Gut microbiome and metabolome profiling in Framingham heart study reveals cholesterol-metabolizing bacteria.

Accumulating evidence suggests that cardiovascular disease (CVD) is associated with an altered gut microbiome. Our understanding of the underlying mechanisms has been hindered by lack of matched multi-omic data with diagnostic biomarkers. To comprehensively profile gut microbiome contributions to CVD, we generated stool metagenomics and metabolomics from 1,429 Framingham Heart Study participants. We identified blood lipids and cardiovascular health measurements associated with microbiome and metabolome composition. Integrated analysis revealed microbial pathways implicated in CVD, including flavonoid, γ-butyrobetaine, and cholesterol metabolism. Species from the Oscillibacter genus were associated with decreased fecal and plasma cholesterol levels. Using functional prediction and in vitro characterization of multiple representative human gut Oscillibacter isolates, we uncovered conserved cholesterol-metabolizing capabilities, including glycosylation and dehydrogenation. These findings suggest that cholesterol metabolism is a broad property of phylogenetically diverse Oscillibacter spp., with potential benefits for lipid homeostasis and cardiovascular health.

Critical Assessment of Metagenome Interpretation: the second round of challenges.

Evaluating metagenomic software is key for optimizing metagenome interpretation and focus of the Initiative for the Critical Assessment of Metagenome Interpretation (CAMI). The CAMI II challenge engaged the community to assess methods on realistic and complex datasets with long- and short-read sequences, created computationally from around 1,700 new and known genomes, as well as 600 new plasmids and viruses. Here we analyze 5,002 results by 76 program versions. Substantial improvements were seen in assembly, some due to long-read data. Related strains still were challenging for assembly and genome recovery through binning, as was assembly quality for the latter. Profilers markedly matured, with taxon profilers and binners excelling at higher bacterial ranks, but underperforming for viruses and Archaea. Clinical pathogen detection results revealed a need to improve reproducibility. Runtime and memory usage analyses identified efficient programs, including top performers with other metrics. The results identify challenges and guide researchers in selecting methods for analyses.

Characterization of metallothionein genes from Broussonetia papyrifera: metal binding and heavy metal tolerance mechanisms.

BACKGROUND: Broussonetia papyrifera is an economically significant tree with high utilization value, yet its cultivation is often constrained by soil contamination with heavy metals (HMs). Effective scientific cultivation management, which enhances the yield and quality of B. papyrifera, necessitates an understanding of its regulatory mechanisms in response to HM stress. RESULTS: Twelve Metallothionein (MT) genes were identified in B. papyrifera. Their open reading frames ranged from 186 to 372 bp, encoding proteins of 61 to 123 amino acids with molecular weights between 15,473.77 and 29,546.96 Da, and theoretical isoelectric points from 5.24 to 5.32. Phylogenetic analysis classified these BpMTs into three subclasses: MT1, MT2, and MT3, with MT2 containing seven members and MT3 only one. The expression of most BpMT genes was inducible by Cd, Mn, Cu, Zn, and abscisic acid (ABA) treatments, particularly BpMT2e, BpMT2d, BpMT2c, and BpMT1c, which showed significant responses and warrant further study. Yeast cells expressing these BpMT genes exhibited enhanced tolerance to Cd, Mn, Cu, and Zn stresses compared to control cells. Yeasts harboring BpMT1c, BpMT2e, and BpMT2d demonstrated higher accumulation of Cd, Cu, Mn, and Zn, suggesting a chelation and binding capacity of BpMTs towards HMs. Site-directed mutagenesis of cysteine (Cys) residues indicated that mutations in the C domain of type 1 BpMT led to increased sensitivity to HMs and reduced HM accumulation in yeast cells; While in type 2 BpMTs, the contribution of N and C domain to HMs' chelation possibly corelated to the quantity of Cys residues. CONCLUSION: The BpMT genes are crucial in responding to diverse HM stresses and are involved in ABA signaling. The Cys-rich domains of BpMTs are pivotal for HM tolerance and chelation. This study offers new insights into the structure-function relationships and metal-binding capabilities of type-1 and - 2 plant MTs, enhancing our understanding of their roles in plant adaptation to HM stresses.

