Comparison of the Efficacy Among Nilotinib, Dasatinib, Flumatinib and Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia Patients: A Real-World Multi-Center Retrospective Study.

BACKGROUND: There are limited data comprehensively comparing therapy responses and outcomes among nilotinib, dasatinib, flumatinib and imatinib for newly diagnosed chronic-phase chronic myeloid leukemia in a real-world setting. PATIENTS AND METHODS: Data from patients with chronic-phase CML receiving initial a second-generation tyrosine-kinase inhibitor (2G-TKI, nilotinib, dasatinib or flumatinib) or imatinib therapy from 77 Chinese centers were retrospectively interrogated. Propensity-score matching (PSM) analyses were performed to to compare therapy responses and outcomes among these 4 TKIs. RESULTS: 2,496 patients receiving initial nilotinib (n = 512), dasatinib (n = 134), flumatinib (n = 411) or imatinib (n = 1,439) therapy were retrospectively interrogated in this study. PSM analyses indicated that patients receiving initial nilotinib, dasatinib or flumatinib therapy had comparable cytogenetic and molecular responses (p = .28-.91) and survival outcomes including failure-free survival (FFS, p = .28-.43), progression-free survival (PFS, p = .19-.93) and overall survival (OS) (p values = .76-.78) but had significantly higher cumulative incidences of cytogenetic and molecular responses (all p values < .001) and higher probabilities of FFS (p < .001-.01) than those receiving imatinib therapy, despite comparable PFS (p = .18-.89) and OS (p = .23-.30). CONCLUSION: Nilotinib, dasatinib and flumatinib had comparable efficacy, and significantly higher therapy responses and higher FFS rates than imatinib in newly diagnosed CML patients. However, there were no significant differences in PFS and OS among these 4 TKIs. These real-world data may provide additional evidence for routine clinical assessments to identify more appropriate therapies.

Enhancing Systemic Translocation of Insecticides via Nanoformulations Incorporating ß-Cyclodextrin Octadecarboxylate as a Carrier.

The conversion of contact-killing pesticides into systemic pesticides can significantly enhance the bioavailability of pesticides, thereby reducing pesticide usage and environmental harm. A series of ß-cyclodextrin fatty acid esters with varying branch chains were synthesized and employed as carriers in nanoformulation of insecticide. The investigation revealed that nanoformulations prepared using ß-cyclodextrin octadecarboxylate (ß-CDs) exhibited superior stability and remarkable systemic translocation within plants. Six contact-killing insecticide nanoformulations were developed utilizing ß-CDs as carriers, and tests indicated that ß-CDs significantly enhanced the systemic translocation of insecticides in plants compared to carrier-free nanoformulations. It was found that ß-CDs increased the level of systemic translocation of insecticides by 5-12 times. Additionally, characterization results from λ-cyhalothrin-ß-CDs nanoformulation demonstrated their superior ability to improve photolysis resistance, prolong release time, and extend insecticidal duration. Consequently, ß-CDs can be utilized as a green additive in pesticide production to enhance the systemic translocation of pesticides in plants and increase their bioavailability.

Patient Versus Physician Perspective in the Management of Chronic Myeloid Leukemia During Treatment with Tyrosine Kinase Inhibitors.

