The interaction of RELN-DNMT genes involving in neurotrophin signaling pathway contributes to schizophrenia susceptibility.

OBJECTIVE: Schizophrenia belongs to a severe mental illness with complicated clinical presentations, an ill-defined pathogenesis, and no known cause. Many genetic studies imply that polygenic interaction is important in the development of schizophrenia. The main mechanism of the RELN-BDNF-CREB-DNMT signaling pathway in neurodevelopment involves RELN, brain-derived neurotrophic factor (BDNF), transcription factor cyclic adenosine monophosphate response element binding protein (CREB), DNA methyltransferase 1 (DNMT1), as well as DNA methyltransferase 3B (DNMT3B). An early case-control research on 15 polymorphisms in the RELN, CREB, BDNF, DNMT1, and DNMT3B genes was done. A single gene variation has little effect on the pathogenesis of schizophrenia, but the combination of intergenic variation loci has a bigger impact because schizophrenia is a complex polygenic disorder. The objective of the current study sought to explore the impact of genetic interactions between RELN, BDNF, CREB, DNMT1, and DNMT3B on schizophrenia in order to further highlight the genetic factors influencing the risk of schizophrenia. METHODS: Taking the case-control study design, with the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) to be the evaluation norm, 134 individuals suffering from schizophrenia hospitalized in the Third People's Hospital of Zhongshan City within January 2018 to April 2020 (case group) were selected, and 64 healthy individuals (control group) from the same geographical area had been chosen as well. MassArray identified DNMT1 gene single nucleotide polymorphisms (rs2114724 and rs2228611) and DNMT3B gene SNPs (rs2424932, rs1569686, rs6119954, and rs2424908). Using the generalized multifactor dimensionality reduction (GMDR), the RELN-BDNF-CREB-DNMT pathway's gene interactions were examined for their impact on schizophrenia. RESULTS: GMDR analysis showed that the three-order interaction model RELN (rs2073559, rs2229864)-DNMT3B (rs2424908) was the optimal model (p = 0.001), with the consistency of cross-validation of 10/10 and the test accuracy of 0.8711. CONCLUSION: The interaction between the RELN (rs2073559, rs2229864)-DNMT3B (rs2424908) may be related to schizophrenia, and large sample sizes should be verified in different population.

Association of NUDT15 gene polymorphism with adverse reaction, treatment efficacy, and dose of 6-mercaptopurine in patients with acute lymphoblastic leukemia: a systematic review and meta-analysis.

6-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene polymorphism on the risk of myelosupression, hepatotoxicity and interruption of 6-MP, as well as treatment efficacy and dose of 6-MP in ALL patients. A total of 24 studies with 3,374 patients were included in this meta-analysis. We found 9-fold higher risk of 6-MP induced leukopenia (odds ratio [OR] =9.00, 95% confidence interval [CI]: 3.73-21.74) and 2.5-fold higher risk of 6-MP-induced neutropenia (OR=2.52, 95% CI: 1.72-3.69) for NUDT15 c.415C>T variant carriers in the dominant model. Moreover, we found that the dose intensity of 6-MP in ALL patients with one NUDT15 c.415C>T variant alleles (CT) was 19% less than that in wild-type patients (CC) (mean differences: 19.43%, 95% CI: -25.36 to -13.51). The tolerable dose intensity of 6-MP in NUDT15 c.415C>T homozygote variant (TT) and heterozygote variant (CT) carriers was 49% and 15% less than that in wild-type patients, respectively. The NUDT15 c.415C>T variant group (CT+TT) had seven times (OR=6.98, 95% CI: 2.83-17.22) higher risk of developing 6-MP intolerance than the CC group. However, NUDT15 c.415C>T polymorphism did not appear significantly associated with hepatotoxicity, treatment interruption or relapse incidence. We concluded that NUDT15 c.415C>T was a good predictor for 6-MP-induced myelosuppression in ALL patients. The dose intensity of 6-MP in ALL patients with NUDT15 c.415C>T variants was significantly lower than that in wild-type patients. This research provided a basis for further investigation into relations between NUDT15 gene and adverse reaction, treatment efficacy and dose intensity of 6-MP.

