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Supplementary Table S1, related to Figure 1. A total of 182 transposon insertions were identified in 27 resistant clones. Provided as a separate Excel file

Supplementary Table S2, related to Figure 6. Mutations in ciliary genes were identified from whole-exome sequencing data of untreated and resistant BCC samples previously published (1). Ciliary genes were determined using the SYSCILIA gold standard list of 303 genes for known ciliary components (2). Provided as a separate Excel file.

Supplementary Figures, tables, methods and references

Figure S1. Growth and survival of SMB cells depends on Shh signaling. Figure S2. SMB cell lines are a faithful model to study resistance to Smo inhibitors. Table S1. List of candidate genes with mutations used in the study. Figure S3. RAS signaling confers resistance to Smo inhibitor LDE225. Figure S4. FGF/RAS signaling abrogates dependence on Shh signaling. Figure S5. FGF/RAS-driven resistance to Smo inhibition is reversible and can be treated with MEK inhibitors. Figure S6. MEK inhibitors have therapeutic potential for HRAS SMB cells. Figure S7. Morphology of SMB(HRAS) cells differs from SMB parental cells. Figure S8. Immunohistochemistry of SFRP1, pERK and FGF in primary and metastatic samples from human Shh-subtype medulloblastoma patients. Table S2. Clinical diagnosis for human patient samples shown in Figure 5.

Background/ObjectivesThere is no predictive model available to address early stage malignant intraductal papillary mucinous neoplasm (IPMN) including high grade dysplasia (HGD) and pT1a (invasive component≤0.5 cm). The aim of this study was to establish an objective and sufficient model to predict the degree of malignancy in patients with IPMN, which can be easily applied in daily practice and adopted for any type of lesion.MethodsA retrospective cohort study of 309 patients who underwent surgical resection for IPMN was performed. Members of the cohort were randomly allocated to the training or testing set. A detection tree model and random forest model were used for a 3-class classification to distinguish low grade dysplasia (LGD), HGD/pT1a IPMN, and invasive intraductal papillary mucinous cancer (I-IPMC) beyond pT1a.ResultsOf the 309 patients, 54 (17.4%) had early stage malignancy (19 HGD, 35 pT1a), 49 (15.9%) had I-IPMC beyond pT1a, and 206 (66.7%) had LGD IPMN. We proposed a 3-class classification model using a random forest algorithm, and the model had an accuracy of 99.5% with the training set, and displayed an accuracy of 96.0% with the testing set. We used SHAP for interpretation of the model and showed the top five factors (mural nodule size, main pancreatic duct diameter, CA19-9 levels, lesion edge and common bile duct dilation) were most likely to influence the 3-class classification results in terms of interpretation of the random forest model.ConclusionsThis predictive model will help assess an individual’s risk for different stages of IPMN malignancy and may help identify patients with IPMN who require surgery.

To investigate whether BP is related to postbiopsy bleeding in patients undergoing native percutaneous kidney biopsy (PKB) and to evaluate the dynamic changes in blood pressure (BP) pre- and post-kidney biopsy.A retrospective cross-sectional study was conducted. The whole-procedural systolic (SBP) and diastolic (DBP) BP for patients undergoing ultrasound-guided native PKB from October 2017 to December 2020 were recorded in the study. Propensity score matching was used to minimize selection bias. SBP and DBP were analyzed as the main risk factors for bleeding complications. Receiver operating characteristic (ROC) curves were employed to explore the optimal BP thresholds to differentiate between bleeding and nonbleeding. The rates of major bleeding complications were analyzed according to BP thresholds through logistic analysis.Of 1146 biopsies, 432 (37.7%) patients suffered from postbiopsy bleeding, 88 (7.7%) patients had major bleeding complications, and 344 (30.0%) patients had minor bleeding complications. In the original data, for patients with SBP ≥ 160 mmHg before PKB, the rate of major bleeding complications was 17.6% (7.5% for SBP 160 mmHg), and the rate of major bleeding complications was 19.0% in patients with DBP ≥ 100 mmHg (7.5% for DBP 100 mmHg). For patients with DBP ≥ 85 mmHg to 100 mmHg after PKB, the rate of major bleeding complications ranged from 9.5 to 17.5%. The rate of major bleeding complications was lower (6.6-7.3%) in patients with DBP 100 mmHg to 85 mmHg.Patients who have high-level BP during the native PKB perioperative period are at higher risk for postbiopsy bleeding. High-level BP here does not refer to traditional hypertension according to the guidelines for the diagnosis and treatment of hypertension, but rather BP above a certain threshold related to bleeding risk.

