A rapid method for the determination of stable hydrogen isotope ratios of acetic acid in vinegar.

RATIONALE: Vinegar is an everyday condiment made from fermented grains or fruits. It contains acetic acid which is the main organic material produced by fermentation. Vinegar suffers from the authenticity problem of exogenous adulteration due to the indistinguishability of low-cost chemical sources of synthetic acetic acid from acetic acid produced by fermentation. It is necessary to establish a simple and rapid measurement technique. METHODS: Determination was according to the total acid content of vinegar diluted with acetone to a certain concentration. Online separation and determination of acetic acid δD in vinegar were carried out using gas chromatography-pyrolysis-isotope ratio mass spectrometry. RESULTS: An HP-Plot/U column was selected for online separation of acetic acid and water with molecular sieve characteristics. At the same time, combined with the instrument blowback function to remove water. Dilute solvent acetone was treated with a molecular sieve to remove trace water. The reproducibility of this method is less than 3‰. The long-term stability is within a reasonable error range. The accuracy correlation coefficient is greater than 0.99. The δD values of acetic acid in vinegar (-264.5 ± 20.3‰) and from chemical sources (-30.5 ± 90.8‰) were obtained. CONCLUSIONS: A rapid method was developed for identification of different sources of acetic acid. These different sources of acetic acid exhibited significant hydrogen isotope distribution characteristics. Additionally, it was observed that the carboxyl hydrogen of acetic acid exhibited facile exchange with water. In future investigations, we aim to mitigate this interference.

Innovations in chemical degradation technologies for the removal of micro/nano-plastics in water: A comprehensive review.

Micro/nanoplastics (M/NPs) in water have raised global concern due to their potential environmental risks. To reestablish a M/NPs free world, enormous attempts have been made toward employing chemical technologies for their removal in water. This review comprehensively summarizes the advances in chemical degradation approaches for M/NPs elimination. It details and discusses promising techniques, including photo-based technologies, Fenton-based reaction, electrochemical oxidation, and novel micro/nanomotors approaches. Subsequently, critical influence factors, such as properties of M/NPs and operating factors, are analyzed in this review specifically. Finally, it concludes by addressing the current challenges and future perspectives in chemical degradation. This review will provide guidance for scientists to further explore novel strategies and develop feasible chemical methods for the improved control and remediation of M/NPs in the future.

Melatonin Alleviates Acute Respiratory Distress Syndrome by Inhibiting Alveolar Macrophage NLRP3 Inflammasomes Through the ROS/HIF-1α/GLUT1 Pathway.

Sepsis-induced acute respiratory distress syndrome (ARDS) is a devastating clinically severe respiratory disorder, and no effective therapy is available. Melatonin (MEL), an endogenous neurohormone, has shown great promise in alleviating sepsis-induced ARDS, but the underlying molecular mechanism remains unclear. Using a lipopolysaccharide (LPS)-treated mouse alveolar macrophage cell line (MH-S) model, we found that MEL significantly inhibited NOD-like receptor protein 3 (NLRP3) inflammasome activation in LPS-treated macrophages, whereas this inhibitory effect of MEL was weakened in MH-S cells transfected with glucose transporter 1 (GLUT1) overexpressing lentivirus. Further experiments showed that MEL downregulated GLUT1 via inhibition of hypoxia-inducible factor 1 (HIF-1α). Notably, hydrogen peroxide (H2O2), a donor of reactive oxygen species (ROS), significantly increased the level of intracellular ROS and inhibited the regulatory effect of MEL on the HIF-1α/GLUT1 pathway. Interestingly, the protective effect of MEL was attenuated after the knockdown of melatonin receptor 1A (MT1) in MH-S cells. We also confirmed in vivo that MEL effectively downregulated the HIF-1α/GLUT1/NLRP3 pathway in the lung tissue of LPS-treated mice, as well as significantly ameliorated LPS-induced lung injury and improved survival in mice. Collectively, these findings revealed that MEL regulates the activation of the ROS/HIF-1α/GLUT1/NLRP3 pathway in alveolar macrophages via the MT1 receptor, further alleviating sepsis-induced ARDS.

