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Abstract Although Alzheimer’s disease (AD) and intracranial aneurysm (IA) were two different types of diseases that occurred in the brain, ruptured IA (RIA) survivors may experience varying degrees of cognitive dysfunction. Neither AD nor IA is easily recognizable by an early onset so that the incidence of adverse clinical outcomes would be on the rise. Therefore, we focused on the exploration of the shared genes and molecular mechanisms between AD and IA, which would be significant for the efficiency of co-screening and co-diagnosis. Two GEO datasets were selected for the weighted gene co-expression network analysis (WGCNA) and differentially expressed gene screening, obtaining 78 overlapped genes. Next, 9 hub genes were identified by the protein-protein interaction network, including PIK3CA, GAB1, IGF1R, PLCB1, PGR, PDGFRB, PLCE1, FGFR3, and SYNJ1. The interactions among the hub genes, miRNA, and TFs were also explored. Meanwhile, we performed GO and KEGG pathway enrichment analyses for the results of WGCNA and hub genes, which showed that the Ras signaling and Rap1 signaling were the main shared pathogenesis. In conclusion, the present bioinformatics analysis revealed that AD and IA had the shared genes and molecular mechanisms, and these outcomes were associated with inflammation and calcium homeostasis, which could provide research clues for further studies.

Abstract Large language models (LLMs) have shown remarkable abilities recently, including passing advanced professional exams and demanding benchmark tests. This performance has led many to suggest that they are close to achieving humanlike or “true” understanding of language, and even artificial general intelligence (AGI). Here, we provide a new open-source benchmark, the Two Word Test (TWT), that can assess semantic abilities of LLMs using two-word phrases in a task that can be performed relatively easily by humans without advanced training. Combining multiple words into a single concept is a fundamental linguistic and conceptual operation routinely performed by people. The test requires meaningfulness judgments of 1768 noun-noun combinations that have been rated as meaningful (e.g., baby boy) or as having low meaningfulness (e.g., goat sky) by human raters. This novel test differs from existing benchmarks that rely on logical reasoning, inference, puzzle-solving, or domain expertise. We provide versions of the task that probe meaningfulness ratings on a 0–4 scale as well as binary judgments. With both versions, we conducted a series of experiments using the TWT on GPT-4, GPT-3.5, Claude-3-Optus, and Gemini-1-Pro-001. Results demonstrated that, compared to humans, all models performed relatively poorly at rating meaningfulness of these phrases. GPT-3.5-turbo, Gemini-1.0-Pro-001 and GPT-4-turbo were also unable to make binary discriminations between sensible and nonsense phrases, with these models consistently judging nonsensical phrases as making sense. Claude-3-Opus made a substantial improvement in binary discrimination of combinatorial phrases but was still significantly worse than human performance. The TWT can be used to understand and assess the limitations of current LLMs, and potentially improve them. The test also reminds us that caution is warranted in attributing “true” or human-level understanding to LLMs based only on tests that are challenging for humans.

Abstract PANoptosis induces programmed cell death (PCD) through extensive crosstalk and is associated with development of cancer. However, the functional mechanisms, clinical significance, and potential applications of PANoptosis-related genes (PRGs) in colorectal cancer (CRC) have not been fully elucidated. Functional enrichment of key PRGs was analyzed based on databases, and relationships between key PRGs and the immune microenvironment, immune cell infiltration, chemotherapy drug sensitivity, tumor progression genes, single-cell cellular subgroups, signal transduction pathways, transcription factor regulation, and miRNA regulatory networks were systematically explored. This study identified 5 key PRGs associated with CRC: BCL10, CDKN2A, DAPK1, PYGM and TIMP1. Then, RT-PCR was used to verify expression of these genes in CRC cells and tissues. Clinical significance and prognostic value of key genes were further verified by multiple datasets. Analyses of the immune microenvironment, immune cell infiltration, chemotherapy drug sensitivity, tumor progression genes, single-cell cellular subgroups, and signal transduction pathways suggest a close relationship between these key genes and development of CRC. In addition, a novel prognostic nomogram model for CRC was successfully constructed by combining important clinical indicators and the key genes. In conclusion, our findings offer new insights for understanding the pathogenesis of CRC, predicting CRC prognosis, and identifying multiple therapeutic targets for future CRC therapy.

