A role for the cerebellum in motor-triggered alleviation of anxiety.

Physical exercise is known to reduce anxiety, but the underlying brain mechanisms remain unclear. Here, we explore a hypothalamo-cerebello-amygdalar circuit that may mediate motor-dependent alleviation of anxiety. This three-neuron loop, in which the cerebellar dentate nucleus takes center stage, bridges the motor system with the emotional system. Subjecting animals to a constant rotarod engages glutamatergic cerebellar dentate neurons that drive PKCδ+ amygdalar neurons to elicit an anxiolytic effect. Moreover, challenging animals on an accelerated rather than a constant rotarod engages hypothalamic neurons that provide a superimposed anxiolytic effect via an orexinergic projection to the dentate neurons that activate the amygdala. Our findings reveal a cerebello-limbic pathway that may contribute to motor-triggered alleviation of anxiety and that may be optimally exploited during challenging physical exercise.

Complete chloroplast genome features and phylogenetic analysis of Abies ernestii var. salouenensis (Bordères and Gaussen) W. C. Cheng and L. K. Fu from southwest China.

Abies ernestii var. salouenensis (Bordères & Gaussen) W. C. Cheng & L. K. Fu is endemic to southwest China, including the southeastern Tibetan Plateau and the northwestern Yunnan Province. The taxonomic relationships between A. ernestii var. salouenensis and two other closely related fir species (A. chensiensis Tiegh. and A. ernestii Rehd.) still need to be determined. Here, we report for the first time the whole chloroplast genome of A. ernestii var. salouenensis. Its genome is 121,759 bp long and is characterized by a circular structure with 68 peptide-encoding genes, 16 tRNAs, six ORFs, and four rRNAs. We also identified 70 microsatellite repeat sequences and 14 tandem repeat sequences in the chloroplast genome of A. ernestii var. salouenensis. Comparative genome analysis indicated considerable variation in ycf1 and ycf2. Phylogenetic analysis supported the monophyly of A. ernestii var. salouenensis, A. chensiensis Tiegh., and A. ernestii Rehd. The relationships among them should be surveyed using more samples at the species level. This study will facilitate taxonomic studies and the development of suitable chloroplast markers for fir species.

Robust electrical impedance tomography for biological application: A mini review.

Electrical impedance tomography (EIT) has been used by researchers across several areas because of its low-cost and no-radiation properties. Researchers use complex conductivity in bioimpedance experiments to evaluate changes in various indicators within the image target. The diverse volumes and edges of biological tissues and the large impedance range impose dedicated demands on hardware design. The EIT hardware with a high signal-to-noise ratio (SNR), fast scanning and suitable for the impedance range of the image target is a fundamental foundation that EIT research needs to be equipped with. Understanding the characteristics of this technique and state-of-the-art design will accelerate the development of the robust system and provide a guidance for the superior performance of next-generation EIT. This review explores the hardware strategies for EIT proposed in the literature.

Effects and mechanisms of 6-hydroxykaempferol 3,6-di-O-glucoside-7-O-glucuronide from Safflower on endothelial injury in vitro and on thrombosis in vivo.

