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1.
Microbiol Spectr ; : e0100424, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39101825

RESUMO

Growing evidence have indicated the crucial role of intratumor microbiome in a variety of solid tumor. However, the intratumoral microbiome in gynecological malignancies is largely unknown. In the present study, a total of 90 Han patients, including 30 patients with cancer in cervix, ovary, and endometrium each were enrolled, the composition of intratumoral microbiome was assessed by 16S rDNA amplicon high throughput sequencing. We found that the diversity and metabolic potential of intratumoral microbiome in all three cancer types were very similar. Furthermore, all three cancer types shared a few taxa that collectively take up high relative abundance and positive rate, including Pseudomonas sp., Comamonadaceae gen. sp., Bradyrhizobium sp., Saccharomonospora sp., Cutibacterium acnes, Rubrobacter sp., Dialister micraerophilus, and Escherichia coli. Additionally, Haemophilus parainfluenzae and Paracoccus sp. in cervical cancer, Pelomonas sp. in ovarian cancer, and Enterococcus faecalis in endometrial cancer were identified by LDA to be a representative bacterial strain. In addition, in cervical cancer patients, alpha-fetoprotein (AFP) (correlation coefficient = -0.3714) was negatively correlated (r = 0.4, 95% CI: 0.03 to 0.7) with Rubrobacter sp. and CA199 (correlation coefficient = 0.3955) was positively associated (r = 0.4, 95% CI: 0.03 to 0.7) with Saccharomonospora sp.. In ovarian cancer patients, CA125 (correlation coefficient = -0.4451) was negatively correlated (r = -0.4, 95% CI: -0.7 to -0.09) with Porphyromonas sp.. In endometrial cancer patients, CEA (correlation coefficient = -0.3868) was negatively correlated (r = -0.4, 95% CI: -0.7 to -0.02) with Cutibacterium acnes. This study promoted our understanding of the intratumoral microbiome in gynecological malignancies.IMPORTANCEIn this study, we found the compositional spectrum of tumor microbes among gynecological malignancies were largely similar by sharing a few taxa and differentiated by substantial species owned uniquely. Certain species, mostly unreported, were identified to be associated with clinical characteristics. This study prompted our understanding of gynecological malignancies and offered evidence for tumor microbes affecting tumor biology among cancers in the female reproductive system.

3.
EMBO Mol Med ; 16(5): 1091-1114, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38589651

RESUMO

PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSCM70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSCM70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Doença de Charcot-Marie-Tooth , Proteínas do Citoesqueleto , Mutação de Sentido Incorreto , Animais , Humanos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/patologia , Modelos Animais de Doenças , Drosophila/genética , Proteínas Nucleares , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/patologia , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo
4.
RSC Adv ; 14(7): 4543-4555, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38312726

RESUMO

Due to their high wavelength selectivity and strong anti-interference capability, solar-blind UV photodetectors hold broad and important application prospects in fields like flame detection, missile warnings, and secure communication. Research on solar-blind UV detectors for amorphous Ga2O3 is still in its early stages. The presence of intrinsic defects related to oxygen vacancies significantly affects the photodetection performance of amorphous Ga2O3 materials. This paper focuses on growing high quality amorphous Ga2O3 films on silicon substrates through atomic layer deposition. The study investigates the impact of annealing atmospheres on Ga2O3 films and designs a blind UV detector for Ga2O3. Characterization techniques including atomic force microscopy (AFM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) are used for Ga2O3 film analysis. Ga2O3 films exhibit a clear transition from amorphous to polycrystalline after annealing, accompanied by a decrease in oxygen vacancy concentration from 21.26% to 6.54%. As a result, the response time of the annealed detector reduces from 9.32 s to 0.47 s at an external bias of 10 V. This work demonstrates that an appropriate annealing process can yield high-quality Ga2O3 films, and holds potential for advancing high-performance solar blind photodetector (SBPD) development.

