High-performance and frost-resistance MXene co-ionic liquid conductive hydrogel printed by electrohydrodynamic for flexible strain sensor.

Conductive hydrogels with high performance and frost resistance are essential for flexible electronics, electronic skin, and soft robots. Nonetheless, the preparation of hydrogel-based flexible strain sensors with rapid response, wide strain detection range, and high sensitivity remains a considerable challenge. Furthermore, the inevitable freezing and evaporation of water in sub-zero temperatures and dry environments lead to the loss of flexibility and conductivity in hydrogels, which seriously limits their practical application. In this work, ionic liquids (ILs) and MXene are introduced into gelatin/polyacrylamide (PAM) precursor solution, and a PAM/gelatin/ILs/MXene/glycerol (PGIMG) hydrogel-based flexible strain sensor with MXene co-ILs ion-electron composite conductive network is prepared by combining the electrohydrodynamic (EHD) printing method and in-situ photopolymerization. The introduction of ILs provides an ionic conductive channel for the hydrogel. The introduction of MXene nanosheets forms an interpenetrating network with gelatin and PAM, which not only provides a conductive channel, but also improves the mechanical and sensing properties of the hydrogel-based flexible strain sensor. The prepared PGIMG hydrogel with the MXene co-ILs ion-electron composite conductive network demonstrates a tensile strength of 0.21 MPa at 602.82 % strain, the conductivity of 1.636 × 10-3 S/cm, high sensitivity (Gauge Factor, GF = 4.17), a wide strain detection range (1-600 %), and the response/recovery times (73 ms and 74 ms). In addition, glycerol endows the hydrogel with excellent freezing (-60 °C) and water retention properties. The application of the hydrogel-based flexible strain sensor in the field of human motion detection and information transmission shows the great potential of wearable devices, electronic skin, and information encryption transmission.

Aldosterone is Associated with New-onset Cerebrovascular Events in Patients with Hypertension and White Matter Lesions: A cohort study.

OBJECTIVE: White matter lesions (WMLs) increase the risk of stroke, stroke recurrence, and death. Higher plasma aldosterone concentration (PAC) increases the risk of stroke, acute myocardial infarction, and hypertension. To evaluate the relationship between PAC and cerebrovascular events in patients with hypertension and WMLs. METHODS: We conducted a retrospective cohort study that included 1041 participants hospitalized. The outcome was new-onset cerebrovascular events including intracerebral hemorrhage and stroke. A Cox regression model was used to evaluate the relationship between baseline PAC and the risk of cerebrovascular events. RESULTS: The mean age of participants was 60.9±10.2 years, and 565 (53.4%) were males. The median follow-up duration was 42 months (interquartile range [IQR]: 25-67), and 92 patients experienced new-onset cerebrovascular events. In a multivariate-adjusted model, with PAC as a continuous variable, higher PAC increased the risk of cerebrovascular events; patient risk increased per 1 (hazard ratio [HR: 1.03], 95% confidence interval [CI]: 1.01-1.06, P < 0.01), per 5 (HR: 1.17, 95% CI: 1.06-1.31, P < 0.01), and per 10 ng/dL (HR: 1.41, 95%: 1.14-1.75, P < 0.01) increase in PAC. When PAC was expressed as a categorical variable (quartile: Q1-Q4), patients in Q4 (HR: 2.12, 95% CI: 1.18-3.79, P < 0.05) exhibited an increased risk of cerebrovascular events compared to Q1. Restrictive spline regression showed a linear association between PAC and the risk of new-onset cerebrovascular events after adjusting for all possible variables. CONCLUSIONS: Our study identified a linear association between PAC and the risk of new-onset cerebrovascular events in patients with hypertension and WMLs.

Gut microbiota affects mPXR agonist PCN-induced hepatomegaly by regulating PXR and YAP activation.

