Progesterone improved the behavior of PC12 cells under OGD/R by reducing FABP5 expression and inhibiting TLR4/NF-κB signaling pathway.

Herein, PC12 cells were applied to detect the impact of progesterone under oxygen glucose deprivation/reperfusion (OGD/R) stimulation. The cell proliferation of PC12 cells was evaluated by cell counting kit-8 assay, and the concentrations of MDA, ROS and SOD were examined by their corresponding Enzyme Linked Immunosorbent Assay kits. The invasion and migration properties of PC12 cells were evaluated by transwell and wound healing assays, respectively. The expression patterns of related genes were evaluated by western blot and qPCR. Under OGD/R stimulation, progesterone treatment could elevate the viability of PC12 cells, reduce the levels of MDA and ROS, and elevate the concentration of SOD. Moreover, progesterone treatment could strengthen the invasion and migration abilities of PC12 cells under OGD/R condition, as well as decrease the apoptosis and inflammation. FABP5 expression was significantly increased in PC12 cells under OGD/R stimulation, which was reversed after progesterone stimulation. Under OGD/R stimulation, the protective effects of progesterone on PC12 cells were strengthened after si-FABP5 treatment. The protein levels of TLR4, p-P65 NF-κB, and P65 NF-κB in OGD/R-induced PC12 cells were increased, which were inhibited after progesterone treatment. Progesterone exerted protective effects on PC12 cells by targeting FABP5 under OGD/R stimulation.

Short-term culture for rapid identification by mass spectrometry and automated antimicrobial susceptibility testing from positive bottles.

BACKGROUND: Early and appropriate antibiotic treatment improves the clinical outcome of patients with sepsis. There is an urgent need for rapid identification (ID) and antimicrobial susceptibility testing (AST) of bacteria that cause bloodstream infection (BSI). Rapid ID and AST can be achieved by short-term incubation on solid medium of positive blood cultures using MALDI-TOF mass spectrometry (MS) and the BD M50 system. The purpose of this study is to evaluate the performance of rapid method compared to traditional method. METHODS: A total of 124 mono-microbial samples were collected. Positive blood culture samples were short-term incubated on blood agar plates and chocolate agar plates for 5 ∼ 7 h, and the rapid ID and AST were achieved through Zybio EXS2000 MS and BD M50 System, respectively. RESULTS: Compared with the traditional 24 h culture for ID, this rapid method can shorten the cultivation time to 5 ∼ 7 h. Accurate organism ID was achieved in 90.6% of Gram-positive bacteria (GP), 98.5% of Gram-negative bacteria (GN), and 100% of fungi. The AST resulted in the 98.5% essential agreement (EA) and 97.1% category agreements (CA) in NMIC-413, 99.4% EA and 98.9% CA in PMIC-92, 100% both EA and CA in SMIC-2. Besides, this method can be used for 67.2% (264/393) of culture bottles during routine work. The mean turn-around time (TAT) for obtaining final results by conventional method is approximately 72.6 ± 10.5 h, which is nearly 24 h longer than the rapid method. CONCLUSIONS: The newly described method is expected to provide faster and reliable ID and AST results, making it an important tool for rapid management of blood cultures (BCs). In addition, this rapid method can be used to process most positive blood cultures, enabling patients to receive rapid and effective treatment.

Risk factors and predicting nomogram for the clinical deterioration of non-severe community-acquired pneumonia.

