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Background: Atypical teratoid rhabdoid tumors (ATRT) is a rare but aggressive malignancy in the central nervous system, predominantly occurring in early childhood. Despite aggressive treatment, the prognosis of ATRT patients remains poor. RRM2, a subunit of ribonucleotide reductase, has been reported as a biomarker for aggressiveness and poor prognostic conditions in several cancers. However, little is known about the role of RRM2 in ATRT. Uncovering the role of RRM2 in ATRT will further promote the development of feasible strategies and effective drugs to treat ATRT., Methods: Expression of RRM2 was evaluated by molecular profiling analysis and was confirmed by IHC in both ATRT patients and PDX tissues. Follow-up in vitro studies used shRNA knockdown RRM2 in three different ATRT cells to elucidate the oncogenic role of RRM2. The efficacy of COH29, an RRM2 inhibitor, was assessed in vitro and in vivo. Western blot and RNA-sequencing were used to determine the mechanisms of RRM2 transcriptional activation in ATRT., Results: RRM2 was found to be significantly overexpressed in multiple independent ATRT clinical cohorts through comprehensive bioinformatics and clinical data analysis in this study. The expression level of RRM2 was strongly correlated with poor survival rates in patients. In addition, we employed shRNAs to silence RRM2, which led to significantly decrease in ATRT colony formation, cell proliferation, and migration. In vitro experiments showed that treatment with COH29 resulted in similar but more pronounced inhibitory effect. Therefore, ATRT orthotopic mouse model was utilized to validate this finding, and COH29 treatment showed significant tumor growth suppression and prolong overall survival. Moreover, we provide evidence that COH29 treatment led to genomic instability, suppressed homologous recombinant DNA damage repair, and subsequently induced ATRT cell death through apoptosis in ATRT cells., Conclusions: Collectively, our study uncovers the oncogenic functions of RRM2 in ATRT cell lines, and highlights the therapeutic potential of targeting RRM2 in ATRT. The promising effect of COH29 on ATRT suggests its potential suitability for clinical trials as a novel therapeutic approach for ATRT., (© 2023. The Author(s).)

Background: Receptivity of the uterus is essential for embryo implantation and progression of mammalian pregnancy. Acquisition of receptivity involves major molecular and cellular changes in the endometrial lining of the uterus from a non-receptive state at ovulation, to a receptive state several days later. The precise molecular mechanisms underlying this transition and their upstream regulators remain to be fully characterized. Here, we aimed to generate a comprehensive profile of the endometrial transcriptome in the peri-ovulatory and peri-implantation states, to define the genes and gene pathways that are different between these states, and to identify new candidate upstream regulators of this transition, in the mouse., Results: High throughput RNA-sequencing was utilized to identify genes and pathways expressed in the endometrium of female C57Bl/6 mice at estrus and on day 3.5 post-coitum (pc) after mating with BALB/c males (n = 3-4 biological replicates). Compared to the endometrium at estrus, 388 genes were considered differentially expressed in the endometrium on day 3.5 post-coitum. The transcriptional changes indicated substantial modulation of uterine immune and vascular systems during the pre-implantation phase, with the functional terms Angiogenesis, Chemotaxis, and Lymphangiogenesis predominating. Ingenuity Pathway Analysis software predicted the activation of several upstream regulators previously shown to be involved in the transition to receptivity including various cytokines, ovarian steroid hormones, prostaglandin E2, and vascular endothelial growth factor A. Our analysis also revealed four candidate upstream regulators that have not previously been implicated in the acquisition of uterine receptivity, with growth differentiation factor 2, lysine acetyltransferase 6 A, and N-6 adenine-specific DNA methyltransferase 1 predicted to be activated, and peptidylprolyl isomerase F predicted to be inhibited., Conclusions: This study confirms that the transcriptome of a receptive uterus is vastly different to the non-receptive uterus and identifies several genes, regulatory pathways, and upstream drivers not previously associated with implantation. The findings will inform further research to investigate the molecular mechanisms of uterine receptivity., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: With the decline in local malaria transmission in Vietnam as a result of the National Malaria Control Program (NMCP) elimination activities, a greater focus on the importation and potential reintroduction of transmission are essential to support malaria elimination objectives., Methods: We conducted a multi-method assessment of the demographics, epidemiology, and clinical characteristics of imported malaria among international laborers returning from African or Southeast Asian countries to Vietnam. Firstly, we conducted a retrospective review of hospital records of patients from January 2014 to December 2016. Secondly, we conducted a mixed-methods prospective study for malaria patients admitted to the study sites from January 2017 to May 2018 using a structured survey with blood sample collection for PCR analysis and in-depth interviews. Data triangulation of the qualitative and quantitative data was used during analysis., Results: International laborers were young (median age 33.0 years IQR 28.0-39.5 years), predominantly male (92%) adults returning mostly from the African continent (84%) who stayed abroad for prolonged periods (median time 13.5 months; IQR 6.0-331.5 months) and were involved in occupations that exposed them to a higher risk of malaria infection. Epidemiological trends were also similar amongst study strands and included the importation of Plasmodium falciparum primarily from African countries and P. vivax from Southeast Asian countries. Of 11 P. malariae and P. ovale infections across two study strands, 10 were imported from the African continent. Participants in the qualitative arm demonstrated limited knowledge about malaria prior to travelling abroad, but reported knowledge transformation through personal or co-worker's experience while abroad. Interestingly, those who had a greater understanding of the severity of malaria presented to the hospital for treatment sooner than those who did not; median of 3 days (IQR 2.0-7.0 days) versus 5 days (IQR 4.0-9.5 days) respectively., Conclusion: To address the challenges to malaria elimination raised by a growing Vietnamese international labor force, consideration should be given to appropriately targeted interventions and malaria prevention strategies that cover key stages of migration including pre-departure education and awareness, in-country prevention and prophylaxis, and malaria screening upon return., (© 2022. The Author(s).)

