Characterization of YABBY transcription factors in Osmanthus fragrans and functional analysis of OfYABBY12 in floral scent formation and leaf morphology.

BACKGROUND: The plant-specific YABBY transcription factor family plays important roles in plant growth and development, particularly leaf growth, floral organ formation, and secondary metabolite synthesis. RESULTS: Here, we identified a total of 13 OfYABBY genes from the Osmanthus fragrans genome. These 13 OfYABBY genes were divided into five subfamilies through phylogenetic analysis, and genes in the same subfamily showed similar gene structures and conserved protein motifs. Gene duplication promoted the expansion of the OfYABBY family in O. fragrans. Tissue-specific expression analysis showed that the OfYABBY family was mainly expressed in O. fragrans leaves and floral organs. To better understand the role of OfYABBY genes in plant growth and development, OfYABBY12 was selected for heterologous stable overexpression in tobacco, and OfYABBY12-overexpressing tobacco leaves released significantly fewer volatile organic compounds than wild-type tobacco leaves. Overexpression of OfYABBY12 led to the downregulation of NtCCD1/4 and decreased ß-ionone biosynthesis. Correspondingly, a dual-luciferase assay showed that OfYABBY12 negatively regulated the expression of OfCCD4, which promotes ß-ionone synthesis. Furthermore, tobacco leaves overexpressing OfYABBY12 were curled and wrinkled and had significantly reduced leaf thickness and leaf inclusions and significantly extended flower pistils (styles). CONCLUSION: Overall, the results suggest that the OfYABBY gene family may influence the biosynthesis of the floral scent (especially ß-ionone) in O. fragrans and may regulate leaf morphogenesis and lateral organs.

Triglyceride-glucose index is associated with myocardial ischemia and poor prognosis in patients with ischemia and no obstructive coronary artery disease.

BACKGROUND: Ischemia and no obstructive coronary artery disease (INOCA) is increasingly recognized and associated with poor outcomes. The triglyceride-glucose (TyG) index is a reliable alternative measure of insulin resistance significantly linked to cardiovascular disease and adverse prognosis. We investigated the association between the TyG index and myocardial ischemia and the prognosis in INOCA patients. METHODS: INOCA patients who underwent both coronary angiography and myocardial perfusion imaging (MPI) were included consecutively. All participants were divided into three groups according to TyG tertiles (T1, T2, and T3). Abnormal MPI for myocardial ischemia in individual coronary territories was defined as summed stress score (SSS) ≥ 4 and summed difference score (SDS) ≥ 2. SSS refers to the sum of all defects in the stress images, and SDS is the difference of the sum of all defects between the rest images and stress images. All patients were followed up for major adverse cardiac events (MACE). RESULTS: Among 332 INOCA patients, 113 (34.0%) had abnormal MPI. Patients with higher TyG index had a higher rate of abnormal MPI (25.5% vs. 32.4% vs. 44.1%; p = 0.012). Multivariate logistic analysis showed that a high TyG index was significantly correlated with abnormal MPI in INOCA patients (OR, 1.901; 95% CI, 1.045-3.458; P = 0.035). During the median 35 months of follow-up, 83 (25%) MACE were recorded, and a higher incidence of MACE was observed in the T3 group (T3 vs. T2 vs. T1: 36.9% vs. 21.6% vs. 16.4%, respectively; p = 0.001). In multivariate Cox regression analysis, the T3 group was significantly associated with the risk of MACE compared to the T1 group (HR, 2.338; 95% CI 1.253-4.364, P = 0.008). CONCLUSION: This study indicates for the first time that the TyG index is significantly associated with myocardial ischemia and poor prognosis among INOCA patients.

Polydopamine Enhanced Interactions of Graphene Nanosheets to Fabricate Graphene/Polydopamine Aerogels with Effectively Clear Organic Pollutants.

