Influence of environmental parameters on workers' dust inhalation in underground mines.

Much dust is generated in underground coal mining processes, posing threats to workers' health and safety production. Dust enters the human body mainly through inhalation, primarily determined by the dust concentration around workers. In this study, the airflow field and dust distribution in the tunnel are simulated with FLUENT software. The breathing zone for a worker was defined to clarify the extent of external dust distribution influencing dust inhalation. The effects of human respiration, dust production rates, air supply velocities, and workers' positions on dust concentration in the breathing zone were investigated. The results show that there is upward airflow around the worker standing in the center of the air circulation. Human breath barely influences the airflow distribution and respirable dust concentrations in the breathing zone. Reducing the dust production rate in the tunnel can decrease the respirable dust concentration in the breathing zone by almost the same proportion. While increasing the air supply velocity by 50% would reduce only 20% of dust in the breathing zone. The dust concentrations vary along the roadway, in which the low concentration zone is located in the middle, more than 1.0 m away from the dust-producing surface and the wind surface. The research contributes to reducing workers' dust exposure with suggestions regarding ventilation optimization and working position selection.

Suspension characteristics of the coal-quartz dust mixture in the working environment during the fully mechanized mining process.

Dust exposures during mining activity can result in lung diseases such as coal workers' pneumoconiosis (CWP) and silicosis, and it is closely related to quartz dust. In the present study, coal-quartz dust mixture were investigated considering the particle size and the specific constituents. Multiple numerical techniques, including computational fluid dynamics and discrete element method (CFD-DEM), hard sphere model, and direct Monte Carlo simulation (DSMC), were presented, and the dust diffusion processes were investigated. According to the validation of the numerical method, the suspension characteristics of the polydisperse mixed dust were analyzed in detail. The results show that PM10 responds quickly, has a large diffusion range, and is easily affected by the reflux. The particle size increases gradually from top to bottom. When the air velocity is low, the percentage of coal dust in the breathing zone tends to be 50%. The results provide theoretical guidance for the comprehensive prevention of the mixed dust in underground coal mines.

Transcriptome analysis identifies the role of Class I histone deacetylase in Alzheimer's disease.

Epigenetics modification is a process that does not change the sequence of deoxyribonucleic acid (DNA) in disease progression but can alter the genetic expression of the brain in Alzheimer's disease (AD). In this study, we deployed the weighted gene co-expression network analysis (WGCNA) to explore the role of Class I histone deacetylases (HDACs) in AD, which included HDAC1, HDAC2, HDAC3, and HDAC8. The aim of the study was to find how Class I HDACs affected AD pathology by analyzing the Gene Expression Omnibus (GEO) microarray datasets GSE33000. We found that HDAC1 and HDAC8 were more highly expressed in the cortex of AD patients than in Controls, while HDAC2 and HDAC3 were lower expressed. By WGCNA analysis, we found the blue module was associated with HDAC1 and HDAC8, and the turquoise module was related to HDAC2 and HDAC3. Functional enrichment analysis revealed that the Wnt signaling pathway and synaptic plasticity played an important role in the modification of HDAC1 and HDAC8 while gap junction and cell-cell junction were involved in the regulation of HDAC2 and HDAC3 in the disease progression of AD. By Receiver Operating Characteristics (ROC) analysis, we concluded that HDAC1 might be the most probable diagnostic biomarker of Class I HDACs for AD. Our study provided a comprehensive understanding of Class I HDACs and provided new insight into the function of HDAC1 in AD disease progression.

Coal dust dispersion with the moving conveyance in a high-rise building for the mine hoist system.

The present study investigates dust generated from the unloading process in a high-rise building for the mine hoist system and analyzes dust dispersion with the moving conveyance in the building. First, the gas-solid two-phase flow in the building was investigated based on the CFD-DPM method. In particular, the moving conveyance was considered in detail and treated via the dynamic mesh technology. Then, the airflow and dust distribution were investigated in the building. The airflow and the dust concentration at selected points show good agreement with the relative results of field measurements by ourselves. It is found that the descending conveyance significantly influences the surrounding flow field and the spatial and temporal distribution of dust. Dust concentration before the dust source (2 m × 2 m) is high, which extends downward with the conveyance. Dust concentration of the lower floors increases obviously when compared with that of the condition without the movement of the conveyance. The descending velocity of the conveyance also affects the amount of PM2.5 discharged from the return air outlet. The fitting functions are provided to predict PM2.5 emissions to the surrounding atmosphere. The research results are of great significance for the improvement of the dust control system for cleaner production technology.

