Search

Recent studies focused on exploring phosphodiesterase type 5 inhibitors (PDE5Is)-related hearing impairment. This study aimed to comprehensively explore real-world hearing impairment associated with PDE5Is based on the US Food and Drug Administration Adverse Event Reporting System (FAERS). The characteristics and correlation of PDE5Is-related hearing impairment reported in the FAERS database from the fourth quarter of 2003 to the second quarter of 2023 were analyzed using disproportionality analysis. The Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) were used to analyze the adverse events (AEs) of hearing impairment. A total of 1,438 reported cases of hearing impairment were associated with four PDE5Is, revealing statistically significant reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) with the SMQ. The average age of all patients was more than 55 years, over 70% of AEs were reported in men. Most of the reported cases were from the United States. Reports for all the drugs indicated an increase since 2008, except for avanafil. This study showed that the disability rates of PDE5Is were 8.14–40%, the rates of initial or prolonged hospitalization were 6.21–10.24%, and the rates of required intervention were 3.31–9.45%. The pharmacovigilance study identified a potential risk of hearing impairment associated with PDE5Is, indicating the need for continuous monitoring and appropriate management. [ABSTRACT FROM AUTHOR]

Tornadoes are incredibly powerful and destructive natural events, yet the microphysical characteristics of the parent storm and its effects on tornadogenesis remain unclear. This study analyzed polarization radar data of a tornadic supercell that occurred in Jiangsu Province of China on 14 May 2021, in comparison with another tornadic supercell and two non-tornadic supercells that occurred in the same region in 2023. The two tornadic supercells exhibited lower differential reflectivity (ZDR) in the hook echo region compared with the non-tornadic supercells, indicating smaller median drop sizes. A distinct increase in ZDR from the melting of frozen hydrometeors, observed between 2.5- and 4.0-km altitude in the non-tornadic storms, was absent in the tornadic cases. The non-tornadic supercells also displayed substantially higher specific differential phase (KDP) below the melting level, likely aroused from enhanced melting and cooling. These findings suggest fundamental microphysical contrasts between tornadic and non-tornadic supercells. Specifically, tornadic supercells have smaller droplets and may reduce melting in hook echoes. Moreover, greater separation between the ZDR arc and the KDP foot was observed during tornadogenesis. The vertical gradient of KDP related to the cooling pool strength of the hook echo, regulating rear-flank downdraft thermodynamics. Despite the limited number of cases investigated, the findings of this study indicate that monitoring ZDR, KDP, and drop size distribution trends could assist with tornado prediction and warnings. [ABSTRACT FROM AUTHOR]

When implementing the gradient descent method in low precision, the employment of stochastic rounding schemes helps to prevent stagnation of convergence caused by the vanishing gradient effect. Unbiased stochastic rounding yields zero bias by preserving small updates with probabilities proportional to their relative magnitudes. This study provides a theoretical explanation for the stagnation of the gradient descent method in low-precision computation. Additionally, we propose two new stochastic rounding schemes that trade the zero bias property with a larger probability to preserve small gradients. Our methods yield a constant rounding bias that, on average, lies in a descent direction. For convex problems, we prove that the proposed rounding methods typically have a beneficial effect on the convergence rate of gradient descent. We validate our theoretical analysis by comparing the performances of various rounding schemes when optimizing a multinomial logistic regression model and when training a simple neural network with an 8-bit floating-point format. [ABSTRACT FROM AUTHOR]

The chromatin-based rule governing the selection and activation of replication origins in metazoans remains to be investigated. Here we report that NFIB, a member of Nuclear Factor I (NFI) family that was initially purified in host cells to promote adenoviral DNA replication but has since mainly been investigated in transcription regulation, is physically associated with the pre-replication complex (pre-RC) in mammalian cells. Genomic analyses reveal that NFIB facilitates the assembly of the pre-RC by increasing chromatin accessibility. Nucleosome binding and single-molecule magnetic tweezers shows that NFIB binds to and opens up nucleosomes. Transmission electron microscopy indicates that NFIB promotes nucleosome eviction on parental chromatin. NFIB deficiency leads to alterations of chromosome contacts/compartments in both G1 and S phase and affects the firing of a subset of origins at early-replication domains. Significantly, cancer-associated NFIB overexpression provokes gene duplication and genomic alterations recapitulating the genetic aberrance in clinical breast cancer and empowering cancer cells to dynamically evolve growth advantage and drug resistance. Together, these results point a role for NFIB in facilitating replication licensing by acting as a genome organizer, shedding new lights on the biological function of NFIB and on the replication origin selection in eukaryotes. The precise rule of replication origin selection and activation in metazoans remains unclear. Here, the authors identify NFIB as a genome organizer and replication pioneer by facilitating nucleosome remodeling and chromatin assembly of the pre-RC. [ABSTRACT FROM AUTHOR]

The airfoils for flying wing aircraft need good aerodynamic, trim and stealth performance, and these unconventional requirements would lead to multimodality in airfoil design optimizations. It would be time-consuming for a single-point sequence sampling method, like the Efficient Global Optimization method (EGO), to obtain the global optima over the entire design space, and the traditional multi-start sampling approach would tend to find the local minima which were well-explored by the surrogate model. Thus, the Niching-based Adaptive Space Reconstruction method (NASR) was introduced to enhance the performance of the EGO for aerodynamic/stealth optimizations in this paper. The proposed method adopted a Niching-based multiple points sampling method to simultaneously search out the locations of multiple local minima of the EI function, which did not rely on the starting points and avoided converging to the same local minima. Moreover, it would check the neighborhood of the local minima and focus on the local minima which were not well-explored to decrease computational cost. To decrease the risk of missing promising regions, different expansion strategies were applied to adjust the size of design intervals in different iterations. Several numerical and structural optimization problems were studied to test and verify the efficiency and robustness of NASR. Then, airfoil optimizations considering aerodynamic, stealth and aero/stealth performance by NASR were conducted. It was shown that the aerodynamic performance of the aerodynamic optimized result was comparable with the aero/stealth optimization, and the stealth performance of the stealth optimized result was better than the aero/stealth optimization. The conflictions between Radar Cross Sections (RCS) reduction and drag reduction were not very prominent. Moreover, although the pitch positive moment constraint would damage the lift-drag characteristics, it could be beneficial to RCS reduction based on the current study. [ABSTRACT FROM AUTHOR]

