Investigating Shear Stress of Ice Accumulated on Surfaces with Various Roughnesses: Effects of a Quasi-Water Layer.

The investigation of the anti-icing/deicing is essential because the icing phenomenon deteriorates the natural environment and various projects. By conducting molecular dynamics simulation, this work analyzes the effect of the quasi-water layer on the ice shear stress over smooth and rough surfaces, along with the underlying physics of the quasi-water layer. The results indicate that the thickness of the quasi-water layer monotonically increases with temperature, resulting in a monotonic decrease in the ice shear stress on the smooth surface. Due to the joint effects of the smooth surface wettability and the quasi-water layer, the ice shear stress increases and then decreases to almost a constant value when the surface changes from a hydrophobic to a hydrophilic one. For rough surfaces with stripe nanostructures, when the width of the bump for one case equals the depression for the other case, the variations of shear stress with height for these two cases are almost the same. The rough surface is effective in reducing the ice shear stress compared to the smooth surface due to the thickening of the quasi-water layer. Each molecule in the quasi-water layer and its four nearest neighboring molecules gradually form a tetrahedral ice-like structure along the direction away from the surface. The radial distribution function also shows that the quasi-water layer resembles the liquid water rather than the ice structure. These findings shed light on developing anti-icing and deicing techniques.

Charged Fibrous Dressing to Promote Diabetic Chronic Wound Healing.

Diabetic chronic wounds cause a significant amount of pain to patients because of their low cure rates and high recurrence rates. Traditional approaches to treating diabetic chronic wounds often involve the delivery of drugs or cytokines that regulate the microenvironment and eliminate bacterial infection in the wound area, but they are passive in controlling cell behaviors and may lead to drug resistance. Emerging drug-free wound treatments are important for convenient, effective, and safe treatment strategies. However, the current approaches cannot fully promote tissue regeneration or prevent bacterial infections. Here, the efficacy of a negatively charged fiber dressing in promoting diabetic chronic wound healing is investigated. The negatively charged fiber dressing can generate reactive oxygen species to inhibit bacterial reproduction with the assistance of ultrasound during the inflammatory phase. Furthermore, the dressing provides an electrostatic field that regulates cellular behavior during the inflammatory and proliferative phases. In particular, the dressing can promote fibroblast migration and induce macrophage polarization and neovascularization without any additional drugs. It is demonstrated that this strategy enables the healing of diabetic chronic wounds in a mouse model, achieving effective wound closure over a 12-day treatment cycle and providing a drug-free therapeutic strategy for diabetic chronic wound care.

Ultrasensitive and Quantitative DNA Methylation Detection Method Based on the MutS Protein.

DNA methylation is closely related to cancer. It is generally accepted that DNA methylation detection is crucial in cancer diagnosis, prognosis, and treatment monitoring. Therefore, there is an urgent demand for developing a simple, rapid, highly sensitive, and highly specific methylation detection method to detect DNA methylation at specific sites quantitatively. In this work, we introduce a DNA methylation detection method based on MutS and methylation-specific PCR, named MutS-based methylation-specific PCR (MB-MSP), which has the advantages of simplicity, speed, high specificity, sensitivity, and broad applicability. Utilizing the MutS's ability to bind mismatched base pairs, we inhibit not only the amplification of unmethylated DNA but also nonspecific primer amplification. We achieved a detection sensitivity of 0.5% for the methylated genes of ACP1, CLEC11A, and SEPT9 by MB-MSP. It has a good linear relationship and a detection time of only 1.5 h. To validate the feasibility of the MB-MSP method in clinical application, we conducted methylation detection on plasma-circulating tumor DNA samples from 10 liver cancer patients and 5 healthy people, achieving a 100% accuracy rate. In conclusion, MB-MSP, as a novel and reliable DNA methylation detection tool, holds significant application value and potential for advancing early cancer diagnosis.

Recognition of galactose by a scaffold protein recruits a transcriptional activator for the GAL regulon induction in Candida albicans.

