Search

Xiaomei Cui,1,2 Ting Zhang,2 Tao Xie,2 Fang-xi Guo,2 Yu-ying Zhang,2 Yuan-jia Deng,2 Qi Wang,1,2 Yi-xing Guo,1,2 Ming-hua Dong,1,2 Xiao-ting Luo1,3 1Key Laboratory of Cardio Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China; 2School of Public Health and Health Management, Gannan Medical University, Ganzhou, People’s Republic of China; 3School of General Medicine, Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Xiao-ting Luo, Golden Campus of Gannan Medical University, Zhanggong District, Ganzhou City, Jiangxi Province, People’s Republic of China, Tel +86 13677975578, Email xtluo76@163.comAbstract: Among cardiovascular diseases, hypertension is the most important risk factor for morbidity and mortality worldwide, and its pathogenesis is complex, involving genetic, dietary and environmental factors. The characteristics of the gut microbiota can vary in response to increased blood pressure (BP) and influence the development and progression of hypertension. This paper describes five aspects of the relationship between hypertension and the gut microbiota, namely, the different types of gut microbiota, metabolites of the gut microbiota, sympathetic activation, gut–brain interactions, the effects of exercise and dietary patterns and the treatment of the gut microbiota through probiotics, faecal microbiota transplantation (FMT) and herbal remedies, providing new clues for the future prevention of hypertension. Diet, exercise and traditional Chinese medicine may contribute to long-term improvements in hypertension, although the effects of probiotics and FMT still need to be validated in large populations. Keywords: blood pressure, metabolites, gut-brain, treatment

Sheng-Long Li,1,* Fang-Yan Jing,1–3,* Li-Li Ma,2,3 Li-Li Guo,2,3 Feng Na,2,3 Sheng-Li An,4 Yan Ye,5 Jun-Ming Yang,1 Ming Bao,1 Dong Kang,1 Xiao-Lan Sun,1 Yong-Jian Deng2,3 1Department of Anorectal Surgery, 2Department of Pathology, Nanfang Hospital, 3Department of Pathology, School of Basic Medical Sciences, 4Department of Biostatistics, Southern Medical University, 5Department of General Surgery, Xintang Hospital, Zengcheng, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: The etiology and pathogenesis of hemorrhoids is unclear, although hemorrhoids are a worldwide disease in men and women, with peak prevalence at 45–65 years of age. Hemorrhoidal cushions as the anal venous plexi are normal anatomical structures from infancy. This study attempts to reveal the angiodysplasia and other pathological changes in association with different degrees of symptomatic hemorrhoids.Materials and methods: A total of 281 patients with internal hemorrhoids from degree I to IV underwent hemorrhoidectomy. The vascular changes were analyzed by microscopic assessment and software analysis, with Masson’s trichrome, CD34, and smooth muscle actin.Results: The hemorrhoidal tissues exhibited abnormal vessels in the mucosae and submucosae that we termed them as myofibrotic malformation vessels (MMVs). MMVs are not ascribed to arteries or veins because they exhibit enlarged and tortuous lumens with smooth muscle dysplasia and fibrotic deposition in the walls without overlying mucosal ulceration. The muscularis mucosae also showed smooth muscle dysplasia and fibrosis, even if it were interrupted by the intruding MMVs. The statistical data indicated that the severity of all the changes correlate positively with the progression of hemorrhoids (P

Tea plants (Camellia sinensis (L.) O. Kuntze) belong to Theaceae family, in the section Thea. Tea plants are widely distributed in subtropical and tropical regions in the word. α-carotene and β-carotene in the tea leaves belong to carotenoids, which are associated with the aroma and color of the tea. Phytoene synthase (PSY) is a rate-limiting enzyme in carotenoids biosynthesis. We identified three CsPSY genes in 'Shuchazao', named CsPSY1, CsPSY2, and CsPSY3. Structural analysis of three CsPSY genes showed that CsPSY1 had a longer intro structure. The cis-acting elements of CsPSYs promoter were mainly associated with light-responsiveness, abiotic stress-responsiveness, and hormone-responsiveness. CsPSY1 exhibited expression in all tissues of the tea plants, whereas CsPSY2 and CsPSY3 were trace expression levels in all tissues. The positive expression of CsPSY1 under hormonal and abiotic stresses suggested its role in plant development and defense responses. The amino acid sequence of CsPSY1 was highly conserved in eight tea cultivars. The recombinant vector pCAMBIA1301-CsPSY1 was constructed to stabilize the overexpression of CsPSY1 in carrot. The contents of α-carotene and β-carotene in transgenic carrot callus were significantly increased. This study provides a foundational basis for further research on the function of CsPSYs and carotenoids accumulation in tea plants., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To compare efficacy of proximal and distal laparoscopic ureteroureterostomy (UU) for complete duplex kidneys in children., Methods: Patients who underwent laparoscopic UU for complete duplex kidneys between December 2016 and July 2022 were reviewed retrospectively. 71 patients who had normal lower pole moiety without vesicoureteral reflux (VUR) were recruited. All of them underwent ultrasound, voiding cystourethrography (VCUG), renal scintigraphy, and magnetic resonance urography preoperatively. Proximal laparoscopic UU was performed in 35 patients and distal laparoscopic UU in 36 patients. Double J stents were placed in normal lower pole moieties. Clinical data, including general information, diagnosis, surgical management, imaging characteristics, clinical symptoms and postoperative complications (classified according to the modified Clavien-Dindo classification), and length of stay were recorded. Measurement date comparisons between groups were performed by t test, counting date were analyzed by chi-square test., Results: The study consisted of 71 patients (56 females and 15 males) with complete duplex kidneys (41 in left kidney and 30 in right kidney). The patients' mean age was 34 m (range 3-161 m) and follow-up ranged from 25 to 81 m. No significant difference was found in age and follow-up time between the two groups. Laparoscopic UU was performed in all patients successfully. The operation time of the two groups was 108.42 ± 26.95 min for distal UU vs 121.46 ± 35.15 min for proximal UU(p = 0.14). No significant difference in postoperative complications was seen between the two groups (22.2% vs 31.4%, p = 0.345). However, in terms of the grading of postoperative complications, the proximal UU group had a higher grade (3 of them had a grade of IV) and more serious complications., Conclusions: There was no significant difference in the overall incidence of complications between distal and proximal UU. Compared with proximal laparoscopic UU, distal laparoscopic UU is easier to perform with less injury to the peripheral tissues. Postoperative complications of proximal UU are more serious and more difficult to manage. We recommend complete duplex kidney ureteral reconstruction with distal UU., (© 2024. The Author(s).)

