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The ongoing COVID-19 pandemic is causing huge impact on health, life, and global economy, which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity, and immune persistence were investigated in preclinical studies using seven different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies, and seroconversion. These results consistent with the results obtained from preclinical data on the safety.

HOCN and HNCO abundance ratio in molecular gas can tell us the information of their formation mechanism. We performed high-sensitivity mapping observations of HOCN, HNCO, and HNC18O lines around Sagittarius B2 (Sgr B2) with the IRAM 30 m telescope at the 3 mm wavelength. HNCO 404–303 and HOCN 404–303 are used to obtain the abundance ratio of HNCO to HOCN. The ratio of HNCO 404–303 to HNC18O 404–303 is used to calculate the optical depth of HNCO 404–303. The abundance ratio of HOCN and HNCO is observed to range from 0.4% to 0.7% toward most positions, which agrees well with the gas-grain model. However, the relative abundance of HOCN is observed to be enhanced toward the direction of Sgr B2 (S), with HOCN to HNCO abundance ratio of ∼0.9%. The reason for that still needs further investigation. Based on the intensity ratio of HNCO and HNC18O lines, we updated the isotopic ratio of 16O/18O to be 296 ± 54 in Sgr B2.

Background: COVID-19 has had a wide impact on the mental health of college students. This study aims to explore the relationship between time perception, risk perception, and the mental health of college students during COVID-19 through a questionnaire survey.Subjects: One thousand two hundred and eighteen college students, 449 male and 769 female, who studied online during the COVID-19 epidemic were selected.Methods: Time Perception Scale, Risk Perception Scale, and SCL-90 were used to investigate the relationship using correlation analysis.Results: During the COVID-19 period, mental health problems of college students were widespread, and 65.93% of college students reported moderate to severe mental health problems. The correlation analysis showed that risk perception, time perception, and the mental health of college students were significantly related. Risk perception played a partial mediating role between present enjoyment and mental health, and risk perception played a partial mediating role between future time perception and mental health.Conclusion: In the case of sudden public crises, we should pay close attention to the mental health of college students, adjust their attitude toward the present and the future, and pay attention to their perception of risk so as to improve their mental health level under crisis.

Hydraulic connections between a river and an adjacent aquifer are controlled by the river resistance and aquifer diffusivity. In this paper, we derive a spectral solution linking the power spectrum ...

We developed a label-free microfluidic acoustic flow cytometer (AFC) based on interleaved detection of ultrasound backscatter and photoacoustic waves from individual cells and particles flowing through a microfluidic channel. The AFC uses ultra-high frequency ultrasound, which has a center frequency of 375 MHz, corresponding to a wavelength of 4 μm, and a nanosecondpulsed laser, to detect individual cells. We validate the AFC by using it to count different color polystyrene microparticles and comparing the results to data from fluorescence-activated cell sorting (FACS). We also identify and count red and white blood cells in a blood sample using the AFC, and observe an excellent agreement with results obtained from FACS. This new label-free, non-destructive technique enables rapid and multi-parametric studies of individual cells of a large heterogeneous population using parameters such as ultrasound backscatter, optical absorption, and physical properties, for cell counting and sizing in biomedical and diagnostics applications.

Lithology variations, which are recognized as rock type differences, significantly affect the physical properties of rock masses in red beds. In this paper, we introduce a statistical method for quantitatively evaluating the degree of lithology variations in layered red beds with depth. The core of this method is to use borehole logs as random variables for statistical analysis to calculate the percentage of a specified lithology at a given elevation, which involves seven steps of attitude calculation, reference point selection, distance calculation, elevation modification, data discretization, data statistics, and curve plotting. The Yellow River Guxian Dam is chosen as a field case study. We classify rock types of feldspar sandstone, fine sandstone, and conglomerate into hard rocks and that rock types of calcareous siltstone, argillaceous siltstone, and mudstone into soft rocks. Borehole logs recorded during the geological investigation are used to plot the percentage curve of hard rocks. We find that the degree of lithology variations for each lithology group differs greatly, the general behaviors of lithology variations on two sides of the Guxian Dam riverbed are quite similar but still with some differences, and that some thick lithology groups can be finely divided into several subgroups. On the basis of the hard rock percentage curve, we introduce a lithology variation index to quantitatively characterize the degree of lithology variations, which can be used as an important index to supplement the traditional methods when performing rock mass classifications in red beds. We also plot the trilithology percentage curve of sandstone, calcareous siltstone, and argillaceous siltstone, which serves for the determination of physical parameters of the dam foundation rock mass, the identification of the potential shear sliding surface, and the search for an impervious grouting bottom. Moreover, we find that the crest and trough, which are local high and low points in the hard rock percentage curve, can be used to show some characteristics of shear zones. The locations of shear zones are well represented in the form of troughs and that the development of shear zones has a good linear relationship with the hard rock percentage of the corresponding crest. The method proposed in this paper can be promoted and applied in similar projects or studies.

The rise and fall of the groundwater level can drive air flow in the vadose zone. In turn, the air flow can interact with the water flow. When the unconfined aquifer is covered by a low-permeability media, the coupling of the water flow and the air flow is more obvious. In this study, a conceptual model is established for coupling of air flow and water flow in the vadose zone in response to rapid fluctuations of the water table. Water injection and drainage experiments are conducted in a double-layered sand column with a thick layer (80.5 cm) of coarse sand and a thin layer of fine sand as a low-permeability cap. Different cap thickness (2 cm, 5 cm, 7.5 cm) and different thickness of the vadose zone (30 cm, 40 cm) are set for the experiments. Negative pressure (NP)/positive pressure (PP) of the air in the vadose zone is observed in the drainage/injection experiments, with higher pressure in experiments of thicker cap layer. In each experiment, NP or PP increases rapidly to reach a maximum in the early stage, and gradually becomes zero in the late stage. Analytical solutions on three subdivided stages indicate the permeability and thickness of the cap layer, as well as permeability and porosity of the media in the vadose zone are the key controlling factors on the process of coupling of air flow and water flow. The solutions also reveal the formation mechanism of air pressure in the vadose zone with a low-permeability cap. This study has both theoretical significance and engineering applications.

