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Background: Chronic stress induces cognitive deficits. There is a well-established connection between the enteric and central nervous systems through the microbiota-gut-brain (MGB) axis. However, the effects of the gut microbiota on cognitive deficits remain unclear. The present study aimed to elucidate the microbiota composition in cognitive deficits and explore its potential in predicting chronic stress-induced cognitive deficits., Methods: Mice were randomly divided into control and chronic restraint stress (CRS) groups. The mice subjected to CRS were further divided into cognitive deficit (CRS-CD) and non-cognitive deficit (CRS-NCD) groups using hierarchical cluster analysis of novel object recognition test results. The composition and diversity of the gut microbiota were analyzed., Results: After being subjected to chronic restraint distress, the CRS-CD mice travelled shorter movement distances (p = 0.034 vs. CRS-NCD; p < 0.001 vs. control) and had a lower recognition index than the CRS-NCD (p < 0.0001 vs. CRS-NCD; p < 0.0001 vs. control) and control mice. The results revealed that 5 gut bacteria at genus levels were significantly different in the fecal samples of mice in the three groups. Further analyses demonstrated that Muricomes were not only significantly enriched in the CRS-CD group but also correlated with a decreased cognitive index. The area under the receiver operating curve of Muricomes for CRS-induced cognitive deficits was 0.96., Conclusions: Our study indicates that the composition of the gut microbiota is involved in the development of cognitive deficits induced by chronic restraint stress. Further analysis revealed that Muricomes have the potential to predict the development of chronic stress-induced cognitive deficits in mice., (© 2024. The Author(s).)

Objective: The objective of this study was to assess the global burden of disease for developmental and intellectual disabilities caused by iodine deficiency from 1990 to 2019., Methods: Using data from the global burden of disease (GBD) 2019, we conducted a cross-country inequity analysis to examine the worldwide burden of developmental and intellectual disabilities caused by the issue of iodine deficiency from 1990 to 2019. Absolute and relative inequality were assessed by the slope index of inequality and the concentration index, respectively. After summarising the latest evidence, we also projected the age-standardized prevalence and years lived with disability (YLD) rates up to 2030 using the BAPC and INLA packages in R statistical software., Results: In 2019, the global age-standardized prevalence and YLD rates for developmental and intellectual disabilities due to iodine deficiency were 22.54 per 100,000 population (95% UI 14.47 to 29.23) and 4.12 per 100,000 population (95% UI 2.25 to 6.4), respectively. From 1990 to 2019, the age-standardized prevalence and YLD rates of developmental and intellectual disabilities due to iodine deficiency decreased significantly. Geographic distribution showed that areas with lower socio-demographic indices (SDI) were the most affected. The correlation between higher SDI and lower prevalence highlights the role of economic and social factors in the prevalence of the disease. Cross-national inequity analysis shows that disparities persist despite improvements in health inequalities. In addition, projections suggest that the disease burden may decline until 2030., Conclusion: This research underscores the necessity for targeted interventions, such as enhancing iodine supplementation and nutritional education, especially in areas with lower SDI. We aim to provide a foundation for policymakers further to research effective preventative and potential alternative treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Liu, Liu, He, Li, Li, Wu, Manyande, Feng and Xiang.)

Background: Numerous studies have already identified an association between excessive consumption of red meat and colorectal cancer (CRC). However, there has been a lack of detailed understanding regarding the disease burden linked to diet high in red meat and CRC., Objective: We aim to offer evidence-based guidance for developing effective strategies that can mitigate the elevated CRC burden in certain countries., Methods: We used the data from the Global Burden of Disease (GBD) Study 2019 to evaluate global, regional, and national mortality rates and disability-adjusted Life years (DALYs) related to diet high in red meat. We also considered factors such as sex, age, the socio-demographic index (SDI), and evaluated the cross-national inequalities. Furthermore, we utilized DALYs data from 204 countries and regions to measure cross-country inequalities of CRC by calculating the slope index of inequality and concentration index as standard indicators of absolute and relative inequalities., Discussion: The results show that globally, the age-standardized mortality rate (ASMR) and age-standardized disability adjusted life year rate (ASDR) related to CRC due to diet high in red meat have decreased, with estimated annual percent change (EAPCs) of -0.32% (95% CI -0.37 to -0.28) and-0.18% (95% CI -0.25 to -0.11). Notably, the burden was higher among males and the elderly. The slope index of inequality rose from 22.0 (95% CI 18.1 to 25.9) in 1990 to 32.9 (95% CI 28.3 to 37.5) in 2019 and the concentration index fell from 59.5 (95% CI 46.4 to 72.6) in 1990 to 48.9 (95% CI 34.6 to 63.1) in 2019. Also, according to our projections, global ASDR and ASMR might tend to increase up to 2030., Conclusion: ASMR and ASDR for CRC associated with high red meat diets declined globally from 1990 to 2019, but the absolute number of cases is still rising, with men and the elderly being more affected. CRC associated with diets high in red meat exhibits significant income inequality, placing a disproportionate burden on wealthier countries. Moreover, according to our projections, ASMR and ASDR are likely to increase globally by 2030. In order to address this intractable disease problem, understanding changes in global and regional epidemiologic trends is critical for policy makers and others., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Wu, Liu, He, Manyande, Fu and Xiang.)

