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Abstract Background Early pregnancy is a critical window for neural system programming; however, the association of first-trimester fetal size with children’s neurodevelopment remains to be assessed. This study aimed to explore the association between first-trimester fetal size and children’s neurodevelopment and to examine whether intrauterine accelerated growth could compensate for the detrimental effects of first-trimester restricted growth on childhood neurodevelopment. Methods The participants were from a birth cohort enrolled from March 2014 to March 2019 in Wuhan, China. A total of 2058 fetuses with crown to rump length (CRL) (a proxy of first-trimester fetal size) measurements in the first trimester and neurodevelopmental assessment at age 2 years were included. We measured the first-trimester CRL and defined three fetal growth patterns based on the growth rate of estimated fetal weight from mid to late pregnancy. The neurodevelopment was assessed using the Bayley Scales of Infant Development of China Revision at 2 years. Results Each unit (a Z score) increase of first-trimester CRL was associated with increased scores in mental developmental index (MDI) (adjusted beta estimate = 1.19, (95% CI: 0.42, 1.95), P = 0.03) and psychomotor developmental index (PDI) (adjusted beta estimate = 1.36, (95% CI: 0.46, 2.26), P

Abstract Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy (RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system’s anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) are refractory or relapse to standard chemotherapy, and most of them are activated B cell-like DLBCLs (ABC-DLBCL) and germinal center B cell-like DLBCLs (GCB-DLBCL). SNS-032, a novel and selective CDK7/9 inhibitor, that the first phase clinical trials approved by US FDA for cancer treatment have been completed. In this study, we investigated the anti-tumor effect of SNS-032 in ABC- and GCB-DLBCL subtypes. We report that SNS-032 induced growth inhibition and cell apoptosis in both DLBCL cells in vitro, and inhibited the growth of both DLBCL xenografts in nude mice. Mechanistically, SNS-032 inhibited RNA polymerase II, which led to transcriptional-dependent suppression of NF-κB signaling pathway and its downstream targets involved in cell survival; SNS-032 also downregulates BCL-2 and c-MYC in both mRNA and protein levels. Significantly, these findings provide pre-clinical evidence for application of targeting the CDK7/9 in DLBCL.

Phototherapy, which generally refers to photothermal therapy (PTT) and photodynamic therapy (PDT), has received significant attention over the past few years since it is non-invasive, has effective selectivity, and has few side effects. As a result, it has become a promising alternative to traditional clinical treatments. At present, two-dimensional materials (2D materials) have proven to be at the forefront of the development of advanced nanomaterials due to their ultrathin structures and fascinating optical properties. As a result, much work has been put into developing phototherapy platforms based on 2D materials. This review summarizes the current developments in 2D materials beyond graphene for phototherapy, focusing on the novel approaches of PTT and PDT. New methods are being developed to go above and beyond conventional treatment to fully use the potential of 2D materials. Additionally, the efficacy of cutting-edge phototherapy is assessed, and the existing difficulties and future prospects of 2D materials for phototherapy are covered.

Abstract Background Chronic myeloid leukaemia (CML) is a haematological cancer featured by the presence of BCR‐ABL fusion protein with abnormal tyrosine kinase activation. Classical tyrosine kinase inhibitor (TKI)‐based therapies are available to patients with CML. However, acquired resistance to TKI has been a challenging obstacle, especially stubborn T315I mutation is the most common cause. Therefore, it is especially urgent to find more effective targets to overcome TKI resistance induced by BCR‐ABLT315I. Proteasomal deubiquitinases (USP14 and UCHL5) have fundamental roles in the ubiquitin‐proteasome system and possess multiple functions during cancer progression. Methods The human peripheral blood mononuclear cells were collected to measure the mRNA expression of USP14 and UCHL5, as well as to detect the toxicity effect of b‐AP15. We explored the effect of b‐AP15 on the activity of proteasomal deubiquitinases. We detected the effects of b‐AP15 on BCR‐ABLWT and BCR‐ABLT315I CML cells in vitro and in the subcutaneous tumour model. We knocked down USP14 and/or UCHL5 by shRNA to explore whether these proteasomal deubiquitinases are required for cell proliferation of CML. Results In this study, we found that increased expression of the proteasomal deubiquitinase USP14 and UCHL5 in primary cancer cells from CML patients compared to healthy donors. b‐AP15, an inhibitor of USP14 and UCHL5, exhibited potent tumour‐killing activity in BCR‐ABLWT and BCR‐ABLT315I CML cell lines, as well as in CML xenografts and primary CML cells. Mechanically, pharmacological or genetic inhibition of USP14 and UCHL5 induced cell apoptosis and decreased the protein level of BCR‐ABL in CML cells expressing BCR‐ABLWT and BCR‐ABLT315I. Moreover, b‐AP15 synergistically enhanced the cytotoxic effect caused by TKI imatinib in BCR‐ABLWT and BCR‐ABLT315I CML cells. Conclusion Collectively, our results demonstrate targeting USP14 and UCHL5 as a potential strategy for combating TKI resistance in CML.

Background: Combination of the prodrug technique with an albumin nano drug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives. Methods: In this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the NabTM technology of paclitaxel palmitate (PTX-PA). Results: Our experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin nanoparticles (Nab-PTX-PA) remained in the tumor for a longer time post-injection. Compared with saline and paclitaxel albumin nanoparticles (AbraxaneVR), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs, and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organs, and it inhibited tumor cell proliferation more effectively as compared with commercial paclitaxel albumin nanoparticles. Conclusions: This carrier strategy for small molecule drugs is based on naturally evolved interactions between long-chain fatty acids (LCFAs) and Human Serum Albumin (HSA), demonstrated here for PTX. Nab-PTX-PA shows higher antitumor efficacy in vivo in breast cancer models. On the whole, this novel injectable Nab-PTX-PA has great potential as an effective drug delivery system in the treatment of breast cancer. [ABSTRACT FROM AUTHOR]