Porcine parvovirus 1 (PPV1) mainly induces severe reproductive failure in pregnant swine, and causes huge economic losses to the swine industry. Cell apoptosis induced by PPV1 infection has been identified the major cause of reproductive failure. However, the molecular mechanism was not fully elucidated. In this study, the potential mechanism of PPV1 induced apoptosis in PK-15 cells was investigated. Our results showed that PPV1 induced apoptosis in PK-15 cells. Further studies revealed toll-like receptor 2 (TLR2) was involved in the PPV1-mediated apoptosis. TLR2 siRNA significantly decreased the apoptosis. Finally, our study showed NF-κB was activated by TLR2 during PPV1-induced apoptosis. The activation of NF-κB signaling was demonstrated by the phosphorylation of p65, p65 nuclear translocation and degradation of inhibitor of kappa B α (IκBα). Together, these results provided evidence that the recognition between PPV1 and PK-15 cells was mainly through TLR2, and then induction of the NF-κB signaling pathway activation, which further induces apoptosis. Our study could provide information to understand the molecular mechanisms of PPV1 infection. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy resistance is the major cause of recurrence in patients with colorectal cancer (CRC). A previous study found that Fusobacterium (F.) nucleatum promoted CRC chemoresistance. Additionally, metformin rescued F. nucleatum-induced tumorigenicity of CRC. Here, we aimed to investigate whether metformin could revert F. nucleatum-induced chemoresistance and explore the mechanism.Methods: The role of metformin in F. nucleatum-infected CRC cells was confirmed using cell counting kit 8 assays and CRC xenograft mice. Stemness was identified by tumorsphere formation. Bioinformatic analyses were used to explore the regulatory molecules involved in metformin and F. nucleatum-mediated regulation of the sonic hedgehog pathway.Results: We found that metformin abrogated F. nucleatum-promoted CRC resistance to chemotherapy. Furthermore, metformin attenuated F. nucleatum-stimulated stemness by inhibiting sonic hedgehog signaling. Mechanistically, metformin diminished sonic hedgehog signaling proteins by targeting the MYC/miR-361-5p cascade to reverse F. nucleatum-induced stemness, thereby rescuing F. nucleatum-triggered chemoresistance in CRC.Conclusions: Metformin acts on F. nucleatum-infected CRC via the MYC/miR-361-5p/sonic hedgehog pathway cascade, subsequently reversing stemness and abolishing F. nucleatum-triggered chemoresistance. Our results identified metformin intervention as a potential clinical treatment for patients with chemoresistant CRC with high amounts of F. nucleatum. [ABSTRACT FROM AUTHOR]

Although the performance of the self-standing electrode has been enhanced for aqueous zinc-ion batteries (AZIBs), it is necessary to explore and analyse the deep modification mechanism (especially interface effects). Herein, density functional theory (DFT) calculations are applied to investigate the high-performance cathode based on the VO2/carbon cloth composites with heterostructures interface (H-VO2@CC). The adsorption energy comparisons and electron structure analyses verify that H-VO2@CC has extra activated sites at the interface, enhanced electrical conductivity, and structural stability for achieving high-performance AZIBs due to the presence of built-in electric field at the interfaces. Accordingly, the designed self-standing H-VO2@CC cathode delivers higher rate capacity, longer-life cyclability, and faster electronic/ion transmission kinetics benefiting from the synergistic effects. The risks of active material shedding and dissolution during the dis/charge process of two cathodes were evaluated via ex-situ ultraviolet—visible (UV-vis) spectrum and inductively coupled plasma-atomic emission spectroscopy (ICP-AES) technique. Finally, this investigation also explores the charge storage mechanism of H-VO2@CC through various ex-situ and in-situ characterization techniques. This finding can shed light on the significant potential of heterostructures interface engineering in practical applications and provide a valuable direction for the development of cathode materials for AZIBs and other metal-ion batteries. [ABSTRACT FROM AUTHOR]

The optimal systemic treatment of advanced large cell neuroendocrine carcinoma (LCNEC) is still controversial. We intend to explore advanced LCNEC through SEER database, construct nomogram model of advanced LCNEC, and understand the effect of different treatment regimens on LCNEC. We collected 909 patients, divided them into a training set validation set, constructed nomograms using Cox proportional hazards regression models, and evaluated nomogram discrimination and calibration by C-index and calibration curves. Kaplan–Meier will also be used to compare OS in different groups of patients and to explore the impact of different treatment regimens on advanced LCNEC. On the nomogram plotted, the nomogram predicted AUC values over time were always greater than 0.7, the C-index was 0.681 (95% CI 0.656–0.706) and 0.663 (95% CI 0.628–0.698) in the training and validation sets, respectively, and patients were divided into two groups according to risk, and a significant difference in OS was observed between the high-risk and low-risk groups in the training and validation cohorts. Different treatment analyses showed that chemotherapy is still the best treatment for advanced LCNEC. This nomogram provides a convenient and reliable tool for individual assessment and clinical decision-making of patients with advanced LCNEC. [ABSTRACT FROM AUTHOR]

