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1.
Immunity ; 57(5): 1087-1104.e7, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38640930

RESUMO

Macrophages are critical to turn noninflamed "cold tumors" into inflamed "hot tumors". Emerging evidence indicates abnormal cholesterol metabolites in the tumor microenvironment (TME) with unclear function. Here, we uncovered the inducible expression of cholesterol-25-hydroxylase (Ch25h) by interleukin-4 (IL-4) and interleukin-13 (IL-13) via the transcription factor STAT6, causing 25-hydroxycholesterol (25HC) accumulation. scRNA-seq analysis confirmed that CH25Hhi subsets were enriched in immunosuppressive macrophage subsets and correlated to lower survival rates in pan-cancers. Targeting CH25H abrogated macrophage immunosuppressive function to enhance infiltrating T cell numbers and activation, which synergized with anti-PD-1 to improve anti-tumor efficacy. Mechanically, lysosome-accumulated 25HC competed with cholesterol for GPR155 binding to inhibit the kinase mTORC1, leading to AMPKα activation and metabolic reprogramming. AMPKα also phosphorylated STAT6 Ser564 to enhance STAT6 activation and ARG1 production. Together, we propose CH25H as an immunometabolic checkpoint, which manipulates macrophage fate to reshape CD8+ T cell surveillance and anti-tumor response.


Assuntos
Hidroxicolesteróis , Lisossomos , Macrófagos , Microambiente Tumoral , Animais , Hidroxicolesteróis/metabolismo , Camundongos , Macrófagos/imunologia , Macrófagos/metabolismo , Humanos , Lisossomos/metabolismo , Microambiente Tumoral/imunologia , Fator de Transcrição STAT6/metabolismo , Adenilato Quinase/metabolismo , Camundongos Endogâmicos C57BL , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Transdução de Sinais , Reprogramação Metabólica
2.
Nature ; 615(7954): 823-829, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36991190

RESUMO

Neural networks based on memristive devices1-3 have the ability to improve throughput and energy efficiency for machine learning4,5 and artificial intelligence6, especially in edge applications7-21. Because training a neural network model from scratch is costly in terms of hardware resources, time and energy, it is impractical to do it individually on billions of memristive neural networks distributed at the edge. A practical approach would be to download the synaptic weights obtained from the cloud training and program them directly into memristors for the commercialization of edge applications. Some post-tuning in memristor conductance could be done afterwards or during applications to adapt to specific situations. Therefore, in neural network applications, memristors require high-precision programmability to guarantee uniform and accurate performance across a large number of memristive networks22-28. This requires many distinguishable conductance levels on each memristive device, not only laboratory-made devices but also devices fabricated in factories. Analog memristors with many conductance states also benefit other applications, such as neural network training, scientific computing and even 'mortal computing'25,29,30. Here we report 2,048 conductance levels achieved with memristors in fully integrated chips with 256 × 256 memristor arrays monolithically integrated on complementary metal-oxide-semiconductor (CMOS) circuits in a commercial foundry. We have identified the underlying physics that previously limited the number of conductance levels that could be achieved in memristors and developed electrical operation protocols to avoid such limitations. These results provide insights into the fundamental understanding of the microscopic picture of memristive switching as well as approaches to enable high-precision memristors for various applications. Fig. 1 HIGH-PRECISION MEMRISTOR FOR NEUROMORPHIC COMPUTING.: a, Proposed scheme of the large-scale application of memristive neural networks for edge computing. Neural network training is performed in the cloud. The obtained weights are downloaded and accurately programmed into a massive number of memristor arrays distributed at the edge, which imposes high-precision requirements on memristive devices. b, An eight-inch wafer with memristors fabricated by a commercial semiconductor manufacturer. c, High-resolution transmission electron microscopy image of the cross-section view of a memristor. Pt and Ta serve as the bottom electrode (BE) and top electrode (TE), respectively. Scale bars, 1 µm and 100 nm (inset). d, Magnification of the memristor material stack. Scale bar, 5 nm. e, As-programmed (blue) and after-denoising (red) currents of a memristor are read by a constant voltage (0.2 V). The denoising process eliminated the large-amplitude RTN observed in the as-programmed state (see Methods). f, Magnification of three nearest-neighbour states after denoising. The current of each state was read by a constant voltage (0.2 V). No large-amplitude RTN was observed, and all of the states can be clearly distinguished. g, An individual memristor on the chip was tuned into 2,048 resistance levels by high-resolution off-chip driving circuitry, and each resistance level was read by a d.c. voltage sweeping from 0 to 0.2 V. The target resistance was set from 50 µS to 4,144 µS with a 2-µS interval between neighbouring levels. All readings at 0.2 V are less than 1 µS from the target conductance. Bottom inset, magnification of the resistance levels. Top inset, experimental results of an entire 256 × 256 array programmed by its 6-bit on-chip circuitry into 64 32 × 32 blocks, and each block is programmed into one of the 64 conductance levels. Each of the 256 × 256 memristors has been previously switched over one million cycles, demonstrating the high endurance and robustness of the devices.