The GAL pathway of yeasts has long served as a model system for understanding of how regulatory mode of eukaryotic metabolic pathways evolves. While Gal4 mode has been well-characterized in Saccharomycetaceae clade, little is known about the regulation of the GAL pathway in other yeasts. Here, we find that Rep1, a Ndt80-like family transcription factor, serves as a galactose sensor in the commensal-pathogenic fungus Candida albicans. It is presented at the GAL gene promoters independent of the presence of galactose. Rep1 recognizes galactose via a direct physical interaction. The net result of this interaction is the recruitment of a transcriptional activator Cga1 (Candida galactose gene activator, orf19.4959) and transcription of the GAL genes proceeds. Rep1 and Cga1 are conserved across the CTG species. Rep1 itself does not possess transcriptional activity. Instead, it provides a scaffold to recruit different factors for transcriptional regulation. Rep1-Cga1 mode of regulation represents a new example of network rewiring in fungi, which provides insight into how C. albicans evolves transcriptional programs to colonize diverse host niches.

Zcf24, a zinc-finger transcription factor, is required for lactate catabolism and inhibits commensalism in Candida albicans.

Candida albicans is a normal resident of humans and also a prevalent fungal pathogen. Lactate, a nonfermentative carbon source available in numerous anatomical niches, can be used by C. albicans as a carbon source. However, the key regulator(s) involved in this process remain unknown. Here, through a genetic screen, we report the identification of a transcription factor Zcf24 that is specifically required for lactate utilization in C. albicans. Zcf24 is responsible for the induction of CYB2, a gene encoding lactate dehydrogenase that is essential for lactate catabolism, in response to lactate. Chromatin immunoprecipitation showed a significantly higher signal of Zcf24 on the CYB2 promoter in lactate-grown cells than that in glucose-grown cells. Genome-wide transcription profiling indicates that, in addition to CYB2, Zcf24 regulates genes involved in the ß-oxidation of fatty acids, iron transport, and drug transport. Surprisingly, deleting ZCF24 confers enhanced commensal fitness. This could be attributed to Crz1-activated ß-glucan masking in the zcf24 mutant. The orthologs of Zcf24 are distributed in species most closely to C. albicans and some filamentous fungal species. Altogether, Zcf24 is the first transcription factor identified to date that regulates lactate catabolism in C. albicans and it is also involved in the regulation of commensalism.

PAM-independent ultra-specific activation of CRISPR-Cas12a via sticky-end dsDNA.

Although CRISPR-Cas12a [clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 12a] combining pre-amplification technology has the advantage of high sensitivity in biosensing, its generality and specificity are insufficient, which greatly restrains its application range. Here, we discovered a new targeting substrate for LbaCas12a (Lachnospiraceae bacterium Cas12a), namely double-stranded DNA (dsDNA) with a sticky-end region (PAM-SE+ dsDNA). We discovered that CRISPR-Cas12a had special enzymatic properties for this substrate DNA, including the ability to recognize and cleave it without needing a protospacer adjacent motif (PAM) sequence and a high sensitivity to single-base mismatches in that substrate. Further mechanism studies revealed that guide RNA (gRNA) formed a triple-stranded flap structure with the substrate dsDNA. We also discovered the property of low-temperature activation of CRISPR-Cas12a and, by coupling with the unique DNA hybridization kinetics at low temperature, we constructed a complete workflow for low-abundance point mutation detection in real samples, which was fast, convenient and free of single-stranded DNA (ssDNA) transformation. The detection limits were 0.005-0.01% for synthesized strands and 0.01-0.05% for plasmid genomic DNA, and the mutation abundances provided by our system for 28 clinical samples were in accordance with next-generation sequencing results. We believe that our work not only reveals novel information about the target recognition mechanism of the CRISPR-Cas12a system, but also greatly broadens its application scenarios.

Janus Charged Droplet Manipulation Mediated by Invisible Charge Walls.

The ability to control the mobility and function of droplets is fundamental to developing open surface microfluidics. Despite notable progress in the manipulation of droplets, the existing strategies are still limited in functionalizing droplets. Herein, the coupling of droplet motion and functionalization elicited by an invisible charge wall is reported. The charged superamphiphobic surface is overlapped with a conductor to induce free charge, creating the invisible charge wall at the overlapping boundary. The charge wall can trap droplets and polarize them into Janus charged state. It is found that the trapping degree and the charge distribution in the Janus charged droplet depend on the original surface charge on the superamphiphobic surface. The invisible charge wall can also be established at diverse boundary curvatures, allowing to design pathways for droplet manipulations. Furthermore, the enrichment of protein and nanomaterial in the manipulated Janus charged droplet is demonstrated. The strategy provides a potential microfluidic platform with orthogonal functionalities.