Abstract To date, the types of fuels used in pottery kilns during the Western Zhou Dynasty have not been adequately addressed. Samples from updraft kilns and semi-downdraft kilns at the Fengjing site, the capital in the late Western Zhou period, were selected for analysis. Through phytolith and wood charcoal analysis, various grasses mainly Panicoideae, Pooideae, and Eragrostidoideae, as well as millet, rice, and wheat crops were identified. Additionally, wood primarily from trees of the Quercus, Ulmus, and Liquidambar taxa was found. These findings suggest that different pottery kilns used similar fuels, demonstrating a broad-spectrum rather than specialized fuel utilization during the Zhou period.

Abstract The educational environment plays a vital role in the development of students who participate in athletic pursuits both in terms of their physical health and their ability to detect fatigue. As a result of recent advancements in deep learning and biosensors benefitting from edge computing resources, we are now able to monitor the physiological fatigue of students participating in sports in real time. These devices can then be used to analyze the data using contemporary technology. In this paper, we present an innovative deep learning framework for forecasting fatigue in athletic students following physical exercise. It addresses the issue of lack of precision computational models and extensive data analysis in current approaches to monitoring students’ physical activity. In our study, we classified fatigue and non-fatigue based on photoplethysmography (PPG) signals. Several deep learning models are compared in the study. Using limited training data, determining the optimal parameters for PPG presents a significant challenge. For datasets containing many data points, several models were trained using PPG signals: a deep residual network convolutional neural network (ResNetCNN) ResNetCNN, an Xception architecture, a bidirectional long short-term memory (BILSTM), and a combination of these models. Training and testing datasets were assigned using a fivefold cross validation approach. Based on the testing dataset, the model demonstrated a proper classification accuracy of 91.8%.

Abstract Citri Reticulatae Pericarpium is a traditional Chinese medicine with extremely high health benefits as well as clinical value. In vivo and in vitro tests have proved that its main active secondary metabolites are flavonoids. However, they have not been comprehensively analyzed up to now mainly due to lack of suitable analysis method. To solve this problem, a novel strategy based on precursor ions locked and targeted MS/MS analysis was proposed. Firstly, the database of the flavonoids previously isolated from Citri Reticulatae Pericarpium was established to obtain the characteristics of their precursor ions. Secondly, after performing the full MS scan of the extract, all compounds in the total ion chromatogram were extracted by Compound Discoverer software. Thirdly, the precursor ions of the flavonoids were locked from the extracted compounds according to their characteristics, forming a precursor ions list. Finally, the precursor ions in the constructed list were performed targeted MS/MS analysis for structures characterization. As a result, total 187 flavonoids were successfully identified, and except for flavones, flavonols as well as dihydroflavones, some chalcones were also characterized from Citri Reticulatae Pericarpium for the first time.

Abstract Lockdown is a common policy used to deter the spread of COVID-19. However, the question of how our society comes back to life after a lockdown remains an open one. Understanding how cities bounce back from lockdown is critical for promoting the global economy and preparing for future pandemics. Here, we propose a novel computational method based on electricity data to study the recovery process, and conduct a case study on the city of Hangzhou. With the designed Recovery Index, we find a variety of recovery patterns in main sectors. One of the main reasons for this difference is policy; therefore, we aim to answer the question of how policies can best facilitate the recovery of society. We first analyze how policy affects sectors and employ a change-point detection algorithm to provide a non-subjective approach to policy assessment. Furthermore, we design a model that can predict future recovery, allowing policies to be adjusted accordingly in advance. Specifically, we develop a deep neural network, TPG, to model recovery trends, which utilizes the graph structure learning to perceive influences between sectors. Simulation experiments using our model offer insights for policy-making: the government should prioritize supporting sectors that have greater influence on others and are influential on the whole economy.

Abstract We aimed to establish a computerized diagnostic model to predict placenta accrete spectrum (PAS) disorders based on T2-weighted MR imaging. We recruited pregnant women with clinically suspected PAS disorders between January 2015 and December 2018 in our institution. All preoperative T2-weighted imaging (T2WI) MR images were manually outlined on the picture archive communication system terminal server. A nnU-Net network for automatic segmentation and the corresponding radiomics features extracted from the segmented region were applied to build a radiomics-clinical model for PAS disorders identification. Taking the surgical or pathological findings as the reference standard, we compared this computerized model’s diagnostic performance in detecting PAS disorders. In the training cohort, our model combining both radiomics and clinical characteristics yielded an accuracy of 0.771, a sensitivity of 0.854, and a specificity of 0.750 in identifying PAS disorders. In the testing cohort, this model achieved a segmentation mean Dice coefficient of 0.890 and yielded an accuracy of 0.825, a sensitivity of 0.830 and a specificity of 0.822. In the external validation cohort, this computer-aided diagnostic model yielded an accuracy of 0.690, a sensitivity of 0.929 and a specificity of 0.467 in identifying placenta increta. In the present study, a machine learning model based on preoperative T2WI-based imaging had high accuracy in identifying PAS disorders in respect of surgical and histological findings.

