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There is insufficient evidence to guide dose and frequency optimization with repeated-dose ketamine for depression. This study assessed the value of symptomatic non-improvement after the first few ketamine infusions as a predictor of overall non-response in depression for early decision-making to discontinue treatment. A total of 135 individuals with major depressive disorder or bipolar disorder experiencing a current major depressive episode were administered six repeated doses of intravenous ketamine. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, 4 h after the first infusion, and 24 h after each infusion. Improvement, partial response, and response were defined as a reduction rate of ≥ 20%, 30%, and 50% in MADRS scores, respectively. This study examined the relationship between improvement (as opposed to non-improvement after each infusion or consecutive non-improvements after the first few infusions) and partial response and response after the sixth infusion. This analysis was summarized using sensitivity, specificity, and other diagnostic test parameters. The sensitivities of improvement at 24 h post-infusion 4 and improvement at 24 h post-infusion 3, vs. three consecutive non-improvements, as predictors for overall partial response and response exceeded 90%. No significant reduction in depressive symptoms was seen in non-improvers following the remaining infusions after the above-identified point. Our study suggests that non-improvement after four infusions, or more conservatively three consecutive non-improvements after three infusions, could serve as a signal of overall non-response to repeated-dose intravenous ketamine for depression and that subsequent treatments would not be warranted.
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Trastorno Bipolar , Trastorno Depresivo Mayor , Ketamina , Humanos , Ketamina/administración & dosificación , Trastorno Bipolar/tratamiento farmacológico , Femenino , Masculino , Adulto , Trastorno Depresivo Mayor/tratamiento farmacológico , Persona de Mediana Edad , Infusiones Intravenosas , Escalas de Valoración Psiquiátrica , Resultado del Tratamiento , Antidepresivos/administración & dosificación , Antidepresivos/uso terapéuticoRESUMEN
Pollution fluxes from rivers into the sea are currently the main source of pollutants in nearshore areas. Based on the source-sink process of the basin-estuary-coastal waters system, the pollution fluxes into the sea and their spatiotemporal heterogeneity were estimated. A deep learning-based model was established to simplify the estimation of pollution fluxes into the sea, with socio-economic drivers and meteorological data as input variables. A method for estimating the contribution rate of pollution fluxes from different spatial gradient was proposed. In this study, we found that (1) the pollution fluxes into the sea of total nitrogen (TN) and total phosphorus (TP) from the Bohai Sea Rim Basin (BSRB) in 1980, 1990, 2000, 2010, and 2020 were 25.38 × 104, 26.12 × 104, 27.27 × 104, 29.82 × 104, 25.31 × 104 and 1.32 × 104, 2.14 × 104, 2.09 × 104, 1.87 × 104, 1.68 × 104 tons, respectively. (2) The proportion of rural life and livestock to the TN was the highest, accounting for 39.18 % and 21.19 %, respectively. The proportion of livestock to the TP was the highest, accounting for 39.20 %, followed by rural life, accounting for 24.72 %. The results indicated that the pollution fluxes in the BSRB were related to human economic activities and relevant environmental protection measures. (3) The deep learning-based model established to estimate runoff pollution fluxes into the sea had the accuracy of over 90 %. (4) As for contribution rate, in terms of the elevation, the range of 0-100 m had the highest proportion, accounting for 39.65 %. The range of 50-100 km from the coastline had the highest proportion, accounting for 18.11 %. In terms of the district, coastal area has the highest proportion, accounting for 38.00 %. This study revealed the changing trends and driving mechanisms of pollution fluxes into the sea over the past 40 years and established a simplified deep learning-based model for estimating pollution fluxes into the sea. Then, we identified regions with high pollution contribution rate. The results can provide scientific references for the adaptive management of the nearshore areas based on the ecosystem.