Graphene/polydopamine aerogels (GPDXAG, where X represents the weight ratio of DA·HCl to GO) were prepared by the chemical reduction of graphene oxide (GO) using dopamine (DA) and l-ascorbic acid as reducing agents. During the gelation process, DA was polymerized to form polydopamine (PDA). The introduction of PDA in the gelation of aerogels led to a deeper reduction of GO and stronger interactions between graphene nanosheets forced by covalent cross-linking and noncovalent bonding including π-π stacking and hydrogen bonding. The weight ratio of DA·HCl to GO influencing the formation and morphology of GPDXAG was explored. With the increasing content of DA in gelation, the reduction of GO and the cross-linking degree of graphene nanosheets were enhanced, and the resulting GPDXAG had a more regular pore distribution. Additionally, introducing PDA into GPDXAG improved its hydrophobicity because of the adhesion of PDA to a network of aerogels. GPDXAG exhibited a higher removal efficiency for organic pollutants than the controlled graphene aerogels (GAG). Specifically, the adsorption capacity of GPDXAG for organic solvents was superior to that of GAG, and organic solvent was completely separated from the oil/water mixture by GPDXAG. The equilibrium adsorption capacity of GPDXAG for malachite green (MG) was measured to be 768.50 mg/g, which was higher than that for methyl orange (MO). In MG/MO mixed solutions, aerogels had obvious adsorption selectivity for the cationic dye. The adsorption mechanism of aerogels for MG was also discussed by simulating adsorption kinetic models and adsorption isothermal models.

Rational control of the typical surface defects of hybrid perovskite using tetrahexylammonium iodide.

There are numerous defects existing on the surface and grain boundary of perovskite, which adversely affect the performance and stability of perovskite solar cell devices. Systematic first-principles calculations show that the I vacancy (VI), Pb vacancy (VPb), Pb-I antisite (PbI), and I-Pb antisite (IPb) defects can significantly affect the electronic properties of the surface of formamidinium lead triiodide (FAPbI3); in particular the VPb, PbI and IPb surface defects can introduce defect energy levels in the band gap. Tetrahexylammonium iodide (THAI) that is strongly adsorbed on the (1 0 0) surface of FAPbI3 by forming Pb-I coordination bonds and I⋯H hydrogen bonds could eliminate or reduce the defect states near the band edge or in the band gap by transferring electrons between THAI and the surface of FAPbI3. In particular, the defect states introduced by VPb could be completely eliminated after the adsorption of THAI. This study shows an in-depth understanding of the influence of defects on the electronic properties of the surface of FAPbI3, as well as the passivation mechanism of organic salts on the surface defects of perovskite.

Metabolites from Lysobacter gummosus YMF3.00690 Against Meloidogyne javanica.

The strains in Lysobacter spp. have the potential to control plant-parasitic nematodes. In our experiment, L. gummosus YMF3.00690 showed antagonistic effects against plant root-knot nematode. Nine metabolites were isolated and identified from cultures of L. gummosus YMF3.00690, of which compound 1 was identified as a new metabolite tetrahydro-4,4,6-trimethyl-6-[(tetrahydro-6,6-dimethyl-2-oxo-4(1H)-pyrimidinylidene) methyl]-2(1H)-pyrimidinone. The activity assay showed that two compounds, 5-(hydroxymethyl)-1H-pyrrole-2-carbaldehyde (2) and 1H-pyrrole-2-carboxylic acid (3), had nematicidal activities against Meloidogyne javanica with mortalities of 69.93 and 90.54% at 400 ppm for 96 h, respectively. These two compounds were further tested for the inhibition activity of eggs hatching, and compound 3 showed a significant inhibition rate of 63.36% at 50 ppm for 48 h. In the chemotactic activity assay, three compounds (1 to 3) were found to have concentration-dependent chemotactic activity, of which compound 1 showed attractive activity. This experiment explored the active metabolites of L. gummosus YMF3.00690 against M. javanica and laid the foundation for biopesticide development.

Circular RNA CircACAP2 regulates temporomandibular joint osteoarthritis via miR-21-5p/PLAG1 axis.

