Nanostructured lipid carriers promote percutaneous absorption and hair follicle targeting of tofacitinib for treating alopecia areata.

Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8+NKG2D+T cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata.

The effect of temperature on infectious diarrhea disease: A systematic review.

This study aimed to ascertain the delayed effects of various exposure temperatures on infectious diarrhea. We performed a Bayesian random-effects network meta-analysis to calculate relative risks (RR) with 95 % confidence intervals (95 % CI). The heterogeneity was analyzed by subgroup analysis. There were 25 cross-sectional studies totaling 6858735 patients included in this analysis, with 12 articles each investigating the effects of both hyperthermia and hypothermia. Results revealed that both high temperature (RRsingle = 1.22, 95%CI:1.04-1.44, RRcum = 2.96, 95%CI:1.60-5.48, P < 0.05) and low temperature (RRsingle = 1.17, 95%CI:1.02-1.37, RRcum = 2.19, 95%CI:1.33-3.64, P < 0.05) significantly increased the risk of infectious diarrhea, while high temperature caused greater. As-sociations with strengthening in bacillary dysentery were found for high temperatures (RRcum = 2.03, 95%CI:1.41-3.01, P < 0.05; RRsingle = 1.17, 95%CI:0.90-1.62, P > 0.05), while the statistical significance of low temperatures in lowering bacterial dysentery had vanished. This investigation examined that high temperature and low temperature were the conditions that posed the greatest risk for infectious diarrhea. This research offers fresh perspectives on preventing infectious diarrhea and will hopefully enlighten future studies on the impact of temperature management on infectious diarrhea.

Development and validation of risk prediction model for bacterial infections in acute liver failure patients.

Infections significantly increase mortality in acute liver failure (ALF) patients, and there are no risk prediction models for early diagnosis and treatment of infections in ALF patients. This study aims to develop a risk prediction model for bacterial infections in ALF patients to guide rational antibiotic therapy. The data of ALF patients admitted to the Second Hospital of Hebei Medical University in China from January 2017 to January 2022 were retrospectively analyzed for training and internal validation. Patients were selected according to the updated 2011 American Association for the Study of Liver Diseases position paper on ALF. Serological indicators and model scores were collected within 24 h of admission. New models were developed using the multivariate logistic regression analysis. An optimal model was selected by receiver operating characteristic (ROC) analysis, Hosmer-Lemeshow test, the calibration curve, the Brier score, the bootstrap resampling, and the decision curve analysis. A nomogram was plotted to visualize the results. A total of 125 ALF patients were evaluated and 79 were included in the training set. The neutrophil-to-lymphocyte ratio and sequential organ failure assessment (SOFA) were integrated into the new model as independent predictive factors. The new SOFA-based model outperformed other models with an area under the ROC curve of 0.799 [95% confidence interval (CI): 0.652-0.926], the superior calibration and predictive performance in internal validation. High-risk individuals with a nomogram score ≥26 are recommended for antibiotic therapy. The new SOFA-based model demonstrates high accuracy and clinical utility in guiding antibiotic therapy in ALF patients.

The cellular response and molecular mechanism of superoxide dismutase interacting with superparamagnetic iron oxide nanoparticles.

This study explored the response of superoxide dismutase (SOD) under superparamagnetic iron oxide nanoparticles (SPIONs)-induced oxidative stress using combined cellular and molecular methods. Results found that SPIONs induced the inhibition of catalase activity, the U-inverted change of SOD activity and the accumulation of reactive oxygen species (ROS), leading to oxidative damage and cytotoxicity. The change of intracellular SOD activity was resulted from the increase of molecular activity induced by directly interacting with SPIONs and ROS-inhibition of activity. The increase of molecular activity could be attributed to the structural and conformational changes of SOD, which were caused by the direct interaction of SOD with SPIONs. The SOD-SPIONs interaction and its interacting mechanism were explored by multi-spectroscopy, isothermal titration calorimetry and zeta potential assays. SOD binds to SPIONs majorly via hydrophobic forces with the involvement of electrostatic forces. SPIONs approximately adsorb 11 units of SOD molecule with the binding affinity of 2.99 × 106 M-1. The binding sites on SOD were located around Tyr residues, whose hydrophilicity increased upon interacting with SPIONs. The binding to SPIONs loosened the peptide chains, changed the secondary structure and reduced the aggregation state of SOD.

