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Background Administration of drugs by inhalation is a common route for the treatment of chronic airway diseases. The ability of patients to use an inhaler device is a key factor in the effectiveness of treatment. Recently, a new type of quantitative assessment instrument for inhalation drugs has been developed in China, which can measure peak inspiratory flow (PIF) and inspiratory volume (VI) under conditions with various internal resistance of inhalers, thereby accurately assessing the ability of patients to use inhaler. However, there are no quality testing methods and adoption standards for this type of instrument at home and abroad. Objective To perform quality testing of the inhalation drug quantitative assessment instrument and evaluate its technical performance, in order to explore the application value of the method. Methods Various internal resistance of dry powder inhalers (DPI) was simulated by the inhalation drug quantitative assessment instrument (PF810) in 5 different gears (R1-R5 from low to high) . A standard flow/volume simulator was used to test the flow, volume and impedance performance of the PF810 for inhalation. The flow test was performed at a fixed volume (3.000 L) and different flow rates (in the range of 0-2.000 L/s, with 0.250 L/s as the interval stepwise) . The volume was carried out at three flow rates of low (0.500 L/s) , medium (1.000 L/s) and high (1.500 L/s) , and at different volumes (1.000 L as the interval stepwise in the range of 1.000-4.000 L) . The Bland-Altman analysis chart method of GraphPad prism 9.0 software was used to evaluate the consistency of PIF and VI measurements of the inhalation drug quantitative assessment instrument with the actual values output by the simulator at different resistance gears. Results The results of quality control evaluation of flow detection showed that the percentages of repeatability, accuracy and linearity of flow detection meeting the performance requirements were 100.00% (40/40) , 95.00% (38/40) and 94.29% (33/35) . The accuracy and linearity of PF810 at R5 gear 1.500L /s and above did not meet the performance testing requirements, while those of other gears and flow rates met the requirements. The Bland-Altman consistency test showed 95% limit of agreement (LOA) of (-0.271- 0.107) L/s, with 96.00% (192/200) data points within the 95%LOA range. The results of volume test quality control evaluation showed that the pass rates of volume test repeatability, accuracy and linearity were all 100.00% (60/60, 60/60, 45/45) . The Bland-Altman consistency test showed that 95%LOA was (-0.058-0.017) L, and 100.00% (180/180) data points were within the 95%LOA range. The impedance measurement quality control evaluation results showed that the relative errors between the impedance value of PF810 and the internal resistance of the corresponding inhaler were all

Simple Summary: The bursa of Fabricius, unique to birds, is critical in the immune system. LPS in waterfowl breeding environments can damage the BF in goslings. Atractylodes macrocephala polysaccharides (PAMKs), an active component from the traditional Chinese medicine Atractylodes macrocephala, enhance immune function. This study found that PAMKs mitigated the LPS-induced BF damage in goslings, reduced the inflammatory cytokine levels, and improved the antioxidant capacity. Transcriptome sequencing identified 373 differentially expressed genes, with enrichment analysis showing EREG's key role in activating the MAPK and ErbB signaling pathways. Cell validation confirmed PAMKs' inhibition of EREG, reduction of LPS-induced apoptosis, promotion of cell cycle progression, and decrease in apoptotic protein expression. This study concluded that PAMKs effectively alleviated the LPS-induced BF injury, providing a reference for enhancing waterfowl immunity. The bursa of Fabricius (BF) plays crucial roles in the goslings' immune system. During waterfowl breeding, the presence of lipopolysaccharides (LPSs) in the environment can induce inflammatory damage in geese. Polysaccharides of Atractylodes macrocephala Koidz (PAMKs), as the main active component of the Chinese medicine Atractylodes macrocephala, have significant immune-enhancing effects. Accordingly, this study intended to investigate the effect of PAMKs on LPS-induced BF injury in goslings. Two hundred 1-day-old goslings (half male and half female) were selected and randomly divided into control, PAMK, LPS, and PAMK + LPS groups. The control and LPS groups were fed the basal diet, and the PAMK and PAMK + LPS groups were fed the basal diet containing PAMKs at 400 mg/kg. The goslings in the LPS and PAMK + LPS groups were injected intraperitoneally with LPS at a concentration of 2 mg/kg on days 24, 26, and 28 of this study. The control and PAMK groups were injected with equal amounts of saline. On the 28th day, 1 h after the LPS injection, the BF and serum were collected and analyzed for organ indices, cytokines, antioxidant indicators, and histological observations. Histological examination and HE staining demonstrated that the PAMK treatment ameliorated the LPS-induced BF atrophy, structural damage, increased cellular exudation, and reticulocyte hyperplasia in the goslings. The cytokine and antioxidant marker analyses in the BF cells demonstrated that the PAMK treatment mitigated the LPS-induced increase in the interleukin-1β (IL-1β), malondialdehyde (MDA), and inducible nitric oxide synthase (iNOS) levels, as well as the decrease in the transforming growth factor-β (TGF-β) and superoxide dismutase (SOD) activities. Further transcriptome sequencing identified a total of 373 differentially expressed genes (DEGs) between the LPS and PAMK + LPS groups. The KEGG enrichment pathway analysis showed that the DEGs were significantly enriched in the Toll-like receptor, p53, MAPK, GnRH, and ErbB signaling pathways. Among them, EREG played key roles in the activation of the MAPK, GnRH, and ErbB signaling pathways. Further research showed that the addition of PAMKs significantly inhibited the LPS-induced EREG expression, increased the cell viability, promoted the cell cycle entry into the S and G2 phases, and inhibited apoptosis. Meanwhile, PAMKs can reduce the protein expression of p-JNKs and c-FOS by inhibiting EREG. In summary, this study found that PAMKs could alleviate LPS-induced BF injury in goslings by inhibiting the expression of EREG. [ABSTRACT FROM AUTHOR]

