Germline Mutations in 32 Cancer Susceptibility Genes by Next-Generation Sequencing among Breast Cancer Patients.

INTRODUCTION: BRCA1/2 germline mutations are the most well-known genetic determinants for breast cancer. However, the distribution of germline mutations in non-BRCA1/2 cancer susceptibility genes in Chinese breast cancer patients is unclear. The association between clinical characteristics and germline mutations remains to be explored. METHODS: Consecutive breast cancer patients from Peking University People's Hospital were enrolled. Clinical characteristics were collected, and next-generation sequencing was performed using blood samples of participants to identify pathogenic/likely pathogenic (P/LP) germline mutations in 32 cancer susceptibility genes including homologous recombination repair (HRR) genes. RESULTS: A total of 885 breast cancer patients underwent the detection of germline mutations. 107 P/LP germline mutations of 17 genes were identified in 116 breast cancer patients including 79 (8.9%) in BRCA1/2 and 40 (4.5%) in 15 non-BRCA1/2 genes. PALB2 was the most frequently mutated gene other than BRCA1/2 but still relatively rare (1.1%). There were 38 novel P/LP germline variants detected. P/LP germline mutations in BRCA1/2 were significantly associated with onset age (p < 0.001), the family history of breast/ovarian cancer (p = 0.010), and molecular subtype (p < 0.001), while being correlated with onset age (p < 0.001), site of breast tumor (p = 0.028), and molecular subtype (p < 0.001) in HRR genes. CONCLUSIONS: The multiple-gene panel prominently increased the detection rate of P/LP germline mutations in 32 cancer susceptibility genes compared to BRCA1/2 alone. Onset younger than or equal to 45 years of age, bilateral and triple-negative breast cancer patients may be more likely to be recommended for detecting P/LP germline mutations in HRR genes.

The association between visceral adiposity index and leukocyte telomere length in adults: results from National Health and Nutrition Examination Survey.

BACKGROUND: Leukocyte telomere length (LTL) is a robust marker of biological aging, which is associated with obesity. Recently, the visceral adiposity index (VAI) has been proposed as an indicator of adipose distribution and function. OBJECTIVE: To evaluated the association between VAI and LTL in adult Americans. METHODS: There were 3193 participants in U.S. National Health and Nutrition Examination Surveys (1999-2002) included in this analysis. LTL was measured using quantitative PCR (qPCR) and expressed as telomere to single-gene copy ratio (T/S ratio). We performed multiple logistic regression models to explore the association between VAI and LTL by adjusting for potential confounders. RESULTS: Among all participants, VAI was associated with the shorter LTL (ß: - 14.81, 95% CI - 22.28 to - 7.34, p < 0.001). There were significant differences of LTL in VAI tertiles (p < 0.001). Participants in the higher VAI tertile had the shorter LTL (1.26 ≤ VAI < 2.46: ß = - 130.16, 95% CI [ - 183.44, - 76.87]; VAI ≥ 2.46: ß = - 216.12, 95% CI [ - 216.12, - 81.42], p for trend: < 0.001) comparing with the lower VAI tertile. We also found a non-linear relationship between VAI and LTL. VAI was negatively correlated with LTL when VAI was less than 2.84. CONCLUSIONS: The present study demonstrates that VAI is independently associated with telomere length. A higher VAI is associated with shorter LTL. The results suggest that VAI may provide prediction for LTL and account for accelerating the biological aging.

Germline Variants in 32 Cancer-Related Genes among 700 Chinese Breast Cancer Patients by Next-Generation Sequencing: A Clinic-Based, Observational Study.