In this study, the estrogenic effect of GL-1, a component of the

Straightforward solutions have long been expected for the analysis of multiwell aquifer tests. In this paper, we derive series analytical solutions of steady-state groundwater flow in a rectangular-shaped aquifer with pumping/injection wells for both confined and unconfined conditions. Double Fourier Transform (DFT) technique is applied to deal with different combinations of impermeable and specified head boundaries on sides. The obtained solutions are compact and concise in mathematics and flexible in terms of well number, well locations, and pumping/injection rates. Hatoucaidang, a groundwater resource field in the Ordos Plateau, Northwestern China, is introduced as a field case study, where a multiwell aquifer test was conducted. One of the analytical solutions derived herein is used to estimate hydraulic conductivities by applying a direct calculation method and a least square estimation method regarding observed versus calculated drawdowns. By comparing with nearby single-well pumping tests, the reliability of the derived analytical solutions is proven. This study facilitates utilizing the multiwell aquifer test to analyze the general behavior of groundwater movement in aquifer systems.

Accurate estimation of evaporation (E0) over open water bodies in arid regions (e.g., lakes in the desert) is of great importance for local water resource management. Due to the ability to accurately determine sensible (H) and latent (LE) heat fluxes over scales of hundreds to thousands of meters, scintillometers are more and more appreciated. In this study, a scintillometer was installed on both sides of the shore over the Sumu Barun Jaran Lake in the Badain Jaran Desert and was applied to estimate the sensible and latent heat fluxes and evaporation to be compared with the data of an evaporation pan and an aerodynamic model. Based on the field data, we further analyzed the seasonal differences in the flux evaluation using water temperature at different depths at half-hour and daily time scales, respectively. The results showed that in cold seasons, values of H were barely affected by the changes of shallow water temperature, whereas in hot seasons, the values were changed by 20%&ndash, 30% at the half-hour time scale and 6.2%&ndash, 18.3% at the daily time scale. In different seasons, shallow water temperature at different depths caused changes in the range of 0%&ndash, 20% of LE (E0). This study contributes to a better understanding of uncertainties in measurements by large-aperture scintillometers in open-water environments.

Groundwater sampled at the outlets of uncased flowing wells in a thick unconfined aquifer, which has undergone mixing, has been found to have hydrochemistry similar to deep groundwater in discharge areas. To identify the hydrodynamic causes, transient models of groundwater flow and age in a three-dimensional homogeneous unit basin with flowing wells are constructed to obtain flow rates in wells and groundwater mean age around wells. Inflow of groundwater to the well in the deep part leads to mixing of groundwater from different sources, and the finally mixed groundwater is found to have the same age as groundwater in the aquifer at a specific depth, termed the equivalent position (EP). EP is always found in the lower half of the flowing well, indicating that a mixed sample at the outlet could represent deep groundwater. Outflow from the well to the unconfined aquifer in the shallow part results in aging of groundwater around the well. For fully penetrating flowing wells in confined aquifers, EP is found in the upper half of the aquifer. The different relative depths of EP to the screen interval in the two types of flowing wells are mainly due to the profiles of horizontal velocity in the inflow segment, which is basically uniform in a confined aquifer but increases from zero to a maximum value in unconfined aquifers. Thus, groundwater at the outlets of topography-controlled flowing wells is a window of the deep part of a basin, and existing long-screen wells could have the potential for groundwater sampling.

The Ordos Basin is one of the most intensively studied groundwater basins in China. The Ordos Plateau, located in the north part of the Ordos Basin, is ideal to study the pattern of regional groundwater circulation induced by water-table undulations due to the wavy topography and the relatively simple aquifer systems with macroscopically homogeneous sandstone. In catchments located near the first-order divide, the water table is found to be a subdued replica of the topography, and the nonclosed water-table contours in topographic highs of a catchment are indicative of regional groundwater outflow to other catchments. In topographic lows, groundwater-fed lakes/rivers, topography-driven flowing wells, water-loving and/or salt-tolerant vegetation, and soap holes are all indicative of discharge areas. In discharge areas, although groundwater inflow from recharge areas is relatively stable, seasonal variations in groundwater recharge and evapotranspiration lead to significant seasonal fluctuations in the water table, which can be used to estimate groundwater inflow and evapotranspiration rates based on water balance at different stages of water-table change. In the lowest reaches of a complex basin, superposition of local flow systems on regional flow systems has been identified based on groundwater samples collected from wells with different depths and geophysical measurements of apparent resistivity, both of which can be used for characterizing groundwater flow systems. This study enhances understanding of the pattern of regional groundwater circulation in the Ordos Plateau, and also tests the effectiveness of methods for groundwater flow-system characterization.