OBJECTIVES: The pathogenesis of temporomandibular joint osteoarthritis (TMJOA) remains not fully understood. Our previous studies demonstrated that miR-21-5p may participate in the TMJOA development and the interaction between circRNA-ACAP2 (CircACAP2) and miR-21-5p. Our present study aimed to explore the biological functions and regulatory mechanisms of CircACAP2 in TMJOA. MATERIALS AND METHODS: The differential expression pattern of CircACAP2 in OA and normal tissues or cells was detected. CircACAP2 biological functions experiments were performed in chondrocytes by overexpression and interference techniques. The interaction of CircACAP2 with miR-21-5p and downstream target mRNA, polymorphic adenoma gene 1 (PLAG1), was predicted by bioinformatic databases and then demonstrated by dual-luciferase reporter assay. The biological role of CircACAP2 in TMJOA was investigated and validated in a mouse model. RESULTS: The expression level of CircACAP2 was markedly reduced in OA cartilage and directly related to chondrocyte proliferation and apoptosis as well as ECM metabolism in the cartilage. CircACAP2 functioned in chondrocytes via targeting miR-21-5p and PLAG1. Overexpressing of CircACAP2 alleviated TMJOA in mouse models. CONCLUSIONS: The present study unveiled that CircACAP2/miR-21-5p/PLAG1 axis may play an important regulatory role in TMJOA progression, which may highlight a potentially effective intervention and therapeutic strategy for the treatment of TMJOA.

De novo transcriptional analysis of the response to starvation stress in the white ridgetail prawn, Exopalaemon carinicauda.

To study the mechanism of the biomolecular response in Exopalaemon carinicauda to starvation stress, we subjected muscle tissue RNA samples from four stress points, including 0 d(control group), 10 d, 20 d, and 30 d, to starvation stress on white ridgetail prawn with a body weight of 1.41 + 0.42 g, aquaculture water temperature of 23-25 °C, salinity of 26, dissolved oxygen ≥5 mg/L, and pH 8-8.5, Then performed de novo transcriptome assembly and gene expression analysis using BGISEQ-500 with a tag-based digital gene expression (DGE) system. By de novo assembling at the four times, we obtained 28,167, 21,115, 24,497, and 27,080 reads, respectively. The results showed that the stress at 10 d led to no significant difference in the expressed genes, while the stress at 20 d and 30 d showed a significant increase (or decrease) in the expression of 97 (276) and 143 (410) genes, respectively, which were involved in 8 different metabolic pathways. In addition, we detected 2647 unigene transcription factors. Eleven upregulated and sixteen downregulated genes from the different starvation stress groups were choose to verify the reliability of the transcriptome data, and the results showed that the expression trends of these genes were consistent with the results shown by the transcriptome. The analysis of the experimental data and our discussion of the response mechanism of white ridgetail prawn under starvation stress provides a foundation for further screening of the key genes of starvation stress and may help to elucidate their functions.

Floral Volatile Organic Compounds Change the Composition and Function of the Endophytic Fungal Community in the Flowers of Osmanthus fragrans.

Endophytic fungi in flowers influence plant health and reproduction. However, whether floral volatile organic compounds (VOCs) affect the composition and function of the endophytic fungal community remains unclear. Here, gas chromatography-mass spectrometry (GC-MS) and high-throughput sequencing were used to explore the relationship between floral VOCs and the endophytic fungal community during different flower development stages in Osmanthus fragrans 'Rixiang Gui'. The results showed that the composition of the endophytic fungal community and floral VOCs shifted along with flowering development. The highest and lowest α diversity of the endophytic fungal community occurred in the flower fading stage and full blooming stage, respectively. The dominant fungi, including Dothideomycetes (class), Pleosporales (order), and Neocladophialophora, Alternaria, and Setophoma (genera), were enriched in the flower fading stage and decreased in the full blooming stage, demonstrating the enrichment of the Pathotroph, Saprotroph, and Pathotroph-Saprotroph functions in the flower fading stage and their depletion in the full blooming stage. However, the total VOC and terpene contents were highest in the full blooming stage and lowest in the flower fading stage, which was opposite to the α diversity of the endophytic fungal community and the dominant fungi during flowering development. Linalool, dihydro-ß-ionone, and trans-linalool oxide(furan) were key factors affecting the endophytic fungal community composition. Furthermore, dihydro-ß-ionone played an extremely important role in inhibiting endophytic fungi in the full blooming stage. Based on the above results, it is believed that VOCs, especially terpenes, changed the endophytic fungal community composition in the flowers of O. fragrans 'Rixiang Gui'. These findings improve the understanding of the interaction between endophytic fungi and VOCs in flowers and provide new insight into the mechanism of flower development.

