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1.
Proc Natl Acad Sci U S A ; 121(40): e2408711121, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39325424

RESUMO

Effective colonization by microbe in the rhizosphere is critical for establishing a beneficial symbiotic relationship with the host plant. Bacillus subtilis, a soil-dwelling bacterium that is commonly found in association with plants and their rhizosphere, has garnered interest for its potential to enhance plant growth, suppress pathogens, and contribute to sustainable agricultural practices. However, research on the dynamic distribution of B. subtilis within the rhizosphere and its interaction mechanisms with plant roots remains insufficient due to limitations in existing in situ detection methodologies. To achieve dynamic in situ detection of the rhizosphere environment, we established iRhizo-Chip, a microfluidics-based platform. Using this device to investigate microbial behavior within the rhizosphere, we found obvious diurnal fluctuations in the growth of B. subtilis in the rhizosphere. Temporal dynamic analysis of rhizosphere dissolved oxygen (DO), pH, dissolved organic carbon, and reactive oxygen species showed that diurnal fluctuations in the growth of B. subtilis are potentially related to a variety of environmental factors. Spatial dynamic analysis also showed that the spatial distribution changes of B. subtilis and DO and pH were similar. Subsequently, through in vitro control experiments, we proved that rhizosphere DO and pH are the main driving forces for diurnal fluctuations in the growth of B. subtilis. Our results show that the growth of B. subtilis is driven by rhizosphere DO and pH, resulting in diurnal fluctuations, and iRhizo-Chip is a valuable tool for studying plant rhizosphere dynamics.


Assuntos
Bacillus subtilis , Rizosfera , Microbiologia do Solo , Bacillus subtilis/metabolismo , Bacillus subtilis/fisiologia , Raízes de Plantas/microbiologia , Raízes de Plantas/metabolismo , Dispositivos Lab-On-A-Chip , Ritmo Circadiano/fisiologia , Oxigênio/metabolismo , Oxigênio/análise , Concentração de Íons de Hidrogênio , Espécies Reativas de Oxigênio/metabolismo
2.
J Biol Chem ; 300(2): 105591, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38141769

RESUMO

Long noncoding RNAs (lncRNAs) are specifically expressed in different diseases and regulate disease progression. To explore the functions of rheumatoid arthritis (RA)-specific lncRNA, we determined the lncRNA expression profile of fibroblast-like synoviocytes (FLS) obtained from patients with RA and osteoarthritis (OA) using a LncRNA microarray and identified up-regulated LncNFYB in RA as a potential therapeutic target. Using gain- and loss-of-function studies, LncNFYB was proven to promote FLS proliferation and cell cycle progress but not affect their invasion, migration, and apoptotic abilities. Further investigation discovered that LncRNA could combine with annexin A2 (ANXA2) and enhance the level of phospho-ANXA2 (Tyr24) in the plasma membrane area, which induced the activation of ERK1/2 to promote proliferation. These findings provide new insights into the biological functions of LncNFYB on modification of FLS, which may be exploited for the therapy of RA.


Assuntos
Anexina A2 , Artrite Reumatoide , Sistema de Sinalização das MAP Quinases , RNA Longo não Codificante , Sinoviócitos , Humanos , Anexina A2/genética , Anexina A2/metabolismo , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/fisiopatologia , Proliferação de Células/genética , Células Cultivadas , Ativação Enzimática/genética , Fibroblastos/citologia , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Osteoartrite/genética , Osteoartrite/metabolismo , Osteoartrite/fisiopatologia , Fosforilação/genética , Ligação Proteica/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Sinoviócitos/citologia , Sinoviócitos/metabolismo
3.
Drug Resist Updat ; 77: 101142, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39214042

RESUMO

The spread of antibiotic resistance genes (ARGs), particularly those carried on plasmids, poses a major risk to global health. However, the extent and frequency of ARGs transfer in microbial communities among human, animal, and environmental sectors is not well understood due to a lack of effective tracking tools. We have developed a novel fluorescent tracing tool, CRISPR-AMRtracker, to study ARG transfer. It combines CRISPR/Cas9 fluorescence tagging, fluorescence-activated cell sorting, 16S rRNA gene sequencing, and microbial community analysis. CRISPR-AMRtracker integrates a fluorescent tag immediately downstream of ARGs, enabling the tracking of ARG transfer without compromising the host cell's antibiotic susceptibility, fitness, conjugation, and transposition. Notably, our experiments demonstrate that sfGFP-tagged plasmid-borne mcr-1 can transfer across diverse bacterial species within fecal samples. This innovative approach holds the potential to illuminate the dynamics of ARG dissemination and provide valuable insights to shape effective strategies in mitigating the escalating threat of antibiotic resistance.

