Impact of COVID-19 vaccination status on hospitalization and disease severity: A descriptive study in Nagasaki Prefecture, Japan.

Coronavirus disease 2019 (COVID-19) was extraordinarily harmful, with high rates of infection and hospitalization. This study aimed to evaluate the impact of COVID-19 vaccination status and other factors on hospitalization and disease severity, using data from Nagasaki Prefecture, Japan. Confirmed cases of COVID-19 infection with vaccination status were included and the differences in characteristics between different vaccination statuses, hospitalization or not, and patients with varying levels of disease severity were analyzed. Furthermore, logistic regression was used to calculate odds ratio (ORs) and 95% confidence intervals (CI) to evaluate the association of various factors with hospitalization and disease severity. From March 14, 2020 to August 31, 2022, 23,139 patients were unvaccinated 13,668 vaccinated the primary program with one or two doses, and 4,575 completed the booster. Vaccination reduced the risk of hospitalization with an odd ratio of 0.759 (95% CI: 0.654-0.881) and the protective effect of completed booster vaccination was more pronounced (OR: 0.261, 95% CI: 0.207-0.328). Similarly, vaccination significantly reduced the risk of disease severity (vaccinated primary program: OR: 0.191, 95% CI: 0.160-0.228; completed booster vaccination: OR: 0.129, 95% CI: 0.099-0.169). Overall, unvaccinated, male, elderly, immunocompromised, obese, and patients with other severe illness factors were all risk factors for COVID-19-related hospitalization and disease severity. Vaccination was associated with a decreased risk of hospitalization and disease severity, and highlighted the benefits of completing booster.

Fractional extraction of lignin from coffee beans with low cytotoxicity, excellent anticancer and antioxidant activities.

Lignin, a biopolymer generated from renewable resources, is widely present in terrestrial plants and possesses notable biosafety characteristics. The objective of this work was to assess the edible safety, in vitro antioxidant, and anti-cancer properties of various lignin fractions isolated from commercially available coffee beans often used for coffee preparation. The findings suggest that the phenolic hydroxyl content increased from 3.26 mmol/g (ED70L) to 5.81 mmol/g (ED0L) with decreasing molecular weight, which resulted in more significant antioxidant properties of the low molecular weight lignin fraction. The findings of the study indicate that the viability of RAW 264.7 and HaCaT cells decreased as the quantity of lignin fractions increased. It was observed that concentrations below 200 µg/mL did not exhibit any harmful effects on normal cells. The results of the study demonstrated a significant reduction of cancer cell growth (specifically A375 cells) at a concentration of 800 µg/mL for all lignin fractions, with an observed inhibition rate of 95 %. The results of this study indicate that the lignin extracts derived from coffee beans exhibit significant potential in mitigating diseases resulting from excessive radical production. Furthermore, these extracts show promise as natural antioxidants and anti-cancer agents.

The effect and safety assessment of monitoring ethanol concentration in exhaled breath combined with intelligent control of renal pelvic pressure on the absorption of perfusion fluid during flexible ureteroscopic lithotripsy.

PURPOSE: Previously, we designed a ureteral access sheath with the capability of renal pelvic pressure (RPP) measurement and a medical perfusion and aspiration platform, allowing for the intelligent control of RPP. However, the effect of different RPP levels on perfusion fluid absorption remains unclear. This randomized controlled trial aimed to investigate the effects of exhaled ethanol concentration monitoring and intelligent pressure control on perfusion fluid absorption during flexible ureteroscopic lithotripsy. METHODS: Eighty patients scheduled for flexible ureteroscopic lithotripsy were randomly divided into four groups. In groups A, B, and C, the RPPs were set at 0, - 5, and - 10 mmHg, respectively. Group D was regarded as the controls with unfixed RPP. Isotonic saline containing 1% ethanol was used as the irrigation fluid, with an average irrigation flow rate of 100 mL/min. The primary outcome of this study was the absorption of perfusion fluid that was calculated based on the exhaled ethanol concentration. The secondary outcomes included duration of operation and amounts of perfusion fluid used. Postoperative complications, pre- and postoperative renal function, infection markers, and blood gas analysis were also recorded for safety assessment. RESULTS: In all, 76 patients were involved in this study, whose demographic characteristics and preoperative conditions were comparable among groups. Under the same perfusion flow rate, the groups with fixed RPP exhibited reduced absorption of perfusion fluid, duration of operation, and perfusion volume. In particular, the lowest values were observed in group C (RPP = - 10 mmHg). In contrast to the unfixed RPP group, no considerable difference were observed in levels of BUN, Scr, WBC, CRP, and blood gas values among the fixed RPP groups. Moreover, postoperative complications showed no significant difference among groups. CONCLUSION: In flexible ureteroscopic lithotripsy, the groups with fixed RPP had less absorption of perfusion fluid and perfusion volume, shorter duration of surgery, and higher safety than the unfixed group.