Pregnane X receptor (PXR) is essential in the regulation of liver homeostasis and the gut microbiota is closely linked to liver physiological and pathological status. We previously found that activation of PXR significantly promotes liver enlargement through interaction with yes-associated protein (YAP). However, whether gut microbiota is contributed to PXR-induced hepatomegaly and the involved mechanisms remain unclear. In this study, C57BL/6 mice were administered the mouse-specific agonist PCN for 5 days. Depletion of gut microbiota was achieved using broad-spectrum antibiotics (ABX) and fecal microbiota transplantation (FMT) was performed to restore the gut microbial. The composition of gut microbiota was analyzed by 16S rRNA sequencing, while the expression of PXR, YAP and their downstream target genes and proteins were assessed. The results indicated that PCN treatment altered the composition and abundance of specific bacterial taxa. Furthermore, depletion of gut microbiota using ABX significantly attenuated PCN-induced hepatomegaly. FMT experiment further demonstrated that the fecal microbiota from PCN-treated mice could induce liver enlargement. Mechanistic studies revealed that ABX treatment impeded the PXR and YAP activation induced by PCN, as evidenced by decreased expression of PXR, YAP, and their downstream targets. Moreover, alterations in PXR and YAP activation were likely contributing to hepatomegaly in recipient mice following FMT from PCN-treated mice. Collectively, the current study demonstrated that gut microbiota is involved in PCN-induced hepatomegaly via regulating PXR and YAP activation, providing potential novel insights into the involvement of gut microbiota in PXR-mediated hepatomegaly. Significance Statement This work describes that the composition of gut microbiota is altered in mPXR agonist PCN-induced hepatomegaly. The treatment with an antibiotic cocktail (ABX) depletes the intestinal microbiota, leading to the impairment of liver enlargement caused by PCN. Besides, fecal microbiota transplantation (FMT) from PCN-treated mice induces liver enlargement. Further study revealed that gut microbiota is involved in hepatomegaly via regulating PXR and YAP activation.

Anti-inflammatory discovery of sesquiterpenoids and a jasmonic acid derivative from Artemisia stolonifera.

Eleven previously undescribed sesquiterpenoids (8-18), one undescribed jasmonic acid derivative (35) and 28 known compounds were isolated from the leaves of Artemisia stolonifera. Undescribed compounds with their absolute configurations were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction and ECD calculation. Compound 8 was identified as a rare sesquiterpenoid featuring a rearranged 5/8 bicyclic ring system, whereas compound 17 was found to be an unprecedented monocyclic sesquiterpenoid with methyl rearrangement. Evaluation of biological activity showed that compounds 1-5 and 7 displayed cytotoxicity against six tumor cells. In the meantime, compounds 11, 12, 18 and 35 exhibited inhibitory effects against LPS-stimulated NO production in RAW 264.7 macrophage cells and reduced the transcription of IL-6 and IL-1ß in a dose-dependent manner at 25, 50 and 100 µM. Moreover, the anti-inflammatory-based network pharmacology and molecular docking analyses revealed potential target proteins of 11, 12, 18 and 35.

Long-Term Follow-Up Defines the Population That Benefits from Early Interception in a High-Risk Smoldering Multiple Myeloma Clinical Trial Using the Combination of Ixazomib, Lenalidomide, and Dexamethasone.

