Persistent pollution of genetic materials in a typical laboratory environment.

From the onset of coronavirus disease (COVID-19) pandemic, there are concerns regarding the disease spread and environmental pollution of biohazard since studies on genetic engineering flourish and numerous genetic materials were used such as the nucleic acid test of the severe acute respiratory syndrome coronavirus (SARS-CoV-2). In this work, we studied genetic material pollution in an institute during a development cycle of plasmid, one of typical genetic materials, with typical laboratory settings. The pollution source, transmission routes, and pollution levels in laboratory environment were examined. The Real-Time quantitative- Polymerase Chain Reaction results of all environmental mediums (surface, aerosol, and liquid) showed that a targeted DNA segment occurred along with routine experimental operations. Among the 79 surface and air samples collected in the genetic material operation, half of the environment samples (38 of 79) are positive for nucleic acid pollution. Persistent nucleic acid contaminations were observed in all tested laboratories and spread in the public area (hallway). The highest concentration for liquid and surface samples were 1.92 × 108 copies/uL and 5.22 × 107 copies/cm2, respectively. Significant amounts of the targeted gene (with a mean value of 74 copies/L) were detected in the indoor air of laboratories utilizing centrifuge devices, shaking tables, and cell homogenizers. Spills and improper disposal of plasmid products were primary sources of pollution. The importance of establishing designated experimental zones, employing advanced biosafety cabinets, and implementing highly efficient cleaning systems in laboratories with lower biosafety levels is underscored. SYNOPSIS: STATEMENT. Persistent environmental pollutions of genetic materials are introduced by typical experiments in laboratories with low biosafety level.

Incidence and influence factors of venous thromboembolism in traumatic rib fracture patient: a multicenter study.

BACKGROUND: This study aimed to determine the incidence and influencing factors of venous thromboembolism (VTE) in patients with traumatic rib fractures. METHODS: The retrospective study analyzed medical records of patients with traumatic rib fractures from 33 hospitals. RESULTS: The overall incidence of VTE in hospitalized patients with traumatic rib fractures was 8.1%. Patients with isolated traumatic rib fractures had a significantly lower incidence of VTE (4.4%) compared to patients with rib fractures combined with other injuries (12.0%). Multivariate analysis identified the number of rib fractures as an independent risk factor for thrombosis. Surgical stabilization of isolated rib fractures involving three or more ribs was associated with a lower VTE incidence compared to conservative treatment. CONCLUSIONS: Patients with rib fractures have a higher incidence of VTE, positively correlated with the number of rib fractures. However, the occurrence of thrombosis is relatively low in isolated rib fractures. Targeted thromboprophylaxis strategies should be implemented for these patients, and surgical stabilization of rib fractures may be beneficial in reducing the risk of VTE.

Effects of Intestinal Microbiota on the Biological Transformation of Arsenic in Zebrafish: Contribution and Mechanism.

Both the gut microbiome and their host participate in arsenic (As) biotransformation, while their exact roles and mechanisms in vivo remain unclear and unquantified. In this study, as3mt-/- zebrafish were treated with tetracycline (TET, 100 mg/L) and arsenite (iAsIII) exposure for 30 days and treated with probiotic Lactobacillus rhamnosus GG (LGG, 1 × 108 cfu/g) and iAsIII exposure for 15 days, respectively. Structural equation modeling analysis revealed that the contribution rates of the intestinal microbiome to the total arsenic (tAs) and inorganic As (iAs) metabolism approached 44.0 and 18.4%, respectively. Compared with wild-type, in as3mt-/- zebrafish, microbial richness and structure were more significantly correlated with tAs and iAs, and more differential microbes and microbial metabolic pathways significantly correlated with arsenic metabolites (P < 0.05). LGG supplement influenced the microbial communities, significantly up-regulated the expressions of genes related to As biotransformation (gss and gst) in the liver, down-regulated the expressions of oxidative stress genes (sod1, sod2, and cat) in the intestine, and increased arsenobetaine concentration (P < 0.05). Therefore, gut microbiome promotes As transformation and relieves As accumulation, playing more active roles under iAs stress when the host lacks key arsenic detoxification enzymes. LGG can promote As biotransformation and relieve oxidative stress under As exposure.

