Single-cell transcriptome reveals a novel mechanism of C-Kit+-liver sinusoidal endothelial cells in NASH.

AIM: To understand how liver sinusoidal endothelial cells (LSECs) respond to nonalcoholic steatohepatitis (NASH). METHODS: We profiled single-LSEC from livers of control and MCD-fed mice. The functions of C-Kit+-LSECs were determined using coculture and bone marrow transplantation (BMT) methods. RESULTS: Three special clusters of single-LSEC were differentiated. C-Kit+-LSECs of cluster 0, Msr1+-LSECs of cluster 1 and Bmp4+Selp+-VECs of cluster 2 were revealed, and these cells with diverse ectopic expressions of genes participated in regulation of endothelial, fibrosis and lipid metabolism in NASH. The number of C-Kit+-primary LSECs isolated from MCD mice was lower than control mice. Immunofluorescence co-staining of CD31 and C-KIT showed C-Kit+-LSECs located in hepatic sinusoid were also reduced in NASH patients and MCD mice, compared to AIH patients and control mice respectively. Interestingly, lipotoxic hepatocytes/HSCs cocultured with C-Kit+-LSECs or the livers of MCD mice receipting of C-Kit+-BMCs (bone marrow cells) showed less steatosis, inflammation and fibrosis, higher expression of prolipolytic FXR and PPAR-α, lower expression of TNF-α and α-SMA. Furthermore, coculturing or BMT of C-Kit+-endothelial derived cells could increase the levels of hepatic mitochondrial LC3B, decrease the degree of mitochondrial damage and ROS production through activating Pink1-mediated mitophagy pathway in NASH. CONCLUSIONS: Hence, a novel transcriptomic view of LSECs was revealed to have heterogeneity and complexity in NASH. Importantly, a cluster of C-Kit+-LSECs was confirmed to recovery Pink1-related mitophagy and NASH progression.

Design of pH-responsive antimicrobial peptide melittin analog-camptothecin conjugates for tumor therapy.

Melittin, a classical antimicrobial peptide, is a highly potent antitumor agent. However, its significant toxicity seriously hampers its application in tumor therapy. In this study, we developed novel melittin analogs with pH-responsive, cell-penetrating and membrane-lytic activities by replacing arginine and lysine with histidine. After conjugation with camptothecin (CPT), CPT-AAM-1 and CPT-AAM-2 were capable of killing tumor cells by releasing CPT at low concentrations and disrupting cell membranes at high concentrations under acidic conditions. Notably, we found that the C-terminus of the melittin analogs was more suitable for drug conjugation than the N-terminus. CPT-AAM-1 significantly suppressed melanoma growth in vivo with relatively low toxicity. Collectively, the present study demonstrates that the development of antitumor drugs based on pH-responsive antimicrobial peptide-drug conjugates is a promising strategy.

Si/Ge phototransistor with responsivity >1000A/W on a silicon photonics platform.

In this article, we report a Si/Ge waveguide phototransistor with high responsivity and low dark current under low bias voltages, due to an engineered electric field distribution. The photodetector consists of n-i-p-i-n doping regions and shows a responsivity of 606 A/W at 1 V bias, and 1032 A/W at 2.8V bias with an input optical power of -50 dBm, and dark current of 4 µA and 42 µA respectively. This is achieved by placing two p+-doped regions in the silicon slab region beneath the Ge epitaxial layer. A measured small signal -3 dB bandwidth of 1.5 GHz with a -80 dBc/Hz phase noise response at 1 KHz frequency offset were demonstrated experimentally.

Revealing How Polyvinyl Chloride Microplastic Physicochemically Affect the Anaerobic Digestion of Waste Activated Sludge.

Recent studies have shown that the microplastics in waste activated sludge (WAS) can directly reduce the microbial activity and influence the performance of anaerobic digestion. Unfortunately, few studies paid attention on the interactions between WAS and MPs, since MPs could impact the contact between sludge flocs and microorganisms. We found that PVC-MP changed the interfacial energy properties of the WAS surface and affected methane production. Low concentration (40 mg/L) of PVC-MP changed the water affinity and greatly reduced the energy barrier of interfacial reaction. Simultaneously, WAS surface charge characteristics changed with increasing MPs concentration, which made the sludge difficult to contact with microorganisms. The change process of WAS surface functional groups also indicated that PVC-MP first cover the sludge surface to prevent from being utilized by microorganisms, and then affect the surface protein structure before toxic substances leaching. Our study provides new insights into how MPs affect anaerobic digestion.