Many organisms have complex pigmentation patterns. However, how these patterns are formed remains largely unknown. In wild carrot (Daucus carota subsp. carota), which is also known as Queen Anne's lace, one or several purple central flowers occur in white umbels. Here, we investigated the unique central flower pigmentation pattern in wild carrot umbels. Using wild and cultivated carrot (D. carota subsp. sativus L.) accessions, transcriptome analysis, protein interaction, stable transformation, and CRISPR/Cas9-mediated knockout, an anthocyanin-activating R2R3-myeloblastosis (MYB) gene, Purple Central Flower (DcPCF), was identified as the causal gene that triggers only central flowers to possess the purple phenotype. The expression of DcPCF was only detected in tiny central flowers. We propose that the transition from purple to nonpurple flowers in the center of the umbel occurred after 3 separate adverse events: insertion of transposons in the promoter region, premature termination of the coding sequence (caused by a C-T substitution in the open reading frame), and the emergence of unknown anthocyanin suppressors. These 3 events could have occurred either consecutively or independently. The intriguing purple central flower pattern and its underlying mechanism may provide evidence that it is a remnant of ancient conditions of the species, reflecting the original appearance of Umbelliferae (also called Apiaceae) when a single flower was present., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Colorectal polyps, which are characterized by a high recurrence rate, represent preneoplastic conditions of the intestine. Due to unclear mechanisms of pathogenesis, first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection. Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps, the exact compositions and roles of bacteria in the mucosa around the lesions, rather than feces, remain unsettled., Aim: To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps., Methods: Mucosal samples were collected from four patients consistently with adenomatous polyps (Ade), seven consistently with non-Ade (Pol), ten with current Pol but previous Ade, and six healthy individuals, and bacterial patterns were evaluated by 16S rDNA sequencing. Linear discriminant analysis and Student's t -tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes. Pearson's correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators., Results: The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals. These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps, but also existed in histologically normal tissue 10 cm distal from the lesions. Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions, Pol, and Ade. Increased abundance of Gram-negative bacteria, including Klebsiella , Plesiomonas , and Cronobacter , was observed in Pol group and Ade group, suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment. Meanwhile, age and gender were linked to bacteria changes, indicating the potential involvement of sex hormones., Conclusion: These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps, especially adenoma. Targeting specific pathogenic bacteria may attenuate the recurrence of polyps., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Capsanthin and capsorubin are red κ-xanthophylls exclusively found in a handful of other plant species. Currently, capsanthin and capsorubin are only extracted from red pepper. Here, high purity production of capsanthin and capsorubin has been achieved in carrot taproot by synthetic metabolic engineering strategy. Expression of a capsanthin-capsorubin synthase gene (CaCCS) from pepper resulted in dominant production of capsanthin whereas expression of a LiCCS gene from tiger lily resulted in production of both capsanthin and capsorubin in carrot taproot. The highest content of capsanthin and capsorubin was obtained in LiC-1 carrot taproot hosting the LiCCS gene, 150.09 μg/g DW (dry weight). Co-expression of DcBCH1 with CCS could improve the purity of capsanthin and capsorubin by eliminating the non-target carotenoids (eg. α-carotene and β-carotene). The highest purity of capsanthin and capsorubin was obtained in BLiC-1 carrot taproot hosting DcBCH1+LiCCS genes, 91.10% of total carotenoids. The non-native pigments were esterified partially and stored in the globular chromoplast of carrot taproot. Our results demonstrated the possibility of employing carrot taproot as green factories for high purity production of capsanthin and capsorubin. The capsanthin/capsorubin carrot germplasms were also valuable materials for breeding colorful carrots cultivars., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear., Methods: We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients., Results: A functional assay identified that transforming growth factor-β1 (TGF-β1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-β1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD., Conclusions: These findings provide compelling evidence for the involvement of TGF-β1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-β1 may be used alone or combined with hOM-MSCs therapy for treating PD., (© 2024. The Author(s).)

Fusarium wilt is a worldwide soil-borne fungal disease caused by Fusarium oxysporum that causes serious damage to agricultural products. Therefore, preventing and treating fusarium wilt is of great significance. In this study, we purified ten single lipopeptide fengycin components from Bacillus subtilis FAJT-4 and found that C 17 fengycin B inhibited the growth of F. oxysporum FJAT-31362. We observed early apoptosis hallmarks, including reactive oxygen species accumulation, mitochondrial dysfunction, and phosphatidylserine externalization in C 17 fengycin B-treated F. oxysporum cells. Further data showed that C 17 fengycin B induces cell apoptosis in a metacaspase-dependent manner. Importantly, we found that the expression of autophagy-related genes in the TOR signaling pathway was significantly upregulated; simultaneously, the accumulation of acidic autophagy vacuoles in F. oxysporum cell indicated that the autophagy pathway was activated during apoptosis induced by C 17 fengycin B. Therefore, this study provides new insights into the antifungal mechanism of fengycin.

Solidification/stabilization technology is commonly used in the rehabilitation of dredged sediment due to its cost-effectiveness. However, traditional solidification/stabilization technology relies on cement, which increases the risk of soil alkalization and leads to increased CO 2 emissions during cement production. To address this issue, this study proposed an innovative approach by incorporating bentonite and citrus peel powder as additives in the solidifying agent, with the aim of reducing cement usage in the dredged sediment solidification process. The research results showed that there is a significant interaction among cement, bentonite, and citrus peel powder. After response surface methodology (RSM) optimization, the optimal ratio of the cementitious mixture was determined to be 14.86 g/kg for cement, 5.85 g/kg for bentonite, and 9.31 g/kg for citrus peel powder. The unconfined compressive strength (UCS) of the solidified sediments reached 3144.84 kPa. The reaction products of the solidification materials, when mixed with sediment, facilitated adsorption, gelation, and network structure connection. Simultaneously, the leaching concentration of heavy metals was significantly decreased with five heavy metals (Zn, As, Cd, Hg, and Pb) leaching concentrations decreasing by more than 50%, which met the prescribed thresholds for green planting. This study demonstrated the ecological benefits of employing bentonite and citrus peel powder in the solidification process of dredged sediment, providing an effective solution for sediment solidification., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The bioactivity of interferon-γ (IFN-γ) in cancer cells in the tumor microenvironment (TME) is not well understood in the current immunotherapy era. We found that IFN-γ has an immunosuppressive effect on colorectal cancer (CRC) cells. The tumor volume in immunocompetent mice was significantly increased after subcutaneous implantation of murine CRC cells followed by IFN-γ stimulation, and RNA sequencing showed high expression of B7 homologous protein 4 (B7H4) in these tumors. B7H4 promotes CRC cell growth by inhibiting the release of granzyme B (GzmB) from CD8 + T cells and accelerating apoptosis in CD8 + T cells. Furthermore, interferon regulatory factor 1 (IRF1), which binds to the B7H4 promoter, is positively associated with IFN-γ stimulation-induced expression of B7H4. The clinical outcome of patients with CRC was negatively related to the high expression of B7H4 in cancer cells or low expression of CD8 in the microenvironment. Therefore, B7H4 is a biomarker of poor prognosis in CRC patients, and interference with the IFN-γ/IRF1/B7H4 axis might be a novel immunotherapeutic method to restore the cytotoxic killing of CRC cells., (© 2024. The Author(s).)

