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1.
Bioact Mater ; 43: 48-66, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39318638

RESUMO

Excessive inflammation caused by bacterial infection is the primary cause of implant failure. Antibiotic treatment often fails to prevent peri-implant infection and may induce unexpected drug resistance. Herein, a non-antibiotic strategy based on the synergy of silver ion release and macrophage reprogramming is proposed for preventing infection and bacteria-induced inflammation suppression by the organic-inorganic hybridization of silver nanoparticle (AgNP) and quercetin (Que) into a polydopamine (PDA)-based coating on the 3D framework of porous titanium (SQPdFT). Once the planktonic bacteria (e.g., Escherichia coli, Staphylococcus aureus) reach the surface of SQPdFT, released Que disrupts the bacterial membrane. Then, AgNP can penetrate the invading bacterium and kill them, which further inhibits the biofilm formation. Simultaneously, released Que can regulate macrophage polarization homeostasis via the peroxisome proliferators-activated receptors gamma (PPARγ)-mediated nuclear factor kappa-B (NF-κB) pathway, thereby terminating excessive inflammatory responses. These advantages facilitate the adhesion and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), concomitantly suppressing osteoclast maturation, and eventually conferring superior mechanical stability to SQPdFT within the medullary cavity. In summary, owing to its excellent antibacterial effect, immune remodeling function, and pro-osteointegration ability, SQPdFT is a promising protective coating for titanium-based implants used in orthopedic replacement surgery.

2.
Food Chem ; 462: 140704, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-39226642

RESUMO

Clove (Syzygium aromaticum) is one of the most commonly used spices in stewed beef to enrich and improve its aroma during the stewing process. Gas chromatography ion mobility spectroscopy (GC-IMS), Q Exactive GC-Orbitrap-MS-O (QE-GC-MS/O), combined with sensory evaluation were employed to analyze the flavor endowment of aroma-active compounds in cloves to stewed beef. A total of 173 volatiles were identified in the clove powder (CP), stewed beef with clove (SBC), and stewed beef with salt (SBS), of which 21 volatiles were considered as aroma-active compounds. The concept of flavor endowment of aroma-active compounds in cloves was defined innovatively, and the endowment rate values (ERVs) of stewed beef were calculated. Nine aroma-active compounds in cloves were found to have a flavor endowment effect on stewed beef, while the terpenoids exhibited high ERVs. Despite the low ERV of eugenol, it still significantly impacted the aroma profile of SBC due to its high odor activity value (OAV) and flavor dilution (FD) factor. These volatiles offered mainly the clove, herbal, anise, and floral odor to stewed beef, which was also confirmed by sensory evaluation. These findings indicated that the terpenoids, phenolics and ethers in cloves had a significant influence on the overall aroma of stewed beef through the flavor endowment, which contributed to the precise use of cloves and improved the aroma of stewed beef.


Assuntos
Aromatizantes , Cromatografia Gasosa-Espectrometria de Massas , Odorantes , Syzygium , Paladar , Compostos Orgânicos Voláteis , Syzygium/química , Bovinos , Compostos Orgânicos Voláteis/química , Odorantes/análise , Humanos , Animais , Aromatizantes/química , Adulto , Feminino , Masculino , Especiarias/análise , Culinária , Adulto Jovem , Carne Vermelha/análise
3.
Clin Chim Acta ; 564: 119907, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-39127297

