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Improving apple water-use efficiency (WUE) is increasingly desirable in the face of global climate change. Melatonin is a pleiotropic molecule that functions in plant development and stress tolerance. In apple, exogenous application of melatonin has been largely investigated, but melatonin biosynthesis and its physiological roles remain elusive. In the plant biosynthetic pathway of melatonin, the last and key step is that N -acetylserotonin methyltransferase (ASMT) converts N -acetylserotonin into melatonin. Here, we identified an apple ASMT gene, MdASMT9 , using homology-based cloning and in vitro enzyme assays. Overexpression of MdASMT9 significantly increased melatonin accumulation in transgenic apple lines. Moreover, an enhanced WUE was observed in the MdASMT9 -overexpressing apple lines. Under well-watered conditions, this increase in WUE was attributed to an enhancement of photosynthetic rate and stomatal aperture via a reduction in abscisic acid biosynthesis. By contrast, under long-term moderate water deficit conditions, regulations in photoprotective mechanisms, stomatal behavior, osmotic adjustment and antioxidant activity enhanced the WUE in transgenic apple lines. Taken together, our findings shed light on the positive effect of MdASMT9 on improving WUE of apple by modulating melatonin biosynthesis. [ABSTRACT FROM AUTHOR]

The high accumulation of phloridzin makes apple (Malus domestica) unique in the plant kingdom, which suggests a vital role of its biosynthesis in physiological processes. In our previous study, silencing MdUGT88F1 (a key UDP-GLUCOSE: PHLORETIN 2'-O-GLUCOSYLTRANSFERASE gene) revealed the importance of phloridzin biosynthesis in apple development and Valsa canker resistance. Here, results from MdUGT88F1 -silenced lines showed that phloridzin biosynthesis was indispensable for normal chloroplast development and photosynthetic carbon fixation by maintaining MdGLK1/2 (GOLDEN2-like1/2) expression. Interestingly, increased phloridzin biosynthesis did not affect plant (or chloroplast) development, but reduced nitrogen accumulation, leading to chlorophyll deficiency, light sensitivity, and sugar accumulation in MdUGT88F1- overexpressing apple lines. Further analysis revealed that MdUGT88F1-mediated phloridzin biosynthesis negatively regulated the cytosolic glutamine synthetase1-asparagine synthetase-asparaginase (GS1-AS-ASPG) pathway of ammonium assimilation and limited chlorophyll synthesis in apple shoots. The interference of phloridzin biosynthesis in the GS1-AS-ASPG pathway was also assumed to be associated with its limitation of the carbon skeleton of ammonium assimilation through metabolic competition with the tricarboxylic acid cycle. Taken together, our findings shed light on the role of MdUGT88F1-mediated phloridzin biosynthesis in the coordination between carbon and nitrogen accumulation in apple trees. [ABSTRACT FROM AUTHOR]

Polygalacturonases ( PGs ) are pectin degrading enzymes, which are involved in various plant developmental processes, such as fruit ripening, organ abscission, and pollen ripening. Through using homolog searching and protein domain identifying method, 74 MtPG genes were distinguished from the Medicago truncatula genome. According to multiple alignments and phylogenetic analysis results, the genes were classified into six subfamilies, including 9, 7, 4, 11, 18, and 25 MtPG gene members. Besides, chromosomal location analysis shows that the MtPG genes in M. truncatula were unevenly distributed among the eight chromosomes, varying from two to sixteen members on every chromosome. Meanwhile, numerous duplication events were identified in the PG gene family, which indicates that MtPG genes expanded through gene duplication events in M. truncatula. Finally, their expressional profiles were assessed using public RNA-Seq data, and results show that MtPG genes were expressed in the root, nodule, blade, bud, seedpod, and flower. The 31 MtPG genes were clustered into four groups ( Cluster Group I to VI) based on their expression levels, and most of the PG gene family members showed the highest expression levels in nodule and/or flower, which suggests their significant roles in tissues development process, especially for flower and root. In summary, these findings will be valuable for determining detailed MtPG genes functions in M. truncatula. [ABSTRACT FROM AUTHOR]

