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1.
Hellenic J Cardiol ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38844023

ABSTRACT

OBJECTIVE: We aimed to examine biventricular remodeling and function after Ebstein anomaly (EbA) surgical correction using echocardiographic techniques, particularly, the relations between the biventricular changes and the EbA types. METHODS: From April 2015 to August 2022, 110 patients with EbA were included in this retrospective study based on the Carpentier classification. Echocardiography assessments during the preoperative, early, and mid-term postoperative periods were performed. RESULTS: The 54 patients with types A and B EbA were included in group 1, whereas the 56 patients with types C and D were in group 2. Seventy-eight patients underwent surgical correction of EbA. The median age at operation was 8.8 years. During the mid-term follow-up, only 9.1% of the patients had moderate or severe tricuspid regurgitation. Right ventricular (RV) systolic function worsened in group 2 at discharge (fractional area change: 27.6 ± 11.2 vs. 35.4 ± 11.5 [baseline], P < 0.05; global longitudinal strain: -10.8 ± 4.4 vs. -17.9 ± 4.7 [baseline], P = 0.0001). RV function slowly recovered at a mean of 12 months of follow-up. Regarding left ventricular (LV) and RV systolic function, no statistical difference was found between before and after surgery in group 1. CONCLUSION: A high success rate of surgical correction of EbA, with an encouraging durability of the valve, was noted. Biventricular systolic function was maintained fairly in most patients with types A and B postoperatively. A late increase in RV systolic function after an initial reduction and unchanged LV systolic function were observed in the patients with types C and D postoperatively.

2.
Biomed Environ Sci ; 37(5): 445-456, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38843918

ABSTRACT

Objective: The leptin receptor, encoded by the LEPR gene, is involved in tumorigenesis. A potential functional variant of LEPR, rs1137101 (Gln223Arg), has been extensively investigated for its contribution to the risk of digestive system (DS) cancers, but results remain conflicting rather than conclusive. Here, we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods: A total of 1,727 patients with cancer (gastric/liver/colorectal: 460/480/787) and 800 healthy controls were recruited. Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and confirmed using Sanger sequencing. Twenty-four eligible studies were included in the meta-analysis. Results: After Bonferroni correction, the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population. The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS, gastric, and liver cancer in the Chinese population. Conclusion: The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers (especially liver and gastric cancer) in the Chinese population.


Subject(s)
Digestive System Neoplasms , Genetic Predisposition to Disease , Receptors, Leptin , Female , Humans , Male , Middle Aged , Case-Control Studies , China/epidemiology , Digestive System Neoplasms/genetics , Polymorphism, Single Nucleotide , Receptors, Leptin/genetics , Risk Factors , East Asian People/genetics
3.
Burns Trauma ; 12: tkae004, 2024.
Article in English | MEDLINE | ID: mdl-38817684

ABSTRACT

Background: Extracellular cold-inducible RNA-binding protein (eCIRP) plays a vital role in the inflammatory response during cerebral ischaemia. However, the potential role and regulatory mechanism of eCIRP in traumatic brain injury (TBI) remain unclear. Here, we explored the effect of eCIRP on the development of TBI using a neural-specific CIRP knockout (KO) mouse model to determine the contribution of eCIRP to TBI-induced neuronal injury and to discover novel therapeutic targets for TBI. Methods: TBI animal models were generated in mice using the fluid percussion injury method. Microglia or neuron lines were subjected to different drug interventions. Histological and functional changes were observed by immunofluorescence and neurobehavioural testing. Apoptosis was examined by a TdT-mediated dUTP nick end labelling assay in vivo or by an annexin-V assay in vitro. Ultrastructural alterations in the cells were examined via electron microscopy. Tissue acetylation alterations were identified by non-labelled quantitative acetylation via proteomics. Protein or mRNA expression in cells and tissues was determined by western blot analysis or real-time quantitative polymerase chain reaction. The levels of inflammatory cytokines and mediators in the serum and supernatants were measured via enzyme-linked immunoassay. Results: There were closely positive correlations between eCIRP and inflammatory mediators, and between eCIRP and TBI markers in human and mouse serum. Neural-specific eCIRP KO decreased hemispheric volume loss and neuronal apoptosis and alleviated glial cell activation and neurological function damage after TBI. In contrast, eCIRP treatment resulted in endoplasmic reticulum disruption and ER stress (ERS)-related death of neurons and enhanced inflammatory mediators by glial cells. Mechanistically, we noted that eCIRP-induced neural apoptosis was associated with the activation of the protein kinase RNA-like ER kinase-activating transcription factor 4 (ATF4)-C/EBP homologous protein signalling pathway, and that eCIRP-induced microglial inflammation was associated with histone H3 acetylation and the α7 nicotinic acetylcholine receptor. Conclusions: These results suggest that TBI obviously enhances the secretion of eCIRP, thereby resulting in neural damage and inflammation in TBI. eCIRP may be a biomarker of TBI that can mediate the apoptosis of neuronal cells through the ERS apoptotic pathway and regulate the inflammatory response of microglia via histone modification.

