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1.
Nucleic Acids Res ; 49(D1): D201-D211, 2021 01 08.
Article in English | MEDLINE | ID: mdl-33179749

ABSTRACT

Splicing is an essential step of RNA processing for multi-exon genes, in which introns are removed from a precursor RNA, thereby producing mature RNAs containing splice junctions. Here, we develope the RJunBase (www.RJunBase.org), a web-accessible database of three types of RNA splice junctions (linear, back-splice, and fusion junctions) that are derived from RNA-seq data of non-cancerous and cancerous tissues. The RJunBase aims to integrate and characterize all RNA splice junctions of both healthy or pathological human cells and tissues. This new database facilitates the visualization of the gene-level splicing pattern and the junction-level expression profile, as well as the demonstration of unannotated and tumor-specific junctions. The first release of RJunBase contains 682 017 linear junctions, 225 949 back-splice junctions and 34 733 fusion junctions across 18 084 non-cancerous and 11 540 cancerous samples. RJunBase can aid researchers in discovering new splicing-associated targets and provide insights into the identification and assessment of potential neoepitopes for cancer treatment.


Subject(s)
Alternative Splicing , Databases, Nucleic Acid , Gene Expression Regulation, Neoplastic , Neoplasms/genetics , RNA Splice Sites , RNA, Messenger/genetics , Exons , Gene Expression Profiling , Humans , Internet , Introns , Neoplasms/diagnosis , Neoplasms/mortality , Neoplasms/pathology , RNA, Messenger/metabolism , Sequence Analysis, RNA , Software , Survival Analysis
2.
Nano Lett ; 22(8): 3465-3472, 2022 Apr 27.
Article in English | MEDLINE | ID: mdl-35435694

ABSTRACT

HgTe colloidal quantum dots (CQDs) are promising absorber systems for infrared detection due to their widely tunable photoresponse in all infrared regions. Up to now, the best-performing HgTe CQD photodetectors have relied on using aggregated CQDs, limiting the device design, uniformity and performance. Herein, we report a ligand-engineered approach that produces well-separated HgTe CQDs. The present strategy first employs strong-binding alkyl thioalcohol ligands to enable the synthesis of well-dispersed HgTe cores, followed by a second growth process and a final postligand modification step enhancing their colloidal stability. We demonstrate highly monodisperse HgTe CQDs in a wide size range, from 4.2 to 15.0 nm with sharp excitonic absorption fully covering short- and midwave infrared regions, together with a record electron mobility of up to 18.4 cm2 V-1 s-1. The photodetectors show a room-temperature detectivity of 3.9 × 1011 jones at a 1.7 µm cutoff absorption edge.

3.
Phys Rev Lett ; 129(23): 236601, 2022 Dec 02.
Article in English | MEDLINE | ID: mdl-36563198

ABSTRACT

Kagome lattice materials have attracted growing interest for their topological properties and flatbands in electronic structure. We present a comprehensive study on the anisotropy and out-of-plane electric transport in Fe_{3}Sn_{2}, a metal with bilayer of Fe kagome planes and with massive Dirac fermions that features high-temperature noncollinear magnetic structure and magnetic skyrmions. For the electrical current path along the c axis, in micron-size crystals, we found a large topological Hall effect over a wide temperature range down to spin-glass state. Twofold and fourfold angular magnetoresistance are observed for different magnetic phases, reflecting the competition of magnetic interactions and magnetic anisotropy in kagome lattice that preserve robust topological Hall effect for inter-kagome bilayer currents. This provides new insight into the anisotropy in Fe_{3}Sn_{2}, of interest in skyrmionic-bubble application-related micron-size devices.

4.
Inorg Chem ; 61(34): 13586-13590, 2022 Aug 29.
Article in English | MEDLINE | ID: mdl-35972888

ABSTRACT

We report on the giant anisotropy found in the thermoelectric power factor (S2σ) of marcasite structure-type PtSb1.4Sn0.6 single crystal. PtSb1.4Sn0.6, synthesized using an ambient pressure flux growth method upon mixing Sb and Sn on the same atomic site, is a new phase different from both PtSb2 and PtSn2, which crystallize in the cubic Pa3̅ pyrite and Fm3̅m fluorite unit cell symmetry, respectively. The large difference in S2σ for heat flow applied along different principal directions of the orthorhombic unit cell stems mostly from anisotropic Seebeck coefficients.