Adrenomedullin/FOXO3 enhances sunitinib resistance in clear cell renal cell carcinoma by inhibiting FDX1 expression and cuproptosis.

Cuproptosis, a new type of copper-induced cell death, is involved in the antitumor activity and resistance of multiple chemotherapeutic drugs. Our previous study revealed that adrenomedullin (ADM) was engaged in sunitinib resistance in clear cell renal cell carcinoma (ccRCC). However, it has yet to be investigated whether and how ADM regulates sunitinib resistance by cuproptosis. This study found that the ADM expression was elevated in sunitinib-resistant ccRCC tissues and cells. Furthermore, the upregulation of ADM significantly enhanced the chemoresistance of sunitinib compared with their respective control. Moreover, cuproptosis was involved in ADM-regulated sunitinib resistance by inhibiting mammalian ferredoxin 1 (FDX1) expression. Mechanically, the upregulated ADM activates the p38/MAPK signaling pathway to promote Forkhead box O3 (FOXO3) phosphorylation and its entry into the nucleus. Consequently, the increased FOXO3 in the nucleus inhibited FDX1 transcription and cell cuproptosis, promoting chemoresistance. Collectively, cuproptosis has a critical effector role in ccRCC progress and chemoresistance and thus is a relevant target to eradicate the cell population of sunitinib resistance.

DoSDefender: A Kernel-Mode TCP DoS Prevention in Software-Defined Networking.

The limited computation resource of the centralized controller and communication bandwidth between the control and data planes become the bottleneck in forwarding the packets in Software-Defined Networking (SDN). Denial of Service (DoS) attacks based on Transmission Control Protocol (TCP) can exhaust the resources of the control plane and overload the infrastructure of SDN networks. To mitigate TCP DoS attacks, DoSDefender is proposed as an efficient kernel-mode TCP DoS prevention framework in the data plane for SDN. It can prevent TCP DoS attacks from entering SDN by verifying the validity of the attempts to establish a TCP connection from the source, migrating the connection, and relaying the packets between the source and the destination in kernel space. DoSDefender conforms to the de facto standard SDN protocol, the OpenFlow policy, which requires no additional devices and no modifications in the control plane. Experimental results show that DoSDefender can effectively prevent TCP DoS attacks in low computing consumption while maintaining low connection delay and high packet forwarding throughput.

High Carrier Mobility and Controllable Electronic Property of the h-BN/SnSe2 Heterostructure.

Building two-dimensional (2D) vertical van der Waals heterostructures (vdWHs) is one of the effective methods to regulate the properties of single 2D materials. In this paper, we stack the hexagonal boron nitride (h-BN) monolayer (ML) on the SnSe2 ML to construct the stable h-BN/SnSe2 vdWH, of which the crystal and electronic structures, together with the optical properties, are also analyzed by the first-principles calculations. The results show that the h-BN/SnSe2 vdWH belongs to a type-I heterostructure with an indirect bandgap of 1.33 eV, in which the valence band maximum and conduction band minimum are both determined by the component SnSe2 ML. Interestingly, the h-BN/SnSe2 vdWH under the tensile strain or electric field undergoes the transitions both from type-I to type-II heterostructure and from the indirect to direct bandgap semiconductor. In addition, the carrier mobility of the h-BN/SnSe2 heterostructure has a significant enhancement relative to that of the SnSe2 ML, up to 104 cm2 V-1 s-1. Meanwhile, the h-BN/SnSe2 heterostructure presents the superb optical absorption and unique type-II hyperbolic property. Our findings will broaden the potential applications of SnSe2 ML and provide theoretical guidance for the related experimental studies.

Development and validation of a pulmonary complications prediction model based on the Yang's index.