Adverse drug events in Chinese elder inpatients: a retrospective review for evaluating the efficiency of the Global Trigger Tool.

Background: Elderly patients frequently experience a high incidence of adverse drug events (ADEs) due to the coexistence of multiple diseases, the combination of various medications, poor medication compliance, and other factors. Global Trigger Tool (GTT) is a new method for identifying ADEs, introducing the concept of a trigger, that is, clues including abnormal laboratory values, reversal drugs, and clinical symptoms that may suggest ADEs, and specifically locating information related to ADEs in the medical record to identify ADEs. The aim of this study was to establish a GTT-based trigger tool for adverse medication events in elderly patients and to investigate the risk variables associated with such events. Methods: The triggers were identified by reviewing the frequency of ADEs in elderly patients in Sichuan, China, retrieving relevant literature, and consulting experts. A retrospective analysis was carried out to identify adverse medication occurrences among 480 elderly inpatients in Sichuan People's Hospital. Results: A total of 56 ADEs were detected in 51 patients (10.62%), 13.04 per 1,000 patient days, and 11.67 per 100 admissions. The overall positive predictive value (PPV) of the triggers was 23.84, and 94.64% of ADEs caused temporary injury. Gastrointestinal system injury (27.87%) and metabolic and nutritional disorders (24.53%) were the primary organ-systems affected by ADEs. The majority of ADEs were caused by drugs used to treat cardiovascular diseases. 71.43% of ADE occurred within 2 days of administration and the risk factor analysis of ADE revealed that the number of medicines had a significant correlation. Conclusion: This study demonstrated GTT's value as a tool for ADEs detection in elderly inpatients in China. It enhances the level of medication management and comprehensively reflects the situation of ADE of the elderly.

Association between healthy lifestyle factors and health-related quality of life among Chinese adolescents: the moderating role of gender.

BACKGROUND: To examine the associations of the independent and combined healthy lifestyle factors with health-related quality of life (HRQOL) in adolescents, and to test the moderating role of gender. METHODS: This cross-sectional study included 5125 adolescents aged between 11 and 20 years. They provided self-reported data on six healthy lifestyle factors, including never smoking, never drinking, good sleep quality, sufficient sleep duration, appropriate Internet use, and adequate physical activity. Adolescents' HRQOL was evaluated using the Pediatric Quality of Life Inventory version 4.0. Linear regression models were conducted to explore the association of individual and combined healthy lifestyle factors with adolescents' HRQOL. We further performed stratified analyses and likelihood ratio test to explore the moderating role of gender in these associations. RESULTS: Of the included adolescents, the proportions with 0-2, 3, 4, and 5-6 healthy lifestyle factors were 13.6%, 26.4%, 44.3%, and 15.7%, respectively. Compared to adolescents with composite healthy lifestyle scores of 0-2, those with scores of 3, 4, or 5-6 had significantly higher HRQOL scores across all dimensions, summary scales, and total scale in both unadjusted and adjusted models. Specifically, adolescents with 5-6 healthy lifestyle factors had a total scale score that was 19.03 (95%CI: 17.76 to 20.30) points higher than their counterparts who only had 0-2 healthy lifestyle factors. Significant dose-response patterns were also observed in aforementioned associations. Gender was a significant moderator in the associations between composite healthy lifestyle groups and HRQOL scores, except for the social functioning dimension. CONCLUSIONS: Our results confirmed that combined healthy lifestyle factors were associated with improved HRQOL among adolescents, with a stronger association observed in girls. These findings underscore the necessity for education and healthcare authorities to design health-promoting strategies that encourage multiple healthy lifestyle factors in adolescents, with the objective of enhancing their overall health outcomes.

Mechanistic study of the effect of potassium ferrate and straw fiber on the enhancement of strength in cement-based solidified municipal sludge.

