Glassy gels toughened by solvent.

Glassy polymers are generally stiff and strong yet have limited extensibility1. By swelling with solvent, glassy polymers can become gels that are soft and weak yet have enhanced extensibility1-3. The marked changes in properties arise from the solvent increasing free volume between chains while weakening polymer-polymer interactions. Here we show that solvating polar polymers with ionic liquids (that is, ionogels4,5) at appropriate concentrations can produce a unique class of materials called glassy gels with desirable properties of both glasses and gels. The ionic liquid increases free volume and therefore extensibility despite the absence of conventional solvent (for example, water). Yet, the ionic liquid forms strong and abundant non-covalent crosslinks between polymer chains to render a stiff, tough, glassy, and homogeneous network (that is, no phase separation)6, at room temperature. Despite being more than 54 wt% liquid, the glassy gels exhibit enormous fracture strength (42 MPa), toughness (110 MJ m-3), yield strength (73 MPa) and Young's modulus (1 GPa). These values are similar to those of thermoplastics such as polyethylene, yet unlike thermoplastics, the glassy gels can be deformed up to 670% strain with full and rapid recovery on heating. These transparent materials form by a one-step polymerization and have impressive adhesive, self-healing and shape-memory properties.

DP7-C/mir-26a system promotes bone regeneration by remodeling the osteogenic immune microenvironment.

OBJECTIVE: This study investigates the DP7-C/miR-26a complex as a stable entity resulting from the combination of miR-26a with the immunomodulatory peptide DP7-C. Our focus is on utilizing DP7-C loaded with miR-26a to modulate the immune microenvironment in bone and facilitate osteogenesis. METHODS: The DP7-C/miR-26a complex was characterized through transmission electron microscopy, agarose electrophoresis, and nanoparticle size potentiometer analysis. Transfection efficiency and cytotoxicity of DP7-C were assessed using flow cytometry and the CCK-8 assay. We validated the effects of DP7-C/miR-26a on bone marrow mesenchymal stem cells (BMSCs) and macrophages RAW 264.7 through gene expression and protein synthesis assays. A comprehensive evaluation of appositional bone formation involved micro-CT imaging, histologic analysis, and immunohistochemical staining. RESULTS: DP7-C/miR-26a, a nanoscale, and low-toxic cationic complex, demonstrated the ability to enter BMSCs and RAW 264.7 via distinct pathways. The treatment with DP7-C/miR-26a significantly increased the synthesis of multiple osteogenesis-related factors in BMSCs, facilitating calcium nodule formation in vitro. Furthermore, DP7-C/miR-26a promoted M1 macrophage polarization toward M2 while suppressing the release of inflammatory factors. Coculture studies corroborated these findings, indicating significant repair of rat skull defects following treatment with DP7-C/miR-26a. CONCLUSION: The DP7-C/miR-26a system offers a safer, more efficient, and feasible technical means for treating bone defects.

A Selective Review on Information Criteria in Multiple Change Point Detection.

Change points indicate significant shifts in the statistical properties in data streams at some time points. Detecting change points efficiently and effectively are essential for us to understand the underlying data-generating mechanism in modern data streams with versatile parameter-varying patterns. However, it becomes a highly challenging problem to locate multiple change points in the noisy data. Although the Bayesian information criterion has been proven to be an effective way of selecting multiple change points in an asymptotical sense, its finite sample performance could be deficient. In this article, we have reviewed a list of information criterion-based methods for multiple change point detection, including Akaike information criterion, Bayesian information criterion, minimum description length, and their variants, with the emphasis on their practical applications. Simulation studies are conducted to investigate the actual performance of different information criteria in detecting multiple change points with possible model mis-specification for the practitioners. A case study on the SCADA signals of wind turbines is conducted to demonstrate the actual change point detection power of different information criteria. Finally, some key challenges in the development and application of multiple change point detection are presented for future research work.

Involvement of the 4-coumarate:coenzyme A ligase 4CL4 in rice phosphorus acquisition and rhizosphere microbe recruitment via root growth enlargement.

