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Abstract Erectile dysfunction (ED) is a common and difficult to treat disease, and has a high incidence rate worldwide. As a marker of vascular disease, ED usually occurs in cardiovascular disease, 2–5 years prior to cardiovascular disease events. The extracellular matrix (ECM) network plays a crucial role in maintaining cardiac homeostasis, not only by providing structural support, but also by promoting force transmission, and by transducing key signals to intracardiac cells. However, the relationship between ECM and ED remains unclear. To help fill this gap, we profiled single-cell RNA-seq (scRNA-seq) to obtain transcriptome maps of 82,554 cavernous single cells from ED and non-ED samples. Cellular composition of cavernous tissues was explored by uniform manifold approximation and projection. Pseudo-time cell trajectory combined with gene enrichment analysis were performed to unveil the molecular pathways of cell fate determination. The relationship between cavernous cells and the ECM, and the changes in related genes were elucidated. The CellChat identified ligand-receptor pairs (e.g., PTN-SDC2, PTN-NCL, and MDK-SDC2) among the major cell types in the cavernous tissue microenvironment. Differential analysis revealed that the cell type-specific transcriptomic changes in ED are related to ECM and extracellular structure organization, external encapsulating structure organization, and regulation of vasculature development. Trajectory analysis predicted the underlying target genes to modulate ECM (e.g., COL3A1, MDK, MMP2, and POSTN). Together, this study highlights potential cell–cell interactions and the main regulatory factors of ECM, and reveals that genes may represent potential marker features of ED progression.

Abstract Tests of the brain’s ability to process complex sounds (central auditory tests) correlate with overall measures of neurocognitive performance. In the low- middle-income countries where resources to conduct detailed cognitive testing is limited, tests that assess the central auditory system may provide a novel and useful way to track neurocognitive performance. This could be particularly useful for children living with HIV (CLWH). To evaluate this, we administered central auditory tests to CLWH and children living without HIV and examined whether central auditory tests given early in a child’s life could predict later neurocognitive performance. We used a machine learning technique to incorporate factors known to affect performance on neurocognitive tests, such as education. The results show that central auditory tests are useful predictors of neurocognitive performance and perform as well or in some cases better than factors such as education. Central auditory tests may offer an objective way to track neurocognitive performance in CLWH.

Abstract Several new statistical methods have been developed to identify the overall impact of an exposure mixture on health outcomes. Weighted quantile sum (WQS) regression assigns the joint mixture effect weights to indicate the overall association of multiple exposures, and quantile-based g-computation is a generalized version of WQS without the restriction of directional homogeneity. This paper proposes an adaptive-mixture-categorization (AMC)-based g-computation approach that combines g-computation with an optimal exposure categorization search using the F statistic. AMC-based g-computation reduces variance within each category and retains the variance between categories to build more powerful predictors. In a simulation study, the performance of association analysis was improved using categorizing by AMC compared with quantiles. We applied this method to assess the association between a mixture of 12 trace element concentrations measured from toenails and the risk of non-muscle invasive bladder cancer. Our findings suggested that medium-level (116.7–145.5 μg/g) vs. low-level (39.5–116.2 μg/g) of toenail zinc had a statistically significant positive association with bladder cancer risk.

Abstract We developed a disease registry to collect all incident amyotrophic lateral sclerosis (ALS) cases diagnosed during 2016–2018 in Ohio. Due to incomplete case ascertainment and limitations of the traditional capture-recapture method, we proposed a new method to estimate the number of cases not recruited by the Registry and their spatial distribution. Specifically, we employed three statistical methods to identify reference counties with normal case-population relationships to build a Poisson regression model for estimating case counts in target counties that potentially have unrecruited cases. Then, we conducted spatial smoothing to adjust outliers locally. We validated the estimates with ALS mortality data. We estimated that 119 total cases (95% CI [109, 130]) were not recruited, including 36 females (95% CI [31, 41]) and 83 males (95% CI [74, 99]), and were distributed unevenly across the state. For target counties, including estimated unrecruited cases increased the correlation between the case count and mortality count from r = 0.8494 to 0.9585 for the total, from 0.7573 to 0.8270 for females, and from 0.6862 to 0.9292 for males. The advantage of this method in the spatial perspective makes it an alternative to capture-recapture for estimating cases missed by disease registries.

Abstract Rice products marketed in the USA, including baby rice cereal, contain inorganic arsenic, a putative immunotoxin. We sought to determine whether the timing of introduction of rice cereal in the first year of life influences occurrence of infections, respiratory symptoms, and allergy. Among 572 infants from the New Hampshire Birth Cohort Study, we used generalized estimating equation, adjusted for maternal smoking during pregnancy, marital status, education attainment, pre-pregnancy body mass index, maternal age at enrollment, infant birth weight, and breastfeeding history. Among 572 infants, each month earlier of introduction to rice cereal was associated with increased risks of subsequent upper respiratory tract infections (relative risk, RR = 1.04; 95% CI: 1.00–1.09); lower respiratory tract infections (RR = 1.19; 95% CI: 1.02–1.39); acute respiratory symptoms including wheeze, difficulty breathing, and cough (RR = 1.10; 95% CI: 1.00–1.22); fever requiring a prescription medicine (RR = 1.22; 95% CI: 1.02–1.45) and allergy diagnosed by a physician (RR = 1.20; 95% CI: 1.06–1.36). No clear associations were observed with gastrointestinal symptoms. Our findings suggest that introduction of rice cereal earlier may influence infants’ susceptibility to respiratory infections and allergy.

Abstract No current in vitro tumor model replicates a tumor’s in vivo microenvironment. A culturing technique that better preserves a tumor’s pathophysiological conditions is needed for some important clinical applications, including personalized drug-sensitivity/resistance assays. In this study, we utilized autologous serum or body fluid to build a 3D scaffold and grow a patient’s tumor. We named this technique “3D-ACM” (autologous culture method). Forty-five clinical samples from biopsies, surgically removed tumor tissues and malignant body fluids were cultured with 3D-ACM. Traditional 3D-FBS (fetal bovine serum) cultures were performed side-by-side for comparison. The results were that cells cultured in 3D-ACM rebuilt tissue-like structures, and retained their immuno-phenotypes and cytokine productions. In contrast, the 3D-FBS method promoted mesenchymal cell proliferation. In preliminary chemo drug-sensitivity assays, significantly higher mortality was always associated with FBS-cultured cells. Accordingly, 3D-ACM appears to more reliably preserve a tumor’s biological characteristics, which might improve the accuracy of drug-testing for personalized cancer treatment.

Abstract Pseudomonas aeruginosa is a formidable pathogen that is responsible for a diverse spectrum of human infectious diseases, resulting in considerable annual mortality rates. Because of biofilm formation and its ability of rapidly acquires of resistance to many antibiotics, P. aeruginosa related infections are difficult to treat, and therefore, developing an effective vaccine is the most promising method for combating infection. In the present study, we designed a novel trivalent vaccine, PcrV28-294-OprI25-83-Hcp11-162 (POH), and evaluated its protective efficacy in murine pneumonia and burn models. POH existed as a dimer in solution, it induced better protection efficacy in P. aeruginosa lethal pneumonia and murine burn models than single components alone when formulated with Al(OH)3 adjuvant, and it showed broad immune protection against several clinical isolates of P. aeruginosa. Immunization with POH induced strong immune responses and resulted in reduced bacterial loads, decreased pathology, inflammatory cytokine expression and inflammatory cell infiltration. Furthermore, in vitro opsonophagocytic killing assay and passive immunization studies indicated that the protective efficacy mediated by POH vaccination was largely attributed to POH-specific antibodies. Taken together, these data provided evidence that POH is a potentially promising vaccine candidate for combating P. aeruginosa infection in pneumonia and burn infections.