Background: Blunt chest trauma patients with pulmonary contusion are susceptible to pulmonary complications, and severe cases may develop respiratory failure. Some studies have suggested the extent of pulmonary contusion to be the main predictor of pulmonary complications. However, no simple and effective method to assess the severity of pulmonary contusion has been available yet. A reliable prognostic prediction model would facilitate the identification of high-risk patients, so that early intervention can be given to reduce pulmonary complications; however, no suitable model based on such an assumption has been available yet. Methods: In this study, a new method for assessing lung contusion by the product of the three dimensions of the lung window on the computed tomography (CT) image was proposed. We conducted a retrospective study on patients with both thoracic trauma and pulmonary contusion admitted to 8 trauma centers in China from January 2014 to June 2020. Using patients from 2 centers with a large number of patients as the training set and patients from the other 6 centers as the validation set, a prediction model for pulmonary complications was established with Yang's index and rib fractures, etc., being the predictors. The pulmonary complications included pulmonary infection and respiratory failure. Results: This study included 515 patients, among whom 188 developed pulmonary complications, including 92 with respiratory failure. Risk factors contributing to pulmonary complications were identified, and a scoring system and prediction model were constructed. Using the training set, models for adverse outcomes and severe adverse outcomes were developed, and area under the curve (AUC) of 0.852 and 0.788 were achieved in the validation set. In the model performance for predicting pulmonary complications, the positive predictive value of the model is 0.938, the sensitivity of the model is 0.563 and the specificity of the model is 0.958. Conclusions: The generated indicator, called Yang's index, was proven to be an easy-to-use method for the evaluation of pulmonary contusion severity. The prediction model based on Yang's index could facilitate early identification of patients at risk of pulmonary complications, yet the effectiveness of the model remains to be validated and its performance remains to be improved in further studies with larger sample sizes.

First-principles study on the catalytic performance of transition metal atom-doped CrSe2 for the oxygen reduction reaction.

Since the oxygen reduction reaction (ORR) is the cathodic reaction of energy storage and conversion devices such as fuel cells and metal-air batteries, the search for catalysts with high-performance toward ORR has become the focus of attention. Transition metal dichalcogenides (TMDs) have the advantages of easy integration, inexpensive, harmless, good stability, and have vast application prospects in stabilizing the single atom. Hence, in this study, we investigated the feasibility of several 4d/5d single transition metals (TM = Rh, Pd, Ag, Ir, Pt, and Au) doped with CrSe2 for ORR electrocatalysis on the basis of density functional theory (DFT) calculations. Our results demonstrated that most of the TM-doped systems are stable, exhibiting metal conductivity, and can well activate the adsorbed O2. Interestingly, compared with end-on adsorption configuration, O2 is more likely to be adsorbed on the catalysts by a side-on adsorption configuration. Among all the candidate ORR catalysts, Pd-doped and Pt-doped CrSe2 have the best catalytic performance with a low overpotential of 0.43 and 0.50 V, respectively, making them good ORR candidate high performance catalysts. Our DFT work helps to understand the interaction between the O2 molecule and transition metal single atoms on CrSe2 supports and provides ideas for designing stable and efficient ORR catalysts.

Two pan-SARS-CoV-2 nanobodies and their multivalent derivatives effectively prevent Omicron infections in mice.

With the widespread vaccinations against coronavirus disease 2019 (COVID-19), we are witnessing gradually waning neutralizing antibodies and increasing cases of breakthrough infections, necessitating the development of drugs aside from vaccines, particularly ones that can be administered outside of hospitals. Here, we present two cross-reactive nanobodies (R14 and S43) and their multivalent derivatives, including decameric ones (fused to the immunoglobulin M [IgM] Fc) that maintain potent neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after aerosolization and display not only pan-SARS-CoV-2 but also varied pan-sarbecovirus activities. Through respiratory administration to mice, monovalent and decameric R14 significantly reduce the lung viral RNAs at low dose and display potent pre- and post-exposure protection. Furthermore, structural studies reveal the neutralizing mechanisms of R14 and S43 and the multiple inhibition effects that the multivalent derivatives exert. Our work demonstrates promising convenient drug candidates via respiratory administration against SARS-CoV-2 infection, which can contribute to containing the COVID-19 pandemic.

The fecal arsenic excretion, tissue arsenic accumulation, and metabolomics analysis in sub-chronic arsenic-exposed mice after in situ arsenic-induced fecal microbiota transplantation.