INTRODUCTION: Chronic myeloid leukemia (CML) is a chronic disease with treatment-free remission (TFR) increasingly regarded as a feasible goal of treatment. However, various factors may influence adherence to international guidelines for CML management. This study aimed to compare the reporting of care between patients with CML and their treating doctors. METHODS: Parallel patient and physician online surveys were conducted between September 22, 2021, and March 15, 2022, which focused on the perceptions of 1882 adult patients with CML and 305 physicians regarding tyrosine kinase inhibitor (TKI) treatment options, monitoring and toxicities, TFR, and challenges faced. RESULTS: Among the enrolled patients, 69.9% received first-line imatinib treatment, 18.6% received nilotinib, and 4.7% received dasatinib. Among the patients treated with imatinib, 36.7% switched to other TKIs due to imatinib resistance/intolerance (71.1%), exploration of more potent TKIs to achieve TFR (8.9%), and treating physicians' recommendation (14.0%), with a median duration of initial treatment of 14 months [interquartile range (IQR) 6-36]. Most (91.8%) physicians agreed that the breakpoint cluster region-Abelson 1 (BCR::ABL1) transcript level should be assessed every 3 months, but only 42.7% of individuals committed to 3-monthly testing and only 17.8% strictly followed their treating physicians' recommendation. Half of the patients aimed for TFR; however, just 45.2% of physicians considered TFR as one of the top three goals for their patients. The major concern in obtaining TFR was patients' adherence. Fatigue was often distressing for patients with TKIs, while physicians were more concerned about platelet and neutrophil counts. A total of 12% and 20.8% of patients reported moderate/severe anxiety and depression, respectively, while only 53.7% of physicians had concerns about their patients' mental health. During the coronavirus disease 2019 (COVID-19) pandemic, 69.2% of patients reported a reduction in their income. Among these patients, 61.8% maintained their current treatment, while 7.3% switched to cheaper alternatives or discontinued treatment, with over 80% of these patients belonging to the low-income group. CONCLUSIONS: Overcoming challenges in patient-physician communication and treatment access is key to improving disease management and quality of life, especially for patients with low income. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05092048.

18 months follow-up of deep molecular response 4.5 (MR4.5) with nilotinib in patients with newly diagnosed chronic-phase chronic myeloid leukemia: a prospective, multi-center study in China.

Introduction: Early stable deep molecular response (DMR) to nilotinib is associated with goal of treatment-free remission (TFR) in patients with chronic-phase chronic myeloid leukemia (CML-CP). It is important to early distinguish between patients who can achieve a DMR and those who are fit for TFR. Methods: We performed a multicenter study to explore the early cumulative MR4.5 rate at 18 months with nilotinib in patients with newly diagnosed CML-CP (ND-CML-CP) in China. Of the 29 institutes, 106 patients with ND-CML-CP received nilotinib (300 mg BID). Results and discussion: The cumulative MR4.5 rate of nilotinib treatment at 18 months was 69.8% (74/106). The cumulative MMR and MR4.0 rates for nilotinib at 18 months were 94.3% (100/106) and 84.9% (90/106), respectively. Patients with an ultra-early molecular response (u-EMR) at 6 weeks were not significantly different in obtaining DMR or MMR by 24 months compared with those without u-EMR (p = 0.7584 and p = 0.9543, respectively). Our study demonstrated that nilotinib treatment in patients with ND-CML-CP contributed to obtain high early MR4.5.

Semantic Segmentation and Depth Estimation Based on Residual Attention Mechanism.

Semantic segmentation and depth estimation are crucial components in the field of autonomous driving for scene understanding. Jointly learning these tasks can lead to a better understanding of scenarios. However, using task-specific networks to extract global features from task-shared networks can be inadequate. To address this issue, we propose a multi-task residual attention network (MTRAN) that consists of a global shared network and two attention networks dedicated to semantic segmentation and depth estimation. The convolutional block attention module is used to highlight the global feature map, and residual connections are added to prevent network degradation problems. To ensure manageable task loss and prevent specific tasks from dominating the training process, we introduce a random-weighted strategy into the impartial multi-task learning method. We conduct experiments to demonstrate the effectiveness of the proposed method.

Discovery and biological evaluation of pregnenolone selenocyanoamides with potential anticancer and antimicrobial activities.

