L-histidine attenuates NEFA-induced inflammatory responses by suppressing Gab2 expression.

Non-esterified fatty acids (NEFAs), key to energy metabolism, may become pathogenic at elevated levels, potentially eliciting immune reactions. Our laboratory's findings of reduced L-histidine in ketotic states, induced by heightened NEFA concentrations, suggest an interrelation with NEFA metabolism. This observation necessitates further investigation into the mitigating role of L-histidine on the deleterious effects of NEFAs. Our study unveiled that elevated NEFA concentrations hinder the proliferation of Bovine Mammary Epithelial Cells (BMECs) and provoke inflammation in a dose-responsive manner. Delving into L-histidine's influence on BMECs, RNA sequencing revealed 2124 genes differentially expressed between control and L-histidine-treated cells, with notable enrichment in pathways linked to proliferation and immunity, such as cell cycle and TNF signaling pathways. Further analysis showed that L-histidine treatment positively correlated with an increase in EdU-555-positive cell rate and significantly suppressed IL-6 and IL-8 levels (p < 0.05) compared to controls. Crucially, concurrent treatment with high NEFA and L-histidine normalized the number of EdU-555-positive cells and cytokine expression to control levels. Investigating the underlying mechanisms, Gab2 (Grb2-associated binder 2) emerged as a central player; L-histidine notably reduced Gab2 expression, while NEFA had the opposite effect (p < 0.05). Gab2 overexpression escalated nitric oxide (NO) production and IL6 and IL8 expression. However, L-histidine addition to Gab2-overexpressing cells resulted in NO concentrations indistinguishable from controls. Our findings collectively indicate that L-histidine can counteract NEFA-induced inflammation in BMECs by inhibiting Gab2 expression, highlighting its therapeutic potential against NEFA-related metabolic disturbances.

Genetic parameters for udder conformation traits derived from Cartesian coordinates generated by robotic milking systems in North American Holstein cattle.

Udder conformation is directly related to milk yield, cow health, workability, and welfare. Automatic milking systems (AMS, also known as milking robots) have become popular worldwide, and the number of dairy farms adopting these systems have increased considerably over the past years. In each milking visit, AMS record the location of the 4 teats as Cartesian coordinates in a xyz plan, which can then be used to derive udder conformation traits. AMS generate a large amount of per milking visit data for individual cows, which contribute to an accurate assessment of important traits such as udder conformation without the addition of human classifier errors (in subjective scoring systems). Therefore, the primary objectives of this study were to estimate genomic-based genetic parameters for udder conformation traits derived from AMS records in North American Holstein cattle and to assess the genetic correlation between the derived traits for evaluating the feasibility of multi-trait genomic selection for breeding cows that are more suitable for milking in AMS. The Cartesian teat coordinates measured during each milking visit were collected by 36 milking robots in 4,480 Holstein cows from 2017 to 2021, resulting in 5,317,488 records. A total of 4,118 of these Holstein cows were also genotyped for 57,600 single nucleotide polymorphisms. Five udder conformation traits were derived: udder balance (UB, mm), udder depth (UD, mm), front teat distance (FTD, mm), rear teat distance (RTD, mm), and distance front-rear (DFR, mm). In addition, 2 traits directly related to cow productivity in the system were added to the study: daily milk yield (DY) and milk electroconductivity (EC; as an indicator of mastitis). Variance components and genetic parameters for UB, UD, FTD, RTD, DFR, DY, and EC were estimated based on repeatability animal models. The estimates of heritability (±standard error, SE) for UB, UD, FTD, RTD, DFR, DY, and EC were 0.41 ± 0.02, 0.79 ± 0.01, 0.53 ± 0.02, 0.40 ± 0.02, 0.65 ± 0.02, 0.20 ± 0.02, and 0.46 ± 0.02, respectively. The repeatability estimates (±SE) for UB, UD, FTD, RTD, and DFR were 0.82 ± 0.01, 0.93 ± 0.01, 0.87 ± 0.01, 0.83 ± 0.01, and 0.88 ± 0.01, respectively. The strongest genetic correlations were observed between the FTD and RTD (0.54 ± 0.03), UD and DFR (-0.47 ± 0.03), DFR and FTD (0.32 ± 0.03), and UD and FTD (-0.31 ± 0.03). These results suggest that udder conformation traits derived from Cartesian coordinates from AMS are moderately to highly heritable. Furthermore, the moderate genetic correlations between these traits should be considered when developing selection sub-indexes. The most relevant genetic correlations between traits related to cow milk productivity and udder conformation traits were between UD and EC (-0.25 ± 0.03) and between DFR and DY (0.30 ± 0.04), in which both genetic correlations are favorable. These findings will contribute to the design of genomic selection schemes for improving udder conformation in North American Holstein cattle, especially in precision dairy farms.