Investigating Novel Therapeutic Approaches for Idiopathic Short Stature: Targeting siRNA and Growth Hormone Delivery to the Growth Plate Using Exosome Nanoparticles.

Idiopathic short stature (ISS) is a common childhood condition with largely unknown underlying causes. Recent research highlights the role of circulating exosomes in the pathogenesis of various disorders, but their connection to ISS remains unexplored. In the experiments, human chondrocytes are cocultured with plasma exosomes from ISS patients, leading to impaired chondrocyte growth and bone formation. Elevated levels of a specific long non-coding RNA (lncRNA), ISSRL, are identified as a distinguishing factor in ISS, boasting high specificity and sensitivity. Silencing ISSRL in ISS plasma exosomes reverses the inhibition of chondrocyte proliferation and bone formation. Conversely, overexpression of ISSRL in chondrocytes impedes their growth and bone formation, revealing its mechanism of action through the miR-877-3p/GZMB axis. Subsequently, exosomes (CT-Exo-siISSRL-oeGH) with precise cartilage-targeting abilities are engineered, loaded with customized siRNA for ISSRL and growth hormone. This innovative approach offers a therapeutic strategy to address ISS by rectifying abnormal non-coding RNA expression in growth plate cartilage and delivering growth hormone with precision to promote bone growth. This research provides valuable insights into ISS diagnosis and treatment, highlighting the potential of engineered exosomes.

Social class, schadenfreude, and children's prosocial behavior in moral contexts.

Previous research has shown mixed results regarding the relationship between social class and children's prosocial behavior. The current study aims to further our understanding of these findings by exploring the relationship between social class and children's prosocial behavior in a moral context. Study 1 (N = 833) found that when a target child pursued a morally negative goal and subsequently experienced misfortune, children from higher social class, compared to those from lower social class, experienced greater schadenfreude and exhibited less prosocial behavior. The relation between social class and prosocial behavior was mediated by schadenfreude. Study 2 (N = 389) investigated whether the greater schadenfreude experienced by children from higher social class was due to a weaker empathic response to misfortune or a stronger sense of deservingness. The results revealed a sequential mediation effect of social class on prosocial behavior through deservingness and schadenfreude. These findings provide insight into the impact of social class on the development of children's moral judgment, emotions, and behavior. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Epigallocatechin-3-gallate-induced tolerance to cadmium stress involves increased flavonoid synthesis and nutrient homeostasis in tomato roots.

Cadmium (Cd) is a toxic heavy metal, increasingly accumulating in the environment and its presence in various environmental compartments represents a significant risk to human health via the food chain. Epigallocatechin-3-Gallate (EGCG) is a prominent secondary metabolite, which can safeguard plants from biotic and abiotic stress. However, the role of EGCG in flavonoid synthesis, nutrient acquisition and reactive oxygen species (ROS) metabolism under Cd stress remains unclear. Here, we examined the effects of EGCG and Cd treatment on leaf photochemical efficiency, cell ultrastructure, essential element acquisition, antioxidant system, and secondary metabolism in tomato (Solanum lycopersicum L.). The results showed that O2•-, H2O2, and malondialdehyde levels increased after Cd treatment, but Fv/Fm decreased significantly, suggesting that Cd induced oxidative stress and photoinhibition. However, EGCG mitigated the adverse effects of Cd-induced phytotoxicity in both the roots and leaves. A decrease in ROS accumulation under EGCG + Cd treatment was mainly attributed to the significant enhancement in antioxidant enzyme activity, flavonoid content, and PHENYLALANINE AMMONIA-LYASE expression in roots. Moreover, EGCG reduced Cd content but increased some essential nutrient contents in tomato plants. Transmission electron microscopy-based observations revealed that EGCG treatment safeguards leaf and root cell ultrastructure under Cd stress. This implies that tomato plants subjected to Cd stress experienced advantageous effects upon receiving EGCG treatment. The present work elucidated critical mechanisms by which EGCG induces tolerance to Cd, thereby providing a basis for future investigations into environmentally sustainable agricultural practices in areas contaminated with heavy metals, for utilizing naturally occurring substances found in plants.