3.
Semin Cancer Biol ; 95: 75-87, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37499847

RESUMO

Radiomics is the extraction of predefined mathematic features from medical images for predicting variables of clinical interest. Recent research has demonstrated that radiomics can be processed by artificial intelligence algorithms to reveal complex patterns and trends for diagnosis, and prediction of prognosis and response to treatment modalities in various types of cancer. Artificial intelligence tools can utilize radiological images to solve next-generation issues in clinical decision making. Bone tumors can be classified as primary and secondary (metastatic) tumors. Osteosarcoma, Ewing sarcoma, and chondrosarcoma are the dominating primary tumors of bone. The development of bone tumor model systems and relevant research, and the assessment of novel treatment methods are ongoing to improve clinical outcomes, notably for patients with metastases. Artificial intelligence and radiomics have been utilized in almost full spectrum of clinical care of bone tumors. Radiomics models have achieved excellent performance in the diagnosis and grading of bone tumors. Furthermore, the models enable to predict overall survival, metastases, and recurrence. Radiomics features have exhibited promise in assisting therapeutic planning and evaluation, especially neoadjuvant chemotherapy. This review provides an overview of the evolution and opportunities for artificial intelligence in imaging, with a focus on hand-crafted features and deep learning-based radiomics approaches. We summarize the current application of artificial intelligence-based radiomics both in primary and metastatic bone tumors, and discuss the limitations and future opportunities of artificial intelligence-based radiomics in this field. In the era of personalized medicine, our in-depth understanding of emerging artificial intelligence-based radiomics approaches will bring innovative solutions to bone tumors and achieve clinical application.


Assuntos
Inteligência Artificial , Neoplasias Ósseas , Humanos , Diagnóstico por Imagem , Prognóstico , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/terapia
4.
J Am Chem Soc ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869376

RESUMO

Photothermal hydrogenation of carbon dioxide (CO2) into value-added products is an ideal solution for addressing the energy crisis and mitigating CO2 emissions. However, achieving high product selectivity remains challenging due to the simultaneous occurrence of numerous competing intermediate reactions during CO2 hydrogenation. We present a novel approach featuring isolated single-atom nickel (Ni) anchored onto indium oxide (In2O3) nanocrystals, serving as an effective photothermal catalyst for CO2 hydrogenation into methane (CH4) with a remarkable near-unity (∼99%) selectivity. Experiments and theoretical simulations have confirmed that isolated Ni sites on the In2O3 surface can effectively stabilize the intermediate products of the CO2 hydrogenation reaction and reduce the transition state energy barrier, thereby changing the reaction path to achieve ultrahigh selective methanation. This study provides comprehensive insights into the design of single-atom catalysts for the highly selective photothermal catalytic hydrogenation of CO2 to methane.