Background: Early therapeutic intervention in high-risk SMM (HR-SMM) has demonstrated benefit in previous studies of lenalidomide with or without dexamethasone. Triplets and quadruplet studies have been examined in this same population. However, to date, none of these studies examined the impact of depth of response on long-term outcomes of participants treated with lenalidomide-based therapy, and whether the use of the 20/2/20 model or the addition of genomic alterations can further define the population that would benefit the most from early therapeutic intervention. Here, we present the results of the phase II study of the combination of ixazomib, lenalidomide, and dexamethasone in patients with HR-SMM with long-term follow-up and baseline single-cell tumor and immune sequencing that help refine the population to be treated for early intervention studies. Methods: This is a phase II trial of ixazomib, lenalidomide, and dexamethasone (IRD) in HR-SMM. Patients received 9 cycles of induction therapy with ixazomib 4mg on days 1, 8, and 15; lenalidomide 25mg on days 1-21; and dexamethasone 40mg on days 1, 8, 15, and 22. The induction phase was followed by maintenance with ixazomib 4mg on days 1, 8, and 15; and lenalidomide 15mg d1-21 for 15 cycles for 24 months of treatment. The primary endpoint was progression-free survival after 2 years of therapy. Secondary endpoints included depth of response, biochemical progression, and correlative studies included single-cell RNA sequencing and/or whole-genome sequencing of the tumor and single-cell sequencing of immune cells at baseline. Results: Fifty-five patients, with a median age of 64, were enrolled in the study. The overall response rate was 93%, with 31% of patients achieving a complete response and 45% achieving a very good partial response or better. The most common grade 3 or greater treatment-related hematologic toxicities were neutropenia (16 patients; 29%), leukopenia (10 patients; 18%), lymphocytopenia (8 patients; 15%), and thrombocytopenia (4 patients; 7%). Non-hematologic grade 3 or greater toxicities included hypophosphatemia (7 patients; 13%), rash (5 patients; 9%), and hypokalemia (4 patients; 7%). After a median follow-up of 50 months, the median progression-free survival (PFS) was 48.6 months (95% CI: 39.9 - not reached; NR) and median overall survival has not been reached. Patients achieving VGPR or better had a significantly better progression-free survival (p<0.001) compared to those who did not achieve VGPR (median PFS 58.2 months vs. 31.3 months). Biochemical progression preceded or was concurrent with the development of SLiM-CRAB criteria in eight patients during follow-up, indicating that biochemical progression is a meaningful endpoint that correlates with the development of end-organ damage. High-risk 20/2/20 participants had the worst PFS compared to low- and intermediate-risk participants. The use of whole genome or single-cell sequencing of tumor cells identified high-risk aberrations that were not identified by FISH alone and aided in the identification of participants at risk of progression. scRNA-seq analysis revealed a positive correlation between MHC class I expression and response to proteasome inhibition and at the same time a decreased proportion of GZMB+ T cells within the clonally expanded CD8+ T cell population correlated with suboptimal response. Conclusions: Ixazomib, lenalidomide and dexamethasone in HR-SMM demonstrates significant clinical activity with an overall favorable safety profile. Achievement of VGPR or greater led to significant improvement in time to progression, suggesting that achieving deep response is beneficial in HR-SMM. Biochemical progression correlates with end-organ damage. Patients with high-risk FISH and lack of deep response had poor outcomes. ClinicalTrials.gov identifier: (NCT02916771).

Targeting BMAL1 reverses drug resistance of acute myeloid leukemia cells and promotes ferroptosis through HMGB1-GPX4 signaling pathway.

PURPOSE: Acute myeloid leukemia (AML) is a refractory hematologic malignancy that poses a serious threat to human health. Exploring alternative therapeutic strategies capable of inducing alternative modes of cell death, such as ferroptosis, holds great promise as a viable and effective intervention. METHODS: We analyzed online database data and collected clinical samples to verify the expression and function of BMAL1 in AML. We conducted experiments on AML cell proliferation, cell cycle, ferroptosis, and chemotherapy resistance by overexpressing/knocking down BMAL1 and using assays such as MDA detection and BODIPY 581/591 C11 staining. We validated the transcriptional regulation of HMGB1 by BMAL1 through ChIP assay, luciferase assay, RNA level detection, and western blotting. Finally, we confirmed the results of our cell experiments at the animal level. RESULTS: BMAL1 up-regulation is an observed phenomenon in AML patients. Furthermore, there existed a strong correlation between elevated levels of BMAL1 expression and inferior prognosis in individuals with AML. We found that knocking down BMAL1 inhibited AML cell growth by blocking the cell cycle. Conversely, overexpressing BMAL1 promoted AML cell proliferation. Moreover, our research results revealed that BMAL1 inhibited ferroptosis in AML cells through BMAL1-HMGB1-GPX4 pathway. Finally, knocking down BMAL1 can enhance the efficacy of certain first-line cancer therapeutic drugs, including venetoclax, dasatinib, and sorafenib. CONCLUSION: Our research results suggest that BMAL1 plays a crucial regulatory role in AML cell proliferation, drug resistance, and ferroptosis. BMAL1 could be a potential important therapeutic target for AML.

MdARF3 switches the lateral root elongation to regulate dwarfing in apple plants.