Visible Light-Activated Ultralong-Lived Triplet Excitons of Carbon Dots for White-Light Manipulated Anti-Counterfeiting.

Room temperature phosphorescence (RTP) has emerged as an interesting but rare phenomenon with multiple potential applications in anti-counterfeiting, optoelectronic devices, and biosensing. Nevertheless, the pursuit of ultralong lifetimes of RTP under visible light excitation presents a significant challenge. Here, new phosphorescent materials that can be excited by visible light with record-long lifetimes are demonstrated, realized through embedding nitrogen doped carbon dots (N-CDs) into a poly(vinyl alcohol) (PVA) film. The RTP lifetime of the N-CDs@PVA film is remarkably extended to 2.1 s excited by 420 nm, representing the highest recorded value for visible light-excited phosphorescent materials. Theoretical and experimental studies reveal that the robust hydrogen bonding interactions can effectively reduce the non-radiative decay rate and radiative transition rate of triplet excitons, thus dramatically prolong the phosphorescence lifetime. Notably, the RTP emission of N-CDs@PVA film can also be activated by easily accessible low-power white-light-emitting diode. More significantly, the practical applications of the N-CDs@PVA film in state-of-the-art anti-counterfeiting security and optical information storage domains are further demonstrated. This research offers exciting opportunities for utilizing visible light-activated ultralong-lived RTP systems in a wide range of promising applications.

Choroidal vascularity features of fundus tessellation in adults with high myopia.

BACKGROUND: To investigate alterations in choroidal vascularity index among highly myopic adults with fundus tessellation, utilizing optical coherence tomography. METHODS: Total of 143 highly myopic adults (234 eyes) with fundus tessellation were collected in this cross-sectional study, which was stratified into different lesion groups based on the novel tessellated fundus classification. Subfoveal choroidal thickness (SFCT), choroidal luminal area (LA), stromal area (SA), total choroidal area (TCA), and choroidal vascularity index (CVI) were analyzed utilizing optical coherence tomography (OCT) with enhanced depth imaging (EDI) mode, enabling precise quantification of these parameters. RESULTS: Comparison analysis demonstrated notable distinctions in spherical equivalent (SE), axial length (AL), and SFCT across the four tessellation grades (p < 0.001). Analysis of the choroidal vascularity parameters, including LA, TCA, and CVI, demonstrated notable disparities across the four groups (p < 0.001), while no significant variations were observed in SA when comparing Grade 1 versus Grade 2, as well as Grade 2 versus Grade 3 (p > 0.05). Logistic regression analyses illustrated that the higher grade of tessellated exhibited a positive association with AL (OR = 1.701, p = 0.027), while negatively associated with SFCT (OR = 0.416, p = 0.007), LA (OR = 0.438, p = 0.010) and CVI (OR = 0.529, p = 0.004). Multiple regression analyses demonstrated a significant negative association between CVI and both SE and AL after adjusting for age, while positively associated with SFCT (p < 0.05). CONCLUSION: Subtle choroidal vascularity changes may have a meaningful contribution to the development and progression of fundus tessellation. CVI and LA dramatically decreased during the early stages of tessellation development and maintained a relatively stable status when in the severe tessellated grades.

Progression of Myopic Maculopathy Based on the ATN Classification System.