5.
Appl Environ Microbiol ; 90(4): e0015724, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38477530

RESUMO

Per- and polyfluoroalkyl substances (PFAS) are highly fluorinated synthetic organic compounds that have been used extensively in various industries owing to their unique properties. The PFAS family encompasses diverse classes, with only a fraction being commercially relevant. These substances are found in the environment, including in water sources, soil, and wildlife, leading to human exposure and fueling concerns about potential human health impacts. Although PFAS degradation is challenging, biodegradation offers a promising, eco-friendly solution. Biodegradation has been effective for a variety of organic contaminants but is yet to be successful for PFAS due to a paucity of identified microbial species capable of transforming these compounds. Recent studies have investigated PFAS biotransformation and fluoride release; however, the number of specific microorganisms and enzymes with demonstrable activity with PFAS remains limited. This review discusses enzymes that could be used in PFAS metabolism, including haloacid dehalogenases, reductive dehalogenases, cytochromes P450, alkane and butane monooxygenases, peroxidases, laccases, desulfonases, and the mechanisms of microbial resistance to intracellular fluoride. Finally, we emphasize the potential of enzyme and microbial engineering to advance PFAS degradation strategies and provide insights for future research in this field.


Assuntos
Fluorocarbonos , Poluentes Químicos da Água , Humanos , Animais , Fluoretos , Alcanos , Animais Selvagens , Biodegradação Ambiental
6.
Opt Express ; 32(9): 16307-16318, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38859261

RESUMO

Aiming at the difficulty of traditional chaotic-shift-keying (CSK) systems in resisting return map attacks, we propose an optical chaotic communication system based on time-delayed shift keying and common-signal-induced synchronization. This scheme combines amplified spontaneous emission (ASE) noise, phase modulator (PM), and fiber Bragg grating (FBG) to achieve dual masking in both intensity and phase fields, achieving 10Gb/s information transmission. A common-signal-induced method is used to achieve the synchronization of the system. Moreover, by shifting the time delay as the message-feeding method, the return map attack is effectively resisted, to prevent the amplitude and frequency information of the chaotic attractor from being exposed. In terms of confidentiality and communication performance, this scheme demonstrates good performance of time delay signatures (TDSs) concealment and long-distance transmission capability. In addition, this scheme maintains high sensitivity to key parameters and achieves better confidentiality while increasing the key space.

7.
Arch Insect Biochem Physiol ; 115(1): e22079, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38288491

RESUMO

HSP90 is a highly conserved chaperone that facilitates the proliferation of many viruses, including silkworm (bombyx mori) nucleopolyhedrovirus (BmNPV), but the underlying regulatory mechanism was unclear. We found that suppression of HSP90 by 17-AAG, a HSP90-specific inhibitor, significantly reduced the expression of BmNPV capsid protein gp64 and viral genome replication, whereas overexpression of B. mori HSP90(BmHSP90) promoted BmNPV replication. Furthermore, in a recent study of the lysine acetylome of B. mori infected with BmNPV, we focused on the reduced viral proliferation due to changes of BmHSP90 lysine acetylation. Site-directed introduction of acetylated (K/Q) or deacetylated (K/R) mimic mutations into BmHSP90 revealed that lysine 64 (K64) acetylation activated the JAK/STAT pathway and reduced BmHSP90 ATPase activity, leading to diminished chaperone activity and ultimately inhibiting BmNPV proliferation. In this study, a single lysine 64 acetylation change of BmHSP90 was elucidated as a model of posttranslational modifications occurring in the wake of host-virus interactions, providing novel insights into potential antiviral strategies.


Assuntos
Bombyx , Nucleopoliedrovírus , Animais , Bombyx/genética , Nucleopoliedrovírus/genética , Acetilação , Lisina , Janus Quinases/metabolismo , Proteínas de Insetos/metabolismo , Transdução de Sinais , Fatores de Transcrição STAT/metabolismo , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo
8.
Photochem Photobiol Sci ; 22(3): 631-640, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36436206

RESUMO

This work describes two new colorimetric methods for smartphone-based point-of-care nanosensing of toxic Ag+ ions. They were based on the analyte-triggered in situ "off-on" of Tyndall effect (TE) of non-plasmonic colloid or plasmonic metal nanoprobes. The first TE-inspired assay (TEA) focused on the initial analytical application of precipitation reactions where a non-plasmonic AgCl colloid could be formed once mixing the analyte with a NaCl solution. Such AgCl colloid displayed strong visual TE signals after their irradiation by a laser pointer pen, which unexpectedly achieved a detection limit of ~ 400 nM. The second TEA was further designed to reduce the limit down to ~ 78 nM using the analyte's oxidizability towards 3,3',5,5'-tetramethylbenzidine molecules. The redox reaction could create positively charged products that could make negatively charged plasmonic gold nanoparticles aggregate through electrostatic interactions to remarkably amplify their TE responses. Both limits were lower than the minimum allowable Ag+ level (~ 460 nM) in drinking water issued by the World Health Organization. The satisfactory recovery results for detecting Ag+ ions in river, pond, tap, and drinking water additionally demonstrated good selectivity, accuracy and practicality of the proposed methods for potential point-of-need uses in environmental analysis, public health, water safety, etc.

