC device development. Their quantum yields in the powder state were obtained between 2.3% and 19.9%. Through the incorporation of OCBs into a PVA hydrogel (OCB@PVA), we achieved the successful fabrication of flexible EFC devices, including electronic paper and smart panels. When electric potentials (-2.4 and +2.4 V) were applied in OCB@PVA, fluorescence color changes were observed by an electrochemically induced pH change owing to electrohydrolysis of water. These devices demonstrated the potential of OCB@PVA hydrogels in the realm of flexible electronics. They could be used to create innovative and versatile devices with stimuli-responsive fluorescence properties.

A rare case of straight-back syndrome causing airway obstruction.

Straight-back syndrome is a rare congenital condition involving the loss of the normal dorsal curvature of the upper thoracic spine. This leads to flattening of the upper thoracic cavity, resulting in compression of the underlying vasculature and airways. In this case report, we discuss the management of an 18-year-old male with straight-back syndrome who was referred to our interventional pulmonary clinic for further management of his stridor and apneic events. A trial of airway stenting was done which resolved the patient's respiratory symptoms. Definitive surgical correction was not applicable due to other significant medical conditions, but tracheostomy provided a sustainable alternative treatment. Tracheostomy tube placement and airway stenting are reasonable alternatives to surgery for patients who experience airway obstruction due to straight-back syndrome. Stent placement may also relieve respiratory symptoms but is associated with a higher rate of complications.

Epidemiology, treatment and outcomes of primary renal sarcomas in adult patients.

To assess epidemiology, clinical presentation, treatment and overall survival of adult patients with renal sarcomas, the 2004-2016 SEER and NCDB databases were queried for adult patients diagnosed with renal sarcoma, calculating average annual age-adjusted incidence rates (AAIR) and average annual percentage change (AAPC) as well as overall survival (OS). In n = 1279 included renal sarcoma patients, AAIR remained constant over the study period (average 0.53 cases/1million; AAPC = 0.7, p = 0.6). Leiomyosarcoma (AAIR 0.14 cases/1 million) and malignant rhabdoid tumors (0.06 cases/1 million) were most common. Sarcoma histiotypes demonstrated considerable heterogeneity regarding demographic and cancer-related variables. Patients presented with advanced local extent (T3 33.3%; T4 14.2%) or distant metastases (29.1%) and commonly underwent surgical resection (81.6%). Longer OS was independently associated with younger age, female sex, lower comorbidity index, low T stage, negative surgical margins, absence of tumor necrosis or distant metastases and leiomyosarcoma histiotype (multivariable p < 0.05 each). Treatment efficacy varied according to sarcoma histiotype (interaction p < 0.001). Accounting for 0.25% of renal malignancies, renal sarcomas include 43 histiotypes with distinct epidemiology, clinical presentation, outcomes and sensitivity to systemic therapy, thereby reflecting soft-tissue sarcoma behavior. Renal sarcoma treatment patterns follow recommendations by renal cancer guidelines with surgical resection as the cornerstone of therapy.

Electrochemical Synthesis of Hollow Nanoparticles via Anodic Transformation of Metastable Core-Shell Precursors.

Recent advances in electrosynthesis of nanomaterials expanded structural and compositional variations accessible by the electrochemical method; however, reliably synthesizable morphological variety fall shy of that available by conventional solvothermal synthesis. In this communication, electrochemical preparation of surfactant-free hollow nanoparticles is demonstrated. By anodic conversion of core-shell precursors with metastable cores, hollowed nickel nanoparticles with uniform dimensions were synthesized and characterized. Implementation of TEM grids as the working electrodes, identical location tracking of the morphological evolution of single particles to anodic stimulus has been demonstrated. The synthesized nanoparticles were employed as catalysts for the alkaline hydrogen evolution reaction and exhibited catalytic rates that compare favorably to the Pt/C benchmark. This marks the first pure electrochemical synthesis of hollow nanoparticles and shall contribute to the structural diversification of electrosynthesized nanomaterials.

Driving Triplet State Population in Benzothioxanthene Imide Dyes: Let's twist!

Controlling the formation of photoexcited triplet states is critical for many (photo)chemical and physical applications. Here, we demonstrate that a permanent out-of-plane distortion of the benzothioxanthene imide (BTI) dye promotes intersystem crossing by increasing spin-orbit coupling. This manipulation was achieved through a subtle chemical modification, specifically the bay-area methylation. Consequently, this simple yet efficient approach expands the catalog of known molecular engineering strategies for synthesizing heavy atom-free, dual redox-active, yet still emissive and synthetically accessible photosensitizers.

Local Heating Induced Single-Crystalline Phase Control in Electrochemical Synthesis of Nanomaterials.

