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Objectives: This study describes the detection and tracking of emergency neurosurgical cross-transmission infections with carbapenem-resistant Klebsiella oxytoca (CRKO). Methods: We conducted an epidemiological investigation and a rapid screening of 66 surveillance samples using the chromogenic selective medium. Two CRKO isolates from infected patients and three from the preoperative shaving razors had similar resistance profiles identified by the clinical laboratory. Results: The whole genome sequencing (WGS) results identified all isolates as Klebsiella michiganensis (a species in the K. oxytoca complex) with sequence type 29 (ST29) and carrying resistance genes bla KPC-2 and bla OXY-5, as well as IncF plasmids. The pairwise average nucleotide identity values of 5 isolates ranged from 99.993% to 99.999%. Moreover, these isolates displayed a maximum genetic difference of 3 among 5,229 targets in the core genome multilocus sequence typing scheme, and the razors were confirmed as the contamination source. After the implementation of controls and standardized shaving procedures, no new CRKO infections occurred. Conclusion: Contaminated razors can be sources of neurosurgical site infections with CRKO, and standard shaving procedures need to be established. Chromogenic selective medium can help rapidly identify targeted pathogens, and WGS technologies are effective mean in tracking the transmission source in an epidemic or outbreak investigation. Our findings increase the understanding of microbial transmission in surgery to improve patient care quality.
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Infecções por Klebsiella , Klebsiella oxytoca , Tipagem de Sequências Multilocus , Sequenciamento Completo do Genoma , Humanos , Klebsiella oxytoca/genética , Klebsiella oxytoca/isolamento & purificação , Klebsiella oxytoca/efeitos dos fármacos , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/transmissão , Carbapenêmicos/farmacologia , Antibacterianos/farmacologia , Infecção Hospitalar/microbiologia , beta-Lactamases/genética , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Compostos Cromogênicos , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Genoma Bacteriano/genética , Procedimentos Neurocirúrgicos/efeitos adversos , Masculino , FemininoRESUMO
Cys-loop receptors are a large superfamily of pentameric ligand-gated ion channels with various physiological roles, especially in neurotransmission in the central nervous system. Among them, zinc-activated channel (ZAC) is a Zn2+-activated ion channel that is widely expressed in the human body and is conserved among eukaryotes. Due to its gating by extracellular Zn2+, ZAC has been considered a Zn2+ sensor, but it has undergone minimal structural and functional characterization since its molecular cloning. Among the families in the Cys-loop receptor superfamily, only the structure of ZAC has yet to be determined. Here, we determined the cryo-EM structure of ZAC in the apo state and performed structure-based mutation analyses. We identified a few residues in the extracellular domain whose mutations had a mild impact on Zn2+ sensitivity. The constriction site in the ion-conducting pore differs from the one in other Cys-loop receptor structures, and further mutational analysis identified a key residue that is important for ion selectivity. In summary, our work provides a structural framework for understanding the ion-conducting mechanism of ZAC.
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Microscopia Crioeletrônica , Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína , Zinco , Zinco/metabolismo , Humanos , Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/metabolismo , Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/química , Receptores de Canais Iônicos de Abertura Ativada por Ligante com Alça de Cisteína/genética , Modelos Moleculares , Mutação , Conformação Proteica , Ativação do Canal IônicoRESUMO
BACKGROUND: In addition to their established action of synthetic lethality in tumor cells, poly(ADP-ribose) polymerase inhibitors (PARPis) also orchestrate tumor immune microenvironment (TIME) that contributes to suppressing tumor growth. However, it remains not fully understood whether and how PARPis trigger tumor-targeting immune responses. METHODS: To decode the immune responses reshaped by PARPis, we conducted T-cell receptor (TCR) sequencing and immunohistochemical (IHC) analyses of paired clinical specimens before and after niraparib monotherapy obtained from a prospective study, as well as ID8 mouse ovarian tumors. To validate the induction of immunogenic cell death (ICD) by PARPis, we performed immunofluorescence/IHC staining with homologous recombination deficiency tumor cells and patient-derived xenograft tumor tissues, respectively. To substantiate that PARPis elicited tumor cell pyroptosis, we undertook comprehensive assessments of the cellular morphological features, cleavage of gasdermin (GSDM) proteins, and activation of TNF-caspase signaling pathways through genetic downregulation/depletion and selective inhibition. We also evaluated the critical role of pyroptosis in tumor suppression and immune activation following niraparib treatment using a syngeneic mouse model with implanting CRISPR/Cas9 edited Gsdme-/ - ID8 tumor cells into C57BL/6 mice. RESULTS: Our findings revealed that PARPis augmented the proportion of neoantigen-recognized TCR clones and TCR clonal expansion, and induced an inflamed TIME characterized by increased infiltration of both innate and adaptive immune cells. This PARPis-strengthened immune response was associated with the induction of ICD, specifically identified as pyroptosis, which possessed distinctive morphological features and GSDMD/E cleavage. It was validated that the cleavage of GSDMD/E was due to elevated caspase 8 activity downstream of the TNFR1, rather than FAS and TRAIL-R. On PARP inhibition, the NF-κB signaling pathway was activated, leading to increased secretion of TNF-α and subsequent initiation of the TNFR1-caspase 8 cascade. Impeding pyroptosis through the depletion of Gsdme significantly compromised the tumor-suppressing effects of PARP inhibition and undermined the anti-immune response in the syngeneic ID8 mouse model. CONCLUSIONS: PARPis induce a specific type of ICD called pyroptosis via TNF-caspase 8-GSDMD/E axis, resulting in an inflamed TIME and augmentation of tumor-targeting immune responses. These findings deepen our understanding of PARPis activities and point toward a promising avenue for synergizing PARPis with immunotherapeutic interventions. TRIAL REGISTRATION NUMBER: NCT04507841.