9.
Environ Sci Technol ; 57(38): 14226-14236, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37713595

RESUMO

Vertical distribution of phytoplankton is crucial for assessing the trophic status and primary production in inland waters. However, there is sparse information about phytoplankton vertical distribution due to the lack of sufficient measurements. Here, we report, to the best of our knowledge, the first Mie-fluorescence-Raman lidar (MFRL) measurements of continuous chlorophyll a (Chl-a) profiles as well as their parametrization in inland water. The lidar-measured Chl-a during several experiments showed good agreement with the in situ data. A case study verified that MFRL had the potential to profile the Chl-a concentration. The results revealed that the maintenance of subsurface chlorophyll maxima (SCM) was influenced by light and nutrient inputs. Furthermore, inspired by the observations from MFRL, an SCM model built upon surface Chl-a concentration and euphotic layer depth was proposed with root mean square relative difference of 16.5% compared to MFRL observations, providing the possibility to map 3D Chl-a distribution in aquatic ecosystems by integrated active-passive remote sensing technology. Profiling and modeling Chl-a concentration with MFRL are expected to be of paramount importance for monitoring inland water ecosystems and environments.


Assuntos
Clorofila , Ecossistema , Clorofila A , Fluorescência , Fitoplâncton , Água
10.
Thromb J ; 21(1): 9, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36691024

RESUMO

BACKGROUND: Portal vein thrombosis is a common complication of liver cirrhosis and hepatocellular carcinoma; however, few studies have reported its long-term clinical prognosis. This study aimed to establish and validate easy-to-use nomograms for predicting gastrointestinal bleeding, portal vein thrombosis resolution, and mortality of patients with portal vein thrombosis. METHODS: This multicenter retrospective cohort study included 425 patients with portal vein thrombosis who were divided into training (n = 334) and validation (n = 91) sets. Prediction models were developed using multivariate Cox regression analysis and evaluated using the consistency index and calibration plots. RESULTS: Predictors of gastrointestinal bleeding included a history of gastrointestinal bleeding, superior mesenteric vein thrombosis, red color sign observed during endoscopy, and hepatic encephalopathy. Meanwhile, predictors of resolution of portal vein thrombosis included a history of abdominal infection, C-reactive protein and hemoglobin levels, and intake of thrombolytics. Predictors of death included abdominal infection, abdominal surgery, aspartate aminotransferase level, hepatic encephalopathy, and ascites. All models had good discriminatory power and consistency. Anticoagulation therapy significantly increased the probability of thrombotic resolution without increasing the risk of bleeding or death. CONCLUSIONS: We successfully developed and validated three prediction models that can aid in the early evaluation and treatment of portal vein thrombosis.

11.
Anal Bioanal Chem ; 415(10): 1889-1896, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36820910

RESUMO

Thiophenes and sulfides are the dominant sulfur-containing compounds in petroleum and have been widely of concern in the fields of petroleum refining and geochemistry. In this study, a novel approach was developed for selective separation and characterization of petroleum-derived thiophenic and sulfide compounds. Thiophenic compounds were selectively converted to sulfonates in the presence of vitriolic acid and can be characterized by negative ion electrospray mass spectrometry. Thiophenic sulfonates were further separated from the oil by silica chromatography and enabled the molecular characterization of sulfides in the residual oil. Various model sulfur compounds and a vacuum gas oil were used to validate the method; thiophenic and sulfide biomarker compounds in a well-documented crude oil were selectively characterized. The results indicate that the approach is feasible for molecular characterization of thiophenic and sulfide compounds, which is complementary to recently developed methods for separation and/or ionization of sulfur compounds in petroleum.

