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Interleukin 15 (IL-15) is one of the most important cytokines that regulate the biology of natural killer (NK) cells1. Here we identified a signaling pathway-involving the serine-threonine kinase AKT and the transcription factor XBP1s, which regulates unfolded protein response genes2,3-that was activated in response to IL-15 in human NK cells. IL-15 induced the phosphorylation of AKT, which led to the deubiquitination, increased stability and nuclear accumulation of XBP1s protein. XBP1s bound to and recruited the transcription factor T-BET to the gene encoding granzyme B, leading to increased transcription. XBP1s positively regulated the cytolytic activity of NK cells against leukemia cells and was also required for IL-15-mediated NK cell survival through an anti-apoptotic mechanism. Thus, the newly identified IL-15-AKT-XBP1s signaling pathway contributes to enhanced effector functions and survival of human NK cells.
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Interleucina-15/metabolismo , Células Asesinas Naturales/inmunología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas de Dominio T Box/metabolismo , Proteína 1 de Unión a la X-Box/metabolismo , Supervivencia Celular , Células Cultivadas , Citotoxicidad Inmunológica , Regulación de la Expresión Génica , Granzimas/genética , Granzimas/metabolismo , Humanos , Fosforilación , Unión Proteica , Estabilidad Proteica , Transducción de Señal , Ubiquitinación , Respuesta de Proteína DesplegadaRESUMEN
Phase segregation is ubiquitously observed in immiscible mixtures, such as oil and water, in which the mixing entropy is overcome by the segregation enthalpy1-3. In monodispersed colloidal systems, however, the colloidal-colloidal interactions are usually non-specific and short-ranged, which leads to negligible segregation enthalpy4. The recently developed photoactive colloidal particles show long-range phoretic interactions, which can be readily tuned with incident light, suggesting an ideal model for studying phase behaviour and structure evolution kinetics5,6. In this work, we design a simple spectral selective active colloidal system, in which TiO2 colloidal species were coded with spectral distinctive dyes to form a photochromic colloidal swarm. In this system, the particle-particle interactions can be programmed by combining incident light with various wavelengths and intensities to enable controllable colloidal gelation and segregation. Furthermore, by mixing the cyan, magenta and yellow colloids, a dynamic photochromic colloidal swarm is formulated. On illumination of coloured light, the colloidal swarm adapts the appearance of incident light due to layered phase segregation, presenting a facile approach towards coloured electronic paper and self-powered optical camouflage.
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Although tumor-intrinsic fatty acid ß-oxidation (FAO) is implicated in multiple aspects of tumorigenesis and progression, the impact of this metabolic pathway on cancer cell susceptibility to immunotherapy remains unknown. Here, we report that cytotoxicity of killer T cells induces activation of FAO and upregulation of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme of FAO in cancer cells. The repression of CPT1A activity or expression renders cancer cells more susceptible to destruction by cytotoxic T lymphocytes. Our mechanistic studies reveal that FAO deficiency abrogates the prosurvival signaling in cancer cells under immune cytolytic stress. Furthermore, we identify T cell-derived IFN-γ as a major factor responsible for induction of CPT1A and FAO in an AMPK-dependent manner, indicating a dynamic interplay between immune effector cells and tumor targets. While cancer growth in the absence of CPT1A remains largely unaffected, established tumors upon FAO inhibition become significantly more responsive to cellular immunotherapies including chimeric antigen receptor-engineered human T cells. Together, these findings uncover a mode of cancer resistance and immune editing that can facilitate immune escape and limit the benefits of immunotherapies.