4.
Proc Natl Acad Sci U S A ; 119(18): e2202713119, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35476517

RESUMO

Protein secondary structure discrimination is crucial for understanding their biological function. It is not generally possible to invert spectroscopic data to yield the structure. We present a machine learning protocol which uses two-dimensional UV (2DUV) spectra as pattern recognition descriptors, aiming at automated protein secondary structure determination from spectroscopic features. Accurate secondary structure recognition is obtained for homologous (97%) and nonhomologous (91%) protein segments, randomly selected from simulated model datasets. The advantage of 2DUV descriptors over one-dimensional linear absorption and circular dichroism spectra lies in the cross-peak information that reflects interactions between local regions of the protein. Thanks to their ultrafast (∼200 fs) nature, 2DUV measurements can be used in the future to probe conformational variations in the course of protein dynamics.


Assuntos
Aprendizado de Máquina , Redes Neurais de Computação , Proteínas , Análise Espectral
5.
Proc Natl Acad Sci U S A ; 119(34): e2207767119, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35969749

RESUMO

Untethered soft miniature robots capable of accessing hard-to-reach regions can enable new, disruptive, and minimally invasive medical procedures. However, once the control input is removed, these robots easily move from their target location because of the dynamic motion of body tissues or fluids, thereby restricting their use in many long-term medical applications. To overcome this, we propose a wireless spring-preloaded barbed needle release mechanism, which can provide up to 1.6 N of force to drive a barbed needle into soft tissues to allow robust on-demand anchoring on three-dimensional (3D) surfaces. The mechanism is wirelessly triggered using radio-frequency remote heating and can be easily integrated into existing untethered soft robotic platforms without sacrificing their mobility. Design guidelines aimed at maximizing anchoring over the range of the most biological tissues (kPa range) and extending the operating depth of the device inside the body (up to 75%) are also presented. Enabled by these advances, we achieve robust anchoring on a variety of ex vivo tissues and demonstrate the usage of such a device when integrated with existing soft robotic platforms and medical imaging. Moreover, by simply changing the needle, we demonstrate additional functionalities such as controlled detachment and subsurface drug delivery into 3D cancer spheroids. Given these capabilities, our proposed mechanism could enable the development of a new class of biomedical-related functionalities, such as local drug delivery, disease monitoring, and hyperthermia for future untethered soft medical robots.


Assuntos
Robótica , Sistemas de Liberação de Medicamentos , Movimento (Física) , Robótica/métodos
6.
Clin Infect Dis ; 78(4): 880-888, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38015658

RESUMO

BACKGROUND: Postherpetic neuralgia (PHN) is the most common chronic complication of herpes zoster (HZ) and results in severe refractory neuropathic pain. This study aimed at evaluating the efficacy of premedication with duloxetine in the prevention of PHN. METHODS: The PROCESS trial is a multicenter, randomized, open-label, blinded-endpoint trial used a 1:1 duloxetine:control ratio. Adults 50 years or older with HZ who presented with vesicles within 72 hours were recruited. The primary outcome was the incidence of PHN at 12 weeks. PHN was defined as any pain intensity score other than 0 mm on the visual analog scale (VAS) at week 12 after the onset of the rash. The secondary outcomes were the number of participants with VAS >0 and VAS ≥3. The modified intention-to-treat (mITT) principle and per-protocol (PP) principle were used for the primary outcome analysis. RESULTS: A total of 375 participants were randomly assigned to the duloxetine group and 375 were assigned to the control group. There was no significant difference in the incidence of PHN in the duloxetine group compared with the control group in the mITT analysis (86 [22.9%] of 375 vs 108 [28.8%] of 375; P = .067). PP analysis produced similar results. However, there were significant differences between the 2 groups in the number of participants with VAS >0 and VAS ≥3 (P < .05 for all comparisons). CONCLUSIONS: Although absolute prevention of PHN does not occur, this trial found that premedication with duloxetine can reduce pain associated with HZ, and therefore can have clinically relevant benefits. Clinical Trials Registration. Clinicaltrials.gov, NCT04313335. Registered on 18 March 2020.


