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1.
Cell ; 187(11): 2838-2854.e17, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38744282

RESUMO

Retrospective lineage reconstruction of humans predicts that dramatic clonal imbalances in the body can be traced to the 2-cell stage embryo. However, whether and how such clonal asymmetries arise in the embryo is unclear. Here, we performed prospective lineage tracing of human embryos using live imaging, non-invasive cell labeling, and computational predictions to determine the contribution of each 2-cell stage blastomere to the epiblast (body), hypoblast (yolk sac), and trophectoderm (placenta). We show that the majority of epiblast cells originate from only one blastomere of the 2-cell stage embryo. We observe that only one to three cells become internalized at the 8-to-16-cell stage transition. Moreover, these internalized cells are more frequently derived from the first cell to divide at the 2-cell stage. We propose that cell division dynamics and a cell internalization bottleneck in the early embryo establish asymmetry in the clonal composition of the future human body.


Assuntos
Blastômeros , Linhagem da Célula , Embrião de Mamíferos , Feminino , Humanos , Blastômeros/citologia , Blastômeros/metabolismo , Divisão Celular , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário , Camadas Germinativas/citologia , Camadas Germinativas/metabolismo , Masculino , Animais , Camundongos
2.
Nature ; 610(7930): 143-153, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36007540

RESUMO

Embryonic stem (ES) cells can undergo many aspects of mammalian embryogenesis in vitro1-5, but their developmental potential is substantially extended by interactions with extraembryonic stem cells, including trophoblast stem (TS) cells, extraembryonic endoderm stem (XEN) cells and inducible XEN (iXEN) cells6-11. Here we assembled stem cell-derived embryos in vitro from mouse ES cells, TS cells and iXEN cells and showed that they recapitulate the development of whole natural mouse embryo in utero up to day 8.5 post-fertilization. Our embryo model displays headfolds with defined forebrain and midbrain regions and develops a beating heart-like structure, a trunk comprising a neural tube and somites, a tail bud containing neuromesodermal progenitors, a gut tube, and primordial germ cells. This complete embryo model develops within an extraembryonic yolk sac that initiates blood island development. Notably, we demonstrate that the neurulating embryo model assembled from Pax6-knockout ES cells aggregated with wild-type TS cells and iXEN cells recapitulates the ventral domain expansion of the neural tube that occurs in natural, ubiquitous Pax6-knockout embryos. Thus, these complete embryoids are a powerful in vitro model for dissecting the roles of diverse cell lineages and genes in development. Our results demonstrate the self-organization ability of ES cells and two types of extraembryonic stem cells to reconstitute mammalian development through and beyond gastrulation to neurulation and early organogenesis.


Assuntos
Embrião de Mamíferos , Gastrulação , Modelos Biológicos , Neurulação , Organogênese , Animais , Linhagem da Célula , Embrião de Mamíferos/citologia , Embrião de Mamíferos/embriologia , Células-Tronco Embrionárias/citologia , Endoderma/citologia , Endoderma/embriologia , Coração/embriologia , Mesencéfalo/embriologia , Camundongos , Tubo Neural/embriologia , Fator de Transcrição PAX6/deficiência , Fator de Transcrição PAX6/genética , Prosencéfalo/embriologia , Somitos/embriologia
3.
J Infect Dis ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39189826

RESUMO

BACKGROUND: National treatment guidelines of China evolving necessitates population-level surveillance of transmitted drug resistance (TDR) to inform or update HIV treatment strategies. METHODS: We analyzed the demographic, clinical, and virologic data obtained from people with HIV (PWH) residing in 31 provinces of China who were newly diagnosed between 2018 and 2023. Evidence of TDR was defined by the World Health Organization list for surveillance of drug resistance mutations. RESULTS: Among the 22 124 PWH with protease and reverse transcriptase sequences, 965 (4.36%; 95% CI, 4.1-4.63) had at least 1 TDR mutation. The most frequent TDR mutations were nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.39%; 95% CI, 2.19%-2.59%), followed by nucleoside reverse transcriptase inhibitor mutations(1.35%; 95% CI, 1.2%-1.5%) and protease inhibitor mutations (1.12%; 95% CI, .98%-1.26%). The overall protease and reverse transcriptase TDR increased significantly from 4.05% (95% CI, 3.61%-4.52%) in 2018 to 5.39% (95% CI, 4.33%-6.57%) in 2023. A low level of integrase strand transfer inhibitor TDR was detected in 9 (0.21%; 95% CI, .1%-.38%) of 4205 PWH. CONCLUSIONS: Presently, the continued use of NNRTI-based first-line antiretroviral therapy regimen for HIV treatment has been justified.