Uniform and compact Zn deposition-dissolution is essential to achieve high Coulombic efficiency and long lifespan for Zn anodes. More attention has been commonly focused on the suppression of macroscopic Zn dendrites in the previous reports. The rational control of the microstructure of Zn deposition to prevent the intrinsic volume expansion and pulverization of Zn metal so as to stabilize Zn anodes is less discussed. Herein, we construct a three-dimensional topological Zn deposition at the nanoscale through an in situ electrochemical process in the optimal hybrid aqueous electrolyte. The topological electrode structure can efficiently accommodate microscopic strain and volume variation and thus largely preserve the macroscopic integrity and electrical contact of Zn anodes, leading to enhanced reversibility and stability. With the unique topological structure of Zn deposition, the Coulombic efficiency of Zn anodes could reach99.9% with excellent cycling over 1182 h at 2 mA cm

Postoperative chyle leakage (CL) is a rare but severe complication after neck dissection, and most patients with this complication can be treated conservatively. However, in patients with high-flow leakage, efficient and well-tolerated conservative treatment options are still lacking, and the treatments can be complicated. In this study, we report a case with CL of 1100 ml/day after neck dissection that was successfully treated by balloon compression.

Advanced oxidation processes (AOPs) can effectively degrade ranitidine, a pharmaceutical that is a typical precursor of nitrosamine dimethylamine (NDMA), an extremely potent human carcinogen. Herein, novel magnetic Ti3C2-based MXene nanosheets decorated with nanoscale zero-valent iron particles (nZVIPs@Ti3C2 nanosheets) were synthesized to boost catalytic peroxymonosulfate (PMS) activation, exhibiting remarkable reactivity and stability for the rapid removal of ranitidine under mild conditions. The response surface methodology (RSM) confirmed that the initial solution pH and PMS dosage were the main factors affecting the heterogeneous oxidation process. The long-lasting catalytic activity was mainly attributed to the rapid charge transfer between dual electron-rich active centers (≡Fe and ≡Ti), with SO4˙− and HO˙ derived from PMS activation being responsible for ranitidine degradation, among which SO4˙− was the major contributor. Density functional theory (DFT) calculations also confirmed that the as-synthesized nZVIPs@Ti3C2 nanosheets provided bi-active centers for PMS activation, and this process triggered a series of thermodynamically favorable reactions. This study demonstrates a recyclable oxidation method for the rapid removal of ranitidine, which may be applicable to the degradation of other challenging pollutants.

In this study, different carbon quantum dots (CQDs)/NaBiO3 hybrid materials were synthesized as photocatalysts to effectively utilize visible light for the photocatalytic degradation of contaminants effectively. These hybrid materials exhibit an enhanced photocatalytic reduction of hexavalent chromium (Cr(VI)) in the aqueous medium. Zero-dimensional nanoparticles of CQDs were embedded within the two-dimensional NaBiO3 nanosheets by the hydrothermal process. Compared with that of the pure NaBiO3 nanosheets, the photocatalytic performance of the hybrid catalysts was significantly high and 6 wt.% CQDs/NaBiO3 catalyst exhibited better photocatalytic performance. We performed the first-principles density functional theory calculations to study the interfacial properties of pure NaBiO3 nanosheets and hybrid photocatalysts, and confirmed the CQDs played an important role in the CQDs/NaBiO3 composites. The experimental results indicated that the enhanced reduction of Cr(VI) was probably due to the high loading of CQDs (electron acceptor) on NaBiO3, which made NaBiO3 nanomaterials to respond in visible light and significantly improved their electron-hole separation efficiency.

High speed free-space optical interconnection (FSOI) is an effective strategy to overcome the bottleneck of short-reach electronic interconnection from chip scale to board level, due to its wide bandwidth, high energy efficiency, low latency and high interconnect density. Here, we propose an accelerating beam enabled reconfigurable FSOI scheme by harnessing its characteristics of diffraction-free, self-healing, and specifically designed trajectory. Then we experimentally demonstrate a proof-of-concept 100 Gbps full duplex FSOI enabled by dual-band 2D Airy beams over 40 cm free-space optical link with a receiver sensitivity of −17.3 dBm at bit error ratio (BER) of ${1}{{0}^{{{ - 9}}}}$ . Both O-band and C-band 2D Airy beams can be successfully generated and detected with the help of two C-band spatial light modulators (SLMs). In addition, we experimentally investigate the impact of an obstacle occurring at the free-space optical link on the BER performance. Our experimental results indicate that, the performance of accelerating beam based FSOI is superior to the conventional Gaussian beam enabled FSOI under the same free-space optical link condition.

