Bibliometric analysis of hot literature on neural circuit research.

Numerous brain diseases have been attributed to abnormalities in the connections of neural circuits. Exploration of neural circuits may give enlightenment in treating some intractable brain diseases. Here, we screened all publications on neural circuits in the Web of Science database from 2007 to 2022 and analyzed the research trends through VOSviewer, CiteSpace, Microsoft Excel 2019, and Origin. The findings revealed a consistent upward trend in research on neural circuits during this period. The United States emerged as the leading contributor, followed by China and Japan. Among the top 10 institutions with the largest number of publications, both the United States and China have a strong presence. Notably, the Chinese Academy of Sciences demonstrated the highest publication output, closely followed by Stanford University. In terms of influential authors, Karl Deisseroth stood out as one of the most prominent investigators. During this period, the majority of publications and citations on neural circuit research were found in highly influential journals including NEURON, NATURE JOURNAL OF NEUROSCIENCE, and so forth. Keyword clustering analysis highlighted the increasing focus on neural circuits and photogenetics in neuroscience research, and the reconstruction of neural circuits has emerged as a crucial research direction in brain science. In conclusion, over the past 15 years, the increasing high-quality publications have facilitated research development of neural circuits, indicating a promising prospect for investigations on neurological and psychiatric diseases.

Electroacupuncture regulates microglial polarization via inhibiting NF-κB/COX2 pathway following traumatic brain injury.

BACKGROUND: Neuroinflammation and oxidative stress are important pathological mechanisms following traumatic brain injury (TBI). The NF-κB/COX2 pathway regulates neuroinflammation and oxidative damage, while microglia also play an important role in neuroinflammation. Since NF-κB is involved in microglial polarization, targeting this pathway and microglial polarization is a critical component of TBI treatment. Currently, electroacupuncture (EA) is widely used to treat various symptoms after TBI, but the mechanisms of EA remain poorly understood. Additionally, the optimal frequency of EA remains unclear, which affects its efficacy. This study focuses on exploring the optimal frequency parameters of EA on TBI and investigating the underlying mechanisms of EA through NF-κB/COX2 pathway and microglial polarization. METHODS: The study was divided into two parts. In Experiment 1, 42 Sprague Dawley (SD) rats were induced and randomly divided into seven groups (n = 6). Except for the sham group, all rats underwent controlled cortical impact (CCI) to establish TBI model. Four EA groups (with different frequencies) and manual acupuncture (without current stimulation) received stimulation on the acupoints of Shuigou (GV26), Fengchi (GB20) and Neiguan (PC6) once a day for 7 days. The neurological function was assessed by modified Neurological Severity Scores (mNSS), and the rats' memory and learning were examined by the Morris water maze (MWM). SOD, MDA, and GSH-Px were detected to evaluate the levels of oxidative stress. The levels of IL-1ß, IL-6, and TNF-α were evaluated by Enzyme Linked Immunosorbent Assay (ELISA). Detection of the above indicators indicated a treatment group that exerted the strongest neuroprotection against TBI, we then conducted Experiment 2 using this screened acupuncture treatment to investigate the mechanism of acupuncture. 48 rats were randomly divided into four groups (n = 12): sham, TBI model, acupuncture and PDTC (NF-κB inhibitor). Evaluations of mNSS, MWM test, SOD, MDA, GSH-Px, IL-1ß, IL-6, TNF-α, and IL-10 were the same as in Experiment 1. Western blot was applied for detecting the expression levels of NF-κB, p-NF-κB, COX2, and Arg-1. TUNEL was used to examine neuronal apoptosis. Brain structure was observed by H&E. Iba-1, COX2, and Arg-1 were investigated by immunofluorescence staining. RESULTS: EA with frequency of 2/100 Hz markedly improved neuronal and cognitive function as compared to the other treatment groups. Moreover, it downregulated the expression of MDA, IL-6, IL-1ß, and TNF-α and upregulated the levels of SOD and GSH-Px. In addition, Both EA with 2/100 Hz and PDTC reduced the levels of p-NF-κB, COX2 and M1 markers (COX2, IL-6, IL-1ß, TNF-α) and increased the levels of M2 markers (Arg-1, IL-10). Moreover, they had similar effects on reducing inflammation, oxidative stress and apoptosis, and improving neuronal and cognitive function. CONCLUSIONS: The collective findings strongly suggest that EA with 2/100 Hz can improve neurologic function by suppressing neuroinflammation, oxidative stress and apoptosis. Additionally, we confirm that EA promotes microglial polarization towards the M2 phenotype through the suppression of NF-κB/COX2 pathway, thus exerting neuroprotective effects after TBI.