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Carnitina O-Palmitoiltransferasa , Neoplasias , Humanos , Carnitina O-Palmitoiltransferasa/genética , Citotoxicidad Inmunológica , Ácidos Grasos , Metabolismo de los Lípidos , Neoplasias/terapia , Linfocitos T CitotóxicosRESUMEN
Drosophila melanogaster is an ideal model organism for investigating spermatogenesis due to its powerful genetics, conserved genes and visible morphology of germ cells during sperm production. Our previous work revealed that ocnus (ocn) knockdown resulted in male sterility, and CG9920 was identified as a significantly downregulated protein in fly abdomen after ocn knockdown, suggesting a role of CG9920 in male reproduction. In this study, we found that CG9920 was highly expressed in fly testes. CG9920 knockdown in fly testes caused male infertility with no mature sperms in seminal vesicles. Immunofluorescence staining showed that depletion of CG9920 resulted in scattered spermatid nuclear bundles, fewer elongation cones that did not migrate to the anterior region of the testis, and almost no individualization complexes. Transmission electron microscopy revealed that CG9920 knockdown severely disrupted mitochondrial morphogenesis during spermatogenesis. Notably, we found that CG9920 might not directly interact with Ocn, but rather was inhibited by STAT92E, which itself was indirectly affected by Ocn. We propose a possible novel pathway essential for spermatogenesis in D. melanogaster, whereby Ocn indirectly induces CG9920 expression, potentially counteracting its inhibition by the JAK-STAT signaling pathway.
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Proteínas de Drosophila , Drosophila melanogaster , Mitocondrias , Espermatogénesis , Testículo , Animales , Espermatogénesis/genética , Espermatogénesis/fisiología , Masculino , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Mitocondrias/metabolismo , Testículo/metabolismo , Morfogénesis/genética , Transducción de Señal , Infertilidad Masculina/genética , Infertilidad Masculina/metabolismo , Técnicas de Silenciamiento del Gen , Factores de Transcripción STAT/metabolismo , Espermátides/metabolismoRESUMEN
Radiative thermal management provides a zero-energy strategy to reduce the demands of fossil energy for active thermal management. However, whether solar heating or radiative cooling, one-way temperature control will exacerbate all-season energy consumption during hot summers or cold winters. Inspired by the Himalayan rabbit's hair and Mimosa pudica's leaves, we proposed a dual-mode thermal-management device with two differently selective electromagnetic spectrums. The combination of visible and infrared "thermochromism" enables this device to freely switch between solar heating and radiative cooling modes by spontaneously perceiving the temperature without any external energy consumption. Numerical prediction shows that a dual-mode device exhibits an outstanding potential for all-season energy saving in terms of thermal management beyond most static or single-wavelength, range-regulable, temperature-responsive designs. Such a scalable and cost-efficient device represents a more efficient radiative thermal-management strategy toward applying in a practical scenario with dynamic daily and seasonal variations.
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BACKGROUND: Gut bacteria are beneficial to the host, many of which must be passed on to host offspring. During metamorphosis, the midgut of holometabolous insects undergoes histolysis and remodeling, and thus risks losing gut bacteria. Strategies employed by holometabolous insects to minimize this risk are obscure. How gut bacteria affect host insects after entering the hemocoel and causing opportunistic infections remains largely elusive. RESULTS: We used holometabolous Helicoverpa armigera as a model and found low Lactobacillus load, high level of a C-type lectin (CTL) gene CD209 antigen-like protein 2 (CD209) and its downstream lysozyme 1 (Lys1) in the midgut of the wandering stage. CD209 or Lys1 depletion increased the load of midgut Lactobacillus, which further translocate to the hemocoel. In particular, CD209 or Lys1 depletion, injection of Lactobacillus plantarum, or translocation of midgut L. plantarum into the hemocoel suppressed 20-hydroxyecdysone (20E) signaling and delayed pupariation. Injection of L. plantarum decreased triacylglycerol and cholesterol storage, which may result in insufficient energy and 20E available for pupariation. Further, Lysine-type peptidoglycan, the major component of gram-positive bacterial cell wall, contributed to delayed pupariation and decreased levels of triacylglycerols, cholesterols, and 20E, in both H. armigera and Drosophila melanogaster. CONCLUSIONS: A mechanism by which (Lactobacillus-induced) opportunistic infections delay insect metamorphosis was found, namely by disturbing the homeostasis of lipid metabolism and reducing 20E production. Moreover, the immune function of CTL - Lys was characterized for insect metamorphosis by maintaining gut homeostasis and limiting the opportunistic infections.