Classical understanding on basin-scale groundwater flow patterns is based on Toth’s findings of a single flow system in a unit basin (Toth, 1962) and nested flow systems in a complex basin (Toth, 1963), both of which were based on steady state models. Vandenberg (1980) extended Toth (1962) by deriving a transient solution under a periodically changing water table in a unit basin and examined the flow field distortion under different dimensionless response time, τ∗. Following Vandenberg’s (1980) approach, we extended Toth (1963) by deriving the transient solution under a periodically changing water table in a complex basin and examined the transient behavior of nested flow systems. Due to the effect of specific storage, the flow field is asymmetric with respect to the midline, and the trajectory of internal stagnation points constitutes a non-enclosed loop, whose width decreases when τ∗ decreases. The distribution of the relative magnitude of hydraulic head fluctuation, Δ h ∗ , is dependent on the horizontal distance away from a divide and the depth below the land surface. In the shallow part, Δ h ∗ decreases from 1 at the divide to 0 at its neighboring valley under all τ∗, while in the deep part, Δ h ∗ reaches a threshold, whose value decreases when τ∗ increases. The zones with flowing wells are also found to change periodically. As water table falls, there is a general trend of shrinkage in the area of zones with flowing wells, which has a lag to the declining water table under a large τ∗. Although fluxes have not been assigned in our model, the recharge/discharge flux across the top boundary can be obtained. This study is critical to understand a series of periodically changing hydrogeological phenomena in large-scale basins.

Nested groundwater flow systems have been revealed in Toth's theory as the structural property of basin-scale groundwater circulation but were only well known with two-dimensional (2D) profile models. The method of searching special streamlines across stagnation points for partitioning flow systems, which has been successfully applied in the 2D models, has never been implemented for three-dimensional (3D) Tothian basins because of the difficulty in solving the dual stream functions. Alternatively, a new method is developed to investigate 3D nested groundwater flow systems without determination of stagnation points. Connective indices are defined to quantify the connection between individual recharge and discharge zones along streamlines. Groundwater circulation cells (GWCCs) are identified according to the distribution of the connective indices and then grouped into local, intermediate and regional flow systems. This method requires existing solution of the flow velocity vector and is implemented via particle tracking technique. It is applied in a hypothetical 3D Tothian basin with an analytical solution of the flow field and in a real-world basin with a numerical modeling approach. Different spatial patterns of flow systems compared to 2D profile models are found. The outcrops boundaries of GWCCs on water table may significantly deviate from and are not parallel to the nearby water table divides. Topological network is proposed to represent the linked recharge–discharge zones through closed and open GWCCs. Sensitivity analysis indicates that the development of GWCCs depends on the basin geometry, hydraulic parameters and water table shape.

Although it has been increasingly acknowledged that groundwater flow pattern is complicated in the three-dimensional (3-D) domain, two-dimensional (2-D) water table-induced flow models are still widely used to delineate basin-scale groundwater circulation. However, the validity of 2-D cross-sectional flow field induced by water table has been seldom examined. Here, we derive the analytical solution of 3-D water table-induced hydraulic head in a Tothian basin and then examine the validity of 2-D cross-sectional models by comparing the flow fields of selected cross sections calculated by the 2-D cross-sectional model with those by the 3-D model, which represents the “true” cases. For cross sections in the recharge or discharge area of the 3-D basin, even if head difference is not significant, the 2-D cross-sectional models result in flow patterns absolutely different from the true ones. For the cross section following the principal direction of groundwater flow, although 2-D cross-sectional models would overestimate the penetrating depth of local flow systems and underestimate the recharge/discharge flux, the flow pattern from the cross-sectional model is similar to the true one and could be close enough to the true one by adjusting the decay exponent and anisotropy ratio of permeability. Consequently, to determine whether a 2-D cross-sectional model is applicable, a comparison of hydraulic head difference between 2-D and 3-D solutions is not enough. Instead, the similarity of flow pattern should be considered to determine whether a cross-sectional model is applicable. This study improves understanding of groundwater flow induced by more natural water table undulations in the 3-D domain and the limitations of 2-D models accounting for cross-sectional water table undulation only.

Previous studies on the characterization of hierarchically nested groundwater flow systems have mainly been based on the spatial distribution analyses of groundwater pathways. In this paper, by considering the discrete nature of the temporal behavior induced by different hierarchical flow systems, a new approach is proposed. The core of this approach is to use the critical residence times defined by the late-time peaks of residence time distributions (RTDs) to divide the groundwater flow field into local, intermediate and regional systems as described by Toth (1963). We first introduce Tothian basins of a 2D cross section and a 3D domain as synthetic test cases. The feasibility of the approach is demonstrated by comparing the partitioning results given by the dividing streamlines associated with internal stagnation points in the 2D Tothian basin and by the hydraulic connections between recharge and discharge zones in the 3D Tothian basin. Then, the Dosit River Watershed in Northwestern China is introduced as a field case study. Using the calibrated 3D groundwater flow model, one distinct late-time peak is identified from the RTD and indicates that the Dosit River Watershed can generally be regarded as a two-order nested flow structure with local and regional flow systems. This approach can be used to identify the volumes occupied by different orders of flow systems in 3D, and therefore opens up a new perspective in the study of the 3D nature of basin-scale groundwater flow.

