Effect of polymorphism in Rhinolophus affinis ACE2 on entry of SARS-CoV-2 related bat coronaviruses.

Bat coronavirus RaTG13 shares about 96.2% nucleotide sequence identity with that of SARS-CoV-2 and uses human and Rhinolophus affinis (Ra) angiotensin-converting enzyme 2 (ACE2) as entry receptors. Whether there are bat species other than R. affinis susceptible to RaTG13 infection remains elusive. Here, we show that, among 18 different bat ACE2s tested, only RaACE2 is highly susceptible to transduction by RaTG13 S pseudovirions, indicating that the bat species harboring RaTG13 might be very limited. RaACE2 has seven polymorphic variants, RA-01 to RA-07, and they show different susceptibilities to RaTG13 S pseudovirions transduction. Sequence and mutagenesis analyses reveal that residues 34, 38, and 83 in RaACE2 might play critical roles in interaction with the RaTG13 S protein. Of note, RaACE2 polymorphisms have minimal effect on S proteins of SARS-CoV-2 and several SARS-CoV-2 related CoVs (SC2r-CoVs) including BANAL-20-52 and BANAL-20-236 in terms of binding, membrane fusion, and pseudovirus entry. Further mutagenesis analyses identify residues 501 and 505 in S proteins critical for the recognition of different RaACE2 variants and pangolin ACE2 (pACE2), indicating that RaTG13 might have not been well adapted to R. affinis bats. While single D501N and H505Y changes in RaTG13 S protein significantly enhance the infectivity and minimize the difference in susceptibility among different RaACE2 variants, an N501D substitution in SARS-CoV-2 S protein displays marked disparity in transduction efficiencies among RaACE2 variants with a significant reduction in infectivity on several RaACE2 variants. Finally, a T372A substitution in RaTG13 S protein not only significantly increases infectivity on all RaACE2 variants, but also markedly enhances entry on several bat ACE2s including R. sinicus YN, R. pearsonii, and R. ferrumeiqunum. However, the T372A mutant is about 4-fold more sensitive to neutralizing sera from mice immunized with BANAL-20-52 S, suggesting that the better immune evasion ability of T372 over A372 might contribute to the natural selective advantage of T372 over A372 among bat CoVs. Together, our study aids a better understanding of coronavirus entry, vaccine design, and evolution.

Increased arterial pressure volume index and cardiovascular risk score in China.

BACKGROUND AND OBJECTIVE: The new non-invasive arterial stiffness indices, arterial pressure volume index (API) is explored as a novel marker of residual stress in the wall of the peripheral muscular arteries at zero-stress state in clinical settings. The present study aimed to study the association of API with cardiovascular disease (CVD) risk in China (China-PAR). METHODS: According to China-PAR score, participants were divided into three groups: low risk (< 5%), medium risk (5-9.9%), and high risk (≥ 10.0%). API ≥ 31 was defined as high API, and the incidences of high API were compared. Logistic regression models were used to analyze the risk factors of high API and high risk China-PAR categories. The association between China-PAR and API was analyzed by restrictive cubic spline. RESULTS: The study included 4311 participants. After adjustments for confounding factors, high API was independent factor associated with high risk China-PAR categories, and the probability of high API was 1.366 times higher than that in normal API subjects. While, the independent factors associated with high API were BMI, blood pressure and heart rate. Furthermore, API had a significant U-shaped association with China-PAR. CVD risk was lowest with API of 19 units, the fastest increase at 26 units and the flattest starting point at 59 units. CONCLUSION: API, an indicator of arterial stiffness and residual stress, had a U-shaped association with China-PAR score and might play an important role in predicting CVD risk in Chinese natural populations.

Coupling Fe3 C Nanoparticles and N-Doping on Wood-Derived Carbon to Construct Reversible Cathode for Zn-Air Batteries.

Electrochemical reduction of oxygen plays a critical role in emerging electrochemical energy technologies. Multiple electron transfer processes, involving adsorption and activation of O2 and generation of protons from water molecules, cause the sluggish kinetics of the oxygen reduction reaction (ORR). Herein, a double-active-site catalyst of Fe3 C nanoparticles coupled to paulownia wood-derived N-doped carbon (Fe3 C@NPW) is fabricated via an active-site-uniting strategy. One site on Fe3 C nanoparticles contributes to activating water molecules, while another site on N-doped carbon is responsible for activating oxygen molecules. Benefiting from the synergistic effect of double active sites, Fe3 C@NPW delivers a remarkable catalytic activity for ORR with a half-wave potential of 0.87 V (vs. RHE) in alkaline electrolyte, outperforming commercial Pt/C catalyst. Moreover, zinc-air batteries (ZABs) assembled with Fe3 C@NPW as a catalyst on cathode achieve a large specific capacity of 804.4 mA h gZn-1 and a long-term stability of 780 cycles. The model solid-state ZABs also display satisfactory performances with an open-circuit voltage of 1.39 V and a high peak power density of 78 mW cm-2 . These outstanding performances reach the level of first-rank among the non-noble metal electrode materials. This work offers a promising approach to creating double-active-site catalysts by the active-site-uniting strategy for energy conversion fields.

