Humid heat environment causes anxiety-like disorder via impairing gut microbiota and bile acid metabolism in mice.

Climate and environmental changes threaten human mental health, but the impacts of specific environmental conditions on neuropsychiatric disorders remain largely unclear. Here, we show the impact of a humid heat environment on the brain and the gut microbiota using a conditioned housing male mouse model. We demonstrate that a humid heat environment can cause anxiety-like behaviour in male mice. Microbial 16 S rRNA sequencing analysis reveals that a humid heat environment caused gut microbiota dysbiosis (e.g., decreased abundance of Lactobacillus murinus), and metabolomics reveals an increase in serum levels of secondary bile acids (e.g., lithocholic acid). Moreover, increased neuroinflammation is indicated by the elevated expression of proinflammatory cytokines in the serum and cortex, activated PI3K/AKT/NF-κB signalling and a microglial response in the cortex. Strikingly, transplantation of the microbiota from mice reared in a humid heat environment readily recapitulates these abnormalities in germ-free mice, and these abnormalities are markedly reversed by Lactobacillus murinus administration. Human samples collected during the humid heat season also show a decrease in Lactobacillus murinus abundance and an increase in the serum lithocholic acid concentration. In conclusion, gut microbiota dysbiosis induced by a humid heat environment drives the progression of anxiety disorders by impairing bile acid metabolism and enhancing neuroinflammation, and probiotic administration is a potential therapeutic strategy for these disorders.

A novel homozygous CLN6 Tyr142Cys variant in a nonconsanguineous family with Kufs disease.

BACKGROUND: Neuronal ceroid lipofuscinoses are a genetically heterogeneous group of inherited lysosomal storage disorders. Kufs disease is the predominant form of neuronal ceroid lipofuscinosis in adults, but it's rare and challenging to diagnose. CASE DESCRIPTION: The proband initially presented with cognitive deterioration and parkinsonian traits. At 35, he was admitted to hospital following a tonic-clonic seizure. Brain magnetic resonance imaging showed atrophy of the cerebral cortex and cerebellum, enlarged ventricles, and thinned corpus callosum. The proband's younger brother and sister were also affected, and the clinical phenotype within the family was consistent. Whole-exome Sequencing of the proband revealed a novel homozygous mutation in CLN6 (NM_017882: c.425A > G, p. Tyr142Cys). Co-segregation analysis revealed that two other affected individuals carried a homozygous mutation at the same locus, with both parents exhibiting heterozygous mutations of c.425A > G. CONCLUSION: Our study not only provides insights into the clinical presentation and development of the disease within the affected family but also expanded the mutational and phenotypical spectrum of the CLN6 gene.

A sustainable process for selective recovery of metals from gallium-bearing waste generated from LED industry.

With the rapid development of the LED industry, gallium (Ga)-bearing waste generated is regarded as one of the most hazardous as it typically contains heavy metals and combustible organics. Traditional technologies are characterized by long processing routes, complex metal separation processes and significant secondary pollution emission. In this study, we proposed an innovative and green strategy to selectively recovery Ga from Ga-bearing waste by using a quantitative phase-controlling transition process. In the phase-controlling transition process, the gallium nitride (GaN) and indium (In) are converted to alkali-soluble gallium (III) oxide (Ga2O3) and alkali-insoluble indium oxides (In2O3) by oxidation calcination, while nitrogen is converted into diatomic nitrogen gas instead of ammonia/ammonium (NH3/NH4+). By selective leaching with NaOH solution, nearly 92.65% of Ga can be recycled with a leaching selectivity of 99.3%, while little emissions of NH3/NH4+. Ga2O3 with a purity of 99.97% was obtained from the leachate which is also economy promising by economic assessment. Therefore, the proposed methodology compared to the conventional acid and alkali leaching methods is potentially greener and more efficient process for extracting valuable metals from nitrogen-bearing solid waste.

Celsr3 Inactivation in the Brainstem Impairs Rubrospinal Tract Development and Mouse Behaviors in Motor Coordination and Mechanic-Induced Response.

Inactivation of Celsr3 in the forebrain results in defects of longitudinal axonal tracts such as the corticospinal tract. In this study, we inactivated Celsr3 in the brainstem using En1-Cre mice (Celsr3 cKO) and analyzed axonal and behavioral phenotypes. Celsr3 cKO animals showed an 83% reduction of rubrospinal axons and 30% decrease of corticospinal axons in spinal segments, associated with increased branching of dopaminergic fibers in the ventral horn. Decreases of spinal motoneurons, neuromuscular junctions, and electromyographic signal amplitude of the biceps were also found in mutant animals. Mutant mice had impaired motor coordination and defective response to heavy mechanical stimulation, but no disability in walking and food pellet handling. Transsynaptic tracing demonstrated that rubrospinal axons synapse on spinal neurons in the deep layer of the dorsal horn, and mechanical stimulation of hindpaws induced strong calcium signal of red nuclei in control mice, which was less prominent in mutant mice. In conclusion, Celsr3 regulates development of spinal descending axons and the motor network in cell and non-cell autonomous manners, and the maturation of the rubrospinal system is required for motor coordination and response to mechanical stimulation.

Human adipose tissue- and umbilical cord-derived stem cells: which is a better alternative to treat spinal cord injury?