Arsenic can be specifically enriched by rice, and the health hazards caused by high arsenic rice are gradually attracting attention. This study aimed to explore the potential of microbial detoxification via gut microbiome in the treatment of sub-chronic arsenic poisoning. We first exposed mice to high-dose arsenic feed (30 mg/kg, rice arsenic composition) for 60 days to promote arsenic-induced microbes in situ in the gastrointestinal tract, then transplanted their fecal microbiota (FMT) into another batch of healthy recipient mice, and dynamically monitored the microbial colonization by 16S rRNA sequencing and ITS sequencing. The results showed that in situ arsenic-induced fecal microbiome can stably colonized and interact with indigenous microbes in the recipient mice in two weeks, and established a more stable network of gut microbiome. Then, the recipient mice continued to receive high-dose arsenic exposure for 52 days. After above sub-chronic arsenic exposure, compared with the non-FMT group, fecal arsenic excretion, liver and plasma arsenic accumulation were significantly lower (P < 0.05), and that in kidney, hair, and thighbone present no significant differences. Metabolomics of feces- plasma-brain axis were also disturbed, some up-regulated metabolites in feces, plasma, and cerebral cortex may play positive roles for the host. Therefore, microbial detoxification has potential in the treatment of sub-chronic arsenic poisoning. However, gut flora is an extremely complex community with different microorganisms have different arsenic metabolizing abilities, and various microbial metabolites. Coupled with the matrix effects, these factors will have various effects on the efflux and accumulation of arsenic. The definite effects (detoxification or non-detoxification) could be not assured based on the current study, and more systematic and rigorous studies are needed in the future.

High-density volatile organic compound monitoring network for identifying pollution sources.

The elusive sources of air pollution have hampered effective control across all sectors, with long-term consequences for the greenhouse effect and human health. Multiple monitoring systems have been highly desired for locating the sources. However, when faced with extensive sources, diverse air environments and meteorological conditions, the low spatiotemporal resolution, poor reliability and high cost of existing monitors were significant obstacles to their applications. Extending our previous demonstration of sensitive and reliable electrochemical sensors, we here present a machine-learning-assisted sensor arrays for monitoring typical volatile organic compounds (VOCs), which shows the consistent response with gas chromatography-mass spectrometry in the actual air environment. As a proof-of-concept, a low-cost and high-resolution VOC network of 152 sets of monitors across ~55 km2 of mixed-used land is established in southwest Beijing. Benefiting from the strong reliability, the pollution sources are revealed by the VOC network and supported by the joint mobile sampling of a vehicle-mounted gas chromatography-mass spectrometry system. With the sustained help of the network, the sources polluted by the local industrial facilities, traffic, and restaurants are effectively site-specific abatement by the local authorities and enterprises during the next half-year. Our findings open up a promising path toward more effective tracing of regional pollution sources, as well as accelerate the long-term transformation of industry and cities.

Measurement of atmospheric nanoparticles: Bridging the gap between gas-phase molecules and larger particles.

Atmospheric nanoparticles are crucial components contributing to fine particulate matter (PM2.5), and therefore have significant effects on visibility, climate, and human health. Due to the unique role of atmospheric nanoparticles during the evolution process from gas-phase molecules to larger particles, a number of sophisticated experimental techniques have been developed and employed for online monitoring and characterization of the physical and chemical properties of atmospheric nanoparticles, helping us to better understand the formation and growth of new particles. In this paper, we firstly review these state-of-the-art techniques for investigating the formation and growth of atmospheric nanoparticles (e.g., the gas-phase precursor species, molecular clusters, physicochemical properties, and chemical composition). Secondly, we present findings from recent field studies on the formation and growth of atmospheric nanoparticles, utilizing several advanced techniques. Furthermore, perspectives are proposed for technique development and improvements in measuring atmospheric nanoparticles.

Clinical application of directional dilation in transurethral columnar balloon dilation of the prostate.