The color of purple carrot taproots mainly depends on the anthocyanins sequestered in the vacuoles. Glutathione S-transferases (GSTs) are key enzymes involved in anthocyanin transport. However, the precise mechanism of anthocyanin transport from the cytosolic surface of the endoplasmic reticulum (ER) to the vacuoles in carrots remains unclear. In this study, we conducted a comprehensive analysis of the carrot genome, leading to the identification of a total of 41 DcGST genes. Among these, DcGST1 emerged as a prominent candidate, displaying a strong positive correlation with anthocyanin pigmentation in carrot taproots. It was highly expressed in the purple taproot tissues of purple carrot cultivars, while it was virtually inactive in the non-purple taproot tissues of purple and non-purple carrot cultivars. DcGST1, a homolog of Arabidopsis thaliana TRANSPARENT TESTA 19 (TT19), belongs to the GSTF clade and plays a crucial role in anthocyanin transport. Using the CRISPR/Cas9 system, we successfully knocked out DcGST1 in the solid purple carrot cultivar 'Deep Purple' ('DPP'), resulting in carrots with orange taproots. Additionally, DcMYB7, an anthocyanin activator, binds to the DcGST1 promoter, activating its expression. Compared with the expression DcMYB7 alone, co-expression of DcGST1 and DcMYB7 significantly increased anthocyanin accumulation in carrot calli. However, overexpression of DcGST1 in the two purple carrot cultivars did not change the anthocyanin accumulation pattern or significantly increase the anthocyanin content. These findings improve our understanding of anthocyanin transport mechanisms in plants, providing a molecular foundation for improving and enhancing carrot germplasm., (© 2023 Society for Experimental Biology and John Wiley & Sons Ltd.)

Ursolic acid (UA) is a naturally occurring pentacyclic triterpenoid widely found in fruits and vegetables. It has been reported that UA has anti-inflammatory effects. However, its efficacy and mechanism of action in the treatment of chronic prostatitis (CP) remain unclear. This study aimed to investigate the efficacy of UA treatment in CP and further explore the underlying mechanism. CP rat and pyroptosis cell models were established in vivo and in vitro, respectively. The efficacy of UA in inhibiting CP was evaluated via haematoxylin-eosin (HE) staining and measurement of inflammatory cytokines. RNA sequencing and molecular docking were used to predict the therapeutic targets of UA in CP. The expression of pyroptosis-related proteins was examined using various techniques, including immunohistochemistry, immunofluorescence, and flow cytometry. UA significantly ameliorated pathological damage and reduced the levels of proinflammatory cytokines in the CP model rats. RNA sequencing analysis and molecular docking suggested that NLRP3, Caspase-1, and GSDMD may be key targets. We also found that UA decreased ROS levels, alleviated oxidative stress, and inhibited p-NF-κB protein expression both in vivo and in vitro. UA improved pyroptosis morphology as indicated by electron microscope and inhibited the expression of the pyroptosis-related proteins NLRP3, Caspase-1, ASC, and GSDMD, reversed the levels of IL-1β, IL-18, and lactate dehydrogenase in vivo and in vitro. UA can mitigate CP by regulating the NLRP3 inflammasome-mediated Caspase-1/GSDMD pathway. Therefore, UA may be a potential for the treatment of CP., (© 2023 John Wiley & Sons Ltd.)

Objective: To explore the discriminatory diagnostic value of multimodal ultrasound(US) combined with blood cell analysis (BCA) for Granulomatous Lobular Mastitis (GLM) and Invasive Ductal Carcinoma (IDC) of the breast., Methods: A total of 157 breast disease patients were collected and divided into two groups based on postoperative pathological results: the GLM group (57 cases with 57 lesions) and the IDC group (100 cases with 100 lesions). Differences in multimodal ultrasound features and the presence of BCA were compared between the two groups. The receiver operating characteristic (ROC) curve was used to calculate the optimal cutoff values, sensitivity, specificity, 95% confidence interval (CI), and the area under the curve (AUC) for patient age, lesion size, lesion resistive index (RI), and white blood cell (WBC) count in BCA. Sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and AUC were calculated for different diagnostic methods., Results: There were statistically significant differences (P < 0.05) observed between GLM and IDC patients in terms of age, breast pain, the factors in Conventional US (lesion size, RI, nipple delineation, solitary/multiple lesions, margin, liquefaction area, growth direction, microcalcifications, posterior echogenicity and abnormal axillary lymph nodes), the factors in CEUS (contrast agent enhancement intensity, enhancement pattern, enhancement range, and crab-like enhancement) and the factors in BCA (white blood cells, neutrophils, lymphocytes and monocytes). ROC curve analysis results showed that the optimal cutoff values for distinguishing GLM from IDC were 40.5 years for age, 7.15 cm for lesion size, 0.655 for lesion RI, and 10.525*109/L for white blood cells. The diagnostic accuracy of conventional US combined with CEUS (US-CEUS) was the highest (97.45%). The diagnostic performance AUCs for US-CEUS, CEUS, and US were 0.965, 0.921 and 0.832, respectively., Conclusion: Multifactorial analysis of multimodal ultrasound features and BCA had high clinical application value in the differential diagnosis of GLM and IDC.

