Structural and Functional Characterization of a Fish Type I Subgroup d IFN Reveals Its Binding to Receptors.

Teleost fish type I IFNs and the associated receptors from the cytokine receptor family B (CRFB) are characterized by remarkable diversity and complexity. How the fish type I IFNs bind to their receptors is still not fully understood. In this study, we demonstrate that CRFB1 and CRFB5 constitute the receptor pair through which type I subgroup d IFN (IFNd) from large yellow croaker, Larimichthys crocea, activates the conserved JAK-STAT signaling pathway as a part of the antiviral response. Our data suggest that L. crocea IFNd (LcIFNd) has a higher binding affinity with L. crocea CRFB5 (LcCRFB5) than with LcCRFB1. Furthermore, we report the crystal structure of LcIFNd at a 1.49-Å resolution and construct structural models of LcIFNd in binary complexes with predicted structures of extracellular regions of LcCRFB1 and LcCRFB5, respectively. Despite striking similarities in overall architectures of LcIFNd and its ortholog human IFN-ω, the receptor binding patterns between LcIFNd and its receptors show that teleost and mammalian type I IFNs may have differentially selected helices that bind to their homologous receptors. Correspondingly, key residues mediating binding of LcIFNd to LcCRFB1 and LcCRFB5 are largely distinct from the receptor-interacting residues in other fish and mammalian type I IFNs. Our findings reveal a ligand/receptor complex binding mechanism of IFNd in teleost fish, thus providing new insights into the function and evolution of type I IFNs.

Molecular and Structural Basis of Receptor Binding and Signaling of a Fish Type I IFN with Three Disulfide Bonds.

In mammals, type I IFNs, which commonly contain one or two disulfide bonds, activate the JAK-STAT signaling pathway through binding to the common cell surface receptor formed by IFN-α/ß receptor (IFNAR)1 and IFNAR2 subunits. Although type I IFNs are also known to be essential for antiviral defense in teleost fish, very little is known about mechanisms underlying the recognition of fish type I IFNs by associated receptors. In this study, we demonstrate that a type I IFN of large yellow croaker Larimichthys crocea (LcIFNi), belonging to a new subgroup of fish type I IFNs, triggers antiviral response via the conserved JAK-STAT pathway through stable binding with a heterodimeric receptor comprising subunits LcCRFB5 and LcCRFB2. LcIFNi binds to LcCRFB5 with a much higher affinity than to LcCRFB2. Furthermore, we determined the crystal structure of LcIFNi at a 1.39 Å resolution. The high-resolution structure is, to our knowledge, the first reported structure of a type I IFN with three disulfide bonds, all of which were found to be indispensable for folding and stability of LcIFNi. Using structural analysis, mutagenesis, and biochemical assays, we identified key LcIFNi residues involved in receptor interaction and proposed a structural model of LcIFNi bound to the LcCRFB2-LcCRFB5 receptor. The results show that LcIFNi-LcCRFB2 exhibits a similar binding pattern to human IFN-ω-IFNAR2, whereas the binding pattern of LcIFNi-LcCRFB5 is quite different from that of IFN-ω-IFNAR1. Altogether, our findings reveal the structural basis for receptor interaction and signaling of a type I IFN with three disulfide bonds and provide new insights into the mechanisms underlying type I IFN recognition in teleosts.

Exposure and health risk assessment of volatile organic compounds among drivers and passengers in long-distance buses.