Pecan (Carya illinoinensis (Wangenh.) K. Koch) nuts as an emerging source of protein: extraction, physicochemical and functional properties.

BACKGROUND: The increasing demand for sustainable alternatives to traditional protein sources, driven by population growth, underscores the importance of protein in a healthy diet. Pecan (Carya illinoinensis (Wangenh.) K. Koch) nuts are currently underutilized as plant-based proteins but hold great potential in the food industry. However, there is insufficient information available on pecan protein, particularly its protein fractions. This study aimed to explore the physicochemical and functional properties of protein isolate and the main protein fraction glutelin extracted from pecan nuts. RESULTS: The results revealed that glutelin (820.67 ± 69.42 g kg-1) had a higher crude protein content compared to the protein isolate (618.43 ± 27.35 g kg-1), while both proteins exhibited amino acid profiles sufficient for adult requirements. The isoelectric points of protein isolate and glutelin were determined to be pH 4.0 and pH 5.0, respectively. The denaturation temperature of the protein isolate (90.23 °C) was higher than that of glutelin (87.43 °C), indicating a more organized and stable conformation. This is further supported by the fact that the protein isolate had a more stable main secondary structure than glutelin. Both proteins demonstrated improved solubility, emulsifying, and foaming properties at pH levels deviating from their isoelectric points in U-shaped curves. Compared to the protein isolate, glutelin displayed superior water and oil absorption capacity along with enhanced gelling ability. CONCLUSION: The protein isolate and glutelin from pecan nuts exhibited improved stability and competitive functional properties, respectively. The appropriate utilization of these two proteins will support their potential as natural ingredients in various food systems. © 2024 Society of Chemical Industry.

Exenatide and Metformin Improve Serum Indices and Intestinal Flora in patients with Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease.

The aim of the study was to investigate th e in flue nce of Exenatide comb ined with Met formin on fasti ng blood glucose, postpr andial glucose, triglycerides, total cholesterol, alanine aminotransferase, aspartate aminotransferase, and inte s tinal flora in typ e 2 diab etes mellitus cases with non-alcoholic fatty liver disease. A total of 128 type 2 diabetes mellitus patients with non-alcoholic fatty liver disease, diagnosed from Januar y 2019 to January 2022, were included and randomly assigned to either G roup A (n=64) or Gro up B (n =64). Group A received Metformin, while Group B received Exenatide injection and Metfor min. After 24 weeks of treat ment, blood glucose indices (fasting blood glucose and postprandial glucose), blood lipid indices (triglycerides and total cholesterol), liver func tion indices (alanine aminotransferase and aspar tate aminotransferase) were all lower in Group B than in Group A (p<0.001 for all). Counts o f Escherichia coli and Enterococcus faecalis were lower in Group B than in Group A (both p<0.05), counts of Bifidobacteria and Lactobacillus were highe r i n Group B than in Grou p A (both p<0.05). Combin ation of Exenati de and Metformi n may have synergistic effects in improving metabo lic an d hepatic pa rameters, a s well as re gulat ing intestinal flora, which cou ld provide a pro misin g therapeutic option for the management of these patients.

Analysis on the physiological changes of residents before and during the COVID-19 pandemic: A cross-sectional study.