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BACKGROUND: Benzene exposure has been associated with increased leukemia and other cancer risk; however, epidemiological evidence is inconsistent for the latter and confounding from smoking and alcohol was rarely adjusted. METHODS: We investigated associations of occupational benzene exposure and risk of leukemia, lymphoma, myeloma, lung, stomach, liver, and kidney cancers in a population-based cohort of 61,377 men ages 40-74. A job-exposure matrix, constructed by industrial hygienists specifically for the study population, was used to derive cumulative benzene exposure from all jobs held. Cox regressions were performed to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for benzene-cancer risk associations with adjustment for potential confounders. RESULTS: Over 15-years of follow-up, 1,145 lung, 656 stomach, 445 liver, 243 kidney cancer cases, 100 leukemia, 124 lymphoma, and 46 myeloma cases were identified. Benzene exposure >550mg/m3 was associated with increased leukemia (aHR=2.3, 95%CI=1.1-4.5), lung (aHR=1.2, 95%CI=1.0-1.6), and stomach (aHR=1.4, 95%CI=1.0-1.9) cancer risk; benzene-exposure was associated with early cancer diagnosis age. The benzene-leukemia and -stomach cancer associations followed a linear dose-response pattern (Plinear=0.016 and 0.023), whereas benzene-lung cancer association was evident at higher exposure levels (Pnon-linear=0.027). Alcohol consumption modified the benzene-leukemia association (HR=3.0, 95%CI=1.1-8.3 for drinkers, aHR=0.9, 95%CI=0.4-2.0 for non-drinkers, Pinteraction=0.047). CONCLUSIONS: Benzene exposure was associated with increased leukemia, stomach, and lung cancer risk. Alcohol consumption may modify the benzene-leukemia association, although estimates are imprecise. IMPACT: Our study provides additional evidence that benzene exposure increases cancer risk beyond leukemia, information important for policymakers to develop programs to mitigate cancer risk among benzene-exposed workers.
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BACKGROUND: Within the tumor microenvironment, survival pressures are prevalent with potent drivers of tumor progression, angiogenesis, and therapeutic resistance. N6-methyladenosine (m6A) methylation has been recognized as a critical post-transcriptional mechanism regulating various aspects of mRNA metabolism. Understanding the intricate interplay between survival pressures and m6A modification provides new insights into the molecular mechanisms underlying hepatocellular carcinoma (HCC) progression and highlights the potential for targeting the survival pressures-m6A axis in HCC diagnosis and treatment. DATA SOURCES: A literature search was conducted in PubMed, MEDLINE, and Web of Science for relevant articles published up to April 2024. The keywords used for the search included hepatocellular carcinoma, cellular survival, survival pressure, N6-methyladenosine, tumor microenvironment, stress response, and hypoxia. RESULTS: This review delves into the multifaceted roles of survival pressures and m6A RNA methylation in HCC, highlighting how survival pressures modulate the m6A landscape, the impact of m6A modification on survival pressure-responsive gene expression, and the consequent effects on HCC cell survival, proliferation, metastasis, and resistance to treatment. Furthermore, we explored the therapeutic potential of targeting this crosstalk, proposing strategies that leverage the understanding of survival pressures and m6A RNA methylation mechanisms to develop novel, and more effective treatments for HCC. CONCLUSIONS: The interplay between survival pressures and m6A RNA methylation emerges as a complex regulatory network that influences HCC pathogenesis and progression.
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The cytoskeleton is essential for mechanical signal transduction and autophagy. However, few studies have directly demonstrated the contribution of the cytoskeleton to mechanical stress-induced autophagy. We explored the role of the cytoskeleton in response to compressive force-induced autophagy in human cell lines. Inhibition and activation of cytoskeletal polymerization using small chemical molecules revealed that cytoskeletal microfilaments are required for changes in the number of autophagosomes, whereas microtubules play an auxiliary role in mechanical stress-induced autophagy. The intrinsic mechanical properties and special intracellular distribution of microfilaments may account for a large proportion of compression-induced autophagy. Our experimental data support that microfilaments are core components of mechanotransduction signals.
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Objective: This study aimed to elucidate the risk factors associated with alcohol use disorders (AUDs) among inpatients with schizophrenia at a specialized mental hospital in Baoding city, China. Methods: This cross-sectional survey comprised 301 comorbid patients. Three binary logistic regression models were used to investigate the factors linked to AUDs in patients with schizophrenia. Propensity score matching analysis was conducted to validate inconsistent variables identified by the regression models. Results: Significant differences were observed between the comorbid and non-comorbid groups concerning sex (P < .001), disposition (P = .049), smoking habits (P < .001), place of residence (P = .010), family relationships (P = .002), family history of mental disorders (P = .008), history of alcoholism (P = .003), onset latency (P = .005), impulsivity (P < .001), suicide or self-injury history (P < .001), and obvious aggressive behavior (P < .001) in univariate analyses. The area under the curve values for the three regression models were 0.83 (P < .001), 0.80 (P < .001), and 0.81 (P < .001), respectively. Binary logistic regression and propensity score matching analyses indicated that introverted disposition, smoking, acute onset, impulsivity, and suicide or self-injury history were independent risk factors associated with AUDs in inpatients with schizophrenia with an odds ratio of > 1. Conclusion: Introverted disposition, smoking, acute onset, impulsivity, and suicide or self-injury history were independently associated with the AUDs in inpatients with schizophrenia. Future studies should prioritize longitudinal studies to discern the evolving dynamics of potential confounding risk factors.
