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The infralimbic (IL) cortex dysfunction has been implicated in major depressive disorder (MDD), yet the precise cellular and molecular mechanisms remain poorly understood. In this study, we investigated the role of layer V pyramidal neurons in a mouse model of MDD induced by repeated lipopolysaccharide (LPS) administration. Our results demonstrate that three days of systemic LPS administration induced depressive-like behavior and upregulated mRNA levels of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-β (TGF-β) in the IL cortex. Electrophysiological recordings revealed a significant decrease in the intrinsic excitability of layer V pyramidal neurons in the IL following systemic LPS exposure. Importantly, chemogenetic activation of IL pyramidal neurons ameliorated LPS-induced depressive-like behavior. Additionally, LPS administration significantly increased microglial activity in the IL, as evidenced by a greater number of Ionized calcium binding adaptor molecule-1 (IBA-1)-positive cells. Morphometric analysis further unveiled enlarged soma, decreased branch numbers, and shorter branch lengths of microglial cells in the IL cortex following LPS exposure. Moreover, the activation of pyramidal neurons by clozapine-N-oxide increased the microglia branch length but did not change branch number or cytosolic area. These results collectively suggest that targeted activation of pyramidal neurons in the IL cortex mitigates microglial response and ameliorates depressive-like behaviors induced by systemic LPS administration. Therefore, our findings offer potential therapeutic targets for the development of interventions aimed at alleviating depressive symptoms by modulating IL cortical circuitry and microglial activity., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The role of the epigenome in phenotypic plasticity is unclear presently. Here we used a multiomics approach to explore the nature of the epigenome in developing honey bee (Apis mellifera) workers and queens. Our data clearly showed distinct queen and worker epigenomic landscapes during the developmental process. Differences in gene expression between workers and queens become more extensive and more layered during the process of development. Genes known to be important for caste differentiation were more likely to be regulated by multiple epigenomic systems than other differentially expressed genes. We confirmed the importance of two candidate genes for caste differentiation by using RNAi to manipulate the expression of two genes that differed in expression between workers and queens were regulated by multiple epigenomic systems. For both genes the RNAi manipulation resulted in a decrease in weight and fewer ovarioles of newly emerged queens compared to controls. Our data show that the distinct epigenomic landscapes of worker and queen bees differentiate during the course of larval development., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The anterior nucleus of the paraventricular thalamus (aPVT) integrates various synaptic inputs and conveys information to the downstream brain regions for arousal and pain regulation. Recent studies have indicated that the PVT plays a crucial role in the regulation of chronic pain, but the plasticity mechanism of neuronal excitability and synaptic inputs for aPVT neurons in neuropathic pain remains unclear. Here, we report that spinal nerve ligation (SNL) significantly increased the neuronal excitability and reset the excitatory/inhibitory (E/I) synaptic inputs ratio of aPVT neurons in mice. SNL significantly increased the membrane input resistance, firing frequency, and the half-width of action potential. Additionally, SNL enlarged the area of afterdepolarization and prolonged the rebound low-threshold spike following a hyperpolarized current injection. Further results indicate that an inwardly rectifying current density was decreased in SNL animals. SNL also decreased the amplitude, but not the frequency of spontaneous excitatory postsynaptic currents (sEPSCs), nor the amplitude or frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) of aPVT neurons. Moreover, SNL disrupted the E/I synaptic ratio, caused a decrease in weighted tau and half-width of averaged sIPSCs, but did not change these physiological properties of averaged sEPSCs. Finally, pharmacological activation of the GABA A receptor at aPVT could effective relieve SNL-induced mechanical allodynia in mice. These results reveal the plasticity of intrinsic neuronal excitability and E/I synaptic balance in the aPVT neurons after nerve injury and it may play an important role in the development of pain sensitization., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The relationship between variability in cardiometabolic and inflammatory parameters and cognitive changes is unknown. This study investigates the association of visit-to-visit variability in BMI, mean arterial pressure, total cholesterol, triglycerides, HbA1c, high-sensitivity C-reactive protein, ferritin, and fibrinogen with cognitive decline., Methods: This population-based cohort study included 2,260 individuals (mean age=63.0 [SD=7.5] years) free