4.
Environ Res ; 257: 119267, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38815718

ABSTRACT

Natural pyrethrins are widely used in agriculture because of their good insecticidal activity. Meanwhile, natural pyrethrins play an important role in the safety evaluation of pyrethroids as precursors for structural development of pyrethroid insecticides. However, there are fewer studies evaluating the neurological safety of natural pyrethrins on non-target organisms. In this study, we used SH-SY5Y cells and zebrafish embryos to explore the neurotoxicity of natural pyrethrins. Natural pyrethrins were able to induce SH-SY5Y cells damage, as evidenced by decreased viability, cycle block, apoptosis and DNA damage. The apoptotic pathway may be related to the involvement of mitochondria and the results showed that natural pyrethrins induced a rise in Capase-3 viability, Ca2+ overload, a decrease in adenosine triphosphate (ATP) and a collapse of mitochondrial membrane potential in SH-SY5Y cells. Natural pyrethrins may mediate DNA damage in SH-SY5Y cells through oxidative stress. The results showed that natural pyrethrins induced an increase in reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and catalase (CAT) activity, and induced a decrease in glutathione peroxidase (GPx) activity in SH-SY5Y cells. In vivo, natural pyrethrins induced developmental malformations in zebrafish embryos, which were mainly characterized by pericardial edema and yolk sac edema. Meanwhile, the results showed that natural pyrethrins induced damage to the Huc-GFP axis and disturbed lipid metabolism in the head of zebrafish embryos. Further results showed elevated ROS levels and apoptosis in the head of zebrafish embryos, which corroborated with the results of the cell model. Finally, the results of mRNA expression assay of neurodevelopment-related genes indicated that natural pyrethrins exposure interfered with their expression and led to neurodevelopmental damage in zebrafish embryos. Our study may raise concerns about the neurological safety of natural pyrethrins on non-target organisms.

5.
iScience ; 27(3): 109169, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38433889

ABSTRACT

Only a small number of avian species inhabit salty environments. To understand how they adapted, we examined the evolution of kidney sizes, supraorbital salt glands (SSGs), and the utilization of salty habitats across 230 species spanning 25 avian orders. Phylogenetic analysis indicates that SSGs, large kidneys, and thriving in salty habitats emerged convergently in birds. Transition rate analysis reveals that species possessing SSGs and large kidneys tended to move from low-to high-salinity environments, while others moved in the opposite direction. However, habitat salinity also influenced kidney evolution; lineages residing in high-salinity environments tended to develop larger kidneys than those in low-salinity environments. Our findings suggest that SSGs and large kidneys may have evolved through adaptation to high salinity. Overall, habitat conditions and physiological traits influenced avian adaptation to salty environments in a reciprocal manner. These results shed the new light on the evolutionary mechanisms underlying functional diversity in birds.

