Bidirectional crosstalk between the epithelial-mesenchymal transition and immunotherapy: A bibliometric study.

Immunotherapy has recently attracted considerable attention. However, currently, a thorough analysis of the trends associated with the epithelial-mesenchymal transition (EMT) and immunotherapy is lacking. In this study, we used bibliometric tools to provide a comprehensive overview of the progress in EMT-immunotherapy research. A total of 1,302 articles related to EMT and immunotherapy were retrieved from the Web of Science Core Collection (WOSCC). The analysis indicated that in terms of the volume of research, China was the most productive country (49.07%, 639), followed by the United States (16.89%, 220) and Italy (3.6%, 47). The United States was the most influential country according to the frequency of citations and citation burstiness. The results also suggested that Frontiers in Immunotherapy can be considered as the most influential journal with respect to the number of articles and impact factors. "Immune infiltration," "bioinformatics analysis," "traditional Chinese medicine," "gene signature," and "ferroptosis" were found to be emerging keywords in EMT-immunotherapy research. These findings point to potential new directions that can deepen our understanding of the mechanisms underlying the combined effects of immunotherapy and EMT and help develop strategies for improving immunotherapy.

Screening potential biomarkers associated with insulin resistance in high-fat diet-fed mice by integrating metagenomics and untargeted metabolomics.

Insulin resistance is the primary pathophysiological basis for metabolic syndrome and type 2 diabetes. Gut microbiota and microbiota-derived metabolites are pivotal in insulin resistance. However, identifying the specific microbes and key metabolites with causal roles is a challenging task, and the underlying mechanisms require further exploration. Here, we successfully constructed a model of insulin resistance in mice induced by a high-fat diet (HFD) and screened potential biomarkers associated with insulin resistance by integrating metagenomics and untargeted metabolomics. Our findings showed a significant increase in the abundance of 30 species of Alistipes in HFD mice compared to normal diet (ND) mice, while the abundance of Desulfovibrio and Candidatus Amulumruptor was significantly lower in HFD mice than in ND mice. Non-targeted metabolomics analysis identified 21 insulin resistance-associated metabolites, originating from the microbiota or co-metabolized by both the microbiota and the host. These metabolites were primarily enriched in aromatic amino acid metabolism (tryptophan metabolism, tyrosine metabolism, and phenylalanine metabolism) and arginine biosynthesis. Further analysis revealed a significant association between the three distinct genera and 21 differentiated metabolites in the HFD and ND mice. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of representative genomes from 12 species of the three distinct genera further revealed the functional potential in aromatic amino acid metabolism and arginine biosynthesis. This study lays the groundwork for future investigations into the mechanisms through which the gut microbiota and its metabolites impact insulin resistance. IMPORTANCE: In this study, we aim to identify the microbes and metabolites linked to insulin resistance, some of which have not been previously reported in insulin resistance-related studies. This adds a complementary dimension to existing research. Furthermore, we establish a correlation between alterations in the gut microbiota and metabolite levels. These findings serve as a foundation for identifying the causal bacterial species and metabolites. They also offer insights that guide further exploration into the mechanisms through which these factors influence host insulin resistance.

A Multi-Center Cross-Sectional Study on Visual Impairment and Depression Among Students - Jiangsu Province, China, 2017-2022.

What is already known about this topic?: China exhibits a significantly high prevalence of myopia compared to other countries globally. Children with vision impairment have been found to engage less in physical activities, achieve lower academic performance, and have increased vulnerability to depression. What is added by this report?: During a six-year observational study, a population-level correlation was identified between varying degrees of visual impairment and the presence of depressive symptoms among students. Specifically, individuals with a visual acuity below 4.0 had a significantly higher odds ratio of 1.90 (95% confidence interval: 1.53-2.37) compared to individuals with normal vision (visual acuity ≥5.0). What are the implications for public health practice?: This study highlights the importance of holistic health interventions that address both visual and psychological aspects. Understanding common mechanisms and influential factors can guide the development of more impactful public health strategies.