Starting with pregnenolone, a 20-carbonyl group was converted into an amino group through a series of chemical reactions. This amino group was further converted into selenocyanoalkylamide, leading to the synthesis of six pregnenolone selenocyanoalkylamide derivatives. These compounds were then screened for antitumor activity in vitro, yielding promising results. Compounds 4b-4f show higher inhibitory activity than the positive control abiraterone and 2-methoxyestradiol, with IC50 values lower than 10 µmol/L against breast, ovarian, and cervical cancer cell lines that closely related to human hormone expression levels. The Annexin V assay of compound 4f revealed that compounds inhibited tumor cell proliferation primarily through the induction of programmed apoptosis. The zebrafish test results indicated that compound 4d had significant inhibitory activity against MCF-7 cell xenografts in vivo. Moreover, the antibacterial test indicated that compounds 4a and 4d-4e had better inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) than the positive controls vancomycin and ampicillin. These results suggest that these compounds may hold promise as novel antitumor agents or antimicrobial agents for further study.

A Simple Method for Synthesis of Chitosan Nanoparticles with Ionic Gelation and Homogenization.

Chitosan nanoparticles (CNPs) are known to have great utility in many fields (pharmaceutical, agricultural, food industry, wastewater treatment, etc.). In this study we aimed to synthesize sub-100 nm CNPs as a precursor of new biopolymer-based virus surrogates for water applications. We present a simple yet efficient synthesis procedure for obtaining high yield, monodisperse CNPs with size 68-77 nm. The CNPs were synthesized by ionic gelation using low molecular weight chitosan (deacetylation 75-85%) and tripolyphosphate as crosslinker, under rigorous homogenization to decrease size and increase uniformity, and purified by passing through 0.1 µm polyethersulfone syringe filters. The CNPs were characterized using dynamic light scattering, tunable resistive pulse sensing, and scanning electron microscopy. We demonstrate reproducibility of this method at two separate facilities. The effects of pH, ionic strength and three different purification methods on the size and polydispersity of CNP formation were examined. Larger CNPs (95-219) were produced under ionic strength and pH controls, and when purified using ultracentrifugation or size exclusion chromatography. Smaller CNPs (68-77 nm) were formulated using homogenization and filtration, and could readily interact with negatively charge proteins and DNA, making them an ideal precursor for the development of DNA-labelled, protein-coated virus surrogates for environmental water applications.

Comparative reductions of norovirus, echovirus, adenovirus, Campylobacter jejuni and process indicator organisms during water filtration in alluvial sand.

Sand filtration is a cost-effective means of reducing microbial pathogens in drinking-water treatment. Our understanding of pathogen removal by sand filtration relies largely on studies of process microbial indicators, and comparative data from pathogens are sparse. In this study, we examined the reductions of norovirus, echovirus, adenovirus, bacteriophage MS2 and PRD1, Campylobacter jejuni, and Escherichia coli during water filtration through alluvial sand. Duplicate experiments were conducted using 2 sand columns (50 cm long, 10 cm diameter) and municipal tap water sourced from chlorine-free untreated groundwater (pH 8.0, 1.47 mM) at filtration rates of 1.1-1.3 m/day. The results were analysed using colloid filtration theory and the HYDRUS-1D 2-site attachment-detachment model. The average log10 reduction values (LRVs) of the normalised dimensionless peak concentrations (Cmax/C0) over 0.5 m were: MS2: 0.28; E. coli: 0.76; C. jejuni: 0.78; PRD1: 2.00; echovirus: 2.20; norovirus: 2.35; and adenovirus: 2.79. The relative reductions largely corresponded to the organisms' isoelectric points rather than their particle sizes or hydrophobicities. MS2 underestimated virus reductions by 1.7-2.5 log, and the LRVs, mass recoveries relative to bromide, collision efficiencies, and attachment and detachment rates differed mostly by ∼1 order of magnitude. Conversely, PRD1 reductions were comparable with those of all 3 viruses tested, and its parameter values were mostly within the same orders of magnitude. E. coli seemed an adequate process indicator for C. jejuni with similar reductions. Comparative data describing pathogen and indicator reductions in alluvial sand have important implications for sand filter design, risk assessments of drinking-water supplies from riverbank filtration and the determination of safe setback distances for drinking-water supply wells.