Assuntos
Herpes Zoster , Neuralgia Pós-Herpética , Adulto , Humanos , Neuralgia Pós-Herpética/tratamento farmacológico , Neuralgia Pós-Herpética/prevenção & controle , Neuralgia Pós-Herpética/epidemiologia , Cloridrato de Duloxetina/uso terapêutico , Herpes Zoster/complicações , Herpes Zoster/tratamento farmacológico , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3 , Medição da Dor/efeitos adversos , Medição da Dor/métodos
7.
Mol Med ; 30(1): 15, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254035

RESUMO

BACKGROUND: In heart failure (HF), mitochondrial dysfunction and metabolic remodeling lead to a reduction in energy productivity and aggravate cardiomyocyte injury. Supplementation with α-ketoglutarate (AKG) alleviated myocardial hypertrophy and fibrosis in mice with HF and improved cardiac insufficiency. However, the myocardial protective mechanism of AKG remains unclear. We verified the hypothesis that AKG improves mitochondrial function by upregulating NAD+ levels and activating silent information regulator 2 homolog 1 (SIRT1) in cardiomyocytes. METHODS: In vivo, 2% AKG was added to the drinking water of mice undergoing transverse aortic constriction (TAC) surgery. Echocardiography and biopsy were performed to evaluate cardiac function and pathological changes. Myocardial metabolomics was analyzed by liquid chromatography‒mass spectrometry (LC‒MS/MS) at 8 weeks after surgery. In vitro, the expression of SIRT1 or PINK1 proteins was inhibited by selective inhibitors and siRNA in cardiomyocytes stimulated with angiotensin II (AngII) and AKG. NAD+ levels were detected using an NAD test kit. Mitophagy and ferroptosis levels were evaluated by Western blotting, qPCR, JC-1 staining and lipid peroxidation analysis. RESULTS: AKG supplementation after TAC surgery could alleviate myocardial hypertrophy and fibrosis and improve cardiac function in mice. Metabolites of the malate-aspartate shuttle (MAS) were increased, but the TCA cycle and fatty acid metabolism pathway could be inhibited in the myocardium of TAC mice after AKG supplementation. Decreased NAD+ levels and SIRT1 protein expression were observed in heart of mice and AngII-treated cardiomyocytes. After AKG treatment, these changes were reversed, and increased mitophagy, inhibited ferroptosis, and alleviated damage in cardiomyocytes were observed. When the expression of SIRT1 was inhibited by a selective inhibitor and siRNA, the protective effect of AKG was suppressed. CONCLUSION: Supplementation with AKG can improve myocardial hypertrophy, fibrosis and chronic cardiac insufficiency caused by pressure overload. By increasing the level of NAD+, the SIRT-PINK1 and SIRT1-GPX4 signaling pathways are activated to promote mitophagy and inhibit ferroptosis in cardiomyocytes, which ultimately alleviates cardiomyocyte damage.


Assuntos
Estenose da Valva Aórtica , Ferroptose , Insuficiência Cardíaca , Ácidos Cetoglutáricos , Mitofagia , Angiotensina II , Cromatografia Líquida , Ferroptose/efeitos dos fármacos , Fibrose , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Hipertrofia , Ácidos Cetoglutáricos/farmacologia , Ácidos Cetoglutáricos/uso terapêutico , Mitofagia/efeitos dos fármacos , Miócitos Cardíacos , NAD , Proteínas Quinases , RNA Interferente Pequeno , Sirtuína 1 , Espectrometria de Massas em Tandem , Animais , Camundongos
8.
Small ; : e2405683, 2024 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-39396368