Altered brain network centrality in patients with orbital fracture: A resting­state functional MRI study.

The present study aimed to investigate potential functional network brain-activity abnormalities in individuals with orbital fracture (OF) using the voxel-wise degree centrality (DC) technique. The present study included 20 patients with OF (12 males and 8 females) and 20 healthy controls (HC; 12 males and 8 females), who were matched for gender, age and educational attainment. Functional magnetic resonance imaging (fMRI) in the resting state has been widely applied in several fields. Receiver operating characteristic (ROC) curves were calculated to distinguish between patients with OF and HCs. In addition, correlation analyses were performed between behavioral performance and average DC values in various locations. The DC technique was used to assess unprompted brain activity. Right cerebellum 9 region (Cerebelum_9_R) and left cerebellar peduncle 2 area (Cerebelum_Crus2_L) DC values of patients with OF were increased compared with those in HCs. Cerebelum_9_R and Cerebelum_Crus2_L had area under the ROC curve values of 0.983 and 1.000, respectively. Patients with OF appear to have several brain regions that exhibited aberrant brain network characteristics, which raises the possibility of neuropathic causes and offers novel therapeutic options.

Evaluating the cytotoxicity mechanism of the cell-penetrating peptide TP10 on Jurkat cells.

TP10, a classic cell-penetrating peptide, shows a high degree of similarity to AMPs in structure. Although TP10 has been widely used in drug delivery, the mechanism underlying its cytotoxicity is yet to be elucidated. Herein, we explored the cell-killing mechanism of TP10 against human leukemia Jurkat cells. TP10 induced necrosis in Jurkat cells via rapid disruption of cell membranes, particularly at high concentrations. Although mitochondria in Jurkat cells were damaged by TP10, mitochondria-mediated apoptosis did not occur, possibly due to intracellular ATP depletion. Necroptosis in TP10-treated Jurkat cells became an alternative route of apoptosis. Our results demonstrate that necrosis and necroptosis rather than apoptosis are involved in the cell-killing mechanism of TP10, which contributes to the understanding of its toxicity.

Morphological and transcriptomic responses/acclimations of erect-type submerged macrophyte Hydrilla verticillata both at low-light exposure and light recovery phases.

Light intensity is a determinant for submerged macrophytes. Little is known about their molecular responses to low-light exposure, despite more informative and responsive than morphological traits. For erect-type submerged macrophytes, the stem is more crucial relative to the leaf in acclimation to low-light stress, but receives less attention. We determined morphological and stem transcriptomic responses/acclimations of Hydrilla verticillata to extremely and mildly low light (7.2 and 36 µmol photons m-2 s-1, respectively), that is, EL and ML, with the radiation intensity of 180 µmol photons m-2 s-1 as the control. Low-light exposure continued for 9 days, followed by a 7-day recovery phase (180 µmol photons m-2 s-1). At the exposure phase, the low-light treatments, in particular the EL, decreased the relative growth ratio, but induced greater height and longer stem internode distance and epidermal cell. Such responses/acclimations continued into the recovery phase, despite more or less changes in the magnitude. Transcriptome showed that the photosynthetic system was inhibited at the exposure phase, but the macrophyte adjusted hormone synthesis relating to cell division and elongation. Moreover, the EL activated cell stress responses such as DNA repair. Following light recovery, the macrophyte exhibited a strong-light response, although energy metabolism enhanced. Especially, the EL enriched the pathways relating to anthocyanin synthesis at such phase, indicating an activation of photoprotective mechanism. Our findings suggest that negative influences of low light occur at both low-light exposure and recovery phases, but submerged macrophytes would acclimate to light environments. Transcriptome can show molecular basis of plant responses/acclimations, including but not limited to morphology. This study establishes a bridge connecting morphological and molecular responses/acclimations.

Event-Triggered Adaptive Antidisturbance Switching Control for Switched Systems With Dynamic Neural Network Disturbance Modeling.