Designing the antimicrobial peptide with centrosymmetric and amphipathic characterizations for improving antimicrobial activity.

Antibiotic-resistant bacterial infections are becoming a serious health issue and will cause 10 million deaths per year by 2050. As a result, the development of new antimicrobial agents is urgently needed. Antimicrobial peptides (AMPs) are found in the innate immune systems of various organisms to effectively fend off invading pathogens. In this study, we designed a series of AMPs (THL-2-1 to THL-2-9) with centrosymmetric and amphipathic properties, through substituting different amino acids on the hydrophobic side and at the centrosymmetric position to improve their antimicrobial activity. The results showed that leucine as a residue on the hydrophobic side of the peptide could enhance its antimicrobial activity and that glutamic acid as a centrosymmetric residue could increase the salt resistance of the peptide. Thus, the THL-2-3 peptide (KRLLRELKRLL-NH2 ) showed the greatest antimicrobial activity (MIC90 of 16 µM) against Gram-negative bacteria and had the highest salt resistance and cell selectivity among all the designed peptides. In summary, the results of this study provide useful references for the design of AMPs to enhance antimicrobial activity.

ELK3 Targeting AEG1 Promotes Migration and Invasion of Ovarian Cancer Cells under Hypoxia.

Ovarian cancer (OC) is one of the most common tumors in female reproductive organs with a five-year survival rate of less than 45%. Metastasis is a crucial contributor to OC development. ETS transcription factor (ELK3), as a transcriptional factor, have been involved in multiple tumor development. However, its role in OC remains elusive. In this study, we observed high expression of ELK3 and AEG1 in human OC tissues. OVCAR-3 and SKOV3 cells were treated with hypoxia to mimic tumor microenvironment in vivo. We found that the expression of ELK3 was significantly increased in cells under hypoxia compared with normoxia. ELK3 knockdown inhibited cell migration and invasion abilities under hypoxia. Moreover, ELK3 knockdown decreased ß-catenin expression and inhibited the activation of Wnt/ß-catenin pathway in SKOV3 cells under hypoxia. Astrocyte-elevated gene-1 (AEG1) has been reported to promote OC progression. Our results showed that the mRNA level of AEG1 was decreased when ELK3 knockdown under hypoxia. Dural luciferase assay confirmed that ELK3 bound to gene AEG1 promoter (-2005-+15) and enhanced its transcriptional activity under hypoxia. Overexpression of AEG1 increased the migration and invasion abilities of SKOV3 cell with ELK3 knockdown. In the absence of ELK3, the activation of ß-catenin was recovered by AEG1 overexpression. To sum up, we conclude that ELK3 promotes AEG1 expression by binding to its promoter. ELK3 could promote migration and invasion of OC cells by targeting AEG1, which provides a potential basis for therapeutic approaches to OC.

CT target scanning in the diagnosis of solid pseudopapillary tumor of the pancreas.

OBJECTIVE: To discuss the value of computed tomography (CT) iterative reconstruction technique combined with target scanning in the diagnosis of solid pseudopapillary tumor of the pancreas (SPTP). METHODS: The clinical information and CT examination data of 27 patients with SPTP were retrospectively analyzed, and the general condition and CT performance of the patients were observed. The CT image reconstruction algorithm of all patients used iterative reconstruction technique combined with the application of target scanning technique. RESULTS: A total of 27 patients were included in this study, including 6 males and 21 females, aged 14-72 years with a mean age of 39.6 ± 13.6 years. SPTP was more common in young and middle-aged females, with a low level of tumor markers, dominated by cystic-solid tumors. The combination of CT iterative reconstruction technology and targeted scanning revealed the following: the capsule of SPTP was clear and complete, where calcifications were visible, solid components were progressively enhanced, and rare pancreatic and bile duct dilation was seen. Tumors were cystic-solid in 18 of 27 patients with SPTP, of which the solid components showed isodensity or slightly low-density, with calcifications. The solid components and cyst walls were mildly enhanced during the arterial phase, and were progressively enhanced during the parenchymal phase, portal vein phase, and delayed phase, with their enhancement degree lower than that of normal pancreatic parenchyma, and pancreatic and bile duct dilation was rare. There were no statistical differences in tumor location, morphology, growth pattern, integrity of capsule, cystic or solid, calcifications, and enhancement features between the male group and the female group (P > 0.05). CONCLUSION: The iterative reconstruction combined with target scanning clearly displayed the CT features of tumors, helping the diagnosis and clinical treatment of the disease.

