A Horizontal and Longitudinal Study on the Changes of Aging Thyroid Function in Elderly Male Population.

OBJECTIVES: There are few follow-up studies on thyroid function in the same group for many years. Therefore, the purpose of this study was to retrospectively analyze the changes of thyroid function in a group of people for 8 years and to explore the changes of thyroid function in elderly men with normal thyroid function with age. METHODS: Reviewing the records of elderly men who underwent physical examination in the Beijing Hospital physical examination center from 2013 to 2020, 354 subjects were included in the study. According to age, they are divided into 4 groups. The differences in thyrotropin (TSH), anti-triiodothyronine (rT3), free triiodothyronine (FT3), and free thyroid hormone (FT4) among different age groups in initial time (2013) were compared. Longitudinal comparison of changes of thyroid function in the same age group for 8 years was compared too. RESULTS: At the initial time, age was negatively correlated with FT3 (r = 0.349, p < 0.001), positively correlated with rT3 and TSH (r = 0.182, p < 0.001, r = 0.212, p < 0.001), but not correlated with FT4. The results of eight years of analysis show that, for TSH, during the whole follow-up period, the TSH of the >80 years group was higher than that of the <60 years and 60-69 years groups, and the difference was statistically significant. The 70-79 age group was higher than the <60 years group at different time points, except for the age group <60 years. The other three groups showed an increasing trend with age, especially in the group of ≥80 years. For FT3, in 2013, the age ≥80 years group was significantly lower than that of the 70-79 years, 60-69 years, and <60 years old groups (p < 0.05). The analysis results at different time points in each age group showed a downward trend and then an upward trend. For FT4, there was no significant difference in FT4 among different age groups in 2013. Still, during the follow-up period, the age group ≥80 was lower than other age groups in 2019 and lower than the <60 years groups in 2014, 2015, 2019, and 2020, and the difference was statistically significant. The change rule of FT4 with the increase of age was not clear. For rT3, during the whole follow-up period, the rT3 of the >80 years group was higher than that of the <60 years and 60-69 years groups, and the difference was statistically significant. The analysis results at different time points in each age group showed a trend of rising first, then falling, and finally rising. After 2017, the rT3 of the 70-79 years and ≥80 years groups increased with age. CONCLUSIONS: The thyroid function index of elderly men changes with age. In transverse analysis, the value of TSH is the highest, and FT3 is the lowest in the group ≥80 years old. There are differences between the changes in the longitudinal analysis and the results of the horizontal analysis. Therefore, the law of thyroid function changing with age in different individuals is not the same as that of the same individual with age, which should be paid more attention in medical research and clinical diagnosis and treatment.

Epidemiological characterization and risk assessment of rabbit haemorrhagic disease virus 2 (RHDV2/b/GI.2) in the world.

A novel variant of rabbit haemorrhagic disease virus, designated RHDV2/b/GI.2, was first discovered in France in 2010. Subsequently, RHDV2 rapidly spread to Africa, North America, Australia, and Asia. RHDV2 outbreaks have resulted in significant economic losses in the global rabbit industry and disrupted the balance of natural ecosystems. Our study investigated the seasonal characteristics of RHDV2 outbreaks using seasonal indices. RHDV2 is prone to causing significant outbreaks within domestic and wild rabbit populations during the spring season and is more likely to induce outbreaks within wild rabbit populations during late autumn in the Southern Hemisphere. Furthermore, based on outbreak data for domestic and wild rabbits and environmental variables, our study established two MaxEnt models to explore the relationship between RHDV2 outbreaks and the environmental factors and conducted outbreak risk predictions for RHDV2 in global domestic and wild rabbit populations. Both models demonstrated good predictive performance, with AUC values of 0.960 and 0.974, respectively. Road density, isothermality, and population density were identified as important variables in the outbreak of RHDV2 in domestic rabbits, while road density, normalized difference vegetation index, and mean annual solar radiation were considered key variables in the outbreak of RHDV2 in wild rabbits. The environmental factors associated with RHDV2 outbreaks identified in our study and the outbreak risk prediction maps generated in our study will aid in the formulation of appropriate RHDV2 control measures to reduce the risk of morbidity in domestic and wild rabbits.

Met-Exo attenuates mitochondrial dysfunction after hepatic ischemia-reperfusion injury in rats by modulating AMPK/SIRT1 signaling pathway.