MAIN CONCLUSION: The 4-coumarate:coenzyme A ligase 4CL4 is involved in enhancing rice P acquisition and use in acid soil by enlarging root growth and boosting functional rhizosphere microbe recruitment. Rice (Oryza sativa L.) cannot easily acquire phosphorus (P) from acid soil, where root growth is inhibited and soil P is fixed. The combination of roots and rhizosphere microbiota is critical for plant P acquisition and soil P mobilization, but the associated molecular mechanism in rice is unclear. 4CL4/RAL1 encodes a 4-coumarate:coenzyme A ligase related to lignin biosynthesis in rice, and its dysfunction results in a small rice root system. In this study, soil culture and hydroponic experiments were conducted to examine the role of RAL1 in regulating rice P acquisition, fertilizer P use, and rhizosphere microbes in acid soil. Disruption of RAL1 markedly decreased root growth. Mutant rice plants exhibited decreased shoot growth, shoot P accumulation, and fertilizer P use efficiency when grown in soil-but not under hydroponic conditions, where all P is soluble and available for plants. Mutant ral1 and wild-type rice rhizospheres had distinct bacterial and fungal community structures, and wild-type rice recruited some genotype-specific microbial taxa associated with P solubilization. Our results highlight the function of 4CL4/RAL1 in enhancing rice P acquisition and use in acid soil, namely by enlarging root growth and boosting functional rhizosphere microbe recruitment. These findings can inform breeding strategies to improve P use efficiency through host genetic manipulation of root growth and rhizosphere microbiota.

CXCL20a, a Teleost-Specific Chemokine That Orchestrates Direct Bactericidal, Chemotactic, and Phagocytosis-Killing-Promoting Functions, Contributes to Clearance of Bacterial Infections.

The major role of chemokines is to act as a chemoattractant to guide the migration of immune cells to the infectious sites. In the current study, we found that CiCXCL20a, a teleost-specific chemokine from grass carp (Ctenopharyngodon idella), demonstrates broad-spectrum, potent, direct bactericidal activity and immunomodulatory functions to bacterial infections, apart from the chemotaxis. CiCXCL20a kills bacteria by binding, mainly targeting acid lipids, perforating bacterial membrane, resulting in bacterial cytoplasm leakage and death. CiCXCL20a aggregates and neutralizes LPS, agglutinates Gram-negative bacteria, and binds to peptidoglycan and Gram-positive bacteria, but not agglutinate them. All the complexes may be phagocytized and cleared away. CiCXCL20a chemoattracts leukocytes, facilitates phagocytosis of myeloid leukocytes, not lymphoid leukocytes, and enhances the bacteria-killing ability in leukocytes. We further identified its receptor CiCXCR3.1b1. Furthermore, we investigated the physiological roles of CiCXCL20a against Aeromonas hydrophila infection in vivo. The recombinant CiCXCL20a increases the survival rate and decreases the tissue bacterial loads, edema, and lesions. Then, we verified this function by purified CiCXCL20a Ab blockade, and the survival rate decreases, and the tissue bacterial burdens increase. In addition, zebrafish (Danio rerio) DrCXCL20, an ortholog of CiCXCL20a, was employed to verify the bactericidal function and mechanism. The results indicated that DrCXCL20 also possesses wide-spectrum, direct bactericidal activity through membrane rupture mechanism. The present study, to our knowledge, provides the first evidence that early vertebrate chemokine prevents from bacterial infections by direct bactericidal and phagocytosis-killing-promoting manners. The results also demonstrate the close functional relationship between chemokines and antimicrobial peptides.

Broad-Spectrum Robust Direct Bactericidal Activity of Fish IFNφ1 Reveals an Antimicrobial Peptide-like Function for Type I IFNs in Vertebrates.