Quasi-water layer sandwiched between hexagonal ice and wall and its influences on the ice tensile stress.

The presence of a quasi-water/premelting layer at the interface between wall and ice when the temperature (T) is below the melting point was extensively observed in experiments. In this work, molecular dynamics simulations are performed to analyze the underlying physics of the quasi-water layer and the effects of the layer on the ice tensile stress. The results indicate that each molecule and its four nearest neighbours in the quasi-water layer representing an equilibrium structure gradually form a tetrahedral ice-like arrangement from an unstructured liquid-like structure along the direction away from the wall. The average density of the quasi-water layer is equal to or higher than the bulk density of water at T ≥ 240 K or T ≤ 240 K respectively, and reaches 1.155 g cm-3 at T = 210 K, suggesting a structural correlation with the high-density liquid phase of water. Depending on the temperature and wall wettability, the thickness of the quasi-water layer (Hq) ranges from ∼2 Å to ∼25 Å. For prescribed hydrophilic walls, Hq increases monotonically with temperature, and is almost proportional to(Tm - T)-1/3, where Tm is the melting temperature of ice. Hq keeps an almost constant value (2 Å) as the temperature increases and rises sharply after passing a threshold temperature of T ≈ 250 K. In the joint effects of the wall wettability and quasi-water layer's thickness, the ice tensile stress decreasing monotonically at a larger temperature shows an upward trend and then reduces to almost a constant value as the wall changes from a hydrophobic to a hydrophilic one. The results reveal the potential development of anti-icing/de-icing techniques by heating the wall or modifying its surface to increase Hq.

A case of primary hepatic stromal tumour misdiagnosed as a liver cyst.

Primary hepatic stromal tumours are very rare and there are only sporadic reports in the literature. Due to the lack of specificity in their clinical manifestations and imaging features, these tumours are easily misdiagnosed. This current report presents a case of primary liver stromal tumour that was misdiagnosed as a liver cyst. The 72-year-old male patient was admitted to the hospital due to right upper abdomen fullness and discomfort for more than 2 weeks. Colour Doppler ultrasonography and enhanced computed tomography examinations revealed a cystic mass in the right lobe of the liver. The preoperative diagnosis was a liver cyst and the laparoscopic fenestration was performed. The pathological examination demonstrated that it was a primary hepatic stromal tumour. Gastroenteroscopy was performed postoperatively and no lesions were found in the gastrointestinal tract. Imatinib mesylate was given orally as the salvage therapy and a radical operation was planned at the patient's request. This current case serves as a reminder that clinicians should consider the possibility that it could be a primary hepatic stromal tumour rather than a hepatic cyst. A multidisciplinary team is necessary for the diagnosis and treatment of patients with a primary hepatic stromal tumour.

Antibacterial surfaces: Strategies and applications.

Antibacterial surfaces are surfaces that can resist bacteria, relying on the nature of the material itself. It is significant for safe food and water, human health, and industrial equipment. Biofilm is the main form of bacterial contamination on the material surface. Preventing the formation of biofilm is an efficient way to develop antibacterial surfaces. The strategy for constructing the antibacterial surface is divided into bacteria repelling and bacteria killing based on the formation of the biofilm. Material surface wettability, adhesion, and steric hindrance determine bacteria repelling performance. Bacteria should be killed by surface chemistry or physical structures when they are attached to a material surface irreversibly. Killing approaches are usually in the light of the cell membrane of bacteria. This review summarizes the fabrication methods and applications of antibacterial surfaces from the view of the treatment of the material surfaces. We also present several crucial points for developing long-term stability, no drug resistance, broad-spectrum, and even programable antibacterial surfaces.

Comprehensive genomic profiling of upper tract urothelial carcinoma and urothelial carcinoma of the bladder identifies distinct molecular characterizations with potential implications for targeted therapy & immunotherapy.