In this article, a dynamic event-triggered adaptive antidisturbance (ETAAD) switching control strategy is proposed for switched systems subject to multisource disturbances. The disturbances are divided into two categories: the available unmodeled disturbance and the unavailable dynamic neural network modeled disturbance. First, a dynamic ET criterion is set based on the system state. Then, a novel dynamic ETA disturbance estimator is introduced to observe the modeled disturbance. Furthermore, according to the ET rule and adaptive disturbance observer, a switched controller is designed. Next, under the controller and switching criterion with the average dwell time limitation, sufficient conditions are given to force the switched systems to realize multisource disturbance suppression (DS), trajectory tracking, and communication resource (CR) saving simultaneously. Meanwhile, the Zeno phenomenon may be caused by the ET rule being excluded. In addition, the presented ETAAD approach is also applicable to the nonswitched systems case. Finally, a simulation case is given to validate the effectiveness of the dynamic ETAAD switching control method.

Mechanism of microbial regulation on methane metabolism in saline-alkali soils based on metagenomics analysis.

Saline-alkali soils constitute a globally important carbon pool that plays a critical role in soil carbon dioxide (CO2) and methane (CH4) fluxes. However, the relative importance of microorganisms in the regulation of CH4 emissions under elevated salinity remains unclear. Here, we report the composition of CH4 production and oxidation microbial communities under five different salinity levels in the Yellow River Delta, China. This study also obtained the gene number of microbial CH4 metabolism via testing the soil metagenomes, and further investigated the key soil factors to determine the regulation mechanism. Spearman correlation analysis showed that the soil electrical conductivity, salt content, and Na+, and SO42- concentrations showed significantly negative correlations with the CO2 and CH4 emission rates, while the NO2--N concentration and NO2-/NO3- ratio showed significantly positive correlations with the CO2 and CH4 emission rates. Metabolic pathway analysis showed that the mcrA gene for CH4 production was highest in low-salinity soils. By contrast, the relative abundances of the fwdA, ftr, mch, and mer genes related to the CO2 pathway increased significantly with rising salinity. Regarding CH4 oxidation processes, the relative abundances of the pmoA, mmoB, and mdh1 genes transferred from CH4 to formaldehyde decreased significantly from the control to the extreme-salinity plot. The greater abundance and rapid increase of methanotrophic bacteria compared with the lower abundance and slow increase in methanogenic archaea communities in saline-alkali soils may have increased CH4 oxidation and reduced CH4 production in this study. Only CO2 emissions positively affected CH4 emissions from low- to medium-salinity soils, while the diversities of CH4 production and oxidation jointly influenced CH4 emissions from medium- to extreme-salinity plots. Hence, future investigations will also explore more metabolic pathways for CH4 emissions from different types of saline-alkali lands and combine the key soil enzymes and regulated biotic or abiotic factors to enrich the CH4 metabolism pathway in saline-alkali soils.

The emerging role of snoRNAs in human disease.

Small nucleolar RNAs (snoRNAs) play critical roles in various biological processes. The aberrant expression or depletion of snoRNAs is related to various diseases. In previous research, most of the snoRNAs were categorized as C/D box snoRNAs and H/ACA box snoRNAs, whose typical functions were thought of as regulation of 2'-O-ribose methylation and pseudouridylation of ribosome RNAs, respectively. However, in the past two decades, studies have revealed an increasing number of snoRNAs without specific targets or determined cell functions. These findings indicated that some potential roles of snoRNAs are still unknown. Numerous studies have indicated the correlation of snoRNAs with human diseases. SnoRNAs play various roles in abundant biological processes, and they have great potential in controlling human diseases. This new and rising field could benefit from investigations of the disease pathogenesis, biomarker identification, and the determination of novel therapeutic targets. This review summarized the reports on snoRNAs and the regulation of different diseases in recent years.

PiRNA hsa_piR_019914 Promoted Chondrocyte Anabolic Metabolism By Inhibiting LDHA-Dependent ROS Production.

