GM130-silencing may aggravate blood-brain barrier damage and affect microglia polarization by down-regulating PD-L1 expression after experimental intracerebral hemorrhage.

BACKGROUND: In addition to primary injury, secondary injuries related to BBB disruption and immune-inflammatory response also play an important role in intracerebral hemorrhage (ICH). And the Golgi apparatus play an important role in the state of ICH. METHODS: ICH model and GM130-silencing ICH model were established in SD rats. The Garcia score was used to score the neurological defects of the rats. Blood-brain barrier (BBB) integrity were assessed by amount of extravasated Evans blue, and tight junction proteins. The expression of PD-L1 and GM130were detected through Western-blot and the subtype of microglia was showing with Immunofluorescence staining. RESULTS: Compared with the ICH group, GM130-silencing ICH rats got a worsened neurological deficit and enlarged volume of the hematoma. Evan's blue extravasation aggravated as well. The expression of GM130 in peri-hematoma tissue was further decreased, and the morphology and structure of the Golgi apparatus were further damaged. Meanwhile, the GM130 deficit resulted in decreased expression of PD-L1 and more polarization of microglia to the M1 subtype. CONCLUSION: We demonstrate that GM130 could influence the integrity of BBB and plays a role in neuroinflammation via regulation of PD-L1 after ICH. The manipulation of GM130 might be a promising therapeutical target in ICH.

Effectiveness of Platelet-Rich Plasma in the Treatment of Androgenic Alopecia: A Meta-Analysis.

BACKGROUND: Androgenetic alopecia (AGA) is a common yet difficult-to-treat condition, which is an important psychosocial problem. Platelet-rich plasma (PRP) therapy has been considered as a promising treatment for AGA. However, the current evidence on the efficacy of PRP for treating AGA is still controversial. This study evaluated the efficacy of PRP monotherapy in the treatment of AGA. METHODS: We searched PubMed, Embase, Cochrane Library and Web of Science to collect randomized controlled trials on use of PRP in AGA for a meta-analysis. RESULTS: Ten trials with a total 555 treatment units were identified. The hair density in PRP group was significantly higher than control group [MD = 25.09, 95%CI: 9.03-41.15, p = 0.002], but there was no significant difference in hair diameter between two groups [SMD = 0.57, 95%CI: - 0.23 to 1.38, p = 0.16]. Subgroup analyses indicated that hair density was significantly higher among the male-only trials than in the mixed-sex samples (p = 0.02). In addition, neither the split-head design nor the year of publication affected hair density (p = 0.05, p = 0.06). However, hair density was significantly higher in trials with a sample size less than 30 (p = 0.0004). CONCLUSIONS: PRP treatment increased hair density in participants with AGA, but not hair diameter. In terms of hair density, PRP elicits stronger effects in male patients. There was a trend toward differed treatment effect by gender with PRP injection, which warrants further investigation. Especially in the case of female. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

Myasthenia gravis coexisting with HINT1-related motor axonal neuropathy without neuromyotonia: a case report.

BACKGROUND: HINT1 mutations cause an autosomal recessive axonal neuropathy with neuromyotonia. This is a first case report of coexistence of myasthenia gravis (MG) and HINT1-related motor axonal neuropathy without neuromyotonia. CASE PRESENTATION: A 32-year-old woman presented with recurrent ptosis for 8 years, diplopia for 2 years and limb weakness for 1 year and a half. Neostigmine test, elevated AChR antibody level and positive repetitive nerve stimulation supported the diagnosis of MG. Electroneurography (ENG) and electromyography (EMG) examinations revealed a motor axonal neuropathy without neuromyotonic or myokymic discharges. Next-generation sequencing and Sanger sequencing were performed to identify the gene responsible for suspected hereditary neuropathy. Genetic testing for a HINT1 mutation was performed and revealed a homozygous mutation at c.278G>T (p. G93V). The patient was treated with pyridostigmine, oral prednisolone and azathioprine. Her ptosis and diplopia have significantly improved at 6-month follow-up. CONCLUSIONS: Concurrence of MG and hereditary motor axonal neuropathy without neuromyotonia is quite rare. Detection of ptosis with or without ophthalmoplegia, distribution of limb weakness, and reflex can help in recognizing the combination of MG and peripheral neuropathy. Early diagnosis is important for initial treatment and prognosis. The novel homozygous variant c.278G>T(p.G93V) contributes to the pathogenic variants spectrum of the HINT1 gene.

