Role and Regulatory Mechanism of circRNA_14820 in the Proliferation and Differentiation of Goat Skeletal Muscle Satellite Cells.

Skeletal muscle satellite cells (SMSCs), a type of myogenic stem cell, play a pivotal role in postnatal muscle regeneration and repair in animals. Circular RNAs (circRNAs) are a distinct class of non-coding RNA molecules capable of regulating muscle development by modulating gene expression, acting as microRNAs, or serving as protein decoys. In this study, we identified circ_14820, an exonic transcript derived from adenosine triphosphatase family protein 2 (ATAD2), through initial RNA-Seq analysis. Importantly, overexpression of circ_14820 markedly enhanced the proliferation of goat SMSCs while concomitantly suppressing their differentiation. Moreover, circ_14820 exhibited predominant localization in the cytoplasm of SMSCs. Subsequent small RNA and mRNA sequencing of circ_14820-overexpressing SMSCs systematically elucidated the molecular regulatory mechanisms associated with circ_14820. Our preliminary findings suggest that the circ_14820-miR-206-CCND2 regulatory axis may govern the development of goat SMSCs. These discoveries contribute to a deeper understanding of circRNA-mediated mechanisms in regulating skeletal muscle development, thereby advancing our knowledge of muscle biology.

Size-resolved gas-particle partitioning of polycyclic aromatic hydrocarbons in a large temperature range of 50 ℃.

Size-resolved gas-particle partitioning of semi-volatile organic compounds (SVOCs) can affect their environmental behaviors and health effects, which has not been widely studied in comparing with the gas-total suspended particle partitioning. Herein, the size-resolved gas-particle partitioning quotient (KPi) of polycyclic aromatic hydrocarbons (PAHs) in a large temperature range (-20.6 â„ƒ ∼ 29.4 â„ƒ) was firstly comprehensively studied. The log KPi values of PAHs related to fine particles were significantly higher than those related to coarse particles. When the logarithm of subcooled liquid-vapor pressure (log PL0) ∈ [-7, -1), the regression slopes of log KPi vs log PL0 related to the particle size > 1.0 µm were shallower than those with the particle size range of 0.10-1.0 µm, which indicated the influence of particle size on KPi. Among the three previous prediction equations of gas-particle partitioning quotient, the empirical equation based on the ambient temperature matched better with the measured log KPi. Therefore, a new prediction equation including ambient temperature and particle size as the two major parameters was established. For most particle size ranges, the new equation showed better prediction performance than the three previous equations. In summary, this study provided new insights for the size-resolved gas-particle partitioning mechanism and quotient.

Post-Translational Modification of PTEN Protein: Quantity and Activity.

Post-translational modifications play crucial roles in regulating protein functions and stabilities. PTEN is a critical tumor suppressor involved in regulating cellular proliferation, survival, and migration processes. However, dysregulation of PTEN is common in various human cancers. PTEN stability and activation/suppression have been extensively studied in the context of tumorigenesis through inhibition of the PI3K/AKT signaling pathway. PTEN undergoes various post-translational modifications, primarily including phosphorylation, acetylation, ubiquitination, SUMOylation, neddylation, and oxidation, which finely tune its activity and stability. Generally, phosphorylation modulates PTEN activity through its lipid phosphatase function, leading to altered power of the signaling pathways. Acetylation influences PTEN protein stability and degradation rate. SUMOylation has been implicated in PTEN localization and interactions with other proteins, affecting its overall function. Neddylation, as a novel modification of PTEN, is a key regulatory mechanism in the loss of tumor suppressor function of PTEN. Although current therapeutic approaches focus primarily on inhibiting PI3 kinase, understanding the post-translational modifications of PTEN could help provide new therapeutic strategies that can restore PTEN's role in PIP3-dependent tumors. The present review summarizes the major recent developments in the regulation of PTEN protein level and activity. We expect that these insights will contribute to better understanding of this critical tumor suppressor and its potential implications for cancer therapy in the future.