In recent years, navigation technology has rapidly developed. System-level calibration technology for inertial navigation system (INS) has been widely used because it does not rely on high-precision equipment. However, INS introduces a bad coupling error in high-precision ring laser gyroscope (RLG) scale-factor error estimation, accompanied by a large accelerometer-slope bias error. To solve this problem, an improved system-level fitting calibration method is proposed, which changes the 90° rotation increment to 450°, while maintaining the original calibration sequence. Compared with the traditional system-level calibration method, the calibration error of the gyroscope scale-factor error is reduced to 0.2 times, under simulation conditions, without affecting the calibration accuracy of the other parameters. The extreme difference of the gyroscope scale-factor calibration error on multiple experiments reduces from 4.75 to 1.40 ppm under experimental-verification conditions. The mean values of the gyroscope scale factor were closer to the real reference values (no more than 2 ppm). The integral calibration results meet the requirements of a high-precision RLG INS. The proposed method maintains the original calibration sequence and exhibits small changes with high practicability. The proposed method is suitable for applications with high requirements for gyroscope scale factor accuracy, such as highly dynamic aircraft.

A novel β-1,3-1,4-glucanase in the glycoside hydrolase family 5 (GH5) has been identified in the secretome of Paenibacillus polymyxa KF-1. The recombinant GH5 enzyme PpBglu5A shows broad substrate specificity, with strong lichenase activity, medium β-1,3-glucanase activity, and minimal cellulase activity. Barley β-glucan, lichenan, curdlan, and carboxymethyl cellulose are hydrolyzed to varying degrees by PpBglu5A, with the highest catalytic activity being observed with barley β-glucan. Hydrolysates from barley β-glucan or lichenan are primarily glucan oligosaccharides with degrees of polymerization from 2 to 4. PpBglu5A also hydrolyzes oat bran into oligosaccharides mainly consisted of di-, tri-, and tetra- oligosaccharides that are useful in the preparation of gluco-oligosaccharides. In addition to hydrolytic activity, transglycosylation was also observed with PpBglu5A and cellotriose as substrate. An in vitro assay indicated that the recombinant PpBglu5A has antifungal activity and can inhibit the growth of Canidia albicans. These results suggest that PpBglu5A exhibits unique properties and may be useful as an antifungal agent.

Objective: To investigate the value of magnetically guided capsule endoscopy (MGCE) and magnetic resonance enterography (MRE) in assessing the activity of pediatric Crohn’s disease.Methods: Clinical data from 82 subjects with pediatric Crohn’s disease, who underwent MGCE and MRE from October 2018 to March 2021 were analyzed retrospectively. Pairwise comparisons of several indexes, including MaRIA, CECDAI, PCDAI, and SES-CD, were performed by Spearman’s rank correlation test and kappa consistency analysis. CECDAI and MaRIA values predicted whether patients were moderately or severely active (PCDAI ≥30) clinically by logistic regression analysis. The area under the receiver operating characteristic curve (AUC) quantified the evaluation value of moderate to severe activity of pediatric CD.Results: In judging the severity of CD in the small intestine, the correlation coefficient between CECDAI and MaRIA was 0.406 (p < 0.05), and the kappa value of the consistency analysis was 0.299 (p < 0.05). MaRIA was weakly correlated with PCDAI (r = 0.254, p < 0.05), and they were weakly consistent in assessing the activity of Crohn’s disease (kappa = 0.135, p < 0.05). For predicting clinically moderate to severe activity, the fitted AUC based on CECDAI and MarRIA was 0.917, which was higher than applying a single parameter (CECDAI = 0.725, MarRIA = 0.899, respectively). MaRIA and serum albumin were significantly and negatively correlated (r = −1.064, p < 0.05). The consistency of the detection rate of gastric ulcers by MGCE and gastroscopy was moderate (kappa = 0.586, p < 0.05), and the detection rate of ulcers in the terminal ileum between MGCE and colonoscopy showed high consistency (kappa = 0.609, p < 0.05).Conclusions: MGCE and MRE are valuable, non-invasive methods for evaluating small bowel lesions in children with CD. The combined application of MGCE and MRE can better characterize the disease activity.