The steroidal saponin RCE‑4 (1β, 3β, 5β, 25S)‑spirostan‑1, 3‑diol 1‑[α‑L‑rhamnopyranosyl‑(1→2)‑β‑D‑xylopyranoside], isolated from Reineckia carnea, exerts significant anti‑cervical cancer activity by inducing apoptosis. The potential effect of RCE‑4 on proliferation inhibition and autophagy induction has rarely been studied. Therefore, the focus of the present study was to investigate the effects of RCE‑4 on proliferation, and to elucidate the detailed mechanisms involved in autophagy induction in cervical cancer cells. CaSki cells were treated with RCE‑4 or/and autophagy inhibitors, and the effect of RCE‑4 on cellular proliferation was assessed by MTT assay. The pro‑autophagic properties of RCE‑4 were subsequently confirmed using monomeric red fluorescent protein‑green fluorescent protein‑microtubule‑associated proteins 1A/1B light chain 3B (LC3) adenoviruses and CYTO‑ID autophagy assays, and by assessing the accumulation of lipid‑modified LC3 (LC3II). The mechanisms of RCE‑4‑induced autophagy were investigated by western blot analysis. The results demonstrated that inhibiting autophagy significantly promoted RCE‑4‑induced cell death, indicating that autophagy served a protective role following RCE‑4 treatment. In addition, RCE‑4‑induced autophagy was reflected by increased expression levels of the serine/threonine‑protein kinase ULK1, phosphorylated (p)‑ULK1, p‑Beclin‑1 and LC3II, the formation of autophagosomes and autolysosomes, and sequestosome 1 (p62) degradation. Subsequent analysis indicated that RCE‑4 activated the AMP‑activated protein kinase (AMPK) pathway by upregulating AMPK and p‑AMPK, and also inhibited the PI3K and extracellular signal‑regulated kinase (ERK) signaling pathways by downregulating p‑PI3K, p‑Akt, p‑mTOR, Ras, c‑Raf, p‑c‑Raf, dual specificity mitogen‑activated protein kinase kinase (MEK)1/2, p‑MEK1/2 and p‑Erk1/2. Additionally, with increased treatment times RCE‑4 may impair lysosomal cathepsin activity and inhibit autophagy flux by suppressing the expression of AMPK, p‑AMPK, ULK1, p‑ULK1 and p‑Beclin‑1, and upregulating that of p62. These results indicated that the dual RCE‑4‑induced inhibition of the PI3K and ERK pathways may result in a more significant anti‑tumor effect and prevent chemoresistance, compared with the inhibition of either single pathway; furthermore, dual blockade of PI3K and ERK, and the AMPK pathway may be involved in the regulation of autophagy caused by RCE‑4. Taken together, RCE‑4 induced autophagy to protect cancer cells against apoptosis, but AMPK‑mediated autophagy was inhibited in the later stages of RCE‑4 treatment. In addition, autophagy inhibition improved the therapeutic effect of RCE‑4. These data highlight RCE‑4 as a potential candidate for cervical cancer treatment.

The aim of this paper was to observe the combination therapy with total triterpenoids of Chaenomeles speciosa and omeprazole on indomethacin-induced gastric ulcer in rats, and explore its possible mechanism. Rats were randomly divided into normal group, model group, omeprazole monotherapy(3.6 mg·kg~(-1)) group, total triterpenoids of C. speciosa monotherapy(100 mg·kg~(-1)) group, total triterpenoids of C. speciosa and omeprazole combination therapy(100 mg·kg~(-1)+3.6 mg·kg~(-1)) group. Except for the normal group, the other groups were given indomethacin(20 mg·kg~(-1)) by oral once a day for 7 consecutive days. Then the treated groups were given corresponding drugs by gavage, once a day for 14 consecutive days. The next day after the last administration, half of the rats in each group were measured the gastric mucosal blood flow, gastric juice volume and serum TNF-α, IL-1β, IL-6, IL-4 and IL-10. After the remaining rats in each group were underwent pyloric ligation 4 hours after the last administration, the gastric endocrine volume, pH value and total acidity of gastric secretion were measured, then histological analysis was performed, MPO activity, cAMP content and histomorphological analysis were conducted. Real-time PCR was applied to detect the mRNA expressions of gastric tissue TNF-α,IL-1β, IL-6, IL-4, IL-10, VEGFA, A_(2A)R; the protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue were detected by Western blot. The results indicated that total triterpenoids of C. speciosa and omeprazole combination therapy might significantly increase gastric mucosal blood flow, gastric mucus volume, reduce gastric endocrine volume, secretion acidity and mucosal damage, decrease the levels of TNF-α,IL-1β and IL-6, increase the levels of IL-4 and IL-10 in blood and gastric tissue, inhibit the activity of MPO, increase the content of cAMP in gastric tissue, up-regulate the mRNA expressions of VEGFA, A_(2A)R and protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue, elevate p-PKA/PKA, p-CREB/CREB and p-EFGR/EFGR. Moreover, the combination therapy with total triterpenoids of C. speciosa and omeprazole was more obvious than those of two monotherapies. These aforementioned findings suggested that the combination therapy with total triterpenoids of C. speciosa and omeprazole on indomethacin-induced gastric ulcer have significant therapeutic effect on indomethacin induced gastric ulcer in rats, its mechanism might be related to regulating A_(2A)R/AKT/CREB, A_(2A)R/VEGFA, EGF/EGFR and MUC6/TFF2 signaling pathways, inhibiting pro-inflammatory factors, increasing gastric mucosal blood flow, up-regulating mucosal cell proliferation factors and promoting mucosal protective factors.