RESUMO

BACKGROUND: Various biomarkers reportedly predict persistent acute kidney injury (AKI) despite their varying predictive performance across clinical trials. This study aims to compare the accuracy of various biomarkers in predicting persistent AKI in different populations and regions. METHODS: In this meta-analysis, we searched for urinary C-C motif chemokine ligand 14 (CCL14), Tissue inhibitor of metalloproteinase-2&insulin-like growth factor-binding protein-7 (TIMP-2&IGFBP7), Neutrophil Gelatinase-Associated Lipocalin (NGAL), plasma Cystatin C (pCysC), Soluble urokinase plasminogen activator receptor (suPAR), Proenkephalin (PenK) and urinary dickkopf-3:urinary creatinine (uDKK3:uCr) from various databases including Medline, PubMed, Embase, and Cochrane. This was geared towards predicting persistent AKI in adults (>18 years). Hierarchically summarized subject work characteristic curves (HSROC) and diagnostic odds ratio (DOR) values were used to summarize the diagnostic accuracy of the biomarkers. Further, meta-regression and subgroup analyses were carried out to identify sources of heterogeneity as well as evaluate the best predictive biomarkers in different populations and regions. RESULTS: We screened 31 studies from 2,356 studies and assessed the diagnostic value of 7 biomarkers for persistent AKI. Overall, CCL14 had the best diagnostic efficacy with an AUC of 0.79 (95 % CI 0.75-0.82), whereas TIMP-2 & IGFBP7, NGAL, and pCysC had diagnostic efficacy of 0.75 (95 % CI 0.71-0.79),0.71 (95 % CI 0.67-0.75), and 0.7007, respectively. Due to a limited number of studies, PenK, uDKK3:uCr, and suPAR were not subjected to meta-analysis; however, relevant literature reported diagnostic efficacy above 0.70. Subgroup analyses based on population, region, biomarker detection time, AKI onset time, and AKI duration revealed that in the intensive care unit (ICU) population, the AUC of CCL14 was 0.8070, the AUC of TIMP-2 & IGFBP7 was 0.726, the AUC of pCysC was 0.72, and the AUC of NGAL was 0.7344; in the sepsis population, the AUC of CCL14 was 0.85, the AUC of TIMP-2&IGFBP7 was 0.7438, and the AUC of NGAL was 0.544; in the post-operative population, the AUC of CCL14 was 0.83-0.93, the AUC of TIMP-2&IGFBP7 was 0.71, and the AUC of pCysC was 0.683. Regional differences were observed in biomarker prediction of persistent kidney injury, with AUCs of 0.8558 for CCL14, 0.7563 for TIMP-2 & IGFBP7, and 0.7116 for NGAL in the Eurasian American population. In the sub-African population, TIMP-2 & IGFBP7 had AUCs of 0.7945, 0.7418 for CCL14, 0.7097 for NGAL, and 0.7007 for pCysC. for TIMP-2 & IGFBP7 was 0.7945, AUC for CCL14 was 0.7418, AUC for NGAL was 0.7097, and AUC for pCysC was 0.7007 in the sub-African population. Duration of biomarker detection, AKI onset, and AKI did not influence the optimal predictive performance of CCL14. Subgroup analysis and meta-regression of CCL14-related studies revealed that CCL14 is the most appropriate biomarker for predicting persistent stage 2-3 AKI, with heterogeneity stemming from sample size and AKI staging. CONCLUSION: This meta-analysis discovered CCL14 as the best biomarker to predict persistent AKI, specifically persistent stage 2-3 AKI.


Assuntos
Injúria Renal Aguda , Biomarcadores , Humanos , Biomarcadores/sangue , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/sangue , Injúria Renal Aguda/urina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue
4.
J Med Chem ; 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39485242

RESUMO

Despite the development of highly effective therapies for the treatment of estrogen receptor α (ERα)-positive human breast cancer, clinical resistance to current therapies requires the development of novel therapeutic strategies. Herein, we report the discovery of ERD-1233 as a potent and orally efficacious ERα degrader designed using the PROTAC technology. ERD-1233 was developed based on Lasofoxifene as the ER binding moiety and a novel cereblon ligand through extensive optimization of the linker. ERD-1233 potently and effectively reduces the ERα protein in vitro and achieves excellent oral bioavailability in mice and rats. Oral administration of ERD-1233 effectively reduces ER protein in ER+ tumors and achieves tumor regression in the ER wild-type MCF-7 xenograft tumor model and strong tumor growth inhibition in the ESR1Y537S mutated model in mice. Our data demonstrate that ERD-1233 is a promising ER PROTAC degrader for extensive evaluation as a new therapy for the treatment of ER+ human breast cancer.