With the aggravation of fire and smoke pollution, it is urgent to develop green, lower-cost and high-performance Foamed Wood–Plastic Composite (FWPC) to meet the standards of antistatic and flame retardant in practical application. Therefore, the flame retardant and antistatic FWPCs were prepared by compression molding in this study. High-density polyethylene (PE-HD) and Salix wood flour were used as main raw materials, and azodicarbonamide (AC) was used as foaming agent; Nano-carbon black (Nano-CB) was used as antistatic filler, and ammonium polyphosphate (APP) and zinc borate (ZB) were used as flame retardants. The static bending strength and elastic modulus of FWPC-20 were up to 30.01 MPa and 2636 MPa, respectively, which can meet the commercial application of wood–plastic decorative board. The logarithm of surface resistivity and volume resistivity of FWPC-20 was kept at eight, indicating that it has antistatic effect. The residual carbon rate of FWPC-20 increased to 38.58% at 800 °C, indicating that FWPC had high thermal stability. The minimum heat release rate of FWPC-20 was 226.75 kw/m2, and the average heat release rate was 110.53 kw/m2. The total heat release was 66.96 MJ/m2, and the Limit Oxygen Index was 27.3%, which indicated that FWPC-20 had flame retardant and smoke suppression effects. This study provides a low-cost and simple method for the design of flame retardant, antistatic and high-performance FWPC, and has broad application prospects in the fields of packaging and construction.

Over the past few years, persistent organic pollutants (POPs) exhibiting high ecotoxicity have been widely detected in the environment. Persulfate-oxidation hybrid system is one of the most widely used novel advanced oxidation techniques and is based on the persulfate generation of SO

Micro (Nano)plastics are ubiquitous in the environment and can potentially affect the toxic effects of other chemicals, such as heavy metals. Although the interaction of micro (nano)plastics and heavy metals as well as their effects on aquatic organisms have been widely investigated, studies on their influence on terrestrial plants are limited. Therefore, in this study, the effects of polystyrene (PS), carboxy-modified PS (CPS) and amino-modified PS (APS) nanoparticles on the accumulation and toxicity of Pb on dandelion (Taraxacum asiaticum Dahlst) were investigated using hydroponic cultivation. The presence of the three PS caused cell damage and destroyed the tertiary structure of the ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and dehydrogenase (DHA) enzymes, thereby inhibiting Rubisco and root activities, which hindered nutrient uptake and photosynthesis. The inhibition of APS on the biomass of dandelion was greater than that of PS and CPS. Confocal laser scanning microscope and transmission electron microscopy analysis showed that APS was more likely to enter the roots of dandelion than PS and CPS. The presence of Pb induced more PS, CPS, and APS to enter dandelion roots, and Pb aggravated PS and CPS toxicities on dandelion rather than APS toxicity. This is because the complex formed by CPS and Pb can affect the structure of Rubisco and DHA through covalent and coordination bonds, and Pb increased the surface positive charge on CPS, according to Gaussian analysis. The presence of both PS and CPS significantly reduced Pb uptake by dandelion, and they did not exacerbate the toxicity of Pb. In contrast, APS slightly inhibited Pb accumulation, but aggravated Pb toxicity in dandelion. Our findings revealed that the changes in the uptake of nanoplastics and Pb by dandelion potentially resulted in a cascade of events that increased the toxicity and inhibited the growth of dandelion seedlings.

This study investigated if artemisinin-chrysosplenetin combination (ART-CHR) improved ART antimalarial efficacy against resistant Plasmodium berghei K173 via depressing host ABC transporter and potential molecular mechanism. Parasitaemia% and inhibition% were calculated and gene/protein expressions of ABC transporters or PXR/CAR/NF-κB p52 were detected by Western-blot and RT-qPCR. In vitro transcription of PXR/CAR was studied by dual-luciferase reporter assay. Our data indicated that ART-CHR improved ART efficacy against resistant parasites. P-gp inhibitor verapamil and CHR showed a stronger effect in killing resistant parasites while vehicle and Bcrp inhibitor novobiocin did not. ART activated intestinal ABCB1/ABCG2 and CHR inhibited them. ART decreased Bcrp protein whereas CHR increased it. ART ascended ABCC1/ABCC4/ABCC5 mRNA but ART-CHR descended them. CHR as well as rifampin (RIF) or 5-fluorouracil (5-FU) increased transcription levels of PXR/CAR while showed a versatile regulation on in vivo hepatic and enternal PXR/CAR in Mdr1a+/+ (WT) or Mdr1a-/- (KO) mice infected with sensitive or resistant parasites. Oppositely, hepatic and enteric N-κB p52 mRNA was conformably decreased in WT but increased in KO-resistant mice. NF-κB pathway should potentially involved in the mechanism of CHR on inhibiting ABC transporters and ART resistance while PXR/CAR play a more complicated role in this mechanism.

