Whole-genome landscape of histone H3K4me3 modification during sperm cell lineage development in tomato.

BACKGROUND: During male gametogenesis of flowering plants, sperm cell lineage (microspores, generative cells, and sperm cells) differentiated from somatic cells and acquired different cell fates. Trimethylation of histone H3 on lysine 4 (H3K4me3) epigenetically contributes to this process, however, it remained unclear how H3K4me3 influences the gene expression in each cell type. Here, we conducted chromatin immunoprecipitation sequencing (ChIP-seq) to obtain a genome-wide landscape of H3K4me3 during sperm cell lineage development in tomato (Solanum lycopersicum). RESULTS: We show that H3K4me3 peaks were mainly enriched in the promoter regions, and intergenic H3K4me3 peaks expanded as sperm cell lineage differentiated from somatic cells. H3K4me3 was generally positively associated with transcript abundance and served as a better indicator of gene expression in somatic and vegetative cells, compared to sperm cell lineage. H3K4me3 was mutually exclusive with DNA methylation at 3' proximal of the transcription start sites. The microspore maintained the H3K4me3 features of somatic cells, while generative cells and sperm cells shared an almost identical H3K4me3 pattern which differed from that of the vegetative cell. After microspore division, significant loss of H3K4me3 in genes related to brassinosteroid and cytokinin signaling was observed in generative cells and vegetative cells, respectively. CONCLUSIONS: Our results suggest the asymmetric division of the microspore significantly reshapes the genome-wide distribution of H3K4me3. Selective loss of H3K4me3 in genes related to hormone signaling may contribute to functional differentiation of sperm cell lineage. This work provides new resource data for the epigenetic studies of gametogenesis in plants.

Microcystin-LR Induces Estrogenic Effects at Environmentally Relevant Concentration in Black-Spotted Pond Frogs (Pelophylax nigromaculatus): In Situ, In Vivo, In Vitro, and In Silico Investigations.

Harmful cyanobacterial blooms are frequent and intense worldwide, creating hazards for aquatic biodiversity. The potential estrogen-like effect of Microcystin-LR (MC-LR) is a growing concern. In this study, we assessed the estrogenic potency of MC-LR in black-spotted frogs through combined field and laboratory approaches. In 13 bloom areas of Zhejiang province, China, the MC-LR concentrations in water ranged from 0.87 to 8.77 µg/L and were correlated with sex hormone profiles in frogs, suggesting possible estrogenic activity of MC-LR. Tadpoles exposed to 1 µg/L, an environmentally relevant concentration, displayed a female-biased sex ratio relative to controls. Transcriptomic results revealed that MC-LR induces numerous and complex effects on gene expression across multiple endocrine axes. In addition, exposure of male adults significantly increased the estradiol (E2)/testosterone (T) ratio by 3.5-fold relative to controls. Downregulation of genes related to male reproductive endocrine function was also identified. We also showed how MC-LR enhances the expression of specific estrogen receptor (ER) proteins, which induce estrogenic effects by activating the ER pathway and hypothalamic-pituitary-gonadal (HPG) axis. In aggregate, our results reveal multiple lines of evidence demonstrating that, for amphibians, MC-LR is an estrogenic endocrine disruptor at environmentally relevant concentrations. The data presented here support the need for a shift in the MC-LR risk assessment. While hepatoxicity has historically been the focus of MC-LR risk assessments, our data clearly demonstrate that estrogenicity is a major mode of toxicity at environmental levels and that estrogenic effects should be considered for risk assessments on MC-LR going forward.

Structural effects of water clusters on viscosity at high shear rates.