5.
Research (Wash D C) ; 7: 0514, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39434839

RESUMO

Transmissive metasurfaces are essentially conducive to stealth, absorbers, and communications. However, most of the current schemes only allow microwave to transmit and generally adopt multilayer structures or thick dielectric substrates to improve the electromagnetic performance, restricting optical transmission and conformal application. In addition, most metasurfaces still require metal wires and external power suppliers for programmability. Here, we propose and design an intelligent transmissive microwave metasurface with optical sensing and transparency, which provides both microwave and optical channels without redundant optical devices and power suppliers, and the 2 transmission channels are associated with each other. The metasurface is realized by validly integrating photosensitive materials into microwave meta-structures. As a demonstration, we fabricate an ultrathin optically transparent transmissive metasurface based on polyethylene terephthalate substrate and photoresistors, whose thickness is only 0.125 mm. We further construct cross-wavelength transmission links based on the metasurface sample and experimentally validate that the microwave transmissions vary with light intensities under full-polarization and large-angle incidences, and this metasurface possesses high optical transparency. The intelligent transmissive microwave metasurface with optical sensing and transparency has potential applications in optical-microwave hybrid transmission devices and stealth technology.

6.
Int J Biol Sci ; 20(13): 5375-5395, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39430250

RESUMO

Nucleolar and spindle-associated protein 1 (NUSAP1), a microtubule-associated protein, has been recently identified to exhibit aberrant expression patterns that correlate with malignant tumorigenesis and progression across various cancer types. However, the specific regulatory mechanisms and potential targeting therapies of NUSAP1 in lung adenocarcinoma (LUAD) remain largely elusive. In this study, by conducting bioinformatics analyses as well as in vitro and in vivo experiments, we identified that NUSAP1 was significantly upregulated in LUAD, with a notable correlation with poorer overall survival, higher scores for immunogenicity and immune infiltration, as well as increased sensitivity to conventional chemotherapeutic drugs such as paclitaxel, docetaxel and vinorelbine in LUAD. Functionally, NUSAP1 overexpression significantly promoted LUAD cell proliferation, while its knockdown markedly suppressed this process. Interestingly, our results revealed that NUSAP1 upregulation was mediated by estrogen via ERß activation. Furthermore, we identified entinostat as a novel inhibitor of NUSAP1. Pharmacological targeting ERß/NUSAP1 axis with fulvestrant (ERß antagonist) or entinostat (novel NUSAP1 inhibitor) significantly reduced LUAD growth both in vitro and in vivo, which may represent effective alternative therapeutic strategies for patients with LUAD.


Assuntos
Adenocarcinoma de Pulmão , Proliferação de Células , Estrogênios , Neoplasias Pulmonares , Proteínas Associadas aos Microtúbulos , Humanos , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Estrogênios/metabolismo , Animais , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Linhagem Celular Tumoral , Camundongos , Proliferação de Células/efeitos dos fármacos , Regulação para Cima , Camundongos Nus , Feminino , Adenocarcinoma/metabolismo , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/genética , Regulação Neoplásica da Expressão Gênica , Receptor beta de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Camundongos Endogâmicos BALB C
7.
Nano Lett ; 24(42): 13118-13125, 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39365010

RESUMO

Peptide vaccines induce specific neutralizing antibodies and are effective in disease prevention and treatment. However, peptide antigens have a low immunogenicity and are unstable, requiring efficient vaccine carriers to enhance their immunogenicity. Here, we develop a tobacco mosaic virus (TMV)-based peptide vaccine for transdermal immunization using a tip-loaded dissolving microneedle (MN) patch. TMV is decorated with the model peptide antigen PEP3. The prepared TMV-PEP3 promotes dendritic cell maturation and induces dendritic cells to overexpress MHC II, costimulatory factors, and pro-inflammatory factors. By encapsulation of TMV-PEP3 in the tips of a trehalose MN, TMV-PEP3 can be delivered by MN and significantly promote local immune cell infiltration. In vivo studies show that both subcutaneous injection and MN administration of TMV-PEP3 increase the production of anti-PEP3 IgG antibodies and the harvested serum can induce complement-dependent cytotoxicity. This work provides a promising strategy for constructing efficient and health-care-friendly peptide vaccines.