OBJECTIVES: Osteoarthritis (OA) is the most common joint disease. The occurrence and progression of OA are regulated by epigenetics. A large number of studies have shown the important regulatory role of noncoding RNAs in joint diseases. As the largest class of noncoding small RNAs, the importance of piRNAs in many diseases, especially cancer, has been increasingly recognized. However, few studies have explored the role of piRNAs in OA. Our study showed that hsa_piR_019914 decreased significantly in OA. This study aimed to demonstrate the role of hsa_piR_019914 as a potential biological target of OA in chondrocytes. DESIGN: The GEO database and bioinformatics analysis were used for a series of screenings, and the OA model using human articular chondrocytes (C28/I2 cells), SW1353 cells under inflammatory factor stimulation was used to determine that hsa_piR_019914 was significantly downregulated in OA. Overexpression or inhibition of hsa_piR_019914 in C28/I2 cells was achieved by transfecting mimics or inhibitors. The effect of hsa_piR_019914 on the biological function of chondrocytes was verified by qPCR, flow cytometry, and colony formation assays in vitro. The target gene of hsa_piR_019914, lactate dehydrogenase A (LDHA), was screened by small RNA sequencing and quantitative polymerase chain reaction (qPCR), LDHA was knocked out in C28/I2 cells by the transfection of siRNA LDHA, and the relationship between hsa_piR_019914, LDHA, and reactive oxygen species (ROS) production was verified by flow cytometry. RESULTS: The piRNA hsa-piR-019914 was significantly downregulated in osteoarthritis (OA). Hsa-piR-019914 reduced inflammation-mediated chondrocyte apoptosis and maintained cell proliferation and clone formation in vitro. Hsa-piR-019914 reduced the production of LDHA-dependent ROS through targeted regulation of LDHA expression, maintained chondrocyte-specific gene expression of ACAN and COL2, and inhibited the gene expression of MMP3 and MMP13. CONCLUSIONS: Collectively, this study showed that hsa_piR_019914 was negatively correlated with the expression of LDHA, which mediates ROS production. Under the stimulation of inflammatory factors, overexpression of hsa_piR_019914 had a protective effect on chondrocytes in vitro, and the absence of hsa_piR_019914 exacerbated the negative effect of inflammation on chondrocytes. Studies on piRNAs provide new therapeutic interventions for OA.

Assessment of the coronal root canal morphology of permanent maxillary first molars using digital 3D-reconstruction technology based on micro-computed tomography data.

Background: The design of minimally invasive access has become a hotspot. This study aimed to evaluate the coronal root canal morphology of permanent maxillary first molars to facilitate the design of endodontic access cavities for minimally invasive linear access. Materials and methods: A selection of 91 permanent maxillary first molars was evaluated. Three-dimensional tooth models were reconstructed using micro-computed tomography data. Root canal prevalence and coronal root canal landmarks were recorded. The positional coordinates of landmarks in the horizontal plane and the angles and directions of coronal root canal curvature in the horizontal and axial planes were also assessed. Results: The detection rates of the mesiobuccal (MB), distobuccal (DB), and palatal (P) canals were 100%, whereas that of the second mesiobuccal (MB2) canals was 68.1%. All landmarks were located near the central fossa. In the axial plane, the average angles of coronal root canal curvature were DB (27.05°) > MB (25.43°) > P (20.71°) in teeth with three canals, and MB2 (33.20°) > MB (29.61°) > DB (28.40°) > P (23.69°) in teeth with four canals. In the horizontal plane, the average angles were P (78.15°) > DB (42.34°) > MB (32.41°) in teeth with three canals, and P (81.26°) > DB (43.44°) > MB (41.22°) > MB2 (9.41°) in teeth with four canals. Conclusion: In maxillary first molars, coronal root canals tend to converge towards the occlusal surface. The results of this study could be applied to improve the precision of endodontic access cavity designs of minimally invasive access.

Piperlonguminine attenuates renal fibrosis by inhibiting TRPC6.