Genome-wide analysis of CtNF-YB and lipid synthesis regulation of CtNF-YB12 in Carthamus tinctorius L.

KEY MESSAGE: The nuclear Factor YB of Carthamus tinctorius L. increased the content of unsaturated fatty acids by regulating the expression of genes involved in fatty acid synthesis and oil accumulation. Safflower (Carthamus tinctorius L.) seed oil is rich in linoleic acid and is widely used in food and medicine. Therefore, key genes regulating oil synthesis were mined through genetic engineering to provide genetic resources for improving oil content. Based on the conserved domain of the NF-YB, we screened and identified 14 CtNF-YB transcription factors in the safflower genome and divided them into three subfamilies through phylogenetic analysis. Regulatory motif analysis of the CtNF-YB promoter revealed specific cis-regulatory elements related to abiotic stress, growth, and development. Expression analysis of CtNF-YB family genes showed that non-Leafy Cotyledon 1(non-LEC1) genes were highly expressed in roots, leaves, and flowers; Leafy Cotyledon 1(LEC1) genes were highly expressed during early seed development; and Dr1-like genes were highly expressed in roots, stems, and leaves. CtNF-YB12 was identified as a LEC1 transcription factor based on phylogeny and BLAST alignment. Heterologous CtNF-YB12 expression in Arabidopsis thaliana increased seed pod length and seed size. Moreover, CtNF-YB12 overexpression increased the oil content of seeds, upregulated genes involved in fatty acid biosynthesis and glycolysis, and altered the content of unsaturated fatty acids, including oleic acid (C18:1), linoleic acid (C18:2), and linolenic acid (C18:3), as well as of sucrose, fructose, and glucose. CtNF-YB12 may increase the oil content by regulating key enzyme genes of oil synthesis, so it can be used as a reliable target.

The age-specific pathological changes of ß-amyloid plaques in the cortex and hippocampus of APP/PS1 transgenic AD mice.

OBJECTIVE: Numerous pathological variations and complex interactions are involved in the long period prior to cognitive decline in brains with Alzheimer's disease (AD). Thus, elucidation of the pathological disorders can facilitate early AD diagnosis. The aim of this study was to investigate the age-specific pathological changes of ß-amyloid plaques in brain tissues of AD mice at different ages. METHODS: We arranged the most widely available APP/PS1 transgenic AD models into six age groups: 3, 4 and 6 months (these three groups mimicked early-clinical stage AD), 9, 12 and 15 months (these three groups mimicked late-clinical stage AD). Cell morphology and arrangement in the cortex and hippocampus were observed by hematoxylin and eosin (HE) staining. Congo red staining and immunohistochemical staining were performed to exhibit the distribution of ß-amyloid plaques in the cortex and hippocampus of AD brains. RESULTS: Our results found that as age increased, the nuclei of cortical and hippocampal cells in AD mice were severely damaged. The number and area of ß-amyloid plaques increased in AD mice in correspondence with age revealed by histological experiments. Importantly, ß-amyloid plaques were detected in the cortex and hippocampus of 6-month-old AD mice shown by Congo red staining while detected in the cortex and hippocampus of 4-month-old AD mice shown by immunohistochemical staining. CONCLUSIONS: The current study revealed the age-related pathological changes of ß-amyloid plaques in the cortex and hippocampus of AD mice and displayed a higher specificity of immunohistochemical staining than Congo red staining when detecting pathological changes of brain tissues.

CHCHD10 Modulates Thermogenesis of Adipocytes by Regulating Lipolysis.

Brown and beige adipocytes dissipate energy in a nonshivering thermogenesis manner, exerting beneficial effects on metabolic homeostasis. CHCHD10 is a nuclear-encoded mitochondrial protein involved in cristae organization; however, its role in thermogenic adipocytes remains unknown. We identify CHCHD10 as a novel regulator for adipocyte thermogenesis. CHCHD10 is dramatically upregulated during thermogenic adipocyte activation by PPARγ-PGC1α and positively correlated with UCP1 expression in adipose tissues from humans and mice. We generated adipocyte-specific Chchd10 knockout mice (Chchd10-AKO) and found that depleting CHCHD10 leads to impaired UCP1-dependent thermogenesis and energy expenditure in the fasting state, with no effect in the fed state. Lipolysis in adipocytes is disrupted by CHCHD10 deficiency, while augmented lipolysis through ATGL overexpression recovers adipocyte thermogenesis in Chchd10-AKO mice. Consistently, overexpression of Chchd10 activates thermogenic adipocytes. Mechanistically, CHCHD10 deficiency results in the disorganization of mitochondrial cristae, leading to impairment of oxidative phosphorylation complex assembly in mitochondria, which in turn inhibits ATP generation. Decreased ATP results in downregulation of lipolysis by reducing nascent protein synthesis of ATGL, thereby suppressing adipocyte thermogenesis. As a result, Chchd10-AKO mice are prone to develop high-fat diet-induced metabolic disorders. Together, our findings reveal an essential role of CHCHD10 in regulating lipolysis and the thermogenic program in adipocytes.