4.
J Infect Dis ; 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39186695

RESUMO

BACKGROUND: In 2016, China has implemented the World Health Organization's "treat all" policy. We aimed to assess the impact of significant improvements in the 95-95-95 targets on population-level human immunodeficiency virus (HIV) transmission dynamics and incidence. METHODS: We focused on 3 steps of the HIV care continuum: diagnosed, on antiretroviral therapy, and achieving viral suppression. The molecular transmission clusters were inferred using HIV-TRACE. New HIV infections were estimated using the incidence method in the European Centre for Disease Prevention and Control HIV Modelling Tool. RESULTS: Between 2004 and 2023, the national HIV epidemiology database recorded 2.99 billion person-times of HIV tests and identified 1 976 878 new diagnoses. We noted a roughly "inverted-V" curve in the clustering frequency, with the peak recorded in 2014 (67.1% [95% confidence interval, 63.7%-70.5%]), concurrent with a significant improvement in the 95-95-95 targets from 10-13-<71 in 2005 to 84-93-97 in 2022. Furthermore, we observed a parabolic curve for a new infection with the vertex occurring in 2010. CONCLUSIONS: In general, it was suggested that the improvements in the 95-95-95 targets were accompanied by a reduction in both the population-level HIV transmission rate and incidence. Thus, China should allocate more effort to the first "95" target to achieve a balanced 95-95-95 target.

5.
Int J Cancer ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985144

RESUMO

The precise delivery of drugs to tumor sites and the thermoresistance of tumors remain major challenges in photothermal therapy (PTT). Somatostatin receptor 2 (SSTR2) is proposed as an ideal target for the precise treatment of SCLC. We developed a targeting nano-drug delivery system comprising anti-SSTR2 monoclonal antibody (MAb) surface-modified nanoparticles co-encapsulating Cypate and gambogic acid (GA). The formed SGCPNs demonstrated excellent monodispersity, physiological stability, preferable biocompatibility, and resultant efficient photothermal conversion efficacy. SGCPNs were quickly internalized by SSTR2-overexpressing SCLC cells, triggering the release of GA under acidic and near-infrared (NIR) laser irradiation environments, leading to their escape from lysosomes to the cytosol and then diffusion into the nucleus. SGCPNs can not only decrease the cell survival rate but also inhibit the activity of heat shock protein 90 (HSP90). SGCPNs can be precisely delivered to xenograft tumors of SSTR2-positive SCLC in vivo. Upon NIR laser irradiation, therapy of SGCPNs showed significant tumor regression. In conclusion, SGCPNs provide a new chemo-photothermal synergistic treatment strategy for targeting SCLC.

6.
Small ; 20(22): e2309009, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38100243

RESUMO

Using seeds to control the crystallization of perovskite film is an effective strategy for achieving high-efficiency perovskite solar cells (PSCs). Owing to their excellent environmental stability brought by their long alkyl chain, n-butylammonium (BA) cations are widely used for fabricating efficient and stable PSCs. However, BA-based 2D perovskite is seldom been investigated as a seed. Here, BA2PbI4 is employed to regulate the crystallization of PbI2, acting as nucleation centers. As a result, porous PbI2 film with high crystallinity is obtained, which allows the realization of perovskite film with preferential crystal orientations of (001) and large grain size of over 2 µm. The corresponding PSC achieves a high power conversion efficiency (PCE) of 24.30% and exhibits satisfactory stability, retaining 91.70% of the initial PCE after 300 h of thermal aging at 85°C.

