Efficacy Analysis of Arthroscopic Surgery Combined with Intra-articular Chitosan Injection for Stage II-III Knee Osteoarthritis in Patients with Abnormal Body Weight.

OBJECTIVE: Weight is an influential factor in knee osteoarthritis (KOA). However, the effect of abnormal body weight on chitosan's efficacy in treating KOA is unclear. This study aimed to explore the differences in the effectiveness of arthroscopic surgery combined with intra-articular chitosan injection for KOA in patients with abnormal body weight. METHODS: Patients with stage II-III KOA (Kellgren-Lawrence rating, K-L) undergoing arthroscopic surgery were recruited for this clinical study from January 2020 to September 2021. Based on body mass index (BMI) and intra-articular chitosan injection, patients with KOA undergoing arthroscopic surgery (138 patients) were divided into four groups: low-weight-non-injection (Lw-N, BMI <18.5); low-weight-chitosan injection (Lw-CS, BMI <18.5); overweight-non-injection (Ow-N, BMI ≥25); overweight-chitosan injection (Ow-CS, BMI ≥25). A 2-year follow-up was conducted to evaluate various indicators, including the visual analogue scale (VAS) and the Western Ontario and McMaster Universities osteoarthritis index score (WOMAC). Statistical analyses were performed using relevant parametric or non-parametric tests. RESULTS: In total, 138 patients with KOA were included in this study. There were no significant differences in gender, age, and incidence of chronic residual pain after arthroscopy among the four groups (p > 0.05). The proportion of patients undergoing subsequent knee arthroplasty during the 2-year follow-up period was significantly higher in the Ow-CS group (20/35) than in the Lw-CS group (12/39) (p < 0.05). The K-L rating showed an overall increasing trend over time, with the K-L rating in the Ow-N and Ow-CS groups significantly higher than that in the Lw-CS group at the final follow-up (p < 0.05). VAS and WOMAC scores significantly decreased at 1 and 3 months post-arthroscopy and then increased. One month after arthroscopy, VAS was significantly lower (p < 0.05) in the intra-articular chitosan injection groups (Lw-CS and Ow-CS) compared with the non-injection groups (Lw-N and Ow-N). VAS was lower in the Ow-CS group than in the Lw-CS group (p < 0.05). There was no significant difference in WOMAC between the intra-articular chitosan injection and non-injection groups at each time point (Lw-N vs. Lw-CS, Ow-N vs. Ow-CS, p > 0.05). CONCLUSION: Arthroscopic surgery combined with intra-articular chitosan injection shows short-term positive effects in treating KOA. Intra-articular chitosan injection appears to have a greater short-term pain relief effect in obese patients.

Nanoimprint-induced strain engineering of two-dimensional materials.

The high stretchability of two-dimensional (2D) materials has facilitated the possibility of using external strain to manipulate their properties. Hence, strain engineering has emerged as a promising technique for tailoring the performance of 2D materials by controlling the applied elastic strain field. Although various types of strain engineering methods have been proposed, deterministic and controllable generation of the strain in 2D materials remains a challenging task. Here, we report a nanoimprint-induced strain engineering (NISE) strategy for introducing controllable periodic strain profiles on 2D materials. A three-dimensional (3D) tunable strain is generated in a molybdenum disulfide (MoS2) sheet by pressing and conforming to the topography of an imprint mold. Different strain profiles generated in MoS2 are demonstrated and verified by Raman and photoluminescence (PL) spectroscopy. The strain modulation capability of NISE is investigated by changing the imprint pressure and the patterns of the imprint molds, which enables precise control of the strain magnitudes and distributions in MoS2. Furthermore, a finite element model is developed to simulate the NISE process and reveal the straining behavior of MoS2. This deterministic and effective strain engineering technique can be easily extended to other materials and is also compatible with common semiconductor fabrication processes; therefore, it provides prospects for advances in broad nanoelectronic and optoelectronic devices.

Long noncoding RNAs underlie multiple domestication traits and leafhopper resistance in soybean.

