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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

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]

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-1β, and TNF-α, TCA pretreatment significantly inhibited LPS-induced production of NO and expression of iNOS, COX-2, and IL-1β and recovered the morphological changes in BV2 cells. TCA markedly attenuated microglial activation and neuroinflammation by blocking nuclear factor kappa B (NF-κB) 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. [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]

• Novel loci that affect the backfat thickness and chest circumference were noted. • Imputation increased the detection power of genome-wide association study for growth and fatness traits. • Sujiang pigs are derived from the Duroc and Chinese indigenous pigs. • The molecular basis underlying growth and fatness traits in pigs was elucidated. • Molecular markers for selective breeding in Sujiang pigs were identified. Sujiang pigs are a synthetic breed derived from Jiangquhai, Fengjing, and Duroc pigs. In this study, we sequenced the genome of 62 pigs with a coverage depth of 10× to 20×, including 27 Sujiang and 35 founder breed pigs, and we collected 360 global pigs' genome sequence data from public databases including 39 Duroc pigs. We obtained a high-quality variant dataset of 365 Sujiang pigs by imputing the porcine 80 K single nucleotide polymorphism (SNP) Beadchip to the whole-genome scale with a total of 422 pigs as a reference panel. A dataset of 365 imputated Sujiang pigs was used to perform single-trait genome-wide association study (GWAS) and meta-analyses for growth and fatness traits. Single-trait GWAS identified 1 907, 18, and 14 SNPs surpassing the suggestively significant threshold for backfat thickness, chest circumference, and chest width, respectively. Meta-analyses identified 2 400 genome-wide significant SNPs and 520 suggestively significant SNPs for backfat thickness and chest circumference, and 719 genome-wide significant SNPs and 1 225 suggestively significant SNPs for all seven traits. According to the meta-analysis of backfat thickness and chest circumference, a remarkable region of 2.69 Mb on Sus scrofa chromosome 4 containing FAM110B , IMPAD1 , LYN , MOS , PENK , PLAG1 , SDR16C5 and XKR4 was identified as a candidate region. The haplotype heat map of the 2.69 Mb region verified that Sujiang pigs were derived from Duroc and Chinese indigenous pigs, especially Jiangquhai pigs. The Kruskal-Wallis test showed that haplotypes of the 2.69 Mb region significantly affected backfat thickness and chest circumference traits. We then focused on PLAG1 , an important growth-related gene, and identified two synonymous SNPs with obvious differences among different breeds in the PLAG1 gene. We then performed genotyping of 365 Sujiang, 150 Duroc, 95 Jiangquhai, and 100 Fengjing pigs to confirm the above result and verified that the two variants significantly affected phenotypes of growth and fatness traits. Our findings not only provide insights into the genetic architecture of porcine growth and fatness traits but also provide potential markers for selective breeding of these traits in Sujiang pigs. [ABSTRACT FROM AUTHOR]

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]

This study investigated physiological and biochemical changes in pakchoi at different growth stages (25 and 50 d) under different tris-(1-chloro-2-propyl) phosphate (TCIPP) treatments (10, 100, 500, and 1000 μg kg−1). The uptake and accumulation of TCIPP by pakchoi and variation of TCIPP speciation in soil were also determined. TCIPP decreased the length and fresh weight of pakchoi root compared with those in blank controls, and this effect was significant when the concentration of TCIPP was higher than 100 μg kg−1. The fresh weight of pakchoi stems and leaves, the chlorophyll content, and the activities of superoxide dismutase, peroxidase, and catalase in the leaves first increased and then decreased with increasing TCIPP concentration. The inflection point of the variation in these indices was 100 μg kg−1 TCIPP in soil. The contents of proline and malondialdehyde increased continuously with increasing TCIPP concentration. The uptake of TCIPP by pakchoi increased linearly with increasing TCIPP concentration, and the highest TCIPP concentrations in the roots, stems, and leaves were 275.9, 80.0, and 2126.3 μg kg−1, respectively. TCIPP was easily transferred from the roots to leaves of pakchoi, with translocation factor of up to 12.6. The content of bioavailable TCIPP in soil was high, accounting for 46.5%. Planting pakchoi could significantly reduce the content of bioavailable TCIPP, with removal rate of 39.9%–54.1%. After 50 d of planting pakchoi, the removal rate of TCIPP in soil (10.4%–18.6%) was significantly higher than that in the control without plant, but the contribution of phytoextraction was small, accounting for 2.62%–26.6%. [Display omitted] • TCIPP treatment induced physiological and biochemical changes in pakchoi. • TCIPP uptake by pakchoi increased linearly with increasing TCIPP concentration. • TCIPP was easily transferred from the roots to leaves of pakchoi, with TF up to 12.6. • The content of bioavailable TCIPP in soil was high, accounting for 46.5%. • Planting pakchoi could significantly increase the removal rate of TCIPP in soil. [ABSTRACT FROM AUTHOR]