Hepatic ischemia-reperfusion injury (IRI) results in significant postoperative liver dysfunction, and the intricate mechanism of IRI poses challenges in developing effective therapeutic drugs. Mitigating the damage caused by hepatic IRI and promoting the repair of postoperative liver injury have become focal points in recent years, holding crucial clinical significance. Adipose mesenchymal stem cell derived exosomes (ADSCs-Exo) and metformin (Met) can play a mitochondrial protective role in the treatment of hepatic IRI, but whether there is a synergistic mechanism for their intervention is not yet known. Combining the unique advantages of exosomes as drug carriers, the aim of this study was to investigate the protective effects and mechanisms of the constructed Met and ADSCs-Exo complex (Met-Exo) on the liver IRI combined with partial resection injury in rat and hypoxic reoxygenation injury of rat primary hepatocytes (HCs). In this study, firstly, we detected that mitochondrial morphology and function were severely affected in hepatic tissues after hepatic IRI combined with partial resection, and then verified by in vitro experiments that Met-Exo could promote mitochondrial biosynthesis and fusion-associated protein expression and inhibit mitochondrial fission-related protein expression by modulating the AMPK/SIRT1 signalling pathway. This indicates that ADSCs-Exo can not only play a targeting role as a drug carrier but also has a great potential to act as a vehicle to act synergistically with drugs in the treatment of tissue and organ damage, which provides a new therapeutic strategy and experimental basis for the treatment of liver injury in medical science and clinical veterinary.

Multifaceted analysis of temporal and spatial distribution and risk factors of global poultry HPAI-H5N1, 2005-2023.

The purpose of this study was to analyze the characteristics of occurrence and spread of highly pathogenic avian influenza H5N1 (HPAI-H5N1) globally, understand its spatiotemporal characteristics, investigate the risk factors influencing outbreaks, and identify high-risk areas for disease occurrence. We collected the data on global poultry HPAI-H5N1 outbreaks from January 2005 to April 2023, and conducted a thorough analysis of the spatial and temporal characteristics of the disease through time series decomposition and directional distribution analysis. Additionally, an ecological niche model was established to explore the major factors influencing the occurrence of HPAI-H5N1 and to pinpoint high-risk areas. Our findings revealed that HPAI-H5N1 outbreaks were cyclical, and seasonal, exhibiting a rising trend, with a predominant northwest-southeast transmission direction. The ecological niche model highlighted that species factors and economic trade factors are critical in influencing the outbreak of HPAI-H5N1. Variables such as chicken and duck density, population density, isothermality, and road density, contributed to importantly risk of outbreaks. High-risk areas for HPAI-H5N1 occurrence were primarily identified in Europe, West Africa, Southeast Asia, and Southeast China. This study provided valuable insights into the spatial and temporal distribution characteristics and risk factors of global poultry HPAI-H5N1 outbreaks. The identification of high-risk areas provides essential information that can be used to develop more effective prevention and control policies.

Seasonal prediction of the distribution of three major malaria vectors in China: Based on an ecological niche model.

Against the backdrop of a global malaria epidemic that remains severe, China has eradicated indigenous malaria but still has to be alert to the risk of external importation. Understanding the distribution of vectors can provide an adequate and reliable basis for the development and implementation of vector control strategies. However, with the decline of malaria prevalence in recent years, the capacity of vector monitoring and identification has been greatly weakened. Here we have used new sampling records, climatic data, and topographic data to establish ecological niche models of the three main malaria vectors in China. The model results accurately identified the current habitat suitability areas for the three species of Anopheles and revealed that in addition to precipitation and temperature as important variables affecting the distribution of Anopheles mosquitoes, topographic variables also influenced the distribution of Anopheles mosquitoes. Anopheles sinensis is the most widespread malaria vector in China, with a wide region from the northeast (Heilongjiang Province) to the southwest (Yunnan Province) suitable for its survival. Suitable habitat areas for Anopheles lesteri are concentrated in the central, eastern, and southern regions of China. The suitable habitat areas of Anopheles minimus are the smallest and are only distributed in the border provinces of southern China. On this basis, we further assessed the seasonal variation in habitat suitability areas for these three major malaria vectors in China. The results of this study provide new and more detailed evidence for vector monitoring. In this new era of imported malaria prevention in China, regular reassessment of the risk of vector transmission is recommended.

BamA-targeted antimicrobial peptide design for enhanced efficacy and reduced toxicity.

