Dynamically changing antineutrophil cytoplasmic antibodies in granulomatosis with polyangiitis: A case report.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is one of the most prevalent forms of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. GPA is characterized histologically by necrotizing granulomatous inflammation in addition to vasculitis. The diagnosis of GPA depends on clinical presentation, serological evidence of a positive ANCA, and/or histological evidence of necrotizing vasculitis or granulomatous destructive parenchymal inflammation. Cytoplasmic ANCA (c-ANCA) is positive in 65%-75% of GPA patients, accompanied by proteinase 3 (PR3), the main target antigen of c-ANCA, another 5% of GPA patients had negative ANCA. CASE SUMMARY: The patient, a 52-year-old male, presented with unexplained nasal congestion, tinnitus, and hearing loss. After a duration of 4 months experiencing these symptoms, the patient subsequently developed fever and headache. The imaging examination revealed the presence of bilateral auricular mastoiditis and partial paranasal sinusitis, and the ANCA results were negative. The anti-infective therapy proved to be ineffective, but the patient's symptoms and fever were quickly relieved after 1 wk of treatment with methylprednisolone 40 mg once a day. However, after continuous use of methylprednisolone tablets for 3 months, the patient experienced a recurrence of fever accompanied by right-sided migraine, positive c-ANCA and PR3, and increased total protein in cerebrospinal fluid. The patient was diagnosed with GPA. After receiving a treatment regimen of intravenous methylprednisolone 40 mg/d and cyclophosphamide 0.8 g monthly, the patient experienced alleviation of fever and headache. Additionally, the ANCA levels became negative and there has been no recurrence. CONCLUSION: For GPA patients with negative ANCA, there is a potential for early missed diagnosis. The integration of histopathological results and multidisciplinary communication plays a crucial role in facilitating ANCA-negative GPA.

Circular RNA HSDL2 promotes breast cancer progression via miR-7978 ZNF704 axis and regulating hippo signaling pathway.

Circular RNAs (circRNAs) are a new group of endogenous RNAs recently found to be involved in the development of various diseases, including their confirmed involvement in the progression of several types of cancers. Unluckily, the abnormal expression and functions of circRNAs in breast cancer shall be further investigated. This work aims to elucidate the action and molecular mechanism of circHSDL2 in the malignant progression of breast cancer. Differential expression profiles of circRNAs in breast cancer tissues relative to normal breast tissues and in the exosomes of breast cancer patients compared to healthy women were analyzed from databases to identify potentially functional circRNAs. CircHSDL2 was selected for further investigation. Cell proliferation, migration and invasion assays were done to assess the effect of circHSDL2 overexpression on breast cancer cells. Bioinformatics test and dual-luciferase reporter experiments were done to explore the interaction between circHSDL2 and miRNA. Downstream target genes were further investigated through proteomics analysis and Western blotting. The influence of circHSDL2 on breast cancer in vivo was evaluated through xenograft experiments in nude mice. Functional analysis demonstrated circHSDL2 overexpression promoted the division, movement, and invasion of breast cancer cells both in vivo and in vitro. Mechanistically, circHSDL2 acted as a sponge for miR-7978 to affect ZNF704 expression and thereby regulate the Hippo pathway in breast cancer cells. In conclusion, circHSDL2 regulates the Hippo pathway through the miR-7978/ZNF704 axis to facilitate the malignancy of breast cancer. This may be a potential biomarker and treatment target.

A new perspective on hematological malignancies: m6A modification in immune microenvironment.

Immunotherapy for hematological malignancies is a rapidly advancing field that has gained momentum in recent years, primarily encompassing chimeric antigen receptor T-cell (CAR-T) therapies, immune checkpoint inhibitors, and other modalities. However, its clinical efficacy remains limited, and drug resistance poses a significant challenge. Therefore, novel immunotherapeutic targets and agents need to be identified. Recently, N6-methyladenosine (m6A), the most prevalent RNA epitope modification, has emerged as a pivotal factor in various malignancies. Reportedly, m6A mutations influence the immunological microenvironment of hematological malignancies, leading to immune evasion and compromising the anti-tumor immune response in hematological malignancies. In this review, we comprehensively summarize the roles of the currently identified m6A modifications in various hematological malignancies, with a particular focus on their impact on the immune microenvironment. Additionally, we provide an overview of the research progress made in developing m6A-targeted drugs for hematological tumor therapy, to offer novel clinical insights.