INTRODUCTION: Myopic maculopathy is a sight-threatening disease, which causes irreversible vision faults and central vision loss. The purpose of this study is evaluating the risk factors of the myopic maculopathy progression according to the ATN classification system. METHODS: Clinic data of 69 high myopia patients aged older than 40 years with a follow-up time of more than 2 years, who underwent fundus photography and OCT examination were retrospectively collected. Fundus changes were evaluated with ATN classification at the first and last follow-up times. The related factors affecting progress including axial length (AL), spherical equivalence (SE), subfoveal choroidal thickness (SFCT), disc-foveal distance (DFD), optic disc tilt, and parapapillary atrophy (PPA) were analyzed. RESULTS: This study included 69 high-myopia patients with mean age 54.29 ± 10.41 years. The progression rate of myopic maculopathy (MM) was approximately 25.56%. Elongated DFD (5.37 ± 0.11 mm vs. 4.86 ± 0.37 mm; p < 0.001) and thinner SFCT (138.52 ± 29.38 µm vs. 184.87 ± 48.72 µm; p = 0.008) at baseline were linked with MM progression. In multiple logistic regression analysis, DFD was a substantial hazard risk factor (adjusted OR = 1.672, 95% CI: 1.135-2.498, p < 0.05) after adjusting for age, AL and SFCT. Receiver operating characteristic curve showed that DFD might serve as a predictor to discriminate the MM progression with a cut-off value of 5.15 mm and a substantial receiver operating characteristic curve area (AUC: 0.794). Compared with the non-progression group, the progression group had older age (p < 0.001), longer AL (p = 0.001), higher optic disc tilt rate (p < 0.001), and higher proportion of pre-existing PPA (p = 0.038) at baseline, the differences were statistically significant. CONCLUSION: Based on the ATN classification system, we found that the progression of MM was related to older age, longer AL, high disc tilt, pre-existing PPA, thinner SFCT, and longer DFD. The parameter of DFD was an important factor affecting the progression of MM, which is considered to have a higher probability of progression when the length is beyond 5.15 mm.

Migraine-like headache in subjects with isolated Lambl's excrescences: a case series and literature review.

AIM: Lambl's excrescences are mobile, thin, fibrinous connective tissue strands typically found on left-sided cardiac values. Migraine is positively associated with structural cardiac anomalies. However, it remains unclear whether Lambl's excrescences are associated with migraine. METHODS: Retrospective review of 182 inpatients with Lambl's excrescences confirmed by transesophageal echocardiogram in Chinese PLA General Hospital since January 2010. Among them, those with isolated Lambl's excrescences presented with migraine-like headache were included. We collected information on the demographics and clinical profiles of all participants, and performed follow-up visits. RESULTS: A total of 8 patients presented with migraine-like headache among 15 patients with isolated Lambl's excrescences. They included 2 men and 6 women, with an average age of 44.63 ± 12.24 years. Among these patients, 3 had visual aura, and 6 manifested infarct-like lesions on magnetic resonance imaging, of which 2 developed lesions after first visit. During follow-up, 4 patients suffering from intervention for Lambl's excrescences dramatically reduced headache recurrence compared to the other 4 patients only receiving migraine preventive medications. CONCLUSIONS: This study supports the hypothesis that microemboli from isolated Lambl's excrescences could cause migraine-like headache. And intervention for Lambl's excrescences may be crucial for preventing headache recurrence.

This study supports the hypothesis that microemboli from isolated Lambl's excrescences could cause migraine-like headache.The small sample size study fails to make management recommendations.

Brain-wide mapping of c-Fos expression in nitroglycerin-induced models of migraine.