The emergence of drug-resistant superbugs has necessitated a pressing need for innovative antibiotics. Antimicrobial peptides (AMPs) have demonstrated broad-spectrum antibacterial activity, reduced susceptibility to resistance, and immunomodulatory effects, rendering them promising for combating drug-resistant microorganisms. This study employed computational simulation methods to screen and design AMPs specifically targeting ESKAPE pathogens. Particularly, AMPs were rationally designed to target the BamA and obtain novel antimicrobial peptide sequences. The designed AMPs were assessed for their antibacterial activities, mechanisms, and stability. Molecular docking and dynamics simulations demonstrated the interaction of both designed AMPs, 11pep and D-11pep, with the ß1, ß9, ß15, and ß16 chains of BamA, resulting in misfolding of outer membrane proteins and antibacterial effects. Subsequent antibacterial investigations confirmed the broad-spectrum activity of both 11pep and D-11pep, with D-11pep demonstrating higher potency against resistant Gram-negative bacteria. D-11pep exhibited MICs of 16, 8, and 32 µg/mL against carbapenem-resistant Escherichia coli, carbapenem-resistant Pseudomonas aeruginosa, and multi-drug-resistant Acinetobacter baumannii, respectively, with a concomitant lower resistance induction. Mechanism of action studies confirmed that peptides could disrupt the bacterial outer membrane, aligning with the findings of molecular dynamics simulations. Additionally, D-11pep demonstrated superior stability and reduced toxicity in comparison to 11pep. The findings of this study underscore the efficacy of rational AMP design that targets BamA, along with the utilization of D-amino acid replacements as a strategy for developing AMPs against drug-resistant bacteria.

Distribution areas and monthly dynamic distribution changes of three Aedes species in China: Aedes aegypti, Aedes albopictus and Aedes vexans.

BACKGROUND: Mosquitoes play an absolute role in the spread of epidemic arbovirus diseases. Worldwide, Aedes aegypti and Aedes albopictus are the main vectors responsible for the spread of these mosquito-borne diseases. Aedes vexans, a mosquito species native to China, also carries mosquito-borne viruses, such as dengue fever virus and Japanese encephalitis virus, but research on this mosquito has been inadequate. Mapping the potential distribution range of and monthly change in the distribution of these three Aedes species is of particular importance for mosquito surveillance, eradication and disease control. METHODS: Monitoring data were collected for the three Aedes species in China. Long-term temperature and precipitation data (2001-2021) and land cover data were used to represent various climate and environmental conditions. An ecological niche model was developed using a maximum entropy modeling method to predict the current optimum habitat areas for the three Aedes species and to obtain important variables influencing their monthly distribution. RESULTS: The distribution model for the three Aedes species performed well, with an area under the receiver operating characteristic curve value of 0.991 for Ae. aegypti, 0.928 for Ae. albopictus and 0.940 for Ae. vexans. Analysis of the distribution change and mapping of the optimum habitat range for each Aedes species for each month demonstrated that temperature, precipitation and construction land were important factors influencing the distribution of these three Aedes species. CONCLUSIONS: In China, Aedes aegypti is mainly concentrated in a few tropical regions and along the Yunnan border; Aedes albopictus is widely distributed throughout most of the country, except for the arid and semi-arid regions of northwest China; and Aedes vexans is mainly found in the northern regions. Our results provide a basis for the timing and location of surveillance efforts for high-priority mosquitoes.

Prediction of the Lotus Effect on Solid Surfaces by Machine Learning.

Superhydrophobic surfaces with the "lotus effect" have wide applications in daily life and industry, such as self-cleaning, anti-freezing, and anti-corrosion. However, it is difficult to reliably predict whether a designed superhydrophobic surface has the "lotus effect" by traditional theoretical models due to complex surface topographies. Here, a reliable machine learning (ML) model to accurately predict the "lotus effect" of solid surfaces by designing a set of descriptors about nano-scale roughness and micro-scale topographies in addition to the surface hydrophobic modification is demonstrated. Geometrical and mathematical descriptors combined with gray level cooccurrence matrices (GLCM) offer a feasible solution to the puzzle of accurate descriptions of complex topographies. Furthermore, the "black box" is opened by feature importance and Shapley-additive-explanations (SHAP) analysis to extract waterdrop adhesion trends on superhydrophobic surfaces. The accurate prediction on as-fabricated superhydrophobic surfaces strongly affirms the extensionality of the ML model. This approach can be easily generalized to screen solid surfaces with other properties.

