Regulation of TREM2 expression by transcription factor YY1 and its protective effect against Alzheimer's disease.

TREM2 encoding the transmembrane receptor protein TREM2 is a risk gene of Alzheimer's disease (AD), and the impairment of TREM2 functions in microglia due to mutations in TREM2 may significantly increase the risk of AD by promoting AD pathologies. However, how the expression of TREM2 is regulated and the transcription factors required for TREM2 expression are largely unknown. By luciferase assay, DNA pull-down, and in silico predictions, we identified Yin Yang 1(YY1) as a binding protein of the minimal promoter of the TREM2 gene, and the binding was further confirmed by EMSA and DNA pull-down assay. shRNA-mediated YY1 silencing significantly reduced the activity of the TREM2 minimal promoter and TREM2 protein levels in the microglial cell line BV2 and the neuroblastoma Neuro2A. Furthermore, we found that the levels of TREM2 and YY1 were both downregulated in lipopolysaccharide-treated BV2 cells and in the brain of AD model mice. These results demonstrated that YY1 plays a crucial role in the regulation of TREM2 expression. Our study suggests that microglial YY1 could be targeted to maintain TREM2 expression for AD prevention and therapy.

Intelligent Reconfiguration-Promoted Cellular Internalization of Core-Shell DNA Nanoprobe Equipped with Successive Dual Stimuli-Responsive Protective Satellites for Amplification Fluorescence Imaging of Tumor Cells.

Although DNA probes have attracted increasing interest for precise tumor cell identification by imaging intracellular biomarkers, the requirement of commercial transfection reagents, limited targeting ligands, and/or non-biocompatible inorganic nanostructures has hampered the clinic translation. To circumvent these shortcomings, a reconfigurable ES-NC (Na+ -dependent DNAzyme (E)-based substrate (S) cleavage core/shell DNA nanocluster (NC)) entirely from DNA strands is assembled for precise imaging of cancerous cells in a successive dual-stimuli-responsive manner. This nanoprobe is composed of a strung DNA tetrahedral satellites-based protective (DTP) shell, parallelly aligned target-responsive sensing (PTS) interlayer, and hydrophobic cholesterol-packed innermost layer (HCI core). Tetrahedral axial rotation-activated reconfiguration of DTP shell promotes the exposure of interior hydrophobic moieties, enabling cholesterol-mediated cellular internalization without auxiliary elements. Within cells, over-expressed glutathione triggers the disassembly of the DTP protective shell (first stimulus), facilitating target-stimulated signal transduction/amplification process (second stimuli). Target miRNA-21 is detected down to 10.6 fM without interference from coexisting miRNAs. Compared with transfection reagent-mediated counterpart, ES-NC displays a higher imaging ability, resists nuclease degradation, and has no detectable damage to healthy cells. The blind test demonstrates that the ES-NC is suitable for the identification of cancerous cells from healthy cells, indicating a promising tool for early diagnosis and prediction of cancer.

Midbrain FA initiates neuroinflammation and depression onset in both acute and chronic LPS-induced depressive model mice.

Both exogenous gaseous and liquid forms of formaldehyde (FA) can induce depressive-like behaviors in both animals and humans. Stress and neuronal excitation can elicit brain FA generation. However, whether endogenous FA participates in depression occurrence remains largely unknown. In this study, we report that midbrain FA derived from lipopolysaccharide (LPS) is a direct trigger of depression. Using an acute depressive model in mice, we found that one-week intraperitoneal injection (i.p.) of LPS activated semicarbazide-sensitive amine oxidase (SSAO) leading to FA production from the midbrain vascular endothelium. In both in vitro and in vivo experiments, FA stimulated the production of cytokines such as IL-1ß, IL-6, and TNF-α. Strikingly, one-week microinfusion of FA as well as LPS into the midbrain dorsal raphe nucleus (DRN, a 5-HT-nergic nucleus) induced depressive-like behaviors and concurrent neuroinflammation. Conversely, NaHSO3 (a FA scavenger), improved depressive symptoms associated with a reduction in the levels of midbrain FA and cytokines. Moreover, the chronic depressive model of mice injected with four-week i.p. LPS exhibited a marked elevation in the levels of midbrain LPS accompanied by a substantial increase in the levels of FA and cytokines. Notably, four-week i.p. injection of FA as well as LPS elicited cytokine storm in the midbrain and disrupted the blood-brain barrier (BBB) by activating microglia and reducing the expression of claudin 5 (CLDN5, a protein with tight junctions in the BBB). However, the administration of 30 nm nano-packed coenzyme-Q10 (Q10, an endogenous FA scavenger), phototherapy (PT) utilizing 630-nm red light to degrade FA, and the combination of PT and Q10, reduced FA accumulation and neuroinflammation in the midbrain. Moreover, the combined therapy exhibited superior therapeutic efficacy in attenuating depressive symptoms compared to individual treatments. Thus, LPS-derived FA directly initiates depression onset, thereby suggesting that scavenging FA represents a promising strategy for depression treatment.