6.
Heliyon ; 10(1): e24306, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38268603

ABSTRACT

Biochemical analyzers are vital instruments that utilize the principle of photoelectric colorimetry to quantify a specific chemical composition in body fluids. This analysis provides critical data for the diagnosis, treatment, prognosis, and overall health status of various diseases in clinical practice. However, the performance of a biochemical analyzer can vary significantly between different brands or over time within the same brand. Therefore, it is imperative to regularly assess the performance of the analyzer to ensure consistent results for longitudinal studies and to maintain day-to-day data consistency. Additionally, when multiple analyzers are utilized, it is necessary to evaluate the performance of each instrument to ensure accurate results across multiple platforms. In this study, we developed and verified an experimental evaluation scheme for the analytical performance of the instrument, chemometrics for biochemical analyzers, utilizing national reference materials and patient sera as the experimental subjects. We evaluated the performance of the optical system, temperature control system, sample-adding system, and detection system to confirm the feasibility of this scheme. We also compared the analytical performance of different brands of biochemical analyzers for routine biochemical tests, such as liver function, kidney function, ion, blood lipids, blood glucose, and myocardial enzyme spectrum. Using the AU 5400 as a control and the ADVIA 2400 as the comparison system, the relative variation in inter-instrument comparison data was found to be acceptable at the clinical medicine decision level. In conclusion, the performance of a biochemical analyzer can vary significantly between different brands or over time within the same brand. Regular evaluations are necessary to ensure accurate and consistent results across different analyzers. This study provides a feasible scheme for evaluating the analytical performance of biochemical analyzers that can be used to ensure the accuracy and consistency of the results of different brands of automatic chemical analyzers in the laboratory.

7.
Evol Appl ; 17(1): e13630, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38288030

ABSTRACT

Populations of Eurasian otters Lutra lutra, one of the most widely distributed apex predators in Eurasia, have been depleted mainly since the 1950s. However, a lack of information about their genomic diversity and how they are organized geographically in East Asia severely impedes our ability to monitor and conserve them in particular management units. Here, we re-sequenced and analyzed 20 otter genomes spanning continental East Asia, including a population at Kinmen, a small island off the Fujian coast, China. The otters form three genetic clusters (one of L. l. lutra in the north and two of L. l. chinensis in the south), which have diverged in the Holocene. These three clusters should be recognized as three conservation management units to monitor and manage independently. The heterozygosity of the East Asian otters is as low as that of the threatened carnivores sequenced. Historical effective population size trajectories inferred from genomic variations suggest that their low genomic diversity could be partially attributed to changes in the climate since the mid-Pleistocene and anthropogenic intervention since the Holocene. However, no evidence of genetic erosion, mutation load, or high level of inbreeding was detected in the presumably isolated Kinmen Island population. Any future in situ conservation efforts should consider this information for the conservation management units.

8.
Org Biomol Chem ; 22(7): 1453-1457, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38276970

ABSTRACT

With dimethyl sulfoxide (DMSO) as the methylthio source, a KF-catalyzed strategy was employed for the direct thiomethylation of carboxylic acids with DMSO for the preparation of methyl thioesters. In this process, a wide range of methyl thioesters were obtained in moderate to excellent yields. This novel strategy features the first use of DMSO as a methylthiolating agent for the construction of methyl thioesters, transition metal-free conditions, inexpensive reagents, easy workup, broad substrate scope and sustainability. Additionally, this procedure can be readily scaled up to a gram scale.

9.
Article in English | MEDLINE | ID: mdl-38289442

ABSTRACT

Time-of-death extrapolation has always been one of the most important issues in forensic practice. For a complicated case in which a corpse is destroyed with little evidence, judging the time of death of the deceased is a major challenge, which also enables criminals to escape legal sanctions. To find a method to roughly judge the time of death of a corpse with only a small amount of skin tissue, in this study, we established an early death model by using mice; furthermore, the postmortem interval was estimated by determining the protein and mRNA levels of Bax and Bcl-2 in the skin. In this process, 0 h after death was used as the control group, and the expression levels of Bax and Caspase-3 reached the maximum value at 8-12 h, while Bcl-2, as an inhibitor of apoptosis protein, peaked after 24 h. The mRNA expression levels of related proteins in postmortem skin tissues were also different. The results of these data indicate that the protein and mRNA levels of Bax and Bcl-2 in the skin have potential application in early time-of-death estimation.