5.
Opt Lett ; 49(4): 1029-1032, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38359234

RESUMO

Directional emission of electromagnetic waves plays an essential role in laser radar and free-space communication. For most directional antennas, bandwidth and miniaturization are a pair of contradictions due to their underlying interference mechanism. Connection-type metamaterials exhibit exotic electromagnetic response near zero-frequency, which relies on the global topology of mesh connectivity rather than resonance and thus has a broad working bandwidth. In this Letter, we investigate the broadband orientation-dependent coupling effect of a 3D double mesh metamaterial. Based on this effect, we achieve a broadband directional emission (relative bandwidth of 37.72%) using a compact structure (compared to twice working wavelength). Our work provides a novel, to the best of our knowledge, scheme to manipulate a long-wavelength wave and may pave the way to a miniaturized directional antenna.

6.
Ren Fail ; 46(1): 2310081, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38321925

RESUMO

Background and purpose: Acute kidney injury (AKI) is a common serious complication in sepsis patients with a high mortality rate. This study aimed to develop and validate a predictive model for sepsis associated acute kidney injury (SA-AKI). Methods: In our study, we retrospectively constructed a development cohort comprising 733 septic patients admitted to eight Grade-A tertiary hospitals in Shanghai from January 2021 to October 2022. Additionally, we established an external validation cohort consisting of 336 septic patients admitted to our hospital from January 2017 to December 2019. Risk predictors were selected by LASSO regression, and a corresponding nomogram was constructed. We evaluated the model's discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) and clinical impact curves (CIC) in both internal and external validation. Results: AKI incidence was 53.2% in the development cohort and 48.2% in the external validation cohort. The model included five independent indicators: chronic kidney disease stages 1 to 3, blood urea nitrogen, procalcitonin, D-dimer and creatine kinase isoenzyme. The AUC of the model in the development and validation cohorts was 0.914 (95% CI, 0.894-0.934) and 0.923 (95% CI, 0.895-0.952), respectively. The calibration plot, DCA, and CIC demonstrated the model's favorable clinical applicability. Conclusion: We developed and validated a robust nomogram model, which might identify patients at risk of SA-AKI and promising for clinical applications.


Assuntos
Injúria Renal Aguda , Sepse , Humanos , Nomogramas , Estudos Retrospectivos , China
7.
Anal Sci ; 40(3): 399-411, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38079106

RESUMO

Whole milk powder and skimmed milk powder are suitable for different groups of people due to their differences in composition. Therefore, a rapid classification method for whole milk powder and skimmed milk powder is urgently needed. In this paper, a novel strategy based on laser-induced breakdown spectroscopy (LIBS) and feature processing methods combined with logistic regression (LR) was constructed for the classification of milk powder. A LR classification model based on mini-batch gradient descent (MGD) was employed first. As indicated by the research results, the accuracy of the MGD-LR model for the milk powder samples in the test set is 96.33% and the modeling time is 33.07 s. The modeling efficiency is low and needs to be improved. Principal components analysis (PCA) and mutual information (MI) were used as feature processing methods to reduce the high dimensional LIBS data into fewer features for improving the modeling efficiency of the classification model. The research results indicate that the accuracy of the PCA-MGD-LR model and the MI-MGD-LR model for the test set of milk powder samples was 99.33% and 99.67%, respectively. Compared with MGD-LR model, the modeling efficiency of PCA-MGD-LR and MI-MGD-LR models has increased by 89.7% and 74.8%, respectively. The results fully demonstrate the feasibility of rapid milk powder classification based on LIBS and feature processing methods combined with LR, and it will provide a new technology for the identification and classification of milk powder.


Assuntos
Lasers , Leite , Humanos , Animais , Leite/química , Pós/análise , Modelos Logísticos , Análise Espectral/métodos
8.
J Colloid Interface Sci ; 659: 11-20, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38157722

RESUMO

Piezocatalytic hydrogen evolution is a promising strategy to generate sustainable energy. In this report, nitrogen-doped (N-doped) TiO2@ carbon nanosheets (N-TiO2@C NSs) was successfully synthesized using C3N4 as a multifunctional template. During the synthesis, the two-dimensional (2D) architecture of C3N4 nanosheets directed the synthesis of TiO2 nanosheets. In addition, nitrogens of C3N4 were doped into the TiO2 lattice. Simultaneously, C3N4 was transformed into N-doped carbon nanosheets. N doping broke the crystal symmetry of TiO2, which endowed TiO2 with promising piezoelectric properties. The N-doped carbon nanosheets derived from C3N4 improved charge carrier separation efficiency and served as a flexible support to inhibit structural damage under sonication. Therefore, the N-TiO2@C NSs exhibited highly efficient activity for piezocatalytic H2 production (6.4 mmol·g-1·h-1) in the presence of methanol, much higher than those of the previously reported piezocatalysts. Our method is hoped to provide a new strategy for designing highly efficient piezocatalysts.