The new generation of smart meters need to realize the requirements of flexible expansion of advanced applications and transplantation of application software across hardware platforms. The software platform composed of operating system and middle layer service components is conducive to reducing the cost of software and hardware development and management. This paper first introduces the research and development background of the new generation smart meter, then introduces its overall software and hardware architecture and management unit hardware development platform, then introduces the construction of development environment and development tools and the basic functions based on the software platform, and finally introduces the development practice of application software. The large-scale promotion of the new generation of smart meters has become a development trend. This paper has a good reference for the application software development based on the new generation of smart meter software platform and is conducive to promoting the large-scale application of the new generation of smart meters.

The narrow light-response range and high electron/hole recombination rate greatly restrict the widespread use of photocatalytic technology. The integration of exposing dominant facet of semiconductor and Z-scheme heterostructures designing is expected to break those barriers. Herein，In this work, hydrothermal and ultrasonic stirring methods were used to selectively exposed the (001) and (110) facet of BiOI to construct the BiOI/CdS heterostructures. The obtained BiOI(001)/CdS material shown the maximum degradation for tetracycline-based antibiotics (Oxytetracycline, Tetracycline and Doxycycline), and excellent reduction of hexavalent chromium. Combining the electron spin resonance and scavenger experiments, the superior photocatalytic capacity was attributed to the generation of superoxide and hydroxyl radicals. DFT calculation results shown BiOI(001)/CdS performed high binding energy and adsorption energy for hexavalent chromium, and the different work function between BiOI(001) and CdS confirmed the building of internal electric field, thereby increased the charge separation. Finally, the Gaussian 09 and HPLC-MS program investigated the attack sites of free radicals and degradation pathways in the degradation of antibiotics. This study not only provides a potential photocatalyst, also gives an in-depth understanding of the photocatalytic properties of heterojunctions constructed by different exposed crystal facets.

This study for the first time proposed an efficient microbial electrolyte/UV system for Methyl Orange decomposition. With an external applied voltage of 0.2 V and cathode aeration of 20 mL/min, H2O2 could be in-situ generated from two-electron reduction of oxygen in cathode, reaching to 8.1 mg/L in 2 hr and continued to increase. The pollutant removal efficiency of approximate 94.7% was achieved at initial neutral pH, with the activation of •OH in the presence of UV illumination. Although the nature of its guiding principles remain on the vista of practical exploration, this proof-of-concept study provides an alternative operation pattern of solar–microbial hybrid technology for future wastewater treatment from a basic but multidisciplinary view.

Biothiols, generally including glutathione (GSH), cysteine (CySH), and homocysteine (HcySH), are important biomarkers and closely related to many diseases. In this work, a simple method for the spectrophotometric determination of the three biothiols was developed. The proposed method was based on the fact that Fe3+ could oxidize 3, 3′, 5, 5′-tetramethylbenzidine (TMB) to oxidized TMB (ox-TMB) and induce a blue color solution corresponding to an absorption peak centered at 652 nm. However, the introduction of a biothiol compound could cause the reduction of ox-TMB which resulted in a blue color fading and a decrease of the absorbance. Based on this finding, we developed a method for the determination of biothiols with the help of UV–vis spectroscopy, and the influence of different factors including pH, temperature, and incubation time was studied when glutathione worked as an example. The detection limits for GSH, CySH, and HcySH were 1.04, 0.82, and 2.09 μM, respectively. More importantly, the suggested method was successfully applied for the determination of GSH in human serum samples with the recovery of 97%–112%. This method is simple, fast and without the use of complicated nanomaterials.

