Indole induces anxiety-like behaviour in mice mediated by brainstem locus coeruleus activation.

The gut microbiota produces metabolites that enrich the host metabolome and play a part in host physiology, including brain functions. Yet the biological mediators of this gut-brain signal transduction remain largely unknown. In this study, the possible role of the gut microbiota metabolite indole, originating from tryptophan, was investigated. Oral administration of indole to simulate microbial overproduction of this compound in the gut consistently led to impaired locomotion and anxiety-like behaviour in both C3H/HeN and C57BL/6J mice. By employing c-Fos protein expression mapping in mice, we observed a noticeable increase in brain activation within the dorsal motor nucleus of the vagus nerve (DMX) and the locus coeruleus (LC) regions in a dose-dependent manner. Further immune co-labelling experiments elucidated that the primary cells activated within the LC were tyrosine hydroxylase positive. To delve deeper into the mechanistic aspects, we conducted chemogenetic activation experiments on LC norepinephrine neurons with two doses of clozapine N-oxide (CNO). Low dose of CNO at 0.5 mg/kg induced no change in locomotion but anxiety-like behaviour, while high dose of CNO at 2 mg/kg resulted in locomotion impairment and anxiety-like behaviour. These findings support the neuroactive roles of indole in mediating gut-brain communication. It also highlights the LC as a novel hub in the gut-brain axis, encouraging further investigations.

Multilocular thymic cysts can be easily misdiagnosed as malignant tumor on computer tomography: A case report.

BACKGROUND: Multilocular thymic cyst (MTC) is a rare mediastinal lesion which is considered to occur in the process of acquired inflammation. It is usually characterized by well-defined cystic density and is filled with transparent liquid. CASE SUMMARY: We report on a 39-year-old male with a cystic-solid mass in the anterior mediastinum. Computer tomography (CT) imaging showed that the mass was irregular with unclear boundaries. After injection of contrast agent, there was a slight enhancement of stripes and nodules. According to CT findings, it was diagnosed as thymic cancer. CONCLUSION: After surgery, MTC accompanied by bleeding and infection was confirmed by pathological examination. The main lesson of this case was that malignant thymic tumor and MTC of the anterior mediastinum sometimes exhibit similar CT findings. Caution is necessary in clinical work to avoid misdiagnosis.

Effective Activation of Strong C-Cl Bonds for Highly Selective Photosynthesis of Bibenzyl via Homo-Coupling.

Carbon-carbon (C-C) coupling of organic halides has been successfully achieved in homogeneous catalysis, while the limitation, e.g., the dependence on rare noble metals, complexity of the metal-ligand catalylst and the poor catalyst stability and recyclability, needs to be tackled for a green process. The past few years have witnessed heterogeneous photocatalysis as a green and novel method for organic synthesis processes. However, the study on C-C coupling of chloride substrates is rare due to the extremely high bond energy of C-Cl bond (327 kJ mol-1 ). Here, we report a robust heterogeneous photocatalyst (Cu/ZnO) to drive the homo-coupling of benzyl chloride with high efficiency, which achieves an unprecedented high selectivity of bibenzyl (93 %) and yield rate of 92 % at room temperature. Moreover, this photocatalytic process has been validated for C-C coupling of 10 benzylic chlorides all with high yields. In addition, the excellent stability has been observed for 8 cycles of reactions. With detailed characterization and DFT calculation, the high selectivity is attributed to the enhanced adsorption of reactants, stabilization of intermediates (benzyl radicals) for the selective coupling by the Cu loading and the moderate oxidation ability of the ZnO support, besides the promoted charge separation and transfer by Cu species.

LPS-Induced Systemic Inflammation Caused mPOA-FSH/LH Disturbance and Impaired Testicular Function.