Exercise-Induced Reduction of IGF1R Sumoylation Attenuates Neuroinflammation in APP/PS1 Transgenic Mice.

INTRODUCTION: Alzheimer's Disease (AD), a progressive neurodegenerative disorder, is marked by cognitive deterioration and heightened neuroinflammation. The influence of Insulin-like Growth Factor 1 Receptor (IGF1R) and its post-translational modifications, especially sumoylation, is crucial in understanding the progression of AD and exploring novel therapeutic avenues. OBJECTIVES: This study investigates the impact of exercise on the sumoylation of IGF1R and its role in ameliorating AD symptoms in APP/PS1 mice, with a specific focus on neuroinflammation and innovative therapeutic strategies. METHODS: APP/PS1 mice were subjected to a regimen of moderate-intensity exercise. The investigation encompassed assessments of cognitive functions, alterations in hippocampal protein expressions, neuroinflammatory markers, and the effects of exercise on IGF1R and SUMO1 nuclear translocation. Additionally, the study evaluated the efficacy of KPT-330, a nuclear export inhibitor, as an alternative to exercise. RESULTS: Exercise notably enhanced cognitive functions in AD mice, possibly through modulations in hippocampal proteins, including Bcl-2 and BACE1. A decrease in neuroinflammatory markers such as IL-1ß, IL-6, and TNF-α was observed, indicative of reduced neuroinflammation. Exercise modulated the nuclear translocation of SUMO1 and IGF1R in the hippocampus, thereby facilitating neuronal regeneration. Mutant IGF1R (MT IGF1R), lacking SUMO1 modification sites, showed reduced SUMOylation, leading to diminished expression of pro-inflammatory cytokines and apoptosis. KPT-330 impeded the formation of the IGF1R/RanBP2/SUMO1 complex, thereby limiting IGF1R nuclear translocation, inflammation, and neuronal apoptosis, while enhancing cognitive functions and neuron proliferation. CONCLUSION: Moderate-intensity exercise effectively mitigates AD symptoms in mice, primarily by diminishing neuroinflammation, through the reduction of IGF1R Sumoylation. KPT-330, as a potential alternative to physical exercise, enhances the neuroprotective role of IGF1R by inhibiting SUMOylation through targeting XPO1, presenting a promising therapeutic strategy for AD.

[Influence of anterior fracture line on anterior cortical reduction loss after cephalomedullary nail fixation in intertrochanteric fractures].

Objective: To investigate the position of the anterior fracture line in AO/Orthopaedic Trauma Association (AO/OTA) type A2 unstable intertrochanteric fractures and its impact on the incidence of anterior cortical reduction loss after cephalomedullary nail fixation. Methods: A clinical data of 95 patients with intertrochanteric fractures who met the selection criteria between April 2020 and February 2023 was retrospectively analyzed. All patients were treated with cephalomedullary nail fixation, and the intra- and post-operative imaging data were complete. Among them, there were 37 males and 58 females. The age ranged from 61 to 97 years, with an average of 79.6 years. The time from injury to operation ranged from 7 hours to 11 days, with an average of 2.8 days. According to the 2018-AO/OTA classification standard, there were 39 cases of type 31-A2.2 and 56 cases of type 31-A2.3. Intraoperative fluoroscopy was used to record the number of patients with satisfactory fracture alignment. The preoperative CT data were imported into Mimics17.0 software to simulate the fracture reduction and measure the distance between the anterior fracture line and the intertrochanteric line bony ridge. The fractures were classified as transcapsular fractures, extra-capsular fractures, and intra-capsular fractures according to the distance. CT three-dimensional reconstruction was performed within 2 weeks after operation to observe the number of patients with anterior cortical reduction loss. The postoperative anterior cortical reduction loss incidence in patients with satisfactory fracture alignment, and the relationship between postoperative anterior cortical reduction loss and the position of the anterior fracture line were observed. Results: There were 52 cases (54.7%) of transcapsular fractures, 24 cases (25.3%) of extra-capsular fractures, and 19 cases (20.0%) of intra-capsular fractures. Among them, 41 of the 52 transcapsular fractures had satisfactory fracture alignment, and 4 (9.8%) of them experienced anterior cortical reduction loss after operation; 19 of the 24 extra-capsular fractures had satisfactory fracture alignment, and no anterior cortical reduction loss occurred; 16 of the 19 intra-capsular fractures had satisfactory fracture alignment, and 7 (43.8%) of them experienced anterior cortical reduction loss after operation. There was a significant difference in the incidence of anterior cortical reduction loss between groups ( χ 2=8.538， P=0.003). All patients were followed up 3-26 months (mean, 9 months). Among them, 91 cases had fracture healing, and 4 cases had nonunion. Conclusion: In AO/OTA type A2 unstable intertrochanteric fractures, where the anterior fracture line is located within the joint capsule, there is a high risk of anterior cortical reduction loss after operation.