Background: Cardiac chamber dimensions and left ventricle (LV) wall thickness change with the cardiac cycle, in which researchers have set different time points for systole and diastole., Objective: This study aimed to provide characteristics of normal heart and choose the correct cardiac cycle to measure maximum cardiac parameters for cardiovascular disease., Methods: The parameters of left atrium (LA), LV, right atrium (RA), and right ventricle (RV), as well as the wall thickness of LV, were measured in different cardiac phases using cardiac computed tomography (CT). Then, their differences in different phases and the correlation between these parameters and traditional risk factors were analyzed. In addition, receiver operator characteristic curve (ROC) analyses was performed to estimate LA enlargement., Results: The dimensions of LA and RA as well as the wall thickness of LV reached the maximum at the phase of 35% – 45%, while the dimensions of LV and RV reached the maximum at 95% – 5%. However, the changes of LA-B (antero-posterior diameter), LV-D1 (basal dimension), RA-B (minor dimension), and RV-D2 (mid cavity dimension) were relatively more stable than other diameters during the cardiac cycle. The maximum LA-B diameter, LV-D1 diameter, RA-B diameter, and RV-D2 diameter as well as the maximum interventricular septum thickness were acquired. Heart rate (HR) and smoking were potential indicators of LV-D2 (mid cavity dimension), while HR and LV myocardial mass were potential indicators of LV-D3 (apical-basal dimension). In phase 45%, the cut-off value of LA-B was 37.12 mm, with high sensitivity for predicting LA enlargement., Conclusion: Choosing the adaptive cardiac phase for evaluating cardiac chamber dimensions and wall thickness obtained by cardiac CT could provide a more accurate clinical measurement of the heart.

Objectives: This study aims to identify the key senescence genes and potential regulatory mechanisms that contribute to the etiology of intervertebral disc degeneration (IDD). Method: We analyzed GSE34095 and GSE70362 datasets, identifying key senescence-related differentially expressed genes (DEGs) in IDD using lasso regression. Risk scores classified patients into high- and low-risk groups. We compared pathways, functions, and immune infiltration between these groups. Diagnostic ability was assessed using ROC curves and a nomogram predicted IDD incidence. In single-cell dataset GSE165722, we evaluated expression of key senescence-related DEGs. Results: We identified 12 key senescence-related DEGs distinguishing high- and low-risk IDD patients. Enrichment analysis revealed cellular stress response, apoptotic signaling pathway, and protein kinase activation differences. Immune cell analysis showed elevated eosinophils in low-risk group and increased effector memory CD8 T, central memory CD4 T, myeloid-derived suppressor, natural killer, monocyte, Type 1 T helper, plasmacytoid dendritic, and natural killer T cells in high-risk group. A nomogram using AUC >0.75 genes (CXCL8, MAP4K4, MINK1, and TNIK) predicted IDD incidence with good diagnostic power. High senescence scores were observed in neutrophils. Conclusion: Our diagnostic model, based on key senescence-related DEGs and immune cell infiltration, offers new insights into IDD pathogenesis and immunotherapy strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Deng, Wang, Li, Wang, Li, Ma, Xue, Tian, Liu, Liu, Zhang and Yuan.)

Cancer receives enduring international attention due to its extremely high morbidity and mortality. Immunotherapy, which is generally expected to overcome the limits of traditional treatments, serves as a promising direction for patients with recurrent or metastatic malignancies. Bacteria-based vectors such as Listeria monocytogenes take advantage of their unique characteristics, including preferential infection of host antigen presenting cells, intracellular growth within immune cells, and intercellular dissemination, to further improve the efficacy and minimize off-target effects of tailed immune treatments. Listeria monocytogenes can reshape the tumor microenvironment to bolster the anti-tumor effects both through the enhancement of T cells activity and a decrease in the frequency and population of immunosuppressive cells. Modified Listeria monocytogenes has been employed as a tool to elicit immune responses against different tumor cells. Currently, Listeria monocytogenes vaccine alone is insufficient to treat all patients effectively, which can be addressed if combined with other treatments, such as immune checkpoint inhibitors, reactivated adoptive cell therapy, and radiotherapy. This review summarizes the recent advances in the molecular mechanisms underlying the involvement of Listeria monocytogenes vaccine in anti-tumor immunity, and discusses the most concerned issues for future research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ding, Shu, He, Chen, Deng, Zhou, Xiong and Deng.)

The first domesticated carrots were thought to be purple carrots rich in anthocyanins. The anthocyanins biosynthesis in solid purple carrot taproot was regulated by DcMYB7 within P 3 region containing a gene cluster of six DcMYBs. Here, we described a MYB gene within the same region, DcMYB11c, which was highly expressed in the purple pigmented petioles. Overexpression of DcMYB11c in 'Kurodagosun' (KRD G , orange taproot carrot with green petioles) and 'Qitouhuang' (QTH G , yellow taproot carrot with green petioles) resulted in deep purple phenotype in the whole carrot plants indicating anthocyanins accumulation. Knockout of DcMYB11c in 'Deep Purple' (DPP P , purple taproot carrot with purple petioles) through CRISPR/Cas9-based genome editing resulted in pale purple phenotype due to the dramatic decrease of anthocyanins content. DcMYB11c could induce the expression of DcbHLH3 and anthocyanins biosynthesis genes to jointly promote anthocyanins biosynthesis. Yeast one-hybrid assay (Y1H) and dual-luciferase reporter assay (LUC) revealed that DcMYB11c bound to the promoters of DcUCGXT1 and DcSAT1 and directly activated the expression of DcUCGXT1 and DcSAT1 responsible for anthocyanins glycosylation and acylation, respectively. Three transposons were present in the carrot cultivars with purple petioles but not in the carrot cultivars with green petioles. We revealed the core factor, DcMYB11c, involved in anthocyanins pigmentation in carrot purple petioles. This study provides new insights into precise regulation mechanism underlying anthocyanins biosynthesis in carrot. The orchestrated regulation mechanism in carrot might be conserved across the plant kingdom and useful for other researchers working on anthocyanins accumulation in different tissues., (© 2023 John Wiley & Sons Ltd.)