BackgroundThere are daytime variability in pulmonary function indexes such as peak expiratory flow (PEF) and forced expiratory volume in 1 second (FEV1) in asthma patients. Studies evaluating the effects of drug therapy on lung function and airway hyperresponsiveness (AHR) in asthma patients all required patients to perform spirometry and bronchial challenge test in the same time point of the days. However, whether there is a daily diurnal AHR variability is still not clear.ObjectiveTo explore the characteristics and diurnal variability of AHR in asthma patients.MethodsThe data of 202 patients with asthma who consulted in respiratory department of the First Affiliated Hospital of Guangzhou Medical University from January 2018 to September 2020 were included for statistical analysis. All patients completed the methacholine bronchial provocation tests, they were divided into the morning detection group (morning group) with 81 cases and the afternoon detection group (afternoon group) with 121 cases; according to the disease course, 98 cases were divided into the initial diagnosis group if the disease course was ≤6 months, and 104 cases were divided into the follow-up group if the disease course was >6 months. The initial diagnosis group and the follow-up group were divided into the initial diagnosis morning group, the initial diagnosis afternoon group, the follow-up morning group, and the follow-up afternoon group according to the detection time; according to the AHR, the patients were divided into very mild, mild, moderate and severe groups. The characteristics of AHR and the main pulmonary function indexes including FVC%pred, FEV1%pred, PEF%pred, MMEF%pred, MEF50%pred, MEF25%pred, PD20-FEV1, PD20-PEF, PD20-MMEF, PD20-MEF25%, PD20-MEF50% of these groups were analyzed and compared.ResultsThere were no significant differences of the math pulmonary function indexes and PD20 between morning and afternoon groups (P0.05) . In follow-up group, MMEF%pred and MEF50%pred were higher in afternoon than in morning (P0.05) .ConclusionThe longer the duration of asthma, more serious impairment of lung function found in asthma, while the AHR had no significant difference between morning and afternoon.

BackgroundPulmonary examination is a measurement technique in medicine, and the quality of examination equipment is a key factor associated with the accuracy of examination results. Guidelines for mechanical lung function measurements have proposed that the spirometer should be calibrated each time it is used by the calibration cylinder for quality control, so the accuracy of the calibration cylinder will directly associate with that of the spirometer. However, there are no reports on the accuracy, and eligible standards, as well as calibration procedure regarding spirometer calibration cylinders measured by relevant research institutions (including calibration cylinder manufacturers) .ObjectiveTo develop a method, and use it to measure the performance of volume calibration cylinders commonly applied in China to assess its application value.MethodsAccording to the standards for 3 L calibration syringe proposed in the Standardization of Spirometry 2019 Update issued by the American Thoracic Society (ATS) /European Respiratory Society (ERS) , the 1180 cylinder verifier (produced by Hans Rudolph, inc.) was used in the leak test and volume accuracy test for measuring the performance of five brands of imported/domestic calibration cylinders (Two were produced by Germany's CareFusion, and Vyaire, respectively, one by MGC Diagnostics, USA, and the other two by China's Zhejiang U-Breath, and Ningbo Wendi Medical Instrument CO, LTD, respectively) .ResultsOf the five brands of calibration cylinders, 4/5 had less than 1 ml/min in the pressure attenuation leakage test, 4/5 had a volume error of less than 0.5% of the target volume, with an error range of less than 0.05% of the target volume, 3/5 passed both tests.ConclusionIn this study, the method of directly measuring the change of gas volume of volume calibration cylinder is used for quality detection. The method is simple and feasible. It is recommended that the calibration cylinder should be regularly checked for assuring the accuracy.

To fully unleash the performance potential of the Wheel Drive Driverless Vehicle (WDDV) and enhance its handling stability across a wide range of extreme operating conditions, this paper proposes a novel approach for designing a multi-directional motion coupling control system. Firstly, an analysis of the unmanned driving modes of the WDDV is conducted, followed by the establishment of a method for defining the control target parameter set for handling stability. Subsequently, a coupled dynamic model that considers the wheel drive counter force is developed. Building this model, a method for estimating the handling stability state is introduced, focusing on improving both handling and stability aspects. Furthermore, by combining the sliding mode control algorithm with the coupled dynamic model, a design methodology for a multi-directional motion coupling control law that adapts to extreme operating conditions is proposed. Finally, through comprehensive simulation experiments and testbed, the effectiveness of the proposed multi-directional motion coupling control system is validated, demonstrating superior handling stability compared to the decoupled control system. [ABSTRACT FROM AUTHOR]

Simple Summary: Shitou geese are the exclusive representative of a large-sized goose breed in China, typically exhibiting gray feathers but also possessing a recessive white plumage. However, the precise mechanism underlying the formation of this white plumage coloration in Shitou geese remains unclear. Here, a transcriptome sequencing analysis was conducted to identify candidate genes and microRNAs (miRNAs) that may be associated with the white plumage color in Shitou geese. A number of pigmentation genes and miRNAs were identified as candidates that may regulate white plumage color formation in Shitou geese. This result may be important for understanding the genetic mechanism underlying the formation of white plumage color in Shitou geese. The Shitou goose, a highly recognized indigenous breed with gray plumage originating from Chaozhou Raoping in Guangdong Province, China, is renowned for being the largest goose species in the country. Notably, during the pure breeding process of Shitou geese, approximately 2% of the offspring in each generation unexpectedly exhibited white plumage. To better understand the mechanisms underlying white plumage color formation in Shitou geese, we conducted a comparative transcriptome analysis between white and gray feather follicles, aiming to identify key genes and microRNAs that potentially regulate white plumage coloration in this unique goose breed. Our results revealed a number of pigmentation genes, encompassing TYR, TYRP1, EDNRB2, MLANA, SOX10, SLC45A2, GPR143, TRPM1, OCA2, ASIP, KIT, and SLC24A5, which were significantly down-regulated in the white feather follicles of Shitou geese. Among these genes, EDNRB2 and KIT emerged as the most promising candidate genes for white plumage coloration in Shitou geese. Additionally, our analysis also uncovered 46 differentially expressed miRNAs. Of these, miR-144-y may play crucial roles in the regulation of feather pigmentation. Furthermore, the expression of novel-m0086-5p, miR-489-y, miR-223-x, miR-7565-z, and miR-3535-z exhibits a significant negative correlation with the expression of pigmentation genes including TYRP1, EDNRB2, MLANA, SOX10, TRPM1, and KIT, suggesting these miRNAs may indirectly regulate the expression of these genes, thereby influencing feather color. Our findings provide valuable insights into the genetic mechanisms underlying white plumage coloration in Shitou geese and contribute to the broader understanding of avian genetics and coloration research. [ABSTRACT FROM AUTHOR]