In Situ Probing of the Intrinsic Adhesion Strength of Single Anaerobic Microbial Cells.

Probing the single-cell mechanobiology in situ is imperative for microbial processes in the medical, industrial, and agricultural realms, but it remains a challenge. Herein, we present a single-cell force microscopy method that can be used to measure microbial adhesion strength under anaerobic conditions in situ. This method integrates atomic force microscopy with an anaerobic liquid cell and inverted fluorescence microscopy. We obtained the nanomechanical measurements of the single anaerobic bacterium Ethanoligenens harbinense YUAN-3 and the methanogenic archaeon Methanosarcina acetivorans C2A and their nanoscale adhesion forces in the presence of sulfoxaflor, a successor of neonicotinoid pesticides. This study presents a new tool for in situ single-cell force measurements of various anoxic and anaerobic species and provides new perspectives for evaluating the potential environmental risk of neonicotinoid applications in ecosystems.

A novel lytic polysaccharide monooxygenase from enrichment microbiota and its application for shrimp shell powder biodegradation.

Lytic polysaccharide monooxygenases (LPMO) are expected to change the current status of chitin resource utilization. This study reports that targeted enrichment of the microbiota was performed with chitin by the selective gradient culture technique, and a novel LPMO (M2822) was identified from the enrichment microbiota metagenome. First, soil samples were screened based on soil bacterial species and chitinase biodiversity. Then gradient enrichment culture with different chitin concentrations was carried out. The efficiency of chitin powder degradation was increased by 10.67 times through enrichment, and chitin degradation species Chitiniphilus and Chitinolyticbacter were enriched significantly. A novel LPMO (M2822) was found in the metagenome of the enriched microbiota. Phylogenetic analysis showed that M2822 had a unique phylogenetic position in auxiliary activity (AA) 10 family. The analysis of enzymatic hydrolysate showed that M2822 had chitin activity. When M2822 synergized with commercial chitinase to degrade chitin, the yield of N-acetyl glycosamine was 83.6% higher than chitinase alone. The optimum temperature and pH for M2822 activity were 35°C and 6.0. The synergistic action of M2822 and chitin-degrading enzymes secreted by Chitiniphilus sp. LZ32 could efficiently hydrolyze shrimp shell powder. After 12 h of enzymatic hydrolysis, chitin oligosaccharides (COS) yield reached 4,724 µg/mL. To our knowledge, this work is the first study to mine chitin activity LPMO in the metagenome of enriched microbiota. The obtained M2822 showed application prospects in the efficient production of COS.

Memory of stochastic single-cell apoptotic signaling promotes chemoresistance in neuroblastoma.

Gene expression noise is known to promote stochastic drug resistance through the elevated expression of individual genes in rare cancer cells. However, we now demonstrate that chemoresistant neuroblastoma cells emerge at a much higher frequency when the influence of noise is integrated across multiple components of an apoptotic signaling network. Using a JNK activity biosensor with longitudinal high-content and in vivo intravital imaging, we identify a population of stochastic, JNK-impaired, chemoresistant cells that exist because of noise within this signaling network. Furthermore, we reveal that the memory of this initially random state is retained following chemotherapy treatment across a series of in vitro, in vivo, and patient models. Using matched PDX models established at diagnosis and relapse from individual patients, we show that HDAC inhibitor priming cannot erase the memory of this resistant state within relapsed neuroblastomas but improves response in the first-line setting by restoring drug-induced JNK activity within the chemoresistant population of treatment-naïve tumors.

Enhancer trap lines with GFP driven by smad6b and frizzled1 regulatory sequences for the study of epithelial morphogenesis in the developing zebrafish inner ear.