10.
Eur J Prev Cardiol ; 31(1): 23-37, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-37665956

ABSTRACT

AIMS: This study aims to analyse the worldwide trends in hypertensive heart disease (HHD) mortality and associations with age, period, and birth cohort and predict the future burden of HHD deaths. METHODS AND RESULTS: Mortality estimates were obtained from Global Burden of Disease 2019 study. We used age-period-cohort (APC) model to examine the age, period, and cohort effects on HHD mortality between 1990 and 2019. Bayesian APC model was utilized to predict HHD deaths to 2034. The global HHD deaths were 1.16 million in 2019 and were projected to increase to 1.57 million in 2034, with the largest increment in low- and middle-income countries (LMICs). Between 1990 and 2019, middle/high-middle socio-demographic index (SDI) countries had the largest mortality reductions (annual percentage change = -2.06%), whereas low SDI countries saw a lagging performance (annual percentage change = -1.09%). There was a prominent transition in the age distribution of deaths towards old-age population in middle/high-middle SDI countries, while the proportion of premature deaths (aged under 60 years) remained at 24% in low SDI countries in 2019. Amongst LMICs, Brazil, China, and Ethiopia showed typically improving trends both over time and in recent birth cohorts, whereas 63 countries including Indonesia, the Philippines, and Pakistan had unfavourable or worsening risks for recent periods and birth cohorts. CONCLUSION: The HHD death burden in 2019 is vast and is expected to increase rapidly in the next decade, particularly for LMICs. Limited progress in HHD management together with high premature mortality would exact huge human and medical costs in low SDI countries. The examples from Brazil, China, and Ethiopia suggest that efficient health systems with action on improving hypertension care can reduce HHD mortality effectively in LMICs.


This study provides the first comprehensive analysis of the age, period, and cohort trends in mortality for hypertensive heart disease (HHD) across 204 countries and territories from 1990 to 2019, with projection to 2034. The death burden of HHD is substantial and growing rapidly in most of the world, particularly in low- and middle-income countries (LMICs). Wide disparities exist within LMICs in HHD management, with most low socio-demographic index countries showing little progress in reducing HHD mortality. The examples from Brazil, China, and Ethiopia suggest that prevention policies for HHD can reduce risks for younger birth cohorts and shift the risks for all age groups over time.


Subject(s)
Heart Diseases , Hypertension , Humans , Aged , Middle Aged , Global Burden of Disease , Bayes Theorem , Age Distribution , Global Health , Heart Diseases/diagnosis , Hypertension/diagnosis , Quality-Adjusted Life Years
11.
BMC Cancer ; 23(1): 1141, 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-38001428

ABSTRACT

OBJECTIVE: Lung adenocarcinoma (LA) is one of the most common malignancies and is responsible for the greatest number of tumor-related deaths. Our research aimed to explore the molecular subtype signatures of LA to clarify the correlation among the immune microenvironment, clinical outcomes, and therapeutic response. METHODS: The LA immune cell marker genes (LICMGs) identified by single-cell RNA sequencing (scRNA-seq) analysis were used to discriminate the molecular subtypes and homologous immune and metabolic traits of GSE72094 LA cases. In addition, the model-building genes were identified from 1441 LICMGs by Cox-regression analysis, and a LA immune difference score (LIDscore) was developed to quantify individual differences in each patient, thereby predicting prognosis and susceptibility to immunotherapy and chemotherapy of LA patients. RESULTS: Patients of the GSE72094 cohort were divided into two distinct molecular subtypes based on LICMGs: immune activating subtype (Cluster-C1) and metabolically activating subtype (cluster-C2). The two molecular subtypes have distinct characteristics regarding prognosis, clinicopathology, genomics, immune microenvironment, and response to immunotherapy. Among the LICMGs, LGR4, GOLM1, CYP24A1, SFTPB, COL1A1, HLA-DQA1, MS4A7, PPARG, and IL7R were enrolled to construct a LIDscore model. Low-LIDscore patients had a higher survival rate due to abundant immune cell infiltration, activated immunity, and lower genetic variation, but probably the higher levels of Treg cells in the immune microenvironment lead to immune cell dysfunction and promote tumor immune escape, thus decreasing the responsiveness to immunotherapy compared with that of the high-LIDscore patients. Overall, high-LIDscore patients had a higher responsiveness to immunotherapy and a higher sensitivity to chemotherapy than the low-LIDscore group. CONCLUSIONS: Molecular subtypes based on LICMGs provided a promising strategy for predicting patient prognosis, biological characteristics, and immune microenvironment features. In addition, they helped identify the patients most likely to benefit from immunotherapy and chemotherapy.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Prognosis , Genes, Regulator , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Phenotype , Immunotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Tumor Microenvironment/genetics , Membrane Proteins
12.
J Fungi (Basel) ; 9(10)2023 Sep 23.
Article in English | MEDLINE | ID: mdl-37888215