This study aimed to assess the outcomes of modified onlay island flap (MOIF) urethroplasty for hypospadias reoperation. A retrospective analysis was conducted using clinical data on children reoperated with MOIF or tubularized incised plate (TIP) urethroplasty for hypospadias in the Children's Hospital of Nanjing Medical University (Nanjing, China) from December 2016 to September 2020. A total of 90 children with hypospadias who failed primary repair and were reoperated on with MOIF (MOIF group, n = 46) or TIP urethroplasty (TIP group, n = 44) were recruited. All children were postoperatively followed up for at least 6 months. Six patients with postoperative urinary fistula, 2 patients with glans dehiscence, and 1 patient with urethral diverticulum were reported in the MOIF group, while 7 patients with postoperative urinary fistula, 2 patients with urethral stricture, and 1 patient with glans dehiscence were reported in the TIP group. Postoperative infection, flap necrosis and other complications were not recorded. A total of 37 (80.4%) patients in the MOIF group and 34 (77.3%) patients in the TIP group were successfully reoperated. Although the success rates of MOIF and TIP urethroplasty are comparable, pediatricians should master different types of repair techniques for individualized hypospadias reoperation. MOIF urethroplasty can be recommended after failure of the primary repair., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Background: Betalain is a natural pigment with important nutritional value and broad application prospects. Previously, we produced betanin biosynthesis transgenic carrots via expressing optimized genes CYP76AD1S, cDOPA5GTS and DODA1S. Betanin can accumulate throughout the whole transgenic carrots. But the effects of betanin accumulation on the metabolism of transgenic plants and whether it produces unexpected effects are still unclear., Results: The accumulation of betanin in leaves can significantly improve its antioxidant capacity and induce a decrease of chlorophyll content. Transcriptome and metabolomics analysis showed that 14.0% of genes and 33.1% of metabolites were significantly different, and metabolic pathways related to photosynthesis and tyrosine metabolism were markedly altered. Combined analysis showed that phenylpropane biosynthesis pathway significantly enriched the differentially expressed genes and significantly altered metabolites., Conclusions: Results showed that the metabolic status was significantly altered between transgenic and non-transgenic carrots, especially the photosynthesis and tyrosine metabolism. The extra consumption of tyrosine and accumulation of betanin might be the leading causes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: Bone immune disorders are major contributors to osteoporosis development. This study aims to identify potential diagnostic markers and molecular targets for osteoporosis treatment from an immunological perspective. Method: We downloaded dataset GSE56116 from the Gene Expression Omnibus database, and identified differentially expressed genes (DEGs) between normal and osteoporosis groups. Subsequently, differentially expressed immune-related genes (DEIRGs) were identified, and a functional enrichment analysis was performed. A protein-protein interaction network was also constructed based on data from STRING database to identify hub genes. Following external validation using an additional dataset (GSE35959), effective biomarkers were confirmed using RT-qPCR and immunohistochemical (IHC) staining. ROC curves were constructed to validate the diagnostic values of the identified biomarkers. Finally, a ceRNA and a transcription factor network was constructed, and a Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed to explore the biological functions of these diagnostic markers. Results: In total, 307 and 31 DEGs and DEIRGs were identified, respectively. The enrichment analysis revealed that the DEIRGs are mainly associated with Gene Ontology terms of positive regulation of MAPK cascade, granulocyte chemotaxis, and cytokine receptor. protein-protein interaction network analysis revealed 10 hub genes: FGF8 , KL , CCL3 , FGF4 , IL9 , FGF9 , BMP7 , IL17RA , IL12RB2 , CD40LG . The expression level of IL17RA was also found to be significantly high. RT-qPCR and immunohistochemical results showed that the expression of IL17RA was significantly higher in osteoporosis patients compared to the normal group, as evidenced by the area under the curve Area Under Curve of 0.802. Then, we constructed NEAT1 -hsa-miR-128-3p- IL17RA , and SNHG1 -hsa-miR-128-3p- IL17RA ceRNA networks in addition to ERF - IL17RA , IRF8 - IL17RA , POLR2A - IL17RA and ERG - IL17RA transcriptional networks. Finally, functional enrichment analysis revealed that IL17RA was involved in the development and progression of osteoporosis by regulating local immune and inflammatory processes in bone tissue. Conclusion: This study identifies the immune-related gene IL17RA as a diagnostic marker of osteoporosis from an immunological perspective, and provides insight into its biological function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Deng, Li, Wang, Li, Ma, Xue, Tian, Liu, Zhang and Yuan.)

Objective: This systematic review and meta-analysis study aimed to evaluate the effectiveness of probiotics supplementation on glycaemic control in patients with type 2 diabetes mellitus (T2DM) based on the data from the randomised clinical trials (RCTs)., Methods: PubMed, Web of Sciences, Embase, and Cochrane Library were searched from the inception to October 2022, and RCTs about probiotics and T2DM were collected. The standardised mean difference (SMD) with 95% confidence interval (CI) was used to estimate the effects of probiotics supplementation on glycaemic control related parameters, e.g. fasting blood glucose (FBG), insulin, haemoglobin A1c (HbA1c), and homeostasis model of assessment of insulin resistance (HOMA-IR)., Results: Thirty RCTs including 1,827 T2MD patients were identified. Compared with the placebo group, the probiotics supplementation group had a significant decrease in the parameters of glycaemic control, including FBG (SMD = - 0.331, 95% CI  - 0.424 to - 0.238, P effect  < 0.001), insulin (SMD = - 0.185, 95% CI  - 0.313 to - 0.056, P effect  = 0.005), HbA1c (SMD = - 0.421, 95% CI  - 0.584 to - 0.258, P effect  < 0.001), and HOMA-IR (SMD = - 0.224, 95% CI  - 0.342 to - 0.105, P effect  < 0.001). Further subgroup analyses showed that the effect was larger in the subgroups of Caucasians, high baseline body mass index (BMI ≥ 30.0 kg/m 2 ), Bifidobacterium and food-type probiotics (P subgroup  < 0.050)., Conclusion: This study supported that probiotics supplementation had favourable effects on glycaemic control in T2DM patients. It may be a promising adjuvant therapy for patients with T2DM., (© 2023. The Author(s).)

Treatment of esophageal perforation or rupture is complicated and controversial, especially in advanced cases. In fact, it is generally accepted that this disease must be treated individually according to the location, causes and clinical features of rupture or perforation. A very rare case was admitted to our department, who was injured 5 days ago by high-pressure gas of a running air compressor and resulted in a long-term longitudinal rupture of the thoracic esophagus. Although the patient suffered from empyema and mediastinitis at the same time, and his condition was very serious, the debridement and desquamation of empyema were still implemented, followed by left thoracic esophagectomy and left neck approach esophagogastrostomy in the same period successfully. The patient got a good result finally., (© 2023. The Author(s).)

This study was aim at investigating antifungal activities of Bacillus velezensis FJAT-52631 and its lipopeptides against Colletotrichum acutatum ex situ and in situ. The results showed that the strain FJAT-52631 and its crude lipopeptides (10 mg/ml) exhibited strong inhibitory effects on growth of C. acutatum FJAT-30256 with an inhibition rate of 75.3% and an inhibition zone diameter of 17.66 mm, respectively. Both the viable bacterial cultures and lipopeptides of FJAT-52631 could delay the onset of loquat anthracnose by 1 day and lower the incidence of loquat anthracnose in situ. The whole cultures of B. velezensis FJAT-52631 displayed a 50% biocontrol efficacy on loquat anthracnose at the fourth day after inoculation, but the crude lipopeptides not. The average lesion diameter of the whole-culture treated group was 5.62 mm, which was smaller than that of control group (6.81 mm). All the three types of lipopeptides including iturin A, fengycin, and surfactin A secreted from the strain FJAT-52631 exhibited antifungal activities. Among them, surfactin A displayed higher antifungal activity at a concentration of 1.25 mg/mL than other two lipopeptides even if at a concentration of 60 mg/mL. Thus, the results indicated that surfactin A produced by FJAT-52631 played a major role in the biocontrol of the loquat anthracnose. Scanning electron microscopy (SEM) observation revealed the structural deformities in the mycelia of C. acutatum. The above results suggested that the antifungal lipopeptides from B. velezensis FJAT-52631 would be potential in biocontrol against anthracnose disease of loquat caused by C. acutatum., (© 2023 Wiley-VCH GmbH.)