of cognitive diseases who underwent ≥3 clinical measurements from 2004 to 2019. Variability was expressed as variability independent of the mean across visits. Participants were divided on the basis of quartiles of variability score, a scoring system generated to explore the composite effect of parameter variability (range=0-24), where 0 points were assigned for Quartile 1, 1 point was assigned for Quartile 2, 2 points were assigned for Quartile 3, and 3 points were assigned for Quartile 4, each for the variability of 8 parameters measured as variability independent of the mean. Linear mixed models evaluated the longitudinal associations with cognitive decline in memory and verbal fluency. All analyses were conducted in 2020-2021., Results: Higher BMI, mean arterial pressure, total cholesterol, HbA1c, and ferritin variability were linearly associated with cognitive decline irrespective of their mean values. In addition, participants in the highest quartile of variability score had a significantly worse cognitive decline rate in memory (-0.0224 points/year, 95% CI= -0.0319, -0.0129) and verbal fluency (-0.0088 points/year, 95% CI= -0.0168, -0.0008) than those in the lowest quartile., Conclusions: A higher variability in cardiometabolic and inflammatory parameters was significantly associated with cognitive decline. Stabilizing these parameters may serve as a target to preserve cognitive functioning., (Copyright © 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to investigate the differences in bone mineral density (BMD) and hip structure between femoral neck and trochanteric fractures in elderly Chinese individuals using quantitative computed tomography (QCT). A total of 625 Chinese patients (mean age 75.8 years) who sustained low-energy hip fractures (female: 293 femoral neck, 175 trochanteric; male: 82 femoral neck, 75 trochanteric) were recruited. Each patient underwent a hip QCT scan. The areal BMD (aBMD) of the contralateral normal hip was obtained using a computed tomography X-ray absorptiometry module. Using the bone investigation toolkit (BIT) module, the femoral neck was divided into four quadrants: supero-anterior (SA), infero-anterior (IA), infero-posterior (IP), and supero-posterior (SP). Estimated cortical thickness, cortical BMD, and trabecular BMD were measured in each quadrant. Using the hip structure analysis (HSA) function, several parameters were calculated. Stratified by sex, covariance analyses were applied to compare the femoral neck fractures group with trochanteric fractures group after adjustments for age, height, and weight. In women, trochanteric fractures exhibited lower trabecular BMD and estimated cortical thickness at three quadrants of the femoral neck (IA: P = 0.02, P < 0.01; IP: P < 0.01, P = 0.01; SP: P = 0.01, P < 0.01), and lower aBMD at the trochanter area (P < 0.01); femoral neck fractures exhibited lower cortical BMD and estimated cortical thickness at the SA quadrant (P = 0.04, P = 0.01). Differences in HSA parameters were not statistically significant. Among all parameters, the most valuable ones to discrimination of hip fracture type are estimated cortical thickness of the SA quadrant of femoral neck and the aBMD of the trochanter area. In men, only lower cortical BMD at the SP quadrant and aBMD at the trochanter were found in the trochanteric fractures (P = 0.02, P < 0.01). QCT outcomes indicate that spatial differences are helpful to explore the pathogenesis of different type of hip fractures. In women, trochanteric fractures are related to severer osteoporosis, whereas cortical fragility in the SA region of the femoral neck predominates in cases of femoral neck fractures. In men, trochanteric fractures are related to more bone loss of trochanter., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Chemokines and their receptors have been demonstrated to be important contributors to the development and maintenance of chronic pain. Recent studies showed that chemokine (C-X-C motif) ligand 1 (CXCL1) and its major receptor CXCR2 are respectively expressed in astrocytes and neurons in the spinal cord and are involved in the maintenance of neuropathic pain and inflammatory pain via astrocytic-neuronal interaction. Here we investigated how CXCL1 and CXCR2 are regulated in the dorsal root ganglion (DRG) after peripheral injection of complete Freund's adjuvant (CFA) and its implication in inflammatory pain. CFA induced rapid increase of CXCL1 mRNA and protein in the DRG. Double immunostaining showed that CXCL1 was colocalized with calcitonin gene-related peptide (CGRP), isolectin B4 (IB4), and neurofilament 200 (NF200). Furthermore, CXCR2 mRNA was increased 3h after CFA injection and maintained for more than 3 days. CXCR2 protein was also increased and colocalized with CGRP, IB4, and NF200. Finally, perisciatic nerve injection of CXCR2 siRNA to specifically knock down CXCR2 in the DRG effectively attenuated CFA-induced mechanical allodynia and heat hyperalgesia, and the effect maintained for more than 5 days. Taken together, our results demonstrated that CXCL1 and CXCR2 may regulate the maintenance of inflammatory pain via an autocrine/paracrine way in DRG