Astrocytes constitute a major part of the central nervous system and the delineation of their activity patterns is conducive to a better understanding of brain network dynamics. This study aimed to develop a magnetic resonance imaging (MRI)-based method in order to monitor the brain-wide or region-specific astrocytes in live animals. Adeno-associated virus (AAVs) vectors carrying the human glial fibrillary acidic protein (GFAP) promoter driving the EGFP-AQP1 (Aquaporin-1, an MRI reporter) fusion gene were employed. The following steps were included: constructing recombinant AAV vectors for astrocyte-specific expression, detecting MRI reporters in cell culture, brain regions, or whole brain following cell transduction, stereotactic injection, or tail vein injection. The astrocytes were detected by both fluorescent imaging and Diffusion-weighted MRI. The novel AAV mutation (Site-directed mutagenesis of surface-exposed tyrosine (Y) residues on the AAV5 capsid) significantly increased fluorescence intensity (p < 0.01) compared with the AAV5 wild type. Transduction of the rAAV2/5 carrying AQP1 induced the titer-dependent changes in MRI contrast in cell cultures (p < 0.05) and caudate-putamen (CPu) in the brain (p < 0.05). Furthermore, the MRI revealed a good brain-wide alignment between AQP1 levels and ADC signals, which increased over time in most of the transduced brain regions. In addition, the rAAV2/PHP.eB serotype efficiently introduced AOP1 expression in the whole brain via tail vein injection. This study provides an MRI-based approach to detect dynamic changes in astrocytes in live animals. The novel in vivo tool could help us to understand the complexity of neuronal and glial networks in different pathophysiological conditions., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Cognitive dysfunction is a common comorbidity in patients with chronic pain. Activation of Liver X receptors (LXRs) plays a potential role in improving cognitive disorders in central nervous diseases. In this study, we investigated the role of LXRs in cognitive deficits induced by neuropathic pain., Methods: We established the spared nerve injury (SNI) model to investigate pain-induced memory dysfunction. Pharmacological activation of LXRs with T0901317 or inhibition with GSK2033 was applied. PI3K inhibitor LY294002 was administered to explore the underlying mechanism of LXRs. Changes in neuroinflammation, microglia polarization, and synaptic plasticity were assessed using biochemical technologies., Results: We found that SNI-induced cognitive impairment was associated with reduced LXRβ expression, increased M1-phenotype microglia, decreased synaptic proteins, and inhibition of PI3K/AKT signaling pathway in the hippocampus. Activation of LXRs using T0901317 effectively alleviated SNI-induced cognitive impairment. Additionally, T0901317 promoted the polarization of microglia from M1 to M2, reduced pro-inflammatory cytokines, and upregulated synaptic proteins in the hippocampus. However, administration of GSK2033 or LY294002 abolished these protective effects of T0901317 in SNI mice., Conclusions: LXRs activation alleviates neuropathic pain-induced cognitive impairment by modulating microglia polarization, neuroinflammation, and synaptic plasticity, at least partly via activation of PI3K/AKT signaling in the hippocampus. LXRs may be promising targets for addressing pain-related cognitive deficits., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Aims: Hepatic ischemia-reperfusion injury (HIRI) resulting from hepatic inflow occlusion, which is a common procedure in liver surgery is inevitable. Previous research has confirmed that the cognitive dysfunction induced by HIRI is closely related to dysbiosis of the gut microbiota. This research aims to investigate the mechanisms underlying this complication., Methods: C57BL/6 mice underwent hepatic ischemia experimentally through the occlusion of the left hepatic artery and portal vein. To assess the HDAC2-ACSS2 axis, gut microbiota transplantation. Enzyme-linked immunosorbent assay and LC/MS short-chain fatty acid detection were utilized., Results: The findings indicated a notable decline in ACSS2 expression in the hippocampus of mice experiencing hepatic ischemia-reperfusion injury, emphasizing the compromised acetate metabolism in this particular area. Furthermore, the cognitive impairment phenotype and the dysregulation of the HDAC2-ACSS2 axis could also be transmitted to germ-free mice via fecal microbial transplantation. Enzyme-linked immunosorbent assay revealed reduced Acetyl-coenzyme A (acetyl-CoA) and Acetylated lysine levels in the hippocampus., Conclusion: These findings suggest that acetate metabolism is impaired in the hippocampus of HIRI-induced cognitive impairment mice and related to dysbiosis, leading to compromised histone acetylation., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Lipoxygenase (LOX) has the harmful effect of accelerating lipid oxidation, and polyphenols have the inhibitory effect on lipoxygenase. However, there were rare researches investigated on the interactions between polyphenols and LOX. In this study, the binding mechanisms between polyphenols (Jaceosidin-JSD and baicalein-BCL) and LOX were investigated by multi-spectroscopic analysis and computational study. Both JSD and BCL binding to LOX resulted in static fluorescence quenching, and the complexes of JSD-LOX and BCL-LOX were built at a molar ratio of 1:1, respectively. The binding constants of LOX-JSD (72.18 × 10 5  L/mol at 298 K) and LOX-BCL (12.43 × 10 5  L/mol at 298 K) indicated that LOX had stronger binding affinity to JSD compared to BCL. Compared with BCL-LOX, the JSD-LOX system formed more hydrogen bonds which ensured a stronger bond between JSD and LOX. The studies in molecular dynamics also demonstrated that the JSD-LOX complex is more stable, and the addition of JSD is more conducive to the complex formation. The current study provides some new insights for the study on the inhibition of lipid oxidation and affords a new strategy for the discovery of novel food preservatives., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Spinal cord injuries, often resulting from spine fractures, can lead to severe lifelong symptoms such as paraplegia and even mortality. Over the past few decades, there has been a concerning increase in the annual incidence and mortality rates of spinal cord injuries, which has also placed a growing financial strain on healthcare systems. This review aims to offer a comprehensive overview of spinal cord injuries by estimating their global incidence, prevalence, and the impact in terms of years lived with disability, using data obtained from the 2019 Global Burden of Disease Study., Method: In this study, we utilized data from the 2019 Global Burden of Disease Study, a widely recognized source for global health data. Our methodology involved estimating the global incidence and prevalence of spinal cord injuries while also assessing the impact on years lived with a disability. We analyzed this data comprehensively to identify patterns and trends and made predictions., Finding: This research delved into the evolving trends in the global burden of spinal cord injuries, identified key risk factors, and examined variations in incidence and disability across different Socio-demographic Index (SDI) levels and age groups. Briefly, in 2019, the global incidence and burden of YLDs of SCI significantly increased compared to 1990. While males had higher incidence rates compared to females. Falls were identified as the primary cause of SCI. Trend projections up to 2030 revealed a slight decrease in ASIR for males, an upward trend in age-specific incidence rates for both sexes and a similar pattern in age-standardized YLD rates. Additionally, our findings provided crucial groundwork for shaping future policies and healthcare initiatives, with the goal of mitigating the burden of spinal cord injuries, enhancing patient outcomes, and fortifying prevention efforts., Interpretation: Understanding the global burden of spinal cord injuries is essential for designing effective healthcare policies and prevention strategies. With the alarming increase in prevalence rates and their significant impact on individuals and healthcare systems, this research contributes vital insights to guide future efforts in reducing the incidence of spinal cord injuries, improving the quality of life for affected individuals, and reducing the economic burden on healthcare systems worldwide., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Yang, He, Li, Li, Wu, Manyande, Feng and Xiang.)

Background and Objective: Since its initial report by James Parkinson in 1817, Parkinson's disease (PD) has remained a central subject of research and clinical advancement. The disease is estimated to affect approximately 1% of adults aged 60 and above. Deep brain stimulation, emerging as an alternative therapy for end-stage cases, has offered a lifeline to numerous patients. This review aimed to analyze publications pertaining to the impact of deep brain stimulation on the motor pathway in patients with PD over the last decade., Methods: Data were obtained from the Web of Science Core Collection through the library of Huazhong University of Science and Technology (China). The search strategy encompassed the following keywords: "deep brain stimulation", "Parkinson's disease", "motor pathway", and "human", from January 1, 2012, to December 1, 2022. Additionally, this review visualized the findings using the Citespace software., Results: The results indicated that the United States, the United Kingdom, Germany, and China were the primary contributors to this research field. University College London, Capital Medical University, and Maastricht University were the top 3 research institutions in the research area. Tom Foltynie ranked first with 6 publications, and the journals of Brain and Brain Stimulation published the greatest number of relevant articles. The prevailing research focal points in this domain, as determined by keywords "burst analysis", "encompassed neuronal activity", "nucleus", "hyper direct pathway", etc. CONCLUSION: This study has provided a new perspective through bibliometric analysis of the deep brain stimulation therapy for treating patients with PD, which can shed light on future research to advance our comprehension of this particular field of study., (© 2023. Huazhong University of Science and Technology.)

Background: Hepatic ischemia-reperfusion injury (HIRI) is a common complication of liver surgery, which can lead to extrahepatic metabolic disorders, such as cognitive impairment. Recent observations have emphasized the critical effects of gut microbial metabolites in regulating the development of liver injury. Herein, we investigated the potential contribution of gut microbiota to HIRI-related cognitive impairment., Methods: HIRI murine models were established by ischemia-reperfusion surgery in the morning (ZT0, 08:00) and evening (ZT12, 20:00), respectively. Antibiotic-induced pseudo-germ-free mice were gavaged with fecal bacteria of the HIRI models. Behavioral test was used to assess cognitive function. 16S rRNA gene sequencing and metabolomics were used for microbial and hippocampal analysis., Results: Our results established that cognitive impairment caused by HIRI underwent diurnal oscillations; HIRI mice performed poorly on the Y-maze test and the novel object preference test when surgery occurred in the evening compared with the morning. In addition, fecal microbiota transplantation (FMT) from the ZT12-HIRI was demonstrated to induce cognitive impairment behavior. The specific composition and metabolites of gut microbiota were analyzed between the ZT0-HIRI and ZT12-HIRI, and bioinformatic analysis showed that the differential fecal metabolites were significantly enriched in lipid metabolism pathways. After FMT, the hippocampal lipid metabolome between the P-ZT0-HIRI and P-ZT12-HIRI groups was analyzed to reveal a series of lipid molecules with significant differences., Conclusions: Our findings indicate that gut microbiota are involved in circadian differences of HIRI-related cognitive impairment by affecting hippocampal lipid metabolism., (© 2023. The Author(s).)