Objective: To investigate the influence of sleep fragmentation in infancy and toddler period on emotional and behavioral problems at the age of 6 years. Methods: Using a prospective cohort design, 262 children were extracted from mother-child birth cohort recruited from May 2012 to July 2013 in Renji Hospital, School of Medicine, Shanghai Jiao Tong University. Children's sleep and physical activities were assessed using actigraphy at 6, 12, 18, 24, and 36 months of age, from which the sleep fragmentation index (FI) at each follow-up point was calculated. Children's emotional and behavioral problems at 6 years of age were assessed using the strengths and difficulties questionnaire. Group-based trajectory model was applied to determine sleep FI in infancy and toddler period trajectory groups with Bayesian information criteria being used to determine the best fitting model. Children's emotional and behavioral problems between groups were examined with independent t test and linear regression models, etc. Results: A total of 177 children, with 91 boys and 86 girls, were included in the final analysis and were divided into 2 groups: high FI group ( n =30) and low FI group ( n =147). Compared with children in the low FI group, those in the high FI group presents with higher total difficulties score and higher hyperactivity or inattention score ((11.0±4.9) vs. (8.9±4.1), (4.9±2.7) vs. (3.7±2.3) scores, t =2.17, 2.23, both P <0.05, respectively), with the differences remaining significant after adjusting for covariates ( t =2.08, 2.09, both P< 0.05 respectively). Conclusion: High sleep fragmentation in infancy and toddler period is associated with more emotional and behavioral problems, especially hyperactivity or inattention problems, at 6 years of age.

Introduction: Cuproptosis seems to promote the progression of diverse diseases. Hence, we explored the cuproptosis regulators in human spermatogenic dysfunction (SD), analyzed the condition of immune cell infiltration, and constructed a predictive model. Methods: Two microarray datasets (GSE4797 and GSE45885) related to male infertility (MI) patients with SD were downloaded from the Gene Expression Omnibus (GEO) database. We utilized the GSE4797 dataset to obtain differentially expressed cuproptosis-related genes (deCRGs) between SD and normal controls. The correlation between deCRGs and immune cell infiltration status was analyzed. We also explored the molecular clusters of CRGs and the status of immune cell infiltration. Notably, weighted gene co-expression network analysis (WGCNA) was used to identify the cluster-specific differentially expressed genes (DEGs). Moreso, gene set variation analysis (GSVA) was performed to annotate the enriched genes. Subsequently, we selected an optimal machine-learning model from four models. Finally, nomograms, calibration curves, decision curve analysis (DCA), and the GSE45885 dataset were utilized to verify the predictions' accuracy. Results: Among SD and normal controls, we confirmed that there are deCRGs and activated immune responses. Through the GSE4797 dataset, we obtained 11 deCRGs. ATP7A, ATP7B, SLC31A1, FDX1, PDHA1, PDHB, GLS, CDKN2A, DBT, and GCSH were highly expressed in testicular tissues with SD, whereas LIAS was lowly expressed. Additionally, two clusters were identified in SD. Immune-infiltration analysis showed the existing heterogeneity of immunity at these two clusters. Cuproptosis-related molecular Cluster2 was marked by enhanced expressions of ATP7A, SLC31A1, PDHA1, PDHB, CDKN2A, DBT, and higher proportions of resting memory CD4 + T cells. Furthermore, an eXtreme Gradient Boosting (XGB) model based on 5-gene was built, which showed superior performance on the external validation dataset GSE45885 (AUC = 0.812). Therefore, the combined nomogram, calibration curve, and DCA results demonstrated the accuracy of predicting SD. Conclusion: Our study preliminarily illustrates the relationship between SD and cuproptosis. Moreover, a bright predictive model was developed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Yu, Liu, Deng, Zhao, Guo and Gao.)

In this paper, a novel liquid level sensing system is proposed to enhance the capacity of the sensing system, as well as reduce the cost and increase the sensing accuracy. The proposed sensing system can monitor the liquid level of several points at the same time in the sensing unit. Additionally, for cost efficiency, the proposed system employs only one sensor at each spot and all the sensors are multiplexed. In multiplexed systems, when changing the liquid level inside the container, the float position is changed and leads to an overlap or cross-talk between two sensors. To solve this overlap problem and to accurately predict the liquid level of each container, we proposed a deep neural network (DNN) approach to properly identify the water level. The performance of the proposed DNN model is evaluated via two different scenarios and the result proves that the proposed DNN model can accurately predict the liquid level of each point. Furthermore, when comparing the DNN model with the conventional machine learning schemes, including random forest (RF) and support vector machines (SVM), the DNN model exhibits the best performance.

Betalains are tyrosine-derived plant pigments exclusively found in the Caryophyllales order and some higher fungi and generally classified into two groups: red-violet betacyanins and yellow-orange betaxanthins. Betalains attract great scientific and economic interest because of their relatively simple biosynthesis pathway, attractive colors and health-promoting properties. Co-expressing two core genes BvCYP76AD1 and BvDODA1 with or without a glycosyltransferase gene MjcDOPA5GT allowed the engineering of carrot (an important taproot vegetable) to produce a palette of unique colors. The highest total betalains content, 943.2 μg·g -1 DW, was obtained in carrot taproot transformed with p35S:RUBY which produces all of the necessary enzymes for betalains synthesis. Root-specific production of betalains slightly relieved tyrosine consumption revealing the possible bottleneck in betalains production. Furthermore, a unique volcano-like phenotype in carrot taproot cross-section was created by vascular cambium-specific production of betalains. The betalains-fortified carrot in this study is thus anticipated to be used as functional vegetable and colorful carrot germplasm in breeding to promote health., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

The largest solid organ of the male genitalia, the prostate gland, is comprised of a variety of cells such as prostate epithelial cells, smooth muscle cells, fibroblasts, and endothelial cells. Prostate diseases, especially prostate cancer and prostatitis, are often accompanied by acute/chronic inflammatory responses or even cell death. Pyroptosis, a cell death distinct from necrosis and apoptosis, which mediate inflammation may be closely associated with the development of prostate disease. Pyroptosis is characterized by inflammasome activation via pattern recognition receptors (PRR) upon recognition of external stimuli, which is manifested downstream by translocation of gasdermin (GSDM) protein to the membrane to form pores and release of inflammatory factors interleukin (IL)-1β and IL-18, a process that is Caspase-dependent. Over the past number of years, many studies have investigated the role of inflammation in prostate disease and have suggested that pyroptosis may be an important driver. Understanding the precise mechanism is of major consequence for the development of targeted therapeutic strategies. This review summarizes the molecular mechanisms, regulation, and cellular effects of pyroptosis briefly and then discuss the current pyroptosis studies in prostate disease research and the inspiration for us., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Guo, Gao, Wang, Wang, Wang, Liu, Deng, Zhao, Zhang and Yu.)