Mindfulness training reduces slippery slope effects in moral decision-making and moral judgment.

Extant research has demonstrated the positive intrapersonal effects of mindfulness training. However, the cognitive mechanisms underlying the effects of mindfulness training on interpersonal processes are less clear. Here, we combined a randomized control mindfulness training design with computational approach to moral decision-making and moral judgments. Participants were randomly assigned to a Training group (N = 32) who received an 8-week mindfulness training or a Control group (N = 26) who waited for the same period of time. Before and after the 8-week period, participants completed a moral decision-making task, where they made tradeoff between money for themselves and unpleasant electric shocks to another person, and a moral judgment task, where they evaluated the blameworthiness of someone else's choices in the same moral decision-making task. Trait mindfulness, as measured by the Five-Facet Mindfulness Questionnaire, significantly increased from the pre- to post-training session for the Training group, but not the Control group, demonstrating the effectiveness of the mindfulness manipulation. For the Control group, participants' moral preference in both the decision-making task and the judgment task declined over time, exhibiting a "slippery slope" effect. In contrast, for the Training group, mindfulness training prevented moral preferences from declining. Computational modeling revealed that mindfulness training specifically reduced the increase in the weights of money over time in both the decision-making and judgment tasks, thereby curbing the "slippery slope" effects. These findings provide a cognitive account of the prosocial effects of mindfulness training on moral decision-making and moral judgments.

An Angiogenic Gene Signature for Prediction of the Prognosis and Therapeutic Responses of Hepatocellular Carcinoma.

Among cancer-related deaths worldwide, hepatocellular carcinoma (HCC) ranks second. The hypervascular feature of most HCC underlines the importance of angiogenesis in therapy. This study aimed to identify the key genes which could characterize the angiogenic molecular features of HCC and further explore therapeutic targets to improve patients' prognosis. Public RNAseq and clinical data are from TCGA, ICGC, and GEO. Angiogenesis-associated genes were downloaded from the GeneCards database. Then, we used multi-regression analysis to generate a risk score model. This model was trained on the TCGA cohort (n = 343) and validated on the GEO cohort (n = 242). The predicting therapy in the model was further evaluated by the DEPMAP database. We developed a fourteen-angiogenesis-related gene signature that was distinctly associated with overall survival (OS). Through the nomograms, our signature was proven to possess a better predictive role in HCC prognosis. The patients in higher-risk groups displayed a higher tumor mutation burden (TMB). Interestingly, our model could group subsets of patients with different sensitivities to immune checkpoint inhibitors (ICIs) and Sorafenib. We also predicted that Crizotinib, an anti-angiogenic drug, might be more sensitive to these patients with high-risk scores by the DEPMAP. The inhibitory effect of Crizotinib in human vascular cells was obvious in vitro and in vivo. This work established a novel HCC classification based on the gene expression values of angiogenesis genes. Moreover, we predicted that Crizotinib might be more effective in the high-risk patients in our model.

Environment-friendly bio-based controlled-release phosphate fertilizer with waste kitchen oil as coating material: Preparation, characterization, and mechanisms.

Recently, Bio-based polyurethane controlled-release fertilizers (BPCF) have been developed rapidly owing to their environmental friendliness, renewability, and low cost. However, the unsatisfying controlled release prohibits their large-scale direct application in agricultural production. Here, we prepared bio-based controlled-release phosphate (P) fertilizers using harmful waste kitchen oils (WKO) as coating materials. The membrane shell surface was modified with multi-walled carbon nanotubes (CNT), and superhydrophobic controlled-release phosphorus fertilizers (SCRF) were obtained. After CNT modification, the controlled release period of SCRF was greatly improved. Phosphorus released period of SCRF reached over 67 d while that of BPCF was merely ∼49 d. Additionally, the surface energy, cracks, roughness, microstructure, cross-linking degree, etc., of the membrane shells were measured. The results showed that CNT greatly improved the hydrophobic properties of the membrane shells. The findings indicated the application of modified WKO with great agricultural value in preparing environment-friendly BPCFs.