Abstract Epiretinal membrane (ERM) is a common ophthalmological disorder of high prevalence. Its symptoms include metamorphopsia, blurred vision, and decreased visual acuity. Early diagnosis and timely treatment of ERM is crucial to preventing vision loss. Although optical coherence tomography (OCT) is regarded as a de facto standard for ERM diagnosis due to its intuitiveness and high sensitivity, ophthalmoscopic examination or fundus photographs still have the advantages of price and accessibility. Artificial intelligence (AI) has been widely applied in the health care industry for its robust and significant performance in detecting various diseases. In this study, we validated the use of a previously trained deep neural network based-AI model in ERM detection based on color fundus photographs. An independent test set of fundus photographs was labeled by a group of ophthalmologists according to their corresponding OCT images as the gold standard. Then the test set was interpreted by other ophthalmologists and AI model without knowing their OCT results. Compared with manual diagnosis based on fundus photographs alone, the AI model had comparable accuracy (AI model 77.08% vs. integrated manual diagnosis 75.69%, χ2 = 0.038, P = 0.845, McNemar’s test), higher sensitivity (75.90% vs. 63.86%, χ2 = 4.500, P = 0.034, McNemar’s test), under the cost of lower but reasonable specificity (78.69% vs. 91.80%, χ2 = 6.125, P = 0.013, McNemar’s test). Thus our AI model can serve as a possible alternative for manual diagnosis in ERM screening.

Abstract As a severe public health problem, methamphetamine (METH) abuse places a heavy burden on families and society. A growing amount of evidence has indicated communication between gut microbiota and the CNS in drug addiction, with associations to neural, endocrine and immune pathways. Thus, we searched for alterations in the gut microbiota and their potential effects in METH users through 16S rRNA gene sequencing. A decreased Shannon index indicated lower bacterial diversity in the METH users than in the age-matched control group. The gut microbial community composition in the METH users was also altered, including reductions in Deltaproteobacteria and Bacteroidaceae abundances and increases in Sphingomonadales, Xanthomonadales, Romboutsia and Lachnospiraceae abundances. Moreover, the Fusobacteria abundance was correlated with the duration of METH use. Enterobacteriaceae, Ruminococcaceae, Bacteroides, and Faecalibacterium had statistically significant correlations with items related to the positive and negative symptoms of schizophrenia and to general psychopathology in the METH users, and all have previously been reported to be altered in individuals with psychotic syndromes, especially depression. Abstraction, one of the items of the cognitive assessment, was positively related to Blautia. These findings revealed alterations in the gut microbiota of METH users, and these alterations may play a role in psychotic syndrome and cognitive impairment. Although the mechanisms behind the links between these disorders and METH abuse are unknown, the relationships may indicate similarities in the pathogenesis of psychosis induced by METH abuse and other causes, providing a new paradigm for addiction and METH use disorder treatment.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Abstract Gout is a chronic disease resulting from elevated serum urate (SU). Previous genome-wide association studies (GWAS) have identified dozens of susceptibility loci for SU/gout, but few have been conducted for Chinese descent. Here, we try to extensively investigate whether these loci contribute to gout risk in Han Chinese. A total of 2255 variants in linkage disequilibrium (LD) with GWAS identified SU/gout associated variants were analyzed in a Han Chinese cohort of 1255 gout patients and 1848 controls. Cumulative genetic risk score analysis was performed to assess the cumulative effect of multiple “risk” variants on gout incidence. 23 variants (41%) of LD pruned variants set (n = 56) showed nominal association with gout in our sample (p