Type I IFNs (IFN-Is) play pivotal roles in host defense against viral infections but remain enigmatic against bacterial pathogens. In this study, we recombinantly expressed and purified intact grass carp (Ctenopharyngodon idella) IFNφ1 (gcIFNφ1), a teleost IFN-I. gcIFNφ1 widely powerfully directly kills both Gram-negative and Gram-positive bacteria in a dose-dependent manner. gcIFNφ1 binds to LPS or peptidoglycan and provokes bacterial membrane depolarization and disruption, resulting in bacterial death. Furthermore, gcIFNφ1 can efficiently protect zebrafish against Aeromonas hydrophila infection and significantly reduce the bacterial loads in tissues by an infection model. In addition, we wonder whether antibacterial IFN-I members exist in other vertebrates. The amino acid compositions of representative IFN-Is with strong positive charges from Pisces, Amphibia, reptiles, Aves, and Mammalia demonstrate high similarities with those of 2237 reported cationic antimicrobial peptides in antimicrobial peptide database. Recombinant intact representative IFN-I members from the nonmammalian sect exhibit potent broad-spectrum robust bactericidal activity through bacterial membrane depolarization; in contrast, the bactericidal activity is very weak from mammalian IFN-Is. The findings display a broad-spectrum potent direct antimicrobial function for IFN-Is, to our knowledge previously unknown. The results highlight that IFN-Is are important and robust in host defense against bacterial pathogens, and unify direct antibacterial and indirect antiviral bifunction in nonmammalian jawed vertebrates.

Novel Antioxidant Peptides Identified from Arthrospira platensis Hydrolysates Prepared by a Marine Bacterium Pseudoalteromonas sp. JS4-1 Extracellular Protease.

Crude enzymes produced by a marine bacterium Pseudoalteromonas sp. JS4-1 were used to hydrolyze phycobiliprotein. Enzymatic productions showed good performance on DPPH radical and hydroxyl radical scavenging activities (45.14 ± 0.43% and 65.11 ± 2.64%, respectively), especially small peptides with MWCO <3 kDa. Small peptides were fractioned to four fractions using size-exclusion chromatography and the second fraction (F2) had the highest activity in hydroxyl radical scavenging ability (62.61 ± 5.80%). The fraction F1 and F2 both exhibited good antioxidant activities in oxidative stress models in HUVECs and HaCaT cells. Among them, F2 could upregulate the activities of SOD and GSH-Px and reduce the lipid peroxidation degree to scavenge the ROS to protect Caenorhabditis elegans under adversity. Then, 25 peptides total were identified from F2 by LC-MS/MS, and the peptide with the new sequence of INSSDVQGKY as the most significant component was synthetized and the ORAC assay and cellular ROS scavenging assay both illustrated its excellent antioxidant property.

Characteristics and Application of a Novel Cold-Adapted and Salt-Tolerant Protease EK4-1 Produced by an Arctic Bacterium Mesonia algae K4-1.

Mesonia algae K4-1 from the Arctic secretes a novel cold-adapted and salt-tolerant protease EK4-1. It has the highest sequence similarity with Stearolysin, an M4 family protease from Geobacillus stearothermophilus, with only 45% sequence identity, and is a novel M4 family protease. Ek4-1 has a low optimal catalytic temperature (40 °C) and is stable at low temperatures. Moreover, EK4-1 is still active in 4 mol/L NaCl solution and is tolerant to surfactants, oxidizing agents and organic solvents; furthermore, it prefers the hydrolysis of peptide bonds at the P1' position as the hydrophobic residues, such as Leu, Phe and Val, and amino acids with a long side chain, such as Phe and Tyr. Mn2+and Mg2+ significantly promoted enzyme activity, while Fe3+, Co+, Zn2+ and Cu2+ significantly inhibited enzyme activity. Amino acid composition analysis showed that EK4-1 had more small-side-chain amino acids and fewer large-side-chain amino acids. Compared with a thermophilic protease Stearolysin, the cold-adapted protease EK4-1 contains more random coils (48.07%) and a larger active pocket (727.42 Å3). In addition, the acidic amino acid content of protease EK4-1 was higher than that of the basic amino acid, which might be related to the salt tolerance of protease. Compared with the homologous proteases EB62 and E423, the cold-adapted protease EK4-1 was more efficient in the proteolysis of grass carp skin, salmon skin and casein at a low temperature, and produced a large number of antioxidant peptides, with DPPH, ·OH and ROO· scavenging activities. Therefore, cold-adapted and salt-tolerant protease EK4-1 offers wide application prospects in the cosmetic and detergent industries.