Aims: Although the influences of coastal embankments on soil physicochemical properties and carbon (C) and nitrogen (N) cycling have been widely reported, the mechanisms of their effects on soil microbial ecologies remain poorly understood. Thus, the aim of this study was to investigate the variations in the diversity and composition of soil bacterial and archaeal communities between natural and embanked saltmarshes, as well as the determinants that drive these variations. Methods: 16S rRNA gene sequence analysis was performed to assess the impacts of coastal embankments on the bacterial and archaeal communities of native Suaeda salsa, Phragmites australis, and invasive Spartina alterniflora saltmarshes on the east coast of China. Results: Embankments were found to significantly decrease the microbial diversity of S. alterniflora salt marsh, while increased the OTU richness of P. australis salt marsh. Embankments modified the compositions of soil bacterial and archaeal communities in both S. alterniflora and P. australis salt marshes. However, variations in the microbial diversity, richness, and community compositions between the native and embanked S. salsa salt marshes were insignificant. Conclusions: These results were possibly because the embankment significantly altered soil nutrient substrate levels (e.g., soil organic C and N) by variations in plant residues and soil physiochemical properties in S. alterniflora and P. australis saltmarshes, whereas the embankment had no observable changes in the soil nutrient substrate and plant residue in S. salsa saltmarsh. This study also elucidated the effects of coastal embankments on biogeochemical cycles, and highlighted their potential hazards to ecosystems. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Zhejiang University: Science B is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The dormancy survival regulator (DosR) antigens upgraded during latency and resuscitation-promoting factors (Rpfs) expressed over the reactivation from dormant Mycobacterium tuberculosis (M. tuberculosis) could be used to diagnose tuberculosis (TB) at different stages. We performed a retrospective cohort study based on four groups, including healthy controls (HCs), active tuberculosis infections (ATBs), latent tuberculosis infections (LTBIs), and relapse tuberculosis infections (RTBs) enrolled between November 2020 and June 2021. Compared to the fusion protein E6-C10, combined with early secreted antigenic target 6 kDa (ESAT-6) and culture filtrate of 10 kDa (CFP-10), the DosR- or Rpf-encoded antigens could not elicit significant IFN-γ concentration for the diagnosis of ATB. Of note, the DosR antigens produce significantly more antigen-specific IFN-γ in LTBIs than Rpfs, and the levels of antigen-specific IFN-γ elicited in RTBs stimulated by Rpfs were higher than the DosR antigens. Among the DosR antigens, Rv2003c was the most immunogenic in diagnosing LTBIs, followed by Rv2007c and Rv2005c. As far as Rpfs are concerned, Rv0867c was the best antigen to identify RTBs, followed by Rv2389c and Rv1009. Both Rv2450c and Rv1884c showed relatively limited IFN-γ concentration in RTBs. Besides, the selected DosR antigens and Rpfs showed ideal specificity and inadequate sensitivity, which could have been enhanced by the fusion antigens prepared by the DosR antigens or Rpfs, respectively. The results of this study can provide more accurate detection methods for LTBIs and RTBs and could be used for screening the dormant M. tuberculosis throughout reactivation. [ABSTRACT FROM AUTHOR]

The clinical similarity among different neuropsychiatric disorders (NPDs) suggested a shared genetic basis. We catalogued 23,109 coding de novo mutations (DNMs) from 6511 patients with autism spectrum disorder (ASD), 4,293 undiagnosed developmental disorder (UDD), 933 epileptic encephalopathy (EE), 1022 intellectual disability (ID), 1094 schizophrenia (SCZ), and 3391 controls. We evaluated that putative functional DNMs contribute to 38.11%, 34.40%, 33.31%, 10.98% and 6.91% of patients with ID, EE, UDD, ASD and SCZ, respectively. Consistent with phenotype similarity and heterogeneity in different NPDs, they show different degree of genetic association. Cross-disorder analysis of DNMs prioritized 321 candidate genes (FDR < 0.05) and showed that genes shared in more disorders were more likely to exhibited specific expression pattern, functional pathway, genetic convergence, and genetic intolerance. [ABSTRACT FROM AUTHOR]

Soil moisture is a limiting factor of ecosystem development in the semi-arid Loess Plateau. Characterizing the soil moisture response to its dominant controlling factors, such as land use and topography, and quantifying the soil-water carrying capacity for revegetation is of great significance for vegetation restoration in this region. In this study, soil moisture was monitored to a depth of 2 m in three land use types (native grassland, introduced grassland, and forestland), two landforms (hillslope and gully), and two slope aspects (sunny and shady) in the Nanxiaohegou watershed of the Loess Plateau, Northwest China. The MIKE SHE model was then applied to simulate the soil moisture dynamics under different conditions and determine the optimal plant coverage. Results showed that the average soil moisture was higher in native grassland than in introduced grassland and Platycladus orientalis forestland for a given topographic condition; however, a high soil moisture content was found in Robinia pseudoacacia forestland, with a value that was even higher than the native grassland of a sunny slope. The divergent results in the two forestlands were likely attributed to the differences in plant coverage. Gully regions and shady slopes usually had higher soil moisture, while lower soil moisture was usually distributed on the hillslope and sunny slope. Furthermore, the mean absolute relative error and Nash-Sutcliffe efficiency coefficient of the MIKE SHE model ranged between 2.8%–7.8% and 0.550–0.902, respectively, indicating that the model could effectively simulate the soil moisture dynamics. The optimal plant coverage was thus determined for hillslope P. orientalis by the model, corresponding to a leaf area index (LAI) value of 1.92. Therefore, for sustainable revegetation on the Loess Plateau, selecting suitable land use types (natural vegetation), controlling the planting density/LAI, and selecting proper planting locations (gully and shady slope regions) should be considered by local policy makers to avoid the over-consumption of soil water resources. [ABSTRACT FROM AUTHOR]