Development of synthetic strategies selectively yielding single crystals is desired owing to the facet-dependent chemical reactivities. Recent advances in electrochemical materials synthesis yielded nanomaterials that are surfactant-free, however, typically in polycrystalline forms. In this work, an electrochemical synthetic strategy selectively yielding single-crystalline nanoparticles by implementation of surface-selective heating of the working electrode is developed. Single crystals of copper, silver, gold, and platinum are afforded, and the crystallinity verified by electron diffraction and chemical reactivity studies. Notably, Cu (100) surface prepared by electrochemical synthesis yielded high single product selectivity when applied to electrochemical CO2 reduction catalysis.

Comprehensive genome­wide analysis of the chicken heat shock protein family: identification, genomic organization, and expression profiles in indigenous chicken with highly pathogenic avian influenza infection.

BACKGROUND: Heat shock proteins (HSPs) function as molecular chaperones with critical roles in chicken embryogenesis, immune response to infectious diseases, and response to various environmental stresses. However, little is known on HSP genes in chicken. In this study, to understand the roles of chicken HSPs, we performed genome-wide identification, expression, and functional analyses of the HSP family genes in chicken. RESULTS: A total of 76 HSP genes were identified in the chicken genome, which were further classified into eight distinct groups (I-VIII) based on phylogenetic tree analysis. The gene-structure analysis revealed that the members of each clade had the same or similar exon-intron structures. Chromosome mapping suggested that HSP genes were widely dispersed across the chicken genome, except in chromosomes 16, 18, 22, 25, 26, and 28-32, which lacked chicken HSP genes. On the other hand, the interactions among chicken HSPs were limited, indicating that the remaining functions of HSPs could be investigated in chicken. Moreover, KEGG pathway analysis showed that the HSP gene family was involved in the regulation of heat stress, apoptotic, intracellular signaling, and immune response pathways. Finally, RNA sequencing data revealed that, of the 76 chicken HSP genes, 46 were differentially expressed at 21 different growth stages in chicken embryos, and 72 were differentially expressed on post-infection day 3 in two indigenous Ri chicken lines infected with highly pathogenic avian influenza. CONCLUSIONS: This study provides significant insights into the potential functions of HSPs in chicken, including the regulation of apoptosis, heat stress, chaperone activity, intracellular signaling, and immune response to infectious diseases.

MicroRNA expression profiling in the lungs of genetically different Ri chicken lines against the highly pathogenic avian influenza H5N1 virus.

The highly pathogenic avian influenza (HPAI) virus triggers infectious diseases, resulting in pulmonary damage and high mortality in domestic poultry worldwide. This study aimed to analyze miRNA expression profiles after infection with the HPAI H5N1 virus in resistant and susceptible lines of Ri chickens.For this purpose, resistant and susceptible lines of Vietnamese Ri chicken were used based on the A/G allele of Mx and BF2 genes. These genes are responsible for innate antiviral activity and were selected to determine differentially expressed (DE) miRNAs in HPAI-infected chicken lines using small RNA sequencing. A total of 44 miRNAs were DE after 3 days of infection with the H5N1 virus. Computational program analysis indicated the candidate target genes for DE miRNAs to possess significant functions related to cytokines, chemokines, MAPK signaling pathway, ErBb signaling pathway, and Wnt signaling pathway. Several DE miRNA-mRNA matches were suggested to play crucial roles in mediating immune functions against viral evasion. These results revealed the potential regulatory roles of miRNAs in the immune response of the two Ri chicken lines against HPAI H5N1 virus infection in the lungs.

Chicken miR-148a-3p regulates immune responses against AIV by targeting the MAPK signalling pathway and IFN-γ.

MicroRNAs are involved in the immune systems of host animals and play essential roles in several immune-related pathways. In the current study, we investigated the systemic biological function of the chicken miRNA gga-miR-148a-3p on immune responses in chicken lines resistant and susceptible to HPAIV-H5N1. We found that gga-miR-148a expression in the lung tissue of H5N1-resistant chickens was significantly downregulated during HPAIV-H5N1 infection. Overexpression of gga-miR-148a and a reporter construct with wild type or mutant IFN-γ, MAPK11, and TGF-ß2 3' untranslated region (3' UTR)-luciferase in chicken fibroblasts showed that gga-miR-148a acted as a direct translational repressor of IFN-γ, MAPK11, and TGF-ß2 by targeting their 3' UTRs. Furthermore, miR-148a directly and negatively influenced the expression of signalling molecules related to the MAPK signalling pathway, including MAPK11, TGF-ß2, and Jun, and regulated antiviral responses through interferon-stimulated genes and MHC class I and class II genes by targeting IFN-γ. Downstream of the MAPK signalling pathway, several proinflammatory cytokines such as IL-1ß, IFN-γ, IL-6, TNF-α, IFN-ß, and interferon-stimulated genes were downregulated by the overexpression of gga-miR-148a. Our data suggest that gga-miR-148a-3p is an important regulator of the MAPK signalling pathway and antiviral response. These findings improve our understanding of the biological functions of gga-miR-148a-3p, the mechanisms underlying the MAPK signalling pathway, and the antiviral response to HPAIV-H5N1 infection in chickens as well as the role of gga-miR-148a-3p in improving the overall performance of chicken immune responses for breeding disease-resistant chickens.