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Microbioma Gastrointestinal , Lisina , Animales , Drosophila melanogaster , Disbiosis , Bacterias , InmunidadRESUMEN
BACKGROUND: Frailty is associated with an increased risk of all-cause death and cardiovascular events. However, it is uncertain whether frailty modifies the efficacy and safety of intensive blood pressure control. METHODS: Data from SPRINT (Systolic Blood Pressure Intervention Trial) were used to construct a frailty index. Subgroup differences in intensive blood pressure control treatment effects and safety outcomes were measured on a relative and an absolute scale in patients with and without frailty (defined as a frailty index >0.21) using Cox proportional hazard models and generalized linear models, respectively. The primary outcome was a composite of myocardial infarction, acute coronary syndrome without myocardial infarction, stroke, heart failure, and cardiovascular death. RESULTS: A total of 9306 patients (mean age, 67.9±9.4 years), 2560 (26.7%) of whom had frailty, were included in our study. Over a median follow-up of 3.22 years, 561 primary outcomes were observed. Patients with frailty had a significantly higher risk of primary outcome in both the intensive and standard blood pressure control arms (adjusted hazard ratio, 2.10 [95% CI, 1.59-2.77] and 1.85 [95% CI, 1.46-2.35], respectively). Intensive treatment effects on primary and secondary outcomes were not significantly different on a relative scale (except for cardiovascular death [hazard ratio in patients with and without frailty, 0.91 (95% CI, 0.52-1.60) versus 0.30 (95% CI, 0.16-0.59), respectively; Pinteraction=0.01]) or absolute scale. There was no significant interaction between frailty and risks for serious adverse events with intensive treatment. CONCLUSIONS: Frailty status was a marker of high cardiovascular risk. Patients with frailty benefit similarly to other patients from intensive blood pressure control without an increased risk of serious adverse events.
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Fragilidad , Hipertensión , Infarto del Miocardio , Anciano , Humanos , Persona de Mediana Edad , Antihipertensivos/efectos adversos , Presión Sanguínea , Fragilidad/diagnóstico , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Hipertensión/complicaciones , Infarto del Miocardio/tratamiento farmacológico , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Effects of intensive blood pressure (BP) control on cognitive outcomes in patients with excess orthostatic BP changes are unclear. We aimed to evaluate whether orthostatic BP changes modified the effects of BP intervention on cognitive impairment. METHODS: We analyzed 8547 participants from the Systolic Blood Pressure Intervention Trial Memory and cognition IN Decreased Hypertension. Associations between orthostatic BP changes and incident cognitive outcomes were evaluated by restricted cubic spline curves based on Cox models. The interactions between orthostatic BP changes and intensive BP intervention were assessed. RESULTS: The U-shaped associations were observed between baseline orthostatic systolic BP changes and cognitive outcomes. However, there were insignificant interactions between either change in orthostatic systolic BP (P for interaction = 0.81) or diastolic BP (P for interaction = 0.32) and intensive BP intervention for the composite outcome of probable dementia or mild cognitive impairment (MCI). The hazard ratio of intensive versus standard target for the composite cognitive outcome was 0.82 (95% CI 0.50-1.35) in those with an orthostatic systolic BP reduction of >20 mmHg and 0.41 (95% CI 0.21-0.80) in those with an orthostatic systolic BP increase of >20 mmHg. Results were similar for probable dementia and MCI. The annual changes in global cerebral blood flow (P for interaction = 0.86) consistently favored intensive BP treatment across orthostatic systolic BP changes. CONCLUSION: Intensive BP control did not have a deteriorating effect on cognitive outcomes among hypertensive patients experiencing significant postural BP changes.