Exposure to volatile organic compounds (VOCs) such as benzene, toluene, ethylbenzene, xylene, and formaldehyde from long-distance buses has been reported to adversely affect human health. This study investigates the concentrations of these five VOCs and evaluates their health risks to drivers and passengers on board. Ten trips from Taipei to Taichung were performed during the warm and cold seasons of 2021-2022. Two locations inside the bus were established to collect air samples by a 6-liter canister for drivers and passengers. Exposure concentrations of benzene, toluene, ethylbenzene, and xylene were analyzed via gas chromatography with a flame ionization detector and the formaldehyde concentration was monitored using a formaldehyde meter. Subsequently, a Monte Carlo simulation was conducted to evaluate the carcinogenic and non-carcinogenic risks of the five VOCs. Formaldehyde emerged as the highest detected compound (9.06 ± 3.77 µg/m3), followed by toluene (median: 6.11 µg/m3; range: 3.86-14.69 µg/m3). In particular, formaldehyde was identified to have the significantly higher concentration during non-rush hours (10.67 ± 3.21 µg/m3) than that during rush hours (7.45 ± 3.41 µg/m3) and during the warm season (10.71 ± 2.97 µg/m3) compared with that during the cold season (7.41 ± 4.26 µg/m3). Regarding non-carcinogenic risks to drivers and passengers, the chronic hazard indices for these five VOCs were under 1 to indicate an acceptable risk. In terms of carcinogenic risk, the median risks of benzene and formaldehyde for drivers were 2.88 × 10-6 (95% confidence interval [CI]: 2.11 × 10-6 - 5.13 × 10-6) and 1.91 × 10-6 (95% CI: 4.54 × 10-7 - 3.44 × 10-6), respectively. In contrast, the median carcinogenic risks of benzene and formaldehyde for passengers were less than 1 × 10-6 to present an acceptable risk. This study suggests that benzene and formaldehyde may present carcinogenic risks for drivers. Moreover, the non-carcinogenic risk for drivers and passengers is deemed acceptable. We recommended that the ventilation frequency be increased to mitigate exposure to VOCs in long-distance buses.

Histone demethylase AMX-1 is necessary for proper sensitivity to interstrand crosslink DNA damage.

Histone methylation is dynamically regulated to shape the epigenome and adjust central nuclear processes including transcription, cell cycle control and DNA repair. Lysine-specific histone demethylase 2 (LSD2) has been implicated in multiple types of human cancers. However, its functions remain poorly understood. This study investigated the histone demethylase LSD2 homolog AMX-1 in C. elegans and uncovered a potential link between H3K4me2 modulation and DNA interstrand crosslink (ICL) repair. AMX-1 is a histone demethylase and mainly localizes to embryonic cells, the mitotic gut and sheath cells. Lack of AMX-1 expression resulted in embryonic lethality, a decreased brood size and disorganized premeiotic tip germline nuclei. Expression of AMX-1 and of the histone H3K4 demethylase SPR-5 is reciprocally up-regulated upon lack of each other and the mutants show increased H3K4me2 levels in the germline, indicating that AMX-1 and SPR-5 regulate H3K4me2 demethylation. Loss of AMX-1 function activates the CHK-1 kinase acting downstream of ATR and leads to the accumulation of RAD-51 foci and increased DNA damage-dependent apoptosis in the germline. AMX-1 is required for the proper expression of mismatch repair component MutL/MLH-1 and sensitivity against ICLs. Interestingly, formation of ICLs lead to ubiquitination-dependent subcellular relocalization of AMX-1. Taken together, our data suggest that AMX-1 functions in ICL repair in the germline.

Versatile Magnetic Mesoporous Carbon Derived Nano-Adsorbent for Synchronized Toxic Metal Removal and Bacterial Disinfection from Water Matrices.

Contamination of water resources by toxic metals and opportunistic pathogens remains a serious challenge. The development of nano-adsorbents with desired features to tackle this problem is a continuously evolving field. Here, magnetic mesoporous carbon nanospheres grafted by antimicrobial polyhexamethylene biguanidine (PHMB) are reported. Detailed mechanistic investigations reveal that the electrostatic stabilizer modified magnetic nanocore interfaced mesoporous shell can be programmatically regulated to tune the size and related morphological properties. The core-shell nano-adsorbent shows tailorable shell thickness (≈20-55 nm), high surface area (363.47 m2 g-1 ), pore volume (0.426 cm3 g-1 ), radially gradient pores (11.26 nm), and abundant biguanidine functionality. Importantly, the nano-adsorbent has high adsorption capacity for toxic thallium (Tl(I) ions (≈559 mg g-1 ), excellent disinfection against Staphylococcus aureus and Escherichia coli (>99.99% at 2 and 2.5 µg mL-1 ), ultrafast disinfection kinetics rate (>99.99% within ≈4 min), and remarkable regeneration capability when exposed to polluted water matrices. The Tl(I) removal is attributed to surface complexation and physical adsorption owing to open ended mesopores, while disinfection relies on contact of terminal biguanidines with phospholipid head groups of membrane. The significance of this work lies in bringing up effective synchronic water purification technology to combat pathogenic microorganisms and toxic metal.