9.
Clin Chem Lab Med ; 62(1): 187-198, 2024 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-37531579

RESUMO

OBJECTIVES: Epstein-Barr virus (EBV) C promoter (Cp) hypermethylation, a crucial factor for EBV latent infection of nasopharyngeal epithelial cells, has been recognized as a promising biomarker for nasopharyngeal carcinoma (NPC) detection. In this study, we develop a novel EBV Cp methylation quantification (E-CpMQ) assay and evaluate its diagnostic performance for NPC detection. METHODS: A novel qPCR assay for simultaneous quantification of methylated- and unmethylated EBV Cp was developed by the combinational modification of MethyLight and QASM, with an innovative calibrator to improve the detection accuracy and consistency. The NP swab samples and synthetic standards were used for the analytical validation of the E-CpMQ. The diagnostic efficacy of the developed E-CpMQ assay was validated in 137 NPC patients and 137 non-NPC controls. RESULTS: The E-CpMQ assay can detect the EBV Cp methylation ratio in one reaction system under 10 copies with 100 % recognition specificity, which is highly correlated to pyrosequencing with a correlation coefficient over 0.99. The calibrated E-CpMQ assay reduces the coefficient of variation by an average of 55.5 % with a total variance of less than 0.06 units standard deviation (SD). Linear methylation ratio detection range from 4.76 to 99.01 %. The sensitivity and specificity of the E-CpMQ respectively are 96.4 % (95 % CI: 91.7-98.8 %), 89.8 % (95 % CI: 83.5-94.3 %). CONCLUSIONS: The developed E-CpMQ assay with a calibrator enables accurate and reproducible EBV Cp methylation ratio quantification and offers a sensitive, specific, cost-effective method for NPC early detection.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/genética , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/genética , DNA Viral/genética , Nasofaringe , Metilação de DNA
10.
Natl Sci Rev ; 10(8): nwac289, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37389141

RESUMO

Chern insulators have been generalized to many classical wave systems and thereby lead to many potential applications such as robust waveguides, quantum computation and high-performance lasers. However, the band structure of a material can be either topologically trivial or non-trivial, depending on how the crystal structure is designed. Here, we propose a second Chern crystal in a four-dimensional parameter space by introducing two extra synthetic translation dimensions. Since the topology of the bulk bands in the synthetic translation space is intrinsically non-trivial, our proposed four-dimensional crystal is guaranteed to be topologically non-trivial regardless of the crystal's detailed configuration. We derive the topologically protected modes on the lower dimensional boundaries of such a crystal via dimension reduction. Remarkably, we observe the one-dimensional gapless dislocation modes and confirm their robustness in experiments. Our findings provide novel perspectives on topologically non-trivial crystals and may inspire designs of classical wave devices.

11.
Chem Commun (Camb) ; 59(47): 7204-7207, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37218995

RESUMO

The separation and especially the removal of morpholine (MOR) impurities from N-ethyl morpholine (NEM) is of great significance in the fine chemical industry. Herein, we offer a novel strategy for the selective adsorption of MOR over NEM by tetralactam solids. The adsorbent realized the purification of NEM by adsorbing traces of MOR impurities, such that the purity can be improved from around 98% to over 99.5%. Single crystal structures indicate that N-H⋯O and N-H⋯N hydrogen bonding interactions are essential in the selective separation.


Assuntos
Indústria Química , Morfolinas , Adsorção , Ligação de Hidrogênio
12.
Bioeng Transl Med ; 8(3): e10505, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37206220

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disease with limited treatment and no cure, hence, broadening PD drug spectrum is of great significance. At present, engineered microorganisms are attracting increasing attention. In this study, we constructed an engineered strain of Clostridium butyricum-GLP-1, a C. butyricum (a probiotic) that consistently expresses glucagon-like peptide-1 (GLP-1, a peptide-based hormone with neurological advantage) in anticipation of its use in PD treatment. We further investigated the neuroprotective mechanism of C. butyricum-GLP-1 on PD mice models induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The results indicated that C. butyricum-GLP-1 could improve motor dysfunction and ameliorate neuropathological changes by increasing TH expression and reducing the expression of α-syn. Moreover, we confirmed that C. butyricum-GLP-1 improved microbiome imbalance of PD mice by decreasing the relative abundance of Bifidobacterium at the genus level, improved gut integrity, and upregulated the levels of GPR41/43. Surprisingly, we found it could exert its neuroprotective effects via promoting PINK1/Parkin mediated mitophagy and attenuating oxidative stress. Together, our work showed that C. butyricum-GLP-1 improves PD by promoting mitophagy, which provides an alternative therapeutic modality for PD.