Synergistic Effect between 3'-Terminal Noncoding and Adjacent Coding Regions of the Influenza A Virus Hemagglutinin Segment on Template Preference.

The influenza A virus genome is comprised of eight single-stranded negative-sense viral RNA (vRNA) segments. Each of the eight vRNA segments contains segment-specific nonconserved noncoding regions (NCRs) of similar sequence and length in different influenza A virus strains. However, in the subtype-determinant segments, encoding hemagglutinin (HA) and neuraminidase (NA), the segment-specific noncoding regions are subtype specific, varying significantly in sequence and length at both the 3' and 5' termini among different subtypes. The significance of these subtype-specific noncoding regions (ssNCR) in the influenza virus replication cycle is not fully understood. In this study, we show that truncations of the 3'-end H1-subtype-specific noncoding region (H1-ssNCR) resulted in recombinant viruses with decreased HA vRNA replication and attenuated growth phenotype, although the vRNA replication was not affected in single-template RNP reconstitution assays. The attenuated viruses were unstable, and point mutations at nucleotide position 76 or 56 in the adjacent coding region of HA vRNA were found after serial passage. The mutations restored the HA vRNA replication and reversed the attenuated virus growth phenotype. We propose that the terminal noncoding and adjacent coding regions act synergistically to ensure optimal levels of HA vRNA replication in a multisegment environment. These results provide novel insights into the role of the 3'-end nonconserved noncoding regions and adjacent coding regions on template preference in multiple-segmented negative-strand RNA viruses. IMPORTANCE While most influenza A virus vRNA segments contain segment-specific nonconserved noncoding regions of similar length and sequence, these regions vary considerably both in length and sequence in the segments encoding HA and NA, the two major antigenic determinants of influenza A viruses. In this study, we investigated the function of the 3'-end H1-ssNCR and observed a synergistic effect between the 3'-end H1-ssNCR nucleotides and adjacent coding nucleotide(s) of the HA segment on template preference in a multisegment environment. The results unravel an additional level of complexity in the regulation of RNA replication in multiple-segmented negative-strand RNA viruses.

Wood-Derived Integral Air Electrode for Enhanced Interfacial Electrocatalysis in Rechargeable Zinc-Air Battery.

Zinc-air batteries (ZABs) are promising as energy storage devices owing to their high energy density and the safety of electrolytes. Construction of abundant triple-phase boundary (TPB) effectively facilitates cathode reactions occurring at TPB. Herein, a wood-derived integral air electrode containing Co/CoO nanoparticles and nitrogen-doped carbonized wood (Co/CoO@NWC) is constructed with a dual catalytic function. The potential gap between oxygen reduction and evolution is shortened to 0.77 V. Liquid ZABs using Co/CoO@NWC as cathode exhibit high discharge specific capacity (800 mAh gZn-1 ), low charge-discharge gap (0.84 V), and long-term cycling stability (270 h). Co/CoO@NWC also shows distinguished catalytic activity and stability in all-solid-state ZABs. The inherent layered porous and pipe structures of wood are well maintained in catalytically active carbon. The different hydrophilicity of carbonized wood and Co/CoO endow abundant TPBs for battery reaction. The Co/CoO located on TPB provides main active sites for oxygen reactions. The inherent pipe structures of wood carbon and the interaction between Co/CoO and NWC effectively prevent nanoparticles from aggregation. The design and preparation of this monolithic electrocatalyst contribute to the broad-scale application of ZABs and promote the development of next-generation biomass-based storage devices.

Identification of a Type-Specific Promoter Element That Differentiates between Influenza A and B Viruses.