Apple rootstock dwarfing and dense planting are common practices in apple farming. However, the dwarfing mechanisms are not understood. In our study, the expression of MdARF3 in the root system of dwarfing rootstock 'M9' was lower than in the vigorous rootstock from Malus micromalus due to the deletion of the WUSATAg element in the promoter of the 'M9' genotype. Notably, this deletion variation was significantly associated with dwarfing rootstocks. Subsequently, transgenic tobacco (Nicotiana tabacum) cv. Xanthi was generated with the ARF3 promoter from 'M9' and M. micromalus genotypes. The transgenic apple with 35S::MdARF3 was also obtained. The transgenic tobacco and apple with the highly expressed ARF3 had a longer root system and a higher plant height phenotype. Furthermore, the yeast one-hybrid, luciferase, electrophoretic mobility shift assays, and Chip-qPCR identified MdWOX4-1 in apples that interacted with the pMm-ARF3 promoter but not the pM9-ARF3 promoter. Notably, MdWOX4-1 significantly increased the transcriptional activity of MdARF3 and MdLBD16-2. However, MdARF3 significantly decreased the transcriptional activity of MdLBD16-2. Further analysis revealed that MdARF3 and MdLBD16-2 were temporally expressed during different stages of lateral root development. pMdLBD16-2 was mainly expressed during the early stage of lateral root development, which promoted lateral root production. On the contrary, pMmARF3 was expressed during the late stage of lateral root development to promote elongation. The findings in our study will shed light on the genetic causes of apple plant dwarfism and provide strategies for molecular breeding of dwarfing apple rootstocks.

S-scheme electron transfer promoted by novel indium oxide quantum dot-loaded carbon nitride heterojunctions promoted using oxidized indium monomers.

The graphitic carbon nitride (g-C3N4) photocatalysis has emerged as a clean method for cleaving lignin-linked bonds due to its mild and sunlight-driven reaction conditions. The fast electron-hole pair complex of g-C3N4 constrains its degradation efficiency, making the heterojunction construction a popular solution. The conventional methods of preparing g-C3N4 heterojunctions by physical mixing destroy π-conjugations in g-C3N4, reducing the adsorption of lignin containing benzene rings. In this study, a novel indium oxide (In2O3) quantum dot-g-C3N4 0D/2D heterojunction was prepared through the high-temperature oxidation of pre-prepared indium-doped g-C3N4. The introduction of In2O3 at the quantum dot level minimizes the interference with lignin adsorption capacity. The strong combination of the two (In2O3 and g-C3N4) increases the intersection interface area, promoting the S-scheme transfer route of the photogenerated electrons. Consequently, this enhances the photoelectric conversion efficiency and carrier lifetime of the heterojunction, and inhibits the rapid recombination of photogenerated electron-hole pairs in g-C3N4. The proposed heterojunction was 3 times more efficient than g-C3N4 alone for selective cleavage of lignin ß-O-4 bonds after 2 h of sunlight irradiation. Combined with inhibitor experiments and gas chromatography-mass spectrometry analysis, this paper defines the reactive oxides and proposes a cleavage pathway for the lignin ß-O-4 bonds in In2O3-g-C3N4 heterojunction system.

Boosting thermoelectric performance of single-walled carbon nanotubes-based films through rational triple treatments.

Single-walled carbon nanotubes (SWCNTs)-based thermoelectric materials, valued for their flexibility, lightweight, and cost-effectiveness, show promise for wearable thermoelectric devices. However, their thermoelectric performance requires significant enhancement for practical applications. To achieve this goal, in this work, we introduce rational "triple treatments" to improve the overall performance of flexible SWCNT-based films, achieving a high power factor of 20.29 µW cm-1 K-2 at room temperature. Ultrasonic dispersion enhances the conductivity, NaBH4 treatment reduces defects and enhances the Seebeck coefficient, and cold pressing significantly densifies the SWCNT films while preserving the high Seebeck coefficient. Also, bending tests confirm structural stability and exceptional flexibility, and a six-legged flexible device demonstrates a maximum power density of 2996 µW cm-2 at a 40 K temperature difference, showing great application potential. This advancement positions SWCNT films as promising flexible thermoelectric materials, providing insights into high-performance carbon-based thermoelectrics.

Ecological risk assessment and spatial-temporal differentiation of soil and water resources in the Hefei metropolitan area.