Relationship between Severity of Disease and Postoperative Neurological Recovery in Patients with Cervical Spondylotic Myelopathy Combined with Developmental Spinal Stenosis.

Objective: The study aimed to investigate the correlation between the severity of disease and postoperative neurological recovery in patients with cervical spondylotic myelopathy (CSM) combined with developmental spinal stenosis. Methods: A retrospective analysis of the clinical data of 114 CSM patients combined with developmental spinal stenosis admitted to our hospital from June 2019 to June 2020 was performed. All of the patients who underwent posterior cervical unidoor vertebroplasty were divided into the mild, moderate, and severe groups according to the Torg-Pavlov ratio. The clinical data including patients' age, course of spinal cord high signal change, and first onset age were collected. The recovery time, preoperative, and postoperative Japanese Orthopaedic Association (JOA) scores of patients in each group were compared with the calculation of the improvement rate. The correlation between the severity of disease and postoperative neurological recovery in CSM patients combined with developmental spinal stenosis was analyzed by Pearson correlation. The factors influencing postoperative neurological recovery were analyzed using multivariate logistic regression analysis. The receiver operating characteristic curve (AUC) was used to evaluate the value of each influencing factor in predicting postoperative recovery. Results: Significant differences were observed in the proportion of linear hyperintensity changes in the spinal cord, the age of first onset, the course of the disease, and the Torg-Pavlov ratio among the mild, moderate, and severe groups (P < 0.05). The postoperative recovery time of the moderate and severe groups was significantly higher than that of the mild group, while the preoperative JOA score was significantly lower than that of the mild group. On the other hand, the postoperative recovery time of the severe group was prominently higher than that of the moderate group, whereas the preoperative JOA score was observably lower than that of the moderate group (P < 0.05). Pearson correlation analysis showed that the postoperative recovery time was significantly negatively correlated with the Torg-Pavlov ratio, age at first onset, and disease course (r = -0.359, -0.502, -0.368, P < 0.05), while it was positively correlated with spinal cord linear high-signal changes (r = 0.641, P < 0.05). Multifactorial logistic regression analysis revealed that the Torg-Pavlov ratio, age at first onset, and disease course were protective factors, while spinal cord linear high-signal alterations were risk factors affecting the recovery time of postoperative neurological function (P < 0.05). The area under the curve (AUC) of the Torg-Pavlov ratio, linear hyperintensity changes in the spinal cord, age at first onset, and disease duration in predicting the postoperative neurological recovery time were 0.794, 0.767, 0.772, and 0.802, respectively. The AUC predicted by the combined detection of each factor was 0.876, which was better than the area under the curve of single prediction. Conclusion: Patients with CSM combined with developmental spinal stenosis were characterized by younger age of onset, a short course of the disease, and linear changes in the spinal cord high signal. The degree of developmental spinal stenosis may affect the postoperative recovery time of neurological function in CSM patients but had little effect on postoperative neurological recovery. The Torg-Pavlov ratio, age of first onset, course of the disease, and changes in the spinal cord linear hyperintensity were the factors that affected postoperative neurological recovery, which may provide a basis for reasonably predicting a postoperative neurological recovery in patients with CSM combined with developmental spinal stenosis.

Complanatoside A targeting NOX4 blocks renal fibrosis in diabetic mice by suppressing NLRP3 inflammasome activation and autophagy.