Metal-Phenolic Networks Assembled on TiO2 Nanospikes for Antimicrobial Peptide Deposition and Osteoconductivity Enhancement in Orthopedic Applications.

The lack of antimicrobial and osteoconductive activities of titanium (Ti) for orthopedic implants has led to problems such as infection and structural looseness, which bring physical and psychological sufferings to patients as well as economic burden on the healthcare system. To endow Ti implants with anti-infective function and bioactivity, in this study, we successfully constructed TiO2 nanospike (TNS) structure on the surface of Ti followed by assembling metal-polyphenol networks (MPNs) and depositing antimicrobial peptides (AMPs). The TNSs' structure can disrupt the bacteria by physical puncture, and it was also proved to have excellent photothermal conversion performance upon near-infrared light irradiation. Furthermore, with the assistance of contact-active chemo bactericidal efficacy of AMPs, TNS-MPN-AMP nanocoating achieved physical/photothermal/chemo triple-synergistic therapy against pathogenic bacteria. The anti-infective efficiency of this multimodal treatment was obviously improved, with an antibacterial ratio of >99.99% in vitro and 95.03% in vivo. Moreover, the spike-like nanostructure of TNSs and the bioactive groups from MPNs and AMPs not only demonstrated desirable biocompatibility but also promoted the surface hydroxyapatite formation in simulated body fluid for further osseointegration enhancement. Altogether, this multifaceted TNS-MPN-AMP nanocoating endowed Ti implants with enhanced antibacterial activity, excellent cytocompatibility, and desirable osteoconductive ability.

The identification and expression of an interleukin-21 receptor in large yellow croaker (Larimichthys crocea).

BACKGROUND: We identified a homologue of IL-21R (LcIL-21R) in large yellow croaker (Larimichthys crocea, Lc). Our investigation focused on understanding the molecular structural features and immune function of LcIL-21R. METHODS: We cloned the LcIL-21R gene from the genome of Larimichthys crocea by RT‒PCR, and the molecular and structural characteristics of LcIL-21R were analyzed by a series of protein analysis tools. We used real-time PCR to investigate the tissue distribution of LcIL-21R, and LcIL-21R gene expression regulation was also measured in head kidney leukocytes under trivalent bacterial vaccine or poly (I:C) stimulation. RESULTS: The open reading frame (ORF) of the LcIL-21R gene is 1629 bp long and encodes a precursor protein of 542 amino acids (aa), with a 23-aa signal peptide and a 519-aa mature peptide containing four putative N-glycosylation sites. LcIL-21R has two fibronectin type III (FNIII)-like domains (D1 and D2), a transmembrane domain, and a cytoplasmic region. A conserved WSXWS motif was also found in the D2 domain. The predicted structure of the extracellular region of LcIL-21R (LcIL-21R-Ex) is highly similar to that of human IL-21R. LcIL-21R was constitutively expressed in all tissues examined, and LcIL-21R mRNA levels were increased in the head kidney and spleen upon inactivated trivalent bacterial vaccine or poly(I:C) stimulation. CONCLUSIONS: Our results suggest that LcIL-21R shares structural and functional properties with IL-21Rs found in other vertebrates, indicating its potential involvement in the IL-21-mediated immune response to pathogenic infections. These findings contribute to our understanding of the evolutionary conservation of IL-21 signaling and its role in the immune system.

Deoxyelephantopin, a germacrane-type sesquiterpene lactone from Elephantopus scaber, induces mitochondrial apoptosis of hepatocarcinoma cells by targeting Hsp90α in vitro and in vivo.

Hepatocellular carcinoma has been known as the most frequent subtype of liver cancer with a high rate of spread, metastases, and recurrence, also dismal treatment effects. However, effective therapies for HCC are still required. Nowadays, natural products have been known as a valuable source for drug discovery. In this research, 44 sesquiterpene lactones isolated from the Elephantopus scaber Linn. (Asteraceae) were tested by MTT assay for the antitumor activities. Deoxyelephantopin (DET) was found to exert significant cytotoxicity on HepG2 and Hep3B cells. Moreover, we found that DET treatment markedly reduced the growth of HCC cells in a concentration-dependent manner, which was better than sorafenib. Furthermore, DET induced mitochondrial dysfunction, oxidative stress, and cellular apoptosis. Additionally, we found that DET and sorafenib synergistically induced apoptosis and mitochondrial dysfunction in HCC cells. DET combined with sorafenib was also efficacious in tumor xenograft model. Molecular docking experiments revealed that DET had a potentially high binding affinity with Hsp90α. Moreover, Drug Affinity Responsive Target Stability assay suggested that DET could directly target Hsp90α. Additionally, the expression of Hsp90α was both decreased in vitro and in vivo. Altogether, this study revealed that DET might be a promising agent for HCC therapy by targeting Hsp90α.