Corrigendum: MicroRNA339 Targeting PDXK Improves Motor Dysfunction and Promotes Neurite Growth in the Remote Cortex Subjected to Spinal Cord Transection.

[This corrects the article DOI: 10.3389/fcell.2020.00577.].

Research Progress of Preparation Technology of Ion-Exchange Resin Complexes.

As insoluble polymer materials, ion-exchange resins (IERs) can exchange their own ions with desirable charged ions in the solution. According to the affinity of active moieties for soluble counterions, IERs could be categorized into the following four types: strongly acidic cation, weakly acidic cation, strongly basic anion, and weakly basic anion exchange resins. Due to their relative safety and high drug-loading capacity, IERs have garnered extensive attention in the pharmaceutical field since the 1950s. As numerous investigations combine drugs with IERs, this article summarizes the technologies employed in these studies from four aspects: IER screening principles, combining technologies, characterization methods, and in vitro and in vivo release of drug-resinate complexes. In addition, the advantages and disadvantages of various technologies and their scope are expounded. The article provides new insights on the preparation of ion-exchange resin complexes.

[Stability research of Xiaoer Ganmaoning Oral Liquid based on chromatographic peak matching and image sensory evaluation].

The high performance liquid chromatography(HPLC) characteristic chromatogram of Xiaoer Ganmaoning Oral Liquid(oral liquid for short) was established. The medicinal materials corresponding to characteristic peaks, their index components and ranges of similarity with the reference chromatograms were clarified. The similarity between the characteristic chromatograms of 10 batches of the oral liquid and the reference chromatogram was higher than 0.994. Eighteen characteristic peaks were identified, which were derived from different medicinal materials including Scutellariae Radix, Arctii Fructus, Lonicerae Japonicae Flos, Gardeniae Fructus and Forsythiae Fructus. Further, 11 characteristic peaks were assigned by the comparison with reference substances as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, baicalin, baicalein, wogonin, scutellarin, forsythiaside A and arctiin. Also, the characteristic chromatogram of precipitate in the oral liquid was established, and the similarity between characteristic chromatograms of 10 batches of the precipitate and the reference chromatogram was higher than 0.940. The 14 characteristic peaks originating from the precipitate and those from the oral liquid were consistent in retention time, and the content of all index components in the precipitate was lower than 5% of that in the oral liquid. Moreover, the stability of precipitate during the accelerated stability test was explored with filtration and Matlab-based image sensory evaluation. The precipitate mass and precipitation degree both increased over the stability test duration significantly. The stability of the oral liquid was used as a model system in this study to establish the integrated quality control system which related to medicinal materials, preparations and precipitate with HPLC characteristic chromatograms and image sensory evaluation, which lays a foundation for the exploration of the quantity value transfer of the oral liquid.

Corrigendum: Vi4-miR-185-5p-Igfbp3 Network Protects the Brain From Neonatal Hypoxic Ischemic Injury via Promoting Neuron Survival and Suppressing the Cell Apoptosis.

[This corrects the article DOI: 10.3389/fcell.2020.529544.].

Discovery of FtsZ inhibitors by virtual screening as antibacterial agents and study of the inhibition mechanism.

Inhibition of bacterial cell division is a novel mechanistic action in the development of new antimicrobial agents. The FtsZ protein is an important antimicrobial drug target because of its essential role in bacterial cell division. In the present study, potential inhibitors of FtsZ were identified by virtual screening followed by in vivo and in vitro bioassays. One of the candidates, Dacomitinib (S2727), shows for the first time its potent inhibitory activity against the MRSA strains. The binding mode of Dacomitinib in FtsZ was analyzed by docking, and Asp199 and Thr265 are thought to be essential residues involved in the interactions.

Major limb amputation and mortality in patients with neuro-ischaemic lower extremity wounds managed in a tertiary hospital: Focus on the differences among patients with diabetes, peripheral arterial disease and both.