BACKGROUND: Currently, there remains insufficient focus on non-severe community-acquired pneumonia (CAP) patients who are at risk of clinical deterioration, and there is also a dearth of research on the related risk factors. Early recognition of hospitalized patients at risk of clinical deterioration will be beneficial for their clinical management. METHOD: A retrospective study was conducted in The First Affiliated Hospital of Wenzhou Medical University, China, spanning from January 1, 2018 to April 30, 2022, and involving a total of 1,632 non-severe CAP patients. Based on whether their condition worsened within 72 h of admission, patients were divided into a clinical deterioration group and a non-clinical deterioration group. Additionally, all patients were randomly assigned to a training set containing 75% of patients and a validation set containing 25% of patients. In the training set, risk factors for clinical deterioration in patients with non-severe CAP were identified by using LASSO regression analysis and multivariate logistic regression analysis. A nomogram was developed based on identified risk factors. The effectiveness of the nomogram in both the training and validation sets was assessed using Receiver Operating Characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Age, body mass index (BMI), body temperature, cardiovascular comorbidity, respiratory rate, LDH level, lymphocyte count and D-dimer level were identified as risk factors associated with the clinical deterioration of non-severe CAP within 72 h of admission. The area under curve (AUC) value of the nomogram was 0.78 (95% CI: 0.74-0.82) in the training set and 0.75 (95% CI: 0.67-0.83) in the validation set. Furthermore, the calibration curves for both the training and validation sets indicated that the predicted probability of clinical deterioration aligned with the actual probability. Additionally, DCA revealed clinical utility for the nomogram at a specific threshold probability. CONCLUSION: The study successfully identified the risk factors linked to the clinical deterioration of non-severe CAP and constructed a nomogram for predicting the probability of deterioration. The nomogram demonstrated favorable predictive performance and has the potential to aid in the early identification and management of non-severe CAP patients at elevated risk of deterioration.

Assessing Swallowing Dysfunction Aggravation in Chronic Obstructive Pulmonary Disease Patients Using Ultrasonic Measurements With Swallowing Movement Parameters.

OBJECTIVE: To investigate the correlation between ultrasonic measurements of swallowing movement parameters and aggravation of swallowing dysfunction in patients with chronic obstructive pulmonary disease (COPD). METHODS: COPD patients with swallowing dysfunction (n = 120) and COPD patients with normal swallowing function (n = 100) treated in our hospital between January 2020 and January 2023 were included in observation and control groups, respectively. The correlation between ultrasonic measurements of swallowing movement parameters and COPD with swallowing dysfunction was analyzed. The observation group was divided into mild and severe groups according to their Gugging Swallowing Screen (GUSS) scores. The correlation between ultrasonic measurements of swallowing movement parameters and COPD exacerbation combined with swallowing dysfunction was analyzed. RESULTS: In the observation group, Hyoid muscle thickness, hyoid bone displacement, geniohyoid muscle movement distance, HLAS, and CSR were lower compared to the control group, negatively associated with COPD-related swallowing issues. Conversely, geniohyoid muscle movement time and minimum hyohyoid distance (NHLA) were higher in the observation group, positively correlated with COPD-related swallowing dysfunction. In COPD patients with swallowing problems, the severe group exhibited lower values for lingual muscle thickness, hyoid bone displacement, geniohyoid muscle movement distance, HLAS, and CSR compared to the mild group, while geniohyoid muscle movement time and NHLA were higher in the severe group. Receiver operating characteristic (ROC) curves were created, indicating the promising diagnostic utility of these parameters for assessing the presence and severity of swallowing dysfunction in COPD patients. CONCLUSION: The ultrasonic measurement of swallowing motion parameters can effectively assess swallowing dysfunction in COPD patients.

In vivo pharmacokinetic study of vanillic acid in monocrotaline-induced pulmonary arterial hypertension rats and its tissue distribution.

Vanillic acid (VA) is a bioactive chemical present in many food plants and fruits. It has been shown to have a protective effect on pulmonary tissues in monocrotaline-induced pulmonary arterial hypertension, as well as an intervention effect on right ventricular remodeling. The purpose of this study was to develop and test a reliable method for assessing VA utilizing ultra-performance liquid chromatography-high resolution mass spectrometry using caffeic acid as the internal standard. Across diverse substrates, the correlation coefficient for VA ranged from 0.9992 to 0.9995. The method's intraday precision was <13.53% (RSD), and its accuracy (RE) ranged from -9.88 to 4.35%. The precision across days was <13.69% (RSD), while the accuracy ranged from 2.16 to 10.94% (RE). The extraction recoveries ranged from 80.30 to 118.81%, with a lower limit of quantification of 20 ng/mL. The approach was successfully applied to pharmacokinetic and tissue distribution studies of VA in rat plasma after gavage administration, and the pharmacokinetic parameters of VA in the plasma of the monocrotaline-induced pulmonary arterial hypertension were significantly different from those of the control group.