Effects of Differential Shading on Summer Tea Quality and Tea Garden Microenvironment.

Shading is an effective agronomic technique to protect tea plants from intense sunlight. However, there are currently very few studies on more effective shading methods to improve the quality of summer tea. In this study, 'Longjing43' plants were grown under four different shading treatments for 14 days, with no shading as the control. Among the four shading treatments, double-layer-net shadings had the most positive impact on the tea quality, resulting in higher levels of amino acids but lower levels of tea polyphenols. Additionally, double-layer-net shadings provided more suitable microenvironments for tea plants. The tea leaves in T4 (double nets 50 cm above the plant canopy) contained 16.13 mg∙g-1 of umami and sweet amino acids, which was significantly higher than in other treatments. T4 had the lowest air temperature and the most suitable and stable soil water content. Interestingly, the ratio of red light to far-red light in T4 was only 1.65, much lower than other treatments, which warrants further study. In conclusion, the microenvironment induced by shading can greatly affect the tea quality, and double-layer-net shading is better for improving the quality of summer tea.

A catchment-wide microplastic pollution investigation of the Yangtze River: The pollution and ecological risk of tributaries are non-negligible.

The Yangtze River is an important global channel for plastics and microplastics (MPs) to enter the sea. However, the existing research on MPs in the Yangtze River has primarily focused on the mainstream region, without regarding the occurrence, spatial distribution, and ecological risks associated with tributaries, as well as their relationship with the mainstream. To address this knowledge gap, we conducted a large-scale catchment-wide investigation of the surface water in the Yangtze River, encompassing MPs (48 µm-5 mm) of the mainstream and 15 important tributaries. Tributaries and upstream regions exhibited relatively higher levels of MPs compared with the mainstream and different sections of the river. The distribution of MPs is primarily influenced by the emission of arable land and the pH of water. Notably, the upstream tributary areas demonstrated the highest ecological risks associated with MPs. Further analysis highlighted that the tributaries accounted for a contribution ranging from 16% to 67% in quantity and from 14% to 90% in mass of the microplastics observed in the mainstream. Our results suggest that the pollution of tributaries and their associated ecological risk migration must be effectively regulated.

Regulating microstructures of aerogels by controlling phase separation mechanism for improving specific surface area and energy harvesting.

Aerogels with 3D porous structures have been attracting increasing attention among functional materials due to their advantages of being lightweight and high specific surface area. Precise control of the porous structure of aerogel is essential to improve its performance. In this work, polylactic acid (PLA) aerogels with distinctly different microstructures were fabricated by precisely controlling the phase separation behavior of the ternary solution system. Rheological and theoretical analyses have revealed that the interactions between polymer molecules, solvents and non-solvents play a crucial role in determining the nucleation and growth of poor olymer and rich polymer phases. By adjusting the non-solvent type and the solution composition, aerogels with spider network structure, bead-like connected microsphere structure, and cluster petal structure were obtained. Ideal spinodal phase separation conditions were obtained to produce aerogels with a homogeneous fiber network structure. The optimum PLA aerogel achieved an extremely porosity of 96 % and a high specific surface area of 114 m2/g, which rendered it with excellent triboelectric generation performance. Thus, this work provides fundamental insights into the precise regulation of the phase separation behavior and the structure of the aerogel, which can help boost the performance and expand the applications of PLA aerogels.