Research simultaneously examining building energy consumption and outdoor thermal comfort within urban environments remains limited. Few studies have delved into the sensitivity of design parameters based on building energy consumption and outdoor thermal comfort. The purpose of this study is to investigate the correlations between urban morphological design parameters and performance indicators, focusing on building energy consumption and outdoor thermal comfort (UTCI), across different urban block layouts in hot-humid regions, like Guangzhou. By establishing six fundamental morphological models—three individual unit layouts and three group layouts—the research explores both control and descriptive parameters through extensive simulation studies. Scatter plot visualizations provide insights into the impacts of various design parameters on energy consumption and UTCI, facilitating a comprehensive analysis of trends and quantitative relationships. Additionally, the study conducts sensitivity analyses on design parameters under different layout conditions to highlight their influences on target performance indicators. The findings reveal common trends, such as the significant impacts of plan dimensions and the Floor Area Ratio (FAR) on energy efficiency and outdoor comfort, as well as differential patterns, such as the varying sensitivities of the Shape Factor (S/V) and the Sky View Factor (SVF), across individual and collective layouts. Ultimately, this study offers a nuanced understanding of urban block morphology's role in creating sustainable, comfortable, and energy-efficient urban environments, providing valuable guidelines for urban form design in hot-humid climates. [ABSTRACT FROM AUTHOR]

BACKGROUND: At present, robust quality criteria and methods for the assessment of Peak inspiratory flow meter performance are lacking. OBJECTIVE: A standard flow-volume simulator for quality control analyses of an inhalation assessment device was utilized with different simulated resistance levels in order to propose a quality testing method and associated standard for this device type. METHODS: A standard flow-volume simulator was utilized to assess the performance of an In-Check DIAL ® (Device I) and an intelligent inhalation assessment device (Device P) at a fixed volume and flow rate. Indices used to evaluate these two instruments included repeatability, accuracy, linearity, and impedance. RESULTS: Both devices exhibited good repeatability ( < ± 3 L/min). The difference between test results and standard simulator values for Device P was less than ± 5 L/min at resistance level R1 but higher than ± 5 L/min at resistance levels R2–5, while Device I were greater than 5 L/min at all resistance levels. The relative error for Device P was < ± 10% at resistance levels R1, R2, and R4, but > 10% at resistance levels R3 and R5. The relative error values for Device I at all five resistance levels were > 10%. Device P passed the linearity test at the R2 resistance level, while Device I partially passed the linearity test at all five resistance levels. CONCLUSION: Standard monitoring methods and standards provide a valuable approach to the more reliable clinical assessment and application of these instruments. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) has become the fifth most prevalent cause of cancer-related morbidity, attracting significant attention from researchers due to its heightened malignancy and drug resistance. Conventional chemotherapy approaches have proven inadequate in addressing all BC subtypes, highlighting the urgent need for novel therapeutic approaches or drugs. Curcumin (CUR), a phytochemical derived from Curcuma longa (turmeric), has shown substantial potential in inhibiting BC cell migration, metastasis, and proliferation. However, the use of CUR in this context comes with challenges due to its dynamic and easily degradable nature, poor aqueous solubility, low bioavailability, rapid metabolism, and swift systemic elimination, collectively limiting its clinical applications. As such, we provide an overview of the properties, synthesis, and characterization of the hybridization of CUR and its analogue with chemo-drug building blocks. We reviewed research from the last five years on CUR's biogenesis with respect to the regulation of BC, revealing that CUR participates in arresting BC cells in the cell cycle and significantly induces apoptosis in BC cells. Information on the chemotherapeutic and antitumor mechanisms of CUR in BC, including regulation of the cell cycle, increased cell apoptosis, and inhibition of multidrug resistance (MDR), was compiled. Additionally, we provide an overview of CUR loaded into nanomaterials that are cotreated with other chemotherapeutic drugs, such as paclitaxel, thymoquinone, and tamoxifen. In this review, we discuss different types of nanoparticles that can be used for CUR delivery, such as polymeric nanoparticles, carbon nanotubes, and liposomes. By comparing the size, entrapment efficiency, drug-loading capacity, release time, biocompatibility, pharmaceutical scale, and reproducibility of various nanomaterials, we aimed to determine which formulations are better suited for loading CUR or its analogue. Ultimately, this review is expected to offer inspiring ideas, promising strategies, and potential pathways for developing advanced anti-BC strategy nanosystems in clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: The meat production performance of pigeons is largely determined by the growth and development of skeletal muscle, and the pectoral muscle accounts for a large proportion of skeletal muscle. The incubation period of pigeons is around 18 days. In order to better investigate the developmental phenotypic differences and hub differentially expressed genes (DEGs) in the pectoral muscles between the European meat pigeon Mimas strain and the Shiqi pigeon during the whole embryonic stages, we selected embryonic day 6 (E6), day 10 (E10), day 14 (E14) and day 1 after birth (P1), representing early embryonic development, mid-embryonic development, late-embryonic development, and the first day after hatching. H&E staining and RNA-seq at different embryonic stages were analyzed. It was found that myofiber density was significantly higher in the Shiqi pigeon than that of the European meat pigeon on E6, and myofibers with a diameter in the range of 1~50 μm in the Shiqi pigeon were significantly higher than those in the European meat pigeon on P1. In addition, we found several myogenic DEGs (CLU, PTGS1, NXK6-1, NR1H4, HNF1A, ABCB11, PLA2G12B and BPHL) which may play roles in regulating distinct embryonic pectoral muscle development between two pigeon breeds. This study provides basic data for revealing the distinct embryonic developmental mechanisms of pectoral muscle between European meat pigeons and Shiqi pigeons. In avian muscle development, embryonic muscle development determines the number of myofibers after birth. Therefore, in this study, we investigated the phenotypic differences and the molecular mechanism of pectoral muscle development of the European meat pigeon Mimas strain (later called European meat pigeon) and Shiqi pigeon on embryonic day 6 (E6), day 10 (E10), day 14 (E14) and day 1 after birth (P1). The results showed that the myofiber density of the Shiqi pigeon was significantly higher than that of the European meat pigeon on E6, and myofibers with a diameter in the range of 50~100 μm of the Shiqi pigeon on P1 were significantly higher than those of European meat pigeon. A total of 204 differential expressed genes (DEGs) were obtained from RNA-seq analysis in comparison between pigeon breeds at the same stage. DEGs related to muscle development were found to significantly enrich the cellular amino acid catabolism, carboxylic acid catabolism, extracellular matrix receptor interaction, REDOX enzyme activity, calcium signaling pathway, ECM receptor interaction, PPAR signaling pathway and other pathways. Using Cytoscape software to create mutual mapping, we identified 33 candidate genes. RT-qPCR was performed to verify the 8 DEGs selected—DES, MYOD, MYF6, PTGS1, MYF5, MYH1, MSTN and PPARG—and the results were consistent with RNA-seq. This study provides basic data for revealing the distinct embryonic development mechanism of pectoral muscle between European meat pigeons and Shiqi pigeons. [ABSTRACT FROM AUTHOR]