Assessing the risk of human exposure to bioaccessible arsenic from total diet through market food consumption in Chengdu, China.

To assess the daily intake of total arsenic (tAs) and arsenic speciation and their potential health risks, different food groups, including vegetables, rice, meat, viscera, freshwater fish, and seafood from Chengdu, China were analyzed. The concentrations of tAs ranged from 41.3 to 1185 µg kg-1 with a median of 238 µg kg-1, and 26.0% of tAs in the food groups was of inorganic toxic form. The median concentration of As(V) in rice (184 ± 21.6 µg kg-1) was approximately 2 to 6 times higher than those in other food groups. The bioaccessible inorganic arsenic (iAs) concentrations of the food items obtained from the local markets of Chengdu ranged from 1.07 to 24.6 µg kg-1 (mean of 6.04 µg kg-1). Rice contributed toward the largest amount of daily iAs intake (66.2%). The mean daily iAs intake from vegetable, meat and viscera contributed 10.7%, 12.5% and 6.04% of total iAs intake, respectively. The actual concentration of arsenic in the food exposed to the human body depends on oral bioaccessible fraction. The oral bioaccessibility estimated daily intake (µg kg-1 bw d-1) of tAs and iAs for the residents of Chengdu was 0.32 and 0.16. Health risk assessments carried out based on bioaccessible iAs concentrations showed that the food items were safe for consumption from the iAs perspective.

Selenium toxicity and bioaccumulation in selenium-enriched fly (Chrysomya megacephala) maggots.

Selenium (Se) is an essential trace element for human health, and as a potential animal feed, the Chrysomya megacephala (Fabricius) fly is rich in protein and fat. By using different concentrations of sodium selenite (0, 30, 50, 70 mg kg-1), the possibility of biological Se enrichment in C. megacephala (Fabricius) maggots (CMMs) was investigated. The accumulation, Se speciation, enzymatic activity, and concentrations of copper (Cu), zinc (Zn), chromium (Cr), and cadmium (Cd) in the maggots were also determined. Transcriptomics was also used to investigate the mechanism of the Se response to CMM genes. The results showed that the CMMs had a survival rate of > 80% at Se exposure concentrations ranging from 0 to 100 mg kg-1. The optimal concentration of sodium selenite for CMM growth was 50 mg kg-1, and the weight, protein content, and total Se accumulation of the larvae (10.8 g, 53.5%, and 72.6 ± 3.36 mg kg-1 (DW), respectively) were considerably higher than the control and other exposure doses (p < 0.05). In addition, Se improved the ability of maggots to absorb Cu and Zn, decreased malondialdehyde (MDA) and lipid peroxidation, but improved the antioxidant activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Furthermore, Se negatively affected the absorption of Cd and Cr. According to the transcriptomic findings, Se supplementation can boost protein synthesis and control both antioxidant and non-antioxidant enzyme activity in CMMs. Therefore, our findings showed that Se-enriched CMMs may counteract the toxicity of Cd and Cr, and Se is an effective supplement for improving the consumption safety of cultured animals fed containing CMMs.

Antibacterial and antibiofilm activities of novel antimicrobial peptide DP7 against the periodontal pathogen Porphyromonas gingivalis.