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Neoplasias Ovarianas , Inibidores de Poli(ADP-Ribose) Polimerases , Piroptose , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Gasderminas , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Proteínas de Ligação a Fosfato/metabolismo , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Piroptose/efeitos dos fármacos , Transdução de Sinais , Microambiente Tumoral , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To evaluate the clinical effect of a new three-phase Chinese medicine (CM) external treatment for acute lateral ankle ligament injuries. METHODS: From July to December 2023, 64 patients with acute lateral ankle ligament injuries were randomly assigned to receive either the new three-phase CM external treatment combined with the POLICE(protect, optimal loading, ice, compression, elevation) treatment (observation group) or the POLICE treatment (control group), with 32 cases in each group. The observation group consisted of 17 males and 15 females, with an average age of(30.59±3.10) years old ranging from 25 to 36 years old, while the control group included 14 males and 18 females, with an average age of(30.03±3.19) years old ranging from 24 to 37 years old. Visual analogue scale (VAS) evaluation and Figure of 8 measurement were used to evaluate the degree of ankle joint pain and swelling of the subjects at the initial enrollment and after 1 week and sixth weeks of treatment. At the same time, the American Orthopaedic Foot and Ankle Society (AOFAS) and Karlsson Ankle Function Score System were used to evaluate the improvement of ankle joint function in patients at all stages. MRI imaging was employed to observe the degree of biological healing of the anterior talofibular ligament, with the signal to noise ratio(SNR) indicating the level of healing. A lower SNR suggests better ligament healing, as it represents lower water content in the ligament. RESULTS: All patients completed a 6-week follow-up. There was no significant difference in VAS, AOFAS score and Karlsson score between the two groups before treatment (P>0.05). After 1 week and 6 weeks of treatment, the VAS, AOFAS score and Karlsson score of the two groups were significantly improved (P<0.05). After 1 week of treatment, the VAS score of the observation group (3.21±0.87) was lower than that of the control group (4.21±1.50), and the difference was statistically significant (P<0.05). After 1 weeks of treatment, the AOFAS and Karlsson scores [(50.84±4.70) points, (49.97±4.00) points] of the observation group were higher than those [(46.91±5.56) points, (46.66±5.36) points]of the control group (P<0.05). MRI images showed that after 6 weeks of treatment, the SNR value of the observation group was significantly lower than that of the control group, and the difference was statistically significant(SNR of the observation group was 75.25±16.59, the contral gruop was 85.81±15.55), (P<0.05). CONCLUSION: Compared with the control group, the new three-phase CM external treatment is significantly effective in reducing pain and swelling, enhancing ligament repair quality, and promoting functional recovery of the ankle joint in patients with acute lateral malleolar ligament injuries.