Type A and type B influenza viruses (FluA and FluB viruses) are two major human pathogens that share common structural and functional features. FluA and FluB viruses can reassort within each type but never between the types. Here, we bioinformatically analyzed all promoter sequences of FluA and FluB viruses and confirmed the presence of the type-specific promoter elements. We then studied the promoter elements with cell-based in vivo assays and an in vitro replication initiation assay. Our results identified, for the first time, a type-specific promoter element-the nucleotide at position 5 in the 3' end of the viral RNA (vRNA)-that plays a key role(s) in modulating polymerase activity in a type-specific manner. Interestingly, swapping the promoter element between FluA and FluB recombinant viruses showed different tolerances: the replacement of FluA virus-specific U5 with FluB virus-specific C5 in influenza virus A/WSN/33 (H1N1) could be reverted to U5 after 2 to 3 passages, while the replacement of FluB virus-specific C5 with FluA virus-specific U5 in influenza virus B/Yamagata/88 could be maintained, but with significantly reduced replication efficiency. Therefore, our findings indicate that the nucleotide variation at position 5 in the 3' end of the vRNA promoter between FluA and FluB viruses contributes to their RNP incompatibility, which may shed new light on the mechanisms of intertypic exclusion of reassortment between FluA and FluB viruses.IMPORTANCE Genetic reassortment of influenza virus plays a key role in virus evolution and the emergence of pandemic strains. The reassortment occurs extensively within either FluA or FluB viruses but never between them. Here, we bioinformatically compared available promoter sequences of FluA and FluB viruses and confirmed the presence of the type-specific promoter elements. Our in vivo and in vitro mutagenesis studies showed that a type-specific promoter element-the nucleotide at position 5 in the 3' end of vRNA promoters-plays key roles in modulating polymerase activity. Interestingly, FluA and FluB viruses showed different tolerances upon key promoter element swapping in the context of virus infections. We concluded that the nucleotide at position 5 in the 3' end of the vRNA promoters of FluA and FluB viruses is a critical type-specific determinant. This work has implications for further elucidating the mechanisms of the intertypic exclusion of reassortment between FluA and FluB viruses.

Long-Term Spatiotemporal Variations in Soil Moisture in North East China Based on 1-km Resolution Downscaled Passive Microwave Soil Moisture Products.

It is very important to analyze and monitor agricultural drought to obtain high temporal-spatial resolution soil moisture products. To overcome the deficiencies of passive microwave soil moisture products with low resolution, we construct a spatial fusion downscaling model (SFDM) using Moderate Resolution Imaging Spectroradiometer (MODIS) data. To eliminate the inconsistencies in soil depth and time among different microwave soil moisture products (Advanced Microwave Scanning Radiometer on the Earth Observing System (AMSR-E) and its successor (AMSR2) and the Soil Moisture Ocean Salinity (SMOS)), a time series reconstruction of the difference decomposition (TSRDD) method is developed to create long-term multisensor soil moisture datasets. Overall, the downscaled soil moisture (SM) products were consistent with the in situ measurements (R > 0.78) and exhibited a low root mean square error (RMSE < 0.10 m3/m3), which indicates good accuracy throughout the time series. The downscaled SM data at a 1-km spatial resolution were used to analyze the spatiotemporal patterns and monitor abnormal conditions in the soil water content across North East China (NEC) between 2002 and 2018. The results showed that droughts frequently appeared in western North East China and southwest of the Greater Khingan Range, while drought centers appeared in central North East China. Waterlogging commonly appeared in low-terrain areas, such as the Songnen Plain. Seasonal precipitation and temperature exhibited distinct interdecadal characteristics that were closely related to the occurrence of extreme climatic events. Abnormal SM levels were often accompanied by large meteorological and natural disasters (e.g., the droughts of 2008, 2015, and 2018 and the flooding events of 2003 and 2013). The spatial distribution of drought in this region during the growing season shows that the drought-affected area is larger in the west than in the east and that the semiarid boundary extends eastward and southward.

Dual Roles of the Hemagglutinin Segment-Specific Noncoding Nucleotides in the Extended Duplex Region of the Influenza A Virus RNA Promoter.

