Decreased circulating leptin and increased neuropeptide Y gene expression are implicated in food deprivation-induced hyperactivity in striped hamsters, Cricetulus barabensis.

Physiological and behavioral adjustments of small mammals are important strategies in response to variations in food availability. Although numerous of studies have been carried out in rodents, behavioral patterns in response to food deprivation and re-feeding (FD-RF) are still inconsistent. Here we examined effects of a 24h FD followed by RF on general activity, serum leptin concentrations and gene expression of orexigenic and anorexigenic hypothalamic neuropeptides in striped hamsters (Cricetulus barabensis) with/without leptin supplements. The time spent on activity was increased by 2.5 fold in FD hamsters compared with controls fed ad libitum (P<0.01). Body mass, fat mass as well as serum leptin concentrations were significantly decreased in FD hamsters in comparison with ad libitum controls, which were in parallel with hyperactivity. During re-feeding, leptin concentrations increased rapidly to pre-deprivation levels by 12h, but locomotor activity decreased gradually and did not return to pre-deprivation levels until 5days after re-feeding. Leptin administration to FD hamsters significantly attenuated the increased activity. Gene expression of hypothalamic neuropeptide Y (NPY) was upregulated in FD hamsters and fell down to control levels when hamsters were re-fed ad libitum, similar to that observed in activity behavior. Leptin supplement induced increases in serum leptin concentrations (184.1%, P<0.05) in FD hamsters and simultaneously attenuated the increase in activity (45.8%, P<0.05) and NPY gene expression (35%, P<0.05). This may allow us to draw a more generalized conclusion that decreased leptin concentrations function as a starvation signal in animals under food shortage; to induce an increase in activity levels, leading animals to forage and/or migrate, and consequently increasing the chance of survival. Decreased concentrations of serum leptin in animals subjected to food shortage may induce an upregulation of gene expression of hypothalamus NPY, consequently driving a significant increase in foraging behavior.

Toxic mechanism of three azole fungicides and their mixture to green alga Chlorella pyrenoidosa.

Currently, few studies have investigated the joint toxicity mechanism of azole fungicides at different exposure times and mixed at the relevant environmental concentrations. In this study, three common azole fungicides, namely, myclobutanil (MYC), propiconazole (PRO), and tebuconazole (TCZ), were used in studying the toxic mechanisms of a single substance and its ternary mixture exposed to ambient concentrations of Chlorella pyrenoidosa. Superoxide dismutase (SOD), catalase (CAT), chlorophyll a (Chla), and total protein (TP), were used as physiological indexes. Results showed that three azole fungicides and ternary mixture presented obvious time-dependent toxicities at high concentrations. MYC induced a hormetic effect on algal growth, whereas PRO and TCZ inhibit algal growth in the entire range of the tested concentrations. The toxicities of the three azole fungicides at 7 days followed the order PRO > TCZ > MYC. Three azole fungicides and their ternary mixture induced different levels of SOD and CAT activities in algae at high concentrations. The ternary mixture showed additive effects after 4 and 7 days exposure, but no effect was observed at actual environmental concentrations. The toxic mechanisms may be related to the continuous accumulation of reactive oxygen species, which not only affected protein structures and compositions but also damaged thylakoid membranes, hindered the synthesis of proteins and chlorophyll a, and eventually inhibited algal growth. These findings increase the understanding of the ecotoxicity of azole fungicides and use of azole fungicides in agricultural production.

Intravenous immunoglobulin treatment for patients with severe COVID-19: a retrospective multicentre study.

OBJECTIVES: Intravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcome of such treatment remains unclear. This study evaluated the effectiveness of IVIG treatment in severe COVID-19 patients. METHODS: This retrospective multicentre study evaluated 28-day mortality in severe COVID-19 patients with or without IVIG treatment. Each patient treated with IVIG was matched with one untreated patient. Logistic regression and inverse probability weighting (IPW) were used to control confounding factors. RESULTS: The study included 850 patients (421 IVIG-treated patients and 429 non-IVIG-treated patients). After matching, 406 patients per group remained. No significant difference in 28-day mortality was observed after IPW analysis (average treatment effect (ATE) = 0.008, 95% CI -0.081 to 0.097, p 0.863). There were no significant differences between the IVIG group and non-IVIG group for acute respiratory distress syndrome, diffuse intravascular coagulation, myocardial injury, acute hepatic injury, shock, acute kidney injury, non-invasive mechanical ventilation, invasive mechanical ventilation, continuous renal replacement therapy and extracorporeal membrane oxygenation except for prone position ventilation (ATE = -0.022, 95% CI -0.041 to -0.002, p 0.028). DISCUSSION: IVIG treatment was not associated with significant changes in 28-day mortality in severe COVID-19 patients. The effectiveness of IVIG in treating patients with severe COVID-19 needs to be further investigated through future studies.