7.
BMC Microbiol ; 24(1): 286, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090543

RESUMO

BACKGROUND: Bile acids (BAs) are steroid-derived molecules with important roles in digestion, the maintenance of host metabolism, and immunomodulation. Primary BAs are synthesized by the host, while secondary BAs are produced by the gut microbiome through transformation of the former. The regulation of microbial production of secondary BAs is not well understood, particularly the production of 7-dehydroxylated BAs, which are the most potent agonists for host BA receptors. The 7-dehydroxylation of cholic acid (CA) is well established and is linked to the expression of a bile acid-inducible (bai) operon responsible for this process. However, little to no 7-dehydroxylation has been reported for other host-derived BAs (e.g., chenodeoxycholic acid, CDCA or ursodeoxycholic acid, UDCA). RESULTS: Here, we demonstrate that the 7-dehydroxylation of CDCA and UDCA by the human isolate Clostridium scindens is induced when CA is present, suggesting that CA-dependent transcriptional regulation is required for substantial 7-dehydroxylation of these primary BAs. This is supported by the finding that UDCA alone does not promote expression of bai genes. CDCA upregulates expression of the bai genes but the expression is greater when CA is present. In contrast, the murine isolate Extibacter muris exhibits a distinct response; CA did not induce significant 7-dehydroxylation of primary BAs, whereas BA 7-dehydroxylation was promoted upon addition of germ-free mouse cecal content in vitro. However, E. muris was found to 7-dehydroxylate in vivo. CONCLUSIONS: The distinct expression responses amongst strains indicate that bai genes are regulated differently. CA promoted bai operon gene expression and the 7-dehydroxylating activity in C. scindens strains. Conversely, the in vitro activity of E. muris was promoted only after the addition of cecal content and the isolate did not alter bai gene expression in response to CA. The accessory gene baiJ was only upregulated in the C. scindens ATCC 35704 strain, implying mechanistic differences amongst isolates. Interestingly, the human-derived C. scindens strains were also capable of 7-dehydroxylating murine bile acids (muricholic acids) to a limited extent. This study shows novel 7-dehydroxylation activity in vitro resulting from the presence of CA and suggests distinct bai gene expression across bacterial species.


Assuntos
Ácidos e Sais Biliares , Ácido Cólico , Ácido Cólico/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Camundongos , Humanos , Clostridium/metabolismo , Clostridium/genética , Regulação Bacteriana da Expressão Gênica , Hidroxilação , Óperon , Ácido Quenodesoxicólico/metabolismo , Ácido Ursodesoxicólico/metabolismo , Microbioma Gastrointestinal
8.
Opt Express ; 32(4): 4954-4973, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439234

RESUMO

In response to the challenges encountered in solving the integral equations and the disadvantages of requiring additional calibration parameters in the existing three-channel wide-spectrum temperature measurement, a wavelength-based Taylor series de-integration method is proposed. By combining the coefficient of determination, which characterizes the approximation effect, the selection criterion of characteristic wavelength (optimal expansion wavelength, OEW) is constructed. In the influence analysis of spectral emissivity on the de-integration method, the insensitivity of OEW to spectral emissivity is revealed. The feasibility of using blackbody OEW for de-integration processing is proved when the spectral emissivity is unknown, which provides necessary theoretical support for the selection of characteristic wavelengths in practical application. Based on this integration method, algebraic temperature measurement equations in the forms of graybody, three-channel fusion, and two-color are derived, and the theoretical errors of each form are discussed from both horizontal and longitudinal perspectives. Furthermore, thermometry experiments with multiple acquisition parameters and diverse samples were conducted corresponding to three solution forms, the universality of acquisition parameters and sample applicability are proven.

9.
Opt Express ; 32(3): 3501-3511, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297570

RESUMO

An amorphous germanium-tin (a-Ge0.83Sn0.17) waveguide bolometer featuring a one-dimension (1D) metasurface absorber is proposed for mid-infrared photodetection at room-temperature. The device is based on the germanium-on-silicon (GOS) photonic platform. The impacts of the 1D metasurface on the performances of the waveguide bolometer are investigated. The responsivity of the a-Ge0.83Sn0.17 waveguide bolometer could be significantly enhanced by the metasurface. A responsivity of around -3.17%/µW within the 4.1 ∼ 4.3 µm wavelength range is achieved. In addition, a 3-dB roll-off frequency higher than 10 kHz is obtained.