Prospective cohort study of topical versus general anaesthesia for flexible bronchoscopy.

BACKGROUND: Topical anaesthesia (TA) and general anaesthesia (GA) are performed for flexible bronchoscopy (FB) worldwide. However, few studies have compared the two anaesthesia methods in terms of perioperative discomforts. METHODS: 648 patients undergoing FB were recruited in Shanghai Pulmonary Hospital, a specialised medical centre in China, from January 2019 to December 2019. The patients underwent FB under TA or GA. The TA group received 1% lidocaine by nasal route, and the GA group received total intravenous anaesthesia. The level of perioperative discomfort and patient satisfaction were assessed. The investigators were blind to the group allocation. RESULTS: Finally, 239 patients received TA and 182 patients received GA. The basic demographic properties were comparable between two groups. There were no significant differences in terms of sore throat, 61.5% in TA group vs 57.1% in GA group. However, there was a significant difference in terms of postoperative nausea and vomiting (34.3% in TA group vs 56.6% in GA group), and dizziness (37.7% in TA group vs 78% in GA group). There was a significant difference in terms of total complication scores (17.2 ± 5.1 in TA group vs 7.7 ± 4.3 in GA group) and satisfaction degree of patients (2.6 ± 1.1 in TA group vs 4.3 ± 0.8 in GA group). CONCLUSIONS: Compared with TA, GA significantly reduced the total complication scores of perioperative discomforts and improved the satisfaction score of patients for FB. TRIAL REGISTRATION NUMBER: This clinical trial was registered with www.chictr.org.cn (ChiCTR1800019971).

New insights into the degradation mechanism and risk assessment of HFPO-DA by advanced oxidation processes based on activated persulfate in aqueous solutions.

Hexafluoropropylene oxide dimer acid (HFPO-DA) is widely used as a substitute for perfluorooctanoic acid (PFOA). HFPO-DA exhibits high water solubility and low adsorption potential, conferring significant fluidity in aquatic environments. Given that the toxicity of HFPO-DA is similar to PFOA, it is necessary to control its content in aquatic environments. Electrochemical and thermally-activated persulfates have been successfully used to degrade HFPO-DA, but UV-activated persulfates cannot degrade the compound. Given that research on degradation mechanisms is still incomplete and lacks kinetic research, the mechanism and kinetic calculations of oxidative degradation were studied in detail using DFT calculations. And the toxicity of HFPO-DA degradation intermediates and products was evaluated to reveal the feasibility of using advanced oxidation process (AOP) technology based on persulfate to degrade HFPO-DA in wastewater. The results showed that the committed step of HFPO-DA degradation was initiated by the electron transfer reaction of SO4•- radicals. This reaction is not spontaneous at room temperature and requires sufficient electrical or thermal energy to be absorbed from the external environment. The perfluoroalcohol produced during this reaction can subsequently undergo four possible reactions: H atom abstraction from alcohol groups by an OH radical; H atom abstraction by SO4•-; direct HF removal; and HF removal with water as the catalyst. The final degradation products of HFPO-DA mainly include CO2, CF3CF2COOH, CF3COOH, FCOOH and HF, which has been identified through previous experimental analysis. Ecotoxicity assessment indicates that degradation does not produce highly toxic intermediates, and that the final products are non-toxic, supporting the feasibility of persulfate-based AOP technologies.

Prevalence of smoking among nurses and its association with blood pressure: A cross-sectional study in 11 cities of China.