Catalase-integrated metal-organic framework with synergetic catalytic activity for colorimetric sensing.

As a platform for enzyme immobilization, metal-organic frameworks (MOFs) can protect enzyme activity from the interference of external adverse environment. Although these strategies have been proven to produce good results, little consideration has been given to the functional similarity of MOFs to the encapsulated enzyme. Here, catalase (CAT) was encapsulated in Fe-BTC with peroxidase-like activity to obtain a stable composite (CAT@Fe-BTC) with synergistic catalytic activity. Depending on the superior selectivity and high catalytic activity of CAT@Fe-BTC, colorimetric sensing for the detection of hydrogen peroxide and phenol was developed. This work demonstrates that the integration of functional MOFs with natural enzyme can be well applied to the construction of efficient catalysts.

Fabrication of Pt doped TiO2-ZnO@ZIF-8 core@shell photocatalyst with enhanced activity for phenol degradation.

Phenol's presence in aqueous solution due to the pollution from chemical and agricultural industries (e.g., coking tobacco leaves) causes severe environmental problems. As a result, many scientists and engineers search for catalysts to remove phenol from water by photodegradation. Thus, we synthesized Pt-doped TiO2-ZnO@ZIF-8 core@shell particles (Pt/TiO2-ZnO@ZIF-8) by a simple method involving crystallization, absorption, pyrolysis and growth steps. The resulting materials were analyzed by the powder X-ray diffraction (XRD), scanning and transmission electron microscopies (SEM and TEM, respectively), surface area measurements and UV-vis absorption spectroscopy. The photocatalytic activities of our materials were evaluated by phenol degradation in aqueous solutions. Pt-doped TiO2-ZnO particles possessed a polyhedral structure and exhibited broad absorption above 400 nm. Coating with ZIF-8 increased the specific surface area of the Pt-doped TiO2-ZnO particles. Both Pt doping and ZIF-8 coating significantly enhanced the photocatalytic performance of TiO2-ZnO. Pt/TiO2-ZnO@ZIF-8 decomposed 99.7 % of phenol after the corresponding solution was exposed to UV light for 24 min. This performance was significantly better than the phenol decomposition ability of TiO2-ZnO, Pt/TiO2-ZnO and TiO2, which degraded 76.1 %, 95.2 % and 86.9 % of phenol, respectively. Pt/TiO2-ZnO@ZIF-8 also demonstrated excellent recycling stability. All these properties, including photostability, made our novel Pt/TiO2-ZnO@ZIF-8 catalyst a promising material for practical applications in environmental remediation.

Design, Synthesis and Molecular Docking of Novel Quinazolinone Hydrazide Derivatives as EGFR Inhibitors.

A series of novel quinazolinone hydrazide derivatives were designed and synthesized as EGFR inhibitors. The results indicated that most of the aimed compounds had potential anti-tumor cell proliferation and EGFR inhibitory activities. In the comprehensive analysis of all the tested compounds, the target compound 9c showed the best anti-tumor cell proliferation activity, (IC50 =1.31 µM for MCF-7, IC50 =1.89 µM for HepG2, IC50 =2.10 µM for SGC), and IC50 =0.59 µM for the EGFR inhibitory activity. Docking results showed that compound 9c could ideally insert the active site and interact with the critical amino acid residues (Val702, Lys721, Met769, Asp831) in the active site.

Aureonitol Analogues and Orsellinic Acid Esters Isolated from Chaetomium elatum and Their Antineuroinflammatory Activity.