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Traumatismos do Tornozelo , Ligamentos Laterais do Tornozelo , Humanos , Masculino , Feminino , Adulto , Traumatismos do Tornozelo/terapia , Ligamentos Laterais do Tornozelo/lesões , Resultado do Tratamento , Medicina Tradicional Chinesa , Tratamento Conservador/métodos , Adulto JovemRESUMO
Background and Objectives: This study aimed to investigate the association between insulin resistance, as measured by the triglyceride-glucose index (TyG index), and hearing impairment in middle-aged women in Korea. Materials and Methods: This cross-sectional survey utilized data from the Korea National Health and Nutrition Examination Survey (KNHANES) IV (2007-2009), specifically from the period after July 21, 2009, when hearing test results became available, and from the KNHANES V (2010-2012). This study was conducted on 5416 women aged 40 to 69 who had completed both the health examination survey and audiometric tests, excluding those with missing data on menopausal status and the use of hormone replacement therapy. Results: In the study group, the prevalence of high-frequency hearing loss according to the TyG index was significantly higher in the mild hearing loss group (OR = 1.29; 95% CI: 1.12, 1.49, p < 0.001) and the moderate hearing loss group (OR = 1.27; 95% CI: 1.09, 1.48, p = 0.002). Conversely, the prevalence of low-frequency hearing loss did not show a significant difference in either the mild hearing loss group (OR = 1.17; 95% CI: 0.99, 1.37, p = 0.065) and the moderate hearing loss group (OR = 1.13; 95% CI: 0.94, 1.35, p = 0.199) Conclusions: Since diabetes can induce hearing impairment in women, it is recommended that women with a high TyG index undergo early hearing tests.
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Glicemia , Perda Auditiva , Inquéritos Nutricionais , Triglicerídeos , Humanos , Feminino , República da Coreia/epidemiologia , Pessoa de Meia-Idade , Estudos Transversais , Perda Auditiva/epidemiologia , Perda Auditiva/sangue , Perda Auditiva/diagnóstico , Triglicerídeos/sangue , Adulto , Idoso , Glicemia/análise , Prevalência , Resistência à InsulinaRESUMO
COVID-19 survivors concerning about the rehabilitation and sustained sequelae of Coronavirus Disease 2019 (COVID-19) infection. We aimed to investigate the sequelae of patients' psychological and physical condition and its related factors in the early and late stages. This longitudinal study tracked 281 COVID-19 patients discharged from hospitals in Guangdong, China, for one year. Assessments occurred at 2,4,12,24 and 48 weeks post-discharge. We define 2 weeks, 4 weeks, and 12 weeks as early stage, and 24 weeks and 48 weeks as late stage. Psychological health was measured using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), and Pittsburgh Sleep Quality Index (PSQI) scales. Physical health was assessed through laboratory tests, chest computed tomography (CT) scans, and pulmonary function tests. Data were analyzed using multivariate regression models to evaluate the influence of demographic and clinical variables on health outcomes. COVID-19 survivors exhibited psychological and physical sequelae in both the early and late stages. Compared to the early stage, the proportions of patients with depression (early stage 14.6%, late stage 4.6%), anxiety (early stage 8.9%, late stage 5.3%), PTSD(early stage 3.6%, late stage 0.7%), abnormal liver function (early stage 24.6%, late stage 11.0%), abnormal cardiac function (early stage 10.0%, late stage 7.8%), abnormal renal function (early stage 20.6%, late stage 11.0%) and abnormal pulmonary function (early stage 40.9%, late stage 13.5%) were significantly reduced in the late stage. Factors such as gender, age, severity of COVID-19, hospitalization duration, and various comorbidities were significantly associated with these sequelae. We noticed that psychological and physical sequelae occurred to COVID-19 survivors in short and long stages, and these would gradually decrease as time went on. Male gender, age > 50 years old, severe clinical condition, longer hospitalization time and comorbidity history were related factors that significantly affected the rehabilitation of COVID-19 patients.