Assuntos
Administração Cutânea , Células Dendríticas , Agulhas , Vírus do Mosaico do Tabaco , Vacinas de Subunidades Antigênicas , Animais , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/administração & dosagem , Camundongos , Vírus do Mosaico do Tabaco/imunologia , Vírus do Mosaico do Tabaco/química , Células Dendríticas/imunologia , Imunização , Peptídeos/química , Peptídeos/imunologia , Vacinas de Subunidades Proteicas
8.
3D Print Addit Manuf ; 11(3): e1394-e1406, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39359609

RESUMO

In recent years, the application of 3D printing technology in the energetic materials field has proved its ability to innovate traditional charging methods and fabricate complex structures to improve combustion/detonation performance. The melt extrusion technology is the most promising way to fabricate complex structures and multiple components of melt-cast explosives. In this study, a paraffine-based composite was used to substitute melt-cast explosives, and a Design of Experiments approach based on central composite design was adopted to investigate the influence of layer thickness, percent infill, extrusion temperature, and printing velocity on the roughness of printed samples. The results showed that layer thickness and printing velocity could significantly influence the roughness of printed specimens, and no obvious voids or cracks inside the specimens can be detected in computed tomography. In addition, a composite-shaped grain was successfully fabricated via the EAM-D-1 printer, which proved the feasibility of 3D printing melt-cast explosives with complex structures. This work will greatly help to achieve 3D printing melt-cast explosives with complex structures and higher accuracy.

10.
J Hazard Mater ; 480: 136068, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39378596

RESUMO

Microplastics (MPs) potentially alter physicochemical and transformation of heavy metals (HMs) in soils, which may depend on the specific characteristics of soil types. However, the dynamical and long-term mechanisms remain to be elucidated. A five-year incubation experiment was conducted to evaluate the influence of MPs on the chemical speciation of Pb, Ni, Cu, Cr, Cd, and As in the meadow, tidal, cinnamon, saline-alkali, and brown soils. From the first year to the fifth year, the clay value of the meadow, tidal, cinnamon, and saline-alkali soils was increased by 31.35 %, 9.63 %, 30.12 %, and 33.12 %, respectively; the pH values of the cinnamon and saline-alkali soils were increased by 15.02 % and 15.86 %, respectively. Besides, speciation distribution results suggested that the application of MPs reduced the liable available (LB) form (F2-dissolved and F3-ion exchangeable) of HMs and increased the potentially available (PB) form (F5-minerals and F6-organic-bound fraction) of HMs in all soils. Compared with other forms, F2 HMs fraction was the most responsive to MPs. Furthermore, the average bioconcentration factor (BCF) of Cr and Pb decreased by 73.75 % and 70.41 % in soils, respectively. Interestingly, soil type showed more impact on the form of HMs, which was associated with the different physicochemical parameters of soils, while application time displayed more impact on the bioavailability of HMs. Moreover, our results suggested that soils with higher clay content and pH values (such as cinnamon and saline-alkali soils) may mitigate the bioavailability of HMs more effectively in the presence of MPs, while soils with lower clay content may be more vulnerable to HMs contamination over time. This work highlights the importance of long-term monitoring of the impact of MPs on HMs dynamics for effective mitigation of soil contamination risks. Our study provides valuable guidance for soil remediation strategies and environmental quality management across different soil types.

11.
Comput Struct Biotechnol J ; 23: 3418-3429, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39386942

RESUMO

Dysregulation of adenosine-to-inosine (A-to-I) RNA editing has been implicated in cancer progression. However, a comprehensive understanding of how A-to-I RNA editing is incorporated into miRNA regulation to modulate gene expression in cancer remains unclear, given the lack of effective identification methods. To this end, we introduced an information theory-based algorithm named REMR to systematically identify 12,006 A-to-I RNA editing-mediated miRNA regulatory triplets (RNA editing sites, miRNAs, and genes) across ten major cancer types based on multi-omics profiling data from The Cancer Genome Atlas (TCGA). Through analyses of functional enrichment, transcriptional regulatory networks, and protein-protein interaction (PPI) networks, we showed that RNA editing-mediated miRNA regulation potentially affects critical cancer-related functions, such as apoptosis, cell cycle, drug resistance, and immunity. Furthermore, triplets can serve as biomarkers for classifying cancer subtypes with distinct prognoses or drug responses, highlighting the clinical relevance of such regulation. In addition, an online resource (http://www.jianglab.cn/REMR/) was constructed to support the convenient retrieval of our findings. In summary, our study systematically dissected the RNA editing-mediated miRNA regulations, thereby providing a valuable resource for understanding the mechanism of RNA editing as an epitranscriptomic regulator in cancer.