neurons., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In our continuing search for natural product-based spin-labeled antitumor drugs, 20 novel spin-labeled camptothecin derivatives were synthesized via a Cu-catalyzed one pot reaction and evaluated for cytotoxicity against four human tumor cell lines (A-549, MDA-MB-231, KB, and KBvin). Eighteen of the target compounds (9a, 9b, 9d-9k, 9m-9t) exhibited significant in vitro antiproliferative activity against these four tested tumor cell lines. Compounds 9e and 9j (IC50 0.057 and 0.072μM, respectively) displayed the greatest cytotoxicity against the multidrug-resistant (MDR) KBvin cell line and merit further development into preclinical and clinical drug candidates for treating cancer including MDR phenotype., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Encephalitis is a major cause of death and disability in adults and children; different members in the family Parvoviridae are known to be associated with encephalitis to some extent., Objectives: To determine the presence of human bocaviruses (HBoVs) and corresponding HBoV-specific immunoglobulins (Igs) in cerebrospinal fluid from children with suspected viral encephalitis., Study Design: Employing real-time PCR and nested touchdown PCR, 67 cerebrospinal fluid (CSF) samples from children with suspected viral encephalitis were screened for HBoV and routine encephalitis-causing viruses. Using ELISA, Western blot and IFA, HBoV-specific Ig were determined in the samples., Results: Nine samples (134%) were HBoV1 DNA-positive, while one sample (15%) was HBoV2 DNA-positive. HBoV-specific IgM and IgG antibodies were detected in the CSF samples from three children; two samples were HBoV1 DNA-positive and one sample was negative. One death was recorded; CSF from this child was the only HBoV-IgM-positive CSF samples among the 67 CSF tested., Conclusion: We screened CSF samples obtained from children with encephalitis for the presence of HBoV1 and HBoV2 and specific IgM- or IgG-responses. Detection of viral DNA and/or immunological response to HBoV1/HBoV2 highlights the significance of these viruses as causes of encephalitis in children. Further studies are needed to examine the role of HBoV infection in children encephalitis., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: A 3H-leucine (3H-Leu) single-injection method was proposed for determining the endogenous amino acid losses of broilers. This method was based on the hypothesis that the ratio of the specific radioactivity (SR) of endogenous Leu in excreta (SRe) to that of free Leu in trichloroacetic acid-soluble plasma (SRp) remains constant after a single subcutaneous injection of 3H-Leu into birds fed different diets., Methods: Two experiments were designed to clarify this hypothesis. In experiment 1, 40 female broilers were randomly divided into four groups and were force-fed a nitrogen-free diet (NFD), NFD plus enzyme-hydrolyzed casein (EHC), 5% crude protein (CP) and SBM (soybean meal), or 20% CP-SBM. In experiment 2, 24 broilers were randomly divided into four groups and were fasted or force-fed the NFD, 20% CP-SBM, or 20% CP and cottonseed meal (CSM) diet. After the forced feeding, broilers were administered 3H-Leu by a single subcutaneous injection at a rate of 30 μCi/kg of body weight. Blood samples were taken at 5 min, 30 min, 4 h, 24 h, 36 h, and 48 h after the injection. The excreta were totally collected and pooled over the 48-h experiment., Results: The ratios of SRe to SRp remained the same for the birds force-fed the NFD, NFD+EHC, and 5% CP-SBM diets in experiment 1 and for the birds fasted and force-fed the NFD diet in experiment 2. The proportions of endogenous Leu to total Leu in excreta were 72.8%, 61.4%, and 57.5% for birds force-fed with the 20% CP-SBM diet in experiment 1 and 20% CP-SBM and 20% CP-CSM diets in experiment 2, respectively. Broilers fed the 5% CP-SBM and 20% CP-SBM diets excreted more (P<0.05) endogenous Leu than those fed the NFD and NFD+EHC diets in experiment 1. Broilers fed the 20% CP-SBM diet excreted more (P<0.05) endogenous Leu than those fed the NFD diet and fasted and the 20% CP-CSM diet was intermediate (P>0.05) in experiment 2., Conclusion: The present study verified the hypothesis that the ratio of SRe to SRp remains constant after a single subcutaneous injection of 3H-Leu into broilers and proposes a new method to determine endogenous amino acid losses of broilers., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

The complete mitochondrial genome of Bufo gargarizans was sequenced using overlapping polymerase chain reaction (PCR) amplicons (GenBank Accession No. DQ275350). The genome is 17,277 base pairs in length, containing 13 protein-coding genes (ATP6, ATP8, COI-III, ND1-6, ND4L, Cyt b), 2 ribosomal RNAs (12S rRNA and 16S rRNA), 22 transfer RNAs and a putative control region. We analyzed the sequence using bioinformatics methods comparing the obtained mtDNA sequence with other toads and frogs. Based on the concatenated nucleotide sequences of protein-coding genes, we constructed a phylogenetic tree with maximum likelihood (ML) and maximum parsimony (MP) methods and discussed the phylogenetic relationships among 11 species of Anura.