Enantioselective Nickel-Catalyzed Denitrogenative Transannulation En Route to N-N Atropisomers.

Nickel-catalyzed transannulation reactions triggered by the extrusion of small gaseous molecules have emerged as a powerful strategy for the efficient construction of heterocyclic compounds. However, their use in asymmetric synthesis remains challenging because of the difficulty in controlling stereo- and regioselectivity. Herein, we report the first nickel-catalyzed asymmetric synthesis of N-N atropisomers by the denitrogenative transannulation of benzotriazones with alkynes. A broad range of N-N atropisomers was obtained with excellent regio- and enantioselectivity under mild conditions. Moreover, density functional theory (DFT) calculations provided insights into the nickel-catalyzed reaction mechanism and enantioselectivity control.

Mechanism and Origins of Enantioselectivity in the Nickel-catalyzed Asymmetric Synthesis of Silicon-Stereogenic Benzosiloles.

As important π-skeletons, benzosiloles often possess unique electronic and optical properties and have been widely used in semiconductor materials. Therefore, great attention has been drawn to the area of developing novel synthetic methods for various benzosiloles. However, the synthesis of enantioenriched silicon-stereogenic benzosiloles is still at an early stage and remains to be explored. Herein, we performed systematic density functional theory studies on the recently reported nickel-catalyzed asymmetric synthesis of silicon-stereogenic benosiloles, which was enabled by an enantioselective desymmetrization of (2-alkenyl)aryl-substituted silacyclobutanes. Our computational study shows that the reaction mechanism involves ligand exchange, oxidative addition, alkene insertion, and hydrogen-transfer coupled reductive-demetalation steps. The proposed transmetalation and ß-hydride elimination mechanism was not found, which might be due to the unfavorable ring strain of the multicyclic intermediates. The novel hydrogen-transfer coupled reductive-demetalation mechanism was shown to be reasonable for the generation of the silicon-stereogenic benzosilole. Noncovalent interactions (including C-H···π and hydrogen bonding) in the rate-determining alkene insertion transition state account for the origins of the enantioselectivity. Our computational study sheds light on the detailed reaction mechanism and also provides insights for the development of novel approaches for synthesis of high-value silicon-stereogenic compounds.

Eosinophil peroxidase promotes bronchial epithelial cells to secrete asthma-related factors and induces the early stage of airway remodeling.

Asthma is a heterogeneous disease characterized by chronic airway inflammation, reversible airflow limitation, and airway remodeling. Eosinophil peroxidase (EPX) is the most abundant secondary granule protein unique to activated eosinophils. In this study, we aimed to illustrate the effect of EPX on the epithelial-mesenchymal transition (EMT) in BEAS-2B cells. Our research found that both EPX and ADAM33 were negatively correlated with FEV1/FVC and FEV1%pred, and positively correlated with IL-5 levels. Asthma patients had relatively higher levels of ADAM33 and EPX compared to the healthy control group. The expression of TSLP, TGF-ß1 and ADAM33 in the EPX intervention group was significantly higher. Moreover, EPX could promote the proliferation, migration and EMT of BEAS-2B cells, and the effect of EPX on various factors was significantly improved by the PI3K inhibitor LY294002. The findings from this study could potentially offer a novel therapeutic target for addressing airway remodeling in bronchial asthma, particularly focusing on EMT.