5.
Clin Infect Dis ; 73(9): e3250-e3258, 2021 11 02.
Article in English | MEDLINE | ID: mdl-33099614

ABSTRACT

BACKGROUND: DNA from many pathogens can be detected in saliva. However, the presence and quantity of Treponema pallidum DNA in patients with syphilis in saliva is unknown. METHODS: 234 patients with syphilis with different stages and 30 volunteers were enrolled. Paired saliva and plasma samples were collected from all participants. Consecutive saliva samples from 9 patients were collected every 4 hours following treatment. Treponema pallidum DNA in samples was determined by nested polymerase chain reaction (PCR) and droplet digital PCR targeting polA and Tpp47. RESULTS: Treponema pallidum DNA detection rates in saliva and plasma were 31.0% (9/29) and 51.7% (15/29) in primary syphilis (P = .11), 87.5% (63/72) and 61.1% (44/72) in secondary syphilis (P < .001), 25.6% (21/82) and 8.5% (7/82) in latent syphilis (P = .004), and 21.6% (11/51) and 5.9% (3/51) in symptomatic neurosyphilis (P = .021), respectively. Median (range) loads of Tpp47 and polA in saliva were 627 (0-101 200) and 726 (0-117 260) copies/mL, respectively, for patients with syphilis. In plasma, however, loads of Tpp47 and polA were low: medians (range) of 0 (0-149.6) and 0 (0-176) copies/mL, respectively. Loads of T. pallidum DNA in saliva during treatment fluctuated downward; the clearance time was positively correlated with the loads of T. pallidum DNA before treatment. CONCLUSIONS: Collection of saliva is noninvasive and convenient. The high loads of T. pallidum DNA in saliva and reduction after treatment indicated that saliva can be not only a diagnostic fluid for syphilis but also an indicator of therapeutic effectiveness.


Subject(s)
Neurosyphilis , Syphilis, Latent , Syphilis , DNA, Bacterial/genetics , Humans , Saliva , Syphilis/diagnosis , Treponema pallidum/genetics
6.
Hepatology ; 72(2): 548-568, 2020 08.
Article in English | MEDLINE | ID: mdl-31815296

ABSTRACT

BACKGROUND AND AIMS: Alternative splicing (AS) is a key step that increases the diversity and complexity of the cancer transcriptome. Recent evidence has highlighted that AS has an increasingly crucial role in cancer. Nonetheless, the mechanisms underlying AS and its dysregulation in hepatocellular carcinoma (HCC) remain elusive. Here, we report that the expression of RNA-binding protein p54nrb /non-POU domain-containing octamer-binding protein (NONO) is frequently increased in patients with HCC and is associated with poor outcomes. APPROACH AND RESULTS: Knockdown of NONO significantly abolished liver cancer cell proliferation, migration, and tumor formation. RNA-sequencing revealed that NONO regulates MYC box-dependent interacting protein 1 (or bridging integrator 1 [BIN1]; also known as amphiphysin 2 3P9) exon 12a splicing. In the normal liver, BIN1 generates a short isoform (BIN1-S) that acts as a tumor suppressor by inhibiting the binding of c-Myc to target gene promoters. In HCC, NONO is highly up-regulated and produces a long isoform (BIN1-L, which contains exon 12a) instead of BIN1-S. High levels of BIN1-L promote carcinogenesis by binding with the protein polo-like kinase 1 to enhance its stability through the prevention of ubiquitin/proteasome-dependent cullin 3 degradation. Further analysis revealed that NONO promotes BIN1 exon 12a inclusion through interaction with DExH-box helicase 9 (DHX9) and splicing factor proline and glutamine-rich (SFPQ). Notably, frequent coexpression of DHX9-NONO-SFPQ is observed in patients with HCC. CONCLUSIONS: Taken together, our findings identify the DHX9-NONO-SFPQ complex as a key regulator manipulating the oncogenic splicing switch of BIN1 and as a candidate therapeutic target in liver cancer.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Alternative Splicing , Carcinogenesis , Carcinoma, Hepatocellular/genetics , DNA-Binding Proteins/physiology , Liver Neoplasms/genetics , Nuclear Proteins/genetics , RNA-Binding Proteins/physiology , Tumor Suppressor Proteins/genetics , Cell Line, Tumor , Cohort Studies , Female , Humans , Male , Middle Aged , Protein Isoforms
7.
Hepatology ; 69(1): 359-375, 2019 01.
Article in English | MEDLINE | ID: mdl-30014619