Objectives: To investigate the clinical efficacy and safety of directional dilation in transurethral columnar balloon dilation of the prostate (TUCBDP), and summarize relevant experience. Methods: Retrospective analysis was performed on the clinical data of 38 patients with prostatic hyperplasia admitted to the Department of Urology, The Second Hospital of Hebei Medical University from October 2017 to January 2020 who underwent TUCBDP with directional dilation (12 o'clock direction). Complications related to surgery including hemorrhage, urinary incontinence and pain were analyzed. Moreover, patients were followed up for six months postoperatively, and their preoperative and postoperative maximum urine flow rate (Qmax), residual bladder volume (PVR), international prostate symptom score (IPSS), and quality of life score (QoL) were compared. Results: Thirty-eight patients underwent TUCBDP successfully, with dilation positions all in the 12 o'clock direction and no ectopic dilation point. All patients had no severe hematuria postoperatively. Numeric rating scales (NRS) was utilized twice at 8h and 24hour postoperatively to score the pain degree, with no statistically significant difference (P=0.157). Hb was reexamined on the first day postoperatively, with no statistically significant difference compared with that preoperatively (P>0.05). The bladder irrigation time was 1-2 Day postoperatively, while the urethra was removed five days postoperatively, with no severe hematuria in all patients. Two patients developed mild urinary incontinence, which disappeared on the 2nd and 5th day after extubation, respectively, while no patients had dysuria and urinary retention. All 38 patients were detected for Qmax and PVR after urethral removal, with a statistically significant difference compared with those preoperatively (P<0.001), and were reexamined three months postoperatively for Qmax and PVR, with a statistically significant difference compared with those postoperatively (P<0.001); IPSS and QoL were significantly different from those preoperatively with statistically significance (P<0.001). At the follow-up six months postoperatively, Qmax, PVR and IPSS showed statistically significant differences compared with that at three months postoperatively (P<0.05), while QoL showed no statistically significant differences compared with that at 3 months postoperatively (P=0.088). Conclusion: Directional dilation is improved in TUCBDP as having the advantages of safety and effectiveness, and it is worthy of clinical promotion.

Two key Geobacter species of wastewater-enriched electroactive biofilm respond differently to electric field.

Electroactive biofilms have attracted increasing attention due to their unique ability to exchange electrons with electrodes. Geobacter spp. are widely found to be dominant in biofilms in acetate-rich environments when an appropriate voltage is applied, but it is still largely unknown how these bacteria are selectively enriched. Herein, two key Geobacter spp. that have been demonstrated predominant in wastewater-enriched electroactive biofilm after long-term operation, G. sulfurreducens and G. anodireducens, responded to electric field (EF) differently, leading to a higher abundance of EF-sensitive G. anodireducens in the strong EF region after cocultivation with G. sulfurreducens. Transcriptome analysis indicated that two-component systems containing sensor histidine kinases and response regulators were the key for EF sensing in G. anodireducens rather than in G. sulfurreducens, which are closely connected to chemotaxis, c-di-GMP, fatty acid metabolism, pilus, oxidative phosphorylation and transcription, resulting in an increase in extracellular polymeric substance secretion and rapid cell proliferation. Our data reveal the mechanism by which EF select specific Geobacter spp. over time, providing new insights into Geobacter biofilm formation regulated by electricity.

Contrast-enhanced ultrasound targeted versus conventional ultrasound guided systematic prostate biopsy for the accurate diagnosis of prostate cancer: A meta-analysis.