Synthesis of Alginate Nanoparticles Using Hydrolyzed and Enzyme-Digested Alginate Using the Ionic Gelation and Water-in-Oil Emulsion Method.

Alginate nanoparticles (AlgNPs) are attracting increasing interest for a range of applications because of their good biocompatibility and their ability to be functionalized. Alginate is an easily accessible biopolymer which is readily gelled by the addition of cations such as calcium, facilitating a cost-effective and efficient production of nanoparticles. In this study, AlgNPs based on acid hydrolyzed and enzyme-digested alginate were synthesized by using ionic gelation and water-in-oil emulsification, with the goal to optimize key parameters to produce small uniform (<200 nm) AlgNPs. By the ionic gelation method, such AlgNPs were obtained when sample concentrations were 0.095 mg/mL for alginate and CaCl2 in the range of 0.03-0.10 mg/mL. Alginate and CaCl2 concentrations > 0.10 mg/mL resulted in sizes > 200 nm with relatively high dispersity. Sonication in lieu of magnetic stirring proved to further reduce size and increase homogeneity of the nanoparticles. In the water-in-oil emulsification method, nanoparticle growth was confined to inverse micelles in an oil phase, resulting in lower dispersity. Both the ionic gelation and water-in-oil emulsification methods were suitable for producing small uniform AlgNPs that can be further functionalized as required for various applications.

Synthesis and antitumor activity of some cholesterol-based selenocyanate compounds.

The introduction of selenium-containing functional groups into steroids to study the biological activities of related derivatives is rarely reported in the literature. In the present study, using cholesterol as raw material, four cholesterol-3-selenocyanoates and eight B-norcholesterol selenocyanate derivatives were synthesized, respectively. The structures of the compounds were characterized by NMR and MS. The results of the in vitro antiproliferative activity test showed that the cholesterol-3-selenocyanoate derivatives did not exhibit obvious inhibitory on the tested tumor cell lines. However, the B-norcholesterol selenocyanate derivatives obtained by structural modification of cholesterol showed good inhibitory activity against the proliferation of tumor cell. Among them, compounds 9b-c, 9f and 12 showed similar inhibitory activity against tested tumor cells as positive control 2-methoxyestradiol, and better than Abiraterone. At the same time, these B-norcholesterol selenocyanate derivatives displayed a strong selective inhibitory against Sk-Ov-3 cell line. Except for compound 9g, the IC50 value of all B-norcholesterol selenocyanate compounds against Sk-Ov-3 cells was less than 10 µM, and compound 9d was 3.4 µM. In addition, Annexin V-FITC/PI double staining was used to analyze the cell death mechanism. The results showed that compound 9c could induce Sk-Ov-3 cells to enter programmed apoptosis in a dose-dependent manner. Furthermore, the in vivo antitumor experiments of compound 9f against zebrafish xenograft tumor showed that 9f displayed obvious inhibitory effect on the growth of human cervical cancer (HeLa) xenograft tumor in zebrafish. Our results provide new thinking for the study of such compounds as new antitumor drugs.

Straightforward synthesis of steroidal selenocyanates through oxidative umpolung selenocyanation of steroids and their antitumor activity.

Straightforward access to steroidal selenocyanates in a single assembly step from steroids remains a significant challenge. However, the development of novel method for the synthesis of steroidal selenocyanates and further investigation of their bioactivities have largely lagged behind. In this work, selenocyano groups were directly introduced into the 17- or 21-position of pregnenolone, the 2-position of estradiol, and the 16-position of estrone. A total of 16 estrogen selenocyanate derivatives with diverse structures were synthesized, and the tumor cell lines closely related to the expression level of estrogen were used to investigate the inhibitory activity of the target products on tumor cell proliferation in vitro. The results revealed that the 17-selenocyano-substituted pregnenolone selenocyanate derivatives 1b-3b exhibit obvious inhibitory activity against the tested tumor cell lines. Additionally, the 2-selenocyano-substituted estradiol derivatives and 16-selenocyano-substituted estrone derivatives exhibit selective inhibitory on HeLa cell lines. Among them, 2-selenocyano-3-methoxyestradiol-17-benzoate (7e) displayed an IC50 value of 4.1 µM against HeLa cells and induced programmed apoptosis in HeLa cancer cells. Furthermore, compound 7e could significantly inhibit the growth of human cervical cancer xenografts in zebrafish in vivo. This approach provides new insights for future steroid antitumor drug design.