ABSTRACT

Alternative splicing (AS) is assumed to be a pivotal determinant for the generation of diverse transcriptional variants in cancer. However, the comprehensive dysregulation of AS and the prospective biological and clinical relevance in hepatocellular carcinoma (HCC) remain obscure. Here, we identified and depicted the AS landscape in HCC by performing reference-based assembly of sequencing reads from over 600 RNA sequencing (RNA-seq) libraries. We detected various differentially spliced ASEs across patients covering not only protein-coding genes, but also considerable numbers of noncoding genes. Strikingly, alternative transcription initiation was found to frequently occur in HCC. These differential ASEs were highly related to "cancer hallmarks" and involved in metabolism-related pathways in particular. In addition, 243 differential ASEs were identified as risk predictors for HCC patient survival. The isoform switch of metabolism-related gene UGP2 (UDP-glucose pyrophosphorylase 2) might play an essential role in HCC. We further constructed regulatory networks between RNA-binding protein (RBP) genes and the corresponding ASEs. Further analysis demonstrated that the regulated networks were enriched in a variety of metabolism-related pathways. Conclusion: Differential ASEs are prevalent in HCC, where alternative transcription initiation was found to frequently occur. We found that genes having differential ASEs were significantly enriched in metabolism-related pathways. The expression variations, binding relations, and even mutations of RBP genes largely influenced differential ASEs in HCC.


Subject(s)
Alternative Splicing/physiology , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , Transcriptome/physiology , Gene Expression Profiling , Humans , Tumor Cells, Cultured
8.
BMC Ophthalmol ; 20(1): 383, 2020 Sep 25.
Article in English | MEDLINE | ID: mdl-32977792

ABSTRACT

BACKGROUND: To report a new technique for iris capture of the posterior chamber intraocular lens (IOL) implanted in patients with a posterior capsule defect. METHODS: In this retrospective case series, a rectangular loop ciliary body suture technique was performed to rectify iris capture. The suture passes between the IOL and iris in a direction perpendicular to the iris edge capturing the IOL. RESULTS: A total of three IOLs with iris capture underwent a rectangular loop suture technique. No recapture was observed postoperatively. In one case, large astigmatism appeared after the surgery but recovered at 1 month post operation. No further complications were found. CONCLUSIONS: The rectangular loop suture technique is an effective, convenient, and minimally invasive method for iris capture of the IOL.


Subject(s)
Lenses, Intraocular , Humans , Iris/surgery , Lens Implantation, Intraocular , Retrospective Studies , Suture Techniques , Sutures
9.
Int Ophthalmol ; 40(1): 141-149, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31463622

ABSTRACT

PURPOSE: To compare the anatomical and functional outcomes of the inverted internal limiting membrane (ILM) flap technique and the autologous blood clot (ABC) to ILM insertion technique for the repair of refractory macular hole (RMH). METHODS: Fifty-two consecutive patients (52 eyes) diagnosed with RMH with a minimum diameter more than 700 µm were enrolled. All patients underwent vitrectomy and gas tamponade. Of these, 25 patients undergo inverted ILM flap combination with ABC (Group A). The remaining 27 patients underwent ILM insertion (Group B). The main outcome measures were macular hole (MH) closure, foveal configuration, logarithm of the minimum angle of resolution (logMAR), best-corrected visual acuity (BCVA), superficial foveal avascular zone (FAZ) and superficial parafoveal vessel density. RESULTS: Three months post-operation, MH was successfully anatomic closed in 24 of 25 eyes (96%) in Group A and 25 of 27 eyes (92.5%) in Group B (P = 0.599). A concave foveal configuration of MH closure was observed in 23 of 25 eyes (92%) in Group A and 2 of 27 eyes (7.4%) in Group B (P < 0.001). Mean BCVA (logMAR) had improved from 1.31 ± 0.61 to 0.68 ± 0.40 in Group A (P < 0.001) and from 1.34 ± 0.39 to 1.29 ± 0.62 in Group B (P = 0.584) at 3 months. Average superficial FAZ area and superficial parafoveal vessel density were 0.29 ± 0.08 mm2 and 51.41 ± 2.79% in Group A and 0.73 ± 0.15 mm2 and 43.77 ± 2.71% in Group B, respectively. There was a significant difference in both the average superficial FAZ area and parafoveal vessel density between Groups A and B (P < 0.001 for both). CONCLUSION: Anatomical foveal configuration, mean BCVA (logMAR), mean superficial FAZ and parafoveal vessel density outcomes for the inverted ILM flap combined with ABC approach were better than the outcomes obtained with ILM insertion in the treatment of RMH. This approach may promote better long-term, vision function outcomes for patients diagnosed with RMH.