People's lifestyles have changed dramatically during the coronavirus disease 2019 (COVID-19) pandemic, yet data on physical examinations in the Chinese population before and during the pandemic are rarely reported. The study was based on the data from the physical examination center of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. We collected the data of physical examinations information between January 2017 and March 2022. The data of participants before December 31, 2019 were classified as "before COVID-19 pandemic group," while data after December 31, 2019 were classified as "during COVID-19 pandemic group." We used t-test and χ2  test to compare the differences before and during COVID-19 pandemic. A total of 72 257 individuals participated in the physical examinations, and finally retained 65 629 individuals for analysis. During the COVID-19 pandemic, body mass index (BMI), high-density lipoprotein, total cholesterol levels, as well as pulmonary nodule and thyroid nodule proportion of participants were higher than those before the pandemic, and the levels of systolic blood pressure and diastolic blood pressure of participants were lower than those before the pandemic. Ongoing assessment and surveillance are necessary to assess whether lifestyle changes caused by the COVID-19 pandemic are likely to increase chronic disease risk in the future.

Ultra-narrowband interference circuits enable low-noise and high-rate photon counting for InGaAs/InP avalanche photodiodes.

Afterpulsing noise in InGaAs/InP single photon avalanche photodiodes (APDs) is caused by carrier trapping and can be suppressed successfully through limiting the avalanche charge via sub-nanosecond gating. Detection of faint avalanches requires an electronic circuit that is able to effectively remove the gate-induced capacitive response while keeping photon signals intact. Here we demonstrate a novel ultra-narrowband interference circuit (UNIC) that can reject the capacitive response by up to 80 dB per stage with little distortion to avalanche signals. Cascading two UNIC's in a readout circuit, we were able to enable a high count rate of up to 700 MC/s and a low afterpulsing of 0.5 % at a detection efficiency of 25.3 % for 1.25 GHz sinusoidally gated InGaAs/InP APDs. At a temperature of -30 ∘C, we measured an afterpulsing probability of 1 % at a detection efficiency of 21.2 %.

Association between the atherogenic index of plasma and adverse long-term prognosis in patients diagnosed with chronic coronary syndrome.

BACKGROUND: The Atherogenic Index of Plasma (AIP) is a newly identified biomarker associated with lipid metabolism, demonstrating significant prognostic capabilities in individuals diagnosed with cardiovascular disease. However, its impact within the context of chronic coronary syndromes (CCS) remains unexplored. Thus, the present investigation sought to examine the potential association between AIP levels and long-term clinical outcomes in patients diagnosed with CCS. METHODS: A total of 404 patients diagnosed with CCS and who underwent coronary angiography were included in this study. The AIP index was calculated as log (triglycerides / high-density lipoprotein-cholesterol). The patients were categorized into four groups based on their AIP values: Q1 (< -0.064), Q2 (-0.064 to 0.130), Q3 (0.130 to 0.328), and Q4 (> 0.328). The occurrence of major adverse cardiovascular events (MACE) was monitored during the follow-up period for all patients. Cox regression analysis and Kaplan-Meier curve analysis were employed to examine the relationship between AIP and MACE. Furthermore, ROC analysis was utilized to determine the optimal cut-off value of AIP for predicting clinical MACE. RESULTS: During the median 35 months of follow-up, a total of 88 patients experienced MACE. Notably, the group of patients with higher AIP values (Q4 group) exhibited a significantly higher incidence of MACE compared to those with lower AIP values (Q1, Q2, and Q3 groups) (31.7% vs. 16.8%, 15.7%, and 23.0% respectively; P = 0.023). The Kaplan-Meier curves illustrated those patients in the Q4 group had the highest risk of MACE relative to patients in the other groups (log-rank P = 0.014). Furthermore, the multivariate Cox regression analysis demonstrated that individuals in the Q4 group had a 7.892-fold increased risk of MACE compared to those in the Q1 group (adjusted HR, 7.892; 95% CI 1.818-34.269; P = 0.006). Additionally, the ROC curve analysis revealed an optimal AIP cut-off value of 0.24 for predicting clinical MACE in patients with CCS. CONCLUSION: Our data indicate, for the first time, that AIP is independently associated with poor long-term prognosis in patients suffering from CCS. The optimal AIP cut-off value for predicting clinical MACE among CCS patients was 0.24.

