Modelling the impact of human behavior using a two-layer Watts-Strogatz network for transmission and control of Mpox.

PURPOSE: This study aims to evaluate the effectiveness of mitigation strategies and analyze the impact of human behavior on the transmission of Mpox. The results can provide guidance to public health authorities on comprehensive prevention and control for the new Mpox virus strain in the Democratic Republic of Congo as of December 2023. METHODS: We develop a two-layer Watts-Strogatz network model. The basic reproduction number is calculated using the next-generation matrix approach. Markov chain Monte Carlo (MCMC) optimization algorithm is used to fit Mpox cases in Canada into the network model. Numerical simulations are used to assess the impact of mitigation strategies and human behavior on the final epidemic size. RESULTS: Our results show that the contact transmission rate of low-risk groups and susceptible humans increases when the contact transmission rate of high-risk groups and susceptible humans is controlled as the Mpox epidemic spreads. The contact transmission rate of high-risk groups after May 18, 2022, is approximately 20% lower than that before May 18, 2022. Our findings indicate a positive correlation between the basic reproduction number and the level of heterogeneity in human contacts, with the basic reproduction number estimated at 2.3475 (95% CI: 0.0749-6.9084). Reducing the average number of sexual contacts to two per week effectively reduces the reproduction number to below one. CONCLUSION: We need to pay attention to the re-emergence of the epidemics caused by low-risk groups when an outbreak dominated by high-risk groups is under control. Numerical simulations show that reducing the average number of sexual contacts to two per week is effective in slowing down the rapid spread of the epidemic. Our findings offer guidance for the public health authorities of the Democratic Republic of Congo in developing effective mitigation strategies.

The chromatin remodeler ERCC6 and the histone chaperone NAP1 are involved in apurinic/apyrimidinic endonuclease-mediated DNA repair.

During base excision repair (BER), the apurinic or apyrimidinic (AP) site serves as an intermediate product following base excision. In plants, APE-redox protein (ARP) represents the major AP site of cleavage activity. Despite the well-established understanding that the nucleosomal structure acts as a barrier to various DNA-templated processes, the regulatory mechanisms underlying BER at the chromatin level remain elusive, especially in plants. In this study, we identified plant chromatin remodeler Excision Repair Cross-Complementing protein group 6 (ERCC6) and histone chaperone Nucleosome Assembly Protein 1 (NAP1) as interacting proteins with ARP. The catalytic ATPase domain of ERCC6 facilitates its interaction with both ARP and NAP1. Additionally, ERCC6 and NAP1 synergistically contribute to nucleosome sliding and exposure of hindered endonuclease cleavage sites. Loss-of-function mutations in Arabidopsis (Arabidopsis thaliana) ERCC6 or NAP1 resulted in arp-dependent plant hypersensitivity to 5-fluorouracil, a toxic agent inducing BER, and the accumulation of AP sites. Furthermore, similar protein interactions are also found in yeast cells, suggesting a conserved recruitment mechanism employed by the AP endonuclease to overcome chromatin barriers during BER progression.

Light Activates Cdc42-Mediated Needle-Shaped Filopodia Formation via the Integration of Small GTPases.

Introduction: Cdc42 has been linked to multiple human cancers and is implicated in the migration of cancer cells. Cdc42 could be activated via biochemical and biophysical factors in tumor microenvironment, the precise control of Cdc42 was essential to determine its role to cell behaviors. Needle-shaped protrusions (filopodia) could sense the extracellular biochemical cues and pave the path for cell movement, which was a key structure involved in the regulation of cancer cell motility. Methods: We used the photoactivatable Cdc42 to elucidate the breast cancer cell protrusions, the mutation of Cdc42 was to confirm the optogenetic results. We also inhibit the Cdc42, Rac or Rho respectively by the corresponding inhibitors. Results: We identified that the activation of Cdc42 by light could greatly enhance the formation of filopodia, which was positive for the contribution of cell movement. The expression of Cdc42 active form Cdc42-Q61L in cells resulted in the longer and more filopodia while the Cdc42 inactive form Cdc42-T17N were with the shorter and less filopodia. Moreover, the inhibition of Cdc42, Rac or Rho all significantly reduced the filopodia numbers and length in the co-expression of Cdc42-Q61L, which showed that the integration of small GTPases was necessary in the formation of filopodia. Furthermore, photoactivation of Cdc42 failed to enhance the filopodia formation with the inhibition of Rac or Rho. However, with the inhibition of Cdc42, the photoactivation of Cdc42 could partially recover back the filopodia formations, which indicated that the integration of small GTPases was key for the filopodia formations. Conclusions: Our work highlights that light activates Cdc42 is sufficient to promote filopodia formation without the destructive structures of small GTPases, it not only points out the novel technique to determine cell structure formations but also provides the experimental basis for the efficient small GTPases-based anti-cancer strategies.