How do lateral septum projections to the ventral CA1 influence sociability?

JOURNAL/nrgr/04.03/01300535-202408000-00033/figure1/v/2023-12-16T180322Z/r/image-tiff Social dysfunction is a risk factor for several neuropsychiatric illnesses. Previous studies have shown that the lateral septum (LS)-related pathway plays a critical role in mediating social behaviors. However, the role of the connections between the LS and its downstream brain regions in social behaviors remains unclear. In this study, we conducted a three-chamber test using electrophysiological and chemogenetic approaches in mice to determine how LS projections to ventral CA1 (vCA1) influence sociability. Our results showed that gamma-aminobutyric acid (GABA)-ergic neurons were activated following social experience, and that social behaviors were enhanced by chemogenetic modulation of these neurons. Moreover, LS GABAergic neurons extended their functional neural connections via vCA1 glutamatergic pyramidal neurons, and regulating LSGABA→vCA1Glu neural projections affected social behaviors, which were impeded by suppressing LS-projecting vCA1 neuronal activity or inhibiting GABAA receptors in vCA1. These findings support the hypothesis that LS inputs to the vCA1 can control social preferences and social novelty behaviors. These findings provide new insights regarding the neural circuits that regulate sociability.

Roles of rRNA N-methyladenosine modification in the function of ribosomes.

The N-methyladenosine (m6A) modification of ribosomal RNA (rRNA) plays critical roles in regulating the function of ribosomes, the essential molecular machines that translate genetic information from mRNA into proteins. Specifically, m6A modification affects ribosome biogenesis, stability, and function by regulating the processing and maturation of rRNA, the assembly and composition of ribosomes, and the accuracy and efficiency of translation. Furthermore, m6A modification allows for dynamic regulation of translation in response to environmental and cellular signals. Therefore, a deeper understanding of the mechanisms and functions of m6A modification in rRNA will advance our knowledge of ribosome-mediated gene expression and facilitate the development of new therapeutic strategies for ribosome-related diseases.

Relationship of sleep-quality and social-anxiety in patients with breast cancer: a network analysis.

BACKGROUND: There is a complex relationship between social anxiety and sleep quality. However, network analysis studies of associations between social anxiety and sleep quality are lacking, particularly among patients with breast cancer. The current study aimed to extend this research to a sample of patients with breast cancer and to examine symptom-level associations between social anxiety and sleep quality using network analysis. METHODS: Network analysis was conducted to explore their associations and identify bridge items of social anxiety and sleep quality. RESULTS: The network structure revealed 9 important edges between social anxiety and sleep quality. "Subjective sleep quality" had the highest EI value in the network. "Working difficulty under watching" and "Sleep disorders" had the highest BEI values in their own communities. CONCLUSION: There are complex pathological correlation pathways between social anxiety and sleep quality in breast cancer patients. "Subjective sleep quality", "Working difficulty under watching" and "Sleep disorders" have the potential to be intervention targets for sleep disorder-social anxiety comorbidity. Medical staff can take corresponding interventions according to the the centrality indices and bridge centrality indicators identified in this study, which is likely to effectively reduce the comorbidity of sleep disorders and social anxiety.

Chronic unpredictable stress induces depression/anxiety-related behaviors and alterations of hippocampal monoamine receptor mRNA expression in female mice at different ages.