Purpose: To investigate the effect of endothelin-1 (ET-1) in excessive accumulation of extracellular matrix (ECM) of the trabecular meshwork (TM) and its role in intraocular pressure (IOP) regulation., Methods: Cultured human TM cells (HTMCs) were treated with ET-1, ET-1 + ETA receptor (ETAR) antagonist BQ123, ET-1 + ETB receptor (ETBR) antagonist BQ788. The expressions of fibronectin (FN) and collagen type IV (Col IV) were evaluated by western blotting and immunofluorescence. A time course effect of ET-1 on the transcription level of connective tissue growth factor (CTGF) was investigated by qRT-PCR. Next, the transcription level of CTGF was downregulated by using antisense oligodeoxynucleotide sequence. Then HTMCs were treated with ET-1, and the expression levels of FN and Col IV were evaluated by western blotting. In addition, by using an ex-vivo model of cultured anterior eye segment, we explored the effect of ET-1 on IOP changes and the expressions of FN and Col IV., Results: In cultured HTMCs, the expressions of FN and Col IV were significantly increased after ET-1 treatment, which were blocked by the pretreatment of ETAR antagonist BQ123, rather than ETBR antagonist BQ788. Besides, the CTGF mRNA level increased significantly and reached a peak after 48 h of ET-1 treatment. However, the effect of ET-1 on increasing the expressions of FN and Col IV in HTMCs could be inhibited by the downregulation of CTGF. In an ex-vivo model, IOP increased significantly after ET-1 administration, which could be blocked by BQ123 but not by BQ788. Furthermore, elevated expressions of FN and Col IV in TM were observed after ET-1 perfusion, and could be inhibited by BQ123 pretreatment., Conclusion: Excessive ET-1 in aqueous humor could lead to the abnormal accumulation of FN and Col IV in TM via the ETA-CTGF pathway, thereby increasing IOP., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Sleep disorders can profoundly affect neurological function. We investigated changes in social and anxiety-related brain functional connectivity induced by sleep deprivation, and the potential therapeutic effects of the general anaesthetics propofol and sevoflurane in rats., Methods: Twelve-week-old male Sprague-Dawley rats were subjected to sleep deprivation for 20 h per day (from 14:00 to 10:00 the next day) for 4 consecutive weeks. They were free from sleep deprivation for the remaining 4 h during which they received propofol (40 mg kg -1 i.p.) or sevoflurane (2% for 2 h) per day or no treatment. These cohorts were instrumented for EEG/EMG recordings on days 2, 14, and 28. Different cohorts were used for open field and three-chambered social behavioural tests, functional MRI, nuclear magnetic resonance spectroscopy, and positron emission tomography imaging 48 h after 4 weeks of sleep deprivation., Results: Propofol protected against sleep deprivation-induced anxiety behaviours with more time (44.7 [8.9] s vs 24.2 [4.1] s for the sleep-deprivation controls; P<0.001) spent in the central area of the open field test and improved social preference index by 30% (all P<0.01). Compared with the sleep-deprived rats, propofol treatment enhanced overall functional connectivity by 74% (P<0.05) and overall glucose metabolism by 30% (P<0.01), and improved glutamate kinetics by 20% (P<0.05). In contrast, these effects were not found after sevoflurane treatment., Conclusions: Unlike sevoflurane, propofol reduced sleep deprivation-induced social and anxiety-related behaviours. Propofol might be superior to sevoflurane for patients with sleep disorders who receive anaesthesia, which should be studied in clinical studies., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The ventral tegmental area (VTA) contains heterogeneous cell populations. The dopaminergic neurons in VTA play a central role in reward and cognition, while CamKIIα-positive neurons, composed mainly of glutamatergic and some dopaminergic neurons, participate in the reward learning and locomotor activity behaviors. The differences in brain-wide functional and structural networks between these two neuronal subtypes were comparatively elucidated., Methods: In this study, we applied a method combining Designer Receptors Exclusively Activated by Designer Drugs (DREADD) and fMRI to assess the cell type-specific modulation of whole-brain neural networks. rAAV encoding the cre-dependent hM3D was injected into the right VTA of DAT-cre or CamKIIα-cre transgenic rats. The global brain activities elicited by DREADD stimulation were then detected using BOLD-fMRI. Furthermore, the cre-dependent antegrade transsynaptic viral tracer H129ΔTK-TT was applied to label the outputs of VTA neurons., Results: We found that DREADD stimulation of dopaminergic neurons induced significant BOLD signal changes in the VTA and several VTA-related regions including mPFC, Cg and Septum. More regions responded to selective activation of VTA CamKIIα-positive neurons, resulting in increased BOLD signals in VTA, Insula, mPFC, MC&#95;R (Right), Cg, Septum, Hipp, TH&#95;R, PtA&#95;R, and ViC&#95;R. Along with DREADD-BOLD analysis, further neuronal tracing identified multiple cortical (MC, mPFC) and subcortical (Hipp, TH) brain regions that are structurally and functionally connected by VTA dopaminergic and CamKIIα-positive neurons., Conclusions: Our study dissects brain-wide structural and functional networks of two neuronal subtypes in VTA and advances our understanding of VTA functions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The current study investigated the effects of various cooking styles (boiling, frying, and steaming) and seasoning methods (home cooking and ready-to-eat commodity) on levels of nine heavy metals in the crayfish (Procambarus clarkii) muscle. The estimated daily intake (EDI), target hazard quotients (THQ), and target cancer risk (TCR) were used to assess the health risk in the crayfish muscle. The results showed that cooking processes significantly increased the concentration of Cu, which raises a potential risk for children (the THQ values > 1). The levels of toxic heavy metals in the ready-to-eat crayfish muscle were significantly higher than those in household cooking. Especially for As, the THQ values rose to 7.1 and 13.2 for adults and children respectively. Therefore, home cooking is safer than ready-to-eat crayfish, and children should consume crayfish within a limited range. The recommended consumption of the cooked abdominal muscle of crayfish should be 257 and 58 g/day, for children (16 kg) and adults (70 kg), respectively., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Patients with liver disease are prone to various cognitive impairments. It is undeniable that cognitive impairment is often regulated by both the nervous system and the immune system. In this review our research focused on the regulation of mild cognitive impairment associated with liver disease by humoral factors derived from the gastrointestinal tract, and revealed that its mechanisms may be involved with hyperammonemia, neuroinflammation, brain energy and neurotransmitter metabolic disorders, and liver-derived factors. In addition, we share the emerging research progress in magnetic resonance imaging techniques of the brain during mild cognitive impairment associated with liver disease, in order to provide ideas for the prevention and treatment of mild cognitive impairment in liver disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sun, Feng, Manyande, Xiang, Xiong and He.)

Pork and grass carp are commonly consumed animal protein sources, classified as red meat and white meat, respectively. This study aimed to better understand the differences in digestive behavior, nutrition, and functionality during digestion between these two types of meat after fat removal. The results showed that grass carp was more easily digested than pork, with a higher degree of hydrolysis, a smaller protein particle size, and a greater release of oligopeptides and amino acids ( p < 0.05). During gastric digestion, all α-helix structures were destroyed, and the effect of the whole digestion process on the secondary and tertiary structure of pork protein was greater than that of grass carp. The antioxidant properties of the digestive fluids from the two types of meat showed different strengths in various assays, but the correlation analysis revealed that TCA-soluble peptides, random coil content, and particle size significantly influenced both types of meat. These findings provide new insights into the structural state and antioxidant properties of protein in meat digestion, which contribute to our understanding of the nutritional value of pork and grass carp.