Skeletal muscle development from embryonic stages to hatching is critical for poultry muscle growth, during which DNA methylation plays a vital role. However, it is not yet clear how DNA methylation affects early embryonic muscle development between goose breeds of different body size. In this study, whole genome bisulfite sequencing (WGBS) was conducted on leg muscle tissue from Wuzong (WZE) and Shitou (STE) geese on embryonic day 15 (E15), E23, and post-hatch day 1. It was found that at E23, the embryonic leg muscle development of STE was more intense than that of WZE. A negative correlation was found between gene expression and DNA methylation around transcription start sites (TSSs), while a positive correlation was observed in the gene body near TTSs. It was also possible that earlier demethylation of myogenic genes around TSSs contributes to their earlier expression in WZE. Using pyrosequencing to analyze DNA methylation patterns of promoter regions, we also found that earlier demethylation of the MyoD1 promoter in WZE contributed to its earlier expression. This study reveals that DNA demethylation of myogenic genes may contribute to embryonic leg muscle development differences between Wuzong and Shitou geese. [ABSTRACT FROM AUTHOR]

BACKGROUND: Peak expiratory flow meters (PEFMs) have emerged as primary tools used for diagnosing and monitoring a range of respiratory diseases including asthma and chronic obstructive pulmonary disease, and the performance of these meters will thus impact disease evaluation. OBJECTIVE: The aim of this study was therefore to assess the technical performance of mechanical and electronic PEFMs commonly used in clinical practice. METHODS: The accuracy, repeatability, airflow resistance, frequency response, and linearity of five electronic and seven mechanical PEFMs were measured using a standard flow/volume simulator in accordance with nine A-waveforms and three B-waveforms defined in ISO 23747:2015 issued by the International Standards Organization (ISO). RESULTS: The accuracy, repeatability, linearity, airflow resistance, and frequency response pass rates for these 12 different PEFM brands were 41.67%, 75.00%, 50.00%, 75.00%, and 25.00%, respectively. Just 16.67% (2/12) of the tested PEFMs met all evaluated criteria, whereas the remaining PEFMs partially met these criteria. There were no significant differences between the two tested PEFM types in the low flow rate waveform test (P > 0.05), although there were significant differences in the medium and high flow rate waveform test (P < 0.05). In addition, the overall PEFMs test had poor accuracy and good repeatability, although most of the repeatability errors occurred in the BTPS state. CONCLUSION: PEFMs commonly used in clinical settings exhibit variable technical performance, and relevant departments need to strengthen PEFM quality control and management in China. [ABSTRACT FROM AUTHOR]

Purpose: To develop and internally validate a nomogram for predicting the risk of incorrect inhalation techniques in patients with chronic airway diseases. Methods: A total of 206 patients with chronic airway diseases treated with inhaled medications were recruited in this study. Patients were divided into correct (n=129) and incorrect (n=77) cohorts based on their mastery of inhalation devices, which were assessed by medical professionals. Data were collected on the basis of questionnaires and medical records. The least absolute shrinkage and selection operator method (LASSO) and multivariate logistic regression analyses were conducted to identify the risk factors of incorrect inhalation techniques. Then, calibration curve, Harrell's C-index, area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA) and bootstrapping validation were applied to assess the apparent performance, clinical validity and internal validation of the predicting model, respectively. Results: Seven risk factors including age, education level, drug cognition, self-evaluation of curative effect, inhalation device use instruction before treatment, post-instruction evaluation and evaluation at return visit were finally determined as the predictors of the nomogram prediction model. The ROC curve obtained by this model showed that the AUC was 0.814, with a sensitivity of 0.78 and specificity of 0.75. In addition, the C-index was 0.814, with a Z value of 10.31 (P< 0.001). It was confirmed to be 0.783 by bootstrapping validation, indicating that the model had good discrimination and calibration. Furthermore, analysis of DCA showed that the nomogram had good clinical validity. Conclusion: The application of the developed nomogram to predict the risk of incorrect inhalation techniques during follow-up visits is feasible. [ABSTRACT FROM AUTHOR]