AIM: Smoking is harmful to human health. However, the relationship between smoking and blood pressure (BP) has not been consistent. This study aimed to analyse nurses' smoking behaviours and their relationship with BP. METHODS: This cross-sectional study recruited 128 009 nurses in 11 cities in China. They were surveyed with questionnaires including BP measurements. The main contents of the questionnaire included smoking status and other factors that might be associated with hypertension. Multiple linear regression analyses and binary logistic regression analyses were used to analyse the data. RESULTS: The results showed there was a significant difference in the smoking rate among nurses with different characteristics (P < 0.05). For both male and female nurses, smoking was associated with increased diastolic BP and mean arterial pressure, but only with increased systolic BP of male nurses. The prevalence of hypertension among male and female nurses was not related to smoking. CONCLUSION: Despite a relatively low overall smoking rate, rates among some groups are high. Different cities, hospitals, and departments can combine local data and conditions to formulate targeted tobacco control measures to improve nurses' physical and mental health.

Discovery of a Novel Class of Acylthiourea-Containing Isoxazoline Insecticides against Plutella xylostella.

Isoxazoline structures are widely found in natural products and are rich in biological activities. This study discloses the development of a series of novel isoxazoline derivatives by introducing acylthiourea fragments to access insecticidal activity. All synthetic compounds were examined for their insecticidal activity against Plutella xylostella, with results showing moderate to strong activity. Based on this, the structure-activity relationship analysis was carried out via the constructed three-dimensional quantitative structure-activity relationship model to further guide the structure optimization, resulting in the optimal compound 32. The LC50 of compound 32 against Plutella xylostella was 0.26 mg/L, demonstrating better activity than the positive control, ethiprole (LC50 = 3.81 mg/L), avermectin (LC50 = 12.32 mg/L), and compounds 1-31. The insect GABA enzyme-linked immunosorbent assay demonstrated that compound 32 might act on the insect GABA receptor, and the molecular docking assay further illustrated the mode of action of compound 32 with the GABA receptor. In addition, the proteomics analysis indicated that the action of compound 32 on Plutella xylostella was multi-pathway.

Serum fructose concentrations are positively correlated with dyslipidaemia in women with polycystic ovary syndrome.

RESEARCH QUESTION: Is there an association between fructose and dislipidaemia in polycystic ovary syndrome (PCOS)? DESIGN: Serum fructose levels were measured in 250 women with PCOS (113 with dislipidaemia, 137 with normolipidaemia) and 460 controls (70 with dislipidaemia, 390 with normolipidaemia). Logistic regression was used to model the relationship between serum fructose levels and dyslipidaemia. Receiver operating characteristic curve analysis was used to assess the ability of serum fructose levels to predict dislipidaemia in women with PCOS, and PCOS in women with dislipidaemia. RESULTS: Patients with PCOS and dislipidaemia had higher serum fructose levels. Triglycerides, total cholesterol and low-density lipoprotein cholesterol increased with increasing serum fructose quartiles in patients with PCOS, whereas high-density lipoprotein cholesterol decreased (all P < 0.001). Among the lipid metabolism-related indicators, triglycerides were most associated with fructose (R = 0.626, P < 0.001). Serum fructose at a cut-off value of 9.79 pmol/µl had a sensitivity of 83.2% and specificity of 66.4% for predicting dislipidaemia in women with PCOS. Lower serum fructose levels were strongly associated with a decreased risk of dislipidaemia in women with PCOS (P < 0.001; OR 0.067; 95% CI 0.027 to 0.170). Moreover, high fructose levels are predictive of PCOS in women with dislipidaemia, with a better diagnostic performance than the androgens typically used as markers. CONCLUSION: Serum fructose levels are significantly correlated with dislipidaemia in women with PCOS, highlighting the importance of investigating the role of fructose in lipid metabolism of PCOS.

Prospective cohort study of topical versus general anaesthesia for flexible bronchoscopy.

