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Background/Aims: Circular RNAs (circRNAs), a type of RNA that is widely expressed in human cells, have essential roles in the development and progression of cancer. CircRNAs contain microRNA (miRNA) binding sites and can function as miRNA sponges to regulate gene expression by removing the inhibitory effect of an miRNA on its target gene. Methods: We used the bioinformatics software TargetScan and miRanda to predict circRNA-miRNA and miRNAi-Mrna interactions. Rate of inhibiting of proliferation was measured using a WST-8 cell proliferation assay. Clone formation ability was assessed with a clone formation inhibition test. Cell invasion and migration capacity was evaluated by performing a Transwell assay. Relative gene expression was assessed using quantitative real-time polymerase chain reaction and relative protein expression levels were determined with western blotting. circRNA and miRNA interaction was confirmed by dual-luciferase reporter and RNA-pull down assays. Results: In the present study, the miRNA hsa-miR-21-5p was a target of circRNA-ACAP2, and T lymphoma invasion and metastasis protein 1 (Tiam1) was identified as a target gene of hsa-miR-21-5p. CircRNA-ACAP2 and Tiam1 were shown to be highly expressed in colon cancer tissue and colon cancer SW480 cells, but miR-21-5p was expressed at a low level. SW480 cell proliferation was suppressed when the expression of circRNA-ACAP2 and Tiam1 was decreased and the expression of miR-21-5p was increased in vivo and in vitro. SW480 cell migration and invasion were also inhibited under the same circumstance. The circRNA-ACAP2 interaction regulated the expression of miR-21-5p, and miR-21-5p regulated the expression of Tiam1. Down-regulation of circRNA-ACAP2 promoted miR-21-5p expression, which further suppressed the transcription and translation of Tiam1. Conclusion: The present study shows that the circRNA-ACAP2/hsa-miR-21-5p/Tiam1 regulatory feedback circuit could affect the proliferation, migration, and invasion of colon cancer SW480 cells. This was probably due to the fact that circRNA-ACAP2 could act as a miRNA sponge to regulate Tiam1 expression by removing the inhibitory effect of miR-21-5p on Tiam1 expression. The results from this study have revealed new insights into the pathogenicity of colon cancer and may provide novel therapeutic targets for the treatment of colon cancer.

Patchoulol, a valuable compound belonging to the sesquiterpenoid family, is the primary component of patchouli oil produced by Pogostemon cablin ( P. cablin ). It has a variety of pharmacological and biological activities and is widely used in the medical and cosmetic industries. However, despite its significance, there is a lack of research on the transcriptional modulation of patchoulol biosynthesis. Salicylic acid (SA), is a vital plant hormone that serves as a critical signal molecule and plays an essential role in plant growth and defense. However, to date, no studies have explored the modulation of patchoulol biosynthesis by SA. In our study, we discovered that the application of SA can enhance the production of patchoulol. Utilizing transcriptome analysis of SA-treated P. cablin , we identified a crucial downstream transcription factor, PatWRKY71. The transcription level of PatWRKY71 was significantly increased with the use of SA. Furthermore, our research has revealed that PatWRKY71 was capable of binding to the promoter of PatPTS , ultimately leading to an increase in its expression. When PatWRKY71 was silenced by a virus, the expression of both PatWRKY71 and PatPTS was reduced, resulting in the down-regulation of patchoulol production. Through our studies, we discovered that heterologous expression of PatWRKY71 leads to an increase in the sensitivity of Arabidopsis to salt and Cd, as well as an outbreak of reactive oxygen species (ROS). Additionally, we uncovered the regulatory role of PatWRKY71 in both patchoulol biosynthesis and plant defense response. This discovery provided a theoretical basis for the improvement of the content of patchoulol and the resistance of P. cablin through genetic engineering.

This study aimed to investigate the effects and safety of 308 nm excimer laser (308 nm EL) and tacrolimus ointment (TO) in the treatment of facial vitiligo (FV). We searched Cochrane Library, PUBMED, EMBASE, CNKI, and WANGFANG from inception to June 1, 2023. Outcomes included overall response rate (ORR), total adverse reaction rate (TARR), recurrence rate at 3-month (RR-3) and recurrence rate at 6-month (RR-6). The outcome data were presented as odds ratios (OR) with 95% confidence intervals (CI). The risk of bias was assessed by Cochrane risk-of-bias tool and data analysis was performed by RevMan 5.4 software. This study included a total of 19 trials involving 2085 patients. When comparing 308 nm EL monotherapy with 308 nm EL plus TO, significant differences in the ORR (OR = 4.29, 95% CI [2.97, 6.19], I2 = 0%, P < 0.001), RR-3 (OR = 0.18, 95% CI [0.05, 0.69], I2 = 0%, P = 0.01), and RR-6 (OR = 0.38, 95% CI [0.14, 1.03], I2 = 39%, P = 0.06) were found between the two managements. When comparing TO monotherapy with TO plus 308 nm EL, its results showed significant differences in the ORR (OR = 4.21, 95% CI [2.90, 6.11], I2 = 0%, P < 0.001), TARR (OR = 0.42, 95% CI [0.22, 0.81], I2 = 4%, P = 0.009), and RR-3 (OR = 0.32, 95% CI [0.01, 8.03], P = 0.49) between the two modalities. The results of this study suggest that the combination of 308 nm EL and TO is more effective than either treatment alone for the treatment of FV.

