Photoactivated Circularly Polarized Luminescent Organic Radicals in Doped Amorphous Polymer.

Luminescent organic radicals, especially those with photoactivated circularly polarized luminescence (CPL) features, hold great significance for cutting-edge optoelectronic applications, but their development still remains a challenge. In this study, we propose a novel strategy to achieve photoactivated CPL radicals by bonding two phosphine centers within an axial chiral system, yielding a compound of R/S-5,5-bis(diphenylphosphino)-4,4'-bibenzo[d][1,3]dioxole (R/S-BDP). The photoactivated R/S-BDP molecules in polymer matrix display a robust quantum yield of 19.8 % and a dissymmetry factor (glum) of 1.2×10-4, marking this work as the first example of photoactivated CPL radicals. Furthermore, the glum is improved to 1.0×10-2 by using a liquid crystal as host. Experimental and theoretical analyses reveal that R/S-BDP molecules, endowed with double phosphine cores in axial chirality, offer a direct way for intramolecular electron transfer upon photoirradiation. This leads to the generation of radical ionic pairs, which subsequently trigger the donor-acceptor arrangement through intermolecular electron transfer, thereby resulting in stable radical emission. The extended photoactivated BDP-F exhibits a remarkably high quantum efficiency of 57.8%. Ultimately, the distinctive photo-responsive CPL radical luminescence has been successfully used for information displays and anti-counterfeiting.

Quarter-Wave Plate Metasurfaces for Generating Multi-Channel Vortex Beams.

Metasurfaces of quarter-wave plate (QWP) meta-atoms have exhibited high flexibility and versatile functionalities in the manipulation of light fields. However, the generation of multi-channel vortex beams with the QWP meta-atom metasurfaces presents a significant challenge. In this study, we propose dielectric metasurfaces composed of QWP meta-atoms to manipulate multi-channel vortex beams. QWP meta-atoms, systematically arranged in concentric circular rings, are designed to introduce the modulations via the propagation phase and geometric phase, leading to the generation of co- and cross-polarized vortex beams in distinct channels. Theoretical investigations and simulations are employed to analyze the modulation process, confirming the capability of QWP meta-atom metasurfaces for generating the multi-channel vortex beams. This study presents prospective advancements for the compact, integrated, and multifunctional nanophotonic platforms, which have potential applications in classical physics and quantum domains.

Chestnut tannin extract modulates growth performance and fatty acid composition in finishing Tan lambs by regulating blood antioxidant capacity, rumen fermentation, and biohydrogenation.

Tannins as plant extracts have emerged as promising and potential alternatives for antibiotics in modern livestock cultivation systems. This study investigates the effect of dietary chestnut tannin extract (CTE) in finishing Tan lambs. Twenty-seven male Tan lambs were randomly divided into three groups: (1) control group (CON; basal diet); (2) low-dose CTE group (LCTE; basal diet + 2 g/kg CTE, dry matter [DM] basis); (3) high-dose CTE group (HCTE; basal diet + 4 g/kg CTE, DM basis). The HCTE group exhibited markedly higher average daily gain (ADG) and DM intake than CON (P < 0.01). The ruminal total volatile fatty acid concentration increased linearly with increasing CTE supplementation (P < 0.01), while the opposite trend was observed for butyrate molar proportion (P < 0.01). Upon increasing CTE dosage, plasma glucose, high-density lipoprotein cholesterol, glutathione peroxidase, and superoxide dismutase content increased linearly (P < 0.05), whereas low-density lipoprotein cholesterol and urea nitrogen decreased linearly or quadratically (P < 0.05), respectively. A linear increase was also observed in ruminal t6 C18:1 and t9, c12 C18:2 proportions (P < 0.01), and plasma C18:2n-6 and n-6 polyunsaturated fatty acids proportions with increased CTE supplementation (P < 0.01). In the longissimus dorsi muscle, the atherogenic index decreased linearly (P < 0.05), while c11 C18:1 and C20:5n-3 increased linearly (P < 0.05). Moreover, c9, t11 conjugated linoleic acids proportion increased in subcutaneous fat with CTE supplementation (P < 0.01). In conclusion, Dietary CTE enhances the ADG of finishing Tan lambs in a dose-dependent manner, modulates plasma metabolites and antioxidant capacity, and improves rumen fermentation and body fatty acid composition. These results provide a reference for the rational application of CTE in ruminant production.