Backgrounds: Despite the genomic landscape of urothelial carcinomas (UC) patients, especially those with UC of bladder (UCB), has been comprehensively delineated and associated with pathogenetic mechanisms and treatment preferences, the genomic characterization of upper tract UC (UTUC) has yet to be fully elucidated. Materials and methods: A total of 131 Chinese UTUC (74 renal pelvis & 57 ureter) and 118 UCB patients were enrolled in the present study, and targeted next-generation sequencing (NGS) of 618 cancer-associated genes were conducted to exhibit the profile of somatic and germline alterations. The COSMIC database, including 30 mutational signatures, were utilized to evaluate the mutational spectrums. Moreover, TCGA-UCB, MSKCC-UCB, and MSKCC-UTUC datasets were retrieved for preforming genomic alterations (GAs) comparison analysis between Western and Chinese UC patients. Results: In our cohort, 93.98% and 56.63% of UC patients were identified with oncogenic and actionable somatic alterations, respectively. Meanwhile, 11.24% of Chinese UC patients (of 14.50% and 7.63% of UTUC and UCB cases, respectively) were identified to harbor a total of 32 pathogenic/likely-pathogenic germline variants in 22 genes, with DNA damage repair (DDR)-associated BRCA1 (1.20%) and CHEK2 (1.20%) being the most prevalent. Chinese UTUC and UCB patients possessed distinct somatic genomic characteristics, especially with significantly different prevalence in KMT2D/C/A, GNAQ, ERCC2, RB1, and PPM1D. In addition, we also found notable differences in the prevalence of ELF3, TP53, PMS2, and FAT4 between renal pelvis and ureter carcinomas. Moreover, 22.90% and 33.90% of UTUC and UCB patients, respectively, had at least one deleterious/likely deleterious alteration in DDR related genes/pathways. Subsequently, mutational signature analysis revealed that UC patients with mutational signature 22, irrespective of UTUC or UCB, consistently had the markedly higher level of tumor mutational burden (TMB), which was proved to be positively correlated with the objective complete/partial response rate in the IMvigor210 cohort. By comparison, Chinese and Western UTUC patients also differed regrading GAs in oncogenic-related genes/pathways, especially in TP53, RTK/RAS, and PI3K pathways; besides, more alterations in WNT pathway but less TP53, RTK/RAS, HIPPO, and PI3K pathways were identified in Chinese UCB. Discussions: The in-depth analysis of genomic mutational landscapes revealed distinct pathogenetic mechanisms between Chinese UTUC and UCB, and specific genomic characterizations could identify high risk population of UTUC/UCB and provided information regarding the selection of alternative therapeutic regimens.

A sensitive electrochemiluminescence biosensor for assay of cancer biomarker (MMP-2) based on NGQDs-Ru@SiO2 luminophore.

A sensitive biosensor that can be used for the determination of matrix metalloproteinase 2 (MMP-2) was proposed. The biosensor was developed by using an excellent self-enhanced nanocomposites as an illuminant and a peptide as a recognition element. For the electrostatic attraction between Ru(bpy)32+ and nitrogen-doped graphene quantum dots (NGQDs), the self-enhanced electrochemiluminescence (ECL) nanocomposites of NGQDs-Ru(bpy)32+-doped silica nanoparticles (NGQDs-Ru@SiO2) were synthesized through a simple sol-gel process. Then, a specific peptide (labeled sulfhydryl) was combined with the self-enhanced ECL nanocomposites (carboxyl in NGQDs) via acylation reaction to obtain the peptide-NGQDs-Ru@SiO2 nanoprobe, which was fabricated onto the gold electrode surface via Au-S bond. The peptide of the ECL nanoprobe was exposed to cleavage in the presence of MMP-2, which caused the signal substance to move farther away from the electrode, leading to a decrease of the ECL signal. The proposed NGQDs-Ru@SiO2-labeled peptide ECL biosensor displayed a lower detection limit of 6.5 pg mL-1 than those of reported ECL methods. The proposed biosensor provided an outlook for future applications in other disease-associated biomarkers.

In situ tunable droplet adhesion on a super-repellent surface via electrostatic induction effect.