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The corpus callosum is an oligodendrocyte-enriched brain region, replenished by newborn oligodendrocytes from oligodendrocyte progenitor cells (OPCs) in subventricular zone (SVZ). Lead (Pb) exposure has been associated with multiple sclerosis, a disease characterized by the loss of oligodendrocytes. This study aimed to investigate effects of Pb exposure on oligodendrogenesis in SVZ and myelination in corpus callosum. Adult female mice were used for a disproportionately higher prevalence of multiple sclerosis in females. Acute Pb exposure (one ip-injection of 27 mg Pb/kg as PbAc2 24 hrs before sampling) caused mild Pb accumulation in corpus callosum. Ex vivo assay using isolated SVZ tissues collected from acute Pb-exposed brains showed a diminished oligodendrogenesis in SVZ-derived neurospheres compared to controls. In vivo subchronic Pb exposure (13.5 mg Pb/kg by daily oral gavage 4 wks) revealed significantly decreased newborn BrdU+/MBP+ oligodendrocytes in corpus callosum, suggesting demyelination. Mechanistic investigations indicated decreased Rictor in SVZ OPCs, defective self-defense pathways, and reactive gliosis in corpus callosum. Given the interwined pathologies between multiple sclerosis and Alzheimers's disease, effect of Pb on myelination was evalued in AD-modeled APP/PS1 mice. Myelin MRI on mice following chronic exposure (1000 ppm Pb in drinking water as PbAc2 for 20 wks) revealed a profound demyelination in corpus callosum compared to controls. Immunostaining of choroid plexus showed diminished signalling molecule (Klotho, OTX2) expressions in Pb-treated animals. These observations suggest that Pb caused demyelination in corpus callosum, likely by disrupting oligodendrogenesis from SVZ OPCs. Pb-induced demyelination represents a crucial pathogenic pathway in Pb neurotoxicity, including multiple sclerosis.
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Panax notoginseng and Panax quinquefolium are important economic plants that utilize dried roots for medicinal and food dual purposes; there is still insufficient research of their stems and leaves, which also contain triterpenoid saponins. The extraction process was developed with a total saponin content of 12.30 ± 0.34% and 12.19 ± 0.64% for P. notoginseng leaves (PNL) and P. quinquefolium leaves (PQL) extracts, respectively. PNL and PQL saponin extracts showed good antioxidant, antihypertensive, hypoglycemic, and anti-inflammatory properties in vitro and RAW264.7 cells. A total of 699 metabolites were identified in PNL and PQL saponin extracts, with the majority being triterpenoid saponins, flavonoids and amino acids. Fourteen ginsenosides, 18 flavonoids or alkaloids, and 16 amino acids were enriched in both saponin extracts. Overall, the utilization of saponins from medicinal plants PNL and PQL has been developed to facilitate systematic research in the functional food and natural product industries.
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The synthesis of novel water-soluble polymers with biodegradability is an effective way to mitigate their negative environmental impacts. In this study, semi-aromatic copolyester poly(butylene succinate-co-butylene terephthalate) (PBST) with exceptional biodegradability is used as the resin matrix. Anionic sodium 1-3-isophthalate-5-sulfonate (SIPA) is introduced as a fourth monomer to prepare random poly(butylene succinate-co-butylene terephthalate-co-butylene 5-sodiosulfoisophthalate) (PBSTS) copolyesters by melt copolymerization. The incorporation of ionic groups enhances the hydrophilicity and water absorption of the copolyesters, resulting in water-soluble materials that exhibit ionic and temperature responsivity. Furthermore, the ionized biodegradable copolyesters demonstrate distinct pH-dependent degradation, which is accelerated at pH = 5.5 and 8.5 but inhibited at pH = 7.2. Degradation assessments in simulated body fluids reveal that the PBSTS copolyesters exhibit significant degradation in gastric fluids at pH = 1.5 with minimal degradation in intestinal fluids at pH = 6.8 and in body fluids at pH = 7.0. This unique degradation performance highlights the potential of these materials for addressing the challenges associated with selective drug delivery and localized controlled release in the human body.