Wet 3D printing of biodegradable porous scaffolds to enable room-temperature deposition modeling of polymeric solutions for regeneration of articular cartilage.

Tissue engineering has emerged as an advanced strategy to regenerate various tissues using different raw materials, and thus it is desired to develop more approaches to fabricate tissue engineering scaffolds to fit specific yet very useful raw materials such as biodegradable aliphatic polyester like poly (lactide-co-glycolide) (PLGA). Herein, a technique of 'wet 3D printing' was developed based on a pneumatic extrusion three-dimensional (3D) printer after we introduced a solidification bath into a 3D printing system to fabricate porous scaffolds. The room-temperature deposition modeling of polymeric solutions enabled by our wet 3D printing method is particularly meaningful for aliphatic polyester, which otherwise degrades at high temperature in classic fuse deposition modeling. As demonstration, we fabricated a bilayered porous scaffold consisted of PLGA and its mixture with hydroxyapatite for regeneration of articular cartilage and subchondral bone. Long-termin vitroandin vivodegradation tests of the scaffolds were carried out up to 36 weeks, which support the three-stage degradation process of the polyester porous scaffold and suggest faster degradationin vivothanin vitro. Animal experiments in a rabbit model of articular cartilage injury were conducted. The efficacy of the scaffolds in cartilage regeneration was verified through histological analysis, micro-computed tomography (CT) and biomechanical tests, and the influence of scaffold structures (bilayerversussingle layer) onin vivotissue regeneration was examined. This study has illustrated that the wet 3D printing is an alternative approach to biofabricate tissue engineering porous scaffolds based on biodegradable polymers.

Comparative Analysis of the Complete Mitochondrial Genomes of Three Sisoridae (Osteichthyes, Siluriformes) and the Phylogenetic Relationships of Sisoridae.

The family Sisoridae is one of the largest and most diverse Asiatic catfish families, with most species occurring in the water systems of the Qinhai-Tibetan Plateau and East Himalayas. At present, the phylogenetic relationship of the Sisoridae is relatively chaotic. In this study, the mitochondrial genomes (mitogenomes) of three species Creteuchiloglanis kamengensis, Glaridoglanis andersonii, and Exostoma sp. were systematically investigated, the phylogenetic relationships of the family were reconstructed and to determine the phylogenetic position of Exostoma sp. within Sisoridae. The lengths of the mitogenomes' sequences of C. kamengensis, G. andersonii, and Exostoma sp. were 16,589 bp, 16,531 bp, and 16,529 bp, respectively. They all contained one identical control region (D-loop), two ribosomal RNAs (rRNAs), 13 protein-coding genes (PCGs) and 22 transfer RNA (tRNA) genes. We applied two approaches, Bayesian Inference (BI) and Maximum Likelihood (ML), to construct phylogenetic trees. Our findings revealed that the topological structure of both ML and BI trees exhibited significant congruence. Specifically, the phylogenetic tree strongly supports the monophyly of Sisorinae and Glyptosternoids and provides new molecular biological data to support the reconstruction of phylogenetic relationships with Sisoridae. This study is of great scientific value for phylogenetic and genetic variation studies of the Sisoridae.

Hydrolysis reactivity reveals significant seasonal variation in the composition of organic peroxides in ambient PM2.5.