Genome‐wide SNP profiling has yielded insights into the genetic structure of China indigenous pigs, but has focused on a limited number of populations. Here, we present an analysis of population structure and signals of positive selection in 42 Chinese pig populations that represent the most extensive pig phenotypic diversity in China, using genotype data of 1.1 million SNPs on customized Beadchips. This unravels the fine‐scale genetic diversity, phylogenic relationships, and population structure of these populations, which shows remarkably concordance between genetic clusters and geography with few exceptions. We also reveal the genetic contribution to North Chinese pigs from European modern pigs. Furthermore, we identify possible targets of selection in the Tibetan pig, including the well‐characterized hypoxia gene (EPAS1) and several previously unrecognized candidates. Intriguingly, the selected haplotype in the EPAS1 gene is associated with higher hemoglobin contents in Tibetan pigs, which is different from the protective role of EPAS1 in the high‐altitude adaptation in Tibetan dogs and their owners. Additionally, we present evidence for the causality between EDNRB variants and the two‐end‐black (TEB) coat color phenotype in all Chinese pig populations except the Jinhua pig. We hypothesize that distinct targets have been independently selected for the formation of the TEB phenotype in Chinese pigs of different geographic origins. This highlights the importance of characterizing population‐specific genetic determinants for heritable phenotype in diverse pig populations. [ABSTRACT FROM AUTHOR]

The Duroc × (Landrace × Large White) hybrid pig (DLY) is the most popular commercial pig used in the Chinese pig industry. DLY pigs are usually white but sometimes show colored phenotypes. Colored DLY pigs are not favored by slaughterhouses and retailers, thus causing certain economic losses to farmers in China. In this study, we first conducted a genome-wide association study and RNA sequencing to demonstrate that KIT variants are responsible for diversifying coat color phenotypes segregating in a DLY population. We then defined the precise sizes and locations of four duplications (DUP1-4), four candidate causative mutations at the KIT locus, in the pig reference genome using the whole-genome sequence data of representative colored individuals. The sequence data also enabled us to identify a list of new KIT alleles. By investigating the association between these new alleles and coat color phenotypes, we provide further evidence that DUP2 is another causative mutation for the solid white coat color in pigs. DUP1 (the KIT gene duplication), DUP2 and the splice mutation are all required for the manifestation of a solid white coat color. DUP4 had a more significant effect on the formation of the belt phenotype compared with DUP3. Given the necessity of DUP2 for the solid white coat color, we detected IN / IN homozygotes lacking DUP2 in Large White and Landrace pigs and found that French Landrace pigs had the highest frequency (8.98%) of IN / IN individuals. This study not only advances our understanding of the molecular mechanism of the color phenotype in pigs, but also establishes a simple and accurate method for the screening of KIT IN / IN homozygotes in Large White and Landrace that would cause colored DLY pigs. [ABSTRACT FROM AUTHOR]

Increasing in cases involving drugs of abuse leads to heavy burden for law enforcement agencies, exacerbating demand for rapid screening technique. In this study, atmospheric pressure ionization technologies including direct analysis in real time (DART) ion source coupled to a time-of-flight mass spectrometer (DART-TOF-MS)as well asdopant-assisted positive photoionization ion mobility spectrometry (DAPP-IMS) without radioactivity were utilized together as the powerful analytical tool for the rapid screening and identification of 53 abused drugs.The limits of detection (LOD) were 0.05-2μg/mL when using DART-TOF-MS and 0.02-2μg when using DAPP-IMS which could satisfy the actual requirement in forensic science laboratory. The advantages of this method included fast response, high-throughput potential, high specificity, and minimal sample preparation. A screening library of reduced mobility (K0), accurate mass of informative precursor ion ([M+H]+) and fragment ions was established respectively by employing a bench-top DAPP-IMS and TOF-MS in-source collision induced dissociation (CID) mode. Then the standardized screening procedure was developed with criteria for the confirmation of positive result. A total of 50 seized drug samples provided by local forensic laboratory we reanalyzed to testify the utility of the method. This study suggests that a method combing DART-TOF-MS and DAPP-IMS is promising for the rapid screening and identification of abused drugs with minimal sample preparation and absence of chromatography. [ABSTRACT FROM AUTHOR]

Morinda morindoidesis an important Liberian traditional medicine for the treatment of malaria, fever, worms etc. The plant was subjected to integrated approaches including phytochemical screening and gas chromatography mass spectrometry (GC–MS) analyses. Phytochemical investigation of the powdered plant revealed the presence of phenolics, tannins, flavonoids, saponins, terpenes, steroidal compounds and volatile oil. Steam distillation followed by GC–MS resulted in the identification of 47 volatiles in its aerial parts: 28 were in common including various bioactive volatiles. Major constituents of leaves were phytol (43.63%), palmitic acid (8.55%) and geranyl linalool (6.95%) and stem were palmitic acid (14.95%), eicosane (9.67%) and phytol (9.31%), and hence, a significant difference in the percentage composition of aerial parts was observed. To study seasonal changes, similarity analysis was carried out by calculating correlation coefficient (r) and vector angle cosine (z) that were more than 0.91 for stem-to-stem and leaf-to-leaf batches indicating considerable consistency. [ABSTRACT FROM PUBLISHER]