Factors affecting local alveolar bone thickness in unilateral maxillary canine-lateral incisor transposition.

INTRODUCTION: This study aimed to use 3-dimensional data to investigate the factors affecting local alveolar bone thickness in unilateral maxillary canine-lateral incisor transposition. METHODS: Pretreatment cone-beam computed tomography data of 34 patients with unilateral maxillary canine-lateral transposition were imported into Dolphin Imaging software (version 11.8; Dolphin Imaging and Management Solutions, Chatsworth, Calif) for 3-dimensional reconstruction. The age, gender, and type of transposition at the beginning of treatment were recorded. The thickness and height of the transposed canine, the labiopalatal and distomedial distance from the transposed canine to the apex of the lateral incisor, the inclination of the transposed lateral incisor, the apical height of the lateral incisor, and the alveolar bone thickness in the apical plane were measured. Multiple linear regression analyses were applied to investigate the factors affecting alveolar bone thickness in the apical plane of the transposed lateral incisor. Two sample t test were applied to assess the difference of alveolar bone thickness in patients of different ages. RESULTS: The 10 boys and 24 girls had a mean age of 12.26 ± 2.34 years. In all 34 participants, the apical alveolar bone thickness of transposed lateral incisors was significantly higher than that of the unaffected side (P <0.05). Based on multiple regression analyses, factors associated with a wider alveolar bone thickness were as follows: age (ß = -0.237; P = 0.008), the labiopalatal distance from the transposed canine to the apex of the lateral incisor (ß = 0.675; P <0.001), and the inclination of the transposed lateral incisor (ß = 0.048; P = 0.032). Patients aged <11 years had significantly thicker alveolar bone than that of patients aged >11 years (P <0.05). CONCLUSIONS: Patients with younger age, greater lateral incisor inclination, and greater labiopalatal distance between canine and lateral incisor had more alveolar bone thickness. Early treatment permits tooth movement within the thicker alveolar bone.

Liver Metabolic Dysregulation Induced by Polypropylene Nano- and Microplastics in Nile Tilapia Using Internal Extractive Electrospray Ionization Mass Spectrometry.

Understanding the metabolic disorders induced by nano- and microplastics in aquatic organisms at the molecular level could help us understand the potential toxicity of nano- and microplastics more thoroughly and provide a fundamental scientific basis for regulating the usage and management of plastic products. In this research, the effect of polypropylene nanoplastics (PP-NPs) and microplastics (PP-MPs) on metabolites in the tilapia liver was comprehensively investigated by internal extractive electrospray ionization mass spectrometry (iEESI-MS). A partial least-squares discriminant analysis (PLS-DA) and a one-component analysis of variance (ANOVA) were used for selecting 46 differential metabolites, including phospholipids, amino acids, peptides, carbohydrates, alkaloids, purines, pyrimidines, and nucleosides. Pathway enrichment analysis showed significant effects on glycerophospholipid metabolism, arginine and proline metabolism, and aminoacyl-tRNA biosynthesis after tilapia were exposed to PP-N/MPs. Dysregulation of these metabolites is mainly reflected in the possible induction of hepatitis, oxidative stress, and other symptoms. The application of iEESI-MS technology without sample pretreatment to the study of metabolic disorders in aquatic organisms under the interference of nano- and microplastics provides a promising analytical method for environmental toxicology research.

High-Strength, Freeze-Resistant, Recyclable, and Biodegradable Polyvinyl Alcohol/Glycol/Wheat Protein Complex Organohydrogel for Wearable Sensing Devices.