A high-throughput droplet digital PCR system aiming eight DNA methylation targets for age prediction.

The droplet digital Polymerase Chain Reaction (ddPCR) has garnered recognition for its distinctive attribute of absolute quantification. And it has found practical utility in age prediction through DNA methylation profiles. However, a prevalent limitation in current ddPCR methodologies is the restricted capacity to detect only two targets concurrently in most instruments, leading to high costs, sample wastage, and labor-intensive procedures. To address the limitations, a novel high-throughput ddPCR system allowing for the simultaneous detection of eight targets was developed. Through the implementation of a new 8-plex ddPCR assay, coupled with comprehensive linear regression analyses involving primers and probes ratios, diverse inputs of single CpG sites with distinct primers and probes, and varying plex assay configurations, stable DNA methylation values for four CpGs and stable measurement precisions for distinct multiplex systems were consistently observed. These findings pave the way for advancing the field of chemistry science by enabling more efficient and cost-effective methods. Furthermore, the comparative validation of ddPCR and SNaPshot demonstrated a remarkable concordance in results, and the system also displayed well in the field of various aspects, including species specificity, DNA input, and aged samples. In this study, the recommended input of bisulfite-converted DNA was determined to be 10-50 ng due to the double-positive droplets. Notably, the Pearson correlation coefficient squared values of four CpGs were 0.4878 (ASPA), 0.4832 (IGSF1), 0.6881 (COL1A1), and 0.6475 (MEIS1-AS3). And the testing set exhibited a mean absolute error of 4.5923 years, indicating the robustness and accuracy of the age-predictive model.

Explore variation of salivary bacteria across time and geolocations.

Saliva is an informative body fluid that can be found at various crime scenes, and the salivary bacterial community has been revealed it is a potential auxiliary target for forensic identification. However, the variation of salivary bacterial community composition across time and geolocation needs to be explored. The study was designed to be carried out during the winter vacation that was across about 50 days and eight geographic locations. The high throughput sequencing was performed with the V3-V4 region of the16S rRNA gene to explore salivary bacterial community composition. An overall slight fluctuation of the salivary bacteria was observed, which primarily occurred in the relative abundance of the salivary bacterial taxa. The results of principal coordinate analysis and hierarchical clustering showed samples were clustered by the individuals. All individuals could be correctly identified with the random forest model. In summation, although the relative abundance of salivary bacteria varied across the changes of time and geolocation, the individualized characteristic of salivary bacteria remained steady, which is beneficial for the salivary bacterial application in personal identification.

Serabelisib regulates GSDMD-mediated pyroptosis, apoptosis and migration of hepatoma cells via the PI3K/Akt/E-cadherin signaling pathway.

