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In vitro follicle growth is a promising technology to preserve fertility for cancer patients. We previously developed a three-dimensional (3-D) ovarian tissue culture system supported by mouse tumor cell-derived Matrigel. When murine ovarian tissues at 14 days old were cultured in Matrigel drops, antrum formation and oocyte competence were significantly enhanced compared with those cultured without Matrigel. In this study, we tested whether nonanimal-derived dextran hydrogels can support a 3-D ovarian tissue culture. We employed chemically defined dextran hydrogels consisting of dextran polymers crosslinked with polyethylene glycol (PEG)-based cell-degradable crosslinker. To determine the optimal gel elasticity for the 3-D tissue culture, we measured Young's modulus of dextran hydrogels at four concentrations (1.75, 2.25, 2.75, and 3.25 mmol/L), and cultured ovarian tissues in these gels for 7 days. As a result, 2.25 mmol/L dextran hydrogel with Young's modulus of 224 Pa was appropriate to provide physical support as well as to promote follicle expansion in the 3-D system. To mimic the natural extracellular matrix (ECM) environment, we modified the dextran hydrogels with two bioactive factors: ECM-derived Arg-Gly-Asp (RGD) peptides as a cell-adhesive factor, and activin A. The ovarian tissues were cultured in 2.25 mmol/L dextran hydrogels under four different conditions: Activin-/RGD- (A-R-), A + R-, A-R+, and A + R+. On Day 7 of culture, follicle and oocyte sizes were significantly increased in the RGD-modified conditions compared with those without RGD. The RGD-modified hydrogels also promoted mRNA levels of steroidogenic-related genes and estradiol production in the 3-D ovarian tissue culture. In vitro maturation and developmental competence of follicular oocytes were remarkably improved in the presence of RGD. In particular, blastocyst embryos were obtained only from A-R+ or A+R+ conditions after in vitro fertilization. We also determined synergistic effects of the RGD peptides and activin A on follicle growth and oocyte development in the 3-D tissue culture. In conclusion, our results suggest that RGD-modified dextran hydrogels provide an ECM-mimetic bioactive environment to support folliculogenesis in a 3-D ovarian tissue culture system.

Tear film lipid layer (TFLL) is the outmost layer of the tear film. It plays a crucial role in stabilizing the tear film by reducing surface tension and retarding evaporation of the aqueous layer. Dysfunction of the TFLL leads to dysfunctional tear syndrome, with dry eye disease (DED) being the most prevalent eye disease, affecting 10%–30% of the world population. To date, except for treatments alleviating dry eye symptoms, effective therapeutic interventions in treating DED are still lacking. Therefore, there is an urgent need to understand the biophysical properties of the TFLL with the long-term goal to develop translational solutions in effectively managing DED. Here, we studied the composition-function correlations of an artificial TFLL, under physiologically relevant conditions, using a novel experimental methodology called constrained drop surfactometry. This artificial TFLL was composed of 40% behenyl oleate and 40% cholesteryl oleate, representing the most abundant wax ester and cholesteryl ester in the natural TFLL, respectively, and 15% phosphatidylcholine and 5% palmitic-acid-9-hydroxy-stearic-acid (PAHSA), which represent the two predominant polar lipid classes in the natural TFLL. Our study suggests that the major biophysical function of phospholipids in the TFLL is to reduce the surface tension, whereas the primary function of PAHSA is to optimize the rheological properties of the TFLL. These findings have novel implications in better understanding the physiological and biophysical functions of the TFLL and may offer new translational insight to the treatment of DED.

A novel regime of self-compression is proposed for plasma-based backward Raman amplification(BRA) upon flying focus. By using a pumping focus moving with a speed equal to the group velocity of stimulated Raman backscattering(SRBS), only a short part of SRBS which does always synchronize with the flying focus can be amplified. Due to the asymmetrical amplification, the pulse can be directly compressed in the linear stage of BRA. Therefore, instead of a short pulse, the Raman spontaneous or a long pulse can seed the BRA amplifiers. The regime is supported by the 2D particle-in-cell(PIC) simulation without a seed, presenting that the pump pulse is compressed from 26ps to 116fs, with an output amplitude comparable with the case of a well-synchronized short seed. This method provides a significant way to simplify the Raman amplifiers and overcome the issue of synchronization jitter between the pump and the seed.

Almost all Langmuir-Blodgett (LB) films were prepared with the classical Langmuir film balance, developed more than a century ago. To date, the success of the classical Langmuir film balance and the LB transfer technique is primarily restricted to the study of self-assembled monolayers at the air-water surface. It is challenging to study self-assembled monolayers at the oil-water interface, since the Langmuir film balance requires stacked oil and water layers. We hypothesize that a newly developed experimental method, called constrained drop surfactometry (CDS), is capable of preparing and characterizing LB films from the oil-water interface.We have developed a novel droplet-based LB transfer technique capable of preparing LB films from the oil-water interface. In conjunction with atomic force microscopy, we have demonstrated the capacity of the CDS in studying a natural pulmonary surfactant film self-assembled at the perfluorocarbon-water interface, and have compared to the LB films prepared from the air-water surface using the classical Langmuir film balance.Our findings have demonstrated a novel paradigm for studying self-assembled monolayers and for preparing LB films from the oil-water interface. The CDS holds great promise for expanding the applicability of the traditional LB transfer technique from the air-water surface to the oil-water interface.