Atmospheric organic peroxides (POs) play a key role in the formation of O3 and secondary organic aerosol (SOA), impacting both air quality and human health. However, there still remain technical challenges in investigating the reactivity of POs in ambient aerosols due to the instability and lack of standards for POs, impeding accurate evaluation of their environmental impacts. In the present study, we conducted the first attempt to categorize and quantify POs in ambient PM2.5 through hydrolysis, which is an important transformation pathway for POs, thus revealing the reactivities of various POs. POs were generally categorized into hydrolyzable POs (HPO) and unhydrolyzable POs (UPO). HPO were further categorized into three groups: short-lifetime HPO (S-HPO), intermediate-lifetime HPO (I-HPO), and long-lifetime HPO (L-HPO). S-HPO and L-HPO are typically formed from Criegee intermediate (CI) and RO2 radical reactions, respectively. Results show that L-HPO are the most abundant HPO, indicating the dominant role of RO2 pathway in HPO formation. Despite their lower concentration compared to L-HPO, S-HPO make a major contribution to the HPO hydrolysis rate due to their faster rate constants. The hydrolysis of PM2.5 POs accounts for 19 % of the nighttime gas-phase H2O2 growth during the summer observation, constituting a noteworthy source of gas-phase H2O2 and contributing to the atmospheric oxidation capacity. Seasonal and weather conditions significantly impact the composition of POs, with HPO concentrations in summer being significantly higher than those in winter and elevated under rainy and nighttime conditions. POs are mainly composed of HPO in summer, while in winter, POs are dominated by UPO.

Life cycle assessment of post-combustion carbon capture and storage for the ultra-supercritical pulverized coal power plant.

In this paper, different emerging post-combustion technologies, i.e., monoethanolamine (MEA), aqueous ammonia, pressure swing adsorption (PSA), temperature swing adsorption (TSA), membrane and calcium looping, were applied to an ultra-supercritical coal-fired power plant for carbon capture. A 'cradle-to-grave' life cycle assessment (LCA) was conducted to evaluate the technical performance and environmental impacts of the power plant with six emerging carbon capture technologies. Carbon capture significantly influences the impact categories directly associated with flue gas emission. The application of carbon capture reduced the GWP in the range of 49-75 %. TAP also reduced in the range of 18-51 %. However, the human toxicity potential, eutrophication potential, ecotoxicity potential and particulate matter formation potential increased due to energy and resource consumption in the upstream and downstream processes. For the life cycle water consumption potential, it decreased by 8 % with calcium looping, whereas it increased in the range of 36-75 % with other post-combustion technologies. The highest reduction in GWP and the least reduction in power efficiency was observed in calcium looping because of the high-temperature heat recovery from flue gas and elimination of complex solvent manufacturing. The plant with aqueous ammonia and membrane separation had the second and third highest reductions in GWP. In addition, the lowest values for TAP, FEP, and MEP were obtained in the membrane system. With MEA for CO2 capture, the total GWP value of the plant is slightly higher than these three technologies mentioned above, and the highest HTPc, FETP, and METP can be observed in this case. TSA and PSA have the most significant environmental impacts in most categories due to higher energy requirements.

A Mesoporous Silica-Loaded Multi-Functional Hydrogel Enhanced Tendon Healing via Immunomodulatory and Pro-Regenerative Effects.

Tendon injuries are pervasive orthopedic injuries encountered by the general population. Nonetheless, recovery after severe injuries, such as Achilles tendon injury, is limited. Consequently, there is a pressing need to devise interventions, including biomaterials, that foster tendon healing. Regrettably, tissue engineering treatments have faced obstacles in crafting appropriate tissue scaffolds and efficacious nanomedical approaches. To surmount these hurdles, an innovative injectable hydrogel (CP@SiO2), comprising puerarin and chitosan through in situ self-assembly, is pioneered while concurrently delivering mesoporous silica nanoparticles for tendon healing. In this research, CP@SiO2 hydrogel is employed for the treatment of Achilles tendon injuries, conducting extensive in vivo and in vitro experiments to evaluate its efficacy. This reults demonstrates that CP@SiO2 hydrogel enhances the proliferation and differentiation of tendon-derived stem cells, and mitigates inflammation through the modulation of macrophage polarization. Furthermore, using histological and behavioral analyses, it is found that CP@SiO2 hydrogel can improve the histological and biomechanical properties of injured tendons. This findings indicate that this multifaceted injectable CP@SiO2 hydrogel constitutes a suitable bioactive material for tendon repair and presents a promising new strategy for the clinical management of tendon injuries.

Comparative Metabolomic Profiling of L-Histidine and NEFA Treatments in Bovine Mammary Epithelial Cells.