Background: The florets of Carthamus tinctorius L. (Safflower) is an important traditional medicine for promoting blood circulation and removing blood stasis. However, its bioactive compounds and mechanism of action need further clarification. Objective: This study aims to investigate the effect and possible mechanism of 6-hydroxykaempferol 3,6-di-O-glucoside-7-O-glucuronide (HGG) from Safflower on endothelial injury in vitro, and to verify its anti-thrombotic activity in vivo. Methods: The endothelial injury on human umbilical vein endothelial cells (HUVECs) was induced by oxygen-glucose deprivation followed by reoxygenation (OGD/R). The effect of HGG on the proliferation of HUVECs under OGD/R was evaluated by MTT, LDH release, Hoechst-33342 staining, and Annexin V-FITC apoptosis assay. RNA-seq, RT-qPCR, Enzyme-linked immunosorbent assay and Western blot experiments were performed to uncover the molecular mechanism. The anti-thrombotic effect of HGG in vivo was evaluated using phenylhydrazine (PHZ)-induced zebrafish thrombosis model. Results: HGG significantly protected OGD/R induced endothelial injury, and decreased HUVECs apoptosis by regulating expressions of hypoxia inducible factor-1 alpha (HIF-1α) and nuclear factor kappa B (NF-κB) at both transcriptome and protein levels. Moreover, HGG reversed the mRNA expression of pro-inflammatory cytokines including IL-1ß, IL-6, and TNF-α, and reduced the release of IL-6 after OGD/R. In addition, HGG exhibited protective effects against PHZ-induced zebrafish thrombosis and improved blood circulation. Conclusion: HGG regulates the expression of HIF-1α and NF-κB, protects OGD/R induced endothelial dysfunction in vitro and has anti-thrombotic activity in PHZ-induced thrombosis in vivo.

Diploic vein as a newly treatable cause of pulsatile tinnitus: A case report.

BACKGROUND: Pulsatile tinnitus (PT) is an annoying sound that can be eliminated with targeted treatment of the cause. However, the causes of PT have not been fully elucidated. CASE SUMMARY: A 38-year-old woman with right-sided objective PT underwent preoperative computed tomography arteriography and venography (CTA/V). A 3.8 mm vine diploic vein (DV), which passed through the mastoid air cells posteriorly in a dehiscent canal and was continuous with the transverse-sigmoid sinus, was thought to be the causative finding. Four-dimensional flow magnetic resonance (4D flow MR) imaging showed that the blood in the DV flowed toward the transverse-sigmoid sinus. The closer the blood was to the transverse-sigmoid sinus, the higher the velocity. No vortex or turbulence was found in the DV or adjacent transverse sinus. The sound was eliminated immediately after ligation of the DV with no recurrence during a three-month follow-up. No flow signal of the DV was noted on postoperative 4D flow MR. CONCLUSION: A DV may be a treatable cause of PT. CTA/V and 4D flow MR could be utilized to determine the morphological and hemodynamic characteristics of the DV.

Attaching a Dipeptide to Fullerene as an Antioxidant Hybrid against DNA Oxidation.

Emerging evidence has revealed that oxidative damages of DNA correlate with the pathogenesis of some diseases, and numerous investigations have also suggested that supplementation of antioxidants is beneficial for keeping health by rectifying in vivo redox status. Here, we construct antioxidative dipeptides with the Ugi four-component reaction (comprising p-aminobenzyl alcohol, benzaldehyde, or vanillin, a series of antioxidative carboxylic acids and isocyanides as reagents) and then attempt to attach the dipeptides to [60]fullerene by the Bingel reaction. However, this endeavor does not lead to the amelioration of the radical-scavenging property because abilities of fullerenyl dipeptides to trap 2,2'-diphenyl-1-picrylhydrazyl and galvinoxyl radicals are still dependent upon the phenolic hydroxyl group in the dipeptide scaffold rather than upon the fullerenyl group. Alternatively, when the obtained fullerenyl dipeptides are evaluated in a peroxyl radical-induced oxidation of DNA, it is found that introducing a fullerene moiety into dipeptide enables antioxidative effect to be enhanced 20-30% because the fullerene moiety facilitates the corresponding dipeptide to intercalate with DNA strands, and thus, to increase the antioxidative efficacy. Our results suggest that connecting an antioxidative skeleton with the hydrophobic fullerene moiety might lead to a series of novel antioxidant hybrids applied for the inhibition of DNA oxidation.

Disulfiram-loaded lactoferrin nanoparticles for treating inflammatory diseases.

