EISA-EXPOSOME: One Highly Sensitive and Autonomous Exposomic Platform with Enhanced in-Source Fragmentation/Annotation.

Lacking a highly sensitive exposome screening technique is one of the biggest challenges in moving exposomic research forward. Enhanced in-source fragmentation/annotation (EISA) has been developed to facilitate molecular identification in untargeted metabolomics and proteomics. In this work, with a mixture of 50 pesticides at three concentration levels (20, 4, and 0.8 ppb), we investigated the analytical performance of the EISA technique over the well-accepted targeted MS/MS mode (TMM) in the detection and identification of chemicals at low levels using a quadrupole time-of-flight (qTOF) instrument. Compared with the TMM method, the EISA technique can recognize additional 1, 20, and 23 chemicals, respectively, at the three concentration levels (20, 4, and 0.8 ppb, respectively) investigated. At the 0.8 ppb level, intensities of precursor ions and fragments observed using the EISA technique are 30-1,154 and 3-80 times higher, respectively, than those observed at the TMM mode. A higher matched fragment ratio (MFR) between the EISA technique and the TMM method was recognized for most chemicals. We further developed a chemical annotation informatics algorithm, EISA-EXPOSOME, which can automatically search each precursor ion (m/z) in the MS/MS library against the EISA MS1 spectra. This algorithm then calculated a weighted score to rank the candidate features by comparing the experimental fragment spectra to those in the library. The peak intensity, zigzag index, and retention time prediction model as well as the peak correlation coefficient were further adopted in the algorithm to filter false positives. The performance of EISA-EXPOSOME was demonstrated using a pooled dust extract with a pesticide mixture (n = 200) spiked at 5 ppb. One urine sample spiked with a contaminant mixture (n = 50) at the 5 ppb level was also used for the validation of the pipeline. Proof-of-principal application of EISA-EXPOSOME in the real sample was further evaluated on the pooled dust sample with a modified T3DB database (n = 1650). Our results show that the EISA-EXPOSOME algorithm can remarkably improve the detection and annotation coverage at trace levels beyond the traditional approach as well as facilitate the high throughput screening of suspected chemicals.

Eight novel brominated flame retardants in indoor and outdoor dust samples from the E-waste recycling industrial park: Implications for human exposure.

As alternatives for legacy brominated flame retardants, novel brominated flame retardants (NBFRs) have a wide array of applications in the electronic and electrical fields. The shift of recycling modes of electronic and electrical waste (e-waste) from informal recycling family workshop to formal recycling facilities might come with the change the chemical landscape emitted including NBFRs, however, little information is known about this topic. This study investigated the occurrence characteristics, distribution, and exposure profiles of eight common NBFRs and their derivatives in an e-waste recycling industrial park in central China and illustrated the differences in various functional zones in the recycling park. The highest level of ΣNBFRs in dust samples was found in e-waste storage area at median concentration of 27,400 ng/g, followed by e-waste dismantling workshops (23,300 ng/g), workshop outdoor area (7770 ng/g), and residential area outdoor (536 ng/g). In the e-waste dismantling associated dust samples, tetrabromobisphenol A bis(2,3-dibromopropyl ether) (TBBPA-BDBPE), tetrabromobisphenol A (TBBPA) and 2,4,6-tris(2,4,6-tribromophenoxy)-1,3,5-triazine (TTBP-TAZ) were the predominant components. This paper presented the first evidence regarding the occurrence characteristic and distribution of tetrabromobisphenol S (TBBPS), tetrabromobisphenol A bismethyl ether (TBBPA-BME) and tetrabromobisphenol S bis(2,3-dibromopropyl ether) (TBBPS-BDBPE) in the e-waste associated dust samples. By comparing with previous studies performed in China, this paper also noticed the significant decrease of TBBPA concentrations in the dust probably due to the shift of e-wastes sources and recycling modes. We further assessed the risk of occupational workers exposure to NBFRs. The median EDI (estimated daily intake) value of ΣNBFRs among e-waste dismantling workers was 9.71 ng/kg BW/d with the maximum EDI value being 19.6 ng/kg BW/d, hundreds of times higher than those exposed by general population. The study raises great concern for the health risk of occupational exposure to NBFRs in the e-waste recycling industrial park.

