Surface microtopography and micromechanics of various rank coals

For a long time,coalbed gas has brought about various problems to the safety of coal mine production.In addition,the mining of gas and coalbed methane(CBM)has attracted much attention.The occurrence and migration of CBM are believed to be closely related to the micro-surface properties of coal.To further explore the characteristics of CBM occurrence and migration,in this study,the micro-surface topography,adhesion,and elastic modulus of five metamorphic coals were measured by atomic force microscopy(AFM).The results show that the microtopography of coal fluctuates around 40 nm,reaching a maximum of 66.5 nm and the roughness of the surface decreases with the increase of metamorphism.The elastic modulus of coal micro-surface varies from 95.40 to 9626.41 MPa,while the adhesion varies from 15.08 to 436.22 nN,and they both exhibit a trend of"M"shape with the increase of metamorphism.Furthermore,a high correlation exists between adhesion and microtopography fluctuation.In most cases,the adhesion is larger in the concavity area and smaller in the convexity area.The research results may provide a new method for revealing the occurrence and migration of CBM and ensure efficient and safe CBM exploitation.

Design and Analysis of Traffic Information Transmission System Based on Visible Light Communication

Visible Light Communication( VLC) based on LED is a new wireless communication technology with high response rate and good modulation characteristics in the wavelengths of 380- 780 nm. Compared with conventional methods,the waveband of VLC is harmless to human and safe to communication because of no magnetism radiation. An audio information transmission system using LED traffic lights is presented based on VLC technology. The system is consisted of transmitting terminal,receiving terminal and communication channel. Some experiments were made under real communication environment. The experimental results showed that the traffic information transmission system works steadily with good communication quality and achieves the purpose of transmitting audio information through LED traffic lights,with a data transfer rate up to 250 kbps over a distance of 5 meters.

Effects of mucosolvan combined with fiberoptic bronchoscopy on respiratory function, inflammatory response and stress state in patients with severe pneumonia

Objective: To investigate the effect of mucosolvan combined with fiberoptic bronchoscopy on respiratory function, inflammatory response and stress state in patients with severe pneumonia. Methods: From January 2017 to June 2018, 82 patients with severe pneumonia were randomly divided into observation group and control group (all 41 cases). Patients in the control group received conventional anti-infective treatment, and the observation group was treated with fiberoptic bronchoscopy combined with mucosolvan on the basis of the control group. Respiratory function, inflammatory response and stress status were compared between the two groups. Results: Before treatment, there was no significant difference in Cdyn, WOB and PaO2/FiO2 between the two groups. After treatment, Cdyn and PaO2/FiO2 in the observation group were (36.28±4.28) mL/cmH2O and (376.23±24.21) mmHg respectively, while those in the control group were (26.89±3.76) mL/cmH2O and (322.12±23.16) mmHg, respectively. The levels of Cdyn and PaO2/FiO2 in the observation group were higher than those in the control group. After treatment, the WOB in the observation group was (7.81±0.72) J/L, and the WOB in the control group was (8.33±1.23) J/L. WOB of both groups was lower than that before treatment, and in observation group WOB was lower than that of control group, the difference was statistically significant. In CRP, PCT and sTREM-1 levels, there was no significant difference between the two groups before treatment. After treatment, CRP, PCT and sTREM-1 in the observation group were (39.10±6.03) mg/L, (14.57±2.05) ng/L, (15.02±3.02) ng/L respectively, while those in the control group were (59.72±8.81) mg/L, (20.03±3.09) ng/L, (34.21±5.28) ng/L, respectively. CRP, PCT, sTREM-1 in both groups were lower than those before treatment, and CRP, PCT, sTREM-1 in observation group were lower than those in control group. Before treatment, there was no significant difference with Cor, Ang-I and Ang-II in two groups. After treatment, the levels of Cor, Ang-I and Ang-II in the observation group were (114.76±15.85) ng/mL, (6.72±0.64) ng/mL, (27.28±3.43) ng/mL respectively, while those in the control group were (193.15±22.64) ng/mL, (12.10±1.68) ng/mL, (43.02±5.57) ng/mL, respectively. In the observation group, the levels of Cor, Ang-I and Ang-II were lower than those in the control group. Conclusion: Mucosolvan combined with fiberoptic bronchoscopy can effectively improve the respiratory function of patients with severe pneumonia, and reduce inflammation and stress state of the body.

Alport syndrome combined with lupus nephritis in a Chinese family:A case report

BACKGROUND Alport syndrome(ATS)is a rare hereditary disease caused by mutations in genes such as COL4A3,COL4A4,and COL4A5.ATS involves a spectrum of phenotypes ranging from isolated hematuria that is nonprogressive to progressive renal disease with extrarenal abnormalities.Although ATS can be combined with other diseases or syndromes,ATS combined with lupus nephritis has not been reported before.CASE SUMMARY A Chinese family with ATS was recruited for the current study.Clinical characteristics(including findings from renal biopsy)of ATS patients were collected from medical records,and potential causative genes were explored by whole-exome sequencing.A heterozygous substitution in intron 22 of COL4A3(NM_000091 c.2657-1G>A)was found in the patients,which was further confirmed by quantitative polymerase chain reaction.CONCLUSION Heterozygous substitution of a COL4A3 gene splice site was identified by wholeexome sequencing,revealing the molecular pathogenic basis of this disorder.In general,identification of pathogenic genes can help to fully understand the molecular mechanism of disease and facilitate precise treatment.