12.
Environ Res ; 237(Pt 1): 116857, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37579963

RESUMO

Against the backdrop of global warming, rapid urbanization has caused the aggregation of urban building spaces and the heat island effect is becoming increasingly serious, hindering sustainable urban development. In order to investigate the potential and methods of green roofs in different types of neighborhoods to mitigate the urban heat island effect, this study used multivariate data for surface temperature inversion and local climate zone (LCZ), and the potential of green roofs to reduce the heat island effect was evaluated by combining LCZ zoning and ENVI-met prediction model. Finally, a multi-scenario analysis with economic factors was conducted to derive the optimal implementation path for green roofs. The results show that in LCZs 1-9, the green roof can reduce the daytime average air temperature by a maximum of 0.41 °C for 0.5 m of the LCZ8 roof and 0.37 °C for 1.2 m of the LCZ6 pedestrian. Based on the surface cooling efficiency of LCZ green roofs get the best green roof construction order: LCZ3, LCZ6, LCZ8 > LCZ2, LCZ5, LCZ7 > LCZ1, LCZ4, LCZ9. The construction of green roofs for the heat island areas within the fifth ring road of Beijing can reduce the area of high-temperature and sub-high-temperature zones by 52.55% and 29.17%, respectively, compared with the area without green roof construction. The study clarifies the technical methodology system of cooling efficiency of green roofs in different types of neighborhoods and the reduction of the urban-scale heat island effect, which provides a reference for the planning of green roofs for urban buildings.

13.
Biochem Genet ; 2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37950843

RESUMO

DNA methylation plays a critical role in the modulation of gene expression. The role of DNA methylation in sex determination was investigated in spinach. The differentiated cytosine CpG methylation profiles of CCGG motifs were assessed with methylation sensitivity amplification polymorphism (MSAP) in spinach. Among 442 DNA fragments from four plants, 134 methylated fragments were found. Relative proportions of methylation sites were 28.8% in male plants and 31.8% in female plants. At the same time, cytosine methylation levels were higher in females than in males in CCGG motifs of genomes in the spinach. These findings suggest that methylation of CG islands is involved in sex determination and differentiation in spinach.

14.
Molecules ; 28(8)2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37110816

RESUMO

Procyanidins (PCs), which are organic antioxidants, suppress oxidative stress, exhibit anti-apoptotic properties, and chelate metal ions. The potential defense mechanism of PCs against cerebral ischemia/reperfusion injury (CIRI) was investigated in this study. Pre-administration for 7 days of a PC enhanced nerve function and decreased cerebellar infarct volume in a mouse middle cerebral artery embolization paradigm. In addition, mitochondrial ferroptosis was enhanced, exhibited by mitochondrial shrinkage and roundness, increased membrane density, and reduced or absent ridges. The level of Fe2+ and lipid peroxidation that cause ferroptosis was significantly reduced by PC administration. According to the Western blot findings, PCs altered the expression of proteins associated with ferroptosis, promoting the expression of GPX4 and SLC7A11 while reducing the expression of TFR1, hence inhibiting ferroptosis. Moreover, the treatment of PCs markedly elevated the expression of HO-1 and Nuclear-Nrf2. The PCs' ability to prevent ferroptosis due to CIRI was decreased by the Nrf2 inhibitor ML385. Our findings showed that the protective effect of PCs may be achieved via activation of the Nrf2/HO-1 pathway and inhibiting ferroptosis. This study provides a new perspective on the treatment of CIRI with PCs.


Assuntos
Isquemia Encefálica , Ferroptose , Proantocianidinas , Traumatismo por Reperfusão , Animais , Camundongos , Proantocianidinas/farmacologia , Fator 2 Relacionado a NF-E2 , Transdução de Sinais , Traumatismo por Reperfusão/tratamento farmacológico
15.
Sheng Li Xue Bao ; 75(6): 946-952, 2023 Dec 25.
Artigo em Zh | MEDLINE | ID: mdl-38151356