The application of flexible wearable sensing devices based on conductive hydrogels in human motion signal monitoring has been widely studied. However, conventional conductive hydrogels contain a large amount of water, resulting in poor mechanical properties and limiting their application in harsh environments. Here, a simple one-pot method for preparing conductive hydrogels is proposed, that is, polyvinyl alcohol (PVA), wheat protein (WP), and lithium chloride (LiCl) are dissolved in an ethylene glycol (EG)/water binary solvent. The obtained PVA/EG/WP (PEW) conductive organohydrogel has good mechanical properties, and its tensile strength and elongation at break reach 1.19 MPa and 531%, respectively, which can withstand a load of more than 6000 times its own weight without breaking. The binary solvent system composed of EG/water endows the hydrogel with good frost resistance and water retention. PEW organohydrogel as a wearable strain sensor also has good strain sensitivity (GF = 2.36), which can be used to detect the movement and physiological activity signals in different parts of the human body. In addition, PEW organohydrogels exhibit good degradability, reducing the environmental footprint of the flexible sensors after disposal. This research provides a new and viable way to prepare a new generation of environmentally friendly sensors.

Ag nanoparticle modified porous Si microspheres as high-performance anodes for Li-ion batteries.

This study aimed to address the challenges associated with silicon (Si) anode materials in Li-ion batteries, such as their large volume effect and poor electrical conductivity. To overcome these limitations, a novel composite microsphere called pSi/Ag was developed using quartz waste through a combination of high-energy ball-milling, spray drying, and magnesiothermic reduction techniques. The morphology and structure of the pSi/Ag composite were thoroughly characterized using various methods, including X-ray diffraction, field-emission scanning electron microscopy, and transmission electron microscopy. The results revealed that the Ag nanoparticles were uniformly dispersed within the porous micron-sized Si sphere particles, leading to enhanced electrochemical performance compared to pure porous silicon that did not undergo the spray drying process. The use of micron-sized Si prevented the excessive formation of the solid electrolyte interphase film, and the pSi/Ag-5 anode, prepared with 5 wt% AgNO3 as a precursor, demonstrated an impressive initial Coulombic efficiency of 92.8%. Moreover, a high specific capacity of 1251.4 mA h g-1 over 300 cycles at a current density of 4000 mA g-1 was attributed to the improved conductivity provided by the Ag nanoparticles in the Si matrix. The straightforward synthesis method employed in this study to produce pSi/Ag presents a promising approach for the future development of high-performance silicon anodes in Li-ion batteries.

Development and Core Technologies for Intelligent SWaP3 Infrared Cameras: A Comprehensive Review and Analysis.

With the development of infrared detection and imaging technology, infrared cameras (IRCs) play an important role in many fields, such as military, industry, and civilian. Additionally, the requirements for the size, performance, and intelligence of IRCs are becoming more and more strict. Consequently, the associated research and development (R&D) of IRCs is gradually focused on the aspects of miniaturization, high performance, intelligence, low power consumption, and low cost, involving many frontier fields, including artificial intelligence, new materials, new optical systems, and electronics systems. In fact, there are continual studies on intelligent SWaP3 IRCs, but unfortunately, a systematic arrangement and analysis are lacking. Therefore, a systematical and comprehensive review for the developments and core technologies of the intelligent SWaP3 IRCs is really needed. In this paper, in terms of the aforementioned requirements, we conduct a review and analysis of current intelligent SWaP3 IRCs based on 90 literature and statistics in recent decades to provide the relevant developers with a helpful reference for facilitating the indicator optimization of intelligent SWaP3 IRCs with new developed technologies. We analyze the development of SWaP3 IRCs in the aspects of lightweight, miniaturization, low price, and high performance, including hyperspectral resolution, high spatial resolution, large field of view (FOV), and wide dynamic elaborately. Moreover, the development in low power consumption and intelligence is also discussed in detail. Additionally, we briefly summarize the primary applications of intelligent SWaP3 IRCs in military, scientific, and civil. Then, the core technologies comprising high-integration, lightweight, hyperspectral imaging (HSI), low-power consumption, as well as the realization of high performance such as high-resolution, high-frame, and wide-dynamic range of SWaP3 IRCs are discussed and analyzed in detail. Finally, we prospect for the intelligent SWaP3 IRCs that it is necessary to continuously expand the concept of SWaP3 by reliability, stability, extensibility, and safety. In addition, it is useful to embed cutting-edge technologies such as small pixel pitch array, multi-sensors fusion, and deploy intelligent algorithms to IRCs. Additionally, the improvement of the whole machine from multi-dimension such as chip, camera, and system is expected and needs to be taken more seriously. It is hoped that this paper can provide a reference for the R&D of intelligent SWaP3 IRCs in the future.