The dramatic impact of COVID-19 on humans worldwide has initiated an extraordinary search for effective treatment approaches. One of these is the administration of exogenous surfactant, which is being tested in ongoing clinical trials.Exogenous surfactant is a life-saving treatment for premature infants with neonatal respiratory distress syndrome. This treatment has also been tested for acute respiratory distress syndrome (ARDS) with limited success possibly due to the complexity of that syndrome. The 60-year history of successes and failures associated with surfactant therapy distinguishes it from many other treatments currently being tested for COVID-19 and provides the opportunity to discuss the factors that may influence the success of this therapy.Clinical data provide a strong rationale for using exogenous surfactant in COVID-19 patients. Success of this therapy may be influenced by the mechanical ventilation strategy, the timing of treatment, the doses delivered, the method of delivery and the preparations utilized. In addition, future development of enhanced preparations may improve this treatment approach. Overall, results from ongoing trials may not only provide data to indicate if this therapy is effective for COVID-19 patients, but also lead to further scientific understanding and improved treatment strategies.

With an increasing prevalence of electronic cigarette (e-cigarette) use, especially among youth, there is an urgent need to better understand the biological risks and pathophysiology of health conditions related to e-cigarettes. A majority of e-cigarette aerosols are in the submicron size and would deposit in the alveolar region of the lung, where they must first interact with the endogenous pulmonary surfactant. To date, little is known whether e-cigarette aerosols have an adverse impact on the pulmonary surfactant. We have systematically studied the effect of individual e-cigarette ingredients on an animal-derived clinical surfactant preparation, bovine lipid extract surfactant, using a combination of biophysical and analytical techniques, including in vitro biophysical simulations using constrained drop surfactometry, molecular imaging with atomic force microscopy, chemical assays using carbon nuclear magnetic resonance and circular dichroism, and in silico molecular dynamics simulations. All data collectively suggest that flavorings used in e-cigarettes, especially menthol, play a predominant role in inhibiting the biophysical function of the surfactant. The mechanism of biophysical inhibition appears to involve menthol interactions with both phospholipids and hydrophobic proteins of the natural surfactant. These results provide novel insights into the understanding of the health impact of e-cigarettes and may contribute to better regulation of e-cigarette products.

The suspension stability of aluminum-based adjuvant (Alum) plays an important role in determining the Alum-antigen interaction and vaccine efficacy. Inclusion of excipients has been shown to stabilize antigens in vaccine formulations. However, there is no mechanistic study to tune the characteristics of Alum for improved suspension stability. Herein, a library of self-assembled rice-shaped aluminum oxyhydroxide nanoadjuvants i.e., nanorices (NRs), was synthesized through intrinsically controlled crystallization and atomic coupling-mediated aggregations. The NRs exhibited superior suspension stability in both water and a saline buffer. After adsorbing hepatitis B surface antigen (HBsAg) virus-like particles (VLPs), human papillomavirus virus (HPV) VLPs, or bovine serum albumin, NR-antigen complexes exhibited less sedimentation. Further mechanistic study demonstrated that the improved suspension stability was due to intraparticle aggregations that led to the reduction of the surface free energy. By using HBsAg in a murine vaccination model, NRs with higher aspect ratios elicited more potent humoral immune responses. Our study demonstrated that engineered control of particle aggregation provides a novel material design strategy to improve suspension stability for a diversity of biomedical applications.

To elucidate the biological role of miR-4282 in influencing metastasis of epithelial ovarian cancer (EOC) by regulating MIER1.MiR-4282 expressions in 45 cases of EOC specimens and normal controls were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between miR-4282 and clinical features in EOC patients, including pathological indicators and overall survival, was analyzed. After intervening miR-4282 level in SKOV3 and 3AO cells by plasmid transfection, changes in migratory and invasive abilities were determined by transwell assay and wound healing assay. The target gene of miR-4282 was observed by Dual-Luciferase reporter assay, followed by exploration of its involvement in EOC progression via rescue experiments.MiR-4282 was downregulated in EOC specimens than normal controls. EOC patients expressing low level of miR-4282 had higher incidences of lymphatic metastasis and distant metastasis, as well as worse prognosis than those overexpressing miR-4282. Overexpression of miR-4282 in SKOV3 cells weakened metastatic ability, and conversely, knockdown of miR-4282 in 3AO cells yielded the promotive trends. MIER1 was confirmed to be the target gene binding miR-4282, which was highly expressed in EOC specimens. MIER1 was able to reverse the regulatory effect of miR-4282 on EOC cell metastasis.Lowly expressed miR-4282 in EOC specimens is closely linked to the incidence of metastasis and overall survival. MiR-4282 prevents EOC metastasis by a negative regulation on MIER1.

Both n-butane and iso-butane are important petrochemical raw materials, and their separation is of great significance and full of challenge because of their close boiling characteristic. The ZIF-8 slurry formed with a novel mixed solvent M-water solution as sorption media was adopted to separate the mixture with high efficiency. The iso-/n-butane selectivity of ZIF-8/M-water slurries is as high as 890 with high kinetic performance, even transcending the upper limit of the new materials or membranes. More encouragingly, continuous pilot separation device was established and test results show that the purity and recovery ratio of iso-butane product achieved 99.46 mol% and 87% respectively, which are remarkably superior to the corresponding performance (98.56 mol% and 54%) of the industrial distillation tower. To our best knowledge, this is the first industrial pilot test using MOFs for gas separation, and also an important step forward to the commercial application of MOFs in gas separation.