Anti-Melanoma Activity of Single Intratumoral Injection of ZnPc Micelles Mixed With in situ Gel in B16 Bearing Mouse.

Photodynamic therapy (PDT) is a potential treatment strategy for melanoma. As a second-generation photosensitizer, Zinc phthalocyanine (ZnPc) has many advantages for anti-tumor PDTs, such as strong absorption in the red and near infrared regions, high photo and chemical stability, etc. However, ZnPc has a poor water solubility and is apt to aggregate due to the π-π interaction between molecules, which limits its applications. In this study, various solvents and surfactants were screened for dissolving ZnPc and preparing ZnPc@SDC-TPGS micelle and thermosensitive in situ gel. After the cytotoxic effects of thermosensitive gels on PDT were tested, the antitumor effects on PDT of them in mice by intratumoral injection were evaluated, including body weight, and tumor weight, volume and morphology. The cell death pathway and the relationship of reactive oxygen species yield with apoptotic rate of tumor cells induced by ZnPc in situ gel were investigated. The results were that N-methyl-pyrrolidone (NMP) mixed with 2 % SDC and aqueous solution containing 2 % TPGS and 2 % SDC were used to synthesize ZnPc@SDC-TPGS micelle and the thermosensitive in situ gel. The cytotoxic effects of thermosensitive gels showed good tumor suppression of ZnPc@SDC-TPGS in situ gel and no toxicity of the blank gel. Intratumoral injection in situ gel containing 3 µg ZnPc under irradiation demonstrated good tumor inhibition in mice with melanoma. Apoptosis has been established as the primary pathway of cell death, and the production of reactive oxygen species (ROS) plays a crucial role in cellular apoptosis induced by ZnPc@SDC-TPGS in situ gel. In conclusion, the intratumoral injection of ZnPc@SDC-TPGS thermosensitive in situ gel provides a promising local treatment option for melanoma.

Molecular Structure Characterization of Micro/Nanoplastics by 193 nm Ultraviolet Photodissociation Mass Spectrometry.

The degradation of macroplastics results in micro/nanoplastics (MNPs) in the natural environment, inducing high health risks worldwide. It remains challenging to characterize the accurate molecular structures of MNPs. Herein, we integrate 193 nm ultraviolet photodissociation (UVPD) with mass spectrometry to interrogate the molecular structures of poly(ethylene glycol) terephthalate and polyamide (PA) MNPs. The backbones of the MNP polymer can be efficiently dissociated by UVPD, producing rich types of fragment ions. Compared to high-energy collision dissociation (HCD), the structural informative fragment ions and corresponding sequence coverages obtained by UVPD were all improved 2.3 times on average, resulting in almost complete sequence coverage and precise structural interrogation of MNPs. We successfully determine the backbone connectivity differences of MNP analogues PA6, PA66, and PA610 by improving the average sequence coverage from 26.8% by HCD to 89.4% by UVPD. Our results highlight the potential of UVPD in characterizing and discriminating backbone connectivity and chain end structures of different types of MNPs.

Biosensor model based on single hairpin structure for highly sensitive detection of multiple targets.