10.
Opt Express ; 32(10): 17525-17534, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858934

RESUMO

The anisotropic optical properties of aluminum scandium nitride (Al1-xScxN) thin films for both ordinary and extraordinary light are investigated. A quantitative analysis of the band structures of the wurtzite Al1-xScxN is carried out. In addition, Al1-xScxN photonic waveguides and bends are fabricated on 8-inch Si substrates. With x = 0.087 and 0.181, the light propagation losses are 5.98 ± 0.11 dB/cm and 8.23 ± 0.39 dB/cm, and the 90° bending losses are 0.05 dB/turn and 0.08 dB/turn at 1550 nm wavelength, respectively.

11.
Toxicol Appl Pharmacol ; 486: 116946, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38679241

RESUMO

The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD.


Assuntos
Anti-Hipertensivos , Transtorno do Deficit de Atenção com Hiperatividade , Comportamento Animal , Captopril , Microbioma Gastrointestinal , Efeitos Tardios da Exposição Pré-Natal , Ratos Endogâmicos SHR , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Gravidez , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Feminino , Anti-Hipertensivos/farmacologia , Captopril/farmacologia , Masculino , Ratos , Comportamento Animal/efeitos dos fármacos , Labetalol/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipertensão Induzida pela Gravidez/induzido quimicamente , Dopamina/metabolismo
12.
Opt Lett ; 49(11): 3162-3165, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824353

RESUMO

Lithium niobate (LN) photonics has gained significant interest for their distinct material properties. However, achieving monolithically integrated photodetectors on lithium niobate on an insulator (LNOI) platform for communication wavelengths remains a challenge due to the large bandgap and extremely low electrical conductivity of LN material. A two-dimensional (2D) material photodetector is an ideal solution for LNOI photonics with a strong light-matter interaction and simple integration technique. In this work, a van der Waals heterostructure photodiode composed of a p-type black phosphorus layer and an n-type MoS2 layer is successfully demonstrated for photodetection at communication wavelengths on a LNOI platform. The LNOI waveguide-integrated BP-MoS2 photodetector exhibits a dark current as low as 0.21 nA and an on/off ratio exceeding 200 under zero voltage bias with an incident power of 13.93 µW. A responsivity as high as 1.46 A/W is achieved at -1 V bias with a reasonable dark current around 2.33 µA. With the advantages of high responsivity, low dark current, and simple fabrication process, it is promising for the monolithically integrated photodetector application for LNOI photonic platforms at communication wavelengths.

13.
FASEB J ; 37(4): e22857, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36906292

RESUMO

Adipogenesis is a finely controlled process and its dysfunction may contribute to metabolic disorders such as obesity. Metastasis suppressor 1 (MTSS1) is a player in tumorigenesis and metastasis of various types of cancers. To date, it is not known whether and how MTSS1 plays a role in adipocyte differentiation. In the current study, we found that MTSS1 was upregulated during adipogenic differentiation of established mesenchymal cell lines and primary cultured bone marrow stromal cells. Gain-of-function and loss-of-function experiments uncovered that MTSS1 facilitated adipocyte differentiation from mesenchymal progenitor cells. Mechanistic explorations revealed that MTSS1 bound and interacted with FYN, a member of Src family of tyrosine kinases (SFKs), and protein tyrosine phosphatase receptor-δ (PTPRD). We demonstrated that PTPRD was capable of inducing the differentiation of adipocytes. Overexpression of PTPRD attenuated the impaired adipogenesis induced by the siRNA targeting MTSS1. Both MTSS1 and PTPRD activated SFKs by suppressing the phosphorylation of SFKs at Tyr530 and inducing the phosphorylation of FYN at Tyr419. Further investigation showed that MTSS1 and PTPRD were able to activate FYN. Collectively, our study has for the first time unraveled that MTSS1 plays a role in adipocyte differentiation in vitro through interacting with PTPRD and thereby activating SFKs such as FYN tyrosine kinase.