A field sampling method based on magnetic core–shell silica nanoparticles was developed for field sampling and the enrichment of low concentrations of pesticides in aqueous samples. The magnetic nanoparticles could be easily extracted from water samples by a custom-made magnetic nanoparticle collector. The recovery of 15 mg of magnetic particles from a 500 mL water sample was 90.8%. Mixtures of seven pesticides spiked into pure water and pond water were used as marker samples to evaluate the field sampling method. The average recoveries at three levels of spiking were in the range 60.0–104.7% with relative standard deviations <7.1%. The proposed method has good linearity with a correlation coefficient >0.9990 in the concentration range 0.5–15 μg L−1. The results of the analysis of a sample of poisoned pond water indicate that this method is fast, convenient and efficient for the field sampling and enrichment of pesticides in aqueous samples. [ABSTRACT FROM AUTHOR]

This study was designed to develop a sensitive and reliable RP-HPLC method for the separation of aerial parts ofJologbo. Different extraction methods were used and compared to obtain the maximum number of constituents. Different chromatographic conditions were optimized to achieve optimum separation. A total of 98 peaks were obtained in the optimized separation method. Seasonal variation and difference in chemical composition among aerial parts of the plant were evaluated. Significant difference in the chemical composition was observed and statistical data processing supported the results. The correlation coefficient and vector cosine were calculated by chemometric analysis to evaluate peak retention times, peak areas, and peak heights between various batches (using selected peaks) which showed good repeatability. Gallic and protocatechuic acids were identified from the plant and their intra-day and inter-day repeatability values were calculated and convincing results were obtained. [ABSTRACT FROM AUTHOR]

A novel capillary zone electrophoresis separation coupled to electro spray ionization time-of-flight mass spectrometry method was developed for the simultaneous analysis of six toxic alkaloids: brucine, strychnine, atropine sulfate, anisodamine hydrobromide, scopolamine hydrobromide and anisodine hydrobromide in human plasma and urine. To obtain optimal sensitivity, a solid-phase extraction method using Oasis MCX cartridges (1 mL, 30 mg; Waters, USA) for the pretreatment of samples was used. All compounds were separated by capillary zone electrophoresis at 25 kV within 12 min in an uncoated fused-silica capillary of 75 μm id × 100 cm and were detected by time-of-flight mass spectrometry. This method was validated with regard to precision, accuracy, sensitivity, linear range, limit of detection (LOD), and limit of quantification (LOQ). In the plasma and urine samples, the linear calibration curves were obtained over the range of 0.50-100 ng/mL. The LOD and LOQ were 0.2-0.5 ng/mL and 0.5-1.0 ng/mL, respectively. The intra- and interday precision was better than 12% and 13%, respectively. Electrophoretic peaks could be identified by mass analysis. [ABSTRACT FROM AUTHOR]

Background Pigs were domesticated independently from European and Asian wild boars nearly 10,000 years ago. Chinese indigenous pigs have been historically introduced to improve Europe local pigs. However, the geographic origin and biological functions of introgressed Chinese genes in modern European pig breeds remain largely unknown. Results Here we explored whole-genome sequencing data from 266 Eurasian wild boars and domestic pigs to produce a fine-scale map of introgression between French Large White (FLW) and Chinese pigs. We show that FLW pigs had historical admixture with both Southern Chinese (SCN) and Eastern Chinese (ECN) pigs ∼200–300 years ago. Moreover, a set of SCN haplotypes was shown to be beneficial for improving disease resistance and ECN haplotypes are favorable for improved reproductive performance in FLW pigs. In addition, we confirm human-mediated introgression events at the AHR locus, at which the haplotype of most likely ECN origin contributes to increased fertility of FLW pigs. Conclusions This study advances our understanding of the breeding history of global domestic pigs and highlights the importance of artificial introgression in the formation of phenotypic characteristics in domestic animals. [ABSTRACT FROM AUTHOR]

Skeletal muscle fiber characteristics (MFCs) have been extensively studied due to their importance to human health and athletic ability, as well as to the quantity and quality of livestock meat production. Hence, we performed a genome-wide association study (GWAS) on nine muscle fiber traits by using whole genome sequence data in an eight-breed crossed heterogeneous stock pig population. This GWAS revealed 67 quantitative trait loci (QTLs) for these traits. The most significant GWAS signal was detected in the region of Sus scrofa chromosome 12 (SSC12) containing the MYH gene family. Notably, we identified a significant SNP rs322008693 (P = 7.52E-09) as the most likely causal mutation for the total number of muscle fibers (TNMF) QTL on SSC1. The results of EMSA and luciferase assays indicated that the rs322008693 SNP resided in a functional element. These findings provide valuable molecular markers for pig meat production selection as well as for deciphering the genetic mechanisms of the muscle fiber physiology. [Display omitted] • GWAS were conducted in an eight-breed crossed heterogeneous stock pig population. • 67 QTLs for nine muscle fiber characteristics were revealed, of which 57 are novel. • Most significant GWAS signals was detected on SSC12 containing the MYH gene family. • SNP rs322008693 was the most likely causal mutation for the QTL on SSC1 for TNMF. • TNNT2 , TNNI1 , LMOD1 , CCD88C and CSRP1 genes were also correlated with the MFCs. [ABSTRACT FROM AUTHOR]