Targeted isolation of cytotoxic germacranolide sesquiterpenes from Elephantopus scaber L. using small molecule accurate recognition technology.

Small molecule accurate recognition technology (SMART) is an emerging method for the rapid structural prediction of major constituents from crude extracts and fractions. In the present study, a targeted isolation of an Elephantopus scaber extract by SMART resulted in the obtention of 15 new (1-15) and five known germacranolide sesquiterpenes (16-20). Their structures were assigned by extensively analyzing HRESIMS, NMR, X-ray crystallographic analyses, modified Mosher's method results, and quantum chemical calculate electronic circular dichroism (ECD) spectra. All germacranolide sesquiterpenes were screened to determine their inhibitory effects with two hepatoma cell lines (HepG2 and Hep3B), and compounds 14, 16, 18, 19 and 20 showed significant cytotoxic activities against the HepG2 (IC50, 3.3-9.9 µM) and Hep3B (IC50, 4.5-8.6 µM) cell lines. Further study suggested that 18 can induce the apoptosis of hepatoma cells via mitochondrial dysfunction.

The efficacy and safety of combined immune checkpoint inhibitors (nivolumab plus ipilimumab): a systematic review and meta-analysis.

BACKGROUND: Currently, nivolumab and ipilimumab are the most widely used immune checkpoint inhibitors. We performed a meta-analysis to evaluate the efficacy and treatment-related adverse events (TRAEs) of nivolumab plus ipilimumab therapy in cancer treatment. METHODS: We examined data from PubMed, Web of Science, EBSCO, and Cochrane Library. Eleven articles fulfilled our criteria, which we divided into 3 groups: nivolumab plus ipilimumab versus nivolumab (the dose used for monotherapy is 3 mg/kg), nivolumab plus ipilimumab versus ipilimumab (the dose used for monotherapy is 3 mg/kg), and nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3) versus nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1). We measured the complete response (CR), partial response (PR), objective response rate (ORR), and TRAEs in any grade and grade 3 or higher. RESULTS: The overall effect estimate favored the combined immunotherapy group in terms of the ORR (RR: 1.40, p < 0.001) and PR (RR: 1.50, p < 0.001) than nivolumab alone. Compared with ipilimumab alone, the combined immunotherapy group had better CR (RR: 4.89, p < 0.001), PR (RR: 2.75, p < 0.001), and ORR (RR: 3.31, p < 0.001). Finally, N1I3 showed better PR (RR: 1.35, p = 0.006) and ORR (RR: 1.21, p = 0.03) than N3I1. The incidence of any TRAEs was similar between both groups (RR: 1.05, p = 0.06). However, the incidence of serious adverse events (grade 3 or higher) was lower in group N3I1 than group N1I3 (RR: 1.51, p < 0.001). CONCLUSION: This meta-analysis showed that the curative effect of nivolumab plus ipilimumab was better than that of nivolumab or ipilimumab monotherapy. In the combined immunotherapy group, N1I3 was more effective than N3I1. Although the side effects were slightly increased in N1I3 group, overall safety was acceptable.

New tirucallane triterpenoids from Picrasma quassioides with their potential antiproliferative activities on hepatoma cells.

Seven new tirucallane-type triterpenoids (1-7), kumuquassin A-G, along with 20 known analogues (8-27) were isolated from the stems of Picrasma quassioides. The structures and the absolute configurations of new compounds were elucidated by spectroscopic data, electronic circular dichroism (ECD) spectroscopic analyses and quantum ECD calculations. Notably, kumuquassin A (1) contains a rare Δ17, 20 double bond, kumuquassin B (2) is the first example of tirucallane triterpenoid possessing a 5/3 biheterocyclic ring system at the side chain. All the compounds were screened for the cytotoxicity against two human hepatoma cell lines, HepG2 and Hep3B, and several compounds exhibited promising activity. The most potential compound 3 was selected for cell cycle analysis, which showed that 3 could cause an accumulation of HepG2 cells at subG1 peak. Annexin V-FITC/PI staining further confirmed that compound 3 caused death of hepatoma cells through apoptosis induction.