Selenium, a crucial antioxidant in the body, has been linked to all-cause and cause-specific mortality. However, the relationship between selenium and mortality in the general population remains unclear. A total of 5449 participants in the National Health and Nutrition Examination Survey (NHANES) (2003-2004, 2011-2016) were analyzed to track participant mortality until December 31, 2019. The COX proportional hazard model, Kaplan‒Meier survival analysis and restricted cubic spline regression analysis were used to investigate the associations. Subgroup analysis was conducted on the basis of age (≤ 60, > 60), sex (male, female), and smoking status (nonsmoker, former smoker, and current smoker). The second quartile was associated with lower all-cause mortality and noncardiovascular mortality (HR and 95% CI 0.61,0.45-0.83;0.59,0.42-0.83, respectively). The third quartile was associated with lower cardiovascular-related mortality (HR and 95% CI 0.49, 0.32-0.76). Elevated serum selenium concentrations were associated with lower all-cause mortality, noncardiovascular mortality (range ≤ 129.82 μg/L), and cardiovascular mortality (range ≤ 129.08 μg/L). Subgroup analysis revealed a positive correlation between the serum selenium concentration (range ≥ 129.82 μg/L) and all-cause mortality among the subgroup of current smokers (p < 0.001). This study indicates that the protective effect of the serum selenium concentration on cause-specific mortality decreases beyond a certain range in the general population, potentially increasing the risk of death among current smokers., (© 2024. The Author(s).)

Human induced pluripotent stem cell-derived sensory neuron (iPSC-dSN) models are a valuable resource for the study of neurotoxicity but are affected by poor replicability and reproducibility, often due to a lack of optimization. Here, we identify experimental factors related to culture conditions that substantially impact cellular drug response in vitro and determine optimal conditions for improved replicability and reproducibility. Treatment duration and cell seeding density were both found to be significant factors, while cell line differences also contributed to variation. A replicable dose-response in viability was demonstrated after 48-h exposure to docetaxel or paclitaxel. Additionally, a replicable dose-dependent reduction in neurite outgrowth was demonstrated, demonstrating the applicability of the model for the examination of additional phenotypes. Overall, we have established an optimized iPSC-dSN model for the study of taxane-induced neurotoxicity., (© 2024. The Author(s).)

Members of the Metal Tolerance Protein (MTP) family are critical in mediating the transport and tolerance of divalent metal cations. Despite their significance, the understanding of MTP genes in mustard (Brassica juncea) remains limited, especially regarding their response to heavy metal (HM) stress. In our study, we identified MTP gene sets in Brassica rapa (17 genes), Brassica nigra (18 genes), and B. juncea (33 genes) using the HMMER (Cation&#95;efflux; PF01545) and BLAST analysis. For the 33 BjMTPs, a comprehensive bioinformatics analysis covering the physicochemical properties, phylogenetic relationships, conserved motifs, protein structures, collinearity, spatiotemporal RNA-seq expression, GO enrichment, and expression profiling under six HM stresses (Mn 2+ , Fe 2+ , Zn 2+ , Cd 2+ , Sb 3+ , and Pb 2+ ) were carried out. According to the findings of physicochemical characteristics, phylogenetic tree, and collinearity, the allopolyploid B. juncea's MTP genes were inherited from its progenitors, B. rapa and B. nigra, with minimal gene loss during polyploidization. Members of the BjMTP family exhibited conserved motifs, promoter elements, and expression patterns across subgroups, consistent with the seven evolutionary branches (G1, G4-G9, and G12) of the MTPs. Further, spatiotemporal expression profiling under HM stresses successfully identified specific genes and crucial cis-regulatory elements associated with the response of BjMTPs to HM stresses. These findings may contribute to the genetic improvement of B. juncea for enhanced HM tolerance, facilitating the remediation of HM-contaminated areas., (© 2024. The Author(s).)

Idiopathic pulmonary fibrosis (IPF) is believed to be associated with a notable disruption of cellular energy metabolism. By detecting the changes of energy metabolites in the serum of patients with pulmonary fibrosis, we aimed to investigate the diagnostic and prognostic value of energy metabolites in IPF, and further elucidated the mechanism of their involvement in pulmonary fibrosis. Through metabolomics research, it was discovered that the TCA cycle intermediates changed dramatically in IPF patients. In another validation cohort of 55 patients with IPF compared to 19 healthy controls, it was found that succinate, an intermediate product of TCA cycle, has diagnostic and prognostic value in IPF. The cut-off levels of serum succinate were 98.36 μM for distinguishing IPF from healthy controls (sensitivity, 83.64%; specificity, 63.16%; likelihood ratio, 2.27, respectively). Moreover, a high serum succinate level was independently associated with higher rates of disease progression (OR 13.087, 95%CI (2.819-60.761)) and mortality (HR 3.418, 95% CI (1.308-8.927)). In addition, accumulation of succinate and increased expression of the succinate receptor GPR91 were found in both IPF patients and BLM mouse models of pulmonary fibrosis. Reducing succinate accumulation in BLM mice alleviated pulmonary fibrosis and 21d mortality, while exogenous administration of succinate can aggravate pulmonary fibrosis in BLM mice. Furthermore, GPR91 deficiency protected against lung fibrosis caused by BLM. In vitro, succinate promoted the activation of lung fibroblasts by activating ERK pathway through GPR91. In summary, succinate is a promising biomarker for diagnosis and prognosis of IPF. The accumulation of succinate may promote fibroblast activation through GPR91 and pulmonary fibrosis., (© 2024. The Author(s).)

To quantitatively assess the diagnostic efficacy of multiple parameters derived from multi-b-value diffusion-weighted imaging (DWI) using turbo spin echo (TSE)-based acquisition techniques in patients with solitary pulmonary lesions (SPLs). A total of 105 patients with SPLs underwent lung DWI using single-shot TSE-based acquisition techniques and multiple b values. The apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM) parameters, and lesion-to-spinal cord signal intensity ratio (LSR), were analyzed to compare the benign and malignant groups using the Mann-Whitney U test and receiver operating characteristic analysis. The D star values observed in lung cancer were slightly lower than those observed in pulmonary benign lesions (28.164 ± 31.950 versus 32.917 ± 34.184; Z = -2.239, p = 0.025). The LSR values were significantly higher in lung cancer than in benign lesions (1.137 ± 0.581 versus 0.614 ± 0.442; Z = - 4.522, p < 0.001). Additionally, the ADC 800 , ADC total , and D values were all significantly lower in lung cancer than in the benign lesions (Z = - 5.054, -5.370, and -6.047, respectively, all p < 0.001), whereas the f values did not exhibit any statistically significant difference between the two groups. D had the highest area under the curve (AUC = 0.887), followed by ADC total (AUC = 0.844), ADC 800 (AUC = 0.824), and LSR (AUC = 0.789). The LSR, ADC 800 , ADC total , and D values did not differ statistically significantly in diagnostic effectiveness. Lung DWI using TSE is feasible for differentiating SPLs. The LSR method, conventional DWI, and IVIM have comparable diagnostic efficacy for assessing SPLs., (© 2024. The Author(s).)

