Psilocybin, a naturally occurring hallucinogenic component of magic mushrooms, has significant psychoactive effects in both humans and rodents. But the underlying mechanisms are not fully understood. ...Blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is a useful tool in many preclinical and clinical trials to investigate psilocybin-induced changes of brain activity and functional connectivity (FC) due to its noninvasive nature and widespread availability. However, fMRI effects of psilocybin on rats have not been carefully investigated. This study aimed to explore how psilocybin affects resting-state brain activity and FC, through a combination of BOLD fMRI and immunofluorescence (IF) of EGR1, an immediate early gene (IEG) closely related to depressive symptoms. Ten minutes after psilocybin hydrochloride injection (2.0 mg/kg, i.p.), positive brain activities were observed in the frontal, temporal, and parietal cortex (including the cingulate cortex and retrosplenial cortex), hippocampus, and striatum. And a region-of-interest (ROI) -wise FC analysis matrix suggested increased interconnectivity of several regions, such as the cingulate cortex, dorsal striatum, prelimbic, and limbic regions. Further seed-based analyses revealed increased FC of cingulate cortex within the cortical and striatal areas. Consistently, acute psilocybin increased the EGR1 level throughout the brain, indicating a consistent activation thought the cortical and striatal areas. In conclusion, the psilocybin-induced hyperactive state of rats is congruent to that of humans, and may be responsible for its pharmacological effects.
Objective:
The mechanism of CD4
+
T-cell dysfunction in systemic lupus erythematosus (SLE) has not been fully understood. Increasing evidence show that long noncoding RNAs (lncRNAs) can regulate ...immune responses and take part in some autoimmune diseases, while little is known about the lncRNA expression and function in CD4
+
T of SLE. Here, we aimed to detect the expression profile of lncRNAs in lupus CD4
+
T cells and explore the mechanism that how lincRNA00892 in CD4
+
T cells is involved in the pathogenesis of SLE.
Methods:
The expression profiles of lncRNAs and mRNAs in CD4
+
T cells from SLE patients and healthy controls were detected by microarray. LincRNA00892 and CD40L were chosen for validation by quantitative real-time PCR (qRT-PCR). Coexpression network was conducted to predict the potential target genes of lincRNA00892. Then lincRNA00892 was overexpressed in normal CD4
+
T cells via lentivirus transfection. The expression of lincRNA00892 was detected by qRT-PCR. The expression of CD40L was detected by qRT-PCR, western blotting, and flow cytometry, respectively. The expression of CD69 and CD23 was measured by flow cytometry. The secretion of IgG was determined by enzyme-linked immunosorbent assay (ELISA). The proteins targeted by lincRNA00892 were measured by RNA pulldown and subsequent mass spectrometry (MS). The interaction between heterogeneous nuclear ribonucleoprotein K (hnRNP K) and lincRNA00892 or CD40L was detected by RNA immunoprecipitation (RIP) assay.
Results:
A total of 1887 lncRNAs and 3375 mRNAs were found to be aberrantly expressed in CD4
+
T cells of SLE patients compared to healthy controls. LincRNA00892 and CD40L were confirmed to be upregulated in CD4
+
T cells of SLE patients by qRT-PCR. The lncRNA–mRNA coexpression network analysis indicated that CD40L was a potential target of lincRNA00892. Overexpression of lincRNA00892 enhanced CD40L protein levels while exerting little influence on CD40L mRNA levels in CD4
+
T cells. In addition, lincRNA00892 could induce the activation of CD4
+
T cells. Furthermore, lincRNA00892 led to the activation of B cells and subsequent secretion of IgG in a CD4
+
T-cell–dependent manner. Finally, hnRNP K was found to be among the proteins pulled down by lincRNA00892, and hnRNP K could bind to lincRNA00892 or CD40L directly.
Conclusion:
Our results showed that the lncRNA expression profile was altered in CD4
+
T cells of SLE. LincRNA00892 possibly contributed to the pathogenesis of SLE by targeting hnRNP K and subsequently upregulating CD40L expression to activate CD4
+
T and B cells. These provided us a potential target for further mechanistic studies of SLE pathogenesis.
In the context of big data, based on the space analysis function in GIS, using the nearest neighbor index, kernel density analysis and the model of gravity center migration, this article studies ...spatial distribution and its evolution characteristics of A-grade scenic spots. The results showed that: 1) The number of A-grade scenic spots of Xinjiang grows rapidly and the grade structure is constantly optimized. 2) The spatial distribution characteristics of A-grade scenic spots of Xinjiang are as follows: the spatial distribution of scenic spots is in the pattern of "large dispersion and small agglomeration", mainly along 120km around the city and 10km on both sides of the traffic trunk lines, presenting a "cluster" distribution. 3) The spatial evolution characteristics of A- grade scenic spot in Xinjiang are as follows: the center of gravity of the scenic spot is gradually moving to the west, the overall distribution scope is constantly expanding, and the degree of local agglomeration is constantly increasing, formed three core distribution areas: Urumqi-changji, Yili and Kashgar. 4) The spatial distribution and evolution characteristics of A-grade scenic spots of Xinjiang are mainly affected by topography, the nearby city, population scale and traffic conditions.