Assuntos
Adipogenia , Proteínas dos Microfilamentos , Proteínas de Neoplasias , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores , Humanos , Diferenciação Celular , Proteínas dos Microfilamentos/genética , Proteínas de Neoplasias/genética , Fosforilação , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética
14.
Cell Commun Signal ; 22(1): 111, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347641

RESUMO

Macroautophagy/autophagy is a lysosome-dependent catabolic process induced by various cellular stress conditions, maintaining the homeostasis of cells, tissues and organs. Autophagy is a series of membrane-related events involving multiple autophagy-related (ATG) proteins. Most studies to date have focused on various signaling pathways affecting ATG proteins to control autophagy. However, mounting evidence reveals that the actin cytoskeleton acts on autophagy-associated membranes to regulate different events of autophagy. The actin cytoskeleton assists in vesicle formation and provides the mechanical forces for cellular activities that involve membrane deformation. Although the interaction between the actin cytoskeleton and membrane makes the role of actin in autophagy recognized, how the actin cytoskeleton is recruited and assembles on membranes during autophagy needs to be detailed. Nucleation-promoting factors (NPFs) activate the Arp2/3 complex to produce actin cytoskeleton. In this review, we summarize the important roles of the actin cytoskeleton in autophagy regulation and focus on the effect of NPFs on actin cytoskeleton assembly during autophagy, providing new insights into the occurrence and regulatory mechanisms of autophagy. Video Abstract.


Assuntos
Citoesqueleto de Actina , Actinas , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Citoesqueleto/metabolismo , Autofagia/fisiologia , Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo
15.
Anticancer Drugs ; 35(2): 129-139, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37615540

RESUMO

Colorectal cancer (CRC) is one of the world's most common and deadly cancers. According to GLOBOCAN2020's global incidence rate and mortality estimates, CRC is the third main cause of cancer and the second leading cause of cancer-related deaths worldwide. The US Food and Drug Administration has approved auranofin for the treatment of rheumatoid arthritis. It is a gold-containing chemical that inhibits thioredoxin reductase. Auranofin has a number of biological activities, including anticancer activity, although it has not been researched extensively in CRC, and the mechanism of action on CRC cells is still unknown. The goal of this research was to see how Auranofin affected CRC cells in vivo and in vitro . The two chemical libraries were tested for drugs that make CRC cells more responsive. The CCK-8 technique was used to determine the cell survival rate. The invasion, migration, and proliferation of cells were assessed using a transwell test and a colony cloning experiment. An electron microscope was used to observe autophagosome formation. Western blotting was also used to determine the degree of expression of related proteins in cells. Auranofin's tumor-suppressing properties were further tested in a xenograft tumor model of human SW620 CRC cells. Auranofin dramatically reduced the occurrence of CRC by decreasing the proliferation, migration, and invasion of CRC cells, according to our findings. Through a mTOR-dependent mechanism, auranofin inhibits the epithelial-mesenchymal transition (EMT) and induces autophagy in CRC cells. Finally, in-vivo tests revealed that auranofin suppressed tumor growth in xenograft mice while causing no harm. In summary, auranofin suppresses CRC cell growth, invasion, and migration. Auranofin inhibits the occurrence and progression of CRC by decreasing EMT and inducing autophagy in CRC cells via a mTOR-dependent mechanism. These findings suggest that auranofin could be a potential chemotherapeutic medication for the treatment of human CRC.


Assuntos
Auranofina , Neoplasias Colorretais , Humanos , Animais , Camundongos , Auranofina/farmacologia , Auranofina/uso terapêutico , Linhagem Celular Tumoral , Serina-Treonina Quinases TOR/metabolismo , Neoplasias Colorretais/patologia , Autofagia , Transição Epitelial-Mesenquimal , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica
16.
Circ Res ; 131(9): e120-e134, 2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36164984

