Can ship travel contain COVID-19 outbreak after re-opening: a Bayesian meta-analysis.

Large gatherings of people on cruise ships and warships are often at high risk of COVID-19 infections. To assess the transmissibility of SARS-CoV-2 on warships and cruise ships and to quantify the effectiveness of the containment measures, the transmission coefficient (ß), basic reproductive number (R0), and time to deploy containment measures were estimated by the Bayesian Susceptible-Exposed-Infected-Recovered model. A meta-analysis was conducted to predict vaccine protection with or without non-pharmaceutical interventions (NPIs). The analysis showed that implementing NPIs during voyages could reduce the transmission coefficients of SARS-CoV-2 by 50%. Two weeks into the voyage of a cruise that begins with 1 infected passenger out of a total of 3,711 passengers, we estimate there would be 45 (95% CI:25-71), 33 (95% CI:20-52), 18 (95% CI:11-26), 9 (95% CI:6-12), 4 (95% CI:3-5), and 2 (95% CI:2-2) final cases under 0%, 10%, 30%, 50%, 70%, and 90% vaccine protection, respectively, without NPIs. The timeliness of strict NPIs along with implementing strict quarantine and isolation measures is imperative to contain COVID-19 cases in cruise ships. The spread of COVID-19 on ships was predicted to be limited in scenarios corresponding to at least 70% protection from prior vaccination, across all passengers and crew.

Effect of indoor air quality on the association of long-term exposure to low-level air pollutants with cognition in older adults.

BACKGROUND: How indoor air quality affects the temporal associations of long-term exposure to low-level air pollutants with cognition remains unclear. METHODS: This cohort study (2011-2019) included 517 non-demented older adults at baseline with four repeated cognitive assessments. The time-varying exposure to PM2.5, PM10, NO2, SO2, CO, and O3 was estimated for each participant from 1994 to 2019. Indoor air quality was determined by ventilation status and daily indoor time. Generalized linear mixed models were used to analyze the association of air pollutants, indoor air quality, and cognition adjusting for important covariates. RESULTS: Over time, per 2.97 µg/m3 (i.e., an interquartile range) increment of PM2.5 was associated with the poor performance of memory (Z score of a cognitive test, ߈:-0.14), attention (߈:-0.13), and executive function (߈:-0.20). Similarly, per 2.05 µg/m3 increase in PM2.5-10 was associated with poor global cognition [adjusted odds ratio (aOR): 1.48, ߈:-0.28], attention (߈:-0.07), and verbal fluency (߈:-0.09); per 4.94 µg/m3 increase in PM10 was associated with poor global cognition (aOR: 1.78; ߈:-0.37). In contrast, per 2.74 ppb increase in O3 was associated with better global cognition (߈:0.36 to 0.47). These associations became more evident in participants with poor ventilation or short daily indoor time (<12.5 h/day). For global cognition, the exposure to a 10-µg/m3 increment in PM2.5, PM2.5-10, and PM10 corresponded to 1.4, 5.8, and 2.8 years of aging, respectively. CONCLUSION: This study demonstrated how indoor air quality in areas using clean fuels differentially affected the associations of long-term exposure to low-level air pollutants with cognition. Tightening air quality standards may help prevent dementia.

Recommendations for ventilation of remodeled negative-pressure isolation wards for COVID-19 patients: A comparison of international guidelines.

This mini-review provides the practice guideline recommendations for ventilation of remodeled negative-pressure isolation wards for COVID-19 Patients. Remodeled "quasi-negative-pressure" isolation wards had been proved a feasible, inexpensive, safe, and effective measure to contain nosocomial outbreaks. We should first determine the minimum required ventilation volume of an isolation ward based on the severity of COVID-19 patients. Mechanical ventilation remains the mainstay for achieving the requirement, while the assistance of recirculation is also helpful. Beyond adequate ventilation volume, the "clean to less-clean" directional airflow remains the golden rule for the solution of indoor ventilation. The virus-laden exhaust should be treated with HEPA/UV device or be kept away from living organisms, buildings, and air inlets.

Association between urinary manganese and pulmonary function in young adults: A cross-sectional design with a longitudinal cohort validation.

