Peripheral blood T Regulatory cell counts may not predict transplant rejection

<p>Abstract</p> <p>Background</p> <p>Recent evidence shows that allograft survival rates show a positive correlation with the number of circulating T regulatory cells (Tregs). This study investigated both the number and the cytokine profiles exhibited by Foxp3⁺Tregs in blood, spleen and lymph nodes of Lewis rat recipients of BN rat cardiac allografts after a single-dose of Rapamycin (RAPA).</p> <p>Results</p> <p>Rats were divided into three groups: control group (containing healthy control and acute rejection group), and recipients treated with a single dose of RAPA on either Day 1 (1D group)or Day 3 (3D group) post-transplant. We analyzed the number of Foxp3+Tregs and the expression of Foxp3 and cytokines in the peripheral blood and the peripheral lymphoid tissues. No difference was found in the numbers of circulating Foxp3+ Tregs between these three groups. RAPA administration significantly increased Foxp3 expression in peripheral lymphoid tissues after a single dose of RAPA on Day 3 post-transplant. Foxp3+Tregs inhibited the activity of effector T cells (T_eff) via the secretion of TGF-β1.</p> <p>Conclusion</p> <p>The number of Tregs in the recipient's blood may not be a good predictor of transplant rejection. Foxp3+Tregs inhibit the activity of T_effcells mainly in the peripheral lymphoid tissues.</p

Hydrogen Sulfide Protects against Chemical Hypoxia-Induced Injury by Inhibiting ROS-Activated ERK1/2 and p38MAPK Signaling Pathways in PC12 Cells

Hydrogen sulfide (H2S) has been proposed as a novel neuromodulator and neuroprotective agent. Cobalt chloride (CoCl2) is a well-known hypoxia mimetic agent. We have demonstrated that H2S protects against CoCl2-induced injuries in PC12 cells. However, whether the members of mitogen-activated protein kinases (MAPK), in particular, extracellular signal-regulated kinase1/2(ERK1/2) and p38MAPK are involved in the neuroprotection of H2S against chemical hypoxia-induced injuries of PC12 cells is not understood. We observed that CoCl2 induced expression of transcriptional factor hypoxia-inducible factor-1 alpha (HIF-1α), decreased cystathionine-β synthase (CBS, a synthase of H2S) expression, and increased generation of reactive oxygen species (ROS), leading to injuries of the cells, evidenced by decrease in cell viability, dissipation of mitochondrial membrane potential (MMP) , caspase-3 activation and apoptosis, which were attenuated by pretreatment with NaHS (a donor of H2S) or N-acetyl-L cystein (NAC), a ROS scavenger. CoCl2 rapidly activated ERK1/2, p38MAPK and C-Jun N-terminal kinase (JNK). Inhibition of ERK1/2 or p38MAPK or JNK with kinase inhibitors (U0126 or SB203580 or SP600125, respectively) or genetic silencing of ERK1/2 or p38MAPK by RNAi (Si-ERK1/2 or Si-p38MAPK) significantly prevented CoCl2-induced injuries. Pretreatment with NaHS or NAC inhibited not only CoCl2-induced ROS production, but also phosphorylation of ERK1/2 and p38MAPK. Thus, we demonstrated that a concurrent activation of ERK1/2, p38MAPK and JNK participates in CoCl2-induced injuries and that H2S protects PC12 cells against chemical hypoxia-induced injuries by inhibition of ROS-activated ERK1/2 and p38MAPK pathways. Our results suggest that inhibitors of ERK1/2, p38MAPK and JNK or antioxidants may be useful for preventing and treating hypoxia-induced neuronal injury

Neurogenetic dissection of the Drosophila lateral horn reveals major outputs, diverse behavioural functions, and interactions with the mushroom body.

Animals exhibit innate behaviours to a variety of sensory stimuli including olfactory cues. In Drosophila, one higher olfactory centre, the lateral horn (LH), is implicated in innate behaviour. However, our structural and functional understanding of the LH is scant, in large part due to a lack of sparse neurogenetic tools for this region. We generate a collection of split-GAL4 driver lines providing genetic access to 82 LH cell types. We use these to create an anatomical and neurotransmitter map of the LH and link this to EM connectomics data. We find ~30% of LH projections converge with outputs from the mushroom body, site of olfactory learning and memory. Using optogenetic activation, we identify LH cell types that drive changes in valence behavior or specific locomotor programs. In summary, we have generated a resource for manipulating and mapping LH neurons, providing new insights into the circuit basis of innate and learned olfactory behavior

Hydrogen Sulfide Protects against Chemical Hypoxia-Induced Cytotoxicity and Inflammation in HaCaT Cells through Inhibition of ROS/NF-κB/COX-2 Pathway