Nowadays, due to the genetic information carried by nucleic acids, they can serve as a biomarker for the early diagnosis of diseases, including tumors and cardiovascular disease, among others, making genetic testing a hotspot of biomedicine. Therefore, we have designed a universal fluorescence biosensor that can detect multiple DNA sequences with good performance. In our designed biosensor, λ exonuclease is used due to its ability to digest double-stranded DNA from the phosphorylated 5'- end and promote the targeted cycle. The exonuclease is introduced into a DNA hairpin containing a target recognition sequence. Hence, with the target, λ exonuclease-assisted targeted recycling can be activated. The hydrolyzed DNA hairpin triggers a strand displacement reaction between the hairpin probe (H1) and F-Q double DNA strand (F-Q), increasing the distance between the fluorescent chain (F) and quenching chain (Q); thus the fluorescence signal is emitted. It is exciting that the detection limit of the biosensor is 300 fM, which is relatively low, and there is an excellent linear relationship between fluorescence intensity and target concentration. Moreover, the biosensor we designed has universal applicability in the detection of other genes, and the range of RSD is 1.28-2.45%. Hence, it has good application prospects and practical value in the early detection of some diseases and the design of fluorescent biosensors.

Orthohantavirus infections in humans and rodents in the Yichun region, China, from 2016 to 2021.

BACKGROUND: Rodents are the predominant natural hosts of orthohantavirus and the source of human infection, hemorrhagic fever with renal syndrome (HFRS) caused by orthohantavirus is a severe public health problem in the Yichun region, Jiangxi Province, China. However, little information is known about the infection of orthohantavirus in humans and rodents, and the genetic characteristics of the epidemic orthohantavirus in the region. METHODS: The clinical data of HFRS cases in 2016-2021 was analyzed. Virus infection in rodents was analyzed by orthohantavirus antigen detection using immunofluorescent assay, and the species of orthohantaviruses in rodents and patients were identified by real-time RT-PCR and gene sequencing. The S and M segments of orthohantaviruses from rodents and patients were recovered and analyzed. RESULTS: A total of 1,573 HFRS cases were reported in the Yichun region from 2016 to 2021, including 11 death cases. HFRS cases peaked twice each year: in winter from November to January and early summer from May to June. Farmers constituted the predominant population suffering from HFRS. The orthohantavirus antigen was identified in five species of rodents: Apodemus agrarius (A. agrarius), Rattus norvegicus (R. norvegicus), Sorex araneus, Rattus losea (R. losea), and Niviventer confucianus (N. confucianus). The real-time RT-PCR test and genetic analysis results showed that Hantaan orthohantavirus (HTNV), Seoul orthohantavirus (SEOV), and Dabieshan orthohantavirus (DBSV) were circulated in the rodents. HTNV, SEOV, and DBSV from the rodents were distantly related to other known orthohantaviruses and belonged to novel genetic lineages. SEOV and HTNV were found in HFRS patients, but 97.8% (90/92) of the infections were caused by HTNV. Winter and early summer peaks were both caused by HTNV. The HTNV sequences recovered from HFRS cases were closely related to those from A. agrarius. CONCLUSIONS: In the Yichun region, the orthohantaviruses transmitted in rodents include HTNV, SEOV, and DBSV, which have obvious genetic characteristics and high genetic diversity. At the same time, this region is an HFRS mixed epidemic area dominated by HTNV, with two peaks every year, which deserves our high attention.

Clustered Regularly Interspaced Short Palindromic Repeats and Clustered Regularly Interspaced Short Palindromic Repeats-Associated Protein 9 System: Factors Affecting Precision Gene Editing Efficiency and Optimization Strategies.

The clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated (Cas) system is a powerful genomic DNA editing tool. The increased applications of gene editing tools, including the CRISPR-Cas system, have contributed to recent advances in biological fields, such as genetic disease therapy, disease-associated gene screening and detection, and cancer therapy. However, the major limiting factor for the wide application of gene editing tools is gene editing efficiency. This review summarizes the recent advances in factors affecting the gene editing efficiency of the CRISPR-Cas9 system and the CRISPR-Cas9 system optimization strategies. The homology-directed repair efficiency-related signal pathways and the form and delivery method of the CRISPR-Cas9 system are the major factors that influence the repair efficiency of gene editing tools. Based on these influencing factors, several strategies have been developed to improve the repair efficiency of gene editing tools. This review provides novel insights for improving the repair efficiency of the CRISPR-Cas9 gene editing system, which may enable the development and improvement of gene editing tools.