Introduction: Owing to advancements in non-invasive magnetic resonance imaging, many studies have repeatedly showed that diabetes affects the central nervous system in the presence of peripheral neuropathy, suggesting a common or interacting pathological mechanism for both complications., Methods: We aimed to investigate the role of abnormal gut microbiota in rats with diabetic peripheral neuropathy (DPN) combined with cognitive dysfunction. Glucose-compliant rats with nerve conduction deficits were screened as a successful group of DPN rats. The DPN group was then divided into rats with combined cognitive impairment (CD) and rats with normal cognitive function (NCD) based on the results of the Novel object recognition test. Rat feces were then collected for 16S rRNA gene sequencing of the intestinal flora., Results and Discussion: The results revealed that abnormalities in Firmicutes , Ruminococcaceae , Bacteroidia , and Actinobacteria-like microorganisms may induce DPN complicated by cognitive dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Lin, Sun, Deng, Manyande, Xiang, Zhao and Hong.)

Introduction: Dorsal root ganglia (DRG) are anatomically well-defined structures that contain all primary sensory neurons and are distension nodules of the dorsal root in the spinal cord near the medial surface of each foramen. Therefore, DRG is considered to be a desirable target for injection to manage chronic pain. But it presents a limitation in probing deep into it without in vivo injection technology., Methods: Here, we described a technique for administering intraganglionic injections of lumbar DRG under direct vision. We use partial osteotomy rather than laminectomy, which removes more bone, to preserve spinal structures while gaining adequate DRG access. To monitor the intraoperative progress of the DRG injection, a non-toxic dye was utilized. The effectiveness of the injection on the diffusion of AAV (adeno-associated virus) within the ganglion was assessed by histopathology at postoperative day 21., Results: Behavioral tests showed that neither motor nor sensory abilities were affected by saline or AAV injections. Meanwhile, the decreased pain threshold of SNI (spared nerve injury) was considerably restored by pharmacological inhibition of DRG neurons., Discussion: Our research achieved a new minimally invasive and intuitive intra-ganglionic injection in mice. In addition, the present protocol may serve as a valuable resource for planning preclinical studies of DRG injection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yuan, Han, Zhao, Manyande, Gao, Wang, Zhang and Tian.)

With the emergence of the scientific research field of tumor microenvironment, the idea that tumor growth and propagation cannot be separated from the tumor microenvironment has become common. The autonomic nervous system is involved in the whole process of growth and development of the organism, and it is undeniable that the tumor microenvironment is equally regulated by both the autonomic nervous system and the immune system. Our research focused on the cancer-nerve crosstalk process and revealed the regulatory mechanisms between the autonomic nervous system and prostate, gastric, pancreatic ductal and breast cancers, mainly elucidating that (1) the release of neurotransmitters and their receptors by autonomic nerves may be important for solid tumor progression, and (2) in combination with the latest targeted small molecule imaging technology, we summarized the biological pathways related to neurotransmitters as small molecule tracers to track solid tumor progression. This research focused on combining targeted small molecules and imaging techniques to observe sympathetic and parasympathetic processes that promote or inhibit cancer development, providing new potential therapeutic targets for prostate, gastric, pancreatic ductal and breast cancers. It also provided cutting-edge research evidence for the development of biological small molecule drugs and targeted tracers in cancer therapy., Competing Interests: None., (AJCR Copyright © 2023.)

Backgroud: Studies have shown that the activation of microglia is the main mechanism of neuropathic pain. Kv1.3 channel is a novel therapeutic target for treating neuroinflammatory disorders due to its crucial role in subsets of microglial cells. As such, it may be involved in the processes of neuropathic pain, however, whether Kv1.3 plays a role in neuroinflammation following peripheral nerve injury is unclear., Method: The spared nerve injury model (SNI) was used to establish neuropathic pain. Western blot and immunofluorescence were used to examine the effect of Kv1.3 in the SNI rats. PAP-1, a Kv1.3 specific blocker was administered to alleviate neuropathic pain in the SNI rats., Results: Neuropathic pain and allodynia occurred after SNI, the levels of M1 (CD68, iNos) and M2 (CD206, Arg-1) phenotypes were up-regulated in the spinal cord, and the protein levels of NLRP3, caspase-1 and IL-1β were also increased. Pharmacological blocking of Kv1.3 with PAP-1 alleviated hyperpathia induced by SNI. Meanwhile, intrathecal injection of PAP-1 reduced M1 polarization and decreased NLRP3, caspase-1 and IL-1β expressions of protein levels., Conclusion: Our research indicates that the Kv1.3 channel in the spinal cord contributes to neuropathic pain by promoting microglial M1 polarization and activating the NLRP3 inflammasome., (© 2022 European Pain Federation - EFIC ®.)

Preoperative sleep loss can amplify post-operative mechanical hyperalgesia. However, the underlying mechanisms are still largely unknown. In the current study, rats were randomly allocated to a control group and an acute sleep deprivation (ASD) group which experienced 6 h ASD before surgery. Then the variations in cerebral function and activity were investigated with multi-modal techniques, such as nuclear magnetic resonance, functional magnetic resonance imaging, c-Fos immunofluorescence, and electrophysiology. The results indicated that ASD induced hyperalgesia, and the metabolic kinetics were remarkably decreased in the striatum and midbrain. The functional connectivity (FC) between the nucleus accumbens (NAc, a subregion of the ventral striatum) and the ventrolateral periaqueductal gray (vLPAG) was significantly reduced, and the c-Fos expression in the NAc and the vLPAG was suppressed. Furthermore, the electrophysiological recordings demonstrated that both the neuronal activity in the NAc and the vLPAG, and the coherence of the NAc-vLPAG were suppressed in both resting and task states. This study showed that neuronal activity in the NAc and the vLPAG were weakened and the FC between the NAc and the vLPAG was also suppressed in rats with ASD-induced hyperalgesia. This study highlights the importance of preoperative sleep management for surgical patients., (© 2022. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Accumulating evidence suggests that neuroinflammation is the main mechanism in cognitive dysfunction and that brain-derived neurotrophic factor (BDNF) is involved in learning and memory by binding to tyrosine kinase B (TrkB) receptors. Herein, we tested the roles of the BDNF-TrkB signaling pathway and its downstream cascade in lipopolysaccharide (LPS) induced cognitive dysfunction in mice. Mice were treated with LPS (0.25 mg/kg) for 7 days, and learning and memory function was evaluated by the novel object recognition test (NORT). Western blotting was performed to elucidate roles of the BDNF-TrkB signaling pathway and its downstream cascades in LPS mice. The NORT showed that LPS induced learning and memory deficits in mice. The levels of IL-1β, IL-6, and TNF-α in the serum and central nervous system decreased in LPS mice. In addition, LPS reduced the protein levels of BDNF, p-TrkB, Bcl-2, p-ERK1/2, p-CaMK2, p-CREB and p-GluR1 and increased the expression of Bax in the hippocampus and medial prefrontal cortex regions. In the entorhinal cortex, the protein levels of BDNF, p-TrkB, Bcl-2, p-CaMK2 and p-CREB were decreased, and the protein level of Bax was increased in LPS mice. Interestingly, 7,8-DHF alleviated these disorders in LPS mice and improved learning and memory function; however, the TrkB antagonist ANA12 effectively reversed effects of 7,8-DHF. Therefore, we conclude that the BDNF-TrkB signaling pathway and its downstream cascades disorders in different regions are main mechanisms of cognitive dysfunction, and 7,8-DHF maybe useful as a new treatment for preventing or treating cognitive dysfunction induced by neuroinflammation in neurodegenerative diseases., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.)