Temperature dependence of the rain-gas and snow-gas partition coefficients for nearly a thousand chemicals.

Compared to the particle-gas partition coefficients (KPG), the rain-gas (KRG) and snow-gas (KSG) partition coefficients are also essential in studying the environmental behavior and fate of chemicals in the atmosphere. While the temperature dependence for the KPG have been extensively studied, the study for KRG and KSG are still lacking. Adsorption coefficients between water surface-air (KIA) and snow surface-air (KJA), as well as partition coefficients between water-air (KWA) and octanol-air (KOA) are vital in calculating KRG and KSG. These four basic adsorption and partition coefficients are also temperature-dependent, given by the well-known two-parameters Antoine equation logKXY = AXY + BXY/T, where KXY is the adsorption or partition coefficients, AXY and BXY are Antoine parameters (XY stand for IA, JA, WA, and OA), and T is the temperature in Kelvin. In this study, the parameters AXY and BXY are calculated for 943 chemicals, and logKXY can be estimated at any ambient temperature for these chemicals using these Antoine parameters. The results are evaluated by comparing these data with published experimental and modeled data, and the results show reasonable accuracy. Based on these coefficients, temperature-dependence of logKRG and logKSG is studied. It is found that both logKRG and logKSG are linearly related to 1/T, and Antoine parameters for logKRG and logKSG are also estimated. Distributions of the 943 chemicals in the atmospheric phases (gas, particle, and rain/snow), are illustrated in a Chemical Space Map. The findings reveal that, at environmental temperatures and precipitation days, the dominant state for the majority of chemicals is the gaseous phase. All the AXY and BXY values for logKSG, logKRG, and basic adsorption and partition coefficients, both modeled by this study and collected from published work, are systematically organized into an accessible dataset for public utilization.

Trans-electrode pressure of gas-diffusion electrodes significantly influencing the electrochemical hydrogen peroxide production.

Hydrogen peroxide (H2O2) synthesis by electrochemical two-electron oxygen reduction has garnered increasing interest as a wide range of potential applications. Gas diffusion electrodes (GDEs) can effectively promote the H2O2 production efficiency by overcoming the oxygen mass transfer limitations but strongly influenced by the electrowetting process along the long-term operation. In this study, the effect of trans-electrode pressure (TEP) of GDE cathode on the electrowetting process was further elucidated. We controlled the TEP values of four types of GDEs: two Ni-based GDEs and two carbon cloth GDEs prepared by hot-pressing or brushing carbon black. SBA-15 was further used to regulate the microstructure of one Ni-based GDE. It was found that an optimal range of TEP occurred for all tested GDEs in terms of the max. concentration, the yield efficiency, the energy consumption, and the stability because TEP may change the triple-phase interface and influence the anti-electrowetting effect. The porosity of hot-pressed Ni GDE can maintain the TEP window and thus enhance the production of H2O2, likely via creating oxygen-containing functional groups and a bimodal pore structure on the electrode, revealed with several characterization techniques including SEM, CA, XPS, Raman spectra, CV and EIS. The porous Ni GDE presented an efficient and stable production of H2O2 for 10 cycles: yielding H2O2 at 4393.2-4602.2 mmol m-2 h-1 with current efficiencies of 94.2-98.7%. The best accumulated H2O2 concentration can reach up to 3.58 ωt% H2O2 at 10 h. The results provide an important reference for the industrial scaleup of electro-production of H2O2 with GDEs.

Nanosphere-reinforced polysaccharide self-healing hydrogels for infected wound healing.