There are important ways to solve the ecological risk problems of regional water resources and soil resources, and to promote the benign development of soil and water resources, involving scientific evaluation of the ecological risk of soil and water resources in Hefei metropolitan area, clarifying the intrinsic evolution law of ecological risk and identifying the characteristics of spatial and temporal variations. Based on the conceptual model of "ST-QS-RR", the evaluation indicator system is constructed, the CRITIC method is used to assign weights, and the TOPSIS method, kernel density method, markov chain and resistance model are used to measure and analyse the spatial and temporal characteristics of ecological risk of soil and water resources, and to explore the main factors that cause ecological risk of soil and water resources. The results of the study show that: (1) Hefei metropolitan area and its cities show a steady decline and the characteristics of "high in the north and low in the south, high in the west and low in the east". (2) Most of the subsystems in the Hefei metropolitan area and the cities show a decreasing trend, with its resistance factors mainly concentrated in the QS system. (3) There is club convergence in Hefei metropolitan area. When the type of adjacent domain is higher, the change of risk type is more sensitive.

Infodemiology of Influenza-like Illness: Utilizing Google Trends' Big Data for Epidemic Surveillance.

Background: Influenza-like illness (ILI) encompasses symptoms similar to influenza, affecting population health. Surveillance, including Google Trends (GT), offers insights into epidemic patterns. Methods: This study used multiple regression models to analyze the correlation between ILI incidents, GT keyword searches, and climate variables during influenza outbreaks. It compared the predictive capabilities of time-series and deep learning models against ILI emergency incidents. Results: The GT searches for "fever" and "cough" were significantly associated with ILI cases (p < 0.05). Temperature had a more substantial impact on ILI incidence than humidity. Among the tested models, ARIMA provided the best predictive power. Conclusions: GT and climate data can forecast ILI trends, aiding governmental decision making. Temperature is a crucial predictor, and ARIMA models excel in forecasting ILI incidences.

Fire acupuncture for plaque psoriasis case series.

OBJECTIVE: To investigate the clinical efficacy of fire acupuncture (FA) on plaque psoriasis (PP), exploring its suitable syndrome types, in order to achieve better therapeutic effects, accelerate the possibility of psoriasis skin lesion recovery, and provide assistance for clinical treatment. METHODS: A total of 8 patients with PP aged between 18 and 60 years were recruited and treated with FA once a week, and the lesion area and severity index (PASI), visual analog scale and pruritus were measured before, 2, 4 and 8 weeks after treatment and at the follow-up period (week 12), respectively. Visual analog scale, and dermoscopy were used for assessment. RESULTS: All patients showed improvement in pruritus after 1 FA treatment, and lesions were reduced to varying degrees after 2 weeks. Except for patients 5 and 8, who only achieved effective results due to severe disease, all other patients with psoriasis achieved significant results at 8 weeks after treatment. CONCLUSION: FA can significantly control the development of lesions, reduce the symptoms of PP lesions and pruritus, and help prevent psoriasis recurrence.

Discovery of digallic acid as XOD/URAT1 dual target inhibitor for the treatment of hyperuricemia.

The development of XOD/URAT1 dual target inhibitors has emerged as a promising therapeutic strategy for the management of hyperuricemia. Here, through virtual screening, we have identified digallic acid as a novel dual target inhibitor of XOD/URAT1 and subsequently evaluated its pharmacological properties, pharmacokinetics, and toxicities. Digallic acid inhibited URAT1 with an IC50 of 5.34 ± 0.65 µM, which is less potent than benzbromarone (2.01 ± 0.36 µM) but more potent than lesinurad (10.36 ± 1.23 µM). Docking and mutation analysis indicated that residues S35, F241 and R477 of URAT1 confer a high affinity for digallic acid. Digallic acid inhibited XOD with an IC50 of 1.04 ± 0.23 µM. Its metabolic product, gallic acid, inhibited XOD with an IC50 of 0.91 ± 0.14 µM. Enzyme kinetic studies indicated that both digallic acid and gallic acid act as mixed-type XOD inhibitors. It shares the same binding mode as digallic acid, and residues E802, R880, F914, T1010, N768 and F1009 contribute to their high affinity. The anion group (carboxyl) of digallic acid contribute significantly to its inhibition activity on both XOD and URAT1 as indicated by docking analysis. Remarkably, at a dosage of 10 mg/kg in vivo, digallic acid exhibited a stronger urate-lowering and uricosuric effect compared to the positive drug benzbromarone and lesinurad. Pharmacokinetic study indicated that digallic acid can be hydrolyzed into gallic acid in vivo and has a t1/2 of 0.77 ± 0.10 h. Further toxicity evaluation indicated that digallic acid exhibited no obvious renal toxicity, as reflected by CCK-8, biochemical analysis (CR and BUN) and HE examination. The findings of our study can provide valuable insights for the development of XOD/URAT1 dual target inhibitors, and digallic acid deserves further investigation as a potential anti-hyperuricemic drug.