BACKGROUND: Liver cancer is a malignant tumor commonly seen in infants and young children. Serabelisib is a novel and effective phosphoinositide-3-kinase (PI3Kα) inhibitor, currently in trials for solid malignancy treatment, such as bladder cancer. However, it is unclear whether serabelisib affects liver cancer. OBJECTIVES: To explore the effects of serabelisib on the proliferation, apoptosis, invasion, and metastasis of HepG2 and HuH-6 cells, and elucidate the relevant molecular mechanisms. MATERIAL AND METHODS: The HepG2 cells were treated with 2 µM, 4 µM or 8 µM serabelisib, while the 0-µM group was used as a control. A plate clone formation assay was utilized to measure colony formation ability in each group, a 5-ethynyl-2'-deoxyuridine (EdU) assay examined cell proliferation, a Cell Counting Kit-8 (CCK-8) assay assessed cell viability, flow cytometry measured the cell cycle and apoptosis, JC-1 staining determined mitochondrial membrane potential, and transmission electron microscopy evaluated cell morphology. In addition, gene and protein expression levels of apoptosis markers, epithelial-mesenchymal transition (EMT), Gasdermin D (GSDMD), and the PI3K/protein kinase B (AKT) signaling pathway were measured. RESULTS: After serabelisib intervention, HepG2 and HuH-6 cells formed fewer colonies, proliferated more slowly, and had reduced viability. The number of HepG2 and HuH-6 cells in the G2 and S phases decreased, apoptosis and the number of apoptotic bodies increased, and mitochondrial membrane potential decreased. Serabelisib treatment also reduced the migration and invasion capacity of the cells. Furthermore, genes and proteins of the PI3K/AKT signaling pathway were downregulated, while those that promote apoptosis and pyroptosis or inhibit EMT were upregulated. CONCLUSIONS: Serabelisib inhibited the PI3K/AKT signaling pathway, thereby inhibiting EMT and promoting apoptosis and pyroptosis in HepG2 and HuH-6 cells.

JANet: A joint attention network for balancing accuracy and speed in left ventricular ultrasound video segmentation.

Multiple cardiac diseases are closely associated with functional parameters of the left ventricle, but functional parameter quantification still requires manual involvement, a time-consuming and less reproducible task. We develop a joint attention network (JANet) and expand it into two versions (V1 and V2) that can be used to segment the left ventricular region in echocardiograms to assist physicians in diagnosis. V1 is a smaller model with a size of 56.3 MB, and V2 has a higher accuracy. The proposed JANet V1 and V2 achieve a mean dice score (DSC) of 93.59/93.69(V1/V2), respectively, outperforming the state-of-the-art models. We grade 1264 patients with 87.24/87.50 (V1/V2) accuracy when using the 2-level classification criteria and 83.62/84.18 (V1/V2) when using the 5-level classification criteria. The results of the consistency analysis show that the proposed method is comparable to that of clinicians.

A forensic population database of autosomal STR and X-STR markers in the Qiang ethnic minority of China.

The Qiang ethnic group is one of the oldest ethnic groups in China and is the most active ethnic group among all the populations along the Tibetan-Yi corridor. They have had a profound impact nationally and internationally. The paternal and maternal genetic feature of the Qiang ethnic group has been revealed, leaving the question of the genetic characteristics from autosomes and X chromosome not answered. The aim of this study was to explore the potential of 36 A-STR (Microreader™ 36A ID System) and 19 X-STR (Microreader™ 19X System) for application in the Qiang population and to elucidate their genetic diversity in southwest China. The cumulative probability of exclusion (CPE) for autosomal STRs is 1-1.3814 × 10-15 and the mean paternity exclusion chance (MEC) for X-STRs is 1-1.7323 × 10-6. Forensic parameters suggest that the STRs analyzed here are well-suited for forensic applications. The results of phylogenetic, interpopulation differentiation, and principal coordinates analysis (PCoA) indicate that the Qiang people have extensive connections with ethnic minorities in China, supporting the view that the Qiang people are the oldest group in the entire Sino-Tibetan language family. The Qiang appeared genetically more associated with most ethnic groups in China, especially the Han. The calculation of random matching probability (RMP) was improved by Fst correction of allele frequencies to make RMP more accurate and reasonable. This study can fill in the gaps in the Qiang STR reference database, providing valuable frequency data for forensic applications and evidence for the Qiang's genetic pattern as an important ancestral position in the Sino-Tibetan populations.

Disparity in hospital beds' allocation at the county level in China: an analysis based on a Health Resource Density Index (HRDI) model.