BACKGROUND: The impact of heavy metals on pulmonary function among young adults has been scarcely studied, especially by a longitudinal cohort study. METHODS: We prospectively enrolled 974 young adults (aged 20-45 years) during 2017-2019 and measured pulmonary function and urinary heavy metals, including manganese, copper, chromium, iron, nickel, zinc, cadmium, and lead. Among them, 461 participants had examination of the same urinary heavy metals during 2006-2008, which could be used as a cohort for long-term effect of urinary metals on pulmonary function. RESULTS: In the 974 enrolled participants, urinary heavy metals were within normal range. The urinary manganese level was the only significant factor for the observed/predicted ratios of forced vital capacity (FVC %)(ß coefficient: -1.217, p = 0.030), forced expiratory volume in one second (FEV1%)(ß: -1.664, p < 0.001), and FEV1/FVC% of predicted (ß: -0.598, p = 0.047) in multivariable linear regression under cross sectional design. In cohort analysis, the urinary manganese level was also negatively associated with the FEV1% (ß: -1.920, p = 0.021). There was no significance between other urinary heavy metals and pulmonary function for all participants. The urinary manganese significantly negatively correlated with FVC%, FEV1% and FEV1/FVC% in female subgroup whereas copper and iron were significantly negatively correlated with FVC% in male subgroup. CONCLUSIONS: Among urinary heavy metals, urinary manganese level was associated with pulmonary function negatively, even the level was within normal range. In addition, women might be more susceptible to manganese. There is emergent need to conduct further investigation to confirm the respiratory hazardous effects of manganese.

Imaging early embryonic calcium activity with GCaMP6s transgenic zebrafish.

Intracellular Ca2+ signaling regulates cellular activities during embryogenesis and in adult organisms. We generated stable Tg[ßactin2:GCaMP6s]stl351 and Tg[ubi:GCaMP6s]stl352 transgenic lines that combine the ubiquitously-expressed Ca2+ indicator GCaMP6s with the transparent characteristics of zebrafish embryos to achieve superior in vivo Ca2+ imaging. Using the Tg[ßactin2:GCaMP6s]stl351 line featuring strong GCaMP6s expression from cleavage through gastrula stages, we detected higher frequency of Ca2+ transients in the superficial blastomeres during the blastula stages preceding the midblastula transition. Additionally, GCaMP6s also revealed that dorsal-biased Ca2+ signaling that follows the midblastula transition persisted longer during gastrulation, compared with earlier studies. We observed that dorsal-biased Ca2+ signaling is diminished in ventralized ichabod/ß-catenin2 mutant embryos and ectopically induced in embryos dorsalized by excess ß-catenin. During gastrulation, we directly visualized Ca2+ signaling in the dorsal forerunner cells, which form in a Nodal signaling dependent manner and later give rise to the laterality organ. We found that excess Nodal increases the number and the duration of Ca2+ transients specifically in the dorsal forerunner cells. The GCaMP6s transgenic lines described here enable unprecedented visualization of dynamic Ca2+ events from embryogenesis through adulthood, augmenting the zebrafish toolbox.

Dachsous1b cadherin regulates actin and microtubule cytoskeleton during early zebrafish embryogenesis.

Dachsous (Dchs), an atypical cadherin, is an evolutionarily conserved regulator of planar cell polarity, tissue size and cell adhesion. In humans, DCHS1 mutations cause pleiotropic Van Maldergem syndrome. Here, we report that mutations in zebrafish dchs1b and dchs2 disrupt several aspects of embryogenesis, including gastrulation. Unexpectedly, maternal zygotic (MZ) dchs1b mutants show defects in the earliest developmental stage, egg activation, including abnormal cortical granule exocytosis (CGE), cytoplasmic segregation, cleavages and maternal mRNA translocation, in transcriptionally quiescent embryos. Later, MZdchs1b mutants exhibit altered dorsal organizer and mesendodermal gene expression, due to impaired dorsal determinant transport and Nodal signaling. Mechanistically, MZdchs1b phenotypes can be explained in part by defective actin or microtubule networks, which appear bundled in mutants. Accordingly, disruption of actin cytoskeleton in wild-type embryos phenocopied MZdchs1b mutant defects in cytoplasmic segregation and CGE, whereas interfering with microtubules in wild-type embryos impaired dorsal organizer and mesodermal gene expression without perceptible earlier phenotypes. Moreover, the bundled microtubule phenotype was partially rescued by expressing either full-length Dchs1b or its intracellular domain, suggesting that Dchs1b affects microtubules and some developmental processes independent of its known ligand Fat. Our results indicate novel roles for vertebrate Dchs in actin and microtubule cytoskeleton regulation in the unanticipated context of the single-celled embryo.