This paper proposes a smartphone-based method for measuring Blood Pressure (BP) using the oscillometric method. For oscillometry, it is necessary to measure (1) the pressure applied to the artery and (2) the local blood volume change. This is accomplished by performing an oscillometric measurement at the finger's digital artery, whereby a user presses down on the phone's camera with steadily increasing force. The camera is used to capture the blood volume change using photoplethysmography. We devised a novel method for measuring the force applied of the finger without the use of specialized smartphone hardware with a technique called Vibrometric Force Estimation (VFE). The fundamental concept of VFE relies on a phenomenon where a vibrating object is dampened when an external force is applied on to it. This phenomenon can be recreated using the phone's own vibration motor and measured using the phone's Inertial Measurement Unit (IMU). A cross device reliability study with three smartphones of different manufacturers, shape, and prices results in similar force estimation performance across all smartphone models. In an N = 24 proof of concept study of the BP measurement, the smartphone technique achieves a mean absolute error of 9.21 mmHg and 7.77 mmHg of systolic and diastolic BP, respectively, compared to an FDA approved BP cuff. The vision for this technology is not necessarily to replace existing BP monitoring solutions, but rather to introduce a downloadable smartphone software application that could serve as a low-barrier hypertension screening measurement fit for widespread adoption., (© 2024. The Author(s).)

We first established percentile reference curves for infant length and head circumference in Hainan Province based on gender and age in months and compared them with the 2022 national standards and World Health Organization (WHO) standards. This cross-sectional survey involved 2736 infants (1471 boys and 1265 girls) in 18 cities and counties in Hainan Province. Standardized instruments were used to measure head circumference and length. Reference values for Hainan infants' length and head circumference were determined using the LMS method. Curves were generated using the LMS Chart Maker software. According to the newly established reference curves, the length and head circumference of Hainan infants exhibited a consistent trend of steady growth. However, the average head circumference was below the 2022 national reference values and WHO standards. The mean length was lower than the new national reference values but roughly consistent with the WHO standards. Differences exist in infant length and head circumference in Hainan compared to national and global averages. To enhance infant length and head circumference growth, the health department should encourage exclusive breastfeeding for the first 6 months, ensure infants' sleep needs at night, and promote the regularity of vitamin D supplementation during the perinatal period., (© 2024. The Author(s).)

The dosage-dependent recruitment of RNA polymerase II (Pol II) at the promoters of genes related to neurodevelopment and stem cell maintenance is required for transcription by the fine-tuned expression of SET-domain-containing protein 5 (SETD5). Pol II O-GlcNAcylation by O-GlcNAc transferase (OGT) is critical for preinitiation complex formation and transcription cycling. SETD5 dysregulation has been linked to stem cell-like properties in some cancer types; however, the role of SETD5 in cancer cell stemness has not yet been determined. We here show that aberrant SETD5 overexpression induces stemness in colorectal cancer (CRC) cells. SETD5 overexpression causes the upregulation of PI3K-AKT pathway-related genes and cancer stem cell (CSC) markers such as CD133, Kruppel-like factor 4 (KLF4), and estrogen-related receptor beta (ESRRB), leading to the gain of stem cell-like phenotypes. Our findings also revealed a functional relationship between SETD5, OGT, and Pol II. OGT-catalyzed Pol II glycosylation depends on SETD5, and the SETD5-Pol II interaction weakens in OGT-depleted cells, suggesting a SETD5-OGT-Pol II interdependence. SETD5 deficiency reduces Pol II occupancy at PI3K-AKT pathway-related genes and CD133 promoters, suggesting a role for SETD5-mediated Pol II recruitment in gene regulation. Moreover, the SETD5 depletion nullified the SETD5-induced stemness of CRC cells and Pol II O-GlcNAcylation. These findings support the hypothesis that SETD5 mediates OGT-catalyzed O-GlcNAcylation of RNA Pol II, which is involved in cancer cell stemness gain via CSC marker gene upregulation., (© 2023. The Author(s).)

The results of association between Obstructive Sleep Apnea (OSA) and gout are not consistent. Participants aged 20 years or older in the National Health and Nutrition Examination Survey (NHANES) 2007-2008 and 2015-2018 were included. Weighted univariable and multivariable logistic regressions were used to evaluate the association between OSA symptoms and gout. The subgroup and sensitivity analyses were also performed. Among the 15,947 participants in this study, the mean age was 47.8 years old, 48.87% of whom were male, 4891 had OSA symptoms, and 842 had gout. In multivariable logistic regression analyses, OSA symptoms were positively associated with gout in all models. The odds ratio (OR) was 1.315 and 95% confidence interval (CI) was 1.070-1.616 in fully adjusted model 4. In the subgroup analyses, we found a considerable interaction between OSA symptoms and gender with gout (P for interaction = 0.003). In the sensitivity analyses, the association between OSA symptoms and gout remained stable after adjustment for congestive heart failure and diuretics using. OSA symptoms were associated with an increased likelihood of gout. This association could especially be found in female participants., (© 2023. The Author(s).)