Subject(s)
Basement Membrane/surgery , Blood Transfusion, Autologous/methods , Retinal Perforations/surgery , Surgical Flaps , Tomography, Optical Coherence/methods , Visual Acuity , Vitrectomy/methods , Basement Membrane/diagnostic imaging , Female , Follow-Up Studies , Humans , Macula Lutea/pathology , Male , Middle Aged , Retinal Perforations/diagnosis , Retrospective Studies
10.
Hepatology ; 67(1): 171-187, 2018 01.
Article in English | MEDLINE | ID: mdl-28746790

ABSTRACT

Long noncoding RNAs can serve as oncogenes or tumor suppressors in human cancer; however, their biological functions and underlying mechanism in hepatocarcinogenesis are largely unknown. Here, we report a novel tumor suppressor long noncoding RNA on chromosome 8p12 (termed TSLNC8) that is frequently deleted and down-regulated in hepatocellular carcinoma (HCC) tissues. The loss of TSLNC8 is highly associated with the malignant features of HCC and serves as a prognostic indicator for HCC patients. TSLNC8 significantly suppresses the proliferation and metastasis of HCC cells in vitro and in vivo. TSLNC8 exerts its tumor suppressive activity by competitively interacting with transketolase and signal transducer and activator of transcription 3 (STAT3) and modulating the STAT3-Tyr705 and STAT3-Ser727 phosphorylation levels and STAT3 transcriptional activity, thus resulting in inactivation of the interleukin-6-STAT3 signaling pathway in HCC cells. CONCLUSION: TSLNC8 is a promising prognostic predictor for patients with HCC, and the TSLNC8-transketolase-STAT3 axis is a potential therapeutic target for HCC treatment. (Hepatology 2018;67:171-187).


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/pathology , Interleukin-6/metabolism , Liver Neoplasms/pathology , RNA, Long Noncoding/metabolism , STAT3 Transcription Factor/metabolism , Analysis of Variance , Biopsy, Needle , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cytokine Receptor gp130/metabolism , Down-Regulation , Genes, Tumor Suppressor , Humans , Immunohistochemistry , Liver Neoplasms/metabolism , Phosphorylation , Pilot Projects , Prognosis , Proportional Hazards Models , RNA, Long Noncoding/genetics , ROC Curve , STAT3 Transcription Factor/genetics , Signal Transduction
12.
Phys Chem Chem Phys ; 18(38): 26602-26608, 2016 Sep 29.
Article in English | MEDLINE | ID: mdl-27711699

ABSTRACT

The development of novel materials with excellent performance depends not only on the constituents but also on their remarkable micro/nanostructures. In this work, manganese oxide (Mn3O4) hausmannite structures with a uniform three-dimensional (3D) flower-like hierarchical architecture have been successfully synthesized by a novel chemical route using surfactants as structure-directing agents. Microstructure analysis indicates that the obtained 3D flower-like Mn3O4 superstructure consists of a large number of two-dimensional (2D) Mn3O4 nanosheets, which is different from the reported 3D Mn3O4 hierarchical structures based on zero-dimensional nanoparticles or one-dimensional nanowires and nanorods. This 3D Mn3O4 hierarchical architecture provides us with another type of manganese oxide with different superstructural characteristics, which may have potential practical applications in the catalytic degradation of organic pollutants. The catalytic performance of this hierarchical Mn3O4 superstructure, which was prepared by three different types of structure-directing agents, including cetyltrimethylammonium bromide (CTAB), poly(vinylpyrrolidone) (PVP), and poly(ethylene oxide)-poly(propylene oxide) (P123), was evaluated for the catalytic degradation of organic pollutants, e.g. methylene blue. Interestingly, the hierarchical Mn3O4 superstructure prepared using CTAB as a template showed efficient catalytic degradation. The formation processes and possible growth mechanism of this novel 3D Mn3O4 hierarchical superstructure assembled by 2D Mn3O4 nanosheets are discussed in detail.