BACKGROUND: Migraine is a neurological disorder characterized by complex, widespread, and sudden attacks with an unclear pathogenesis, particularly in chronic migraine (CM). Specific brain regions, including the insula, amygdala, thalamus, and cingulate, medial prefrontal, and anterior cingulate cortex, are commonly activated by pain stimuli in patients with CM and animal models. This study employs fluorescence microscopy optical sectioning tomography (fMOST) technology and AAV-PHP.eB whole-brain expression to map activation patterns of brain regions in CM mice, thus enhancing the understanding of CM pathogenesis and suggesting potential treatment targets. METHODS: By repeatedly administering nitroglycerin (NTG) to induce migraine-like pain in mice, a chronic migraine model (CMM) was established. Olcegepant (OLC) was then used as treatment and its effects on mechanical pain hypersensitivity and brain region activation were observed. All mice underwent mechanical withdrawal threshold, light-aversive, and elevated plus maze tests. Viral injections were administered to the mice one month prior to modelling, and brain samples were collected 2 h after the final NTG/vehicle control injection for whole-brain imaging using fMOST. RESULTS: In the NTG-induced CMM, mechanical pain threshold decreased, photophobia, and anxiety-like behavior were observed, and OLC was found to improve these manifestations. fMOST whole-brain imaging results suggest that the isocortex-cerebral cortex plate region, including somatomotor areas (MO), somatosensory areas (SS), and main olfactory bulb (MOB), appears to be the most sensitive area of activation in CM (P < 0.05). Other brain regions such as the inferior colliculus (IC) and intermediate reticular nucleus (IRN) were also exhibited significant activation (P < 0.05). The improvement in migraine-like symptoms observed with OLC treatment may be related to its effects on these brain regions, particularly SS, MO, ansiform lobule (AN), IC, spinal nucleus of the trigeminal, caudal part (Sp5c), IRN, and parvicellular reticular nucleus (PARN) (P < 0.05). CONCLUSIONS: fMOST whole-brain imaging reveals c-Fos + cells in numerous brain regions. OLC improves migraine-like symptoms by modulating brain activity in some brain regions. This study demonstrates the activation of the specific brain areas in NTG-induced CMM and suggests some regions as a potential treatment mechanism according to OLC.

Alleviation of migraine related pain and anxiety by inhibiting calcium-stimulating AC1-dependent CGRP in the insula of adult rats.

BACKGROUND: Recent animal and clinical findings consistently highlight the critical role of calcitonin gene-related peptide (CGRP) in chronic migraine (CM) and related emotional responses. CGRP antibodies and receptor antagonists have been approved for CM treatment. However, the underlying CGRP-related signaling pathways in the pain-related cortex remain poorly understood. METHODS: The SD rats were used to establish the CM model by dural infusions of inflammatory soup. Periorbital mechanical thresholds were assessed using von-Frey filaments, and anxiety-like behaviors were observed via open field and elevated plus maze tests. Expression of c-Fos, CGRP and NMDA GluN2B receptors was detected using immunofluorescence and western blotting analyses. The excitatory synaptic transmission was detected by whole-cell patch-clamp recording. A human-used adenylate cyclase 1 (AC1) inhibitor, hNB001, was applied via insula stereotaxic and intraperitoneal injections in CM rats. RESULTS: The insular cortex (IC) was activated in the migraine model rats. Glutamate-mediated excitatory transmission and NMDA GluN2B receptors in the IC were potentiated. CGRP levels in the IC significantly increased during nociceptive and anxiety-like activities. Locally applied hNB001 in the IC or intraperitoneally alleviated periorbital mechanical thresholds and anxiety behaviors in migraine rats. Furthermore, CGRP expression in the IC decreased after the hNB001 application. CONCLUSIONS: Our study indicated that AC1-dependent IC plasticity contributes to migraine and AC1 may be a promising target for treating migraine in the future.

Unveiling the therapeutic potential of Dl-3-n-butylphthalide in NTG-induced migraine mouse: activating the Nrf2 pathway to alleviate oxidative stress and neuroinflammation.

