Megasphaera elsdenii Lactate Degradation Pattern Shifts in Rumen Acidosis Models

Background: Megasphaera elsdenii is an ecologically important rumen bacterium that metabolizes lactate and relieves rumen acidosis (RA) induced by a high-grain-diet. Understanding the regulatory mechanisms of the lactate metabolism of this species in RA conditions might contribute to developing dietary strategies to alleviate RA. Methods: Megasphaera elsdenii was co-cultured with four lactate producers (Streptococcus bovis, Lactobacilli fermentum, Butyrivibrio fibrisolvens, and Selenomonas ruminantium) and a series of substrate starch doses (1, 3, and 9 g/L) were used to induce one normal and two RA models (subacute rumen acidosis, SARA and acute rumen acidosis, ARA) under batch conditions. The associations between bacterial competition and the shift of organic acids' (OA) accumulation patterns in both statics and dynamics manners were investigated in RA models. Furthermore, we examined the effects of substrate lactate concentration and pH on Megasphaera elsdenii's lactate degradation pattern and genes related to the lactate utilizing pathways in the continuous culture. Results and Conclusion: The positive growth of M. elsdenii and B. fibrisolvens caused OA accumulation in the SARA model to shift from lactate to butyrate and resulted in pH recovery. Furthermore, both the quantities of substrate lactate and pH had remarkable effects on M. elsdenii lactate utilization due to the transcriptional regulation of metabolic genes, and the lactate utilization in M. elsdenii was more sensitive to pH changes than to the substrate lactate level. In addition, compared with associations based on statics data, associations discovered from dynamics data showed greater significance and gave additional explanations regarding the relationships between bacterial competition and OA accumulation

Modeling Study of the Air Quality Impact of Record-Breaking Southern California Wildfires in December 2017

We investigate the air quality impact of record‐breaking wildfires in Southern California during 5–18 December 2017 using the Weather Research and Forecasting model with Chemistry in combination with satellite and surface observations. This wildfire event was driven by dry and strong offshore Santa Ana winds, which played a critical role in fire formation and air pollutant transport. By utilizing fire emissions derived from the high‐resolution (375 × 375 m²) Visible Infrared Imaging Radiometer Suite active fire detections, the simulated magnitude and temporal evolution of fine particulate matter (PM_(2.5)) concentrations agree reasonably well with surface observations (normalized mean bias = 4.0%). Meanwhile, the model could generally capture the spatial pattern of aerosol optical depth from satellite observations. Sensitivity tests reveal that using a high spatial resolution for fire emissions and a reasonable treatment of plume rise (a fair split between emissions injected at surface and those lifted to upper levels) is important for achieving decent PM_(2.5) simulation results. Biases in PM_(2.5) simulation are relatively large (about 50%) during the period with the strongest Santa Ana wind, due to a possible underestimation of burning area and uncertainty in wind field variation. The 2017 December fire event increases the 14‐day averaged PM_(2.5) concentrations by up to 231.2 μg/m³ over the downwind regions, which substantially exceeds the U.S. air quality standards, potentially leading to adverse health impacts. The human exposure to fire‐induced PM_(2.5) accounts for 14–42% of the annual total PM_(2.5) exposure in areas impacted by the fire plumes

Responses of gaseous sulfuric acid and particulate sulfate to reduced SO2 concentration : A perspective from long-term measurements in Beijing

SO2 concentration decreased rapidly in recent years in China due to the implementation of strict control policies by the government. Particulate sulfate (pSO(4)(2-)) and gaseous H2SO4 (SA) are two major products of SO2 and they play important roles in the haze formation and new particle formation (NPF), respectively. We examined the change in pSO(4)(2-) and SA concentrations in response to reduced SO2 concentration using long-term measurement data in Beijing. Simulations from the Community Multiscale Air Quality model with a 2-D Volatility Basis Set (CMAQ/2D-VBS) were used for comparison. From 2013 to 2018, SO2 concentration in Beijing decreased by similar to 81% (from 9.1 ppb to 1.7 ppb). pSO(4)(2-) concentration in submicrometer particles decreased by similar to 60% from 2012-2013 (monthly average of similar to 10 mu g.m(-3)) to 2018-2019 (monthly average of similar to 4 mu g.m(-3)). Accordingly, the fraction of pSO(4)(2-) in these particles decreased from20-30% to b10%. Increased sulfur oxidation ratio was observed both in the measurements and the CMAQ/2D-VBS simulations. Despite the reduction in SO2 concentration, there was no obvious decrease in SA concentration based on data from several measuring periods from 2008 to 2019. This was supported by the increased SA:SO2 ratio with reduced SO2 concentration and condensation sink. NPF frequency in Beijing between 2004 and 2019 remains relatively constant. This constant NPF frequency is consistent with the relatively stable SA concentration in Beijing, while different from some other cities where NPF frequency was reported to decrease with decreased SO2 concentrations. (C) 2020 Elsevier B.V. All rights reserved.Peer reviewe