Multiple types of stem cells have been proposed for the treatment of spinal cord injury, but their comparative information remains elusive. In this study, a rat model of T10 contusion spinal cord injury was established by the impactor method. Human umbilical cord-derived mesenchymal stem cells (UCMSCs) or human adipose tissue-derived mesenchymal stem cells (ADMSCs) (2.5 µL/injection site, 1 × 105 cells/µL) was injected on rostral and caudal of the injury segment on the ninth day after injury. Rats injected with mesenchymal stem cell culture medium were used as controls. Our results show that although transplanted UCMSCs and ADMSCs failed to differentiate into neurons or glial cells in vivo, both significantly improved motor and sensory function. After spinal cord injury, UCMSCs and ADMSCs similarly promoted spinal neuron survival and axonal regeneration, decreased glial scar and lesion cavity formation, and reduced numbers of active macrophages. Bio-Plex analysis of spinal samples showed a specific increase of interleukin-10 and decrease of tumor necrosis factor α in the ADMSC group, as well as a downregulation of macrophage inflammatory protein 3α in both UCMSC and ADMSC groups at 3 days after cell transplantation. Upregulation of interleukin-10 and interleukin-13 was observed in both UCMSC and ADMSC groups at 7 days after cell transplantation. Isobaric tagging for relative and absolute quantitation proteomics analyses showed that UCMSCs and ADMSCs induced changes of multiple genes related to axonal regeneration, neurotrophy, and cell apoptosis in common and specific manners. In conclusion, UCMSC and ADMSC transplants yielded quite similar contributions to motor and sensory recovery after spinal cord injury via anti-inflammation and improved axonal growth. However, there were some differences in cytokine and gene expression induced by these two types of transplanted cells. Animal experiments were approved by the Laboratory Animal Ethics Committee at Jinan University (approval No. 20180228026) on February 28, 2018, and the application of human stem cells was approved by the Medical Ethics Committee of Medical College of Jinan University of China (approval No. 2016041303) on April 13, 2016.

Effects of acid etching and adhesive treatments on host-derived cysteine cathepsin activity in dentin.

PURPOSE: To analyze the effects of different processes during bonding on endogenous cysteine cathepsin activity in dentin. MATERIALS AND METHODS: Dentin powder, prepared from extracted human third molars, was divided into 10 groups. Two lots of dentin powder were used to detect the effects of the procedure of protein extraction on endogenous cathepsin activity. The others were used to study effects of different acid-etching or adhesive treatments on enzyme activity. Concentrations of 37% phosphoric acid or 10% phosphoric acid, two etch-and-rinse adhesive systems, and two self-etching adhesive systems were used as dentin powder treatments. The untreated mineralized dentin powder was set as the control. After treatment, the proteins of each group were extracted. The total cathepsin activity in the extracts of each group was monitored with a fluorescence reader. RESULTS: In the control group, there were no significant differences in cathepsin activity between the protein extract before EDTA treatment and the protein extract after EDTA treatment (p > 0.05). The cathepsin activities of the three different extracts in the 37% phosphoric acid-treated group were different from each other (p < 0.05). The two acid-etching groups and two etch-and-rinse groups showed significant enzyme activity reduction vs the control group (p < 0.05). There were no significant differences between those four groups (p > 0.05). Treating the dentin powder with any of the two self-etching adhesives resulted in an increase in cathepsin activity (p < 0.05). CONCLUSIONS: The activity of cysteine cathepsins can be detected in dentin powder. Treatment with EDTA during protein extraction exerted an influence on cathepsin activity. Acid etching or etch-and-rinse adhesive systems may reduce the activity of endogenous cathepsins in dentin. Self-etching adhesive systems may increase the enzyme activity.

[Effect of baicalein and quercetin on enzymatic resistance of dentin collagen].

OBJECTIVE: To investigate the effect of baicalein and quercetin on the enzymatic resistance of dentin matrix collagen. METHODS: Baicalein, quercetin and proanthocyanidin were dissolved in 20% dimethyl sulfoxide (DMSO) ethanol and prepared into pretreatment agents with a concentration of 50 g/L. Demineralized dentin specimens were prepared and immersed in pretreatment agents at 37 °C for 24 h, then they were digested in solution containing type?collagenase. The pretreatment agents of blank control group and negative control group were 20% DMSO ethanol, blank control group were digested in solution without collagenase. The ultimate tensile strength (UTS) and the hydroxyproline content of enzymolysis liquid in each group were measured respectively after collagenase digestion for 24 h, the dentin collagen morphology were observed under a field emission scanning electron microscopic (FE-SEM) after collagenase digestion for 12 h. RESULTS: After collagenase digestion for 24 h, the baicalein group had the highest UTS [(16.00±1.31) MPa], followed by proanthocyanidin group [(12.64±0.91) MPa], blank control group [(7.84±1.18) MPa], quercetin group [(3.20±1.07) MPa], and negative control group (0 MPa). Significant differences were detected among the UTS in each two group (P < 0.01). The hydroxyproline content in blank control group was the lowest [(0.40 ± 0.16) mg/L], followed by baicalein group[(2.95 ± 0.18) mg/L], proanthocyanidin group [(4.78±0.38) mg/L], quercetin group[(28.22±1.53) mg/L], and negative control group [(34.39±0.39) mg/L]. There were significant differences among the hydroxyproline contents in each group (P < 0.01). After collagenase digestion for 12 h, intact collagen network could be seen in blank control group under a FE-SEM. Collagen network in negative control group suffered nearly complete destruction and collapsed. In quercetin group, most of collagen collapsed. In proanthocyanidin group, a small portion of collagen destruction and collapse could be seen. In baicalein group, collagen network remained intact. CONCLUSIONS: The use of baicalein and quercetin could improve enzymatic resistance of dentin matrix collagen at a concentration of 50 g/L. The effect of baicalein was better than that of proanthocyanidin while the effect of quercetin was weaker than that of proanthocyanidin.