The multi-fidelity metamodeling method can dramatically improve the efficiency of metamodeling for computationally expensive engineering problems when multiple levels of fidelity data are available. In this paper, an efficient and novel adaptive multi-fidelity sparse polynomial chaos-Kriging (AMF-PCK) metamodeling method is proposed for accurate global approximation. This approach, by first using low-fidelity computations, builds the PCK model as a model trend for the high-fidelity function and captures the relative importance of the significant sparse polynomial bases selected by least angle regression (LAR). Then, by using high-fidelity model evaluations, the developed method utilizes the trend information to adaptively refine a scaling PCK model using an adaptive correction polynomial expansion-Gaussian process modeling. Here, the most relevant sparse polynomial basis set and the optimal correction expansion are adaptively identified and constructed based on a devised nested leave-one-out cross-validation-based LAR procedure. As a result, the optimal AMF-PCK metamodel is adaptively established, which combines advantages of high flexibility and strong nonlinear modeling ability. Moreover, an adaptive sequential sampling approach is specially developed to further improve the multi-fidelity metamodeling efficiency. The developed method is evaluated by several benchmark functions and two practically challenging transonic aerodynamic modeling applications. A comprehensive comparison with the popular hierarchical Kriging, universal Kriging, and LAR-PCK approaches demonstrates that the proposed method is the most efficient and provides the best global approximation accuracy, with particular superiority for quantities of interest in the multimodal and highly nonlinear landscape. This novel method is very promising for efficient uncertainty analysis and surrogate-based optimization of expensive engineering problems. [ABSTRACT FROM AUTHOR]

Introduction: This phase I clinical trial was conducted to evaluate the safety of RP22 as a skin test reagent for tuberculosis (TB) diagnosis and to explore the appropriate dosage. Methods: We used a randomized, double-blind, placebo-controlled identification allergen (IA) skin test. A total of 72 healthy adult volunteers with negative chest X-ray results were randomized into six groups and given a QuantiFERON-TB Gold (QFT) test. Of the 12 participants in each group, eight received RP22 and four received placebo. The doses of RP22 in the six experimental groups ranged from 0.1 to 4.0 μg in a single intradermal injection of 0.1 ml. Skin reactions and adverse events were recorded at intervals. Results: All doses of RP22 except the highest were well tolerated and safe. No serious adverse events associated with the injection were observed in all groups. There were 11 participants who had positive QFT results, eight had a skin reaction with a redness or induration area diameter of greater than 10 mm at 48–72 h, one had no skin reaction. Among the 60 negative-QFT participants, none had a reaction area diameter of greater than 10 mm. Conclusion: The RP22 skin test was well tolerated and safe, it could play a key role in screening for latent tuberculosis infection (LTBI) by providing a much-wanted alternative to the tuberculin skin test (TST) and interferon-γ release assays (IGRAs). [ABSTRACT FROM AUTHOR]

We aimed to detect the causative gene in five unrelated families with recessive inheritance pattern neurological disorders involving the central nervous system, and the potential function of the NEMF gene in the central nervous system. Exome sequencing (ES) was applied to all families and linkage analysis was performed on family 1. A minigene assay was used to validate the splicing effect of the relevant discovered variants. Immunofluorescence (IF) experiment was performed to investigate the role of the causative gene in neuron development. The large consanguineous family confirms the phenotype-causative relationship with homozygous frameshift variant (NM_004713.6:c.2618del) as revealed by ES. Linkage analysis of the family showed a significant single-point LOD of 4.5 locus. Through collaboration in GeneMatcher, four additional unrelated families' likely pathogenic NEMF variants for a spectrum of central neurological disorders, two homozygous splice-site variants (NM_004713.6:c.574+1G>T and NM_004713.6:c.807-2A>C) and a homozygous frameshift variant (NM_004713.6: c.1234_1235insC) were subsequently identified and segregated with all affected individuals. We further revealed that knockdown (KD) of Nemf leads to impairment of axonal outgrowth and synapse development in cultured mouse primary cortical neurons. Our study demonstrates that disease-causing biallelic NEMF variants result in central nervous system impairment and other variable features. NEMF is an important player in mammalian neuron development. [ABSTRACT FROM AUTHOR]

LAT1 (SLC7A5) is one of the representative light chain proteins of heteromeric amino acid transporters, forming a heterodimer with its heavy chain partner 4F2hc (SLC3A2). LAT1 is overexpressed in many types of tumors and mediates the transfer of drugs and hormones across the blood-brain barrier. Thus, LAT1 is considered as a drug target for cancer treatment and may be exploited for drug delivery into the brain. Here, we synthesized three potent inhibitors of human LAT1, which inhibit transport of leucine with IC50 values between 100 and 250 nM, and solved the cryo-EM structures of the corresponding LAT1-4F2hc complexes with these inhibitors bound at resolution of up to 2.7 or 2.8 Å. The protein assumes an outward-facing occluded conformation, with the inhibitors bound in the classical substrate binding pocket, but with their tails wedged between the substrate binding site and TM10 of LAT1. We also solved the complex structure of LAT1-4F2hc with 3,5-diiodo-l-tyrosine (Diiodo-Tyr) at 3.4 Å overall resolution, which revealed a different inhibition mechanism and might represent an intermediate conformation between the outward-facing occluded state mentioned above and the outward-open state. To our knowledge, this is the first time that the outward-facing conformation is revealed for the HAT family. Our results unveil more important insights into the working mechanisms of HATs and provide a structural basis for future drug design. [ABSTRACT FROM AUTHOR]

Iron tailings have few macropores which severely inhibit infiltration and transport of soil water. Polyacrylamide (PAM) can regulate soil water, but it is rarely used when remediating tailings matrix. In this research, PAM of four molecular weights of 300w, 600w, 800w, and 1000w were selected as amendments, and were each applied at five mass concentrations of 0% (CK), 0.01%, 0.04%, 0.08%, and 0.16% to observe their effects on water transport in iron tailings using column simulations in the laboratory. After adding PAM, the water retention and saturated water content of iron tailings increased significantly (P < 0.05). With increases in PAM molecular weight and mass concentration, the saturated hydraulic conductivity showed a downward trend, but the saturated hydraulic conductivity increased after a dry–wet cycle. With the increase of PAM mass concentration, adding PAM of 1000w molecular weight to iron tailing decreased infiltration capacity, but treatments of other molecular weights all initially increased then decreased infiltration capacity. The greatest improvement on infiltration capacity of iron tailings was observed with the addition of PAM of 300w molecular weight and 0.01% mass concentration. Adding PAM increased the vertical depth of the saturation zone of iron tailings (P < 0.05) with a maximum depth of 20.83 cm. The Kostiakov model more accurately simulated water infiltration of iron tailings compared with the Horton and Philip models. On the whole, when PAM of low molecular weight and concentration was added to iron tailings, PAM increased stable infiltration, saturated water content, and water retention. It also inhibited saturated hydraulic conductivity of iron tailings. Therefore, in practice, it is necessary to select the appropriate molecular weight and mass concentration of PAM according to the dominant limiting factors and remediation needs of the matrix. [ABSTRACT FROM AUTHOR]