We recently reported that the segment-specific noncoding regions (NCRs) of the hemagglutinin (HA) and neuraminidase (NA) segments are subtype specific, varying significantly in sequence and length at both the 3' and 5' ends. Interestingly, we found that nucleotides CC at positions 13 and 14 at the 3' end and GUG at positions 14 to 16 at the 5' end (termed 14' and 16' to distinguish them from 3' positions) are absolutely conserved among all HA subtype-specific NCRs. These HA segment-specific NCR nucleotides are located in the extended duplex region of the viral RNA promoter. In order to understand the significance of these highly conserved HA segment-specific NCR nucleotides in the virus life cycle, we performed extensive mutagenesis on the HA segment-specific NCR nucleotides and studied their functional significance in regulating influenza A virus replication in the context of the HA segment with both RNP reconstitution and virus infection systems. We found that the base pairing of the 3'-end 13 position with the 5'-end 14' position (3'13-5'14') position is critical for RNA promoter activity while the identity of the base pair is critical in determining HA segment packaging. Moreover, the identity of the residue at the 3'-end 14 position is functionally more important in regulating virus genome packaging than in regulating viral RNA synthesis. Taken together, these results demonstrated that the HA segment-specific NCR nucleotides in the extended duplex region of the promoter not only form part of the promoter but also play a key role in controlling virus selective genome packaging. IMPORTANCE: The segment-specific complementary nucleotides (13 to 15 in the 3' end and 14' to 16' in the 5' end) in the extended duplex region of the influenza virus RNA promoter vary significantly among different segments and have rarely been studied. Here, we performed mutagenesis analysis of the highly conserved HA segment-specific nucleotides in the extended duplex region and examined their effects on virus replication in the context of the influenza A/WSN/33 (WSN) virus infection. We found that these HA segment-specific nucleotides not only act as a part of the RNA promoter but also play a critical role in HA segment packaging. Therefore, we showed experimentally, for the first time, the requirement of the nucleotides in the extended duplex region for the RNA promoter and also identified specific noncoding residues in regulating HA segment packaging. This work has implications for the development of attenuated vaccine strains and for elucidation the mechanisms of the virus genome packaging.

Structural Requirements of Strigolactones for Shoot Branching Inhibition in Rice and Arabidopsis.

The structural requirements of strigolactones (SLs) involved in germination induction of root parasitic plants and hyphal branching in arbuscular mycorrhizal (AM) fungi have been extensively studied. However, our knowledge of the requirements of SLs involved in shoot branching inhibition in plants is still limited. To address this question, we investigated the structure-activity relationships of SLs in shoot branching inhibition in rice and Arabidopsis. SLs possess a four-ring structure, with a tricyclic lactone (ABC-rings) connected to a methylbutenolide part (D-ring) via an enol ether bridge. Here, we show that the the (R) configuration at C-2', which determines the steric position of the D-ring relative to the enol ether olefin bond, is critical for the hormonal activity in rice. Replacement of the enol ether moiety by an alkoxy or imino ether resulted in a severe reduction in biological activity in rice. Moreover, yeast two-hybrid experiments using a possible SL receptor, DWARF14 (D14), and a repressor in the SL signaling pathway, DWARF53 (D53), showed that D14 can interact with D53 in the presence of (2'R) stereoisomers of SLs, but not (2'S) stereoisomers, suggesting that the stereostructure of SLs is crucial for the interaction of these proteins. When GR5, an AB-ring-truncated analog, was applied to the hydroponic culture medium, strong inhibition of shoot branching was observed both in rice and in Arabidopsis. However, GR5 was only weakly active when directly applied to the axillary buds of Arabidopsis. Our results indicate that the difference in plant species and application methods greatly influences the apparent SL biological activity.

Influenza A virus utilizes a suboptimal Kozak sequence to fine-tune virus replication and host response.

The segment-specific non-coding regions (NCRs) of influenza A virus RNA genome play important roles in controlling viral RNA transcription, replication and genome packaging. In this report, we present, for the first time to our knowledge, a full view of the segment-specific NCRs of all influenza A viruses by bioinformatics analysis. Our systematic functional analysis revealed that the eight segment-specific NCRs identified could differentially regulate viral RNA synthesis and protein expression at both transcription and translation levels. Interestingly, a highly conserved suboptimal nucleotide at -3 position of the Kozak sequence, which downregulated protein expression at the translation level, was only present in the segment-specific NCR of PB1. By reverse genetics, we demonstrate that recombinant viruses with an optimized Kozak sequence at the -3 position in PB1 resulted in a significant multiple-cycle replication reduction that was independent of PB1-F2 expression. Our detailed dynamic analysis of virus infection revealed that the mutant virus displays slightly altered dynamics from the wild-type virus on both viral RNA synthesis and protein production. Furthermore, we demonstrated that the level of PB1 expression is involved in regulating type I IFN production. Together, these data reveal a novel strategy exploited by influenza A virus to fine-tune virus replication dynamics and host antiviral response through regulating PB1 protein expression.

DnaJA1/Hsp40 is co-opted by influenza A virus to enhance its viral RNA polymerase activity.