Overexpression of various pro-inflammatory factors in microglial cells tends to induce neurodegenerative diseases, for which there is no effective therapy available. Aureonitol (1) and seven analogues, including six previously undescribed [elatumenol A-F (2-4, 6-8, respectively)], along with two new orsellinic acid esters [elatumone A and B (9 and 10)], were isolated from Chaetomium elatum. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including high-resolution mass spectra and one- and two-dimensional NMR, and absolute configurations determined by the Mosher method, dimolybdenum tetraacetate-induced circular dichroism, and theoretical calculations including electronic circular dichroism and NMR. Metabolites 3, 4, 7, and 8 exhibited antineuroinflammatory activity by attenuating the production of inflammatory mediators, such as nitric oxide, interleukin-6, interleukin-1ß, tumor necrosis factor-α, and reactive oxygen species. Western blot results indicated 8 decreases the level of inducible nitric oxide synthase and cyclooxygenase-2 and suppresses the expression of Toll-like receptor 4 and nuclear factor kappa-B (NF-κB) as well as the phosphorylation of the inhibitor of NF-κB and p38 mitogen-activated protein kinases in lipopolysaccharide-activated BV-2 microglial cells.

Intravoxel Incoherent Motion Diffusion-Weighted Imaging of Lung Cancer: Comparison Between Turbo Spin-Echo and Echo-Planar Imaging.

OBJECTIVE: The aim of the study was to compare intravoxel incoherent motion diffusion-weighted imaging (DWI) for evaluating lung cancer using single-shot turbo spin-echo (TSE) and single-shot echo-planar imaging (EPI) in a 3T MR system. METHODS: Both single-shot TSE-DWI and single-shot EPI-DWI were scanned twice respectively for 15 patients with lung cancer. Distortion ratio, signal-to-noise ratio, and contrast-to-noise ratio were compared between the 2 techniques. The Bland-Altman analysis was performed to analyze reproducibility between the parameters of TSE-DWI and EPI-DWI. Short-term test-retest repeatability, as well as interobserver agreement, was evaluated using the coefficient of variation (CV) and the intraclass correlation coefficient (ICC). RESULT: Turbo spin-echo DWI has lower signal-to-noise ratio and similar contrast-to-noise ratio compared with EPI-DWI. Distortion ratio of TSE-DWI was significantly smaller than that of EPI-DWI. The apparent diffusion coefficient (ADC) and true diffusivity (D) of TSE-DWI showed higher values than those of EPI-DWI. The Bland-Altman analysis showed unacceptable limits of agreement between these 2 sequences. Test-retest repeatability was good for ADC and D of EPI-DWI (CV, 14.11%-16.60% and 17.08%-19.53%) and excellent for ADC and D of TSE-DWI (CV, 4.8%-6.19% and 6.05%-8.71%), but relatively poor for perfusion fraction (f) and pseudo-diffusion coefficient (D*) (CV, 25.95%-27.70% and 56.92%-71.84% for EPI, 23.67%-28.67% and 60.85%-70.17% for TSE). For interobserver agreement, both techniques were good to excellent in ADC and D (The lower limit of 95% confidence interval for ICC was almost all greater than 0.75), whereas D* and f had higher interobserver variabilities with D* of TSE-DWI showing poorest reproducibility (ICC, -0.27 to 0.12). CONCLUSIONS: Lung DWI or IVIM using TSE could provide distortion-free images and improve the test-retest robustness of ADC and D as compared with EPI-DWI; however, it might exert a negative effect on perfusion parameter D*.

Differentiating between malignant and benign solid solitary pulmonary lesions: are intravoxel incoherent motion and diffusion kurtosis imaging superior to conventional diffusion-weighted imaging?