Elimination of catastrophic optical mirror damage in continuous-wave high-power laser diodes using multi-section waveguides.

One of the persistent obstacles for high-power laser diodes (LDs) has been the catastrophic optical mirror damage (COMD), which limits the operating power level and lifetime of commercial high-power LDs. The output facet of LD reaches a critical temperature resulting in COMD, which is an irreversible device failure. Here, we fabricate multi-section LDs by tailoring the waveguide structure along the cavity that separates the output facet from the heat-generating lasing region. In this method, the LD waveguide is divided into electrically isolated laser and window sections along the cavity. The laser section is pumped at a high current to achieve high output power, and the window is biased at a low current with negligible heat generation. This design restricts the thermal impact of the laser section on the facet, and the window section allows lossless transport of the laser to the output facet. The lasers were operated continuous-wave up to the maximum achievable power. While standard LDs show COMD failures, the multi-section waveguide LDs are COMD-free. Our technique and results provide a pathway for high-reliability LDs, which would find diverse applications in semiconductor lasers.

Discovering the key genes and important DNA methylation regions in breast cancer.

BACKGROUND: Breast cancer is the malignant tumor with the highest incidence in women. DNA methylation has an important effect on breast cancer, but the effect of abnormal DNA methylation on gene expression in breast cancer is still unclear. Therefore, it is very important to find therapeutic targets related to DNA methylation. RESULTS: In this work, we calculated the DNA methylation distribution and gene expression level in cancer and para-cancerous tissues for breast cancer samples. We found that DNA methylation in key regions is closely related to gene expression by analyzing the relationship between the distribution characteristics of DNA methylation in different regions and the change of gene expression level. Finally, the 18 key genes (17 tumor suppressor genes and 1 oncogene) related to prognosis were confirmed by the survival analysis of clinical data. Some important DNA methylation regions in these genes that result in breast cancer were found. CONCLUSIONS: We believe that 17 TSGs and 1 oncogene may be breast cancer biomarkers regulated by DNA methylation in key regions. These results will help to explore DNA methylation biomarkers as potential therapeutic targets for breast cancer.

Occurrence of Phthalates in Bottled Drinks in the Chinese Market and Its Implications for Dietary Exposure.

Ubiquitous occurrences of phthalic acid esters (PAEs) or phthalates in a variety of consumer products have been demonstrated. Nevertheless, studies on their occurrence in various types of bottled drinks are limited. In this study, fifteen PAEs were analyzed in six categories of bottled drinks (n = 105) collected from the Chinese market, including mineral water, tea drinks, energy drinks, juice drinks, soft drinks, and beer. Among the 15 PAEs measured, DEHP was the most abundant phthalate with concentrations ranging from below the limit of quantification (LOQ) to 41,000 ng/L at a detection rate (DR) of 96%, followed by DIBP (DR: 88%) and DBP (DR: 84%) with respective concentration ranges of below LOQ to 16,000 and to 4900 ng/L. At least one PAE was detected in each drink sample, and the sum concentrations of 15 PAEs ranged from 770 to 48,004 ng/L (median: 6286 ng/L). Significant differences with respect to both PAE concentrations and composition profiles were observed between different types of bottled drinks. The median sum concentration of 15 PAEs in soft drinks was over five times higher than that detected in mineral water; different from other drink types. Besides DEHP, DBIP, and DBP, a high concentration of BMEP was also detected in a tea drink. The estimated daily dietary intake of phthalates (EDIdrink) through the consumption of bottled drinks was calculated based on the concentrations measured and the daily ingestion rates of bottled drink items. The EDIdrink values for DMP, DEP, DIBP, DBP, BMEP, DAP, BEEP, BBP, DCP, DHP, BMPP, BBEP, DEHP, DOP, and DNP through the consumption of bottled mineral water (based on mean concentrations) were 0.45, 0.33, 12.5, 3.67, 2.10, 0.06, 0.32, 0.16, 0.10, 0.09, 0.05, 0.81, 112, 0.13, and 0.20 ng/kg-bw/d, respectively, for Chinese adults. Overall, the EDIdrink values calculated for phthalates through the consumption of bottled drinks were below the oral reference doses suggested by the United States Environmental Protection Agency (U.S. EPA).