Effects of Noise Exposure and Mental Workload on Physiological Responses during Task Execution.

Twelve healthy male students were recruited to investigate the physiological response to different noise exposure and mental workload (MW) conditions, while performing multi-attribute task battery (MATB) tasks. The experiments were conducted under three noise exposure conditions, with different sound pressure levels and sharpness. After adaptation to each noise condition, the participants were required to perform the resting test and the MATB task tests with low, medium, and high MW. The electroencephalogram (EEG), electrocardiogram (ECG), and eye movement data were obtained, during the periods when participants were in the resting and task taking state. The results showed that subjects' physiological responses at rest were unaffected by noise exposure conditions. However, during the execution of MATB tasks, the elevated sound pressure level and increased sharpness were significantly correlated with increased mean pupil diameter and heart rate variability (HRV). These responses suggested that the human body defends itself through physiological regulation when noise causes adverse effects. If the negative effects of noise were more severe, this could damage the body's health and result in a significant drop in task performance. The elevated mental demands led to increased stress on the subjects, which was reflected in a considerable increase in theta relative power. Either high or low MW was related with reduced saccade amplitude and a decrease in weighted task performance, indicating an inverted U-shaped relationship between workload level and work performance.

Use of a Novel DNA-Loaded Alginate-Calcium Carbonate Biopolymer Surrogate to Study the Engulfment of Legionella pneumophila by Acanthamoeba polyphaga in Water Systems.

The engulfment of Legionella pneumophila by free-living amoebae (FLA) in engineered water systems (EWS) enhances L. pneumophila persistence and provides a vehicle for rapid replication and increased public health risk. Despite numerous legionellosis outbreaks worldwide, effective tools for studying interactions between L. pneumophila and FLA in EWS are lacking. To address this, we have developed a biopolymer surrogate with a similar size, shape, surface charge, and hydrophobicity to those of stationary-phase L. pneumophila. Parallel experiments were conducted to observe the engulfment of L. pneumophila and the surrogate by Acanthamoeba polyphaga in dechlorinated, filter-sterilised tap water at 30°C for 72 h. Trophozoites engulfed both the surrogate and L. pneumophila, reaching maximum uptake after 2 and 6 h, respectively, but the peak surrogate uptake was ~2-log lower. Expulsion of the engulfed surrogate from A. polyphaga was also faster compared to that of L. pneumophila. Confocal laser scanning microscopy confirmed that the surrogate was actively engulfed and maintained within vacuoles for several hours before being expelled. L. pneumophila and surrogate phagocytosis appear to follow similar pathways, suggesting that the surrogate can be developed as a useful tool for studying interactions between L. pneumophila and FLA in EWS. IMPORTANCE The internalization of L. pneumophila within amoebae is a critical component of their life cycle in EWS, as it protects the bacteria from commonly used water disinfectants and provides a niche for their replication. Intracellularly replicated forms of L. pneumophila are also more virulent and resistant to sanitizers. Most importantly, the bacteria's adaptation to the intracellular environments of amoebae primes them for the infection of human macrophages, posing a significant public health risk in EWS. The significance of our study is that a newly developed L. pneumophila biopolymer surrogate can mimic the L. pneumophila engulfment process in A. polyphaga, a free-living amoeba. With further development, the surrogate has the potential to improve the understanding of amoeba-mediated L. pneumophila persistence in EWS and the associated public health risk management.