Bacterial infection remarkably impedes wound healing, with antibiotics traditionally serving as the primary therapeutic intervention. However, the escalating misuse of antibiotics and the emergence of bacterial resistance present substantial treatment challenges for infected wounds. Consequently, the development of antibiotic-free antimicrobial dressings holds pertinent research and clinical relevance. To this end, this study aimed to introduce an all-natural hydrogel dressing, amalgamating polyphenols and polysaccharides, exhibiting pronounced antibacterial and antioxidant properties without relying on antibiotics. First, we constructed curcumin-tannic acid­zinc ion nanospheres (CTZN) through self-assembly. Our experimental results showed that the nanospheres had excellent biocompatibility, antioxidant, and antimicrobial abilities. Subsequently, we prepared carboxymethylated chitosan/oxidized sodium alginate hydrogels via Schiff base reactions. Incorporation of CTZN into the hydrogel system not only improves the inherent qualities of the hydrogel but also confers multifunctional properties, including antimicrobial, antioxidant, and anti-inflammatory abilities. In this study, we enhanced the physicochemical properties and biological activity of hydrogels by introducing natural material nanospheres, offering a novel approach that could pave the way for the development of purely natural biomaterial dressings.

Microenvironment Remodeling Self-Healing Hydrogel for Promoting Flap Survival.

Random flap grafting is a routine procedure used in plastic and reconstructive surgery to repair and reconstruct large tissue defects. Flap necrosis is primarily caused by ischemia-reperfusion injury and inadequate blood supply to the distal flap. Ischemia-reperfusion injury leads to the production of excessive reactive oxygen species, creating a pathological microenvironment that impairs cellular function and angiogenesis. In this study, we developed a microenvironment remodeling self-healing hydrogel [laminarin-chitosan-based hydrogel-loaded extracellular vesicles and ceria nanozymes (LCH@EVs&CNZs)] to improve the flap microenvironment and synergistically promote flap regeneration and survival. The natural self-healing hydrogel (LCH) was created by the oxidation laminarin and carboxymethylated chitosan via a Schiff base reaction. We loaded this hydrogel with CNZs and EVs. CNZs are a class of nanomaterials with enzymatic activity known for their strong scavenging capacity for reactive oxygen species, thus alleviating oxidative stress. EVs are cell-secreted vesicular structures containing thousands of bioactive substances that can promote cell proliferation, migration, differentiation, and angiogenesis. The constructed LCH@EVs&CNZs demonstrated a robust capacity for scavenging excess reactive oxygen species, thereby conferring cellular protection in oxidative stress environments. Moreover, these constructs notably enhance cell migration and angiogenesis. Our results demonstrate that LCH@EVs&CNZs effectively remodel the pathological skin flap microenvironment and marked improve flap survival. This approach introduces a new therapeutic strategy combining microenvironmental remodeling with EV therapy, which holds promise for promoting flap survival.

Research Trends of Acupuncture Therapy for Chronic Pain-Related Depression or Anxiety from 2003 to 2023: A Bibliometric Analysis.

Background: Chronic pain (CP) as a long-lasting stressor can often cause mood disorders, such as depression or anxiety. The comorbidity of CP and mood disorders poses challenges for treatment and increases healthcare costs. Acupuncture has emerged as a widely utilized approach to alleviate both CP and mood disorders. However, there is a lack of well-established bibliometric analyses in this area of research. Therefore, this study aimed to identify the current hotspots and research trends regarding the use of acupuncture for treating CP-related depression or anxiety. Methods: We searched the Web of Science Core Collection spanning from 2003 to 2023 to identify relevant literature about the use of acupuncture for treating CP-related depression or anxiety. Bibliometric and visualization analyses were performed using CiteSpace 5.7.R5 and Vosviewer 1.6.19 software. Results: A total of 254 articles published between 2003 and 2023 were included, revealing an upward trajectory with some fluctuations in publication numbers over the past two decades. China and the Beijing University of Chinese Medicine were the most productive country and institution in this field. Fang JQ and Vickers AJ ascended as the most prolific and influential authors, respectively. Trials was the journal with the highest number of publications, while Pain and BMJ-British Medical Journal exhibited the highest citation and centrality, respectively. "Acupuncture", "depression", and "chronic pain" were the top three keywords. The hotspots in this domain encompass types of chronic pain that predispose to negative mood, including fibromyalgia, irritable bowel syndrome (IBS), and neuropathic pain. Randomized controlled trials (RCTs), mechanisms, and evidence-based evaluations are the main research directions. Conclusion: This study uses bibliometric techniques to analyze the research hotspots and forefronts of acupuncture as a therapeutic approach for CP-related depression or anxiety. Our objective is to provide researchers with valuable references and identify research focal points for future investigations.