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COVID-19 , Alta do Paciente , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , COVID-19/complicações , Masculino , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Adulto , Prognóstico , Estudos Longitudinais , Idoso , SARS-CoV-2/isolamento & purificação , Ansiedade/epidemiologia , Depressão/epidemiologia , Depressão/etiologia , Pandemias , Sobreviventes , Transtornos de Estresse Pós-Traumáticos/epidemiologiaRESUMO
Introduction: This study compared, in high responders undergoing IVF treatment, GnRH agonist-only trigger and dual trigger on oocyte retrieval rate and cumulative live birth rate (LBR). The aim was to determine if the GnRH agonist-only triggers had provided outcomes comparable to dual trigger, while minimizing the risk of ovarian hyperstimulation syndrome (OHSS). Materials and methods: A retrospective, matched case-control study was conducted at Taichung Veterans General Hospital, Taiwan, including women who underwent IVF/ICSI between January 1, 2014, and December 31, 2022. Inclusion criteria were: GnRH antagonist protocol and estrogen level >3,000 pg/ml on trigger day. Exclusion criteria were: immune/metabolic diseases, donated oocytes, and mixed stimulation cycles. Propensity score matching was applied to balance age, AMH level, and oocyte number between the GnRH agonist-only and dual trigger groups. Outcomes were analyzed for patients who had complete treatment cycles, focusing on oocyte retrieval rate and cumulative LBR. Results: We analyzed 116 cycles in the agonist-only group, and 232 cycles in the dual trigger group. No inter-group difference was found in their age, BMI, and AMH levels. The dual trigger group had a higher oocyte retrieval rate (93% vs. 80%; p <0.05), while fertilization rates, blastocyst formation rates, and cumulative LBR were comparable. Notably, no OHSS cases had been reported in the GnRH agonist-only group, compared with 7 cases in the dual trigger group. Conclusion: GnRH agonist-only triggers resulted in a lower oocyte retrieval rate compared to dual triggers but did not significantly affect cumulative LBR in high responders. This approach effectively reduces OHSS risk without compromising pregnancy outcomes, making it a preferable option in freeze-all strategies, despite a longer oocyte pick-up duration and a medium cost. GnRH agonist-only trigger, however, may not be suitable for fresh embryo transfers or patients with low serum LH levels on trigger day.
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Coeficiente de Natalidade , Fertilização in vitro , Hormônio Liberador de Gonadotropina , Recuperação de Oócitos , Síndrome de Hiperestimulação Ovariana , Indução da Ovulação , Humanos , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Adulto , Recuperação de Oócitos/métodos , Indução da Ovulação/métodos , Estudos Retrospectivos , Gravidez , Estudos de Casos e Controles , Fertilização in vitro/métodos , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Síndrome de Hiperestimulação Ovariana/epidemiologia , Nascido Vivo/epidemiologia , Taxa de Gravidez , Fármacos para a Fertilidade Feminina/uso terapêutico , Fármacos para a Fertilidade Feminina/administração & dosagem , Taiwan/epidemiologia , Injeções de Esperma Intracitoplásmicas/métodosRESUMO
BACKGROUND/PURPOSE: Introducing complementary foods to infants is a critical stage in their healthy growth and development process. In this study, we analyzed the feeding habits and choices of caregivers in Taiwan during this essential transition period. METHODS: Data from the 2013-2016 Nutrition and Health Survey in Taiwan were analyzed. Using a multistage stratified sampling technique, we collected data through questionnaires on the feeding practices, challenges, and information sources associated with complementary feeding. We also investigated the timing of introducing various foods. Certain feeding indicators recommended by the World Health Organization were modified and used for analysis. RESULTS: Among 439 caregivers of infants aged 2-24 months, complementary feeding typically began at 5 months, and it primarily began with cereals and pureed foods. At 6-8 months of age, 98.29% of the infants received these foods. Only 48.39% of infants aged 6-24 months consumed eggs or flesh foods. Among the primary challenges for caregivers were concerns regarding infants' adaptation to new foods (38.2%), refusal of foods by infants (37.1%), and uncertainty regarding which foods to introduce (11.4%). The main sources of information were friends and family (46.9%), the Internet (46.5%), and baby care books (35.6%). Notably, approximately 51% of the respondents used commercial baby foods. CONCLUSION: In Taiwan, although the majority of infants begin complementary feeding on time, the introduction of eggs and flesh foods is typically delayed. Given the growing reliance on the Internet in the modern age, accurate feeding information should be disseminated online.
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BACKGROUND: Recent studies have shown an association between trace elements and systemic lupus erythematosus (SLE), but the relationship between trace elements and SLE is still unclear. This study aims to determine the distribution of plasma trace elements in newly diagnosed SLE patients and the association between these essential and toxic element mixtures and SLE. METHODS: In total, 110 SLE patients and 110 healthy controls were included. Blood samples were collected. 15 plasma trace elements were quantified using an inductively coupled plasma mass spectrometer (ICP-MS). Multivariate logistic regression, restricted cubic spline (RCS), weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) are used to analyze the association between single and mixed exposure of elements and SLE. RESULTS: The logistic regression model shows that, plasma lithium (Li) [OR (95â¯% CI): 1.963 (1.49-2.586)], vanadium (V) [OR (95â¯% CI): 2.617(1.645-4.166)] and lead (Pb) [OR (95â¯% CI): 1.603(1.197-2.145)] were positively correlated with SLE, while selenium (Se) [OR (95â¯% CI): 0.055(0.019-0.157)] and barium (Ba) [OR (95â¯% CI): 0.792(0.656-0.957)] had been identified as protective factors for SLE. RCS results showed a non-linear correlation between the elements Li, V, Ni, copper, Se, rubidium and SLE. In addition, WQS regression, qgcomp, and BKMR models consistently revealed significant positive effects of plasma Li and Pb on SLE, as well as significant negative effects of plasma Se. CONCLUSIONS: Exposure to heavy metals such as Li and Pb is significantly positively correlated with SLE, but Se may be protective factors for SLE. In addition, there is a nonlinear correlation between the elements Li and Se and SLE, and there are complex interactions between the elements. In the future, larger populations and prospective studies are needed to confirm these associations.