BACKGROUND: Migraine stands as a prevalent primary headache disorder, with prior research highlighting the significant involvement of oxidative stress and inflammatory pathways in its pathogenesis and chronicity. Existing evidence indicates the capacity of Dl-3-n-butylphthalide (NBP) to mitigate oxidative stress and inflammation, thereby conferring neuroprotective benefits in many central nervous system diseases. However, the specific therapeutic implications of NBP in the context of migraine remain to be elucidated. METHODS: We established a C57BL/6 mouse model of chronic migraine (CM) using recurrent intraperitoneal injections of nitroglycerin (NTG, 10 mg/kg), and prophylactic treatment was simulated by administering NBP (30 mg/kg, 60 mg/kg, 120 mg/kg) by gavage prior to each NTG injection. Mechanical threshold was assessed using von Frey fibers, and photophobia and anxious behaviours were assessed using a light/dark box and elevated plus maze. Expression of c-Fos, calcitonin gene-related peptide (CGRP), Nucleus factor erythroid 2-related factor 2 (Nrf2) and related pathway proteins in the spinal trigeminal nucleus caudalis (SP5C) were detected by Western blotting (WB) or immunofluorescence (IF). The expression of IL-1ß, IL-6, TNF-α, Superoxide dismutase (SOD) and malondialdehyde (MDA) in SP5C and CGRP in plasma were detected by ELISA. A reactive oxygen species (ROS) probe was used to detect the expression of ROS in the SP5C. RESULTS: At the end of the modelling period, chronic migraine mice showed significantly reduced mechanical nociceptive thresholds, as well as photophobic and anxious behaviours. Pretreatment with NBP attenuated nociceptive sensitization, photophobia, and anxiety in the model mice, reduced expression levels of c-Fos and CGRP in the SP5C and activated Nrf2 and its downstream proteins HO-1 and NQO-1. By measuring the associated cytokines, we also found that NBP reduced levels of oxidative stress and inflammation. Most importantly, the therapeutic effect of NBP was significantly reduced after the administration of ML385 to inhibit Nrf2. CONCLUSIONS: Our data suggest that NBP may alleviate migraine by activating the Nrf2 pathway to reduce oxidative stress and inflammation in migraine mouse models, confirming that it may be a potential drug for the treatment of migraine.

The crucial role of locus coeruleus noradrenergic neurons in the interaction between acute sleep disturbance and headache.

BACKGROUND: Both epidemiological and clinical studies have indicated that headache and sleep disturbances share a complex relationship. Although headache and sleep share common neurophysiological and anatomical foundations, the mechanism underlying their interaction remains poorly understood. The structures of the diencephalon and brainstem, particularly the locus coeruleus (LC), are the primary sites where the sleep and headache pathways intersect. To better understand the intricate nature of the relationship between headache and sleep, our study focused on investigating the role and function of noradrenergic neurons in the LC during acute headache and acute sleep disturbance. METHOD: To explore the relationship between acute headache and acute sleep disturbance, we primarily employed nitroglycerin (NTG)-induced migraine-like headache and acute sleep deprivation (ASD) models. Initially, we conducted experiments to confirm that ASD enhances headache and that acute headache can lead to acute sleep disturbance. Subsequently, we examined the separate roles of the LC in sleep and headache. We observed the effects of drug-induced activation and inhibition and chemogenetic manipulation of LC noradrenergic neurons on ASD-induced headache facilitation and acute headache-related sleep disturbance. This approach enabled us to demonstrate the bidirectional function of LC noradrenergic neurons. RESULTS: Our findings indicate that ASD facilitated the development of NTG-induced migraine-like headache, while acute headache affected sleep quality. Furthermore, activating the LC reduced the headache threshold and increased sleep latency, whereas inhibiting the LC had the opposite effect. Additional investigations demonstrated that activating LC noradrenergic neurons further intensified pain facilitation from ASD, while inhibiting these neurons reduced this pain facilitation. Moreover, activating LC noradrenergic neurons exacerbated the impact of acute headache on sleep quality, while inhibiting them alleviated this influence. CONCLUSION: The LC serves as a significant anatomical and functional region in the interaction between acute sleep disturbance and acute headache. The involvement of LC noradrenergic neurons is pivotal in facilitating headache triggered by ASD and influencing the effects of headache on sleep quality.

AMPK activation attenuates central sensitization in a recurrent nitroglycerin-induced chronic migraine mouse model by promoting microglial M2-type polarization.