Live imaging in the zebrafish embryo using tissue-specific expression of fluorescent proteins can yield important insights into the mechanisms that drive sensory organ morphogenesis and cell differentiation. Morphogenesis of the semicircular canal ducts of the vertebrate inner ear requires a complex rearrangement of epithelial cells, including outgrowth, adhesion, fusion and perforation of epithelial projections to generate pillars of tissue that form the hubs of each canal. We report the insertion sites and expression patterns of two enhancer trap lines in the developing zebrafish embryo, each of which highlight different aspects of epithelial cell morphogenesis in the inner ear. A membrane-linked EGFP driven by smad6b regulatory sequences is expressed throughout the otic epithelium, most strongly on the lateral side of the ear and in the sensory cristae. A second enhancer trap line, with cytoplasmic EGFP driven by frizzled1 (fzd1) regulatory sequences, specifically marks cells of the ventral projection and pillar in the developing ear, and marginal cells in the sensory cristae, together with variable expression in the retina and epiphysis, and neurons elsewhere in the developing central nervous system. We have used a combination of methods to identify the insertion sites of these two transgenes, which were generated through random insertion, and show that Targeted Locus Amplification is a rapid and reliable method for the identification of insertion sites of randomly inserted transgenes.

Single bubble probe atomic force microscope and impinging-jet technique unravel the interfacial interactions controlled by long chain fatty acid in anaerobic digestion.

Anaerobic digestion of lipid-rich wastewater generally suffers from foaming induced by long chain fatty acid (LCFA). However, a systematic understanding of LCFA inhibition, especially the physical inhibition on interfacial interaction still remains unclear. Here, we combined bubble probe atomic force microscope and impinging-jet technique to unravel the interfacial interactions controlled by long chain fatty acids in anaerobic digestion. We showed that LCFA had a significant inhibition on methane production in anaerobic reactors for the inhibition of the conversion of VFAs to methane. By measuring the LCFA influence on methanogenic archaea Methanosarcina acetivorans C2A, the results demonstrated that methanogenesis was limited for substrates utilization but not metabolic pathways. The impinging-jet technique results indicated that LCFA enhanced bubble separation from anaerobic granules and reduced the bubble-bubble coalescence probability. In addition, the bubble probe atomic force microscope (AFM) revealed that LCFA enhanced the adhesion force between bubbles by enhancing electrical double layer (EDL) repulsion and decreasing hydrophobic interactions. Overall, these results complement framework of LCFA inhibition in anerobic digestion and provide a nanomechanical insight into the fundamental interfacial interactions related to bubbles in anaerobic reactors.

Dust dispersion during the pulse-jet cleaning process with the diffuser effect of the cartridge filter.

A special conical diffuser was presented and fixed on the top of the filter cartridge to improve the flow field. The existence of the diffuser can disperse the jet flow from the nozzle, and the high-speed airflow can act on more areas of the filter cartridge, including the top area of the filter cartridge. To improve the cleaning efficiency, the present study is aimed at optimizing the structure of the filter cartridge. The DPM model was used to simulate the dust dispersion process and the falling dust sedimentation from the filter under the action of the pulsed airflow. To validate the established model, the pressure values at the monitoring points were analyzed and compared with the related experimental results. It is found that the pressure values are consistent with the experimental results. Moreover, the installation distance and the size of the diffuser were studied and their influence on the dust distribution on the surface of the filter cartridge. It is found that the dust removal effect is relatively better when the installation distance is 90 mm and the size radius is 25 mm. The maximum dust concentration can be reduced by 15 mg/m3. The present research results can provide theoretical guidance for the cleaning process of the filter cartridge and finally improve the dust-removal efficiency of the dust collector.

Intestinal dysbiosis mediates cognitive impairment via the intestine and brain NLRP3 inflammasome activation in chronic sleep deprivation.

Growing evidence suggests the involvement of the microbiota-gut-brain axis in cognitive impairment induced by sleep deprivation (SD), however how the microbiota-gut-brain axis work remains elusive. Here, we discovered that chronic SD induced intestinal dysbiosis, activated NLRP3 inflammasome in the colon and brain, destructed intestinal/blood-brain barrier, and impaired cognitive function in mice. Transplantation of "SD microbiota" could almost mimic the pathological and behavioral changes caused by chronic SD. Furthermore, all the behavioral and pathological abnormalities were practically reversed in chronic sleep-deprived NLRP3-/- mice. Regional knockdown NLRP3 expression in the gut and hippocampus, respectively. We observed that down-regulation of NLRP3 in the hippocampus inhibited neuroinflammation, and ameliorated synaptic dysfunction and cognitive impairment induced by chronic SD. More intriguingly, the down-regulation of NLRP3 in the gut protected the intestinal barrier, attenuated the levels of peripheral inflammatory factors, down-regulated the expression of NLRP3 in the brain, and improved cognitive function in chronic SD mice. Our results identified gut microbiota as a driver in chronic SD and highlighted the NLRP3 inflammasome as a key regulator within the microbiota-gut-brain axis.