Background Medulloblastoma (MB) is one of the most frequent malignant brain tumors of children, and a large set of these tumors is characterized by aberrant activation of the sonic hedgehog (SHH) pathway. While some tumors initially respond to inhibition of the SHH pathway component Smoothened (SMO), tumors ultimately recur due to downstream resistance mechanisms, indicating a need for novel therapeutic options. Methods Here we performed a targeted small-molecule screen on a stable, SHH-dependent murine MB cell line (SMB21). Comprehensive isotype profiling of histone deacetylase (HDAC) inhibitors was performed, and effects of HDAC inhibition were evaluated in cell lines both sensitive and resistant to SMO inhibition. Lastly, distinct mouse models of SHH MB were used to demonstrate pharmacologic efficacy in vivo. Results A subset of the HDAC inhibitors tested significantly inhibit tumor growth of SMB21 cells by preventing SHH pathway activation. Isotype profiling of HDAC inhibitors, together with genetic approaches suggested that concerted inhibition of multiple class I HDACs is necessary to achieve pathway inhibition. Of note, class I HDAC inhibitors were also efficacious in suppressing growth of diverse SMO inhibitor‒resistant clones of SMB21 cells. Finally, we show that the novel HDAC inhibitor quisinostat targets multiple class I HDACs, is well tolerated in mouse models, and robustly inhibits growth of SHH MB cells in vivo as well as in vitro. Conclusions Our data provide strong evidence that quisinostat or other class I HDAC inhibitors might be therapeutically useful for patients with SHH MB, including those resistant to SMO inhibition.

As a carcinogenic byproduct in drinking water treatment, bromate has raised global concerns on environmental and health hazard, calling for effective treatments. In the current work, a novel reduced graphene oxide supported polyaniline/WO2.72 nanobelt-flower (RGO/PANI/WO2.72) ternary composite was prepared through a solvent volatilization method for photocatalytic reduction of bromate. The prepared sample was characterized, and the influence of aqueous pH, ions and dissolved oxygen on the bromate reduction was explored. As expected, the introduction of RGO and PANI on the WO2.72 exhibited great synergistic effects on the separation of photogenerated carriers. The calculated reduction rate constant of RGO/PANI/WO2.72 was about six times as high as that of pure WO2.72. Specially, the prepared photocatalyst possessed strong optical absorption in a broad range of 250–2500 nm, and thus displaying excellent catalytic performance in utilization of all solar spectrum energy. Moreover, the RGO/PANI/WO2.72 exhibited stable photocatalytic activity in cycling test. Considered holistically, the present study offered a valuable approach for rational construction of heterogeneous structure in the development of bromate-catalyzed reduction.

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a re-emerging environmental contaminant used as a suitable substitute for brominated flame retardants. The objective of this study was to evaluate the effects of TDCIPP on thyroid disruption and growth inhibition in zebrafish (Danio rerio) offspring after chronic parental exposure, and to examine the possible molecular mechanisms involved. When adult zebrafish (4 months old) were exposed to 5.66, 25.55, or 92.8 μg TDCIPP/L for 90 days, bioconcentration of TDCIPP and its metabolic product [bis(1,3-dichloro-2-propyl) phosphate, BDCIPP] was observed in 7-day postfertilization (dpf) F1 larvae, which suggests the transfer of this compound from adult fish to their offspring. Our results demonstrated that parental exposure to TDCIPP induced thyroid disruption in the offspring, demonstrated by significantly decreased thyroxine (T4) and increased 3,5,3'-triiodothyronine (T3) levels, and disruption of the transcription of several genes and expression of proteins involved in the hypothalamic-pituitary-thyroid (HPT) axis in F1 larvae. Parental exposure to TDCIPP resulted in developmental abnormalities in offspring; the smaller body length that was recorded might be partly the result of the perturbation of the HPT axis. In addition, the results revealed that growth inhibition also resulted from the downregulation of the transcription of genes and expression of proteins involved in the growth hormone/insulin-like growth factor (GH/IGF) axis. Our study provides a new set of evidence showing that parental exposure to TDCIPP can induce thyroid disruption and inhibition of growth in offspring, and that perturbation of the HPT axis and GH/IGF axis contribute to these adverse effects.

Photocatalysis using solar energy is the most promising green technology for nitrite removal. However, effective photocatalytic performance is often challenged by the limited light absorption, utilization of expensive noble metals and undesired products (nitrate and ammonium). Here, we report for the first time that a full solar light response polyaniline-decorated three dimensional W18O49 composite (PANI@W18O49), a noble metal-free photocatalyst, possesses excellent photocatalytic activity for aqueous nitrite removal with high N2 selectivity. The prepared sample was thoroughly identified via XRD, Raman, FTIR, SEM, TEM, UV–vis DRS and PL. The catalytic results demonstrated that over 80% N2 selectivity (initial concentration 1.0 mM) was achieved through the PANI@W18O49 without sacrificial agent under 300 W Xe lamp irradiation for 60 min. Such advantages were attributed to the built-in junction between n-type W18O49 and p-type PANI, offering suitable redox levels of electron-hole pairs for NO2− reaction. The modification of PANI also benefited the light harvesting ability and activated carriers migration, the calculated rate constant of PANI@W18O49 is about four times as high as that of W18O49. The current study not only prepared a promising photocatalyst, but also provides new insights into improving the photocatalytic activity and N2 selectivity for nitrite treatment.