RESUMO

BACKGROUND: Despite available clinical management strategies, chronic kidney disease (CKD) is associated with severe morbidity and mortality worldwide, which beckons new solutions. Host-microbial interactions with a depletion of Faecalibacterium prausnitzii in CKD are reported. However, the mechanisms about if and how F prausnitzii can be used as a probiotic to treat CKD remains unknown. METHODS: We evaluated the microbial compositions in 2 independent CKD populations for any potential probiotic. Next, we investigated if supplementation of such probiotic in a mouse CKD model can restore gut-renal homeostasis as monitored by its effects on suppression on renal inflammation, improvement in gut permeability and renal function. Last, we investigated the molecular mechanisms underlying the probiotic-induced beneficial outcomes. RESULTS: We observed significant depletion of Faecalibacterium in the patients with CKD in both Western (n=283) and Eastern populations (n=75). Supplementation of F prausnitzii to CKD mice reduced renal dysfunction, renal inflammation, and lowered the serum levels of various uremic toxins. These are coupled with improved gut microbial ecology and intestinal integrity. Moreover, we demonstrated that the beneficial effects in kidney induced by F prausnitzii-derived butyrate were through the GPR (G protein-coupled receptor)-43. CONCLUSIONS: Using a mouse CKD model, we uncovered a novel beneficial role of F prausnitzii in the restoration of renal function in CKD, which is, at least in part, attributed to the butyrate-mediated GPR-43 signaling in the kidney. Our study provides the necessary foundation to harness the therapeutic potential of F prausnitzii for ameliorating CKD.


Assuntos
Faecalibacterium prausnitzii , Insuficiência Renal Crônica , Animais , Butiratos/farmacologia , Butiratos/uso terapêutico , Modelos Animais de Doenças , Inflamação , Rim/fisiologia , Receptores Acoplados a Proteínas G/genética
17.
Clin Radiol ; 79(3): e453-e461, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38160104

RESUMO

AIM: To establish an artificial neural network (ANN) model to predict subsolid nodules (SSNs) before percutaneous core-needle biopsy (PCNB). The results of the two methods were compared to provide guidance on the treatment of SSNs. MATERIALS AND METHODS: This was a single-centre retrospective study using data from 1,459 SSNs between 2013 and 2021. The ANN was developed using data from patients who underwent surgery following computed tomography (CT) (SFC) and validated using data from patients who underwent surgery following biopsy (SFB). The prediction results of the ANN for the PCNB group and the histopathological results obtained after biopsy were compared with the histopathological results of lung nodules in the same group after surgery. Additionally, the choice of predictors for PCNB was analysed using multivariate analysis. RESULTS: There was no significant difference between the accuracies of the ANN and PCNB in the SFB group (p=0.086). The sensitivity of PCNB was lower than that of the ANN (p=0.000), but the specificity was higher (p=0.001). PCNB had better diagnostic ability than the ANN. The incidence of precursor lesions and non-neoplastic lesions in the SFB group was lower than that in the SFC group (p=0.000). A history of malignant tumours, size (2-3 cm), volume (>400 cm3) and mean CT value (≥-450 HU) are important factors for selecting PCNB. CONCLUSIONS: Both ANN and PCNB have comparable accuracy in diagnosing SSNs; however, PCNB has a slightly higher diagnostic ability than ANN. Selecting appropriate patients for PCNB is important for maximising the benefit to SSN patients.


Assuntos
Neoplasias Pulmonares , Nitrobenzenos , Tomografia Computadorizada por Raios X , Humanos , Estudos Retrospectivos , Biópsia , Biópsia com Agulha de Grande Calibre , Tomografia Computadorizada por Raios X/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia
18.
Cell Mol Biol Lett ; 29(1): 112, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39169280