UNLABELLED: The RNA-dependent RNA polymerase (RdRp) of influenza A virus is a heterotrimeric complex composed of the PB1, PB2, and PA subunits. The interplay between host factors and the three subunits of the RdRp is critical to enable viral RNA synthesis to occur in the nuclei of infected cells. In this study, we newly identified host factor DnaJA1, a member of the type I DnaJ/Hsp40 family, acting as a positive regulator for influenza virus replication. We found that DnaJA1 associates with the bPB2 and PA subunits and enhances viral RNA synthesis both in vivo and in vitro. Moreover, DnaJA1 could be translocated from cytoplasm into the nucleus upon influenza virus infection. The translocation of DnaJA1 is specifically accompanied by PB1-PA nuclear import. Interestingly, we observed that the effect of DnaJA1 on viral RNA synthesis is mainly dependent on its C-terminal substrate-binding domain and not on its typical J domain, while the J domain normally mediates the Hsp70-DnaJ interaction required for regulating Hsp70 ATPase activity. Therefore, we propose that DnaJA1 is co-opted by the influenza A virus to enter the nucleus and to enhance its RNA polymerase activity in an Hsp70 cochaperone-independent manner. IMPORTANCE: The interplay between host factors and influenza virus RNA polymerase plays a critical role in determining virus pathogenicity and host adaptation. In this study, we newly identified a host protein, DnaJA1/Hsp40, that is co-opted by influenza A virus RNA polymerase to enhance its viral RNA synthesis in the nuclei of infected cells. We found that DnaJA1 associates with both PB2 and PA subunits and translocates into the nucleus along with the nuclear import of the PB1-PA dimer during influenza virus replication. Interestingly, the effect of DnaJA1 is mainly dependent on its C-terminal substrate-binding domain and not on its typical J domain, which is required for its Hsp70 cochaperone function. To our knowledge, this is the first report on a member of the Hsp40s that is specifically involved in regulating influenza virus RNA polymerase. Targeting the interactions between polymerase subunits and DnaJA1 may provide a novel strategy to develop antiviral drugs.

New insights into the nonconserved noncoding region of the subtype-determinant hemagglutinin and neuraminidase segments of influenza A viruses.

UNLABELLED: The noncoding regions (NCRs) of the eight-segmented viral RNAs (vRNAs) of influenza A virus consist of the highly conserved promoter region and the nonconserved segment-specific NCRs at both the 3' and 5' ends. The roles of the segment-specific NCRs of the eight segments have been extensively studied. However, the diversities in the same region of the two subtype-determinant hemagglutinin (HA) and neuraminidase (NA) segments have received little attention. In this study, we bioinformatically analyzed all available NCRs of HA and NA vRNAs of influenza A viruses and found that nucleotides in the segment-specific NCRs of HA and NA vRNAs are subtype specific and vary significantly in sequence and length at both the 3' and 5' ends among different subtypes. We then systematically studied the biological significance of the HA subtype-specific NCRs (HA ssNCRs) of the common HA subtypes (H1 to H7 and H9) in the context of the WSN (H1N1) reverse genetics system. We found that the HA ssNCRs play a critical role in HA vRNA virion incorporation. Upon HA vRNA incorporation, the 3'-end HA ssNCR plays a more critical role than the 5'-end HA ssNCR, and no stringent compatibility between the two ends is required. Furthermore, our data imply that, in addition to a particular nucleotide(s), the length of the HA ssNCR is involved in regulating HA vRNA incorporation efficiency. These results provide new insights into the HA segment virion incorporation that is critical for the emergence of epidemic and pandemic influenza A virus strains. IMPORTANCE: The nonconserved noncoding regions (NCRs) of the vRNAs of influenza A virus have been extensively studied, whereas the diversities in the nonconserved NCRs of the two subtype-determinant segments hemagglutinin (HA) and neuraminidase (NA) have received little attention. In this study, we bioinformatically analyzed all available NCRs of HA and NA vRNAs and discovered that the HA and NA vRNAs contain key subtype signatures in the NCRs. Our functional studies of the HA subtype-specific NCRs (HA ssNCRs) of the common HA subtypes in the context of WSN virus (H1N1) demonstrated that the HA ssNCR modulates virus replication efficiency by influencing HA segment virion incorporation. Moreover, we revealed important features of the HA ssNCR in determining HA vRNA incorporation efficiency. These data not only show new genetic characteristics of influenza A viruses, but also provide further evidence for understanding the selective genome packaging of influenza virus required for the emergence of epidemic and pandemic influenza virus strains.

Naturally occurring PAE206K point mutation in 2009 H1N1 pandemic influenza viruses impairs viral replication at high temperatures.