OBJECTIVE: To quantitatively compare the diagnostic values of various diffusion parameters obtained from mono- and biexponential diffusion-weighted imaging (DWI) models and diffusion kurtosis imaging (DKI) in differentiating between benign and malignant solitary pulmonary lesions (SPLs). METHODS: Multiple b-value DWIs and DKIs were performed in 89 patients with SPL by using a 3-T magnetic resonance (MR) imaging unit. The apparent diffusion coefficient (ADC) of various b-value sets, true diffusivity (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), apparent diffusional kurtosis (Kapp), and kurtosis-corrected diffusion coefficient (Dapp) were calculated and compared between the malignant and benign groups using a Mann-Whitney U test. Receiver-operating characteristic analysis was performed for all parameters. RESULT: The ADC(0, 150) values of malignant tumors were lower than those of the benign group (p = 0.01). The ADC(0, 300), ADC(0, 500), ADC(0, 600), ADC(0, 800), ADC(0, 1000), ADCtotal, D, and Dapp of malignant tumors were significantly lower than those of benign lesions (all p < 0.001). D*, f, and Kapp showed no statistically significant differences between the two groups. ADCtotal showed the highest area under the curve (AUC = 0.862), followed by ADC(0, 800)(AUC = 0.844), ADC(0, 600)(AUC = 0.843), D(AUC = 0.834), ADC(0, 1000)(AUC = 0.834) and ADC(0, 500)(AUC = 0.824), Dapp(AUC = 0.796), and ADC(0, 300) (AUC = 0.773). However, the difference in diagnostic efficacy among these parameters was not statistically significant (p > 0.05). CONCLUSION: Intravoxel incoherent motion (IVIM) and DKI-derived parameters have similar performance compared with conventional ADC in differentiating SPLs. KEY POINTS: • Mono- and biexponential DWI and DKI are feasible for differentiating SPLs. • ADC (0, ≥500) has better performance than ADC (0, <500) in assessing SPLs. • IVIM and DKI have similar performance compared with conventional DWI in differentiating SPLs.

[Effect of butylphthalide on blood-brain barrier after cerebral hemorrhage in SD rats and the mechanisms].

OBJECTIVE: To investigate the alteration in Golgi and blood-brain barrier after cerebral hemorrhage in SD rats, and to evaluate the effect of butylphthalide on blood-brain barrier. 
 Methods: Sprague-Dawley rats were randomly distributed into 4 groups: a control group, a sham group, an intracerebral hemorrhage (ICH) group, and a butylphthalide group. Brain tissue was collected at 48 h after the blood brain barrier permeability was examined. Western blotting and real-time polymerase chain reaction (real-time PCR) were conducted to explore the change of GM130, Cdc42 and tight junction protein and mRNA expression in rat brain after ICH. Immunohistochemistry (IHC) was performed to explore the distribution of ZO-1 and Occludin in the cerebral vascular endothelial cells around the hematoma.
 Results: The Evans blue (EB) extravasation in the ICH group were much greater than that in the sham group (P<0.05). Butylphthalide treatment significantly decreased Evans blue extravasation compared to the ICH group (P<0.05). Results of Western blotting and real-time PCR showed that GM130, Cdc42, ZO-1/Occludin were decreased (P<0.05). The intervention of butylphthalide significantly upregulated the expressions of Cdc42 as well as ZO-1/Occludin (P<0.05), but exerted no effect on GM130 (P<0.05). Immunofluorescent staining showed that GM130 was co-localized with Cdc42 and administration of butylphthalide improved the expression of Cdc42 around the hematoma without affecting the expression of GM130. IHC showed that expressions of occludin and ZO-1 around the hematoma were significantly decreased in the ICH group (P<0.05), whereas butylphthalide treatment elevated the expressions of ZO-1 and occludin around the hematoma compared with the ICH group (P<0.05).
 Conclusion: Morphology of Golgi apparatus is altered and the blood-brain barrier is destroyed after ICH. The application of butylphthalide can alleviate neurological impairment and blood-brain barrier disruption, which is related to the up-regulation of Cdc42, but not GM130.

Nano-silver-incorporated biomimetic polydopamine coating on a thermoplastic polyurethane porous nanocomposite as an efficient antibacterial wound dressing.