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Circular RNA (CircRNA)-microRNA (miRNA) interaction (CMI) is an important model for the regulation of biological processes by non-coding RNA (ncRNA), which provides a new perspective for the study of human complex diseases. However, the existing CMI prediction models mainly rely on the nearest neighbor structure in the biological network, ignoring the molecular network topology, so it is difficult to improve the prediction performance. In this paper, we proposed a new CMI prediction method, BEROLECMI, which uses molecular sequence attributes, molecular self-similarity, and biological network topology to define the specific role feature representation for molecules to infer the new CMI. BEROLECMI effectively makes up for the lack of network topology in the CMI prediction model and achieves the highest prediction performance in three commonly used data sets. In the case study, 14 of the 15 pairs of unknown CMIs were correctly predicted.
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Biología Computacional , MicroARNs , ARN Circular , MicroARNs/genética , MicroARNs/metabolismo , MicroARNs/química , ARN Circular/genética , ARN Circular/metabolismo , Humanos , Biología Computacional/métodos , ARN/química , ARN/genética , ARN/metabolismo , Algoritmos , Redes Reguladoras de GenesRESUMEN
INTRODUCTION: Physical inactivity and sedentary behavior are recognized as independent risk factors for many diseases. However, studies investigating their associations with total and cause-specific mortality in low-income and Black populations are limited, particularly among older adults. METHODS: A prospective cohort study was conducted among 8,337 predominantly low-income and Black Americans aged ≥65 years residing in the southern United States. Participants reported their daily sitting time and leisure-time physical activity (LTPA) at baseline (2002-2009), and mortality data were collected through 2019. Analysis was conducted from September 2022 to October 2023. RESULTS: During a median follow-up of 12.25 years, nearly 50% (n=4,111) were deceased. A prolonged sitting time (>10 hours/day versus <4 hours/day) was associated with elevated all-cause mortality (hazard ratios [HR], 1.15; 95% confidence intervals [CI], 1.04-1.27) after adjusting for LTPA and other potential confounders. LTPA was associated with a reduced risk of all-cause mortality, with an adjusted HR of 0.75 (95% CI 0.64, 0.88) associated with 150-300 minutes per week of moderate-intensity physical activity. Individuals who were physically inactive and had a sitting time of >10 hours/day had the highest mortality risk (HR, 1.48; 95% CI, 1.23-1.78), compared with those who were physically active and had low sitting time. These associations were more pronounced for mortality due to cardiovascular diseases. CONCLUSIONS: High sitting time is an independent risk factor for all-cause and cardiovascular disease mortality, and LTPA could partially attenuate the adverse association of prolonged sitting time with mortality.
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This article devises a new dynamic double event-triggered anti-disturbance tracking control scheme for a 2-degree of freedom (DOF) laboratory helicopter subject to external time-varying disturbances and load fluctuation by using the generalized proportional-integral observer technique. The helicopter system is separated into two subsystems in the proposed control method, i.e., the pitch subsystem and the yaw subsystem. Each subsystem includes a discrete-time dynamic double event-triggering mechanism (DDETM), and the control laws of the two subsystems are independent of each other. There are two triggering conditions in the designed double triggering mechanism: one is designed based on the system states and the other is based on the lumped disturbance estimation. These two triggering conditions form a competitive relationship such that the controller updates the control signal as long as one of the triggering conditions is satisfied. Theoretical analysis is provided for achieving the better communication and control performance of the proposed DDETM-based robust control method. Through rigorous stability analysis, it is proved that the closed-loop hybrid system is globally ultimately bounded. At last, numerical simulations show that the suggested control strategy not only reduces the event-triggering number, but also improves the initial dynamic performance of the system.
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Organic-inorganic hybrid manganese(II) halides (OIMnHs) have garnered tremendous interest across a wide array of research fields owing to their outstanding optical properties, abundant structural diversity, low-cost solution processibility, and low toxicity, which make them extremely suitable for use as a new class of luminescent materials for various optoelectronic applications. Over the past years, a plethora of OIMnHs with different structural dimensionalities and multifunctionalities such as efficient photoluminescence (PL), radioluminescence, circularly polarized luminescence, and mechanoluminescence have been newly created by judicious screening of the organic cations and inorganic Mn(II) polyhedra. Specifically, through precise molecular and structural engineering, a series of OIMnHs with near-unity PL quantum yields, high anti-thermal quenching properties, and excellent stability in harsh conditions have been devised and explored for applications in light-emitting diodes (LEDs), X-ray scintillators, multimodal anti-counterfeiting, and fluorescent sensing. In this review, the latest advancements in the development of OIMnHs as efficient light-emitting materials are summarized, which covers from their fundamental physicochemical properties to advanced optoelectronic applications, with an emphasis on the structural and functionality design especially for LEDs and X-ray detection and imaging. Current challenges and future efforts to unlock the potentials of these promising materials are also envisioned.