RESUMO

Transition metal catalysts are widely used in the 2e- ORR due to their cost-effectiveness. However, they often encounter issues related to low activity. Defect engineering are used on developing highly active catalysts, which can effectively modify active sites and promote electron transfer. Here, carbon-coated Ni3S2 (Ni3S2@C), where the additional sulfur vacancies (VS) is prepared induced by the carbon layer is coupled with active nickel sites. Through in situ and ex situ experiments combined with DFT calculations, it is demonstrated that the carbon layer can regulate the quantity of VS in Ni3S2. Materials with a higher concentration of VS exhibit enhanced 2e- ORR activity and higher H2O2 selectivity. In situ Raman spectroscopy confirms that Ni serves as the key active site in this catalyst. DFT calculations indicate that the OOH binding energy (ΔG) decreases with an increase in the number of VS, favoring the protonation of *OOH to generate H2O2. Upon performance testing, the average H2O2 selectivity is 92.3%, with the highest yield reaching up to 3860 mmol gcat-1 h-1. It is noteworthy that Ni3S2@C exhibits high stability, with only a slight decrease in 2e- pathway selectivity after 5000 cycles of ADT.

9.
J Pineal Res ; 76(5): e12987, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38975671

RESUMO

Sleep deprivation (SD) has been associated with a plethora of severe pathophysiological syndromes, including gut damage, which recently has been elucidated as an outcome of the accumulation of reactive oxygen species (ROS). However, the spatiotemporal analysis conducted in this study has intriguingly shown that specific events cause harmful damage to the gut, particularly to goblet cells, before the accumulation of lethal ROS. Transcriptomic and metabolomic analyses have identified significant enrichment of metabolites related to ferroptosis in mice suffering from SD. Further analysis revealed that melatonin could rescue the ferroptotic damage in mice by suppressing lipid peroxidation associated with ALOX15 signaling. ALOX15 knockout protected the mice from the serious damage caused by SD-associated ferroptosis. These findings suggest that melatonin and ferroptosis could be targets to prevent devastating gut damage in animals exposed to SD. To sum up, this study is the first report that proposes a noncanonical modulation in SD-induced gut damage via ferroptosis with a clearly elucidated mechanism and highlights the active role of melatonin as a potential target to maximally sustain the state during SD.


Assuntos
Ferroptose , Melatonina , Camundongos Knockout , Privação do Sono , Animais , Camundongos , Melatonina/metabolismo , Melatonina/farmacologia , Privação do Sono/metabolismo , Masculino , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BL , Peroxidação de Lipídeos , Araquidonato 15-Lipoxigenase/metabolismo , Araquidonato 15-Lipoxigenase/genética , Araquidonato 12-Lipoxigenase
10.
BMC Gastroenterol ; 24(1): 373, 2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39434031

RESUMO

Gastric cancer (GC) is a highly heterogeneous and aggressive malignant tumor that seriously affects the life safety of people all over the world. Its early manifestations are subtle. The present study aimed to investigate the clinical significance of serum lipid profiles, insulin resistance markers including the triglyceride-glucose (TyG) index and the atherosclerotic index (AI), in GC patients. A retrospective analysis encompassed 215 GC patients and 827 healthy individuals. The study results show that the total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein levels, and the TyG index of GC patients were significantly lower than those of the control group before and after propensity score matching analysis. In the GC group, the levels of CEA, CA199, CA125, and CA724 tumor markers were higher than those in the healthy control group. Patients in advanced stages exhibited lower serum levels of serum lipids and TyG index compared to those in early stages. ROC analysis revealed that the TyG index, CA125, and CA199 combination yielded the highest positive prediction rate for GC at 98.6%. TyG index is significantly associated with the risk of adverse reactions after chemotherapy (OR = 1.104, 95% CI 1.028-1.186, P < 0.01). Multiple tumor markers and the TyG index combined detection showed correlations with five adverse reactions caused by chemotherapy (r < 0.6, P < 0.05). Preoperative lipid profiles in the serum show a strong correlation with patients diagnosed with GC. Evaluating a combination of various serum lipids and cancer markers significantly improves diagnostic precision for GC and the ability to predict chemotherapy side effects.