BACKGROUND: Developing an ideal wound dressing that meets the multiple demands of good biocompatibility, an appropriate porous structure, superior mechanical property and excellent antibacterial activity against drug-resistant bacteria is highly desirable for clinical wound care. Biocompatible thermoplastic polyurethane (TPU) membranes are promising candidates as a scaffold; however, their lack of a suitable porous structure and antibacterial activity has limited their application. Antibiotics are generally used for preventing bacterial infections, but the global emergence of drug-resistant bacteria continues to cause social concerns. RESULTS: Consequently, we prepared a flexible dressing based on a TPU membrane with a specific porous structure and then modified it with a biomimetic polydopamine coating to prepare in situ a nano-silver (NS)-based composite via a facile and eco-friendly approach. SEM images showed that the TPU/NS membranes were characterized by an ideal porous structure (pore size: ~ 85 µm, porosity: ~ 65%) that was decorated with nano-silver particles. ATR-FITR and XRD spectroscopy further confirmed the stepwise deposition of polydopamine and nano-silver. Water contact angle measurement indicated improved surface hydrophilicity after coating with polydopamine. Tensile testing demonstrated that the TPU/NS membranes had an acceptable mechanical strength and excellent flexibility. Subsequently, bacterial suspension assay, plate counting methods and Live/Dead staining assays demonstrated that the optimized TPU/NS2.5 membranes possessed excellent antibacterial activity against P. aeruginosa, E. coli, S. aureus and MRSA bacteria, while CCK8 testing, SEM observations and cell apoptosis assays demonstrated that they had no measurable cytotoxicity toward mammalian cells. Moreover, a steady and safe silver-releasing profile recorded by ICP-MS confirmed these results. Finally, by using a bacteria-infected (MRSA or P. aeruginosa) murine wound model, we found that TPU/NS2.5 membranes could prevent in vivo bacterial infections and promote wound healing via accelerating the re-epithelialization process, and these membranes had no obvious toxicity toward normal tissues. CONCLUSION: Based on these results, the TPU/NS2.5 nanocomposite has great potential for the management of wounds, particularly for wounds caused by drug-resistant bacteria.

Protein structure estimation from NMR data by matrix completion.

Knowledge of protein structures is very important to understand their corresponding physical and chemical properties. Nuclear Magnetic Resonance (NMR) spectroscopy is one of the main methods to measure protein structure. In this paper, we propose a two-stage approach to calculate the structure of a protein from a highly incomplete distance matrix, where most data are obtained from NMR. We first randomly "guess" a small part of unobservable distances by utilizing the triangle inequality, which is crucial for the second stage. Then we use matrix completion to calculate the protein structure from the obtained incomplete distance matrix. We apply the accelerated proximal gradient algorithm to solve the corresponding optimization problem. Furthermore, the recovery error of our method is analyzed, and its efficiency is demonstrated by several practical examples.

Synthesis and biological evaluation of glycosides containing triazene-chalcones.

By combining triazenes with chalcones, we designed and synthesized 12 novel glycosides. The antiproliferative activity of all products was screened using an MTT assay against MGC803 cells and PC-3 cells. Compound [Formula: see text] displayed more potent antiproliferative activity than dacarbazine. Furthermore, we explored the preliminary structure activity relationship of all target compounds. The derivatives in this work might serve as bioactive fragments and lead compounds for developing more potent cytotoxic agents.

[Isolation of microorganisms producing enzyme capable of degrading tobacco straw and nicotine].

OBJECTIVE: The aim of this study was to screen tobacco straw and nicotine degrading microorganism. METHODS: The bacterium was isolated from tobacco field soil using medium containing tobacco straw as the sole carbon and nitrogen source. We identified the bacterium through morphological and physiological characterization combined with the result of 16S rRNA gene sequence and data analysis. We also studied the lignocelluloses degradation and enzyme activities related to the degradation of lignin and cellulose in liquid state fermentation of tobacco stalk. RESULTS: The bacterium was identified as Bacillus megaterium and we had demonstrated that it has a good ability to degrade lignin in tobacco straw when fermented in liquid state. It showed the highest laccase production of 418. 52 U/L while the highest lignin peroxides and manganese peroxides activity was 19. 71 U/L and 64. 71 U/L. On the other hand, we also found that nicotine in tobacco stem was totally degraded 20 d after inoculation. CONCLUSION: to the isolated Bacillus megaterium is capable of degrading tobacco straw partially and nicotine totally.

Value of turbo spin echo-based diffusion-weighted imaging in the differential diagnosis of benign and malignant solitary pulmonary lesions.