The high content of organic matter in sludge is the primary reason for the poor solidifying effect and excessive dosage of the cement base. In this study, potassium ferrate and straw fiber are utilized to synergistically enhance the solidifying effect of the cement and elaborate the strength mechanisms. Among them, potassium ferrate was selected to oxidize and crack the structure of organic matter in sludge and consume part of organic matter; straw fiber was used as an adsorption material to absorb some of the organic material and reduce its interference with the cement hydration reaction; the skeleton function of straw fiber in solidified sludge was used to improve the final solidified sludge strength. It is shown that the presence of these two additives significantly improved the cement solidification strength and reduced the moisture content of the solidified body. Moreover, the moisture content and strength followed an obvious linear relationship (adjusted R2 = 0.92), with the strength increasing as the moisture content decreased. After pretreatment with potassium ferrate, the free water content in the dewatered sludge increased by 4.5%, which was conducive to the adequate hydration reaction with cement. The analysis using X-ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDS), and mercury intrusion porosimetry (MIP) revealed potassium ferrate synergizes with straw fibers to promote the production of hemihydrate gypsum and gismondine. However, hemihydrate gypsum, calcium carbonate, and gismondine resulted in structural swelling, which was confirmed by the microscopic morphology and pore structure analysis. However, the adverse effects due to swelling were offset by the increase in strength brought by the above crystalline substances.

Sapap4 deficiency leads to postsynaptic defects and abnormal behaviors relevant to hyperkinetic neuropsychiatric disorder in mice.

Postsynaptic proteins play critical roles in synaptic development, function, and plasticity. Dysfunction of postsynaptic proteins is strongly linked to neurodevelopmental and psychiatric disorders. SAP90/PSD95-associated protein 4 (SAPAP4; also known as DLGAP4) is a key component of the PSD95-SAPAP-SHANK excitatory postsynaptic scaffolding complex, which plays important roles at synapses. However, the exact function of the SAPAP4 protein in the brain is poorly understood. Here, we report that Sapap4 knockout (KO) mice have reduced spine density in the prefrontal cortex and abnormal compositions of key postsynaptic proteins in the postsynaptic density (PSD) including reduced PSD95, GluR1, and GluR2 as well as increased SHANK3. These synaptic defects are accompanied by a cluster of abnormal behaviors including hyperactivity, impulsivity, reduced despair/depression-like behavior, hypersensitivity to low dose of amphetamine, memory deficits, and decreased prepulse inhibition, which are reminiscent of mania. Furthermore, the hyperactivity of Sapap4 KO mice could be partially rescued by valproate, a mood stabilizer used for mania treatment in humans. Together, our findings provide evidence that SAPAP4 plays an important role at synapses and reinforce the view that dysfunction of the postsynaptic scaffolding protein SAPAP4 may contribute to the pathogenesis of hyperkinetic neuropsychiatric disorder.

Feedback Interaction Between Apelin and Endoplasmic Reticulum Stress in the Rat Myocardium.

ABSTRACT: Apelin is an endogenous active peptide, playing a crucial role in regulating cardiovascular homeostasis. This study aimed to investigate the interaction between apelin and endoplasmic reticulum stress (ERS). Tunicamycin (Tm) and dithiothreitol (DTT) were used to induce ERS in the ex vivo cultured myocardium of rats. Myocardial injury was determined by the activities of lactate dehydrogenase and creatine kinase-MB in the culture medium. The protein levels of an ERS-associated molecule, apelin, and its receptor angiotensin domain type 1 receptor-associated proteins (APJ) in the myocardium were determined by western blot analysis. The level of apelin in the culture medium was determined by enzyme immunoassay. Administration of Tm and DTT triggered ERS activation and myocardial injury, and led to a decrease in protein levels of apelin and APJ, in a dose-dependent manner. Integrated stress response inhibitor, an inhibitor of eukaryotic initiation factor 2α phosphorylation that is commonly used to prevent activation of protein kinase R-like ER kinase cascades, blocked ERS-induced myocardial injury and reduction of apelin and APJ levels. The ameliorative effect of integrated stress response inhibitor was partially inhibited by [Ala]-apelin-13, an antagonist of APJ. Furthermore, apelin treatment inhibited activation of the 3 branches of ERS induced by Tm and DTT in a dose-dependent manner, thereby preventing Tm-induced or DTT-induced myocardial injury. The negative feedback regulation between ERS activation and apelin/APJ suppression might play a critical role in myocardial injury. Restoration of apelin/APJ signaling provides a potential target for the treatment and prevention of ERS-associated tissue injury and diseases.

Associations of excessive screen time and early screen exposure with health-related quality of life and behavioral problems among children attending preschools.