Association between the triglyceride-glucose index and the presence and prognosis of coronary microvascular dysfunction in patients with chronic coronary syndrome.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a strong determinant of prognosis in patients with chronic coronary syndrome (CCS). The triglyceride-glucose index (TyG index), an alternative method to evaluate insulin resistance, is positively correlated with the incidence and adverse outcomes of cardiovascular diseases. However, the relationship between the TyG index and the presence and prognosis of CMD in CCS patients has not been investigated. Therefore, we aimed to evaluate the association between the TyG index and the presence and clinical outcomes of CMD among CCS patients. METHODS: CCS patients who underwent coronary angiography between June 2015 to June 2019 were included. The TyG index was calculated as Ln[fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. Coronary angiography­derived index of microvascular resistance (caIMR) was used to measure microvascular function, and CMD was defined as caIMR ≥ 25U. Patients with CMD were divided into three groups (T1, T2, and T3 groups) according to TyG tertiles. The primary endpoint was major adverse cardiac event (MACE). RESULTS: Of 430 CCS patients, 221 patients had CMD. CMD patients had significantly higher TyG index than those without CMD. Sixty-three MACE was recorded during the follow-up duration among CMD patients, and the incidence rate of MACE was higher in the T3 group compared to T1/T2 groups (39.2% vs. 20.5% vs. 25.7%; P = 0.035). Multivariable logistic regression analysis showed that the TyG index was an independent predictor of CMD (OR, 1.436; 95% CI, 1.014-2.034; P = 0.042). Compared to the T1 group, the T3 group strongly correlated with the risk of MACE in CMD patients even after adjusting for additional confounding risk factors (HR, 2.132; 95%CI, 1.066-4.261; P = 0.032). CONCLUSION: TyG index is significantly associated with the risk of CMD, and it is an independent predictor of MACE among CMD patients with CCS. This study suggests that the TyG index has important clinical significance for the early prevention and risk stratification of CMD.

Prognostic value of combined coronary angiography-derived IMR and myocardial perfusion imaging by CZT SPECT in INOCA.

BACKGROUND: A significant proportion of ischemia with non-obstructive coronary artery disease (INOCA) demonstrate coronary microvascular dysfunction (CMD), a condition associated with abnormal myocardial perfusion imaging (MPI) and adverse outcomes. Coronary angiography-derived index of microvascular resistance (caIMR) is a novel non-invasive technique to assess CMD. We aimed to investigate the prognostic value of combined caIMR and MPI by CZT SPECT in INOCA patients. METHODS: Consecutive 151 patients with chest pain and < 50% coronary stenosis who underwent coronary angiography and MPI within 3 months were enrolled. caIMR was calculated by computational pressure-flow dynamics. CMD was defined as caIMR ≥ 25. The endpoint was major adverse cardiac events (MACE: cardiovascular death, nonfatal myocardial infarction, revascularization, angina-related rehospitalization, heart failure, and stroke). RESULTS: Of all INOCA patients, CMD was present in 93 (61.6%) patients. The prevalence of abnormal MPI was significantly higher in CMD compared with non-CMD patients (40.9% vs 13.8%, P < .001). CMD showed a higher risk of MACE than non-CMD patients. Patients with both CMD and abnormal MPI had the worst prognosis, followed by patients with CMD and normal MPI (log-rank P < .001). Cox regression analysis identified CMD (HR 3.121, 95%CI 1.221-7.974, P = .017) and MPI (HR 2.704, 95%CI 1.030-7.099, P = .043) as predictive of MACE. The prognostic value of INOCA patients enhanced significantly by adding CMD and MPI to the model with clinical risk factors (AUC = 0.777 vs 0.686, P = .030). CONCLUSION: caIMR-derived CMD is associated with increased risk of MACE among INOCA patients. Patients with abnormalities on both caIMR and MPI had the worse outcomes.

Superconductivity determined by the S-H framework in CH4-inserted S-H framework hydrides under high pressures.