BACKGROUND: Conventional transrectal ultrasonography (TRUS) guided prostate biopsy is the standard method for accurate diagnosis of prostate cancer (PCa). However, the limitations of this technique in terms of missed diagnosis cannot be ignored. Based on previous studies, contrast-enhanced ultrasound (CEUS) may be able to more distinctly detect malignant lesions with increased microvessels. Therefore, to evaluate the diagnostic efficiency and clinical application prospects of CEUS-guided prostate biopsy for patients with suspected PCa, we performed a meta-analysis comparing CEUS-targeted with TRUS-guided systematic biopsy. METHODS: A systematic search of PubMed, Web of Science, Embase and CNKI was performed up to March, 2022 for the relevant published studies. After data extraction and quality assessment, meta-analysis was performed using the RevMan 5.3 software. RESULTS: The results showed that the overall sensitivity was higher for CEUS targeted biopsy than systematic biopsy (P = .03), so was the accuracy (P = .03). However, significant heterogeneity and inconsistent results from certain subgroup analyses challenged the validity of the results. Meanwhile, CEUS yielded a much higher sensitivity in patients with prostate specific antigen (PSA) level of 4 to 10 ng/mL (P = .007). On the other hand, the positive rate of each core (P < .001) and the detection rate of clinically significant PCa (P = .006) were significantly improved using CEUS. CONCLUSION: CEUS showed the advantage of a higher detection rate of clinically significant PCa, which might provide more specific indications for subsequent treatment. More feasible, real-time data are required to confirm our findings.

Evaluation of a cost-effective roadside sensor platform for identifying high emitters.

High-emission vehicles (high emitters) likely have significantly higher nitrogen oxide and particle number (PN) emission factors compared to other vehicles. Effective identification of these vehicles in road traffic requires efficient and cost-effective instruments. In this study, a compact, cost-effective sensor platform was developed and evaluated in a field experiment. The platform was deployed on a roadside, and we measured pollutant concentrations in the exhaust plumes of four diesel trucks with various aftertreatment systems, cargo loads, and driving speeds. The sensor platform successfully measured carbon dioxide, PN, and nitric oxide (NO) concentrations, and the data were used to derive the plume-based emission factors of these pollutants. By considering both NO and PN emission factors, three diesel trucks with failed or outdated aftertreatment systems were successfully identified as potential high emitters. The NO emission factor obtained by the sensor platform was consistent with that of the benchmark portable emission measurement system. The sensor platform also effectively elucidated the differential influences of aftertreatment systems and driving conditions on emission factors. This pilot test demonstrates the feasibility of a sensor-based system for high emitter identification. Owing to its cost-effective and compact design, the proposed sensor platform has greater potential for mass networked deployment than regular-size instruments, thereby effectively supporting regulatory protocols for screening high emitters on public roads.

In situ analysis of variations of arsenicals, microbiome and transcriptome profiles along murine intestinal tract.

In situ-based studies on microbiome-host interactions after arsenic exposure are few. In this study, the variations in arsenics, microbiota, and host genes along murine intestinal tracts were determined after arsenic exposure for two months. There was a gradual increase in the concentration of total As (CtAs) in feces from ileum to colon, whereas CtAs in the corresponding tissues were relatively stable. Differences in arsenic levels between feces and tissues were significantly different. The proportion of arsenite (iAsⅢ) in feces gradually decreased, however, it gradually increased in tissues. After arsenic exposure, the diversity and abundance of microbial community and networks in each segment were significantly dysregulated. Notably, 328, 579 and 90 differently expressed genes were detected in ileum, cecum, and colon, respectively. In addition, microbiome and transcriptome analyses showed a significant correlation between the abundance of Faecalibaculum and expressions of Plb1, Hspa1b, Areg and Duoxa2 genes. This implies that they may be involved in arsenic biotransformation. In vitro experiments using Biofidobactrium and Lactobacillus showed that probiotics have arsenic transformation abilities. Therefore, gut microbiome may modulate arsenic accumulation, excretion and detoxification along the digestive tract. Moreover, the abundance and diversity of gut microbiome may be related to the changes in host health.

A comparative study on the Efficacy of Retroperitoneoscopic Pyeloplasty and Open Surgery for Ureteropelvic Junction Obstruction in Children.