AIMS: Accumulating evidence suggests that Porphyromonas gingivalis is closely associated with the development of various chronic inflammatory diseases, particularly periodontitis. This study investigated the antibacterial activity and action mechanism of a novel antimicrobial peptide (AMP), DP7, against P. gingivalis. METHODS AND RESULTS: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for DP7 were determined via a broth microdilution method, revealing an MIC of 8 µg ml-1 and MBC of 32 µg ml-1 . Growth inhibition and killing assays confirmed the bactericidal effect of DP7, and treatment with DP7 at MBC eliminated P. gingivalis within 8 h. DP7 had a low cytotoxic effect against human cells. Transmission electron microscopy revealed that DP7 destroyed the bacterial membrane, and confocal laser scanning microscopy revealed its inhibitory effect on P. gingivalis biofilms. Quantitative reverse transcription-polymerase chain reaction revealed DP7-mediated inhibition of several virulence factor genes, partially explaining its antibacterial mechanism. CONCLUSIONS: DP7, a novel AMP with low mammalian cytotoxicity, inhibits both planktonic and biofilm forms of P. gingivalis by destroying the bacterial membrane and reducing virulence factor gene expression. SIGNIFICANCE AND IMPACT OF THE STUDY: DP7 has potential clinical application in the prevention and treatment of P. gingivalis-associated diseases.

Sex-Related Differences in Sitagliptin Treatment in Type 2 Diabetes: Results from the PROLOGUE Trial.

BACKGROUND At present, whether sitagliptin has sex-related differences in effect on atherosclerosis in type 2 diabetes mellitus (T2DM) patients is unknown. The purpose of this study was to investigate whether there is sex-related difference in the effect of sitagliptin on atherosclerosis in T2DM patients. MATERIAL AND METHODS In the PROLOGUE trial, 222 patients were allocated to the sitagliptin group and 220 patients were allocated to the conventional group. Carotid artery intima-media thickness (IMT) was assessed at baseline, 12 months, and 24 months. RESULTS In male patients, sitagliptin significantly reduced the mean IMT (0.84±0.41 mm vs 1.02±0.67 mm, P=0.013) and the maximum IMT (1.14±0.59 mm vs 1.39±0.88 mm, P=0.016) in the right internal carotid arteries (ICA) compared to the conventional group at 12 months. Similarly, sitagliptin significantly reduced the maximum IMT (1.09±0.52 mm vs 1.28±0.77 mm, P=0.049) in the right ICA compared to the conventional group at 24 months, but no difference was found in the mean IMT in the right ICA between groups at 24 months. In female patients, sitagliptin significantly reduced the mean IMT (1.01±0.47 mm vs 1.23±0.51 mm, P=0.049) and the maximum IMT (1.39±0.65 mm vs 1.71±0.77 mm, P=0.042) in the right bulb compared to the conventional group at 12 months. However, the group differences were not observed in mean IMT and maximum IMT at 24 months. CONCLUSIONS Our results suggest that sitagliptin slows the progression of right carotid IMT in male patients. However, more research is needed to validate this finding in female patients.

Polycyclic aromatic hydrocarbons in street dust from different functional areas in Chengdu, China: seasonal variation and health risk assessment.

This is the first investigation that identified seasonal variation, possible sources and health risk of 16 PAHs in street dust sampled park area (PA), educational area (EA), commercial area (CA), residential area (RA), and traffic area (TA) of Chengdu, one of the new first-tier cities in China. The total PAHs (∑16PAHs) concentrations of averaging over two seasons varied from 2.15 to 10.6 mg/kg with a median value of 4.61 mg/kg and in winter (5.48 ± 1.52 mg/kg) were significantly higher than that in summer (4.04 ± 0.91 mg/kg). The highest ∑16PAHs concentration was found in TA (median 6.74 mg/kg). Statistical analysis results indicated that mixture sources of petroleum combustion and combustion of biomass and coal seem to be the primary source of the PAHs in street dust. Carcinogenic risk by incremental lifetime cancer risk (ILCR) model for PAHs in street dust indicates an acceptable potential cancer risk for residents. The same sequences of cancer risk to be observed for both children and adults among different functional areas: TA > CA > EA > RA > PA. The results provided advice for habitants in Chengdu to encourage outdoor activities in parks and residential areas and minimize traffic areas and commercial areas.