Recently, a debate is raising the concern of possible carbonaceous sulfur hydrides with room-temperature superconductivity around 270 GPa. In order to systematically investigate the structural information and relevant natures of C-S-H superconductors, we performed an extremely extensive structure search and first-principles calculations under high pressures. As a result, the metastable stoichiometries of CSH7, C2SH14, CS2H10, and CS2H11 were unveiled under high pressure, which can be viewed as CH4 units inserted into the S-H framework. Given the super-high superconductivity of Im3̄m-SH3, we performed electron-phonon coupling calculations of these compounds,the metastable of R3m-CSH7, Cm-CSH7, Cm-CS2H10, P3m1-CS2H10, Cm-CS2H11, and Fmm2-CS2H11 are predicted to become good phonon-mediated superconductors that could reach Tc of 130, 120, 72, 74, 92, and 70 K at 270 GPa, respectively. Furthermore, we identified that high Tc is associated with the large contribution of the S-H framework to the electron density of states near the Fermi level. Our results highlight the importance of the S-H framework in superconductivity and verify that the suppression of density of states of these carbonaceous sulfur hydrides by CH4 units results in Tc lower than that of Im3̄m-SH3, which could act as a useful guidance in the design and optimization of high-Tc superconductors in these and related systems.

Screening and verifying the mutations in the LDLR and APOB genes in a Chinese family with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder. The primary objective of this study was to identify the major pathogenic mutations in a Chinese family with FH. METHODS: Whole-genome sequencing (WGS) was used to identify variants of FH-related genes, including low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9). Bioinformatics software was used to predict signal peptides, transmembrane structures, and spatial construction information of the mutated sequences. Western blotting was performed on the mutant protein to determine the presence of the major structural domains of the LDLR. The PCSK9 and APOB genes were screened and analyzed. Moreover, the proband and his brother were treated with a PCSK9 inhibitor for 1 year, and the effect of the treatment on lipid levels was assessed. RESULTS: WGS revealed two potentially pathogenic mutations in the LDLR gene. One was a novel mutation, c.497delinsGGATCCCCCAGCTGCATCCCCCAG (p. Ala166fs), and the other was a known pathogenic mutation, c.2054C>T (p. Pro685Leu). Bioinformatics prediction and in vitro experiments revealed that the novel mutation could not be expressed on the cell membrane. Numerous gene variants were identified in the APOB gene that may have a significant impact on the family members with FH. Thus, it is suggested that the severe manifestation of FH in the proband primarily resulted from the cumulative genetic effects of variants in both LDLR and APOB. However, a subsequent study indicated that treatment with a PCSK9 inhibitor (Evolocumab) did not significantly reduce the blood lipid levels in the proband or his brother. CONCLUSIONS: The cumulative effect of LDLR and APOB variants was the primary cause of elevated blood lipid levels in this family. However, PCSK9 inhibitor therapy did not appear to be beneficial for the proband. This study emphasizes the importance of genetic testing in determining the most suitable treatment options for patients with FH.

A nomogram prediction of citrate reaction during mononuclear cell collection in solid tumor patients.

PURPOSE: Citrate reaction is one of the main adverse events in peripheral blood mononuclear cell (MNC) collection. The aim of this study was to elucidate the risk factors for citrate reaction in patients with advanced solid tumor collection and to construct a nomogram to predict the risk. METHODS: One hundred forty-eight patients with advanced solid tumor who underwent peripheral blood MNC collection in our hospital between January 2021 to December 2021 were selected. The general data, creatinine level before collection, Ca2+ concentration before collection, absolute value of monocyte lymphocytes before collection, circulating blood volume, anticoagulant dosage, and blood collection duration were included in Logistic regression analysis to identify the risk factors of citrate reaction. According to the results of the multivariate logistic model, nomogram was established and receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the model. RESULTS: Among the 148 solid tumor patients, 35 patients (23.6%) of the 148 patients developed citrate reaction. Multivariate analysis showed that the risk factors for citrate reaction in the process of collection included sex (odds ratio [OR] = 6.718; 95% confidence interval [95% CI]: 2.191-20.594, P = .001), age (OR = 0.957; 95% CI: 0.921-0.996, P = .03), and processed circulating blood volume (OR = 1.001; 95% CI: 1.000-1.002, P = .01). Logistic regression can analyze independent risk factors and establish risk prediction model. The predictive performance of the model is good, and the area under ROC curve is 0.799. CONCLUSIONS: The MNC collection process is safe. The incidence of citrate reaction in the collection of peripheral blood MNCs from patients with advanced solid tumor is related to the age, gender, and processed circulating blood volume of patients. The nomogram can be used to assess a patient's risk of citrate reaction.