Megasphaera elsdenii Lactate Degradation Pattern Shifts in Rumen Acidosis Models

Background:Megasphaera elsdenii is an ecologically important rumen bacterium that metabolizes lactate and relieves rumen acidosis (RA) induced by a high-grain-diet. Understanding the regulatory mechanisms of the lactate metabolism of this species in RA conditions might contribute to developing dietary strategies to alleviate RA.Methods:Megasphaera elsdenii was co-cultured with four lactate producers (Streptococcus bovis, Lactobacilli fermentum, Butyrivibrio fibrisolvens, and Selenomonas ruminantium) and a series of substrate starch doses (1, 3, and 9 g/L) were used to induce one normal and two RA models (subacute rumen acidosis, SARA and acute rumen acidosis, ARA) under batch conditions. The associations between bacterial competition and the shift of organic acids’ (OA) accumulation patterns in both statics and dynamics manners were investigated in RA models. Furthermore, we examined the effects of substrate lactate concentration and pH on Megasphaera elsdenii’s lactate degradation pattern and genes related to the lactate utilizing pathways in the continuous culture.Results and Conclusion: The positive growth of M. elsdenii and B. fibrisolvens caused OA accumulation in the SARA model to shift from lactate to butyrate and resulted in pH recovery. Furthermore, both the quantities of substrate lactate and pH had remarkable effects on M. elsdenii lactate utilization due to the transcriptional regulation of metabolic genes, and the lactate utilization in M. elsdenii was more sensitive to pH changes than to the substrate lactate level. In addition, compared with associations based on statics data, associations discovered from dynamics data showed greater significance and gave additional explanations regarding the relationships between bacterial competition and OA accumulation

Padronização da pesquisa de linfonodos sentinelas em estômago por métodos combinados

Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Pós-Graduação em Ciências da Cirurgia, Campinas, 2012.Introdução - Com os estudos de Gould et al. (1960), Cabanas (1977) e Morton et al. (1992), estabeleceu-se o conceito da pesquisa do linfonodo sentinela. Esse se baseia na teoria de que ao identificar a presença ou ausência de metástase no primeiro linfonodo que recebe a drenagem linfática a partir do tumor (sentinela), poderia representar o estado de acometimento dos outros linfonodos. Isto evitaria a realização desnecessária de linfadenectomias. Com o passar dos anos, foi consagrada para ser aplicada em casos de melanoma e câncer de mama. Nesta última década, tenta-se estender os princípios da utilização da pesquisa de linfonodo sentinela para os cânceres do aparelho digestivo. Entretanto, no caso do estômago, existem algumas dificuldades, como: presença de sistema de drenagem linfática multidirecional, ocorrência de metástases saltatórias e identificação de mais de um linfonodo sentinela por indivíduo. Objetivo - Criar e padronizar um modelo animal para o treinamento de pesquisa de linfonodos sentinelas em estômago. Método - Trinta e dois coelhos, saudáveis, foram submetidos à anestesia exclusivamente intramuscular. Por meio de laparotomia, foi injetado na subserosa da parede anterior do corpo gástrico, 0,1 ml de fitato marcado com tecnécio-99m (0,2 mCi), em seguida pelo mesmo orifício, de 0,2 ml de Azul Patente V® 2,5%. A cavidade abdominal foi avaliada, in vivo , para pesquisa de suspeitas de linfonodos azuis (corados em azul) e com detector manual de radiação gamma aos 5, 10 e 20 minutos para detecção de suspeitas de linfonodos radioativos (radioatividade identificada superior a 10X o valor apresentado pelo fundo). Após 20 minutos, realizou-se ressecção e exérese total do estômago, baço e suspeitas de linfonodos, para posterior avaliação da radioatividade ex vivo . A seguir, encaminharam-se as suspeitas de linfonodos para estudo histológico para identificação de tecido linfóide. Resultados - Foram identificados linfonodos em 30 coelhos (93,75%) com média de 2,2 por animal. Das 90 suspeitas de linfonodos detectadas, em 70 casos (77,77%) obteve-se confirmação histológica para tecido linfóide. Dessas, a maioria foi identificada e localizada na região entre o esôfago e o fundo gástrico durante a avaliação in vivo aos 5 minutos. Dois coelhos faleceram durante os experimentos (Taxa de mortalidade = 6,25%). Conclusão - O modelo experimental em coelhos para pesquisa de linfonodos sentinelas em estômago por métodos combinados foi factível, de fácil execução e baixa mortalidade, podendo ser usado para treinamento.Abstract : Introduction - The concept of sentinel lymph node was established by the studies of Gould et al. (1960), Cabanas (1977) and Morton et al. (1992). It is based on the theory that, whenever the presence or absence of metastasis is identified in the first lymph node that receives the lymphatic drainage from the tumor (sentinel) the status of involvement of other lymph nodes might be infered. This could avoid the performance of unnecessary lymphadenectomies. Over the years, its use was consecrated by its application in melanoma and breast cancer. In the last decade, attempts have been made to extend the principles of sentinel lymph node investigation to cancers of the digestive tract. In the case of stomach cancer, additional difficulties were found, such as multiple and aberrant lymphatic routes, the occurrence of skip metastasis and the possible identification of more than one sentinel lymph node in the same patient. Aim - To develop and evaluate an animal model for training sentinel lymph node navigation in the stomach. Methods - Thirtytwo healthy rabbits, were prepped and given intramuscular anesthesia. Through a formal laparotomy, they received a subserosal injection of 0.1 ml of phytate labeled with technetium-99m (0.2 mCi) in the anterior wall of the gastric corpus, followed by 0.2 ml of Blue Patent ® V 2.5%, through the same puncture site. Suspicious lymph nodes were searched in-vivo at 5, 10 and 20 minutes, both visually (Blue Patent stained lymph nodes) and with a manual gamma radiation detector (to detect suspected radioactive lymph nodes, displaying radioactivity levels over 10X the value displayed by the background). En-block resection of the stomach, spleen, visible limph nodes and local fat tissue was then performed and the specimen was assessed "ex vivo" for radioactivity. Suspected lymph nodes were sent for histological study to evaluate the presence of lymphoid tissue. Results Radiolabeled or stained lymph nodes were identified in 30 rabbits (93.75%) with an average of 2.2 specimens per animal; of the 90 suspicious lymph nodes detected, histology confirmed lymphoid tissue in 70 cases (77.77%). Most lymph nodes were identified at the 5-minute in-vivo evaluation and their most common location was found to be in the region between the esophagus and the gastric fundus. Two rabbits died during the procedure resulting in a 6.25% mortality. Conclusion - The rabbit model proved adequate for training in sentinel node navigation in the stomach by combined methods (dye and radiocolloid) being easy to execute and associated with low mortality

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

The Application of Nanoparticle-Based Drug Delivery Systems in Checkpoint Blockade Cancer Immunotherapy

Tumor is the most serious threat to human beings. Although war against cancer has been launched over forty years, cancer treatment is still far away from being satisfactory. Immunotherapy, especially checkpoint blockade immunotherapy, is a rising star that shows a promising future. To fulfill the requirement of depleting primary tumor and inhibiting tumor metastasis and recurrence, many researchers combined checkpoint blockade immunotherapy with other treatment strategies to extend the treatment outcome. Photodynamic therapy could induce immunogenic cell death, and checkpoint blockade could further accelerate the immunity; therefore, combining these two strategies publishes many papers. Additionally, photothermal therapy and immunotherapy were also utilized for combining with checkpoint blockade, which were also reviewed in this paper. Furthermore, antibodies, siRNA, and small molecule inhibitors are developed to block the checkpoint; therefore, we categorized the papers into three sections, combination nanoparticles with checkpoint blockade antibody, combination nanoparticles with checkpoint blockade siRNA, and combination nanoparticles with small molecule checkpoint inhibitors, and related researches were summarized. In conclusion, the combination nanoparticle with checkpoint blockade cancer immunity is a promising direction that may fulfill the requirement of cancer treatment

Responses of milk production of dairy cows to jugular infusions of a mixture of essential amino acids with or without exclusion leucine or arginine