Novel casein antimicrobial peptides for the inhibition of oral pathogenic bacteria.

Milk casein is a rich source of antimicrobial peptides (AMPs) and the most common way to produce AMPs is enzymatic hydrolysis in vitro. In this study, active casein antimicrobial peptide (CAMPs) mixtures were generated by optimized proteolytic cleavage of milk casein. These natural-safe CAMPs mixtures exhibited high activity in the inhibition of Streptococcus mutans and Porphyromonas gingivalis. Morphological characterization suggested the pathogenic bacteria presented incomplete or irregular collapsed membrane surface after the treatment with active CAMPs mixtures. The CAMPs inhibition activity was also effective in the attachment and development of microbial biofilm. Potential CAMPs sequences were unambiguously determined by unbiased proteomic analysis and 301 potential CAMPs were obtained. The activity of 4 novel CAMPs was successfully confirmed by using synthetic standards. This study provides a promising milk CAMPs resource for the development of safe agents in oral bacteria inhibition and functional foods.

Soluble thrombomodulin alleviates Diquat-induced acute kidney injury by inhibiting the HMGB1/IκBα/NF-κB signalling pathway.

Our research aimed to investigate whether soluble thrombomodulin (sTM) relieved Diquat (DQ)-induced acute kidney injury (AKI) via HMGB1/IκBα/NF-κB signaling pathways. An AKI rat model was constructed using DQ. Pathological changes in renal tissue were detected by HE and Masson staining. Gene expression was determined using qRT-PCR, IHC, and western blotting. Cell activity and apoptosis were analysed using CCK-8 and Flow cytometry, respectively. An abnormal kidney structure was observed in DQ rats. The levels of blood urea nitrogen (BUN), creatinine (CRE), uric acid (UA), oxidative stress, and inflammatory responses in the DQ group increased on the 7th day but decreased on the 14th day, compared with the control group. Additionally, HMGB1, sTM, and NF-kappaB (NF-κB) expression had increased in the DQ group compared with the control group, while the IκKα and IκB-α levels had decreased. In addition, sTM relieved the damaging effects of diquat on renal tubular epithelial cell viability, apoptosis, and the inflammatory response. The levels of HMGB1, TM, and NF-κB mRNA and protein were significantly decreased in the DQ + sTM group compared with the DQ group. These findings indicated that sTM could relieve Diquat-induced AKI through HMGB1/IκBα/NF-κB signaling pathways, which provides a treatment strategy for Diquat-induced AKI.

Fluoroamide-Directed Regiodivergent C-Alkylation of Nitroalkanes.

Herein, by exploiting different activation modes of fluoroamides, we achieved α- and δ-C(sp3)-H alkylation of nitroalkanes with switchable regioselectivity. Cu catalysis enabled the interception of a distal C-centered radical by a N-centered radical to couple nitroalkanes and unactivated δ-C-H bonds. In addition, imines generated in situ by fluoroamides were trapped by nitroalkanes to realize the α-C-H alkylation of amides. Both of those scalable protocols have broad substrate scopes and good functional group tolerance.

Low-Temperature NH3-SCR over Hierarchical MnO x Supported on Montmorillonite Prepared by Different Methods.

Hierarchical MnO x pillared or supported on montmorillonite were prepared by three methods, i.e., impregnation (IM), chemical precipitation (CP), and in situ deposition (SP). The catalysts were characterized by low-temperature N2 adsorption (BET), XRD, XPS, SEM, TEM, H2-TPR, NH3-TPD, NO-TPD, TPSR, in situ DRIFTS, and evaluation of catalytic performance for NH3-SCR. The best catalytic performance was obtained for catalysts prepared by SP in terms of activity and selectivity, obtaining >90% NO conversion with >95% selectivity to N2 in 100-300 °C and GHSV of 70,000 h-1. Compared to IM and CP, SP greatly simplified catalyst preparation, resulting in higher BET surface areas; a spongy pore structure; more highly dispersed, pillared MnO x species; and higher density of acid sites distributed on catalysts surface, which all contributed to its superior performance for NH3-SCR. The activity for low-temperature NH3-SCR of manganese catalysts could be widely tailored by preparation methods.