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In the contemporary landscape of technological advancements, the burgeoning demand for portable electronics and flexible wearable devices has necessitated the development of energy storage systems with superior volumetric performance. Tungsten oxide (WO3), known for its high density and theoretical capacitance, is a promising electrode material for supercapacitors. However, low conductivity and poor cycling stability are still the key bottlenecks for its application. Herein, a novel composite comprising hollow porous WO3 spheres (HPWS) derived by template method was electrostatic self-assembled on the surface of the Ti3C2Tx nanosheets. The resulting electrodes exhibited ultra-high volumetric capacitance of 1930 F cm-3 at 1 A g-1 and rate capability of 46% at 50 A g-1, attributed to enhanced ion accessibility from microporous structure and electron transport from conductive network of Ti3C2Tx even at a high packing density of 3.86 g cm-3. Utilizing HPWS/Ti3C2Tx as the negative electrode and porous carbon as the positive electrode, the assembled asymmetric supercapacitor achieved an energy density of 31 Wh kg-1 at a power density of 650 W kg-1 with over 107% capacitance retention after 5000 cycles. This work provides a promising approach for developing next-generation supercapacitors with ultra-high volumetric capacitance.
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mRNA-4157 (V940) is an individualized neoantigen therapy (INT) targeting up to 34 patient-specific tumor neoantigens to induce T cell responses and potentiate anti-tumor activity. We report mechanistic insights into the immunogenicity of mRNA-4157 via characterization of T cell responses to neoantigens from the first-in-human phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non-small cell lung cancer (Part A: 1mg mRNA-4157, n = 4) or resected cutaneous melanoma (Part D: 1mg mRNA-4157 + 200mg pembrolizumab, n = 12). Safety, tolerability, and immunogenicity were assessed. All patients experienced ≥1 treatment-emergent adverse event (AE); there were no grade 4/5 AEs or dose-limiting toxicities. mRNA-4157 alone induced consistent de novo, and strengthened pre-existing, T cell responses to targeted neoantigens. Following combination therapy, sustained mRNA-4157-induced neoantigen-specific T cell responses and expansion of cytotoxic CD8 and CD4 T cells were observed. These findings show the potential of a novel mRNA INT approach in oncology.
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Aldosterone is a mineralocorticoid hormone involved in controlling electrolyte balance, blood pressure and cellular signaling. It plays a pivotal role in cardiovascular and metabolic physiology. Excess aldosterone activates mineralocorticoid receptors, leading to subsequent inflammatory responses, increased oxidative stress, and tissue remodeling. Various mechanisms have been reported to link aldosterone with cardiovascular and metabolic diseases. However, mitochondria, responsible for energy generation through oxidative phosphorylation, have received less attention regarding their potential role in aldosterone-related pathogenesis. Excess aldosterone leads to mitochondrial dysfunction, and this may play a role in the development of cardiovascular and metabolic diseases. Aldosterone has the potential to affect mitochondrial structure, function, and dynamic processes, such as mitochondrial fusion and fission. In addition, aldosterone has been associated with the suppression of mitochondrial DNA, mitochondria-specific protein, and ATP production in the myocardium through mineralocorticoid receptor, nicotinamide adenine dinucleotide phosphate oxidase, and reactive oxygen species pathways. In this review, we explore the mechanisms underlying aldosterone-induced cardiovascular and metabolic mitochondrial dysfunction, including mineralocorticoid receptor activation and subsequent inflammatory responses, as well as increased oxidative stress. Furthermore, we review potential therapeutic targets aimed at restoring mitochondrial function in the context of aldosterone-associated pathologies. Understanding these mechanisms is vital, as it offers insights into novel therapeutic strategies to mitigate the impact of aldosterone-induced mitochondrial dysfunction, thereby potentially improving the outcomes of individuals affected by cardiovascular and metabolic disorders.