4-Terpineol attenuates pulmonary vascular remodeling via suppressing PI3K/Akt signaling pathway in hypoxia-induced pulmonary hypertension rats.

The hyperproliferation of pulmonary arterial smooth muscle cells (PASMCs) plays a pivotal role in pulmonary arterial remodeling (PAR) of hypoxia-induced pulmonary hypertension (HPH). 4-Terpineol is a constituent of Myristic fragrant volatile oil in Santan Sumtang. Our previous study found that Myristic fragrant volatile oil alleviated PAR in HPH rats. However, the effect and pharmacological mechanism of 4-terpineol in HPH rats remain unexplored. Male Sprague-Dawley rats were exposed to hypobaric hypoxia chamber (simulated altitudes of 4500 m) for 4 weeks to establish an HPH model in this study. During this period, rats were intragastrically administrated with 4-terpineol or sildenafil. After that, hemodynamic indexes and histopathological changes were assessed. Moreover, a hypoxia-induced cellular proliferative model was established by exposing PASMCs to 3% O2. PASMCs were pretreated with 4-terpineol or LY294002 to explore whether 4-terpineol targeted PI3K/Akt signaling pathway. The PI3K/Akt-related proteins expression was also accessed in lung tissues of HPH rats. We found that 4-terpineol attenuated mPAP and PAR in HPH rats. Then, cellular experiments showed 4-terpineol inhibited hypoxia-induced PASMCs proliferation via down-regulating PI3K/Akt expression. Furthermore, 4-terpineol decreased the p-Akt, p-p38, and p-GSK-3ß protein expression, as well as reduced the PCNA, CDK4, Bcl-2 and Cyclin D1 protein levels, while increasing levels of cleaved caspase 3, Bax, and p27kip1in lung tissues of HPH rats. Our results suggested that 4-terpineol mitigated PAR in HPH rats by inhibiting the proliferation and inducing apoptosis of PASMCs through suppression of the PI3K/Akt-related signaling pathway.

Kaempferol ameliorates pulmonary vascular remodeling in chronic hypoxia-induced pulmonary hypertension rats via regulating Akt-GSK3ß-cyclin axis.

Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) is considered a major contributor to elevated pulmonary vascular resistance and a key mechanism of vascular remodeling in hypoxia-induced pulmonary hypertension (HPH). Kaempferol is a natural flavonoid compound and can be derived from numerous common medicinal herbs and vegetables, which exhibit antiproliferative and proapoptotic properties, however, the effects of kaempferol on vascular remodeling in HPH remain unexplored. In this study, SD rats were placed in a hypobaric hypoxia chamber for four weeks to establish a pulmonary hypertension model and given either kaempferol or sildenafil (an inhibitor of PDE-5) during days 1-28, after which the hemodynamic parameter and pulmonary vascular morphometry were assessed. Furthermore, primary rat PASMCs were exposed to hypoxic conditions to generate a cell proliferation model, then incubated with either kaempferol or LY294002 (an inhibitor of PI3K). Immunoblotting and real-time quantitative PCR assessed the protein and mRNA expression levels in HPH rat lungs and PASMCs. We found that kaempferol reduced pulmonary artery pressure and pulmonary vascular remodeling, and alleviated right ventricular hypertrophy in HPH rats. The mechanistic analysis demonstrated that kaempferol reduced the protein levels of phosphorylation of Akt and GSK3ß, leading to decreased expression of pro-proliferation (CDK2, CDK4, Cyclin D1, and PCNA) and anti-apoptotic related proteins (Bcl-2) and increased expression of pro-apoptosis proteins (Bax and cleaved caspase 3). These results collectively demonstrate that kaempferol ameliorates HPH in rats by inhibiting PASMC proliferation and pro-apoptosis via modulation of the Akt/GSK3ß/CyclinD axis.

Efficacy of dynamic interpersonal therapy for major depressive disorder in China: results of a multicentered, three-arm, randomized, controlled trial.