The association of moderate-to-vigorous physical activity and sedentary behaviour with abdominal aortic calcification.

BACKGROUND AND AIMS: The increasing prevalence of metabolic and cardiovascular diseases poses a significant challenge to global healthcare systems. Regular physical activity (PA) is recognized for its positive impact on cardiovascular risk factors. This study aimed to investigate the relationship between moderate-to-vigorous physical activity (MVPA), sedentary behavior (SB), and abdominal aortic calcification (AAC) using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: The study used data from NHANES participants aged 40 and above during the 2013-2014 cycle. AAC scores were assessed using the Kauppila scoring system, and MVPA and SB were self-reported. Sociodemographic variables were considered, and multivariable linear regression models were used to analyze associations between MVPA, SB, and AAC scores. Subgroup analyses were conducted based on age, sex, BMI, hypertension, and diabetes. RESULTS: The study included 2843 participants. AAC prevalence was higher in older age groups, smokers, and those with diabetes or hypertension. Lower socioeconomic status was associated with higher AAC prevalence. Individuals engaged in any level of MVPA exhibited lower AAC rates compared to inactive individuals. Not engaging in occupational MVPA (ß = 0.46, 95% confidence interval = 0.24‒0.67, p < .001) and prolonged SB (ß = 0.28, 95% confidence interval = 0.04‒0.52, p = .023) were associated with higher AAC scores. However, no significant associations were found for transportation and leisure time MVPA. Subgroup analysis revealed age and hypertension as effect modifiers in the MVPA-AAC relationship. CONCLUSIONS: This study highlights the potential benefits of engaging in occupational MVPA and reducing SB in mitigating AAC scores, particularly among older individuals and those with hypertension.

Mapping of major QTL and candidate gene analysis for hull colour in foxtail millet (Setaria italica (L.) P. Beauv.).

BACKGROUND: Hull colour is an important morphological marker for selection in seed production of foxtail millet. However, the molecular mechanisms underlying hull colour variation remain unknown. RESULTS: An F7 recombinant inbred line (RIL) population containing 215 lines derived from Hongjiugu × Yugu18 was used to analyze inheritance and detect the quantitative trait loci (QTL) for four hull colour traits using major gene plus polygene mixed inheritance analysis and composite interval mapping (CIM) in four environments. Genetic analysis revealed that the hull colour L* value (HCL*) was controlled by two major genes plus additive polygenes, the hull colour a* value (HCa*) was controlled by three major genes, the hull colour b* value (HCb*) was controlled by two major genes plus polygenes, and the hull colour C* value (HCC*) was controlled by four major genes. A high-density genetic linkage map covering 1227.383 cM of the foxtail millet genome, with an average interval of 0.879 cM between adjacent bin markers, was constructed using 1420 bin markers. Based on the genetic linkage map and the phenotypic data, a total of 39 QTL were detected for these four hull colour traits across four environments, each explaining 1.50%-49.20% of the phenotypic variation. Of these, six environmentally stable major QTL were co-localized to regions on chromosomes 1 and 9, playing a major role in hull colour. There were 556 annotated genes within the two QTL regions. Based on the functions of homologous genes in Arabidopsis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) gene annotations, five genes were predicted as candidate genes for further studies. CONCLUSIONS: This is the first study to use an inheritance model and QTL mapping to determine the genetic mechanisms of hull colour trait in foxtail millet. We identified six major environmentally stable QTL and predicted five potential candidate genes to be associated with hull colour. These results advance the current understanding of the genetic mechanisms underlying hull colour traits in foxtail millet and provide additional resources for application in genomics-assisted breeding and potential isolation and functional characterization of the candidate genes.