Pattern of multiple human papillomavirus infection and type competition: An analysis in healthy Chinese women aged 18-45 years.

To assess the pattern of multiple human papillomavirus infection to predict the type replacement postvaccination. A total of 7372 women aged 18-45y from a phase III trial of an Escherichia coli-produced HPV-16/18 vaccine were analyzed at enrollment visit before vaccination. Hierarchical multilevel logistic regression was used to evaluate HPV vaccine type and nonvaccine-type interactions with age as a covariate. Binary logistic regression was construed to compare multiple infections with single infections to explore the impact of multiple-type infections on the risk of cervical disease. Multiple HPV infections were observed in 25.2% of HPV-positive women and multiple infections were higher than expected by chance. Statistically significant negative associations were observed between HPV16 and 52, HPV18 and HPV51/52/58, HPV31 and HPV39/51/52/53/54/58, HPV33 and HPV52/58, HPV58 and HPV52, HPV6 and HPV 39/51/52/53/54/56/58. Multiple HPV infections increased the risk of CIN2+ and HSIL+, with the ORs of 2.27(95%CI: 1.41, 3.64) and 2.26 (95%CI: 1.29, 3.95) for multiple oncogenic HPV infection separately. However, no significant evidence for the type-type interactions on risk of CIN2+ or HSIL+. There is possibility of type replacement between several pairs of vaccine and nonvaccine HPV type. Multiple HPV infection increased the risk of cervical disease, but coinfection HPV types seem to follow independent disease processes. Continued post-vaccination surveillance for HPV 51/52/58 types and HPV 39/51 types separately was essential after the first and second generation of HPV vaccination implementation in China.

Bioaccumulation and trophic transfer of per- and polyfluoroalkyl substances in a subtropical mangrove estuary food web.

Mangrove estuaries are an important land-sea transitional ecosystem that is currently under various pollution pressures, while there is a lack of research on per- and polyfluoroalkyl substances (PFAS) in the organisms of mangrove estuaries. In this study, we investigated the distribution and seasonal variation of PFAS in the tissues of organisms from a mangrove estuary. The PFAS concentrations in fish tissues varied from 0.45 ng/g ww to 17.67 ng/g ww and followed the order of viscera > head > carcass > muscle, with the highest tissue burden found in the fish carcass (39.59 ng). The log BAF values of PFDoDA, PFUnDA, and PFDA in the whole fish exceeded 3.70, indicating significant bioaccumulation. The trophic transfer of PFAS in the mangrove estuary food web showed a dilution effect, which was mainly influenced by the spatial heterogeneity of PFAS distribution in the estuarine environment, and demonstrated that the gradient dilution of PFAS in the estuary habitat environment can disguise the PFAS bio-magnification in estuarine organisms, and the larger the swimming ranges of organisms, the more pronounced the bio-dilution effect. The PFOA-equivalent HRs of category A and B fish were 3.48-5.17 and 2.59-4.01, respectively, indicating that mangrove estuarine residents had a high PFAS exposure risk through the intake of estuarine fish.

Akkermansia muciniphila: a potential candidate for ameliorating metabolic diseases.

Metabolic diseases are comprehensive disease based on obesity. Numerous cumulative studies have shown a certain correlation between the fluctuating abundance of Akkermansia muciniphila and the occurrence of metabolic diseases. A. muciniphila, a potential probiotic candidate colonized in the human intestinal mucus layer, and its derivatives have various physiological functions, including treating metabolic disorders and maintaining human health. This review systematically explicates the abundance change rules of A. muciniphila in metabolic diseases. It also details the high efficacy and specific molecules mechanism of A. muciniphila and its derivatives in treating obesity, type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease.

[Characteristics of VOCs Emissions and Ozone Formation Potential for Typical Chemicals Industry Sources in China].