The origin and functionality of long noncoding RNA (lncRNA) remain poorly understood. Here, we show that multiple quantitative trait loci modulating distinct domestication traits in soybeans are pleiotropic effects of a locus composed of two tandem lncRNA genes. These lncRNA genes, each containing two inverted repeats, originating from coding sequences of the MYB genes, function in wild soybeans by generating clusters of small RNA (sRNA) species that inhibit the expression of their MYB gene relatives through post-transcriptional regulation. By contrast, the expression of lncRNA genes in cultivated soybeans is severely repressed, and, consequently, the corresponding MYB genes are highly expressed, shaping multiple distinct domestication traits as well as leafhopper resistance. The inverted repeats were formed before the divergence of the Glycine genus from the Phaseolus-Vigna lineage and exhibit strong structure-function constraints. This study exemplifies a type of target for selection during plant domestication and identifies mechanisms of lncRNA formation and action.

ACBP4-WRKY70-RAP2.12 module positively regulates submergence-induced hypoxia response in Arabidopsis thaliana.

ACYL-CoA-BINDING PROTEINs (ACBPs) play crucial regulatory roles during plant response to hypoxia, but their molecular mechanisms remain poorly understood. Our study reveals that ACBP4 serves as a positive regulator of the plant hypoxia response by interacting with WRKY70, influencing its nucleocytoplasmic shuttling in Arabidopsis thaliana. Furthermore, we demonstrate the direct binding of WRKY70 to the ACBP4 promoter, resulting in its upregulation and suggesting a positive feedback loop. Additionally, we pinpointed a phosphorylation site at Ser638 of ACBP4, which enhances submergence tolerance, potentially by facilitating WRKY70's nuclear shuttling. Surprisingly, a natural variation in this phosphorylation site of ACBP4 allowed A. thaliana to adapt to humid conditions during its historical demographic expansion. We further observed that both phosphorylated ACBP4 and oleoyl-CoA can impede the interaction between ACBP4 and WRKY70, thus promoting WRKY70's nuclear translocation. Finally, we found that the overexpression of orthologous BnaC5.ACBP4 and BnaA7.WRKY70 in Brassica napus increases submergence tolerance, indicating their functional similarity across genera. In summary, our research not only sheds light on the functional significance of the ACBP4 gene in hypoxia response, but also underscores its potential utility in breeding flooding-tolerant oilseed rape varieties.

The super-pangenome of Populus unveils genomic facets for its adaptation and diversification in widespread forest trees.

Understanding the underlying mechanisms and links between genome evolution and adaptive innovations stands as a key goal in evolutionary studies. Poplars, among the world's most widely distributed and cultivated trees, exhibit extensive phenotypic diversity and environmental adaptability. In this study, we present a genus-level super-pangenome comprising 19 Populus genomes, revealing the likely pivotal role of private genes in facilitating local environmental and climate adaptation. Through the integration of pangenomes with transcriptomes, methylomes, and chromatin accessibility mapping, we unveil that the evolutionary trajectories of pangenes and duplicated genes are closely linked to local genomic landscapes of regulatory and epigenetic architectures, notably CG methylation in gene-body regions. Further comparative genomic analyses have enabled the identification of 142 202 structural variants across species that intersect with a significant number of genes and contribute substantially to both phenotypic and adaptive divergence. We have experimentally validated a ∼180-bp presence/absence variant affecting the expression of the CUC2 gene, crucial for leaf serration formation. Finally, we developed a user-friendly web-based tool encompassing the multi-omics resources associated with the Populus super-pangenome (http://www.populus-superpangenome.com). Together, the present pioneering super-pangenome resource in forest trees not only aids in the advancement of breeding efforts of this globally important tree genus but also offers valuable insights into potential avenues for comprehending tree biology.

Deciphering PDH1's role in mung bean domestication: a genomic perspective on pod dehiscence.