BACKGROUND: Topical anaesthesia (TA) and general anaesthesia (GA) are performed for flexible bronchoscopy (FB) worldwide. However, few studies have compared the two anaesthesia methods in terms of perioperative discomforts. METHODS: 648 patients undergoing FB were recruited in Shanghai Pulmonary Hospital, a specialised medical centre in China, from January 2019 to December 2019. The patients underwent FB under TA or GA. The TA group received 1% lidocaine by nasal route, and the GA group received total intravenous anaesthesia. The level of perioperative discomfort and patient satisfaction were assessed. The investigators were blind to the group allocation. RESULTS: Finally, 239 patients received TA and 182 patients received GA. The basic demographic properties were comparable between two groups. There were no significant differences in terms of sore throat, 61.5% in TA group vs 57.1% in GA group. However, there was a significant difference in terms of postoperative nausea and vomiting (34.3% in TA group vs 56.6% in GA group), and dizziness (37.7% in TA group vs 78% in GA group). There was a significant difference in terms of total complication scores (17.2 ± 5.1 in TA group vs 7.7 ± 4.3 in GA group) and satisfaction degree of patients (2.6 ± 1.1 in TA group vs 4.3 ± 0.8 in GA group). CONCLUSIONS: Compared with TA, GA significantly reduced the total complication scores of perioperative discomforts and improved the satisfaction score of patients for FB. TRIAL REGISTRATION NUMBER: This clinical trial was registered with www.chictr.org.cn (ChiCTR1800019971).

Tetrazine-Induced Bioorthogonal Activation of Vitamin E-Modified siRNA for Gene Silencing.

The temporal activation of siRNA provides a valuable strategy for the regulation of siRNA activity and conditional gene silencing. The bioorthogonal bond-cleavage reaction of benzonorbonadiene and tetrazine is a promising trigger in siRNA temporal activation. Here, we developed a new method for the bio-orthogonal chemical activation of siRNA based on the tetrazine-induced bond-cleavage reaction. Small-molecule activatable caged siRNAs were developed with the 5'-vitamin E-benzonobonadiene-modified antisense strand targeting the green fluorescent protein (GFP) gene and the mitotic kinesin-5 (Eg5) gene. The addition of tetrazine triggered the reaction with benzonobonadiene linker and induced the linker cleavage to release the active siRNA. Additionally, the conditional gene silencing of both exogenous GFP and endogenous Eg5 genes was successfully achieved with 5'-vitamin E-benzonobonadiene-caged siRNAs, which provides a new uncaging strategy with small molecules.

An Overview of Potential Therapeutic Agents Targeting WNT/PCP Signaling.

Since the discovery of the proto-oncogene Wnt1 (Int1) in 1982, WNT signaling has been identified as one of the most important pathways that regulates a wide range of fundamental developmental and physiological processes in multicellular organisms. The canonical WNT signaling pathway depends on the stabilization and translocation of ß-catenin and plays important roles in development and homeostasis. The WNT/planar cell polarity (WNT/PCP) signaling, also known as one of the ß-catenin-independent WNT pathways, conveys directional information to coordinate polarized cell behaviors. Similar to WNT/ß-catenin signaling, disruption or aberrant activation of WNT/PCP signaling also underlies a variety of developmental defects and cancers. However, the pharmacological targeting of WNT/PCP signaling for therapeutic purposes remains largely unexplored. In this review, we briefly discuss WNT/PCP signaling in development and disease and summarize the known drugs/inhibitors targeting this pathway.

Disease-causing mutation in α-actinin-4 promotes podocyte detachment through maladaptation to periodic stretch.

α-Actinin-4 (ACTN4) bundles and cross-links actin filaments to confer mechanical resilience to the reconstituted actin network. How this resilience is built and dynamically regulated in the podocyte, and the cause of its failure in ACTN4 mutation-associated focal segmental glomerulosclerosis (FSGS), remains poorly defined. Using primary podocytes isolated from wild-type (WT) and FSGS-causing point mutant Actn4 knockin mice, we report responses to periodic stretch. While WT cells largely maintained their F-actin cytoskeleton and contraction, mutant cells developed extensive and irrecoverable reductions in these same properties. This difference was attributable to both actin material changes and a more spatially correlated intracellular stress in mutant cells. When stretched cells were further challenged using a cell adhesion assay, mutant cells were more likely to detach. Together, these data suggest a mechanism for mutant podocyte dysfunction and loss in FSGS-it is a direct consequence of mechanical responses of a cytoskeleton that is brittle.

Phosphorylation of ACTN4 Leads to Podocyte Vulnerability and Proteinuric Glomerulosclerosis.