BACKGROUND: Dynamic interpersonal therapy (DIT) is a brief, structured psychodynamic psychotherapy with demonstrated efficacy in treating major depressive disorder (MDD). The aim of the study was to determine whether DIT is an acceptable and efficacious treatment for MDD patients in China. METHOD: Patients were randomized to 16-week treatments with either DIT plus antidepressant medication (DIT + ADM; n = 66), general supportive therapy plus antidepressant medication (GST + ADM; n = 75) or antidepressant medication alone (ADM; n = 70). The Hamilton Depression Rating Scale (HAMD) administered by blind raters was the primary efficacy measure. Assessments were completed during the acute 16-week treatment and up to 12-month posttreatment. RESULTS: The group × time interaction was significant for the primary outcome HAMD (F = 2.900, df1 = 10, df2 = 774.72, p = 0.001) in the acute treatment phase. Pairwise comparisons showed a benefit of DIT + ADM over ADM at weeks 12 [least-squares (LS) mean difference = -3.161, p = 0.007] and 16 (LS mean difference = -3.237, p = 0.004). Because of the unexpected high attrition during the posttreatment follow-up phase, analyses of follow-up data were considered exploratory. Differences between DIT + ADM and ADM remained significant at the 1-, 6-, and 12-month follow-up (ps range from 0.001 to 0.027). DIT + ADM had no advantage over GST + ADM during the acute treatment phase. However, at the 12-month follow-up, patients who received DIT remained less depressed. CONCLUSIONS: Acute treatment with DIT or GST in combination with ADM was similarly efficacious in reducing depressive symptoms and yielded a better outcome than ADM alone. DIT may provide MDD patients with long-term benefits in symptom improvement but results must be viewed with caution.

Fluorescence sensing and glycosidase inhibition effect of multivalent glycosidase inhibitors based on Naphthalimide-deoxynojirimycin conjugates.

Synthetic glycoconjugates as chemical probes have been widely developed for the detection of glycosidase enzymes. However, the binding interactions between iminosugar derivatives and glycosidases were limited, especially for the binding interactions between multivalent glycosidase inhibitors and α-glycosidases. In this paper, three naphthalimide-DNJ conjugates were synthesized. Furthermore, the binding interactions and glycosidase inhibition effects of them were investigated. It was found that the strong binding interactions of multivalent glycosidase inhibitors with enzymes were related to the efficient inhibitory activity against glycosidase. Moreover, the lengths of the chain between DNJ moieties and the triazole ring for the naphthalimide-DNJ conjugates influenced the self-assembly properties, binding interactions and glycosidase inhibition activities with multisource glycosidases. Compound 13 with six carbons between the DNJ moiety and triazole ring showed the stronger binding interactions and better glycosidase inhibition activities against α-mannosidase (jack bean) and α-glucosidase (aspergillus niger). In addition, compound 13 showed an effective PBG inhibition effect in mice with 51.18 % decrease in blood glucose at 30 min. This result opens a way for detection of multivalent glycosidase inhibition effect by a fluorescent sensing method.

Risk estimation for postoperative nausea and vomiting: development and validation of a nomogram based on point-of-care gastric ultrasound.

BACKGROUND: We aimed to develop a nomogram that can be combined with point-of-care gastric ultrasound and utilised to predict postoperative nausea and vomiting (PONV) in adult patients after emergency surgery. METHODS: Imaging and clinical data of 236 adult patients undergoing emergency surgery in a university hospital between April 2022 and February 2023 were prospectively collected. Patients were divided into a training cohort (n = 177) and a verification cohort (n = 59) in a ratio of 3:1, according to a random number table. After univariate analysis and multivariate logistic regression analysis of the training cohort, independent risk factors for PONV were screened to develop the nomogram model. The receiver operating characteristic curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the prediction efficiency, accuracy, and clinical practicability of the model. RESULTS: Univariate analysis and multivariate logistic regression analysis showed that female sex, history of PONV, history of migraine and gastric cross-sectional area were independent risk factors for PONV. These four independent risk factors were utilised to construct the nomogram model, which achieved significant concordance indices of 0.832 (95% confidence interval [CI], 0.771-0.893) and 0.827 (95% CI, 0.722-0.932) for predicting PONV in the training and validation cohorts, respectively. The nomogram also had well-fitted calibration curves. DCA and CIC indicated that the nomogram had great clinical practicability. CONCLUSIONS: This study demonstrated the prediction efficacy, differentiation, and clinical practicability of a nomogram for predicting PONV. This nomogram may serve as an intuitive and visual guide for rapid risk assessment in patients with PONV before emergency surgery.