Electrochemical oxidation is an effective mean to degrade non-biodegradable organics from the contaminated waters. However, its current efficiency is very low for the low-concentration organic pollutants treatment. In this work, combining with the outstanding adsorption property of CNT and the effective electrocatalytic oxidation performance of β-PbO2, we constructed novel layer-by-layer carbon nanotube/PbO2 anodes (CNT/PbO2-3, CNT/PbO2-4 and CNT/PbO2-5) with high adsorbability to enhance the electrochemical degradation efficiency of low-concentration sodium pentachlorophenate (PCP Na). In electrochemical oxidation tests, the PCP-Na was rapidly enriched in the CNT/PbO2 film through adsorption/electrosorption and then efficiently degraded in site. The removal efficiency of low-concentration PCP-Na (5 mg/L) on CNT/PbO2-4 reached 73.8% after only 5 min of electrolysis, whereas that on pure PbO2 was only 9.9%. To further clarify the mechanism of improvement of PCP-Na removal on CNT/PbO2-4 anode, the generation capacity of·OH radicals, oxygen evolution overpotential, voltammetric charge quantity, interface resistance, and specific surface area of CNT/PbO2-4 anode were also assessed and compared with those of other three anodes. Results showed that, in addition to the synergistic effect of adsorption/electrosorption and electrocatalysis, the more active sites, smaller electron transfer resistance and higher direct oxidation capacity of CNT/PbO2-4 anode also contributed to improving degradation rate of PCP-Na on CNT/PbO2-4 anode. Additionally the electrochemical degradation pathway of PCP-Na was also proposed based on the gas chromatography-mass spectrometry analysis. Finally, CNT/PbO2-4 electrode exhibited longer accelerated lifetime of 116 h than pure PbO2 electrode (91 h). Thus, these findings provide a new anode to improve the removal of low-concentration organic pollutants through combining electrochemical oxidation and adsorption/electrosorption processes.

Lewy bodies are characteristic spherical inclusions in Parkinson's disease (PD) that are formed by α-synuclein fibrils. Ferruginol (Fer) is an amonomeric compound isolated from a traditional Chinese herb. Here, we show that Fer exerted potent neuroprotective effects in both in vitro and in vivo PD models. Neuronal cells transfected with A53T mutant (A53T) α-synuclein plasmids and treated with Fer exhibited attenuated the cytotoxicity induced by pathogenic A53T α-synuclein overexpression. Further, when we transfected neuronal cells with siRNA-SNCA (alpha-synuclein) plasmids and incubated them with Fer, the protective role of Fer decreased. We also found that Fer was a potent α-synuclein inhibitor in neuronal cells, which promotes the clearance of αsynuclein in dopaminergic neurons exposed to 1-Methyl-4-phenylpyridinium (MPP +). Fer could inhibit abnormal α-synuclein aggregation and dopaminergic neuron depletion in A53T-Tg mice, suggesting that a role for Fer in α-synuclein accumulation and nigrostriatal pathway injury. Our study revealed that Fer strongly alleviated neurodegeneration by promoting α-synuclein clearance, indicating a neuroprotective role against α-synuclein oligomer-induced neurodegeneration, which makes it a promising candidate for the treatment of PD and other neurodegenerative diseases.