BACKGROUND: Energy metabolism disorders and neurogenic inflammation play important roles in the central sensitization to chronic migraine (CM). AMP-activated protein kinase (AMPK) is an intracellular energy sensor, and its activation regulates inflammation and reduces neuropathic pain. However, studies on the involvement of AMPK in the regulation of CM are currently lacking. Therefore, this study aimed to explore the mechanism underlying the involvement of AMPK in the central sensitization to CM. METHODS: Mice with recurrent nitroglycerin (NTG)-induced CM were used to detect the expression of AMPK protein in the trigeminal nucleus caudalis (TNC). Following intraperitoneal injection of the AMPK activator 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) and inhibitor compound C, the mechanical pain threshold, activity level, and pain-like behaviors in the mice were measured. The expression of calcitonin gene-related peptide (CGRP) and cytokines, M1/M2 microglia, and NF-κB pathway activation were detected after the intervention. RESULTS: Repeated NTG injections resulted in a gradual decrease in AMPK protein expression, and the negative regulation of AMPK by increased ubiquitin-like plant homeodomain and RING finger domain 1 (UHRF1) expression may counteract AMPK activation by increasing ADP/ATP. AICAR can reduce the hyperalgesia and pain-like behaviors of CM mice, improve the activity of mice, reduce the expression of CGRP, IL-1ß, IL-6, and TNF-α in the TNC region, and increase the expression of IL-4 and IL-10. Moreover, AMPK in TNC was mainly located in microglia. AICAR could reduce the expression of inducible NO synthase (iNOS) in M1 microglia and increase the expression of Arginase 1 (Arg1) in M2 microglia by inhibiting the activation of NF-κB pathway. CONCLUSIONS: AMPK was involved in the central sensitization of CM, and the activation of AMPK reduced neuroinflammation in NTG-induced CM mice. AMPK may provide new insights into interventions for energy metabolism disorders and neurogenic inflammation in migraine.

Abdominal Aortic Aneurysm and PET/CT: From Molecular Mechanisms to Potential Molecular Imaging Targets.

Abdominal aortic aneurysm (AAA) is the most common and critical aortic disease. Bleeding is the most serious complication from a ruptured AAA, which often results in death. Therefore, early diagnosis and treatment are the only effective means to reduce AAA associated mortality. Positron emission tomography/computed tomography (PET/CT) combines functional and anatomical imaging. The expanded application of PET/CT in the medical field could have benefits for the diagnosis and treatment of patients with AAA. This review explores the efficiency of PET/CT in the diagnosis of AAA based on our understanding of the underlying molecular mechanisms of AAA development.

GLIS Family Zinc Finger 3 Promotes Triple-Negative Breast Cancer Progression by Inducing Cell Proliferation, Migration and Invasion, and Activating the NF-κB Signaling Pathway.

Triple-negative breast cancer (TNBC) puts a great threat to women's health. GLIS family zinc finger 3 (GLIS3) belongs to the GLI transcription factor family and acts as a critical factor in cancer progression. Nevertheless, the part of GLIS3 played in TNBC is not known. Immunohistochemical (IHC) staining analysis displayed that GLIS3 was highly expressed in TNBC tissues. The effect of GLIS3 on the malignant phenotype of TNBC was tested in two different cell lines according to GLIS3 regulation. Upregulation of GLIS3 promoted the proliferation, migration, and invasion of TNBC cell lines, whereas the knockdown of GLIS3 suppressed these tumor activities. Inhibition of GLIS3 induced TNBC cell apoptosis. Furthermore, study as immunofluorescence and electrophoretic mobility shift assay confirmed that the nuclear factor-κB (NF-κB) signaling pathway activated by GLIS3 played an important role in TNBC cells' malignant phenotype. In conclusion, the present work demonstrated that GLIS3 acts as a crucial element in TNBC progression via activating the NF-κB signaling pathway. Accordingly, above mentioned findings indicated that modulation of GLIS3 expression is a potential tactic to interfere with the progression of TNBC.

Intraoperative ultrasound is valuable for detecting intracranial hematoma progression and decreasing mortality in traumatic brain injury.