BACKGROUND: Both excessive screen time and early screen exposure have been linked to children's health outcomes, but few studies considered these two exposures simultaneously. The aim of this study was to explore the independent and interactive associations of excessive screen time and early screen exposure with health-related quality of life (HRQOL) and behavioral problems among Chinese children attending preschools. METHODS: A cross-sectional study of 4985 children aged between 3 and 6 years was conducted in Chengdu, China. Each parent has finished an online questionnaire regarding their children's screen use, HRQOL, and behavioral problems. Children with screen time over 1 h/day were considered as having excessive screen time. Early screen exposure was defined if the children had started using screen-based media before the age of 2 years. HRQOL was assessed by the Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0), while behavioral problems were confirmed with the 48-item Conners' Parent Rating Scale (CPRS-48). RESULTS: Of the 4985 children (2593 boys and 2392 girls) included, the mean age was 4.6 (SD: 1.0) years. After adjustment for confounders and early screen exposure, excessive screen time was significantly associated with worse HRQOL scores in all dimensions and summary scales, as well as each type of behavioral problems (all p values < 0.05). We also found that compared to children with later initiation of screen exposure, those with screen use before the age of 2 years had significantly lower emotional functioning score (ß: - 2.13, 95%CI: - 3.17, - 1.09) and psychosocial health summary score (ß: - 0.82, 95%CI: - 1.54, - 0.10) of HRQOL, as well as higher risks of conduct problems, learning problems, psychosomatic problems, impulsive-hyperactive, and hyperactivity index, which were independent of excessive screen use. Furthermore, there were significant interactive effects of excessive screen time and early screen exposure on emotional functioning domain of HRQOL scores and conduct problems. CONCLUSION: Excessive screen time and early screen exposure are two independent and interactive factors to children's HRQOL and behavioral problems. Our findings support current guidelines to limit screen exposure in children. Appropriate screen use may represent an important intervention target to improve children's HRQOL and reduce their behavioral problems.

Effects of Melatonin for Delirium in Elderly Acute Heart Failure Patients: A Randomized, Single-Center, Double-Blind, and Placebo-Controlled Trial.

BACKGROUND: Delirium is a common, life-threatening, typical clinical syndrome with the main clinical manifestations of temporary organic mental disorder without specific drug treatment. The aim of the study was to explore the benefits of melatonin for the treatment of delirium after acute heart failure in elderly patients. METHODS: This was a randomized, double-blind, and placebo-controlled trial. This study enrolled patients aged more than 60 years after acute heart failure. A computer-generated randomization sequence (in a 1:1 ratio) was used to randomly assign patients to receive either melatonin (3 mg/day, 7 days) or placebos. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method during the first 7 days. Analyses were performed by intention-to-treat and safety populations. RESULTS: Between October 2015 and October 2019, 584 patients were assessed. A total of 497 patients randomly were assigned to receive either placebo (N = 249) or melatonin (N = 248). The incidence of delirium was significantly lower in the melatonin group than in the placebo group (27.0% vs. 36.9%, P = 0.021). Regarding safety, the occurrence of rhabdomyolysis and abnormal hepatic function did not differ between the two groups. CONCLUSION: The current study (clinical trial registered number: CHWX-904-201511) suggests that acute melatonin treatment can reduce the incidence of delirium for elderly acute heart failure. It also can reduce the time of hospital stays and hospitalization costs. The therapy was safe and worth spreading.

Sensitive fluorescent biosensor based on a europium-based metal-organic framework for protein kinase activity analysis.

Protein kinases play crucial regulatory roles in the physiological activities in the human body. Understanding protein kinase activity and its inhibition is essential for the management of human diseases. Considering the limitations of the existing protein kinase-related analysis methods, the aim of the present study was to develop a fluorescent biosensor based on Eu(BTC) (H2O)6 (BTC = 1,3,5-Benzenetricarboxylic acid) for evaluating protein kinase activity and the relevant inhibitors. A fluorophore-labelled substrate polypeptide was phosphorylated under the catalysis of protein kinase. This phosphorylated peptide can be coordinated explicitly with the europium site of Eu(BTC) (H2O)6 to detect the protein kinase. The developed biosensor performed well, with a detection limit of 0.00003 U µL-1, and it showed good selectivity and universality. Protein kinase activity could also be detected in MCF-7 cells using this method. Furthermore, in terms of inhibitor screening using the Eu(BTC) (H2O)6-based sensor, both H-89 and ellagic acid were found to inhibit protein kinase activity with IC50 values of 1.09 and 19.88 nmol L-1, respectively. Overall, this biosensor has broad application prospects in monitoring and controlling protein kinase activity.