BACKGROUND: As approximately 3/4 of the population lives in county-level divisions in China, the allocation of health resources at the county level will affect the realization of health equity. This study aims to evaluate the disparity in hospital beds at the county level in China, analyze its causes, and discuss measures to optimize the allocation. METHODS: Data were drawn from the Chinese County/City Statistical Yearbook (2001-2020). The health resource density index (HRDI) was applied to mediate between the influence of demographic and geographical factors on the allocation of hospital beds. The trends of HRDI allocation were evaluated through the growth incidence curve and the probability density function. The regional disparity in the HRDI was examined through the Lorenz curve, and Dagum Gini coefficient. The contribution of the Gini coefficient and its change were assessed by using the Dagum Gini decomposition method. RESULTS: From 2000 to 2019, the number of hospital beds per thousand people at the county level in China increased dramatically by 1.49 times. From the aspect of the HRDI, there were large regional disparities at the national level, with a Gini coefficient of 0.367 in 2019 and in the three subregions. In 2019, the Gini coefficient of the HRDI exhibited regional variations, with the highest value observed in the western region, followed by the central region and the eastern region. Decomposition reveals that the contribution of interregional disparity changed from the dominant factor to the least important factor, accounting for 29.79% of the overall disparity and the contribution of trans-variation intensity increased from 29.19% to 39.75%, whereas the intraregional disparity remained stable at approximately 31% and became the second most important factor. CONCLUSION: The regional disparity in hospital beds allocation at the county level in China was large and has not improved substantially. Trans-variation intensity was the main reason for the overall disparity and changes, and the intraregional disparity was more important than the interregional disparity for the overall disparity.

The analysis of HPV integration sites based on nanopore sequencing and the profiling changes along the course of photodynamic therapy.

OBJECTIVE: To detect the HPV genotype and integration sites in patients with high-risk HPV infection at different stages of photodynamic therapy using nanopore technology and to evaluate the treatment effect. METHODS: Four patients with HPV infection were selected and subjected to photodynamic therapy, and cervical exfoliated cell was sampled at before treatment, after three courses of treatment and six courses of treatment, their viral abundance and insertion sites were analyzed by nanopore technology, and pathological examinations were performed before and after treatment. In this study, we developed a novel assay that combined viral sequence enrichment and Nanopore sequencing for identification of HPV genotype and integration sites at once. The assay has obvious advantages over qPCR or NGS-based methods, as it has better sensitivity after viral sequences enrichment and can generate long-reads (kb to Mb) for better detection rate of structure variations, moreover, fast turn-around time for real-time viral sequencing and analysis. RESULTS: The pathological grade was reduced in all four patients after photodynamic therapy. Virus has been cleared in two cases after treatment, the virus amount reduced after treatment but not completely cleared in one case, and two type viruses were cleared and one type virus persisted after treatment in the last patient with multiple infection. Viral abundance and the number of integration sites were positively correlated. Gene enrichment analysis showed complete viral clearance in 1 patient and 3 patients required follow-up. CONCLUSION: Nanopore sequencing can effectively monitor the abundance of HPV viruses and integration sites to show the presence status of viruses, and combined with the results of gene enrichment analysis, the treatment effect can be dynamically assessed.

Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures.

Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.

Clinical Efficacy and Safety of AdV-tk Gene Therapy for Patients with Cervical Squamous Intraepithelial Lesion: A Prospective Study.