DI-3-n-butylphthalide mitigates stress-induced cognitive deficits in mice through inhibition of NLRP3-Mediated neuroinflammation.

Our previous study has demonstrated that chronic stress could cause cognitive deficits and tau pathology. However, the underlying mechanism and whether/how DI-3-n-Butylphthalide (NBP) ameliorates these effects are still unclear. Here, Wild-type mice were subjected to chronic unpredictable and mild stress (CUMS) for 8 weeks. Following the initial 4 weeks, the stressed animals were separated into susceptible (depressive) and unsusceptible (resilient) groups based on behavioral tests. Then, NBP (30 mg/kg i.g) was administered for 4 weeks. Morris water maze (MWM), Western-blot, Golgi staining, immunofluorescence staining and ELISA were used to examine behavioral, biochemical, and pathological changes. The results showed that both depressive and resilient mice displayed spatial memory deficits and an accumulation of tau in the hippocampus. Activated microglia and NLRP3 inflammasome were found after 8-week chronic stress. We also found a decreased level of postsynaptic density (PSD) related proteins (PSD93 and PSD95) and decreased the number of dendritic spines in the hippocampus. Interestingly, almost all the pathological changes in depressive and resilient mice previously mentioned could be reversed by NBP treatment. To further investigate the role of NLRP3 inflammasome in chronic stress-induced cognitive deficits, NLRP3 KO mice were also exposed to chronic stress. And these changes induced by chronic stress could not be found in NLRP3 KO mice. These results show an important role for the NLRP3/caspase-1/IL-1ß axis in chronic stress-induced cognitive deficits and NBP meliorates cognitive impairments and selectively attenuates phosphorylated tau accumulation in stressed mice through regulation of NLRP3 inflammatory signaling pathway.

Comparison of the disinfection effect of iodophor at two different temperatures on the skin of surgical field and its influence on blood pressure and heart rate of patients.

OBJECTIVE: To compare the disinfection effect of iodophor at two different temperatures on the skin of surgical field and its influence on blood pressure and heart rate of patients. METHODS: The clinical data of 150 patients who underwent surgery in the Seventh People's Hospital of Shanghai University of TCM were collected and divided into two groups based on different disinfection temperatures; the observation group (constant 36°C) and the control group ((24±2)°C), with 75 patients in each. The postoperative disinfection effects of the two groups were evaluated including the disinfection effect, blood pressure, heart rate, body temperature, cold sensation, gastrointestinal reactions, stress response, incidence of complications in the perioperative period, incision healing and satisfaction rate. RESULTS: The disinfection efficacy of the observation group was 96.00%, which was higher than that of the control group (81.33%, P<0.01); the blood pressure and heart rate of patients in the observation group after disinfection were lower than those in the control group (P<0.001); the body temperature was higher than that of the control group (P<0.001); the cold sensation was weaker and gastrointestinal adverse reactions were less than those of the control group (P<0.05); the MDA, GSH-PX and SOD levels after disinfection in the observation group were lower than those of the control group (P<0.001); the incidence rate of complications in the observation group was lower than that of the control group (P<0.05) and the incision healing rate was higher than that of the control group (P<0.05). Patients in observation group were more satisfied with disinfection method, disinfection effect, prevention of complications, postoperative recovery and disinfection times than patients in the control group (P<0.01). CONCLUSION: Iodophor at constant temperature is more effective in skin disinfection of the surgical field, with little influence on blood pressure, heart rate and body temperature. This helps to reduce the cold sensation of skin, the incidence rate of gastrointestinal adverse reactions and complications, promote incision healing and improve the satisfaction rate of the surgery. It is worthy of wide application and promotion.

Field measurement and numerical simulation of dust migration in a high-rise building of the mine hoisting system.