A microfluidic demonstration of "cluster-sprout-infiltrating" mode for hypoxic mesenchymal stem cell guided cancer cell migration.

Mesenchymal stem cells (MSCs) play a critical role in tumor metastasis. However, the dynamic process of MSCs-mediated cancer cell invasion remains inconclusive. In breast cancer mouse models, we observed that MSCs promoted lung metastasis. We constructed a microfluidic-based 3D co-culture device to monitor MSCs-mediated cancer cell invasion in a nutrient-deficient hypoxic microenvironment. On biomimetic microfluidic devices, MSCs guided cancer cell migration in a "cluster-sprout-infiltrating" mode. Importantly, hypoxic conditions significantly promoted MSCs migration at the infiltration stage, leading to accelerated breast cancer cell invasion. Moreover, hypoxia related LncRNA analysis showed that H19 was dramatically upregulated in response to hypoxic conditions. Conversely, H19 depletion impaired MSCs-directed breast cancer cell invasion. Mechanistically, H19 functions as a competitive endogenous RNA (ceRNA) which sequesters miRNA let-7 to release its target matrix metalloproteinase-1 (MMP1). Intriguingly, aspirin dramatically suppressed H19 and MMP1 expression and blocked MSCs infiltration under hypoxic conditions, resulting in alleviated breast cancer cell invasion. These findings point to the metastatic promoting role of MSCs in tumor stroma and suggest that MSCs might be a therapeutic target for metastatic breast cancer.

Dual Carbon Design Strategy for Anodes of Sodium-Ion Battery: Mesoporous CoS2/CoO on Open Framework Carbon-Spheres with rGO Encapsulating.

Transition metal sulfides and oxides with high theoretical capacities have been regarded as promising anode candidates for a sodium-ion battery (SIB); however, they have critical issues including sluggish electrochemical kinetics and poor long-term stability. Herein, a dual carbon design strategy is proposed to integrate with highly active heterojunctions to overcome the above issues. In this new design, CoS2/CoO hollow dodecahedron heterojunctions are sandwiched between open framework carbon-spheres (OFCs) and a reduced graphene oxide (rGO) nanomembrane (OFC@CoS2/CoO@rGO). The CoS2/CoO heterojunctions effectively promote electron transfer on their surface and provide more electrochemical active sites through their hierarchical hollow structures assembled by nanodots. Meanwhile, the dual-carbon framework forms a highly conductive network that enables a better rate capability. More importantly, the dual carbon can greatly buffer volume expansion and stable reaction interfaces of electrode material during the charge/discharge process. Benefitting from their synergistical effects, the OFC@CoS2/CoO@rGO electrode achieves a high reversible capacity of 460 mAh g-1 at 0.05 A g-1 and still maintains 205.3 mAh g-1 even when current density is increased by 200 times when used as an anode material for SIBs. Their cycling property is also remarkable with a maintained capacity of 161 mAh g-1 after 3500 charging/discharging cycles at a high current density of 1 A g-1. The dual-carbon strategy is demonstrated to be effective for enhanced reaction kinetics and long-term cycling property, providing siginificant guidance for preparing other high-performance electrode materials.

Kinetic analysis of wetting and spreading at high temperatures: A review.