Depression and anxiety are the most common mental health disorders. Though they affect people at any age and occur more often in females, the pathophysiological changes under these conditions are less investigated. In the present study, we examined the effects of age and stress on depression- and anxiety-related behaviors in female mice. Saccharin preference and the open field test were carried out before and after chronic unpredictable stress in 4-, 14- and 25-month-old female mice. After behavioral tests, mRNA levels of monoamine receptors in the hippocampus were measured by real-time RT-PCR. Chronic unpredictable stress decreased saccharin preference in 4-, 14- and 25-month-old mice and the time spent in the center in the open field test in 25-month-old mice. For monoamine receptors, analysis of variance revealed significant effects of age on mRNA levels of Htr1a, Htr2a, Htr6, Adra1a, Adrb2, and Adrb3, significant effects of stress on mRNA levels of Htr4, Adra2c, Adrb1, and Adrb2, and interactions of age × stress on mRNA levels of Htr1a, Htr5b, Adra1d, Adra2a, Adra2c, and Adrb1. Chronic unpredictable stress decreased mRNA levels of Htr4, Htr5b, Adra2c, and Adrb1 in 4-month-old female mice. Correlations were observed between saccharin preference and mRNA levels of Htr4, Htr5b, Htr6, Adra1d, Adra2a, and Adra2c in 4-month-old mice and between the time spent in the center in the open field test and mRNA levels of Htr1b in 4-month-old mice, Htr3a, Htr7, and Adrb2 in 14-month-old mice, and Drd2 in 4- and 14-month-old mice. Our findings support that stress induces depression- and anxiety-related behaviors and the expression of hippocampal monoamine receptors in an age-dependent manner in female mice.

Two new species of the subfamily Mydaeinae (Diptera: Muscidae) from China.

Keys of the genera Hebecnema Schnabl, 1887 and Mydaea Robineau-Desvoidy, 1830 from China based on males are provided, including two new species Hebecnema kongi Wang, Li & Yang, sp. nov. and Mydaea apicinigra Wang, Li & Yang, sp. nov., respectively. Photographs of habitus and male genitalia as well as illustrations of the male genitalia of the new species are given.

Implemented impediment of extracellular electron transfer-dependent anammox process :Unstable nitrogen removal efficiency and decreased abundance of anammox bacteria.

The present study investigates the extracellular electron transfer (EET)-dependent anammox process as a promising approach for sustainable wastewater treatment. The study examines the performance and metabolic pathway of the EET-dependent anammox process in comparison to the nitrite-dependent anammox process. The EET-dependent reactor successfully achieved nitrogen removal with a maximum removal efficiency of 93.2%, although it exhibited a lower ability to sustain high nitrogen removal load when compared to the nitrite-dependent anammox process, which poses opportunity and challenge for ammonia-wastewater treatment under applied voltage conditions. Nitrite was identified as a critical factor responsible for the changes in microbial community structure, resulting in a significant reduction in nitrogen removal load in the absence of nitrite. The study further suggests that the Candidatus Kuenenia species could dominate the EET-dependent anammox process, while nitrifying and denitrifying bacteria also contribute to the nitrogen removal in this system.

Medial prefrontal cortical PPM1F alters depression-related behaviors by modifying p300 activity via the AMPK signaling pathway.

AIMS: Protein phosphatase Mg2+/Mn2+-dependent 1F (PPM1F) is a serine/threonine phosphatase, and its dysfunction in depression in the hippocampal dentate gyrus has been previously identified. Nevertheless, its role in depression of another critical emotion-controlling brain region, the medial prefrontal cortex (mPFC), remains unclear. We explored the functional relevance of PPM1F in the pathogenesis of depression. METHODS: The gene expression levels and colocalization of PPM1F in the mPFC of depressed mice were measured by real-time PCR, western blot and immunohistochemistry. An adeno-associated virus strategy was applied to determine the impact of knockdown or overexpression of PPM1F in the excitatory neurons on depression-related behaviors under basal and stress conditions in both male and female mice. The neuronal excitability, expression of p300 and AMPK phosphorylation levels in the mPFC after knockdown of PPM1F were measured by electrophysiological recordings, real-time PCR and western blot. The depression-related behavior induced by PPM1F knockdown after AMPKα2 knockout or the antidepressant activity of PPM1F overexpression after inhibiting acetylation activity of p300 was evaluated. RESULTS: Our results indicate that the expression levels of PPM1F were largely decreased in the mPFC of mice exposed to chronic unpredictable stress (CUS). Behavioral alterations relevant to depression emerged with short hairpin RNA (shRNA)-mediated genetic knockdown of PPM1F in the mPFC, while overexpression of PPM1F produced antidepressant activity and ameliorated behavioral responses to stress in CUS-exposed mice. Molecularly, PPM1F knockdown decreased the excitability of pyramidal neurons in the mPFC, and restoring this low excitability decreased the depression-related behaviors induced by PPM1F knockdown. PPM1F knockdown reduced the expression of CREB-binding protein (CBP)/E1A-associated protein (p300), a histone acetyltransferase (HAT), and induced hyperphosphorylation of AMPK, resulting in microglial activation and upregulation of proinflammatory cytokines. Conditional knockout of AMPK revealed an antidepressant phenotype, which can also block depression-related behaviors induced by PPM1F knockdown. Furthermore, inhibiting the acetylase activity of p300 abolished the beneficial effects of PPM1F elevation on CUS-induced depressive behaviors. CONCLUSION: Our findings demonstrate that PPM1F in the mPFC modulates depression-related behavioral responses by regulating the function of p300 via the AMPK signaling pathway.