Male reproductive function is key to the continuation of species and is under sophisticated regulation, challenged by various stressors including inflammation. In the lipopolysaccharide (LPS) intraperitoneal injection-induced acute systemic inflammation, male fecundity was compromised with decreased testosterone level, damaged spermatogenesis, and downregulations of testicular gene expression levels involved in steroidogenesis regulation and blood-testis barrier. It is also noteworthy that the testis is more sensitive to acute stress caused by LPS-induced systemic inflammation. LPS treatment resulted in lower testicular gene expression levels of steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme, and cytochrome P450 family 11 subfamily B member 1 after LPS treatment, while no such decrease was found in the adrenal gland. In parallel to the significant decreases in testicular intercellular adhesion molecule 1, tight junction protein 1, and gap junction alpha-1 protein gene expression with LPS treatment, no decrease was found in the epididymis. In the brain, LPS treatment caused higher medial preoptic area (mPOA) activation in the hypothalamus, which is accompanied by elevated blood follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, suggesting a disturbed hypothalamic-pituitary-gonad axis function. Besides mPOA, brain c-fos mapping and quantitative analysis demonstrated a broad activation of brain nuclei by LPS, including the anterior cingulate cortex, lateral septum, paraventricular nucleus of the hypothalamus, basolateral amygdala, ventral tegmental area, lateral habenular nucleus, locus coeruleus, Barrington's nucleus, and the nucleus of the solitary tract, accompanied by abnormal animal behavior. Our data showed that LPS-induced inflammation caused not only local testicular damage but also a systemic disturbance at the brain-testis axis level.

Radiomics Features on Computed Tomography Combined With Clinical-Radiological Factors Predicting Progressive Hemorrhage of Cerebral Contusion.

Background: Traumatic brain injury (TBI) is the main cause of death and severe disability in young adults worldwide. Progressive hemorrhage (PH) worsens the disease and can cause a poor neurological prognosis. Radiomics analysis has been used for hematoma expansion of hypertensive intracerebral hemorrhage. This study attempts to develop an optimal radiomics model based on non-contrast CT to predict PH by machine learning (ML) methods and compare its prediction performance with clinical-radiological models. Methods: We retrospectively analyzed 165 TBI patients, including 89 patients with PH and 76 patients without PH, whose data were randomized into a training set and a testing set at a ratio of 7:3. A total of 10 different machine learning methods were used to predict PH. Univariate and multivariable logistic regression analyses were implemented to screen clinical-radiological factors and to establish a clinical-radiological model. Then, a combined model combining clinical-radiological factors with the radiomics score was constructed. The area under the receiver operating characteristic curve (AUC), accuracy and F1 score, sensitivity, and specificity were used to evaluate the models. Results: Among the 10 various ML algorithms, the support vector machine (SVM) had the best prediction performance based on 12 radiomics features, including the AUC (training set: 0.918; testing set: 0.879) and accuracy (training set: 0.872; test set: 0.834). Among the clinical and radiological factors, the onset-to-baseline CT time, the scalp hematoma, and fibrinogen were associated with PH. The radiomics model's prediction performance was better than the clinical-radiological model, while the predictive nomogram combining the radiomics features with clinical-radiological characteristics performed best. Conclusions: The radiomics model outperformed the traditional clinical-radiological model in predicting PH. The nomogram model of the combined radiomics features and clinical-radiological factors is a helpful tool for PH.

Dopamine modulates visual threat processing in the superior colliculus via D2 receptors.

Innate defensive responses, unlearned behaviors improving individuals' chances of survival, have been found to involve the dopamine (DA) system. In the superior colliculus (SC), known for its role in defensive behaviors to visual threats, neurons expressing dopaminergic receptors of type 1 (Drd1+) and of type 2 (Drd2+) have been identified. We hypothesized that SC neurons expressing dopaminergic receptors may play a role in promoting innate defensive responses. Optogenetic activation of SC Drd2+ neurons, but not Drd1+ neurons, triggered defensive behaviors. Chemogenetic inhibition of SC Drd2+ neurons decreased looming-induced defensive behaviors, as well as pretreatment with the pharmacological Drd2+ agonist quinpirole, suggesting an essential role of Drd2 receptors in the regulation of innate defensive behavior. Input and output viral tracing revealed SC Drd2+ neurons mainly receive moderate inputs from the locus coeruleus (LC). Our results suggest a sophisticated regulatory role of DA and its receptor system in innate defensive behavior.