Lower Adenoma Miss Rate of Computer-Aided Detection-Assisted Colonoscopy vs Routine White-Light Colonoscopy in a Prospective Tandem Study.

BACKGROUND AND AIMS: Up to 30% of adenomas might be missed during screening colonoscopy-these could be polyps that appear on-screen but are not recognized by endoscopists or polyps that are in locations that do not appear on the screen at all. Computer-aided detection (CADe) systems, based on deep learning, might reduce rates of missed adenomas by displaying visual alerts that identify precancerous polyps on the endoscopy monitor in real time. We compared adenoma miss rates of CADe colonoscopy vs routine white-light colonoscopy. METHODS: We performed a prospective study of patients, 18-75 years old, referred for diagnostic, screening, or surveillance colonoscopies at a single endoscopy center of Sichuan Provincial People's Hospital from June 3, 2019 through September 24, 2019. Same day, tandem colonoscopies were performed for each participant by the same endoscopist. Patients were randomly assigned to groups that received either CADe colonoscopy (n=184) or routine colonoscopy (n=185) first, followed immediately by the other procedure. Endoscopists were blinded to the group each patient was assigned to until immediately before the start of each colonoscopy. Polyps that were missed by the CADe system but detected by endoscopists were classified as missed polyps. False polyps were those continuously traced by the CADe system but then determined not to be polyps by the endoscopists. The primary endpoint was adenoma miss rate, which was defined as the number of adenomas detected in the second-pass colonoscopy divided by the total number of adenomas detected in both passes. RESULTS: The adenoma miss rate was significantly lower with CADe colonoscopy (13.89%; 95% CI, 8.24%-19.54%) than with routine colonoscopy (40.00%; 95% CI, 31.23%-48.77%, P<.0001). The polyp miss rate was significantly lower with CADe colonoscopy (12.98%; 95% CI, 9.08%-16.88%) than with routine colonoscopy (45.90%; 95% CI, 39.65%-52.15%) (P<.0001). Adenoma miss rates in ascending, transverse, and descending colon were significantly lower with CADe colonoscopy than with routine colonoscopy (ascending colon 6.67% vs 39.13%; P=.0095; transverse colon 16.33% vs 45.16%; P=.0065; and descending colon 12.50% vs 40.91%, P=.0364). CONCLUSIONS: CADe colonoscopy reduced the overall miss rate of adenomas by endoscopists using white-light endoscopy. Routine use of CADe might reduce the incidence of interval colon cancers. chictr.org.cn study no: ChiCTR1900023086.

Genomic insight into the population history of Central Han Chinese.

BACKGROUND: In recent decades, considerable attention has been paid to exploring the population genetic characteristics of Han Chinese, mainly documenting a north-south genetic substructure. However, the central Han Chinese have been largely underrepresented in previous studies. AIM: To infer a comprehensive understanding of the homogenisation process and population history of Han Chinese. SUBJECTS AND METHODS: We collected samples from 122 Han Chinese from seven counties of Hubei province in central China and genotyped 534,000 genome-wide SNPs. We compared Hubei Han with both ancient and present-day Eurasian populations using Principal Component Analysis, ADMIXTURE, f statistics, qpWave and qpAdm. RESULTS: We observed Hubei Han Chinese are at a genetically intermediate position on the north-south Han Chinese cline. We have not detected any significant genetic substructure in the studied groups from seven different counties. Hubei Han show significant evidence of genetic admixture deriving about 63% of ancestry from Tai-Kadai or Austronesian-speaking southern indigenous groups and 37% from Tungusic or Mongolic related northern populations. CONCLUSIONS: The formation of Han Chinese has involved extensive admixture with Tai-Kadai or Austronesian-speaking populations in the south and Tungusic or Mongolic speaking populations in the north. The convenient transportation and central location of Hubei make it the key region for the homogenisation of Han Chinese.