Fever is a systemic inflammatory response of the body to pyrogens. Nuclear factor κB (NF-κB) is a central signalling molecule that causes the excessive secretion of various proinflammatory factors induced by pyrogens. This study explored the feasibility of a novel reporter gene assay (RGA) for pyrogen detection using RAW 264.7 cells stably transfected with the NF-κB reporter gene as a pyrogenic marker. Pyrogen was incubated with the transgenic cells, and the intensity of the fluorescence signal generated by luciferase secreted by the reporter gene was used to reflect the degree of activation of NF-κB, so as to quantitatively detect the pyrogens. The RGA could detect different types of pyrogens, including the lipopolysaccharide (LPS) of gram-negative bacteria, the lipoteichoic acid (LTA) of gram-positive bacteria, and the zymosan of fungi, and a good dose-effect relationship was observed in terms of NF-κB activity. The limits of detection of the RGA to those pyrogens were 0.03 EU/ml, 0.001 μg/ml, and 1 μg/ml, respectively. The method had good precision and accuracy and could be applied to many biological products (e.g., nivolumab, rituximab, bevacizumab, etanercept, basiliximab, haemophilus influenzae type b conjugate vaccine, 23-valent pneumococcal polysaccharide vaccine, and group A and group C meningococcal conjugate vaccine). The results of this study suggest that the novel RGA has a wide pyrogen detection spectrum and is sufficiently sensitive, stable, and accurate for various applications.ImportancePyrogen testing is mandatory and a critical method to ensure the safety of parenteral products including vaccines.Currently, only two pharmacological tests, including the rabbit pyrogen test and the bacterial endotoxins test (BET), are applied to evaluate pyrogenic contamination in parenteral pharmaceuticals by most of state pharmacopoeias. Although generally reliable, both of these assays have shortcomings. The rabbit test is not quantitative but is expensive and involves the use of animals. It can also produce varying responses depending on the strain, age and housing conditions of the rabbits. The BET, however, does not detect pyrogens other than gram-negative bacterial endotoxins and is often problematic when used to test solutions with a high protein content.To overcome these shortcomings and satisfy the growing need for new methods prompted by the constantly increasing production of biological compounds, it is necessary to develop the novel assay for pyrogen detection.HighlightsThis novel reporter gene assay can detect different types of pyrogens, including the lipopolysaccharide of gram-negative bacteria, the lipoteichoic acid of gram-positive bacteria, and the zymosan of fungi.The novel reporter gene assay is sufficiently sensitive, stable, and accurate for various applications.

We use a novel acoustic-based flow cytometer to detect individual nanobubbles flowing in a microfluidic channel using high-frequency ultrasound and photoacoustic waves. Each individual nanobubble (or cluster of nanobubbles) flowing through the foci of high-frequency ultrasound (center frequency 375 MHz) and nanosecond laser (532 nm) pulses interacts with both pulses to generate ultrasound backscatter and photoacoustic waves. We use in-house generated nanobubbles, made of lipid shells and octafluoropropane gas core, to detect ultrasound backscatter signals using an acoustic flow cytometer. Nanobubble solutions sorted in size through differential centrifugation are diluted to 1:10,000 v/v in phosphate buffered saline solution to maximize the probability that the detected signals are from individual nanobubbles. Nanobubble populations were sized using resonant mass measurement. Results show that the amplitude of the detected ultrasound backscatter signal is dependent on the nanobubble size. The average amplitude of the ultrasound backscatter signals from at least 950 nanobubbles with an average diameter of 150 nm, 225 nm, and 350 nm was 5.1±2.5 mV, 5.3±2.3 mV, and 6.4±1.8 mV, respectively. Similarly, we detected interleaved ultrasound backscatter and photoacoustic signals from nanobubbles tagged with Sudan Black B dye. The average amplitude of the ultrasound backscatter and photoacoustic signals from these black nanobubbles with an average diameter of 238 nm is 10±11 mV and 54±75 mV, respectively. The presence of the dye on the shell suppressed unique features seen in the ultrasound backscatter from the nanobubbles without dye. At present, there is no robust commercial technique able to analyze the ultrasonic response of individual nanobubbles. The acoustic flow cytometer can potentially be used to analyze physical parameters, such as size and ultrasonic response, of individual nanobubbles.

Background The development of a Sabin strain-based inactivated poliovirus vaccine (Sabin-IPV) is imperative to protecting against vaccine-associated paralytic poliomyelitis in developing countries. Methods In this double-blinded, parallel-group, noninferiority trial, eligible infants aged 60-90 days were randomly assigned in a ratio of 1:1 to receive either 3 doses of Sabin-IPV or Salk strain-based IPV (Salk-IPV) at 30-day intervals and a booster at the age of 18 months. Immunogenicity and safety were assessed on the basis of a protocol. Results Of 1438 infants, 1200 eligible infants were recruited and received either Sabin-IPV or Salk-IPV. From the Sabin-IPV and Salk-IPV groups, 570 and 564 infants, respectively, completed the primary immunization and formed the per-protocol population. The seroconversion rates of the participants who received Sabin-IPV were 100%, 94.9%, and 99.0% (types I, II, and III, respectively), and those of the participants who received Salk-IPV were 94.7%, 91.3%, and 97.9% 1 month after the completion of primary immunization. An anamnestic response for poliovirus types I, II, and III was elicited by a booster in both groups. Except in the case of fever, other adverse events were similar between the 2 groups. Conclusions The immune response induced by Sabin-IPV was not inferior to that established with Salk-IPV.

FSH plays a key role in the function of the reproductive system of human beings and is widely used both diagnostically and therapeutically in reproductive medicine. With the growing incidence of infertility, the demand for FSH pharmaceutical products is increasing. For this reason, the quality control process for FSH products is becoming more stringent. An accurate determination of bioactivity is crucial for the safety and efficacy of recombinant human follicle stimulating hormone (rhFSH). Up to now, in-vivo bioassay based on FSH-induced increases in rat ovarian weight has been the only method widely accepted by different pharmacopoeias. However this method has such drawbacks as the complex procedures, long assay period and high variability. Here, we established a reporter gene assay (RGA) based on the CHO-K1-FSHR-CRE-Luc cell line that stably expresses human follicle stimulating hormone receptor (hFSHR), as well as a luciferase reporter under the control of cyclic adenosine monophosphate (cAMP) response elements (CRES). Our study showed that our new assay not only has good dose-dependent responsiveness to rhFSH, but it also performs excellently in terms of specificity, precision, linearity, and simplicity compared with in-vivo rat bioassays. These results implied that this robust reporter gene assay may be a viable supplement to the animal in-vivo bioassay and may be employed in potency determination of rhFSH pharmaceutical products.