Ecological niche modeling based on ensemble algorithms to predicting current and future potential distribution of African swine fever virus in China.

African swine fever (ASF) is a tick-borne infectious disease initially described in Shenyang province China in 2018 but is now currently present nationwide. ASF has high infectivity and mortality rates, which often results in transportation and trade bans, and high expenses to prevent and control the, hence causing huge economic losses and a huge negative impact on the Chinese pig farming industry. Ecological niche modeling has long been adopted in the epidemiology of infectious diseases, in particular vector-borne diseases. This study aimed to establish an ecological niche model combined with data from ASF incidence rates in China from August 2018 to December 2021 in order to predict areas for African swine fever virus (ASFV) distribution in China. The model was developed in R software using the biomod2 package and ensemble modeling techniques. Environmental and topographic variables included were mean diurnal range (°C), isothermality, mean temperature of wettest quarter (°C), precipitation seasonality (cv), mean precipitation of warmest quarter(mm), mean precipitation of coldest quarter (mm), normalized difference vegetation index, wind speed (m/s), solar radiation (kJ /day), and elevation/altitude (m). Contribution rates of the variables normalized difference vegetation index, mean temperature of wettest quarter, mean precipitation of coldest quarter, and mean precipitation of warmest quarter were, respectively, 47.61%, 28.85%, 10.85%, and 7.27% (according to CA), which accounted for over 80% of contribution rates related to variables. According to model prediction, most of areas revealed as suitable for ASF distribution are located in the southeast coast or central region of China, wherein environmental conditions are suitable for soft ticks' survival. In contrast, areas unsuitable for ASFV distribution in China are associated with arid climate and poor vegetation, which are less conducive to soft ticks' survival, hence to ASFV transmission. In addition, prediction spatial suitability for future ASFV distribution suggests narrower areas for ASFV spread. Thus, the ensemble model designed herein could be used to conceive more efficient prevention and control measure against ASF according to different geographical locations in China.

Vascular cell behavior on heparin-like polymers modified silicone surfaces: The prominent role of the lotus leaf-like topography.

Vascular cell behavior on material surfaces, such as heparin-like polymers, can be affected by the surface chemical composition and surface topological structure. In this study, the effects of heparin-like polymers and lotus leaf-like topography on surface vascular cell behavior are considered. By combining multicomponent thermo-curing and replica molding, a polydimethylsiloxane surface containing bromine (PDMS-Br) with lotus leaf-like topography is obtained. Heparin-like polymers with different chemical compositions are grafted onto PDMS-Br surfaces using visible-light-induced graft polymerization. Compared with unmodified PDMS-Br, surfaces modified by sulfonate-containing polymers are more friendly to vascular cells, while those modified by a glyco-polymer are much more resistant to vascular cells. The introduction of lotus leaf-like topography results in different degrees of decrease in cell density on different heparin-like polymer-modified surfaces. In addition, the combination of heparin-like polymers and lotus leaf-like topography results in the change in protein adsorption, indicating that the two factors may affect the surface vascular cell behavior by affecting the adsorption of relative proteins. The combination of bionic surface topography and different chemical components of heparin-like polymers on material surfaces suggests a new way of engineering cell-material interactions.

The role of carboxylic groups in heparin-mimicking polymer-functionalized surfaces for blood compatibility: Enhanced vascular cell selectivity.

Blood compatibility is an eternal topic of biomedical materials. The effect of heparin-mimicking polymers (HMPs) on blood compatibility has been well studied, especially the synergistic effect of sugar unit and sulfonate/sulfate unit. However, carboxylic groups also play an important role in HMPs. In this work, copolymers of sodium 4-vinyl-benzenesulfonate (SS) and 2-methacrylamido glucopyranose (MAG) (poly(SS-co-MAG)) and poly(acrylate acid) (PAA) were self-assembled on Au surfaces with different feed ratios. When self-assembly of poly(SS-co-MAG) alone, the optimized feed ratio of SS and MAG for vascular cell selectivity was 1:1 (PS1M1); at this ratio the Au-PS1M1 surface showed the highest human umbilical vein endothelial cells (HUVECs) density and the lowest human umbilical vein smooth muscle cells (HUVSMCs) density. When self-assembly of PAA alone (surface designated as Au-PAA), the proliferation of both HUVECs and HUVSMCs was inhibited. Compared with either PS1M1 or PAA alone, the surfaces modified with both PAA and PS1M1 at the feed ratio of 1:1 (material designated as Au-PSM/PAA-2) showed enhanced promoting effect on HUVECs as well as enhanced inhibiting effect on HUVSMCs, indicating stronger vascular cell selectivity of carboxylic groups in the presence of sugar and sulfonate units.