Breast cancer (BC) is associated with hereditary components, and some deleterious germline variants have been regarded as effective therapeutic targets. We conducted a clinic-based, observational study to better understand the distribution of deleterious germline variants and assess any clinicopathological predictors related to the variants among Chinese BC patients using a 32 cancer-related genes next-generation sequencing panel. Between November 2020 and February 2022, a total of 700 BC patients were recruited, and 13.1% (92/700) of them carried deleterious germline variants in 15 cancer-related genes, including 37 (37/700, 5.3%) in BRCA2, 29 (29/700, 4.1%) in BRCA1, 8 (8/700, 1.1%) in PALB2, 4 (4/700, 0.6%) in NBN, 3 (3/700, 0.4%) in MRE11A, 3 (3/700, 0.4%) in TP53 and 12 (12/700, 1.7%) in other genes. There were 28 novel variants detected: 5 in BRCA1, 14 in BRCA2, and 9 in non-BRCA1/2 genes. The variants in panel genes, HRR (homologous recombination repair)-related genes, and BRCA1/2 were significantly associated with the following clinicopathological factors: age at the initial diagnosis of BC, family history of any cancer, molecular subtype, Ki-67 index, and hereditary risk. In conclusion, we further expanded the spectrum of germline deleterious variants in Chinese BC patients, and the clinicopathological predictors of variants were identified to facilitate clinical genetic testing and counseling for appropriate individuals.

Infection of Epstein-Barr Virus is Associated with the Decrease of Helios+FoxP3+Regulatory T Cells in Active Ulcerative Colitis Patients.

Background: Loss of immune homeostasis to enteric pathogens is considered to be involved in the pathogenesis of ulcerative colitis (UC), and regulatory T cells (Tregs) are key for this immune homeostasis. Helios exhibits an important effect on regulating the suppressive function of Tregs. Epstein-Barr virus (EBV) is more commonly detected in UC. However, whether there is an association between EBV infection and Helios+Tregs and its impact on disease activity of UC remain unclear. We aimed to explore the clinical significance of Helios+Tregs and their potential association with EBV infection in UC. Methods: Seventy-six UC patients and 38 controls were consecutively enrolled. Helios+FoxP3+Tregs were analyzed using flow cytometry and compared among groups. Eight active UC patients treated with 5-aminosalicylic acid were followed up. Correlation analyses were conducted between Helios+FoxP3+Tregs and disease activity indicators. In addition, EBV viral loads in the mucosal lesion were quantified in active UC by quantitative polymerase chain reaction and were comprehensively analyzed in subgroups of different disease severity, and their associations with Helios+FoxP3+Tregs were also analyzed. Results: Helios+FoxP3+Tregs were significantly decreased in active UC and were inversely correlated with serum C-reactive protein and Mayo score. Moreover, we observed the recovery of Helios+FoxP3+Tregs in followed-up active UC achieving remission after treatment. EBV loads were higher in active UC, and levels of Helios+FoxP3+Tregs in the EBV-positive subgroup were lower than the EBV-negative subgroup in moderate and severe active patients. Most importantly, we found that Helios+FoxP3+Tregs were significantly negatively correlated with EBV viral loads. Conclusion: Helios+FoxP3+Tregs are likely to play a pivotal role in disease activity of UC and may be influenced by EBV infection.

A Compound Heterozygosis of Two Novel Mutations Causes Factor X Deficiency in a Chinese Pedigree.

BACKGROUND: Mutations in the F10-coding gene can cause factor X (FX) deficiency, leading to abnormal coagulation activity and severe tendency for hemorrhage. Therefore, identifying mutations in F10 is important for diagnosing congenital FX deficiency. METHODS: We studied a 63-year-old male patient with FX deficiency and 10 of his family members. Clotting and immunological methods were used to determine activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen levels, FX activity, and FX antigen levels. The platelet count was determined. A mixing study was performed to eliminate the presence of coagulation factor inhibitors and lupus anticoagulant. Mutations were searched using whole-exome sequencing and certified by Sanger sequencing. RESULTS: Genetic analysis of the proband identified two single-base substitutions: c.1085G>A (p.Ser362Asn) and c.1152C>A (p.Tyr384Ter, termination codon, caused by the DNA sequence TAA). His FX activity and antigen levels were 1.7% and 408.53 pg/mL, respectively; aPTT and PT were 52.3 and 48.0 s, respectively. One brother had the same compound heterozygous mutations, and his FX activity and antigen levels were 1.3% and 465.47 pg/mL, respectively; his aPTT and PT were 65.2 and 54.5 s, respectively. His mother, another brother, and one sister were heterozygous for c.1085G>A (p.Ser362Asn), and his daughter and grandson (6 years old) were heterozygous for c.1152C>A (p.Tyr384Ter). CONCLUSION: The heterozygous variants p.Ser362Asn or p.Tyr384Ter indicate mild FX deficiency, but the compound heterozygous mutation of the two causes severe congenital FX deficiency and bleeding. Genetic analysis of these two mutations may help characterize the bleeding tendency and confirm congenital FX deficiency.