Ovarian cancer is the most lethal gynecologic malignancy in women with an increasing number of cases worldwide. Chemoresistance is the main obstacle for ovarian cancer treatment during clinical therapy. Previous studies found that programmed cell death 1 ligand 1 (PD-L1) was associated with chemoresistance of cancer. However, there were little reports about the function of PD-L1 involved in chemoresistance of ovarian cancer. In our study, cisplatin (DDP)-resistant SKOV3 and A2780 ovarian cancer cell lines (SKOV3/DDP and A2780/DDP) were established. We found that the expression of PD-L1 was increased and miR-34a-5p was decreased in DDP-resistant cells. PD-L1 silencing inhibited chemoresistance of DDP-resistant ovarian cancer cells to DDP, as evidenced by decreased proliferation, G1-phase cell cycle arrest and increased apoptosis. Western blot assay showed that in the presence of DDP, PD-L1 silencing decreased multidrug resistance protein 1 and Cyclin D1 protein levels, whereas increased cleaved-caspase-3 and cleaved-PARP protein levels in these cells. Moreover, we demonstrated that miR-34a-5p negatively regulated the expression of PD-L1 by targeting its 3'-untranslated region. The effects of miR-34a-5p mimic on DDP-treated SKOV3/DDP cells were reversed by the overexpression of PD-L1. Moreover, the tumorigenicity of DDP-resistant ovarian cancer cells in nude mice treated with DDP was attenuated by miR-34a-5p in vivo. The combined data indicate that miR-34a-5p/PD-L1 axis regulates DDP chemoresistance of ovarian cancer cells, providing a deeper insight into the treatment for ovarian cancer.

Phospholipids are ubiquitous components of biomembranes and common biomaterials used in many bioengineering applications. Understanding adsorption of phospholipids at the air-water surface plays an important role in the study of pulmonary surfactants and cell membranes. To date, however, the biophysical mechanisms of phospholipid adsorption are still unknown. It is challenging to reveal the molecular structure of adsorbed phospholipid films. Using combined experiments with constrained drop surfactometry and molecular dynamics simulations, here, we studied the biophysical mechanisms of dipalmitoylphosphatidylcholine (DPPC) adsorption at the air-water surface. It was found that the DPPC film adsorbed from vesicles showed distinct equilibrium surface tensions from the DPPC monolayer spread via organic solvents. Our simulations revealed that only the outer leaflet of the DPPC vesicle is capable of unzipping and spreading at the air-water surface, whereas the inner leaflet remains intact and forms an inverted micelle to the interfacial monolayer. This inverted micelle increases the local curvature of the monolayer, thus leading to a loosely packed monolayer at the air-water surface and hence a higher equilibrium surface tension. These findings provide novel insights, to our knowledge, into the mechanism of the phospholipid and pulmonary surfactant adsorption and may help understand the structure-function correlation in biomembranes.

Although the process by which the cortical tissues of the brain fold has been the subject of considerable study and debate over the past few decades, a single mechanistic description of the phenomenon has yet to be fully accepted. Rather, two competing explanations of cortical folding have arisen in recent years; known as the axonal tension and the differential tangential expansion models. In the present review, these two models are introduced by analyzing the computational, theoretical, materials-based, and cell studies which have yielded them. Then Four-dimensional bioprinting is presented as a powerful technology which can not only be used to test both models of cortical folding de novo, but can also be used to explore the reciprocal effects that folding associated mechanical stresses may have on neural development. Therein, the fabrication of “smart” tissue models which can accurately simulate the in vivo folding process and recapitulate physiologically relevant stresses are introduced. We also provide a general description of both cortical neurobiology as well as the cellular basis of cortical folding. Our discussion also entails an overview of both 3D and 4D bioprinting technologies, as well as a brief commentary on recent advancements in printed central nervous system tissue engineering.

Satellite altimetry has been used to observe the Arctic sea ice in long term and large scale, and the records show a continued decline for Arctic sea ice thickness over decades. In this study, the sea ice freeboard in Beaufort Sea of Arctic have been estimated using CryoSat-2 data, and validated with Upward Looking Sonar (ULS) data of Beaufort Gyre Exploration Project (BGEP). The results show an obvious seasonal variation of the Beaufort Sea with a high reliability estimation of the sea ice freeboard. The average height of the sea ice freeboard increase from January to March and achieve the maximum value 0.38 m in March. The sea ice melts after March and the average height of the sea ice freeboard reduces to the minimum 0.12 m in August. In the next few months the sea water begins to freeze and the average height of the sea ice freeboard will increase to the maximum value.

Introduction E-cigarette (EC) and vaping use continue to remain popular amongst teenage and young adult populations, despite several reports of vaping associated lung injury. One of the first compounds that EC aerosols comes into contact within the lungs during a deep inhalation is pulmonary surfactant. Impairment of surfactant’s critical surface tension reducing activity can contribute to lung dysfunction. Currently, information on how EC aerosols impacts pulmonary surfactant remains limited. We hypothesized that exposure to EC aerosol impairs the surface tension reducing ability of surfactant. Methods Bovine Lipid Extract Surfactant (BLES) was used as a model surfactant in a direct exposure syringe system. BLES (2ml) was placed in a syringe (30ml) attached to an EC. The generated aerosol was drawn into the syringe and then expelled, repeated 30 times. Biophysical analysis after exposure was completed using a constrained drop surfactometer (CDS). Results Minimum surface tensions increased significantly after exposure to the EC aerosol across 20 compression/expansion cycles. Mixing of non-aerosolized e-liquid did not result in significant changes. Variation in device used, addition of nicotine, or temperature of the aerosol had no additional effect. Two e-liquid flavours, menthol and red wedding, had further detrimental effects, resulting in significantly higher surface tension than the vehicle exposed BLES. Menthol exposed BLES has the highest minimum surface tensions across all 20 compression/expansion cycles. Alteration of surfactant properties through interaction with the produced aerosol was observed with a basic e-liquid vehicle, however additional compounds produced by added flavourings appeared to be able to increase inhibition. Conclusion EC aerosols alter surfactant function through increases in minimum surface tension. This impairment may contribute to lung dysfunction and susceptibility to further injury.