13.
Nat Commun ; 14(1): 2027, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37041134

RESUMO

Besides chiral edge states, the hallmark of quantum Hall insulators, antichiral edge states can exhibit unidirectional transport behavior but in topological semimetals. Although such edge states provide more flexibility for molding the flow of light, their realization usually suffers from time-reversal breaking. In this study, we propose the realization of antichiral surface states in a time-reversal-invariant manner and demonstrate our idea with a three-dimensional (3D) photonic metacrystal. Our system is a photonic semimetal possessing two asymmetrically dispersed Dirac nodal lines. Via dimension reduction, the nodal lines are rendered a pair of offset Dirac points. By introducing synthetic gauge flux, each two-dimensional (2D) subsystem with nonzero kz is analogous to a modified Haldane model, yielding a kz-dependent antichiral surface transport. Through microwave experiments, the bulk dispersion with asymmetric nodal lines and associated twisted ribbon surface states are demonstrated in our 3D time-reversal-invariant system. Although our idea is demonstrated in a photonic system, we propose a general approach to realize antichiral edge states in time-reversal-invariant systems. This approach can be easily extended to systems beyond photonics and may pave the way for further applications of antichiral transport.

14.
Microb Biotechnol ; 16(4): 799-812, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36528874

RESUMO

Hypertension is a significant risk factor of cardiovascular diseases (CVDs) with high prevalence worldwide, the current treatment has multiple adverse effects and requires continuous administration. The glucagon-like peptide-1 receptor (GLP-1R) agonists have shown great potential in treating diabetes mellitus, neurodegenerative diseases, obesity and hypertension. Butyric acid is a potential target in treating hypertension. Yet, the application of GLP-1 analogue and butyric acid in reducing blood pressure and reversing ventricular hypertrophy remains untapped. In this study, we combined the therapeutic capability of GLP-1 and butyric acid by transforming Clostridium butyricum (CB) with recombinant plasmid pMTL007 encoded with hGLP gene to construct the engineered probiotics Clostridium butyricum-pMTL007-GLP-1 (CB-GLP-1). We used spontaneous hypertensive rat (SHR) models to evaluate the positive effect of this strain in treating hypertension. The results revealed that the intragastric administration of CB-GLP-1 had markedly reduced blood pressure and improved cardiac marker ACE2, AT2R, AT1R, ANP, BNP, ß-MHC, α-SMA and activating AMPK/mTOR/p70S6K/4EBP1 signalling pathway. The high-throughput sequencing further demonstrated that CB-GLP-1 treatments significantly improved the dysbiosis in the SHR rats via downregulating the relative abundance of Porphyromonadaceae at the family level and upregulating Lactobacillus at the genus level. Hence, we concluded that the CB-GLP-1 greatly improves blood pressure and cardiomegaly by restoring the gut microbiome and reducing ventricular hypertrophy in rat models. This is the first time using engineered CB in treating hypertension, which provides a new idea for the clinical treatment of hypertension.


Assuntos
Clostridium butyricum , Microbioma Gastrointestinal , Hipertensão , Probióticos , Ratos , Animais , Pressão Sanguínea/fisiologia , Peptídeo 1 Semelhante ao Glucagon/genética , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Ratos Endogâmicos SHR , Microbioma Gastrointestinal/fisiologia , Clostridium butyricum/metabolismo , Ácido Butírico/farmacologia , Hipertensão/terapia , Hipertrofia
15.
Chemphyschem ; 24(7): e202200701, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-36454657

RESUMO

Thorium oxide has many important applications in industry. In this article, theoretical calculations have been carried out to explore the hydrolysis reactions of the ThOn (n=1-3) clusters. The reaction mechanisms of the O-deficient ThO and the O-rich ThO3 are compared with the stoichiometric ThO2 . The theoretical results show good agreement with the prior experiments. It is shown that the hydrolysis mainly occurred on the singlet potential surface. The overall reactions consist of two hydrolysis steps which are all favourable in energy. The effects of oxygen content on the hydrolysis are elucidated. Interestingly, among them, the peroxo group O2 2- in ThO3 is converted to the HOO- ligand, behaving like the terminal O2- in the hydrolysis which is transformed into the HO- groups. In addition, natural bond orbital (NBO) analyses were employed to further understand the bonding of the pertinent species and to interpret the differences in hydrolysis.