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ß-Lactam antibiotics are a class of antibiotics commonly used to treat bacterial infections. However, the effects of ß-lactam antibiotics on term neonatal intestinal flora have not been fully elucidated. Hospitalized full-term newborns receiving ß-lactam antibiotics formed the antibiotic group (n = 67), while those without antibiotic treatment comprised the non-antibiotic group (n = 47). A healthy group included healthy full-term newborns (n = 16). Stool samples were collected for 16 S rDNA sequencing to analyze gut microbiota variations. Further investigation was carried out within the ß-lactam antibiotic group, exploring the effects of antibiotic use on the newborns' gut microbiota in relation to the duration and type of antibiotic administration, delivery method, and feeding practices. The antibiotic group exhibited significant difference of microbial community composition compared to the other groups. Genera like Klebsiella, Enterococcus, Streptococcus, Alistipes, and Aeromonas were enriched, while Escherichia-Shigella, Clostridium sensu stricto 1, Bifidobacterium, and Parabacteroides were reduced. Klebsiella negatively correlated with Escherichia-Shigella, positively with Enterobacter, while Escherichia-Shigella negatively correlated with Enterococcus and Streptococcus. Regardless of neonatal age, ß-lactam antibiotics induced an elevated abundance of Klebsiella and Enterococcus. The impact on gut microbiota varied with the duration and type of antibiotic (cefotaxime or ampicillin/sulbactam). Compared to vaginal delivery, cesarean delivery after ß-lactam treatment heightened the abundance of Klebsiella, Enterobacteriaceae_Unclassified, Lactobacillales_Unclassified, and Pectobacterium. Feeding patterns minimally influenced ß-lactam-induced alterations. In conclusion, ß-lactam antibiotic treatment for neonatal pneumonia and sepsis markedly disrupted intestinal microbiota, favoring Klebsiella, Enterococcus, Streptococcus, Alistipes, and Aeromonas. The impact of ß-lactam varied by duration, type, and delivery method, emphasizing heightened disruptions post-cesarean delivery.
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Bacterias , Heces , Microbioma Gastrointestinal , Antibióticos Betalactámicos , Femenino , Humanos , Recién Nacido , Masculino , Bacterias/efectos de los fármacos , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Antibióticos Betalactámicos/farmacología , Heces/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , ARN Ribosómico 16S/genéticaRESUMEN
While grit is considered essential to EFL learners as they navigate the challenges and setbacks of foreign language learning, it has been largely overlooked by EFL researchers. In this sequential mixed methods study with qualitative data and structural equation modeling (SEM), we examined the role of teacher confirmation and emotional support in predicting L2 grit among 309 low-proficiency Chinese EFL learners who were majoring in music, fine arts, and physical education at Chinese universities. Our results revealed positive correlations between teacher confirmation, emotional support, and L2 grit, with both teacher confirmation and emotional support significantly predicting L2 grit in our presumptive model. Qualitatively, we analyzed 22 participants' responses to three open-ended questions from a semi-structured interview. Interviewees named a spectrum of interpersonal, learner, context, teacher, and task related factors they believed to be affecting their L2 grit. Among the interpersonal factors, teacher-student communication variables were most frequently named, echoing our quantitative findings. We discussed the limitations, pedagogical implications, and recommended future directions of this research.
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Two-dimensional organic-inorganic hybrid layered perovskites have emerged as a new generation of optoelectronic materials. However, the thermochromism in organic-inorganic hybrid layered perovskites has been rarely explored in depth. A further understanding of the mechanism is necessary and favorable for the application. Here, transparent centimeter-sized single crystals of the organic-inorganic hybrid layered perovskite (C6H5C2H4NH3)2PbBr4 (PEA2PbBr4) were synthesized using an improved evaporation method. As a typical organic-inorganic hybrid layered perovskite, the PEA2PbBr4 single crystal shows high-contrast and progressive thermochromism exhibiting a change from colorlessness and transparency to lemon yellow in a wide temperature range of 200-450 K. Based on the calculation through the Varshni equation, the temperature-induced bandgap change rate directly associated with the high-contrast thermochromism of PEA2PbBr4 reaching 0.8 meV/K. This value is higher than that of many three-dimensional perovskites and traditional IV-III semiconductors. Furthermore, the temperature-dependent 193 nm photoluminescence spectra suggest that this high temperature-induced bandgap change rate of PEA2PbBr4 is a result of the competitive interaction between lattice thermal expansion and electron-phonon coupling (Fröhlich coupling coefficient ΓLO = 2.215). Based on the characteristics introduced above, PEA2PbBr4 as an organic-inorganic hybrid layered perovskite has a better performance in achieving the balance between high-contrast and high room-temperature transmittance. Therefore, PEA2PbBr4 is a material with great potential in applications like temperature-indicating labels. This work provides valuable insights into the thermochromism of layered perovskites, offering a new material system and approach for developing thermochromic materials with higher sensitivity and efficiency.