Background and Aims: Previous studies showed that inflammation affects depressive symptoms. Dietary fiber may be associated with inflammation and depressive symptoms. We aimed to investigate the relationship between inflammation and depressive symptoms at different levels of dietary fiber intake and to explore whether dietary fiber affects depression through inflammation., Methods: A total of 8,430 National Health and Nutrition Examination Survey (NHANES) samples were collected between 2015 and 2018. Factor analysis was used to determine dietary patterns. Linear regression and logistic regression analysis were used to explore the relationship between nutrients, inflammation, and depressive symptoms, and the mediation analysis was conducted using the bootstrap method., Results: Factor 3 (dietary fiber and vitamins) was inversely associated with depressive symptoms and inflammation. The upper quartile scores of the dietary inflammatory index (DII) and C-reactive protein (CRP) were associated with depressive symptoms compared with controls (DII: OR = 1.851, 95% CI: 1.267-2.705; CRP: OR = 1.737, 95% CI: 1.136-2.656). The DII score and CRP were associated with depressive symptoms in the group with low dietary fiber intake (DII: OR = 2.736, 95% CI: 1.628-4.598; CRP: OR = 2.092, 95% CI: 1.196-3.658) but not in the high dietary fiber intake group. Mediating analysis showed that CRP partially mediated the effect of dietary fiber intake on depressive symptoms (β indirect = -0.0025, 95% CI: -0.0038 to -0.0013), and the mediated proportion was 10.5%., Conclusion: In this study, we found that DII scores and CRP were not associated with depressive symptoms in participants with high dietary fiber intake, and inflammation partially mediates the effect of dietary fiber on depressive symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Cui, Zhang, Xie, Deng, Guo, Wang, Wu, Dong and Luo.)

Background: Thrombophilia is a group of disorders that result in a blood hypercoagulable state and induce thrombosis, which was found widely existed in recurrent pregnancy loss (RPL). More and more research about thrombophilia has been conducted but the association between thrombophilia and RPL remains uncertain. Thus, it's necessary to combine relevant literature to find the research hotspots and analyze the internal link between different study points, and then predict the development trend in RPL with thrombophilia., Methods: Relevant articles between 1970 and 2022 were obtained from the Web of Science (WoS) database. Software VOSviewer and CiteSpace were used to perform the analysis and conduct visualization of scientific productivity and emerging trends., Results: Seven hundred twenty-five articles published in recent 30 years by 3205 authors from 1139 organizations and 68 countries were analyzed. 37authors, 38 countries, and 53 organizations published papers ≥5. The United States was the most productive country and Univ Amsterdam was the most productive institution. Journal thrombosis and haemostasis had the most total citations. In keyword and clusters, factor-v-Leiden, inherited thrombophilia, activated protein-c, low-dose aspirin, molecular-weigh heparin, polymorphism had high-frequency focus on its etiology, diagnostics, and therapeutics. The strongest keyword bursts showed the research hotspots changed over time., Conclusions: There could be differences in the clinical relevance of different type of thrombophilia, as well as single and multiple thrombophilic factors. Anticoagulation and immunotherapy are currently the main treatment options. More clinical trials and basic research are expected and we should attach more attention to the whole management of in-vitro fertilization in the future., (© 2022. The Author(s).)

Urethral plate (UP)-preserving urethroplasty is simple and has few complications, but it may affect the development of penis in the long term and lead to recurrent chordee. In this study, we used obliquely cut UP to repair hypospadias with mild chordee after degloving (15°-30°) and compared the results with onlay urethroplasty to explore its rationality and feasibility. Between April 2018 and October 2020, 108 hypospadias patients underwent onlay urethroplasty or modified onlay urethroplasty. Clinical data were prospectively collected, and medium-term outcomes were assessed at follow-up. The complications were compared between the two groups. Forty-four patients underwent the modified onlay procedure (Group I), with follow-up time (mean ± standard deviation [s.d.]) of 23.2 ± 4.5 (range: 17-31) months. Sixty-four patients underwent a standard onlay procedure (Group II), with follow-up time (mean ± s.d.) of 39.7 ± 3.9 (range: 32-46) months. There was no difference in age at surgery. The urethral defect length and operative time were longer in Group I. Six cases of fistula and one case each of stricture and diverticulum were reported in Group I. In Group II, 11 cases of fistula and one case each of stricture and diverticulum were reported. The complication rates were 18.2% and 20.3% in Group I and Group II, respectively (P &gt; 0.05). These medium-term follow-up results demonstrate that the modified onlay procedure (oblique cut UP urethroplasty) is a safe and feasible technique for hypospadias with mild chordee after degloving. Compared with standard onlay urethroplasty, this modified procedure is conducive to the complete removal of scar tissue underlying the UP without increasing the risk of surgical complications., Competing Interests: None

Purpose: Gefitinib is a widely used therapeutic drug for non-small cell lung cancer (NSCLC), and its acquired resistance has become one of the barriers to the successful use of the drugs to treat NSCLC patients. Long non-coding RNA (lncRNA) has an essential role in developing cancer drug resistance. Hence, this study aimed to investigate the effect and modulatory mechanisms of lncRNA MCF2L-AS1 in Gefitinib resistance in NSCLC., Methods: IBEAS-2B and A549 cells and human NSCLC tissues were used. A549/GR cell line was constructed by continuous exposure to Gefitinib. Cell viability, apoptosis, migration, colony formation, and protein expression studies were done in transfected cells. Interactions of MCF2L-AS1, ELAVL1, and Cyclin D1 (CCND1 was also investigated., Results: In patients with Gefitinib-resistant NSCLC, MCF2L-AS1 and CCND1 were both up-regulated. Knockdown of MCF2L-AS1 reduced Gefitinib-resistant NSCLC cell progression, indicating that inhibition of MCF2L-AS1 restrained Gefitinib-resistant NSCLC. Mechanically, MCF2L-AS1 enhanced CCND1 mRNA stability via combining with ELAVL1, thereby elevating the resistance of NSCLC cells to Gefitinib. Moreover, E2F1 could transcriptionally up-regulate MCF2L-AS1., Conclusion: The results manifest that lncRNA MCF2L-AS1, as an oncogene of NSCLC, controls CCDN1 via ELAVL1 to drive the growth of NSCLC cells and Gefitinib resistance.