Prospects for the Application of Transplantation With Human Amniotic Membrane Epithelial Stem Cells in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a multi-organ and systemic autoimmune disease characterized by an imbalance of humoral and cellular immunity. The efficacy and side effects of traditional glucocorticoid and immunosuppressant therapy remain controversial. Recent studies have revealed abnormalities in mesenchymal stem cells (MSCs) in SLE, leading to the application of bone marrow-derived MSCs (BM-MSCs) transplantation technique for SLE treatment. However, autologous transplantation using BM-MSCs from SLE patients has shown suboptimal efficacy due to their dysfunction, while allogeneic mesenchymal stem cell transplantation (MSCT) still faces challenges, such as donor degeneration, genetic instability, and immune rejection. Therefore, exploring new sources of stem cells is crucial for overcoming these limitations in clinical applications. Human amniotic epithelial stem cells (hAESCs), derived from the eighth-day blastocyst, possess strong characteristics including good differentiation potential, immune tolerance with low antigen-presenting ability, and unique immune properties. Hence, hAESCs hold great promise for the treatment of not only SLE but also other autoimmune diseases.

Intracellular MicroRNA Imaging and Specific Discrimination of Prostate Cancer Circulating Tumor Cells Using Multifunctional Gold Nanoprobe-Based Thermophoretic Assay.

Circulating tumor cells (CTCs) have emerged as powerful biomarkers for diagnosis of prostate cancer. However, the effective identification and concurrently accurate imaging of CTCs for early screening of prostate cancer have been rarely explored. Herein, we reported a multifunctional gold nanoprobe-based thermophoretic assay for simultaneous specific distinguishing of prostate cancer CTCs and sensitive imaging of intracellular microRNA (miR-21), achieving the rapid and precise detection of prostate cancer. The multifunctional gold nanoprobe (GNP-DNA/Ab) was modified by two types of prostate-specific antibodies, anti-PSMA and anti-EpCAM, which could effectively recognize the targeting CTCs, and meanwhile linked double-stranded DNA for further visually imaging intracellular miR-21. Upon the specific internalization of GNP-DNA/Ab by PC-3 cells, target aberrant miR-21 could displace the signal strand to recover the fluorescence signal for sensitive detection at the single-cell level, achieving single PC-3 cell imaging benefiting from the thermophoresis-mediated signal amplification procedure. Taking advantage of the sensitive miR-21 imaging performance, GNP-DNA/Ab could be employed to discriminate the PC-3 and Jurkat cells because of the different expression levels of miR-21. Notably, PC-3 cells were efficiently recognized from white blood cells, exhibiting promising potential for the early diagnosis of prostate cancer. Furthermore, GNP-DNA/Ab possessed good biocompatibility and stability. Therefore, this work provides a great tool for aberrant miRNA-related detection and specific discrimination of CTCs, achieving the early and accurate diagnosis of prostate cancer.

Trends in bronchopulmonary dysplasia and respiratory support among extremely preterm infants in China over a decade.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is one of the most serious complications affecting extremely preterm infants. We aimed to evaluate temporal trends in BPD and administration of respiratory support among extremely preterm infants in China over a decade. METHODS: This was a retrospective study using data from a multicenter database, which included infants born less than 28 weeks' gestation discharged from 68 tertiary neonatal care centers in China between 2010 and 2019. Changes in rates and severity of BPD, as well as modalities and duration of respiratory support, were evaluated. RESULTS: Among 4808 eligible infants with gestational age (GA) of 21+6/7  to 27+6/7 weeks and a mean (SD) birth weight of 980 (177) g, no significant change of median GA was found over time. Overall, 780 (16.2%) infants died before 36 weeks' postmenstrual age, 2415 (50.2%) were classified as having no BPD, 917 (19.1%) developed Grade 1 BPD, 578 (12.0%) developed Grade 2 BPD, and 118 (2.5%) developed Grade 3 BPD. The rate of BPD increased from 20.8% in 2010 to 40.7% in 2019 (aRR for trend, 1.081; 95% confidence interval, 1.062-1.099), especially for Grade 1 and Grade 2. Although survival to discharge improved over the decade, the overall survival without BPD did not change during the study period. The use of invasive mechanical ventilation (IMV) remained unchanged. However, the use of noninvasive ventilation (NIV) increased from 71.5% in 2010 to 89.8% in 2019. Moreover, the median duration of NIV increased over time, from 17.0 (4.8, 34.0) days in 2010 to 33.0 (21.0, 44.0) days in 2019, without significant change in the duration of IMV. CONCLUSIONS: Although survival increased over the decade and respiratory support practices changed significantly between 2010 and 2019 in China, with increased use and duration of NIV, there was an increased rate of BPD and survival without BPD has not improved.