Assuntos
Antígenos Glicosídicos Associados a Tumores , Biomarcadores Tumorais , Resistência à Insulina , Neoplasias Gástricas , Triglicerídeos , Humanos , Masculino , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Biomarcadores Tumorais/sangue , Prognóstico , Triglicerídeos/sangue , Antígenos Glicosídicos Associados a Tumores/sangue , Idoso , Lipídeos/sangue , Glicemia/análise , Glicemia/metabolismo , Antígeno Carcinoembrionário/sangue , Estudos de Casos e Controles , Adulto
11.
Headache ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39193836

RESUMO

OBJECTIVE: To explore the efficacy and safety of 5% lidocaine-medicated plaster (LMP) in patients with trigeminal neuralgia (TN). BACKGROUND: TN is an excruciatingly painful type of neuropathic facial pain. Anti-epileptics are the first-line treatment for TN; however, these oral drugs alone sometimes fail to achieve satisfactory analgesic effects. Two retrospective studies have shown that LMP can be an effective and safe treatment option for some patients with TN. No other high-quality clinical studies have explored the effect and safety of LMP in patients with TN. METHODS: The PATCH trial is an enriched enrollment with randomized withdrawal, double-blind, vehicle-controlled, parallel-group trial performed at five study centers. Eligible patients with TN received LMP during a 3-week initial open-label phase. Patients who met the response criteria entered the double-blind treatment phase and were randomly assigned for treatment with either LMP (LMP group) or vehicle patches (control group) at a 1:1 ratio. Patients who met the criteria for treatment failure were withdrawn from the double-blind treatment phase, and treatment was continued in the remaining patients for up to 28 days. The primary outcome was the number of treatment failures. The secondary endpoints were the time to loss of therapeutic response (LTR) in the double-blind phase and the weekly mean pain severity in both the open-label phase and the double-blind phase of the study. RESULTS: The first patient was enrolled in this study on May 1, 2021, and the enrollment of the last patient was completed on August 26, 2022. A total of 307 patients were initially screened, 226 (74.0%) of whom entered the open-label phase. Of the 226 respondents, 124 (55.0%) were randomized to the double-blind phase. In the double-blind phase, 62 patients were assigned to the LMP group, and 62 were assigned to the control group. For the primary endpoint, 16 (26.0%) patients with LMP and 36 (58.0%) patients with vehicle patches met the treatment failure criteria during the double-blind phase (relative risk, 0.48; 95% confidence interval [CI], 0.31 to 0.75; p < 0.001). The survival curve of the LTR showed that the LTR of LMP was significantly longer than that of the vehicle patches (hazard ratio, 0.275; 95% CI, 0.15 to 0.50; log-rank p < 0.001). LMP also significantly reduced the weekly mean pain severity in the double-blind phase of the study (p = 0.007). CONCLUSIONS: LMP produced partial relief of pain symptoms in some patients with TN. For responders, LMP may be used as an add-on therapy in a multidrug treatment protocol.

12.
Environ Sci Technol ; 58(31): 13833-13844, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39012163

RESUMO

The emerging contaminant triclosan (TCS) is widely distributed both in surface water and in wastewater and poses a threat to aquatic organisms and human health due to its resistance to degradation. The dioxygenase enzyme TcsAB has been speculated to perform the initial degradation of TCS, but its precise catalytic mechanism remains unclear. In this study, the function of TcsAB was elucidated using multiple biochemical and molecular biology methods. Escherichia coli BL21(DE3) heterologously expressing tcsAB from Sphingomonas sp. RD1 converted TCS to 2,4-dichlorophenol. TcsAB belongs to the group IA family of two-component Rieske nonheme iron ring-hydroxylating dioxygenases. The highest amino acid identity of TcsA and the large subunits of other dioxygenases in the same family was only 35.50%, indicating that TcsAB is a novel dioxygenase. Mutagenesis of residues near the substrate binding pocket decreased the TCS-degrading activity and narrowed the substrate spectrum, except for the TcsAF343A mutant. A meta-analysis of 1492 samples from wastewater treatment systems worldwide revealed that tcsA genes are widely distributed. This study is the first to report that the TCS-specific dioxygenase TcsAB is responsible for the initial degradation of TCS. Studying the microbial degradation mechanism of TCS is crucial for removing this pollutant from the environment.