ABSTRACT

Grifola frondosa is a valuable edible fungus with high nutritional and medicinal values. The mating systems of fungi not only offer practical strategies for breeding, but also have far-reaching effects on genetic variability. Grifola frondosa has been considered as a sexual species with a tetrapolar mating system based on little experimental data. In the present study, one group of test crosses and six groups of three-round mating experiments from two parental strains were conducted to determine the mating system in G. frondosa. A chi-squared test of the results of the test-cross mating experiments indicated that they satisfied Mendelian segregation, while a series of three-round mating experiments showed that Mendelian segregation was not satisfied, implying a segregation distortion phenomenon in G. frondosa. A genomic map of the G. frondosa strain, y59, grown from an LMCZ basidiospore, with 40.54 Mb and 12 chromosomes, was generated using genome, transcriptome and Hi-C sequencing technology. Based on the genomic annotation of G. frondosa, the mating-type loci A and B were located on chromosomes 1 and 11, respectively. The mating-type locus A coded for the ß-fg protein, HD1, HD2 and MIP, in that order. The mating-type locus B consisted of six pheromone receptors (PRs) and five pheromone precursors (PPs) in a crossed order. Moreover, both HD and PR loci may have only one sublocus that determines the mating type in G. frondosa. The nonsynonymous SNP and indel mutations between the A1B1 and A2B2 mating-type strains and the reference genome of y59 only occurred on genes HD2 and PR1/2, preliminarily confirming that the mating type of the y59 strain was A1B2 and not A1B1. Based on the genetic evidence and the more reliable molecular evidence, the results reveal that the mating system of G. frondosa is tetrapolar. This study has important implications for the genetics and hybrid breeding of G. frondosa.

13.
Biomed Environ Sci ; 36(8): 779-782, 2023 Aug 20.
Article in English | MEDLINE | ID: mdl-37711091

ABSTRACT

In August 2021, three students with diarrhea from the same school visited a local hospital in the S district of Beijing. An epidemic investigation showed that there were more students with diarrhea in the same school and they had one meal together. Campylobacter jejuni was isolated from both patients with diarrhea and asymptomatic food handlers; however, the latter also carried Campylobacter coli. Phylogenomic analysis showed that there was a campylobacteriosis outbreak among the students, and the asymptomatic food handler may have been the source of the infection. Routine inspection and surveillance for Campylobacter is needed for the food producing staff, particularly those cooking in the cafeteria in schools or other public food services.


Subject(s)
Campylobacter Infections , Campylobacter , Gastroenteritis , Humans , Campylobacter Infections/epidemiology , Diarrhea , Disease Outbreaks
14.
Materials (Basel) ; 16(18)2023 Sep 08.
Article in English | MEDLINE | ID: mdl-37763400