Resonance-Enhanced Charge Delocalization in Carbazole-Oligoyne-Oxadiazole Conjugates.

There are notably few literature reports of electron donor-acceptor oligoynes, even though they offer unique opportunities for studying charge transport through "all-carbon" molecular bridges. In this context, the current study focuses on a series of carbazole-(C≡C)n-2,5-diphenyl-1,3,4-oxadiazoles (n = 1-4) as conjugated π-systems in general and explores their photophysical properties in particular. Contrary to the behavior of typical electron donor-acceptor systems, for these oligoynes, the rates of charge recombination after photoexcitation increase with increasing electron donor-acceptor distance. To elucidate this unusual performance, we conducted detailed photophysical and time-dependent density functional theory investigations. Significant delocalization of the molecular orbitals along the bridge indicates that the bridging states come into resonance with either the electron donor or acceptor, thereby accelerating the charge transfer. Moreover, the calculated bond lengths reveal a reduction in bond-length alternation upon photoexcitation, indicating significant cumulenic character of the bridge in the excited state. In short, strong vibronic coupling between the electron-donating N-arylcarbazoles and the electron-accepting 1,3,4-oxadiazoles accelerates the charge recombination as the oligoyne becomes longer.

Upregulated IL-17A secretion and CCR6 co-expression in Treg subsets are related to the imbalance of Treg/Th17 cells in active UC patients.

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disease, which is characterized with overactive immune response. It is well established that the imbalance between Tregs and Th17 cells plays a pivotal role in pathogenesis of UC. In this study, we investigated the impact of functional changes in Treg subsets on Treg/Th17 ratio and further explored their clinical significance in the activity of UC. Treg subsets were comprehensively analysed using flow cytometry and in vitro cultured in both active and remission UC patients, of which nine active UC patients were further followed up. The correlation analyses were performed to explore the potential associations between Treg subsets and clinical indicators, as well as the impact of serum cytokines, detected by ELISA, on IL-17A secretion and CCR6 co-expression of Treg subsets. In active UC patients, we found CD45RA- FoxP3hi Tregs were obviously decreased and inversely correlated with disease activity, while CD45RA+ FoxP3lo Tregs were increased and positively correlated with disease activity. Meanwhile, IL-17A secretion and CCR6 co-expression levels in Tregs were significantly increased in active UC. Moreover, Tregs co-expressing CCR6 possesses higher level of IL-17A secretion. In nine followed up patients, we observed downregulated IL-17A secreting and CCR6 co-expression when achieving remission from active stage. In addition, IL-17A+ FoxP3+ and IL-17A+ FoxP3+ CCR6+ Tregs were positively correlated with serum IL-21 and disease activity, respectively. These findings suggested that upregulated IL-17A secretion and CCR6 co-expression in Treg subsets may be related to the imbalance between Tregs and Th17 cells and associated with the disease activity in UC patients.

Selective Protein Separation Based on Charge Anisotropy by Spherical Polyelectrolyte Brushes.

Protein purification is of vital importance in the food industry, drug discovery, and other related fields. Among many separation methods, polyelectrolyte (PE)-based phase separation was developed and recognized as a low-cost purification technique. In this work, spherical polyelectrolyte brushes (SPBs) with a high specific surface area were utilized to study the protein accessibility and selective protein binding on highly charged nanoparticles (NPs) as well as the selective phase separation of proteins. The correlation between charge anisotropy, protein binding, and phase separation was investigated on various protein systems including those proteins with similar isoelectric points (pI) such as bovine serum albumin (BSA) and ß-lactoglobulin (BLG), proteins with similar molecular weights such as BSA and hemoglobin (HB), and even protein variants (BLG-A and -B) with a tiny difference of amino acids. The nonspecific electrostatic interaction studied by turbidimetric titrations and isothermal calorimetry titration (ITC) indicates a specific binding between proteins and SPBs arising from the charge anisotropy of proteins. An optimized output based on selective protein binding on SPBs could be correlated for efficient protein separation through tuning external conditions including pH and ionic strength. These findings, therefore, proved that phase separation based on selective protein adsorption by SPBs was an efficient alternative for protein separation compared with the traditional practice.