Evodiamine (EVO) is a natural compound derived from Tetradium ruticarpum (A.Juss.) T.G.Hartley used to treat pain and migraine in traditional Chinese medicine. EVO is the primary active ingredient of Tetradium ruticarpum. However, the preventive effect of EVO against migraine remains unexplored. To investigate the preventive effect of EVO against nitroglycerin (NTG)-induced acute migraine in rats. Male Sprague-Dawley rats were intragastrically administered EVO (45 or 90 mg/kg) for nine days. To establish an acute migraine model, we subcutaneously injected rats with a 10 mg/kg NTG solution. The migraine-like behavior of the rats was evaluated via the formalin test and the warm water tail-withdrawal assay. The periaqueductal gray (PAG) and serum samples were collected from the rats and used to determine the effect of EVO on the levels of serum nitric oxide (NO), CGRP, c-Fos, neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS) and the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor GluA1. The formalin test and the warm water tail-withdrawal assay showed that EVO inhibited the licking foot/shaking response and reversed the shortened tail-withdrawal latency in NTG-treated rats. Additionally, EVO suppressed serum NO levels and reduced the mRNA/protein expression of c-Fos and nNOS, but not iNOS, in the PAG. Furthermore, EVO suppressed total protein expression of the AMPA receptor GluA1 and its phosphorylation at Ser831 and Ser845. This study showed that EVO inhibits the migraine-like pain response and that this beneficial effect might be attributed to the regulation of nNOS and suppression of the AMPA receptor GluA1. We suggest that EVO has the potential to treat migraine as a lead compound of natural origin. Image 1 • Evodiamine inhibits pain response and thermal hyperalgesia in the nitroglycerin-induced acute migraine rats. • Evodiamine suppresses nitric oxide level and reduces neuronal nitric oxide synthase expression. • Evodiamine suppresses AMPA receptor GluA1 expression. • Nitroglycerin-injection increases total AMPA receptor GluA1 expression in the periaqueductal gray. [ABSTRACT FROM AUTHOR]

Copy number variation (CNV) is an important type of genetic variations contributing to phenotypic differences in animals and may serve as an alternative molecular marker to single nucleotide polymorphism (SNP) for molecular breeding. We used whole-genome sequencing data to investigate the characteristic of CNVs and their associations with body weight and size traits for 504 120-day Lion-head geese. We detected 1,184,695 CNVs which consisted of 1,148,401 deletions and 36,294 duplications. Based on these CNVs, we obtained 8,043 CNV regions (CNVRs) including 7,578 deletions, 228 duplications and 237 mixeds, which covered 7.76% of the reference genome. The 81.03% of CNVRs had the length ranging from 50bp to1000bp. We filtered 8,767 high-quality genotyped CNVs (7,960 deletions and 807 duplications) to conduct the association analysis of the body weight and 11 body size traits with these CNVs. We found 42 chromosome-wide significant CNVs, among which 40 were novel, and 2 CNVs had the high linkage disequilibrium (r 2 >0.20) with adjacent SNPs with chromosome-wide significance. According to these significant CNVs, we annotated 47 genes. Among these genes, CEP112, TOM1L1 and STX8 simultaneously influenced body weight and other body size traits, which was worthy of further study., Competing Interests: Declaration of competing interest All authors declare no conflicts of interests., (Copyright © 2025. Published by Elsevier Inc.)

Purpose: To explore the safety and effectiveness of paclitaxel and tegafur, gimeracil and oteracil potassium (S-1) combined with apatinib in the conversion therapy for unresectable advanced gastric cancer., Methods: A total of 66 patients with advanced gastric cancer received treatment with paclitaxel + S-1 + apatinib. Patients evaluated as resectable advanced gastric cancer by the multiple disciplinary team (MDT) underwent the surgery. The clinical efficacy and adverse reactions of the patients receiving conversion therapy and the related indicators of those undergoing operation were recorded. Later, the survival of the patients was compared between successful conversion therapy (surgery) group and unsuccessful conversion therapy (non-surgery) group., Results: All the 66 patients completed 3-7 cycles of chemotherapy, with a median of 5 cycles, and the objective response rate (ORR) after conversion therapy was 71.2% (47/66). Among them, 48 patients received operation for (225.2±37.3) min on average, with the intraoperative blood loss of (168.2±40.9) mL and (50.9±12.3) intraoperative dissected lymph nodes, including 34 (70.8%) cases of R0 resection. According to the postoperative pathological tumor regression grading (TRG), there were 2 (4.2%) TRG 0 cases, 10 (20.8%) TRG 1 cases, 28 (58.3%) TRG 2 cases and 8 (16.7%) TRG 3 cases. The follow-up results revealed that the one-year overall survival (OS) of the patients was 93.8% (45/48) in successful conversion therapy (surgery) group and 61.1% (11/18) in unsuccessful conversion therapy (non-surgery) group., Conclusion: Paclitaxel and S-1 combined with apatinib can achieve a higher R0 resection rate, and improve the survival rate of patients with successful conversion therapy, showing high safety and efficacy.