Dust pollutants generated from the coal transfer process in a high-rise building of the mine hoisting system not only undermine the operating environment but also reduce the surrounding air quality. Therefore, this study aimed to determine the spatiotemporal distribution of coal dust in the high-rise buildings using field measurement and numerical simulation. Based on the discrete phase model (DPM), the dust migration process under the hybrid ventilation system was investigated in detail. Then, the feasibility of the established model to predict the spatiotemporal distribution of dust pollutants was proven through the measurements of both the airflow and the dust concentration. The present study showed that dust distribution is not uniform in time and space, which also differs for different floors. The dust concentration of the 3rd floor is relatively larger when compared with those of other floors. The dust concentration increases for the upper floors when the upward air velocity increases, while those of the lower floors are not always low due to the backflows, particularly for the 2nd floor. PM2.5 takes up more than 20% of all discharged particles.

Platelet-derived growth factor (PDGF)-BB protects dopaminergic neurons via activation of Akt/ERK/CREB pathways to upregulate tyrosine hydroxylase.

AIMS: The neurotropic growth factor PDGF-BB was shown to have vital neurorestorative functions in various animal models of Parkinson's disease (PD). Previous studies indicated that the regenerative property of PDGF-BB contributes to the increased intensity of tyrosine hydroxylase (TH) fibers in vivo. However, whether PDGF-BB directly modulates the expression of TH, and the underlying mechanism is still unknown. We will carefully examine this in our current study. METHOD: MPTP-lesion mice received PDGF-BB treatment via intracerebroventricular (i.c.v) administration, and the expression of TH in different brain regions was assessed by RT-PCR, Western blot, and immunohistochemistry staining. The molecular mechanisms of PDGF-BB-mediated TH upregulation were examined by RT-PCR, Western blot, ChIP assay, luciferase reporter assay, and immunocytochemistry. RESULTS: We validated a reversal expression of TH in MPTP-lesion mice upon i.c.v administration of PDGF-BB for seven days. Similar effects of PDGF-BB-mediated TH upregulation were also observed in MPP+ -treated primary neuronal culture and dopaminergic neuronal cell line SH-SY5Y cells. We next demonstrated that PDGF-BB rapidly activated the pro-survival PI3K/Akt and MAPK/ERK signaling pathways, as well as the downstream CREB in SH-SY5Y cells. We further confirmed the significant induction of p-CREB in PDGF-BB-treated animals in vivo. Using a genetic approach, we demonstrated that the transcription factor CREB is critical for PDGF-BB-mediated TH expression. The activation and nucleus translocation of CREB were promoted in PDGF-BB-treated SH-SY5Y cells, and the enrichment of CREB on the promoter region of TH gene was also increased upon PDGF-BB treatment. CONCLUSION: Our data demonstrated that PDGF-BB directly regulated the expression of TH via activating the downstream Akt/ERK/CREB signaling pathways. Our finding will further support the therapeutic potential of PDGF-BB in PD, and provide the possibility that targeting PDGF signaling can be harnessed as an adjunctive therapy in PD in the future.

Conditional deficiency of m6A methyltransferase Mettl14 in substantia nigra alters dopaminergic neuron function.

N6-Methyladenosine (m6A) is the most prevalent internal modification in messenger RNAs (mRNAs) of eukaryotes and plays a vital role in post-transcriptional regulation. Recent studies demonstrated that m6A is essential for the normal function of the central nervous system (CNS), and the deregulation of m6A leads to a series of CNS diseases. However, the functional consequences of m6A deficiency within the dopaminergic neurons of adult brain are elusive. To evaluate the necessity of m6A in dopaminergic neuron functions, we conditionally deleted Mettl14, one of the most important part of m6A methyltransferase complexes, in the substantia nigra (SN) region enriched with dopaminergic neurons. By using rotarod test, pole test, open-field test and elevated plus maze, we found that the deletion of Mettl14 in the SN region induces impaired motor function and locomotor activity. Further molecular analysis revealed that Mettl14 deletion significantly reduced the total level of m6A in the mRNA isolated from SN region. Tyrosine hydroxylase (TH), an essential enzyme for dopamine synthesis, was also down-regulated upon Mettl14 deletion, while the activation of microglia and astrocyte was enhanced. Moreover, the expression of three essential transcription factors in the regulation of TH including Nurr1, Pitx3 and En1, with abundant m6A-binding sites on their RNA 3'-untranslated regions (UTR), was significantly decreased upon Mettl14 deletion in SN. Our finding first confirmed the significance of m6A in maintaining normal dopaminergic function in the SN of adult mouse.