RESUMO

BACKGROUND: Breast cancer (BC) ranks as the third most fatal malignant tumor worldwide, with a strong reliance on fatty acid metabolism. CLDN6, a candidate BC suppressor gene, was previously identified as a regulator of fatty acid biosynthesis; however, the underlying mechanism remains elusive. In this research, we aim to clarify the specific mechanism through which CLDN6 modulates fatty acid anabolism and its impact on BC growth and metastasis. METHODS: Cell function assays, tumor xenograft mouse models, and lung metastasis mouse models were conducted to evaluate BC growth and metastasis. Human palmitic acid assay, triglyceride assay, Nile red staining, and oil red O staining were employed to investigate fatty acid anabolism. Reverse transcription polymerase chain reaction (RT-PCR), western blot, immunohistochemistry (IHC) assay, nuclear fractionation, immunofluorescence (IF), immunoprecipitation and acyl-biotin exchange (IP-ABE), chromatin immunoprecipitation (ChIP), dual luciferase reporter assay, and co-immunoprecipitation (Co-IP) were applied to elucidate the underlying molecular mechanism. Moreover, tissue microarrays of BC were analyzed to explore the clinical implications. RESULTS: We identified that CLDN6 inhibited BC growth and metastasis by impeding RAS palmitoylation both in vitro and in vivo. We proposed a unique theory suggesting that CLDN6 suppressed RAS palmitoylation through SREBP1-modulated de novo palmitic acid synthesis. Mechanistically, CLDN6 interacted with MAGI2 to prevent KLF5 from entering the nucleus, thereby restraining SREBF1 transcription. The downregulation of SREBP1 reduced de novo palmitic acid synthesis, hindering RAS palmitoylation and subsequent endosomal sorting complex required for transport (ESCRT)-mediated plasma membrane localization required for RAS oncogenic activation. Besides, targeting inhibition of RAS palmitoylation synergized with CLDN6 to repress BC progression. CONCLUSIONS: Our findings provide compelling evidence that CLDN6 suppresses the palmitic acid-induced RAS palmitoylation through the MAGI2/KLF5/SREBP1 axis, thereby impeding BC malignant progression. These results propose a new insight that monitoring CLDN6 expression alongside targeting inhibition of palmitic acid-mediated palmitoylation could be a viable strategy for treating oncogenic RAS-driven BC.


Assuntos
Neoplasias da Mama , Proliferação de Células , Claudinas , Lipoilação , Proteína de Ligação a Elemento Regulador de Esterol 1 , Humanos , Animais , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Camundongos , Claudinas/metabolismo , Claudinas/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Metástase Neoplásica , Proteínas ras/metabolismo , Proteínas ras/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário
19.
BMC Womens Health ; 24(1): 406, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39020328

RESUMO

OBJECTIVE: To study the effects of chemotherapy on cognitive function in breast cancer patients, and to investigate the relationship of MemTrax test of memory and related functions to the FACT-Cog functional self-assessment for the evaluation and management of chemobrain. METHODS: In this prospective cohort study, clinical information of pathologically confirmed female breast cancer patients who decided to receive chemotherapy were collected in a questionnaire which was developed for this study and provided as a supplementary file. The FACT-Cog self-assessment and MemTrax test were administered before and after the chemotherapy treatments. Patients with chemobrain were identified using published criteria based on FACT-Cog scores, and MemTrax scores from chemobrain patients were analyzed. RESULTS: Fifty-six patients participated in this study, of which 41 participants completed 4 or more cycles of chemotherapy and were included in the final analyses here. Using the reported high end of minimal clinical differences (10.6 points) of FACT-Cog before and after chemotherapy, 18 patients suffered from chemobrain in this study. In these 18 chemobrain patients, no cognitive impairments were detected by MemTrax, which paradoxically demonstrated an improvement in the normal cognitive range. CONCLUSION: The cognitive impairment induced by chemotherapy in breast cancer patients is detectable by the FACT-Cog in a Chinese cohort but is not detected by the MemTrax memory test. The fact that the more objective MemTrax could not detect the impairment could alleviate patients' concerns which in turn would be beneficial for patients' mental health.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Testes Neuropsicológicos/estatística & dados numéricos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Comprometimento Cognitivo Relacionado à Quimioterapia/tratamento farmacológico , Idoso , Memória/efeitos dos fármacos , Inquéritos e Questionários , Estudos de Coortes
20.
Appl Opt ; 63(6): 1522-1528, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38437364

RESUMO

A non-uniform distributed silicon optical phased array (OPA) is proposed and numerically demonstrated to realize high directionality and a wide range for beam steering. The OPA is composed of grating antennas with dual-layer corrugations along silicon strip waveguides, which can achieve a high directionality of 0.96 and a small divergence angle of 0.084°. To reduce the crosstalk between adjacent antennas and realize a wide steering range, the genetic algorithm is improved and utilized to arrange the locations of grating antennas. As a proof of concept, a 32-channel non-uniform distributed OPA is designed and thoroughly optimized. The simulation results successfully demonstrate a two-dimensional wide steering range of 70∘×18.7∘ with a side-mode suppression ratio (SMSR) over 10 dB.

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