CancerMHL: the database of integrating key DNA methylation, histone modifications and lncRNAs in cancer.

The discovery of key epigenetic modifications in cancer is of great significance for the study of disease biomarkers. Through the mining of epigenetic modification data relevant to cancer, some researches on epigenetic modifications are accumulating. In order to make it easier to integrate the effects of key epigenetic modifications on the related cancers, we established CancerMHL (http://www.positionprediction.cn/), which provide key DNA methylation, histone modifications and lncRNAs as well as the effect of these key epigenetic modifications on gene expression in several cancers. To facilitate data retrieval, CancerMHL offers flexible query options and filters, allowing users to access specific key epigenetic modifications according to their own needs. In addition, based on the epigenetic modification data, three online prediction tools had been offered in CancerMHL for users. CancerMHL will be a useful resource platform for further exploring novel and potential biomarkers and therapeutic targets in cancer. Database URL: http://www.positionprediction.cn/.

MedChatZH: A tuning LLM for traditional Chinese medicine consultations.

Generative Large Language Models (LLMs) have achieved significant success in various natural language processing tasks, including Question-Answering (QA) and dialogue systems. However, most models are trained on English data and lack strong generalization in providing answers in Chinese. This limitation is especially evident in specialized domains like traditional Chinese medical QA, where performance suffers due to the absence of fine-tuning and high-quality datasets. To address this, we introduce MedChatZH, a dialogue model optimized for Chinese medical QA based on transformer decoder with LLaMA architecture. Continued pre-training on a curated corpus of Chinese medical books is followed by fine-tuning with a carefully selected medical instruction dataset, resulting in MedChatZH outperforming several Chinese dialogue baselines on a real-world medical dialogue dataset. Our model, code, and dataset are publicly available on GitHub (https://github.com/tyang816/MedChatZH) to encourage further research in traditional Chinese medicine and LLMs.

Green waste and sewage sludge feeding ratio alters co-composting performance: Emphasis on the role of bacterial community during humification.

Composting with five levels of green waste and sewage sludge was compared to examine how feeding ratios affected composting performance with special focus on humification, and the underlying mechanisms. The results showed that the raw material ratio persistently affected compost nutrients and stability. Humification and mineralization were promoted by higher proportion of sewage sludge. Bacterial community composition and within-community relationships were also significantly affected by the raw material feeding ratio. Network analysis indicated that clusters 1 and 4 which dominated by Bacteroidetes, Proteobacteria, and Acidobacteria shown significantly positive correlation with humic acid concentration. Notably, the structural equational model and variance partitioning analysis demonstrated that bacterial community structure (explained 47.82% of the variation) mediated the effect of raw material feeding ratio on humification, and exceeded the effect of environmental factors (explained 19.30% of the variation) on humic acid formation. Accordingly, optimizing the composting raw material improves the composting performance.

Release and mobility characteristics of thallium from polluted farmland in varying fertilization: Role of cation exchange.

Batch and column leaching tests were used to study thallium's release and migration behaviour and evaluate its potential toxicity risks in soil. The results indicated that leaching concentrations of Tl using TCLP and SWLP were much higher than the threshold, indicating a high risk of thallium pollution in the soil. Furthermore, the intermittent leaching rate of Tl by Ca2+ and HCl reached its maximum value, demonstrating the easy release of Tl. After HCl leaching, the form of Tl in the soil has changed, and ammonium sulfate has increased its extractability. Additionally, the extensive application of calcium promoted the release of Tl, increasing its potential ecological risk. Spectral analysis showed that Tl was mainly present in minerals such as Kaolinite and Jarosite, and exhibited significant adsorption capacity for Tl. HCl and Ca2+ damaged the crystal structure of the soil, greatly enhancing the migration and mobility of Tl in the environment. More importantly, XPS analysis confirmed that the release of Tl (I) in the soil was the leading cause of increased mobility and bioavailability. Therefore, the results revealed the risk of Tl release in the soil, providing theoretical guidance for its pollution prevention and control.