In this study, we use molecular dynamics simulations of liquid water to investigate how shear thinning affects the viscosity of liquid water by structural changes of the hydrogen bond network. The effect of shear on viscosity can be divided into two parts: shear-induced destruction of the hydrogen bond network and the influence of the water structure on shear viscosity. First, strong shear destroys tetrahedral structures and thus reduces the connectivity of the hydrogen bond network. It is mainly because shear deformation, characterized by compression and expansion axes, respectively, triggers the destruction and formation of hydrogen bonds, resulting in anisotropic effects on water structures. At the same time, shear destroys large clusters and enhances the formation of small ones, resulting in a decrease in average cluster sizes. Second, the change of viscosity obeys a power law relationship with the change of hydrogen bond structures, highlighting a one-to-one correspondence between structure and property. Meanwhile, in order to explain why the structure affects viscosity, we define hydrogen-bond viscosity and find that the cooperative motion of the water structures can promote momentum transfer in the form of aggregations. Hydrogen-bond viscosity accounts for 5%-50% of the total viscosity. Our results elucidate that water structures are the important structural units to explain the change of water properties.

Acupuncture Versus Oral Medications for Acute/Subacute Non-Specific Low Back Pain: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: Pharmacologic intervention do not always achieve benefits in the treatment of acute/subacute non-specific low back pain (NSLBP). We assessed efficacy and safety of acupuncture for acute/subacute NSLBP as alternative treatment. RECENT FINDINGS: We searched PubMed, Web of Science, Embase, Cochrane Library, Scopus, Epistemonikos, CNKI, Wan Fang Database, VIP database, CBMLD, CSTJ, clinical trials, EUCTR, World WHO ICTRP, and ChiCTR for randomized controlled trials, cross-over studies, and cohort studies of NSLBP treated by acupuncture versus oral medication from inception to 23th April 2022. A total of 6 784 records were identified, and 14 studies were included 1 263 participants in this review. The results of the meta-analysis indicated that acupuncture therapy was slightly more effective than oral medication in improving pain (P < 0.00001, I2 = 92%, MD = -1.17, 95% CI [-1.61, -0.72]). According to the results of the meta-analysis, acupuncture therapy exhibited a significant advantage over oral medication with a substantial effect (P < 0.00001, I2 = 90%, SMD = -1.42, 95% CI [-2.22, -0.62]). Based on the results of the meta-analysis, acupuncture therapy was associated with a 12% improvement rate compared to oral medication in patients with acute/subacute NSLBP (P < 0.0001, I2 = 54%, RR = 1.11, 95% CI [1.05, 1.18]). Acupuncture is more effective and safer than oral medication in treating acute/subacute NSLBP. This systematic review is poised to offer valuable guidance to clinicians treating acute/subacute NSLBP and potentially benefit the afflicted patients. REGISTRATION: This review was registered in PROSPERO ( http://www.crd.york.ac.uk/prospero ) with registration number CRD42021278346.

Hierarchical clustering analysis of hydrogen bond networks in aqueous solutions.

To understand the relation between the macroscopic properties and microscopic structure of hydrogen bond networks in solutions, we introduced a hierarchical clustering method to analyze the typical configurations of water clusters in this type of network. Regarding hydrogen bonds as frames, the rings, fragments and clusters are defined and analyzed to provide a comprehensive perspective for the distributional and dynamic characteristics of the hydrogen-bonding network in NaCl solution at different concentrations. The properties of the radial distribution function and hydrogen bonds are first analyzed. Destruction and shorter lifetimes of hydrogen bonds are observed in solutions. In further analysis of the two-dimensional configuration, i.e., ring, and three-dimensional configuration, i.e., fragment, the average number, size and lifetime of these structures consistently decrease as the concentration increases. Ionic effects on disrupting rings and fragments are significant in the first hydration shell, especially with sodium cations, and these effects weaken beyond the first hydration shell. Regarding the clusters obtained using the Louvain algorithm, our results indicate that clusters break and become smaller as the NaCl concentration increases. The presence of ions also leads to the isolation of clusters and therefore the inhibition of changes. The lifetime of clusters increases with NaCl concentration, indicating the slowed breakage and reformation of clusters in NaCl solutions. This method can be further applied to quantitatively characterize hydrogen bond networks to elucidate more properties of aqueous solutions.

A MSALL quantitative method for the determination of Poloxamer 188 in rat plasma by UHPLC-Q-TOF/MS and its application to pharmacokinetic study.