Electroacupuncture attenuates chronic inflammatory pain and depression comorbidity by inhibiting hippocampal neuronal apoptosis via the PI3K/Akt signaling pathway.

In chronic inflammatory pain (CIP) and depression, neuroapoptosis has been identified as a contributing factor. Electroacupuncture (EA) shows promise as an alternative therapy for this comorbidity. However, the underlying mechanism remains unclear. This study aimed to investigate the effects of EA on hippocampal neuronal apoptosis in rats with CIP and depression. Rats received plantar injections of complete Freund's adjuvant (CFA) on days 0 and 14. They were then divided into groups: sham operation, model, EA, and duloxetine. EA was administered at Hegu (LI4) and Taichong (LR3) from days 15 to 28, while the duloxetine group received duloxetine and distilled water daily (0.1 mg/ml). Pain behavior was assessed using the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) tests. Depression-like behavior was evaluated through the sucrose preference test (SPT), open-field test (OFT), and forced swim test (FST). Hematoxylin and eosin (HE) staining was employed to assess pathological changes in the hippocampus. Nerve cell apoptosis was determined using TUNEL fluorescence staining. Western blot analysis was conducted to measure the protein expression of Bcl-2, Bax, p-PI3K/PI3K, and p-Akt/Akt. EA demonstrated significant pain intensity reduction and alleviation of pain-related depressive symptoms. Our findings from the HE staining confirmed that CIP induced by CFA led to morphological changes in the hippocampus, while EA effectively reversed these pathological alterations. Moreover, EA intervention remarkably reduced neuronal apoptosis and exhibited an upregulation of Bcl-2 protein expression accompanied by a decrease in Bax expression. Additionally, EA activated the PI3K/Akt signaling pathway. Overall, our study suggests that EA holds the potential to improve pain and depressive behaviors in rats with CIP and depression comorbidity, potentially mediated through the activation of the PI3K/Akt pathway, leading to a reduction in hippocampal neuronal apoptosis.

Biomaterial-based gene therapy.

Gene therapy, a medical approach that involves the correction or replacement of defective and abnormal genes, plays an essential role in the treatment of complex and refractory diseases, such as hereditary diseases, cancer, and rheumatic immune diseases. Nucleic acids alone do not easily enter the target cells due to their easy degradation in vivo and the structure of the target cell membranes. The introduction of genes into biological cells is often dependent on gene delivery vectors, such as adenoviral vectors, which are commonly used in gene therapy. However, traditional viral vectors have strong immunogenicity while also presenting a potential infection risk. Recently, biomaterials have attracted attention for use as efficient gene delivery vehicles, because they can avoid the drawbacks associated with viral vectors. Biomaterials can improve the biological stability of nucleic acids and the efficiency of intracellular gene delivery. This review is focused on biomaterial-based delivery systems in gene therapy and disease treatment. Herein, we review the recent developments and modalities of gene therapy. Additionally, we discuss nucleic acid delivery strategies, with a focus on biomaterial-based gene delivery systems. Furthermore, the current applications of biomaterial-based gene therapy are summarized.

The Host Protein CAD Regulates the Replication of FMDV through the Function of Pyrimidines' De Novo Synthesis.