The taproot of purple carrot accumulated rich anthocyanin, but non-purple carrot did not. MYB transcription factors (TFs) condition anthocyanin biosynthesis in many plants. Currently, genome-wide identification and evolution analysis of R2R3-MYB gene family and their roles involved in conditioning anthocyanin biosynthesis in carrot is still limited. In this study, a total of 146 carrot R2R3-MYB TFs were identified based on the carrot transcriptome and genome database and were classified into 19 subfamilies on the basis of R2R3-MYB domain. These R2R3-MYB genes were unevenly distributed among nine chromosomes, and Ka / Ks analysis suggested that they evolved under a purified selection. The anthocyanin-related S6 subfamily, which contains 7 MYB TFs, was isolated from R2R3-MYB TFs. The anthocyanin content of rhizodermis, cortex, and secondary phloem in 'Black nebula' cultivar reached the highest among the 3 solid purple carrot cultivars at 110 days after sowing, which was approximately 4.20- and 3.72-fold higher than that in the 'Deep purple' and 'Ziwei' cultivars, respectively. The expression level of 7 MYB genes in purple carrot was higher than that in non-purple carrot. Among them, DcMYB113 ( DCAR&#95;008994 ) was specifically expressed in rhizodermis, cortex, and secondary phloem tissues of 'Purple haze' cultivar, with the highest expression level of 10,223.77 compared with the control 'DPP' cultivar at 70 days after sowing. DcMYB7 ( DCAR&#95;010745 ) was detected in purple root tissue of 'DPP' cultivar and its expression level in rhizodermis, cortex, and secondary phloem was 3.23-fold higher than that of secondary xylem at 110 days after sowing. Our results should be useful for determining the precise role of S6 subfamily R2R3-MYB TFs participating in anthocyanin biosynthesis in carrot.

Objective: To observe the efficacy and safety of Guihuang Formula (GHF) in treating patients with type III prostatitis and Chinese medicine syndrome of dampness-heat and blood stasis., Methods: Sixty-six patients diagnosed with type III prostatitis with dampness-heat and blood stasis syndrome were randomly divided into the treatment group (GHF) and the control group (tamsulosin) using a random number table, with 33 cases each group. The treatment group received GHF twice a day, and the control group received tamsulosin 0.2 mg once daily before bedtime. Patients in both groups received treatment for 6 weeks and was followed up for 2 weeks. The outcomes included the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, Chinese Medicine Symptoms Score (CMSS), expressed prostatic secretions (EPS) and adverse events (AEs)., Results: After treatment, the NIH-CPSI total score and domain scores of pain discomfort, urination and quality of life decreased significantly from the baseline in both groups (P<0.05). The CMSS score decreased in both groups (P<0.05). The WBC count decreased and lecithin body count increased in both groups (P<0.05). GHF showed a more obvious advantage in reducing the pain discomfort and quality of life domain scores of NIH-CPSI, reducing the CMSS score, increasing the improvement rate of the WBC and lecithin body counts, compared with the control group (P<0.05). There were no significant differences in decreasing urination domain score of NIH-CPSI between two groups (P>0.05). In addition, no serious AEs were observed., Conclusion: GHF is effective in treating type III prostatitis patients with dampness-heat and blood stasis syndrome without serious AEs. (Registration No. ChiCTR1900026966)., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Breast cancer (BC) is the most common cancer, which is currently the leading cause of cancer death. Circular RNAs (circRNAs) play important roles in cancer, however, circRNAs serving as vital index in BC for guiding treatment have not yet been identified. The aim of our study is to explore a novel kind of potential biomarker for BC., Materials and Methods: In this retrospective study, the samples used for assays were two groups of breast tumor tissue obtained from four BC patients, including four pairs of tumor tissues and adjacent nontumor samples. The circRNA expression profiles were detected via microarray and validated by real-time quantitative polymerase chain reaction (PCR)., Results: The differentially expressed circRNAs in tested samples were screened and analyzed by using human circRNA microarray. After analysis, considering a fold gene expression change of ≥2.0 and P<0.05, results suggested that 256 circRNAs were significantly up-regulated and 277 circRNAs were significantly down-regulated. Besides, the results of the real-time quantitative PCR assay showed that the expression of hsa&#95;circ&#95;0001583 was significantly up-regulated in BC groups (P<0.05) by real-time quantitative PCR. Therefore, we thought hsa&#95;circ&#95;0001583 might serve as a novel kind of biomarker for BC., Conclusion: Hsa&#95;circ&#95;0001583 showed significant up-regulation in BC patients with paired adjacent tissues. Many cancer immune pathways were related to has&#95;circ&#95;0001583, including autoimmune thyroid disease, chemokine and T-cell receptor signaling pathways.

Anal pain and urinary retention are the two most outstanding complications of the procedure for prolapse and hemorrhoids (PPH) surgery. This study intended to assess the clinical effect and mechanism of Prostant on urinary retention and anal pain after the PPH. Here, 30 patients received PPH surgery. The role and mechanism of Prostant in patients and mice with urinary retention and anal pain were evaluated. ANOVA tests were executed and differences between groups were regarded as statistically significant when p < 0.05. Prostant effectively improved the urination status, lower abdomen symptoms, time to urinate and score of VAS, and the reduction of TNF- α and IL-6. Similarly, Prostant can ameliorate the outcome of urodynamics in urinary retention mice. Mechanically, Prostant reversed the urinary retention-elevated the serum level of hs-CRP and TNF- α , reduction of IL-2, imbalance of Treg/Th17, and level of JAK2 and phosphorylated STAT3. Besides, Prostant ameliorated the pain as shown by the reduction of writhing response, and the elevation of threshold of pain and degree of swelling. Moreover, Prostant antagonized the pain-induced dysregulation of Treg/Th17. Therefore, Prostant can treat patients and mice with anal pain and urinary retention by modulating the balance of Th17/Treg to regulate the secretion and production of inflammatory factors. We hope our results can establish a scientific treatment approach for solving anal pain and urinary retention after PPH surgery of mixed hemorrhoids., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Wei-Min Luo et al.)