Development of trisiloxane surfactant vesicles ultrasonic extraction method combined with ultrahigh-performance liquid chromatography tandem mass spectrometry for the rapid differentiation of Bupleuri Radix based on metabolomics.

INTRODUCTION: Due to the variety, chemical composition and complex structure, the quality control of Bupleuri Radix (BR) is a challenging task. There are still many trace compounds in BR that are difficult to extract and detect. OBJECTIVE: To develop an innovative method of trisiloxane surfactant vesicles ultrasonic extraction (TSVUE) combined with ultrahigh-performance liquid chromatography tandem mass spectrometry for the identification from Bupleurum chinense DC. (BC) to Bupleurum scorzonerifolium Willd (BS) based on metabolomics. METHODS: Based on extraction effect for BR, five different types of surfactants vesicles were prepared and compared. Then, a single-factor test and a response surface methodology study were adopted to obtain the optimal conditions for the surfactant vesicles ultrasonic extraction method. Finally, a non-targeted metabolomics method with information dependent acquisition mode was performed to analyse differential metabolites in BC and BS. RESULTS: Sugar-based surfactant containing trisiloxane [N-3-propyl-methyltrisiloxane-N-glucoheptonamne (Si(3)N-GHA)] displayed higher extraction efficiency compared to other types of surfactants when it comes to being used in pretreatment methods. And a TSVUE method was established and optimised. In total, 131 constituents were identified in two BR herbs, of which 35 were unreported, and 11 were characterised as chemical markers. CONCLUSIONS: This method provides promising perspectives for rapidly identifying trace compounds in complex systems of traditional Chinese medicine (TCM), as well as for laying the foundation in the identification of similar herbs from the same species. Meanwhile, these findings serve as a promising application of trisiloxane surfactant vesicles in the extraction field of TCM.

Shear wave elastography combined with two-dimensional ultrasonography for detecting optic nerve sheath: An effective tool for assessing preeclampsia.

PURPOSE/OBJECTIVE: This study aimed to investigate two-dimensional ultrasound and shear-wave elastography (SWE) in evaluating optic neuropathy in preeclampsia. METHODS: Ninety-one singleton pregnant women (51 with preeclampsia [observation group]; 40 without complications [control group]) admitted between January 2022 and April 2022 participated in this study. Optic nerve sheath diameter (ONSD) and optic nerve stiffness measurement (ONSM) were measured using two-dimensional ultrasound and SWE, respectively, and compared between the two groups. Receiver operating characteristic curves were employed to evaluate the performance of ONSD, ONSM, and combination (ONSD + ONSM) for diagnosing preeclampsia. RESULTS: The observation (preeclampsia) group ONSD and ONSM were significantly higher than those in the control group (p < 0.05). Optimal diagnostic values for ONSD and ONSM were 4.10 mm and 11.20 kPa, respectively. Areas under the curve for diagnosing preeclampsia were 0.958 (95% confidence interval [CI], 0.926-0.990) for ONSD, 0.939 (95% CI, 0.894-0.985) for ONSM, and 0.982 (95% CI, 0.962-1.000) for ONSD + ONSM. There was no significant difference between ONSD and ONSM in diagnosing preeclampsia (p = 0.436). However, ONSD + ONSM was significantly advantageous over ONSD or ONSM alone in diagnosing preeclampsia (p = 0.033; p = 0.014). CONCLUSIONS: Ultrasonic evaluation of the optic nerve can quantitatively assess optic nerve changes in pregnant women with preeclampsia.

Vibronic Exciton-Phonon States in Stack-Engineered van der Waals Heterojunction Photodiodes.