The Amur tiger is currently confronted with challenges of anthropogenic development, leading to its population becoming fragmented into two geographically isolated groups: smaller and larger ones. Small and isolated populations frequently face a greater extinction risk, yet the small tiger population's genetic status and survival potential have not been assessed. Here, a total of 210 samples of suspected Amur tiger feces were collected from this small population, and the genetic background and population survival potentials were assessed by using 14 microsatellite loci. Our results demonstrated that the mean number of alleles in all loci was 3.7 and expected heterozygosity was 0.6, indicating a comparatively lower level of population genetic diversity compared to previously reported studies on other subspecies. The genetic estimates of effective population size (Ne) and the Ne/N ratio were merely 7.6 and 0.152, respectively, representing lower values in comparison to the Amur tiger population in Sikhote-Alin (the larger group). However, multiple methods have indicated the possibility of genetic divergence within our isolated population under study. Meanwhile, the maximum kinship recorded was 0.441, and the mean inbreeding coefficient stood at 0.0868, both of which are higher than those observed in other endangered species, such as the African lion and the grey wolf. Additionally, we have identified a significant risk of future extinction if the lethal equivalents were to reach 6.26, which is higher than that of other large carnivores. Further, our simulation results indicated that an increase in the number of breeding females would enhance the prospects of this population. In summary, our findings provide a critical theoretical basis for further bailout strategies concerning Amur tigers., (© 2024. The Author(s).)

In order to realize the process of player feature extraction and classification from multi-frequency frame-changing football match images more quickly, and complete the tactical plan that is more conducive to the game, this paper puts forward a method for analyzing and judging the tactics of women's football team based on Convolutional Neural Network (CNN). By extracting the players' performance in recent training and competition from continuous video frame data, a multi-dimensional vector input data sample is formed, and CNN is used to analyze the players' hidden ability before the game and the players' mistakes in different positions on the field to cope with different football schedules. Before the formal test, 10 games of 2021-2022 UEFA Women's Champions League were randomly selected and intercepted to train the CNN model. The model showed excellent accuracy in the classification of image features of various football moves and goal angles, and the overall classification accuracy of each category exceeded 95%. The accuracy of classifying a single match is above 88%, which highlights the reliability and stability of the model in identifying and classifying women's football matches. On this basis, the test results show that: according to the analysis of players' personal recessive ability before the game, after model image recognition and comparison, the difference between the four scores of players' personal recessive ability with CNN mode and the manual score of professional coaches was smaller, and the numerical difference was within the minimum unit value, and the numerical calculation results were basically the same. According to the analysis of players' mistakes in different positions on the field, CNN was used to monitor the real-time mistakes. It was found that the two players in the forward position made the highest mistakes, and they were replaced by substitute players at 73.44 min and 65.28 min after the team scored and kept the ball, respectively. After the substitute players played, the team's forward position mistake rate decreased obviously. The above results show that CNN technology can help players get personal recessive ability evaluation closer to professional evaluation in a shorter time, and help the coaching team to analyze the real-time events better. The purpose of this paper is to help the women's football team complete the pre-match tactical training, reduce the analysis time of players' mistakes in the game, deal with different opponents in the game and improve the winning rate of the game., (© 2024. The Author(s).)

Prophylactic pharmacotherapy for health care in patients with high risk of cardiac arrest (CA) is an elusive and less explored strategy. Melatonin has possibilities used as a daily nutraceutical to trigger the cellular adaptation. We sought to find the effects of long-term daily prophylactic supplement with melatonin on the victim of CA. Rats were divided into sham, CA, and melatonin + CA (Mel + CA) groups. The rats in the Mel + CA group received daily IP injection of melatonin 100 mg/kg for 14 days. CA was induced by 8 min asphyxia and followed by manual cardiopulmonary resuscitation. The endpoint was 24 h after resuscitation. Survival, neurological outcome, and hippocampal mitochondrial integrity, dynamics and function were assessed. Survival was significantly higher in the Mel + CA group than the CA group (81 vs. 42%, P = 0.04). Compared to the CA group, neurological damage in the CA1 region and the level of cytochrome c, cleaved caspase-3 and caspase-9 in the Mel + CA group were decreased (P < 0.05). Mitochondrial function and integrity were protected in the Mel + CA group compared to the CA group, according to the results of mitochondrial swelling, ΔΨm, ROS production, oxygen consumption rate, and respiratory control rate (P < 0.05). Melatonin increased SIRT3 and downregulated acetylated CypD. The mitochondrial dynamics and autophagy were improved in the Mel + CA group (P < 0.05). Long-term daily prophylactic supplement with melatonin buy the time from brain injury after CA., (© 2023. The Author(s).)

Sediment contamination jeopardizes wetlands by harming aquatic organisms, disrupting food webs, and reducing biodiversity. Carcinogenic substances like heavy metals bioaccumulate in sediments and expose consumers to a greater risk of cancer. This study reports Pb, Cr, Cu, and Zn levels in sediments from eight wetlands in India. The Pb (51.25 ± 4.46 µg/g) and Cr (266 ± 6.95 µg/g) concentrations were highest in Hirakud, Cu (34.27 ± 2.2 µg/g) in Bhadrak, and Zn (55.45 ± 2.93 µg/g) in Koraput. The mean Pb, Cr, and Cu values in sediments exceeded the toxicity reference value. The contamination factor for Cr was the highest of the four metals studied at Hirakud (CF = 7.60) and Talcher (CF = 6.97). Furthermore, high and moderate positive correlations were observed between Cu and Zn (r = 0.77) and Pb and Cr (r = 0.36), respectively, across all sites. Cancer patients were found to be more concentrated in areas with higher concentrations of Pb and Cr, which are more carcinogenic. The link between heavy metals in wetland sediments and human cancer could be used to make policies that limit people's exposure to heavy metals and protect their health., (© 2023. The Author(s).)

The objective of this study was to investigate the potential association between the use of four frequently prescribed drug classes, namely antihypertensive drugs, statins, selective serotonin reuptake inhibitors, and proton-pump inhibitors, and the likelihood of disease progression from mild cognitive impairment (MCI) to dementia using electronic health records (EHRs). We conducted a retrospective cohort study using observational EHRs from a cohort of approximately 2 million patients seen at a large, multi-specialty urban academic medical center in New York City, USA between 2008 and 2020 to automatically emulate the randomized controlled trials. For each drug class, two exposure groups were identified based on the prescription orders documented in the EHRs following their MCI diagnosis. During follow-up, we measured drug efficacy based on the incidence of dementia and estimated the average treatment effect (ATE) of various drugs. To ensure the robustness of our findings, we confirmed the ATE estimates via bootstrapping and presented associated 95% confidence intervals (CIs). Our analysis identified 14,269 MCI patients, among whom 2501 (17.5%) progressed to dementia. Using average treatment estimation and bootstrapping confirmation, we observed that drugs including rosuvastatin (ATE = - 0.0140 [- 0.0191, - 0.0088], p value < 0.001), citalopram (ATE = - 0.1128 [- 0.125, - 0.1005], p value < 0.001), escitalopram (ATE = - 0.0560 [- 0.0615, - 0.0506], p value < 0.001), and omeprazole (ATE = - 0.0201 [- 0.0299, - 0.0103], p value < 0.001) have a statistically significant association in slowing the progression from MCI to dementia. The findings from this study support the commonly prescribed drugs in altering the progression from MCI to dementia and warrant further investigation., (© 2023. The Author(s).)

Comorbid glucose metabolism abnormalities are very common in patients with major depressive disorder (MDD), and glucose metabolism and lipid metabolism are closely related. However, there are few researches on the incidence and related factors of lipid metabolism abnormalities among MDD patients with comorbid glucose metabolism abnormalities. A cross-sectional study involving 1718 first-episode and drug-naïve (FEDN) MDD patients was conducted. The 17-item Hamilton Depression Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAMA) and Positive and Negative Syndrome Scale (PANSS) positive subscale were utilized to evaluate depressive, anxiety and psychotic symptom, respectively. Serum thyroid function-related parameters, glucose- and lipid-metabolism parameters were measured. The prevalence of abnormal lipid metabolism was significantly higher in FEDN MDD patients with abnormal glucose metabolism than in those without abnormal glucose metabolism (P < 0.001). In MDD patients with abnormal glucose metabolism, TSH, FT3 and body mass index (BMI) levels were significantly higher in the abnormal lipid metabolism subgroup than in the non-abnormal lipid metabolism subgroup. Binary logistic regression analysis showed that TSH, FT3 and BMI were the influencing factors of abnormal lipid metabolism in MDD patients with abnormal glucose metabolism (all P < 0.05). MDD patients with abnormal glucose metabolism have a high prevalence of abnormal lipid metabolism. Moreover, abnormal glucose metabolism was an independent risk factor for abnormal lipid metabolism in patients with MDD. In addition, thyroid hormone function and BMI may contribute to the co-occurrence of abnormal lipid metabolism in MDD patients with abnormal glucose metabolism., (© 2023. The Author(s).)