A mammalian brain contains numerous neurons with distinct cell types for complex neural circuits. Virus-based circuit tracing tools are powerful in tracking the interaction among the different brain regions. However, detecting brain-wide neural networks in vivo remains challenging since most viral tracing systems rely on postmortem optical imaging. We developed a novel approach that enables in vivo detection of brain-wide neural connections based on metal-free magnetic resonance imaging (MRI). The recombinant adeno-associated virus (rAAV) with retrograde ability, the rAAV2-retro, encoding the human water channel aquaporin 1 (AQP1) MRI reporter gene was generated to label neural connections. The mouse was micro-injected with the virus at the Caudate Putamen (CPU) region and subjected to detection with Diffusion-weighted MRI (DWI). The prominent structure of the CPU-connected network was clearly defined. In combination with a Cre-loxP system, rAAV2-retro expressing Cre-dependent AQP1 provides a CPU-connected network of specific type neurons. Here, we established a sensitive, metal-free MRI-based strategy for in vivo detection of cell type-specific neural connections in the whole brain, which could visualize the dynamic changes of neural networks in rodents and potentially in non-human primates., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The technique of organ transplantation is well established and after transplantation the patient might be faced with the problem of nerve regeneration of the transplanted organ. Transplanted organs are innervated by the sympathetic, parasympathetic, and visceral sensory plexuses, but there is a lack of clarity regarding the neural influences on the heart, liver and kidneys and the mechanisms of their innervation. Although there has been considerable recent work exploring the potential mechanisms of nerve regeneration in organ transplantation, there remains much that is unknown about the heterogeneity and individual variability in the reinnervation of organ transplantation. The widespread availability of radioactive nerve tracers has also made a significant contribution to organ transplantation and has helped to investigate nerve recovery after transplantation, as well as providing a direction for future organ transplantation research. In this review we focused on neural tracer imaging techniques in humans and provide some conceptual insights into theories that can effectively support our choice of radionuclide tracers. This also facilitates the development of nuclear medicine techniques and promotes the development of modern medical technologies and computer tools. We described the knowledge of neural regeneration after heart transplantation, liver transplantation and kidney transplantation and apply them to various imaging techniques to quantify the uptake of radionuclide tracers to assess the prognosis of organ transplantation. We noted that the aim of this review is both to provide clinicians and nuclear medicine researchers with theories and insights into nerve regeneration in organ transplantation and to advance imaging techniques and radiotracers as a major step forward in clinical research. Moreover, we aimed to further promote the clinical and research applications of imaging techniques and provide clinicians and research technology developers with the theory and knowledge of the nerve., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, He, Manyande, Feng and Xiang.)

Thus far, when deception behaviors occur, the connectivity patterns and the communication between different brain areas remain largely unclear. In this study, the most important information flows (MIIFs) between different brain cortices during deception were explored. First, the guilty knowledge test protocol was employed, and 64 electrodes' electroencephalogram (EEG) signals were recorded from 30 subjects (15 guilty and 15 innocent). Cortical current density waveforms were then estimated on the 24 regions of interest (ROIs). Next, partial directed coherence (PDC), an effective connectivity (EC) analysis was applied in the cortical waveforms to obtain the brain EC networks for four bands: delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz) and beta (13-30 Hz). Furthermore, using the graph theoretical analysis, the network parameters with significant differences in the EC network were extracted as features to identify the two groups. The high classification accuracy of the four bands demonstrated that the proposed method was suitable for lie detection. In addition, based on the optimal features in the classification mode, the brain "hub" regions were identified, and the MIIFs were significantly different between the guilty and innocent groups. Moreover, the fronto-parietal network was found to be most prominent among all MIIFs at the four bands. Furthermore, combining the neurophysiology significance of the four frequency bands, the roles of all MIIFs were analyzed, which could help us to uncover the underlying cognitive processes and mechanisms of deception.

Connectomics has developed from an initial observation under an electron microscope to the present well-known medical imaging research approach. The emergence of the most popular transneuronal tracers has further advanced connectomics research. Researchers use the virus trans-nerve tracing method to trace the whole brain, mark the brain nerve circuit and nerve connection structure, and construct a complete nerve conduction pathway. This review assesses current methods of studying cortical to muscle connections using viral neuronal tracers and demonstrates their application in disease diagnosis and prognosis., Competing Interests: None., (AJTR Copyright © 2022.)

Polyphenols are inhibitors for lipase, but the binding selectivity and mechanism of polyphenol isomers and how they interact with lipase are not clear. Here, chlorogenic acid (CGA) isomers, neochlorogenic acid (NCGA) and cryptochlorogenic acid (CCGA) were used to explore the binding selectivity and mechanism of lipase. An inhibition assay indicated that both CGA isomers had dose-dependent inhibitory effects on lipase; however, the inhibitory effect of NCGA was better (IC 50 : 0.647 mg/mL) than that of CCGA (IC 50 : 0.677 mg/mL). NCGA and CCGA formed complexes with lipase at a molar ratio of 1:1, and the electrostatic interaction force plays a major role in the lipase-CCGA system. Molecular dynamics studies demonstrated that NCGA had a greater impact on the structure of lipase. The multi-spectroscopic and modeling results explained the effects of micro-structural changes on the binding site, the interaction force and the inhibition rate of the isomers when they combined with lipase., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Chronic pain during adolescence can lead to mental health disorders in adulthood, but the underlying mechanism is still unclear. Furthermore, the homeostasis of cerebral glucose metabolism and neurotransmitter metabolic kinetics are closely associated with cognitive development and pain progression. The present study investigated changes in cognitive function and glucose metabolism in adult rats, which had experienced chronic pain during their adolescence. Here, spared nerve injury (SNI) surgery was conducted in 4-week-old male rats. Mechanical nociceptive reflex thresholds were analyzed, and SNI chronic pain (SNI-CP) animals were screened. Based on animal behavioral tests (open field, three-chambered social, novel object recognition and the Y maze), the SNI-CP animals showed learning and memory impairment and anxiety-like behaviors, compared to SNI no chronic pain (SNI-NCP) animals. The cerebral glucose metabolism in the prefrontal cortex and hippocampus of adult SNI-CP animals was decreased with positron emission tomography/computed tomography. GABA 2 and Glu 4 levels in the metabolic kinetics study were significantly decreased in the hippocampus, frontal cortex, and temporal cortex, and the expression of GLUT3 and GLUT4 was also significantly downregulated in the prefrontal cortex and hippocampus of adult rats in the SNI-CP group. These findings suggest that the rats which suffered chronic pain during adolescence have lower cerebral glucose metabolism in the cortex and hippocampus, which could be related to cognitive function during the development of the central nervous system., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused several outbreaks of highly contagious respiratory diseases worldwide. The respiratory symptoms of Coronavirus Disease-19 (COVID-19) have been closely monitored and studied, while the central nervous system (CNS) and peripheral system (PNS) lesions induced by COVID-19 have not received much attention. Currently, patients with COVID-19-associated encephalopathy present with dizziness, headache, anxiety and depression, stroke, epileptic seizures, the Guillain-Barre syndrome (GBS), and demyelinating disease. The exact pathologic basis for these neurological symptoms is currently not known. Rapid mutation of the SARS-CoV-2 genome leads to the appearance of SARS-CoV-2 variants of concern (VOCs), which have higher infectivity and virulence. Therefore, this narrative review will focus on the imaging assessment of COVID-19 and its VOC. There has been an increase in technologies, such as [ 18 F]fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET) and functional magnetic resonance imaging (fMRI), that have been used to observe changes in brain microstructure over time in patients with COVID-19 recovery. Medical imaging and pathological approaches aimed at exploring the associations between COVID-19 and its VOC, with cranial nerve and abnormal nerve discharge will shed light on the rehabilitation process of brain microstructural changes related to SARS-CoV-2, and aid future research in our understanding of the treatment and prognosis of COVID-19 encephalopathy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Ling, Manyande, Wu and Xiang.)