12.
Am J Med Sci ; 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39389359

RESUMO

PURPOSE: Ubiquitin-conjugating enzymes (E2s) participate in various tumor-promoting processes. UBE2Q1 is a member of the E2 family. This research aimed to detect the expression level of UBE2Q1 in human lung adenocarcinoma and to study its malignant biological function. METHODS: Western blot, qRT-PCR and immunohistochemistry was used to measure the expression of UBE2Q1 in human lung adenocarcinoma tissues. The association between UBE2Q1 expression and clinic-pathological variables in 99 lung adenocarcinoma samples was analyzed by immunohistochemistry. In vitro experiment, establishing UBE2Q1 knockdown pattern, the markers of apoptosis, cell cycle and epithelial-mesenchymal transition (EMT) were analyzed by Western blot. CCK8, colony formation, Transwell and invasion assay analyzed the effect of UBE2Q1 knockdown on the proliferation, metastasis and invasion of lung cancer cells. RESULTS: UBE2Q1 was overexpressed in lung adenocarcinoma, and the expression level of UBE2Q1 was related with TNM stage, tumor size, and lymph node metastasis. The high level of UBE2Q1 expression was also associated with poor survival and was an independent risk factor. In vitro, It was also confirmed that steady downregulation of UBE2Q1 could promote apoptosis, induce G2/M cell cycle arrest and regulate EMT. UBE2Q1 silencing dramatically reduce lung tumor cells proliferation, migration and invasion capacities. CONCLUSIONS: UBE2Q1 may serve as a prognostic biomarker and a new therapeutic target of lung adenocarcinoma.

13.
Cell Death Dis ; 15(10): 734, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39384740

RESUMO

Denticleless E3 ubiquitin protein ligase homolog (DTL), the substrate receptor of the CRL4A complex, plays a central role in genome stability. Even though the oncogenic function of DTL has been investigated in several cancers, its specific role in hepatocellular carcinoma (HCC) still needs further elucidation. Data from a clinical cohort (n = 209), RNA-sequencing, and public database (TCGA and GEO) were analyzed, indicating that DTL is closely related to patient prognosis and could serve as a promising prognostic indicator in HCC. Functionally, DTL promoted the proliferation, metastasis, and sorafenib resistance of HCC in vitro. In the orthotopic tumor transplantation and tail vein injection model, DTL promoted the growth and metastasis of HCC in vivo. Mechanically, we revealed for the first time that DTL was transcriptionally activated by hypoxia-inducible factor 1α (HIF-1α) under hypoxia and functioned as a downstream effector molecule of HIF-1α. DTL promotes the ubiquitination of SAFB-like transcription modulator (SLTM) and subsequently relieves the transcriptional repression of Notch1. These results suggested that DTL may be a potential biomarker and therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas , Sorafenibe , Ubiquitina-Proteína Ligases , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Animais , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Camundongos , Transdução de Sinais/efeitos dos fármacos , Camundongos Nus , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Linhagem Celular Tumoral , Ubiquitinação , Metástase Neoplásica , Ubiquitina/metabolismo , Receptores Notch/metabolismo , Camundongos Endogâmicos BALB C , Masculino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hipóxia Celular
14.
J Inflamm Res ; 17: 7123-7139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39398229