To determine the prognostic CT features in patients with untreated thymic epithelial tumors (TETs). Clinical data and CT imaging features of 194 patients with pathologically confirmed TETs were retrospectively reviewed. The subjects included 113 male and 81 female patients between 15 and 78 years of age, with a mean age of 53.8 years. Clinical outcomes were categorized according to whether relapse, metastasis or death occurred within 3 years after the first diagnosis. Associations between clinical outcomes and CT imaging features were determined using univariate and multivariate logistic regression analyses, while the survival status was analyzed by Cox regression. In this study, we analyzed 110 thymic carcinomas, 52 high-risk thymomas and 32 low-risk thymomas. Percentages of poor outcome and patient death in thymic carcinomas were much higher than those in patients with high-risk and low-risk thymomas. In the thymic carcinomas groups, 46 patients (41.8%) experienced tumor progression, local relapse or metastasis and were categorized as having poor outcomes; vessel invasion and pericardial mass were confirmed to be independent predictors by logistic regression analysis (p < 0.01). In the high-risk thymoma group, 11 patients (21.2%) were categorized as having poor outcomes, and the CT feature pericardial mass was confirmed to be an independent predictor (p < 0.01). In survival analysis, Cox regression showed that CT features of lung invasion, great vessel invasion, lung metastasis and distant organ metastasis were independent predictors for worse survival in the thymic carcinoma group (p < 0.01), while lung invasion and pericardial mass were independent predictors for worse survival in high-risk thymoma group. No CT features were related to poor outcome and worse survival in the low-risk thymoma group. Patients with thymic carcinoma had poorer prognosis and worse survival than those with high-risk or low-risk thymoma. CT can serve as an important tool for predicting the prognosis and survival of patients with TETs. In this cohort, CT features of vessel invasion and pericardial mass were related to poorer outcomes in those with thymic carcinoma and pericardial mass in those with high-risk thymoma. Features including lung invasion, great vessel invasion, lung metastasis and distant organ metastasis indicate worse survival in thymic carcinoma, whereas lung invasion and pericardial mass indicate worse survival in high-risk thymoma., (© 2023. The Author(s).)

Standard cell cultures are performed in aqueous media with a low macromolecule concentration compared to tissue microenvironment. In macromolecular crowding (MMC) experiments, synthetic polymeric crowders are added into cell culture media to better mimic macromolecule concentrations found in vivo. However, their effect on cultured cells is incompletely understood and appears context-dependent. Here we show using human gingival fibroblasts, a cell type associated with fast and scarless wound healing, that MMC (standard medium supplemented with Ficoll 70/400) potently modulates fibroblast phenotype and extracellular matrix (ECM) composition compared to standard culture media (nMMC) over time. MMC significantly reduced cell numbers, but increased accumulation of collagen I, cellular fibronectin, and tenascin C, while suppressing level of SPARC (Secreted Protein Acidic and Cysteine Rich). Out of the 75 wound healing and ECM related genes studied, MMC significantly modulated expression of 25 genes compared to nMMC condition. MMC also suppressed myofibroblast markers and promoted deposition of basement membrane molecules collagen IV, laminin 1, and expression of LAMB3 (Laminin Subunit Beta 3) gene. In cell-derived matrices produced by a novel decellularization protocol, the altered molecular composition of MMC matrices was replicated. Thus, MMC may improve cell culture models for research and provide novel approaches for regenerative therapy., (© 2023. The Author(s).)

This study investigated whether the amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) features could be used as potentially neurological markers to identify chronic insomnia (CI) using resting-state functional MRI and machine learning method logistic regression (LR). This study included 49 CI patients and 47 healthy controls (HC). Voxel-wise features, including the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC), were extracted from resting-state functional magnetic resonance brain images. Then, we divided the data into two independent cohorts for training (44 CI patients and 42 HC patients), and independent validation (5 CI patients and 5 HC patients) by using logistic regression. The model was evaluated using 20 rounds of fivefold cross‑validation for training. In particular, a two-sample t-test (GRF corrected, p-voxel < 0.001, p-cluster < 0.05) was used for feature selection during the model training. Finally, single‑shot testing of the final model was performed on the independent validation cohort. A correlation analysis (Bonferroni correction, p < 0.05/4) was also conducted to determine whether the features contributing to the prediction were correlated with clinical characteristics, including the Insomnia Severity Index (ISI), Pittsburgh sleep quality index (PSQI), self-rating anxiety scale (SAS), and self-rating depression scale (SDS). Results showed that resting-state features had a discrimination accuracy of 86.40%, with a sensitivity of 93.00% and specificity of 79.80%. The area under the curve (AUC) was 0.89 (all [Formula: see text]< 0.001). The ALFF and FC features showed significant differences between the CI patients and HC. The regions contributing to the prediction mainly included the anterior cingulate, prefrontal cortex, orbital part of the frontal lobe, angular gyrus, cingulate gyrus, praecuneus, parietal lobe, temporal gyrus, superior temporal gyrus, and middle temporal gyrus. Furthermore, some specific functional connectivity among related regions was positively correlated with the ISI, and also negatively related to the SDS in correlation analysis. Our current study suggested that ALFF and FC in the regions contributing to diagnostic identification might serve as potential neuromarkers for CI., (© 2023. The Author(s).)

Left ventricular ejection fraction (EF) is a key measure in the diagnosis and treatment of heart failure (HF) and many patients experience changes in EF overtime. Large-scale analysis of longitudinal changes in EF using electronic health records (EHRs) is limited. In a multi-site retrospective study using EHR data from three academic medical centers, we investigated longitudinal changes in EF measurements in patients diagnosed with HF. We observed significant variations in baseline characteristics and longitudinal EF change behavior of the HF cohorts from a previous study that is based on HF registry data. Data gathered from this longitudinal study were used to develop multiple machine learning models to predict changes in ejection fraction measurements in HF patients. Across all three sites, we observed higher performance in predicting EF increase over a 1-year duration, with similarly higher performance predicting an EF increase of 30% from baseline compared to lower percentage increases. In predicting EF decrease we found moderate to high performance with low confidence for various models. Among various machine learning models, XGBoost was the best performing model for predicting EF changes. Across the three sites, the XGBoost model had an F1-score of 87.2, 89.9, and 88.6 and AUC of 0.83, 0.87, and 0.90 in predicting a 30% increase in EF, and had an F1-score of 95.0, 90.6, 90.1 and AUC of 0.54, 0.56, 0.68 in predicting a 30% decrease in EF. Among features that contribute to predicting EF changes, baseline ejection fraction measurement, age, gender, and heart diseases were found to be statistically significant., (© 2023. The Author(s).)