Evaluation of Biopolymer Materials and Synthesis Techniques to Develop a Rod-Shaped Biopolymer Surrogate for Legionella pneumophila.

Biopolymer microparticles have been developed for applications that require biocompatibility and biodegradability, such as drug delivery. In this study, we assessed the production of microparticles using carnauba wax, κ-carrageenan, alginate, and poly (lactic-co-glycolic acid) (PLGA) with the aim of developing a novel, DNA-tracer-loaded, biopolymer surrogate with a size, shape, surface charge, and relative hydrophobicity similar to stationary-phase Legionella pneumophila to mimic the bacteria's mobility and persistence in engineered water systems. We found that the type and concentration of biopolymer, reaction conditions, and synthesis methods affected the morphology, surface charge, relative hydrophobicity, and DNA tracer loading efficiency of the biopolymer microparticles produced. Carnauba wax, κ-carrageenan, and alginate (Protanal®, and low and medium viscosity) produced highly polydisperse microspheres. In contrast, PLGA and alginate-CaCO3 produced uniform microspheres and rod-shaped microparticles, respectively, with high DNA tracer loading efficiencies (PLGA 70% and alginate-CaCO3 95.2 ± 5.7%) and high reproducibilities. Their synthesis reproducibility was relatively high. The relative hydrophobicity of PLGA microspheres closely matched the cell surface hydrophobicity of L. pneumophila but not the bacterial morphology, whereas the polyelectrolyte layer-by-layer assembly was required to enhance the relative hydrophobicity of alginate-CaCO3 microparticles. Following this surface modification, alginate-CaCO3 microparticles represented the best match to L. pneumophila in size, morphology, surface charge, and relative hydrophobicity. This new biopolymer surrogate has the potential to be used as a mimic to study the mobility and persistence of L. pneumophila in water systems where the use of the pathogen is impractical and unsafe.

Degradation and adsorption of synthetic DNA water tracers in environmental matrices.

Synthetic DNA tracers are gaining interest as tools for tracking contamination pathways and hydraulic connections in surface water and groundwater systems. However, few quantitative data exist that describe DNA tracer degradation and adsorption in environmental matrices. We undertook laboratory experiments to quantify the degradation of multiple double-stranded DNA tracers in stream water, groundwater, and domestic and dairy-shed effluent, and adsorption to stream sediments, soils, coastal sand aquifer media and alluvial sandy gravel aquifer media. Faster DNA tracer degradation seemed to be associated with high bacterial concentrations in the liquid phase. Overall, the degradation of the 352 base pair (bp) DNA tracers in the aqueous phase was significantly (P = 0.018) slower than that of the 302 bp DNA tracers. Although the tracers' internal amplicon lengths were similar, the longer non-amplified flanking regions of the 352 bp tracers may better protect them from environmental degradation. Thermodynamic analysis suggests that longer flanking regions contribute to greater tracer stability. This finding may explain our previous field observations that 352 bp tracer mass reductions were often lower than 302 bp tracer mass reductions. The 2 sets of DNA tracers did not differ significantly regarding their adsorption to stream sediment-stream water or aquifer media-groundwater mixtures (P > 0.067), but the 352 bp tracers showed significantly less adsorption to soil-effluent mixtures than the 302 bp tracers (P = 0.005). The DNA tracers' adsorption to soil-effluent mixtures was comparatively less than their adsorption to the aquifer media-groundwater and stream sediment-stream water mixtures, suggesting that DNA tracers may compete with like-charged organic matter for adsorption sites. These findings provide insights into the fate of DNA tracers in the environment. The DNA tracers' degradation rate constants determined in this study for a range of environmental conditions could assist the design of future field investigations.

Combination of resolvin E1 and lipoxin A4 promotes the resolution of pulpitis by inhibiting NF-κB activation through upregulating sirtuin 7 in dental pulp fibroblasts.