A majority of lower extremities neuro-ischaemic wounds (NIU) are related to: (a) only diabetes (DM); (b) only peripheral artery disease (PAD); (c) co-existing diabetes and peripheral artery disease (DM-PAD). This study aims to characterise the major clinical outcomes of forementioned three groups of lower extremity wound patients in Singapore. Patients hospitalised for lower extremity NIU between January 2014 and October 2017 in a tertiary hospital in Singapore were analysed. Patients' major limb amputation and mortality were assessed using Cox regression models. Cumulative survival and amputation-free survival among the three classified groups were calculated using Kaplan-Meier analysis. Compared with patients with only DM, those in the PAD group and the DM-PAD group had higher risk of major limb amputation (adjusted hazard ratio: 2.47, 95% CI: 1.65-3.70; adjusted hazard ratio: 2.01, 95% CI: 1.53-2.65 respectively) and mortality (adjusted hazard ratio: 2.36, 95% CI: 1.57-3.55; adjusted hazard ratio: 2.46, 95% CI: 1.86-3.26 respectively). The 3-year survival and amputation-free survival were lowest in the DM-PAD group (52.1% and 41.5% respectively), followed by the PAD group (53.3% and 44.6% respectively) and the DM group (74.2% and 68.5% respectively). Lower extremity NIU patients with PAD or DM-PAD were found to have poorer clinical prognosis than those with DM only.

Differences between cultured cortical neurons by trypsin and papain digestion.

The objective of this study was to compare the efficiency of trypsin and papain in neuronal digestion and determine which enzyme is more efficient. Cortical tissues were obtained from Sprague-Dawley (SD) rats. According to the different digestive enzymes, the samples were divided into the trypsin group and the papain group. After being digested by each of the two enzymes, cortical neurons were collected from the samples. Then, the morphology of the cortical neurons was determined. Moreover, the cortical neurons were transfected with the negative control (NC) lentivirus. The transfection efficiency and morphology were determined and compared. Compared with the papain group, cortical neurons in the trypsin group were more in number, had larger cell size, had longer axonal length, and had fewer impurities. The transfection efficiency of the trypsin group (57.77%) was higher than that of the papain group (53.83%). The morphology of neurons that was displayed showed that the cell body of most neurons shrank and became smaller, and the axis mutation became shorter and less in the papain group 6 days after transfection with the NC lentivirus. Trypsin is more efficient in digesting neurons because the neurons digested by this enzyme are more in number, have a larger cell body, longer axons, and greater transfection efficiency.

The differentially expressed proteins related to clinical viral encephalitis revealed by proteomics.

To screen out the prospective biomarkers of viral encephalitis (VE), analyze the biological process and signaling pathways involved by differentially expressed proteins (DEPs). A total of 11 cerebrospinal fluid (CSF) samples with VE and 5 with non-nervous system infection were used to perform label-free proteomic techniques. Then, the bioinformatic analysis of DEPs was applied by Interproscan software. Moreover, 73 CSF samples in the VE group and 53 in the control group were used to verify the changes of some DEPs by enzyme-linked immunosorbent assay (ELISA). Thirty-nine DEPs were identified, including 18 upregulated DEPs and 21 downregulated DEPs. DEPs were mainly enriched in cell adhesion molecules by Kyoto Encyclopedia of Genes and Genomes analysis pathway analysis. The DEPs related to axon tissue were obviously downregulated and the most significant downregulated proteins were neurexin 3, neurofascin, and neuroligin 2 (NLGN2). Moreover, the protein expression of NLGN2 in the VE group was significantly higher than that in the control group by ELISA. The correlation analysis of NLGN2 in the VE group revealed that there was a weak positive correlation with CSF protein and a weak negative correlation with CSF chloride. The clinical VE may be closely related to NLGN2 and the cell adhesion molecule pathway.

Gossypol acetate: A natural polyphenol derivative with antimicrobial activities against the essential cell division protein FtsZ.