Monolithic 3D integration of 2D materials-based electronics towards ultimate edge computing solutions.

Three-dimensional (3D) hetero-integration technology is poised to revolutionize the field of electronics by stacking functional layers vertically, thereby creating novel 3D circuity architectures with high integration density and unparalleled multifunctionality. However, the conventional 3D integration technique involves complex wafer processing and intricate interlayer wiring. Here we demonstrate monolithic 3D integration of two-dimensional, material-based artificial intelligence (AI)-processing hardware with ultimate integrability and multifunctionality. A total of six layers of transistor and memristor arrays were vertically integrated into a 3D nanosystem to perform AI tasks, by peeling and stacking of AI processing layers made from bottom-up synthesized two-dimensional materials. This fully monolithic-3D-integrated AI system substantially reduces processing time, voltage drops, latency and footprint due to its densely packed AI processing layers with dense interlayer connectivity. The successful demonstration of this monolithic-3D-integrated AI system will not only provide a material-level solution for hetero-integration of electronics, but also pave the way for unprecedented multifunctional computing hardware with ultimate parallelism.

Analysis of miRNA expression in the trachea of Ri chicken infected with the highly pathogenic avian influenza H5N1 virus.

BACKGROUND: Highly pathogenic avian influenza virus (HPAIV) is considered a global threat to both human health and the poultry industry. MicroRNAs (miRNA) can modulate the immune system by affecting gene expression patterns in HPAIV-infected chickens. OBJECTIVES: To gain further insights into the role of miRNAs in immune responses against H5N1 infection, as well as the development of strategies for breeding disease-resistant chickens, we characterized miRNA expression patterns in tracheal tissues from H5N1-infected Ri chickens. METHODS: miRNAs expression was analyzed from two H5N1-infected Ri chicken lines using small RNA sequencing. The target genes of differentially expressed (DE) miRNAs were predicted using miRDB. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were then conducted. Furthermore, using quantitative real-time polymerase chain reaction, we validated the expression levels of DE miRNAs (miR-22-3p, miR-146b-3p, miR-27b-3p, miR-128-3p, miR-2188-5p, miR-451, miR-205a, miR-203a, miR-21-3p, and miR-200a-3p) from all comparisons and their immune-related target genes. RESULTS: A total of 53 miRNAs were significantly expressed in the infection samples of the resistant compared to the susceptible line. Network analyses between the DE miRNAs and target genes revealed that DE miRNAs may regulate the expression of target genes involved in the transforming growth factor-beta, mitogen-activated protein kinase, and Toll-like receptor signaling pathways, all of which are related to influenza A virus progression. CONCLUSIONS: Collectively, our results provided novel insights into the miRNA expression patterns of tracheal tissues from H5N1-infected Ri chickens. More importantly, our findings offer insights into the relationship between miRNA and immune-related target genes and the role of miRNA in HPAIV infections in chickens.

Prolonged hydrogen production by engineered green algae photovoltaic power stations.

Interest in securing energy production channels from renewable sources is higher than ever due to the daily observation of the impacts of climate change. A key renewable energy harvesting strategy achieving carbon neutral cycles is artificial photosynthesis. Solar-to-fuel routes thus far relied on elaborately crafted semiconductors, undermining the cost-efficiency of the system. Furthermore, fuels produced required separation prior to utilization. As an artificial photosynthesis design, here we demonstrate the conversion of swimming green algae into photovoltaic power stations. The engineered algae exhibit bioelectrogenesis, en route to energy storage in hydrogen. Notably, fuel formation requires no additives or external bias other than CO2 and sunlight. The cellular power stations autoregulate the oxygen level during artificial photosynthesis, granting immediate utility of the photosynthetic hydrogen without separation. The fuel production scales linearly with the reactor volume, which is a necessary trait for contributing to the large-scale renewable energy portfolio.

A pile of pipelines: An overview of the bioinformatics software for metabarcoding data analyses.

Environmental DNA (eDNA) metabarcoding has gained growing attention as a strategy for monitoring biodiversity in ecology. However, taxa identifications produced through metabarcoding require sophisticated processing of high-throughput sequencing data from taxonomically informative DNA barcodes. Various sets of universal and taxon-specific primers have been developed, extending the usability of metabarcoding across archaea, bacteria and eukaryotes. Accordingly, a multitude of metabarcoding data analysis tools and pipelines have also been developed. Often, several developed workflows are designed to process the same amplicon sequencing data, making it somewhat puzzling to choose one among the plethora of existing pipelines. However, each pipeline has its own specific philosophy, strengths and limitations, which should be considered depending on the aims of any specific study, as well as the bioinformatics expertise of the user. In this review, we outline the input data requirements, supported operating systems and particular attributes of thirty-two amplicon processing pipelines with the goal of helping users to select a pipeline for their metabarcoding projects.