First-trimester blood concentrations of drinking water trihalomethanes and neonatal neurobehavioral development in a Chinese birth cohort.

Toxicological evidence indicates that exposure to drinking water trihalomethanes (THMs) can impair neural development. However, no epidemiologic study to date has evaluated the relation of trihalomethanes exposure with neonatal neurobehavioral development. Here we aimed to evaluate if prenatal exposure to THMs during early pregnancy is associated with neonatal neurobehavioral development in 451 Chinese mother-child pairs. First trimester blood THMs [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] were determined by solid phase micro-extraction gas chramatography. Neonatal neurobehavioral development was assessed using neonatal behavioral neurological assessment (NBNA) on the third day after birth. Multivariable linear regression models and restricted cubic spline models were constructed to evaluate the associations between blood THMs and neonatal neurological development scores. Blood concentrations of BDCM, whether modeled as continuous or categorical variables, were inversely associated with total NBNA score of newborns based on the multivariable linear regression. The association was further confirmed in the cubic spline model, and a linear dose-response relationship was observed. Stratified analysis showed that the inverse association between blood BDCM and total NBNA score was more evident in male infants than females. Our findings suggest that exposure to THMs during early pregnancy may be associated with impaired neonatal neurobehavioral development.

The role of leptin in striped hamsters subjected to food restriction and refeeding.

Food restriction (FR) and refeeding (Re) have been suggested to impair body mass regulation and thereby making it easier to regain the lost weight and develop over-weight when FR ends. However, it is unclear if this is the case in small mammals showing seasonal forging behaviors. In the present study, energy budget, body fat and serum leptin level were measured in striped hamsters that were exposed to FR-Re. The effects of leptin on food intake, body fat and genes expressions of several hypothalamus neuropeptides were determined. Body mass, fat content and serum leptin level decreased during FR and then increased during Re. Leptin supplement significantly attenuated the increase in food intake during Re, decreased genes expressions of neuropepetide Y (NPY) and agouti-related protein (AgRP) of hypothalamus and leptin of white adipose tissue (WAT). Hormone-sensitive lipase (HSL) gene expression of WAT increased in leptin-treated hamsters that were fed ad libitum, but decreased in FR-Re hamsters. This indicates that the adaptive regulation of WAT HSL gene expression may be involved in the mobilization of fat storage during Re, which partly contributes to the resistance to FR-Re-induced overweight. Leptin may be involved in the down regulations of hypothalamus orexigenic peptides gene expression and consequently plays a crucial role in controlling food intake when FR ends.

The resolution estimation of wedge and strip anodes.

A new resolution estimation method for wedge and strip anode based on the single photon imaging configuration is provided. The limiting resolution estimation equation is deduced theoretically according to the threshold principle. The relation between the charge cloud and the covered electrodes is discussed, and the equivalent diameter number is calculated. The resolution equation for the position deviation amplitude or FWHM is provided if noise exists. The relation between the position deviation amplitude and the total charge deviation amplitudes is discussed. The constancy of the position deviation amplitudes versus positions is provided. The results calculated from these equations are discussed. According to the equations, it is indicated that the spatial resolution is affected by the detection system configuration and noise. These conclusions may be useful for the designing and performance improvement of future photon imagers.

Repressor of GATA-3 can negatively regulate the expression of T cell cytokines through modulation on inducible costimulator.