We propose an ultra-low-cost at-home blood pressure monitor that leverages a plastic clip with a spring-loaded mechanism to enable a smartphone with a flash LED and camera to measure blood pressure. Our system, called BPClip, is based on the scientific premise of measuring oscillometry at the fingertip to measure blood pressure. To enable a smartphone to measure the pressure applied to the digital artery, a moveable pinhole projection moves closer to the camera as the user presses down on the clip with increased force. As a user presses on the device with increased force, the spring-loaded mechanism compresses. The size of the pinhole thus encodes the pressure applied to the finger. In conjunction, the brightness fluctuation of the pinhole projection correlates to the arterial pulse amplitude. By capturing the size and brightness of the pinhole projection with the built-in camera, the smartphone can measure a user's blood pressure with only a low-cost, plastic clip and an app. Unlike prior approaches, this system does not require a blood pressure cuff measurement for a user-specific calibration compared to pulse transit time and pulse wave analysis based blood pressure monitoring solutions. Our solution also does not require specialized smartphone models with custom sensors. Our early feasibility finding demonstrates that in a validation study with N = 29 participants with systolic blood pressures ranging from 88 to 157 mmHg, the BPClip system can achieve a mean absolute error of 8.72 and 5.49 for systolic and diastolic blood pressure, respectively. In an estimated cost projection study, we demonstrate that in small-batch manufacturing of 1000 units, the material cost is an estimated $0.80, suggesting that at full-scale production, our proposed BPClip concept can be produced at very low cost compared to existing cuff-based monitors for at-home blood pressure management., (© 2023. The Author(s).)

Nonalcoholic fatty liver disease (NAFLD) has become an important risk of type 2 diabetes mellitus (T2DM). Peripheral neuropathy (PN) is regarded as one of the main microvascular complications of diabetes. But the association of NAFLD with PN is still unclear. We aimed to investigate the association between NAFLD and PN in US population by conducting a cross-sectional study. We enrolled 3029 participants aged 40-85 years from National Health and Nutrition Examination Survey (NHANES) 1999-2004. NAFLD was defined as a US Fatty Liver Index (FLI) score ≥ 30, and PN was defined as having one or more insensate areas on either foot. Participants were divided into two groups (with or without PN). We performed multivariate logistic regression models to evaluate the association between NAFLD and PN. Subgroup analyses were used to find out whether the association was stable in different stratified groups. Sensitivity analyses were conducted to assess the robustness of the results. All the analyses were weighted. Among the individuals, 524 (17.3%) had PN and 1250 (41.27%) had NAFLD. In the multivariate logistic regression models, NAFLD was associated with an increased risk of PN (OR 1.44 [1.03 ~ 2.02]) after fully adjusting for covariates. In the subgroup analyses, NAFLD was significantly associated with PN in the age group (40-64 years), compared with those in the age group (65-85 years), (P for interaction: 0.004). The results of association of NAFLD with PN were stable in sensitivity analyses. In this cross-sectional study among US adults aged 40-85 years old, NAFLD was associated with an increased likelihood of prevalent PN., (© 2023. The Author(s).)

Root-knot nematode (Meloidogyne incognita) is chief plant parasitic nematode of various crops globally. Meanwhile, the negative side effects on human health and environmental concerns associated with haphazard uses of chemical nematicides. Hence, the search for a safe and effective approach is more relevant. The present study was aimed to evaluate the nematicidal potential of Snef1216 (Penicillium chrysogenum) against M. incognita at different concentrations (5%, 10%, 25%, 50%, 75% and 100%) and with the nutritious medium. The egg hatching inhibition and mortality of second stage juveniles of M. incognita were assessed after 6, 12, 24, 48 and 72 h exposure. Results revealed that egg hatching inhibition and percent mortality of M. incognita increased with increasing concentration and exposure time. The highest mortality of juveniles was recorded at 100% conc. i.e., 24.20%, 36%, 66%, 78% and 97.8% at 6, 12, 24, 48 and 72 h, respectively. The highest ovicidal activity was recorded at 100% concentration with 5.20% of eggs hatching. The outcome suggested that Snef1216 (P. chrysogenum) resulted in the lowest LC 50 value was recorded as 3718.496 at 6 h exposure period followed by 10479.87, 11186.682, 14838.58 and 24001.430 at 72, 12, 48 and 24 h respectively via ovicidal assay. Whereas, in the larvicidal assay, the lowest LC 50 value demonstrated at 72 h being 17.628% exposure period followed by 28.345, 50.490, 215.710 and 482.595% at 48, 24, 12 and 6 h respectively. It is concluded that Snef1216 has potential being used as a biocontrol agent against M. incognita and can serve as a source of a novel nematicidal agent of fungal origin.