Stack engineering, an atomic-scale metamaterial strategy, enables the design of optical and electronic properties in van der Waals heterostructure devices. Here we reveal the optoelectronic effects of stacking-induced strong coupling between atomic motion and interlayer excitons in WSe2/MoSe2 heterojunction photodiodes. To do so, we introduce the photocurrent spectroscopy of a stack-engineered photodiode as a sensitive technique for probing interlayer excitons, enabling access to vibronic states typically found only in molecule-like systems. The vibronic states in our stack are manifest as a palisade of pronounced periodic sidebands in the photocurrent spectrum in frequency windows close to the interlayer exciton resonances and can be shifted "on demand" through the application of a perpendicular electric field via a source-drain bias voltage. The observation of multiple well-resolved sidebands as well as their ability to be shifted by applied voltages vividly demonstrates the emergence of interlayer exciton vibronic structure in a stack-engineered optoelectronic device.

The Role of Organic Cation Transporters in the Pharmacokinetics, Pharmacodynamics and Drug-Drug Interactions of Tyrosine Kinase Inhibitors.

Tyrosine kinase inhibitors (TKIs) decisively contributed in revolutionizing the therapeutic approach to cancer, offering non-invasive, tolerable therapies for a better quality of life. Nonetheless, degree and duration of the response to TKI therapy vary depending on cancer molecular features, the ability of developing resistance to the drug, on pharmacokinetic alterations caused by germline variants and unwanted drug-drug interactions at the level of membrane transporters and metabolizing enzymes. A great deal of approved TKIs are inhibitors of the organic cation transporters (OCTs). A handful are also substrates of them. These transporters are polyspecific and highly expressed in normal epithelia, particularly the intestine, liver and kidney, and are, hence, arguably relevant sites of TKI interactions with other OCT substrates. Moreover, OCTs are often repressed in cancer cells and might contribute to the resistance of cancer cells to TKIs. This article reviews the OCT interactions with approved and in-development TKIs reported in vitro and in vivo and critically discusses the potential clinical ramifications thereof.

Design, Synthesis and Bioactivity Evaluation of Novel 2-(pyrazol-4-yl)-1,3,4-oxadiazoles Containing an Imidazole Fragment as Antibacterial Agents.

Imidazole alkaloids, a common class of five-membered aromatic heterocyclic compounds, exist widely in plants, animals and marine organisms. Because of imidazole's extensive and excellent biological and pharmacological activities, it has always been a topic of major interest for researchers and has been widely used as an active moiety in search of bioactive molecules. To find more efficient antibacterial compounds, a series of novel imidazole-fragment-decorated 2-(pyrazol-4-yl)-1,3,4-oxadiazoles were designed and synthesized based on our previous works via the active substructure splicing principle, and their bioactivities were systematically evaluated both in vitro and in vivo. The bioassays showed that some of the target compounds displayed excellent in vitro antibacterial activity toward three virulent phytopathogenic bacteria, including Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and Pseudomonas syringae pv. actinidiae (Psa), affording the lowest EC50 values of 7.40 (7c), 5.44 (9a) and 12.85 (9a) µg/mL, respectively. Meanwhile, compound 7c possessed good in vivo protective and curative activities to manage rice bacterial leaf blight at 200 µg/mL, with control efficacies of 47.34% and 41.18%, respectively. Furthermore, compound 9a showed commendable in vivo protective and curative activities to manage kiwifruit bacterial canker at 200 µg/mL, with control efficacies of 46.05% and 32.89%, respectively, which were much better than those of the commercial bactericide TC (31.58% and 17.11%, respectively). In addition, the antibacterial mechanism suggested that these new types of title compounds could negatively impact the cell membranes of phytopathogenic bacteria cells and cause the leakage of the intracellular component, thereby leading to the killing of bacteria. All these findings confirm that novel 2-(pyrazol-4-yl)-1,3,4-oxadiazoles containing an imidazole fragment are promising lead compounds for discovering new bactericidal agents.

Dissection of the practical soybean breeding pipeline by developing ZDX1, a high-throughput functional array.