BACKGROUND: Diabetic nephropathy (DN) is an important cause of end-stage renal disease. Complanatoside A (CA), an active component from Semen Astragali Complanati, has been reported to be a potential candidate for the treatment of kidney diseases. However, the underlying mechanisms and protective effects of CA in DN remain unclear. PURPOSE: In this paper, the effects and the mechanism of CA against ameliorating DN were investigated in vivo and in vitro. STUDY DESIGN: Here, a high-fat diet/streptozotocin-induced diabetic model and TGF-ß1-induced HK-2 cells were used to explore the protective effects and mechanisms of CA on DN in vivo and in vitro. METHODS: Major biochemical indexes, Histopathological morphology, and Immunohistochemistry have explored the therapeutic effect of CA on DN. Subsequently, TGF-ß1-induced HK-2 cells were utilized to investigate the anti-renal fibrosis effect of CA. Finally, the mechanism of CA against renal fibrosis was studied via western blotting, immunofluorescence, transfection, and molecular docking. RESULTS: The results showed that CA attenuated glomerular hypertrophy, collagen matrix deposition, and tubular interstitial fibrosis in diabetic mice. Moreover, the activation of TGF-ß1-inducible epithelial-mesenchymal transition (EMT) was hindered by CA treatment in HK-2 cells. Mechanistically, the data suggested that upregulated NOX4 during diabetes and TGF-ß1 in HK-2 cells was prominently diminished after CA treatment. Furthermore, CA exposure inhibited NLRP3 inflammasome activation and downstream inflammation gene expression such as IL-18 and IL-1ß in vivo and vitro. These findings indicated that CA obstructed the EMT to protect renal tubular epithelial cells against fibrosis via blocking NLRP3 activation, which was associated with inhibiting NOX4. Besides, the markedly raised autophagy levels in the diabetic model characterized by increasing LC3II/LC3I and Beclin1 were reversed after CA treatment, which is also a pivotal mechanism against renal fibrosis. More importantly, specific NOX4 overexpressed in HK-2 cells abolished that CA exposure blocked TGF-ß1-induced-EMT, ROS generation, NLRP3, and autophagy activation. Meanwhile, the inhibition of cell migration, ROS generation, autophagy, and renal inflammation after CA treatment was more pronounced in NOX4-deficient HK-2 cells. CONCLUSION: Our findings provided evidence that CA might be a potential therapeutic agent for DN by ameliorating NLRP3 inflammasome and autophagy activation via targeting NOX4 inhibition.

Modified Acupotomy versus Percutaneous Release for Trigger Thumb: A Retrospective Study.

Background: Acupotomy is now increasingly used for trigger thumb, while recent evidence showed it increased the risk of nerve injury. Based on the close proximity of the neurovascular bundles and the A1 pulley, we designed a modified acupotomy. Given that percutaneous release is the common surgical treatment, this retrospective study aimed to compare the effect and safety of modified acupotomy versus percutaneous release for trigger thumb. Methods: This is a retrospective study. All patients with trigger thumb were retrieved in the electronic records of the Department of Pain Medicine at the Beijing Hospital of Traditional Chinese Medicine from January 2016 to September 2018. Both short-term (3 months) and long-term (2 years) outcomes were evaluated using the criteria established through Gilberts et al.'s questionnaire, including triggering, residual pain, stiffness, digital nerve injury, scar, infection and satisfaction. Chi-square test or Fisher's exact test was used to compare differences between two groups. Results: A total of 305 patients with 334 trigger thumbs treated with either modified acupotomy (n = 194 thumbs) or percutaneous release (n = 140 thumbs) were included. Of them, 221 (72.5%) were female, and the mean age was 56.2 ± 10.0 years. The mean duration of trigger thumb lasted for 7.5 ± 3.6 months. At 3 months, all triggering were alleviated by both therapies. Although more digital nerve injury occurred in the percutaneous release (0 [0%] thumbs vs 5 [3.6%] thumbs, P = 0.012), more residual pain (30 [15.5%] thumbs vs 6 [4.3%] thumbs; rate ratio, 3.61; 95% confidence interval [CI]: 1.54-8.43; P = 0.001) and less satisfaction occurred in the modified acupotomy group. At 2 years, more recurrent triggering, residual pain and digital nerve injury occurred in the percutaneous release group (2 [1.0%] thumbs vs 12 [8.6%] thumbs; rate ratio, 0.12; 95% CI: 0.03-0.53; P = 0.001; 9 [4.6%] thumbs vs 22 [15.7%] thumbs; rate ratio, 0.30; 95% CI: 0.14-0.62 P < 0.001; 0 [0%] thumbs vs 4 [2.9%] thumbs, P = 0.030, respectively). Moreover, satisfaction was significantly better in the modified acupotomy group. Conclusion: The modified acupotomy had better long-term outcomes and satisfaction than the percutaneous release for trigger thumb, although percutaneous release has less residual pain and better satisfaction in the short term. The modified acupotomy is a treatment option for trigger thumb.