Interferon α (IFN-α) plays a crucial role in the host's immune response. In this study, the amino acid sequence of porcine interferon α (PoIFN-α) was analyzed. Seven substitutions, S38F, H40Q, F43L, N78D, Y86C, S151A, and R156T, were mutated and obtained by aligning the sequences of PoIFN-α subtypes. The PoIFN-α mutants were designed, expressed, and purified in E. coli. The antiviral activities of these PoIFN-αs were measured in Vero and swine testis cells against vesicular stomatitis virus (VSV). Their inhibitory abilities on pseudorabies virus (PRV) were also examined. Commercial PoIFN-α was used as a control. We found the ideal inducer concentration of isopropyl β-d-thiogalactoside was 1 mM, and the best time-point for induction was 8 h. The PoIFN-α mutant named PoIFN-α-156s had the highest antiviral activity, which was about 200-fold more than that of PoIFN-α. PoIFN-α-156s could inhibit VSV and PRV replication in a dose-dependent manner in vitro. The half-life of PoIFN-α-156s was longer than that of PoIFN-α in mice, and the effective antiviral action was higher than PoIFN-α. Animal experiments showed that PoIFN-α-156s could decrease the viral load after infection with VSV. Overall, these results suggest that recombinant PoIFN-α-156s has the ability of antivirus, and is feasible for veterinary clinical applications and fundamental research. [ABSTRACT FROM AUTHOR]

Background: Cancer poses a huge disease burden, which could be reduced by adopting healthy lifestyles mainly composed of healthy diet, body weight, physical activity, limited alcohol consumption, and avoidance of smoking. However, no systematic review has summarised the relations of combined lifestyle factors with cancer morbidity and mortality.Methods: EMBASE and PubMed were searched up to April 2019. Cohort studies investigating the association of combined lifestyle factors with risks of incident cancer and cancer mortality were selected. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity and publication bias tests were conducted.Results: The HRs (95% CIs) comparing individuals with the healthiest versus the least healthy lifestyles were 0.71 (0.66-0.76; 16 studies with 1.9 million participants) for incident cancer and 0.48 (0.42-0.54; 30 studies with 1.8 million participants) for cancer mortality. Adopting the healthiest lifestyles was also associated with 17 to 58% lower risks of bladder, breast, colon, endometrial, oesophageal, kidney, liver, lung, rectal, and gastric cancer. The relations were largely consistent and significant among participants with different characteristics in the subgroup analyses.Conclusions: Adopting healthy lifestyles is associated with substantial risk reduction in cancer morbidity and mortality, and thus should be given priority for cancer prevention. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: A healthy lifestyle has been widely recommended for the prevention and management of type 2 diabetes. However, no systematic review has summarised the relationship between combined lifestyle factors (including, but not limited to, smoking, alcohol drinking, physical activity, diet and being overweight or obese) and incident type 2 diabetes and risk of health outcomes among diabetic individuals. Methods: EMBASE and PubMed were searched up to April 2019 without language restrictions. References included in articles in relevant publications were also screened. Cohort studies investigating the combined associations of at least three lifestyle factors with incident type 2 diabetes and health outcomes among diabetic individuals were included. Reviewers were paired and independently screened studies, extracted data and evaluated study quality. Random-effects models were used to calculate summary HRs. Heterogeneity and publication bias tests were also conducted. Results: Compared with participants considered to have the least-healthy lifestyle, those with the healthiest lifestyle had a 75% lower risk of incident diabetes (HR 0.25 [95% CI 0.18, 0.35]; 14 studies with approximately 1 million participants). The associations were largely consistent and significant among individuals from different socioeconomic backgrounds and baseline characteristics. Among individuals with type 2 diabetes (10 studies with 34,385 participants), the HRs (95% CIs) were 0.44 (0.33, 0.60) for all-cause death, 0.51 (0.30, 0.86) for cardiovascular death, 0.69 (0.47, 1.00) for cancer death and 0.48 (0.37, 0.63) for incident cardiovascular disease when comparing the healthiest lifestyle with the least-healthy lifestyle. Conclusions/interpretation: Adoption of a healthy lifestyle is associated with substantial risk reduction in type 2 diabetes and long-term adverse outcomes among diabetic individuals. Tackling multiple risk factors, instead of concentrating on one certain lifestyle factor, should be the cornerstone for reducing the global burden of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: Soil fungal communities play a critical role in ecosystem carbon (C) and nitrogen (N) cycling. Although the effect of plant invasions on ecosystem C and N cycling is well established, its impact on soil fungal communities is not fully understood. The objective of this study was therefore to understand the variations in soil fungal communities as affected by plant invasion, and the mechanisms that drive these changes. Methods: We examined the impacts of invasive Spartina alternifolia Loisel. (SA) on soil fungal abundance, diversity, community composition, trophic modes and functional groups in comparison with bare flat (BF) and native Suaeda salsa (Linn.) Pall. (SS), Scirpus mariqueter Tang et Wang (SM), and Phragmites australis (Cav.) Trin. ex Steud. (PA) communities in coastal salt marshes of eastern China, based on analyses of the quantitative polymerase chain reaction (qPCR) and Illumina MiSeq DNA sequences of fungal internal transcribed spacer (ITS) region. Results: SA invasion increased the soil fungal abundance and diversity compared to BF, SS, SM, and PA soils. The increased soil fungal abundance and diversity were highly related to soil organic carbon (C) and nitrogen (N), water-soluble organic carbon (WSOC), litter C:N ratio, and root C:N ratio. Soil fungal community composition was shifted following SA invasion. Specifically, SA invasion significantly enhanced the relative abundance of Basidiomycota, and reduced the relative abundance of Ascomycota compared with BF, SS, SM, and PA soils. Additionally, SA invasion changed soil fungal trophic modes and functional groups. The relative abundance of saprotrophic fungi significantly increased, while the relative abundances of symbiotic and pathotrophic fungi decreased following SA invasion. Conclusions: Our data revealed that SA invasion altered soil fungal abundance, diversity, community composition, trophic modes and functional groups, which were primarily driven by the quality and quantity of plant residues, soil nutrition substrates, as well as soil physicochemical properties. The changes in soil fungal communities, especially their trophic modes and functional groups following SA invasion would greatly affect soil C and N decomposition and accumulation with potential feedback on climate change. [ABSTRACT FROM AUTHOR]