Synthesis of Antioxidative Conductive Copper Inks with Superior Adhesion.

Conductive films have attracted much attention in the printed electronics industry. To date, expensive conductive silver inks have been utilized widely in these conductive films, which ultimately increase the cost. Hence the alternative low-cost copper inks will be of great interest in the future. This paper will present how to synthesize antioxidative conductive copper inks with superior adhesion to FR4 substrates. The antioxidative conductive copper inks were prepared by dispersing the antioxidative copper nanoparticles in diethylene glycol with the bisphenol-F type BEF170 epoxy resin as a binder and the Methyl-5-norbornene-2,3-dicarboxylic anhydride (NMA) as a curing agent, then were coated on FR4 substrates to form the copper films, followed by sintering at 250 °C in nitrogen atmosphere for 20 minutes. We found that the formation of three-dimensional structure between BFE170 binder and curing agent NMA don't affect the conductivities of copper films, and meanwhile can enhance the adhesion strength on FR4 substrates. The lowest resistivity of 158 µΩ · cm determined by using the four-point probe method and the highest adhesion of no peeling after the 10 times peel-off test with 3 M Scotch 600 tape were achieved with the copper ink composed of 1 wt% of BEF170 epoxy resin binder mixed with curing agent NMA in an equivalent ratio of 1:1.

Wnt Protein Signaling Reduces Nuclear Acetyl-CoA Levels to Suppress Gene Expression during Osteoblast Differentiation.

Developmental signals in metazoans play critical roles in inducing cell differentiation from multipotent progenitors. The existing paradigm posits that the signals operate directly through their downstream transcription factors to activate expression of cell type-specific genes, which are the hallmark of cell identity. We have investigated the mechanism through which Wnt signaling induces osteoblast differentiation in an osteoblast-adipocyte bipotent progenitor cell line. Unexpectedly, Wnt3a acutely suppresses the expression of a large number of genes while inducing osteoblast differentiation. The suppressed genes include Pparg and Cebpa, which encode adipocyte-specifying transcription factors and suppression of which is sufficient to induce osteoblast differentiation. The large scale gene suppression induced by Wnt3a corresponds to a global decrease in histone acetylation, an epigenetic modification that is associated with gene activation. Mechanistically, Wnt3a does not alter histone acetyltransferase or deacetylase activities but, rather, decreases the level of acetyl-CoA in the nucleus. The Wnt-induced decrease in histone acetylation is independent of ß-catenin signaling but, rather, correlates with suppression of glucose metabolism in the tricarboxylic acid cycle. Functionally, preventing histone deacetylation by increasing nucleocytoplasmic acetyl-CoA levels impairs Wnt3a-induced osteoblast differentiation. Thus, Wnt signaling induces osteoblast differentiation in part through histone deacetylation and epigenetic suppression of an alternative cell fate.

Efficient homologous recombination-mediated genome engineering in zebrafish using TALE nucleases.

Custom-designed nucleases afford a powerful reverse genetic tool for direct gene disruption and genome modification in vivo. Among various applications of the nucleases, homologous recombination (HR)-mediated genome editing is particularly useful for inserting heterologous DNA fragments, such as GFP, into a specific genomic locus in a sequence-specific fashion. However, precise HR-mediated genome editing is still technically challenging in zebrafish. Here, we establish a GFP reporter system for measuring the frequency of HR events in live zebrafish embryos. By co-injecting a TALE nuclease and GFP reporter targeting constructs with homology arms of different size, we defined the length of homology arms that increases the recombination efficiency. In addition, we found that the configuration of the targeting construct can be a crucial parameter in determining the efficiency of HR-mediated genome engineering. Implementing these modifications improved the efficiency of zebrafish knock-in generation, with over 10% of the injected F0 animals transmitting gene-targeting events through their germline. We generated two HR-mediated insertion alleles of sox2 and gfap loci that express either superfolder GFP (sfGFP) or tandem dimeric Tomato (tdTomato) in a spatiotemporal pattern that mirrors the endogenous loci. This efficient strategy provides new opportunities not only to monitor expression of endogenous genes and proteins and follow specific cell types in vivo, but it also paves the way for other sophisticated genetic manipulations of the zebrafish genome.