Non-esterified fatty acids (NEFAs) are pivotal in energy metabolism, yet high concentrations can lead to ketosis, a common metabolic disorder in cattle. Our laboratory observed lower levels of L-histidine in cattle suffering from ketosis, indicating a potential interaction between L-histidine and NEFA metabolism. This relationship prompted us to investigate the metabolomic alterations in bovine mammary epithelial cells (BMECs) induced by elevated NEFA levels and to explore L-histidine's potential mitigating effects. Our untargeted metabolomic analysis revealed 893 and 160 metabolite changes in positive and negative models, respectively, with VIP scores greater than 1 and p-values below 0.05. Notable metabolites like 9,10-epoxy-12-octadecenoic acid were upregulated, while 9-Ethylguanine was downregulated. A pathway analysis suggested disruptions in fatty acid and steroid biosynthesis pathways. Furthermore, L-histidine treatment altered 61 metabolites in the positive model and 34 in the negative model, with implications for similar pathways affected by NEFA. Overlaying differential metabolites from both conditions uncovered a potential key mediator, 1-Linoleoylglycerophosphocholine, which was regulated in opposite directions by NEFA and L-histidine. Our study uncovered that both NEFA L- and histidine metabolomics analyses pinpoint similar lipid biosynthesis pathways, with 1-Linoleoylglycerophosphocholine emerging as a potential key metabolite mediating their interaction, a discovery that may offer insights for therapeutic strategies in metabolic diseases.

Arctigenin induces activated HSCs quiescence via AMPK-PPARγ pathway to ameliorate liver fibrosis in mice.

Arctigenin (ATG), a traditional Chinese herbal medicine, is a natural lignan compound extracted from the seeds of burdock (Arctium lappa L, Asteraceae). As a natural product with multiple biological activities, the effect and mechanism of ATG against liver fibrosis are not fully elucidated yet. In current work, we first discovered that ATG could improve CCl4-induced liver injury reflected by lower plasma ALT and AST levels, liver coefficient and pathological scoring of ballooning. Furthermore, it also could reduce the positive areas of Masson, Sirius red and α-SMA staining, inhibit the expression of fibrosis-related genes (Col1a1, Col3a1, Acta2), and decrease the content of hydroxyproline, indicated ATG treatment had benefits in alleviating CCl4-induced liver fibrosis. In vitro, we observed that ATG can inhibit collagen production stimulated by TGF-ß1 in LX2 cells. By analysis of the information obtained from SymMap and GeneCards databases and in vitro validation experiments, ATG was proven to be an indirect PPARγ agonist and its effect on collagen production was dependent on PPARγ. Subsequently, we confirmed that ATG activating AMPK was the contributor of its effect on PPARγ and collagen production. Finally, the transformation of activated hepatic stellate cells was determined after treated with ATG, in which ATG treatment could return activated LX2 cells to quiescence because of the elevated quiescent markers and lipid droplets. Our work has highlighted the potential of ATG in the treatment of liver fibrosis and clarified that ATG can activate AMPK/PPARγ pathway to restore the activated hepatic stellate cell to quiescence thereby improving liver fibrosis.

Strontium-Doped Hydroxyapatite Coating Improves Osteo/Angiogenesis for Ameliorative Graft-Bone Integration via the Macrophage-Derived Cytokines-Mediated Integrin Signal Pathway.

Polyethylene terephthalate (PET) artificial ligaments, renowned for their superior mechanical properties, have been extensively adopted in anterior cruciate ligament (ACL) reconstruction surgeries. However, the inherent bio-inertness of PET introduces formidable barriers to graft-bone integration, a critical aspect of rehabilitation. Previous interventions, ranging from surface roughening to chemical modifications, have aimed to address this challenge; however, consistently effective techniques for inducing graft-bone integration remain scarce. Our study employed advanced surface-coating methodologies to introduce strontium-doped hydroxyapatite (SrHA) onto PET ligaments. Detailed scanning electron microscopy (SEM) examinations revealed a uniform and integrative coating of SrHA on PET fibers. Furthermore, spectroscopic analysis confirmed the steady release of strontium ions from the coated surface under physiological conditions. In-depth cellular studies proved that extracellular strontium emanating from SrHA-coated PET (PET@SrHA) ligaments actively steers the M2 macrophage polarization. Additionally, macrophages (Mφs) manifested a heightened secretion of prohealing cytokines when exposed to PET@SrHA. Subsequent investigations showed that these cytokines acted as mediators, activating integrin signaling pathways among macrophages, vascular endothelial cells, and osteoblasts. As a direct consequence, an increased rate of angiogenesis and osteogenic differentiation was observed, vital for graft-bone integration following ACL reconstruction with PET@SrHA ligaments. From a biochemical standpoint, our results pinpoint strontium ions as influential immunomodulators, sculpting the graft-bone interface's immune environment. This insight presents the SrHA-coating technique as a viable therapeutic strategy, holding sound promise for improving angiogenesis and osseointegration outcomes during ACL reconstruction using PET-based grafts.