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Disfunción Cognitiva , Demencia , Hipertensión , Hipotensión Ortostática , Humanos , Presión Sanguínea , Cognición , Hipertensión/tratamiento farmacológico , Hipotensión Ortostática/psicologíaRESUMEN
BACKGROUND: Co-morbid hypertension is strong predictor of adverse cardiovascular (CV) outcomes in patients with atrial fibrillation (AF) but the optimal target for blood pressure (BP) control in this patient population has not been clearly defined. METHOD: The Cardiovascular Risk reduction in patients with Atrial Fibrillation Trial (CRAFT) is an investigator-initiated and conducted, international, multicenter, open-label, parallel-group, blinded outcome assessed, randomized controlled trial of intensive BP control in patients with AF. The aim is to determine whether intensive BP control (target home systolic blood pressure [SBP] <120 mmHg) is superior to standard BP control (home SBP <135 mmHg) on the hierarchical composite outcome of time to CV death, number of stroke events, time to the first stroke, number of myocardial infarction (MI) events, time to the first MI, number of heart failure hospitalization (HFH) events, and time to the first HFH. A sample size of 1675 patients is estimated to provide 80% power to detect a win-ratio of 1.50 for intensive versus standard BP control on the primary composite outcome. Study visits are conducted at 1, 2, 3, and 6 months post-randomization, and every 6 months thereafter during the study. CONCLUSION: This clinical trial aims to provide reliable evidence of the effects of intensive BP control in patients with AF.
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Fibrinogen is a protein that reflects systemic inflammation and regulates the immune response to disease. However, there is a scarcity of data on fibrinogen in recurrent aphthous stomatitis (RAS). We aimed to test the hypothesis that fibrinogen is involved in the aetiology of RAS. Between November 2016 and November 2018, we included 109 minor RAS patients and 29 age- and sex-matched controls in a single-center, observational study. Their clinical history and ulcer manifestations led to the diagnosis of minor RAS. The ulcer severity score (USS) was used to assess disease severity, and fibrinogen was also collected. We conducted three analyses: Analysis 1 (comparison of fibrinogen levels between patients and controls), Analysis 2 (comparison of fibrinogen levels between high and low USS patients) and Analysis 3 (comparison of fibrinogen levels between before and after anti-inflammatory treatment in patients). The fibrinogen levels in the 109 minor RAS patients were statistically higher than in the 29 controls (mean [SD], 2.6 [0.5] vs. 2.3 [0.3]; Student's t-test, p < 0.001). However, there were no significant differences in fibrinogen levels among the 43 patients with high USS and the 39 patients with low USS (mean [SD], 2.7 [0.5] vs. 2.6 [0.4]; Student's t-test, p = 0.278). Furthermore, fibrinogen levels were significantly higher before anti-inflammatory treatment in comparison to those after anti-inflammatory treatment in the 35 paired patients (mean [SD], 2.6 [0.4] vs. 2.5 [0.4]; Student's t-test, p = 0.026). Interestingly, fibrinogen levels were significantly higher in the 35 paired patients after anti-inflammatory treatment compared to the 29 control subjects (mean [SD], 2.5 [0.4] vs. 2.3 [0.3]; Student's t-test, p = 0.026]. Fibrinogen may play a role in the aetiology of RAS and may be a drug target for RAS treatment. Clinicians should be alert that high serum fibrinogen levels might be associated with the risk of RAS.
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Estomatitis Aftosa , Humanos , Estomatitis Aftosa/complicaciones , Estomatitis Aftosa/tratamiento farmacológico , Úlcera/complicaciones , Úlcera/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Fibrinógeno , ChinaRESUMEN
Proton tunneling is believed to be nonlocal in ice, but its range has been shown to be limited to only a few molecules. Here, we measured the thermal conductivity of ice under pressure up to 50 GPa and found it increases with pressure until 20 GPa but decreases at higher pressures. We attribute this nonmonotonic thermal conductivity to the collective tunneling of protons at high pressures, supported by large-scale quantum molecular dynamics simulations. The collective tunneling loops span several picoseconds in time and are as large as nanometers in space, which match the phonon periods and wavelengths, leading to strong phonon scattering at high pressures. Our results show direct evidence of global quantum motion existing in high-pressure ice and provide a new perspective to understanding the coupling between phonon propagation and atomic tunneling.