16.
Pharmaceutics ; 14(12)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36559282

RESUMO

Programmed cell death protein 1/Programmed cell death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors are the most promising treatments for malignant tumors currently, but the low response rate limits their further clinical utilization. To address this problem, our group constructed an engineered strain of VNP20009-Abvec-Igκ-mPD-1 [V-A-mPD-1 (mPD-1, murine PD-1)] to combine oncolytic bacterial therapy with immunotherapy. Further, we evaluated its growth performance and mPD-1 expression ability in vitro while establishing the melanoma mice model to explore its potential anti-cancer effects in tumor therapy. Our results indicated that the V-A-mPD-1 strain has superior growth performance and can invade B16F10 melanoma cells and express PD-1. In addition, in the melanoma mice model, we observed a marked reduction in tumor volume and the formation of a larger necrotic area. V-A-mPD-1 administration resulted in a high expression of mPD-1 at the tumor site, inhibiting tumor cell proliferation via the down-regulation of the expression of rat sarcoma (Ras), phosphorylated mitogen-activated protein kinase (p-MEK)/MEK, and phosphorylated extracellular signal-regulated kinase (p-ERK)/ERK expression significantly inhibited tumor cell proliferation. Tumor cell apoptosis was promoted by down-regulating phosphoinositide 3 kinase (PI3K) and protein kinase B (AKT) signaling pathways, as evidenced by an increased Bcl-2-associated X protein/B cell lymphoma-2 (Bax/Bcl-2) expression ratio. Meanwhile, the expression levels of systemic inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α), were substantially reduced. In conclusion, our research demonstrated that V-A-mPD-1 has an excellent anti-tumor effect, prompting that the combined application of microbial therapy and immunotherapy is a feasible cancer treatment strategy.

17.
Kaohsiung J Med Sci ; 38(10): 981-991, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36053032

RESUMO

Gemcitabine resistance (GR) in pancreatic cancer (PC) results in poor patient outcomes. SMAD family member (Smad4) dysregulation is a significant role of GR in PC, and EZH2 is involved in Smad4 expression in tumor progression. Interestingly, lncRNA small nucleolar RNA host gene 16 (SNHG16) might interact with EZH2, indicating a potential pathway to overcome gemcitabine-resistant PC progression. We investigated the role of the SNHG16/EZH2/Smad4 pathway in gemcitabine-resistant PC cells (PANC-1/GR and SW1990/GR). First, we found that SNHG16 was upregulated both in wild-type PC cells and in gemcitabine-resistant PC cells. SNHG16 overexpression reduced gemcitabine cytotoxicity and apoptosis in PC cells. Meanwhile, SNHG16 upregulation caused p-Akt elevation and Smad4 reduction. However, SNHG16 silencing induced the opposite trend. Then, we found that EZH2 was enriched in SNHG16 based on RIP and RNA pulldown. In particular, SNHG16 overexpression promoted the interaction between EZH2 and the Smad4 promoter according to Chromatin immunoprecipitation-quantitative polymerase chain reaction. Finally, both EZH2 inhibition and Smad4 upregulation increased gemcitabine cytotoxicity and apoptosis in PC cells during SNHG16 overexpression. Moreover, both treatments decreased p-Akt and increased Smad4. Collectively, lncRNA SNHG16 decreased Smad4 to induce GR in PC via EZH2-mediated epigenetic modification.