Adenylyl cyclase 3 deficiency results in dysfunction of blood-testis barrier during mouse spermiogenesis.

Human infertility has become a global medical and social health problem. Mice deficient in type 3 adenylyl cyclase (AC3), a key enzyme that synthesizes cyclic adenosine monophosphate (cAMP), develop male infertility, although the underlying molecular mechanisms remain unknown. We performed a label-free quantitative (LFQ) proteomics analyses to identify testicular differentially expressed proteins (DEPs) and their respective biological processes. Furthermore, histological examination demonstrated that AC3 deficiency in mice led to mild impairment of spermatogenesis, including the thinning of seminiferous epithelium and local lesions in the testis. We further identified that the integrity of the blood-testis barrier (BTB) was impaired in AC3 knockout (AC3-/-) mice accompanied with the reduction in the expression of tight junctions (TJs) and ectoplasmic specialization (ESs)-related proteins. In addition, the deletion of AC3 in mice also reduced the germ cell proliferation, increased apoptosis, and decreased lipid deposition in the seminiferous tubules. Collectively, our results revealed a role of AC3 in regulating the BTB integrity during spermatogenesis. Thus, our findings provide new perspectives for future research in male infertility.

Telomere length in peripheral leukocytes is a sensitive marker for assessing genetic damage among workers exposed to isopropanol, lead and noise: the case of an electronics manufacturer.

BACKGROUND: Workers in electronics manufacturers may be exposed to various occupational hazards such as isopropanol, lead, and noise. Telomeres are special segments of cap-like DNA protein complex at end of liner chromosomes in eukaryotic cells. Telomere length is a potential marker of genetic damage. The aim of this study is to evaluate the effect of occupational hazards on the relative telomere length (rTL) of peripheral blood cells of workers in an electronics manufacturer, and to explore whether relative telomere length could be a biomarker for assessing genetic damage in the electronics manufacturing industry. METHODS: We investigated a large-scale electronics manufacturer in the Pearl River Delta Region. We ultimately collected 699 qualified workers (248 with isopropanol exposure, 182 with lead exposure, 157 with noise exposure, and 112 controls). During physical examination of the workers, we gave them questionnaires to understand their health statuses and living habits. We also collected peripheral blood samples from these workers to test exposure levels and rTL in the leucocytes. RESULTS: The concentrations of air isopropanol in all monitored workshops was 25.3 mg/m3 and air lead smoke was 0.020 mg/m3. The maximum equivalent continuous A sound level noise exposure position was 82.2dB (A). All were lower than those in the Occupational Exposure Limits in Workplaces in China. Urinary acetone in the isopropanol exposed group was 1.04 (0, 1.50) mg/L, and cumulative urinary acetone was 1.48 (0, 5.09) mg-years/L. Blood lead levels (BLLs) were 28.57 (22.77, 37.06) µg/dL, and cumulative blood lead levels (CBLLs) were 92.75 (55.47, 165.13) µg-years/dL. rTL was different between occupational exposed workers and controls: rTL was 0.140 units (95 % CI: 0.022, 0.259) shorter in lead exposed workers and 0.467 units (95 % CI: 0.276-0.658) shorter in noise exposed workers compared to the controls. There is no statistical difference in rTL between isopropanol exposure workers and the controls. In order to elucidate the relationship between rTL and occupational hazards exposure, we divided the isopropanol exposure workers into three groups (0, ~1.43 mg/L, and >1.43 mg/L). None of the rTL difference was statistically significant among exposed workers at different uroacetone levels (P>0.05). The groups with ≥100 µg/dL blood lead had shorter rTL than the group with blood lead below 100 µg/dL (F=4.422, P=0.013). We incorporated age, gender, birthplace, race, education level, smoking, and alcohol consumption into the linear regression equation. Only blood lead concentration (X) was entered into the regression equation, yielding a multivariate linear regression equation of Y=0.397-0.124X (F=8.091, P=0.005). Workers with different hearing loss also had statistically significant differences in rTL (F=5.731, P=0.004). rTL was a protective factor for the occurrence of noise-induced hearing loss (NIHL). The longer the rTL, the lower the risk of NIHL [OR=0.64 (0.42, 0.98)]. CONCLUSIONS: rTL was shorter in lead exposed workers and noise exposed workers, and it was a protective factor for the occurrence of the noise-induced hearing loss. Thus, rTL of peripheral blood may be a sensitive marker of genetic damage among workers in environments with lead and noise exposure.