Spatiotemporal Trends of Malaria in Relation to Economic Development and Cross-Border Movement along the China-Myanmar Border in Yunnan Province.

The heterogeneity and complexity of malaria involves political and natural environments, socioeconomic development, cross-border movement, and vector biology; factors that cannot be changed in a short time. This study aimed to assess the impact of economic growth and cross-border movement, toward elimination of malaria in Yunnan Province during its pre-elimination phase. Malaria data during 2011-2016 were extracted from 18 counties of Yunnan and from 7 villages, 11 displaced person camps of the Kachin Special Region II of Myanmar. Data of per-capita gross domestic product (GDP) were obtained from Yunnan Bureau of Statistics. Data were analyzed and mapped to determine spatiotemporal heterogeneity at county and village levels. There were a total 2,117 malaria cases with 85.2% imported cases; most imported cases came from Myanmar (78.5%). Along the demarcation line, malaria incidence rates in villages/camps in Myanmar were significantly higher than those of the neighboring villages in China. The spatial and temporal trends suggested that increasing per-capita GDP may have an indirect effect on the reduction of malaria cases when observed at macro level; however, malaria persists owing to complex, multi-faceted factors including poverty at individual level and cross-border movement of the workforce. In moving toward malaria elimination, despite economic growth, cooperative efforts with neighboring countries are critical to interrupt local transmission and prevent reintroduction of malaria via imported cases. Cross-border workers should be educated in preventive measures through effective behavior change communication, and investment is needed in active surveillance systems and novel diagnostic and treatment services during the elimination phase.

Ratiometric Nanoparticle Array-Based Near-Infrared Fluorescent Probes for Quantitative Protein Sensing.

Quantitative detection of protein biomarkers is crucial to medical diagnosis. Fluorescent probes have been frequently used for protein detection, but they suffered from various weaknesses such as lack of versatility. In particular, most of the reported probes were not capable of simultaneous qualitative and quantitative detection for various proteins. In this paper, we developed novel nanoparticle array-based near-infrared (NIR) ratiometric probes for potent protein analysis, in which the specific protein was able to be distinguished and quantitated within a group of 11 common proteins. The activity of ß-galactosidases (ß-gal) was temporarily inhibited by the adsorption to magnetic nanoparticles and restored to certain content by replacement with detected proteins, leading to distinctive readout of the enzyme-activatable NIR probe (DCM-ß-gal). The readout of the sensor array against 11 proteins, as verified by isothermal titration calorimetry, was processed and transformed into canonical factors with the help of linear discrimination analysis. Moreover, the ratiometric signals of DCM-ß-gal were translated to quantitatively detect proteins within the concentration range of 0-100 µg/mL. Based on clear differentiation within both two-dimensional and three-dimensional plots, different proteins could be detected with 100% accuracy with their concentration simultaneously determined, which endowed the sensing system with great potential in clinical diagnosis.

A Case-Control Study of the Association of the Polymorphisms of MTHFR and APOE with Risk Factors and the Severity of Coronary Artery Disease.