Discovered Key CpG Sites by Analyzing DNA Methylation and Gene Expression in Breast Cancer Samples.

Breast cancer is the most common cancer in the world, and DNA methylation plays a key role in the occurrence and development of breast cancer. However, the effect of DNA methylation in different gene functional regions on gene expression and the effect of gene expression on breast cancer is not completely clear. In our study, we computed and analyzed DNA methylation, gene expression, and clinical data in the TCGA database. Firstly, we calculated the distribution of abnormal DNA methylated probes in 12 regions, found the abnormal DNA methylated probes in down-regulated genes were highly enriched, and the number of hypermethylated probes in the promoter region was 6.5 times than that of hypomethylated probes. Secondly, the correlation coefficients between abnormal DNA methylated values in each functional region of differentially expressed genes and gene expression values were calculated. Then, co-expression analysis of differentially expressed genes was performed, 34 hub genes in cancer-related pathways were obtained, of which 11 genes were regulated by abnormal DNA methylation. Finally, a multivariate Cox regression analysis was performed on 27 probes of 11 genes. Three DNA methylation probes (cg13569051 and cg14399183 of GSN, and cg25274503 of CAV2) related to survival were used to construct a prognostic model, which has a good prognostic ability. Furthermore, we found that the cg25274503 hypermethylation in the promoter region inhibited the expression of the CAV2, and the hypermethylation of cg13569051 and cg14399183 in the 5'UTR region inhibited the expression of GSN. These results may provide possible molecular targets for breast cancer.

The effect of key DNA methylation in different regions on gene expression in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common cancer with high morbidity and mortality. As we all know, the alteration of DNA methylation has a crucial impact on the occurrence of HCC. However, the mechanism of the effect of DNA methylation in different regions on gene expression is still unclear. Here, by computing and analyzing the distribution of differential methylation in 12 different regions in HCC tissues and adjacent normal tissues, not only the hypermethylation of CpG islands and global hypomethylation were found, but also a stable distribution pattern of differential methylation in HCC was found. Then the correlations between DNA methylations in different regions and gene expressions were calculated, and the diversity of correlations in different regions was determined. The key genes of differential methylation and differential expression related to the survival of HCC patients were obtained by using Cox regression analysis, a four-gene prognostic risk scoring model was constructed, and the prognostic performance was well verified. The regions of the differentially methylated CpG sites corresponding to the four key genes were located and their influences on the expression were analyzed. The results indicate that the promoter, first exon, 5'UTR, sixth exon, N_Shore, and S_Shore hypomethylation promotes the expression of key oncogenes, which together lead to the occurrence of HCC. These results might help to study the role of DNA methylation in HCC and provide potential biomarkers for the diagnosis of HCC.

A nationwide survey of 20 legacy brominated flame retardants in indoor dust from China: continuing occurrence, national distribution, and implication for human exposure.

Despite the restrictions on polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDDs), these chemicals are still ubiquitous environmental pollutants. In this study, we measured the concentrations and profiles of 17 PBDE congeners and 3 HBCDD isomers in indoor dust samples collected from 23 provinces and cities across China. The summed concentrations of PBDEs (Σ17PBDEs) ranged from 4.19 to 817 ng/g, with an average of 171 ± 184 ng/g. BDE-209 was the most abundant congener. The concentrations of HBCDDs ranged from 6.65 to 1335 ng/g, with an average of 236 ± 324 ng/g. Unlike commercial HBCDD formulations, α-HBCDD was the predominant isomer in the indoor dust samples analyzed. Geographical distributions showed that the concentrations of PBDEs and HBCDDs varied significantly among different regions. Higher PBDE and HBCDD levels were observed in samples from eastern coastal and economically developed regions. Further, we estimated the daily intakes of PBDEs and HBCDDs through the routes of dust ingestion and dust dermal absorption for different age groups. Dust dermal absorption is an unneglectable exposure pathway to PBDEs and HBCDs for the Chinese population. Among the age groups, infants had the highest exposure via dust dermal absorption, and toddlers had the highest exposure via dust ingestion. Compared with the threshold values, the exposure doses of PBDEs and HBCDDs are unlikely to pose significant health concerns for both infants and adults in China. This is the first national survey of PBDEs and HBCDDs in indoor dust samples across China after the restriction.