[Effects of soil matrix potential regulation at various growth states on cotton growth and soil water and salt distribution]. / 不同生育期土壤基质势调控对棉花生长和土壤水盐分布的影响.

Water shortage and soil salinization are two main limiting factors for cotton production in southern Xinjiang. We examined the effects of soil matrix potential (SMP) regulation at various growth stages on cotton growth, soil water and salt distribution, to provide theoretical basis for water saving, salts control, and efficient production in cotton fields. The mulched drip irrigation experiments were conducted to monitor cotton growth, aboveground biomass, cotton yield, soil water and salt distribution and other indicators. Three SMP thresholds, i.e.,W1(-20 kPa), W2(-30 kPa) and W3(-40 kPa) were set at the seedling stage (A), seedling stage + budding stage (B), and seedling stage + budding stage + flowering stage (C), with SMP of -50 kPa at 20 cm soil depth below the emitter as the CK. The results showed that plant height, leaf area index (LAI) and aboveground biomass followed the order of WC>WB>WA>CK, when SMP were changed at various growth stages. Plant height, LAI and aboveground biomass increased with increasing SMP thresholds, with the values under W1C and W2C being significantly higher than the other treatments. The effective bolls per plant, single boll weight and lint percentage all increased with the increases of SMP thresholds. The yields of W1C and W2C were similar, which were significantly higher than those of other treatments. However, the water use efficiency of W2C was significantly higher than that of W1C. Controlling the SMP threshold at -20 or -30 kPa at different growth stages could improve soil moisture status of the primary cotton root zone. All treatments presented shallow salt accumulation (0-40 cm) at the harvest stage, with the bare land having greater salt accumulation than the inner film. The higher the SMP threshold was, the less salt was accumulated in the primary root zone (0-40 cm) under film. The salt accumulation (0-40 cm) under W1C and W2C were reduced by 24% compared with other treatments. Considering the efficient production of cotton, water saving and salt control, it was recommended to maintain the SMP threshold of -30 kPa during irrigation at various growth stages in cotton fields without leaching salts during the local off-crop period.

Vascular cell responses to silicone surfaces grafted with heparin-like polymers: surface chemical composition vs. topographic patterning.

Heparin-like polymers are promising synthetic materials with biological functionalities, such as anticoagulant ability, growth factor binding to regulate cellular functions, and inflammation mediation, similar to heparin. The biocompatibility of heparin-like polymers with well-defined chemical structures has inspired many researchers to design heparin-like surfaces to explore their biological applications. The concept of the recombination of functional heparin structural units (sulfonate- and glyco-containing units) was proven to be successful in designing heparin-mimicking surfaces. However, besides surface structural units, topographic patterning is also an important contributor to the biological activity of the surfaces modified with heparin-like polymers. In this work, both surface structural units and topographic patterning were taken into account to investigate the vascular cell behaviors on the silicone surfaces. A facile method for the production of patterned bromine-containing polydimethylsiloxane surface (PDMS-Br) was developed from a one-step multicomponent thermocuring procedure and replica molding using a nanohole-arrayed silicon template. Different structural units of heparin-like polymers, i.e. homopolymer of sulfonate-containing sodium 4-vinylbenzenesulfonate (pSS), homopolymer of glyco-containing 2-(methacrylamido)glucopyranose (pMAG), and copolymers of MAG and SS (pSG), were then introduced on the flat and patterned PDMS-Br surface using visible light-induced graft polymerization. For the flat surfaces, compared with the PDMS-Br surface, pSS-grafted and pSG-grafted surfaces significantly increased cell densities of both human umbilical vein endothelial cells (HUVECs) and human umbilical vein smooth muscle cells (HUVSMCs), indicating that they are "vascular cell-friendly". In contrast, the pMAG-grafted surface showed decreased cell attachment of both HUVECs and HUVSMCs, indicating that the pMAG-grafted surface is "vascular cell-resistant". Moreover, surface topographic patterning enhanced the cell responses to the corresponding flat surfaces. That is to say, surface patterning can make the "vascular cell-friendly" surface still friendly, and the "vascular cell-resistant" surface much more resistant. The combination of surface structural units and topographic patterning shows promise in the preparation of new heparin-like surfaces with improved cell compatibility that is suitable for blood-compatible biomaterials.