Effects of intensive insulin therapy on immune function, inflammatory markers, matrix metalloproteinase and stress response in patients with severe pneumonia

Objective:To explore the effects of intensive insulin therapy on immune function, inflammatory markers, matrix metalloproteinase and stress response in patients with severe pneumonia.Methods: From January 2016 to December 2017, 80 cases of severe pneumonia in ICU of our hospital were selected as the subjects of this study, according to the principle of randomization, they were divided into control group (40 cases) and observation group (40 cases). The control group was given routine insulin + routine treatment, and the observation group was given insulin intensification + routine treatment. The changes of immune function, inflammation index, matrix metalloproteinase and stress level were compared between the two groups before and after treatment.Results: After treatment, the levels of IgA, IgG and IgM in the two groups were significantly higher than those before treatment, and the levels of IgA, IgG and IgM in the observation group were significantly higher than those in the control group;the levels of TNF-α, sTREM1 and CRP in the two groups were significantly lower than those before treatment, and the levels of TNF-α, sTREM1 and CRP in the observation group were significantly lower than those in the control group;the levels of TIMP-1, MMP-9 and MMP-9/TIMP-1 in the two groups were significantly lower than those before treatment, and the levels of TIMP-1, MMP-9 and MMP-9/TIMP-1 in the observation group were significantly lower than those in the control group;the levels of SF and LPO in the two groups were significantly lower than those before treatment, while the levels of SOD in the observation group were significantly higher than those before treatment, and the levels of SF and LPO in the observation group were significantly lower than those in the control group, while the levels of SOD in the observation group were significantly higher than those in the control group. Conclusions:Intensive insulin therapy can effectively improve the immune function of severe pneumonia patients, reduce their inflammatory reaction, matrix metalloproteinase levels and oxidative stress injury.

The interplay of aging,genetics and environmental factors in the pathogenesis of Parkinson’s disease

Background:Parkinson’s disease(PD)is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta and intracellular inclusions called Lewy bodies(LB).During the course of disease,misfoldedα-synuclein,the major constituent of LB,spreads to different regions of the brain in a prion-like fashion,giving rise to successive non-motor and motor symptoms.Etiology is likely multifactorial,and involves interplay among aging,genetic susceptibility and environmental factors.Main body:The prevalence of PD rises exponentially with age,and aging is associated with impairment of cellular pathways which increases susceptibility of dopaminergic neurons to cell death.However,the majority of those over the age of 80 do not have PD,thus other factors in addition to aging are needed to cause disease.Discovery of neurotoxins which can result in parkinsonism led to efforts in identifying environmental factors which may influence PD risk.Nevertheless,the causality of most environmental factors is not conclusively established,and alternative explanations such as reverse causality and recall bias cannot be excluded.The lack of geographic clusters and conjugal cases also go against environmental toxins as a major cause of PD.Rare mutations as well as common variants in genes such as SNCA,LRRK2 and GBA are associated with risk of PD,but Mendelian causes collectively only account for 5%of PD and common polymorphisms are associated with small increase in PD risk.Heritability of PD has been estimated to be around 30%.Thus,aging,genetics and environmental factors each alone is rarely sufficient to cause PD for most patients.Conclusion:PD is a multifactorial disorder involving interplay of aging,genetics and environmental factors.This has implications on the development of appropriate animal models of PD which take all these factors into account.Common converging pathways likely include mitochondrial dysfunction,impaired autophagy,oxidative stress and neuroinflammation,which are associated with the accumulation and spread of misfoldedα-synuclein and neurodegeneration.Understanding the mechanisms involved in the initiation and progression of PD may lead to potential therapeutic targets to prevent PD or modify its course.

Clinical significance of skip lymph-node metastasis in pN1 gastric-cancer patients after curative surgery

Background:In addition to the stepwise manner of lymph-node metastasis from the primary tumour,the skip lymph-node metastasis(SLNM)was identified as a low-incidence metastasis of gastric cancer(GC).So far,both the mechanism and outcome of SLNM have not been elucidated completely.The purpose of this study was to analyse the clinical significance and the potential mechanism of SLNM in GC patients who had lymph-node metastasis.Methods:Clinicopathological data and follow-up information of 505 GC patients who had lymph-node metastasis were analysed to demonstrate the significance of SLNM in evaluating the prognostic outcome.According to the pathological results,all GC patients who had lymph-node metastasis were categorized into three groups:patients with the perigastric lymphnode metastasis,patients with the perigastric and extragastric lymph-node metastasis and patients with SLNM.Results:Among the 505 GC patients who had lymph-node metastasis,24(4.8%)had pathologically identified SLNM.The location of lymph-node metastasis was not significantly associated with 5-year survival rate and overall survival(OS)(P=0.194).The stratified survival analysis results showed that the status of SLNM was significantly associated with the OS in patients with pN1 GC(P=0.001).The median OS was significantly shorter in 19 pN1 GC patients with SLNM than in 100 patients with perigastric lymph-node metastasis(P<0.001).The case–control matched logistic regression analysis results showed that tumour size(P=0.002)was the only clinicopathological factor that may predict SLNM in pN1 GC patients undergoing curative surgery.Among the 19 pN1 GC patients with SLNM,17(89.5%)had metastatic lymph nodes along the common hepatic artery,around the celiac artery or in the hepatoduodenal ligament.Conclusions:SLNM may be considered a potentially practicable indicator for prognosis among various subgroups of pN1 GC patients.