The emergence of influenza virus A pandemic H1N1 in April 2009 marked the first pandemic of the 21st century. In this study, we observed significant differences in the polymerase activities of two clinical 2009 H1N1 influenza A virus isolates from Chinese and Japanese patients. Sequence comparison of the three main protein subunits (PB2, PB1, and PA) of the viral RNA-dependent RNA polymerase complex and subsequent mutational analysis revealed that a single amino acid substitution (E206K) was responsible for the observed impaired replication phenotype. Further in vitro experiments showed that presence of PAE206K decreased the replication of influenza A/WSN/33 virus in mammalian cells and a reduction in the virus's pathogenicity in vivo. Mechanistic studies revealed that PAE206K is a temperature-sensitive mutant associated with the inability to transport PB1-PA complex to the nucleus at high temperature (39.5 â€‹°C). Hence, this naturally occurring variant in the PA protein represents an ideal candidate mutation for the development of live attenuated influenza vaccines.

Effects of dietary Chinese yam polysaccharide copper complex on growth performance, immunity, and antioxidant capacity of broilers.

Chinese yam polysaccharide (CYP) has received attention in recent years owing to its positive nutritional and medicinal characteristics. Copper is an essential trace metal in animals, which plays an important role in iron absorption and hemoglobin synthesis. However, no published study has evaluated Chinese yam polysaccharide copper complex (CYP-Cu) as a dietary additive in broilers. This study was conducted to investigate the effects of dietary CYP-Cu on growth performance, immunity, and oxidative resistance in broilers. A total of 360 1-day-old 817 broiler chickens were randomly divided into 4 groups, with 3 replicates of 30 birds each and were fed a basal diet with the addition of 0 (control group), 0.02, 0.10, and 0.50 g/kg CYP-Cu. The feeding trial lasted 48 days. On day 28 and day 48, 6 broilers in each group were slaughtered, respectively. Then the parameters of growth and carcass, serum biochemistry, immunity, and antioxidation, and the expression level of hepatic antioxidative genes were investigated. The results showed that compared with the control group, the supplementation of dietary CYP-Cu could improve the indexes of the growth, carcass, serum biochemistry, immunity and oxidation resistance in broilers, such as average daily gain (ADG), the slaughter percentage (SP), semi-evisceration weight percentage (SEWP), eviscerated carcass weight percentage (EWP), breast muscle percentage (BMP), leg muscle percentage (LMP), serum albumin (ALB), high density lipoprotein (HDL), insulin-like growth factor I (IGF-I), triiodothyronine (T3), thyroxine (T4), growth hormone (GH), insulin (INS), immunoglobulin M (IgM), immunoglobulin G (IgG), immunoglobulin A (IgA), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), complement 3 (C3), complement 4 (C4), total superoxide dismutase (T-SOD), total antioxidative capacity (T-AOC), glutathione peroxidase (GSH-Px), and glutathione s-transferase (GSH-ST); these parameters in the 0.10 g/kg CYP-Cu treated group were significantly increased (P < 0.05) in the total trial period, with the exceptions that feed conversion ratio (FCR) and serum low density lipoprotein (LDL), malondialdehyde (MDA) were decreased in the total trial period. In addition, the antioxidative gene mRNA expression of Nuclear factor E2-related factor 2 (Nrf 2), Superoxide dismutase 1 (SOD 1), Superoxide dismutase 2 (SOD 2), and Catalase (CAT) were upregulated in the liver (P < 0.05). These results indicated that the supplementation of dietary CYP-Cu improved the growth, immunity, and oxidation resistance of broilers, and the addition of 0.10 g/kg CYP-Cu in broiler diets is recommended, which suggests that CYP-Cu may be a promising green feed additive in the poultry industry.

Vinylene-Linked Emissive Covalent Organic Frameworks for White-Light-Emitting Diodes.

Covalent organic frameworks (COFs) have gained considerable attention due to their highly conjugated π-skeletons, rendering them promising candidates for the design of light-emitting materials. In this study, we present two vinylene-linked COFs, namely, VL-COF-1 and VL-COF-2, which were synthesized through the Knoevenagel condensation of 2,4,6-trimethyl-1,3,5-triazine with terephthalaldehyde or 4,4'-biphenyldicarboxaldehyde. Both VL-COF-1 and VL-COF-2 exhibited excellent chemical and thermal stability. The presence of vinylene linkages between the constituent building blocks in these COFs resulted in broad excitation and emission properties. Remarkably, the designed VL-COFs demonstrated bright emission, fast fluorescence decay, and high stability, making them highly attractive for optoelectronic applications. To assess the potential of these VL-COFs in practical devices, we fabricated white-light-emitting diodes (WLEDs) coated with VL-COF-1 and VL-COF-2. Notably, the WLEDs coated with VL-COF-1 achieved high-quality white light emission, closely approximating standard white light. The promising performance of VL-COF-coated WLEDs suggests the feasibility of utilizing COF materials for stable and efficient lighting applications.