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BACKGROUND: During human early placentation, a proportion of extravillous trophoblasts (EVTs) migrate to the maternal decidua, differentiating into endovascular EVTs to remodel spiral arteries and ensure the establishment of blood circulation at the maternal-fetal interface. Inadequate EVT migration and endovascular differentiation are closely associated with adverse pregnancy outcomes such as miscarriage. Activin A and fibronectin are both secretory molecules abundantly expressed at the maternal-fetal interface. Activin A has been reported to regulate EVT biological functions. However, whether fibronectin mediates activin A-promoted EVT migration and acquisition of endothelial-like phenotype as well as the underlying molecular mechanisms remain unknown. Additionally, the role of fibronectin in pregnancy establishment and maintenance warrants further investigation. METHODS: Primary and immortalized (HTR8/SVneo) human EVTs were used as in vitro study models. Cultured human first-trimester chorionic villous explants were utilized for ex vivo validation. A local fibronectin knockdown model in ICR mouse uteri, achieved by nonviral in vivo transfection with small interfering RNA (siRNA) targeting fibronectin 1 (si-Fn1), was employed to explore the roles of fibronectin in the establishment and maintenance of early pregnancy. RESULTS: Our results showed that activin A treatment significantly induced fibronectin 1 (FN1) mRNA expression and fibronectin protein production, which is essential for human trophoblast migration and endothelial-like tube formation. Both basal and activin A-upregulated fibronectin expression were abolished by the TGF-ß type I receptor inhibitor SB431542 or siRNA-mediated knockdown of activin receptor-like kinase (ALK4) or SMAD4. Moreover, activin A-increased trophoblast migration and endothelial-like tube formation were attenuated following the depletion of fibronectin. Fibronectin knockdown via intrauterine siRNA administration reduced CD31 and cytokeratin 8 (CK8) expression at the maternal-fetal interface, resulting in a decrease in the number of implantation sites and embryos. CONCLUSIONS: Our study demonstrates that activin A promotes trophoblast cell migration and acquisition of endothelial-like phenotype via ALK4-SMAD2/3-SMAD4-mediated fibronectin upregulation. Furthermore, through a local fibronectin knockdown model in mouse uteri, we found that the absence of fibronectin at the maternal-fetal interface impedes endovascular migration of trophoblasts and decidual vascularization, thereby interfering with early embryo implantation and the maintenance of pregnancy. These findings provide novel insights into placental development during early pregnancy establishment and contribute to the advancement of therapeutic approaches for managing pregnancy complications related to trophoblast dysfunction.
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Activinas , Fibronectinas , Placenta , Embarazo , Ratones , Animales , Humanos , Femenino , Ratones Endogámicos ICR , Trofoblastos , ARN Interferente PequeñoRESUMEN
BACKGROUND: Visual-motor integration (VMI) is an essential skill in daily life. The present study aimed to use functional near-infrared spectroscopy (fNIRS) technology to explore the effective connectivity (EC) changes among brain regions during VMI activities of varying difficulty levels. METHODS: A total of 17 healthy participants were recruited for the study. Continuous Performance Test (CPT), Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), and Beery VMI test were used to evaluate attention performance, executive function, and VMI performance. Granger causality analysis was performed for the VMI task data to obtain the EC matrix for all participants. One-way ANOVA analysis was used to identify VMI load-dependent EC values among different task difficulty levels from brain network and channel perspectives, and partial correlation analysis was used to explore the relationship between VMI load-dependent EC values and behavioral performance. RESULTS: We found that the EC values of dorsal attention network (DAN) â default mode network (DMN), DAN â ventral attention network (VAN), DAN â frontoparietal network (FPN), and DAN â somatomotor network (SMN) in the complex condition were higher than those in the simple and moderate conditions. Further channel analyses indicated that the EC values of the right superior parietal lobule (SPL) â right superior frontal gyrus (SFG), right middle occipital gyrus (MOG) â left SFG, and right MOG â right postcentral gyrus (PCG) in the complex condition were higher than those in the simple and moderate conditions. Subsequent partial correlation analysis revealed that the EC values from DAN to DMN, VAN, and SMN were positively correlated with executive function and VMI performance. Furthermore, the EC values of right MOG â left SFG and right MOG â right PCG were positively correlated with attention performance. CONCLUSIONS: The DAN is actively involved during the VMI task and thus may play a critical role in VMI processes, in which two key brain regions (right SPL, right MOG) may contribute to the EC changes in response to increasing VMI load. Meanwhile, bilateral SFG and right PCG may also be closely related to the VMI performance.