A total of 24 surface sediment samples were collected from Liao River, Northeast China. The concentration, spatial distribution, potential source, and ecological risk of 13 organophosphate esters (OPEs) flame retardants and plasticizers were analyzed. The total concentrations of OPEs varied considerably, ranging from 19.7 to 234 ng g−1 dry weight (dw), with the mean concentrations of 64.2 ± 52.2 ng g−1 dw. The OPEs pollution was increasing from upstream to downstream of Liao River. Compared with other sediments of rivers and lakes all over the world, Liao River has been seriously contaminated by OPEs, especially tributyl phosphate (TNBP) and tri-butoxyethyl phosphate (TBOEP). TNBP was the most abundant OPEs, followed by TBOEP and triphenylphosphine oxide. Their mean relative contributions were 26.3%, 12.4% and 11.6%, respectively. Positive matrix factorization indicated that OPEs in sediments from Liao River might be derived from plastic, textile, and polyurethane foam, anti-foam agent, hydraulic fluids, and coatings, indoor release, and chemical process emission. The risk of potential adverse effects of each individually OPEs on aquatic organisms were low (risk quotient less than 0.1). 2-Ethylhexyl diphenyl phosphate was the main substance causing risk. Image 1 • The 13 targets OPEs were detected in surface sediment samples from Liao River with 100% detection frequency. • The OPEs pollution was increasing from upstream to downstream of Liao River. • Liao River has been seriously contaminated by OPEs, especially TNBP and TBOEP. • TNBP was the most abundant OPEs, followed by TBOEP and TPPO. • EHDPP was the main substance causing risk. [ABSTRACT FROM AUTHOR]

Depression is a mental disease that significantly reduces the quality of patients' life. Around 322 million people of all ages carry the heavy burden of depression on a worldwide scale, with a life-time prevalence of 20% according to the WHO. Trans-cinnamaldehyde (TCA) is an excellent COX-2 inhibitor in central nervous system which is a main constituent of GUIZHI as a member of traditional Chinese herb. Furthermore, previous studies demonstrated that TCA suppressed depression-like behavior in chronic unexpected mild stress, plus maze test and open field test. However, the molecular mechanism of TCA anti-depression effect is not clear. We examined the immobility of TCA pretreated male BALB/c mice in the forced swimming test (FST). Results show that TCA (50 mg/kg, po) revealed a significant effect on reduced immobility in the FST, compared with SAL group which indicated that TCA suppressed depression-like behavior. Moreover, TCA elevated the level of 5-HT and decreased the ratio of Glu/GABA in mice hippocampus. Compared with SAL + FST group, TCA + FST group significantly decreased COX-2, TRPV1 and CB1 protein level in mice hippocampus (p < 0.05, p < 0.05, p < 0.01). These findings suggest that TCA treatment exerted anti-depressive effect and was able to regulate neurotransmitters in the FST. This effect may have positive influence on the endocannabinoid (eCB) system. • Trans-cinnamaldehyde treatment significantly reduced immobility in the forced swimming test. • Trans-cinnamaldehyde treatment elevated the level of 5-HT and the radio of Glu/GABA. • Trans-cinnamaldehyde treatment inhibited protein expression of COX-2, TRPV1 and CB1. [ABSTRACT FROM AUTHOR]

The hypothalamic-pituitary-gonad (HPG) axis is vital for reproductive activities in vertebrates. The large-scale comparative analyses of gene expression in the HPG axis across vertebrates have not been carried out yet. Here we collected 175 high-quality RNA-seq samples of hypothalamus, pituitary, ovary and testis from eight species (four mammals and four poultry) to compare transcriptome in the HPG axis, and to detect key pathways and related genes associated with reproduction. We demonstrated the distinguished difference in gene expression of the HPG axis between mammalian and avian species by a series of bioinformatics analysis, including gene differential expression, the phylogeny analysis of gene expression, and their functional annotations. We revealed two pathways, i.e., neuroactive ligand-receptor interaction and calcium signaling pathway, which play important roles in animal reproduction. In these two pathways, we detected 17 differentially expressed genes shared in 4 tissues, while 13, 27, and 27 were specifically differentially expressed genes in hypothalamus, pituitary and ovary, respectively. Our study on the comparative transcriptomics in the HPG axis across species will provide novel knowledge for exploring the molecular mechanism underlying reproductive traits in animals. • The distinguished difference in gene expression of HPG axis of mammals and poultry. • The neuroactive ligand-receptor interaction and calcium signaling pathways shared in 4 tissues. • The 17 DEGs are key for reproductive divergence between mammals and poultry. [ABSTRACT FROM AUTHOR]

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.

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.

The domestication and artificial selection of wild boars have led to dramatic morphological and behavioral changes, especially in East Chinese (ECN) pigs. Here, we provide insights into the population structure and current genetic diversity of representative ECN pig breeds. We identify a 500-kb region containing six tooth development-relevant genes with almost completely different haplotypes between ECN pigs and Chinese wild boars or European domestic pigs. Notably, the c.195A>G missense mutation in exon 2 of AMBN may cause alterations in its protein structure associated with tusk degradation in ECN pigs. In addition, ESR1 may play an important role in the reproductive performance of ECN pigs. A major haplotype of the large lop ear-related MSRB3 gene and eight alleles in the deafness-related GRM7 gene may affect ear morphology and hearing in ECN pigs. Interestingly, we find that the two-end black (TEB) coat color in Jinhua pigs is most likely caused by EDNRB with genetic mechanisms different from other Chinese TEB pigs. This study identifies key loci that may be artificially selected in Chinese native pigs related to the tusk, coat color, and ear morphology, thus providing new insights into the genetic mechanisms of domesticated pigs., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

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., Competing Interests: None of the authors have any competing interests in the manuscript., (© 2019 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

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.