RESUMO

Our previous study has shown that p66Shc plays an important role in the process of myocardial regeneration in newborn mice, and p66Shc deficiency leads to weakened myocardial regeneration in newborn mice. This study aims to explore the role of p66Shc protein in myocardial injury repair after myocardial infarction in adult mice, in order to provide a new target for the treatment of myocardial injury after myocardial infarction. Mouse myocardial infarction models of adult wild-type (WT) and p66Shc knockout (KO) were constructed by anterior descending branch ligation. The survival rate and heart-to-body weight ratio of two models were compared and analyzed. Masson's staining was used to identify scar area of injured myocardial tissue, and myocyte area was determined by wheat germ agglutinin (WGA) staining. TUNEL staining was used to detect the cardiomyocyte apoptosis. The protein expression of brain natriuretic peptide (BNP), a common marker of myocardial hypertrophy, was detected by Western blotting. The results showed that there was no significant difference in survival rate, myocardial scar area, myocyte apoptosis, and heart weight to body weight ratio between the WT and p66ShcKO mice after myocardial infarction surgery. Whereas the protein expression level of BNP in the p66ShcKO mice was significantly down-regulated compared with that in the WT mice. These results suggest that, unlike in neonatal mice, the deletion of p66Shc has no significant effect on myocardial injury repair after myocardial infarction in adult mice.


Assuntos
Infarto do Miocárdio , Estresse Oxidativo , Animais , Camundongos , Peso Corporal , Cicatriz/metabolismo , Camundongos Knockout , Infarto do Miocárdio/genética , Proteínas Adaptadoras da Sinalização Shc/metabolismo , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/genética , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/metabolismo
16.
Angew Chem Int Ed Engl ; 62(49): e202315108, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37860947

RESUMO

Nitrogen heterocycles play a vital role in pharmaceuticals and natural products, with the six-membered aromatic and aliphatic architectures being commonly used. While synthetic methods for aromatic N-heterocycles are well-established, the synthesis of their aliphatic functionalized analogues, particularly piperidine derivatives, poses a significant challenge. In that regard, we propose a stepwise dearomative functionalization reaction for the construction of highly decorated piperidine derivatives with diverse functional handles. We also discuss challenges related to site-selectivity, regio- and diastereoselectivity, and provide insights into the reaction mechanism through mechanistic studies and density functional theory computations.

17.
Microb Pathog ; 173(Pt B): 105890, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36410583

RESUMO

Many studies have confirmed that virus infection cause changes in the expression level and post-translational modifications of tricarboxylic acid cycle (TCA) enzymes. In a previous study, we found that the acetylation level of lysine 336 of Bombyx mori citrate synthase (BmCS) was remarkably unregulated after Bombyx mori nucleopolyhedrovirus (BmNPV) infection. In the present study, we found that BmN cells infected with BmNPV could up-regulate BmCS transient expression and promote the acetylation modification of BmCS. Transient expression vectors for over-expression of wild-type Bmcs and K336 acetylation mimic mutant (K336Q) were constructed to analyze enzyme activity, revealing that acetylation of K336 significantly reduced its activity. The obtained results indicated that BmCS knock-down or K336 acetylation similarly suppressed BmN cellular ATP production and mitochondrial membrane potential. Furthermore, the acetylation of K336 and the reduction of BmCS expression contributed to weakening the replication lever of the BmNPV proliferation and the generation of progeny viruses. In sum, our study on the single lysine 336 acetylation and knock-down of Bmcs revealed the potential mechanism for inhibiting the proliferation of BmNPV, which may provide novel insights for the development of antiviral strategies.


Assuntos
Bombyx , Lisina , Animais , Acetilação , Citrato (si)-Sintase/genética , Metabolismo Energético , Processamento de Proteína Pós-Traducional
18.
BMC Cancer ; 22(1): 122, 2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35093005

RESUMO

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) is increasing at an alarming rate and further studies are needed to identify risk factors and to develop prevention strategies. METHODS: Risk factors significantly associated with EOCRC were identified using meta-analysis. An individual risk appraisal model was constructed using the Rothman-Keller model. Next, a group of random data sets was generated using the binomial distribution function method, to determine nodes of risk assessment levels and to identify low, medium, and high risk populations. RESULTS: A total of 32,843 EOCRC patients were identified in this study, and nine significant risk factors were identified using meta-analysis, including male sex, Caucasian ethnicity, sedentary lifestyle, inflammatory bowel disease, and high intake of red meat and processed meat. After simulating the risk assessment data of 10,000 subjects, scores of 0 to 0.0018, 0.0018 to 0.0036, and 0.0036 or more were respectively considered as low-, moderate-, and high-risk populations for the EOCRC population based on risk trends from the Rothman-Keller model. CONCLUSION: This model can be used for screening of young adults to predict high risk of EOCRC and will contribute to the primary prevention strategies and the reduction of risk of developing EOCRC.