BACKGROUND: The transcription factor, repressor of GATA-3 (ROG), can simultaneously suppress the expression of T helper cells (Th1 and Th2) cytokines. Since the suppression of Th2 cytokines by GATA-3 is well understood, it is postulated that there are other molecular targets of ROG that can suppress the expression of the Th1 cytokines. We hypothesized that ROG might suppress the stimulators of T lymphocyte cytokines such as CD3, CD28, and inducible costimulator (ICOS), or indirectly enhance the expression of cytokine suppressors such as T lymphocyte-associated antigen-4 (CTLA-4) and CD45. The objective of this study was to clarify the molecular targets of ROG involved in suppressing Th1 or Th2 cytokines. METHODS: Real-time quantitative PCR (RT-PCR) and Western blotting were performed to evaluate the mRNA and protein levels of CD3, CD28, ICOS, CTLA-4, and CD45 in Th1 and Th2 cells during various levels of ROG expression. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of interferon-γ (IFN-γ) and interleukin (IL)-4 in culture media of Th1 and Th2 cells. RESULTS: The results showed that the mRNA and protein levels of ROG were relatively low in Th1 and Th2 cells (P < 0.01). After ROG-pcDNA3.1 transfection, the mRNA and protein level of ROG was significantly elevated, while the expression of ICOS, IFN-γ, and IL-4 was markedly down-regulated (P < 0.01). Conversely, transfection of ROG-siRNA led to inhibition of ROG expression and up-regulation of ICOS, IFN-γ and IL-4 (P < 0.01). However, the expression levels of CD3, CD28, CTLA-4 and CD45 did not change in either ROG-pcDNA3.1 or ROG-siRNA-transfected Th1 and Th2 cells (P > 0.05). CONCLUSION: It is concluded that ROG can inhibit the expression of Th1 and Th2 cytokines by down-regulating the expression of ICOS, which might be a potential molecular target for asthma treatment.

[Effects of drought stress and nitrogen fertilization rate on the accumulation of osmolytes in Jatropha curcas seedlings].

A pot experiment with controlled water supply was conducted to study the effects of different drought stress degree (80% FC, 60% FC, 40% FC, and 20% FC) and nitrogen fertilization rate (0 g x pot(-1), 1.2 g x pot(-1), 3.6 g x pot(-1), and 6.0 g x pot(-1)) on the accumulation of osmolytes in different organs of Jatropha curcas seedlings. Under drought stress, the soluble protei and free proline in seedling shoots and roots and the soluble sugar in seedling shoots had a great accumulation, and the free proline content in seedling leaves had a great increase with increasing drought stress degree. Also under drought stress, the Na+, Ca2+, and Mg2+ all highly accumulated in seedling various organs, while K only accumulated greatly in shoots but slightly in leaves and roots. The effects of nitrogen fertilization on the accumulation of osmolytes in seedlings depended on drought stress degree and nitrogen fertilization rate. At 80% FC and 60% FC, increasing nitrogen fertilization rate could markedly promote the accumulation of osmolytes in the organs of J. curcas seedlings; at 40% FC, applying 6.0 g x pot(-1) weakened the promotion effect on the osmolytes accumulation; whereas at 20%, applying 1.2 g x pot(-1) made the plants have a higher capability in osmoregulation, but applying 3.6 g x pot(-1) and 6.0 g x pot(-1) had less promotion effect, and even, inhibited osmolytes accumulation.

Continuous measurement of the arrival times of x-ray photon sequence.

In order to record x-ray pulse profile for x-ray pulsar-based navigation and timing, this paper presents a continuous, high-precision method for measuring arrival times of photon sequence with a common starting point. In this method, a high stability atomic clock is counted to measure the coarse time of arrival photon. A high resolution time-to-digital converter is used to measure the fine time of arrival photon. The coarse times and the fine times are recorded continuously and then transferred to computer memory by way of memory switch. The pulse profile is obtained by a special data processing method. A special circuit was developed and a low-level x-ray pulse profile measurement experiment system was setup. The arrival times of x-ray photon sequence can be consecutively recorded with a time resolution of 500 ps and the profile of x-ray pulse was constructed. The data also can be used for analysis by many other methods, such as statistical distribution of photon events per time interval, statistical distribution of time interval between two photon events, photon counting histogram, autocorrelation and higher order autocorrelation.

Ghosting phenomena in single photon counting imagers with Vernier anode.

We provide the ghosting theory of two-dimensional Vernier anode based imagers. The single photon counting detection system based on Vernier anode is constructed. The ghosting, which occurs during the decoding of two-dimensional Vernier anode, and its possible solutions are described in detail. On the basis of the discussion of the decoding algorithm, the ghosting theoretical model is established. Phase conditions on which imaging ghosting can be avoided and the probability distribution function are proposed; the root causes of ghosting of two-dimensional Vernier anode are also discussed.