To study the chemical constituents and their anti-tumor activity of Eupatorium chinense. Methods: The chemical constituents were separated and purified by the normal phase silica gel column chromatography,preparative thin-layer chromatography,and preparative HPLC. Their structures were determined by various spectral data,their antitumor activity in vitro was determined by MTT assay. Results: Six compounds were isolated from the ethyl acetate extract of Eupatorium chinense,and the structures were identified as eupalinilide G( 1),8β-( 4’-hydroxytigloyloxy)-5-desoxy-8-desacyleuparotin( 2),3-( hydroxymethyl)-1,13,14,15-tetrahydroxy-7,11,15-trimethyl-2,6,10-hexadecatriene( 3),3-( hydroxymethyl)-1,13,15-trihydroxy-7,11,15-trimethyl-2,6,10-hexadecatrien-14-yl acetate( 4),eupafolin( 5) and hiyodorilactone B( 6). Compound 2 showed cytotoxicity against HGC-27 and B16 cancer cell lines with IC50 values of 4. 29 μg/m L and 5. 53 μg/m L,respectively.The chemical constituents were separated and purified by the normal phase silica gel column chromatography,preparative thin-layer chromatography,and preparative HPLC. Their structures were determined by various spectral data,their antitumor activity in vitro was determined by MTT assay.Six compounds were isolated from the ethyl acetate extract of Eupatorium chinense,and the structures were identified as eupalinilide G( 1),8β-( 4’-hydroxytigloyloxy)-5-desoxy-8-desacyleuparotin( 2),3-( hydroxymethyl)-1,13,14,15-tetrahydroxy-7,11,15-trimethyl-2,6,10-hexadecatriene( 3),3-( hydroxymethyl)-1,13,15-trihydroxy-7,11,15-trimethyl-2,6,10-hexadecatrien-14-yl acetate( 4),eupafolin( 5) and hiyodorilactone B( 6). Compound 2 showed cytotoxicity against HGC-27 and B16 cancer cell lines with IC50 values of 4. 29 μg/m L and 5. 53 μg/m L,respectively.Compounds 2 ~ 5 are isolated from the Eupatorium chinense for the first time,and compound 2 has significant cytotoxic activity against HGC-27 cell line.

To investigate the estrogenic activities of alcohol extract from Phellinus lonicerinus( AEPL).Estrogen and anti-estrogen effects were evaluated by cell proliferation experiment in vitro. Through elevating young rat uterine weight, castrated female rats, and adult female rats uterus index serum estradiol( E2) and progesterone( P) were analyzed by enzyme immune methods, and uterine estrogen receptor α( ERα) and estrogen receptor β( ERβ) protein expressions were measeured by immunohistochemisty, and investigated the histopathological of uterus, ovary, and breast of adult female rats.Compared with the control group, AEPL promoted estrogen-sensitive MCF-7 proliferation significantly( P0. 05 or P0. 01) in the doses of 5 ~ 50 μg / m L in vitro experiment; compared with the E2 control group, it also presented anti-estrogenic effect in E2-induced MCF-7 cells at the doses of 10 ~ 100 μg / m L( P0. 05 or P0. 01). In the animal experiments, AEPL remarkably increased serum E2 content and promoted growth of uterus in primary female mice at the dose of 300 mg / kg; and raised the serum E2 and P content, alleviated uterine atrophy caused by estrogen deficiency in castrated rats at the dose of 240 mg / kg. In adult female rats, AEPL markedly increased the serum P content at the dose of 120 mg / kg, and also markedly increased the serum E2 content at the dose of 120,240 mg / kg, and regulated the protein expressions of ERαand ERβ. AEPL has no effects on histopathological changes of uterus, ovary and mammary gland in rats.AEPL shows estrogenic effects with fewer adverse reaction, which possesses the replacement of estrogen application prospects.

Transparent conductive gallium-doped zinc oxide (GZO) thin films with different deposition power (from 75 to 150 W) were prepared on the Coring glass substrate by using R.F. magnetron sputtering method. The resulting GZO thin films were crystalline, displaying a hexagonal wurtzite-type crystal structure with a preferred grain orientation in the (002) direction. The best FOM was obtained at 125 W.

SM03, a chimeric antibody that targets the B-cell restricted antigen CD22, is currently being clinically evaluated for the treatment of lymphomas and other autoimmune diseases in China. SM03 binding to surface CD22 leads to rapid internalization, making the development of an appropriate cell-based bioassay for monitoring changes in SM03 bioactivities during production, purification, storage, and clinical trials difficult. We report herein the development of an anti-idiotype antibody against SM03. Apart from its being used as a surrogate antigen for monitoring SM03 binding affinities, the anti-idiotype antibody was engineered to express as fusion proteins on cell surfaces in a non-internalizing manner, and the engineered cells were used as novel “surrogate target cells” for SM03. SM03-induced complement-mediated cytotoxicity (CMC) against these “surrogate target cells” proved to be an effective bioassay for monitoring changes in Fc functions, including those resulting from minor structural modifications borne within the Fc-appended carbohydrates. The approach can be generally applied for antibodies that target rapidly internalizing or non-surface bound antigens. The combined use of the anti-idiotype antibody and the surrogate target cells could help evaluate clinical parameters associated with safety and efficacies, and possibly the mechanisms of action of SM03.