Acute kidney injury (AKI) has been found to be a serious clinical problem with high morbidity and mortality, and is associated with acute inflammatory response and sympathetic activation that subsequently play an important role in the development of AKI. It is well known that the sympathetic nervous system (SNS) and immune system intensely interact and mutually control each other in order to maintain homeostasis in response to stress or injury. Evidence has shown that the superior cervical sympathetic ganglion (SCG) participates in the bidirectional network between the immune and the SNS, and that the superior cervical ganglionectomy has protective effect on myocardial infarction, however, the role of the SCG in the setting of renal ischemic reperfusion injury has not been studied. Here, we sought to determine whether or not the SCG modulates renal ischemic reperfusion (IR) injury in rats. Our results showed that bilateral superior cervical ganglionectomy (SCGx) 14 days before IR injury markedly reduced the norepinephrine (NE) in plasma, and down-regulated the increased expression of tyrosine hydroxylase (TH) in the kidney and hypothalamus. Sympathetic denervation by SCGx in the AKI group increased the level of blood urea nitrogen (BUN) and kidney injury molecule-1 (KIM-1), and exacerbated renal pathological damage. Sympathetic denervation by SCGx in the AKI group enhanced the expression of pro-inflammatory cytokines in plasma, kidney and hypothalamus, and increased levels of Bax in denervated rats with IR injury. In addition, the levels of purinergic receptors, P2X3R and P2X7R, in the spinal cord were up-regulated in the denervated rats of the IR group. In conclusion, these results demonstrate that the sympathetic denervation by SCGx aggravated IR-induced AKI in rats via enhancing the inflammatory response, thus, the activated purinergic signaling in the spinal cord might be the potential mechanism in the aggravated renal injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Li, Li, Sun, He, Manyande, Xu and Xiang.)

With the COVID-19 epidemic quickly under control in China in the early stage of 2020, global cooperation/communications may pose great challenges to epidemic control and prevention in the country. Large-scale spread by asymptomatic carriers was a concern. We obtained data on new cluster outbreak regions with COVID-19 caused by asymptomatic carriers from June 2020 to May 2021 in China, and reported the epidemiological characteristics, the possible routes of viral transmission and infection, and different control strategies. These results show the importance of regular screening for high-risk populations and differential management strategies for epidemic control, which provide an objective basis for suppressing the spread of the SARS-CoV-2 virus. These experiences can be used as a reference to minimize the subsequent spread of virus mutants in various places., Competing Interests: None., (AJTR Copyright © 2022.)

The diversity and complexity of sympathetic function highlight the importance of fundamental research. Little is known about the interaction of superior cervical sympathetic ganglion (SCG) and gut microbiota. In this study, the engagement of the sympathetic ganglia with gut microbiota was investigated. Bilateral superior cervical ganglionectomy (SCGx) significantly altered the microbiota composition in rats 14 days post-surgery, and these microbiotas may participate in several biological pathways in the host, suggesting the vital role of the cervical sympathetic ganglion in regulating the microbiome-brain axis, and further confirming that the sympathetic nervous system (SNS) regulates the microbiome-brain axis., Competing Interests: None., (AJTR Copyright © 2022.)

Due to the rapid development of the crayfish ( Procambarus clarkii ) industry in Chinese catering, people are paying more attention to the bioaccumulation of heavy metals in crayfish. To evaluate the health risks associated with the consumption of crayfish, nine types of heavy metals in both crayfish and abdominal muscles of crayfish were investigated. Crayfish samples were collected from rice-crayfish-based coculture breeding modes from different areas located in the middle and lower reaches of the Yangtze River. The average concentrations of heavy metals in the whole crayfish were much higher than the abdominal muscle of crayfish. The estimated daily intake (EDI) of heavy metals in the abdomen of crayfish was calculated to assess the noncarcinogenic risk and the overall noncarcinogenic risk including the target hazard quotient (THQ), the hazard index (HI) and carcinogenic risk (CR). The results of the present study showed that the consumption of crayfish may not present an obvious health risk to human associated with heavy metals. However, the THQ values of As in the abdominal muscles of crayfish for adults in EnShi (ES) and children in JiaYu (JY) should be of concern due to the higher contribution to the potential health risks of crayfish compared to other metals. Through X-ray photoelectron spectroscopy (XPS) detection of heavy metal As, it is found that As in crayfish culture environment mainly exists in the form of As 3+ .Therefore, the quality and quantity of crayfish consumption should be moderated to prevent the bioaccumulation of As. The results indicate that crayfish cultured in different areas may have similar pollution levels and/or emissions from the same pollution sources.

As an emerging framework in neuroscience, brain connectomics is well suited for investigating key questions on brain complexity by combining viral transneuronal tracing and whole brain graphic methodologies using analytical tools of network science. Transsynaptic viral tract-tracing in the toolbox of neural labeling methods has been a significant development in the connectomics field to decipher the circuit-level architecture of the cerebral cortex. In the present work, we reviewed the current methods enabling structural connectivity from the viscera to the cerebral cortex mapping with viral transneuronal tracers and showed how such neuroanatomic connectomic data could be used to infer new structural and functional information in viscera-cerebral cortex circuits., Competing Interests: None., (AJTR Copyright © 2021.)

Alcohol addiction is regarded as a series of dynamic changes to neural circuitries. A comparison of the global network during different stages of alcohol addiction could provide an efficient way to understand the neurobiological basis of addiction. Two animal models (P-rats screened from an alcohol preference family, and NP-rats screened from an alcohol non-preference family) were trained for alcohol preference with a two-bottle free choice method for 4 weeks. To examine the changes in the neural response to alcohol during the development of alcohol preference and acute stimulation, different trials were studied with resting-state fMRI methods during different periods of alcohol preference. The correlation coefficients of 28 regions in the whole brain were calculated, and the results were compared for alcohol preference related to the genetic background/training association. The variety of coherence patterns was highly related to the state and development of alcohol preference. We observed significant special brain connectivity changes during alcohol preference in P-rats. The comparison between the P- and NP-rats highlighted the role of genetic background in alcohol preference. The results of this study support the alterations of the neural network connection during the formation of alcohol preference and confirm that alcohol preference is highly related to the genetic background. This study could provide an effective approach for understanding the neurobiological basis of alcohol addiction.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has wreaked havoc on millions of people around the world. Although China quickly brought the Coronavirus disease (COVID-19) under control, there have been several sporadic outbreaks in different regions of China since June 2020. This article described the chronological nosocomial COVID-19 infection events related to several sporadic outbreaks of SARS-CoV-2 in different regions of China. We have reported epidemiological characteristics and management measures of sporadic nosocomial COVID-19 infections from June 2020 to June 2021 and specially focused on the domestic COVID-19 breakthrough infection in China, such as domestic COVID-19 breakthrough infection-a vaccinated healthcare professional working in the isolation ward of a designated COVID-19 hospital., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 He, Xiang, Manyande, Xu, Fan and Xiang.)

The investigation of neural circuits is important for interpreting both healthy brain function and psychiatric disorders. Currently, the architecture of neural circuits is always investigated with fluorescent protein encoding neurotropic virus and ex vivo fluorescent imaging technology. However, it is difficult to obtain a whole-brain neural circuit connection in living animals, due to the limited fluorescent imaging depth. Herein, the noninvasive, whole-brain imaging technique of MRI and the hypotoxicity virus vector AAV (adeno-associated virus) were combined to investigate the whole-brain neural circuits in vivo. AAV2-retro are an artificially-evolved virus vector that permits access to the terminal of neurons and retrograde transport to their cell bodies. By expressing the ferritin protein which could accumulate iron ions and influence the MRI contrast, the neurotropic virus can cause MRI signal changes in the infected regions. For mice injected with the ferritin-encoding virus vector (rAAV2-retro-CAG-Ferritin) in the caudate putamen (CPu), several regions showed significant changes in MRI contrasts, such as PFC (prefrontal cortex), HIP (hippocampus), Ins (insular cortex) and BLA (basolateral amygdala). The expression of ferritin in those regions was also verified with ex vivo fluorescence imaging. In addition, we demonstrated that changes in T2 relaxation time could be used to identify the spread area of the virus in the brain over time. Thus, the neural connections could be longitudinally detected with the in vivo MRI method. This novel technique could be utilized to observe the viral infection process and detect the neural circuits in a living animal., (© 2021 Innovation Academy for Precision Measurement Science and Technology. Human Brain Mapping published by Wiley Periodicals LLC.)