Multi-omic approaches provide insights into the molecular mechanisms of Sojae semen germinatum water extract against overactive bladder.

Sojae semen germinatum (SSG) is derived from mature soybean seeds that have been germinated and dried, typically with sprouts measuring approximately 0.5 cm in length. SSG is traditionally known for its properties in clearing heat and moisture. Nevertheless, limited information was reported on the effects and mechanisms of SSG in alleviating urinary symptoms. This study employed urodynamic parameters to investigate the therapeutic effect of SSG water extract on overactive bladder (OAB) in the rat model with benign prostatic hyperplasia. Through a combination of transcriptomic and metabolomic analyses, the pathways and key proteins of the SSG treatment for OAB were identified and validated by ELISA and Western blotting. Furthermore, network pharmacology elucidated the roles of SSG's isoflavones acting on the target which was identified by above-mentioned multi-omics analysis. Our results indicate that SSG water extract significantly mitigated OAB by down-regulating the PGE2/EP1/PLCß2/p-MLC signaling pathway. It was speculated that the active ingredient in the SSG on EP1 was genistein. This study provided valuable insights into the molecular mechanisms of SSG water extract, emphasizing the multi-target characteristics and critical pathways in improving OAB. Furthermore, this study contributes to the potential utilization of SSG as a functional food.

Modeling phenotypic heterogeneity towards evolutionarily inspired osteosarcoma therapy.

Osteosarcoma is the most common bone sarcoma in children and young adults. While universally delivered, chemotherapy only benefits roughly half of patients with localized disease. Increasingly, intratumoral heterogeneity is recognized as a source of therapeutic resistance. In this study, we develop and evaluate an in vitro model of osteosarcoma heterogeneity based on phenotype and genotype. Cancer cell populations vary in their environment-specific growth rates and in their sensitivity to chemotherapy. We present the genotypic and phenotypic characterization of an osteosarcoma cell line panel with a focus on co-cultures of the most phenotypically divergent cell lines, 143B and SAOS2. Modest environmental (pH, glutamine) or chemical perturbations dramatically shift the success and composition of cell lines. We demonstrate that in nutrient rich culture conditions 143B outcompetes SAOS2. But, under nutrient deprivation or conventional chemotherapy, SAOS2 growth can be favored in spheroids. Importantly, when the simplest heterogeneity state is evaluated, a two-cell line coculture, perturbations that affect the faster growing cell line have only a modest effect on final spheroid size. Thus the only evaluated therapies to eliminate the spheroids were by switching therapies from a first strike to a second strike. This extensively characterized, widely available system, can be modeled and scaled to allow for improved strategies to anticipate resistance in osteosarcoma due to heterogeneity.

Neoadjuvant chemoradiotherapy with capecitabine based regimen in locally advanced rectal cancer: A retrospective study.

Capecitabine-based neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for locally advanced rectal cancer. The objective of this study is to analyze overall survival (OS), disease-free survival (DFS) and prognostic factors of patients with stage II to III rectal cancer treated with nCRT in our institution. Between March 2014 to June 2020, 121 locally advanced rectal cancer patients were retrospectively reviewed and analyzed. All of the enrolled patients were treated with capecitabine-based nCRT (pelvic radiotherapy: 45-50.4 Gy, 1.8 Gy/d plus concomitant capecitabine-based chemotherapy), total mesorectal excision surgery (surgery was carried out 8-12 weeks after the end of CRT), and capecitabine-based adjuvant chemotherapy. We examined the pathological complete response rate, 3-year OS, 3-year DFS and the other prognostic factors. Kaplan-Meier method and Log-rank test were used to estimate and compare survival rate. With a median follow-up of 36 months, 3-year DFS and 3-year OS was 74.4% and 83.2%, respectively. Among the 121 patients, 24 achieved pathological complete remission (19.8%). After multivariate analysis, ypTNM stage (TNM stage after neoadjuvant therapy) was significantly associated with DFS. Positive mesorectal fasciae (MRF) status on magnetic resonance imaging and ypTNM stage were significantly related to OS. CRT with capecitabine based regimen provides high rates of survival and sphincter preservation with acceptable toxicity. YpTNM stage was significantly associated with DFS; magnetic resonance imaging MRF status and ypTNM stage were significant factors for OS after multivariate analysis. Distant metastasis is the dominant mode of treatment failure, and it is crucial to optimize systemic treatment for newly diagnosed patients.