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Encéfalo , Imagen por Resonancia Magnética , Adulto , Humanos , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Función Ejecutiva , Lóbulo ParietalRESUMEN
Oxytocin (OT), a hypothalamic nonaneuropeptide, can extensively modulate mental and physical activities; however, the regulation of its secretion from hypothalamic OT neurons remains poorly understood. OT neuronal activity is generally modulated by neurochemical environment, synaptic inputs, astrocytic plasticity, and interneuronal interactions. By changing intracellular signals and ion channel activity, these extracellular factors dynamically regulate OT neuronal activity and OT release in a microdomain-specific manner. In this process, OT receptor (OTR) and OTR-coupled G proteins are pivotal, typically observed during lactation. Suckling-elicited somatodendritic release of OT causes sequential activation of Gq and Gs proteins to increase the firing rate gradually and trigger burst firing transiently, and then of Gi/o protein to cause post-burst inhibition as a result of potential bolus somatodendritic release of OT during the burst-like discharges. Under chronic social stress like mother-baby separation and cesarean section, excessive somatodendritic secretion of OT and over-excitation of OT neurons cause post-excitation inhibition of OT neuronal activity and reduction of OT secretion. In this process, dominance of G protein that couples to OTR is switched from Gq to Gi/o type because of inhibition of OTR-Gq signaling following negative feedback of downstream Gq signaling or crosstalk of Gq with Gs and Gi signals. This review summarizes our current understandings of OT/OTR signaling in the autoregulation of OT neuronal activity under physiological and pathological conditions.
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Oxitocina , Receptores de Oxitocina , Embarazo , Femenino , Humanos , Oxitocina/metabolismo , Receptores de Oxitocina/metabolismo , Cesárea , Neuronas/metabolismo , Proteínas de Unión al GTP/metabolismo , HomeostasisRESUMEN
BACKGROUND: In this study, we conducted this population-based study to evaluate the genetic diversity and clustering rate of Mycobacterium tuberculosis (MTB) strains using the whole-genome sequencing (WGS), to better understand its transmission in Ordos. METHODS: All patients with culture-positive TB notified in Ordos from January 2021 to December 2022 were recruited. WGS was performed to analyze single-nucleotide polymorphism (SNP) and to identify genotypic drug susceptibilities of MTB isolates. RESULTS: Overall, a total of 186 patients were included in the present study, of whom 35 (18.8%) had no symptoms suggestive of active TB. Lineage 2 was the predominant MTB sublineage, accounting for 186 of isolates tested. When the pairwise SNP difference ≤ 12 was used as the cutoff for WGS-based clusters, we identified 17 genotypic clusters, and 38 isolates belonged to these 17 clusters, resulting in a clustering rate of 20.4%. The Beijing genotype was an independent factor associating with genomic-clustering (adjusted OR 4.219, 95% CI 0.962-18.502). The overall sensitivity on WGS-based resistance prediction was 85.7% for rifampicin, 73.1% for isoniazid, 60.0% for Ethambutol, 72.7% for streptomycin, and 72.7% for fluoroquinolones. CONCLUSION: To conclude, the present study demonstrates the extensive recent transmission of Beijing genotype strains in the community of Ordos. The failure to provide a comprehensive pattern of transmission indicated the missed diagnosis of active TB within the community. A substantial proportion of subclinical TB cases are recognized in the bacteria-positive cases, emphasizing that we must interrupt transmission by finding people with active TB before they infect others.