KEY MESSAGE: We developed the ZDX1 high-throughput functional soybean array for high accuracy evaluation and selection of both parents and progeny, which can greatly accelerate soybean breeding. Microarray technology facilitates rapid, accurate, and economical genotyping. Here, using resequencing data from 2214 representative soybean accessions, we developed the high-throughput functional array ZDX1, containing 158,959 SNPs, covering 90.92% of soybean genes and sites related to important traits. By application of the array, a total of 817 accessions were genotyped, including three subpopulations of candidate parental lines, parental lines and their progeny from practical breeding. The fixed SNPs were identified in progeny, indicating artificial selection during the breeding process. By identifying functional sites of target traits, novel soybean cyst nematode-resistant progeny and maturity-related novel sources were identified by allele combinations, demonstrating that functional sites provide an efficient method for the rapid screening of desirable traits or gene sources. Notably, we found that the breeding index (BI) was a good indicator for progeny selection. Superior progeny were derived from the combination of distantly related parents, with at least one parent having a higher BI. Furthermore, new combinations based on good performance were proposed for further breeding after excluding redundant and closely related parents. Genomic best linear unbiased prediction (GBLUP) analysis was the best analysis method and achieved the highest accuracy in predicting four traits when comparing SNPs in genic regions rather than whole genomic or intergenic SNPs. The prediction accuracy was improved by 32.1% by using progeny to expand the training population. Collectively, a versatile assay demonstrated that the functional ZDX1 array provided efficient information for the design and optimization of a breeding pipeline for accelerated soybean breeding.

Diagnostic value of metagenomic next-generation sequencing of bronchoalveolar lavage fluid for the diagnosis of suspected pneumonia in immunocompromised patients.

BACKGROUND: To evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) in immunocompromised patients for the diagnosis of suspected pneumonia in comparison with that of conventional microbiological tests (CMTs). METHODS: Sixty-nine immunocompromised patients with suspected pneumonia received both CMTs and mNGS of BALF were analyzed retrospectively. The diagnostic value was compared between CMTs and mNGS, using the clinical composite diagnosis as the reference standard. RESULTS: Sixty patients were diagnosed of pneumonia including fifty-two patients with identified pathogens and eight patients with probable pathogens. Taking the composite reference standard as a gold standard, 42 pathogens were identified by CMTs including nine bacteria, 17 fungi, 8 virus, 6 Mycobacterium Tuberculosis, and two Legionella and 19(45%) of which were detected by BALF culture. As for mNGS, it identified 76 pathogens including 20 bacteria, 31 fungi, 14 virus, 5 Mycobacterium Tuberculosis, four Legionella and two Chlamydia psittaci. The overall detection rate of mNGS for pathogens were higher than that of CMTs. However, a comparable diagnostic accuracy of mNGS and CMTs were found for bacterial and viral infections. mNGS exhibited a higher diagnostic accuracy for fungal detection than CMTs (78% vs. 57%, P < 0.05), which mainly because of the high sensitivity of mNGS in patients with Pneumocystis jirovecii pneumonia (PJP) (100% vs. 28%, P < 0.05). Nineteen patients were identified as pulmonary co-infection, mNGS test showed a higher detection rate and broader spectrum for pathogen detection than that of CMTs in co-infection. Moreover, Pneumocystis jirovecii was the most common pathogen in co-infection and mNGS have identified much more co-pathogens of PJP than CMTs. CONCLUSIONS: mNGS of BALF improved the microbial detection rate of pathogens and exhibited remarkable advantages in detecting PJP and identifying co-infection in immunocompromised patients.

Diagnostic performance of the metagenomic next-generation sequencing in lung biopsy tissues in patients suspected of having a local pulmonary infection.