The kinetic factors of the liquid-solid interface formation process are extremely useful in the design of composite preparation methods and the manufacture of comprehensive performance-controlled metal- or ceramic-based composites. Here, we review the available spreading dynamic models, focusing on wetting at high temperatures. There is yet to be developed a general spreading dynamic model with complete physical meaning that can accurately describe complicated surface-interface kinetic processes at high temperatures. In this work, we highlight common analysis errors in the description of the spreading dynamics for metal-ceramic and metal-metal systems. By unifying the expressions of the spreading dynamic models as the function f(v, θd) and fitting the experimental data reported in the literature, we discovered that the molecular-kinetic model commonly used to describe adsorption-controlled spreading at room temperature and reaction-limited spreading model used at high temperature have a certain range of overlap. When the condition σlv(cosθe-cosθd) < <2nkBT is satisfied, these models are consistent in terms of mathematical functional expressions. As a result, distinguishing between them when the spreading behavior includes both adsorption and reaction is challenging.

Acidic microenvironment enhances MT1-MMP-mediated cancer cell motility through integrin ß1/cofilin/F-actin axis.

Tumor acidic microenvironment is the main feature of many solid tumors. As a part of the tumor microenvironment, it has a profound impact on the occurrence and development of tumors. However, the research on how tumor cells sense the changes of the external microenvironment and how the intracellular subcellular structures transmit the signals from extracellular to intracellular is unclear. In this study, we identify that the acidic microenvironment enhances cancer cell motility, and the expression of membrane-anchored membrane type 1-matrix metalloproteinase is also associated with cell motility, which indicates more degradation of the ECM under the acidic microenvironment. Moreover, the expression of cofilin is low in the acidic microenvironment, and the F-actin filaments are distributed more along the cells. The cytoskeletal F-actin changes are consistent with the potential of a high-invasive phenotype. Further study reveals the upstream control of the signal transductions from extracellular to intracellular, that is, the integrin ß1 functions to trigger the biological responses under the acidic microenvironment. Our results demonstrate that the acidic microenvironment enhances cancer cell motility through the integrin ß1/cofilin/F-actin signal axis. This study clearly shows the scheme of the signal transmissions from extracellular to intracellular and further reveals the cytoskeletal roles for the contributions of cancer cell motility under acidic microenvironment, which provides new targets for cancer intervention from the biochemical and biophysical perspectives.

Effects of Acetylene Addition to the Fuel Stream on Soot Formation and Flame Properties in an Axisymmetric Laminar Coflow Ethylene/Air Diffusion Flame.

The effects of adding acetylene to the fuel stream on soot formation and flame properties were investigated numerically in a laminar axisymmetric coflow ethylene/air diffusion flame using the open-source flame code Co-Flame in conjunction with an elementary gas-phase chemistry scheme and detailed transport and thermodynamic database. Radiation heat transfer of the radiating gases (H2O, C2H2, CO, and CO2) and soot was calculated using a statistical narrow-band correlated-k-based wide band model coupled with the discrete-ordinates method. The soot formation was described by the consecutive steps of soot nucleation, surface growth of soot particles via polycyclic aromatic hydrocarbons (PAHs)-soot condensation or the hydrogen abstraction acetylene addition (HACA) mechanism, and soot oxidation. The added acetylene affected the flame structure and soot concentration through not only chemical reactions among different species but also radiation effects. The chemical effect due to the added acetylene had a significant impact on soot formation. Specifically, it was confirmed that the addition of 10% acetylene caused an increase in the peak soot volumetric fraction (SVF) by 14.9% and the peak particle number density by about 21.1% (z = 1.5 cm). Furthermore, increasing acetylene concentration led to higher concentrations of propargyl, benzene, and PAHs and consequently directly enhanced soot nucleation rates. In addition, the increased H mole fractions also accentuated the soot surface growth. In contrast, the radiation effect of the addition of 10% acetylene was much weaker, resulting in slightly lower flame temperature and SVF, which in turn reduced the radiant heat loss.

Whole-brain amide CEST imaging at 3T with a steady-state radial MRI acquisition.