Cervical cancer is the fourth most common type of cancer for women in 2020, and many more women have cervical precancerous lesion-squamous intraepithelial lesion (SIL). Early treatment of cervical SIL to reverse or delay its progression is an important approach to reduce the incidence of cervical cancer. The efficacy and safety of adenovirus-based vectors expressing the thymidine kinase gene (AdV-tk) in the treatment of multiple types of cancers shows promise for its use in gynecology. We aim to provide relevant clinical efficacy and safety data after introducing AdV-tk for the treatment of cervical SIL for the first time through this prospective study. We conducted a maximum of 6 sessions to administer AdV-tk gene therapy to 23 patients (mean age: 35 years old) with cervical low-/high-grade SIL (LSIL/HSIL) who were enrolled from August 2015 to April 2018 and analyzed the clinical characteristics and follow-up outcomes (mean follow-up period: 7.3 months). The present study consisted of 17 patients (73.9%) with cervical HSIL and 6 patients with LSIL confirmed by colposcopy-directed biopsy. We observed an overall histological remission and regression rate of 87.0% (20/23, 95% confidence interval [95% CI]: 73.2-100, p < 0.001) after AdV-tk gene therapy. Eight patients (34.8%) were detected with human papillomavirus (HPV) 16/18 subtypes and 13 patients were found to be positive with at least one of the other 13 high-risk HPV (HR-HPV) subtypes, while 2 patients did not have any of the 15 HR-HPV subtypes. The overall clearance rate of HR-HPV was 76.2% (16/21, 95% CI: 58.0-94.4, p = 0.016) after AdV-tk gene therapy. For safety evaluation, no severe complications were reported in any of the 23 patients. The most commonly reported symptom was fever in 52.2% (12/23) of patients and all symptoms were fully resolved after symptomatic treatment. Our data indicate that AdV-tk gene therapy has high efficacy and safety in the treatment of cervical SIL among gynecological patients. Our findings provide clinical evidence on the potential promotion and application of AdV-tk in the treatment of cervical SIL, and potentially for cervical cancer, among gynecological patients.

Characterization of loss of chromosome Y in peripheral blood cells in male Han Chinese patients with schizophrenia.

BACKGROUND: Schizophrenia (SCZ) has a global prevalence of 1% and increases the risk of mortality, reducing life expectancy. There is growing evidence that the risk of this disorder is higher in males than in females and it tends to develop in early adulthood. The Y chromosome is thought to be involved in biological processes other than sex determination and spermatogenesis. Studies have shown that loss of chromosome Y (LOY) in peripheral blood cells is associated with a variety of diseases (including cancer) and increased all-cause mortality. An analysis of the relationship between LOY and schizophrenia is warranted. METHODS: A total of 442 Chinese males (271 patients with schizophrenia vs. 171 controls) were included in this study. The copy numbers of the Y and X chromosomes were detected by positive droplets targeting the amelogenin gene (AMEL) on the Y chromosome and X chromosome (AMELY and AMELX, respectively), using droplet digital PCR (ddPCR). The LOY percentage was defined as the difference between the concentration of AMELX and the concentration of AMELY divided by the concentration of AMELX, denoted as (X - Y)/X. RESULTS: In the Han Chinese population, the LOY percentage was higher in the schizophrenia group than in the control group (p < 0.05), although there was no significant difference in the presence of LOY between the two groups. A strong correlation was found between the average of the disease duration and the average of the LOY percentage (R2 = 0.506, p = 0.032). The logistic regression analysis implied that the risk of LOY increases by 0.058 and 0.057 per year according to age at onset and duration of disease, respectively (ponset = 0.013, pduration = 0.017). CONCLUSIONS: In the Han Chinese population, the LOY percentage of the disease group was significantly different from that of the control group. The age of onset and duration of schizophrenia might be risk factors for LOY in peripheral blood cells. A larger sample size and expanded clinical information are needed for more in-depth and specific analyses.

Chinese expert consensus on the diagnosis and treatment of thymic epithelial tumors.

Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumor, accounting for less than 1% of all tumors. The incidence of TETs is about 3.93/10000 in China, slightly higher than that of European and American countries. For resectable TETs, complete surgical resection is recommended. Radiotherapy or chemotherapy may be used as postoperative adjuvant treatment. Treatment for advanced, unresectable TETs consist mainly of radiotherapy and chemotherapy, but there is a lack of standard first- and second-line treatment regimens. Recently, targeted therapies and immune checkpoint inhibitors have shown promising outcomes in TETs. Based on the currently available clinical evidences and the opinions of the national experts, the Thymic Oncology Group of Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) established this Chinese expert consensus on the clinical diagnosis and treatment of TETs, covering the epidemiology, diagnosis, treatment, prognosis and follow-up of TETs.