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P2X receptors, a subfamily of ligand-gated ion channels activated by extracellular ATP, are implicated in various physiopathological processes, including inflammation, pain perception, and immune and respiratory regulations. Structural determinations using crystallography and cryo-EM have revealed that the extracellular three-dimensional architectures of different P2X subtypes across various species are remarkably identical, greatly advancing our understanding of P2X activation mechanisms. However, structural studies yield paradoxical architectures of the intracellular domain (ICD) of different subtypes (e.g., P2X3 and P2X7) at the apo state, and the role of the ICD in P2X functional regulation remains unclear. Here, we propose that the P2X3 receptor's ICD has an apo state conformation similar to the open state but with a less tense architecture, containing allosteric sites that influence P2X3's physiological and pathological roles. Using covalent occupancy, engineered disulfide bonds and voltage-clamp fluorometry, we suggested that the ICD can undergo coordinated motions with the transmembrane domain of P2X3, thereby facilitating channel activation. Additionally, we identified a novel P2X3 enhancer, PSFL77, and uncovered its potential allosteric site located in the 1α3ß domain of the ICD. PSFL77 modulated pain perception in P2rx3+/+, but not in P2rx3-/-, mice, indicating that the 1α3ß, a "tunable" region implicated in the regulation of P2X3 functions. Thus, when P2X3 is in its apo state, its ICD architecture is fairly ordered rather than an unstructured outward folding, enabling allosteric modulation of the signaling of P2X3 receptors.
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Sítio Alostérico , Domínios Proteicos , Receptores Purinérgicos P2X3 , Animais , Humanos , Masculino , Camundongos , Trifosfato de Adenosina/metabolismo , Regulação Alostérica , Células HEK293 , Camundongos Endogâmicos C57BL , Receptores Purinérgicos P2X3/metabolismo , Receptores Purinérgicos P2X3/química , Receptores Purinérgicos P2X3/genéticaRESUMO
Ion chromatography is a technique commonly used to separate strongly polar and ionizable substances; it can be used to separate, identify, and quantify ionizable compounds in complex samples when coupled with mass spectrometry, and is currently being used in the application of food analysis, drug analysis, metabolomics and clinical poisoning analysis. Herein, we review the development of ion chromatography-mass spectrometry (IC-MS), its progress over the past 20 years, and future trends in the abovementioned areas. The IC-MS research progress and applications for the determination of inorganic anions, organic acids, polar pesticides, biogenic amines, and sugars in the food field are discussed. Drug analysis applications are discussed mainly in relation to the analysis of drug impurities, identifying drug degradation products, and determination of plasma concentration, while the separation and analysis of strongly polar metabolites, such as organic acids, sugar phosphates, and nucleotides in biological matrices are discussed in relation to metabolomics. Advances in the analysis of strongly polar or ionizable toxic compounds, such as alkyl methylphosphonic acid, methylphosphonic acid, glyphosate, 3-nitropropionic acid, and indandione rodenticides, are mainly discussed in clinical poisoning analysis field. This paper is expected to become a useful reference for the further expansion and application of IC-MS in the life and health fields.