13.
Biochim Biophys Acta Rev Cancer ; 1879(5): 189126, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38849060

ABSTRACT

Neoantigen-based therapy is a promising approach that selectively activates the immune system of the host to recognize and eradicate cancer cells. Preliminary clinical trials have validated the feasibility, safety, and immunogenicity of personalized neoantigen-directed vaccines, enhancing their effectiveness and broad applicability in immunotherapy. While many ongoing oncological trials concentrate on neoantigens derived from mutations, these targets do not consistently provoke an immune response in all patients harboring the mutations. Additionally, tumors like ovarian cancer, which have a low tumor mutational burden (TMB), may be less amenable to mutation-based neoantigen therapies. Recent advancements in next-generation sequencing and bioinformatics have uncovered a rich source of neoantigens from non-canonical RNAs associated with transposable elements (TEs). Considering the substantial presence of TEs in the human genome and the proven immunogenicity of TE-derived neoantigens in various tumor types, this review investigates the latest findings on TE-derived neoantigens, examining their clinical implications, challenges, and unique advantages in enhancing tumor immunotherapy.

14.
Adv Sci (Weinh) ; 11(23): e2310134, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38634567

ABSTRACT

Intraperitoneal dissemination is the main method of epithelial ovarian cancer (EOC) metastasis, which is related to poor prognosis and a high recurrence rate. Circular RNAs (circRNAs) are a novel class of endogenous RNAs with covalently closed loop structures that are implicated in the regulation of tumor development. In this study, hsa_circ_0001546 is downregulated in EOC primary and metastatic tissues vs. control tissues and this phenotype has a favorable effect on EOC OS and DFS. hsa_circ_0001546 can directly bind with 14-3-3 proteins to act as a chaperone molecule and has a limited positive effect on 14-3-3 protein stability. This complex recruits CAMK2D to induce the Ser324 phosphorylation of Tau proteins, changing the phosphorylation status of Tau bound to 14-3-3 and ultimately forming the hsa_circ_0001546/14-3-3/CAMK2D/Tau complex. The existence of this complex stimulates the production of Tau aggregation, which then induces the accumulation of lipid peroxides (LPOs) and causes LPO-dependent ferroptosis. In vivo, treatment with ferrostatin-1 and TRx0237 rescued the inhibitory effect of hsa_circ_0001546 on EOC cell spreading. Therefore, based on this results, ferroptosis caused by Tau aggregation occurs in EOC cells, which is not only in Alzheimer's disease- or Parkinson's disease-related cells and this kind of ferroptosis driven by the hsa_circ_0001546/14-3-3/CAMK2D/Tau complex is LPO-dependent rather than GPX4-dependent is hypothesized.


Subject(s)
Carcinoma, Ovarian Epithelial , Ovarian Neoplasms , RNA, Circular , tau Proteins , Female , Humans , Carcinoma, Ovarian Epithelial/genetics , Carcinoma, Ovarian Epithelial/metabolism , Carcinoma, Ovarian Epithelial/pathology , tau Proteins/metabolism , tau Proteins/genetics , RNA, Circular/genetics , RNA, Circular/metabolism , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Mice , Peritoneal Neoplasms/metabolism , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/secondary , 14-3-3 Proteins/metabolism , 14-3-3 Proteins/genetics , Animals , Disease Models, Animal , Cell Line, Tumor , Lipid Peroxidation/genetics
15.
ACS Appl Mater Interfaces ; 15(12): 15707-15720, 2023 Mar 29.
Article in English | MEDLINE | ID: mdl-36924356

ABSTRACT

The analysis of exhaled breath has opened up new exciting avenues in medical diagnostics, sleep monitoring, and drunk driving detection. Nevertheless, the detection accuracy is greatly affected due to high humidity in the exhaled breath. Here, we propose a regulation method to solve the problem of humidity adaptability in the ethanol-monitoring process by building a heterojunction and hollow-out nanostructure. Therefore, large specific surface area hollow-out Fe2O3-loaded NiO heterojunction nanorods assembled by porous ultrathin nanosheets were prepared by a well-tailored interface reaction. The excellent response (51.2 toward 10 ppm ethanol at 80% relative humidity) and selectivity to ethanol under high relative humidity with a lower operating temperature (150 °C) were obtained, and the detection limit was as low as 0.5 ppb with excellent long-term stability. The superior gas-sensing performance was attributed to the high surface activity of the heterojunction and hollow-out nanostructure. More importantly, GC-MS, diffuse reflectance Fourier transform infrared spectroscopy, and DFT were utilized to analyze the mechanisms of heterojunction sensitization, ethanol-sensing reaction, and high-humidity adaptability. Our integrated low-power MEMS Internet of Things (IoT) system based on Fe2O3@NiO successfully demonstrates the functional verification of ethanol detection in human exhalation, and the integrated voice alarm and IoT positioning functions are expected to solve the problem of real-time monitoring and rapid initial screening of drunk driving. Overall, this novel method plays a vital role in areas such as control of material morphology and composition, breath analysis, gas-sensing mechanism research, and artificial olfaction.