Merocyanine dyes are of great interest amongst researchers due to their nonlinear optical (NLO) properties and solvatochromism. Molecular structure of these dyes constitutes conjugated pathway between the donor and acceptor substituents, with lowest energy transition of [Formula: see text]-[Formula: see text]* character. To rationalize the design of these dyes and deduce structure-property relationship, it is eminent to unravel the excited state dynamics in these complex molecular structures in different solvents. Here we have studied excited state dynamics of a merocyanine dye known as HB194, which has shown commendable efficiency in small molecule based bulk heterojuction solar cells. We have employed femtosecond transient absorption in combination with the quantum chemistry calculations to unravel the solvent dependent charge transfer dynamics of HB194. The excited state decays of the HB194 in different solvents show multi-exponential components. The analysis of the time-resolved data reveals that the polar solvents induce conformationally relaxed intramolecular charge transfer state. In non-polar solvent cyclohexane, only solvent-stabilized ICT state is observed. Additionally, we observe an anomalously red-shifted emission in ethylene glycol centred at [Formula: see text] 750 nm. Our computational calculations suggest the presence of molecular dimers resulting into observed red-shifted emission band. Our work therefore underscores the importance of gathering molecular-level insight into the system-bath interactions for designing next generation merocynanine-based solvatochromic dyes., (© 2022. The Author(s).)

Induced pluripotent stem cells (iPSCs) are a valuable resource for neurological disease-modeling and drug discovery due to their ability to differentiate into neurons reflecting the genetics of the patient from which they are derived. iPSC-derived cultures, however, are highly variable due to heterogeneity in culture conditions. We investigated the effect of passage number on iPSC differentiation to optimize the generation of sensory neurons (iPSC-dSNs). Three iPSC lines reprogrammed from the peripheral blood of three donors were differentiated into iPSC-dSNs at passage numbers within each of the following ranges: low (5-10), intermediate (20-26), and high (30-38). Morphology and pluripotency of the parent iPSCs were assessed prior to differentiation. iPSC-dSNs were evaluated based on electrophysiological properties and expression of key neuronal markers. All iPSC lines displayed similar morphology and were similarly pluripotent across passage numbers. However, the expression levels of neuronal markers and sodium channel function analyses indicated that iPSC-dSNs differentiated from low passage numbers better recapitulated the sensory neuron phenotype than those differentiated from intermediate or high passage numbers. Our results demonstrate that lower passage numbers may be better suited for differentiation into peripheral sensory neurons., (© 2022. The Author(s).)

Corydalis is one of the few lineages that have been reported to have extensive large-scale chloroplast genome (cp-genome) rearrangements. In this study, novel cp-genome rearrangements of Corydalis pinnata, C. mucronate, and C. sheareri are described. C. pinnata is a narrow endemic species only distributed at Qingcheng Mountain in southwest China. Two independent relocations of the same four genes (trnM-CAU-rbcL) were found relocated from the typically posterior part of the large single-copy region to the front of it. A uniform inversion of an 11-14-kb segment (ndhB-trnR-ACG) was found in the inverted repeat region; and extensive losses of accD, clpP, and trnV-UAC genes were detected in all cp-genomes of all three species of Corydalis. In addition, a phylogenetic tree was reconstructed based on 31 single-copy orthologous proteins in 27 cp-genomes. This study provides insights into the evolution of cp-genomes throughout the genus Corydalis and also provides a reference for further studies on the taxonomy, identification, phylogeny, and genetic transformation of other lineages with extensive rearrangements in cp-genomes., (© 2022. The Author(s).)

To understand the current situation of occupational exposure to blood-borne pathogens in a women's and children's hospital and analyze the causes to provide a scientific basis for improving occupational exposure prevention and control measures. We analyzed occupational exposure to blood-borne pathogens in a third-class women's and children's hospital from 2015 to 2018, considering the workers' occupational categories and length of service; the sites, types, and causes of exposure; and the pathogens of the source patients. From 2015 to 2018, there were 146 cases of occupational exposure to blood-borne pathogens, mainly from sharp-instrument injuries (81.5%; 119/146). Trainees represented the highest proportion of occupational exposure (30.1%; 44/146), followed by nurses (29.5%; 43/146). Occupational exposure among staff with less than one year of service accounted for 43.2% (63/146) of cases. Fisher's exact test showed that different occupational groups had different types of occupational exposure, and among the occupationally exposed populations, the proportion of sharp injuries is higher than that of blood and body fluid exposure, and the difference is statistically significant (χ 2  = 12.937, P = 0.008). Different occupational groups faced exposure to different types of pathogens: medical staff were more likely than workmen to be exposed to hepatitis B, while workmen were more likely than medical staff to be exposed to unknown pathogens; these differences were statistically significant (χ 2  = 55.344, P < 0.001). Health records were established for all cases of occupational exposure to blood-borne pathogens, and no staff members contracted a blood-borne disease due to occupational exposure. In order to reduce occupational exposure, regular training in occupational protection for junior medical staff and workers should be strengthened, the monitoring and protection system of occupational exposure to blood-borne pathogens improved, standard prevention measures strengthened, operations standardized, safe injection equipment provided, and comprehensive measures taken., (© 2022. The Author(s).)

The study aims to solve the problems of limited capacity and difficult recovery of lignite to adsort Cu 2+ , Zn 2+ and Pb 2+ in acid mine wastewater (AMD). Magnetically modified lignite (MML) was prepared by the chemical co-precipitation method. Static beaker experiments and dynamic continuous column experiments were set up to explore the adsorption properties of Cu 2+ , Zn 2+ and Pb 2+ by lignite and MML. Lignite and MML before and after the adsorption of heavy metal ions were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared spectrometer (FTIR). Meanwhile, the adsorption mechanisms of Cu 2+ , Zn 2+ and Pb 2+ by lignite and MML were revealed by combining the adsorption isotherm model and the adsorption kinetics model. The results showed that the pH, adsorbent dosage, temperature, initial concentration of heavy metal ions, and contact time had an influence on the adsorption of Cu 2+ , Zn 2+ and Pb 2+ by lignite and MML, and the adsorption processes were more in line with the Langmuir model. The adsorption kinetics experiments showed that the adsorption processes were jointly controlled by multiple adsorption stages. The adsorption of heavy metal ions by lignite obeyed the Quasi first-order kinetic model, while the adsorption of MML was chemisorption that obeyed the Quasi second-order kinetic model. The negative ΔG and positive ΔH of Cu 2+ and Zn 2+ indicated the spontaneous and endothermic nature reaction, while the negative ΔH of Pb 2+ indicated the exothermic nature reaction. The dynamic continuous column experiments showed that the average removal rates of Cu 2+ , Zn 2+ and Pb 2+ by lignite were 78.00, 76.97 and 78.65%, respectively, and those of heavy metal ions by MML were 82.83, 81.57 and 83.50%, respectively. Compared with lignite, the adsorption effect of MML was better. As shown by SEM, XRD and FTIR tests, Fe 3 O 4 was successfully loaded on the surface of lignite during the magnetic modification, which made the surface morphology of lignite coarser. Lignite and MML removed Cu 2+ , Zn 2+ and Pb 2+ from AMD in different forms. In addition, the adsorption process of MML is related to the O-H stretching vibration of carboxylic acid ions and the Fe-O stretching vibration of Fe 3 O 4 particles., (© 2022. The Author(s).)

In this study, a novel AlGaN/GaN heterostructure field-effect transistor based on open-gate technology was fabricated. Sample transistors of different structures and sizes were constructed. Through measurements, it was found that by changing the width of the opening, the threshold voltage of the device could be easily modulated across a larger range. The open-gate device had two working modes with different transconductance. When the gate-source voltage V GS  ≤  - 4.5 V, only the open region was conductive, and a new working mechanism modulated the channel current. Corresponding theoretical analysis and calculations showed that its saturation mechanism was related to a virtual gate formed by electron injection onto the surface. Also, the gate-source voltage modulated the open channel current by changing the channel electron mobility through polarization Coulomb field scattering. When used as class-A voltage amplifiers, open-gate devices can achieve effective voltage amplification with very low power consumption., (© 2021. The Author(s).)