ETHNOPHARMACOLOGICAL RELEVANCE: Liuwei Dihuang (LWDH) is a classic prescription that has been used to the treatment of "Kidney-Yin" deficiency syndrome for more than 1000 years in China. Recent studies have confirmed that LWDH can prevent the progression of renal fibrosis. Numerous studies have demonstrated the critical role that TRPC6 plays in the development of renal fibrosis. Due to the complex composition of LWDH and its remarkable therapeutic effect on renal fibrosis, it is possible to discover new active ingredients targeting TRPC6 for the treatment of renal fibrosis. AIM OF STUDY: This study aimed to identify selective TRPC6 inhibitors from LWDH and evaluate their therapeutical effects on renal fibrosis. MATERIALS AND METHODS: Computer-aided drug design was used to screen the biologically active ingredients of LWDH, and their affinities to human TRPC6 protein were detected by microcalorimetry. TRPC6, TRPC3, and TRPC7 over-expressed HEK293 cells were constructed, and the selective activities of the compounds on TRPC6 were determined by measuring [Ca2+]i in these cells. To establish an in vitro model of renal fibrosis, human renal proximal tubular epithelial HK-2 cells were stimulated with TGF-ß1. The therapeutic effects of LWDH compounds on renal fibrosis were then tested by detecting the related proteins. TRPC6 was knocked-down in HK-2 cells to investigate the effects of LWDH active ingredients on TRPC6. Finally, a unilateral ureteral obstruction model of renal fibrosis was established to test the therapeutic effect. RESULTS: From hundreds of LWDH ingredients, 64 active components with oral bioavailability ≥30% and drug-likeness index ≥0.18 were acquired. A total of 10 active components were obtained by molecular docking with TRPC6 protein. Among them, 4 components had an affinity with TRPC6. Piperlonguminine (PLG) had the most potent affinity with TRPC6 and blocking effect on TRPC6-mediated Ca2+ entry. A 100 µM of PLG showed no detectable inhibition on TRPC1, TRPC3, TRPC4, TRPC5, or TRPC7-mediated Ca2+ influx into cells. In vitro results indicated that PLG concentration-dependently inhibited the abnormally high expression of α-smooth muscle actin (α-SMA), collagen I, vimentin, and TRPC6 in TGF-ß1-induced HK-2 cells. Consistently, PLG also could not further inhibit TGF-ß1-induced expressions of these protein biomarkers in TRPC6 knocked-down HK-2 cells. In vivo, PLG dose-dependently reduced urinary protein, serum creatinine, and blood urea nitrogen levels in renal fibrosis mice and markedly alleviated fibrosis and the expressions of α-SMA, collagen I, vimentin, and TRPC6 in kidney tissues. CONCLUSION: Our results showed that PLG had anti-renal fibrosis effects by selectively inhibiting TRPC6. PLG might be a promising therapeutic agent for the treatment of renal fibrosis.

Development of Neuropeptide Hemokinin-1 Analogues with Antimicrobial and Wound-Healing Activity.

Wound healing is a complex process that can be delayed in some pathological conditions, such as infection and diabetes. Following skin injury, the neuropeptide substance P (SP) is released from peripheral neurons to promote wound healing by multiple mechanisms. Human hemokinin-1 (hHK-1) has been identified as an SP-like tachykinin peptide. Surprisingly, hHK-1 shares similar structural features with antimicrobial peptides (AMPs), but it does not display efficient antimicrobial activity. Therefore, a series of hHK-1 analogues were designed and synthesized. Among these analogues, AH-4 was found to display the greatest antimicrobial activity against a broad spectrum of bacteria. Furthermore, AH-4 rapidly killed bacteria by membrane disruption, similar to most AMPs. More importantly, AH-4 showed favorable healing activity in all tested mouse full-thickness excisional wound models. Overall, this study suggests that the neuropeptide hHK-1 can be used as a desirable template for developing promising therapeutics with multiple functions for wound healing.

Analysis of the network pharmacology and the structure-activity relationship of glycyrrhizic acid and glycyrrhetinic acid.

Licorice, a herbal product derived from the root of Glycyrrhiza species, has been used as a sweetening agent and traditional herbal medicine for hundreds of years. Glycyrrhizic acid (GL) and glycyrrhetinic acid (GA) are the most important active ingredients in licorice. Both GL and GA have pharmacological effects against tumors, inflammation, viral infection, liver diseases, neurological diseases, and metabolic diseases. However, they also exhibit differences. KEGG analysis indicated that licorice is involved in neuroactive ligand‒receptor interactions, while 18ß-GA is mostly involved in arrhythmogenic right ventricular cardiomyopathy. In this article, we comprehensively review the therapeutic potential of GL and GA by focusing on their pharmacological effects and working mechanisms. We systemically examine the structure-activity relationship of GL, GA and their isomers. Based on the various pharmacological activities of GL, GA and their isomers, we propose further development of structural derivatives of GA after chemical structure modification, with less cytotoxicity but higher targeting specificity. More research is needed on the clinical applications of licorice and its active ingredients.