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Espectrometria de Massas , Espectrometria de Massas/métodos , Humanos , Análise de Alimentos/métodos , Cromatografia por Troca Iônica/métodos , MetabolômicaRESUMO
The promotion of gut health, a pervasive problem in modern animal husbandry, positively affects organismal health, productivity, and economics. Porcine intestinal epithelial cells (IPEC-J2) continuously proliferate to maintain intestinal homeostasis, including barrier, immune, and absorptive functions. Gut homeostasis is fundamental to organismal health. ADP-ribosylation factor 1 (Arf1), a small GTPase, plays a crucial role in coordinating mTORC1 in response to nutrients, especially amino acid availability in the gut. mTORC1 is the central hub of proliferation. Thus, it seems likely that Arf1 promotes IPEC-J2 cell proliferation. However, the exact role of Arf1 in the porcine gut remains unclear. Therefore, we evaluated the functional role and possible mechanisms of Arf1 in the porcine intestine through Arf1 overexpression and knockdown in IPEC-J2 cells. Arf1 overexpression and knockdown significantly enhanced and inhibited, respectively, IPEC-J2 cell viability, and PCNA expression varied with Arf1 expression. Moreover, the proportion of Ki67-positive cells was significantly greater in the Arf1-overexpressing group than in the control group. These results suggest that Arf1 improves IPEC-J2 cell proliferation. The underlying mechanism was explored by Western blotting. Arf1 overexpression and knockdown significantly enhanced and suppressed, respectively, the levels of p-S6K1 and p-RPS6, which are key downstream targets of the mTORC1 signaling pathway. Collectively, our findings reveal the role of the Arf1-mTORC1 axis in IPEC-J2 cell proliferation and its potential function in regulating intestinal homeostasis and health.
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Fator 1 de Ribosilação do ADP , Proliferação de Células , Células Epiteliais , Mucosa Intestinal , Alvo Mecanístico do Complexo 1 de Rapamicina , Transdução de Sinais , Animais , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Suínos , Fator 1 de Ribosilação do ADP/metabolismo , Fator 1 de Ribosilação do ADP/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/citologia , Células Epiteliais/metabolismo , Células Epiteliais/citologia , Linhagem Celular , Sobrevivência Celular , Antígeno Nuclear de Célula em Proliferação/metabolismoRESUMO
Drug-resistant bacterial infections pose a significant challenge in the field of bacterial disease treatment. Finding new antibacterial pathways and targets to combat drug-resistant bacteria is crucial. The bacterial quorum sensing (QS) system regulates the expression of bacterial virulence factors. Inhibiting bacterial QS and reducing bacterial virulence can achieve antibacterial therapeutic effects, making QS inhibition an effective strategy to control bacterial pathogenicity. This article mainly focused on the PqsA protein in the QS system of Pseudomonas aeruginosa. An affinity chromatography medium was developed using the SpyTag/SpyCatcher heteropeptide bond system. Berberine, which can interact with the PqsA target, was screened from Phellodendron amurense by affinity chromatography. We characterized its structure, verified its inhibitory activity on P. aeruginosa, and preliminarily analyzed its mechanism using molecular docking technology. This method can also be widely applied to the immobilization of various protein targets and the effective screening of active substances.
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Antibacterianos , Cromatografia de Afinidade , Phellodendron , Pseudomonas aeruginosa , Percepção de Quorum , Percepção de Quorum/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/química , Phellodendron/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Simulação de Acoplamento Molecular , Avaliação Pré-Clínica de Medicamentos , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: A better understanding of the association between chronic kidney disease (CKD) and glaucoma is required to optimize clinical outcomes. Therefore, this study aimed to investigate the association of chronic kidney disease (CKD) with new diagnoses of glaucoma over time from January 2009 to December 2019. METHOD: This retrospective propensity-matched cohort study utilizing Taiwanese electronic health records examined the incidence of newly diagnosed glaucoma in patients with and without chronic kidney disease (CKD). The exposure variable was the diagnosis of CKD, identified through diagnostic codes. The primary outcome was the incidence of new-onset glaucoma. Subgroup analyses on glaucoma risk included age, gender, comorbidities, glaucoma subtypes, and dialysis status. Statistical analyses included Kaplan-Meier analysis, Cox proportional hazards models, and Poisson regression models, with the associated hazard ratios and confidence intervals reported. RESULTS: Seven hundred twenty-three thousand two hundred sixteen patients with CKD (42.3% female; mean [SD] age at index, 66.3 [15.6] years) and 723,216 patients without CKD (42.3% female; mean [SD] age at index, 66.3 [15.7]) were recruited. We showed a significantly increased risk of glaucoma irrespective of subtypes in CKD patients compared to those without CKD (HR: 1.29 [CI: 1.26-1.32], p < 0.001). Kaplan-Meier curves revealed a significantly increased glaucoma risk in both the dialytic subtype and non-dialytic CKD patients when compared to their non-CKD counterparts (p < 0.001). We also showed that all genders (aHR 1.17 [CI: 1.13-1.21] for females vs. aHR 1.39 [CI:1.35-1.43] for males), all ages (< = 49: aHR 1.49 [CI: 1.37-1.62]; 50-59: aHR 1.48 [CI: 1.40-1.56]; 60-69: aHR 1.30 [CI: 1.25-1.6]; 70-79: aHR 1.21 [CI: 1.17-1.26]; > 80: aHR 1.29 [CI: 1.21-1.37]); all income brackets and all urbanization status were associated with significantly increased risk of glaucoma from among the CKD cohort when compared to their respective non-CKD cohort (p < 0.001). CONCLUSIONS: Our cohort study spanning 12 years showed an elevated glaucoma risk following a CKD diagnosis compared to a frequency-matched non-CKD cohort. Our findings have relevance for the clinical practice of at-risk CKD patients. TRIAL REGISTRATION: Due to the retrospective nature of the study, no registration was necessary.