Poloxamer (PL)188 is a commonly used pharmaceutical excipient with unique physicochemical properties. In this study, an MSALL quantitative method for the determination of PL188 in rat plasma by UHPLC-Q-TOF/MS was developed and validated. PL188 was analyzed on PLRP-S reversed-phase column (50 × 4.6 mm, 8 µm, 1,000 Å) with mobile phase 0.1% formic acid-water and 0.1% formic acid in acetonitrile-isopropanol (2:3, v/v). The liner range was 0.1-10.0 µg/ml. A pharmacokinetic study was performed on rats at a dose of 5 mg/kg by intravenous injection. The pharmacokinetic parameters of intravenous injection were as follows: half-life was 2.0 ± 1.1 h, volume of distribution was 5.1 ± 3.2 L/kg, area under the concentration-time curve was 3.0 ± 0.6 µg/L h and clearance was 1.7 ± 0.3 L/h/kg. The results indicated that PL188 could be rapidly distributed to tissues with a high clearance rate. This study can provide a good reference for the further study of PL188.

The acts of opening and closing the eyes are of importance for congenital blindness: Evidence from resting-state fMRI.

Volitional eye closure is observed only in conscious and awake humans, and is rare in animals. It is believed that eye closure can focus one's attention inward and facilitate activities such as meditation and mental imagery. Congenital blind individuals are also required to close their eyes for these activities. Resting-state functional magnetic resonance imaging (RS-fMRI) studies have found robust differences between the eyes-closed (EC) and eyes-open (EO) conditions in some brain regions in the sighted. This study analyzed data from 21 congenital blind individuals and 21 sighted controls by using amplitude of low-frequency fluctuation (ALFF) of RS-fMRI. The blind group and the sighted group shared similar pattern of differences between the EC and EO condition: ALFF was higher in the EC condition than the EO condition in the bilateral primary sensorimotor cortex, bilateral supplementary motor area, and inferior occipital cortex, while ALFF was lower in the EC condition than the EO condition in the medial prefrontal cortex, highlighting the "nature" effect on the difference between the EC and EO conditions. The results of other matrices such as fractional ALFF (fALFF) and regional homogeneity (ReHo) showed similar patterns to that of ALFF. Moreover, no significant difference was observed between the EC-EO pattern of the two subgroups of congenital blind (i.e., with and without light perception), suggesting that the EC-EO difference is irrespective of residual light perception which reinforced the "nature" effect. We also found between-group differences, i.e., more probably "nurture effect", in the posterior insula and fusiform. Our results suggest that the acts of closing and opening the eyes are of importance for the congenital blind, and that these actions and their differences might be inherent in the nature of humans.

Tissue Distribution Study of Poloxamer188 in Rats by Ultra-High-Performance Liquid Chromatography Quadrupole Time of Flight/Mass Spectrometry with MSALL-Based Approach.

Poloxamer188 (PL188), as one of the most commonly used pharmaceutical excipients, has unique physicochemical properties and good biocompatibility, and so is playing an increasingly extensive role in the field of medicine. Currently, there are few studies on the tissue distribution of PL188 in vivo. In this study, the LC-MS method based on MSALL technique of quadrupole time of flight mass spectrometry for absolute quantitative analysis of poloxamer 188 in biological substrates was established for the first time. The tissue distribution of poloxamer188 in SD rats were studied using the established quantitative analysis method. To explore the distribution of PL188 in organs and tissues, PL188 was administered via rat tail vein at a dose of 5 mg/kg. Eight kinds of tissues including heart, liver, spleen, lung, kidney, stomach, muscle and brain of rats were collected at 0.25 h, 1 h and 4 h after administration. Tissue distributions showed the highest level was observed in kidney, then in stomach, which indicated PL188 mainly bioaccumulated in the kidney. This study can provide references for the further study of PL188.

Stress responses and biological residues of sulfanilamide antibiotics in Arabidopsis thaliana.