Detection of Abnormal Spontaneous Brain Activity Patterns in Patients With Orbital Fractures Using Fractional Amplitude of Low Frequency Fluctuation.

Background: To date, no in-depth study has been conducted on the intrinsic pathological relationship between altered brain activity and related behavioral changes in patients with orbital fracture (OF). Purpose: The present research aimed to explore the potential functional network cerebrum activities in patients with OF using resting state functional magnetic resonance imaging-fractional amplitude of low-frequency fluctuation (rsfMRI-fALFF). This technique can reveal dynamic functional changes in specific cerebrum areas. Methods: Twenty patients with OF and 20 healthy controls (HCs) were included, closely matched in terms of gender, age, weight, and education level. To record spontaneous cerebral activity changes, the rsfMRI-fALFF tool was applied. Receiver operating characteristic (ROC) curves and Pearson's correlation analysis were used to analyze mean fALFF values in specific cerebrum regions and to explore changes of behavioral changes in patients with OF. The Hospital Depression and Anxiety scale was applied to reveal the relationship between emotional states and fALFF values of the right superior temporal gyrus in patients with OF. Results: In comparison with HCs, significantly lower fALFF values were detected in the left anterior cingulate gyrus (LACG) and right superior temporal gyrus (RSTG) in patients with OF. ROC curve analysis showed excellent accuracy. The mean fALFF values of the RSTG negatively correlated with the depression score as well as the anxiety score. Conclusion: The finding of abnormal spontaneous activities in cerebral regions may contribute to more comprehensive understanding of the potential neural network changes in patients with OF. The changes of fALFF value in patients with OF may help to gauge their emotional changes and clinical recovery levels.

Influence of chain length on the anticancer activity of the antimicrobial peptide CAMEL with fatty acid modification.

Antimicrobial peptides (AMPs) display promising potential in cancer therapy. Modification with fatty acids is a simple and effective approach to improve the activity of AMPs. In the present study, we investigated the effects of fatty acid chain lengths on the anticancer activity, self-assembly and mechanism of action of CAMEL (CM15, KWKLFKKIGAVLKVL-NH2), an amphipathic AMP with 15 amino acids. Conjugation of fatty acids could obviously improve the in vitro anticancer activity of CAMEL. Among the tested peptides, C12-CAMEL showed the highest anticancer activity, while C16-CAMEL killed cancer cells with the slowest kinetics. This may be related to the self-assembly of C12-CAMEL and C16-CAMEL, which could form spherical nanoparticles and tightened nanofibers, respectively. In addition, necrosis and necroptosis rather than apoptosis were the major mechanisms underlying the anticancer activity of CAMEL, C12-CAMEL and C16-CAMEL, implying that modification with fatty acids did not obviously alter the mechanism of action of CAMEL. Notably, C12-CAMEL, with high and rapid cell-killing activity, exhibited significantly stronger in vivo anticancer activity than CAMEL and C16-CAMEL. Overall, the present work suggests that the choice of a suitable fatty acid for structural modification is necessary for improving the anticancer activity of AMPs.

Similarities and differences among the responses to three chlorinated organophosphate esters in earthworm: Evidences from biomarkers, transcriptomics and metabolomics.