OBJECTIVES: To explore the association between single-nucleotide polymorphisms (SNPs) in MTHFR and APOE and the risk of CAD and, more importantly, the severity of CAD and the profile of serum lipids, we performed a case-control study in a Chinese Han population. METHODS: A total of 1,207 cases of consecutive CAD-suspected inpatients were recruited, and 406 CAD cases and 231 non-CAD controls were enrolled for the final analysis after screening for exclusion criteria. All subjects had undergone coronary angiography, and the severity of CAD was evaluated by 2 cardiologists according to the Gensini scores. The genotypes of MTHFR and APOEwere detected using real-time PCR, and then verified by Sanger sequencing. Environmental risk factors, such as age, sex, smoking, alcohol consumption, hypertension, diabetes, dyslipidemia, and BMI were collected. Statistical analyses (the χ2 test, binary logistic regression analysis, and ordinal polytomous logistic regression analysis) were performed with SPSS v16.0. RESULTS: The genotypes ofall the subjects included in the CAD and non-CAD groups in this study were successfully detected, with an agreement of 100% with Sanger sequencing. The distributions of genotypes CT and TT at MTHFR C667T were higher in CAD cases than in non-CAD controls (OR 1.99, 95% CI 1.34-2.95; OR 1.77, 95% CI 1.18-2.67; p < 0.05), whereas genotype AC at MTHFR A1298Cwas lower in CAD cases (OR 0.71, 95% CI 0.50-1.02; p < 0.05). A significant association was observed in genotypes CT and TT at MTHFR C667T and the risk of CAD (OR 1.44, 95% CI 1.27-3.67; OR 1.56, 95% CI 0.88-2.78; p < 0.05). Both genotypes and alleles of APOE were comparable in the CAD cases and non-CAD controls (p > 0.05). The genotype TT at MTHFR C667T and ε4+ at APOE were more likely to be found in the CAD subgroup with a Gensini score ≥72 (p = 0.040 and p = 0.028, respectively). Meanwhile, in the patients with genotype TT,a higher level of serum Hcy was detected, while genotype ε4+ patients possessed higher levels of serum apolipoprotein E (ApoE) and low-density lipoprotein cholesterol (LDL-C) than other genotypes. CONCLUSION: This study revealed that the SNP site of MTHFR C667Tis associatedwith the risk of CAD in this Chinese Han population. In addition, the genotypes of TT in MTHFR C667T and ε4+in APOE may increase the severity of CAD, and higher Hcy, LDL-C, and ApoE levels may be involved in this pathogenic process.

Meta-analysis of Nicorandil effectiveness on myocardial protection after percutaneous coronary intervention.

BACKGROUND: Using the current meta-analysis as well as systematic review, to determine the curative effect of Nicorandil in comparison of no Nicorandil after elective percutaneous coronary intervention(PCI) on patients. METHODS: Published literatures were identified via a computerized literature search of CENTRAL, PubMed, Cochrane, Embase Databases of Systematic Reviews. A set of randomized trials evaluating Nicorandil in comparison of no Nicorandil administered following PCI in patients harboring coronary artery disease were included. Outcomes were revealed based on the following parameters: peak creatine kinase-MB (CK-MB) value, left ventricular ejection fraction (LVEF), peak troponin I (cTnI), and major adverse cardiovascular events (MACEs) per randomized patients. RESULTS: We included a total of 14 RCTs involving 1864 subjects in the present review. According to this meta-analysis, LVEF was significantly improved in Nicorandil group; the peak CK-MB level and the incidence of adverse cardiovascular events were remarkably lower in Nicorandil group. Nicorandil and no Nicorandil administered group appeared to be equivalent with regards to cTnI. CONCLUSIONS: Nicorandil is effective for patients undergoing elective PCI with coronary artery disease in terms of reducing the incidence of adverse cardiovascular events as well as improving heart function. Nicorandil may exert potential role as a valid and adjunctive therapy accompanied with PCI.

Ionic Strength-Responsive Binding between Nanoparticles and Proteins.

Electrostatic interaction is a strong, dominant nonspecific interaction which was extensively studied in protein-nanoparticle (NP) interactions [ Lounis , F. M. ; J. Phys. Chem. B 2017 , 121 , 2684 - 2694 ; Tavares , G. M. ; Langmuir 2015 , 31 , 12481 - 12488 ; Antonov , M. ; Biomacromolecules 2010 , 11 , 51 - 59 ], whereas the role of hydrophobic interaction arising from the abundant hydrophobic residues of globule proteins upon protein-NP binding between the proteins and charged nanoparticles has rarely been studied. In this work, a series of positively charged magnetic nanoparticles (MNPs) were prepared via atom transfer radical polymerization and surface hydrophobicity differentiation was achieved through postpolymerization quaternization by different halohydrocarbons. The ionic strength- and hydrophobicity-responsive binding of these MNPs toward ß-lactoglobulin (BLG) was studied by both qualitative and quantitative methods including turbidimetric titration, dynamic light scattering, and isothermal titration calorimetry. Judged from the critical binding pH and binding constant for MNP-BLG complexation, the dependence of binding affinity on surface hydrophobicity exhibited an interesting shift with increasing ionic strength, which means that the MNPs with higher surface hydrophobicity exhibits weaker binding affinity at lower ionic strength but stronger affinity at higher ionic strength. This interesting observation could be attributed to the difference in ionic strength responsiveness for hydrophobic and electrostatic interactions. In this way, the well-tuned binding pattern could be achieved with optimized binding affinity by controlling the surface hydrophobicity of MNPs and ionic strength, thus endowing this system with great potential to fabricate separation and delivery system with high selectivity and efficiency.