Effects of Enantiomerically Pure ß-Carboline Alkaloids from Picrasma quassioides on Human Hepatoma Cells.

Four pairs of ß-carboline enantiomers (1A: /1B: -4A: /4B: ), 2 ß-carboline derivatives (5:  - 6: ) with a single enantiomeric configuration, together with 2 known achiral congeners (7:  - 8: ) were isolated from the stems of Picrasma quassioides. Their structures were elucidated on the basis of extensive spectroscopic analyses and quantum mechanical calculations. Compound 5: possesses a 4,5-seco ß-carboline framework and represents the first example of this type of ß-carboline alkaloids from nature. A possible biosynthetic pathway is proposed to generate the racemate 4: and the enantiomerically pure compounds 5: and 6: . All isolates were screened for their cytotoxicity against hepatocellular carcinoma Hep3B and HepG2 cells, which revealed that enantiomeric compounds 4A: and 4B: had distinctive effects in HepG2 cells. Further investigation showed that 4B: could induce apoptosis in HepG2 cells.

Stress resistant rpsU variants of Listeria monocytogenes can become underrepresented due to enrichment bias.

Population heterogeneity is an important component of the survival mechanism of Listeria monocytogenes, leading to cells in a population with diverse stress resistance levels. We previously demonstrated that several ribosomal gene rpsU mutations enhanced the stress resistance of L. monocytogenes and lowered the growth rate at 30 °C and lower temperatures. This study investigated whether these switches in phenotypes could result in a bias in strain detection when standard enrichment-based procedures are applied to a variety of strains. Detailed growth kinetics analysis of L. monocytogenes strains were performed, including the LO28 wild type (WT) and rpsU variants V14 and V15, during two commonly used enrichment-based procedures described in the ISO 11290-1:2017 and the U.S. Food and Drug Administration Bacteriological Analytical Manual (BAM). WT had a higher growth rate than the variants during the enrichment processes. Co-culture growth kinetics predictions for WT and rpsU variants showed that the detection chances of the rpsU mutants were reduced from ∼52 % to less than ∼13 % and âˆ¼ 3 % during ISO and BAM enrichment, respectively, which were further validated through subsequent qPCR experiments. Higher heat stress resistance of rpsU variants did not lead to faster recovery during enrichment after heat treatment, and different pre-culturing temperatures before heat treatment did not significantly affect the growth kinetics of the WT and rpsU variants. Additionally, post-enrichment isolation procedures involving streaking on selective agar plates did not show preferences for isolating WT or rpsU variants nor affect the detection chance of rpsU variants. The difference in detection chance suggests that the selective enrichment procedures inadequately represent the genotypic diversity present in a sample. Hence, the enrichment bias during the L. monocytogenes isolation procedure may contribute to the observed underrepresentation of the rpsU mutation among L. monocytogenes isolates deposited in publicly available genome databases. The underrepresentation of rpsU mutants in our findings suggests that biases introduced by standard isolation and enrichment procedures could inadvertently skew our understanding of genetic diversity when relying on public databases.

Biofilm formation and desiccation survival of Listeria monocytogenes with microbiota on mushroom processing surfaces and the effect of cleaning and disinfection.