Mung bean (Vigna radiata) stands as a crucial legume crop in Asia, contributing to food security. However, our understanding of the underlying genetic foundation governing domesticated agronomic traits, especially those linked to pod architecture, remains largely unexplored. In this study, we delved into the genomic divergence between wild and domesticated mung bean varieties, leveraging germplasm obtained from diverse sources. Our findings unveiled pronounced variation in promoter regions (35%) between the two mung bean subpopulations, suggesting substantial changes in gene expression patterns during domestication. Leveraging transcriptome analysis using distinct reproductive stage pods and subpopulations, we identified candidate genes responsible for pod and seed architecture development, along with Genome-Wide Association Studies (GWAS) and Quantitative Trait Locus (QTL) analysis. Notably, our research conclusively confirmed PDH1 as a parallel domesticated gene governing pod dehiscence in legumes. This study imparts valuable insights into the genetic underpinnings of domesticated agronomic traits in mung bean, and simultaneously highlighting the parallel domestication of pivotal traits within the realm of legume crops.

Exploring m6A-linked aging genes in osteoarthritis and broad cancer spectrum: Prospects for diagnostic and therapeutic advancements.

Osteoarthritis (OA) is a prevalent degenerative joint disease that significantly impacts individuals and healthcare systems worldwide. However, the exploration of N6-methyladenosine (m6A)-related aging genes in OA pathogenesis remains largely underexplored. This study aimed to elucidate the role of m6A-related aging genes in OA and to develop a robust diagnostic model based on their expression profiles. Leveraging publicly available gene expression datasets, we conducted consensus clustering to categorize OA into distinct subtypes, guided by the expression patterns of m6A-related aging genes. Utilizing XGBoost, a cutting-edge machine learning approach, we identified key diagnostic genes and constructed a predictive model. Our investigation extended to the immune functions of these genes, shedding light on potential therapeutic targets and underlying regulatory mechanisms. Our analysis unveiled specific OA subtypes, each marked by unique expression profiles of m6A-related aging genes. We pinpointed a set of pivotal diagnostic genes, offering potential therapeutic avenues. The developed diagnostic model exhibited exceptional capability in distinguishing OA patients from healthy controls. To corroborate our computational findings, we performed quantitative real-time polymerase chain reaction analyses on two cell lines: HC-OA (representing adult osteoarthritis cells) and C-28/I2 (representative of normal human chondrocytes). The gene expression patterns observed were consistent with our bioinformatics predictions, further validating our initial results. In conclusion, this study underscores the significance of m6A-related aging genes as promising biomarkers for diagnosis and prognosis, as well as potential therapeutic targets in OA. Although these findings are encouraging, further validation and functional analyses are crucial for their clinical application.

A graph-based pan-genome of Brassica oleracea provides new insights into its domestication and morphotype diversification.

The domestication of Brassica oleracea has resulted in diverse morphological types with distinct patterns of organ development. Here we report a graph-based pan-genome of B. oleracea constructed from high-quality genome assemblies of different morphotypes. The pan-genome harbors over 200 structural variant hotspot regions enriched in auxin- and flowering-related genes. Population genomic analyses revealed that early domestication of B. oleracea focused on leaf or stem development. Gene flows resulting from agricultural practices and variety improvement were detected among different morphotypes. Selective-sweep and pan-genome analyses identified an auxin-responsive small auxin up-regulated RNA gene and a CLAVATA3/ESR-RELATED family gene as crucial players in leaf-stem differentiation during the early stage of B. oleracea domestication and the BoKAN1 gene as instrumental in shaping the leafy heads of cabbage and Brussels sprouts. Our pan-genome and functional analyses further revealed that variations in the BoFLC2 gene play key roles in the divergence of vernalization and flowering characteristics among different morphotypes, and variations in the first intron of BoFLC3 are involved in fine-tuning the flowering process in cauliflower. This study provides a comprehensive understanding of the pan-genome of B. oleracea and sheds light on the domestication and differential organ development of this globally important crop species.

Erythroid anion Exchanger-1 (band 3) transports nitrite for nitric oxide metabolism.