n-butane and isobutane are important petrochemical raw materials. Their separation is challenging because of their similar properties, including boiling point. Here, we report a zeolitic imidazolate framework-8 (ZIF-8)/N,N-Dimethylpropyleneurea (DMPU)-water slurry as sorption material to separate butane mixtures. The isobutane/n-butane selectivity of ZIF-8/DMPU-water slurries is as high as 890 with high kinetic performance, which transcends the upper limit of various separation materials or membranes reported in the literature. More encouragingly, a continuous pilot separation device was established, and the test results show that the purity and recovery ratio of isobutane product are 99.46 mol% and 87%, respectively, which are superior to the corresponding performance (98.56 mol% and 54%) of the industrial distillation tower. To the best of our knowledge, the use of metal-organic frameworks (MOFs) for gas separation in pilot scale remains underexplored, and thus this work provides a step forward to the commercial application of MOFs in gas separation.

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a newly discovered class of endogenous lipids that consist of two acyl chains connected through a single ester bond. Being a unique species of FAHFAs, (O-acyl)-ω-hydroxy fatty acids (OAHFAs) differ from other FAHFAs in that their hydroxy fatty acid backbones are ultralong and their hydroxy esterification is believed to be solely at the terminal (ω-) position. Only in recent years with technological advances in lipidomics have OAHFAs been identified as an important component of the tear film lipid layer (TFLL). It was found that OAHFAs account for approximately 4 mol% of the total lipids and 20 mol% of the polar lipids in the TFLL. However, their biophysical function and contribution to the TFLL is still poorly understood. Here we studied the molecular biophysical mechanisms of OAHFAs using palmitic-acid-9-hydroxy-stearic-acid (PAHSA) as a model. PAHSA and OAHFAs share key structural similarities that could result in comparable biophysical properties and molecular mechanisms. With combined biophysical experiments, atomic force microscopy observations, and all-atom molecular dynamics simulations, we found that the biophysical properties of a dynamic PAHSA monolayer under physiologically relevant conditions depend on a balance between kinetics and thermal relaxation. PAHSA molecules at the air-water surface demonstrate unique polymorphic behaviors, which can be explained by configurational transitions of the molecules under various lateral pressures. These findings could have novel implications in understanding biophysical functions that FAHFAs, in general, or OAHFAs, specifically, play in the TFLL.

The 3 major subphenotypes observed in patients with nonsyndromic orofacial clefts (NSOFCs) are nonsyndromic cleft lip only (NSCLO), nonsyndromic cleft lip with palate (NSCLP), and nonsyndromic cleft palate only (NSCPO). However, the genetic architecture underlying NSCPO is largely unknown. Here we performed a 2-stage genome-wide association study (GWAS) on NSCPO and replication analyses of selected variants in other NSOFCs from the Chinese Han population. We identified a novel locus (15q24.3) and a known locus (1q32.2) where variants in or near the gene reached genome-wide significance (2.80 × 10−13 < P < 1.72 × 10−08) in a test for association with NSCPO in a case-control design. Although a variant from 15q24.3 was found to be significantly associated with both NSCPO and NSCLP, the direction of estimated effects on risk were opposite. Our functional annotation of the risk alleles within 15q24.3 coupled with previously established roles of the candidate genes within identified risk loci in periderm development, embryonic patterning, and/or regulation of cellular processes supports their involvement in palate development and the pathogenesis of cleft palate. Our study advances the understanding of the genetic basis of NSOFCs and provides novel insights into the pathogenesis of NSCPO.

Understanding rheological properties of surfactant and protein films plays a crucial role in a variety of industrial and research areas, such as food processing, cosmetics, and pharmacology. To determine the surface dilational modulus using drop shape analysis, one needs to measure the dynamic surface tension in response to a sinusoidal oscillation of the surface area of the droplet. Despite many applications of drop shape analysis in studying interfacial rheology, oscillation of the droplet surface area is usually controlled in an indirect manner. Existing methods are only capable of controlling volume oscillations of the droplet rather than its surface area. We have developed an arbitrary waveform generator (AWG) to directly oscillate the surface area of a millimeter-sized droplet in a predefined sinusoidal waveform. Here, we demonstrated the capacity of this AWG, in conjunction with constrained drop surfactometry (CDS), in studying the surface dilational rheology of adsorbed surfactant and protein films. It is found that the surface dilational modulus determined for a dilute surfactant (C12DMPO) and two protein solutions (bovine serum albumin and β-casein) revealed their adsorption mechanisms. Our methods hold promise in studying the interfacial rheology of various thin-film materials, biomembranes, foams, and emulsions.

In 2015, the Asian Radiation Dosimetry Group established a regional network of biological dosimetry laboratories known as the ARADOS-WG03 (Working Group 03; Biological Dosimetry). A survey was conducted in 2017 to evaluate the capabilities and capacities of the participating laboratories for emergency preparedness and responses in large-scale nuclear and/or radiological incidents. The results of this survey were identified and assessed. The data provide important information on the current state of emergency cytogenetic biological dosimetry capabilities in the Asian region.