In this paper, we report a finding that substrate affects the adhesion of charged super-repellent surfaces. Water droplet impacting on a super-repellent surface produces surface charge, whose expression depends on the substrate. The charged super-repellent surface is sticky to droplets for a suspended substrate made of dielectric materials, while it has low adhesion for a conducting substrate or stage attached at the bottom because of electrostatic induction. Theoretical analysis and simulation are conducted to elucidate the mechanism of substrate effect on surface adhesion. Finally, we develop a new approach to reversibly tune the adhesion of super-repellent surface by combining surface-charge-induced adhesion increase and electrostatic-induction-regulated express of net surface charge. As a proof-of-concept experiment, we demonstrate that droplet sorting and manipulations can be realized by using this controllable surface adhesion tuning approach, which has potential applications in advanced lab-on-a-drop platform.

Charge Density Gradient Propelled Ultrafast Sweeping Removal of Dropwise Condensates.

Continuous sweeping of dropwise condensates is an effective form of vapor to liquid transition in terms of thermal transport at a solid/liquid interface. However, using conventional approaches, it is difficult to simultaneously achieve small activating size and fast departure of condensed droplets with high efficiency, due to the insufficient driving force compared to adhesion. Here, we propose an unexplored method to stimulate a frequent sweeping removal of dropwise condensates at ultrahigh efficiency on a superhydrophobic substrate, aided by a charge density gradient (CDG). We show that the CDG can be injected inside a superhydrophobic substrate on which the condensate droplet with jump-induced charges starts to sweep at a small size down to the microscale followed by quick snowball-like growing and chase-like propelling. The incorporation of the CDG on a superhydrophobic substrate enables a continuous, fast, frequent, long-range, and gravity-independent droplet removal during condensation, making this strategy a promising solution for diverse applications in water harvesting, antifogging, and anti-icing.

Efg1 and Cas5 Orchestrate Cell Wall Damage Response to Caspofungin in Candida albicans.

Echinocandins are recommended as the first-line drugs for the treatment of systemic candidiasis. Cas5 is a key transcription factor involved in the response to cell wall damage induced by echinocandins. In this study, through a genetic screen, we identified a second transcription factor, Efg1, that is also crucial for proper transcriptional responses to echinocandins. Like CAS5, deletion of EFG1 confers hypersensitivity to caspofungin. Efg1 is required for the induction of CAS5 in response to caspofungin. However, ectopically expressed CAS5 cannot rescue the growth defect of efg1 mutant in caspofungin-containing medium. Deleting EFG1 in the cas5 mutant exacerbates the cell wall stress upon caspofungin addition and renders caspofungin-resistant Candida albicans responsive to treatment. Genome-wide transcription profiling of efg1/efg1 and cas5/cas5 using transcriptome sequencing (RNA-Seq) indicates that Efg1 and Cas5 coregulate caspofungin-responsive gene expression, but they also independently control induction of some genes. We further show that Efg1 interacts with Cas5 by yeast two-hybrid and in vivo immunoprecipitation in the presence or absence of caspofungin. Importantly, Efg1 and Cas5 bind to some caspofungin-responsive gene promoters to coordinately activate their expression. Thus, we demonstrate that Efg1, together with Cas5, controls the transcriptional response to cell wall stress induced by caspofungin.

Surface-Charge-Assisted Microdroplet Generation on a Superhydrophobic Surface.

The ability to generate and manipulate droplets down to microscales has attracted great attention in a variety of applications, such as in printing, microreactors, and biological assays. However, the production of microdroplets is often limited by special equipment or the size of needles. Here, an unexplored and facile approach is demonstrated; microdroplets can be generated and trapped yet not pinned on a micro-nano-structured superhydrophobic surface by controllable surface charge during drop impact. Tiny droplets with a size at a scale of tens of microns to millimeters are generated by simply changing the impacting velocity, the size of the impact drop, or impact frequency. Theoretical analysis suggests the generation of the microdroplet as a result of the surface-charge-regulated adhesion, competing with liquid dynamic and interfacial energy. The distribution of surface charge which determines the size and the location of the microdroplet is at the top of the micro-nano-structured surface and dependent on the pressure field applied on the surface during the drop impact. The mobility of the resulting microdroplet that can be easily manipulated without liquid retention is also shown, by taking advantage of the shielding property of the surface charge. This facile yet effective method provides a promising candidate for the realization of tiny droplet-generating and -manipulating applications.

Facile Strategy to Generate Charged Droplets with Desired Polarities.