Sepsis is a dysregulated immune response to infection and potentially leads to life-threatening organ dysfunction, which is often seen in serious Covid-19 patients. Disulfiram (DSF), an old drug that has been used to treat alcohol addiction for decades, has recently been identified as a potent inhibitor of the gasdermin D (GSDMD)-induced pore formation that causes pyroptosis and inflammatory cytokine release. Therefore, DSF represents a promising therapeutic for the treatment of inflammatory disorders. Lactoferrin (LF) is a multifunctional glycoprotein with potent antibacterial and anti-inflammatory activities that acts by neutralizing circulating endotoxins and activating cellular responses. In addition, LF has been well exploited as a drug nanocarrier and targeting ligands. In this study, we developed a DSF-LF nanoparticulate system (DSF-LF NP) for combining the immunosuppressive activities of both DSF and LF. DSF-LF NPs could effectively block pyroptosis and inflammatory cytokine release from macrophages. Treatment with DSF-LF NPs showed remarkable therapeutic effects on lipopolysaccharide (LPS)-induced sepsis. In addition, this therapeutic strategy was also applied to treat ulcerative colitis (UC), and substantial treatment efficacy was achieved in a murine colitis model. The underlying mode of action of these DSF-LF-NPs may contribute to efficiently suppressing macrophage-mediated inflammatory responses and ameliorating the complications caused by sepsis and UC. As macrophage pyroptosis plays a pivotal role in inflammation, this safe and effective biomimetic nanomedicine may offer a versatile therapeutic strategy for treating various inflammatory diseases by repurposing DSF.

Evaluation of preoperative dry eye in people undergoing corneal refractive surgery to correct myopia.

AIM: To investigate the incidence of preoperative dry eye and related factors in patients undergoing corneal refractive surgery to correct myopia. METHODS: A total of 141 patients with myopia who underwent corneal refractive surgery were surveyed by questionnaires, tear film break-up time (BUT) test, Schimer I test (SIt), corneal fluorescein staining (FL) test and diagnosed according to the currently recognized domestic diagnostic criteria for dry eye. Correlation analysis of factors such as age, gender, regular wearing of contact lens (CL), diopter (spherical equivalent), corneal thickness, and corneal curvature that may affect the onset of dry eye was carried out to clarify the main influencing factors. RESULTS: There were 64 patients (45.39%) diagnosed with dry eye. The male patients (20.31%) was significantly less than that of non-dry eye subjects (41.56%; χ 2=7.260, P=0.007); the proportion of patients with dry eye wearing CL (81.25%) was significantly higher than that of non-dry eye subjects (51.95%; χ 2=13.234, P<0.001); the median diopter level of dry eye patients was -6.59 (IQR: -8.87, -4.58) D, and the median diopter level of non-dry eye subjects was -5.69 (IQR: -7.15, -4.03) D. The diopter level of dry eye patients was significantly higher (Z=-2.086, P=0.019). However, the age, best corrected visual acuity, and intraocular pressure of dry eye patients were not statistically different from those of non-dry eye subjects (t=-0.257, -0.383 and 0.778, P=0.798, 0.702, and 0.438); the corneal thickness and corneal curvature (K1 and K2) were also not statistically different either (Z=-1.487, -1.036 and -1.707, P=0.137, 0.300, and 0.088). The research further analyzes the three significant factors in the single factor analysis (gender, CL wear, and diopter) in a multi-factor way: CL wear and diopter were the influencing factors of dry eye disease. Among them, CL wear increased the risk of dry eye by 2.934 times compared with no CL wear; for every 1 D increase in diopter, the risk of dry eye increased by 0.761 times. CONCLUSION: Preoperative dry eye is relatively common in patients who undergo corneal refractive surgery to correct myopia, especially in patients who have a history of CL wear and a high diopter level before surgery. Therefore, it is necessary to carry out preoperative screening and timely treatment of dry eye to obtain the best treatment outcome and postoperative satisfaction.

Bone remodeling in sigmoid sinus diverticulum after stenting for transverse sinus stenosis in pulsatile tinnitus: A case report.