Microbial multispecies communities consisting of background microbiota and Listeria monocytogenes could be established on materials used in food processing environments. The presence, abundance and diversity of the strains within these microbial multispecies communities may be affected by mutual interactions and differences in resistance towards regular cleaning and disinfection (C&D) procedures. Therefore, this study aimed to characterize the growth and diversity of a L. monocytogenes strain cocktail (n = 6) during biofilm formation on polyvinyl chloride (PVC) and stainless steel (SS) without and with the presence of a diverse set of background microbiota (n = 18). L. monocytogenes and background microbiota strains were isolated from mushroom processing environments and experiments were conducted in simulated mushroom processing environmental conditions using mushroom extract as growth medium and ambient temperature (20 °C) as culturing temperature. The L. monocytogenes strains applied during monospecies biofilm incubation formed biofilms on both PVC and SS coupons, and four cycles of C&D treatment were applied with a chlorinated alkaline cleaning agent and a disinfection agent based on peracetic acid and hydrogen peroxide. After each C&D treatment, the coupons were re-incubated for two days during an incubation period for 8 days in total, and C&D resulted in effective removal of biofilms from SS (reduction of 4.5 log CFU/cm2 or less, resulting in counts below detection limit of 1.5 log CFU/cm2 after every C&D treatment), while C&D treatments on biofilms formed on PVC resulted in limited reductions (reductions between 1.2 and 2.4 log CFU/cm2, which equals a reduction of 93.7 % and 99.6 %, respectively). Incubation of the L. monocytogenes strains with the microbiota during multispecies biofilm incubation led to the establishment of L. monocytogenes in the biofilm after 48 h incubation with corresponding high L. monocytogenes strain diversity in the multispecies biofilm on SS and PVC. C&D treatments removed L. monocytogenes from multispecies biofilm communities on SS (reduction of 3.5 log CFU/cm2 or less, resulting in counts below detection limit of 1.5 log CFU/cm2 after every C&D treatment), with varying dominance of microbiota species during different C&D cycles. However, C&D treatments of multispecies biofilm on PVC resulted in lower reductions of L. monocytogenes (between 0.2 and 2.4 log CFU/cm2) compared to single species biofilm, and subsequent regrowth of L. monocytogenes and stable dominance of Enterobacteriaceae and Pseudomonas. In addition, planktonic cultures of L. monocytogenes were deposited and desiccated on dry surfaces without and with the presence of planktonic background microbiota cultures. The observed decline of desiccated cell counts over time was faster on SS compared to PVC. However, the application of C&D resulted in counts below the detection limit of 1.7 log CFU/coupon on both surfaces (reduction of 5.9 log CFU/coupon or less). This study shows that L. monocytogenes is able to form single and multispecies biofilms on PVC with high strain diversity following C&D treatments. This highlights the need to apply more stringent C&D regime treatments for especially PVC and similar surfaces to efficiently remove biofilm cells from food processing surfaces.

Application of artificial intelligence algorithms and low-cost sensors to estimate respirable dust in the workplace.

The Internet of Things (IoT) and low-cost sensor technology have become common tools for environmental exposure monitoring; however, their application in measuring respirable dust (RD) in the workplace remains limited. This study aimed to develop a predictive model for RD using artificial intelligence (AI) algorithms and low-cost sensors and subsequently assess its validity using a standard sampling approach. Various low-cost sensors were combined into an RD sensor module and mounted on a portable aerosol monitor (GRIMM 11-D) for two weeks. AI algorithms were used to capture data per minute over 14 days to establish predictive RD models. The best-fitting model was validated using an aluminum cyclone equipped with an air pump and polytetrafluoroethylene filters to sample the 8-hour RD for 5 days at an aircraft manufacturing company. This module was continuously monitored for two weeks to evaluate its stability. The RD concentration measured by GRIMM 11-D in a general outdoor environment over two weeks was 28.1 ± 16.1 µg/m3 (range: 2.4-85.3 µg/m3). Among the various established models, random forest regression was observed to have the best prediction capacity (R2 = 0.97 and root mean square error = 2.82 µg/m3) in comparison to the other 19 methods. Field-based validation revealed that the predicted RD concentration (35.9 ± 4.1 µg/m3, range: 32.7-42.9 µg/m3) closely approximated the results obtained by the traditional method (38.1 ± 8.9 µg/m3, range: 28.1-52.5 µg/m3), and a strong positive Spearman correlation was observed between the two (rs = 0.70). The average bias was -2.2 µg/m3 and the precision was 5.8 µg/m3, resulting in an accuracy of 6.2 µg/m3 (94.2 %). Data completeness was 99.7 % during the continuous two-week monitoring period. The developed sensor module of RD exhibited excellent predictive performance and good data stability that can be applied to exposure assessments in occupational epidemiological studies.

Nonreleasing AgNP Colloids Composite Hydrogel with Potent Hemostatic, Photodynamic Bactericidal and Wound Healing-Promoting Properties.