The wide use of chlorinated organophosphate esters (Cl-OPEs) as additive flame retardants has aroused concern about their potential risks on ecosystem and human health. However, knowledge about the toxicity of Cl-OPEs on soil organisms remains limited. In this study, earthworms, Eisenia fetida, were exposed to three representative Cl-OPEs, i.e., tris(2-chloroethyl) phosphate (TCEP), tris(2-chloro-1-methylethyl) phosphate (TCPP), and tris(1,3-dichloro-2-propyl) phosphate (TDCPP) in artificial soil. Using a combination of biochemical indicators (biomarkers), transcriptomics, and metabolomics, we compared the Cl-OPE-induced toxicity to E. fetida and provide new insight into the related molecular mechanism. All three Cl-OPEs elicited immune defense by the earthworms, as evidenced by increased acid phosphatase and alkaline phosphatase activities, and the genes involved in immune-related pathways (e.g., lysosomal and interleukin-17 signaling pathways). Furthermore, no effects on acetylcholinesterase activity were observed among the three Cl-OPEs. However, the TCPP and TDCPP treatments significantly decreased the neurotransmitter serotonin, suggesting the potential neurotoxicity of Cl-OPEs. Although TCEP affected the genes involved in carbohydrate and amino acid metabolism, the changes in the corresponding metabolites were not statistically significant. In contrast, exposure to TCPP and TDCPP induced oxidative stress, and affected xenobiotic metabolism and energy metabolism, leading to the decreased body weight in E. fetida. Based on these toxic effects, TCPP and TDCPP were more severely toxic than TCEP, despite their structural similarity. Given that the use of TCEP has been tightly regulated, our results suggest the potentially toxic effects of TCPP and TDCPP should not be ignored in future risk assessments of flame retardants.

Three-dimensional analysis of coronal root canal morphology of 136 permanent mandibular first molars by micro-computed tomography.

BACKGROUND/PURPOSE: Minimally invasive endodontic approach become a research hotspot and may prevent the fracture of endodontically-treated teeth. This research aims to measure the coronal root canal morphology of permanent mandibular first molars in 3D and propose a new minimally invasive endodontic approach based on this measurement. MATERIALS AND METHODS: Data of 136 permanent mandibular first molars were involved and reconstructed in 3D models with canals. Then, the morphology characteristics of the coronal root canal were measured. RESULTS: Overall, the distribution of root canal orifices was more centralized than other landmarks. The landmarks were located more mesiobuccally to the center of the occlusal plane of molars. Specifically, the measurements of the maximum curvature of coronal root canals in the axial direction were: in 3-canals 2-rooted teeth, the average angles of curvatures were 23°,25°,11° for mesiobuccal (MB), mesiolingual (ML) and distobuccal (DB) canals, respectively; in 4-canals 2-rooted teeth were 23°,25°,12°,16°for MB, ML, DB, and distolingual (DL) canals, respectively; in 4-canals 3-rooted teeth were 25°,27°,17°,39° for MB, ML, DB, and DL canals, respectively. The degrees of coronal root canal curvatures in the horizontal direction were: in 3-canals teeth, the average angles of curvatures were -1°,47°,-2° for MB, ML and DB canals, respectively; in 4-canals 2-rooted teeth were -4°,41°,-25°,48° for MB, ML, DB, and DL canals, respectively; in 4-canals 3-rooted teeth were -3°,33°,-43°,79° for MB, ML, DB, and DL canals, respectively. CONCLUSION: The results of this study are similar to those previously obtained using CBCT and can help us design endodontic approaches.

Decomposition analysis of industrial pollutant emissions in cities of Jiangsu based on the LMDI method.

Cities are faced with various kinds of pollution issues in the process of economic development, among which industrial pollution has become the most terrifying environmental issue in recent years, so that industrial pollution control should be emphasized. Finding out the key factors influencing industrial pollutant emissions is the basis of taking corresponding measures. Previous studies only focused on one pollutant without a comparative analysis of the contribution of influencing factors to multiple pollutants. Therefore, this study aims to identify the key influencing factors of industrial pollutants in Nanjing, Suzhou, Xuzhou, and Taizhou in Jiangsu Province during the years 2008-2018 by using the logarithmic mean Divisia index (LMDI) method. The results from decomposition indicate the following. (1) Emission intensity (EI) and energy efficiency (EE) are negative factors for decreasing industrial pollutant emissions, while the economic output (EO) and population (P) are positive factors for increasing industrial pollutant emissions. (2) Emission intensity has the most significant influence to industrial wastewater in decreasing emissions; energy efficiency makes the biggest contribution to industrial solid waste in decreasing emissions, economic output and population contribute the most to industrial solid waste in increasing emissions. (3) Nanjing has the highest contribution rate of emission intensity and population, and the contribution rate of energy efficiency and economic output to Taizhou is the highest. Identifying the key driving factors of different pollutants can serve as evidence and guidance for urban environmental governance, therefore reducing emissions ulteriorly, and achieving sustainable development.