To investigate the changes of subcortical gray matter volume and cortical thickness, andexplorethe correlations between regional abnormalities of cortical thickness and cognitive impairment and the effect of modified Bushenyisui decoction ( BSYSD) on the cognitive function of multiple sclerosis (MS).This prospective study was approved by the institutional review board. 92 subjects were recruited, including 46 relapsing-remitting multiple sclerosis (RRMS) patients and 46 healthy controls (HC). Of the 46 patients, 22 patients experienced the treatment of BSYSD for half a year. A conventional three-dimensional T1-weighted sequence were acquired for all participants on a 3.0 tesla magnetic resonance system. Basic information, detailed cognitive scales Montreal Cognitive Assessment (MoCA), symbol digit modalities test (SDMT), immediate memory, delayed recall, and long-term recognition were evaluated. Subcortical gray matter volume and cortical thickness weremeasured by FreeSurfer. The correlations between cortical thickness which MS patients showed reduced with respect to HC and cognitive scales wereanalyzed by Pearson correlation in RRMS patients. The influence of modified BSYSD on MS patients' cognition was analyzed by paired T Test.MoCA, immediate memory, delayed recall, and long-term delayed recognition in RRMS were significantly decreased than those of HC. Gray matter atrophy measured by FreeSurfer showed mainly in thalamus and hippocampus of RRMS patients. Compared with HC, the cortical thickness of several regions in frontal lobe, parietal lobe, temporal lobe, hippocampal, cingulate gyrus, and fusiform gyrus of RRMS patients were decreased with significant difference. The regions of cortical thickness thinning related to MoCA, immediate memory, delayed recall, and long-term delayed recognition were temporal lobe and fusiform gyrus. Modified BSYSD could improve MoCA, SDMT, immediate memory, delayed recall, and long-term delayed recognition of MS patients, and it could promote the recovery of cognitive function in MS patients.Gray matter atrophy and cortical thickness thinning were validated in RRMS. Cortical thickness thinning of temporal lobe and fusiform gyrus strongly related to cognitive deficits in RRMS. The modified BSYSD could promote the recovery of cognitive function in MS.

Analysis of the atmospheric Aerosol Particle Size Distribution (APSD) retrieved from Light Detection and Ranging (Lidar) data is one of the popular fields in atmospheric remote sensing. An APSD retrieval method based on the lognormal particle size distribution, the Mie theory, and the Second Simulation of the Satellite Signal in the Solar Spectrum (6S) were studied. According to the 6S, this method divides the main body of the aerosols into four basic components and calculates the APSD from Lidar data and the optical and microphysical characteristics of these components. Numerical simulation and experimental observations reveal that this method can obtain the APSD for particle sizes of0.15 μm in the different vertical layers with good reliability.

Favorable effects exerted by long-term administration of fingolimod therapy in multiple sclerosis (MS) patients have been reported, but sporadic side effects, such as reversible macular edema, also have been recorded. The present study aimed to determine whether fingolimod therapy is beneficial to the visual system in experimental autoimmune encephalomyelitis (EAE) mice. A decrease in demyelination and axon loss in the optic nerve as well as cellular infiltration, especially the recruited macrophages, was observed in EAE with fingolimod treatment. Fingolimod administration diminished hypergliosis of macroglia, including astrocytes and Müller cells in the retina and optic nerve in EAE. Microglia were hyperactivated in the retina and optic nerve in the EAE mice compared to controls, which could be alleviated by fingolimod treatment. Moreover, apoptosis of retinal ganglion cells (RGC) and oligodendrocytes in the optic nerve was significantly reduced with fingolimod treatment compared to that in the untreated EAE mice. These results suggested that fingolimod exerts neuroprotective and anti-inflammatory effects on the retina and optic nerve in a mouse model of EAE. Considering the paradox of favorable and side effects of fingolimod on visual system, we speculate that side effects including macular oedema caused by fingolimod during MS treatment is tendency to be vasogenic rather than hypergliosis in optic nerve and retina which warrants further neuroophthalmological investigation., Graphical Abstract Our results show that fingolimod is a potential therapeutic approach to prevent EAE-induced visual impairment. Moreover, we show that the observed neuro-ophthalmological protective effects of fingolimod were dependent on hampering hyper-gliosis in the retina and optic nerve.

Photocatalytic oxidation using solar energy is a promising green technology to degrade antibiotic contaminants. Herein, a 2D g-C

In recent years, the mortality rate of respiratory diseases ranks high among the major diseases. Early detection of respiratory diseases is a key factor in reducing the mortality rate and curing diseases. In this paper, we propose the BiGRU Attention-XGBoost model to classify respiratory sounds, in order to assist doctors in the early diagnosis of respiratory diseases. Specifically, we first extract two sets of features, i.e., the time domain and spectral features to encode respiratory sounds. Then, we apply the Gradient Boosting Decision Tree algorithm to select important features for classification. Based on the temporal characteristics of respiratory sounds, we design the BiGRU Attention-XGBoost model to classify them. Finally, to enlarge the training dataset and address the problem of data imbalance, we also implement Griffifin-Lim and WORLD Vocoder, two data augmentation methods. Extensive experiments show the superiority of the proposed model compared to seven state-of the-art models in terms of classification accuracy and Fl-score.

Photocatalysis is an effective method to degrade ranitidine (RAN), which is a typical precursor of nitrosamine dimethylamine (NDMA), an extremely potent human carcinogen. Herein, MXene-Ti