Enhanced chlortetracycline removal by iron oxide modified spent coffee grounds biochar and persulfate system.

Chlortetracycline (CTC) is a tetracycline derivative antibiotic that has been widely used in the livestock industry for prophylactic and therapeutic purposes. Effective measures should be taken to decrease the environmental risks associated with CTC-rich waste. Biochar produced by biomass waste showed great potential for organic contaminants removal by adsorption and catalytic degradation. This study prepared iron oxide-modified coffee grounds biochar (CGF) at different temperatures for enhanced CTC removal by adsorption and degradation. The main mechanism for CTC removal was found to be electrostatic interaction. In addition, pore diffusion, hydrogen bonds, and π-π bonds also contributed to CTC adsorption. Maximum CTC adsorption capacity was 223.63 mg/g for CGF800 (CGF prepared at 800 °C pyrolysis). The free radical content of CGF600 (CFG prepared at 600 °C pyrolysis) was higher than CGF800, and there were no significant advantages in using biochar prepared at a higher temperature for persulfate activation. The ion mass-to-charge ratio (M/z) is used to describe the ratio of mass to charge of an ion or peak, which can infer compound structure. The structure of CTC degradation products was analyzed by UPLC-MS, and the M/z values were determined as 444, 273, and 154. Thus, pyrolysis of coffee grounds at higher temperatures increased CTC adsorption capacity, and CGF can indirectly assist in CTC degradation by persulfate activation.

Genome-Wide Development of Polymorphic Microsatellite Markers and Association Analysis of Major Agronomic Traits in Core Germplasm Resources of Tartary Buckwheat.

Tartary buckwheat (TB; Fagopyrum tataricum Gaertn.) is an important multigrain crop and medicinal plant, but functional genomics and molecular breeding research in this species have been lacking for quite some time. Here, genome-wide screening was performed to develop simple sequence repeat (SSR) markers associated with six major agronomic traits and the rutin contents of 97 core germplasm resources. A total of 40,901 SSR loci were identified; they were uniformly distributed throughout the TB genome, with a mean distance of 11 kb between loci. Based on these loci, 8,089 pairs of SSR primers were designed, and 101 primer pairs for polymorphic SSR loci were used to genotype the 97 core germplasm resources. The polymorphic SSR loci showed high genetic variation in these core germplasm resources, with an average polymorphic information content (PIC) value of 0.48. In addition, multiple SSR markers, such as SXAU8002 [100-grain weight (HGW)] and SXAU8006 [stem diameter (SD)], were found to be associated with agronomic traits in the two environments. Finally, based on gene functional annotation and homology analysis, a candidate gene, FtPinG0007685500, that may affect the node number and SD of the main stem by participating in lignin synthesis was identified. This study reports the mining of genome-wide SSR loci and the development of markers in TB, which can be used for molecular characterization of the germplasm in its gene pool. In addition, the detected markers and candidate genes could be used for marker-assisted breeding and functional gene cloning in TB.

Treatment of Pasteurella multocida infection with dressings containing honey and antibacterials: a case report.

Infections secondary to Pasteurella multocida frequently occur in patients who have been exposed to domestic pets. Human infections caused by Pasteurella multocida vary in severity, and clinical features include localised cellulitis, osteomyelitis, systemic bacteraemia, meningitis and pneumonia. No vaccine has been developed against Pasteurella multocida; it is treated with antibacterial agents and, in most cases, surgical intervention. This article discusses the authors' experience in treating a woman with severe cellulitis and osteomyelitis on her hand caused by Pasteurella multocida. She refused surgical intervention and was successfully treated with honey-containing dressings and antibiotics after failure to heal following conservative treatment using conventional wound dressings combined with antibiotics.