Catabolite control protein C (CcpC) belongs to the LysR-type transcriptional regulator (LTTR) family, which regulates the transcription of genes encoding the tricarboxylic acid branch enzymes of the TCA cycle by responding to a pathway-specific metabolite, citrate. The biological function of CcpC has been characterized several times, but the structural basis for the molecular function of CcpC remains elusive. Here, we report the characterization of a full-length CcpC from Bacillus amyloliquefaciens (BaCcpC-FL) and a crystal structure of the C-terminal inducer-binding domain (IBD) complexed with citrate. BaCcpC required both dyad symmetric regions I and II to recognize the citB promoter, and the presence of citrate reduced citB promoter binding. The crystal structure of CcpC-IBD shows two subdomains, IBD-I and IBD-II, and a citrate molecule buried between them. Ile100, two arginines (Arg147 and Arg260), and three serines (Ser129, Ser189, and Ser191) exhibit strong hydrogen-bond interactions with citrate molecules. A structural comparison of BaCcpC-IBD with its homologues showed that they share the same tail-to-tail dimer alignment, but the dimeric interface and the rotation between these molecules exhibit significant differences. Taken together, our results provide a framework for understanding the mechanism underlying the functional divergence of the CcpC protein., (© 2021. The Author(s).)

We propose a classification method using the radiomics features of CT chest images to identify patients with coronavirus disease 2019 (COVID-19) and other pneumonias. The chest CT images of two groups of participants (90 COVID-19 patients who were confirmed as positive by nucleic acid test of RT-PCR and 90 other pneumonias patients) were collected, and the two groups of data were manually drawn to outline the region of interest (ROI) of pneumonias. The radiomics method was used to extract textural features and histogram features of the ROI and obtain a radiomics features vector from each sample. Then, we divided the data into two independent radiomic cohorts for training (70 COVID-19 patients and 70 other pneumonias patients), and validation (20 COVID-19 patients and 20 other pneumonias patients) by using support vector machine (SVM). This model used 20 rounds of tenfold cross-validation for training. Finally, single-shot testing of the final model was performed on the independent validation cohort. In the COVID-19 patients, correlation analysis (multiple comparison correction-Bonferroni correction, P < 0.05/7) was also conducted to determine whether the textural and histogram features were correlated with the laboratory test index of blood, i.e., blood oxygen, white blood cell, lymphocytes, neutrophils, C-reactive protein, hypersensitive C-reactive protein, and erythrocyte sedimentation rate. The final model showed good discrimination on the independent validation cohort, with an accuracy of 89.83%, sensitivity of 94.22%, specificity of 85.44%, and AUC of 0.940. This proved that the radiomics features were highly distinguishable, and this SVM model can effectively identify and diagnose patients with COVID-19 and other pneumonias. The correlation analysis results showed that some textural features were positively correlated with WBC, and NE, and also negatively related to SPO2H and NE. Our results showed that radiomic features can classify COVID-19 patients and other pneumonias patients. The SVM model can achieve an excellent diagnosis of COVID-19., (© 2021. The Author(s).)

Neuroimaging studies have documented brain structural alterations induced by chronic pain, particularly in gray matter volume. However, the effects of trigeminal neuralgia (TN), a severe paroxysmal pain disorder, on cortical morphology are not yet known. In this study, we recruited 30 TN patients and 30 age-, and gender-matched healthy controls (HCs). Using Computational Anatomy Toolbox (CAT12), we calculated and compared group differences in cortical thickness, gyrification, and sulcal depth with two-sample t tests (p < 0.05, multiple comparison corrected). Relationships between altered cortical characteristics and pain intensity were investigated with correlation analysis. Compared to HCs, TN patients exhibited significantly decreased cortical thickness in the left inferior frontal, and left medial orbitofrontal cortex; decreased gyrification in the left superior frontal cortex; and decreased sulcal depth in the bilateral superior frontal (extending to anterior cingulate) cortex. In addition, we found significantly negative correlations between the mean cortical thickness in left medial orbitofrontal cortex and pain intensity, and between the mean gyrification in left superior frontal cortex and pain intensity. Chronic pain may be associated with abnormal cortical thickness, gyrification and sulcal depth in trigeminal neuralgia. These morphological changes might contribute to understand the underlying neurobiological mechanism of trigeminal neuralgia., (© 2021. The Author(s).)

Two ATP-binding cassette transporters, ABCB1/MDR1 and ABCG2/BCRP, are considered the most critical determinants for chemoresistance in hepatocellular carcinoma. However, their roles in the chemoresistance in liver cancer stem cells remain elusive. Here we explored the role of inhibition of MDR1 or ABCG2 in sensitizing liver cancer stem cells to doxorubicin, the most frequently used chemotherapeutic agent in treating liver cancer. We show that the inhibition of MDR1 or ABCG2 in Huh7 and PLC/PRF/5 cells using either pharmacological inhibitors or RNAi resulted in the elevated level of intracellular concentration of doxorubicin and the accompanied increased apoptosis as determined by confocal microscopy, high-performance liquid chromatography, flow cytometry, and annexin V assay. Notably, the inhibition of MDR1 or ABCG2 led to the reversal of the chemoresistance, as evident from the enhanced death of the chemoresistant liver cancer stem cells in tumorsphere-forming assays. Thus, the elevation of effective intracellular concentration of doxorubicin via the inhibition of MDR1 or ABCG2 represents a promising future strategy that transforms doxorubicin from a traditional chemotherapy agent into a robust killer of liver cancer stem cells for patients undergoing transarterial chemoembolization.

The aim of this study was to analyze initial chest computed tomography (CT) findings in COVID-19 pneumonia and identify features associated with poor prognosis. Patients with RT-PCR-confirmed COVID-19 infection were assigned to recovery group if they made a full recovery and to death group if they died within 2 months of hospitalization. Chest CT examinations for ground-glass opacity, crazy-paving pattern, consolidation, and fibrosis were scored by two reviewers. The total CT score comprised the sum of lung involvement (5 lobes, scores 1-5 for each lobe, range; 0, none; 25, maximum). 40 patients who recovered from COVID-19 and six patients who died were enrolled. The initial chest CTs showed 27 (58.7%) patients had ground-glass opacity, 19 (41.3%) had ground glass and consolidation, and 35 (76.1%) patients had crazy-paving pattern. None of the patients who died had fibrosis in contrast to six (15%) patients who recovered from COVID-19. Most patients had subpleural lesions (89.0%) as well as bilateral (87.0%) and lower (93.0%) lung lobe involvement. Diffuse lesions were present in four (67%) patients who succumbed to coronavirus but only one (2.5%) patient who recovered (p < 0.001). In the death group of patients, the total CT score was higher than that of the recovery group (p = 0.005). Patients in the death group had lower lymphocyte count and higher C-reactive protein than those in the recovery group (p = 0.011 and p = 0.041, respectively). A high CT score and diffuse distribution of lung lesions in COVID-19 are indicative of disease severity and short-term mortality.