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Glaucoma , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Insuficiência Renal Crônica/epidemiologia , Pessoa de Meia-Idade , Taiwan/epidemiologia , Estudos Retrospectivos , Idoso , Glaucoma/epidemiologia , Incidência , Estudos de Coortes , Fatores de Risco , Medição de Risco/métodos , Idoso de 80 Anos ou mais , Modelos de Riscos Proporcionais , Comorbidade , AdultoRESUMO
Background: Insulin resistance contributes to the development of cardiovascular disease and type 2 diabetes mellitus. Smoking leads to an increase in triglyceride levels, which, in turn, increases insulin resistance. Although the number of e-cigarette users has increased in recent years, few studies have investigated the association between ecigarette use and insulin resistance. Therefore, this study aimed to determine the association between e-cigarette use and insulin resistance using the triglyceride-glucose (TyG) index in Korean adults. Methods: This study included 4,404 healthy adults aged ≥20 years who participated in the Korea National Health and Nutrition Examination Survey between 2019 and 2020. Participants were categorized as never-smokers or ecigarette users, and the TyG index was categorized into low- and high-TyG index groups according to the median value (9.22). A logistic regression analysis was performed to determine the association between e-cigarette smoking and insulin resistance. Results: E-cigarette users had a higher TyG index than never smokers (e-cigarette: mean=3.95; never: mean=9.18; P<0.001). The e-cigarette users had a higher risk of being in the high TyG index group than never-smokers (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.03-1.84). In the subgroup analysis stratified by sex, age, and body mass index, a higher OR for a high TyG index was observed in men (OR, 1.46; 95% CI, 1.03-2.08) and individuals aged 60 years or older (OR, 3.74; 95% CI, 1.14-12.30). Conclusion: Our findings suggest that e-cigarette use is significantly associated with insulin resistance.
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BACKGROUND: Premature and small-for-gestational-age (SGA) infants tend to have long-term growth morbidities such as short stature, failure to thrive, and obesity. Although most of these infants show catch-up growth at 2-4 years of age, they are still more susceptible to childhood obesity and related metabolic disorders. Those who fail to achieve catch-up will suffer from pathological short stature and neurodevelopmental impairment through adulthood. This study aims to depict the growth pattern of premature or SGA infants and their growth morbidities in Taiwan. METHODS: Data were obtained from a nationally representative cohort of 24,200 pairs of postpartum women and newborns in the Taiwan Birth Cohort Study (TBCS), using structured questionnaire interviews. A total of 16,358 infants were included and three follow-up surveys were completed at 6, 18, and 36 months after the deliveries. We constructed growth curves to conduct an in-depth investigation into anthropometric data, applying a linear mixed model. Logistic regression was used to model the relevant outcomes, with adjustment for various potential confounding factors. RESULTS: Despite being born shorter and lighter, preterm and SGA infants generally showed catch-up growth and had no higher odds ratios (ORs) of developing short stature or failure to thrive compared to appropriate-for-gestational-age (AGA) term infants before 3 years of age. Preterm SGA infants, particularly females, had higher ORs for obesity at the 36-month follow-up. CONCLUSION: This is the first nationwide population-based study depicting the growth of SGA infants in Taiwan. The growth patterns of preterm and term SGA infants are different from those of preterm and term AGA infants. Further research is necessary to understand the growth trajectories of preterm and SGA infants and their associations with later diseases.