Nitrite (NO2-) interacts with hemoglobin (Hb) in various ways to regulate blood flow. During hypoxic vasodilation, nitrite is reduced by deoxyHb to yield nitric oxide (NO). While NO, a hydrophobic gas, could freely diffuse across the cell membrane, how the reactant nitrite anion could permeate through the red blood cell (RBC) membrane remains unclear. We hypothesized that Cl-/HCO3- anion exchanger-1 (AE1; band 3) abundantly embedded in the RBC membrane could transport NO2-, as HCO3- and NO2- exhibit similar hydrated radii. Here, we monitored NO/N2O3 generated from NO2- inside human RBCs by DAF-FM fluorophore. NO2-, not NO3-, increased intraerythrocytic DAF-FM fluorescence. To test the involvement of AE1-mediated transport in intraerythrocytic NO/N2O3 production from nitrite, we lowered Cl- or HCO3- in the RBC-incubating buffer by 20 % and indeed observed slower rise of the DAF-FM fluorescence. Anti-extracellular AE1, but not anti-intracellular AE1 antibodies, reduced the rates of NO formation from nitrite. The AE1 blocker DIDS similarly reduced the rates of NO/N2O3 production from nitrite in a dose-dependent fashion, confirming that nitrite entered RBCs through AE1. Nitrite inside the RBCs reacted with both deoxyHb and oxyHb, as evidenced by 6.1 % decrease in deoxyHb, 14.7 % decrease in oxyHb, and 20.7 % increase in methemoglobin (metHb). Lowering Cl- in the milieu equally delayed metHb production from nitrite-oxyHb and nitrite-deoxyHb reactions. Thus, AE1-mediated NO2- transport facilitates NO2--Hb reactions inside the red cells, supporting NOx metabolism in circulation.

Pan-genome analysis of 13 Malus accessions reveals structural and sequence variations associated with fruit traits.

Structural variations (SVs) and copy number variations (CNVs) contribute to trait variations in fleshy-fruited species. Here, we assemble 10 genomes of genetically diverse Malus accessions, including the ever-green cultivar 'Granny Smith' and the widely cultivated cultivar 'Red Fuji'. Combining with three previously reported genomes, we assemble the pan-genome of Malus species and identify 20,220 CNVs and 317,393 SVs. We also observe CNVs that are positively correlated with expression levels of the genes they are associated with. Furthermore, we show that the noncoding RNA generated from a 209 bp insertion in the intron of mitogen-activated protein kinase homology encoding gene, MMK2, regulates the gene expression and affects fruit coloration. Moreover, we identify overlapping SVs associated with fruit quality and biotic resistance. This pan-genome uncovers possible contributions of CNVs to gene expression and highlights the role of SVs in apple domestication and economically important traits.

Shot noise in a strange metal.

Strange-metal behavior has been observed in materials ranging from high-temperature superconductors to heavy fermion metals. In conventional metals, current is carried by quasiparticles; although it has been suggested that quasiparticles are absent in strange metals, direct experimental evidence is lacking. We measured shot noise to probe the granularity of the current-carrying excitations in nanowires of the heavy fermion strange metal YbRh2Si2. When compared with conventional metals, shot noise in these nanowires is strongly suppressed. This suppression cannot be attributed to either electron-phonon or electron-electron interactions in a Fermi liquid, which suggests that the current is not carried by well-defined quasiparticles in the strange-metal regime that we probed. Our work sets the stage for similar studies of other strange metals.

Cerebral Abscess Infected by Nocardia gipuzkoensis.