Laminar Inflammation Responses in the Oligofructose Overload Induced Model of Bovine Laminitis.

Bovine laminitis causes substantial economic losses and animal welfare problems in dairy farms worldwide. Previously published studies have reported that the inflammatory response plays a central role in the pathogenesis of the disease. To our knowledge, inflammation associated with bovine laminitis induced by high levels of exposure to oligofructose (OF) has not been reported and characterized. In fact, the disease manifestations in this model closely approximate those of clinical laminitis. The objective of this study was to characterize the inflammatory response in OF-induced bovine laminitis. A total of 12 Chinese Holstein dairy heifers were utilized in this study. The heifers were randomly divided into two groups, treatment (n = 6) and control (n = 6). The treatment group heifers were administered OF solutions via a stomach tube (dose: 17 g/kg of body weight). Upon development of a lameness score of 2 with consecutive positive reactions in the same claw, they would be humanely euthanized. Control heifers were administered deionized water (dose: 2 L/100 kg of body weight) and humanely euthanized at 72 h. Real-time quantitative PCR (qPCR) assays were performed to determine the messenger RNA (mRNA) concentrations of inflammatory mediators in the lamellae. Concentrations of interleukin (IL)-1ß, IL-6, IL-8, C-X-C motif chemokine ligand-1 (CXCL-1), macrophage cationic peptide-2 (MCP-2), E-selectin, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase-1 (iNOS-1), and plasminogen activator inhibitor-1 (PAI-1) were significantly increased (P < 0.05) in the treatment group. No significant difference was found for tumor necrosis factor alpha (TNF-α), IL-10, CXCL-6, and MCP-1. These results demonstrated and characterized the laminar inflammatory response leading to the pathogenesis of bovine laminitis at the early stages.

Effects of Annealing Time on Triple Cation Perovskite Films and Their Solar Cells.

Cesium (Cs) contained triple-cation and mixed halide perovskite (CsFAMA) is broadly employed as light absorption layers for efficient and stable perovskite solar cells (PSCs) fabrication with high reproducibility. On the other hand, thermal annealing is a universal post-treatment method for perovskite films preparation. Moreover, thermal management highly depends on perovskite materials. However, no specialized study has been reported on CsFAMA perovskite to date. Herein, we have systematically investigated the influence of thermal annealing and annealing time on CsFAMA films and their solar cells. We demonstrated that heating time of 45 or 60 min at 100 °C is desirable. More interestingly, we found that the unannealed CsFAMA films exhibit ultrahigh photoluminescence (PL) intensities, much stronger than that of annealed films. Note that PL intensities gradually weaken as a function of annealing time. In particular, the PL intensities of fresh films (after antisolvent dripping) are at least 200 times higher than that of 60 min annealed films. To our knowledge, it is the first time to report this PL behavior. We speculate that it is due to quantum confinement effect of perovskite crystal nuclei and "cage effect" of DMSO intermediates in the fresh films. To this point, the unannealed CsFAMA films may have great potential in PL emission applications.

Genome-wide identification of mitogen-activated protein kinase (MAPK) cascade and expression profiling of CmMAPKs in melon (Cucumis melo L.).

Mitogen-activated protein kinase (MAPK) is a form of serine/threonine protein kinase that activated by extracellular stimulation acting through the MAPK cascade (MAPKKK-MAPKK-MAPK). The MAPK cascade gene family, an important family of protein kinases, plays a vital role in responding to various stresses and hormone signal transduction processes in plants. In this study, we identified 14 CmMAPKs, 6 CmMAPKKs and 64 CmMAPKKKs in melon genome. Based on structural characteristics and a comparison of phylogenetic relationships of MAPK gene families from Arabidopsis, cucumber and watermelon, CmMAPKs and CmMAPKKs were categorized into 4 groups, and CmMAPKKKs were categorized into 3 groups. Furthermore, chromosome location revealed an unevenly distribution on chromosomes of MAPK cascade genes in melon, respectively. Eventually, qRT-PCR analysis showed that all 14 CmMAPKs had different expression patterns under drought, salt, salicylic acid (SA), methyl jasmonate (MeJA), red light (RL), and Podosphaera xanthii (P. xanthii) treatments. Overall, the expression levels of CmMAPK3 and CmMAPK7 under different treatments were higher than those in control. Our study provides an important basis for future functional verification of MAPK genes in regulating responses to stress and signal substance in melon.