The multifunctional protein Y-box binding protein 1 (YBX1), is a critical regulator of transcription and translation, and is widely recognized as an oncogenic driver in several solid tumors, including colorectal cancer (CRC). However, very little is known about the upstream or downstream factors that underlie YBX1's regulation and involvement in CRC. Previously, we demonstrated that YBX1 overexpression correlated with potent activation of nuclear factor κB (NF-κB), a well-known transcription factor believed to be crucial in CRC progression. Here, we report a novel interaction between NF-κB, YBX1 and protein arginine methyltransferase 5 (PRMT5). Our findings reveal for the first time that PRMT5 catalyzes methylation of YBX1 at arginine 205 (YBX1-R205me2), an event that is critical for YBX1-mediated NF-κB activation and its downstream target gene expression. Importantly, when WT-YBX1 is overexpressed, this methylation exists under basal (unstimulated) conditions and is further augmented upon interleukin-1β (IL-1β) stimulation. Mechanistically, co-immunoprecipitation studies reveal that the R205 to alanine (A) mutant of YBX1 (YBX1-R205A) interacted less well with the p65 subunit of NF-κB and attenuated the DNA binding ability of p65. Importantly, overexpression of YBX1-R205A significantly reduced cell growth, migration and anchorage-independent growth of CRC cells. Collectively, our findings shed important light on the regulation of a novel PRMT5/YBX1/NF-κB axis through PRMT5-mediated YBX1-R205 methylation. Given the fact that PRMT5, YBX1 and NF-κB are all among top crucial factors in cancer progression, pharmacological disruption of this pivotal axis could serve as the basis for new therapeutics for CRC and other PRMT5/YBX1/NF-κB-associated cancers.

A novel and simple method was described for preparation of carbonaceous adsorbent (CA) from corncob under phosphoric acid conditions. The method succeeded to introduce oxygen-containing groups onto the product surface through hydrothermal carbonization (HTC) at low temperature of 160 °C. Adsorption of methylene blue (MB) was studied systematically through the effect of pH, contact time and initial dye concentrations. The MB adsorption kinetics and isotherms experiments showed that Langmuir model and pseudo-second-order model could better describe the adsorption behavior, with a maximum adsorption capacity of MB was 140.25 mg/g. The high adsorption capacity could be ascribed to the presence of surface oxygen-containing functional groups and pore channels. In conclusion, it could be a potential adsorbent in the removal of methylene blue from wastewater.

Salicylic acid (SA) is a key natural component that mediates local and systemic resistance to pathogens in many dicotyledonous species. However, its function is controversial in disease resistance in rice plants. Here, we show that the SA signaling is involved in both pathogen-associated-molecular-patterns triggered immunity (PTI) and effector triggered immunity (ETI) to Xanthomonas oryzae pv. Oryzae (Xoo) mediated by the recessive gene xa5, in which OsNPR3.3 plays an important role through interacting with TGAL11. Rice plants containing homozygous xa5 gene respond positively to exogenous SA, and their endogenous SA levels are also especially induced upon infection by the Xoo strain, PXO86. Depletion of endogenous SA can significantly attenuate plant resistance to PXO86, even to 86∆HrpXG (mutant PXO86 with a damaged type III secretion system). These results indicated that SA plays an important role in disease resistance in rice plants, which can be clouded by high levels of endogenous SA and the use of particular rice varieties.

Recent studies have highlighted the value of microRNA-21 (miR-21) as a prognostic biomarker in gliomas. However, the role of miR-21 in predicting prognosis remains controversial. We performed a comprehensive study based upon a meta-analysis and The Cancer Genome Atlas (TCGA) glioma dataset validation to clarify the prognostic significance of miR-21 in glioma patients. In this study, we searched Embase, PubMed, Web of science, CNKI, SinoMed, and Wanfang databases for records up to May 2018. Relevant data were extracted to assess the correlation between miR-21 expression and survival in glioma patients. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to describe association strength. We further used multivariate Cox regression analysis to assess miR-21 expression in the TCGA glioma dataset to validate the relationship between miR-21 expression and survival. Nine studies were included in the meta-analysis. Among them, eight studies provided data on overall survival (OS) with a pooled HR of 1.91 (95% CI: 1.34, 2.73), indicating that higher expression of miR-21 was significantly associated with worse OS in glioma patients; for the other study, which provided data on progression-free survival (PFS), no statistically significant HR was reported for PFS in the glioma patients (HR = 1.23, 95% CI: 0.41, 3.72). A multivariate Cox regression analysis of the miR-21 expression in the TCGA glioma dataset revealed that overexpression of miR-21 was a potential independent prognostic biomarker of poorer OS (HR = 1.27, 95% CI: 1.01, 1.59) and poorer PFS (HR = 1.46, 95% CI: 1.17, 1.82). Our findings suggest that higher expression of miR-21 is correlated with poorer glioma prognosis.

The xa5 gene encodes a basal transcription factor (TFIIAγ) protein with wide spectrum resistance to bacterial blight caused by Xanthomonas oryzae pv. Oryzae (Xoo) in rice. It was only found in a few rice ecotypes, and the recessive characteristics limited its application in breeding. Here, we employed a TALEN-based technique to edit its dominant allelic TFIIAγ5 and obtained many mutant TFIIAγ5 genes. Most of them reduced rice susceptibility to varying degrees when the plants were challenged with the Xoo. In particular, the knocked-out TFIIAγ5 can reduce the rice susceptibility significantly, although it cannot reach the xa5-mediated resistance level, indicating TFIIAγ5 is a major component involved in disease susceptibility. In addition, the mutant encoding the protein with deletion of the 32nd amino acid or amino acid insertion between 32nd and 33rd site confers rice with the similar resistance to that of the knocked-out TFIIAγ5. Thus, the amino acids around 32nd site are also the important action sites of TFIIAγ5 besides the 39th amino acid previously reported. Moreover, the integration of xa5 into TFIIAγ5-knockout plants conferred them with a similar resistance as IRBB5, the rice variety containing the homozygous xa5 gene. Thus, TFIIAγ5 was not simply regarded as a resistant or a susceptible locus, as the substitution of amino acids might shift its functions.

During Cambrian Stage 4 (~514 Ma) the oceans were widely populated with endemic trilobites and three major faunas can be distinguished: olenellids, redlichiids, and paradoxidids. The lower-middle Cambrian boundary in Laurentia was based on the first major trilobite extinction event that is known as the Olenellid Biomere boundary. However, international correlation across this boundary (the Cambrian Series 2-Series 3 boundary) has been a challenge since the formal proposal of a four-series subdivision of the Cambrian System in 2005. Recently, the base of the international Cambrian Series 3 and of Stage 5 has been named as the base of the Miaolingian Series and Wuliuan Stage. This study provides detailed chemostratigraphy coupled with biostratigraphy and sequence stratigraphy across this critical boundary interval based on eight sections in North America and South China. Our results show robust isotopic evidence associated with major faunal turnovers across the Cambrian Series 2-Series 3 boundary in both Laurentia and South China. While the olenellid extinction event in Laurentia and the gradual extinction of redlichiids in South China are linked by an abrupt negative carbonate carbon excursion, the first appearance datum of Oryctocephalus indicus is currently the best horizon to achieve correlation between the two regions.

Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths worldwide. Liver metastasis is the major cause of CRC patient mortality, occurring in 60% patients with no effective therapies. Although studies have indicated the role of miRNAs in CRC, an in-depth miRNA expression analysis is essential to identify clinically relevant miRNAs and understand their potential in targeting liver metastasis. Here we analyzed miRNA expressions in 405 patient tumors from publicly available colorectal cancer genome sequencing project database. Our analyses showed miR-132, miR-378f, miR-605 and miR-1976 to be the most significantly downregulated miRNAs in primary and CRC liver metastatic tissues, and CRC cell lines. Observations in CRC cell lines indicated that ectopic expressions of miR-378f, -605 and -1976 suppress CRC cell proliferation, anchorage independent growth, metastatic potential, and enhance apoptosis. Consistently, CRC patients with higher miR-378f and miR-1976 levels exhibited better survival. Together, our data suggests an anti-tumorigenic role of these miRNAs in CRC and warrant future in vivo evaluation of the molecules for developing biomarkers or novel therapeutic strategies.