[Effect of drought on photosynthetic characteristics and growth of Jatropha curcas seedlings under different nitrogen levels].

A pot experiment with controlled water supply was conducted to study the effects of drought stress (continuous drought for 0 d, 5 d, 10 d, ... 45 d) on the photosynthetic characteristics and growth of Jatropha curcas seedlings under different nitrogen fertilization levels (N0, 0 kg N x hm(-2); N(L), 96 kg N x hm(-2; N(M), 288 kg N x hm(-2); N(H), 480 kg N x hm(-2)). With the enhancement of drought stress, the leaf relative water content (RWC1), height growth (Z(h)), basal diameter growth (Z(d), leaf area (L(a)), net photosynthetic rate ( P(n)), transpiration rate (T(r)), and stomatal conductance (G(s)) decreased significantly (P < 0.01), irrespective of nitrogen fertilization level. The chlorophyll (Chl) content and water use efficiency (WUE) increased first and decreased then, while the intercellular CO2, concentration (C(i)) had an increase after an initial decrease. Under adequate water condition, nitrogen fertilization promoted the photosynthesis and growth of J. curcas seedlings to different degrees, and the effect was increased with increasing nitrogen fertilization level. Under drought stress, the effects of nitrogen nutrition on the photosynthesis and growth were dependent on drought intensity and nitrogen fertilization level. Specifically, increasing nitrogen fertilization level could promote the photosynthesis and growth of J. curcas seedlings under mild drought, the promotion effect of N(M) was higher than that of N(L) and N(H) under moderate drought, and N(L) had the best promotion effect while N(H) weakened the effect or made it negative under severe drought.

The estimation of charge footprint size of ultraviolet photon counting imaging detector with induction readout.

The structure and work principle of an ultraviolet photon counting imaging detector based on wedge and strip anode with induction readout mode are introduced. Two methods of estimating the charge footprint size are presented. One way is theoretical calculation and simulation. The physical course of electrons is simulated from the microchannel plate output side to the readout anode. The calculated results show that the final charge footprint size is sensitive to the thickness of ceramic and not sensitive to the charge footprint size on the Ge layer. The other way is experimental image estimation. The final charge footprint size can be estimated according to the position where the light line of resolution board image begins to bend. Both methods show that the charge footprint size is sensitive to the ceramic substrate. The two methods are simple and effective for estimation of charge footprint size of photon counting imaging detector with induction readout.

Arsenic trioxide inhibits the growth of human lung cancer cell lines via cell cycle arrest and induction of apoptosis at both normoxia and hypoxia.

Arsenic trioxide (As(2)O(3)) has been established to be an effective agent for treating acute promyleocytic leukemia. Laboratory data suggest that As(2)O(3) induces apoptosis of several solid tumor cells including lung cancer cells. Regions of tissue hypoxia often arise in aggressive solid tumors, and hypoxic tumors exhibit augmented invasiveness and metastatic ability in several malignancies. Furthermore, hypoxia may impair the treatment efficiency; therefore, we studied the cytotoxic effect of As(2)O(3) on human lung adenocarcinoma cell lines A549 and A549/R (resistant to vincristine, adriamycin and mitomycin etc.) grown under normoxic and hypoxic (1% oxygen) conditions. At both normoxia and hypoxia, 5, 10 and 15 microM As(2)O(3) induced evident growth inhibition and apoptosis in A549 cells as well as A549/R cells after 48 hours of exposure. In contrast, the conventional chemotherapeutic drug vincristine showed lowered efficiency in hypoxic A549 cells. As(2)O(3) induced G(2)/M cell cycle arrest in both normoxic and hypoxic A549 cells. As(2)O(3) significantly decreased the messenger RNA (mRNA) levels of Cyclin B(1) and survivin and the protein levels of Cyclin B(1), phospho-CDC(2) (Thr 161) and survivin in both normoxic and hypoxic A549 cells. Together, our findings indicated that As(2)O(3) significantly inhibited the proliferation of lung cancer cells via G(2)/M cell cycle arrest and induction of apoptosis at both normoxia and hypoxia, and the induction of apoptosis was associated with down regulation of survivin.