Installation of a flow control device in an inclined air-curtain fume hood to control wake-induced exposure.

An inclined plate for flow control was installed at the lower edge of the sash of an inclined air-curtain fume hood to reduce the effects of the wake around a worker standing in front of the fume hood. Flow inside the fume hood is controlled by the inclined air-curtain and deflection plates, thereby forming a quad-vortex flow structure. Controlling the face velocity of the fume hood resulted in convex, straight, concave, and attachment flow profiles in the inclined air-curtain. We used the flow visualization and conducted a tracer gas test with a mannequin to determine the performance of two sash geometries, namely, the half-cylinder and inclined plate designs. When the half-cylinder design was used, the tracer gas test registered a high leakage concentration at Vf ≦ 57.1 fpm or less. This concentration occurred at the top of the sash opening, which was close to the breathing zone of the mannequin placed in front of the fume hood. When the inclined plate design was used, the containment was good, with concentrations of 0.002-0.004 ppm, at Vf ≦ 63.0 fpm. Results indicate that an inclined plate effectively reduces the leakage concentration induced by recirculation flow structures that form in the wake of a worker standing in front of an inclined air-curtain fume hood.

Effects of boundary-layer separation controllers on a desktop fume hood.

A desktop fume hood installed with an innovative design of flow boundary-layer separation controllers on the leading edges of the side plates, work surface, and corners was developed and characterized for its flow and containment leakage characteristics. The geometric features of the developed desktop fume hood included a rearward offset suction slot, two side plates, two side-plate boundary-layer separation controllers on the leading edges of the side plates, a slanted surface on the leading edge of the work surface, and two small triangular plates on the upper left and right corners of the hood face. The flow characteristics were examined using the laser-assisted smoke flow visualization technique. The containment leakages were measured by the tracer gas (sulphur hexafluoride) detection method on the hood face plane with a mannequin installed in front of the hood. The results of flow visualization showed that the smoke dispersions induced by the boundary-layer separations on the leading edges of the side plates and work surface, as well as the three-dimensional complex flows on the upper-left and -right corners of the hood face, were effectively alleviated by the boundary-layer separation controllers. The results of the tracer gas detection method with a mannequin standing in front of the hood showed that the leakage levels were negligibly small (≤0.003 ppm) at low face velocities (≥0.19 m/s).

A double-negative feedback loop between Wnt-ß-catenin signaling and HNF4α regulates epithelial-mesenchymal transition in hepatocellular carcinoma.

Wnt-ß-catenin signaling participates in the epithelial-mesenchymal transition (EMT) in a variety of cancers; however, its involvement in hepatocellular carcinoma (HCC) and downstream molecular events is largely undefined. HNF4α is the most prominent and specific factor maintaining the differentiation of hepatic lineage cells and a potential EMT regulator in HCC cells. However, the molecular mechanisms by which HNF4α maintains the differentiated liver epithelium and inhibits EMT have not been completely defined. In this study, we systematically explored the relationship between Wnt-ß-catenin signaling and HNF4α in the EMT process of HCC cells. Our results indicated that HNF4α expression was negatively regulated during Wnt-ß-catenin signaling-induced EMT through Snail and Slug in HCC cells. In contrast, HNF4α was found to directly associate with TCF4 to compete with ß-catenin but facilitate transcription co-repressor activities, thus inhibiting expression of EMT-related Wnt-ß-catenin targets. Moreover, HNF4α may control the switch between the transcriptional and adhesion functions of ß-catenin. Overexpression of HNF4α was found to completely compromise the Wnt-ß-catenin-signaling-induced EMT phenotype. Finally, we determined the regulation pattern between Wnt-ß-catenin signaling and HNF4α in rat tumor models. Our studies have identified a double-negative feedback mechanism controlling Wnt-ß-catenin signaling and HNF4α expression in vitro and in vivo, which sheds new light on the regulation of EMT in HCC. The modulation of these molecular processes may be a method of inhibiting HCC invasion by blocking Wnt-ß-catenin signaling or restoring HNF4α expression to prevent EMT.