BACKGROUND: Our aim was to explore the clinical benefit of intraoperative ultrasound in decompressive craniectomy (DC) for traumatic brain injury (TBI). METHODS: From January 1, 2018, through April 30, 2021, 54 patients who developed acute subdural hematoma (SDH) due to blunt injury and underwent DC with or without intraoperative ultrasound assistance were retrospectively included in our study. Logistic regression analyses were performed to compare the therapeutic efficacy in the two groups. RESULTS: In the ultrasound group (14 patients, 25.93%), intraoperative ultrasound was used for assisting hematoma removal and/or ventriculostomy during DC. In the control group (40 patients, 74.07%), ultrasound was not used during the operation and ventriculostomy was not performed. No statistically significant differences in age, sex, initial Glasgow Coma Scale (GCS) score, blood loss, postoperative intracranial pressure (ICP), duration of hyperosmolar therapy, or Glasgow Outcome Scale Extended (GOS-E) score 6 months after injury were observed. No mortality was recorded in the ultrasound group. The mortality rate in the control group during hospitalization was 25% (p < 0.05). CONCLUSIONS: Intraoperative ultrasound is helpful for intracranial hematoma removal and ventriculostomy with cerebrospinal fluid drainage and decreases mortality in experienced hands. The reason for higher mortality rate in the control group might result from poor hematoma clearance rate and poor postoperative intracranial pressure control. It is a useful tool for diagnosing and assisting with treatment in cases of TBI.

Dopaminergic Projections from the Hypothalamic A11 Nucleus to the Spinal Trigeminal Nucleus Are Involved in Bidirectional Migraine Modulation.

Clinical imaging studies have revealed that the hypothalamus is activated in migraine patients prior to the onset of and during headache and have also shown that the hypothalamus has increased functional connectivity with the spinal trigeminal nucleus. The dopaminergic system of the hypothalamus plays an important role, and the dopamine-rich A11 nucleus may play an important role in migraine pathogenesis. We used intraperitoneal injections of glyceryl trinitrate to establish a model of acute migraine attack and chronicity in mice, which was verified by photophobia experiments and von Frey experiments. We explored the A11 nucleus and its downstream pathway using immunohistochemical staining and neuronal tracing techniques. During acute migraine attack and chronification, c-fos expression in GABAergic neurons in the A11 nucleus was significantly increased, and inhibition of DA neurons was achieved by binding to GABA A-type receptors on the surface of dopaminergic neurons in the A11 nucleus. However, the expression of tyrosine hydroxylase and glutamic acid decarboxylase proteins in the A11 nucleus of the hypothalamus did not change significantly. Specific destruction of dopaminergic neurons in the A11 nucleus of mice resulted in severe nociceptive sensitization and photophobic behavior. The expression levels of the D1 dopamine receptor and D2 dopamine receptor in the caudal part of the spinal trigeminal nucleus candalis of the chronic migraine model were increased. Skin nociceptive sensitization of mice was slowed by activation of the D2 dopamine receptor in SP5C, and activation of the D1 dopamine receptor reversed this behavioral change. GABAergic neurons in the A11 nucleus were activated and exerted postsynaptic inhibitory effects, which led to a decrease in the amount of DA secreted by the A11 nucleus in the spinal trigeminal nucleus candalis. The reduced DA bound preferentially to the D2 dopamine receptor, thus exerting a defensive effect against headache.

Proteomics profiling reveals mitochondrial damage in the thalamus in a mouse model of chronic migraine.

BACKGROUND: Migraine, a complex brain disorder, is regarded as a possible clinical manifestation of brain energy dysfunction. The trigeminovascular system is considered the basis for the pathogenesis of migraine, hence we depicted the proteomics profiling of key regions in this system, then focusing on protein alterations related to mitochondrial function. The aim of this study is to illustrate the role of mitochondria in migraine. METHODS: A mouse model of chronic migraine (CM) was established by repeated nitroglycerin (NTG) stimulation and evaluated by von-Frey filaments, a hot plate and a light-dark box. Differentially expressed proteins (DEPs) in some subcortical brain regions of the trigeminovascular system were screened through liquid chromatography-tandem mass spectrometry (LC‒MS/MS) to analyse the specificity of key signaling pathways in different brain regions. And then mitochondrial function, structure and dynamics were determined by qPCR, ELISA, and transmission electron microscope (TEM). Finally, the effect of mitochondrial intervention-Urolithin A (UA) on CM was investigated. RESULTS: Repeated NTG injection triggered photophobia, periorbital and hind paw allodynia in mice. The proteomics profiling of CM model showed that 529, 109, 163, 152 and 419 DEPs were identified in the thalamus, hypothalamus, periaqueductal grey (PAG), trigeminal ganglion (TG) and trigeminocervical complex (TCC), respectively. The most significant changes in the brain region-specific pathways pointed to thalamic mitochondrial impairment. NTG induced mitochondrial structural disruption, dysfunction and homeostatic dysregulation, which could be partially attenuated by UA intervention. CONCLUSION: Our findings highlight the involvement of mitochondrial damage in the thalamus in central sensitization of CM, which provides evidence of possible metabolic mechanisms in migraine pathophysiology.