Sulfonamides (SAs) are antibiotics widely used in clinical practice, livestock and poultry production, and the aquaculture industry. The compounds enter the soil environment largely through livestock and poultry manure application to farmland. SAs not only affect plant growth, but also pose a potential threat to human health through SA residues in plant tissues. In particular, sulfamethoxazole (SMZ) has been classified as a Category 3 carcinogen by the World Health Organization, and thus its soil ecological toxicity and possible health risks are of concern. Using A. thaliana as a model plant, stress responses and biological residues of sulfadiazine (SD), sulfametoxydiazine (SMD), and SMZ were investigated in the present study. Root length and aboveground plant biomass were significantly inhibited by the three types of SA, whereas lateral roots exposed to SMD grew vigorously. The contents of chlorophyll a and chlorophyll b and photosystem II maximum photochemical quantum yield declined with increase in drug concentration, which indicated that exposure to SAs affected photosynthesis and inhibited chlorophyll synthesis in A. thaliana. With increase in drug concentration, reactive oxygen species (ROS) accumulation in the leaves increased significantly. Activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were activated at low SA concentrations, but increased lipid peroxidation occurred with increase in SA concentration. Of the three compounds, SMZ was the most toxic to A. thaliana, followed by SD, and SMD was the least toxic. The results indicated that the risk of SMD entering an organism through the food chain is greater than that for SMZ and SD.

Ultrahigh-throughput absolute quantitative analysis of linezolid in human plasma by direct analysis in real time mass spectrometry without chromatographic separation and its application to a pharmacokinetic study.

Therapeutic drug monitoring (TDM) is necessary in the clinical management of linezolid to improve its efficacy and reduce the risk of time- and dose-dependent toxicity. A novel and ultrahigh-throughput analytical method for the determination of linezolid in human plasma was developed based on direct analysis in real-time tandem mass spectrometry (DART-MS/MS) without chromatographic separation. After solid-phase extraction with Waters Oasis HLB, the linezolid and internal standard linezolid-d3 were detected by positive ion electrospray ionization followed by multiple reaction monitoring (MRM) of the transition at m/z 338.1 → 296.2 and 341.2 → 297.3, respectively. The use of DART-MS obviates the need for chromatographic separation and allowed determination of linezolid in a total run time of only 24 s per sample. The method was linear in the concentration range 0.20-25 µg mL-1 with intraday and interday precision <14.5% and accuracy ranging from -3.85% to 12.7%. The method was successfully applied to a pharmacokinetic study of linezolid in healthy male volunteers after oral administration of a 600 mg tablet. DART-MS/MS provides a rapid and sensitive method for the determination of linezolid that does not require chromatographic separation. It is eminently suitable to meet the high-throughput challenge of clinical TDM. Graphical abstract.

Residual Equinus After the Ponseti Method: An MRI-based 3-Dimensional Analysis.

BACKGROUND: Residual equinus deformity is present in up to 20% of clubfeet treated by the Ponseti method. These patients may require surgical release to restore dorsiflexion. Despite complete posterior release; persistent intraoperative equinus may be present and suggest concurrent joint incongruity. The purpose of this study was to characterize differences in ankle morphology in toddlers with residual equinus following the Ponseti method. METHODS: Preoperative magnetic resonance imaging (MRI) data from 10 patients who underwent reconstruction (17 feet; 7 bilateral, 3 unilateral clubfeet) for persistent equinus were compared with 16 age-matched controls. Through reverse engineering software, MRI data were used to generate 3-dimensional (3D) models. Four talus-based measures were performed on both MRI data and 3D models-neck depth, neck angle, width, and length. Models were also used to calculate talus volume and arc of curvature (plafond and talar dome). Standard statistical analyses were performed. RESULTS: Talus volumes, width, and length were less in clubfeet then in control feet. Although some measures were significant there was no mismatch with the ankle mortise dimensions or arc curvature that could account for any decrease in dorsiflexion. We found that from MRI measures the clubfoot neck depth was 2.3 versus 3.6 mm in controls (P<0.001) and from 3D modeling the clubfoot neck depth was 2.3 and 3.5 mm in controls (P=0.003). With 3D modeling talus clubfoot neck angle was 153.7 versus 140.4 degrees in controls (P=0.01). The clubfoot neck angle obtained from MRI measures were also different yet not significant [126.6 in clubfeet versus 122.5 degrees in controls (P=0.12)]. CONCLUSIONS: In comparison to age-matched feet; we have noted a decrease in talar neck depth and an obtuse talar neck angle in clubfeet treated in the manner of Ponseti. This may result in anterior ankle impingement and be the cause of residual equinus despite posterior release. In these procedures, the surgeon should recognize this possibility when the amount of dorsiflexion is less than expected. LEVEL OF EVIDENCE: Level III-case control study.