Water droplets are usually charged positively via either electrospray or contact electrification at the solid/liquid interface. Herein, we describe a facile two-step strategy to generate charged droplets with desired polarities. In particular, negatively charged droplets can be generated via electrostatic induction using a precharged superamphiphobic substrate as an electret. The interplay of repulsive and attractive interactions between like- and unlike-charged droplets or electret leads to rapid droplet transport and self-assembly of specific highly ordered arrays.

Design of robust superhydrophobic surfaces.

The ability of superhydrophobic surfaces to stay dry, self-clean and avoid biofouling is attractive for applications in biotechnology, medicine and heat transfer1-10. Water droplets that contact these surfaces must have large apparent contact angles (greater than 150 degrees) and small roll-off angles (less than 10 degrees). This can be realized for surfaces that have low-surface-energy chemistry and micro- or nanoscale surface roughness, minimizing contact between the liquid and the solid surface11-17. However, rough surfaces-for which only a small fraction of the overall area is in contact with the liquid-experience high local pressures under mechanical load, making them fragile and highly susceptible to abrasion18. Additionally, abrasion exposes underlying materials and may change the local nature of the surface from hydrophobic to hydrophilic19, resulting in the pinning of water droplets to the surface. It has therefore been assumed that mechanical robustness and water repellency are mutually exclusive surface properties. Here we show that robust superhydrophobicity can be realized by structuring surfaces at two different length scales, with a nanostructure design to provide water repellency and a microstructure design to provide durability. The microstructure is an interconnected surface frame containing 'pockets' that house highly water-repellent and mechanically fragile nanostructures. This surface frame acts as 'armour', preventing the removal of the nanostructures by abradants that are larger than the frame size. We apply this strategy to various substrates-including silicon, ceramic, metal and transparent glass-and show that the water repellency of the resulting superhydrophobic surfaces is preserved even after abrasion by sandpaper and by a sharp steel blade. We suggest that this transparent, mechanically robust, self-cleaning glass could help to negate the dust-contamination issue that leads to a loss of efficiency in solar cells. Our design strategy could also guide the development of other materials that need to retain effective self-cleaning, anti-fouling or heat-transfer abilities in harsh operating environments.

Switchable Cavitation in Silicone Coatings for Energy-Saving Cooling and Heating.

Space cooling and heating currently result in huge amounts of energy consumption and various environmental problems. Herein, a switching strategy is described for efficient energy-saving cooling and heating based on the dynamic cavitation of silicone coatings that can be reversibly and continuously tuned from a highly porous state to a transparent solid. In the porous state, the coatings can achieve efficient solar reflection (93%) and long-wave infrared emission (94%) to induce a subambient temperature drop of about 5 °C in hot weather (≈35 °C). In the transparent solid state, the coatings allow active sunlight permeation (95%) to induce solar heating to raise the ambient temperature from 10 to 28 °C in cold weather. The coatings are made from commercially available, cheap materials via a facile, environmentally friendly method, and are durable, reversible, and patternable. They can be applied immediately to various existed objects including rigid substrates.

Effect of potential HONO sources on peroxyacetyl nitrate (PAN) formation in eastern China in winter.

As an important secondary photochemical pollutant, peroxyacetyl nitrate (PAN) has been studied over decades, yet its simulations usually underestimate the corresponding observations, especially in polluted areas. Recent observations in north China found unusually high concentrations of PAN during wintertime heavy haze events, but the current model still cannot reproduce the observations, and researchers speculated that nitrous acid (HONO) played a key role in PAN formation. For the first time we systematically assessed the impact of potential HONO sources on PAN formation mechanisms in eastern China using the Weather Research and Forecasting/Chemistry (WRF-Chem) model in February of 2017. The results showed that the potential HONO sources significantly improved the PAN simulations, remarkably accelerated the ROx (sum of hydroxyl, hydroperoxyl, and organic peroxy radicals) cycles, and resulted in 80%-150% enhancements of PAN near the ground in the coastal areas of eastern China and 10%-50% enhancements in the areas around 35-40°N within 3 km during a heavy haze period. The direct precursors of PAN were aldehyde and methylglyoxal, and the primary precursors of PAN were alkenes with C > 3, xylenes, propene and toluene. The above results suggest that the potential HONO sources should be considered in regional and global chemical transport models when conducting PAN studies.