In this study, we perform an experimental investigation on the dynamical behaviors of a liquid bridge formed during droplet coalescence. Notably, the two droplets are constrained respectively by two vertically aligned needles. Of particular interest is the pinch-off of the liquid bridge under this constrained condition. We observe three typical behaviors of the liquid bridge: (1) reaching a stable shape after damped oscillations (regime I); (2) pinching off at both sides in the first necking stage with the largest oscillation amplitude (regime II); and (3) pinching off at only the upper side after once or twice necking (regime III). To indicate the condition when the pinch-off of the liquid bridge may occur, we develop a phase diagram based on the radius ratio of the droplet to the needle R d / R n and the Bond number Bo, which respectively characterizes the relative importance of surface tension to the constraint force from needles and that of gravity to surface tension. In general, the dynamical behavior of the liquid bridge transitions from regime II to regime I with R d / R n decreasing, and the critical value for this transition is 1.6. This transition indicates that the constraint force keeps the liquid bridge stable while the surface tension promotes its instability. Surprisingly, once the Bond number is sufficiently high (e.g., Bo > 0.05), regime III (i.e., pinch-off at only the upper side) is observed when R d / R n becomes around the regime II to I transition (i.e., R d / R n = 1.6). It is because the effect of gravity becomes predominant over the surface tension and the constrained force from needles. Moreover, we analyze the pinch-off characteristics of the liquid bridge lying in regimes II and III, including its pinch-off time (i.e., the time interval from the formation and pinch-off of the liquid bridge) and its neck shape at the instant of pinching off.

Due to its antimicrobial properties and low toxicity, human lysozyme (hLYZ) has broad application in the medical field and as a preservative used by the food industry. However, limited availability hinders its widespread use. Hence, we constructed a recombinant avian adeno-associated virus (rAAAV) that would specifically express hLYZ in the chicken oviduct and harvested hLYZ from the egg whites of laying hens. The oviduct-specific human lysozyme expression cassette flanked by avian adeno-associated virus (AAAV) inverted terminal repeats (ITRs) was subcloned into the modified baculovirus transfer vector pFBX, and then the recombinant baculovirus rBac-ITRLYZ was generated. The recombinant avian adeno-associated virus was produced by co-infecting Sf9 cells with rBac-ITRLYZ and the other 2 baculoviruses containing AAAV functional genes and structural genes, respectively. Electron microscopy and real-time PCR revealed that the recombinant viral particles were generated successfully with a typical AAAV morphology and a high titer. After one intravenous injection of each laying hen with 2 × 1011 viral particles, oviduct-specific expression of recombinant human lysozyme (rhLYZ) was detected by reverse transcription-PCR. The expression level of rhLYZ in the first wk increased to 258 ± 11.5 μg/mL, reached a maximum of 683 ± 16.4 μg/mL at the fifth wk, and then progressively declined during the succeeding 7 wk of the study. Western blotting indicated that the oviduct-expressed rhLYZ had the same molecular weight as the natural enzyme. These results indicate that an efficient and convenient oviduct bioreactor mediated by rAAAV has been established, and it is useful for production of other recombinant proteins.

The growing risk of human exposure to airborne nanoparticles (NPs) causes a general concern on the biosafety of nanotechnology. Inhaled NPs can deposit in the deep lung at which they interact with the pulmonary surfactant (PS). Despite the increasing study of nano-bio interactions, detailed molecular mechanisms by which inhaled NPs interact with the natural PS system remain unclear. Using coarse-grained molecular dynamics simulation, we studied the interaction between NPs and the PS system in the alveolar fluid. It was found that regardless of different physicochemical properties, upon contacting the PS, both silver and polystyrene NPs are immediately coated with a biomolecular corona that consists of both lipids and proteins. Structure and molecular conformation of the PS corona depend on the hydrophobicity of the pristine NPs. Quantitative analysis revealed that lipid composition of the corona formed on different NPs is relatively conserved and is similar to that of the bulk phase PS. However, relative abundance of the surfactant-associated proteins, SP-A, SP-B, and SP-C, is notably affected by the hydrophobicity of the NP. The PS corona provides the NPs with a physicochemical barrier against the environment, equalizes the hydrophobicity of the pristine NPs, and may enhance biorecognition of the NPs. These modifications in physicochemical properties may play a crucial role in affecting the biological identity of the NPs and hence alter their subsequent interactions with cells and other biological entities. Our results suggest that all studies of inhalation nanotoxicology or NP-based pulmonary drug delivery should consider the influence of the PS corona.

Pulmonary surfactant (PS) is a lipid-protein complex that adsorbs to the air-water surface of the lung as a thin film. Previous studies have suggested that the adsorbed PS film is composed of an interfacial monolayer, plus a functionally attached vesicular complex, called the surface-associated surfactant reservoir. However, direct visualization of the lateral structure and morphology of adsorbed PS films using atomic force microscopy (AFM) has been proven to be technically challenging. To date, all AFM studies of the PS film have relied on the model of Langmuir monolayers. Here, we showed the first, to our knowledge, AFM imaging of adsorbed PS films under physiologically relevant conditions using a novel, to our knowledge, experimental methodology called constrained drop surfactometry. In conjunction with a series of methodological innovations, including subphase replacement, in situ Langmuir-Blodgett transfer, and real-time surface tension control using closed-loop axisymmetric drop shape analysis, constrained drop surfactometry allowed the study of lateral structure and topography of animal-derived natural PS films at physiologically relevant low surface tensions. Our data suggested that a nucleation-growth model is responsible for the adsorption-induced squeeze-out of the PS film, which likely results in an interfacial monolayer enriched in dipalmitoylphosphatidylcholine with the attached multilayered surface-associated surfactant reservoir. These findings were further supported by frequency-dependent measurements of surface dilational rheology. Our study provides novel, to our knowledge, biophysical insights into the understanding of the mechanisms by which the PS film attains low surface tensions and stabilizes the alveolar surface.