RESUMO

Background: Post-spinal cord injury (SCI) inflammation correlates with neurologic recovery. Through sequencing, we explored the roles of a differentially expressed circRNA in mice after SCI, circGla, on inflammation and recovery of SCI. Methods: The T8-T10 SCI model was established in C57BL6 mice. HE staining and RT-qPCR verified circGla upregulation results after injury obtained through sequencing. RNase R digestion and primer amplification experiments confirmed the circular properties of circGla. Nucleus and cytoplasm isolation experiments and FISH confirmed circGla expression in the astrocyte cytoplasm. AAV was used to establish a circGla knockdown mouse model. Behavioral tests were conducted to assess the recovery of the neurological function. The key inflammatory molecules after SCI were evaluated through MRI, RT-qPCR, and ELISA. For in vitro experiments, circGla was upregulated or knocked down in mouse astrocytes to detect its effect. The binding between miR-488 and circGla was confirmed through RIP and the dual luciferase experiment. RT-qPCR and ELISA confirmed the content correlation of the two molecules and the in vitro inflammatory function of miR-488. The binding experiment in astrocytes confirmed the binding between miR-488 and MEKK1 mRNA. Western blotting of MAPK pathway-related proteins confirmed that MEKK1 is a downstream effector for circGla and miR-488 in astrocytes. Results: Following SCI, the circular RNA circGla levels increased and it existed in the astrocyte cytoplasm. circGla knockdown reduced inflammation and improved neurological recovery in vivo. The correlation between circGla and proinflammatory factors was confirmed in vitro. circGla bound to miR-488, and the high miR-488 level was associated with the low astrocyte inflammatory state. miR-488 bound to MEKK1 mRNA, and upregulation or knockdown of circGla or miR-488 affected MAPK pathway-related protein expression. Conclusion: Following SCI, downregulation of circGla expression in astrocytes can reduce inflammatory manifestations and stimulate long-term functional recovery in mice through miR-488 and MEKK1.

15.
Biotechnol J ; 19(10): e202400328, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39407414

RESUMO

Pichia pastoris possesses the unique ability to utilize methanol as its sole carbon source, which makes it a proper host for producing various high-value-added products via metabolic engineering. Nevertheless, cell death has been observed during the fermentation of modified P. pastoris, with limited literature elucidating the underlying causes and mechanisms. Understanding the death mechanisms during methanol-based fermentation is crucial for optimizing fermentation strategies, enhancing the accumulation of target products, and reducing production costs. Here, we first sought to eliminate the potential causes of cell death during fermentation, such as inadequate inorganic salts and toxic by-product accumulation. The elimination of these potential causes was achieved efficiently utilizing the high-throughput fermentation equipment. Subsequently, we established a correlation between yeast cell death and the duration of the methanol metabolism period by monitoring the growth of the yeast at different fermentation stages. A critical revelation from this work came from analyzing the yeast's transcriptomic data at various stages of methanol metabolism. It was observed that a significant characteristic of yeast cell death during fermentation was the marked down-regulation of transcript levels of key enzymes involved in the methanol assimilation pathway and genes related to their biosynthesis process. The findings of this work are crucial for better understanding the causes and mechanisms of cell death for engineered P. pastoris during methanol-utilized fermentation.


Assuntos
Regulação para Baixo , Fermentação , Regulação Fúngica da Expressão Gênica , Engenharia Metabólica , Metanol , Metanol/metabolismo , Engenharia Metabólica/métodos , Regulação para Baixo/genética , Regulação Fúngica da Expressão Gênica/genética , Saccharomycetales/genética , Saccharomycetales/metabolismo , Pichia/genética , Pichia/metabolismo
16.
JAMA Dermatol ; 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39412780

RESUMO

This case report describes a woman in her 70s with an erythematous plaque with superficial erosion, focal white scale, and surrounding hyperpigmentation located circumferentially around the anus and extending anteriorly to involve the perineum.