BACKGROUND: Pulsatile tinnitus (PT) is a potentially disabling symptom that has received increasing attention. Multiple causes of PT have been confirmed by targeted treatment. However, dynamic changes of related structures in PT patients with multiple causes after stenting for ipsilateral transverse sinus stenosis (TSS) have not been previously reported. We report such a case and present postoperative computed tomography venography (CTV) follow-up findings to demonstrate the decreased sigmoid sinus diverticulum and bone remodeling. CASE SUMMARY: A 45-year-old man suffered from left-sided PT for 15 years that was occasionally accompanied by headache and dizziness. Pre-operative CTV revealed left-sided sigmoid sinus wall anomalies (SSWAs), TSS, outflow dominance, large posterior condylar emissary vein, and an empty sella turcica. A cerebrospinal fluid pressure of 270 mmH2O was further detected. The sound disappeared immediately after stenting for ipsilateral TSS, with no recurrence during 2 years of follow-up. After the procedure, the patient underwent four consecutive CTV examinations. The diverticulum decreased 6 mo after the procedure with new bone remodeling. The density of the remodeled bone was further increased 1 year later, and a hardened edge was formed 2 years later. CONCLUSION: PT associated with SSWAs, TSS, and idiopathic intracranial hypertension can be cured by stenting for TSS alone. And bone remodeling around SSWAs is a more significant finding.

Comparison of correcting myopia and astigmatism with SMILE or FS-LASIK and postoperative higher-order aberrations.

AIM: To compare the effect of myopia and astigmatism correction and postoperative change in higher-order aberration as results of receiving small-incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK). METHODS: A prospective and non-randomized controlled study was conducted. The subjects are divided into two groups according to different operations received: 229 eyes of 116 patients in the SMILE group and 168 eyes of 86 patients in the FS-LASIK group. All subjects were followed up for 3mo by monitoring their uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), spherical equivalent, higher-order aberrations, and the preoperative and postoperative complications. RESULTS: At 1wk, 1, and 3mo post-surgery, 224 eyes (97.8%), 227 eyes (99.1%) and 229 eyes (100%) had UCVA≥20/20 in the SMILE group, while 165 eyes (98.2%), 167 eyes (99.4%) and 167 eyes (99.4%) had UCVA≥20/20 in the FS-LASIK group, respectively (χ 2=0.146, 2.135, and 1.124; all P>0.05). BCVA reduction was not observed in both groups at 1 and 3mo of post-surgery (χ 2=0.734 and 1.898, P>0.05). There was no statistically significant difference in the spherical equivalent between the two groups at 1 and 3mo post-surgery, though the percentage of the spherical equivalent within ±0.50 D at 3mo post-surgery was 98% in the SMILE group, which was higher than that of the FS-LASIK group (92%, χ 2=1.872, P>0.05). The root mean square (RMS) values of total high-order aberration, coma, and spherical aberration of the two groups increased significantly in the early postoperative period and decreased after 3mo, but the values were still higher than the preoperative levels (P<0.05); there was no significant difference between the two groups in the RMS values of total higher-order aberrations and specific higher-order aberrations (P>0.05). The incidence of complications in the SMILE group was lower than that in the FS-LASIK group (χ 2=14.52, P<0.05). CONCLUSION: SMILE and FS-LASIK can effectively treat myopia, significantly improve visual acuity, and increase the total high-order aberration, spherical aberration, and coma. The incidence of complications after SMILE is relatively low.

Network meta-analysis of the treatment efficacy of different lasers for peri-implantitis.