Utility of real-time 3D visualization system in the early stage of phacoemulsification training.

AIM: To determine the teaching effects of a real-time three dimensional (3D) visualization system in the operating room for early-stage phacoemulsification training. METHODS: A total of 10 ophthalmology residents of the first-year postgraduate were included. All the residents were novices to cataract surgery. Real-time cataract surgical observations were performed using a custom-built 3D visualization system. The training lasted 4wk (32h) in all. A modified International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubric (ICO-OSCAR) containing 4 specific steps of cataract surgery was applied. The self-assessment (self) and expert-assessment (expert) were performed through the microsurgical attempts in the wet lab for each participant. RESULTS: Compared with pre-training assessments (self 3.2±0.8, expert 2.5±0.6), the overall mean scores of post-training (self 5.2±0.4, expert 4.7±0.6) were significantly improved after real-time observation training of 3D visualization system (P<0.05). Scores of 4 surgical items were significantly improved both self and expert assessment after training (P<0.05). CONCLUSION: The 3D observation training provides novice ophthalmic residents with a better understanding of intraocular microsurgical techniques. It is a useful tool to improve teaching efficiency of surgical education.

Electrocatalytic oxidation of 5-hydroxymethylfurfural to 2,5-furandicarboxylic acid via metal-organic framework-structured hierarchical Co3O4 nanoplate arrays.

Electrocatalytic oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) was examined as an alternative to thermocatalytic methods in which two-dimensional (2D) cobalt-metal-organic framework (Co-MOF, ZIF-L-Co) nanoplate arrays were prepared on nickel foam (NF) and then transformed into hierarchical porous Co3O4 nanostructures by chemical etching and low temperature annealing to form electrode materials. Hierarchical porous nanoarrays formed during synthesis enlarged the surface area of the as-prepared catalysts introduced a large number of defects and exposed active sites leading to reduced charge diffusion, improved mass transfer and efficient HMF oxidation. Co3O4/NF electrode materials were able to achieve a current density of 10 mA·cm-2 at an overpotential of 105 mV in 1 M KOH with 10 mM HMF, which was reduced by 175 mV compared with water oxidation. Electrocatalytic oxidation experiments afforded 100 % HMF conversion and 96.7 % FDCA yields with a minimum 96.5 % faradaic efficiency at 1.43 V vs RHE. The proposed MOF-structured synthesis method fundamentally reduces charge diffusion, improves mass transfer of electrodes and is generally applicable to fabrication of hierarchical porous nanostructured materials.

The sustainability of urbanized land: Impacts of the growth of urbanized land in prefecture-level cities in China.

The sustainability of land conversion to urban use is an important factor that promotes sustainable urbanization. However, China's local governments have relied too much on the land finance model for urbanization, which has led to disordered growth of urban land, ultimately posing a threat to ecosystem security and socioeconomic development. Effectively evaluating the factors that influence the growth of urban land is critical to improving the sustainability of urban land use. In this study, we explored the factors that affect the growth in the area of urban land using spatial analysis models based on panel data for Chinese prefecture-level cities from 2007 to 2019. We found that fiscal decentralization, infrastructure, industrialization, and industrial upgrading were the main factors responsible for the growth of urban land, but that their degrees of influence differed between regions. Our findings identify the necessity for local governments to design urban land-use policies and perform strategic planning for urban land use to improve sustainability based on the main factors that influenced the growth of urban land in each region.

Abnormal dynamics of brain functional networks in children with Tourette syndrome.

Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder characterized by the presence of multiple motor and vocal tics. Research using resting-state functional magnetic resonance imaging (rfMRI) have found aberrant static functional connectivity (FC) and its topological properties in the brain networks of TS. Our study is the first to investigate the dynamic functional connectivity (dFC) in the whole brain network of TS patients, focusing on the temporal properties of dFC states and the temporal variability of topological organization. The rfMRI data of 36 male children with TS and 27 matched healthy controls were collected and further analyzed by group spatial independent component analysis, sliding windows approach based dFC analysis, k-means clustering analysis, and graph theory analysis. The clustering analysis identified three dFC states. Of these states, state 2, characterized by increased inter-network connections in subcortical network (SCN), sensorimotor network (SMN), and default mode network (DMN), and decreased inter-network connections between salience network (SAN) and executive control network (ECN), was found to have higher fractional window and dwell time in TS, which was also positively correlated with tic severity. TS patients also exhibited higher temporal variability of whole-brain-network global efficiency and local efficiency, and higher temporal variability of nodal efficiency and local efficiency in SCN, DMN, ECN, SAN, and SMN. Additionally, temporal variability of the efficiency and local efficiency in insula was positively correlated with tic severity. Our findings revealed abnormal temporal property of dFC states and temporal variability of topological organization in TS, providing new insights into clinical diagnoses and neuropathology of TS.

Aggregation-caused dual-signal response of gold nanoclusters for ratiometric optical detection of cysteine.

Designing ratiometric sensors for cysteine (Cys) monitoring with high accuracy is of great significance for disease diagnosis and biomedical studies. The current ratiometric methods mainly rely on multiplex probes, which not only complicates the operation but also increases the cost, making it difficult for quantitative Cys detection in resource-limited areas. Herein, one-pot prepared gold nanoclusters (Au NCs) that glow red fluorescent were synthesized by employing glutathione as the stabilizer and reducing agent. When Fe3+ is present with Au NCs, the fluorescence is quenched and the scattering is strong because of the aggregation of Au NCs. With introduction of Cys, Cys can efficiently compete with glutathione-modified Au NCs for Fe3+, which leads to increase of fluorescence and decrease of scattering. The ratiometric determination of Cys can be thereby realized by collecting the fluorescence and SRS spectrum simultaneously. The linear range for Cys was 5-30 µM with a detection limit of 1.5 µM. In addition, the sensing system exhibits good selectivity for Cys and shows potential application in biological samples.

Genome-wide identification glutathione-S-transferase gene superfamily in Daphnia pulex and its transcriptional response to nanoplastics.

Glutathione S-transferases (GSTs) are key multifunctional phase II detoxification enzymes involved in the regulation of growth, development, and stress responses. However, the knowledge of GSTs in the model invertebrate organism Daphnia pulex at the genomic level remains limited. In the present study, 35 GST genes were identified in D. pulex (Dp-GST), belonging to eight subfamilies, with the sigma, mu, and delta/epsilon subfamilies constituting approximately 29 %, 20 %, and 20 % of the GST superfamily, respectively. Chromosome tandem duplication of genes within the same subfamily was observed, which may be the main force driving GST expansion in D. pulex. DpGST genes showed different expression patterns in response to nanoplastic exposure for 96 h and 21 days. Some homologous GST genes in D. pulex showed similar expression patterns in response to nanoplastic exposure, likely owing to their unique motifs. For example, motif 9 is found in all delta/epsilon GST genes, whereas motifs 1, 2, 3, 5, and 7 are highly conserved in sigma GST genes. The characterization of D. pulex GSTs extending the knowledge of GST-mediated environmental contaminants, especially nanoplastics.

Perfluorooctanoic acid and perfluorooctanesulfonic acid induce immunotoxicity through the NF-κB pathway in black-spotted frog (Rana nigromaculata).

Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are widely detected in the environment and wild animals, thus posing a threat to wildlife and public health; however, knowledge about their immunotoxicity and the underlying mechanism remains limited. In the present study, male black-spotted frogs (Rana nigromaculata) were exposed to environmentally relevant concentrations (0, 1, and 10 µg/L) of PFOA or PFOS for 21 days; subsequently, biochemical analysis, molecular docking, and gene expression determination were conducted. The results indicated that exposure to 10 µg/L PFOA decreased the serum levels of immunoglobulin A. PFOS exposure significantly increased the hepatic levels of interleukin-1ß, interleukin-6, tumor necrosis factor-α, interferon-γ, and nitric oxide; but PFOA significantly increased the levels of only tumor necrosis factor-α. Furthermore, PFOA and PFOS exposure significantly decreased the activity of inducible nitric oxide synthase and total nitric oxide synthase. IBRv2 analysis indicated that PFOA and PFOS had a similar effect on these immune indicators, but PFOS was more toxic than PFOA. Molecular docking revealed that PFOA and PFOS can bind to nuclear factor-κB (NF-κB) by forming stable hydrogen bonds. PFOA and PFOS exposure upregulated the gene expression of NF-κB and its downstream genes. Significant correlations between the expression of genes involved in the NF-κB pathway and immune-related indicators suggests that PFOA- and PFOS-induced immunotoxicity was associated with the activation of NF-κB. Our findings provide novel insights into the potential role of NF-κB in immunotoxicity induced by PFOA and PFOS in frogs.

N-Trimethylated chitosan coating white adipose tissue vascular-targeting oral nano-system for the enhanced anti-obesity effects of celastrol.

Oral nanoparticles (NPs) are more suitable for obesity control compared to NPs administered intravenously, as their convenience increases patient compliance. Herein, we developed an oral nano-system to improve the anti-obesity efficacy of celastrol (Cel). The observed enhanced efficacy was mediated by zein core NPs decorated with adipose-homing peptides that were coated with N-trimethylated chitosan. The optimized Cel/AHP-NPs@TMC exhibited spherical morphology by TEM, as well as narrow size distribution (221.76 ± 6.73 nm) and adequate stability in a gastrointestinal environment. Based on the combined delivery advantages of AHP-NPs@TMC - i.e., improved cellular internalization within Caco-2 cells and enhanced white adipose tissue (WAT) vascular targeting - Cel/AHP-NPs@TMC significantly reduced the body weight, blood lipid levels, adipose inflammation, and WAT distribution in diet-induced obese mice without side-effects. In short, this study provides clear evidence that TMC-based oral NPs can effectively improve celastrol for obesity treatment.

Electroacupuncture Ameliorates Depression-Like Behaviors in Post-Stroke Rats via Activating AMPK-Mediated Mitochondrial Function.

Background: Post-stroke depression (PSD) is one of the most common complications of stroke. Electroacupuncture (EA) is an effective traditional Chinese medicine treatment for PSD, which is widely used in clinical settings. EA has a significant therapeutic effect against PSD, but the mechanism is still unclear. This study aimed to determine whether EA ameliorates depression-like behaviors in PSD rats by regulating the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-mediated mitochondrial function. Methods: Middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress (CUMS) were used to develop a PSD rat model. To elucidate the role of AMPK in EA treatment, compound C, a selective inhibitor of AMPK, was injected into the lateral ventricle of rats before EA treatment. EA treatment was performed for 14 consecutive days for 30 min per day after PSD modeling. A modified Zea-Longa five-point scale scoring system was used to determine neurologic function in MCAO rats. Behavioral tests were conducted to evaluate depression-like phenotypes in rats. Depression-like behaviors were tested by sucrose preference test (SPT), novelty suppressed feeding test (NSFT), and open-field test (OFT). The structure and morphology of the prefrontal cortex were observed by histopathological hematoxylin-eosin (HE) and Nissl staining. The mitochondrial morphology and function were analyzed by colorimetry, chemiluminescence, Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR). Results: EA treatment successfully ameliorated depression-like behaviors, upregulated AMPK expression, and improved mitochondrial function. However, AMPK inhibition by Compound C exacerbated depression-like behaviors and aggravated neuronal and mitochondrial injury in PSD rats. Conclusion: EA treatment improved depression-like behaviors in PSD rats and promoted mitochondrial function by activating AMPK.