Efficacy of Ligustrazine Injection as Adjunctive Therapy in Treating Acute Cerebral Infarction: A Systematic Review and Meta-Analysis.

Background: Ligustrazine injection has been widely used as adjunctive therapy in the treatment of acute cerebral infarction (ACI) during the past decades in China, but its clinical efficacy is not yet well confirmed. This study aims to evaluate the efficacy of ligustrazine injection as adjunctive therapy for ACI. Methods: Databases including China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), PubMed, Medline, Google Scholar, Chinese Biomedical Literature Database, Cochrane Library, Embase, Sino-Med, Wanfang Database, and Chinese Science Citation Database were systematically searched for the published randomized controlled trials (RCTs) on ligustrazine injection in the treatment of ACI until November 2020. Meta-analysis was performed on the primary outcome measure (i.e., clinical effective rate) and the secondary outcome measure [i.e., neurological deficit score (NDS), fibrinogen, low shear blood viscosity (LBV), and high shear blood viscosity (HBV)]. The quality of the included RCTs was assessed according to the M scoring system (the refined Jadad scale). Sensitivity analysis and subgroup analysis were conducted according to the methodological quality, years of publication, and sample size. Results: Nineteen RCTs, containing 2022 patients, were included in this study. Meta-analysis indicated that ligustrazine injection combined with Western medicine could achieve a better effect in the treatment of ACI than using Western medicine alone in terms of clinical effective rate (RR = 1.24; 95% CI, 1.19-1.29), NDS (MD = -3.88; 95%CI, -4.51 to -3.61), fibrinogen (MD = -0.59; 95% CI, -0.76 to -0.42), LBV (MD = -2.11; 95% CI, -3.16 to -1.06), and HBV (MD = -0.88; 95% CI, -1.20 to -0.55). Conclusions: This research indicated that ligustrazine injection as adjunctive therapy seemed to be more effective than using western medicine alone in treating ACI. However, more evidence is required to confirm the efficacy of ligustrazine injection due to the low methodological quality of the included RCTs.

A Risk Scoring Model for High-Dose Methotrexate-Induced Liver Injury in Children With Acute Lymphoblastic Leukemia Based on Gene Polymorphism Study.

A study on 70 acute lymphoblastic leukemia (ALL) children (age ≤16 years) treated with high-dose methotrexate (HD-MTX) in Sichuan Provincial People's Hospital was conducted. The aim of the study was to establish a risk-scoring model to predict HD-MTX-induced liver injury, considering gene polymorphisms' effects. Data screening was performed through t-test, chi-square test, and ridge regression, and six predictors were identified: age, MTRR_AA, MTRR_AG, SLCO1B1_11045879_CC, albumin_1 day before MTX administration, and IBIL_1 day before MTX administration (p < 0.1). Then, the risk-scoring model was established by ridge regression and evaluated the prediction performance. In a training cohort (n = 49), the area under the curve (AUC) was 0.76, and metrics including accuracy, precision, sensitivity, specificity, positive predictive value, and negative predictive value were promising (0.86, 0.81, 0.76, 0.91, 0.81, 0.88, respectively). In a test cohort (n = 21), the AUC was 0.62 and negative predictive value was 0.80; other evaluation metrics were not satisfactory, possibly due to the limited sample size. Ultimately, the risk scores were stratified into three groups based on their distributions: low- (≤48), medium- (49-89), and high-risk (>89) groups. This study could provide knowledge for the prediction of HD-MTX-induced liver injury and reference for the clinical medication.