Previous research indicates an unclear relationship between personal initiative (PI) and entrepreneurial intention. Drawing upon existing literature, this study proposes that the two forms of PI (i.e., task- and relationship-oriented PI) influence entrepreneurial intention differently, and that such effects are transited through entrepreneurial self-efficacy. An analyses of 210 employees showed that task-oriented PI is negatively related to entrepreneurial intention, whereas relationship-oriented PI is positively related to entrepreneurial intention. It was further found that the effect of relationship-oriented PI on entrepreneurial intention is mediated by entrepreneurial self-efficacy, whereas the effect of task-oriented PI on entrepreneurial intention is not. Finally, the theoretical and practical implications of our findings are discussed. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is a rare but highly invasive cancer, with its incidence rising in recent years. Currently, surgery remains the most definitive therapeutic option for CCA. However, similar to other malignancies, most CCA patients are not eligible for surgical intervention at the time of diagnosis. The chemotherapeutic regimen of gemcitabine combined with cisplatin is the standard treatment for advanced CCA, but its effectiveness is often hampered by therapeutic resistance. Recent research highlights the remarkable plasticity of tumor-associated macrophages (TAMs) within the tumor microenvironment (TME). TAMs play a crucial dual role in either promoting or suppressing tumor development, depending on the factors that polarize them toward pro-tumorigenic or anti-tumorigenic phenotypes, as well as their interactions with cancer cells and other stromal components. In this review, we critically examine recent studies on TAMs in CCA, detailing the expression patterns and prognostic significance of different TAM subtypes in CCA, the mechanisms by which TAMs influence CCA progression and immune evasion, and the potential for reprogramming TAMs to enhance anticancer therapies. This review aims to provide a framework for deeper 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 © 2024 Chen, Sheng, Li, Gao, Hu, Chen, Fei and Song.)

Clear cell renal cell carcinoma (ccRCC) is a common kidney cancer with subtle early symptoms, high recurrence rates, and low sensitivity to traditional treatments like radiotherapy and chemotherapy. Identifying novel therapeutic targets is critical. The expression level of adenylate kinases 7 (AK7) in ccRCC was examined by the TCGAportal and UALCAN databases. The effect of AK7 on proliferation, invasion and migration of ccRCC cell lines was evaluated by cell assay. The correlation between AK7 expression and prognosis, as well as its direct relationship with immunotherapy efficacy, was analyzed using CANCERTOOL and Kaplan-Meier plotter data. Moreover, the TISIDB database was used to study the relationship between AK7 and immune markers. The effect of overexpressed AK7 combined with PD1 monoclonal antibody on ccRCC was evaluated in animal experiments. The results showed that low level of AK7 expression was observed in ccRCC tissues. The expression of AK7 can regulate the proliferation, invasion, and migration of human ccRCC cell lines. The level of AK7 expression was associated with OS of ccRCC patients. This was potentially due to the negative connection between AK7 expression and CD8+ T cell depletion, indicating that immunotherapy might be less effective in individuals with low AK7 expression. Conversely, augmenting AK7 demonstrated an enhanced effectiveness of anti-PD1 therapy. The findings of our research strongly indicated that AK7 could serve as both a prognostic indicator and therapeutic target for patients with ccRCC. Moreover, the overexpression of AK7 combined with anti-PD1 held promising potential as a therapeutic approach for treating ccRCC.