OBJECTIVES: To determine whether the combination of resolvin E1 (RvE1) and lipoxin A4 (LXA4) could promote resolution of pulpitis and to investigate the mechanism. MATERIALS AND METHODS: Preliminary screening was first conducted in four specialized pro-resolving mediators (SPMs). Real-time quantitative polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay and double-immunofluorescence labelling were employed to assess the expression of RelA, SIRT1, SIRT6, SIRT7 and pro-inflammatory factors. Dental pulp fibroblasts (DPFs) were transfected with siRNA to assess the biological role of SIRT7. A pulpitis model was utilized to evaluate the in vivo curative effect. RESULTS: Preliminary results showed that RvE1 and LXA4 reduced the expression of RelA more markedly than other two SPMs. Both RvE1 and LXA4 treatment downregulated nuclear factor kappa B (NF-κB) activation and increased the expression of SIRT1, SIRT6 and SIRT7, more so in combination than alone. Double-immunofluorescence labelling showed that SIRT7 co-localized with p-p65 and Ac-p65 in the nucleus. Inhibiting ChemR23 and ALX reversed the expression of RelA mRNA, p-p65 and Ac-p65 proteins, pro-inflammatory factors, SIRT1, SIRT6 and SIRT7. Silencing SIRT7 significantly increased p-p65 and Ac-p65 protein levels and decreased SIRT1 and SIRT6 expression. In vivo experiments showed that combined administration of RvE1 and LXA4 promoted pulpitis markedly to resolution. CONCLUSIONS: Combination of RvE1 and LXA4 effectively inhibited NF-κB activation by upregulating SIRT7 expression in DPFs, leading to reduced production of pro-inflammatory factors and promotion of pulpitis resolution.

Reductions of human enteric viruses in 10 commonly used activated carbon, polypropylene and polyester household drinking-water filters.

Drinking-water treatment in non-networked rural communities relies on the use of point-of-use (PoU) household filters. Source waters treated by PoU filters are often microbially contaminated, but information about human enteric virus reductions in these filters is limited. This study evaluated human rotavirus, adenovirus and norovirus reductions in 10 commonly used, new PoU carbon, polypropylene and polyester microfilters. The viruses were spiked into chlorine-free tap water (pH 8.0, ionic strength 1.22 mM), and 3 sequential challenge tests were conducted in each filter under a constant flow rate of 1 L/min. In most of the filters investigated, the norovirus and adenovirus reductions were similar (P > 0.49). Compared with the norovirus and adenovirus reductions, the rotavirus reductions were significantly lower in the carbon filters (P ≤ 0.009), which may relate to rotavirus's higher zeta potential and lower hydrophobicity. Virus reductions appeared to be dictated by the filter media type through electrostatic and hydrophobic interactions; the effects of filter media pore sizes on virus reductions via physical size-exclusion were very limited. The virus reductions in the carbon filters were significantly greater than those in the polypropylene and polyester filters (P ≤ 0.0001), and they did not differ significantly between the polypropylene and polyester filters (P > 0.24). None of the filters met the "protective" rotavirus reduction level (≥3 log10) required for household drinking-water treatment. Our study's findings highlight a critical need for additional water treatment when using PoU microfilters, for example, water boiling or ultraviolet radiation, or the use of effective surface-modified filter media to prevent drinking-waterborne infections from enteric viruses.

KMT2D deficiency disturbs the proliferation and cell cycle activity of dental epithelial cell line (LS8) partially via Wnt signaling.