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Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Epidemiología Molecular , Isoniazida , Genotipo , China/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Farmacorresistencia Bacteriana Múltiple/genéticaRESUMEN
OBJECTIVE: The aim of this study was to evaluate the efficacy, safety, and surgical outcomes of 2-stage management, namely preoperative endoscopic retrograde cholangiopancreatography (ERCP) + laparoscopic cholecystectomy (ERCP+LC) or LC + postoperative ERCP (LC+ERCP), as well as 1-stage management, LC + laparoscopic common bile duct exploration (LCBDE) for treating patients with gallstones and common bile duct stones (CBDS). METHODS: This retrospective study analyzed the data of 180 patients with common bile duct stones (CBDS) who were admitted to the Department of General Surgery at Tongji Hospital, Tongji University, between January 2019 and June 2021. The study included 3 groups: ERCP+LC (group 1), LC+ERCP (group 2), and LC+LCBDE (group 3), each consisting of 60 patients. Clinical metrics of the patients were collected and compared among the groups. RESULTS: Group 3 had the shortest operation duration and hospital stay compared with group 1 and group 2. In addition, group 3 had the lowest long-term postoperative complications, particularly the recurrence rate of CBDS. The total cost was also the lowest in group 3. Furthermore, patients in group 3 had the lowest postoperative amylase levels. All patients in the study achieved successful stone clearance. There were no significant differences in the conversion to other procedures rate, postoperative alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and mortality among the three groups (P > 0.05). CONCLUSIONS: Both 1-stage management and 2-stage management are effective treatments for CBDS. The LC+LCBDE management is a safe treatment option, offering shorter hospital stays and operation duration, lower costs, and fewer complications.
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The identification of hypothermia death (HD) is difficult for cadavers, especially the distinction from death due to alternative causes. A large number of studies have shown that brown adipose tissue (BAT) plays critical roles in thermoregulation of mammals. In this study, BAT of mice was used for the discrimination of HD using attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR). A modified mouse HD model conducted by Feeney DM was used in this study to obtain infrared spectra of BAT. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to establish discrimination models. The PLS-DA and OPLS-DA models exhibit prominent discriminative efficiency, and the accuracy of HD identification using fingerprint regions and ratios of absorption intensity is near 100% in both the calibration and validation sets. Our preliminary study suggests that BAT may be an extremely effective target tissue for identification of cadavers of HD, and ATR-FTIR spectra combined with chemometrics have also shown potential for cadaver identification in forensic practice in a fast and accurate manner.
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Hipotermia , Animales , Ratones , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Análisis Discriminante , Análisis de los Mínimos Cuadrados , Cadáver , MamíferosRESUMEN
OBJECTIVES: To test the hypothesis that cardiovascular diseases and risk factors are associated with ulcer relapse in after-retirement patients with recurrent aphthous stomatitis. SUBJECTS AND METHODS: This retrospective cohort study analyzed the data of 40 minor recurrent aphthous stomatitis patients aged 55-75 years, admitted to Oral Medicine Clinic at one university hospital in China between 2016 and 2018. The diagnosis of minor recurrent aphthous stomatitis was made based on the history and manifestation of oral ulcers. The ulcer relapse was evaluated after a 5-week anti-inflammatory treatment, and the history of systemic diseases was collected. cardiovascular disease/metabolic risk referred to the presence of any cardiovascular diseases and metabolic cardiovascular disease risks. Associations among cardiovascular diseases, risk factors, and ulcer relapse were evaluated. RESULTS: The mean age of 40 patients with minor recurrent aphthous stomatitis was 62.4 years (SD 5.1), and 60% were women. The ulcer relapse rate was 37.5% (95% CI, 0.242-0.530). The proportion of cardiovascular disease/metabolic risk was higher in the relapse group than in the no-relapse group after 5-week anti-inflammatory treatment (Fisher's exact test, p = 0.041). CONCLUSIONS: According to this single-center experience, older patients with cardiovascular disease/metabolic risk may be more prone to oral ulcer recurrence. Nevertheless, larger prospective studies are needed to confirm our findings.