Metabolic insights into the interaction between nitrogen removal and 4-chlorophenol reduction of anammox consortia.

The response characteristic and performance stabilization of anammox process under the stress of the potential organic pollutants support the application of ammonia-nitrogen wastewater treatment. In the present study, nitrogen removal performance was significantly suppressed with the addition of 4-chlorophenol. The activity of anammox process was inhibited by 14.23% (0.1 mg/L), 20.54% (1 mg/L) and 78.15% (10 mg/L), respectively. Metagenomic analysis revealed a significant decrease in the abundance of KEGG pathways associated with carbohydrate and amino acid metabolism with increasing 4-chlorophenol concentration. Metabolic pathway profiles suggest that putrescine is down-regulated at high 4-chlorophenol stress due to inhibition of nitrogen metabolism processes, while it is up-regulated to reduce oxidative damage. In addition, the presence of 4-chlorophenol induced an enhancement of EPS and bacterial debris decomposition, and a partial conversion of 4-chlorophenol to p-nitrophenol. This study unravels the mechanism of effect on anammox consortia in response to 4-CP, which could provide supplementary to facilitate its full-scale application.

A Porous Perovskite Nanofiber with Reinforced Aerophobicity for High-Performance Anion Exchange Membrane Water Splitting.

Perovskite oxides stand out as emerging oxygen evolution reaction (OER) catalysts on account of their effective electrocatalytic performance and low costs. Nevertheless, perovskite oxides suffer from severe bubble overpotential and inhibited electrochemical performance in large current densities due to their small specific surface areas and structural compactness. Herein, the study highlights the electrospun nickel-substituted La0.5 Sr0.5 FeO3-δ (LSF) porous perovskite nanofibers, that is, La0.5 Sr0.5 Fe1-x Nix O3-δ (denoted as ES-LSFN-x, x = 0, 0.1, 0.3, and 0.5), as high-performance OER electrocatalysts. The most effective La0.5 Sr0.5 Fe0.5 Ni0.5 O3-δ (ES-LSFN-0.5) nanofibers suggest a larger specific surface area, higher porosity, and faster mass transfer than the counterpart sample prepared by conventional sol-gel method (SG-LSFN-0.5), showing notably increased geometric and intrinsic activities. The bubble visualization results demonstrate that the enriched and nano-sized porosity of ES-LSFN-0.5 enables reinforced aerophobicity and rapid detachment of oxygen bubbles, thereby reducing the bubble overpotential and enhancing the electrochemical performance. As a result, the ES-LSFN-0.5-based anion exchange membrane water electrolysis delivers a superior stability of 100 h while the SG-LSFN-0.5 counterpart degrades rapidly within 20 h under a current density of 100 mA cm-2 . The results highlight the advantage of porous electrocatalysts in optimizing the performance of large current density water electrolysis devices by reducing the bubble overpotential.