Purpose: Nocardia gipuzkoensis is a novel species that solely identified in patients with pulmonary infections by far. Growing evidence showed the excellent performance of metagenomics next-generation sequencing (mNGS) on pathogenic identification, especially for new species. Here, we described the first case of an elderly female patient suddenly suffering from neurological disorders owing to N. gipuzkoensis infection. And linezolid could effectively treat N. gipuzkoensis infection. Patients and Methods: The results of imaging, laboratory cultures, and mNGS, as well as therapeutic process are shared. Results: An elderly female patient suddenly suffered from neurological disorders with dysphasia and right limb trembles under no obvious causes. Subsequently, she was diagnosed as intracranial space-occupying lesions by magnetic resonance imaging (MRI). The isolate from brain secretion was further identified as N. gipuzkoensis through mNGS. The targeted therapy with linezolid according to the antimicrobial susceptibility was used to treat cerebral abscess induced by N. gipuzkoensis. During the follow-up, no relapse was observed for the patient after surgery for 104 days. Conclusion: Cerebral abscess induced by N. gipuzkoensis is rare disorder with high mortality. mNGS has been identified as a promising tool in pathogen diagnosis for timely therapy. Linezolid as one of the antimicrobial drugs could effectively treat N. gipuzkoensis infection and prevent adverse outcomes.

Metallic Micro-Nano Network-Based Soft Transparent Electrodes: Materials, Processes, and Applications.

Soft transparent electrodes (TEs) have received tremendous interest from academia and industry due to the rapid development of lightweight, transparent soft electronics. Metallic micro-nano networks (MMNNs) are a class of promising soft TEs that exhibit excellent optical and electrical properties, including low sheet resistance and high optical transmittance, as well as superior mechanical properties such as softness, robustness, and desirable stability. They are genuinely interesting alternatives to conventional conductive metal oxides, which are expensive to fabricate and have limited flexibility on soft surfaces. This review summarizes state-of-the-art research developments in MMNN-based soft TEs in terms of performance specifications, fabrication methods, and application areas. The review describes the implementation of MMNN-based soft TEs in optoelectronics, bioelectronics, tactile sensors, energy storage devices, and other applications. Finally, it presents a perspective on the technical difficulties and potential future possibilities for MMNN-based TE development.

Chromosome level genome assembly of colored calla lily (Zantedeschia elliottiana).

The colored calla lily is an ornamental floral plant native to southern Africa, belonging to the Zantedeschia genus of the Araceae family. We generated a high-quality chromosome-level genome of the colored calla lily, with a size of 1,154 Mb and a contig N50 of 42 Mb. We anchored 98.5% of the contigs (1,137 Mb) into 16 pseudo-chromosomes, and identified 60.18% of the sequences (694 Mb) as repetitive sequences. Functional annotations were assigned to 95.1% of the predicted protein-coding genes (36,165). Additionally, we annotated 469 miRNAs, 1,652 tRNAs, 10,033 rRNAs, and 1,677 snRNAs. Furthermore, Gypsy-type LTR retrotransposons insertions in the genome are the primary factor causing significant genome size variation in Araceae species. This high-quality genome assembly provides valuable resources for understanding genome size differences within the Araceae family and advancing genomic research on colored calla lily.

Natural variation in the SVP contributes to the pleiotropic adaption of Arabidopsis thaliana across contrasted habitats.

Coordinated plant adaptation involves the interplay of multiple traits driven by habitat-specific selection pressures. Pleiotropic effects, wherein genetic variants of a single gene control multiple traits, can expedite such adaptations. Until present, only a limited number of genes have been reported to exhibit pleiotropy. Here, we create a recombinant inbred line (RIL) population derived from two Arabidopsis thaliana (A. thaliana) ecotypes originating from divergent habitats. Using this RIL population, we identify an allelic variation in a MADS-box transcription factor, SHORT VEGETATIVE PHASE (SVP), which exerts a pleiotropic effect on leaf size and drought-versus-humidity tolerance. Further investigation reveals that a natural null variant of the SVP protein disrupts its normal regulatory interactions with target genes, including GRF3, CYP707A1/3, and AtBG1, leading to increased leaf size, enhanced tolerance to humid conditions, and changes in flowering time of humid conditions in A. thaliana. Remarkably, polymorphic variations in this gene have been traced back to early A. thaliana populations, providing a genetic foundation and plasticity for subsequent colonization of diverse habitats by influencing multiple traits. These findings advance our understanding of how plants rapidly adapt to changing environments by virtue of the pleiotropic effects of individual genes on multiple trait alterations.