Foot-and-mouth disease virus (FMDV) is a single-stranded picornavirus that causes economically devastating disease in even-hooved animals. There has been little research on the function of host cells during FMDV infection. We aimed to shed light on key host factors associated with FMDV replication during acute infection. We found that HDAC1 overexpression in host cells induced upregulation of FMDV RNA and protein levels. Activation of the AKT-mammalian target of rapamycin (mTOR) signaling pathway using bpV(HOpic) or SC79 also promoted FMDV replication. Furthermore, short hairpin RNA (shRNA)-induced suppression of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD), a transcription factor downstream of the AKT-mTOR signaling pathway, resulted in downregulation of FMDV RNA and protein levels. Coimmunoprecipitation assays showed that the ACTase domain of CAD could interact with the FMDV 2C protein, suggesting that the ACTase domain of CAD may be critical in FMDV replication. CAD proteins participate in de novo pyrimidine synthesis. Inhibition of FMDV replication by deletion of the ACTase domain of CAD in host cells could be reversed by supplementation with uracil. These results revealed that the contribution of the CAD ACTase domain to FMDV replication is dependent on de novo pyrimidine synthesis. Our research shows that HDAC1 promotes FMDV replication by regulating de novo pyrimidine synthesis from CAD via the AKT-mTOR signaling pathway. IMPORTANCE Foot-and-mouth disease virus is an animal virus of the Picornaviridae family that seriously harms the development of animal husbandry and foreign trade of related products, and there is still a lack of effective means to control its harm. Replication complexes would generate during FMDV replication to ensure efficient replication cycles. 2C is a common viral protein in the replication complex of Picornaviridae virus, which is thought to be an essential component of membrane rearrangement and viral replication complex formation. The host protein CAD is a key protein in the pyrimidines de novo synthesis. In our research, the interaction of CAD and FMDV 2C was demonstrated in FMDV-infected BHK-21 cells, and it colocalized with 2C in the replication complex. The inhibition of the expression of FMDV 3D protein through interference with CAD and supplementation with exogenous pyrimidines reversed this inhibition, suggesting that FMDV might recruit CAD through the 2C protein to ensure pyrimidine supply during replication. In addition, we also found that FMDV infection decreased the expression of the host protein HDAC1 and ultimately inhibited CAD activity through the AKT-mTOR signaling pathway. These results revealed a unique means of counteracting the virus in BHK-21 cells lacking the interferon (IFN) signaling pathway. In conclusion, our study provides some potential targets for the development of drugs against FMDV.

[Progress of research on mechanisms of acupuncture and moxibustion in the treatment of rheumatoid arthritis].

In the present paper, we summarize the literature about mechanisms of acupuncture and moxibustion ï¼»including ordinary acupuncture, electroacupuncture, fire needling, warm acupuncture (acupuncture with the needle warmed by burning moxa), cheek acupuncture, wheat-sized moxibustion, suspension moxibustion, etc.ï¼½ treatments of rheumatoid arthritis (RA) both domestically and abroad in recent years. Results indicate that the role of acupuncture and moxibustion therapies in improving RA involves multi-targets and multi-levels. These targets and levels include 1) improving joint and synovial inflammatory response by regulating inflammatory cytokines, inhibiting cell adhesion factor and interferon expression, 2) directly or indirectly regulating immune cell balance, 3) regulating peripheral and central neurotransmitters (plasma CCK-8 and ß-endorphin, hypothalamic prodynorphin, etc.), 4) regulating related signaling pathways (suppressing nuclear factor-kB/vascular endothelial growth factor, Janus tyrosine kinase-signal transducer and activator of transcription, transient receptor potential vanilloid and canonical Wnt/ß-catenin pathways), and activating cholinergic anti-inflammatory pathway, 5) regulating histocyte energy metabolism (improving amino acid supply and reducing negative nitrogen balance to improve immune regulation function), 6) maintaining the balance of bone cells and articular cartilage (by regulating the balance between synthesis and degradation of articular cartilage matrix, and the balance of bone cells and osteoclasts), 7) up-regulating energy metabolism gene (Atp50, Atp6V1B2) expression and regulating biological rhythm gene (clock, Per2, Rev-erb) expression, 8) regulating miRNAs-mediated chondrocyte apoptosis. All these provide experimental basis for acupuncture and moxibustion treatments of RA.

Safe femoral tunnel drilling angles avoid injury to the medial and posteromedial femoral anatomic structures during single-bundle posterior cruciate ligament reconstruction with the inside-out technique.

