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Ovarian clear cell carcinoma (OCCC) is a histological type of ovarian cancer that is refractory to chemotherapy and has poor prognosis, which necessitates the development of novel treatment therapies. In this study, we focused on L-type amino acid transporter 1 (LAT1), which is involved in cancer growth, and investigated the effect of its selective inhibition on cell proliferation in OCCC. The inhibitory effect of nanvuranlat (JPH203), a LAT1 selective inhibitor, on the cellular uptake of [ H] leucine was evaluated using the OCCC cell line JHOC9, which expresses the LAT1 protein. In addition, the kinetics of cell proliferation and changes in phosphorylation of the mTOR pathway were analyzed. The correlation between LAT1 expression and progression-free survival (PFS) was evaluated using clinical specimens of OCCC. Nanvuranlat inhibited [ H] leucine intracellular uptake and cell proliferation in a dose-dependent manner in JHOC9 cells. In addition, it suppressed the activity of the mTOR signaling pathway, which is thought to inhibit cancer cell proliferation. LAT1 expression was most frequent in OCCC among clinical specimens of epithelial ovarian cancer. A correlation between LAT1 expression and PFS was observed in OCCC. LAT1 selective inhibition suppresses cell proliferation via the mTOR pathway by inhibiting leucine uptake in OCCC. This study illustrates the potential of using LAT1 selective inhibition as a treatment strategy for OCCC.

The carbonophosphate Na 3 FePO 4 CO 3 was synthesized by the mechanical ball milling method for the first time. The composition of the obtained sample with a higher amount of Fe 2+ was Na 2.66 Fe 2+ 0.66 Fe 3+ 0.34 PO 4 CO 3 as confirmed by Mössbauer analysis, owing to the good airtight properties of this method. The obtained samples in an organic electrolyte delivered an initial discharge capacity of 124 mAh/g at room temperature, and a larger discharge capacity of 159 mAh/g (1.66 Na + /mole) at 60 °C. With 17 m NaClO 4 aqueous electrolyte, a discharge capacity of 161 mAh/g (1.69 Na + /mole) was delivered because of the high ionic conductivity of the concentrated aqueous electrolyte. During the charge-discharge process, the formation of Fe 4+ after charging up to 4.5 V and the return of Fe 2+ after discharging down to 1.5 V were detected by ex-situ X-ray absorption near edge structure (XANES) analysis.

Despite the remarkable success of mRNA vaccines, improving the translational efficiency of mRNA therapeutics remains a critical challenge to their widespread clinical application. Here we systematically evaluate chemical modifications to improve the translational activity and stability of uncapped mRNA. We employ a primarily chemistry-based synthetic approach, which is crucial for the position-specific introduction of chemical modifications, enabling detailed structure-activity relationship studies, hitherto unattainable with conventional methods. A pivotal innovation herein is the introduction of 2´-F modification at the first nucleoside of the codon in the open reading frame, which significantly bolsters the stability of mRNA without compromising its translation. Additional modifications at the 5´-UTR and poly(A) tail with other types of nucleoside and phosphate analogs also exemplify the importance of terminal modifications for improved translation. Precise control of these modification patterns achieves higher peptide expression than conventional in vitro-transcribed mRNA. These findings offer a unique framework for designing effective mRNA-based therapeutics. Despite the success of mRNA vaccines, improving the translational efficiency of mRNA therapeutics remains a critical challenge to their widespread clinical application. Here, the authors systematically evaluate chemical modifications to improve the translational activity and stability of uncapped mRNA and show that the 2´-F modification at the first nucleoside of the codon in the open reading frame significantly bolsters the stability of mRNA without compromising its translation.

Background A Sister Mary Joseph’s nodule is an umbilical metastasis from an intra-abdominal or pelvic malignancy, associated with a poor prognosis. Three possible metastatic pathways for Sister Mary Joseph’s nodule have been postulated: hematogenous spread, lymphatic dissemination, and direct invasion. However, detailed analyses of these metastatic pathways, particularly those involving gene expression profiling, are lacking in literature. We investigated the metastatic patterns of Sister Mary Joseph’s nodule by performing RNA microarray analysis of the primary tumor and each metastatic site in a case of fallopian tube cancer presenting with Sister Mary Joseph’s nodule and inguinal lymph node metastases. Case presentation A 48-year-old Japanese woman presented with swelling in an inguinal lymph node. Positron emission tomography-computed tomography imaging revealed multiple lymph node metastases, right ovarian tumor, umbilical metastasis, and peritoneal dissemination. The patient underwent a laparoscopic right adnexal resection, left inguinal lymph node biopsy, and umbilical resection. Pathological examination confirmed the diagnosis of primary high-grade serous carcinoma of the right fallopian tube. Metastatic high-grade serous carcinoma was identified in the lymph nodes and umbilical tissue. Tumor tissue samples were collected from the primary lesion, umbilical metastasis, and inguinal lymph node metastasis for RNA microarray analysis. The results showed that genes involved in cell adhesion, migration, and stromal remodeling associated with the metastatic processes were more highly expressed in both inguinal lymph node metastasis and Sister Mary Joseph’s nodule than in the primary lesion. Interestingly, distinct differences in gene expression profiles were observed between umbilical and lymph node metastases, suggesting different metastatic mechanisms. Conclusion Our findings suggest differences in the RNA expression patterns between Sister Mary Joseph’s nodule and lymph node metastases in fallopian tube cancer, indicating the possibility of distinct metastatic mechanisms. Further examination of similar cases and longitudinal studies are necessary to elucidate the metastatic patterns of Sister Mary Joseph’s nodule. This case highlights the potential value of molecular profiling for understanding the complex metastatic processes in gynecological malignancies.