Prognostic biomarkers for recurrence of Oral Squamous Cell Carcinoma (OSCC) are urgently needed. We aimed to independently validate a 4-gene expression signature (MMP1, COL4A1, P4HA2, THBS2) predictive of OSCC recurrence risk. Gene expression was measured using Nanostring nCounter ® in 245 histologically normal surgical resection margins from 62 patients. Association between risk scores for individual patients and recurrence was assessed by Kaplan-Meier analysis. Signature performance was quantified by concordance index (CI), hazard ratio (HR) and the area under receiver operating characteristics (AUC). Risk scores for recurrence were significantly higher than recurrence-free patients (p = 9.58e-7, Welch's t-test). A solid performance of the 4-gene signature was determined: CI = 0.64, HR = 3.38 (p = 1.4E-4; log-rank test), AUC = 0.71. We showed that three margins per patient are sufficient to preserve predictive performance (CI = 0.65; HR = 2.92; p = 2.94e-3; AUC = 0.71). Association between the predicted risk scores and recurrence was assessed and showed HR = 2.44 (p = 9.6E-3; log-rank test, N = 62). Signature performance analysis was repeated using an optimized threshold (70 th percentile of risks), resulting in HR = 3.38 (p = 1.4E-4; log-rank test, N = 62). The 4-gene signature was validated as predictive of recurrence risk in an independent cohort of patients with resected OSCC and histologically negative margins, and is potentially applicable for clinical decision making on adjuvant treatment and disease monitoring.

The anti-inflammatory activity of Quzhou Fructus Aurantii Extract (QFAE) has been reported recently. Thus, present study aims to explore the mechanism of anti-inflammation of QFAE in vitro and in vivo to develop a lung phylactic agent. The anti-inflammatory mechanism of QFAE in RAW 264.7 cells and acute lung injury (ALI) mice model was determined by cytokines analysis, histopathological examination, Western blot assay, immunofluorescence, and immunohistochemistry analysis. The results showed that QFAE restrained mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways in LPS-induced RAW 264.7 cells, whereas AMP-activated protein kinase (AMPK) signaling pathways were activated, as revealed by prominent attenuation of phosphorylation of ERK, JNK, p38, p65, IκBα, RSK and MSK, and overt enhancement of phosphorylation of ACC and AMPKα. The levels of pro-inflammatory cytokines TNF, IL-6, and IL-1β were suppressed, whereas the level of anti-inflammatory cytokine IL-10 increased after pretreatment with QFAE in vivo and in vitro. Moreover, QFAE prevented mice from LPS-provoked ALI, bases on alleviating neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF) and mitigatingpulmonary histological alters, as well as hematological change. The MAPK and NF-κB signaling pathways in LPS-stimulated ALI mice were dampened by QFAE pretreatment, whereas AMPK signaling pathways were accelerated, as testify by significant restraint of phosphorylation of ERK, JNK, p38, p65, and IκBα, and distinct elevation of phosphorylation of ACC and AMPKα. The remarkable anti-inflammatory effect of QFAE is associated with the suppression of MAPK and NF-κB signaling pathways and the initiation of AMPK signaling pathway.