Reactive oxygen species (ROS) produced by noble metallic nanoparticles under visible light is an effective way to combat drug-resistant bacteria colonized on the wound. However, the photocatalytic efficiency of noble metallic nanoparticles is limited by its self-aggregation in water media. Moreover, the fast release of noble metallic ions from nanoparticles might engender cellular toxicity and hazardous environmental issues. Herein, we chose AgNPs, the most common plasmonic noble metallic nanoparticles, as an example, modifying the surface of AgNPs with oleic acid and n-butylamine and imbedded them into calcium alginate (CA) hydrogel that holds tissue adhesion, rapid hemostatic, sunlight-sensitive antibacterial and anti-inflammatory abilities, and thus effectively promotes the healing of wounds. Unlike conventional AgNP-based materials, the constrain of colloids and hydrogel networks hinders the leach of Ag+. Nonetheless, the CA/Ag hydrogels exhibit on-demand photodynamic antibacterial efficacy due to the generation of ROS under visible light. In addition, the CA/Ag hydrogel can effectively stop the hemorrhage in a mouse liver bleeding model due to their skin-adaptive flexibility and tissue adhesiveness. The potent sunlight-responsive antibacterial activity of the CA/Ag hydrogel can effectively kill multidrug-resistant bacteria both in vitro (>99.999%) and in vivo (>99.9%), while the diminished Ag+ release guarantees its biocompatibility. The CA/Ag hydrogel significantly promotes the wound healing process by the downregulation of proinflammatory cytokines (TNF-α and IL-6) in a rodent full-thickness cutaneous wound model. Overall, the proposed multifunctional CA/Ag nanocomposite hydrogel has excellent prospects as an advanced wound dressing.

Associations of particulate matter, gaseous pollutants, and road traffic noise with the prevalence of asthma in children.

The purposes of this study were to elucidate the associations between exposure to particulate matter, gaseous pollutants, and road traffic noise and asthma prevalence and to determine the interaction between exposure to multiple pollutants and asthma in children. A total of 3,246 children were recruited from 11 kindergartens in New Taipei City, Taiwan. Land use regression (LUR) was used to establish predictive models for estimating individual exposure levels of particulate matter, gaseous pollutants, and the 24 h A-weighted equivalent sound pressure level (LAeq,24). Multiple logistic regression was performed to test the associations between exposure to these environmental factors and asthma prevalence in children. Multiple-exposure models revealed that an interquartile-range (IQR) increase in PM2.5 (1.17 µg/m3) and PM10 (10.69 µg/m3) caused a 1.34-fold (95% confidence interval [CI] = 1.05-1.70) and 1.17-fold (95% CI = 1.01-1.36) increase in risk of asthma prevalence in children after adjusting for LAeq,24 and NO2. Co-exposure to PM2.5, LAeq,24, and O3, SO2, or CO, as well as co-exposure to PM10, LAeq,24, and CO produced similar findings. Only exposure to one IQR of SO2 (0.15 ppb) was observed a significant association (odds ratio = 1.16, 95% CI = 1.00-1.34) with the asthma prevalence in children after adjusting for PM10 and LAeq,24. Exposure to PM2.5, PM10, and SO2 may be associated with a higher asthma prevalence in children, while other gaseous pollutants and road traffic noise did not demonstrate significant associations. The interaction of exposure to air pollutants and road traffic noise on asthma prevalence in children was not observed in this study.

Haplotype analysis of long-chain non-coding RNA NONHSAT102891 promoter polymorphisms and depression in Chinese individuals: A case-control association study.

BACKGROUND: Our previous study reported that the single-nucleotide polymorphism (SNP) rs155979 GC in the promoter region of long-chain non-coding RNA (lncRNA) NONHSAT102891 affects depression susceptibility in a Chinese population. AIM: To explored associations of two SNPs and haplotypes in the lncRNA NONHSAT102891 promoter region with depression susceptibility in Chinese population. METHODS: This this case-control association study was approved by the Ethics Committee of Chengdu Medical College (approval number: 201815). Patient diagnosis was based on DSM-IV criteria. We selected a total of 480 patients with depression and 329 healthy controls with no history of psychopathology, and performed genotyping of two SNPs by extracting peripheral venous blood samples from the subjects. The function of the two lncRNA NONHSAT102891 promoter G/C and A/T haplotypes was detected by dual-luciferase reporter assays of human embryonic kidney 293T transfected cells. RESULTS: Stratified analysis of clinical and genotypic characteristics of our cohort showed that the degree of mild depressive episodes associated with the rs6230 TC/CC genotype increased by 1.59 times [TC/CC vs TT: odds ratio (OR) = 1.59, 95% confidence interval (CI): 1.08-2.35, P = 0.019]. The haploid analysis revealed linkage disequilibrium between rs3792747 and rs6230, and the double SNP CG haplotype was more common in the control group compared to case group, indicating that this haplotype significantly reduced the risk of depression (C/G vs T/A: OR = 0.42, 95%CI: 0.21-0.83, P = 0.01). There was no significant difference in the dual-luciferase reporter activity of the G/C and A/T haplotypes compared with the control group (P > 0.05), indicating that the double SNP haplotype has no transcriptional activity. CONCLUSION: The rs3792747 and rs6230 CG haplotypes of the lncRNA NONHSA T102891 promoter may be related to a reduced risk of depression in the Han Chinese population.