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Cancer remains a significant challenge in extending human life expectancy in the 21st century, with staggering numbers projected by the International Agency for Research on Cancer for upcoming years. While conventional cancer therapies exist, their limitations, in terms of efficacy and side effects, demand the development of novel treatments that selectively target cancer cells. Tumor immunotherapy has emerged as a promising approach, but low response rates and immune-related side effects present significant clinical challenges. Researchers have begun combining immunotherapy with nanomaterials to optimize tumor-killing effects. Stimuli-responsive nanomaterials have become a focus of cancer immunotherapy research due to their unique properties. These nanomaterials target specific signals in the tumor microenvironment, such as pH or temperature changes, to precisely deliver therapeutic agents and minimize damage to healthy tissue. This article reviews the recent developments and clinical applications of endogenous and exogenous stimuli-responsive nanomaterials for tumor immunotherapy, analyzing the advantages and limitations of these materials and highlighting their potential for enhancing the immune response to cancer and improving patient outcomes.
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Imunoterapia , Nanoestruturas , Neoplasias , Microambiente Tumoral , Humanos , Imunoterapia/métodos , Neoplasias/terapia , Neoplasias/imunologia , Nanoestruturas/uso terapêutico , Microambiente Tumoral/imunologia , Microambiente Tumoral/efeitos dos fármacos , Animais , Concentração de Íons de HidrogênioRESUMO
The BioRED track at BioCreative VIII calls for a community effort to identify, semantically categorize, and highlight the novelty factor of the relationships between biomedical entities in unstructured text. Relation extraction is crucial for many biomedical natural language processing (NLP) applications, from drug discovery to custom medical solutions. The BioRED track simulates a real-world application of biomedical relationship extraction, and as such, considers multiple biomedical entity types, normalized to their specific corresponding database identifiers, as well as defines relationships between them in the documents. The challenge consisted of two subtasks: (i) in Subtask 1, participants were given the article text and human expert annotated entities, and were asked to extract the relation pairs, identify their semantic type and the novelty factor, and (ii) in Subtask 2, participants were given only the article text, and were asked to build an end-to-end system that could identify and categorize the relationships and their novelty. We received a total of 94 submissions from 14 teams worldwide. The highest F-score performances achieved for the Subtask 1 were: 77.17% for relation pair identification, 58.95% for relation type identification, 59.22% for novelty identification, and 44.55% when evaluating all of the above aspects of the comprehensive relation extraction. The highest F-score performances achieved for the Subtask 2 were: 55.84% for relation pair, 43.03% for relation type, 42.74% for novelty, and 32.75% for comprehensive relation extraction. The entire BioRED track dataset and other challenge materials are available at https://ftp.ncbi.nlm.nih.gov/pub/lu/BC8-BioRED-track/ and https://codalab.lisn.upsaclay.fr/competitions/13377 and https://codalab.lisn.upsaclay.fr/competitions/13378. Database URL: https://ftp.ncbi.nlm.nih.gov/pub/lu/BC8-BioRED-track/https://codalab.lisn.upsaclay.fr/competitions/13377https://codalab.lisn.upsaclay.fr/competitions/13378.
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Mineração de Dados , Processamento de Linguagem Natural , Humanos , Mineração de Dados/métodos , Bases de Dados Factuais , SemânticaRESUMO
BACKGROUND: Breast cancer treatments often have negative effects on fertility, which pose challenges among patients who want to be parents in the future. This study aimed to examine the efficacy of oocyte cryopreservation, embryo cryopreservation, and ovarian tissue cryopreservation in patients with breast cancer. METHODS: This retrospective review evaluated 42 patients with breast cancer who underwent fertility preservation at our center from January 2012 to December 2022. This review encompassed the demographic characteristics of the patients, cancer stages, treatment details, and types of fertility preservation procedures and their outcomes. RESULTS: The average age at disease diagnosis was 33.4 years. Approximately 90.4% of patients presented with early-stage cancer (≤2). Of 42 patients, 26 underwent oocyte cryopreservation; 17, embryo cryopreservation; and 2, ovarian tissue cryopreservation. Further, three patients received mixed treatment. The overall live birth rate was 63.2%. There are more live births in embryo cryopreservation group. The successful pregnancy group was significantly younger and had a remarkably higher quantity of preserved oocytes/embryos than the nonsuccessful pregnancy group. The oocyte and embryo utilization rates in cryopreservation were 7.69% and 52.94%, respectively. These findings underscored the importance of prompt, informed discussions about fertility preservation options. CONCLUSION: Fertility preservation in patients with breast cancer have promising reproductive outcomes, with embryo cryopreservation being particularly effective. Prompt counseling and individualized fertility preservation strategies are important for improving the likelihood of posttreatment pregnancy. Nevertheless, future research on the long-term psychological and emotional effects of different fertility preservation methods must be performed.