Assuntos
Dioxigenases , Triclosan , Triclosan/metabolismo , Dioxigenases/metabolismo , Dioxigenases/genética , Biodegradação Ambiental , Escherichia coli , Sphingomonas/enzimologia , Sphingomonas/metabolismo , Poluentes Químicos da Água/metabolismo
13.
Artigo em Inglês | MEDLINE | ID: mdl-38403735

RESUMO

There is inconsistent evidence for an association of obesity with white matter microstructural alterations. Such inconsistent findings may be related to the cumulative effects of obesity and alcohol dependence. This study aimed to investigate the possible interactions between alcohol dependence and overweight/obesity on white matter microstructure in the human brain. A total of 60 inpatients with alcohol dependence during early abstinence (44 normal weight and 16 overweight/obese) and 65 controls (42 normal weight and 23 overweight/obese) were included. The diffusion tensor imaging (DTI) measures [fractional anisotropy (FA) and radial diffusivity (RD)] of the white matter microstructure were compared between groups. We observed significant interactive effects between alcohol dependence and overweight/obesity on DTI measures in several tracts. The DTI measures were not significantly different between the overweight/obese and normal-weight groups (although widespread trends of increased FA and decreased RD were observed) among controls. However, among the alcohol-dependent patients, the overweight/obese group had widespread reductions in FA and widespread increases in RD, most of which significantly differed from the normal-weight group; among those with overweight/obesity, the alcohol-dependent group had widespread reductions in FA and widespread increases in RD, most of which were significantly different from the control group. This study found significant interactive effects between overweight/obesity and alcohol dependence on white matter microstructure, indicating that these two controllable factors may synergistically impact white matter microstructure and disrupt structural connectivity in the human brain.

14.
Environ Res ; 261: 119690, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39068967

RESUMO

Companion animals have the potential to greatly enhance the physical and mental health of humans, thus leading to an increased focus on the interactions between humans and pets. Currently, the inappropriate and excessive utilization of antimicrobial agents has become prevalent in veterinary clinical practice for pets. This antibiotic contamination phenomenon has a profound impact on the enrichment of antibiotic resistance bacteria (ARB) and antibiotic resistance genes (ARGs) in pets. However, the pet-associated resistome, especially the novel ARGs in pets, represents a relatively neglected area. In this study, we successfully constructed a total of 12 libraries using the functional metagenomics approach to assess the diversity of ARGs in pet cats and dogs from four pet hospitals. Through the integration of functional screening and high-throughput sequencing, a total of 122 antibiotic resistance determinants were identified, of which 15 were classified as putative novel ARGs originating from five classes. Functional assessment demonstrated that 6 novel ARGs including one ß-lactam, two macrolides, two aminoglycosides, and one rifamycin (RIF), namely blaPF, ermPF, msrPF, aac(6')PF, aph(3')PF, and arrPF, exhibited functionally activity in conferring bacterial phenotypic resistance by increasing the minimum inhibitory concentrations (MICs) with a 4- to 128-fold. Genetic context analysis demonstrated that, with the exception of aac(6')PF and arrPF, the remaining four novel ARGs were found adjacent to mobile genetic elements (MGEs) including IS elements or transposases, which provided a prerequisite for horizontal transfer of these novel ARGs, thereby offering an explanation for their detection in diverse samples collected from various sampling sites. The current study has unveiled the significant role of cat and dog feces as one source of reservoirs of diverse novel ARGs, while also highlighting the potential adverse consequences of their further spread to medically significant pathogens and human commensal organisms.