Effect of Flavonoids in Hawthorn and Vitamin C Prevents Hypertension in Rats Induced by Heat Exposure.

BACKGROUND: Excessive oxidative stress is associated with hypertension in professional high-temperature working conditions. Polyphenols exhibit a cardioprotective effect. Hawthorn contains high amounts of flavonoids, though its effect on hypertension protection has yet to be studied. This study aims to investigate this effect of extract of hawthorn (EH) or its combination with vitamin C (Vit. C) in rats induced by working under a hot environment. METHODS: Forty-two male rats were randomly divided into a control group under normal temperature and six treatment groups exposed at 33 ± 1 °C along with 1 h of daily treadmill running. They were orally provided with water, Vit. C (14mg/kg), EH (125, 250, and 500 mg/kg), and EH500 + Vit. C, once a day for four weeks. RESULTS: Both EH and Vit. C alone reduced the systolic and diastolic blood pressure of rats exposed to the heat environment; however, their joint supplementation completely maintained their blood pressure to the normal level throughout the experimental period. No morphological changes were found on the intima of aorta. Moreover, the co-supplementation of EH and Vit. C prevented the changes of heat exposure in inducing oxidative stress markers, such as glutathione peroxidase, catalase, total antioxidant capacity, and nitric oxide; the synergistic action was more effective than either individual treatment of EH and Vit. C. Furthermore, the administration of EH had more potent effects on increasing superoxide dismutase, IL-2, the 70 kilodalton heat shock proteins and high sensitivity C reactive protein, and decreasing serum malondialdehyde and lipofuscin in vascular tissue than those in Vit. C group. CONCLUSIONS: A strong synergistic effect of EH and Vit. C on the prevention of hypertension under heat exposure was established, as they inhibited the oxidative stress state. This study also sets up a novel intervention strategy in animal models for investigation on the early phases of hypertension induced by heat exposure.

Prenylated phenolic compounds from licorice (Glycyrrhiza uralensis) and their anti-inflammatory activity against osteoarthritis.

Osteoarthritis is a significant driver of disability in the elderly with increasing prevalence, and inflammation plays a vital role on its etiology. Licorice is commonly used as a traditional Chinese medicine or food additive, and its prenylated phenolic compounds were recently reported to be able to inhibit osteoarthritis with anti-inflammatory activity. In order to explore more anti-osteoarthritic prenylated phenolic compounds from licorice, we isolated ten compounds (1-10), with three new ones (1-3), from the ethyl acetate extract of Glycyrrhiza uralensis. Compound 2 (glycyuralin R) was a racemic 3-phenoxy-chromanone, and we achieved its chiral separation for the first time. Compounds 1, 2, 7 and 8 showed significant NO inhibitory ability in IL-1ß-stimulated mouse primary chondrocytes, and we further confirmed the anti-inflammatory activity of 1 (glycyuralin Q) by evaluating its effect on osteoarthritis-related iNOS, COX-2, TNF-α, IL-6, MMP3, MMP13 and NF-κB based on various experimental methods. These results clarified the potential of several prenylated phenolic compounds, especially 1 in licorice, as the lead compounds for osteoarthritis.

[Mechanism and research progress of classical prescriptions and non-classical prescriptions in prevention and treatment of side effects of radiotherapy and chemotherapy].