The Most Valuable Predictive Factors for Bronchopulmonary Dysplasia in Very Preterm Infants.

INTRODUCTION: It is urgent to make a rapid screening of infants at the highest risk for bronchopulmonary dysplasia (BPD) via some succinct postnatal biomarkers, such as Ureaplasma Urealyticum (UU) infection and chest radiograph images. METHODS: A retrospective study was performed. Moderate to severe BPD or death was set as the main outcome. The association between putative variables and the main outcome were assessed by bivariate analyses and logistic regression. RESULTS: A total of 134 infants were enrolled. Bivariate analyses showed the gestational age, birth weight, appearances of diffuse opacities or grid shadows/interstitial opacities or mass opacities or cystic lucencies on chest radiographic images, a ductal diameter ≥1.5 mm and whether UU infection was associated with BPD. After adjustment by logistic regression, the risk of BPD with gestational age, sex and specific chest-radiographic manifestations remained significant. CONCLUSIONS: Chest radiograph images (appearance of diffuse opacities or grid shadows/interstitial opacities or mass opacities or cystic lucencies) could provide a quick prediction of developing BPD in clinical practice, in addition to gestational age and sex. UU infection was not an independent risk factor for BPD.

Mulberroside A ameliorates CCl4-induced liver fibrosis in mice via inhibiting pro-inflammatory response.

Liver fibrosis is caused by a variety of pathogenic factors. It is mainly characterized by chronic liver damage mediated by the imbalance between extracellular matrix synthesis and degradation. If the injury factor cannot be removed for a long time, fibrosis will progress to cirrhosis or even cancer. The development of liver fibrosis is a very complex process which is related to the activation of hepatic stellate cells (HSCs), oxidative stress, and cytokines produced by immune cells. At present, screening of substances with anti-inflammatory activity from natural plant extracts has become a new research focus in the prevention and treatment of liver fibrosis. Mulberry twig is a commonly used traditional Chinese medicine. Pharmacological studies have shown that mulberry twig has anti-inflammatory and antioxidant activities. Thus, it is likely that Mulberry twig contains active substances with liver protection functions. The present study aimed to explore the effect of Mulberroside A (MulA), the main active ingredient from Mulberry twig, on acute liver injury induced by CCl4 in mice. MulA treatment could significantly alleviate the CCl4-induced liver injury, as evidenced by histological analysis and Masson staining. However, we observed that MulA inhibited the expressions of collagen I and α-SMA in livers of CCl4-treated mice but did not directly inhibit the proliferation and activation of HSCs. Finally, we analyzed the anti-inflammatory effect of MulA and demonstrated that it could markedly inhibit the pro-inflammatory cytokines release in liver tissues and in cultured macrophages, thereby alleviating liver fibrosis. Our findings suggest MulA as a potential therapeutic candidate for liver injury and inflammatory diseases.

MiR-210-5p promotes the differentiation of human induced pluripotent stem cells into dopaminergic neural precursors by targeting SMAD4 and SUFU and treats parkinsonian rats.