Morphometric evaluation of alveolar bone after orthodontic treatment of multiple impacted teeth in the unilateral maxillary anterior region.

INTRODUCTION: This study aimed to investigate the height and thickness of alveolar bone by cone-beam computed tomography imaging after orthodontic treatment in the unilateral maxillary anterior region and speculate on reasons for the difference in alveolar bone morphology. METHODS: This study selected 11 patients (3 males and 8 females; mean age, 9.42 ± 1.45 years). Cone-beam computed tomography was performed for these 11 patients before and after treatment using Dolphin Imaging software (Dolphin Imaging and Management Solutions, Chatsworth, Calif). Labial and palatal alveolar bone thickness (BT) at root apices and different levels along the roots and loss of alveolar bone height was measured for each impacted tooth and its contralateral homonymous tooth. RESULTS: After orthodontic therapy, all 3 impacted anterior teeth had different degrees of loss of labial alveolar bone height compared with the normal side (central incisor: -1.5 mm, P <0.005; lateral incisor: -1.06 mm, P <0.01; canine: -0.59 mm, P < 0.01). The lateral incisors also showed palatal alveolar bone height loss compared with the unaffected side (-0.8 mm, P <0.005). Alveolar BT at root apices of impacted canines was 1.14 mm thicker than the normal side (P <0.005). Central and lateral incisors were similar to the normal side. The thickness of the alveolar bone at 8, 10, and 12 mm of the impacted canine position was still larger than that on the healthy side, whereas the difference in average thickness between the healthy and affected side had been significantly reduced compared with pretreatment measurements. CONCLUSIONS: There is satisfactory retention of alveolar bone height in canines after orthodontic treatment; however, alveolar bone loss is slightly worse at central and lateral incisors. Retention of alveolar BT was normal for impacted anterior teeth, whereas excess apical alveolar BT at the canines, although still present, was substantially less significant than had been observed before treatment.

Internal extractive electrospray ionization mass spectrometry for investigating the phospholipid dysregulation induced by perfluorooctanoic acid in Nile tilapia.

Direct profiling of endogenous biomolecules in tissue samples is considered as a promising approach to investigate metabolic-related toxicity in organisms induced by emerging pollutants. Herein, we report the application of internal extractive electrospray ionization mass spectrometry (iEESI-MS) to direct phospholipid profiling in the liver and spleen tissues of Nile tilapia exposed to perfluorooctanoic acid (PFOA). Combining positive and negative ion detection modes, 130 phospholipid signals were directly detected and identified by iEESI-MS in the tissues of Nile tilapia, including phosphatidyl cholines (PCs), sphingomyelins (SMs), phosphatidic acids (PAs), phosphatidyl ethanolamines (PEs), phosphatidyl glycerols (PGs), phosphatidyl inositols (PIs) and phosphatidyl serines (PSs). With the help of partial least squares discriminant analysis (PLS-DA) and one-way analysis of variance (ANOVA), several phospholipid signals showed a significant difference in the tissue of Nile tilapia between the control group and PFOA exposure groups. In addition, pathway analysis revealed that PFOA has a significant metabolic impact on the glycerophospholipid metabolism in Nile tilapia. Without complex sample preparation, iEESI-MS was applied to direct phospholipid profiling in the liver and spleen tissues of Nile tilapia treated with PFOA, which provided a promising methodology for investigating environmental toxicity and phospholipid-dysregulation caused by emerging pollutants in aquatic organisms.

Correction: Direct analysis of metabolites in the liver tissue of zebrafish exposed to fiproles by internal extractive electrospray ionization mass spectrometry.

Correction for 'Direct analysis of metabolites in the liver tissue of zebrafish exposed to fiproles by internal extractive electrospray ionization mass spectrometry' by Jun Liu et al., Analyst, 2021, 146, 4480-4486, https://doi.org/10.1039/D1AN00490E.

The relationship between local alveolar bone housing and size of canine in maxillary canine-lateral incisor transposition: A retrospective cone-beam computed tomography-based study.