Development and characterization of an inclined air-curtain (IAC) fume hood.

An inclined air-curtain (IAC) fume hood was developed and characterized using the laser-assisted smoke flow visualization technique and tracer-gas (sulphur hexafluoride) concentration detection method. The IAC fume hood features four innovative design elements: (i) an elongated suction slot installed at the hood roof with an offset towards the rear wall, (ii) an elongated up-blowing planar jet issued from the work surface near the hood inlet, (iii) two deflection plates installed at the left and right side walls, and (iv) a boundary-layer separation controller installed at the sash bottom. Baffles employed in conventional hoods were not used. The suction slot and the up-blowing planar jet formed a rearward-inclined push-pull air curtain. The deflection plates worked with the inclined air curtain to induce four rearward-inclined counter-rotating 'tornados.' The fumes generated in the hood were isolated behind the rearward-inclined air curtain, entrained by the low pressure within the vortical flows, moved up spirally, and finally exhausted through the suction slot. The risk of containment leakage due to the large recirculation vortex that usually exists behind the sash of conventional hoods was reduced by the boundary-layer separation controller. The results of the tracer-gas concentration detection method based on the EN-14175 method showed that the flow field created by the geometric configurations of the IAC hood presented characteristics of low leakage and high resistance to dynamic disturbances at low face velocities. The leakage levels measured by the static, sash movement, and walk-by tests were negligible at a face velocity of 0.26 m s(-1).

Flow characteristics and spillage mechanisms of an inclined quad-vortex range hood subject to influence from draft.

The flow and spillage characteristics of an inclined quad-vortex (IQV) range hood subject to the influence of drafts from various directions were studied. The laser-assisted smoke flow visualization technique was used to reveal the flow characteristics, and the tracer-gas (sulfur hexafluoride) concentration detection method was used to indicate the quantitative values of the capture efficiency of the hood. It was found that the leakage mechanisms of the IQV range hood are closely related to the flow characteristics. A critical draft velocity of about 0.5 m/s and a critical face velocity of about 0.25 m/s for the IQV range hood were found. When the IQV range hood was influenced by a draft with a velocity larger than the critical draft velocity, the spillage of pollutants became significant and the pollutant spillage rate increased with increasing draft velocity. At draft velocities less than or equal to the critical value, no containment leakages induced by the turbulence diffusion, reverse flow, or boundary-layer separation were observed, and the capture efficiency was about 100%. The IQV range hood exhibited a high ability to resist the influences of lateral and frontal drafts. The capture efficiency of the IQV range hood operated at the suction flow rate 5 to 9 m(3)/min is higher than that of the conventional range hood operated at 11 to 15 m(3)/min.

Improving flow patterns and spillage characteristics of a box-type commercial kitchen hood.

A conventional box-type commercial kitchen hood and its improved version (termed the "IQV commercial kitchen hood") were studied using the laser-assisted smoke flow visualization technique and tracer-gas (sulfur hexafluoride) detection methods. The laser-assisted smoke flow visualization technique qualitatively revealed the flow field of the hood and the areas apt for leakages of hood containment. The tracer-gas concentration detection method measured the quantitative leakage levels of the hood containment. The oil mists that were generated in the conventional box-type commercial kitchen hood leaked significantly into the environment from the areas near the front edges of ceiling and side walls. Around these areas, the boundary-layer separation occurred, inducing highly unsteady and turbulent recirculating flow, and leading to spillages of hood containment due to inappropriate aerodynamic design at the front edges of the ceiling and side walls. The tracer-gas concentration measurements on the conventional box-type commercial kitchen hood showed that the sulfur hexafluoride concentrations detected at the hood face attained very large values on an order of magnitude about 10(3)-10(4) ppb. By combining the backward-offset narrow suction slot, deflection plates, and quarter-circular arcs at the hood entrance, the IQV commercial kitchen hood presented a flow field containing four backward-inclined cyclone flow structures. The oil mists generated by cooking were coherently confined in these upward-rising cyclone flow structures and finally exhausted through the narrow suction slot. The tracer-gas concentration measurements on the IQV commercial kitchen hood showed that the order of magnitude of the sulfur hexafluoride concentrations detected at the hood face is negligibly small--only about 10(0) ppb across the whole hood face.