A novel carbonophosphate, Na3MnPO4CO3, was synthesized as a cathode material using a mechanical ball milling method with starting materials of MnCO3 and Na3PO4 without washing or drying. Duo to the formation of nano-size particles and good dispersion of the obtained Na3MnPO4CO3, the initial discharge capacity in an organic electrolyte of 1 M NaPF6/ethylene carbonate (EC): dimethyl carbonate (DMC) (1:1 v/v) was 135 mAh∙g−1 and 116 mAh∙g−1 at 1/30 C and 1/10 C, respectively. We also investigated the cathode properties of Na3MnPO4CO3 in an aqueous electrolyte of 17 m NaClO4. This is the first investigation of the electrochemical performance of Na3MnPO4CO3 with aqueous electrolyte. Na3MnPO4CO3 achieved a discharge capacity as large as 134 mAh g−1 even at a high current density of 2 mA cm−2 (0.5 C), because of the high ionic conductivity of the aqueous electrolyte of 17 m NaClO4.

In vitro selection is typically limited to discovery of peptides, proteins, and nucleic acids. Given the importance of carbohydrate–protein interactions in diverse areas of biology including cell adhesion/recognition, immunoregulation and host–pathogen interactions, directed-evolution-based methods for discovery of potent glycoligands are greatly needed. We have previously reported a method for in vitro selection of glycopeptides that combines mRNA display, alkynyl amino acid incorporation, and CuAAC “click” glycosylation. Herein, we describe extensions of this method that incorporate chemical cyclization, removal of N-terminal glycosylation sites, and next-generation sequencing; as an approach to HIV immunogen design, we have used this method to develop mimics of the High Mannose Patch (HMP), the region on HIV envelope protein gp120 most commonly targeted by HIV broadly neutralizing antibodies (bnAbs). We prepared libraries of 1012–14 glycopeptides about 50 amino acids in length, containing variable placement of high mannose (Man9GlcNAc2) glycans and cyclization sites. From selection, we obtained binders to HIV bnAbs PGT128, PGT122, and gl-PGT121, a germline precursor of PGT122, and chemically synthesized numerous glycopeptide hits. Several glycopeptides bound very tightly to their target HIV bnAb, e.g., with a K D as low as 0.5 nM for PGT128. These glycopeptides are of interest as immunogens and tools for HIV vaccine design.

Mixed gonadal dysgenesis (MGD) is a disorder of sex development caused by mosaicism of the Y chromosome, represented by 45,X/46,XY. Prophylactic gonadectomy is recommended as soon as possible after its diagnosis, owing to a high risk of malignancy. In the present case, a 21-year-old woman presented with primary amenorrhea. Although the patient's external genitalia were female, the patient exhibited a hypoplastic uterus, wherein the ovaries were difficult to identify. The patient's height was 146 cm; they had cubitus valgus and webbing of the neck, leading to the consideration of a disorder of sex development. Chromosomal examination revealed 45,X/46,XY mosaicism. Thus, the patient was diagnosed with MGD. After thorough counseling, laparoscopic bilateral gonadectomy was performed. Pathological examination revealed a gonadoblastoma of the left gonad. Postoperatively, the patient had no recurrence and continued on Kaufmann therapy. In conclusion, prophylactic gonadectomy is recommended immediately following a diagnosis of MGD; however, the timing of the surgery should be carefully considered and adequate counseling should be conducted by a multidisciplinary team.

The carbonophosphate Na FePO CO was synthesized by the mechanical ball milling method for the first time. The composition of the obtained sample with a higher amount of Fe was Na Fe Fe PO CO as confirmed by Mössbauer analysis, owing to the good airtight properties of this method. The obtained samples in an organic electrolyte delivered an initial discharge capacity of 124 mAh/g at room temperature, and a larger discharge capacity of 159 mAh/g (1.66 Na /mole) at 60 °C. With 17 m NaClO aqueous electrolyte, a discharge capacity of 161 mAh/g (1.69 Na /mole) was delivered because of the high ionic conductivity of the concentrated aqueous electrolyte. During the charge-discharge process, the formation of Fe after charging up to 4.5 V and the return of Fe after discharging down to 1.5 V were detected by ex-situ X-ray absorption near edge structure (XANES) analysis.

selection is typically limited to discovery of peptides, proteins and nucleic acids. Given the importance of carbohydrate-protein interactions in diverse areas of biology including cell adhesion/recognition, immunoregulation and host-pathogen interactions, directed-evolution-based methods for discovery of potent glycoligands are greatly needed. We have previously reported a method for selection of glycopeptides that combines mRNA display, alkynyl amino acid incorporation, and CuAAC \"click\" glycosylation. Herein, we describe extensions of this method that incorporate chemical cyclization, removal of N-terminal glycosylation sites and next-generation sequencing; as an approach to HIV immunogen design, we have then used this method to develop mimics of the High Mannose Patch (HMP), which is the region on HIV envelope protein gp120 most commonly targeted by HIV broadly neutralizing antibodies (bnAbs). We prepared libraries of 10 glycopeptides about 50 amino acids in length, containing variable numbers of high mannose (Man GlcNAc ) glycans and cyclization at varied sites. We performed selections to obtain binders of HIV bnAbs PGT128, PGT122, and gl-PGT121, a germline precursor of PGT122, and prepared numerous glycopeptide hits by chemical synthesis. Selected glycopeptides in some cases bound very tightly to their target HIV bnAb, e.g., with a as low as 0.5 nM for PGT128. These glycopeptides are of interest as immunogens and tools for HIV vaccine design.