BACKGROUND: Genetic mutations in α-actinin-4 (ACTN4)-an important actin crosslinking cytoskeletal protein that provides structural support for kidney podocytes-have been linked to proteinuric glomerulosclerosis in humans. However, the effect of post-translational modifications of ACTN4 on podocyte integrity and kidney function is not known. METHODS: Using mass spectrometry, we found that ACTN4 is phosphorylated at serine (S) 159 in human podocytes. We used phosphomimetic and nonphosphorylatable ACTN4 to comprehensively study the effects of this phosphorylation in vitro and in vivo. We conducted x-ray crystallography, F-actin binding and bundling assays, and immunofluorescence staining to evaluate F-actin alignment. Microfluidic organ-on-a-chip technology was used to assess for detachment of podocytes simultaneously exposed to fluid flow and cyclic strain. We then used CRISPR/Cas9 to generate mouse models and assessed for renal injury by measuring albuminuria and examining kidney histology. We also performed targeted mass spectrometry to determine whether high extracellular glucose or TGF-ß levels increase phosphorylation of ACTN4. RESULTS: Compared with the wild type ACTN4, phosphomimetic ACTN4 demonstrated increased binding and bundling activity with F-actin in vitro. Phosphomimetic Actn4 mouse podocytes exhibited more spatially correlated F-actin alignment and a higher rate of detachment under mechanical stress. Phosphomimetic Actn4 mice developed proteinuria and glomerulosclerosis after subtotal nephrectomy. Moreover, we found that exposure to high extracellular glucose or TGF-ß stimulates phosphorylation of ACTN4 at S159 in podocytes. CONCLUSIONS: These findings suggest that increased phosphorylation of ACTN4 at S159 leads to biochemical, cellular, and renal pathology that is similar to pathology resulting from human disease-causing mutations in ACTN4. ACTN4 may mediate podocyte injury as a consequence of both genetic mutations and signaling events that modulate phosphorylation.

Central venous catheterization site choice based on anatomical landmark technique: a systematic review and meta-analysis.

BACKGROUND: Internal jugular vein catheterization (IJVC) and subclavian vein catheterization (SCVC) have been the most preferred central venous catheterizations (CVC) clinically. Individual preference and institutional routine dominate the traditional CVC choice; however, it is lack of high-level evidence. We sought to provide better clinical strategy for CVC site choice based on anatomical landmark technique between IJVC and SCVC. METHODS: We systematically reviewed eligible studies from PubMed, OVID, Cochrane and ClinicalTrials.Gov till February 2020. The primary outcomes were catheterization time and overall success rate, and the secondary outcomes were the first-attempt success rate and the instant mechanical complications. Ethical problems are not applicable. RESULTS: A total of 3378 patients from 7 studies were included in the analyses. Neither difference was found on the catheterization time (SMD 95% CI: -0.095-0.124, p = 0.792), nor any difference on the overall success rate (RR = 1.017, 95% CI: 0.927-1.117, p = 0.721, I2 = 89.6%) between the 2 procedures. However, subgroup analyses showed overall success rate of IJVC was significantly lower than that of SCVC (RR = 0.906, 95% CI: 0.850-0.965, p = 0.002) in adults. The first-attempt success rate of IJVC group was higher in the adults (RR = 1.472, 95% CI: 1.004-2.156, p = 0.047). No significance was detected in arterial injury (RR = 1.137, 95% CI: 0.541-2.387, p = 0.735) and pneumothorax (RR = 0.600, 95% CI: 0.32-1.126, p = 0.112) between the two procedures. Hematoma was significantly more in IJVC group than that in SCVC group (RR = 2.824, 95% CI: 1.181-6.751, p = 0.02). CONCLUSIONS: Compared with IJVC, SCVC shows a higher overall success rate while a lower first-attempt success rate in adults, and has involved with less hematoma. PROSPERO REGISTRATION: CRD42020165444.

[Determination of o-toluidine in workplace air by solvent desorption-gas chromatography].