Background: Gastric cancer (GC) is one of the leading malignancies of the digestive system. Circular RNAs (circRNAs) are well-established to play critical regulatory roles in GC development. The current study sought to explore the effects and regulatory mechanism of circ_0001013 in the course of GC., Methods: First, differential circRNAs and related mechanisms in GC were predicted by microarray analysis. Circ_0001013, microRNA (miR)-136, and TWSG1 expression patterns were subsequently detected in GC clinical samples and cells using RT-qPCR. The relationship among circ_0001013, miR-136, and TWSG1 was further assessed by dual-luciferase reporter assay, biotin-coupled probe pull-down assay, and biotin-coupled miRNA capture. Based on gain- and loss-of-function assays, GC cell proliferation, migration, invasion, and the cell cycle and apoptosis were also measured by 5-ethynyl-2'-deoxyuridine (EdU) assay, scratch test, Transwell assay, and flow cytometry, respectively. Moreover, the effect of circ_0001013 on tumor growth was detected by tumor xenografting in nude mice., Results: Circ_0001013 was predicted to be up-regulated in GC by microarray profiling, which was confirmed by RT-qPCR detection in GC tissues and cells. miR-136 was poorly expressed, and TWSG1 was highly expressed in GC tissues. Mechanistically, circ_0001013 bound to miR-136, which negatively targeted TWSG1 in the GC cells. Silencing circ_0001013 or TWSG1 or over-expressing miR-136 led to decreased GC cell proliferation, migration, invasion, and cell cycle arrest and enhanced apoptosis. Furthermore, silencing circ_0001013 resulted in diminished TWSG1 expression and inhibited transplanted tumor growth in the nude mice., Conclusion: Collectively, our findings indicated that circ_0001013 increased TWSG1 expression by binding to miR-136, thereby exerting oncogenic effects in GC., Competing Interests: None., (AJTR Copyright © 2022.)

Objective: To investigate the expression of Calponin-1 and Transgenlin in the uterine smooth muscles during normal labor on-sets, and to evaluate their effect on initiating the normal labor., Methods: A total of 14 uterine bodies and lower segments of human pregnancy were divided to a non-labor group (NIL) and a labor group(IL). Immunohistochemical technology and Western blot were used to determine the expression of Calponin-1 and Transgelin in the 2 groups., Results: Immunohistochemical detection and Western blot showed that Calponin-1 protein in the uterine smooth muscle tissue of the body and the lower uterine segment of smooth muscle tissues had significant difference (P<0.05). The expression of Transgelin in the uterine body smooth muscle tissue in the IL was higher than that in the NIL(P<0.05). In the lower uterine segments of the smooth muscle, the expression of Transgelin was not significantly different in the 2 groups (P>0.05)., Conclusion: Calponin-1 of the uterine smooth muscle and Transgelin of the uterine body smooth muscle may involve in the regulation of uterine smooth muscle contractility, which is closely related to child birth launch.

Objective: To investigate the effect of Calponin-1 suppression on human myometrium cells through adenovirus mediated siRNA., Methods: Human uterine smooth muscle tissues were digested with enzymes, cultured and confirmed with immunocytochemistry. Adenovirus siRNA-Calponin-1 plasmid was transfected into primary cultured uterine smooth muscle cells in vitro. The expressions of Calponin-1 mRNA and protein were analyzed by RT-PCR and Western blot, respectively., Results: The pAdEasy-pShuttle-U6-Calponin-1 siRNA plasmid was successfully constructed, and Calponin-1 siRNA mediated by recombinant adenovirus resulted in markedly reduced expression of Calponin-1 mRNA and protein in human myometrium cells. The gray values of Calponin-1 mRNA in the uterine smooth muscle cells in the experimental, blank control, and empty vector groups were 316.3+/-39.2, 1048.5+/-126.4 and 1027.2+/-127.5, respectively. The gray values of Calponin-1 protein were 323.3+/-43.2, 1021.5+/-143.4, and 1019.2+/-144.5, respectively. The difference between the experimental group and the blank control group as well as the empty vector group was significant (P< 0.05). There was no significant difference between the empty vector group and the blank control group (P>0.05)., Conclusion: The pAdEasy-pShuttle-U6-Calponin-1 siRNA plasmid can inhibit the expression of Calponin-1 in human myometrium cells in vitro, which may be a useful approach to determine the role of Calponin-1 in delivery.

Objective: To summarize the current progress in the genetic modification of vascular prostheses and to look forward to the future of genetic modification in vascular prostheses., Methods: PubMed online search with the key words of "vascular prostheses, gene" was undertaken to identify articles about the genetic modification of vascular prostheses. Then these articles were reviewed and summarized., Results: To improve long-term patency of vascular prostheses, various genes were transfected into seeded cells. The anti thrombosis activity of local vessels increased., Conclusion: Progresses in tissue engineering and molecular biology make possible endothelialization and genetic modification of vascular prostheses. However, because most relevant researches are still basic experiments, further study is needed before clinical application.