Although targeted therapy and immunotherapy will become the trend of systematic therapy for tumor in the future, radiotherapy and chemotherapy are still regarded as one of the main means to treat cancer due to their low price and wide application. The toxic and side effects of radiotherapy and chemotherapy can limit the therapeutic effect and affect the body immunity, which is very difficult to deal with by modern medical means, and in this process, patients are prone to develop resistance to the application of radiotherapy and chemotherapy, which makes it difficult to implement follow-up treatment, leading to disease progression and ultimately affecting the prognosis of patients. In recent years, a large number of traditional Chinese medicine(TCM)-related clinical studies have found that classical prescriptions and non-classical prescriptions can markedly alleviate the toxic and side effects caused by radiotherapy and chemotherapy, with clear and significant efficacy, and to some extent, they can improve the quality of life and prolong the survival period of patients. Therefore, TCM decoction may provide new opportunities for intervening in the refractory and high-incidence toxic and side effects. To further explore the application of classical prescriptions and non-classical prescriptions in tumor, this study reviewed the mechanism of toxic and side effects caused by radiotherapy and chemotherapy, the mechanism of classical prescriptions and non-classical prescriptions in the treatment of toxic and side effects, and the classical prescriptions and non-classical prescriptions used for treating common toxic and side effects in recent five years. This study was expected to promote the application and development of classical prescriptions and non-classical prescriptions in the field of cancer treatment by systematically summarizing their research progress in the prevention and treatment of toxic and side effects caused by radiotherapy and chemotherapy.

Effectiveness and safety of acupotomy for knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Acupotomy may be effective for KOA, but the evidence is limited. This trial aims to determine the effectiveness and safety of acupotomy for KOA. METHODS/DESIGN: This is a parallel-group, assessor-blinded randomized controlled trial. Two hundred patients with KOA will be recruited and randomly assigned to two groups (group A or group D) in a 1:1 ratio. Patients in group A will receive acupotomy and topical diclofenac diethylamine for 4 weeks, while patients in group D will receive topical diclofenac diethylamine alone for 4 weeks. The primary outcome will be the response rate-the proportion of patients who achieve the minimal clinically important improvement in pain and function at week 4 compared with baseline. Secondary outcomes will include pain, function, quality of life, the use of rescue medicine (loxoprofen sodium), and adverse events at weeks 4, 8, and 24 after randomization. Besides, joint fluid and serum will be collected to assess the level of inflammatory cytokines, like TNF-α, IL-1ß, and MMP-3. DISCUSSION: This study will contribute to a better understanding of the effectiveness and safety of acupotomy in combination with topical nonsteroidal anti-inflammatory drugs. If the hypothesis is confirmed, acupotomy may be recommended as adjunctive therapy for patients with KOA. Results of the study will be of great importance for the guidelines of clinical therapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100043005 Registered on 4 February 2021.

Designer exosomes enabling tumor targeted efficient chemo/gene/photothermal therapy.

Exosomes, endogenous nanosized particles (50-150 nm) secreted and absorbed by cells, have been recently used as diagnostic and therapeutic platforms in cancer treatment. The integration of exosome-based delivery with multiple therapeutic modalities could result in better clinical outcomes and reduced-sided effects. Here, we combined the targeting and biocompatibility of designer exosomes with chemo/gene/photothermal therapy. Our platform consists of exosomes loaded with internalized doxorubicin (DOX, a model cancer drug) and coated with magnetic nanoparticles conjugated with molecular beacons capable of targeting miR-21 for responsive molecular imaging. The coated magnetic nanoparticle enables enrichment of the exosomes at the tumor site by external magnetic field guidance. After the exosomes are gathered at the tumor site, the application of near-infrared radiation (NIR) induces localized hyperthermia and triggers the release of cargoes loaded inside the exosome. The released molecular beacon can target the miR-21 for both imaging and gene silencing. Meanwhile, the released doxorubicin serves to kill the cancer cells. About 91.04 % of cancer cells are killed after treatment with Exo-DOX-Fe3O4@PDA-MB under NIR. The ability of the exosome-based method for cancer therapy has been demonstrated by animal models, in which the tumor size is reduced dramatically by 97.57 % with a magnetic field-guided tumor-targeted chemo/gene/photothermal approach. Thus, we expected this designer exosome-mediated multi-mode therapy to be a promising platform for the next-generation precision cancer nanomedicines.

Elucidation of the Regulatory Network of Flavonoid Biosynthesis by Profiling the Metabolome and Transcriptome in Tartary Buckwheat.