Mechanically Adaptive Polymers Constructed from Dynamic Coordination Equilibria.

Designing materials capable of adapting their mechanical properties in response to external stimuli is the key to preventing failure and extending their service life. However, existing mechanically adaptive polymers are hindered by limitations such as inadequate load-bearing capacity, difficulty in achieving reversible changes, high cost, and a lack of multiple responsiveness. Herein, we address these challenges using dynamic coordination bonds. A new type of mechanically adaptive material with both rate- and temperature-responsiveness was developed. Owing to the stimuli-responsiveness of the coordination equilibria, the prepared polymers, PBMBD-Fe and PBMBD-Co, exhibit mechanically adaptive properties, including temperature-sensitive strength modulation and rate-dependent impact hardening. Benefitting from the dynamic nature of the coordination bonds, the polymers exhibited impressive energy dissipation, damping capacity (loss factors of 1.15 and 2.09 at 1.0 Hz), self-healing, and 3D printing abilities, offering durable and customizable impact resistance and protective performance. The development of impact-resistant materials with comprehensive properties has potential applications in the sustainable and intelligent protection fields.

Exercise potentially prevents colorectal cancer liver metastases by suppressing tumor epithelial cell stemness via RPS4X downregulation.

Background: Colorectal cancer (CRC) is the third most prevalent tumor globally. The liver is the most common site for CRC metastasis, and the involvement of the liver is a common cause of death in patients with late-stage CRC. Consequently, mitigating CRC liver metastasis (CRLM) is key to improving CRC prognosis and increasing survival. Exercise has been shown to be an effective method of improving the prognosis of many tumor types. However, the ability of exercise to inhibit CRLM is yet to be thoroughly investigated. Methods: The GSE157600 and GSE97084 datasets were used for analysis. A pan-cancer dataset which was uniformly normalized was downloaded and analyzed from the UCSC database: TCGA, TARGET, GTEx (PANCAN, n = 19,131, G = 60,499). Several advanced bioinformatics analyses were conducted, including single-cell sequencing analysis, correlation algorithm, and prognostic screen. CRC tumor microarray (TMA) as well as cell/animal experiments are used to further validate the results of the analysis. Results: The greatest variability was found in epithelial cells from the tumor group. RPS4X was generally upregulated in all types of CRC, while exercise downregulated RPS4X expression. A lowered expression of RPS4X may prolong tumor survival and reduce CRC metastasis. RPS4X and tumor stemness marker-CD44 were highly positively correlated and knockdown of RPS4X expression reduced tumor stemness both in vitro and in vivo. Conclusion: RPS4X upregulation may enhance CRC stemness and increase the odds of metastasis. Exercise may reduce CRC metastasis through the regulation of RPS4X.

The Revolution of exosomes: From biological functions to therapeutic applications in skeletal muscle diseases.

Skeletal muscle diseases, a broad category encompassing a myriad of afflictions such as acute muscle injury and muscular dystrophies, pose a significant health burden globally. These conditions often lead to muscle weakness, compromised mobility, and a diminished quality of life. In light of this, innovative and effective therapeutic strategies are fervently sought after. Exosomes, naturally extracellular vesicles with a diameter of 30-150 nm, pervade biological fluids. These microscopic entities harbor a host of biological molecules, including proteins, nucleic acids, and lipids, bearing a significant resemblance to their parent cells. The roles they play in the biological theater are manifold, influencing crucial physiological and pathological processes within the organism. In the context of skeletal muscle diseases, their potential extends beyond these roles, as they present a promising therapeutic target and a vehicle for targeted drug delivery. This potentially paves the way for significant clinical applications. This review aims to elucidate the mechanisms underpinning exosome action, their myriad biological functions, and the strides made in exosome research and application. A comprehensive exploration of the part played by exosomes in skeletal muscle repair and regeneration is undertaken. In addition, we delve into the use of exosomes in the therapeutic landscape of skeletal muscle diseases, providing a valuable reference for a deeper understanding of exosome applications in this realm. The concluding section encapsulates the prospective avenues for exosome research and the promising future they hold, underscoring the tremendous potential these diminutive vesicles possess in the field of skeletal muscle diseases. The Translational Potential of this Article. The comprehensive exploration of exosome's diverse biological functions and translational potential in the context of skeletal muscle diseases presented in this review underscores their promising future as a therapeutic target with significant clinical applications, thus paving the way for innovative and effective therapeutic strategies in this realm.