OsSWEET11b, a potential sixth leaf blight susceptibility gene involved in sugar transport-dependent male fertility.

SWEETs play important roles in intercellular sugar transport. Induction of SWEET sugar transporters by Transcription Activator-Like effectors (TALe) of Xanthomonas ssp. is key for virulence in rice, cassava and cotton. We identified OsSWEET11b with roles in male fertility and potential bacterial blight (BB) susceptibility in rice. While single ossweet11a or 11b mutants were fertile, double mutants were sterile. As clade III SWEETs can transport gibberellin (GA), a key hormone for spikelet fertility, sterility and BB susceptibility might be explained by GA transport deficiencies. However, in contrast with the Arabidopsis homologues, OsSWEET11b did not mediate detectable GA transport. Fertility and susceptibility therefore are likely to depend on sucrose transport activity. Ectopic induction of OsSWEET11b by designer TALe enabled TALe-free Xanthomonas oryzae pv. oryzae (Xoo) to cause disease, identifying OsSWEET11b as a potential BB susceptibility gene and demonstrating that the induction of host sucrose uniporter activity is key to virulence of Xoo. Notably, only three of six clade III SWEETs are targeted by known Xoo strains from Asia and Africa. The identification of OsSWEET11b is relevant for fertility and for protecting rice against emerging Xoo strains that target OsSWEET11b.

BEEM-Static: Accurate inference of ecological interactions from cross-sectional microbiome data.

CONCLUSION: BEEM-Static provides new opportunities for mining ecologically interpretable interactions and systems insights from the growing corpus of microbiome data.

Expression of osteopontin and integrin αvß 3 receptor in retina of diabetic guinea pigs with high myopia.

INTRODUCTION: To investigate the effect of high myopia on the expression of retinal osteopontin (OPN) and integrin αVß 3 receptor in guinea pigs and determined the relationship between high myopia and diabetic retinopathy. METHODS: Ninety 3-week-old male guinea pigs were randomly divided into four groups that included normal control group (NOR，n=18), high myopia group (HM，n=24), diabetes group (DR，n=24), and diabetes with high myopia group (DR+HM，n=24). HM was induced by form deprivation (FDHM) in the right eye. The DR group was injected with 5% streptozotocin(STZ) 280 mg/kg intraperitoneally in the lower left abdomen of guinea pigs. The DRHM group was subjected to the same treatment as the HM and DR groups. Eighteen guinea pigs in each group were randomly selected to complete the experimental measurement. After enucleation of eyeballs, HE and immunohistochemical staining were performed to observe the retina morphology and count the positive rate of OPN and integrin αvß 3 receptor. RESULTS: Diabetic retinal changes were found in group DR and HM+DR. The degree of retinal change in group HM+DR was less than that in group DR. In the DR group, the morphology of retinal tissue was loose, the number of cells decreased, increased retinal microaneurysms, and a small amount of small artery embolism and venous thrombosis were observed. Although the retinal structure in the HM+DR group also became thinner, looser, and disordered, only a small number of microaneurysms were observed compared with the diabetic group. Immunohistochemical staining showed that the expression of OPN and integrin αvß 3 receptors in the diabetic groups (DR, HM+DR) was significantly higher than in the HM and NOR groups. The positive expression rates of OPN and integrin αvß 3 receptors in group HM+DR were significantly lower than those in group DR (P < 0.05). CONCLUSION: The expression of OPN and integrin αvß 3 receptor in the retina of diabetic guinea pigs with high myopia was lower than that of diabetic models, which may be due to the influence of high myopia on neovascularization in DR.