INTRODUCTION: This study aimed to use 3-dimensional data to analyze the relationship between local alveolar bone housing and canine size in maxillary canine-lateral incisor transposition. METHODS: Cone-beam computed tomography study data from 31 patients with maxillary canine-lateral incisor transposition were imported into Dolphin Imaging software (version 11.8; Dolphin Imaging and Management Solutions, Chatsworth, Calif) for measurement. The buccal and palatal alveolar thickness of lateral incisor roots at different heights, the maximal thickness of displaced canine, and canine height were measured. Alveolar height-thickness variation curves at the lateral incisor region and maximal thickness of displaced canine were plotted to calculate the appropriate theoretical minimum alveolar heights of total alveolar housing, buccal alveolar housing after concentrating the bone buccally (TMAH-B1), and original buccal alveolar housing (TMAH-B2) required for correcting the transposition of 2 teeth. RESULTS: Canines could only be moved distally above lateral incisors in 5 patients. The mean value of theoretical minimum alveolar heights of total alveolar housing was 14.57 ± 1.75 mm. It was possible to reposition canines distally by concentrating the alveolar bone buccally in the remaining 26 patients. The mean value of TMAH-B1 was 10.86 ± 3.70 mm. Canines could be repositioned distally directly over the buccal aspect of the lateral incisor in 17 patients. The mean value of TMAH-B2 was 9.30 ± 2.35 mm. Canine height was greater than TMAH-B1 in 18 patients; however, only 10 patients were greater than TMAH-B2. CONCLUSIONS: Correction of transposition was difficult in some patients because of the lack of alveolar bone housing. Repositioning was possible when the height of the canine was higher than a certain height. An accurate assessment of the relationship between alveolar housing and tooth size is recommended.

The position and morphology characteristics of multiple impacted anterior teeth in the unilateral maxillary area: A retrospective study based on cone-beam computed tomography.

INTRODUCTION: This study investigated the position and morphologic characteristics of multiple impacted anterior teeth in the unilateral maxillary area. METHODS: Cone-beam computed tomography images of 21 patients (11 males and 10 females; median age 9.42 years [9.08-11.29]) with multiple teeth impacted were collected and imported into Dolphin Imaging software (Dolphin Imaging and Management Solutions, Chatsworth, Calif). The vertical height, crown orientation, twist direction, and root curvature of each impacted tooth were described. The crown length, root length, and root canal width of impacted and homonym teeth were measured. RESULTS: The positions of the impacted lateral incisors are lower than that of the other 2 anterior teeth. Most crowns of impacted central incisors are positioned distally, labial surfaces in mesial torsion, with most roots, bent toward the distal and labial. Crowns of impacted lateral incisors are positioned mesiolabially, with labial surfaces mostly in distal torsion, and most roots bent toward the mesial and labial. Crowns of impacted canines are mostly positioned mesiolabially, with labial surfaces in mesial torsion. The crowns and roots of the impacted central and lateral incisors were shorter than those of the homonym (P <0.05); however, the difference in crown length is clinically negligible, and there was no difference in root canal widths. There was no difference in the comparison of parameters for the canine group. CONCLUSIONS: There are certain rules in the vertical height, crown orientation, twist direction, and root curvature of multiple impacted anterior teeth in the unilateral maxillary area. Root development of impacted central and lateral incisors was restricted.

The differences of root morphology and root length between different types of impacted maxillary central incisors: A retrospective cone-beam computed tomography study.

INTRODUCTION: The purpose of this trial was to use 3-dimensional data to analyze the differences of root morphology and root length between 3 different types of impacted maxillary central incisors. METHODS: Cone-beam computed tomography images of 126 patients with impacted maxillary central incisors were included in this retrospective study. On the basis of the angle of the impacted incisor to the palatal plane, we categorized the tooth as labial inversely impacted, labially positioned, or palatal impacted incisor. In each category, the early and late dental age groups were classified according to the method of Nolla. The total root length of both impacted and homonym teeth, length of the nondilacerated part of the root, length of the dilacerated part of the root, the angle between the crown and root, and root direction, were measured in the sagittal-view sections using Dolphin Imaging software (version 11.9; Dolphin Imaging and Management Solutions, Chatsworth, Calif). RESULTS: Compared with the early dental age groups, the length of the dilacerated portion of the root and rate of dilaceration for inverse labial and labially positioned impactions increases, and crown-root angle decreases (P <0.05). The dilacerated part of the root bent labially, and the root morphology shows an obvious L-shaped curve. The length of the nondilacerated part of the root for palatal impactions is greater(P <0.05). The dilacerated part of the root bends palatally, and the root morphology shows a continuous C-shaped curve. CONCLUSIONS: Obstruction from the alveolar bone will cause different root morphology. Root morphology of labial impactions shows an obvious L-shaped curve; palatal impactions show a continuous C-shaped curve.