Exploring how suitable habitat and population size of Red-crowned crane Grus japonensis respond to long-term coastal reclamation plays an important role in species conservation and in related coastal management. Here, we combined field data for suitable habitats and wintering population size of G. japonensis with GIS-based information to elucidate the influence of long-term coastal reclamation on this species and related conservation efforts. During 1975-2013, the intensity and spatial extent of coastal reclamation exhibited a temporal change, increasing dramatically in 1975-2000 and lessening considerably in 2000-2013. Under the pressure of long-term coastal reclamation, the decline of suitable habitat of G. japonensis was affected by increasing levels of human disturbance and decreasing availability of natural habitat. Moreover, the wintering population size of G. japonensis exhibited a decreasing trend during 1975-2013 as a result of the decreasing availability of fish ponds, bare tidal flats, and increasing spatial extent of residential areas and P. australis habitat, which were indirectly affected by long-term reclamation. Our results highlight the importance of considering the long-term effects of coastal reclamation on both populations and suitable habitat of G. japonensis, which should be considered in future plans for coastal management and conservation. [ABSTRACT FROM AUTHOR]

To investigate the effect of recharge water temperature on bioclogging processes and mechanisms during seasonal managed aquifer recharge (MAR), two groups of laboratory percolation experiments were conducted: a winter test and a summer test. The temperatures were controlled at ~5±2 and ~15±3 °C, and the tests involved bacterial inoculums acquired from well water during March 2014 and August 2015, for the winter and summer tests, respectively. The results indicated that the sand columns clogged ~10 times faster in the summer test due to a 10-fold larger bacterial growth rate. The maximum concentrations of total extracellular polymeric substances (EPS) in the winter test were approximately twice those in the summer test, primarily caused by a ~200 μg/g sand increase of both loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS). In the first half of the experimental period, the accumulation of bacteria cells and EPS production induced rapid bioclogging in both the winter and summer tests. Afterward, increasing bacterial growth dominated the bioclogging in the summer test, while the accumulation of LB-EPS led to further bioclogging in the winter test. The biological analysis determined that the dominant bacteria in experiments for both seasons were different and the bacterial community diversity was ~50% higher in the winter test than that for summer. The seasonal inoculums could lead to differences in the bacterial community structure and diversity, while recharge water temperature was considered to be a major factor influencing the bacterial growth rate and metabolism behavior during the seasonal bioclogging process. [ABSTRACT FROM AUTHOR]

Objectives This study measures the prevalence of risk factors among pregnant women and young children aged 12-24 months in a rural community in West Bengal, India. Methods Community health workers (CHWs) enrolled women and children into this 2015 cross-sectional study. Pregnant women were evaluated for underweight, anemia, and abnormal blood pressure. Children were evaluated for underweight, abnormal head and upper arm circumferences, and low scores from the Ages and Stages Questionnaire (ASQ). Data were collected on smartphones and tablets or by paper. Results More than half of the 279 women (59.9%) had a risk factor during pregnancy: 48.7% were anemic, 35.1% had low blood pressure, and 7.5% were underweight. Among the 366 children, 59.3% had a risk factor, including 24.0% with low ASQ scores and 49.7% who had abnormal anthropometric measures. Conclusions for Practice Vulnerable populations, such as pregnant women and young children, needed a greater connection to doctors in this rural community. This study demonstrated the feasibility of CHWs to listen to health concerns and connect underserved populations with health care services. [ABSTRACT FROM AUTHOR]

In monitoring health care providers, various outcomes are used to assess the performance and quality of care given. We consider a measure that is normally distributed across the majority of providers with both a within and between component contributing to the overall variability of the measure. In such cases, the inter-unit reliability (IUR) is commonly used to assess the usefulness of a measure for identifying extreme providers. In this article, we define and discuss the IUR and note its role under various assumptions about the source of the between-provider variance. This variability may be due primarily to differences in the patients that are not accounted for in the measured covariates, or differences in the quality of care provided, or a combination of these two. The IUR is a simple population characteristic specifying the proportion of the variation in the measure that is related to between-provider differences without regard to the source of that variation. On the other hand, the IUR does not characterize the suitability of a measure for profiling or identifying outliers except in very special circumstances where all the variation is due to quality of care and there are no outliers. In assessing the reliability of a measure for profiling, the key question is whether outlying providers with poor (or excellent) quality of care give rise to extreme values of the measure. [ABSTRACT FROM AUTHOR]

The Loess Plateau of China has experienced a lengthy drought and severe soil erosion. Changes in precipitation and land use largely determine the dynamics of runoff and sediment yield in this region. Trend and mutation analyses were performed on hydrological data (1981-2012) from the Yanwachuan watershed in the Loess Plateau Gully Region to study the evolution characteristics of runoff and sediment yield. A time-series contrasting method also was used to evaluate the effects of precipitation and soil and water conservation (SWC) on runoff and sediment yield. Annual sediment yield declined markedly from 1981 to 2012 although there was no significant change in annual precipitation and annual runoff. Change points of annual runoff and annual sediment yield occurred in 1996 and 1997, respectively. Compared with that in the baseline period (1981-1996), annual runoff and annual sediment yield in the change period (1997-2012) decreased by 17.0% and 76.0%, respectively, but annual precipitation increased by 6.3%. Runoff decreased in the flood season and normal season, but increased in the dry season, while sediment yield significantly declined in the whole study period. The SWC measures contributed significantly to the reduction of annual runoff (137.9%) and annual sediment yield (135%) and were more important than precipitation. Biological measures (forestland and grassland) accounted for 61.04% of total runoff reduction, while engineering measures (terraces and dams) accounted for 102.84% of total sediment yield reduction. Furthermore, SWC measures had positive ecological effects. This study provides a scientific basis for soil erosion control on the Loess Plateau. [ABSTRACT FROM AUTHOR]