The differentiation of human induced pluripotent stem cells (hiPSCs) into functional dopaminergic neural precursors is the basis of cell therapy for Parkinson's disease (PD). However, the use of small molecule inhibitors/activators in the differentiation of hiPSCs in vitro leads to cell death and low differentiation efficiency. Moreover, the mechanism of differentiation remains unclear. MiR-210-5p was increased during hiPSCs differentiation. Whether it promotes hiPSCs differentiation and transplantation needs further study. Here, we overexpressed miR-210-5p in hiPSCs to study its roles and mechanisms. We found that miR-210-5p promoted the differentiation of hiPSCs into dopaminergic neural precursors and reduced the expression of SMAD4 and SUFU meanwhile. Luciferase assays showed that miR-210-5p binded to SMAD4 and SUFU, which are key molecules in the key signals (TGF-ß and SHH) of hiPSCs differentiation. Furthermore, in the effect evaluation of cell transplantation into parkinsonian rats, the degree of behavioral recovery and the growth of transplanted cells in the group overexpressed miR-210-5p were similar to those in the positive group with all small molecule inhibitors/activators. Therefore, we conclude that miR-210-5p promotes the differentiation of hiPSCs into dopaminergic neural precursors by targeting SMAD4 and SUFU. In the therapeutic evaluation of cell transplantation, miR-210-5p can replace the use of corresponding small molecule inhibitors/activators to reduce cell death. This study provides an experimental basis and a new target for the miRNA-modified differentiation of hiPSCs and cell transplantation in clinical treatment of PD in the future.

Variations in Macrophage Activation Syndrome-associated Cardiac Diseases: A Report on Two Cases.

Macrophage activation syndrome (MAS), a secondary hemophagocytic lymphohistiocytosis characterized by an excessive systemic inflammatory response, is a life-threatening and rare disease. Cardiovascular damage is a common and severe complication of the disease, however, it is easily ignored and not well studied. Herein, we report two cases of patients with MAS-associated heart damage and review the clinical characteristics, mechanism, and treatment. Case 1 along with systemic lupus erythematosus and Kikuchi necrotizing lymphadenitis occurred in fatal acute heart failure, and case 2 complicated adult-onset Still's Disease began with atrial fibrillation and had some improvement with the treatment of high dose corticosteroids. MAS-associated heart damage is a critical issue in clinical settings, and the etiology and mechanisms of MAS-associated cardiovascular diseases are likely multifactorial. The manifestations were various and high levels of the cytokines and cardiac damage may contribute to poor prognosis. Therefore, early intensive immunosuppressive therapy probably improves the treatment outcome.

Disrupting the phase separation of KAT8-IRF1 diminishes PD-L1 expression and promotes antitumor immunity.

Immunotherapies targeting the PD-1/PD-L1 axis have become first-line treatments in multiple cancers. However, only a limited subset of individuals achieves durable benefits because of the elusive mechanisms regulating PD-1/PD-L1. Here, we report that in cells exposed to interferon-γ (IFNγ), KAT8 undergoes phase separation with induced IRF1 and forms biomolecular condensates to upregulate PD-L1. Multivalency from both the specific and promiscuous interactions between IRF1 and KAT8 is required for condensate formation. KAT8-IRF1 condensation promotes IRF1 K78 acetylation and binding to the CD247 (PD-L1) promoter and further enriches the transcription apparatus to promote transcription of PD-L1 mRNA. Based on the mechanism of KAT8-IRF1 condensate formation, we identified the 2142-R8 blocking peptide, which disrupts KAT8-IRF1 condensate formation and consequently inhibits PD-L1 expression and enhances antitumor immunity in vitro and in vivo. Our findings reveal a key role of KAT8-IRF1 condensates in PD-L1 regulation and provide a competitive peptide to enhance antitumor immune responses.

Preliminary study on Bioassay of Capparis spinosa L. seed extract and seed germination.