Relationship of Arterial Stiffness and Central Hemodynamics With Cardiovascular Risk In Hypertension.

BACKGROUND: Hypertension is becoming a serious public health problem and noninvasive estimation of central hemodynamics and artery stiffness have been identified as important predictors of cardiovascular disease. METHODS: The study included 4,311 participants, both sex and aged between 20 and 79 years. Arterial velocity pulse index, arterial pressure-volume index (AVI, API, and the index of artery stiffness), central systolic blood pressure, central artery pulse pressure (CSBP, CAPP, and estimated via oscillometric blood pressure monitor), and 10-year risk score of cardiovascular disease in China (China-PAR) and Framingham cardiovascular risk score (FCVRS) were assessed at baseline. Regression model was performed to identify factors associated with high cardiovascular disease risk stratification. The relationships between CSBP, CAPP and China-PAR, and FCVRS were analyzed by restrictive cubic spline functions. RESULTS: The uncontrolled hypertension group showed the highest values of AVI, API, CSBP, and CAPP. In the regression analysis, CAPP and hypertension subtypes were identified as significant predictors of high cardiovascular risk stratification, and CAPP was strongly correlated with API in this cohort. Finally, CSBP and CAPP showed significant J-shaped relationships with China-PAR and FCVRS. CONCLUSIONS: Subjects with uncontrolled hypertension present with elevated values of CAPP, CSBP, API, AVI, China-PAR, and FCVRS scores. CAPP was independently associated with high cardiovascular risk stratification, and there was a significant J-shaped relationship with China-PAR and FCVRS that may identify people with higher cardiovascular risk.

Microbial ecological clusters structured by environments drive maize residue decomposition at the continental scale.

Environmental factors (e.g., climate and edaphic factors) indirectly regulate residue decomposition via microbial communities. Microbial ecological clusters (eco-clusters) structured by specific environmental factors have consequences for ecosystem functions. However, less is known about how microbial eco-clusters affect residue decomposition, especially over broad geographic scales. We collected agricultural soils from adjacent pairs of upland and paddy fields along a latitudinal gradient from the cold-temperature zone to the tropical zone, and conducted a microcosm experiment with 13C-labelled maize residue to explore the continental pattern of maize residue-derived 13CO2 (RDC), and whether and how microbial eco-clusters drive and predict RDC. Results showed that RDC decreased with latitude in both upland and paddy fields. Further, we identified 21 well-defined eco-clusters according to microbial environmental preferences, which explained 51.15 % of the spatial variations in RDC. The eco-clusters of high-total annual precipitation (TAP), high-mean annual temperature (MAT), low-pH, and some low-nutrient-associated exerted a positive effect on RDC. These eco-clusters contained many taxa belonging to the Actinobacteriota, Firmicutes, and Sordariomycetes, and their relative abundance decreased with latitude. Upland soils displayed 2.40-fold of RDC over paddy soils. Low-pH and high-organic matter (OM) eco-clusters were found to be the most prominent predictors of RDC in upland and paddy fields, respectively. Finally, we constructed a continental atlas of RDC in both upland and paddy fields based on eco-clusters and high-resolution climate and soil data. Overall, our study provides important evidence that historical environment-shaped microbial eco-clusters can drive and predict residue decomposition, providing new insights into how environmental factors indirectly regulate residue decomposition.

The Hierarchical Sequence Requirements of the H1 Subtype-Specific Noncoding Regions of Influenza A Virus.