17.
Appl Radiat Isot ; 214: 111554, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39423459

RESUMO

With the development of nuclear industry, radioactive elements such as 137Cs put a threat on the water environment. It is a challenging task to remove the Cs+ in the nuclear wastewater. In the current study, we prepared a new Cs+-adsorbing material by introducing sulfhydryl group onto the surface of hollow mesoporous silica microspheres, then oxidizing the sulfhydryl group to sulfonic acid group. The obtained HMSS-SO3H material had an excellent adsorption capacity for Cs+ in the aqueous solution, with an adsorption capacity of 51.53 mg g-1 in 30 min. Characterization approaches, such as FT-IR and EDS, were used to confirm the result of modification. Adsorption experiments were carried out under. The influence of various parameters on the adsorption process was investigated under the conditions of changing pH, temperature, and time. The effect of competitive ions was also explored. The results indicated that the adsorption process followed the pseudo-second-order model and the main adsorption mechanisms are electrostatic interaction and coordination. The material had a best adsorption performance at a neutral pH. The adsorption process could well-fit the Langmuir's model, with a theoretical maximum adsorption capacity of 81.31 mg g-1. And the adsorption capacity was slightly affected by competing ions such as Mg2+ and Ca2+. The results indicate that the HMSS-SO3H prepared in this study is a promising adsorbent for Cs+, with the advantages of high adsorption capacity, fast adsorption rate and high selectivity.

18.
Environ Res ; 263(Pt 2): 120111, 2024 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-39401605

RESUMO

The heterotrophic nitrification-aerobic denitrification (HNAD) is a new biological denitrification technology, the present study isolated a new HNAD strain named Cupriavidus metallidurans TX6 with heavy metal resistance. The gene expression, electron transport, enzyme activity and nitrogen removal property of strain TX6 were studied with different influencing factors. Strain TX6 has five nitrogen metabolism pathways (NH4+ → NH2OH → NO → NO2- → NH4+ → GOGAT/GDH; NH4+-N → NH2OH → NO → N2O → N2; NH4+ → NH2OH → NO → NO2- → NO3-; NO3- → NO2- → NH4+ → GOGAT/GDH; NO3-→ NO2- → NH4+ → GOGAT/GDH). Nitrogen balance analysis shows that 29 ± 4 mg/L of N was converted to intracellular nitrogen by assimilation and 50 ± 3 mg/L N loss may be attributed to aerobic denitrification. The results provide a theoretical basis for the HAND bacteria application in nitrogen removal from wastewaters containing heavy metals.

19.
Forensic Sci Int Genet ; 74: 103162, 2024 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-39413461

RESUMO

Kinship testing, which involves genotyping genetic markers and comparing their profiles between individuals, holds significant applications in forensic science. However, the prevalent use of independent markers often lacks the discriminatory power to distinguish pedigrees belong to the same kinship class. While numerous studies have attempted to address this challenge through diverse approaches, the testing efficacy of high-density SNP microarrays in combination with the likelihood approach remains unclear. In this study, we further explored the utilization of linked autosomal SNPs derived from microarrays with the likelihood approach. Several SNP panels with differing numbers of loci were developed and putative pedigrees were constructed to evaluated to test their efficacy in distinguishing second-degree relationships, including grandparent-grandchild, half-siblings, and avuncular. Our findings indicate that the use of high-density SNP microarrays is theoretically feasible for discriminating second-degree relationships, with balanced classification rates ranging from 0.444 to 0.853. Moreover, to optimize the practical effectiveness of discriminating pedigrees belonging to the same kinship class, several other aspects such as adding additional SNPs or an additional relative and examining the effects of genotype errors and population selection were discussed. Our results revealed that the employment of denser marker sets with more accurate genotyping methods may be beneficial. Additionally, the inclusion of additional relatives and the selection of an appropriate reference population also appear to be crucial factors for enhancing the accuracy of kinship testing. In conclusion, our study provides insights into the potential of high-density SNPs in kinship testing and highlights the need for further optimization and examination into various factors that may contribute to enhancing testing efficacy.

20.
Perfusion ; : 2676591241293012, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39417362

RESUMO

Transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of severe aortic stenosis in high-risk patients, offering a minimally invasive alternative to open-heart surgery. However, complications such as hemodynamic instability may require mechanical circulatory support. In some cases, emergent cardiac surgery may be required, necessitating a swift transition to cardiopulmonary bypass (CPB). We modified the CPB circuit allowing for circulatory support and easy transition to CPB. No bleeding or vascular complications were observed. The modified CPB circuit minimizes hemodynamic disruptions and allows for postoperative ECMO support.

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