Hippocampal connectivity and memory decline in cognitively intact APOE ε4 carriers.

INTRODUCTION: Resting-state functional magnetic resonance imaging (fMRI) graph theory may help detect subtle functional connectivity changes affecting memory prior to impairment. METHODS: Cognitively normal apolipoprotein E (APOE) ε4 carriers/noncarriers underwent longitudinal cognitive assessment and one-time MRI. The relationship of left/right hippocampal connectivity and memory trajectory were compared between carriers/noncarriers. RESULTS: Steepness of verbal memory decline correlated with decreased connectivity in the left hippocampus, only among APOE ε4 carriers. Right hippocampal metrics were not correlated with memory and there were no significant correlations in the noncarriers. Verbal memory decline correlated with left hippocampal volume loss for both carriers and noncarriers, with no other significant volumetric findings. DISCUSSION: Findings support early hippocampal dysfunction in intact carriers, the AD disconnection hypothesis, and left hippocampal dysfunction earlier than the right. Combining lateralized graph theoretical metrics with a sensitive measure of memory trajectory allowed for detection of early-stage changes in APOE ε4 carriers before symptoms of mild cognitive impairment are present. HIGHLIGHTS: Graph theory connectivity detects preclinical hippocampal changes in APOE ε4 carriers. The AD disconnection hypothesis was supported in unimpaired APOE ε4 carriers. Hippocampal dysfunction starts asymmetrically on the left.

Synthesis of functionalized 3-aryl-3H-benzofuranone derivatives from aryl acetate via [3 + 2] annulation of 1,4-dihydroxy-2-naphthoic acid ester.

A novel [3 + 2] cascade reaction of aryl acetate with 1,4-dihydroxy-2-naphthoic acid ester by cooperative catalysis of isothiourea and vanadium is developed. The key step of the reaction is that the C1-ammonium enolates generated from aryl acetate will cycloadduct to 1,4-naphthoquinone intermediates. 3-Aryl-3H-benzofuranone derivatives can be prepared in medium to good yields under mild conditions.

Developing a male-specific age predictive model based on Y-CpGs for forensic analysis.

In forensic work, predicting the age of the criminal suspect or victim could provide beneficial clues for investigation. Epigenetic age estimation based on age-correlated DNA methylation has been one of the most widely studied methods of age estimation. However, almost all available epigenetic age prediction models are based on autosomal CpGs, which are only applicable to single-source DNA samples. In this study, we screened the available methylation data sets to identify loci with potential to meet the objectives of this study and then established a male-specific age prediction model based on 2 SNaPshot systems that contain 13 Y-CpGs and the mean absolute deviation (MAD) values were 4-6 years. The multiplex methylation SNaPshot systems and age-predictive model have been validated for sensitivity (the DNA input could be as low as 0.5 ng) and male specificity. They are supposed to have feasibility in forensic practice. In addition, it demonstrated that the method was also applicable to bloodstains, which were commonly found at crime scenes. The results showed good performance (the training set: R2 = 0.9341, MAD = 4.65 years; the test set: R2 = 0.8952, MAD = 5.73 years) in case investigation for predicting male age. For mixtures, when the male to female DNA ratio is 1:1, 1:10, the deviation between the actual age and the predicted age obtained by the model was less than 8 years, which offers great hope for future prediction of the age of males in mixtures and will be a powerful tool for special cases, such as sexual assault. Furthermore, the work provides a basis for the application of Y-CpGs in forensic science.

Pod-based e-liquids impair human vascular endothelial cell function.