The theory of regional groundwater flow is critical for explaining heat transport by moving groundwater in basins. Domenico and Palciauskas’s (1973) pioneering study on convective heat transport in a simple basin assumed that convection has a small influence on redistributing groundwater temperature. Moreover, there has been no research focused on the temperature distribution around stagnation zones among flow systems. In this paper, the temperature distribution in the simple basin is reexamined and that in a complex basin with nested flow systems is explored. In both basins, compared to the temperature distribution due to conduction, convection leads to a lower temperature in most parts of the basin except for a small part near the discharge area. There is a high-temperature anomaly around the basin-bottom stagnation point where two flow systems converge due to a low degree of convection and a long travel distance, but there is no anomaly around the basin-bottom stagnation point where two flow systems diverge. In the complex basin, there are also high-temperature anomalies around internal stagnation points. Temperature around internal stagnation points could be very high when they are close to the basin bottom, for example, due to the small permeability anisotropy ratio. The temperature distribution revealed in this study could be valuable when using heat as a tracer to identify the pattern of groundwater flow in large-scale basins. Domenico PA, Palciauskas VV (1973) Theoretical analysis of forced convective heat transfer in regional groundwater flow. Geological Society of America Bulletin 84:3803–3814

Analytical studies on release/capture zones are often limited to a uniform background groundwater flow. In fact, for basin-scale problems, the undulating water table would lead to the development of hierarchically nested flow systems, which are more complex than a uniform flow. Under the premise that the water table is a replica of undulating topography and hardly influenced by wells, an analytical solution of hydraulic head is derived for a two-dimensional cross section of a drainage basin with horizontal injection/pumping wells. Based on the analytical solution, distributions of hydraulic head, stagnation points and flow systems (including release/capture zones) are explored. The superposition of injection/pumping wells onto the background flow field leads to the development of new internal stagnation points and new flow systems (including release/capture zones). Generally speaking, the existence of n injection/pumping wells would result in up to n new internal stagnation points and up to 2n new flow systems (including release/capture zones). The analytical study presented, which integrates traditional well hydraulics with the theory of regional groundwater flow, is useful in understanding basin-scale groundwater flow influenced by human activities.

Saponins from Rhizoma Panacis Majoris (SRPM), the bioactive component in Rhizoma Panacis Majoris, have been used extensively as a remedy for liver injury diseases and achieved good clinical efficacy, but the underlying mechanisms remain poorly understood. The goal of our present study was to further confirm SRPM hepatoprotective effect, and evaluate that whether SRPM attenuate oxidative stress and fibrosis in carbon tetrachloride (CCl4)-induced hepatic injury, based on these results, investigate the probable mechanisms involved. At first, the separation and purification of SRPM were studied. And then, in the animal experiment, the male Sprague-Dawley rats were randomly divided into control, model, l-SRPM and h-SRPM group. Hepatic fibrosis model were made according to our previous studies reported. At the same time, the experimental rats were treated respectively with relative drugs, once a day for 8 weeks. Hepatoprotective effects of SRPM were evaluated by liver function, total antioxidant capacity and total-superoxide dismutase, histopathological observations and the hepatic fibrosis relative gene expressions. In the study, we found that SRPM significantly improved liver function, serum antioxidation level, reversed the upregulated α-SMA and TIMP1 mRNA expressions, and further increased the MMP1 mRNA expression. Our studies indicated that SRPM exerted beneficially hepatoprotective effects on the CCl4 induced hepatic fibrosis, mainly enhancing liver tissue antioxidant capacity, reducing the lipid peroxidation of hepatocyte membranes, and then alleviating hepatic fibrosis and hepatic cell death.

To analysis the main component of Laetiporus sulphureus primary separation product (LSPSP) and observe the hepatoprotective effect of LSPSP. Silica column and HPLC was adopted to isolate main constituents from LSPSP. The main components were analyzed and identified by HPLC and HNMR. And then its hepatoprotective effect was evaluated, we used Sprague-Dawley rats as experimental rats, and made hepatic fibrosis models induced by carbon tetrachloride (CCl4).The hepatoprotective effects of SPSP on hepatic fibrosis of rats were evaluated by content of AST and ALT, levels of liver cell injury and degree of liver fibrosis. In the study, we found that LSPSP mainly contains eburicoic acid and trametenolic acid B. After treatment with LSPSP, the levels of serum AST and ALT significantly decreased, alleviated liver cell damage, reduced the collagen deposition in the liver tissue, and then inhibited liver fibrosis. Our studies indicated that LSPSP main components areeburicoic acid and trametenolic acid B, it exerted beneficially hepatoprotective effects on the CCl4 induced hepatic fibrosis.

Steroidal saponin: (1β,3β,5β,25S)-spirostan-1,3-diol1-[α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranoside] (RCE-4) is the most abundant and bioactive members in Reineckia carnea, has been reported to possess antiinflammatory activity, but the underlying mechanisms remain largely unknown. The present aim was to study expression of inflammatory cytokines, on the basis of this investigation, the possible mechanism of RCE-4 was elucidated. In the present study, we found that the concentrations of TNF-α, IL-1β and IL-6 released from LPS-stimulated RAW264.7cells significantly increased compared to control (P

Saponins from Rhizoma Panacis Majoris (SRPM), the bioactive component inRhizoma Panacis Majoris, were reported to possess protective effects on myocardial injury, but the underlying mechanisms remain poorly understood. This study was performed to investigate the protective effects and possible mechanism of SRPM on myocardial ischemia/reperfusion (I/R) injury in vivo. Cardioprotective effects of SPRM in I/R rats was evaluated by hemodynamic, infarct size, biochemical values, histopathological observations, antioxidative relative gene expressions; And the antioxidant activity of SPRM was studied using DPPH scavenging and β-carotene/linoleic acid tests. In the study, we found that SRPM possessed significant free radical-scavenging activity and considerable antioxidant activity, and significantly improved cardiac function, serum biochemical index and antioxidation level, decreased infarct size, reversed the down-regulated mRNA expressions of the SOD1, SOD2, SOD3 in I/R rats. The studies demonstrated that oxidative stress caused the overgeneration and accumulation of ROS, which was central of myocardial I/R injury. SPRM exerted beneficially cardioprotective effects on myocardial I/R injury, mainly scavenging oxidative stress-triggered overgeneration and accumulation of ROS, alleviating myocardial I/R injury and apoptotic cell death.