Assuntos
Fezes , Cães , Gatos , Animais , Fezes/microbiologia , Antibacterianos/farmacologia , Genes Bacterianos , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana , Resistência Microbiana a Medicamentos/genética , Animais de Estimação/microbiologia
15.
Environ Toxicol ; 39(5): 2908-2926, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38299230

RESUMO

BACKGROUND: Colorectal cancer (CRC) presents a significant global health burden, characterized by a heterogeneous molecular landscape and various genetic and epigenetic alterations. Programmed cell death (PCD) plays a critical role in CRC, offering potential targets for therapy by regulating cell elimination processes that can suppress tumor growth or trigger cancer cell resistance. Understanding the complex interplay between PCD mechanisms and CRC pathogenesis is crucial. This study aims to construct a PCD-related prognostic signature in CRC using machine learning integration, enhancing the precision of CRC prognosis prediction. METHOD: We retrieved expression data and clinical information from the Cancer Genome Atlas and Gene Expression Omnibus (GEO) datasets. Fifteen forms of PCD were identified, and corresponding gene sets were compiled. Machine learning algorithms, including Lasso, Ridge, Enet, StepCox, survivalSVM, CoxBoost, SuperPC, plsRcox, random survival forest (RSF), and gradient boosting machine, were integrated for model construction. The models were validated using six GEO datasets, and the programmed cell death score (PCDS) was established. Further, the model's effectiveness was compared with 109 transcriptome-based CRC prognostic models. RESULT: Our integrated model successfully identified differentially expressed PCD-related genes and stratified CRC samples into four subtypes with distinct prognostic implications. The optimal combination of machine learning models, RSF + Ridge, showed superior performance compared with traditional methods. The PCDS effectively stratified patients into high-risk and low-risk groups, with significant survival differences. Further analysis revealed the prognostic relevance of immune cell types and pathways associated with CRC subtypes. The model also identified hub genes and drug sensitivities relevant to CRC prognosis. CONCLUSION: The current study highlights the potential of integrating machine learning models to enhance the prediction of CRC prognosis. The developed prognostic signature, which is related to PCD, holds promise for personalized and effective therapeutic interventions in CRC.


Assuntos
Apoptose , Neoplasias Colorretais , Humanos , Prognóstico , Aprendizado de Máquina , Neoplasias Colorretais/genética
16.
Sensors (Basel) ; 24(15)2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39123959

RESUMO

Timely and accurate detection of viruses is crucial for infection diagnosis and treatment. However, it remains a challenge to develop a portable device that meets the requirement of being portable, powerless, user-friendly, reusable, and low-cost. This work reports a compact ∅30 × 48 mm portable powerless isothermal amplification detection device (material cost ∼$1 USD) relying on LAMP (Loop-Mediated Isothermal Amplification). We have proposed chromatographic-strip-based microporous permeation technology which can precisely control the water flow rate to regulate the exothermic reaction. This powerless heating combined with phase-change materials can maintain a constant temperature between 50 and 70 °C for a duration of up to 49.8 min. Compared with the conventional methods, it avoids the use of an additional insulation layer for heat preservation, greatly reducing the size and cost. We have also deployed a color card and a corresponding algorithm to facilitate color recognition, data analysis, and storage using a mobile phone. The experimental results demonstrate that our device exhibits the same limit of detection (LOD) as the ProFlex PCR for SARS-CoV-2 pseudovirus samples, with that for both being 103 copies/µL, verifying its effectiveness and reliability. This work offers a timely, low-cost, and easy way for respiratory infectious disease detection, which could provide support in curbing virus transmission and protecting the health of humans and animals, especially in remote mountainous areas without access to electricity or trained professionals.


Assuntos
COVID-19 , Técnicas de Amplificação de Ácido Nucleico , SARS-CoV-2 , Técnicas de Amplificação de Ácido Nucleico/instrumentação , Técnicas de Amplificação de Ácido Nucleico/métodos , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , Humanos , COVID-19/diagnóstico , COVID-19/virologia , Técnicas de Diagnóstico Molecular/instrumentação , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/economia , Limite de Detecção
17.
Nano Lett ; 23(22): 10236-10242, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37906707

RESUMO

Because of the lack of contact and spacer doping techniques for two-dimensional (2D) transistors, most high-performance 2D devices have been produced with nontypical structures that contain electrical gating in the contact regions. In the present study, we used chloroauric acid (HAuCl4) as a strong p-dopant for WSe2 monolayers used in transistors. The HAuCl4-doped devices exhibited a record-low contact resistance of 0.7 kΩ·µm under a doping concentration of 1.76 × 1013 cm-2. In addition, an extrinsic carrier diffusion phenomenon was discovered in the HAuCl4-WSe2 system. With a suitably designed spacer length for doping, a normally off, high-performance underlap top-gate device can be produced without the application of additional gating in the contact and spacer regions.