T-cell-dependent bispecific antibodies (TDBs) are promising cancer immunotherapies that recruit a patient's T cells to kill cancer cells. There are increasing numbers of TBDs in clinical trials, demonstrating their widely recognized therapeutic potential. Due to the fact that TDBs engage and activate T cells via an anti-CD3 (aCD3) arm, aCD3 homodimer (aCD3 HD) and high-molecular-weight species (HMWS) are product-related impurities that pose a potential safety risk by triggering off-target T-cell activation through bivalent engagement and dimerization of T-cell receptors (TCRs). To monitor and control the level of unspecific T-cell activation, we developed a sensitive and quantitative T-cell-activation assay, which can detect aCD3 HD in TDB drug product by exploiting its ability to activate T cells in the absence of target cells. This assay provides in-vivo-relevant off-target T-cell-activation readout. Furthermore, we have demonstrated that this assay can serve as a platform assay for detecting T-cell-activating impurities across a broad spectrum of aCD3 bispecific molecules. It therefore has the potential to significantly benefit many T-cell-recruiting bispecific programs.

Suitable conditions for thermal extraction of semi-volatile organic compounds have largely been arrived at by univariate optimization or based on the recommendations provided by the manufacturers of the extraction equipment. Herein, we demonstrated the multivariate optimization of Tenax TA-thermal extraction for determining organophosphate esters in the gas phase fraction of air samples. Screening and refining experiments were performed using the eighth fraction factorial and Box-Behnken designs, respectively, and satisfactory models were obtained. Subsequently, the process was optimized by Derringer's desirability function and the global desirability was 0.7299. Following optimization, the analytes were desorbed at 290 °C for 10 minutes at a helium flow of 95 mL min -1 , with the transfer line set at 290 °C. The analytes were then cryofocused at 20 °C and then cryodesorbed into the chromatographic column at 295 °C for 6 minutes. Method validation exhibited high linearity coefficients (>0.99), good precision (CV < 14%) and low detection limits (0.1-0.5 ng m -3 ). The method was tested by pumping 0.024 m 3 of real indoor environment air through Tenax TA sorbent tubes. Furthermore, with multivariate optimization, analysis time and other resources were significantly reduced, and information about experimental factor interaction effects was investigated, as compared to the univariate optimization and other traditional methods.

Ultraviolet (UV) irradiation, particularly ultraviolet A (UVA), stimulates reactive oxygen species (ROS) production in the epidermis and dermis, which plays a major part in the photoageing of human skin. Several studies have demonstrated that cerium oxide nanoparticles (CeO 2 NP) can exhibit an antioxidant effect and free radical scavenging activity. However, the protective role of CeO 2 NP in skin photoageing and the underlying mechanisms are unclear. In this study, we investigated the effects of CeO 2 NP on UVA-irradiated human skin fibroblasts (HSFs) and explored the potential signalling pathway. CeO 2 NP had no apparent cytotoxicity, and could reduce the production of proinflammatory cytokines, intracellular ROS, senescence-associated β-galactosidase activity, and downregulate phosphorylation of c-Jun N-terminal kinases (JNKs) after exposure to UVA radiation. Based on our findings, CeO 2 NPs have great potential against UVA radiation-induced photoageing in HSFs via regulating the JNK signal-transduction pathway to inhibit oxidative stress and DNA damage.

Surface soil samples were collected from Mt. Sygera in the southeast of Tibetan Plateau to investigate the altitudinal distribution of PCBs and PBDEs along the two sides of the mountain. The average concentrations of PCBs and PBDEs were 177 pg g -1 dw and 15 pg g -1 dw, respectively. The relationships between the log-transformed TOC-normalized concentrations and the altitudes showed different trends on the two sides. On the windward side, there was a positive correlation for the heavier PCBs; while on the leeward side, the concentrations increased and then decreased for PCBs and PBDEs at the altitude of 4100-4200 m, corresponding to the change in vegetation. The observed discrepancy on the two sides of the mountain demonstrated different key factors associated with precipitation and the forest canopy. Additionally, values of windward-leeward Enrichment Factors (W/L EFs) for the heavier PCB congeners (PCB-138, 153, and -180) were an order of magnitude higher in sites above 4200 m, which also suggested that vegetation played an important role in the altitudinal accumulation of POPs in soil. This is one of the very few studies that have revealed the differences in altitudinal accumulation of POPs along the two sides of a mountain.

Melanoma is a malignant skin cancer with considerable drug resistance. Increased expression of DNA repair genes have been reported in melanoma, and this contributes to chemotherapy resistance. GADD45A is involved in DNA repair, cell cycle arrest and apoptosis in response to physiologic or environmental stresses. In this study, we investigated the role of GADD45A in chemotherapy response. Firstly, the mRNA expression of profiled DNA repair genes in cisplatin-treated melanoma cells was detected by RT 2 profiler TM PCR array. We found the expression of GADD45A upregulated in a dose- and time- dependent manner. In addition, suppression of GADD45A sensitized melanoma cells to cisplatin and enhanced cisplatin-induced DNA damage. Flow cytometry revealed that downregulating GADD45A released cells from cisplatin-induced G2/M arrest and increased apoptosis. By using a MEK inhibitor, GADD45A was shown to be regulated by MAPK-ERK pathway following cisplatin treatment. Thus, the induction of GADD45A might play important roles in chemotherapy response in human melanoma cancer and could serve as a novel molecular target for melanoma therapy.

We come up with a hybrid liquid exfoliation method to prepare bismuth telluride nanocrystals efficiently and cost-effectively. The nonlinear transmittance of the nanocrystals has been characterized with Z-scan technique, which can manifest its broadband saturable absorption behavior experimentally. The as-fabricated nanocrystals were integrated onto fiber end facet to form a fiber compatible nonlinear absorption device with optical deposition method, which was then used to modulate the fiber laser with different cavity configurations to deliver pulsed laser successfully. The noise-like pulse and dissipative soliton have been obtained with wavelength centered at 1562 nm and 1068 nm, respectively. These results confirm the effectiveness of the hybrid liquid exfoliation method to prepare bismuth telluride into nanocrystals, and the broadband nonlinear optical response and ultrafast photonics application potential of the nanocrystals.

The Saturn-like charge-transfer complex Li 4 &B 36 , which was recently predicted with extensive first-principles theory calculations, were studied as a candidate for hydrogen storage material in the present work. The bonding characters of Li-B, B-B and Li-H 2 bonds were revealed by the quantum theory of atoms in molecules (QTAIM). Each Li atom in Li 4 &B 36 cluster can bind six H 2 molecules at most, which results into the gravimetric density of 10.4%. The adsorption energies of H 2 molecules on Li 4 &B 36 cluster are predicted in the range of 0.08-0.14 eV at the wB97x level of theory.

Connexin 43 (Cx43) is the most ubiquitous connexin in various cells, and presents as hemichannels (HCs) and gap junctions (GJs) on the cell membrane. We have recently shown that Cx43 abundance was strongly reduced in fibroblasts of human gingival wounds, and blocking Cx43 function in cultured human gingival fibroblasts (GFBLs) strongly regulated the expression of wound healing-related genes. However, it is not known whether these responses involved Cx43 HCs or GJs. Here we show that Cx43 assembled into distinct GJ and HC plaques in GFBLs both in vivo and in vitro. Specific blockage of Cx43 HC function by TAT-Gap19, a Cx43 mimetic peptide, significantly upregulated the expression of several MMPs, TGF-β signaling molecules, Tenascin-C, and VEGF-A, while pro-fibrotic molecules, including several extracellular matrix proteins and myofibroblast and cell contractility-related molecules, were significantly downregulated. These changes were linked with TAT-Gap19-induced suppression of ATP signaling and activation of the ERK1/2 signaling pathway. Collectively, our data suggest that reduced Cx43 HC function could promote fast and scarless gingival wound healing. Thus, selective suppression of Cx43 HCs may provide a novel target to modulate wound healing.