Assuntos
MicroRNAs , Neoplasias Pancreáticas , RNA Longo não Codificante , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Desoxicitidina/análogos & derivados , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Epigênese Genética , Humanos , MicroRNAs/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Nucleolar Pequeno , Proteína Smad4/genética , Proteína Smad4/metabolismo , Gencitabina , Neoplasias Pancreáticas
18.
Proteome Sci ; 20(1): 16, 2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36153524

RESUMO

BACKGROUND: Hypoxia is a risk factor for non-alcoholic fatty liver diseases, leading to permanent imbalance of liver lipid homeostasis and steatohepatitis. However, a detailed understanding of the metabolic genes and pathways involved remains elusive. METHODS: In vivo experiments were designed to analyze body weight and lipid metabolism changes of rats under hypoxia. After this, we combined microarray analysis and gene overexpression experiments to validate the core mechanisms involved in the response to hypoxia. RESULTS: The hypobaric hypoxia treated rats exhibited significantly increased serum triglycerides (TG) (p < 0.05), despite no significant changes in serum alanine aminotransferase (ALT) and blood glucose (BG) were observed. In addition, serum high-density lipoprotein cholesterol (HDL-C) greatly increased after 3 days and then returned to normal level at 30 days. Interestingly, serum low-density lipoprotein cholesterol (LDL-C) showed an opposite pattern. Transcriptome analysis, qRT-PCR, ICC revealed that the genes PPARA, ANGPTL4, CPT-I, ACC and LPL play a crucial role in response to hypobaric hypoxia. IPA pathway analysis further confirmed that PPARA-mediated regulation of ANGPTL4 participated in TG clearance and lipoprotein metabolism. Finally, the PPARA-ANGPTL4 pathway was validated in rats and HL 7702 cells treated with Fenofibrate, a PPARA specific agonist. CONCLUSIONS: Our study showed this pathway plays an important role on lipid metabolism caused by hypobaric hypoxia and the potential target genes associated with oxygen-dependent lipid homeostasis in the liver.

19.
Ann Transl Med ; 10(14): 781, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35965826

RESUMO

Background: Existing scoring systems have limitations in predicting the in-hospital mortality of adult sepsis patients. We aimed to develop and validate a novel risk score for predicting the in-hospital mortality of adult sepsis patients. Methods: The clinical data of 1,335 adult sepsis inpatients were retrospectively analyzed. Enrolled patients were randomly divided into a modeling group and a validation group at a 3:2 ratio. The modeling group (n=801) was used to develop the risk score by univariate and multivariate logistic regression analyses. The score's performance was validated in the validation group (n=534). We classified patients into four risk levels according to the novel risk score. Results: Age, central vein catheterization, mechanical ventilation, vasopressin, Charlson comorbidity index (CCI), respiratory rate (RR), heart rate (HR), Glasgow coma scale (GCS) score, platelet (PLT), hematocrit (HCT), aspartate aminotransferase (AST), and activated partial thrombin time (APTT) were independent risk factors for in-hospital death in adult sepsis patients. Continuous variables were converted into classified variables to develop the risk score, with a total score of 39 points. Adult sepsis patients with low, lower medium, higher medium, and high risk levels had in-hospital mortality rates of 9.8%, 24.7%, 55.8%, and 83.5%, respectively. Conclusions: Compared with the Acute Physiology and Chronic Health Evaluation II scoring system (APACHE II) and the Modified Early Warning Score (MEWS), the novel risk score showed good predictive performance for in-hospital mortality in adult sepsis patients.

20.
Phys Rev Lett ; 129(4): 043602, 2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35939028

RESUMO

In periodic systems, nodal lines are loops in the three-dimensional momentum space with each point on them representing a band degeneracy. Nodal lines exhibit rich topological features, as they can take various configurations such as rings, links, chains, and knots. These line nodes are generally protected by mirror or PT symmetry and frequently accompanied by drumhead surface states. Here, we propose and demonstrate a novel type of photonic straight nodal lines in a D_{2D} metacrystal, which are protected by an unusual rotoinversion time (roto-PT) symmetry. These nodal lines are located at the central axis and hinges of the Brillouin zone. They appear as quadrupole sources of Berry curvature flux in contrast to the Weyl points, which are monopoles. Interestingly, topological surface states exist at all three cutting surfaces, as guaranteed by π-quantized Zak phases along all three directions. As frequency changes, the surface state equifrequency contours evolve from closed to open and become straight lines at a critical transition frequency, at which diffractionless surface wave propagations are experimentally demonstrated, paving the way toward development of superimaging topological devices.

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