The genome of influenza A virus consists of eight single-stranded viral RNA (vRNA) segments. The nonconserved noncoding regions (NCRs) at the 3' and 5' termini of each segment show extremely low divergence and mutation rate. They appear as segment specific among the eight segments and also subtype specific among different subtype-determinant hemagglutinin (HA) and neuraminidase (NA) segments. In order to acquire in-depth knowledge on the sequence requirements of the segment-specific or subtype-specific NCRs (ssNCRs), we, in the context of WSN (H1N1) reverse genetics, designed a virus random nucleotide selection assay (vRNSA) in which we generated pHW2000-HA plasmid libraries with random nucleotides in each grouped nucleotide positions in the 3' and 5' H1-ssNCRs, followed by virus rescue, serial passage, and deep sequencing. The resulting sequence logos present a visualized dynamic overview of the hierarchical sequence requirements of the 3' and 5' H1-ssNCRs. It showed that, in the process of continuous passage, the 3' H1-ssNCR, in general, stabilized more quickly than the 5' H1-ssNCR. The nucleotides close to the highly conserved 3' and 5' promoter regions showed higher sequence stringency than nucleotides away from the promoter regions. All stabilized sequences displayed a common feature of high A/U ratios. Especially with our mutational function analyses, we demonstrate that the 3' promoter-proximal nucleotides could cooperatively exert a direct effect on the transcription and replication of the HA segment. Together, these results provide in-depth knowledge for understanding the NCRs of influenza A virus. IMPORTANCE The segment-specific and subtype-specific nonconserved noncoding regions (ssNCRs) at both 3' and 5' ends of viral RNA segments of influenza A virus are largely conserved among the same segments of different viruses. However, the function-related sequence requirements of these ssNCRs remain unclear. In this study, through a novel self-designed vRNSA approach, we present a visualized dynamic overview diagram directly reflecting the hierarchical sequence requirements within and between the 3' and 5' H1-ssNCRs. The in-depth functional mutagenesis analyses further revealed that specific nucleotides in the 3' promoter-proximal region could cooperatively exert a direct effect on viral RNA transcription and replication. This work further advanced our knowledge in understanding the nonconserved noncoding regions of influenza A viruses.

Handheld versus conventional ultrasound for assessing carotid artery in routine volunteers.

AIM: Carotid ultrasound is a key tool for the diagnosis and evaluation of cardio disease, and the measurement of carotid intima-media thickness (CIMT) and hemodynamic parameters is of paramount importance for the imaging method. The aim of this study was to evaluate the feasibility and accuracy of handheld ultrasound devices for measuring carotid parameters. METHODS: We performed a carotid ultrasound on 25 participants using a handheld ultrasound device and a conventional ultrasound machine. For each participant, max and mean CIMT of common carotid artery (CCA) and peak systolic velocity (PSV), end diastolic velocity (EDV) and resistive index (RI) of CCA, bilateral external carotid artery (ECA), internal carotid artery (ICA) and the vertebral artery were measured. Agreement and repeatability were evaluated by linear regression and Bland-Altman analysis. RESULTS: We found a good repeatability and consistent of handheld ultrasound device in measuring mean CIMT (r = 0.68, P < 0.01). Furthermore, there was a moderate to good agreement between handheld and conventional ultrasound systems in measuring max IMT, mean IMT, PSV, EDV and RI of CCA (0.73, 0.79, 0.52, 0.58 and 0.84, respectively). CONCLUSION: Handheld ultrasound devices were able to provide carotid IMT and hemodynamic parameters measurements similar to those of conventional ultrasound. Such capabilities of handheld ultrasound devices might be useful for the primary assessment of carotid in clinical work.

Anti-inflammatory effects of Chaishi Tuire Granules on influenza A treatment by mediating TRAF6/MAPK14 axis.

Objectives: Influenza is an infectious respiratory disease that can cause severe inflammatory reactions and threaten human life. Chaishi Tuire Granules (CSTRG), a Chinese patent medicine widely used clinically in the treatment of respiratory diseases in China, has a definite anti-inflammatory effect. However, the mechanism of CSTRG in the treatment of influenza is still unclear. This study aimed to demonstrate the anti-inflammatory effect of CSTRG on influenza A treatment and potential mechanisms. Methods: Influenza-associated mice pneumonia model was used to explore the antiviral and anti-inflammatory effects of CSTRG in vivo. Bioinformatics analysis methods such as network pharmacology and molecular docking were carried out to predict the main active components and potential anti-inflammatory targets of CSTRG. The anti-inflammatory activity of CSTRG was determined using the lipopolysaccharide (LPS)-induced macrophages RAW264.7 cells in vitro. Results: In vivo results showed that CSTRG can reduce the viral load in the lung tissue of infected mice, reduce the expression of TNF-α and IL-6 in lung tissue and serum, and regulate the host inflammatory response. Additionally, CSTRG treatment markedly improves the sick signs, weight loss, lung index, and lung pathological changes. Bioinformatics analysis predicted that six active compounds of CSTRG including quercetin, kaempferol, luteolin, beta-sitosterol, sitosterol, and stigmasterol could contribute to the anti-influenza activity through regulating the TRAF6/MAPK14 axis. The following research confirmed that CSTRG significantly inhibited pro-inflammatory cytokines (TNF-α and IL-6) by suppressing the expression of TRAF6 and MAPK14 in LPS-stimulated macrophages RAW264.7 cells. Conclusion: CSTRG might inhibit the inflammatory response by mediating the TRAF6/MAPK14 axis. In the future, in-depth research is still needed to verify the mechanism of CSTRG in the treatment of influenza.