Hydrogen sulfide (H2S) has been shown to protect against oxidative stress injury and inflammation in various hypoxia-induced insult models. However, it remains unknown whether H2S protects human skin keratinocytes (HaCaT cells) against chemical hypoxia-induced damage. In the current study, HaCaT cells were treated with cobalt chloride (CoCl2), a well known hypoxia mimetic agent, to establish a chemical hypoxia-induced cell injury model. Our findings showed that pretreatment of HaCaT cells with NaHS (a donor of H2S) for 30 min before exposure to CoCl2 for 24 h significantly attenuated CoCl2-induced injuries and inflammatory responses, evidenced by increases in cell viability and GSH level and decreases in ROS generation and secretions of IL-1β, IL-6 and IL-8. In addition, pretreatment with NaHS markedly reduced CoCl2-induced COX-2 overexpression and PGE2 secretion as well as intranuclear NF-κB p65 subunit accumulation (the central step of NF-κB activation). Similar to the protective effect of H2S, both NS-398 (a selective COX-2 inhibitor) and PDTC (a selective NF-κB inhibitor) depressed not only CoCl2-induced cytotoxicity, but also the secretions of IL-1β, IL-6 and IL-8. Importantly, PDTC obviously attenuated overexpression of COX-2 induced by CoCl2. Notably, NAC, a ROS scavenger, conferred a similar protective effect of H2S against CoCl2-induced insults and inflammatory responses. Taken together, the findings of the present study have demonstrated for the first time that H2S protects HaCaT cells against CoCl2-induced injuries and inflammatory responses through inhibition of ROS-activated NF-κB/COX-2 pathway

Performance of Prestressed Anchor Cables Supporting Deep Foundation Pit of a Subway Station during Spring Thaw

Based on the deep foundation pit for a subway station in Changchun (China), a 3D numerical model of water–heat coupling in a prestressed pile anchor system was established to determine its performance in freezing and thawing seasons in alpine areas. Its reliability was confirmed using field monitoring data on the prestressed anchor cables, which demonstrated changes in surface subsidence, anchor cable axial force, and pile horizontal displacement during spring thaw. The results demonstrated different degrees of elevation of the ground surface at the beginning of the spring thaw depending on whether the ground surface was at 2, 5, or 8 m from the pit excavation surface. Moreover, they demonstrated the occurrence of melting and surface subsidence when the temperature rises above 0°C, and that the axial force of the anchor cables fluctuates at the beginning of spring thaw but stabilizes in its middle and late stages. The phenomenon of pile horizontal displacement during the spring thaw could be roughly divided into three stages, with the second stage resulting in the most significant displacement. These results can provide certain reference for deep foundation pit projects in alpine areas

The Bias Compensation Based Parameter and State Estimation for Observability Canonical State-Space Models with Colored Noise

This paper develops a bias compensation-based parameter and state estimation algorithm for the observability canonical state-space system corrupted by colored noise. The state-space system is transformed into a linear regressive model by eliminating the state variables. Based on the determination of the noise variance and noise model, a bias correction term is added into the least squares estimate, and the system parameters and states are computed interactively. The proposed algorithm can generate the unbiased parameter estimate. Two illustrative examples are given to show the effectiveness of the proposed algorithm

Precipitation characteristic changes due to global warming in a high‐resolution (16 km) ECMWF simulation

Changes in precipitation amount, intensity and frequency in response to global warming are examined using global high-resolution (16 km) climate model simulations based on the European Centre for Medium-range Weather Forecasts (ECMWF) Integrated Forecast System (IFS) conducted under Project Athena. Our study shows the increases of zonal-mean total precipitation in all latitudes except the northern subtropics (15 degrees-30 degrees N) and southern subtropics-to-midlatitudes (30 degrees-40 degrees S). The probability distribution function (PDF) changes in different latitudes suggest a higher occurrence of light precipitation (LP; 1 mm/day) and heavy precipitation (HP; 30 mm/day) at the expense of moderate precipitation reduction (MP; 1-30 mm/day) from Tropics to midlatitudes, but an increase in all categories of precipitation in polar regions. On the other hand, the PDF change with global warming in different precipitation climatological zones presents another image. For all regions and seasons examined, there is an HP increase at the cost of MP, but LP varies. The reduced MP in richer precipitation zones resides in the PDF peak intensities, which linearly increase with the precipitation climatology zones. In particular in the Tropics (20 degrees S to 20 degrees N), the precipitation PDF has a flatter distribution (i.e. HP and LP increases with MP reduction) except for the Sahara Desert. In the primary precipitation zones in the subtropics (20 degrees-40 degrees) of both hemispheres, precipitation over land switches toward higher intensity (HP increases, but MP and LP decrease) in both winter and summer, while precipitation over ocean in both seasons shows a flattening trend in the intensity distribution. For the major precipitation zones of the mid-to-high latitude belt (40 degrees-70 degrees), PDF of precipitation tends to be flatter over ocean in summer, but switches toward higher intensities over land in both summer and winter, as well as over ocean in winter.11Nsciescopu