PURPOSE: This study aims to evaluate the diagnostic application and performance of the metagenomic next-generation sequencing (mNGS) in patients suspected of local pulmonary infection by comparing it to the traditional pathogen detection methods in lung tissue specimens obtained by a computerized tomography-guided biopsy (CT-guided biopsy). METHODS: We retrospectively reviewed patients, admitted to the First Affiliated Hospital of Wenzhou Medical University, China from May 2018 to December 2020, who were suspected of local pulmonary infection. All cases received a CT-guided lung biopsy, tissue samples were sent both for conventional examinations (CE) and mNGS tests. The sensitivity and specificity of the two diagnostic approaches were compared. RESULTS: 106 patients enrolled, 76 patients were diagnosed with a pulmonary infection. Among 49 patients with identified pathogens, CE confirmed pathogenic infections in 32 cases. Mycobacterium spp. and fungi accounted for 37.5% (12/32) and 28.1% (9/32), respectively, with bacteria 34.4% (11/32). The mNGS examination detected extra pathogenic microorganisms in 22 patients that were consistent with the patients' clinical and radiographic pictures. The sensitivity of mNGS was 53.9% vs. 42.1% for the CE, while the specificity was 56.7% versus 96.7%. For detection rate, mNGS was significantly superior to CE in bacterial (96.3% vs. 40.7%, p < 0.05), and mixed infections (100% vs. 50%, p < 0.05), but inferior to CE in fungal (60% vs. 90%, p > 0.05) and Mycobacterium spp. infections (66.7% vs. 100%, p > 0.05) with no significant difference. Among 31 cases diagnosed with lung abscess, the diagnostic performance of the detection rate was 67.7% (21/31) in favour of mNGS compared to 29.0% (9/31) for CE (p < 0.05). Most polymicrobial infections were induced by anaerobic species that coexisted with Streptococcus constellatus. And Klebsiella pneumoniae was the most common isolated monomicrobial infection. CONCLUSIONS: The most commonly detected causative pathogens for local pulmonary infections were bacteria, Mycobacterium spp. and fungi. Compared with the CE, the advantages of mNGS in the pathogens detection lie in the discovery of bacterial and mixed infections, as well as in the detection of lung abscess. Conversely, mNGS is not good enough to be recommendable for the detection of Mycobacterium spp. and fungi.

Twelve New Seco-Pregnane Glycosides from Cynanchum taihangense.

For our interest in the potential biologically active and structurally unique steroidal glycosides, continued phytochemical investigation of Cynanchum taihangense was carried out; twelve new seco-pregnane glycosides, cynataihosides I-L (1-4), M-T (7-14), and two known glycosides, glaucoside A (5) and atratcynoside F (6), were isolated from the 95% ethanol extract of Cynanchum taihangense. Two new aglycones were found among compounds 10, 11, 13, and 14. The structures of the glycosides were elucidated based on 1D and 2D NMR spectroscopic data, HR-ESI-MS analysis, and chemical evidence. The cytotoxicity of compounds against three human tumor cell lines (HL-60, THP-1, and PC-3) were evaluated by MTT assay. Compound 11 displayed significant cytotoxicity against THP-1 and PC-3 cell line with IC50 values of 5.08 and 22.75 µm, respectively. Compounds 3 and 14 exhibited moderate and selective cytotoxicity on HL-60 and THP-1 with IC50 values of 17.78 and 16.02 µm, respectively.

SoySNP618K array: A high-resolution single nucleotide polymorphism platform as a valuable genomic resource for soybean genetics and breeding.

Innovations in genomics have enabled the development of low-cost, high-resolution, single nucleotide polymorphism (SNP) genotyping arrays that accelerate breeding progress and support basic research in crop science. Here, we developed and validated the SoySNP618K array (618,888 SNPs) for the important crop soybean. The SNPs were selected from whole-genome resequencing data containing 2,214 diverse soybean accessions; 29.34% of the SNPs mapped to genic regions representing 86.85% of the 56,044 annotated high-confidence genes. Identity-by-state analyses of 318 soybeans revealed 17 redundant accessions, highlighting the potential of the SoySNP618K array in supporting gene bank management. The patterns of population stratification and genomic regions enriched through domestication were highly consistent with previous findings based on resequencing data, suggesting that the ascertainment bias in the SoySNP618K array was largely compensated for. Genome-wide association mapping in combination with reported quantitative trait loci enabled fine-mapping of genes known to influence flowering time, E2 and GmPRR3b, and of a new candidate gene, GmVIP5. Moreover, genomic prediction of flowering and maturity time in 502 recombinant inbred lines was highly accurate (>0.65). Thus, the SoySNP618K array is a valuable genomic tool that can be used to address many questions in applied breeding, germplasm management, and basic crop research.