LRRK2, GBA and their interaction in the regulation of autophagy: implications on therapeutics in Parkinson’s disease

Mutations in leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA) represent two most common genetic causes of Parkinson’s disease (PD). Both genes are important in the autophagic-lysosomal pathway (ALP), defects of which are associated with α-synuclein (α-syn) accumulation. LRRK2 regulates macroautophagy via activation of the mitogen activated protein kinase/extracellular signal regulated protein kinase (MAPK/ERK) kinase (MEK) and the calcium-dependent adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathways. Phosphorylation of Rab GTPases by LRRK2 regulates lysosomal homeostasis and endosomal trafficking. Mutant LRRK2 impairs chaperone-mediated autophagy, resulting in α-syn binding and oligomerization on lysosomal membranes. Mutations in GBA reduce glucocerebrosidase (GCase) activity, leading to glucosylceramide accumulation, α-syn aggregation and broad autophagic abnormalities. LRRK2 and GBA influence each other: GCase activity is reduced in LRRK2 mutant cells, and LRRK2 kinase inhibition can alter GCase activity in GBA mutant cells. Clinically, LRRK2 G2019S mutation seems to modify the effects of GBA mutation, resulting in milder symptoms than those resulting from GBA mutation alone. However, dual mutation carriers have an increased risk of PD and earlier age of onset compared with single mutation carriers, suggesting an additive deleterious effect on the initiation of PD pathogenic processes. Crosstalk between LRRK2 and GBA in PD exists, but its exact mechanism is unclear. Drugs that inhibit LRRK2 kinase or activate GCase are showing efficacy in pre-clinical models. Since LRRK2 kinase and GCase activities are also altered in idiopathic PD (iPD), it remains to be seen if these drugs will be useful in disease modification of iPD.

Mitochondrial neuronal uncoupling proteins:a target for potential disease-modification in Parkinson’s disease Philip

This review gives a brief insight into the role of mitochondrial dysfunction and oxidative stress in the converging pathogenic processes involved in Parkinson’s disease(PD).Mitochondria provide cellular energy in the form of ATP via oxidative phosphorylation,but as an integral part of this process,superoxides and other reactive oxygen species are also produced.Excessive free radical production contributes to oxidative stress.Cells have evolved to handle such stress via various endogenous anti-oxidant proteins.One such family of proteins is the mitochondrial uncoupling proteins(UCPs),which are anion carriers located in the mitochondrial inner membrane.There are five known homologues(UCP1 to 5),of which UCP4 and 5 are predominantly expressed in neural cells.In a series of previous publications,we have shown how these neuronal UCPs respond to 1-methyl-4-phenylpyridinium(MPP+;toxic metabolite of MPTP)and dopamine-induced toxicity to alleviate neuronal cell death by preserving ATP levels and mitochondrial membrane potential,and reducing oxidative stress.We also showed how their expression can be influenced by nuclear factor kappa-B(NF-
B)signaling pathway specifically in UCP4.Furthermore,we previously reported an interesting link between PD and metabolic processes through the protective effects of leptin(hormone produced by adipocytes)acting via UCP2 against MPP+-induced toxicity.There is increasing evidence that these endogenous neuronal UCPs can play a vital role to protect neurons against various pathogenic stresses including those associated with PD.Their expression,which can be induced,may well be a potential therapeutic target for various drugs to alleviate the harmful effects of pathogenic processes in PD and hence modify the progression of this disease.

LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson’s disease

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are one of the most frequent genetic causes of both familial and sporadic Parkinson’s disease (PD). Mounting evidence has demonstrated pathological similarities between LRRK2-associated PD (LRRK2-PD) and sporadic PD, suggesting that LRRK2 is a potential disease modulator and a thera-peutic target in PD. LRRK2 mutant knock-in (KI) mouse models display subtle alterations in pathological aspects that mirror early-stage PD, including increased susceptibility of nigrostriatal neurotransmission, development of motor and non-motor symptoms, mitochondrial and autophagy-lysosomal defects and synucleinopathies. This review provides a rationale for the use of LRRK2 KI mice to investigate the LRRK2-mediated pathogenesis of PD and implications from current findings from different LRRK2 KI mouse models, and ultimately discusses the therapeutic potentials against LRRK2-associated pathologies in PD.