Background: Although poly(N-acyl dithieno[3,2-b:2',3'-d]pyrrole)s have attracted great attention as a new class of conducting polymers with highly stabilized energy levels, hyperbranched polymers based on this monomer type have not yet been studied. Thus, this work aims at the synthesis of novel hyperbranched polymers containing N-benzoyl dithieno[3,23,2-b:2',3'-d]pyrrole acceptor unit and 3-hexylthiophene donor moiety via the direct arylation polymerization method. Their structures, molecular weights and thermal properties were characterized via 1 H NMR and FTIR spectroscopies, GPC, TGA, DSC and XRD measurements, and the optical properties were investigated by UV-vis and fluorescence spectroscopies., Results: Hyperbranched conjugated polymers containing N-benzoyl dithieno[3,23,2-b:2',3'-d]pyrrole acceptor unit and 3-hexylthiophene donor moiety, linked with either triphenylamine or triphenylbenzene as branching unit, were obtained via direct arylation polymerization of the N-benzoyl dithieno[3,23,2-b:2',3'-d]pyrrole, 2,5-dibromo 3-hexylthiophene and tris(4-bromophenyl)amine (or 1,3,5-tris(4-bromophenyl)benzene) monomers. Organic solvent-soluble polymers with number-average molecular weights of around 18,000 g mol -1 were obtained in 80-92% yields. The DSC and XRD results suggested that the branching structure hindered the stacking of polymer chains, leading to crystalline domains with less ordered packing in comparison with the linear analogous polymers. The results revealed that the hyperbranched polymer with triphenylbenzene as the branching unit exhibited a strong red-shift of the maximum absorption wavelength, attributed to a higher polymer stacking order as a result of the planar structure of triphenylbenzene., Conclusion: Both hyperbranched polymers with triphenylamine/triphenylbenzene as branching moieties exhibited high structural order in thin films, which can be promising for organic solar cell applications. The UV-vis absorption of the hyperbranched polymer containing triphenylbenzene as branching unit was red-shifted as compared with the triphenylamine-containing polymer, as a result of a higher chain packing degree.

Background: Alzheimer's disease (AD) is the most common cause of dementia among the elderly and is characterized by loss of memory and other cognitive functions. An increase in AChE (a key enzyme in the cholinergic nervous system) levels around β-amyloid plaques and neurofibrillary tangles is a common feature of AD neuropathology. Amnesic effects of scopolamine (acetylcholine receptor antagonist) can be investigated in various behavioral tests such as Morris water maze, object recognition, Y-maze, and passive avoidance. In the scope of this paper, we report the anti-AChE, anti-BChE properties of the isolated compound and the in vivo effects of the methanolic extract of Xylia xylocarpa (MEXX) on scopolamine-induced memory deficit., Results: In further phytochemistry study, a new hopan-type triterpenoid, (3β)-hopan-3-ol-28,22-olide (1), together with twenty known compounds were isolated (2-21). Compound 1, 2, 4, 5, 7-9, and 11-13 exhibited potent acetylcholinesterase (AChE) inhibitory activity in a concentration-dependent manner with IC50 values ranging from 54.4 to 94.6 μM. Compound 13 was also shown anti-butyrylcholinesterase (BChE) activity with an IC50 value of 42.7 μM. The Morris water Y-maze, Y-maze, and object recognition test were also carried out., Conclusions: It is noteworthy that MEXX is effective when administered orally to mice, experimental results are consistent with the traditional use of this medicinal plant species.