Subject(s)
Nanostructures , Nanotubes , Humans , Humidity , Exhalation , Ethanol/analysis , Nanostructures/chemistry
16.
BMC Med Genomics ; 16(1): 153, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37393256

ABSTRACT

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly heterogeneous cancer that lacks comprehensive understanding and effective treatment. Although multi-omics study has revealed features and underlying drivers of advanced ESCC, research on molecular characteristics of the early stage ESCC is quite limited. MATERIALS AND METHODS: We presented characteristics of genomics and transcriptomics in 10 matched pairs of tumor and normal tissues of early ESCC patients in the China region. RESULTS: We identified the specific patterns of cancer gene mutations and copy number variations. We also found a dramatic change in the transcriptome, with more than 4,000 genes upregulated in cancer. Among them, more than one-third of HOX family genes were specifically and highly expressed in early ESCC samples of China and validated by RT-qPCR. Gene regulation network analysis indicated that alteration of Hox family genes promoted the proliferation and metabolism remodeling of early ESCC. CONCLUSIONS: We characterized the genomic and transcriptomic landscape of 10 paired normal adjacent and early ESCC tissues in the China region, and provided a new perspective to understand the development of ESCC and insight into potential prevention and diagnostic targets for the management of early ESCC in China.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Squamous Cell Carcinoma/genetics , DNA Copy Number Variations , Esophageal Neoplasms/genetics , Genomics , China
17.
Chem Biol Interact ; 369: 110260, 2023 Jan 05.
Article in English | MEDLINE | ID: mdl-36414028

ABSTRACT

Programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) interaction exerts a vital role in tumor-associated immune evasion. While strategies disrupting PD-1/PD-L1 axis have shown clinical benefits in various cancers, the limited response rate prompts us to investigate the complex mechanisms underlying the molecular regulation of PD-L1. Here, we identify the RNA binding protein RBMS3 as a crucial PD-L1 regulator in triple-negative breast cancer (TNBC). Correlation analysis shows that Rbms3 significantly correlates with immunosuppressive CD274, Rbms1, NT5E and ENTPD1. RBMS3 protein binds to CD274 mRNA specifically in TNBC cells to increase PD-L1 levels. Mechanistically, RBMS3 stabilizes CD274 mRNA by interacting with its 3'UTR, which represents as an intrinsic cancer cell mechanism for driving PL-D1 upregulation in TNBC. RBMS3 depletion not only destabilizes the mRNA stability and protein expression of PD-L1, but also suppresses the migratory abilities of TNBC MDA-MB-231 cells. Importantly, combination of RBMS3 ablation with auranofin (AUF), an FDA-approved thioredoxin reductase inhibitor, facilitates anti-tumor T-cell immunity in vivo and improves AUF-mediated anti-cancer effect. Taken together, our findings reveal RBMS3 as a key post-transcriptional regulator of PD-L1 and how they contribute to immune escape in TNBC, which could lead to novel combinatorial therapeutic strategies to enhance the efficacy of cancer immunotherapy.


Subject(s)
Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Auranofin/pharmacology , Auranofin/therapeutic use , Programmed Cell Death 1 Receptor/metabolism , Programmed Cell Death 1 Receptor/therapeutic use , B7-H1 Antigen/genetics , Antibodies , RNA, Messenger/genetics , Cell Line, Tumor , DNA-Binding Proteins/metabolism , RNA-Binding Proteins , Trans-Activators/metabolism
18.
Eye (Lond) ; 37(14): 2987-2993, 2023 10.
Article in English | MEDLINE | ID: mdl-36841867