PURPOSE: To develop a steady-state saturation with radial readout chemical exchange saturation transfer (starCEST) for acquiring CEST images at 3 Tesla (T). The polynomial Lorentzian line-shape fitting approach was further developed for extracting amideCEST intensities at this field. METHOD: StarCEST MRI using periodically rotated overlapping parallel lines with enhanced reconstruction-based spatial sampling was implemented to acquire Z-spectra that are robust to brain motion. Multi-linear singular value decomposition postprocessing was applied to enhance the CEST SNR. The egg white phantom studies were performed at 3T to reveal the contributions to the 3.5 ppm CEST signal. Based on the phantom validation, the amideCEST peak was quantified using the polynomial Lorentzian line-shape fitting, which exploits the inverse relationship between Z-spectral intensity and the longitudinal relaxation rate in the rotating frame. The 3D turbo spin echo CEST was also performed to compare with the starCEST method. RESULTS: The amideCEST peak showed a negligible peak B1 dependence between 1.2 µT and 2.4 µT. The amideCEST images acquired with starCEST showed much improved image quality, SNR, and motion robustness compared to the conventional 3D turbo spin echo CEST method with the same scan time. The amideCEST contrast extracted by the polynomial Lorentzian line-shape fitting method trended toward a stronger gray matter signal (1.32% ± 0.30%) than white matter (0.92% ± 0.08%; P = .02, n = 5). When calculating the magnetization transfer contrast and T1 -corrected rotating frame relaxation rate maps, amideCEST again was not significantly different for white matter and gray matter. CONCLUSION: Rapid multi-slice amideCEST mapping can be achieved by the starCEST method (< 5 min) at 3T by combing with the polynomial Lorentzian line-shape fitting method.

A twist six-membered rhodamine-based fluorescent probe for hypochlorite detection in water and lysosomes of living cells.

A novel six-membered rhodamine-based fluorescent probe (6G-ClO) was developed from 2-formyl rhodamine (6G-CHO) and used for hypochlorite detection in water and HUVEC cells. Different from planar penta cycle of rhodamine spirolactam, there was a twist six-membered spirocyclic hydrazone in 6G-ClO optimized by Gaussian software at DFT/B3LYP/6-31G(d) level. The high selectivity, high sensitivity and fast response of 6G-ClO towards ClO- would be attributed to the twist six-membered spirocycle. Test-strip prepared with 6G-ClO was successfully used to semi-quantitatively indicate the concentration of ClO- in water. 6G-ClO can also quantitatively detect the concentration of ClO- in tap water and swimming pool water. The detection limit of 6G-ClO was as low as 12 nM. The co-localization staining of HUVEC cells further verified that 6G-ClO could specifically accumulate in lysosomes and capture exogenous/endogenous ClO- in living lysosomes. 6G-ClO would be a practical probe for real-time monitoring of ClO- in the biological and real water samples.

Transcriptome analysis providing novel insights for Cd-resistant tall fescue responses to Cd stress.

Cadmium (Cd) is a severely toxic heavy metal and environmental pollutant. Tall fescue is a cold season turf grass which has high resistance to Cd as well as the ability to enrich it. To investigate the molecular mechanism underlying the adaptability of tall fescue to Cd stress, RNA-Seq was used to examine Cd stress responses of tall fescue at a transcriptional level. A total of 12 cDNA libraries were constructed from the total RNA of roots or leaves of tall fescue with or without Cd treatments. A total of 2594 (1768 up- and 826 down-regulated) differentially expressed genes (DEGs) were detected in the roots of Cd-stressed tall fescue compared with control roots (R_cd vs R_ck), while only 52 (29 up- and 23 down-regulated) DEGs were found in the leaves of Cd-stressed plants versus the controls (L_cd vs L_ck). The genes encoding glutathione S-transferase (GST), transporter proteins including the ABC transporter, ZRT/IRT-like protein, potassium transporter/channel, nitrate transporter, putative iron-phytosiderophore transporter, copper-transporting ATPase or transporter and multidrug and toxic compound extrusion (MATE) proteins, and numerous transcription factors were found to be significantly induced in Cd-treated roots. In addition, pathogenesis/disease-related gene mRNAs were accumulated in Cd-treated roots of tall fescue. Furthermore, the significantly enriched KEGG pathways in roots were related to 'Glutathione metabolism', 'Ribosome', 'alpha-Linolenic acid metabolism', 'Diterpenoid biosynthesis', 'Sulfur metabolism', 'Phenylpropanoid biosynthesis', 'Protein processing in endoplasmic reticulum', 'Protein export' and 'Nitrogen metabolism'. The study provides novel insights for further understanding the molecular mechanisms of tall fescue responses to Cd stress.