Effect of Enteral Immunonutrition in Patients Undergoing Surgery for Gastrointestinal Cancer: An Updated Systematic Review and Meta-Analysis.

Background: The efficacy of enteral immunonutrition (EIN) in patients undergoing gastrointestinal cancer surgery remains debatable. This meta-analysis aimed to investigate the effectiveness of EIN administration in patients undergoing surgery for gastrointestinal cancer. Methods: From January 2000 to January 2022, PubMed, EMBASE, Cochrane Library, and Web of Science were thoroughly searched for randomized controlled trials (RCTs) with EIN versus standard diet or no supplement in patients undergoing surgery for gastrointestinal cancer. Overall complications and infectious complications were the primary outcomes. The secondary results were non-infectious complications, mortality, length of hospital stay, and enteral nutrition-related complications. Results: Thirty-five studies reporting 3,692 patients undergoing surgery for gastrointestinal cancer (including gastric cancer, colorectal cancer, esophageal cancer, periampullary cancer, or pancreatic cancer) were included. Compared with the control group, EIN group had a significantly decreased incidence of overall complications (RR = 0.79, p < 0.001). Infectious complications in patients who received EIN were considerably lower than in the control group (RR = 0.66, p < 0.001). Compared to the control group, the incidence of surgical site infection, abdominal abscess, anastomotic leakage, bacteremia, duration of systemic inflammatory response syndrome (SIRS), and duration of antibiotic therapy was significantly lower in the specific infectious complications treated with EIN. Still, there was no significant difference between the two groups with other infectious complications. Moreover, a substantial shortening in the length of hospital stay was shown in EIN group compared with the control group. Still, no significant effect of EIN was demonstrated in non-infectious complicatios and mortality. The enteral nutrition-related complications had no significant difference between two groups. Conclusions: EIN is safe and effective in reducing overall complications, infectious complications, and hospital stay in patients undergoing gastrointestinal cancer surgery (including gastric cancer, colorectal cancer, esophageal cancer, periampullary cancer, or pancreatic cancer).

Converting lysozyme to hydrogel: A multifunctional wound dressing that is more than antibacterial.

Wounds are usually irregular in shapes, and accompanied with a series of disorders such as hemorrhage and bacteria contamination. Here, we report a multifunctional hydrogel prepared by phase-transited lysozyme (PTL), which presents antimicrobial, injectable, self-healing, tissue adhesive, hemostatic and biodegradable properties that fit the requirements of wound treatment. The lysozyme was unfolded under the action of tris(2-carboxyethyl)phosphine (TCEP), and then self-assembled into a hydrogel (PTLG). The phase transition expanded the antibacterial spectrum of lysozyme, PTLG effectively killed both Gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis) and Gram-negative bacteria (Escherichia coli, Acinetobacter baumannii) on contact. This dynamically cross-linked hydrogel exhibited injectable and self-healing abilities, and was capable of adapting to various wound morphologies. The tissue-adhesive nature derived from phase-transition, endowed PTLG with hemostatic effect. Meanwhile, PTLG exhibited biocompatibility towards mammalian cells. Furthermore, its anti-infective ability in vivo was verified in a mouse subcutaneous infection model, more than 98 % of S. epidermidis was reduced under PTLG injection. And PTLG could be biodegraded within four weeks in mice body. Overall, the proposed PTLG is a promising multifunctional dressing material that could accommodate the various demands of complex and deep wounds.