Gypenosides (Gyps), the major active constituents isolated from
, possess anti-inflammatory and antioxidant activities. Previous studies have demonstrated that Gyps displayed potent ameliorative ...effects on liver fibrosis and renal fibrosis. In this study, we found that Gyps significantly reduced the mortality of bleomycin-induced pulmonary fibrosis mice (40% mortality rate of mice in the model group versus 0% in the treatment group). Masson staining showed that Gyps could reduce the content of collagen in the lung tissue of pulmonary fibrosis mice Masson staining and immunohistochemistry demonstrated that the expression of the collagen gene α-SMA and fibrosis gene Col1 markedly decreased after Gyps treatment. The active mitosis of fibroblasts is one of the key processes in the pathogenesis of fibrotic diseases. RNA-seq showed that Gyps significantly inhibited mitosis and induced the G2/M phase cell cycle arrest. The mTOR/c-Myc axis plays an important role in the pathological process of pulmonary fibrosis. RNA-seq also demonstrated that Gyps inhibited the mTOR and c-Myc signaling in pulmonary fibrosis mice, which was further validated by Western blot and immunohistochemistry. AKT functions as an upstream molecule that regulates mTOR. Our western blot data showed that Gyps could suppress the activation of AKT. In conclusion, Gyps exerted anti-pulmonary fibrosis activity by inhibiting the AKT/mTOR/c-Myc pathway.
The contamination of soils with cadmium (Cd) has become a serious environmental issue that needs to be addressed. Elucidating the mechanisms underlying Cd accumulation may facilitate the development ...of plants that accumulate both high and low amounts of Cd. In this study, a combination of phenotypic, physiological, and comparative transcriptomic analyses was performed to investigate the effects of different Cd concentrations (0, 5, 10, 30, 50 mg/kg) on
L. Our results suggest that
L. seedlings had a degree of tolerance to the 5 mg/kg Cd treatment, whereas higher Cd stress (10-50 mg/kg) could suppress the growth of
L. seedlings. The contents of soluble protein, as well as MDA (malondialdehyde), were increased, but the activities of CAT (catalase) enzymes and the contents of soluble sugar and chlorophyll were decreased, when
L. was under 30 and 50 mg/kg Cd treatment. Comparative transcriptomic analysis indicated that
, and
were down-regulated, but
and
were up-regulated, which might contribute to cell wall integrity maintenance. Moreover, the down-regulation of
and up-regulation of
,
, and
might also play roles in reducing Cd toxicity in roots. Taken together, the results of our study may help to elucidate the mechanisms underlying the response of
L. to various concentrations of Cd.
The anterior nucleus of thalamus (ANT) has been suggested as an extended hippocampal system. The circuit of ANT and hippocampus has been widely demonstrated to be associated with memory function. ...Both lesions to each region and disrupting inter-regional information flow can induce working memory impairment. However, the role of this circuit in working memory precision remains unknown.
To test the role of the hippocampal-anterior thalamic pathway in working memory precision, we delivered intracranially electrical stimulation to the ANT. We hypothesize that ANT stimulation can improve working memory precision.
Presurgical epilepsy patients with depth electrodes in ANT and hippocampus were recruited to perform a color-recall working memory task. Participants were instructed to point out the color they were supposed to recall by clicking a point on the color wheel, while the intracranial EEG data were synchronously recorded. For randomly selected half trials, a bipolar electrical stimulation was delivered to the ANT electrodes.
We found that compared to non-stimulation trials, working memory precision judgements were significantly improved for stimulation trials. ANT electrical stimulation significantly increased spectral power of gamma (30–100 Hz) oscillations and decreased interictal epileptiform discharges (IED) in the hippocampus. Moreover, the increased gamma power during the pre-stimulus and retrieval period predicted the improvement of working memory precision judgements.
ANT electrical stimulation can improve working memory precision judgements and modulate hippocampal gamma activity, providing direct evidence on the role of the human hippocampal-anterior thalamic axis in working memory precision.
•Electrical stimulation to ANT induced the improvement of working memory precision.•Electrical stimulation to ANT increased gamma activity and decreased IED in the hippocampus.•Increased post-stimulation gamma predicted the improvement of working memory precision.
Primary giant cell tumors of soft tissues (GCT-STs) are extremely rare soft tissue tumors located both in superficial and in deep soft tissues. Clinically, GCT-ST manifests as a slow-growing, ...well-defined, painless mass. We report a case of an 88-year-old female patient with upper abdominal distension, fever, and anemia. Laparoscopic exploration revealed a tumor located in the left lobe of the liver with localized rupture and hemorrhage. Postoperative pathology revealed that the tumor was composed of monocytes and osteoclast-like multinucleated giant cells, accompanied by extensive hemorrhage, necrosis, and cytologic atypia. Because mitotic cells are difficult to be detected in pathological diagnosis, combined with immunohistochemistry, the tumor was diagnosed as a giant cell tumor of soft tissue. This case report highlights the primary choice of histology and immunohistochemistry for the correct diagnosis of GCT-ST because preoperative radiological diagnosis is nonspecific and prone to mistakes.