Krüppel-like factor 1 is a core cardiomyogenic trigger in zebrafish.

Cardiac regeneration requires dedifferentiation and proliferation of mature cardiomyocytes, but the mechanisms underlying this plasticity remain unclear. Here, we identify a potent cardiomyogenic role for Krüppel-like factor 1 (Klf1/Eklf), which is induced in adult zebrafish myocardium upon injury. Myocardial inhibition of Klf1 function does not affect heart development, but it severely impairs regeneration. Transient Klf1 activation is sufficient to expand mature myocardium in uninjured hearts. Klf1 directs epigenetic reprogramming of the cardiac transcription factor network, permitting coordinated cardiomyocyte dedifferentiation and proliferation. Myocardial expansion is supported by Klf1-induced rewiring of mitochondrial metabolism from oxidative respiration to anabolic pathways. Our findings establish Klf1 as a core transcriptional regulator of cardiomyocyte renewal in adult zebrafish hearts.

Ube2b-dependent degradation of DNMT3a relieves a transcriptional brake on opiate-induced synaptic and behavioral plasticity.

Compelling evidence suggests that synaptic structural plasticity, driven by remodeling of the actin cytoskeleton, underlies addictive drugs-induced long-lasting behavioral plasticity. However, the signaling mechanisms leading to actin cytoskeleton remodeling remain poorly defined. DNA methylation is a critical mechanism used to control activity-dependent gene expression essential for long-lasting synaptic plasticity. Here, we provide evidence that DNA methyltransferase DNMT3a is degraded by the E2 ubiquitin-conjugating enzyme Ube2b-mediated ubiquitination in dorsal hippocampus (DH) of rats that repeatedly self-administrated heroin. DNMT3a degradation leads to demethylation in CaMKK1 gene promotor, thereby facilitating CaMKK1 expression and consequent activation of its downstream target CaMKIα, an essential regulator of spinogenesis. CaMKK1/CaMKIα signaling regulates actin cytoskeleton remodeling in the DH and behavioral plasticity by activation of Rac1 via acting Rac guanine-nucleotide-exchange factor ßPIX. These data suggest that Ube2b-dependent degradation of DNMT3a relieves a transcriptional brake on CaMKK1 gene and thus activates CaMKK1/CaMKIα/ßPIX/Rac1 cascade, leading to drug use-induced actin polymerization and behavior plasticity.

Molecular Mechanism of Platelet-Derived Growth Factor (PDGF)-BB-Mediated Protection Against MPP+ Toxicity in SH-SY5Y Cells.

As an important endogenous growth factor, PDGF-BB can effectively promote neurogenesis, thus is considered as a potential agent for Parkinson's disease (PD) therapy. However, the protective function of PDGF-BB on neuronal cells, especially the molecular mechanism, remains less clear, which is needed to explore before its clinical practice. In this study, we investigated the function and mechanism of PDGF-BB against 1-methyl-4-phenylpyridinium (MPP+) toxicity in SH-SY5Y cells, a widely used cellular tool for PD-related molecular study. Our results indicated that PDGF-BB exerts a prominent protective effect against neurotoxin MPP+-triggered ROS generation and cellular loss. We further dissected the molecular mechanism involved in this process by using specific pharmacological inhibitors and validated that the distinct signaling pathways PI3K/Akt/GSK-3ß and MEK/ERK are involved in the process against MPP+ toxicity upon PDGF-BB treatment. We also detected that activation of upstream PI3K/Akt/GSK-3ß and MER/ERK signaling pathways contribute to phosphorylation and nuclear translocation of the downstream effector cyclic response element-binding protein (CREB), a known transcription factor to exhibit neuroprotective and growth-promoting effects. Using genetic approach, we further confirmed that the activation of CREB is involved in PDGF-BB-mediated protection in MPP+-exposed SH-SY5Y cells. Together, these data demonstrated the protective effect of PDGF-BB in MPP+-mediated toxicity in SH-SY5Y cells and verified the involved molecular mechanism in PDGF-BB-mediated neuroprotection.