Energy metabolism and neurotransmission are necessary for sustaining normal life activities. Hence, neurological or psychiatric disorders are always associated with changes in neurotransmitters and energy metabolic states in the brain. Most studies have only focused on the most important neurotransmitters, particularly GABA and Glu, however, other metabolites such as NAA and aspartate which are also very important for cerebral function are rarely investigated. In this study, most of the metabolic kinetics information of different brain regions was investigated in awake rats using the [ 1 H- 13 C]-NMR technique. Briefly, rats (n = 8) were infused [1- 13 C] glucose through the tail vein for two minutes. After 20 min of glucose metabolism, the animals were sacrificed and the brain tissue was extracted and treated. Utilizing the 1 H observed/ 13 C-edited nuclear magnetic resonance (POCE-NMR), the enrichment of neurochemicals was detected which reflected the metabolic changes in different brain regions and the metabolic connections between neurons and glial cells in the brain. The results suggest that the distribution of every metabolite differed from every brain region and the metabolic rate of NAA was relatively low at 8.64 ± 2.37 μmol/g/h. In addition, there were some correlations between several 13 C enriched metabolites, such as Glu 4 -Gln 4 (p = 0.062), Glu 4 -GABA 2 (p < 0.01), Glx 2 -Glx 3 (p < 0.001), Asp 3 -NAA 3 (p < 0.001). This correlativity reflects the signal transmission between astrocytes and neurons, as well as the potential interaction between energy metabolism and neurotransmission. In conclusion, the current study systematically demonstrated the metabolic kinetics in the brain which shed light on brain functions and the mechanisms of various pathophysiological states., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The short term micro-flowing purification system (STMFPS) has been shown to improve the flesh quality of freshwater fish. However, few studies have focused on the involved underlying mechanisms. This study explored the effect of STMFPS on the flesh quality of market-size freshwater fish based on the combination of metabolomics and transcriptomics methods. The UPLC-QTOF/MS based metabolomics method was utilized to screen metabolites and predict the possible major metabolic pathways during different STMFPS treatment periods (0 d, 1 d, 5 d and 9 d). Furthermore, the transcriptomic data demonstrated that the differentially expressed genes detected in crucian carp muscle were 2915, 7852 and 7183 after 1 d, 5 d and 9 d STMFPS treatment. Results showed that the TCA cycle, ornithine cycle, purine metabolism and amino acid catabolism play important roles in improving the flesh quality of crucian carp. This study may help to understand the mechanism of improving the flesh quality of aquatic products using STMFPS., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Biofilm composition from fish myofibrillar protein (FMP) and chitosan solution (CS) incorporated with rosemary extract (RE) was developed and applied to monitor the freshness of fish fillets. The effects of different concentrations of RE as well as physical, mechanical, structural and functional properties of FMP/CS films were investigated. Films containing RE showed reduced water solubility and water vapor permeability and enhanced tensile strength and elongation at break. Results also showed good compatibility of the components and good dispersion of RE in the matrix. However, the content of RE (0.2%, v/v) added in the composite films produced aggregations and had negative effects on their film-forming properties. The antioxidant capacity of composite films was related to the level of RE and demonstrated by the DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging assay. Chilled grass carp fillets wrapped with different films to evaluate the preservative effect. Results of thiobarbituric acid reactive substances, pH value, Free amino acid and total volatile basic nitrogen indicated that FMP/CS/RE composite film could protect the fish fillet well and inhibit the lipid oxidation. The developed FMP/CS/RE composite films possess the potential to be applied as edible films in the food packaging industry and food cold chain transportation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

China quickly brought the severe acute respiratory syndrome coronavirus 2 under control during the early stage of 2020; thus, this generated sufficient confidence among the public, which enabled them to respond to several sporadic coronavirus disease 2019 outbreaks. This article presents geographical and epidemiological characteristics of several sporadic coronavirus disease 2019 outbreaks from June to December 2020 in China. The data show that the coronavirus disease may be transmitted by imported cold-chain food and international exchange, and this viewpoint deserves our great attention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Feng, Ling, Xiong, Manyande, Xu and Xiang.)

Metabolomics is widely used as a powerful technique for identifying metabolic patterns and functions of organs and biological systems. Normally, there are multiple groups/targets involved in data processed by discriminant analysis. This is more common in cerebral studies, as there are always several brain regions involved in neuronal studies or brain metabolic dysfunctions. Furthermore, neuronal activity is highly correlated with cerebral energy metabolism, such as oxidation of glucose, especially for glutamatergic (excitatory) and GABAergic (inhibitory) neuronal activities. Thus, regional cerebral energy metabolism recognition is essential for understanding brain functions. In the current study, ten different brain regions were considered for discrimination analysis. The metabolic kinetics were investigated with 13 C enrichments in metabolic products of glucose and measured using the nuclear magnetic spectroscopic method. Multiple discriminative methods were used to construct classification models in order to screen out the best method. After comparing all the applied discriminatory analysis methods, the boost-decision tree method was found to be the best method for classification and every cerebral region exhibited its own metabolic pattern. Finally, the differences in metabolic kinetics among these brain regions were analyzed. We, therefore, concluded that the current technology could also be utilized in other multi-class metabolomics studies and special metabolic kinetic patterns could provide useful information for brain function studies., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

There are occupational disparities in the risk of contracting COVID-19. Occupational characteristics and work addresses play key roles in tracking down "patient zero." The present descriptive analysis for occupational characteristics and management measures of sporadic COVID-19 outbreaks from June to December 2020 in China offers important new information to the international community at this stage of the pandemic. These data suggest that Chinese measures including tracking down "patient zero," launching mass COVID-19 testing in the SARS-CoV-2-positive areas, designating a new high- or medium-risk area, locking down the corresponding community or neighborhood in response to new COVID-19 cases, and basing individual methods of protection on science are effective in reducing the transmission of the highly contagious SARS-CoV-2 across China., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Feng, Ling, Xiong, Manyande, Xu and Xiang.)

BACKGROUNDThe coronavirus disease 2019 (COVID-19) rapidly progressed to a global pandemic. Although some patients totally recover from COVID-19 pneumonia, the disease's long-term effects on the brain still need to be explored.METHODSWe recruited 51 patients with 2 subtypes of COVID-19 (19 mild and 32 severe) with no specific neurological manifestations at the acute stage and no obvious lesions on the conventional MRI 3 months after discharge. Changes in gray matter morphometry, cerebral blood flow (CBF), and white matter (WM) microstructure were investigated using MRI. The relationship between brain imaging measurements and inflammation markers was further analyzed.RESULTSCompared with healthy controls, the decrease in cortical thickness/CBF and the changes in WM microstructure were more severe in patients with severe disease than in those with mild disease, especially in the frontal and limbic systems. Furthermore, changes in brain microstructure, CBF, and tract parameters were significantly correlated (P < 0.05) with the inflammatory markers C-reactive protein, procalcitonin, and interleukin 6.CONCLUSIONIndirect injury related to inflammatory storm may damage the brain, altering cerebral volume, CBF, and WM tracts. COVID-19-related hypoxemia and dysfunction of vascular endothelium may also contribute to neurological changes. The abnormalities in these brain areas need to be monitored during recovery, which could help clinicians understand the potential neurological sequelae of COVID-19.FUNDINGNatural Science Foundation of China.