To analyze the therapeutic efficacy of local block with promethazine and routine surgery in the treatment of popliteal cyst and explore the clinical efficacy of arthroscopy-assisted modified popliteal cyst resection therapy, a total of 116 patients with popliteal cyst treated at the Fuzhou General Hospital of Nanjing Military Command were enrolled. These patients were divided into the control group, who underwent routine surgery and the research group, who were subjected to local block with promethazine, with 58 patients in each group. The therapeutic efficacy was observed and compared. The incision length and surgical time of the research group were significantly lower than that of the control group. By comparing the remission rates of clinical symptoms at 2 d, 1 mo, 2 mo and 1 y after surgery, the magnetic resonance imaging data, the recovery rate and recurrence rate, results showed that the research group had greater advantage over the control group (P

Young neutron stars (NSs) born in core-collapse explosions are promising candidates for the central engines of fast radio bursts (FRBs), since the first localized repeating burst FRB 121102 happens in a star forming dwarf galaxy, which is similar to the host galaxies of superluminous supernovae (SLSNe) and long gamma-ray bursts (LGRBs). However, FRB 180924 and FRB 190523 are localized to massive galaxies with low rates of star formation, compared with the host of FRB 121102. Meanwhile, the offsets between the bursts and host centers are about 4 kpc and 29 kpc for FRB 180924 and FRB 190523, respectively. These properties of hosts are similar to short gamma-ray bursts \textbf{(SGRBs)}, which are produced by mergers of binary neutron star (BNS) or neutron star-black hole (NS-BH). Therefore, the NSs powering FRBs may be formed in BNS mergers. In this paper, we study the BNS merger rates, merger times, and predict their most likely merger locations for different types of host galaxies using population synthesis method. We find that the BNS merger channel is consistent with the recently reported offsets of FRB 180924 and FRB 190523. The offset distribution of short GRBs is well reproduced by population synthesis using galaxy model which is similar to GRB hosts. The event rate of FRBs (including non-repeating and repeating), is larger than those of BNS merger and short GRBs, which requires a large fraction of observed FRBs emitting several bursts. Using curvature radiation by bunches in NS magnetospheres, we also predict the observational properties of FRBs from BNS mergers, including the dispersion measure, and rotation measure. At late times ($t\geq1$yr), the contribution to dispersion measure and rotation measure from BNS merger ejecta could be neglected., Comment: 29 pages, 9 figures, accepted for publication in ApJ

Surfactant protein B (SP-B) is essential for life and plays critical roles in host defense and lowering alveolar surface tension. A single-nucleotide polymorphism (SNP rs1130866) of human SP-B (hSP-B) alters the N-linked glycosylation, thus presumably affecting SP-B function. This study has investigated the regulatory roles of hSP-B genetic variants on lung injury in pneumonia-induced sepsis.Wild-type (WT) FVB/NJ and humanized transgenic SP-B-T and SP-B-C mice (expressing either hSP-B C or T allele without mouse SP-B gene) were infected intratracheally with 50 μL (4 × 10 colony-forming units [CFUs]/mouse) Pseudomonas aeruginosa Xen5 or saline, and then killed 24 or 48 h after infection. Bacterial dynamic growths were monitored from 0 to 48 h postinfection by in vivo imaging. Histopathological, cellular, and molecular changes of lung tissues and bronchoalveolar lavage fluid (BALF) were analyzed. Surface tension of surfactants was determined with constrained drop surfactometry.SP-B-C mice showed higher bioluminescence and CFUs, increased inflammation and mortality, the higher score of lung injury, and reduced numbers of lamellar bodies in type II cells compared with SP-B-T or WT (P 0.05). Minimum surface tension increased dramatically in infected mice (P 0.01) with the order of SP-B-CSP-B-TWT. Levels of multiple cytokines in the lung of infected SP-B-C were higher than those of SP-B-T and WT (P 0.01). Furthermore, compared with SP-B-T or WT, SP-B-C exhibited lower SP-B, higher NF-κB and NLRP3 inflammasome activation, and higher activated caspase-3.hSP-B variants differentially regulate susceptibility through modulating the surface activity of surfactant, cell death, and inflammatory signaling in sepsis.

Recent studies have discovered a class of circular RNAs (circRNAs), which are dysregulated in various tumors and participate in the regulation of tumor progression. In our research, we aim to research the function of circ-SMAD7 in the progression of glioma.Circ-SMAD7 expression was detected by quantitative Real Time Polymerase Chain Reaction (qRT-PCR) in glioma tissue patients. Pearson's Chi-square test was used to determine the association of circ-SMAD7 expression with several clinicopathological factors. Besides, cell proliferation assay, cell cycle assay, transwell assay, and Matrigel assay were conducted to detect the function of circ-SMAD7 in glioma. In addition, the interaction between circ-SMAD7 and proliferating cell nuclear antigen (PCNA) in glioma was studied by performing qRT-PCR and Western blot assay.Circ-SMAD7 expression was observed in glioma tissues when compared with adjacent samples. The expression of circ-SMAD7 was associated with patients' WHO stage and KPS score. Cell proliferation was inhibited and cell cycle was regulated after circ-SMAD7 was downregulated in glioma cells. Besides, cell migration and invasion were inhibited after circ-SMAD7 was downregulated in glioma cells. In addition, the mRNA and protein expression of PCNA was repressed after circ-SMAD7 was knocked down in glioma cells. Furthermore, PCNA expression level positively correlated to circ-SMAD7 expression level in glioma samples.Our study suggests that circ-SMAD7 promotes proliferation and metastasis of glioma via upregulating PCNA. Circ-SMAD7/ PCNA might be a novel therapeutic strategy in glioma.