ABSTRACT

BACKGROUND: Pathological myopia (PM) is closely associated with blinding ocular morbidities. Identifying biomarkers can provide clues on pathogeneses. This study aimed to identify metabolic biomarkers and underlying mechanisms in the vitreous humour (VH) of PM patients with complications. METHODS: VH samples were collected from 39 PM patients with rhegmatogenous retinal detachment (RRD) (n = 23) or macular hole (MH)/myopic retinoschisis (MRS) (n = 16) and 23 controls (MH with axial length < 26 mm) who underwent surgical treatment. VH metabolomic profiles were investigated using ultra-performance liquid chromatography‒mass spectrometry. The area under the receiver operating characteristic curve (AUC) was computed to identify potential biomarkers for PM diagnosis. RESULTS: Bioinformatics analysis identified nineteen and four metabolites altered in positive and negative modes, respectively, and these metabolites were involved in tryptophan metabolism. Receiver operating characteristic analysis showed that seventeen metabolites (AUC > 0.6) in the positive mode and uric acid in the negative mode represent potential biomarkers for PM with complications (AUC = 0.894). Pairwise and pathway analyses among the RRD-PM, MH/MRS-PM and control groups showed that tryptophan metabolism and uric acid were closely correlated with PM. Altered metabolites and pathways in our study were characterized by increased oxidative stress and altered energy metabolism. These results contribute to a better understanding of myopia progression with or without related complications. CONCLUSIONS: Our study provides metabolomic signatures and related immunopathological features in the VH of PM patients, revealing new insight into the prevention and treatment of PM and related complications.


Subject(s)
Macular Degeneration , Myopia, Degenerative , Retinal Detachment , Retinal Perforations , Retinoschisis , Humans , Myopia, Degenerative/complications , Tryptophan , Uric Acid , Retinal Detachment/etiology , Retinal Detachment/surgery , Retinal Detachment/pathology , Retinoschisis/surgery , Retinal Perforations/surgery , Macular Degeneration/complications , Biomarkers , Retrospective Studies
19.
Sci Data ; 10(1): 376, 2023 06 10.
Article in English | MEDLINE | ID: mdl-37301898

ABSTRACT

Chronic liver diseases usually developed through stepwise pathological transitions under the persistent risk factors. The molecular changes during liver transitions are pivotal to improve liver diagnostics and therapeutics yet still remain elusive. Cumulative large-scale liver transcriptomic studies have been revealing molecular landscape of various liver conditions at bulk and single-cell resolution, however, neither single experiment nor databases enabled thorough investigations of transcriptomic dynamics along the progression of liver diseases. Here we establish GepLiver, a longitudinal and multidimensional liver expression atlas integrating expression profiles of 2469 human bulk tissues, 492 mouse samples, 409,775 single cells from 347 human samples and 27 liver cell lines spanning 16 liver phenotypes with uniformed processing and annotating methods. Using GepLiver, we have demonstrated dynamic changes of gene expression, cell abundance and crosstalk harboring meaningful biological associations. GepLiver can be applied to explore the evolving expression patterns and transcriptomic features for genes and cell types respectively among liver phenotypes, assisting the investigation of liver transcriptomic dynamics and informing biomarkers and targets for liver diseases.


Subject(s)
Liver Diseases , Transcriptome , Animals , Humans , Mice , Gene Expression Profiling/methods , Hepatocytes , Liver Diseases/genetics
20.
Adv Sci (Weinh) ; 10(26): e2302778, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37442769

ABSTRACT

Various catalysts are developed to improve the performance of metal oxide semiconductor gas sensors, but achieving high selectivity and response intensity in chemiresistive gas sensors (CGSs) remains a significant challenge. In this study, an in situ-annealing approach to synthesize Cu catalytic sites on ultrathin WO2.72 nanowires for detecting toluene at ultralow concentrations (Ra /Rg = 1.9 at 10 ppb) with high selectivity is developed. Experimental and molecular dynamic studies reveal that the Cu single atoms (SAs) act as active sites, promoting the oxidation of toluene and increasing the affinity of Cu single-atom catalysts (SACs)-containing sensing materials for toluene while weakening the association with carbon dioxide or water vapor. Density functional theory studies show that the selective binding of toluene to Cu SAs is due to the favorable binding sites provided by Cu SAs for toluene molecules over other gaseous species, which aids the adsorption of toluene on WO2.72 nanowires. This study demonstrates the successful atomic-level interface regulation engineering of WO2.72 nanowire-supported Cu SAs, providing a potential strategy for the development of highly active and durable CGSs.

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