ABSTRACT

By experimental methods, 26 specimens were designed to conduct elastic and elastic-plastic buckling tests on cylindrical shells containing cracks. This study discusses the influence of factors such as the length-diameter ratio, the diameter-thickness ratio, the crack length, the inclination of the crack, etc., on the buckling load. Additionally, finite element models were established to compare with experimental results. For the PMMA cylindrical shell, the results showed that as the length-diameter ratio of the cylindrical shell increased, the buckling load first decreased and then increased. For the 6063 aluminum alloy cylindrical shell, with increasing length-diameter ratio, diameter-thickness ratio, and crack length of the cylindrical shell, the buckling load decreased accordingly. However, concerning the crack inclination, as the crack inclination increased, the buckling load increased accordingly. This indicates that the larger the crack inclination, the higher the load capacity of the cylindrical shell containing cracks. Through finite element simulations of cylindrical shells with cracks, it was found that through compressive mechanical properties, both elastic and elastic-plastic buckling loads yielded results that are closer to the experimental results. Additionally, the inclusion of contact effects in numerical simulations further improved the agreement with the experimental results, and the variation trend of the buckling load in the finite element simulation was consistent with the experimental results. The research findings provide valuable references for the assessment of load capacity in structures containing cracks.

15.
J Mol Med (Berl) ; 101(8): 917-929, 2023 08.
Article in English | MEDLINE | ID: mdl-37328669

ABSTRACT

Transcription factor EB, a member of the microphthalmia-associated transcription factor (MiTF/TFE) family, is a master regulator of autophagy, lysosome biogenesis, and TAMs. Metastasis is one of the main reasons for the failure of tumor therapy. Studies on the relationship between TFEB and tumor metastasis are contradictory. On the positive side, TFEB mainly affects tumor cell metastasis via five aspects, including autophagy, epithelial-mesenchymal transition (EMT), lysosomal biogenesis, lipid metabolism, and oncogenic signaling pathways; on the negative side, TFEB mainly affects tumor cell metastasis in two aspects, including tumor-associated macrophages (TAMs) and EMT. In this review, we described the detailed mechanism of TFEB-mediated regulation of metastasis. In addition, we also described the activation and inactivation of TFEB in several aspects, including the mTORC1 and Rag GTPase systems, ERK2, and AKT. However, the exact process by which TFEB regulates tumor metastasis remains unclear in some pathways, which requires further studies.


Subject(s)
Autophagy , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Mechanistic Target of Rapamycin Complex 1/metabolism , Signal Transduction , Lysosomes/metabolism , Phosphorylation
16.
Phytochemistry ; 212: 113728, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37211335

ABSTRACT

Cinnamigones A-C, three undescribed highly oxidized guaiane-type sesquiterpenes were isolated from the fruits of Cinnamomum migao. Cinnamigone A (1), structurally artemisinin-like, is a natural 1,2,4-trioxane caged endoperoxide with an unprecedented tetracyclic 6/6/7/5 ring system. Compounds 2-3 are classic guaiane sesquiterpene featuring different epoxy units. Guaiol (4) is considered to be the precursor of 1-3 in the biosynthesis pathway hypothesis. The planar structures and configurations of cinnamigones A-C were elucidated by spectral analysis, HRESIMS, X-ray crystallography and ECD calculations. Evaluation of the neuroprotective activity of 1-3 on N-methyl-ᴅaspartate (NMDA) toxicity was demonstrated that compounds 1-2 exhibited moderate neuroprotective activity against NMDA-induced neurotoxicity.


Subject(s)
Cinnamomum , Sesquiterpenes , Molecular Structure , N-Methylaspartate , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Sesquiterpenes, Guaiane/pharmacology
17.
Proc Natl Acad Sci U S A ; 120(18): e2207537120, 2023 05 02.
Article in English | MEDLINE | ID: mdl-37098064