The aim of this study was comparing different lasers with conventional non-surgical treatment (CNT) for the management of peri-implantitis, regarding probing depth (PD), plaque index (PLI), clinical attachment level (CAL), and sulcus bleeding index (SBI). Randomized controlled trials (RCTs) on different lasers and CNT for peri-implantitis were searched. Pairwise and network meta-analyses were performed to analyze the PD, PLI, CAL, and SBI outcomes. The risk of bias, evidence quality, statistical heterogeneity, and ranking probability were also evaluated. Eleven studies were included in this study, involving three types of lasers. Diode + CNT had significantly superior efficacy to CNT alone, regarding PD reduction, while Er:YAG + CNT had significantly superior efficacy than CNT in terms of the PLI, CAL, and SBI. The highest probability of being most effective for PD was diode + CNT (49%), while Er:YAG + CNT had the highest probability of improving the PLI, CAL, and SBI (66%, 53%, and 79%, respectively). Diode + CNT was significantly superior for PD management in peri-implantitis compared with CNT alone, while Er:YAG + CNT significantly improved the PLI, CAL, and SBI. Therefore, Er:YAG + CNT might be recommended methods considered for management of peri-implantitis.

Highly enantioselective one-pot sequential synthesis of valerolactones and pyrazolones bearing all-carbon quaternary stereocentres.

Highly enantiopure and bioactive δ-valerolactones and pyrazolones, bearing α-all-carbon quaternary stereocentres, were successfully and sequentially prepared via a one-pot procedure starting from readily available, inexpensive materials, catalysed by a new chiral squaramide under mild reaction conditions. An organocatalytic Michael reaction afforded the valerolactones, while a one-pot Michael-hydrazinolysis-imidization cascade yielded the pyrazolones. This procedure is economically efficient and environmentally benign.

Cerebral blood flow alterations in hemodialysis patients with and without restless legs syndrome: an arterial spin labeling study.

Hemodialysis with restless legs syndrome (HD-RLS) is associated with alterations in neuronal function, the blood-brain barrier and iron deposition, thus affecting cerebral metabolism and perfusion. This study utilized three-dimensional arterial spin labeling (ASL) to identify HD-RLS-related perfusion patterns and potential relationships with disease severity. Twenty-six HD-RLS patients, 30 hemodialysis patients without restless legs syndrome (HD-nRLS) and 30 age-, sex-, and education-matched healthy controls were included in this study. One-way analysis of covariance and post hoc analyses were used to assess differences in cerebral blood flow (CBF) values, demographics and clinical data among the three groups. Pearson's correlation analysis was conducted between altered CBF values in the HD-RLS group and clinical data. Compared with HD-nRLS patients, HD-RLS patients showed increased CBF in the right primary motor cortex (false discovery rate [FDR]-corrected P < 0.05). Compared with the normal controls, both HD subgroups (i.e., those with and without RLS) exhibited consistent CBF changes, including increased CBF in the left medial superior frontal gyrus and bilateral thalamus and decreased CBF in the left insular cortices (FDR-corrected P < 0.05). This abnormal hyperperfusion in the sensorimotor cortex and basal ganglia provides evidence for a sensory processing disorder in RLS that may be involved in the pathogenesis of RLS in HD patients.

Hierarchical integrated processing of reward-related regions in obese males: A graph-theoretical-based study.

Abnormal activities in reward-related regions are associated with overeating or obesity. Preliminary studies have shown that changes in neural activity in obesity include not only regional reward regions abnormalities but also impairments in the communication between reward-related regions and multiple functional areas. A recent study has shown that the transitions between different neural networks are nonrandom and hierarchical, and that activation of particular brain networks is more likely to occur after other brain networks. The aims of this study were to investigate the key nodes of reward-related regions in obese males and explore the hierarchical integrated processing of key nodes. Twenty-four obese males and 24 normal-weight male controls of similar ages were recruited. The fMRI data were acquired using 3.0 T MRI. The fMRI data preprocessing was performed in DPABI and SPM 12. Degree centrality analyses were conducted using GRETNA toolkit, and Granger causality analyses were calculated using DynamicBC toolbox. Decreased degree centrality was observed in left ventral medial prefrontal cortex (vmPFC) and right parahippocampal/hippocampal gyrus in group with obesity. The group with obesity demonstrated increased effective connectivity between left vmPFC and several regions (left inferior temporal gyrus, left supplementary motor area, right insular cortex, right postcentral gyrus, right paracentral lobule and bilateral fusiform gyrus). Increased effective connectivity was observed between right parahippocampal/hippocampal gyrus and left precentral/postcentral gyrus. Decreased effective connectivity was found between right parahippocampal/hippocampal gyrus and left inferior parietal lobule. This study identified the features of hierarchical interactions between the key reward nodes and multiple function networks. These findings may provide more evidence for the existing view of hierarchical organization in reward processing.

Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial.

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS: Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

Patterns of Gray Matter Volume Alterations in Hemodialysis Patients With and Without Restless Legs Syndrome: Evidence From a Voxel-Based Morphometry Study.

PURPOSE: The purpose of this study was to investigate the differences of gray matter volume (GMV) alteration patterns between hemodialysis with restless legs syndrome (HD-RLS) and hemodialysis without restless legs syndrome (HD-nRLS) patients using voxel-based morphometry. METHODS: Twenty-three HD-RLS patients, 27 HD-nRLS patients, and 27 age-, sex-, and education-matched healthy controls were included in this study. One-way analysis of covariance and post hoc analyses were used to assess differences in GMV, demographics, and clinical data among the 3 groups. Pearson correlation analysis was conducted between altered GMV in the HD-RLS group and clinical data. RESULTS: Compared with HD-nRLS patients, HD-RLS patients showed decreased GMV in the left primary motor cortex (false discovery rate corrected, P < 0.05). Compared with the healthy controls, both HD subgroups (ie, those with and without RLS) exhibited consistent GMV changes, including decreased GMV in the bilateral anterior cingulate and paracingulate gyrus and left middle temporal gyrus (false discovery rate corrected, P < 0.05). The GMV values in the left precentral gyrus were negatively correlated with the RLS rating scores (r = 0.2138, P = 0.0263). CONCLUSIONS: This abnormal decreased GMV in the sensorimotor cortex provides evidence for a sensory processing disorder in RLS that may be involved in the pathogenesis of RLS in HD patients.

Abnormal Regional Neural Activity and Reorganized Neural Network in Obesity: Evidence from Resting-State fMRI.

OBJECTIVE: This study aimed to investigate regional neural activity and regulation of patterns in the reorganized neural network of obesity and explore the correlation between brain activities and eating behavior. METHODS: A total of 23 individuals with obesity and 23 controls with normal weight were enrolled. Functional magnetic resonance imaging (fMRI) data were acquired using 3.0-T MRI. Amplitude of low-frequency fluctuation and functional connectivity (FC) analyses were conducted using Data Processing Assistant for resting-state fMRI and Resting-State fMRI Data Analysis Toolkit (REST). RESULTS: The group with obesity showed increased amplitude of low-frequency values in left fusiform gyrus/amygdala, inferior temporal gyrus (ITG), hippocampus/parahippocampal gyrus, and bilateral caudate but decreased values in right superior temporal gyrus. The group with obesity showed increased FC between left caudate and right superior temporal gyrus, left fusiform gyrus/amygdala and left ITG, right caudate and left fusiform gyrus/amygdala, and right caudate and left hippocampus/parahippocampal gyrus. Dutch Eating Behavior Questionnaire-Emotional scores were positively correlated with FC between left hippocampus/parahippocampal gyrus and right caudate but negatively correlated with FC between left fusiform gyrus/amygdala and left ITG. CONCLUSIONS: The study indicated the reorganized neural network presented as a bilateral cross-regulation pattern across hemispheres between reward and various appetite-related functional processing, thus affecting emotional and external eating behavior. These results could provide further evidence for neuropsychological underpinnings of food intake and their neuromodulatory therapeutic potential in obesity.