Impact of extracorporeal membrane oxygenation in immunocompetent children with severe adenovirus pneumonia.

BACKGROUND: Severe adenovirus (Adv.) pneumonia can cause significant mortality in young children. There has been no worldwide consensus on the impact of extracorporeal membrane oxygenation (ECMO) in immunocompetent children with severe Adv. pneumonia. This study aimed to assess the impact of ECMO in immunocompetent children with severe Adv. pneumonia. METHODS: This study evaluated the medical records of 168 hospitalized children with severe Adv. pneumonia at the Guangzhou Women and Children's Medical Center between 2019 and 2020.Nineteen patients in the ECMO group and 149 patients in the non-ECMO group were enrolled. RESULTS: Between these two groups, there were no differences in host factors such as sex, age (all P > 0.05). Significant differences were observed in shortness of breath/increased work of breathing; cyanosis; seizures; tachycardia; the partial pressure of oxygen in arterial blood (PO2); the ratio of PaO2 to the fraction concentration of oxygen in inspired air (FiO2; P/F); white blood cell, lymphocyte, monocytes, lactate dehydrogenase (LDH), serum albumin, and procalcitonin levels; and, pulmonary consolidation (all P < 0.05). There were significant differences in the parameters of mechanical ventilation (MV) therapy and complications such as respiratory failure, acute respiratory distress syndrome, septic shock, length of hospitalization, and death (all P < 0.05). The maximum axillary temperatures, respiratory rates, heart rates and LDH levels after receiving ECMO were significantly lower than those before ECMO (all P < 0.05). Additionally, SPO2, PO2, and P/F were significantly higher than those before ECMO (all P < 0.05). In MV therapy, FiO2, PIP, and PEEP were significantly lower than those before ECMO (all P < 0.05). CONCLUSIONS: In our study, the clinical conditions of the patients in the ECMO group were much more severe than those in the non-ECMO group. Our study showed that ECMO might be beneficial for the patients with severe Adv. pneumonia.

Comparison of purse-string suture versus over-the-scope clip for gastric endoscopic full-thickness closure: traction and leak pressure testing in ex vivo porcine model.

BACKGROUND: The recently developed endoscopic full-thickness resection technique requires reliable closure. The main closure methods are the purse-string suture (PSS) technique and over-the-scope clip (OTSC) technique; however, basic data on the closure strength of each technique are lacking. This study was performed to compare the closure strengths of these two methods in an ex vivo porcine model. METHODS: In the traction test, a virtual 5-cm full-thickness closure line was closed by the following six methods three times each: conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture. The primary endpoint was the tension at the starting point of dehiscence, measured in Newtons (N) by an automatic traction machine. In the leak test, a 15-mm gastric full-thickness defect was closed by PSS or OTSC six times each, and the closed stomach was then pressurized in a water container. The primary endpoint was the leak pressure when air bubbles appeared. The secondary endpoints were the procedure time and presence of complete inverted closure. RESULTS: The mean tension was 2.16, 3.68, 5.15, 18.30, 19.30, and 62.40 N for conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture, respectively. Complete inverted closure was observed for seromuscular PSS, seromuscular OTSC, and surgical suture. The mean leak pressure was 13.7 and 24.8 mmHg in the PSS and OTSC group, respectively (P < 0.01). The mean procedure time was 541 and 169 s in the PSS and OTSC group, respectively (P < 0.01). Complete inverted closure was observed in OTSC alone. CONCLUSION: The OTSC, which allows complete inverted closure, showed greater closure strength than PSS. Considering the size limitation suitable for single OTSC, a therapeutic strategy for closing the larger size is further warranted.