PURPOSE: To investigate the relationship between the medial and posteromedial femoral anatomic structures and the femoral tunnel exit produced by different tunnel orientations when creating the femoral tunnel for posterior cruciate ligament reconstruction (PCLR) using the inside-out (IO) technique and to estimate safe tunnel orientations to minimize the risk of iatrogenic injury to these structures. METHODS: Eleven cadaveric knees were used. The medial and posteromedial aspects of each knee joint were dissected to reveal the "safe zone," which is a bony area that avoids the distribution or attachment of at-risk structures (MCL, PMC structures, and articular cartilage), while remaining 10 mm away from the articular cartilage. The hypothesis of this study was that by creating the femoral tunnel at specific angles using the IO technique, the tunnel outlet would be as close to the safe zone as possible, protecting the at-risk structures from damage. Femoral tunnels were drilled at 20 different angle combinations on each specimen: 0°, 15°, 30°, 45°, and 60° relative to a line parallel to the transepicondylar axis in the axial plane, as well as 15°, 30°, 45°, and 60° relative to a line parallel to the femoral axis in the coronal plane. The positional relationship between each tunnel exit and the safe zone was recorded, and the shortest distance between the exit center and the safe zone boundary was measured. RESULTS: The risk of iatrogenic injury differed depending on the drilling orientation (χ2 = 168.880, P < 0.001). Femoral drilling angle combinations of 45/45°, 45/60°, 60/30°, 60/45°, and 60/60° (axial/coronal) were considered relatively safer than other orientations (P < 0.05). The shortest distance between the tunnel exit and the safe zone boundary was negatively correlated with the angle in the axial plane (P < 0.001, r = - 0.810). CONCLUSIONS: When creating the IO femoral tunnel for single-bundle PCL reconstruction, angle combinations of 45/45°, 45/60°, 60/30°, 60/45°, and 60/60° (axial/oblique coronal) could be utilized to prevent at-risk structures from being damaged. The drilling angles and the safe zone can be employed to optimize the femoral tunnel in PCLR.

3D-bioprinted double-crosslinked angiogenic alginate/chondroitin sulfate patch for diabetic wound healing.

Improving chronic wound healing remains a challenge in the clinical practice. In this study, we developed double-crosslinked angiogenic 3D-bioprinted patches for diabetic wound healing by the photocovalent crosslinking of vascular endothelial growth factor (VEGF) using ultraviolet (UV) irradiation. 3D printing technology can precisely customize the structure and composition of patches to meet different clinical requirements. The biological polysaccharide alginate and chondroitin sulfate methacryloyl were used as biomaterials to construct the biological patch, which could be crosslinked using calcium ion crosslinking and photocrosslinking, thereby improving its mechanical properties. More importantly, acrylylated VEGF could be easily and rapidly photocrosslinked under UV irradiation, which simplified the step of chemically coupling growth factors and prolonged VEGF release time. These characteristics suggest that 3D-bioprinted double-crosslinked angiogenic patches are ideal candidates for diabetic wound healing and other tissue engineering applications.

Discovery of a novel 1H-pyrazole- [3,4-b] pyridine-based lysine demethylase 5B inhibitor with potential anti-prostate cancer activity that perturbs the phosphoinositide 3-kinase/AKT pathway.

Lysine demethylase 5B (KDM5B) is a member of the Jumonji AT-rich interactive domain 1 family. Its main function is to demethylate di/trimethyl histone H3 lysine 4 and it plays a crucial role in the occurrence and development of cancer. In this study, we performed structure-based optimization of KDM5B inhibitors based on our previous work and the most active compound we synthesized was 11ad. Molecular modeling studies and thermal shift assays revealed that 11ad specifically targets KDM5B at the molecular and cellular levels. Crucially, 11ad demonstrated good pharmacokinetic properties and anti-prostate cancer activity in a xenograft model. Furthermore, unexpectedly, the specificity of 11ad for prostate cancer was found to be related to its inhibition of the phosphoinositide 3-kinase/AKT pathway. This is the first report of a KDM5B inhibitor affecting this pathway. Taken together, our findings indicate that 11ad is a novel KDM5B inhibitor that may serve as a lead compound for the development of treatments for prostate cancer.

SMG7-AS1 as a prognostic biomarker and predictor of immunotherapy responses for skin cutaneous melanoma.