Effective regeneration of rat sciatic nerve using nanofibrous scaffolds containing rat ADSCs with controlled release of rhNGF and melatonin molecules for the treatment of peripheral injury model.

Different therapeutic strategies have been designed and developed for the repair and regeneration of peripheral nerve injury (PNI) tissue as a result of advancements in tissue engineering and regenerative medicine. Due to its versatility, controlled delivery and administration of multifunctional therapeutic agents can be regarded of as an effective strategy in treating nerve injury. In this study, melatonin (Mel) molecules and recombinant human nerve growth factor (rhNGF) were loaded on the surface and in the core of polycaprolactone/chitosan (PCL/CS) blended nanofibrous scaffold. To simulate the in vivo microenvironment, a dual-delivery three-dimensional (3-D) nanofibrous matrix was developed and the in vitro neural development of stem cell differentiation process was systematically examined. The microscopic technique with acridine orange and ethidium bromide (AO/EB) fluorescence staining method was used to establish the adipose-derived stem cells (ADSCs) differentiation and cell-cell communications, which demonstrated that the effective differentiation of the ADSCs with nanofibrous matrix. As investigated observations, ADSCs differentiation was further evident through cell migration assay and gene expression analysis. According to the biocompatibility analysis, the nanofibrous matrix did not trigger any adverse immunological reactions. Based on these characteristics, a 5-week in vivo investigation examined the potential of the developed nanofibrous matrix in the regeneration of sciatic nerve of rats. Additionally, compared to the negative control group, the electrophysiological and walking track analyses demonstrated improved sciatic nerve regeneration. This study demonstrates the nanofibrous matrix's ability to regenerate peripheral nerves.

Histological characteristics of exercise-induced skeletal muscle remodelling.

This study aims to analyse the pathological features of skeletal muscle injury repair by using rats to model responses to different exercise intensities. Eighty-four rats were randomly divided into five groups for treadmill exercise. The short-term control, low-intensity, medium-intensity and high-intensity groups underwent gastrocnemius muscle sampling after 6, 8 and 12 weeks of exercise. The long-term high-intensity group underwent optical coherence tomography angiography and sampling after 18 weeks of exercise. RNA sequencing was performed on the muscle samples, followed by the corresponding histological staining. Differentially expressed genes were generally elevated at 6 weeks in the early exercise stage, followed by a decreasing trend. Meanwhile, the study demonstrated a negative correlation between time and the gene modules involved in vascular regulation. The modules associated with muscle remodelling were positively correlated with exercise intensity. Although the expression of many genes associated with common angiogenesis was downregulated at 8, 12 and 18 weeks, we found that muscle tissue microvessels were still increased, which may be closely associated with elevated sFRP2 and YAP1. During muscle injury-remodelling, angiogenesis is characterized by significant exercise time and exercise intensity dependence. We find significant differences in the spatial distribution of angiogenesis during muscle injury-remodelling, which be helpful for the future achievement of spatially targeted treatments for exercise-induced muscle injuries.

Pan-cancer analyses reveal multi-omic signatures and clinical implementations of the forkhead-box gene family.

BACKGROUND: Forkhead box (FOX) proteins belong to one of the largest transcription factor families and play crucial roles in the initiation and progression of cancer. Prior research has linked several FOX genes, such as FOXA1 and FOXM1, to the crucial process of carcinogenesis. However, the overall picture of FOX gene family across human cancers is far from clear. METHODS: To investigate the broad molecular signatures of the FOX gene family, we conducted study on multi-omics data (including genomics, epigenomics and transcriptomics) from over 11,000 patients with 33 different types of human cancers. RESULTS: Pan-cancer analysis reveals that FOX gene mutations were found in 17.4% of tumor patients with a substantial cancer type-dependent pattern. Additionally, high expression heterogeneity of FOX genes across cancer types was discovered, which can be partially attributed to the genomic or epigenomic alteration. Co-expression network analysis reveals that FOX genes may exert functions by regulating the expression of both their own and target genes. For a clinical standpoint, we provided 103 FOX gene-drug target-drug predictions and found FOX gene expression have potential survival predictive value. All of the results have been included in the FOX2Cancer database, which is freely accessible at http://hainmu-biobigdata.com/FOX2Cancer. CONCLUSION: Our findings may provide a better understanding of roles FOX genes played in the development of tumors, and help to offer new avenues for uncovering tumorigenesis and unprecedented therapeutic targets.