Astrocyte growth is driven by the Tre1/S1pr1 phospholipid-binding G protein-coupled receptor.

Astrocytes play crucial roles in regulating neural circuit function by forming a dense network of synapse-associated membrane specializations, but signaling pathways regulating astrocyte morphogenesis remain poorly defined. Here, we show the Drosophila lipid-binding G protein-coupled receptor (GPCR) Tre1 is required for astrocytes to establish their intricate morphology in vivo. The lipid phosphate phosphatases Wunen/Wunen2 also regulate astrocyte morphology and, via Tre1, mediate astrocyte-astrocyte competition for growth-promoting lipids. Loss of s1pr1, the functional analog of Tre1 in zebrafish, disrupts astrocyte process elaboration, and live imaging and pharmacology demonstrate that S1pr1 balances proper astrocyte process extension/retraction dynamics during growth. Loss of Tre1 in flies or S1pr1 in zebrafish results in defects in simple assays of motor behavior. Tre1 and S1pr1 are thus potent evolutionarily conserved regulators of the elaboration of astrocyte morphological complexity and, ultimately, astrocyte control of behavior.

Electronic Spin Alignment within Homologous NiS2/NiSe2 Heterostructures to Promote Sulfur Redox Kinetics in Lithium-Sulfur Batteries.

The catalytic activation of the Li-S reaction is fundamental to maximize the capacity and stability of Li-S batteries (LSBs). Current research on Li-S catalysts mainly focuses on optimizing the energy levels to promote adsorption and catalytic conversion, while frequently overlooking the electronic spin state influence on charge transfer and orbital interactions. Here, hollow NiS2/NiSe2 heterostructures encapsulated in a nitrogen-doped carbon matrix (NiS2/NiSe2@NC) are synthesized and used as a catalytic additive in sulfur cathodes. The NiS2/NiSe2 heterostructure promotes the spin splitting of the 3d orbital, driving the Ni3+ transformation from low to high spin. This high spin configuration raises the electronic energy level and activates the electronic state. This accelerates the charge transfer and optimizes the adsorption energy, lowering the reaction energy barrier of the polysulfides conversion. Benefiting from these characteristics, LSBs based on NiS2/NiSe2@NC/S cathodes exhibit high initial capacity (1458 mAh·g⁻1 at 0.1C), excellent rate capability (572 mAh·g⁻1 at 5C), and stable cycling with an average capacity decay rate of only 0.025% per cycle at 1C during 500 cycles. Even at high sulfur loadings (6.2 mg·cm⁻2), high initial capacities of 1173 mAh·g⁻1 (7.27 mAh·cm⁻2) are measured at 0.1C, and 1058 mAh·g⁻1 is retained after 300 cycles.

Flow and containment characteristics of a sash-less, variable-height inclined air-curtain fume hood.

To increase containment efficiency and reduce energy consumption, a sash-less, variable-height inclined air-curtain fume hood (sIAC hood) was developed and tested by a laser-assisted flow visualization technique and tracer-gas detection method. This novel design requires neither sash nor baffle. The sIAC hood employed the inclined push-pull air-curtain technique and two deflection plates installed on the side walls of the hood to induce a tetra-vortex flow structure. The results of flow visualization showed that the slot for suction flow, offset from the slot for the up-blowing jet, caused the air curtain to incline towards the rear wall, thus enhancing the robustness of the tetra-vortex flow structure. Such a flow structure could reduce the influence of draught and human walk-by across the hood face. The containment around the central area of the hood was isolated by the inclined push-pull air curtain. The pollutants carried by the reverse flow induced by the flow separation were guided by the deflection plates from the side walls towards the rear, thus contributing to the formation of the tetra-vortex flow structure. The up/down movable ceiling positioned the suction slot close to the device's pollutant emission opening, but left room (less than 50 cm) for unrestricted hand movement. Testing was carried out based on the methodology described in EN14175. The results of a static test showed that small face velocities of 0.25 and 0.16 m s(-1) were enough to obtain nearly null leakage levels for low and tall pollutant sources. The results of a traversing plate test showed that the face velocity, 0.32 m s(-1), would cause negligibly small leakage levels. The sIAC hood could obtain significantly higher containment efficiency than a conventional hood by operating at a face velocity significantly lower than that of conventional hoods.