Oxidative stress has been linked to cancer development in previous studies. However, the association between pre-diagnostic oxidatively generated DNA/RNA damage levels and incident cancer has rarely been investigated. Urinary oxidized guanine/guanosine (OxGua) concentrations, including 8-hydroxy-2'-deoxyguanosine, were assessed in 8,793 older adults in a population-based German cohort. 1,540 incident cancer cases, including 207 lung, 196 colorectal, 218 breast and 245 prostate cancer cases were diagnosed during over 14 years of follow-up. Associations of OxGua levels with cancer outcomes were not observed in the total population in multi-variable adjusted Cox regression models. However, in subgroup analyses, colorectal cancer incidence increased by 8%, 9% and 8% with one standard deviation increase in OxGua levels among current non-smokers, female and non-obese participants, respectively. Additionally, among non-smokers, overall and prostate cancer incidences statistically significantly increased by 5% and 13% per 1 standard deviation increase in OxGua levels, respectively. In contrast, OxGua levels were inversely associated with the risk of prostate cancer among current smokers. However, none of the subgroup analyses had p-values below a threshold for statistical significance after correction for multiple testing. Thus, results need to be validated in further studies. There might be a pattern that oxidatively generated DNA/RNA damage is a weak cancer risk factor in the absence of other strong risk factors, such as smoking, obesity and male sex.

Hbs1, which is homologous to the GTPase eRF3, is a small G protein implicated in mRNA quality control. It interacts with a translation-release factor 1-like protein Dom34/Pelota to direct decay of mRNAs with ribosomal stalls. Although both proteins are evolutionarily conserved in eukaryotes, the biological function of Hbs1 in multicellular organisms is yet to be characterized. In Drosophila, pelota is essential for the progression through meiosis during spermatogenesis and germline stem cell maintenance. Here we show that homozygous Hbs1 mutant flies are viable, female-fertile, but male-sterile, which is due to defects in meiosis and spermatid individualization, phenotypes that are also observed in pelota hypomorphic mutants. In contrast, Hbs1 mutants have no obvious defects in germline stem cell maintenance. We show that Hbs1 genetically interacts with pelota during spermatid individualization. Furthermore, Pelota with a point mutation on the putative Hbs1-binding site cannot substitute the wild type protein for normal spermatogenesis. These data suggest that Pelota forms a complex with Hbs1 to regulate multiple processes during spermatogenesis. Our results reveal a specific requirement of Hbs1 in male gametogenesis in Drosophila and indicate an essential role for the RNA surveillance complex Pelota-Hbs1 in spermatogenesis, a function that could be conserved in mammals.

The gist of natural scenes can be extracted very rapidly and even without focal attention. However, it is unclear whether and to what extent the gist of natural scenes can break through the bottleneck of crowding, a phenomenon in which object recognition will be immensely impaired. In the first two experiments, a target scene, either presented alone or surrounded by four flankers, was categorized at basic (Experiment 1) or global levels (Experiment 2). It was showed that the elimination of high-level semantic information of flankers greatly alleviated the crowding effect, demonstrating that high-level information played an important role in crowding of scene gist. More importantly, participants were able to categorize the scenes in crowding at rather high accuracies, suggesting that the extraction of scene gist might be a prioritized process. To test this hypothesis, in Experiment 3 we compared the crowding effect of three types of stimuli, namely, scenes, facial expressions and letter "E"s. The results showed that scenes could be better categorized than the other two types of stimuli in the crowding condition. This scene gist advantage thus supported our hypothesis. Together, the present studies suggest that scene gist is highly recognizable in crowding, probably due to its prioritization in visual processing.

Quzhou Fructus Aurantii (QFA) is an authentic herb of local varieties in Zhejiang, China, which is usually used to treat gastrointestinal illnesses, but its effects on respiratory inflammation have not been reported yet. In our study, the anti-inflammatory activity of QFA extract (QFAE) was evaluated on copper sulfate pentahydrate (CuSO 4 ·5H 2 O)-induced transgenic neutrophil fluorescent zebrafish model. QFAE showed a significant effect of anti-inflammation in CuSO 4 ·5H 2 O-induced zebrafish by reducing the neutrophil number in the inflammatory site. We investigated the anti-inflammatory activity of QFAE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice models and RAW 264.7 cells. QFAE had an anti-inflammatory effect on reducing total cells, neutrophils, and macrophages in BALF and attenuated alveolus collapse, neutrophils infiltration, lung W/D ratio, myeloperoxidase (MPO) protein expression and other pulmonary histological changes in lung tissues, as well as hematological changes. Levels of pro-inflammatory cytokines, including TNF, IL-6, IFN-γ, MCP-1, and IL-12p70, were decreased, whereas anti-inflammatory cytokine IL-10 was increased after treatment with QFAE both in vivo and in vitro. In summary, our results suggested that QFAE had apparent anti-inflammatory effects on CuSO 4 ·5H 2 O-induced zebrafish, LPS-induced ALI mice, and RAW 264.7 cells. Furthermore, QFAE may be a therapeutic drug to treat ALI/ARDS and other respiratory inflammations.