Effects of greater erythroid Cl-/HCO3- transporter (band 3) expression on ventilation and gas exchange during exhaustive exercise.

Band 3 protein is a Cl-/[Formula: see text] transporter on the red blood cell (RBC) surface with an important role in CO2 excretion. Greater band 3 expression by roughly 20% is found in people with the GP.Mur blood type. Intriguingly, a disproportional percentage of those with GP.Mur excel in field-and-track sports. Could higher band 3 activity benefit an individual's physical performance? This study explored the impact of GP.Mur/higher band 3 expression on ventilation and gas exchange during exhaustive exercise. We recruited 36 nonsmoking, elite male athletes (36.1% GP.Mur) from top sports universities to perform incremental exhaustive treadmill cardiopulmonary exercise testing (CPET). We analyzed CPET data with respect to absolute running time and to individual's %running time and %maximal O2 uptake. We found persistently higher respiratory frequencies and slightly lower tidal volume in GP.Mur athletes, resulting in a slightly larger increase of ventilation as the workload intensified. The expiratory duty cycle (Te/Ttot) was persistently longer and inspiratory duty cycle (Ti/Ttot) was persistently shorter for GP.Mur subjects throughout the run. Consequently, end-tidal pressure of carbon dioxide ([Formula: see text], a surrogate marker for alveolar and arterial CO2 tension-[Formula: see text] and [Formula: see text]) was lower in the GP.Mur athletes during the early stages of exercise. In conclusion, athletes with GP.Mur and higher band 3 expression hyperventilate more during exercise in a pattern that uses a greater fraction of time for expiration than inspiration to increase the rate of CO2 excretion than increased tidal volume. This greater ventilation response reduced Pco2 and may help to extend exercise capacity in high-level sports.NEW & NOTEWORTHY Higher expression of the Cl-/[Formula: see text] transporter band 3 anion exchanger-1 (AE1) on the red blood cell membrane, as in people with the GP.Mur blood type, increases the rate of CO2 excretion during exercise.

Epigenetically regulated lncRNAs dissect the intratumoural heterogeneity and facilitate immune evasion of glioblastomas.

Background: Glioblastomas are the most common and malignant central nervous system (CNS) tumors that occupied a highly heterogeneous tumor microenvironment (TIME). Long noncoding RNAs (lncRNAs), whose expression can be modified by DNA methylation, are emerging as critical regulators in the immune system. However, knowledge about the epigenetic changes in lncRNAs and their contribution to the immune heterogeneity of glioma is still lacking. Methods: In this study, we integrated paired methylome and transcriptome datasets of glioblastomas and identified 2 robust immune subtypes based on lncRNA methylation features. The immune characteristics of glioma subtypes were compared. Furthermore, immune-related lncRNAs were identified and their relationships with immune evasion were evaluated. Results: Glioma immunophenotypes exhibited distinct immune-related characteristics as well as clinical and epigenetic features. 149 epigenetically regulated (ER) lncRNAs were recognized that possessed inverse variation in epigenetic and transcriptional levels between glioma subtypes. Immune-related lncRNAs were further identified through the investigation of their correlation with immune cell infiltrations and immune-related pathways. In particular, the 'Hot' glioma subtype with higher immunoactivity while a worse survival outcome was found to character immune evasion features. We finally prioritized candidate ER lncRNAs associated with immune evasion markers and response to glioma immunotherapy. Among them, CD109-AS1 and LINC02447 were validated as novel immunoevasive biomarkers for glioma through in vitro experiments. Conclusion: In summary, our study systematically reveals the crosstalk among DNA methylation, lncRNA, and immune regulation in glioblastomas, and will facilitate the development of epigenetic immunotherapy approaches.