The positive energy of netizens: development and application of fine-grained sentiment lexicon and emotional intensity model.

The outbreak of COVID-19 has led to a global health crisis and caused huge emotional swings. However, the positive emotional expressions, like self-confidence, optimism, and praise, that appear in Chinese social networks are rarely explored by researchers. This study aims to analyze the characteristics of netizens' positive energy expressions and the impact of node events on public emotional expression during the COVID-19 pandemic. First, a total of 6,525,249 Chinese texts posted by Sina Weibo users were randomly selected through textual data cleaning and word segmentation for corpus construction. A fine-grained sentiment lexicon that contained POSITIVE ENERGY was built using Word2Vec technology; this lexicon was later used to conduct sentiment category analysis on original posts. Next, through manual labeling and multi-classification machine learning model construction, four mainstream machine learning algorithms were selected to train the emotional intensity model. Finally, the lexicon and optimized emotional intensity model were used to analyze the emotional expressions of Chinese netizens. The results show that POSITIVE ENERGY expression accounted for 40.97% during the COVID-19 pandemic. Over the course of time, POSITIVE ENERGY emotions were displayed at the highest levels and SURPRISES the lowest. The analysis results of the node events showed after the outbreak was confirmed officially, the expressions of POSITIVE ENERGY and FEAR increased simultaneously. After the initial victory in pandemic prevention and control, the expression of POSITIVE ENERGY and SAD reached a peak, while the increase of SAD was the most prominent. The fine-grained sentiment lexicon, which includes a POSITIVE ENERGY category, demonstrated reliable algorithm performance and can be used for sentiment classification of Chinese Internet context. We also found many POSITIVE ENERGY expressions in Chinese online social platforms which are proven to be significantly affected by nod events of different nature.

Fluorinated Copolypeptide-Stabilized Microbubbles with Maleimide-Decorated Surfaces as Long-Term Ultrasound Contrast Agents.

Gas-filled microbubbles (MBs) have been clinically used as ultrasound (US) contrast agents for disease diagnosis and treatment. However, it remains a great challenge to resolve the dilemma of stability and contrast enhancement of MBs. Herein, amphiphilic copolypeptides bearing fluorinated blocks are synthesized to stabilize perfluorocarbon (PFC)-filled MBs, exhibiting unique stability under both long-term storage and US imaging conditions. The fluorinated inner layer reduces the internal Laplace pressure and greatly improves the stability of MBs, which can be further reinforced by crosslinking of the dipropargyl-containing middle blocks. To overcome the suppressed nonlinear oscillation of polymer shells, maleimide groups are introduced onto the surface of MBs, enabling in situ reaction with plasma proteins to enhance second harmonic signals without compromising the stability of MBs, conferring better US imaging performance than that of SonoVueTM MBs.

Direct analysis of metabolites in the liver tissue of zebrafish exposed to fiproles by internal extractive electrospray ionization mass spectrometry.

Exploring the metabolic disturbance of fipronil and its derivatives in aquatic organisms may provide a more comprehensive understanding of the impact of fipronil on the ecological environment. In this work, internal extractive electrospray ionization mass spectrometry (iEESI-MS) was used to directly analyze metabolites in the liver tissue of zebrafish exposed to fipronil and its three derivatives. Partial least squares-discriminant analysis (PLS-DA) revealed that 32 signals were considered as differential signals in zebrafish after the exposure treatment of fipronil and its derivatives, including phosphatidylcholines (PCs), lysophosphatidylcholines (LPCs), phosphatidylethanolamines (PEs), fatty acids and so on. The pathway analysis result showed that both fipronil and its derivatives have a significant impact on the glycerophospholipid metabolism of zebrafish. Besides, the intensities of PC signals in the liver samples of each group showed such a trend: mixed fiprole exposed group > fipronil sulfone exposed group ≈ fipronil sulfide exposed group > fipronil exposed group > fipronil desulfinyl exposed group > control group, indicating that mixed exposure of fipronil and its derivatives exhibited more significant metabolic disturbance in zebrafish. Taken together, iEESI-MS is applied to environmental toxicology and investigating the metabolic disturbance induced by fipronil and its derivatives in aquatic organisms, providing a new analytical method for this field.