Biological function analysis of ARHGAP39 as an independent prognostic biomarker in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer, with a high morbidity and low survival rate. Rho GTPase activating protein 39 (ARHGAP39) is a crucial activating protein of Rho GTPases, a novel target in cancer therapy, and it was identified as a hub gene for gastric cancer. However, the expression and role of ARHGAP39 in hepatocellular carcinoma remain unclear. Accordingly, the cancer genome atlas (TCGA) data were used to analyze the expression and clinical value of ARHGAP39 in hepatocellular carcinoma. Further, the LinkedOmics tool suggested functional enrichment pathways for ARHGAP39. To investigate in depth the possible role of ARHGAP39 on immune infiltration, we analyzed the relationship between ARHGAP39 and chemokines in HCCLM3 cells. Finally, the GSCA website was used to explore drug resistance in patients with high ARHGAP39 expression. Studies have shown that ARHGAP39 is highly expressed in hepatocellular carcinoma and relevant to clinicopathological features. In addition, the overexpression of ARHGAP39 leads to a poor prognosis. Besides, co-expressed genes and enrichment analysis showed a correlation with the cell cycle. Notably, ARHGAP39 may worsen the survival of hepatocellular carcinoma patients by increasing the level of immune infiltration through chemokines. Moreover, N6-methyladenosine (m6A) modification-related factors and drug sensitivity were also found to be associated with ARHGAP39. In brief, ARHGAP39 is a promising prognostic factor for hepatocellular carcinoma patients that is closely related to cell cycle, immune infiltration, m6A modification, and drug resistance.

An immune genes signature for predicting mortality in sepsis patients.

A growing body of evidence indicates that the immune system plays a central role in sepsis. By analyzing immune genes, we sought to establish a robust gene signature and develop a nomogram that could predict mortality in patients with sepsis. Herein, data were extracted from the Gene Expression Omnibus and Biological Information Database of Sepsis (BIDOS) databases. We enrolled 479 participants with complete survival data using the GSE65682 dataset, and grouped them randomly into training (n = 240) and internal validation (n = 239) sets based on a 1:1 proportion. GSE95233 was set as the external validation dataset (n=51). We validated the expression and prognostic value of the immune genes using the BIDOS database. We established a prognostic immune genes signature (including ADRB2, CTSG, CX3CR1, CXCR6, IL4R, LTB, and TMSB10) via LASSO and Cox regression analyses in the training set. Based on the training and validation sets, the Receiver Operating Characteristic curves and Kaplan-Meier analysis revealed that the immune risk signature has good predictive power in predicting sepsis mortality risk. The external validation cases also showed that mortality rates in the high-risk group were higher than those in the low-risk group. Subsequently, a nomogram integrating the combined immune risk score and other clinical features was developed. Finally, a web-based calculator was built to facilitate a convenient clinical application of the nomogram. In summary, the signature based on the immune gene holds potential as a novel prognostic predictor for sepsis.

A long-term retrospective analysis of the haemorrhagic fever with renal syndrome epidemic from 2005 to 2021 in Jiangxi Province, China.