The present study explored the germination inhibitors present in the seeds of Capparis spinosa L., a plant species that is known for its ecological significance in preventing wind erosion and fixing sand in desertified areas. Additionally, its roots, leaves, and fruits possess medicinal properties, and are used to treat a range of ailments such as rheumatism, tumors, and diabetes. However, the plant's low germination rate under natural conditions is a major limitation. We aimed to improve the germination of C. spinosa seeds by investigating the effects of various infusions of caper seeds on the germination and seedling growth of Chinese cabbage seeds. A range of chemical reagents, hormonal immersions, and sand storage treatments were used to determine the differences in the germination rate of C. spinosa seeds. Our results revealed that among the various water extract concentrations tested, 100% water extract exhibited the strongest inhibitory effect on the germination and growth of the cabbage seeds, with a germination rate of (70.00 ± 0.09)%. Furthermore, the inhibitory effects on the germination and growth of cabbage seeds were found to be strongest when treated with the extract solution 1, yielding a germination rate of (83.33 ± 0.02)%. Notably, the leaves of Chinese cabbage seedlings turned yellow-green and yellow after treatment with the extract solution. These findings highlight the potential inhibitory effects of C. spinosa seed extracts on seed germination and growth and suggest that further research is needed to better understand the underlying mechanisms. The results of the germination experiment with methanol extract showed a sharp decline in the germination rate of Chinese cabbage seeds treated with 50% methanol extract, to (4.67 ± 0.02)%. These findings indicate the presence of germination-inhibiting substances in caper seeds. The highest germination potential was observed when the caper seeds were soaked in 30% PEG, reaching 35.00%. The highest germination rate, 19.33%, was observed when the seeds were soaked in 250 mg/L GA3 and 25 mmol/L NaCl. These results suggest that the germination inhibitor present in caper seeds affects the germination of cabbage seeds as well. The highest germination rate was achieved when the seeds were soaked with gibberellin. It is hoped that the research on the germination-inhibiting substances in caper seeds will provide a scientific foundation for improving and refining the artificial propagation and cultivation methods of this species.

FoxM1 knockdown enhanced radiosensitivity of esophageal cancer by inducing apoptosis.

Radioresistance is a main reason for local recurrence of esophageal squamous cell carcinoma (ESCC). Forkhead box M1 (FoxM1) is implicated in cancer progression and chemoresistance. This study aims to determine the role of FoxM1 in ESCC radioresistance. We found that FoxM1 protein was upregulated in ESCC tissues compared with adjacent normal tissues. In vitro assays revealed that following irradiation, Eca-109, TE-13, and KYSE-150 cells had increased levels of FoxM1 protein. FoxM1 knockdown resulted in significantly reduced colony formation and increased cell apoptosis following irradiation. Moreover, FoxM1 knockdown induced ESCC cells to accumulate in the radiosensitive G2 /M phase and impeded the repair of radiation-induced DNA damage. Mechanistic studies indicated that radiosensitization of ESCC enhanced by FoxM1 knockdown was associated with increased BAX/BCL2 ratio as well as downregulated Survivin and XIAP, followed by the activation of both extrinsic and intrinsic apoptosis pathways. In xenograft mouse model, the combination of radiation and FoxM1-shRNA led to a synergistic anti-tumor effect. In conclusion, FoxM1 is a promising target to enhance radiosensitivity of ESCC.

Cloning and functional analysis of the root-knot nematode resistance gene NtRk1 in tobacco.

Tobacco (Nicotiana tabacum L.) is an economically important crop worldwide. Root-knot nematodes (RKNs) are responsible for yield losses in tobacco and other crops, such as tomato, potato, peanut, and soybean. Therefore, screening for resistance genes that can prevent RKN infestation and the associated damage is crucial. However, there is no report of cloning tobacco RKN resistance genes to date. Here, we cloned the tobacco RKN resistance gene NtRk1 from the resistant variety TI706, using rapid amplification of cDNA ends. NtRk1 has high homology with other RKN resistance genes (CaMi in pepper, Mi-1.1 and Mi-1.2 in tomato). Under normal conditions, NtRk1 was barely expressed in the roots; however, following RKN infection, its expression level rapidly increased. Overexpression of NtRk1 in the susceptible cultivar "Changbohuang" enhanced its resistance to Meloidogyne incognita, while RNA interference of NtRk1 in the resistant cultivar K326 resulted in its susceptibility to M. incognita. Moreover, compared with resistant variety K326, we found the salicylic acid and jasmonic acid contents of RNAi plants decreased after inoculation with M. incognita, and confirmed that the function of NtRk1 is related to these phytohormones. These findings indicate that NtRk1 is an RKN resistance gene, which is abundantly expressed in response to RKN infection and may enhance host defense responses by elevating salicylic acid and jasmonic acid levels.