Aquilaria agallocha can produce fragrant agarwood used for incense, traditional medicine and other products. An efficient plant regeneration system was established via organogenesis from shoots developed from seedlings of Aquilaria agallocha. Shoots generated many buds on MS medium supplemented with 1.3 μmol/L BA （6-benzylaminopurine） in the first 7 weeks, and the buds elongated on MS medium with 1.3 μmol/L BA＋0.5 μmol/L NAA （naphthaleneacetic acid） in another 7 weeks, 2.3 shoots 2 cm in length per explant were obtained within 14 weeks. Plantlets were rooted on l/2 MS medium after being immersed in 5 μmol/L NAA for 48 h, 96.7% of the roots grew up two weeks later. All plantlets that survived acclimatization grew well in the pots.

Background： Mutations of transthyretin （TTR） cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis. Methods： Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014. Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients, for light and electron microscopy examination. The TTR genes from the nine patients were analyzed. Results： The onset age varied from 23 to 68 years. The main manifestations were paresthesia, proximal and/or distal weakness, autonomic dysfunction, cardiomyopathy, vitreous opacity, hearing loss, and glossohypertrophia. Nerve biopsy demonstrated severe loss ofmyelinated fibers in seven cases and amyloid deposits in three. One patient had skin amyloid deposits which were revealed from electron microscopic examination. Genetic analysis showed six kinds of mutations of TTR gene, including Val30Met, Phe33Leu, Ala36Pro, Val30Ala, Phe33Val, and Glu42Gly in exon 2. Conclusions： Since the pathological examinations ofsural nerve were negative for amyloid deposition in most patients, the screening for TTR mutations should be performed in all the adult patients, who are clinically suspected with hereditary TTR amyloidosis.

Background： Human rhinoviruses （HRVs） are divided into three genetic species： HRV-A, HRV-B, and HRV-C. The association of different HRV species with asthma in children in China has not yet been evaluated. This preliminary study aimed to assess the associations between different HRV species, particularly HRV-C, and asthma in young children in China. Methods： A total of 702 nasopharyngeal aspirates were obtained from 155 children with asthma （asthma group）, 461 children with acute respiratory infection （ARI） without asthma （nonasthma ARI group）, and 86 children from the control group. Semi-nested polymerase chain reaction （PCR） was used to detect HRVs, and PCR products were sequenced for species identification. Epidemiological characteristics of HRV-positive cases were analyzed. Results： HRVs were the most common pathogen （ 15.4%; 108/702） in the patients in this study. The prevalence of HRV was significantly different （F = 20.633, P = 0.000） between tile asthma （25.8%） and nonasthma ARI groups （11.1%）. Phylogenetic analysis indicated that in the 108 cases positive for HRVs, 41 were identified as HRV-A, 8 as HRV-B, and 56 as HRV-C, Comparing the asthma with the nonasthlna ARI group, Spearman＇s rank correlation analysis revealed an association between HRV-A （P 〈 0.05） and C （P 〈 0.01） and asthma, confirmed by regression analysis, with odds ratios of 2.2 （HRV-A） and 4.2 （HRV-C）. Conclusions： Our data revealed a high prevalence of HRVs in children in China, regardless of clinical status. HRV-C was the dominant species and may be one of the key factors in the association of HRVs with asthma.

Circular ribonucleic acids (circRNAs) are widely expressed in human cells and play an important role in the pathogenesis of many diseases. Some circRNAs have microRNA (miRNA) binding response elements and interact with miRNA to regulate the expression of target genes.Four patients with a preliminary diagnosis of dengue fever (DF), peripheral whole blood sample in anticoagulant was collected before treatment (pretreatment group) and after effective treatment (posttreatment group), and eight samples were separated and used to screen differentially expressed circRNAs with microarray analysis. The relative expression level of circRNAs was determined using reverse-transcription polymerase chain reaction (RT-PCR). TargetScan v7.1 and miRDB v5 bioinformatics software were used to predict circRNA-binding miRNAs; dual luciferase reporters were constructed to detect binding between circRNA and miRNA. Microarray screening revealed 263 differentially expressed circRNAs in peripheral leukocytes pretreatment versus posttreatment; 107 of these were upregulated and 156 were downregulated. RT-PCR confirmed that hsa_circ_0015962 was significantly upregulated and hsa_circ_0006459 significantly downregulated (P < 0.05). Moreover, hsa_circ_0015962 binds to miR-4683, and hsa_circ_0006459 binds to miR-133b.Downregulation of hsa_circ_0006459 and upregulation of hsa_circ_0015962 affect the treatment response of DF and are potential biomarkers in DF patients. The molecular mechanism involves hsa_circ_0006459-mediated targeted negative regulation of miR-133b and hsa_circ_0015962-mediated targeted negative regulation of miR-4683.