Mulberry (Morus spp.), in family Moraceae, is a plant with important economic value. Many polyploid levels of mulberry have been determined. In the present study, the fluorescence in situ hybridization (FISH) technique was applied in Morus notabilis, using four single-copy sequences, telomere repeats, and 5S and 25S rDNAs as probes. All the mitotic chromosomes were clearly identified and grouped into seven pairs of homologous chromosomes. Three dot chromosome pairs were distinguished by the FISH patterns of the 25S rDNA probe and a simple sequence repeat (SSR2524). According to the FISH signals, chromosome length and morphology, detailed meiotic diakinesis karyotype was constructed. Interestingly, only six bivalent chromosomes were observed in diakinesis cells. The 25S rDNA probe was used to illustrate chromosome alterations. The results indicated that mitotic chromosomes 5 and 7 fused into diakinesis chromosome 5 during the meiotic phase. In mitotic cells, the fused chromosome 5 broke into chromosomes 5 and 7. A chromosomal fusion-fission cycle between the meiotic and mitotic phases in the same individual is reported here for the first time. This finding will contribute to the understanding of karyotype evolution in plants.

Two challenging problems still remain for optical absorbers consisting of an ultrathin planar semiconductor film on top of an opaque metallic substrate. One is the angle-insensitive mechanism and the other is the system design needed for broadband solar energy harvesting. Here, first we theoretically demonstrates that the high refractive index, instead of the ultrathin feature as reported in previous studies, is the physical origin of the angle insensitivity for ultrathin planar optical absorbers. They exhibit omnidirectional resonance for TE polarization due to the high complex refractive index difference between the semiconductor and the air, while for TM polarization the angle insensitivity persists up to an incident angle related to the semiconductor refractive index. These findings were validated by fabricating and characterizing an 18 nm Ge/Ag absorber sample (representative of small band gap semiconductors for photovoltaic applications) and a 22 nm hematite/Ag sample (representative of large band gap semiconductors for photoelectrochemical applications). Then, we took advantage of angle insensitivity and designed a spectrum splitting configuration for broadband solar energy harvesting. The cascaded solar cell and unassisted solar water splitting systems have photovoltaic and photoelectrochemical cells that are also spectrum splitters, so an external spectrum splitting element is not needed.

The comprehensive design approach is established with coupled optical-electrical simulation for perovskite-based solar cell, which emerged as one of the most promising competitors to silicon solar cell for its low-cost fabrication and high PCE. The selection of structured surface, effect of geometry parameters, incident angle-dependence and polarization-sensitivity are considered in the simulation. The optical modeling is performed via the finite-difference time-domain method whilst the electrical properties are obtained by solving the coupled nonlinear equations of Poisson, continuity, and drift-diffusion equations. The optical and electrical performances of five different structured surfaces are compared to select a best structured surface for perovskite solar cell. The effects of the geometry parameters on the optical and electrical properties of the perovskite cell are analyzed. The results indicate that the light harvesting is obviously enhanced by the structured surface. The electrical performance can be remarkably improved due to the enhanced light harvesting of the designed best structured surface. The angle-dependence for s- and p-polarizations is investigated. The structured surface exhibits omnidirectional behavior and favorable polarization-insensitive feature within a wide incident angle range. Such a comprehensive design approach can highlight the potential of perovskite cell for power conversion in the full daylight.

Observational studies have demonstrated an association between elevated homocysteine (Hcy) level and risk of multiple myeloma (MM). However, it remains unclear whether this relationship is causal. We conducted a Mendelian randomization (MR) study to evaluate whether genetically increased Hcy level influences the risk of MM. We used the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism as an instrumental variable, which affects the plasma Hcy levels. Estimate of its effect on plasma Hcy level was based on a recent genome-wide meta-analysis of 44,147 individuals, while estimate of its effect on MM risk was obtained through meta-analysis of case-control studies with 2,092 cases and 4,954 controls. By combining these two estimates, we found that per one standard-deviation (SD) increase in natural log-transformed plasma Hcy levels conferred a 2.67-fold increase in risk for MM (95% confidence interval (CI): 1.12-6.38; P = 2.7 × 10(-2)). Our study suggests that elevated Hcy levels are causally associated with an increased risk of developing MM. Whether Hcy-lowering therapy can prevent MM merits further investigation in long-term randomized controlled trials (RCTs).