The type 3 adenylyl cyclase is crucial for intestinal mucosal neural network in the gut lamina propria.

BACKGROUND: The type 3 adenylyl cyclase (AC3) enzyme is involved in the synthesis of cyclic adenosine monophosphate (cAMP). It is primarily expressed in the central nervous system (CNS) and plays a crucial role in neurogenesis and neural dendritic arborization. However, the AC3's functional role in the gastrointestinal tract remains ambiguous. METHODS: AC3 expression in enteric tissue of AC3+/+ mice was investigated using immunohistochemistry and RT-PCR. AC3 knock-out mice (AC3-/- ) were used to examine the effect of AC3 on the enteric nervous system (ENS) function and the number of cilia and apoptotic cells. Additionally, total gastrointestinal transit time and colonic motility were compared between the AC3-/- and AC3+/+ groups of mice. KEY RESULTS: AC3 was predominately expressed in the myenteric plexus of the large intestine. Colonic-bead expulsion analysis showed accelerated propulsion in the large intestine of the AC3-/- mice. The AC3-/- mice demonstrated reduced nerve fibers and enteric glial cells count in colonic mucosa compared to the AC3+/+ mice. Furthermore, AC3-/- mice exhibited increased cellular apoptosis and reduced ARL13B+ cilium cells in the colonic lamina propria compared to the AC3+/+ mice. CONCLUSIONS: In AC3-/- mice, innervation of the lamina propria in the colonic mucosa was reduced and colonic propulsion was accelerated. AC3 is crucial for the development and function of the adult neural network of ENS. AC3 deficiency caused atrophy in the colonic mucosal neural network of mice.

An Optimum Deployment Algorithm of Camera Networks for Open-Pit Mine Slope Monitoring.

With the growth in demand for mineral resources and the increase in open-pit mine safety and production accidents, the intelligent monitoring of open-pit mine safety and production is becoming more and more important. In this paper, we elaborate on the idea of combining the technologies of photogrammetry and camera sensor networks to make full use of open-pit mine video camera resources. We propose the Optimum Camera Deployment algorithm for open-pit mine slope monitoring (OCD4M) to meet the requirements of a high overlap of photogrammetry and full coverage of monitoring. The OCD4M algorithm is validated and analyzed with the simulated conditions of quantity, view angle, and focal length of cameras, at different monitoring distances. To demonstrate the availability and effectiveness of the algorithm, we conducted field tests and developed the mine safety monitoring prototype system which can alert people to slope collapse risks. The simulation's experimental results show that the algorithm can effectively calculate the optimum quantity of cameras and corresponding coordinates with an accuracy of 30 cm at 500 m (for a given camera). Additionally, the field tests show that the algorithm can effectively guide the deployment of mine cameras and carry out 3D inspection tasks.

Type 3 adenylyl cyclase in the main olfactory epithelium participates in depression-like and anxiety-like behaviours.

BACKGROUND: Deficiency of olfaction is thought to be associated with depression, and type 3 adenylyl cyclase (AC3) genetic knockout and forebrain knockout mice show depression-like behaviours. AC3 is expressed in the main olfactory epithelium (MOE) and hippocampus, which plays an important role in olfactory signal transduction. However, it is unclear whether AC3 in the MOE also plays a role in the pathogenesis of depression. Thus, we aimed to study the relationship between AC3 in the MOE and the pathogenesis of depression. METHODS: We obtained anosmic mice by intranasal perfusion of zinc sulphate (ZnSO4) (ZnSO4 mice), and distinctively knocked down AC3 in the MOE (AC3KD/MOE mice) by CRISPR/cas9 technology. Behavioural tests related to depression and anxiety were employed to evaluate the depression- and anxiety-like behaviours of mice. The mRNA and protein expressions of tyrosine hydroxylase (TH), dopamine receptors (Drds), and N-Methyl D-aspartate receptor subunit 2B (GluN2B) in the hippocampus of mice were investigated by qPCR and western blotting to explore the mechanism of depression and anxiety caused by AC3 in the MOE, preliminarily. RESULTS: Compared with NaCl mice, ZnSO4 mice exhibited depression-like behaviours in tail suspension tests (TST), forced swimming tests, and social (FST) interaction tests (SIT), but showed no anxiety-like behaviours in anxiety-related behavioural tests. The mRNA and protein expressions of Drd3 and GluN2B in the hippocampus of ZnSO4 mice were significantly downregulated. Compared with the negative control mice (NC mice), AC3KD / MOE mice showed depression-like behaviours in TST, FST, and SIT tests, anxiety-like behaviours in light/dark transition test, elevated-plus maze test, and novelty-suppressed feeding test. The protein expressions of Drd3, TH, and GluN2B were significantly downregulated in the hippocampus. LIMITATIONS: We did not further demonstrate that AC3 in the MOE causes depression through the dopaminergic nervous system with dopamine or dopamine receptor agonists. CONCLUSIONS: Our data demonstrate that intranasal infusion of ZnSO4 can cause depression-like behaviours and has no effect on anxiety-like behaviours. Specific knockdown of AC3 in the MOE can cause depression-like and anxiety-like behaviours. The behavioural changes caused by intranasal ZnSO4 and specific knockdown of AC3 in the MOE can be related to the significant downregulation of dopaminergic system and GluN2B expressions in the hippocampus of mice.