The characteristics of flavonoid metabolism in different Tartary buckwheat (TB) tissues and the related gene regulation network are still unclear at present. One hundred forty-seven flavonoids were identified from six TB tissues using the ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. The roadmap of the rutin synthesis pathway was revealed. Through transcriptomic analysis it was revealed that the differentially expressed genes (DEGs) are mainly enriched in the "Phenylpropanoid biosynthesis" pathway. Fifty-two DEGs involved in the "flavonol synthesis" pathway were identified. The weighted gene correlation network analysis revealed four co-expression network modules correlated with six flavonol metabolites. Eventually, 74 genes revealed from MEblue and MElightsteelblue modules were potentially related to flavonol synthesis. Of them, 7 MYB transcript factors had been verified to regulate flavonoid synthesis. Furthermore, overexpressed FtMYB31 enhanced the rutin content in vivo. The present findings provide a dynamic flavonoid metabolism profile and co-expression network related to rutin synthesis and are thus valuable in understanding the molecular mechanisms of rutin synthesis in TB.

Comparative transcriptomic analysis reveals the regulatory mechanism of the gibberellic acid pathway of Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn.) dwarf mutants.

BACKGROUND: Tartary buckwheat is an important minor crop species with high nutritional and medicinal value and is widely planted worldwide. Cultivated Tartary buckwheat plants are tall and have hollow stems that lodge easily, which severely affects their yield and hinders the development of the Tartary buckwheat industry. METHODS: Heifeng No. 1 seeds were treated with ethylmethanesulfonate (EMS) to generate a mutant library. The dwarf mutant ftdm was selected from the mutagenized population, and the agronomic characteristics giving rise to the dwarf phenotype were evaluated. Ultra-fast liquid chromatography-electrospray ionization tandem mass spectrometry (UFLC-ESI-MS/MS) was performed to determine the factors underlying the different phenotypes between the wild-type (WT) and ftdm plants. In addition, RNA sequencing (RNA-seq) was performed via the HiSeq 2000 platform, and the resulting transcriptomic data were analysed to identify differentially expressed genes (DEGs). Single-nucleotide polymorphism (SNP) variant analysis revealed possible sites associated with dwarfism. The expression levels of the potential DEGs between the WT and ftdm mutant were then measured via qRT-PCR and fragments per kilobase of transcript per million mapped reads (FPKM). RESULT: The plant height (PH) of the ftdm mutant decreased to 42% of that of the WT, and compared with the WT, the mutant and had a higher breaking force (BF) and lower lodging index (LI). Lower GA4 and GA7 contents and higher contents of jasmonic acid (JA), salicylic acid (SA) and brassinolactone (BR) were detected in the stems of the ftdm mutant compared with the WT. Exogenous application of GAs could not revert the dwarfism of the ftdm mutant. On the basis of the transcriptomic analysis, 146 homozygous SNP loci were identified. In total, 12 DEGs with nonsynonymous mutations were ultimately identified, which were considered potential candidate genes related to the dwarf trait. When the sequences of eight genes whose expression was downregulated and four genes whose expression was upregulated were compared, SKIP14, an F-box protein whose sequence is 85% homologous to that of SLY1 in Arabidopsis, presented an amino acid change (from Ser to Asn) and was expressed at a lower level in the stems of the ftdm mutant compared with the WT. Hence, we speculated that this amino acid change in SKIP14 resulted in a disruption in GA signal transduction, indirectly decreasing the GA content and downregulating the expression of genes involved in GA biosynthesis or the GA response. Further studies are needed to determine the molecular basis underlying the dwarf phenotype of the ftdm mutant. CONCLUSION: We report a Tartary buckwheat EMS dwarf mutant, ftdm, suitable for high-density planting and commercial farming. A significant decrease in GA4 and GA7 levels was detected in the ftdm mutant, and 12 DEGs expressed in the stems of the ftdm mutant were selected as candidates of the dwarfing gene. One nonsynonymous mutation was detected in the SKIP14 gene in the ftdm mutant, and this gene had a lower transcript level compared with that in the WT.