Assuntos
Regras de Decisão Clínica , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Detecção Precoce de Câncer/métodos , Medição de Risco/métodos , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
19.
Pharmacol Res ; 186: 106512, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36272639

RESUMO

As a high mortality gynecological malignancy, most ovarian cancer patients experience refractory to standard chemotherapy, current immunotherapy or chemoimmunotherapy in clinic and clinical trials. The underlying mechanisms and biomarkers predictive of response for patient selection is quite urgent. In this study, we found that the level of tumor-expressed B7-H3 is positively correlated with the poorer prognosis in ovarian cancer patients. Therapeutically, in syngeneic mouse model of ovarian cancer, deficiency of tumor-expressed B7-H3 significantly potentiates the anti-tumor efficacy of paclitaxel or PD-L1 blockade monotherapy. However, combination of paclitaxel plus anti-PD-L1 has no synergistic effects than PD-L1 blockade monotherapy. Mechanistically, deficiency of tumor-expressed B7-H3 attenuates inflammatory cytokine IL-6 production, upregulates type I interferon (IFN) expression and increases paclitaxel-induced tumor cells apoptosis via caspase 3 activation pathway, resulting in reprogramming the tumor microenvironment including increasing the infiltration of effector T lymphocytes and decreasing the recruitment of Ly6G+CD11b+ myeloid-derived suppressor cells (MDSCs) in vivo. Collectively, these results demonstrate that deficiency of tumor-expressed B7-H3 enhances the anti-tumor efficacy of paclitaxel or PD-L1 blockade monotherapy rather than their combined chemoimmunotherapy in ovarian cancer, suggesting that B7-H3 may be a potential predictive biomarker for beneficial patient stratification and a candidate therapeutic target in ovarian cancer.


Assuntos
Antígenos B7 , Neoplasias Ovarianas , Humanos , Camundongos , Feminino , Animais , Antígenos B7/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Imunoterapia , Microambiente Tumoral , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico
20.
Acta Neurochir (Wien) ; 164(7): 1837-1844, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35347450

RESUMO

BACKGROUND: Moyamoya disease (MMD) is a chronic progressive cerebrovascular disease mainly existing in the Asian population, which can be divided into unilateral and bilateral types. Contralateral progression has been reported in pediatric patients with unilateral MMD, while large series about contralateral progression in Chinese adult patients were rare. The goal of this study is to elucidate the clinical features and incidence of contralateral progression in Chinese MMD adult patients. METHODS: One hundred one Chinese adult patients with unilateral MMD who received surgery treatments between January 2015 and January 2017 in our hospital were enrolled in this study. This study contained 89 patients. Digital subtraction angiography was performed in all patients for initial diagnosis, and magnetic resonance angiography was repeated 6 months from the initial operation and then annually. Clinical characteristics, contralateral progression, and risk factors were studied. Previous related studies were also reviewed and meta-analyzed. RESULTS: Of these 89 patients, contralateral progression was identified in 8 patients (9.0%) within a median follow-up period of 63 months, which was lower than that in previous studies (25.9%). Single-factor analysis and multivariate analysis did not reveal significant risk factors related to the contralateral progression. CONCLUSION: The progress rate in this cohort of Chinese adult patients with unilateral MMD after revascularization was 9.0%, which indicates that some of the unilateral MMD were an early form of bilateral MMD rather than a separate condition. TRIAL REGISTRATION: This work was approved by the Medical Ethics Committee of Zhongnan Hospital of Wuhan University (approval number: Kelun-2017005).


Assuntos
Revascularização Cerebral , Doença de Moyamoya , Adulto , Criança , China/epidemiologia , Progressão da Doença , Humanos , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/cirurgia , Estudos Retrospectivos
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