Effect of Increasing C/N Ratio on Performance and Microbial Community Structure in a Membrane Bioreactor with a High Ammonia Load.

Herein, the responses of the operational performance of a membrane bioreactor (MBR) with a high ammonium-nitrogen (NH4+-N) load and microbial community structure to increasing carbon to nitrogen (C/N) ratios were studied. Variation in the influent C/N ratio did not affect the removal efficiencies of chemical oxygen demand (COD) and NH4+-N but gradually abated the ammonia oxidization activity of sludge. The concentration of the sludge in the reactor at the end of the process increased four-fold compared with that of the seed sludge, ensuring the stable removal of NH4+-N. The increasing influent COD concentration resulted in an elevated production of humic acids in soluble microbial product (SMP) and accelerated the rate of membrane fouling. High-throughput sequencing analysis showed that the C/N ratio had selective effects on the microbial community structure. In the genus level, Methyloversatilis, Subsaxibacter, and Pseudomonas were enriched during the operation. However, the relative abundance of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) involved in nitrification declined gradually and were decreased by 86.54 and 90.17%, respectively, with influent COD increasing from 0 to 2000 mg/L. The present study offers a more in-depth insight into the control strategy of the C/N ratio in the operation of an MBR with a high NH4+-N load.

MicroRNA-9 regulates the proliferation, migration and invasion of human glioma cells by targeting CDH1.

PURPOSE: Glioma causes significant mortality worldwide. The currently available treatment strategies are flawed and the therapeutic targets are limited. Accumulating evidence suggests that microRNAs (miRs) are involved in the development and progression of different cancers. Herein, the therapeutic potential of miR-9 was explored in human glioma cells. METHODS: The qRT-PCR was used for expression analysis. WST-1 assay was used for determination of cell viability. Acridine orange (AO) / ethidium promide (EB) and annexin V/propidium iodide (PI) were used for the detection of apoptosis. Flow cytometry was used for cell cycle analysis. Wound healing and transwell assays were used to monitor cell migration and invasion. Protein expression was determined by western blot analysis. RESULTS: The results showed that miR-9 is significantly downregulated in glioma cells. Overexpression of miR-9 caused significant inhibition in the proliferation of U87 glioma cells. The miR-9-triggered growth inhibition was mainly due to the induction of apoptosis which was concomitant with increase in the Bax/Bcl-2 ratio. Overexpression of miR-9 also induced arrest of U87 glioma cells at G2/M checkpoint of cell cycle. Additionally, transwell and wound healing assays showed that miR-9 caused significant decrease in the migration and invasion of U87 glioma cells. Bioinformatics analysis showed that miR-9 exerts its effects by inhibiting Cadherin-1 (CDH1). However, overexpression of CDH1 could nullify the effects of miR-9 on the growth, migration and invasion of glioma cells. CONCLUSION: Taken together, miR-9 may exhibit therapeutic implications in the treatment of glioma.

Identification of key genes and important histone modifications in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death in the world. It has been reported that HCC is closely related to the changes of histone modifications. However, finding histone modification patterns in key genes which related to HCC is still an important task. In our study, the patterns of 11 kinds of histone modifications in the promoter regions for the different types of genes were analyzed by hierarchical screening for hepatocyte (normal) cell line and HepG2 (tumor) cell line. The important histone modifications and their key modification regions in different types of genes were found. The results indicate that these important genes may play a pivotal role in the occurrence of HCC. By analyzing the differences of histone modifications and gene expression levels for these important genes between the two cell lines, we found that the signals of H3K4me3, H3K27ac, H3K9ac, and H3K4me2 in HCC are significantly stronger. The changed regions of important histone modifications in 17 key genes were also identified. For example, the H3K4me3 signals increased 150 times in regions (-1500, -500) bp and (0, 1000) bp of ARHGAP5 in tumor cell line than in normal cell line. Finally, a prognostic risk scoring model was constructed, and the effects of key genes on the prognosis of HCC were verified by the survival analysis. Our results may provide a more precise potential therapeutic targets for identifying key genes and histone modifications in HCC as new biomarkers.