To quantitatively assess the diagnostic efficacy of multiple parameters derived from multi-b-value diffusion-weighted imaging (DWI) using turbo spin echo (TSE)-based acquisition techniques in patients with solitary pulmonary lesions (SPLs). A total of 105 patients with SPLs underwent lung DWI using single-shot TSE-based acquisition techniques and multiple b values. The apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM) parameters, and lesion-to-spinal cord signal intensity ratio (LSR), were analyzed to compare the benign and malignant groups using the Mann-Whitney U test and receiver operating characteristic analysis. The Dstar values observed in lung cancer were slightly lower than those observed in pulmonary benign lesions (28.164 ± 31.950 versus 32.917 ± 34.184; Z = -2.239, p = 0.025). The LSR values were significantly higher in lung cancer than in benign lesions (1.137 ± 0.581 versus 0.614 ± 0.442; Z = - 4.522, p < 0.001). Additionally, the ADC800, ADCtotal, and D values were all significantly lower in lung cancer than in the benign lesions (Z = - 5.054, -5.370, and -6.047, respectively, all p < 0.001), whereas the f values did not exhibit any statistically significant difference between the two groups. D had the highest area under the curve (AUC = 0.887), followed by ADCtotal (AUC = 0.844), ADC800 (AUC = 0.824), and LSR (AUC = 0.789). The LSR, ADC800, ADCtotal, and D values did not differ statistically significantly in diagnostic effectiveness. Lung DWI using TSE is feasible for differentiating SPLs. The LSR method, conventional DWI, and IVIM have comparable diagnostic efficacy for assessing SPLs.

A novel prognostic related lncRNA signature associated with amino acid metabolism in glioma.

Background: Glioma is one of the deadliest malignant brain tumors in adults, which is highly invasive and has a poor prognosis, and long non-coding RNAs (lncRNAs) have key roles in the progression of glioma. Amino acid metabolism reprogramming is an emerging hallmark in cancer. However, the diverse amino acid metabolism programs and prognostic value remain unclear during glioma progression. Thus, we aim to find potential amino-related prognostic glioma hub genes, elaborate and verify their functions, and explore further their impact on glioma. Methods: Glioblastoma (GBM) and low-grade glioma (LGG) patients' data were downloaded from TCGA and CCGA datasets. LncRNAs associated with amino acid metabolism were discriminated against via correlation analysis. LASSO analysis and Cox regression analysis were conducted to identify lncRNAs related to prognosis. GSVA and GSEA were performed to predict the potential biological functions of lncRNA. Somatic mutation data and CNV data were further built to demonstrate genomic alterations and the correlation between risk scores. Human glioma cell lines U251 and U87-MG were used for further validation in vitro experiments. Results: There were eight amino-related lncRNAs in total with a high prognostic value that were identified via Cox regression and LASSO regression analyses. The high risk-score group presented a significantly poorer prognosis compared with the low risk-score group, with more clinicopathological features and characteristic genomic aberrations. Our results provided new insights into biological functions in the above signature lncRNAs, which participate in the amino acid metabolism of glioma. LINC01561 is one of the eight identified lncRNAs, which was adopted for further verification. In in vitro experiments, siRNA-mediated LINC01561 silencing suppresses glioma cells' viability, migration, and proliferation. Conclusion: Novel amino-related lncRNAs associated with the survival of glioma patients were identified, and a lncRNA signature can predict glioma prognosis and therapy response, which possibly has vital roles in glioma. Meanwhile, it emphasized the importance of amino acid metabolism in glioma, particularly in providing deeper research at the molecular level.

Case report: genetic analysis of a novel frameshift mutation in FMR1 gene in a Chinese family.