Antimicrobial resistance has attracted worldwide attention and remains an urgent issue to resolve. Discovery of novel compounds is regarded as one way to circumvent the development of resistance and increase the available treatment options. Gossypol is a natural polyphenolic aldehyde, and it has attracted increasing attention as a possible antibacterial drug. In this paper, we studied the antimicrobial properties (minimum inhibitory concentrations) of gossypol acetate against both Gram-positive and Gram-negative bacteria strains and dig up targets of gossypol acetate using in vitro assays, including studying its effects on functions (GTPase activity and polymerization) of Filamenting temperature sensitive mutant Z (FtsZ) and its interactions with FtsZ using isothermal titration calorimetry (ITC), and in vivo assays, including visualization of cell morphologies and proteins localizations using a microscope. Lastly, Bacterial membrane permeability changes were studied, and the cytotoxicity of gossypol acetate was determined. We also estimated the interactions of gossypol acetate with the promising target. We found that gossypol acetate can inhibit the growth of Gram-positive bacteria such as the model organism Bacillus subtilis and the pathogen Staphylococcus aureus [both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA)]. In addition, gossypol acetate can also inhibit the growth of Gram-negative bacteria when the outer membrane is permeabilized by Polymyxin B nonapeptide (PMBN). Using a cell biological approach, we show that gossypol acetate affects cell division in bacteria by interfering with the assembly of the cell division FtsZ ring. Biochemical analysis shows that the GTPase activity of FtsZ was inhibited and polymerization of FtsZ was enhanced in vitro, consistent with the block to cell division in the bacteria tested. The binding mode of gossypol acetate in FtsZ was modeled using molecular docking and provides an understanding of the compound mode of action. The results point to gossypol (S2303) as a promising antimicrobial compound that inhibits cell division by affecting FtsZ polymerization and has potential to be developed into an effective antimicrobial drug by chemical modification to minimize its cytotoxic effects in eukaryotic cells that were identified in this work.

Single-cell RNA sequencing reveals B cell-related molecular biomarkers for Alzheimer's disease.

In recent years, biomarkers have been integrated into the diagnostic process and have become increasingly indispensable for obtaining knowledge of the neurodegenerative processes in Alzheimer's disease (AD). Peripheral blood mononuclear cells (PBMCs) in human blood have been reported to participate in a variety of neurodegenerative activities. Here, a single-cell RNA sequencing analysis of PBMCs from 4 AD patients (2 in the early stage, 2 in the late stage) and 2 normal controls was performed to explore the differential cell subpopulations in PBMCs of AD patients. A significant decrease in B cells was detected in the blood of AD patients. Furthermore, we further examined PBMCs from 43 AD patients and 41 normal subjects by fluorescence activated cell sorting (FACS), and combined with correlation analysis, we found that the reduction in B cells was closely correlated with the patients' Clinical Dementia Rating (CDR) scores. To confirm the role of B cells in AD progression, functional experiments were performed in early-stage AD mice in which fibrous plaques were beginning to appear; the results demonstrated that B cell depletion in the early stage of AD markedly accelerated and aggravated cognitive dysfunction and augmented the Aß burden in AD mice. Importantly, the experiments revealed 18 genes that were specifically upregulated and 7 genes that were specifically downregulated in B cells as the disease progressed, and several of these genes exhibited close correlation with AD. These findings identified possible B cell-based AD severity, which are anticipated to be conducive to the clinical identification of AD progression.

LncRNA TCONS_00041002 improves neurological outcomes in neonatal rats with hypoxic-ischemic encephalopathy by inhibiting apoptosis and promoting neuron survival.

It has been reported that Neonatal hypoxic-ischemic encephalopathy (HIE) could induce apoptosis in neonates and result in cognitive and sensory impairments, which are associated with poor developmental outcomes. Despite the improvement in neonatology, there is still no clinically effective treatment for HIE presently. Long non-coding RNAs (lncRNAs) play important roles in cellular homeostasis. Nevertheless, their effects in developing rat brains with HI is little known. Here, we established HIE model in neonate rats and explored the expression and function of lncRNAs in HI, and found the expression of 19 lncRNAs was remarkably changed in the brains of HI rats, compared to the sham group. Among them, three lncRNAs (TCONS_00041002, TCONS_00070547, TCONS_00045572) were enriched in the apoptotic process via gene ontology (GO) and pathway analysis, which were selected for the further qRT-PCR verification. Through lentivirus-mediated overexpression of these three lncRNAs, we found that overexpression of TCONS_00041002 attenuated the cell apoptosis, and increased the vitality of neurons after oxygen-glucose deprivation (OGD), therefore reduced the brain infarction and further promoted the neuron survival as well as improved the neurological disorders in the rats subjected to HIE. What's more, ceRNA network prediction and co-expression verification showed that the expression of TCONS_00041002 was positively associated with Foxe1, Pawr and Nfkbiz. Altogether, this study has exhibited that lncRNA TCONS_00041002 participates in the cell apoptosis and neuronal survival of HIE and represents a potential new target for the treatment of HIE.