Two new steroidal glycosides from Cynanchum wallichii.

Two new C21 steroidal glycosides were isolated from Cynanchum wallichii Wight. Their structures were elucidated as caudatin-3-O-ß-d-glucopyranosyl-(1 → 4)-ß-d-oleandropyranosyl-(1 → 4)-ß-d-cymaropyranosyl-(1 → 4)-ß-d-digitoxopyranoside (1) and caudatin-3-O-ß-d-glucopyranosyl-(1 → 4)-ß-d-cymaropyranosyl-(1 → 4)-ß-d-oleandropyranosyl-(1 → 4)-ß-d-cymaropyranosyl-(1 → 4)-ß-d-digitoxopyranoside (2) by spectroscopic methods including 1D and 2D NMR experiments.

The scalp prefrontal-limbic functional connectivity moderates stress-related rumination effects on stress recovery.

BACKGROUND: Mood disorders are often associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction, and rumination has been implicated in delayed cortisol recovery. However, research findings on the impact of rumination on cortisol recovery have been inconsistent. The moderating effects of scalp prefrontal-limbic connections on the relationship between rumination and cortisol recovery may explain these discrepancies. METHOD: Acute stress was induced by a 5-min simulated job interview. Salivary samples and affective ratings were collected at seven pre-determined time points. After the simulated job interview, 35 healthy adult participants were randomly assigned to either the rumination condition (n = 17) or the distraction condition (n = 18). RESULTS: Inducing stress and rumination led to increased cortisol levels, negative mood, and state rumination. Compared with the distraction group, the rumination group displayed delayed cortisol recovery and decreased scalp prefrontal-limbic connectivities, that is, left ventrolateral prefrontal cortex (LVLPFC) and left temporal area (LTMP) [ps < .05], and right dorsolateral prefrontal cortex (RDLPFC) and anterior cingulate cortex (ACC) [ps < .05]. The relationship between rumination and cortisol recovery was moderated by connectivities between the left dorsolateral prefrontal cortex (LDLPFC) and LTMP, RDLPFC and LTMP, LDLPFC and ACC, and RDLPFC and ACC [B = -0.98 to -0.35, SE = 0.15-0.34, ps < .05]. Higher rumination combined with reduced scalp prefrontal-limbic connectivities to predict delayed cortisol recovery. CONCLUSION: The current findings suggest that scalp prefrontal-limbic connectivity is a neural underpinning related to emotion regulation for the effects of state rumination on stress recovery. These findings also provide a potential target for non-invasive intervention in HPA axis dysregulation.

Engineering Semicarbazide-Bearing Polypeptide Conjugates for Efficient Tumor Chemotherapy and Imaging of Tumor Metastasis.

Polypeptide materials offer scalability, biocompatibility, and biodegradability, rendering them an ideal platform for biomedical applications. However, the preparation of polypeptides with specific functional groups, such as semicarbazide moieties, remains challenging. This work reports, for the first time, the straightforward synthesis of well-defined methoxy-terminated poly(ethylene glycol)-b-polypeptide hybrid block copolymers (HBCPs) containing semicarbazide moieties. This synthesis involves implementing the direct polymerization of environment-stable N-phenoxycarbonyl-functionalized α-amino acid (NPCA) precursors, thereby avoiding the handling of labile N-carboxyanhydride (NCA) monomers. The resulting HBCPs containing semicarbazide moieties enable facile functionalization with aldehyde/ketone derivatives, forming pH-cleavable semicarbazone linkages for tailored drug release. Particularly, the intracellular pH-triggered hydrolysis of semicarbazone moieties restores the initial semicarbazide residues, facilitating endo-lysosomal escape and thus improving therapeutic outcomes. Furthermore, the integration of the hypoxic probe (Ir(btpna)(bpy)2 ) into the pH-responsive nanomedicines allows sequential responses to acidic and hypoxic tumor microenvironments, enabling precise detection of metastatic tumors. The innovative approach for designing bespoke functional polypeptides holds promise for advanced drug delivery and precision therapeutics.