Ethnobiological study on traditional medicinal plants and fungi recorded in the Naxi Dongba sutras.

BACKGROUND: The Naxi people, living in Southwest China, have a long history and rich characteristic culture. Their ancestors recorded their life practices by ancient hieroglyphs and gradually formed the Dongba Sutras, which, among other knowledge, included the traditional knowledge of Naxi medicine. In the past, most studies on the Dongba Sutras focused on the humanistic culture of Naxi people, whereas studies have rarely focused on Naxi herbal medicinal plants and fungi described in the Dongba Sutras. Studying this aspect is helpful for exploring the traditional culture of Naxi people from the perspective of traditional medicine. METHODS: From February to September 2019, we screened the medicinal plants and fungi from the Dongba Sutras with the help of Dongba. Then, we carried out field investigations and collected voucher specimens of traditional medicinal plants and fungi with the help of 104 Naxi folk healers. The specimens were identified and stored in the Herbarium of Yunnan Branch, Institute of Medicinal Plants, Chinese Academy of Medical Sciences (IMDY). Through semi-structured interviews, we obtained ethnobotanical information of medicinal plants and fungi. The obtained quantitative data were analyzed using the informant consensus factor (ICF) method and the number of citations. RESULTS: A total of 85 species of medicinal plants and fungi belonging to 51 families and 71 genera were recorded in the Dongba Sutras. Among them, 25 species were endemic to China, and eight species were only distributed in Naxi distribution areas. These medicinal plants and fungi were mainly obtained from the wild, and 22 species could be used as food. The most frequent method of taking medicinal materials was oral-taking after decoction, followed by topical and sometimes buccal. The methods of processing these medicinal materials included water decoction, warm water flushing, and drinking after soaking. The medicinal plants and fungi in the Dongba Sutras are used to treat 96 conditions classified into 13 disease groups according to the International Classification of Primary Care second edition. Further analysis indicated that most of these species were utilized for treating diseases from the digestive (D) group, followed by those from the respiratory (R) group, musculoskeletal (L) group, general, and unspecified (A) group. Moreover, the Naxi people have a high consensus on the treatments of diseases from these four pathological groups. CONCLUSIONS: The Naxi traditional medicine is characterized by simple materials, easy operation, and distinctive national characteristics. The ancient Naxi people recorded their highly developed medical culture in the Dongba Sutras. Natural plant resources found around them were their primary choices for both medicine and diet therapy. The ecological ethics of Naxi people have positive significance for the conservation of wild resources in their area.

Stress Accelerates Defensive Responses to Looming in Mice and Involves a Locus Coeruleus-Superior Colliculus Projection.

Defensive responses to threatening stimuli are crucial to the survival of species. While expression of these responses is considered to be instinctive and unconditional, their magnitude may be affected by environmental and internal factors. The neural circuits underlying this modulation are still largely unknown. In mice, looming-evoked defensive responses are mediated by the superior colliculus (SC), a subcortical sensorimotor integration center. We found that repeated stress caused an anxiety-like state in mice and accelerated defensive responses to looming. Stress also induced c-fos activation in locus coeruleus (LC) tyrosine hydroxylase (TH)+ neurons and modified adrenergic receptor expression in SC, suggesting a possible Th::LC-SC projection that may be involved in the accelerated defensive responses. Indeed, both anterograde and retrograde neural tracing confirmed the anatomical Th::LC-SC projection and that the SC-projecting TH+ neurons in LC were activated by repeated stress. Optogenetic stimulation of either LC TH+ neurons or the Th::LC-SC fibers also caused anxiety-like behaviors and accelerated defensive responses to looming. Meanwhile, chemogenetic inhibition of LC TH+ neurons and the infusion of an adrenergic receptor antagonist in SC abolished the enhanced looming defensive responses after repeated stress, confirming the necessity of this pathway. These findings suggest that the Th::LC-SC pathway plays a key role in the sophisticated adjustments of defensive behaviors induced by changes in physiological states.