To quantitatively analyze changes in the inner components of the human crystalline lens during accommodation in adults. Eyes of 23 subjects were sequentially examined using CASIA2 Optical Coherence Tomography under 0D, - 3D and - 6D accommodation states. The anterior chamber depth (ACD), anterior and posterior crystalline lens radius of the curvature (ALRC and PLRC) were obtained using built-in software. The lens thickness (LT), lenticular nucleus thickness (NT), anterior cortex thickness (ACT), posterior cortex thickness (PCT), anterior and posterior lenticular nucleus radius of the curvature (ANRC and PNRC), anterior and posterior lenticular nucleus vertex (ANV and PNV) were quantified manually with the Image-pro plus software. During accommodation, the ACD became significantly shallower and LT significantly increased. For changes in the lens, the ALRC decreased by an average magnitude (related to accommodative stimuli) 0.44 mm/D, and PLRC decreased 0.09 mm/D. There was no difference for the ACT and PCT in different accommodation states. For lenticular nucleus response, NT increased on average by 30 μm/D. Both the ANRC and PNRC decreased on average by 212 μm/D and 115 μm/D respectively. The ANV moved forward on average by 0.07 mm under - 3D accommodative stimuli and 0.16 mm for - 6D. However, there was no statistically significant difference between different accommodation states in the PNV movement. Under accommodation stimulation, lens thickness changed mainly due to the lenticular nucleus, but not the cortex. For the lenticular nucleus, both the ANRC and PNRC decreased and ANRC changed the most. The anterior surface of the nucleus moved forward while the posterior surface of the nucleus moved backward but only slightly.

Propofol is the most common intravenous anesthetic agent for induction and maintenance of anesthesia, and has been used clinically for more than 30 years. However, the mechanism by which propofol induces loss of consciousness (LOC) remains largely unknown. The adenosine A 2A receptor (A 2A R) has been extensively proven to have an effect on physiological sleep. It is, therefore, important to investigate the role of A 2A R in the induction of LOC using propofol. In the present study, the administration of the highly selective A 2A R agonist (CGS21680) and antagonist (SCH58261) was utilized to investigate the function of A 2A R under general anesthesia induced by propofol by means of animal behavior studies, resting-state magnetic resonance imaging and c-Fos immunofluorescence staining approaches. Our results show that CGS21680 significantly prolonged the duration of LOC induced by propofol, increased the c-Fos expression in nucleus accumbens (NAc) and suppressed the functional connectivity of NAc-dorsal raphe nucleus (DR) and NAc-cingulate cortex (CG). However, SCH58261 significantly shortened the duration of LOC induced by propofol, decreased the c-Fos expression in NAc, increased the c-Fos expression in DR, and elevated the functional connectivity of NAc-DR and NAc-CG. Collectively, our findings demonstrate the important roles played by A 2A R in the LOC induced by propofol and suggest that the neural circuit between NAc-DR maybe controlled by A 2A R in the mechanism of anesthesia induced by propofol., (© 2020 International Society for Neurochemistry.)

Background: The outbreak of coronavirus disease 2019 (COVID-19) has spread worldwide and continues to threaten peoples' health as well as put pressure on the accessibility of medical systems. Early prediction of survival of hospitalized patients will help in the clinical management of COVID-19, but a prediction model that is reliable and valid is still lacking., Methods: We retrospectively enrolled 628 confirmed cases of COVID-19 using positive RT-PCR tests for SARS-CoV-2 in Tongji Hospital, Wuhan, China. These patients were randomly grouped into a training (60%) and a validation (40%) cohort. In the training cohort, LASSO regression analysis and multivariate Cox regression analysis were utilized to identify prognostic factors for in-hospital survival of patients with COVID-19. A nomogram based on the 3 variables was built for clinical use. AUCs, concordance indexes (C-index), and calibration curves were used to evaluate the efficiency of the nomogram in both training and validation cohorts., Results: Hypertension, higher neutrophil-to-lymphocyte ratio, and increased NT-proBNP values were found to be significantly associated with poorer prognosis in hospitalized patients with COVID-19. The 3 predictors were further used to build a prediction nomogram. The C-indexes of the nomogram in the training and validation cohorts were 0.901 and 0.892, respectively. The AUC in the training cohort was 0.922 for 14-day and 0.919 for 21-day probability of in-hospital survival, while in the validation cohort this was 0.922 and 0.881, respectively. Moreover, the calibration curve for 14- and 21-day survival also showed high coherence between the predicted and actual probability of survival., Conclusions: We built a predictive model and constructed a nomogram for predicting in-hospital survival of patients with COVID-19. This model has good performance and might be utilized clinically in management of COVID-19., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Cancer-induced bone pain (CIBP) is acknowledged as a multifactorial chronic pain that tortures advanced cancer patients, but existing treatment strategies for CIBP have not been satisfactory yet. Investigators have demonstrated that the activation of α7-nAChRs exerts analgesic effects in some chronic pain models. However, the role of spinal α7-nAChRs in CIBP remains unknown. This study was designed to investigate the role of α7-nAChRs in a well-established CIBP model induced by Walker 256 rat mammary gland carcinoma cells., Methods: The paw withdrawal threshold (PWT) of the ipsilateral hind paw was measured using von Frey filament. The expressions of spinal α7-nAChRs and NF-κB were measured with Western blotting analysis. Immunofluorescence was employed to detect the expression of α7-nAChRs and co-expressed of α7-nAChRs with NeuN or GFAP or Iba1., Results: Experiment results showed that the expression of spinal α7-nAChRs was significantly downregulated over time in CIBP rats, and in both CIBP rats and sham rats, most of the α7-nAChRs located in neurons. Behavioral data suggested PNU-282,987, a selective α7-nAChRs agonist, dose-dependently produced analgesic effect and positive allosteric modulator could intensify its effects. Further, repeated administration of PNU-282,987 reversed the expression of α7-nAChRs, inhibited the nuclear factor kappa B (NF-κB) signaling pathway, and attenuates CIBP-induced mechanical allodynia state as well., Conclusion: These results suggest that the reduced expression of spinal α7-nAChRs contributes to the maintenance of CIBP by upregulating NF-κB expression, which implying a novel pharmacological therapeutic target for the treatment of CIBP., Competing Interests: The authors declare that they have no conflicts of interest for this work., (© 2021 Yang et al.)

The high incidence of patients with chronic itch highlights the importance of fundamental research. Recent advances in the interface of gut microbiota have shed new light into exploring this phenomenon. However, it is unknown whether gut microbiota plays a role in chronic itch in rodents with or without cognitive dysfunction. In this study, the role of gut microbiota in diphenylcyclopropenone (DCP)-evoked chronic itch was investigated in mice and hierarchical cluster analysis of novel object recognition test (ORT) results were used to classify DCP-evoked itch model in mice with or without cognitive dysfunction (CD)-like phenotype and 16S ribosomal RNA (rRNA) gene sequencing was used to compare gut bacterial composition between CD (Susceptible) and Non-CD phenotypes (Unsusceptible) in chronic itch mice. Results showed that the microbiota composition was significantly altered by DCP-evoked chronic itch and chronic itch induced novel object recognition-related CD. However, abnormal gut microbiota composition induced by chronic itch may not be correlated with novel object recognition-related CD., Competing Interests: The authors declare that this study received assistance from OEbiotech Co. Ltd. The affiliation was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication., (Copyright © 2021 Li, Zhang, Sun, Liu, Manyande, Xu and Xiang.)