Pod-based electronic (e-) cigarettes more efficiently deliver nicotine using a protonated formulation. The cardiovascular effects associated with these devices are poorly understood. We evaluated whether pod-based e-liquids and their individual components impair endothelial cell function. We isolated endothelial cells from people who are pod users (n = 10), tobacco never users (n = 7), and combustible cigarette users (n = 6). After a structured use, pod users had lower acetylcholine-mediated endothelial nitric oxide synthase (eNOS) activation compared with never users and was similar to levels from combustible cigarette users (overall P = 0.008, P = 0.01 pod vs never; P = 0.96 pod vs combustible cigarette). The effects of pod-based e-cigarettes and their constituents on vascular cell function were further studied in commercially available human aortic endothelial cells (HAECs) incubated with flavored JUUL e-liquids or propylene glycol (PG):vegetable glycerol (VG) at 30:70 ratio with or without 60 mg/mL nicotine salt for 90 min. A progressive increase in cell death with JUUL e-liquid exposure was observed across 0.0001-1% dilutions; PG:VG vehicle with and without nicotine salt induced cell death. A23187-stimulated nitric oxide production was decreased with all JUUL e-liquid flavors, PG:VG and nicotine salt exposures. Aerosols generated by JUUL e-liquid heating similarly decreased stimulated nitric oxide production. Only mint flavored e-liquids increased inflammation and menthol flavored e-liquids enhanced oxidative stress in HAECs. In conclusion, pod e-liquids and their individual components appear to impair endothelial cell function. These findings indicate the potential harm of pod-based devices on endothelial cell function and thus may be relevant to cardiovascular injury in pod type e-cigarette users.

Parkinson's Disease Diagnosis beyond Clinical Features: A Bio-marker using Topological Machine Learning of Resting-state Functional Magnetic Resonance Imaging.

Parkinson's disease (PD) is one of the leading causes of neurological disability, and its prevalence is expected to increase rapidly in the following few decades. PD diagnosis heavily depends on clinical features using the patient's symptoms. Therefore, an accurate, robust, and non-invasive bio-marker is of critical clinical importance for PD. This study proposes to develop a new bio-marker for PD diagnosis using resting-state functional Magnetic Resonance Imaging (rs-fMRI). Unlike most existing rs-fMRI data analytics using correlational analysis, a Topological Machine Learning approach is proposed to construct the bio-marker. The default functional network is identified first using rs-fMRI. Next, rs-fMRI's high dimensional spatial-temporal data structure is mapped on a Riemann Manifold using topological dimensional reduction. Following the topological dimensional reduction, machine learning is used for classification and sensitivity analysis. The proposed methodology is applied to three open fMRI databases for demonstration and validation. The PD diagnosis accuracy can reach 96.4% when the proposed methodology is used. Thus, rs-fMRI and topological machine learning provide a quantifiable and verifiable bio-marker for future PD early detection and treatment evaluation.

Large fragment Sanger sequencing identifies the newly encountered variant that caused null alleles in parentage testing.

Short tandem repeat (STR) is regarded as a crucial tool for personal identification as well as parentage testing. Thus, genotyping errors of STRs could have negative effects on the reliability of forensic identification. A null allele at the combined DNA index system (CODIS) core loci D2S1338 was found in a father-daughter pair with the AGCU Expressmarker 22 kit which was a commonly used commercial kit during our daily laboratory work. This null allele caused the father and daughter to not conform to the laws of inheritance, thus potentially generating erroneous conclusions that excluded parentage. To figure out the reason for this phenomenon, re-amplification with new primers and then large fragment Sanger sequencing was conducted. We found a G to G/T variation at the position which is fifty-nine bases away from the 3' end of the core repeat in both samples. This probably could be considered a novel variant at the primer binding region which had not been reported that resulted in the emergence of the null allele. We also found that there was more than one single-nucleotide polymorphism (SNP) with minor allele frequency (MAF) greater than 0.1 in the upstream and downstream sequences of D2S1338. When designing primers for amplification of D2S1338, the possible adverse results of these SNPs should be taken into account and avoided.