Introduction
Adult intussusception is a rare disease that is difficult to diagnose and treat and is even rarer when it is caused by a lipoma of the small intestine. We reported a case of a small ...intestine lipoma combined with intussusception, which can guide people in future clinical work.
Case Presentation
A 51-year-old female was admitted to the hospital with “abdominal pain for 1 month.” Enhanced computed tomography (CT) of the abdomen suggested a lipoma in the left lower quadrant and a proximal intussusception. After excluding surgical contraindications, laparoscopic exploration was performed on the second day of admission, which showed a small amount of ascites in the abdominal cavity, a small intestine–small intestine-type intussusception about 20 cm from the ileocecal area and about 140 cm from the ileocecal area, and a mass of about 2×4 cm that was palpable by laparoscopic intestinal forceps, which was protruded into the intestinal cavity with a soft texture and sound mobility. A 5 cm-long incision was made above the mass to dissect into the abdomen layer by layer, and the diseased intestine was dislodged outside the abdominal cavity with oval forceps. The intestine was reduced by hand and observed for half an hour after reduction, and the blood circulation and peristalsis of the intestine were observed to be still sound. The intestine was dissected at 2 cm from the upper and lower margins of the mass using linear anastomosis to operate small intestine side-to-side anastomosis. The intestine was opened concurrently and closed with a linear anastomosis, using 3-0 absorbable thread to reinforce anastomosis intermittently. The procedure went smoothly, and the patient was discharged on the 5th postoperative day.
Conclusion
A small intestinal lipoma combined with small intestinal intussusception is rare in clinical practice and needs to be diagnosed by asking history detailedly, physical examination, and relevant ancillary tests such as abdominal CT. Laparoscopic-assisted small incision surgery for adult intussusception combines the advantages of laparoscopic surgery and laparotomy, operating simply and easily.
The close correlation between the incidence of shrimp disease and the surrounding microbial community is well established. However, it remains uncertain whether particular bacterial assemblages are ...indicative of shrimp health status (healthy or diseased). To test this hypothesis, we used 454 pyrosequencing to compare the bacterioplankton composition of ponds with healthy shrimp populations (PHS) with that of ponds with diseased shrimp populations (PDS). The results showed that the bacterial communities in PDS were markedly distinct (P<0.05) from those of PHS but that the diversity was unchanged. This sudden shift in the bacterioplankton communities was accompanied by severe mass mortality of the shrimp. The differentiation of the bacterial communities was primarily shaped by the total phosphate and by the chemical oxygen demand. In particular, we identified 11 indicator orders (in which 6 for healthy status and 5 for diseased status) that differentiated PHS from PDS. In a given pond, especially, the sum of the relative abundance of the disease indicator phylotypes and that of the healthy indicator phylotypes could be used to estimate the health status of the pond. This result suggests that the bacterioplankton composition determines, at least in part, the health status of the shrimp. Overall, this study provides direct evidence that the composition of the bacterioplankton community can serve as a biological indicator to evaluate the occurrence of shrimp diseases.
Psoriasis is a common immune-mediated inflammatory skin disease. Although biological agents have achieved good clinical efficacy in the treatment of moderate-to-severe psoriasis, the phenomenon of ...secondary non-response (SNR) has been gradually recognized. SNR refers to the gradual decline of efficacy after the patient achieves clinical remission with biological agents such as TNF-α biologics. Acitretin, as an immunomodulatory systemic drug for psoriasis, can improve the SNR to biological agents with good tolerance, but there are still individual differences in efficacy. Single-nucleotide polymorphisms (SNPs) of many related inflammatory cytokines have been shown to be important factors of individual differences in drug response in psoriasis, but there have been few reports on the use of pharmacogenomics to alleviate the SNR to biological agents. This study recruited 43 patients with psoriasis and 24 normal controls to investigate whether SNPs of inflammatory cytokines could be used as biomarkers for acitretin to alleviate SNR to TNF-α biologics in psoriasis, including rs1800795 (IL-6), rs6887695 (IL-12b), rs3212227 (IL-12b), rs10484879 (IL-17a), rs4819554 (IL-17ra), rs763780 (IL-17F), rs11209032 (IL23R), rs11209026 (IL23R), and rs2201841 (IL23R). The study also analyzed the correlation between the abovementioned SNPs and the efficacy of acitretin-only patients so as to understand whether the improvement is attributable to the intervention of acitretin on SNR or a simple response of acitretin. We found that in patients with homozygous AA (χ2 = 6.577,
p
= 0.02) at the SNP rs112009032 (IL-23R), acitretin could improve the SNR to TNFα monoclonal antibody. Patients with the genotype of TG (χ2 = 6.124,
p
= 0.035) at rs3212227 (IL-12B) were more sensitive to using acitretin in the treatment of psoriasis. Rs3212227 (χ2 = 7.664,
p
= 0.022) was also associated with the susceptibility to psoriasis. The study might provide a clinical decision reference for personalized treatment of secondary loss of response to psoriasis biologics.
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