Circular ribonucleic acids (circRNAs) are widely expressed in human cells and play an important role in the pathogenesis of many diseases. Some circRNAs have microRNA (miRNA) binding response elements and interact with miRNA to regulate the expression of target genes.Four patients with a preliminary diagnosis of dengue fever (DF), peripheral whole blood sample in anticoagulant was collected before treatment (pretreatment group) and after effective treatment (posttreatment group), and eight samples were separated and used to screen differentially expressed circRNAs with microarray analysis. The relative expression level of circRNAs was determined using reverse-transcription polymerase chain reaction (RT-PCR). TargetScan v7.1 and miRDB v5 bioinformatics software were used to predict circRNA-binding miRNAs; dual luciferase reporters were constructed to detect binding between circRNA and miRNA. Microarray screening revealed 263 differentially expressed circRNAs in peripheral leukocytes pretreatment versus posttreatment; 107 of these were upregulated and 156 were downregulated. RT-PCR confirmed that hsa_circ_0015962 was significantly upregulated and hsa_circ_0006459 significantly downregulated ( P  < 0.05). Moreover, hsa_circ_0015962 binds to miR-4683, and hsa_circ_0006459 binds to miR-133b.Downregulation of hsa_circ_0006459 and upregulation of hsa_circ_0015962 affect the treatment response of DF and are potential biomarkers in DF patients. The molecular mechanism involves hsa_circ_0006459-mediated targeted negative regulation of miR-133b and hsa_circ_0015962-mediated targeted negative regulation of miR-4683.

Assessing axillary lymph node (ALN) tumor burden (low burden: < 3 positive ALNs; high burden: ≥ 3 positive ALNs) preoperatively is essential for guiding treatment strategies. This study aimed to develop a radiomics-based nomogram by integrating clinical data, serologic markers, ultrasound imaging features, and ultrasound-derived radiomics features to predict axillary lymph node metastatic burden in breast cancer. A study was conducted on 234 breast cancer patients. Univariate and multivariate logistic regression analyses were used to identify independent risk factors from ultrasound imaging and clinical pathology, constructing a clinical model. Radiomics features were extracted from ultrasound images, and the best features were selected using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm to construct the Radiomics score. The Radiomics nomogram model was built by combining the Radiomics score and independent risk factors from the clinical model. The performance of the clinical model, radiomics model, and combined model in predicting axillary lymph node tumor burden was evaluated. Model performance was assessed by discrimination, calibration curves, and decision curves. Results showed that US-reported ALN status and CA153 were independent risk factors for high ALN tumor burden. The radiomics nomogram demonstrated good calibration and discrimination, with an area under the ROC curve of 0.815 (95% CI, 0.755-0.876) for the training set and 0.808 (95% CI, 0.678-0.938) for the testing set. Furthermore, compared to the clinical model and radiomics model, The differences in AUC between the nomogram model and the clinical model, as well as between the nomogram model and the radiomics model, were not statistically significant (nomogram model vs. clinical model: P = 0.2078; nomogram model vs. radiomics model: P = 0.4161). But the nomogram model provided greater net benefit for all patients in the probability threshold range of 0.05-0.70. This study highlights the potential of an ultrasound-based radiomics nomogram as a robust and non-invasive predictive tool for evaluating ALN tumor burden, offering valuable guidance for personalized treatment planning in breast cancer.

The mutation of B-Rafv600E is widespread in a variety of human cancers. Its inhibitors vemurafenib and dabrafenib have been launched as drugs for treating unresectable melanoma, demonstrating that B-Rafv600E is an ideal drug target. This study focused on developing novel B-Rafv600E inhibitors as drug leads against various cancers with B-Rafv600E mutation. Using molecular modeling approaches, 200 blockbuster drugs were spliced to generate 283 fragments followed by molecular docking to identify potent fragments. Molecular structures of potential inhibitors of B-Rafv600E were then obtained by fragment reassembly followed by docking to predict the bioactivity of the reassembled molecules. The structures with high predicted bioactivity were synthesized, followed by in vitro study to identify potent B-Rafv600E inhibitors. A highly potent fragment binding to the hinge area of B-Rafv600E was identified via a docking-based structural splicing approach. Using the fragment, 14 novel structures were designed by structural reassembly, two of which were predicted to be as strong as marketed B-Rafv600E inhibitors. Biological evaluation revealed that compound lm is a potent B-Rafv600E inhibitor with an IC50 value of 0.05 μmol/L, which was lower than that of vemurafenib （0.13 μmol/L）. Moreover, the selectivity of lm against B-RafwT was enhanced compared with vemurafenib. In addition, lm exhibits desirable solubility, bioavailability and metabolic stability in in vitro assays, Thus, a highly potent and selective B-Rafv600E inhibitor was designed via a docking-based structural splicing and reassembly strategy and was validated by medicinal synthesis and biological evaluation.