Responses of carbonic anhydrases and Rubisco to abrupt CO2 changes of seawater in two marine diatoms.

Diatoms are experiencing striking fluctuations in seawater carbonate chemistry in the natural marine environment, especially in coastal seawaters. Here, we show that the diatoms Thalassiosira weissflogii and Phaeodactylum tricornutum, which utilize different carbon acquisition mechanisms, respond differently to short-term changes in seawater carbonate chemistry. Our results showed that T. weissflogii showed significantly higher photosynthetic oxygen evolution rates than that of P. tricornutum at low levels of CO2 or HCO3-. This suggests that T. weissflogii had higher affinities for CO2 or HCO3- when their concentrations were not sufficient to support saturated growth and photosynthesis. While the activity of Rubisco in P. tricornutum positively correlated with carbonic anhydrases (CA), we observed negative relationship between Rubisco and CA activity in the diatom T. weissflogii. These contrasting physiological responses of diatoms with varied carbon acquisition mechanisms indicate different abilities to cope up with abrupt changes in seawater carbonate chemistry. We propose that the ability to respond to varying carbonate chemistry may act as one determinant of the diatom distributions and phytoplankton community structures.

Geniposide attenuates epilepsy symptoms in a mouse model through the PI3K/Akt/GSK-3ß signaling pathway.

Previous reports on the pharmacological actions of geniposide have indicated that it has anti-asthmatic, anti-inflammatory and analgesic effects in the liver and gallbladder, and therapeutic effects in neurological, cardiovascular and cerebrovascular diseases. The results of the current study demonstrate that geniposide attenuates epilepsy in a mouse model through the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3ß (GSK-3ß) signaling pathway. A mouse model of epilepsy was induced by maximal electric shock (50 mA, 50 Hz, 1 sec). Epilepsy mice were intragastrically administered with 0, 5, 10 or 20 mg/kg geniposide. Geniposide significantly reduced the incidence and significantly increased the latency of clonic seizures in epileptic mice compared with non-treated epileptic mice (both P<0.01). Geniposide treatment significantly inhibited cyclooxygenase-2 mRNA expression in epilepsy mice (P<0.01). Furthermore, geniposide significantly suppressed the protein expression of activator protein 1, increased the activation of Akt and increased the protein expression of GSK-3ß and PI3K in epilepsy mice (all P<0.01). These results suggest that geniposide attenuates epilepsy in mice through the PI3K/Akt/GSK-3ß signaling pathway.

[Textual research on the original edition of Chongguang buzhu huangdineijing suwen (Revisions and Extensive Notes on the Plain Question of Huangdi's Inner Classic)].

It is generally held that the original edition for the revision of Su wen (Plain Questions) by the Bureau for Revising Medical Books of Northern Song dynasty was Huangdineijing suwen (Plain Questions of the Huangdi's Inner Classic) commented by WANG Bing. However, some doubtful points were found in Chongguang buzhu huangdineijing suwen (Revised and Extensive Notes on the Plain Question of Huangdi's Inner Classic) that the government of the Song dynasty had twice arranged to collate Su Wen after WANG Bing and before LIN Yi; there were also private editors. Through in-depth study of the comments of LIN Yi, it can be concluded that the new revision did not adopt the original edition of the secondary annotated edition, but that of the alternative edition of the secondary annotated edition with commentaries, which ought to be the re-collated edition on the basis of the collation of Tiansheng in the fourth year (1026) by DING Du of Jingyou in the second year (1035).

Low temperature induced synthesis of TiN nanocrystals.

TiN nanocrystals were successfully prepared through the direct reaction between TiCl(4) and NaNH(2) induced at 300 degrees C. The yield based on Ti is approximately 80%. X-ray powder diffraction indicated that the product was cubic TiN with a lattice constant of a = 4.243 A. Transmission electron microscopy revealed that nanocrystalline TiN with a diameter of 10 nm or so and extremely long straight rods were synthesized. The possible formation mechanism was also proposed.