Fragile X syndrome (FXS) [OMIM 300624] is a common X-linked inherited syndrome with an incidence only second to that of trisomy 21. More than 95% of fragile X syndrome is caused by reduced or absent fragile X intellectual disability protein 1 (FMRP) synthesis due to dynamic mutation expansion of the CGG triplet repeat in the 5'UTR and abnormal methylation of the FMR1 (fragile X messenger ribonucleoprotein 1) gene [OMIM 309550]. Less than 5% of cases are caused by abnormal function of the FMRP due to point mutations or deletions in the FMR1 gene. In a proband with clinical suspicion of FXS and no CGG duplication, we found the presence of c.585_586del (p.Lys195AsnfsTer8) in exon 7 of the FMR1 gene using whole exome sequencing (WES). This variant resulted in frameshift and a premature stop codon after 8 aberrant amino acids. This variant is a novel pathogenic mutation, as determined by pedigree analysis, which has not been reported in any database or literature.

Maternal High-Fat Diet Multigenerationally Programs HPA Function and Behaviors in Male Rat Offspring.

Maternal environmental factors have been demonstrated to exert significant influences on the health of offspring. The hypothalamic-pituitary-adrenal (HPA) axis is an important neuroendocrine stress system that can be influenced by early life challenges. Our previous research has revealed that the consumption of a high-fat diet (HFD) by pregnant and lactating rats leads to the programming of HPA axis activity in male offspring of the first generation (referred to as F1HFD/C). The present study aimed to investigate whether the observed remodeling of the HPA axis could be inherited by second-generation male offspring (referred to as F2HFD/C), following maternal HFD exposure. The results showed that F2HFD/C rats exhibited enhanced basal HPA axis activity, similar to their F1HFD/C ancestors. Moreover, F2HFD/C rats displayed exacerbated corticosterone responses to restraint and lipopolysaccharide-induced stress, but not to insulin-induced hypoglycemia stress. Furthermore, maternal HFD exposure significantly aggravated depression-like behavior in the F2 generation subjected to chronic unpredictable mild stress. To investigate the role of central calcitonin gene-related peptide (CGRP) signaling in maternal diet-induced programming of the HPA axis across generations, we conducted central infusion of αCGRP8-37, a CGRP receptor antagonist, in F2HFD/C rats. The results demonstrated that αCGRP8-37 attenuated depression-like behaviors and reduced the hyperresponsiveness of the HPA axis to restraint stress in these rats. Therefore, central CGRP signaling may contribute to maternal diet-induced programming of HPA axis across generations. In conclusion, our study provides evidence that maternal HFD consumption can lead to multigenerational programming of the HPA axis and behaviors in adult male descendants.

Aberrant brain entropy in posttraumatic stress disorder comorbid with major depressive disorder during the coronavirus disease 2019 pandemic.

Aim: Previously, neuroimaging studies on comorbid Posttraumatic-Major depression disorder (PTSD-MDD) comorbidity found abnormalities in multiple brain regions among patients. Recent neuroimaging studies have revealed dynamic nature on human brain activity during resting state, and entropy as an indicator of dynamic regularity may provide a new perspective for studying abnormalities of brain function among PTSD-MDD patients. During the COVID-19 pandemic, there has been a significant increase in the number of patients with PTSD-MDD. We have decided to conduct research on resting-state brain functional activity of patients who developed PTSD-MDD during this period using entropy. Methods: Thirty three patients with PTSD-MDD and 36 matched TCs were recruited. PTSD and depression symptoms were assessed using multiple clinical scales. All subjects underwent functional magnetic resonance imaging (fMRI) scans. And the brain entropy (BEN) maps were calculated using the BEN mapping toolbox. A two-sample t-test was used to compare the differences in the brain entropy between the PTSD-MDD comorbidity group and TC group. Furthermore, correlation analysis was conducted between the BEN changes in patients with PTSD-MDD and clinical scales. Results: Compared to the TCs, PTSD-MDD patients had a reduced BEN in the right middle frontal orbital gyrus (R_MFOG), left putamen, and right inferior frontal gyrus, opercular part (R_IFOG). Furthermore, a higher BEN in the R_MFOG was related to higher CAPS and HAMD-24 scores in the patients with PTSD-MDD. Conclusion: The results showed that the R_MFOG is a potential marker for showing the symptom severity of PTSD-MDD comorbidity. Consequently, PTSD-MDD may have reduced BEN in frontal and basal ganglia regions which are related to emotional dysregulation and cognitive deficits.