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Enfermedades Cardiovasculares , Úlceras Bucales , Estomatitis Aftosa , Humanos , Femenino , Anciano , Adulto , Masculino , Estomatitis Aftosa/tratamiento farmacológico , Estomatitis Aftosa/etiología , Úlcera/complicaciones , Estudios Retrospectivos , Factores de Riesgo , Úlceras Bucales/complicaciones , Antiinflamatorios/uso terapéutico , Enfermedad Crónica , RecurrenciaRESUMEN
BACKGROUND: The causes of vitamin B12 (B12) deficiency are varied and mainly related to gastric disorders. Glossitis is a common oral manifestation of B12 deficiency and is often first seen by dentists. This study aimed to investigate the correlation between B12 deficiency-related glossitis (B12-def glossitis) and gastric serum biomarkers [gastrin-17(G17), pepsinogen I (PGI), pepsinogen II (PGII), and anti-Helicobacter pylori (H. pylori) antibodies], and preliminarily discuss the etiology of B12-def glossitis. METHODS: A cross-sectional study was conducted in patients complaining of glossodynia, burning sensation, or severe recurrent oral ulcers, but patients with a history of gastrectomy were excluded. All subjects underwent a uniform oral examination and hematological tests. RESULTS: Of 243 patients, 133 with B12-def glossitis were in the case group, and 110 with other oral mucosal diseases (non-glossitis) and normal B12 levels were in the control group. In the case group, 84.2% (112/133) showed high G17 and low PGI levels (G17hi PGIlow ). Univariate logistic regression showed that G17hi PGIlow was a high-risk factor for B12-def glossitis (OR: 92.44; 95% CI: 35.91, 238.02). Subgroup analyses in the case group showed that the G17hi PGIlow group presented with lower B12 levels and a lower positive rate of anti-H. pylori antibodies compared to the non-G17hi PGIlow group. CONCLUSION: Gastric serum biomarkers in patients with B12-def glossitis generally showed G17hi PGIlow , suggesting possible atrophy of gastric corpus and fundus mucosa. The G17hi PGIlow and non-G17hi PGIlow groups may represent different etiologies of B12 deficiency.
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Gastrinas , Glositis , Infecciones por Helicobacter , Humanos , Pepsinógeno A , Mucosa Gástrica/patología , Estudios Transversales , Biomarcadores , Glositis/etiología , Glositis/patología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/diagnósticoRESUMEN
Uranium is considered as a very important nuclear energy material because of the huge amount of energy it releases. As the main product of the spontaneous decay of uranium, it is difficult for helium to react with uranium because of its chemical inertness. Therefore, bubbles will be formed inside uranium, which could greatly reduce the performance of uranium or cause safety problems. Additionally, nuclear materials are usually operated in an environment of high-temperature and high-pressure, so it is necessary to figure out the exact state of helium inside uranium under extreme conditions. Here, we explored the structural stability of the U-He system under high pressure and high temperature by using density functional theory calculations. Two metastable phases are found between 50 and 400 GPa: U4He with space group Fmmm and U6He with space group P1Ì. Both are metallic and adopt layered structures. Electron localization function calculation combined with charge density difference analysis indicates that there are covalent bonds between U and U atoms in both Fmmm-U4He and P1Ì-U6He. Regarding the elastic modulus of α-U, the addition of helium has certain influence on the mechanical properties of uranium. Besides, first-principles molecular dynamics simulations were carried out to study the dynamical behavior of Fmmm-U4He and P1Ì-U6He at high-temperature. It was found that Fmmm-U4He and P1Ì-U6He undergo one-dimensional superionic phase transitions at 150 GPa. Our study revealed the exotic structure of U-He compounds beyond the formation of bubbles under high-pressure and high-temperature, which might be relevant to the performance and safety issues of nuclear materials under extreme conditions.