Type 3 adenylyl cyclase in the MOE is involved in learning and memory in mice.

Although olfactory dysfunction is related to learning and memory impairment, the causal relationship between main olfactory epithelium (MOE) disruption and learning and memory is still unknown. The present study aimed to establish whether MOE disruption causes learning and memory impairment and whether the expression of type 3 adenylyl cyclas (AC3) in the MOE is related to learning and memory. First, the buried food test was carried out to confirm that MOE function was disrupted in mice treated with nasal instillation of zinc sulfate (ZnSO4 mice), and mice with specific knockdown of AC3 in the MOE by CRISPR/Cas9 technology (AC3KD/MOE mice). Then, behavioural tasks associated with learning and memory were administered. ZnSO4 mice and AC3KD/MOE mice showed impairments in learning and memory tests, including the novel object recognition test, the step-down passive avoidance test, the Morris water maze test, and the Y-maze test. Our data demonstrate that MOE disruption caused by nasal exposure to ZnSO4 or specific knockdown of AC3 in the MOE resulted in learning and memory impairment, and they further demonstrate that the expression of AC3 in the MOE plays a major role in learning and memory.

Ultraviolet nanolaser of inverted hexagonal ZnO pyramid resonating in helical whispering-gallery-like mode.

ZnO nanocavities have advantage to working as optoelectrical nanodevices integrated on chip at high temperature owing to high exciton binding energy. In this work, a single inverted hexagonal ZnO pyramid (HZOP) nanolaser is fabricated successfully by reducing the defect with chemical vapor deposition (CVD). The optical leakage of HZOP is conquered by the inverted configuration to increase the refractive index contrast between ZnO pyramid and surrounding media. Helical whispering-gallery-like mode is proposed to dominate the lasing of HZOP nanolaser. All of the lasing peaks are found to exist at wavelength longer to the fluorescence emission of ZnO, which is ascribed to the large loss represented by the large imaginary part of ZnO refractive index at shorter wavelength. The threshold and linewidth are measured to be 5.27 mJ/cm2 and 0.27 nm, respectively. HZOP nanolaser is a new ultraviolet coherent light source to be integrated on chip at room temperature or higher temperature.

Temperature-Dependent Lasing of CsPbI3 Triangular Pyramid.

In this work, the lasing performance of a microsized single-crystal CsPbI3 triangular pyramid (MSCTP) is evaluated by measuring the lasing threshold at low temperature. The MSCTPs of well-defined facets are synthesized on a Si/SiO2 substrate with chemical vapor deposition. The MSCTP shows a spontaneous emission around 719 nm at room temperature and a stimulated emission resonant in a single Fabry-Perot mode within 148-223 K. The lasing threshold varies from 21.56 to 53.15 µJ/cm2 and presents a temperature dependence in an empirical exponential function with a characteristic temperature of 72.73 K. The temperature dependence of lasing behavior is ascribed to the competition between the exciton binding energy and thermal disturbance energy of CsPbI3. The results of this work provide us a perspective to engineer and optimize optoelectrical devices based on perovskite materials and a microsized optical cavity to investigate the light-matter interaction in quantum optics.