Metal-Free Fluorine-Doped Carbon Electrocatalyst for CO2 Reduction Outcompeting Hydrogen Evolution.

The electrochemical CO2 reduction (ECDRR), as a key reaction in artificial photosynthesis to implement renewable energy conversion/storage, has been inhibited by the low efficiency and high costs of the electrocatalysts. Herein, we synthesize a fluorine-doped carbon (FC) catalyst by pyrolyzing commercial BP 2000 with a fluorine source, enabling a highly selective CO2 -to-CO conversion with a maximum Faradaic efficiency of 90 % at a low overpotential of 510 mV and a small Tafel slope of 81 mV dec-1 , outcompeting current metal-free catalysts. Moreover, the higher partial current density of CO and lower partial current density of H2 on FC relative to pristine carbon suggest an enhanced inherent activity towards ECDRR as well as a suppressed hydrogen evolution by fluorine doping. Fluorine doping activates the neighbor carbon atoms and facilitates the stabilization of the key intermediate COOH* on the fluorine-doped carbon material, which are also blocked for competing hydrogen evolution, resulting in superior CO2 -to-CO conversion.

Radical-Enhanced Charge Transport in Single-Molecule Phenothiazine Electrical Junctions.

We studied the single-molecule conductance through an acid oxidant triggered phenothiazine (PTZ-) based radical junction using the mechanically controllable break junction technique. The electrical conductance of the radical state was enhanced by up to 200 times compared to the neutral state, with high stability lasting for at least two months and high junction formation probability at room-temperature. Theoretical studies revealed that the conductance increase is due to a significant decrease of the HOMO-LUMO gap and also the enhanced transmission close to the HOMO orbital when the radical forms. The large conductance enhancement induced by the formation of the stable PTZ radical molecule will lead to promising applications in single-molecule electronics and spintronics.

Electrochemical control of single-molecule conductance by Fermi-level tuning and conjugation switching.

Controlling charge transport through a single molecule connected to metallic electrodes remains one of the most fundamental challenges of nanoelectronics. Here we use electrochemical gating to reversibly tune the conductance of two different organic molecules, both containing anthraquinone (AQ) centers, over >1 order of magnitude. For electrode potentials outside the redox-active region, the effect of the gate is simply to shift the molecular energy levels relative to the metal Fermi level. At the redox potential, the conductance changes abruptly as the AQ unit is oxidized/reduced with an accompanying change in the conjugation pattern between linear and cross conjugation. The most significant change in conductance is observed when the electron pathway connecting the two electrodes is via the AQ unit. This is consistent with the expected occurrence of destructive quantum interference in that case. The experimental results are supported by an excellent agreement with ab initio transport calculations.

The synthesis of functionalised diaryltetraynes and their transport properties in single-molecule junctions.

The synthesis and characterisation is described of six diaryltetrayne derivatives [Ar-(C≡C)4-Ar] with Ar=4-NO2-C6H4- (NO24), 4-NH(Me)C6H4- (NHMe4), 4-NMe2C6H4- (NMe24), 4-NH2-(2,6-dimethyl)C6H4- (DMeNH24), 5-indolyl (IN4) and 5-benzothienyl (BTh4). X-ray molecular structures are reported for NO24, NHMe4, DMeNH24, IN4 and BTh4. The stability of the tetraynes has been assessed under ambient laboratory conditions (20 °C, daylight and in air): NO24 and BTh4 are stable for at least six months without observable decomposition, whereas NHMe4, NMe24, DMeNH24 and IN4 decompose within a few hours or days. The derivative DMeNH24, with ortho-methyl groups partially shielding the tetrayne backbone, is considerably more stable than the parent compound with Ar=4-NH2C6H4 (NH24). The ability of the stable tetraynes to anchor in Au|molecule|Au junctions is reported. Scanning-tunnelling-microscopy break junction (STM-BJ) and mechanically controllable break junction (MCBJ) techniques are employed to investigate single-molecule conductance characteristics.