Groundwater flow systems and stagnant zones in drainage basins are critical to a series of geologic processes. Unfortunately, the difficulty of mapping flow system boundaries and no field example of detected stagnant zones restrict the application of the concept of nested flow systems. By assuming the variation in bulk resistivity of an aquifer with uniform porosity is mainly caused by groundwater salinity, the magnetotelluric technique is used to obtain the apparent resistivity of a profile across a groundwater-fed river in the Ordos Plateau, China. Based on the variations in apparent resistivity of the Cretaceous sandstone aquifer, the basin-bottom hydraulic trap below the river has been detected for the first time, and its size is found to be large enough for possible deposition of large ore bodies. The boundaries between local and regional flows have also been identified, which would be useful for groundwater exploration and calibration of large-scale groundwater models.

Discovery of bioactive ingredients from plants and fungi is always the hot spots in medicinal chemistry. The trametenolic acid B was a bioactive lanostane-type triterpenoid inTrametes lactinea(Berk.) Pat. In this work, four semi-synthetic derivatives were synthesized, characterized and evaluated the anti-gastric cancer activities against HGC-27 cells with the aim of obtaining better anti-tumor agents. The compounds2aand3bpossessed good anti-proliferative effects under normal physiological conditions, and their anti-cancer effects increased as the pH decrease to 5.5 with the IC50of 17.55 and 10.63 μM, respectively. These compounds might be further developed as anti-gastric cancer drugs.

Objective To investigate the prevalence and levels of anti-HEV IgG in the population of Jiangsu Province. Methods Total of 2 656 samples from Qindong and 11 463 samples from Anfeng were colleted. The anti- HEV antibody was qualitatively and quantitatively detected using ELISA kits and the references had been established. Results The positive rates of anti-HEV IgG in male and female were 55.6% and 40.1%, respectively. The positive rate of anti-HEV IgM in male and female were both 3.4%. In opposite to anti-HEV IgG, the positive rate of anti-HEV IgM in Anfeng was significant higher than that in Qindong. The mean anti-HEV IgG titers for 6 age groups were 0.94, 0.92, 1.07, 1.46, 1.27, 1.19 and 0.68, 1.31, 1.08, 1.14, 1.31, 1.68 IU/ml, in Qindong and Anfeng region, respectively. The positive rate of anti-HEV IgG tended to increase with age and the titer of anti- HEV IgG was associated with age (R > 0.90). Conclusions The results in this study showed that HEV was widely prevalent in both Qindong and Anfeng of Jiansu Province and the prevalence and the anti-HEV IgG titer were associated with gender and age.

Hydroxylchalcone are known to act on various physiological targets. In this study, a series of nine hydroxychalcones were synthesized via the aldol condensation with the aim of obtaining bioactive small molecules. Their structures were characterized by NMR spectra. The anti-breast cancer activity evaluation indicated the monohydroxychalcones exhibited the better anti-proliferative effect than dihydroxylchalcones against MDA-MB-231 cells, and the compound3bshowed the best anti-breast cancer activities at 18 μM. The bioactive compounds might be used to develop as potential anti-breast cancer agents.

Four bisabolangelone oxime ether derivatives were synthesized and separated as potential anti-ulcer agents. Their structures were characterized by NMR, IR and ESI-MS. Preliminarily H+/K+-ATPase activity evaluation indicated that all the target oxime ethers exhibited the better H+/K+-ATPase inhibitory activities than the commercial omeprazole with the IC50of 17~46 μM. These compounds might be used as potential anti-ulcer agents in the treatment of acid-related diseases.

BACKGROUND Vaccination is considered a top priority for the control of human enterovirus 71 (EV71) infection outbreaks. METHODS On the basis of phase I trial results, we conducted a double-blind, randomized, controlled trial to evaluate the optimal dose, immunogenicity, safety and immune persistence of the vaccine. A total of 480 healthy infants were randomly assigned to receive 2 injections of 100 U of vaccine, 200 U of vaccine, 400 U of vaccine, or placebo. Solicited adverse events (AEs) within 7 days and unsolicited AEs within 28 days after each vaccination were collected for safety evaluation. Blood samples were collected for neutralizing antibody assay. RESULTS EV71 vaccine was well tolerated, and no dose-related safety concerns were observed. Two doses of the vaccine yielded seropositivity frequencies of 92.3%, 95.9%, and 99.0% (with titers ≥1:8) in the 100 U, 200 U, and 400 U groups, respectively. Geometric mean titers measured by neutralizing antibody assay increased to 60.2 (95% confidence interval [CI], 41.9-86.4), 72.8 (95% CI, 50.8-104.3), and 252.1 (95% CI, 180.8-351.6) for the 100 U, 200 U, and 400 U groups, respectively. The dose-response relationship, with the 400 U dose showing higher immunogenicity than the 100 U and 200 U doses, remained until 13 months after the second vaccination, despite waning antibody levels. CONCLUSIONS The 400 U dose was recommended as the optimal dose for the phase III trial because of its good safety profile and higher immunogenicity.