C57BL/6 laboratory mice usually show black coat color. We observed a dilute (gray) coat color phenotype in progenies of two C57BL/6 mice. This phenotype is inherited in an autosomal recessive mode. To uncover the molecular mechanism underlying this naturally occurring phenotypic variation, we performed whole-genome sequencing (25×) on 10 offspring of the two founder mice. The whole-genome DNA sequencing and additional RNA-Seq data reveal that Myo5a is the gene responsible for the coat color dilution in C57BL/6 mice, and novel mutations in the Myo5a gene are likely causal. We further performed reverse transcription-quantitative PCR, and showed increased expression of truncated Myo5a transcripts encoding dysfunctional proteins and decreased expression of Myo5a full-length transcripts encoding functional proteins in mutant individuals. The decrease in full-length messenger RNA abundance was accompanied by reduced Myo5a protein level and deficient melanosome transport, a potential mechanistic link between the Myo5a mutations and the dilute color phenotype. This study not only advances our understanding of the molecular mechanisms of pigmentation in mice, but also provides a typical case of deciphering the molecular basis of phenotypic variation in mice by genomic analyses and subsequent functional work., (© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Objective: Copy number variations (CNVs) are a major source of genetic diversity complementary to single nucleotide polymorphism (SNP) in animals. The aim of the study was to performed a comprehensive genomic analysis of CNVs based on high density whole-genome SNP markers in Chinese Dongxiang spotted pigs., Methods: We used customized Affymetrix Axiom Pig1.4M array plates containing 1.4 million SNPs and the PennCNV algorithm to identify porcine CNVs on autosomes in Chinese Dongxiang spotted pigs. Then, the next generation sequence data was used to confirm the detected CNVs. Next, functional analysis was performed for gene contents in copy number variation regions (CNVRs). In addition, we compared the identified CNVRs with those reported ones and quantitative trait loci (QTL) in the pig QTL database., Results: We identified 871 putative CNVs belonging to 2,221 CNVRs on 17 autosomes. We further discarded CNVRs that were detected only in one individual, leaving us 166 CNVRs in total. The 166 CNVRs ranged from 2.89 kb to 617.53 kb with a mean value of 93.65 kb and a genome coverage of 15.55 Mb, corresponding to 0.58% of the pig genome. A total of 119 (71.69%) of the identified CNVRs were confirmed by next generation sequence data. Moreover, functional annotation showed that these CNVRs are involved in a variety of molecular functions. More than half (56.63%) of the CNVRs (n = 94) have been reported in previous studies, while 72 CNVRs are reported for the first time. In addition, 162 (97.59%) CNVRs were found to overlap with 2,765 previously reported QTLs affecting 378 phenotypic traits., Conclusion: The findings improve the catalog of pig CNVs and provide insights and novel molecular markers for further genetic analyses of Chinese indigenous pigs.

Vertnin ( VRTN ) variants are associated with thoracic vertebral number (TVN) in pigs. However, the biological function of VRTN remains poorly understood. Here we first conducted a range of experiments to demonstrate that VRTN is a responsible gene for TVN and two causative variants in the regulatory region of VRTN additively regulate TVN. Then, we show that VRTN is a novel DNA-binding transcription factor as it localizes exclusively in the nucleus, binds to DNA on a genome-wide scale and regulates the transcription of a set of genes that harbor VRTN binding motifs. Next, we illustrate that VRTN is essential for the development of thoracic vertebrae. Vrtn -null embryos display somitogenesis defect with the failure of axial rotation and fewer somites at the thoracic somite stage. Half of Vrtn heterozygous mice show abnormal spinal development with fewer thoracic vertebrae and ribs than their wild-type littermates. Lastly, we reveal that VRTN could modulate somite segmentation via the Notch signaling pathway. The findings advance our understanding of the mechanisms underlying the development of thoracic vertebrate in mammals, and VRTN causative variants provide a robust tool to improve pork production by selecting the alleles increasing the number of thoracic vertebrae and ribs., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Peroxisome proliferator-activated receptor beta/delta (PPARD) is an important determinant of multiple biological processes. Our previous studies identified a missense mutation in the PPARD gene that significantly reduces its transcription activity, and consequently causes enlarged external ears in pigs. However, the mechanisms underlying the causality has remained largely unknown. Here, we show that PPARD retards the development of auricular cartilage by accelerating the apoptosis of cartilage stem/progenitor cells (CSPCs), the terminal differentiation of cartilage cells and the degradation of cartilage extracellular matrix in the auricle. At the transcription level, PPARD upregulates a set of genes that are associated with CSPCs apoptosis and chondrogenic differentiation, chondroblast differentiation and extracellular matrix degradation. ChIP-seq identified direct target genes of PPARD, including a well-documented gene for cartilage development: PPARG . We further show that compared to wild-type PPARD, the G32E mutant up-regulates the expression of PPARG and subsequently leads to the downregulation of critical genes that inhibit cartilage growth. These findings allow us to conclude that PPARD is an inhibitor of auricular cartilage growth in pigs. The causative mutation (G32E) in the PPARD gene attenuates the PPARD-mediated retardation of cartilage growth in the auricle, contributing to enlarged ears in pigs. The findings advance our understanding of the mechanisms underlying auricular development in mammals, and shed insight into the studies of innate pinna disorders and cartilage regeneration medicine in humans., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Microglial activation contributes to neuroinflammation and neuronal damage in neurodegenerative disorders including Alzheimer's and Parkinson's diseases. It has been suggested that neurodegenerative disorders may be improved if neuroinflammation can be controlled. trans -cinnamaldehyde (TCA) isolated from the stem bark of Cinnamomum cassia possesses potent anti-inflammatory capability; we thus tested whether TCA presents neuroprotective effects on improving neuronal survival by inhibiting neuroinflammatory responses in BV2 microglial cells., Results: To determine the molecular mechanism behind TCA-mediated neuroprotective effects, we assessed the effects of TCA on lipopolysaccharide- (LPS-) induced proinflammatory responses in BV2 microglial cells. While LPS potently induced the production and expression upregulation of proinflammatory mediators, including NO, iNOS, COX-2, IL-1 β , and TNF- α , TCA pretreatment significantly inhibited LPS-induced production of NO and expression of iNOS, COX-2, and IL-1 β and recovered the morphological changes in BV2 cells. TCA markedly attenuated microglial activation and neuroinflammation by blocking nuclear factor kappa B (NF- κ B) signaling pathway. With the aid of microglia and neuron coculture system, we showed that TCA greatly reduced LPS-elicited neuronal death and exerted neuroprotective effects., Conclusions: Our results suggest that TCA, a natural product, has the potential of being used as a therapeutic agent against neuroinflammation for ameliorating neurodegenerative disorders.