Lysine methyltransferase 2D (KMT2D), as one of the key histone methyltransferases responsible for histone 3 lysine 4 methylation (H3K4me), has been proved to be the main pathogenic gene of Kabuki syndrome disease. Kabuki patients with KMT2D mutation frequently present various dental abnormalities, including abnormal tooth number and crown morphology. However, the exact function of KMT2D in tooth development remains unclear. In this report, we systematically elucidate the expression pattern of KMT2D in early tooth development and outline the molecular mechanism of KMT2D in dental epithelial cell line. KMT2D and H3K4me mainly expressed in enamel organ and Kmt2d knockdown led to the reduction in cell proliferation activity and cell cycling activity in dental epithelial cell line (LS8). RNA-sequencing (RNA-seq) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis screened out several important pathways affected by Kmt2d knockdown including Wnt signaling. Consistently, Top/Fop assay confirmed the reduction in Wnt signaling activity in Kmt2d knockdown cells. Nuclear translocation of ß-catenin was significantly reduced by Kmt2d knockdown, while lithium chloride (LiCl) partially reversed this phenomenon. Moreover, LiCl partially reversed the decrease in cell proliferation activity and G1 arrest, and the down-regulation of Wnt-related genes in Kmt2d knockdown cells. In summary, the present study uncovered a pivotal role of histone methyltransferase KMT2D in dental epithelium proliferation and cell cycle homeostasis partially through regulating Wnt/ß-catenin signaling. The findings are important for understanding the role of KMT2D and histone methylation in tooth development.

Attenuation and transport of human enteric viruses and bacteriophage MS2 in alluvial sand and gravel aquifer media-laboratory studies.

Potable groundwater contamination by human enteric viruses poses serious health risks. Our understanding of virus subsurface transport has largely depended on studying bacteriophages as surrogates. Few studies have compared the transport behaviour of enteric viruses, especially norovirus, with phage surrogates. We conducted laboratory column experiments to investigate norovirus and bacteriophage MS2 (MS2) filtration in alluvial sand, and rotavirus, adenovirus and MS2 filtration in alluvial gravel aquifer media in 2 mM NaCl (pH 6.6-6.9) with pore velocities of 4.6-5.4 m/day. The data were analysed using colloid filtration theory and HYDRUS-1D 2-site attachment-detachment modelling. Norovirus removal was somewhat lower than MS2 removal in alluvial sand. The removal of rotavirus and adenovirus was markedly greater than MS2 removal in alluvial gravel. These findings concurred with the log10 reduction values, mass recoveries, attachment efficiencies and irreversible deposition rate constants. The modelling results suggested that the MS2 detachment rates were in the same order of magnitude as norovirus, but they were 1 order of magnitude faster than those of rotavirus and adenovirus. The attachment of viruses and MS2 was largely reversible with faster detachment than attachment rates, favouring free virus transport. These findings highlight the risk associated with continual virus transport through subsurface media if viruses are not inactivated and remobilising previously attached viruses could trigger contamination events. Thus, virus attachment reversibility should be considered in virus transport predictions in subsurface media. Further research is needed to compare surrogates with enteric viruses, especially norovirus, regarding their transport behaviours under different experimental conditions.

The effects of carbon dioxide exposure concentrations on human vigilance and sentiment in an enclosed workplace environment.

In this study, fifteen participants were exposed to different carbon dioxide (CO2 ) concentrations in an enclosed environmental chamber to investigate the potential effects of elevated CO2 concentrations on human vigilance and sentiment. The psychomotor vigilance test (PVT), the Karolinska Sleepiness Scale (KSS), and the Positive and Negative Affect Schedule (PANAS) were measured before and after each 4-hour CO2 exposure session. The statistical analyses of the PVT performance metrics showed that the human vigilance decreased significantly with the elevated CO2 concentration from 1500 ppm to above 3500 ppm, but no significant change was observed in the KSS score. Moreover, although the participants reported less positive and more negative emotions as the CO2 exposure concentration increased, the effect of CO2 concentration on human sentiment was not potent. In sum, the findings suggested a detrimental effect of CO2 exposure concentration on human vigilance at the CO2 concentration of 3500 ppm, which is below the current occupational exposure limit of 5000 ppm. It is worth noting that the order of CO2 exposures was not balanced among the participants, which remains a major limitation of this study.