The surface tension of xylem sap has been traditionally assumed to be close to that of the pure water because decreasing surface tension is thought to increase vulnerability to air seeding and embolism. However, xylem sap contains insoluble lipid-based surfactants, which also coat vessel and pit membrane surfaces, where gas bubbles can enter xylem under negative pressure in the process known as air seeding. Because of the insolubility of amphiphilic lipids, the surface tension influencing air seeding in pit pores is not the equilibrium surface tension of extracted bulk sap but the local surface tension at gas–liquid interfaces, which depends dynamically on the local concentration of lipids per surface area. To estimate the dynamic surface tension in lipid layers that line surfaces in the xylem apoplast, we studied the time-dependent and surface area-regulated surface tensions of apoplastic lipids extracted from xylem sap of four woody angiosperm plants using constrained drop surfactometry. Xylem lipids were found to demonstrate potent surface activity, with surface tensions reaching an equilibrium at ~25 mN m-1 and varying between a minimum of 19 mN m-1 and a maximum of 68 mN m-1 when changing the surface area between 50 and 160% around the equilibrium surface area. It is concluded that xylem lipid films in natural conditions most likely range from nonequilibrium metastable conditions of a supersaturated compression state to an undersaturated expansion state, depending on the local surface areas of gas–liquid interfaces. Together with findings that maximum pore constrictions in angiosperm pit membranes are much smaller than previously assumed, low dynamic surface tension in xylem turns out to be entirely compatible with the cohesion–tension and air-seeding theories, as well as with the existence of lipid-coated nanobubbles in xylem sap, and with the range of vulnerabilities to embolism observed in plants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the novel coronavirus disease 2019 (COVID-19), has caused a global pandemic on a scale not seen for over a century. Increasing evidence suggests that respiratory droplets and aerosols are likely the most common route of transmission for SARS-CoV-2. Since the virus can be spread by presymptomatic and asymptomatic individuals, universal face masking has been recommended as a straightforward and low-cost strategy to mitigate virus transmission. Numerous governments and public health agencies around the world have advocated for or mandated the wearing of masks in public settings, especially in situations where social distancing is not possible. However, the efficacy of wearing a mask remains controversial. This interdisciplinary review summarizes the current, state-of-the-art understanding of mask usage against COVID-19. It covers three main aspects of mask usage amid the pandemic: quality standards for various face masks and their fundamental filtration mechanisms, empirical methods for quantitatively determining mask integrity and particle filtration efficiency, and decontamination methods that allow for the reuse of traditionally disposable N95 and surgical masks. The focus is given to the fundamental physicochemical and engineering sciences behind each aspect covered in this review, providing novel insights into the current understanding of mask usage to curb COVID-19 spread., Graphic abstractUnlabelled Image

Optimization of production depends heavily on crude oil composition and its variation within and across multiple reservoirs. In particular, asphaltene content has enormous impact on crude oil viscosity and the economic value of reservoir fluids. Thus, it is important to understand the primary controls on crude oil composition and asphaltene distributions in reservoirs. This paper examines a complex oilfield in the North Sea that contains seven separate reservoirs. The crude oil is believed to have spilled from deeper into shallower reservoirs during reservoir charging. In-situ asphaltene content is measured by downhole fluid analysis (DFA) and is generally consistent with a spill-fill sequence in reservoir charging. Detailed compositional analysis of crude oil samples by comprehensive two-dimensional gas chromatography (GC × GC) was used to determine the extent of water washing, biodegradation and thermal maturity among the reservoirs. Increased biodegradation and water washing in the shallower reservoirs is consistent with a spill-fill sequence. Aromatic and alkylated aromatic compounds decrease according to a combination of water solubility and susceptibility to biodegradation in the shallower reservoirs. Four thermal maturity biomarker ratios show that the shallower reservoirs contain less mature oil, consistent with a spill-fill sequence. The combination of DFA for bulk compositional analysis and GC × GC for detailed compositional analysis combined with geochemical interpretation is an effective tool to unravel complex oilfield scenarios.

The acute respiratory distress syndrome (ARDS) is characterized by arterial hypoxemia accompanied by severe inflammation and alterations to the pulmonary surfactant system. Published data has demonstrated a protective effect of matrix metalloproteinase-3 (Mmp3) deficiency against the inflammatory response associated with ARDS; however, the effect of Mmp3 on physiologic parameters and alterations to surfactant have not been previously studied. It was hypothesized that Mmp3 deficient (Mmp3−/−) mice would be protected against lung dysfunction associated with ARDS and maintain a functional pulmonary surfactant system. Wild type (WT) and Mmp3−/− mice were subjected to acid-aspiration followed by mechanical ventilation. Mmp3−/− mice maintained higher arterial oxygenation compared with WT mice at the completion of ventilation. Significant increase in functional large aggregate surfactant forms were observed in Mmp3−/− mice compared with WT mice. These findings further support a role of Mmp3 as an attractive therapeutic target for drug development in the setting of ARDS.