Assessment of retrospective dose estimation, with fluorescence in situ hybridization (FISH), of six victims previously exposed to accidental ionizing radiation.

The present study aims to evaluate the use of the fluorescence in situ hybridization (FISH) translocation assay for retrospective dose estimation of acute accidental exposure to radiation in the past. Reciprocal translocation analysis by FISH with three whole-chromosome probes was performed on normal peripheral blood samples. Samples were irradiated with 0-5Gy (60)Co γ-rays in vitro, and dose-effect curves were established. FISH-based translocation analyses for six accident victims were then performed, and biological doses were estimated retrospectively by comparison with the dose-effect curves. Reconstructed doses by FISH were compared with estimated doses obtained by analysis of di-centrics performed soon after exposure, or with dose estimates from tooth-enamel electron paramagnetic resonance (EPR) data obtained at the same time as the FISH analysis. Follow-up FISH analyses for an adolescent victim were performed. Results showed that dose-effect curves established in the present study follow a linear-quadratic model, regardless of the background translocation frequency. Estimated doses according to two dose-effect curves for all six victims were similar. FISH dose estimations of three adult victims exposed to accidental radiation less than a decade prior to analysis (3, 6, or 7 years ago) were consistent with those estimated with tooth-enamel EPR measurements or analyses of di-centrics. Estimated doses of two other adult victims exposed to radiation over a decade prior to analysis (16 or 33 years ago) were underestimated and two to three times lower than the values obtained from analysis of di-centrics or tooth-enamel EPR. Follow-up analyses of the adolescent victim showed that doses estimated by FISH analysis decrease rapidly over time. Therefore, the accuracy of dose estimates by FISH is acceptable only when analysis is performed less than 7 years after exposure. Measurements carried out more than a decade after exposure through FISH analysis resulted in underestimation of the biological doses compared with values obtained through analysis of di-centrics and tooth-enamel EPR.

Epidemiological Characterization of Dengue Fever - Yunnan Province, China, 2010-2021.

Objective: The goal of this study is to analyze the epidemiological patterns of dengue fever across different districts and counties in Yunnan Province from 2010 to 2021. Methods: In this study, we employed joinpoint regression analysis, spatial autocorrelation analysis, and space-time scan analysis to illustrate the spatio-temporal propagation and demographic influence of dengue fever, using both graphical and tabular presentations to clearly demonstrate the findings. Results: Yunnan Province reported 14,098 cases of dengue fever during the period from 2010 to 2021. Of these, 11,513 cases were caused by local transmission, 2,566 were imported internationally, and 19 were inter-provincial imports. Seasonal trends emerged, revealing a surge in incidences during the summer and autumn months. The sex ratio of male to female cases was 1:0.88, with a significant majority of 82.00% of cases involving individuals belonging to the age group of 15-60. Commercial service workers constituted the most impacted occupational group, forming 20.96% of total cases. A spatio-temporal scan identified significant clustering of dengue fever cases across space and time, with the most pronounced cluster observed in southern Yunnan, primarily between 2015 and 2019. Conclusions: Dengue fever in Yunnan Province manifests as biennial outbreaks, underscoring the necessity for increased surveillance, particularly in counties bordering other regions.

LES investigation of the wavy leading edge effect on cavitation noise.

This paper investigates the noise reduction performance of biomimetic hydrofoils with wavy leading edge and the corresponding mechanisms. We employ Large Eddy Simulation (LES) approach and permeable Ffowcs Williams-Hawkings (PFW-H) method to predict cavitation noise around the baseline and biomimetic hydrofoils. The results show that the wavy leading edge can effectively reduce the high-frequency noise, but has little effect on the low-frequency noise. Further analyses and discussions deal with the noise reduction mechanisms. The main source for the low-frequency noise is the cavity volume acceleration, while the wavy leading edge has little effect on it. The high-frequency noise sources, related to the surface pressure fluctuations and the turbulence characteristics, are significantly suppressed by the wavy leading edge, thus decreasing the high-frequency noise intensity. Our investigation indicates that the wavy leading edge has great prospects for cavitation noise reduction technique.