18.
Molecules ; 29(6)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38543035

RESUMO

To investigate the influence of deashing on fusion characteristics, a combined method of water and acid washing with different sequences (water washing followed by acid washing, and acid washing followed by water washing) was used to treat the biochar of bamboo shoot shells (BBSSs). The results show that deashing decreased the K content of the biochar from 50.3% to 1.08% but increased the Si content from 33.48% to 89.15%. The formation of silicates and aluminosilicates from alkali metal oxides with silicon was an inevitable result of ash phase transformation at the high temperatures used to improve the fusion temperature (>1450 °C). The thermochemical behavior of ash mainly occurs at 1000 °C. The deashing treatment significantly reduced the reaction intensity during the high-temperature process. This significantly increased the thermal stability of the ash. The adjustment of the washing sequence had a slight impact on the chemical compositions, but the differences in ash micromorphology were obvious. Deashing treatments with different washing sequences can significantly improve ash fusion properties effectively and reduce the risk of scaling, slagging, and corrosion. This study provides a new and reasonable strategy for the deashing of biochar to commercially utilize bamboo shoot shell resources.


Assuntos
Álcalis , Carvão Vegetal , Carvão Vegetal/química , Temperatura , Água , Cinza de Carvão
19.
Aesthet Surg J ; 44(8): NP574-NP584, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38591553

RESUMO

Non-tuberculous mycobacteria (NTM) infection of the skin and soft tissues is a complication of cosmetic procedures. The incidence of cutaneous NTM infections has increased significantly as aesthetic operations have become more commonplace. With the rise of cosmetic tourism, the geographic expansion of NTM infections is a major concern. Due to the unique pathogenesis of NTM infections, diagnosis and treatment remain significant challenges for clinicians. Clinical management relies on a combination of antibiotic therapy with drug susceptibility testing and appropriate surgical debridement. Some new drugs, photodynamic therapy, and bacteriophage therapy have been developed in recent years, and may improve the aesthetic outcomes. This review summarizes the cosmetic procedures prone to NTM infections in recent years and their clinical features. We propose a 2-stage treatment procedure, including a hospitalization phase and a follow-up phase. We aim to increase the alertness of clinicians to NTM infections for timely detection and treatment.


Assuntos
Antibacterianos , Técnicas Cosméticas , Infecções por Mycobacterium não Tuberculosas , Humanos , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/etiologia , Infecções por Mycobacterium não Tuberculosas/terapia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Técnicas Cosméticas/efeitos adversos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Micobactérias não Tuberculosas/isolamento & purificação
20.
Angew Chem Int Ed Engl ; 63(36): e202407024, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-38864254

RESUMO

Ni-rich cathodes have been intensively adopted in Li-ion batteries to pursuit high energy density, which still suffering irreversible degradation at high voltage. Some unstable lattice O2- species in Ni-rich cathodes would be oxidized to singlet oxygen 1O2 and released at high volt, which lead to irreversible phase transfer from the layered rhombohedral (R) phase to a spinel-like (S) phase. To overcome the issue, the amphiphilic copolymers (UMA-Fx) electrolyte were prepared by linking hydrophobic C-F side chains with hydrophilic subunits, which could self-assemble on Ni-rich cathode surface and convert to stable cathode-electrolyte interphase layer. Thereafter, the oxygen releasing of polymer coated cathode was obviously depressed and substituted by the Co oxidation (Co3+→Co4+) at high volt (>4.2 V), which could suppressed irreversible phase transfer and improve cycling stability. Moreover, the amphiphilic polymer electrolyte was also stable with Li anode and had high ion conductivity. Therefore, the NCM811//UMA-F6//Li pouch cell exhibited outstanding energy density (362.97 Wh/kg) and durability (cycled 200 times at 4.7 V), which could be stalely cycled even at 120°C without short circuits or explosions.

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