Dynamic ROS Production and Gene Expression of Heifers Blood Neutrophil in a Oligofructose Overload Model.

Alimentary oligofructose (OF) overload can induce several diseases in cattle, such as ruminal acidosis, laminitis, and synovitis. The role of blood polymorphonuclear neutrophil (PMN) remains unclear during OF overload. The aim of this study was to investigate the dynamic changes in reactive oxygen species (ROS) production and the expression profile of genes in blood PMN in a model of OF overload. Twelve clinically healthy and non-pregnant Chinese Holstein heifers, aged between 18 and 26 mo, weighing 335-403 kg, BCS (5-point scale) ranges 2.7-3.3 were used for the experiments. OF heifers (n = 6) received 17 g/kg of BW oligofructose dissolved in 2 L/100 kg of BW tap water and the CON heifers (n = 6) received 2 L/100 kg of BW tap water. Blood PMN was isolated for each heifer 0, 6, 12, 18, 24, 36, 48, 60, and 72 h after administration. PMN was analyzed either by endogenous and phorbol myristate acetate (PMA)-induced ROS production or by quantitative real-time PCR. After 12 h, PMA-induced ROS production decreased, which was sustained until 48 h. The expressions of inflammation markers (IL1α, IL1ß, IL6, IL10, TNFα, STAT3, TLR4, MMP9, and HP) and eicosanoids (ALOX5, ALOX5AP, and PLA2G4A) were upregulated. The expression of adhesion and migration (CXCR2, CXCL8, CD62L, ITGA4, ITGAM, and ITGB2) in OF heifers was increased compared with CON heifers. The expression of oxidative stress (SOD2 and S100A8) was upregulated, while SOD1 and MPO were downregulated. In metabolism and receptor genes, the expressions of GRα and INSR decreased after 12 h, while Fas increased until 6 h and then decreased at 18 h. The expression of LDHA and PANX1 did not show any differences after OF overload. These findings indicate that OF overload induced systemic activation of PMN, which provides a step toward a better understanding of the role of innate immune responses in response to oral OF administration.

The changes of inflammatory mediators and vasoactive substances in dairy cows' plasma with pasture-associated laminitis.

BACKGROUND: Hoof disease is one of the three major diseases that often occur in dairy cows. The impact of this disease on dairy farming is second only to mastitis. Laminitis is a diffuse, aseptic, serous, non-purulent inflammation of the dermal papillae and vascular layers of the cow's hoof wall. In the pasture, laminitis occurs mostly in the laminae, that is, inside the hoof shell. No lesions can be seen on the surface. Therefore, laminitis cannot attract the attention of veterinarians. However, laminitis has become a major factor that seriously affects the health and welfare of dairy cows, making it an important cause of hindering the performance of dairy cows. METHODS: The study was conducted at a dairy farm in Harbin, Heilongjiang province, China. We selected a sample of the laminitis cows based on the veterinary diagnosis, took blood from the jugular vein and then separated the plasma, and measured the index with the Elisa kit. In this study, the markers of inflammatory and vasoactive substances status in dairy cows consisted of subclinical laminitis (SCL, n = 20), chronic laminitis (CL, n = 20) and healthy dairy cows (CON, n = 20) under the local management conditions were investigated. RESULTS: Compared with healthy cattle, HIS, IL-6, LPS, and TNF-α in subclinical laminitis group significantly increased (P < 0.05), especially HIS, LPS, TNF-α (P < 0.01); in chronic laminitis cows, COX-2, HIS, IL-6, LPS, and TNF-α increased significantly (P < 0.05), especially COX-2, HIS, TNF-α (P < 0.01). iNOS (P < 0.05), TXB2 (P < 0.01) in chronic laminitis cows had significantly increased. CONCLUSION: This study reported for the first time that pasture laminitis was divided into subclinical laminitis and clinical chronic laminitis. Through research on the inflammatory factors and vasoactive substances of dairy cows, it is found that there is a close relationship between them, which affects the metabolic cycle of dairy cows. These indicators are abnormally expressed and cause hoof microcirculation disorders.