Nanopore sequencing technology and its applications

Abstract Since the development of Sanger sequencing in 1977, sequencing technology has played a pivotal role in molecular biology research by enabling the interpretation of biological genetic codes. Today, nanopore sequencing is one of the leading third‐generation sequencing technologies. With its long reads, portability, and low cost, nanopore sequencing is widely used in various scientific fields including epidemic prevention and control, disease diagnosis, and animal and plant breeding. Despite initial concerns about high error rates, continuous innovation in sequencing platforms and algorithm analysis technology has effectively addressed its accuracy. During the coronavirus disease (COVID‐19) pandemic, nanopore sequencing played a critical role in detecting the severe acute respiratory syndrome coronavirus‐2 virus genome and containing the pandemic. However, a lack of understanding of this technology may limit its popularization and application. Nanopore sequencing is poised to become the mainstream choice for preventing and controlling COVID‐19 and future epidemics while creating value in other fields such as oncology and botany. This work introduces the contributions of nanopore sequencing during the COVID‐19 pandemic to promote public understanding and its use in emerging outbreaks worldwide. We discuss its application in microbial detection, cancer genomes, and plant genomes and summarize strategies to improve its accuracy

Precipitation characteristic changes due to global warming in a high-resolution (16 km) ECMWF simulation

Changes in precipitation amount, intensity and frequency in response to global warming are examined using global high-resolution (16 km) climate model simulations based on the European Centre for Medium-range Weather Forecasts (ECMWF) Integrated Forecast System (IFS) conducted under Project Athena. Our study shows the increases of zonal-mean total precipitation in all latitudes except the northern subtropics (15 degrees-30 degrees N) and southern subtropics-to-midlatitudes (30 degrees-40 degrees S). The probability distribution function (PDF) changes in different latitudes suggest a higher occurrence of light precipitation (LP; 1 mm/day) and heavy precipitation (HP; 30 mm/day) at the expense of moderate precipitation reduction (MP; 1-30 mm/day) from Tropics to midlatitudes, but an increase in all categories of precipitation in polar regions. On the other hand, the PDF change with global warming in different precipitation climatological zones presents another image. For all regions and seasons examined, there is an HP increase at the cost of MP, but LP varies. The reduced MP in richer precipitation zones resides in the PDF peak intensities, which linearly increase with the precipitation climatology zones. In particular in the Tropics (20 degrees S to 20 degrees N), the precipitation PDF has a flatter distribution (i.e. HP and LP increases with MP reduction) except for the Sahara Desert. In the primary precipitation zones in the subtropics (20 degrees-40 degrees) of both hemispheres, precipitation over land switches toward higher intensity (HP increases, but MP and LP decrease) in both winter and summer, while precipitation over ocean in both seasons shows a flattening trend in the intensity distribution. For the major precipitation zones of the mid-to-high latitude belt (40 degrees-70 degrees), PDF of precipitation tends to be flatter over ocean in summer, but switches toward higher intensities over land in both summer and winter, as well as over ocean in winter.11Nsciescopu

Effects of protein sources for milk replacers on growth performance and serum biochemical indexes of suckling calves

This study investigated the effects of protein sources for milk replacers on growth performance and serum biochemical indexes of suckling calves. Fifty Chinese Holstein bull calves with similar BW and age were randomly allocated to 5 groups (1 control and 4 treatments) of 10 calves in each group. Five types of milk replacers were designed to have the same level of energy and protein. The protein source for milk replacers of the control group was full milk protein (MP). The protein source of milk replacers of the 4 treatment groups was composed of MP and one vegetable protein (VP) (30 and 70% of total protein). The 4 types of VP were soybean protein concentrate (SP), hydrolyzed wheat protein (WP), peanut protein concentrate (PP), and rice protein isolate (RP). Results of the experiment showed: 1) there was no significant difference on average daily gain (ADG) and feed:gain ratio (F:G) among the MP, SP and RP groups (P > 0.05), whereas the ADG and F:G of the WP and PP groups were significantly lower compared with the MP group (P  0.05). Thereby the 4 VP milk replacers had no adverse effects on body size of calves; 3) all groups showed no significant difference in the serum contents of urea nitrogen, total protein, albumin, globulin, β-hydroxybutyrate, growth hormone, insulin-like growth factor-1, and the ratio of albumin to globulin (A:G) (P > 0.05). In conclusion, SP or RP (accounts for 70% of the total protein) as calf milk replacers could substitute MP, whereas wheat gluten and PP had a significant adverse effect on growth performance in this experiment