ABSTRACT

Policymakers must make management decisions despite incomplete knowledge and conflicting model projections. Little guidance exists for the rapid, representative, and unbiased collection of policy-relevant scientific input from independent modeling teams. Integrating approaches from decision analysis, expert judgment, and model aggregation, we convened multiple modeling teams to evaluate COVID-19 reopening strategies for a mid-sized United States county early in the pandemic. Projections from seventeen distinct models were inconsistent in magnitude but highly consistent in ranking interventions. The 6-mo-ahead aggregate projections were well in line with observed outbreaks in mid-sized US counties. The aggregate results showed that up to half the population could be infected with full workplace reopening, while workplace restrictions reduced median cumulative infections by 82%. Rankings of interventions were consistent across public health objectives, but there was a strong trade-off between public health outcomes and duration of workplace closures, and no win-win intermediate reopening strategies were identified. Between-model variation was high; the aggregate results thus provide valuable risk quantification for decision making. This approach can be applied to the evaluation of management interventions in any setting where models are used to inform decision making. This case study demonstrated the utility of our approach and was one of several multimodel efforts that laid the groundwork for the COVID-19 Scenario Modeling Hub, which has provided multiple rounds of real-time scenario projections for situational awareness and decision making to the Centers for Disease Control and Prevention since December 2020.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Uncertainty , Disease Outbreaks/prevention & control , Public Health , Pandemics/prevention & control
18.
Drug Resist Updat ; 67: 100929, 2023 03.
Article in English | MEDLINE | ID: mdl-36739809

ABSTRACT

Currently, renal cell carcinoma (RCC) is the most prevalent type of kidney cancer. Targeted therapy has replaced radiation therapy and chemotherapy as the main treatment option for RCC due to the lack of significant efficacy with these conventional therapeutic regimens. Sunitinib, a drug used to treat gastrointestinal tumors and renal cell carcinoma, inhibits the tyrosine kinase activity of a number of receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), c-Kit, rearranged during transfection (RET) and fms-related receptor tyrosine kinase 3 (Flt3). Although sunitinib has been shown to be efficacious in the treatment of patients with advanced RCC, a significant number of patients have primary resistance to sunitinib or acquired drug resistance within the 6-15 months of therapy. Thus, in order to develop more efficacious and long-lasting treatment strategies for patients with advanced RCC, it will be crucial to ascertain how to overcome sunitinib resistance that is produced by various drug resistance mechanisms. In this review, we discuss: 1) molecular mechanisms of sunitinib resistance; 2) strategies to overcome sunitinib resistance and 3) potential predictive biomarkers of sunitinib resistance.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Biomarkers , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Indoles/pharmacology , Indoles/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Pyrroles/pharmacology , Pyrroles/therapeutic use , Receptors, Vascular Endothelial Growth Factor/metabolism , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Sunitinib/pharmacology , Sunitinib/therapeutic use , Vascular Endothelial Growth Factor A , Drug Resistance, Neoplasm
19.
J Fungi (Basel) ; 9(2)2023 Feb 03.
Article in English | MEDLINE | ID: mdl-36836313

ABSTRACT

Four new species of Russula subsection Sardoninae from northern and southwestern China under coniferous and deciduous trees are proposed as R. begonia, R. photinia, R. rhodochroa, and R. rufa. Illustrations and descriptions of R. gracillima, R. leucomarginata, R. roseola, and the above four new species are provided based on evidence of morphological characters and phylogenetic analyses of the internal transcribed spacer (ITS), as well as the multi-locus of mtSSU, nLSU, rpb1, rpb2 and tef1-α. The relationships between these new species and allied taxa are discussed.

20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-973233

ABSTRACT

ObjectiveTo investigate the mechanism of Akkermansia muciniphila (A. muciniphila) regulating the visceral hypersensitivity in irritable bowel syndrome (IBS) rats induced by neonatal maternal separation (MS) and water avoidance stress (WAS). MethodsNeonatal male Sprague-Dawley rats were randomly divided into sham WAS group (blank group), MS+WAS group (IBS model group) and A. muciniphila group. IBS model was established by MS combined with WAS in both IBS model group and A. muciniphila group. Meanwhile, the rats in the A. muciniphila group were given 1 mL 1×109 CFU/mL A. muciniphila by gavage daily for 10 days. Visceral pain responses were detected by behavioral observations and abdominal withdrawal reflex scores. ResultsCompared with IBS model group, A. muciniphila group exhibited significant increase of body weight and visceral pain threshold, significantly decreased numbers of fecal particles and proportions of unformed stools, significantly higher expression levels of cannabinoid receptor type 2 (CB2R) mRNA in colon tissues. ConclusionA. muciniphila may alleviate the visceral hypersensitivity in IBS rats by regulating the expression of CB2R mRNA in colonic tissues.

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