The purpose of this study was to determine effects of jugular infusion of either balanced or imbalanced amino acid mixture on milk production and composition in dairy cows. Eight mid-lactation Holstein cows were randomly assigned to 5-d continuous jugular infusions of saline (CTL), essential amino acid (EAA) mixture prepared on the profile of casein (CSN, 160 g/d), EAA mixture excluding leucine (Leu) (−Leu, 163 g/d) or EAA mixture excluding arginine (Arg) (−Arg, 158 g/d) in a duplicated 4 × 4 Latin square design with 4 infusion periods separated by a 7-d interval period. The basal diet was formulated with corn grain, soybean meal, cottonseed meal, corn silage, alfalfa hay and Chinese wildrye grass hay according to NRC (2001) and supplied 1.6 Mcal net energy for lactation (NEL) and 94.4 g metabolizable protein (MP) per kg dry matter (DM) to meet requirements for lactation. The results showed that the dry matter intake (DMI) and normal physiological status were not affected by amino acid mixture infusions. Compared with CTL treatment, the CSN treatment increased milk yield (14.9%, P < 0.001), milk lactose yield (14.5%, P = 0.001), milk fat yield (16.6%, P = 0.01), milk protein yield (18.2%, P < 0.001) and the contents of αS1-casein (αS1-CN, 11.8%, P = 0.007), β-casein (β-CN, 4.2%, P = 0.035) and κ-casein (κ-CN, 8.5%, P = 0.003). However, the −Leu and −Arg treatments had lower milk yield (6.3%, P = 0.058 and 5.7%, P = 0.073, respectively), milk protein yield (8.8%, P = 0.010 and 8.2%, P = 0.011, respectively) and the contents of αS1-CN (7.3%, P = 0.057 and 8.4%, P = 0.026, respectively), β-CN (4.2%, P = 0.033 and 3.8%, P = 0.048, respectively) and κ-CN (5.8%, P = 0.023 and 7.6%, P = 0.003, respectively) than those of the CSN treatment. Milk lactose yield (5.9%, P = 0.076) tended to decrease when Leu was removed from amino acid mixture infusate. In conclusion, the supply of casein profile can increase milk production in dairy cows, but a deficiency of Leu or Arg had negative effects on milk yield and milk protein yield

Nanoconfined Crystal Growth of Copper-Intercalated Graphene Oxide Interlayers

Recently, graphene oxide (GO) has been taken as a host for ultra-fast self-assembly of metal nanoparticles [Nat. Commun.2016,7, 12332] or synthesis of ultrathin and mechanically robust lithium foils [Nat. Energy2021,6, 790–798]. However, the main factors dominating preparations of these nanoconfined metals are still not clear. In this study, the crystal growth mechanism of copper (Cu) nanosheet-intercalated GO interlayers has been revealed by combining theoretical models with molecular dynamics simulations. Both the interlayer spacing and oxidation degree of GO play key roles in crystal growth velocities, which increase with increasing interlayer spacings but decrease with increasing oxidation degrees. The phenomenon is found to be a consequence of crystal growth being energetically favorable and a small ratio of interfacial van der Waals-affected zones for larger crystal thicknesses and strong hydrophilic properties of GO with higher oxidation degrees. In addition, more smooth surfaces have been observed for nanoconfined metals. These insights provide an effective method for generating nanocrystalline metals in a nanoconfined environment

β-Sitosterol Attenuates High Grain Diet-Induced Inflammatory Stress and Modifies Rumen Fermentation and Microbiota in Sheep

&beta;-sitosterol (BSS) is a plant-derived natural bioactive compound, its cellular mechanism of anti-inflammatory activity has been proven recently. Little information is available regarding the application of BSS on ruminants under high grain diet. The objective of this study was to evaluate the effects of dietary BSS supplementation on inflammatory response, ruminal fermentation characteristics and the composition of the ruminal bacterial community under high grain diet. Eight rumen-cannulated Hu sheep (59.7 &plusmn; 4.8 kg of initial body weight) were randomly assigned into a replicated 4 &times; 4 Latin square design trial. Sheep were fed a high grain diet (non-fiber carbohydrate: neutral detergent fiber = 2.03) supplemented either with 0.25 (LBS), 0.5 (MBS), 1.0 (HBS) or without (CON) g BSS /kg dry matter diet. On day 21 of each period, rumen content samples were obtained at 6 h postfeeding, and blood samples were obtained before morning feeding. The data showed that compared with control group, Dietary BSS supplementation decreased serum concentrations of tumor necrosis factor, interleukin (IL)-6, and IL-1&beta;. The ruminal pH and acetate concentration for BSS treatment were improved, while concentration of propionate, butyrate and lactate was decreased. The result of Illumina MiSeq sequencing of 16S rRNA gene revealed that BSS addition can increase the proportion of Prevotella_1, Rikenellaceae_RC9_gut_group, Prevotella_7, and Selenomonas_1, and decrease the proportion of Lachnospiraceae_NK3A20_group. These results indicated that BSS attenuates high grain diet-induced inflammatory response and modifies ruminal fermentation. In addition, the BSS dietary supplementation at the level of 0.5 g/kg is recommended in sheep