Real-time automatic detection system increases colonoscopic polyp and adenoma detection rates: a prospective randomised controlled study.

OBJECTIVE: The effect of colonoscopy on colorectal cancer mortality is limited by several factors, among them a certain miss rate, leading to limited adenoma detection rates (ADRs). We investigated the effect of an automatic polyp detection system based on deep learning on polyp detection rate and ADR. DESIGN: In an open, non-blinded trial, consecutive patients were prospectively randomised to undergo diagnostic colonoscopy with or without assistance of a real-time automatic polyp detection system providing a simultaneous visual notice and sound alarm on polyp detection. The primary outcome was ADR. RESULTS: Of 1058 patients included, 536 were randomised to standard colonoscopy, and 522 were randomised to colonoscopy with computer-aided diagnosis. The artificial intelligence (AI) system significantly increased ADR (29.1%vs20.3%, p<0.001) and the mean number of adenomas per patient (0.53vs0.31, p<0.001). This was due to a higher number of diminutive adenomas found (185vs102; p<0.001), while there was no statistical difference in larger adenomas (77vs58, p=0.075). In addition, the number of hyperplastic polyps was also significantly increased (114vs52, p<0.001). CONCLUSIONS: In a low prevalent ADR population, an automatic polyp detection system during colonoscopy resulted in a significant increase in the number of diminutive adenomas detected, as well as an increase in the rate of hyperplastic polyps. The cost-benefit ratio of such effects has to be determined further. TRIAL REGISTRATION NUMBER: ChiCTR-DDD-17012221; Results.

ROS-induced HSP70 promotes cytoplasmic translocation of high-mobility group box 1b and stimulates antiviral autophagy in grass carp kidney cells.

Autophagy plays many physiological and pathophysiological roles. However, the roles and the regulatory mechanisms of autophagy in response to viral infections are poorly defined in teleost fish, such as grass carp (Ctenopharyngodon idella), which is one of the most important aquaculture species in China. In this study, we found that both grass carp reovirus (GCRV) infection and hydrogen peroxide (H2O2) treatment induced the accumulation of reactive oxygen species (ROS) in C. idella kidney cells and stimulate autophagy. Suppressing ROS accumulation with N-acetyl-l-cysteine significantly inhibited GCRV-induced autophagy activation and enhanced GCRV replication. Although ROS-induced autophagy, in turn, restricted GCRV replication, further investigation revealed that the multifunctional cellular protein high-mobility group box 1b (HMGB1b) serves as a heat shock protein 70 (HSP70)-dependent, pro-autophagic protein in grass carp. Upon H2O2 treatment, cytoplasmic HSP70 translocated to the nucleus, where it interacted with HMGB1b and promoted cytoplasmic translocation of HMGB1b. Overexpression and siRNA-mediated knockdown assays indicated that HSP70 and HMGB1b synergistically enhance ROS-induced autophagic activation in the cytoplasm. Moreover, HSP70 reinforced an association of HMGB1b with the C. idella ortholog of Beclin 1 (a mammalian ortholog of the autophagy-associated yeast protein ATG6) by directly interacting with C. idella Beclin 1. In summary, this study highlights the antiviral function of ROS-induced autophagy in response to GCRV infection and reveals the positive role of HSP70 in HMGB1b-mediated autophagy initiation in teleost fish.

Tailoring Passivation Molecular Structures for Extremely Small Open-Circuit Voltage Loss in Perovskite Solar Cells.