Jiangxi is one of the provinces in China most seriously affected by the haemorrhagic fever with renal syndrome (HFRS) epidemic. The aim of this paper was to systematically explore the HFRS epidemic in Jiangxi from the perspective of Hantavirus (HV) prevalence in rodents and humans and virus molecular characteristics. Individual information on all HFRS cases in Jiangxi from 2005 to 2021 was extracted from the China Information System for Disease Control and Prevention. All S and M fragment sequences of the Seoul virus and Hantan virus strains uploaded by Jiangxi and its neighbouring provinces and some representative sequences from provinces in China or some countries of Southeast Asia with the highest HV prevalence were retrieved and downloaded from NCBI GenBank. Periodogram and spatial autocorrelation were adopted for temporal periodicity and spatial clustering analysis of the HFRS epidemic. Joinpoint regression was utilized to explore the changing morbidity trend patterns of HFRS. Multiple sequence alignment and amino acid variation analysis were used to explore the homology and variation of strain prevalence in Jiangxi. Based on monthly morbidity time series, the periodogram analysis showed that the prevalence of HFRS had periodicities of 6 months and 12 months. Spatial autocorrelation analysis showed that HFRS distributed in Jiangxi was not random, with a "High-High" clustering area around Gaoan County. HFRS morbidity among the 0 ~ 15-year-old and ~ 61-year-old or older populations in Jiangxi increased significantly during the period of 2008-2015. Generally, HFRS morbidity was significantly positively correlated with the index of rat with virus (IRV) (r = 0.742) in the counties surrounding Gaoan from 2005 to 2019. HTNV strains in Jiangxi were in one independent branch, while the SEOV strains in Jiangxi were relatively more diverse. Both the YW89-15 and GAW30/2021 strains shared approximately 85% nucleotide homology and approximately 97% amino acid homology with their corresponding standard strains and vaccine strains. GAW30/2021 and YW89-15 had some amino acid site variations in nucleoprotein, glycoprotein precursor and RNA-dependent polymerase with their corresponding vaccine strains Z10 (HTNV) and Z37 (SEOV). The HFRS epidemic in Jiangxi has obvious temporal periodicity and spatial clustering, and the significant increase in the non-Immunization Expanded Program (EPI) targeted population (children and elderly) suggests that HFRS vaccination in this population needs to be considered. Although applying the EPI played a certain role in curbing the incidence of HFRS in Jiangxi from the perspective of ecological epidemiology, HTNV and SEOV strains prevalent in Jiangxi have some amino acid site variations compared to their corresponding vaccine strains, suggesting that HV variation needs to be continuously monitored in the future to observe vaccine protective efficiency.

Endosulfan induced kidney cell injury by modulating ACE2 through up-regulating miR-429 in HK-2 cells.

Endosulfan, a typical organochlorine pesticide, is widely used in agricultural countries and was detected in blood samples from the general population. Studies have shown a positive correlation between chronic kidney disease of unknown aetiology (CKDu) and endosulfan. CKDu has become endemic in agricultural countries, with clinical manifestations of tubulointerstitial fibrosis.The goal of this study was to investigate the effects of endosulfan in kidney cell injury in human renal tubular epithelial cells (HK-2), focusing on apoptosis, inflammatory response, and epithelial-mesenchymal transition (EMT). We found that endosulfan induced apoptosis in HK-2 cells by up-regulating the expression of BAX, APAF-1, Caspase-3 and mitochondrial Cytochrome c was released into the cytosol. Endosulfan caused an inflammatory response, showing the increase in the secretion and mRNA expression levels of IL-6/IL-8. Endosulfan triggered EMT, characterized by downregulation of E-cadherin and upregulation of Vimentin. Western blot results showed that p-Smad3 and Smad3 protein expression were elevated while the expression of Smad7 were decreased in endosulfan-exposed groups. Dual luciferase reporter assay confirmed the potential binding capacity of miR-429 to 3'-UTR of ACE2. Endosulfan causes upregulation of miR-429 and downregulation of ACE2 in HK-2 cells. Overexpression of miR-429 or silencing of ACE2 in HK-2 cells caused apoptosis, inflammation and EMT through TGF signaling pathway. These findings suggest that endosulfan can lead to kidney cell injury by modulating ACE2 through up-regulating miR-429, providing new evidence for the pathogenesis of CKDu.

Ultraviolet Photodissociation Reveals the Molecular Mechanism of Crown Ether Microsolvation Effect on the Gas-Phase Native-like Protein Structure.