OBJECTIVE: To establish solvent desorption gas chromatograph method for o-toluidine determination in workplace air. METHODS: The o-toluidine vapour in workplace air was collected with silicone tube, and desorbed with absolute ethanol. Then the desorption solution was separated with polyethylene glycol HP-INNOWax capillary column(30 m×0. 32 mm, 0. 50 µm)and measured with flame ionization detector. RESULTS: Detection limit of the method was 0. 18 µg/mL, quantification limit of the method was 0. 60 µg/mL, quantitative determination range of method was 0. 60-245. 37 µg/mL, and the minimum quantitative determination concentration was 0. 20 mg/m~3(based on 3. 0 L sample). The method had a good reproducibility, the relative standard deviation was 1. 0%-3. 5%, the average of desorption efficiency was 98. 7%, and the average of sampling efficiency was 93. 7%. The penetrating capacity of 200 mg alkaline silicone was over than 2. 1 mg, and the samples at room temperature could be preserved for 15 days at least. Methanol, toluene, chlorobenzene, acetoacetic ester, aniline, N-methylaniline, N, N-dimethylaniline, o-nitroaniline, p-toluidine or m-toluidine coexisted in the air did not interfere during the determination of o-toluidine. CONCLUSION: The method with low determination concentration, high accuracy and precision, is feasible for determination of o-toluidine vapour in workplace air.

[Fruit variation and geographical distribution of citron].

The ripe dried fruit of citron(Citrus medica) is one of the important sources of Chinese herb Citri Fructus. At the same time, it is also grown for edible and ornamental uses. There are many species and abundant genetic variation. To clarify the intraspecific variation and resource distribution of citron, this study investigated the variation in 11 citron fruits, basically covering the main species in China, including Xiaoguo citron(C. medica var. ethrog), Goucheng(C. medica var. yunnanensis), Muli citron(C.medica var. muliensis), Dehong citron(C.medica×Citrus spp.), Fuzhou citron(C.medica×C.grandis?), Mawu(C.medica×C.grandis?), Cangyuan citron, Binchuan citron, Sweet citron, Big citron, and Small citron. The natural communities of citron were proved to be mainly distributed in the southwestern and western Yunnan and southeastern Tibet of China, with Yunnan, Sichuan, Guangxi, Chongqing, Hubei, and Zhejiang identified as the main production areas. Citron has also been widely grown in India, the Mediterranean region, and the Caribbean coast countries. The field investigation revealed the large-scale intraspecific variation of citron fruits. Most of the fruits are oval-like or sphere-like in shape. The fruits are green when raw and yellow when ripe, with oil cell dots on the skin, stripe-likes running from top to bottom, and bulge at the top. Usually, in the smaller citron fruits, the pulp and juice vesicles are better developed and the central columella is tighter. By contrast, the juice vesicles and central columella in larger fruits became more vacant, with carpels visible, and the apex segregation and development of the carpels is one of the reasons for variation. These variations should be given top priority in the future variety selection and breeding, and the quality differences of different citron species and their mechanisms should be further studied. In particular, variety selection and classification management according to their medicinal or edible purposes will provide scientific and technological supports for the orderly, safe, and effective production of citron products consumed as food and medicine.

Efficient Inhibition of SARS-CoV-2 Using Chimeric Antisense Oligonucleotides through RNase L Activation*.

There is an urgent need to develop antiviral drugs and alleviate the current COVID-19 pandemic. Herein we report the design and construction of chimeric oligonucleotides comprising a 2'-OMe-modified antisense oligonucleotide and a 5'-phosphorylated 2'-5' poly(A)4 (4A2-5 ) to degrade envelope and spike RNAs of SARS-CoV-2. The oligonucleotide was used for searching and recognizing target viral RNA sequence, and the conjugated 4A2-5 was used for guided RNase L activation to sequence-specifically degrade viral RNAs. Since RNase L can potently cleave single-stranded RNA during innate antiviral response, degradation efficiencies with these chimeras were twice as much as those with only antisense oligonucleotides for both SARS-CoV-2 RNA targets. In pseudovirus infection models, chimera-S4 achieved potent and broad-spectrum inhibition of SARS-CoV-2 and its N501Y and/or ΔH69/ΔV70 mutants, indicating a promising antiviral agent based on the nucleic acid-hydrolysis targeting chimera (NATAC) strategy.