Revisiting the Ultraviolet Absorption Cross Section of Gaseous Nitrous Acid (HONO): New Insights for Atmospheric HONO Budget.

Nitrous acid (HONO) is an important source of hydroxyl radicals (OH) in the atmosphere. Precise determination of the absolute ultraviolet (UV) absorption cross section of gaseous HONO lays the basis for the accurate measurement of its concentration by optical methods and the estimation of HONO loss rate through photolysis. In this study, we performed a series of laboratory and field intercomparison experiments for HONO measurement between striping coil-liquid waveguide capillary cell (SC-LWCC) photometry and incoherent broadband cavity-enhanced absorption spectroscopy (IBBCEAS). Specified HONO concentrations prepared by an ultrapure standard HONO source were utilized for laboratory intercomparisons. Results show a consistent ∼22% negative bias in measurements of the IBBCEAS compared with a SC-LWCC photometer. It is confirmed that the discrepancies occurring between these techniques are associated with the overestimation of the absolute UV absorption cross sections through careful analysis of possible uncertainties. We quantified the absorption cross section of gaseous HONO (360-390 nm) utilizing a custom-built IBBCEAS instrument, and the results were found to be 22-34% lower than the previously published absorption cross sections widely used in HONO concentration retrieval and atmospheric chemical transport models (CTMs). This suggests that the HONO concentrations retrieved by optical methods based on absolute absorption cross sections may have been underestimated by over 20%. Plus, the daytime loss rate and unidentified sources of HONO may also have evidently been overestimated in pre-existing studies. In summary, our findings underscore the significance of revisiting the absolute absorption cross section of HONO and the re-evaluation of the previously reported HONO budgets.

Regulation of overexpression lncRNA ATP2B1-AS1 on lung adenocarcinoma progression.

BACKGROUND: LncRNA ATP2B1-AS1 (ATP2B1-AS1) is involved in the occurrence and development of various diseases, while the relationship between lung adenocarcinoma (LUAD) and ATP2B1-AS1 is unclear. This study was to investigate the expression of ATP2B1-AS1 in LUAD and its influence on survival and prognosis of patients. METHODS: LUAD tissue samples from patients participating in this study were collected, and the expression levels of ATP2B1-AS1 and miR-141-3p in LUAD sampleswere detected by real-time quantitative polymerase chain reaction (RT-qPCR). The effect of ATP2B1-AS1 on the growth of A549 cells was investigated through cell counting kit-8 (CCK-8) and transwell experiments. Besides, the prognostic value of ATP2B1-AS1 in LUAD was assessed via Kaplan-Meier curve and multivariate Cox regression. RESULTS: ATP2B1-AS1 was downregulated in LUAD tissues and cells, whereas miR-141-3p was upregulated. After pcDNA3.1-ATP2B1-AS1 was transfected into A549 cells, the proliferation ability of A549 cells was decreased, and the migration level and invasion of A549 cells were also inhibited. High expression of ATP2B1-AS1 sponge miR-141-3p exerted prognostic value. CONCLUSIONS: ATP2B1-AS1 sponge miR-141-3p alleviated the progression of LUAD, and ATP2B1-AS1 may be deemed as a prognostic marker for LUAD.

Long-read sequencing-based transcriptomic landscape in longissimus dorsi and transcriptome-wide association studies for growth traits of meat rabbits.