Software transactional memory is an effective mechanism to avoid concurrency bugs in multithreaded programs. However, two problems hinder the adoption of such traditional systems in the wild world: high human cost for equipping programs with transaction functionality and low compatibility with I/O calls and conditional variables. This paper presents Convoider to solve these problems. By intercepting interthread operations and designating code among them as transactions in each thread, Convoider automatically transactionalizes target programs without any source code modification and recompiling. By saving/restoring stack frames and CPU registers on beginning/aborting a transaction, Convoider makes execution flow revocable. By turning threads into processes, leveraging virtual memory protection and customizing memory allocation/deallocation, Convoider makes memory manipulations revocable. By maintaining virtual file systems and redirecting I/O operations onto them, Convoider makes I/O effects revocable. By converting lock/unlock operations to no-ops, customizing signal/wait operations on condition variables, and committing memory changes transactionally, Convoider makes deadlocks, data races, and atomicity violations impossible. Experimental results show that Convoider succeeds in transparently transactionalizing twelve real-world applications with averagely incurring only 28% runtime overhead and perfectly avoid 94% of thirty-one concurrency bugs used in our experiments. This study can help efficiently transactionalize legacy multithreaded applications and effectively improve the runtime reliability of them.

To establish normal values for detection indexes of peripheral skeletal muscle dysfunction (quadriceps femoris) of healthy older subjects, and investigate the functional status of the peripheral skeletal muscle of patients with stable phase COPD.Patients with stable phase COPD and healthy subjects of similar age were included. The assessments of strength and myoelectricity of the quadriceps femoris were recorded. The twitch tension of the quadriceps femoris (TwQ), quadriceps maximum voluntary contraction (QMVC), and endurance time (Tf) were measured. The multiple-parameter malnutrition index (MNI) was used for overall evaluation of the nutritional status of patients. The femoral muscle volume was estimated. All subjects were subjected to a routine pulmonary function test including indexes such as FEV1, FVC, FEV1/FVC (%), and PEF. Enzyme-linked immunoassay (ELISA) was used to measure the levels of myostatin, tumor necrosis factor-α, TNF-like apoptosis-inducing factor (TWEAK), surface active protein D (SPD), C-reactive protein (CRP), interleukin (IL)-1β, and IL-6. The cell immunohistochemical method was used to detect the expression of nuclear factor Kappa B (NF-κB).There were significant differences in body weight, BMI, femoral muscle volume, and physical activity scores between the two groups (p0.01). The MNI of patients in the COPD group was significantly higher than that in the control group (p0.01). The QMVC of 51 male and 16 female patients decreased. All eight tested cytokines increased in the COPD group but there were only significant differences in four cytokines (p0.05).Chronic systemic inflammation is a major risk factor of skeletal muscle dysfunction (SMD) in COPD patients. The levels of SPD, myostatin, TWEAK, and TNF-α decreased significantly in COPD patients.

Accurate quantification of oil-based drilling mud (OBM) filtrate contamination of hydrocarbon samples is still one of the biggest challenges in formation fluid sampling with formation testers. There exist contamination quantification techniques, but they can be technique sensitive, lack a confident level of quality control and apply only to a limited combination of probe types and formation fluid types. In particular, current techniques rely on an assumed absence of mud filtrate coloration at relevant optical channels and on sufficient optical density contrast between mud filtrate and virgin fluids. Such assumed fluid properties may not materialize when, for example, drilling muds are reused in multiple wells or when virgin fluids exhibit little color due to the absence of asphaltenes. In this paper, new mixing rules have been developed for mass density and shrinkage factor and for the newly defined “ f -function” and “ q -function”. The f -function, also referred to as the modified gas/oil ratio, is essentially a combination of gas/oil ratio with shrinkage factor. Similarly, the q -function is referred to as modified composition and is a combination of composition with mass density. OBM filtrate contamination in volume fraction, optical density, f -function, mass density, shrinkage factor, and q -function at a specified downhole sampling station have been found to be mutually linearly related as predicted by the mixing rules. The mutually linear relations are further confirmed by laboratory data for different mixtures of mud filtrate and formation fluids. Application of these mixing rules enables accurate OBM filtrate contamination in hydrocarbon samples if the filtrate properties and virgin fluid properties can be determined. A new methodology has been developed to determine the properties of the virgin formation fluid and mud filtrate, which are referred to as endpoints. The mud filtrate properties are obtained by extrapolating the mutually linear relations established from the cleanup data to zero gas/oil ratio or other known filtrate values such as zero methane composition, and/or zero optical density at specified wavelengths. The virgin fluid properties are determined by the power-law fitting of cleanup data coupled with the flow regime identification which is confirmed by large number of downhole fluid analysis datasets from wireline formation testers and numerical simulation. This novel methodology enables accurate quantification of the OBM filtrate and pure virgin formation fluid. Furthermore, the self-consistency of using multiple independent sensors provides confidence and greatly improves the robustness and quality control of OBM filtrate contamination monitoring downhole. Finally, contamination results can be expressed in volume or weight percent and as live fluid or stock-tank liquid fraction for easy comparison to laboratory results. A latest generation downhole fluid analysis (DFA) tool was employed to measure fluid properties downhole in real time on more than 30 DFA stations acquired with either conventional probes or 3D radial probes. The new methodology was applied to each of the acquired datasets. All the results from the new method are in good agreement with the results of the laboratory analysis.