Maintaining the protein high-order structures and interactions during the transition from aqueous solution to gas phase is essential to the structural analysis of native mass spectrometry (nMS). Herein, we systematically interrogate the effects of charge state and crown ether (CE) complexation on the gas-phase native-like protein structure by integrating nMS with 193 nm ultraviolet photodissociation (UVPD). The alterations of photofragmentation yields of protein residues and the charge site distribution of fragment ions reveal the specific sites and sequence regions where charge and CE take effect. Our results exhibit the CE complexation on protonated residues can largely alleviate the structure disruption induced by the intramolecular solvation of charged side chains. The influences of CE complexation and positive charge on gas-phase protein structure exhibit generally opposite trends because the CE microsolvation avoids the hydrogen-bonding formation between the charged side chains with backbone carbonyls. Thus, CE complexation leads to a more stable and native-like protein structure in the gas phase.

Genome-wide DNA methylation pattern in whole blood of patients with coal-burning arsenic poisoning.

Exposure to coal-burning arsenic leads to an increased risk of cancer, multi-systems damage and chronic diseases, with DNA methylation one potential mechanism of arsenic toxicity. There are few studies on genome-wide methylation in the coal-burning arsenic poisoning population. Illumina 850 K methylation beadchip is the most suitable technology for DNA methylation of epigenome-wide association analysis. This study used 850 K to detect changes in Genome-wide DNA methylation in whole blood samples of 12 patients with coal-burning arsenic poisoning ( Arsenic poisoning group) and four healthy control participants (Healthy control group). There is clearly abnormal genome-wide DNA methylation in coal-burning arsenic poisoning, with 647 significantly different methylation positions, 524 different methylation regions and 335 significantly different methylation genes in arsenic poisoning patients compared with healthy controls. Further functional analysis of Gene ontology (GO) and Kyoto encyclopedia of genes (KEGG) found 592 GO items and 131 KEGG pathways between patients of coal-burning arsenic poisoning and healthy control. Then, analysis of gene degree and combined-score identified NAPRT1, NT5C3B, NEDD4L, SLC22A3 and RAB11B as target genes. Further validation by qRT-PCR indicates that mRNA expression of five genes changes significantly in the arsenic poisoning group (n = 72) compared to the healthy control group (n = 72). These results showed the genome-wide methylation pattern and highlighted five critical genes within the coal-burning arsenic poisoning population that involve Nicotinate and nicotinamide metabolism, Choline metabolism in cancer, and Ubiquitin mediated proteolysis. Next, the methylation profile of coal burning arsenic poisoning will be further excavation and the mechanism of coal burning arsenic poisoning will be further explored from five genes related pathways and functions.

Broadly Applicable Ion Pair-Assisted Nucleophilic Substitution of sp3-Carbon Electrophiles with Alkynyltrifluoroborates.

Alkynyltrifluoroborate nucleophiles react smoothly with a wide range of sp3-carbon electrophiles, including propargyl methanesulfonates and unactivated alkyl triflates, to give Sonogashira-type products, via a novel ion pair-assisted nucleophilic substitution mechanism. An ion pair-organic complex, investigated using computational chemistry and in situ NMR experiments, may play a crucial role in this reaction.

High-performance micro/nanoplastics characterization by MALDI-FTICR mass spectrometry.

Micro/nanoplastics (MNPs) are widespread environmental pollutants that cause high health risks. However, high heterogeneity in particle sizes and chemical compositions of MNPs make their accurate characterization extremely challenging. Herein, we established a matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS) strategy for the unambiguous characterization of different types of MNPs with high performance, including polystyrene, polyethylene glycol terephthalate, polyamide, polymethyl methacrylate, acrylonitrile butadiene styrene copolymer, and polycarbonate. The MNP sample preparation and detection conditions were systematically optimized by using response surface methodology, and the MS detection signal-to-noise ratios were improved 1.5 times on average. The ultrahigh mass resolution of FTICR MS is crucial to the unambiguous elucidation of MNP structures. We demonstrate that this MS strategy is highly efficient in the characterization of polymer constitutions of environmental MNPs derived from foam, bottles, cable ties, and compact discs, providing a promising tool for MNP detection and safety evaluation.