Background and Aim: Accurately differentiating malignant diseases from benign ones in patients having bile duct obstruction is of significant importance and remains a major clinical problem. This study investigated the diagnostic yield of endoscopic retrograde cholangiography/intraductal ultrasound (ERC/IDUS) in distinguishing malignant from benign bile duct obstruction and assessed some image findings from ERC/IDUS which might be useful in differentiation.Methods: From January 2008 to January 2015, patients who underwent ERC/IDUS for bile duct obstruction were enrolled. Patient's ERC/IDUS diagnosis was compared with the final diagnosis determined by pathologic findings and/or clinical outcome of follow-up.Results: One hundred and ninety-three patients with bile duct obstruction were included. IDUS correctly identified 94 of 97 malignant diseases and 76 of 96 benign diseases with sensitivity, specificity, and accuracy rate of 96.91, 79.17, and 88.08 %, respectively. Additionally, the accuracy rate of IDUS for diagnosis of proximal bile duct obstruction was higher than that of distal bile duct obstruction (98.08 vs. 82.73 %, p = 0.006). Besides, there was a significant difference in the length at the obstruction site between benign and malignant diseases (13.76 ± 7.37 vs. 19.97 ± 11.37 mm, p < 0.001) as well as thickness of bile duct wall at the site of obstruction (3.06 ± 0.92 vs. 7.03 ± 3.70 mm, p = 0.008). Biliary wall thickness >7 mm without extrinsic compression had a positive predictive value (PPV) of 100 % for including malignancy, while length ≧20 mm demonstrated a PPV of 93.44 %.Conclusions: ERC/IDUS is effective in distinguishing malignant from benign bile duct obstruction, thus helping in further clinical management. [ABSTRACT FROM AUTHOR]

The identification of tau fragments generated by proteolysis in the neurons of AD patients and in neurofibrillary tangles encourages research on the toxicity of truncated tau. However, the detailed mechanism underlying the proteolysis-induced toxicity of tau is not clear and even controversial in some cases. In the present study, we used Drosophila as a model to evaluate the toxicity of a set of truncated tau fragments in vivo and found that the flies harboring C-terminal-truncated tau exhibited less toxicity due to the unstable characteristic of C-terminal-truncated tau fragments. Further study carried out in cultured Drosophila Kc cells revealed that C-terminal-truncated tau fragments degrade faster than full-length tau or N-terminal-truncated fragments. Collectively, our data implicate proteolysis of tau as an important pathway mediating tau degradation and neurotoxicity in vivo. [ABSTRACT FROM AUTHOR]

The anodic stripping peak current of lead on the glassy carbon electrode surface was greatly increased in the presence of high concentration of copper ion. The effects of supporting electrolyte, concentration of Cu, accumulation potential and accumulation time were studied on the stripping peak current of Pb. As a result, a sensitive, simple and rapid electrochemical method was developed for the detection of lead. In 0.01 M HNO solution containing 800 g,g L Cu, the stripping peak current of Pb increases linearly with its concentration over the range from 2 to 100 μg L. The detection limit is 1 μg L after 4-min accumulation at −0.8 V. It was used to detect the concentration of lead in blood samples, and the results consisted with the values that obtained by atomic absorption spectrometry. [ABSTRACT FROM AUTHOR]

Pulsed electromagnetic field (PEMF) has been shown to increase bone mineral density in osteoporosis patients and prevent bone loss in ovariectomized rats. But the mechanisms through which PEMF elicits these favorable biological responses are still not fully understood. Receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) are cytokines predominantly secreted by osteoblasts and play a central role in differentiation and functional activation of osteoclasts. The purpose of this study was to investigate the effects of PEMF on RANKL and OPG expression in ovariectomized rats. Thirty 3-month-old female Sprague-Dawley rats were randomly divided into three groups: sham-operated control (Sham), ovariectomy control (OVX), and ovariectomy with PEMF treatment (PEMF). After 12-week interventions, the results showed that PEMF increased serum 17β-estradiol level, reduced serum tartrate-resistant acid phosphatase level, increased bone mineral density, and inhibited deterioration of bone microarchitecture and strength in OVX rats. Furthermore, PEMF could suppress RANKL expression and improve OPG expression in bone marrow cells of OVX rats. In conclusion, this study suggests that PEMF can prevent ovariectomy-induced bone loss through regulating the expression of RANKL and OPG. [ABSTRACT FROM AUTHOR]