This study selected five typical types of chemical industry volatile organic compounds (VOCs) emission characteristics in China for analysis. The results from 70 source samples showed that alkanes were the dominant VOCs category from synthetic material industry sources, petrochemical industry sources, and coating industry sources (accounting for 43%, 63%, and 68%, respectively); olefins were the main VOCs category from the daily supplies chemical industry (46%); and halogenated hydrocarbons were the dominate VOCs category from specialty chemicals industry account source emissions (43%). Additionally, the machine learning method was applied in this study to analyze the marker components of the above industries. The results showed that decane and tetrahydrofuran were the source markers of the synthetic material industry; n-butanol and toluene were the markers of the daily supplies industry source; 1,2,3-trimethylbenzene and 1,3,5-trimethylbenzene were the markers of the petrochemical industry source; propylene and 3-methyl pentane were the source markers of the coating industry; and P-Xylene and cumene were the markers of the specialty chemicals industry source. The maximum incremental reactivity method (MIR) was used to estimate the ozone formation potential (OFP) of different VOCs-sources. The calculation results showed that when considering per unit TVOCs concentration emissions, the contribution to the ozone generation potential was in the order of the daily supplies chemical industry, specialty chemical industry, petrochemical industry, synthetic material industry, and coating industry. Therefore, we suggest that more attention should be paid to the key active species emitted by various industry sources rather than only the total amount of VOCs emissions in future ozone prevention and control efforts.

Immunogenicity and safety of an ORF7-deficient skin-attenuated and neuro-attenuated live vaccine for varicella: a randomised, double-blind, controlled, phase 2a trial.

BACKGROUND: The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine). METHODS: We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log10 plaque forming units (PFU; low-dose v7D group), 3·9 log10 PFU (medium-dose v7D group), and 4·2 log10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434. FINDINGS: On Aug 18-21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8-100·0; 87 of 87 participants), 98·9% (93·8-100·0; 87 of 88 participants), 97·8% (92·4-99·7; 91 of 93 participants), and 96·4% (89·8-99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2-36·0), 31·3 (26·7-36·6), 28·2 (23·9-33·2), and 38·5 (31·7-46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related. INTERPRETATION: The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future. FUNDING: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Crosstalk between lncRNAs and Wnt/ß-catenin signaling pathways in lung cancers: From cancer progression to therapeutic response.

Lung cancer (LC) is considered to have the highest mortality rate around the world. Because there are no early diagnostic signs or efficient clinical alternatives, distal metastasis and increasing numbers of recurrences are a challenge in the clinical management of LC. Long non-coding RNAs (lncRNAs) have recently been recognized as a critical regulator involved in the progression and treatment response to LC. The Wnt/ß-catenin pathway has been shown to influence LC occurrence and progress. Therefore, discovering connections between Wnt signaling pathway and lncRNAs may offer new therapeutic targets for improving LC treatment and management. In this review, the purpose of this article is to present possible therapeutic approaches by reviewing particular relationships, key processes, and molecules associated to the beginning and development of LC.

Advanced "turn-on" colorimetric uranium platform based on the enhanced nanozyme activity of a donor-acceptor structured covalent organic framework.

BACKGROUND: The increasing uranium containing wastes generated during uranium mining and finishing pose a huge threat to the environment and human health, and thus robust strategies for on-site monitoring of uranium pollutant are of great significance for environmental protection around uranium tailings. RESULTS: Herein, a facile "turn-on" colorimetric platform that can achieve uranium detection by spectrometry and naked eyes was developed based on the uranium-enhanced nanozyme activity of covalent organic framework (JUC-505). Thanks to the extended π-conjugated skeleton and donor-acceptor (D-A) structure, JUC-505 exhibited superior photo-activated nanozyme activity, which would be prohibited when the cyano group in JUC-505 skeleton was transformed to the amidoxime group. Further results elucidated that the coordination of uranium with amidoxime groups led to the electron transfer between uranium and the JUC-505-AO skeleton, and thus significantly restored the nanozymatic activity of JUC-505-AO with the subsequent remarkable color changes. Moreover, the uranium concentrations in uranium tailing wastewater detected by the present "turn-on" colorimetric method were well agreed with those by ICP-MS, demonstrating a high accuracy of the present method in real samples. SIGNIFICANCE: The D-A structured JUC-505 with superior photocatalytic property and nanozymatic activity was applied to facilitate colorimetric detection of uranium, which displays the advantages of low detection limit, excellent selectivity, fast response and simple operation for uranium detection in real samples, and shows a great potential in on-site monitoring of uranium pollutant around uranium tailings as well as nuclear power plant.