Passivation of electronic defects at the surface and grain boundaries of perovskite materials has become one of the most important strategies to suppress charge recombination in both polycrystalline and single-crystalline perovskite solar cells. Although many passivation molecules have been reported, it remains very unclear regarding the passivation mechanisms of various functional groups. Here, we systematically engineer the structures of passivation molecular functional groups, including carboxyl, amine, isopropyl, phenethyl, and tert-butylphenethyl groups, and study their passivation capability to perovskites. It reveals the carboxyl and amine groups would heal charged defects via electrostatic interactions, and the neutral iodine related defects can be reduced by the aromatic structures. The judicious control of the interaction between perovskite and molecules can further realize grain boundary passivation, including those that are deep toward substrates. Understanding of the underlining mechanisms allows us to design a new passivation molecule, D-4- tert-butylphenylalanine, yielding high-performance p-i-structure solar cells with a stabilized efficiency of 21.4%. The open-circuit voltage ( VOC) of a device with an optical bandgap of 1.57 eV for the perovskite layer reaches 1.23 V, corresponding to a record small VOC deficit of 0.34 V. Our findings provide a guidance for future design of new passivation molecules to realize multiple facets applications in perovskite electronics.

Chitosan reduces the protective effects of IFN-γ2 on grass carp (Ctenopharyngodon idella) against Flavobacterium columnare infection due to excessive inflammation.

IFN-γ is an immunomodulatory factor that has been extensively studied in phenotypes of mammalian macrophages and multifarious inflammatory responses. Usually these studies relied on the classical synergistic activation of IFN-γ with LPS (LipoPolySaccharides). However, non-mammalian vertebrates, and in particular fish, are not very susceptible to LPS, and easily acquire tolerance upon repeated exposure. Therefore, for studies in fish, it is necessary to replace the classical IFN-γ+LPS immune system activation method, and find other pathogen-associated molecular patterns (PAMPs) capable of stimulating the fish immune system. Here we used an important farmed fish species, Ctenopharyngodon idella, to study the effects of CiIFN-γ2 (C. idella IFN-γ2) and chitosan (CS) on its immune responses in vivo and vitro. Our results showed that the combination of CS and CiIFN-γ2 significantly enhanced the activation of macrophages, with an activation intensity even stronger than in CiIFN-γ2 and CiIFN-γ2+LPS groups. In vivo, injection of CiIFN-γ2 could improve the survival rate of C. idella infected with Flavobacterium columnare, while a combined injection of CiIFN-γ2+CS only improved protection in the early stages after the challenge. Notably, both injections reduced the bacterial load of viscera and improved the levels of several plasma parameters (TP, T-SOD, LA, and NO). However, a dramatic up-regulation of inflammatory factors, severe inflammatory damage in the intestines and hepatopancreas, and increased mortality in late stages of infection were observed in the CiIFN-γ2+CS group. Our findings provide new insights into the macrophage activation phenotypes and inflammatory responses in fish. They also demonstrate that CiIFN-γ2 could be used as a potential immunopotentiator, but not in combination with CS. This suggests that selection of immunological adjuvants should be carefully tested experimentally.

LOX-related collagen crosslink changes act as an initiator of bone fragility in a ZDF rats model.

Diabetes mellitus type 2 (DM2) results in bone abnormalities that manifest as increased bone fragility. Bone consists of two phases, the mineral phase and the matrix phase, and disorders in both are seen in DM2. However, the phase in which DM2 mediated bone fragility is initiated is still unknown. In this study, a male Zucker diabetic fatty (fa/fa) (ZDF) rat model was used to investigate the underlying mechanism initiating DM2 mediated bone fragility. The fracture surface morphology, pre- and post-yield bone mechanical behavior, insoluble collagen volume, lysyl oxidase family (LOX) enzyme levels and correlation analysis was performed to determine the relationship between insoluble collagen and post-yield behavior. Four weeks after the induction of diabetes, insoluble collagen was decreased in only the matrix phase in diabetic rats. Consistently, mechanical testing of the bone showed changes only in post-yield behavior. Diabetic rats also had decreased levels of enzymes involved in insoluble collagen formation (LOX and LOXL1 families). Correlation analysis demonstrated that insoluble collagen was a positive regressor of post-yield displacement (R = 0.894, P < 0.001) and post-yield energy (R = 0.918, P < 0.001). Together, these findings suggest that bone fragility in DM2 is initiated in the matrix phase and that the LOX family may play a critical part in the pathogenesis of DM2 mediated bone fragility.