OBJECTIVES: To compare the therapeutic effect of retroperitoneoscopic dismembered pyeloplasty and open ureteropelvic junction plasty on the ureteropelvic junction obstruction (UPJO) in children. METHODS: After the retrospective analysis of clinical data, 78 children with ureteropelvic junction stenosis treated from January, 2012 to June, 2018 were divided into two groups: OP (open pyeloplasty) group (38 cases) and LP (laparoscopic dismembered pyeloplasty) group (40 cases) according to the surgical methods. The operation time, intraoperative bleeding volume, postoperative length of stay (LOS), postoperative complication rate, postoperative hydronephrosis improvement and other indicators were compared between the two groups. RESULTS: All patients underwent surgery successfully, without conversion to open surgery in LP group. The incidence of postoperative urine leakage and the recovery of hydronephrosis between LP group and OP group 12 months after operation showed no statistically significant difference (P>0.05). The intraoperative bleeding volume, the incidence of postoperative retroperitoneal hematoma, and the postoperative LOS in LP group were lower than those in OP group, while the operation time was longer than that in the OP group, with statistically significant difference (P<0.05). CONCLUSION: Retroperitoneoscopic dismembered pyeloplasty had similar effect with open dismembered pyeloplasty, but faster recovery and fewer complications, so it has become the preferred treatment method for UPJO in children.

Changes in metabolomics and lipidomics in brain tissue and their correlations with the gut microbiome after chronic food-derived arsenic exposure in mice.

Arsenic can cause neurodegenerative diseases of the brain, but the definite mechanism is still unknown. In this study, to discuss the disturbances on brain metabolome and lipidome under subchronic arsenic exposure, we treated mice with the arsenic-containing feed (concentration of total arsenic = 30 mg/kg) prepared in accordance with the proportion of rice arsenicals for 16 weeks and performed metabolomics and lipidomics studies respectively using UHPLC-Triple-TOF-MS/MS and UHPLC-Q Exactive Focus MS/MS on mice brain. In addition, the distributions of arsenical metabolites along the feed-gut-blood-brain chain were analyzed by ICP-MS and HPLC-ICP-MS, and fecal microbial variations were investigated by 16 s sequencing. The data showed that although only a tiny amount of arsenic (DMA=0.101 mg/kg, uAs=0.071 mg/kg) enters the brain through the blood-brain barrier, there were significant changes in brain metabolism, including 118 metabolites and 17 lipids. These different metabolites were involved in 30 distinct pathways, including glycometabolism, and metabolisms of lipid, nucleic acid, and amino acid were previously reported to be correlated with neurodegenerative diseases. Additionally, these different metabolites were significantly correlated with 12 gut bacterial OTUs, among which Lachnospiraceae, Muribaculaceae, Ruminococcaceae, and Erysipelotrichaceae were also previously reported to be related to the distortion of metabolism, indicating that the disturbance of metabolism in the brain may be associated with the disturbance of gut microbes induced by arsenic. Thus, the current study demonstrated that the brain metabolome and lipidome were significantly disturbed under subchronic arsenic exposure, and the disturbances also significantly correlated with some gut microbiome and may be associated with neurodegenerative diseases. Although preliminary, the results shed some light on the pathophysiology of arsenic-caused neurodegenerative diseases.

Transthyretin Suppressed Tumor Progression in Nonsmall Cell Lung Cancer by Inactivating MAPK/ERK Pathway.

Background: Lung malignancy is a main source of disease passing all throughout the planet, whereas the transthyretin (TTR) is a specific biomarker for clinical diagnosis. However, its role in lung malignancy stays to be obscure. Materials and Methods: In the current examination, the authors made an endeavor to research impact of abnormal expression of TTR on nonsmall cell lung carcinoma (NSCLC) by overexpression or knockdown of TTR. To further explore the instruments' fundamental mechanism part of TTR in NSCLC, several signal pathways were searched and verified. To confirm the effect of TTR overexpression on tumors, in vivo experiments were conducted. Result: It was found that upregulated TTR clearly stifled cell proliferation, migration, invasion, and expanded apoptosis. Significant suppression of phosphor-extracellular signal-regulated kinase (ERK) was observed in TTR-treated NSCLC cells, implying that TTR was important for cellular progress by regulating mitogen-activated protein kinase/ERK signaling pathway. In in vivo experiment, overexpression of TTR promoted cell apoptosis and inhibited tumor growth. Conclusion: Overall, the results suggest that TTR has a potential antitumor effect in human NSCLC progression, which provides theoretical basis for the diagnosis and treatment of NSCLC. Above all, further understanding of TTR was useful for clinical care. Clinical Trial Registration Number: 2016-08.