Skin cutaneous melanoma (SKCM) is the most life-threatening skin cancer and lacks early detection and effective treatment strategies. Many long noncoding RNAs are associated with the development of tumors and may serve as potential immunotherapeutic targets. In this study, microarray analysis was performed to screen for differentially expressed lncRNAs between SKCM and normal tissues, and SMG7-AS1 was identified as an upregulated lncRNA in SKCM. Subsequently, bioinformatic analysis revealed that dysregulation of SMG7-AS1 influences metastasis and immune infiltration. qRT-PCR of clinical samples demonstrated that the expression of SMG7-AS1 was higher in melanoma tissues. Flow cytometry showed that SMG7-AS1 plays a vital role in the cell cycle. Additionally, SMG7-AS1 was found to be associated with immunotherapy responses. To the best of our knowledge, this study is the first to report that SMG7-AS1 is associated with SKCM and may serve as a prognostic biomarker and predictor of immunotherapy responses in SKCM.

Machine learning model predicts the occurrence of acute kidney injury after open surgery for abdominal aortic aneurysm repair. / æœºå™¨å­¦ä¹ æ¨¡åž‹é¢„æµ‹å¼€æ”¾æ‰‹æœ¯ä¿®å¤è ¹ä¸»åŠ¨è„‰ç˜¤åŽæ€¥æ€§è‚¾æŸä¼¤çš„å‘ç”Ÿ.

OBJECTIVES: Abdominal aortic aneurysm is a pathological condition in which the abdominal aorta is dilated beyond 3.0 cm. The surgical options include open surgical repair (OSR) and endovascular aneurysm repair (EVAR). Prediction of acute kidney injury (AKI) after OSR is helpful for decision-making during the postoperative phase. To find a more efficient method for making a prediction, this study aims to perform tests on the efficacy of different machine learning models. METHODS: Perioperative data of 80 OSR patients were retrospectively collected from January 2009 to December 2021 at Xiangya Hospital, Central South University. The vascular surgeon performed the surgical operation. Four commonly used machine learning classification models (logistic regression, linear kernel support vector machine, Gaussian kernel support vector machine, and random forest) were chosen to predict AKI. The efficacy of the models was validated by five-fold cross-validation. RESULTS: AKI was identified in 33 patients. Five-fold cross-validation showed that among the 4 classification models, random forest was the most precise model for predicting AKI, with an area under the curve of 0.90±0.12. CONCLUSIONS: Machine learning models can precisely predict AKI during early stages after surgery, which allows vascular surgeons to address complications earlier and may help improve the clinical outcomes of OSR.

Extracellular vesicle-loaded hydrogels for tissue repair and regeneration.

Extracellular vesicles (EVs) are a collective term for nanoscale or microscale vesicles secreted by cells that play important biological roles. Mesenchymal stem cells are a class of cells with the potential for self-healing and multidirectional differentiation. In recent years, numerous studies have shown that EVs, especially those secreted by mesenchymal stem cells, can promote the repair and regeneration of various tissues and, thus, have significant potential in regenerative medicine. However, due to the rapid clearance capacity of the circulatory system, EVs are barely able to act persistently at specific sites for repair of target tissues. Hydrogels have good biocompatibility and loose and porous structural properties that allow them to serve as EV carriers, thereby prolonging the retention in certain specific areas and slowing the release of EVs. When EVs are needed to function at specific sites, the EV-loaded hydrogels can stand as an excellent approach. In this review, we first introduce the sources, roles, and extraction and characterization methods of EVs and describe their current application status. We then review the different types of hydrogels and discuss factors influencing their abilities to carry and release EVs. We summarize several strategies for loading EVs into hydrogels and characterizing EV-loaded hydrogels. Furthermore, we discuss application strategies for EV-loaded hydrogels and review their specific applications in tissue regeneration and repair. This article concludes with a summary of the current state of research on EV-loaded hydrogels and an outlook on future research directions, which we hope will provide promising ideas for researchers.