CLINICAL AND GENETIC FINDINGS IN A CHINESE COHORT OF PATIENTS WITH DIGEORGE SYNDROME-RELATED HYPOPARATHYROIDISM.

Objective: Patients with DiGeorge syndrome (DGS) are undiagnosed due to its diverse manifestations. We aimed to characterize the clinical manifestations in a group of Chinese patients of DGS with childhood-onset hypoparathyroidism (HP) as the primary referral, and to report a novel TBX1 mutation. Methods: In this single-center observational study, clinical features and biochemical indices were recorded in 26 patients with DGS and 114 patients with idiopathic HP (IHP). An in vitro functional experiment was launched to analyze the novel TBX1 missense mutation. Results: Compared with 114 patients of IHP (19.1 [13.5, 27.3] years old), 26 patients of DGS (14.9 [10.4, 20.3] years old) had the following differences: an earlier onset age of hypocalcemia; higher levels of serum parathyroid hormone, with a similar disease course; and lower doses of vitamin D preparation therapy. Among the 26 patients of DGS, only 3 of them were clinically diagnosed as this syndrome prior to genetic testing. A total of 25 patients of DGS were verified to have a TBX1 deletion and 1 case with a novel missense mutation of TBX1. The novel p.Y490C mutation in TBX1, located in the transactivation domain, was verified to decrease the transcriptional activity of the TBX1 protein. Conclusion: In this Chinese group of patients with DGS-related HP, a relatively earlier onset age and less severity of HP were found compared to that of patients with IHP. Less common extraparathyroid manifestations are clues for the diagnosis of DGS. Additionally, our discovery of a novel TBX1 missense mutation expands the mutation database of DGS. Abbreviations: DGS = DiGeorge syndrome; HP = hypoparathyroidism; IHP = idiopathic hypoparathyroidism; LCR = low copy repeat; PCR = polymerase chain reaction; PTH = parathyroid hormone; TAD = transactivation domain.

Genetic Screening in a Large Chinese Cohort of Childhood Onset Hypoparathyroidism by Next-Generation Sequencing Combined with TBX1-MLPA.

At least 15 candidate genes have been implicated in hypoparathyroidism (HP). However, comprehensive screening of causative genes for HP is lacking. Here, we investigated the genotype spectrum in a large group of Chinese patients with childhood onset HP. A total of 173 patients with childhood onset HP were analyzed using targeted next-generation sequencing (NGS), including 15 candidate genes combined with multiplex ligation-dependent probe amplification (MLPA) of the TBX1 gene. Twenty-seven pathogenic or likely pathogenic mutations in five genes (TBX1, AIRE, GATA3, FAM111A, and CASR) including 13 novel variants in 23 patients, and 12 variants of uncertain clinical significance in five genes (GATA3, CASR, FAM111A, GCM2, and PTH) in 11 patients, were identified by NGS. Additionally, an entire gene deletion of TBX1 in 25 patients was found by TBX1-MLPA. Combined with clinical data, 26 (15.0%) cases of DiGeorge syndrome (OMIM #188400), nine (5.2%) autoimmune polyglandular syndrome type 1 (OMIM #240300), eight (4.6%) autosomal dominant hypocalcemia type 1 (OMIM #601198), four (2.3%) hypoparathyroidism-deafness-renal dysplasia syndrome (OMIM #146255), and one (0.6%) Kenny-Caffey syndrome type 2 (OMIM #127000) were verified. Among them, 16 of 26 (61.5%) DiGeorge syndrome cases were undiagnosed due to the lack of obvious clinical clues before genetic testing. The onset age of patients with mutations (median [interquartile range], 2.8 [0.1, 9.6] years) was significantly earlier than those without mutations (13.0 [8.8, 15.0] years) (p < 0.001). Family history, early onset age, especially prior to 5 years old, and extraparathyroid manifestations were clues for hereditary HP. The combined targeted NGS and TBX-1 MLPA were conveniently and effectively used for comprehensive genetic screening in this large Chinese cohort of childhood onset HP patients. Genetic defects were identified in 27.7% of early-onset HP patients, including four kinds of syndromic HP and one isolated HP. A total of 13 novel mutations were detected, which expands the mutation spectrum of hypoparathyroidism. © 2019 American Society for Bone and Mineral Research.