The aim of this study is to observe the effect of different treatment time of millimeter wave (MMW) on chondrocyte apoptosis, caspase-3, caspase-8, and matrix metalloproteinase-13 (MMP-13) in rabbit knee osteoarthritis induced by anterior cruciate ligament transection (ACLT). Thirty-two New Zealand White rabbits were randomly assigned into 4 groups: millimeter wave treatment for 20-min group (MWT20); millimeter wave treatment for 40-min group (MWT40); model control group (MC) and normal control group (NC). All groups received anterior cruciate ligament transection in the right knee except NC group. Six weeks after transection, the MWT20 group and MWT40 group were given millimeter wave (MMW) at 37.5 GHz frequency, 8 mm wavelength, and 10 mW/cm power for 20 and 40 min, respectively, for 10 days. Eight weeks after transection, all animals were killed. Modified Mankin Score was assessed for histological assessment. Chondrocytes apoptosis was tested by the TUNEL assessment, and the expressions of related proteins were tested by the immunohistochemistry observation and Western blot. The modified Mankin Score, the chondrocyte apoptosis, and the expression of caspase-3 and MMP-13 in MWT40 group were significantly lower than those in MC group. Only a decreasing trend of modified Mankin Score and caspase-3 and MMP-13 expression was found in MWT20 group. The caspase-8 expression of the treatment groups was lower than model control group and higher than normal control group, but no significant difference was found. This study revealed MWT40 had a better therapeutic benefit to osteoarthritis cartilage structure, decreased the apoptosis of chondrocyte, and caspase-3 and MMP-13 expression compared to MWT20. But only a decreasing trend of caspase-8 expression was found. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the allelic frequency of 4 short terminal repeats (STRs) in Han and She populations from eastern China. Methods: DNA samples from Han (N = 110) and She (N = 110) healthy subjects were amplified using PCR and primers specific for the STRs. D21S11 and D21S1446 (chromosome 21) and D18S865 and D18S535 (chromosome 18). The frequency and homozygocity of different STRs were evaluated. Results: For both populations, D21S11 and D18S535 were more polymorphic than D21S1446 and D18S865, and the D21S1446 1 allele was very common (48.6% and 55.0% for the Han and She groups, respectively).The Han and She groups significantly differed from one another in respect to the distribution of D21S11, D18S865, and D18S535 allelic frequency (all P -values ≤ 0.48) but had a similar allelic distribution for D21S1446 ( P = 0.106). D21S1446 was found to be homozygous about 50% of the time which was significantly greater compared to the other STRs analyzed. Conclusion: This study found that the Han and She differ genetically at 3 autosomal STRs located on chromosome 18 and 21. The STR D21S1146 was often homozygous within these groups, indicating it would be poor marker for analyzing trisomy within these populations. [ABSTRACT FROM AUTHOR]

A novel macrocyclic silver(I)-NHC complex was prepared by the quaternization reaction and anion metathesization reaction from 1-(1 H-Imidazole-1-yl)methylene-1 H-1,2,4-triazole as starting material. Its molecular structure was determined by single crystal X-ray diffraction and NMR spectroscopy, it crystallizes in triclinic space group P − 1 with a = 11.3286(10) Å, b = 11.4226(10) Å, c = 12.3987(12) Å, α = 79.0060(10)°, β = 82.1780(10)°, γ = 84.5930(10)°, V = 1556.5(2) Å3, z = 2. The silver ion was coordinated by the two carbene C atoms of two independent triazolylidene rings in linear geometry. A 20-membered macrometallacycle was formed through the bridged interaction between two silver ions and two carbene ligands. There are weak π–π interactions between two picrate anions or between picrate anion and triazolylidene ring. A novel macrocyclic silver(I) N-heterocyclic carbene complex was prepared by the quaternization reaction and anion metathesization reaction from 1-(1 H-Imidazole-1-yl)methylene-1 H-1,2,4-triazole as starting material.[Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The strength loss mechanism of the phosphate bonded sand mold/core was studied. The morphology and composition of phosphate membrane on the surface of sands was analyzed with electron probe X-ray microanalyzer. Results show that magnesium causes cracks in cured phosphate membrane and results in the decrease of sand molds/cores strength. However, the addition of magnesium significantly enhanced hygroscopy resistance of phosphate membrane. In addition, the phosphate binder added with the magnesium modifier has more rapid hardening reaction speed compared that without or with low magnesium binder. It can be concluded that the phosphate binder with the addition of magnesium modifier is favorably used in high humid and cold circumstance. [ABSTRACT FROM AUTHOR]

Abstract  Many bioactive peptides possess specific biological properties that make these potential ingredients of health-promoting foods. Increasing attention is being focused on physiologically active peptides derived from soybean proteins. In this study, soybean peptides were produced by fermentation of defatted soybean meal with Bacillus subtilis SHZ and purified by ultrafiltration and gel chromatogram. Free radical scavenging property and the effect on anti-fatigue of the peptides were evaluated in vitro and in vivo, respectively. Swimming endurance tests of mice were carried out after 20 days of soybean peptides administration (0, 100, 200, 400 mg/kg BW/day for control, low-dose, middle-dose and high-dose group, respectively). And the blood lactate and hepatic glycogen of mice were determined. Results showed that the purified peptides exhibited significant (P P P  [ABSTRACT FROM AUTHOR]

Objective: To explore the possibility of using traditional Chinese medicine (TCM) in treating β-thalassemia, its clinical effect and molecular mechanism of the action. Methods: According to the TCM theory of 'Shen producing marrow', the composite recipe, Yisui Shenxueling Granule (YSSXL), consisting of Chinese drugs for nourishing Shen and supplementing marrow (NS & SM) was given orally to 78 patients with β-thalassemia (49 of the severe type and 29 of moderate type), 3 times a day, 10 g each time (for children, the dose would be reduced properly), with 3 months as one therapeutic course, and no blood transfusion used in the course. The clinical therapeutic efficacy and hematologic parameters in patients were observed, and systemic gene analysis was conducted with PAGE, PCR, PCR-SSCP, RT-PCR and DNA sequences analysis and mRNA detection, in order to study the molecular mechanism from the relationships between genetic mutation and clinical efficacy, gene expression and its regulation. Results: YSSXL showed obvious therapeutic effect in treating β-thalassemia. Gene analysis revealed that it did not change the genetic mutation type, but could obviously increase hemoglobin, fetal hemoglobin (HbF), γ/(β+γ) globin ratio, γ-globin mRNA expression and GM-CSF mRNA expression in patients, as well as the GM-CSFmRMA in marrow of mice after 60Co radiation. Conclusion: YSSXL has a remarkable therapeutic effect on β-thalassemia, and its possible mechanism is its action in unlocking γ-gene, increasing the γ-globin expression and enhancing HbF synthesis so as to compensate for the gene defect. This study has opened a new path for the treatment of β-thalassemia with TCM. [ABSTRACT FROM AUTHOR]