Rabbits are an attractive meat livestock species that can efficiently convert human-indigestible plant biomass, and have been commonly used in biological and medical researches. Yet, transcriptomic landscape in muscle tissue and association between gene expression level and growth traits have not been specially studied in meat rabbits. In this study Oxford Nanopore Technologies (ONT) long-read sequencing technology was used for comprehensively exploring transcriptomic landscape in Longissimus dorsi for 115 rabbits at 84 days of age, and transcriptome-wide association studies (TWAS) were performed for growth traits, including body weight at 84 days of age and average daily gain during three growth periods. The statistical analysis of TWAS was performed using a mixed linear model, in which polygenic effect was fitted as a random effect according to gene expression level-based relationships. A total of 18,842 genes and 42,010 transcripts were detected, among which 35% of genes and 47% of transcripts were novel in comparison with the reference genome annotation. Furthermore, 45% of genes were widely expressed among more than 90% of individuals. The proportions (±SE) of phenotype variance explained by genome-wide gene expression level ranged from 0.501 ± 0.216 to 0.956 ± 0.209, and the similar results were obtained when explained by transcript expression level. In contrast, neither gene nor transcript was detected by TWAS to be statistically significantly associated with these growth traits. In conclusion, these novel genes and transcripts that have been extensively profiled in a single muscle tissue using long-read sequencing technology will greatly improve our understanding on transcriptional diversity in rabbits. Our results with a relatively small sample size further revealed the important contribution of global gene expression to phenotypic variation on growth performance, but it seemed that no single gene has an outstanding effect; this knowledge is helpful to include intermediate omics data for implementing genetic evaluation of growth traits in meat rabbits.

Machine learning methods for genomic prediction of cow behavioral traits measured by automatic milking systems in North American Holstein cattle.

Identifying genome-enabled methods that provide more accurate genomic prediction is crucial when evaluating complex traits such as dairy cow behavior. In this study, we aimed to compare the predictive performance of traditional genomic prediction methods and deep learning algorithms for genomic prediction of milking refusals (MREF) and milking failures (MFAIL) in North American Holstein cows measured by automatic milking systems (milking robots). A total of 1,993,509 daily records from 4,511 genotyped Holstein cows were collected by 36 milking robot stations. After quality control, 57,600 single nucleotide polymorphisms (SNP) were available for the analyses. Four genomic prediction methods were considered: Bayesian Lasso (LASSO), Multiple Layer Perceptron (MLP), Convolutional Neural Network (CNN), and Genomic Best Linear Unbiased Prediction (GBLUP). We implemented the first 3 methods using the Keras and TensorFlow libraries in Python (v.3.9) while the GBLUP method was implemented using the BLUPF90+ family programs. The accuracy of genomic prediction (Mean Square Error) for MREF and MFAIL was 0.34 (0.08) and 0.27 (0.08) based on LASSO, 0.36 (0.09) and 0.32 (0.09) for MLP, 0.37 (0.08) and 0.30 (0.09) for CNN, and 0.35 (0.09) and 0.31(0.09) based on GBLUP, respectively. Additionally, we observed a lower re-ranking of top selected individuals based on the MLP versus CNN methods compared with the other approaches for both MREF and MFAIL. Although the deep learning methods showed slightly higher accuracies than GBLUP, the results may not be sufficient to justify their use over traditional methods due to their higher computational demand and the difficulty of performing genomic prediction for non-genotyped individuals using deep learning procedures. Overall, this study provides insights into the potential feasibility of using deep learning methods to enhance genomic prediction accuracy for behavioral traits in livestock. Further research is needed to determine their practical applicability to large dairy cattle breeding programs.

Heterogeneous reactions significantly contribute to the atmospheric formation of nitrated aromatic compounds during the haze episode in urban Beijing.

Nitrated aromatic compounds (NACs) are key components of air pollution; however, due to the presence of complex mixtures of primary and secondary species, especially in urban environments, their atmospheric formation is poorly understood. Here we conducted a field campaign during a winter haze episode in urban Beijing, China to monitor gaseous and particulate NACs at 2-h time resolution. Through a standard-independent non-targeted approach, a total of 238 NACs were screened, of which 127 species were assigned chemical formula and 25 structures were confirmed. Four main classes were identified: nitrated aromatic hydrocarbons, nitrophenols, oxygenated nitrated aromatic compounds, and nitrated heterocyclic aromatic compounds. Hierarchical clustering analysis revealed disparate temporal variances of diurnal or nocturnal elevation, among which different nitration formations were captured, i.e., daytime photochemical oxidation and nighttime heterogeneous reactions. Isomeric information, particularly the substitution position of the nitro group on biphenyl, further demonstrated a potential heterogeneous mechanism of electrophilic nitration by NO2+. Assisted by source apportionment, we found that nighttime heterogeneous reactions significantly contributed to NAC formation, e.g., 31.3 % and 60.8 %, respectively, to 2-nitrofluoranthene and 2-nitropyrene, which were previously considered as classical daytime gas-phase products. This study provides comprehensive information on urban NAC species and highlights the importance of unheeded heterogeneous reactions in the atmosphere.