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Abstract Background Corynebacterium glutamicum is a well-known producer of various l-amino acids in industry. During the fermenting process, C. glutamicum unavoidably encounters oxidative stress due to a specific reactive oxygen species (ROS) produced by consistent adverse conditions. To combat the ROS, C. glutamicum has developed many common disulfide bond-based regulatory devices to control a specific set of antioxidant genes. However, nothing is known about the mixed disulfide between the protein thiol groups and the mycothiol (MSH) (S-mycothiolation)-based sensor. In addition, no OhrR (organic hydroperoxide resistance regulator) homologs and none of the organic hydroperoxide reductase (Ohr) sensors have been described in the alkyl hydroperoxide reductase CF-missing C. glutamicum, while organic hydroperoxides (OHPs)-specific Ohr was a core detoxification system. Results In this study, we showed that the C. glutamicum OhsR acted as an OHPs sensor that activated ohr expression. OhsR conferred resistance to cumene hydroperoxide (CHP) and t-butyl hydroperoxide but not H2O2, hypochlorous acid, and diamide; this outcome was substantiated by the fact that the ohsR-deficient mutant was sensitive to OHPs but not inorganic peroxides. The DNA binding activity of OhsR was specifically activated by CHP. Mutational analysis of the two cysteines (Cys125 and Cys261) showed that Cys125 was primarily responsible for the activation of DNA binding. The oxidation of Cys125 produced a sulfenic acid (C125-SOH) that subsequently reacted with MSH to generate S-mycothiolation that was required to activate the ohr expression. Therefore, OhsR regulated the ohr expression using an S-mycothiolation mechanism in vivo. Conclusion This is the first report demonstrating that the regulatory OhsR specifically sensed OHPs stress and responded to it by activating a specific ohr gene under its control using an S-mycothiolated mechanism.

Triticum aestivum xylanase inhibitor (TaXI) gene plays an important role in plant defense. Recently, TaXI–III inhibitor has been shown to play a dual role in wheat resistance to Fusarium graminearum infection. Thus, identifying the members of the TaXI gene family and clarifying its role in wheat resistance to stresses are essential for wheat resistance breeding. However, to date, no comprehensive research on TaXIs in wheat (Triticum aestivum L.) has been conducted. In this study, a total of 277 TaXI genes, including six genes that we cloned, were identified from the recently released wheat genome database (IWGSC RefSeq v1.1), which were unevenly located on 21 chromosomes of wheat. Phylogenetic analysis divided these genes into six subfamilies, all the six genes we cloned belonged to XI-2 subfamily. The exon/intron structure of most TaXI genes and the conserved motifs of proteins in the same subfamily are similar. The TaXI gene family contains 92 homologous gene pairs or clusters, 63 and 193 genes were identified as tandem replication and segmentally duplicated genes, respectively. Analysis of the cis-acting elements in the promoter of TaXI genes showed that they are involved in wheat growth, hormone-mediated signal transduction, and response to biotic and abiotic stresses. RNA-seq data analysis revealed that TaXI genes exhibited expression preference or specificity in different organs and developmental stages, as well as in diverse stress responses, which can be regulated or induced by a variety of plant hormones and stresses. In addition, the qRT-PCR data and heterologous expression analysis of six TaXI genes revealed that the genes of XI-2 subfamily have double inhibitory effect on GH11 xylanase of F. graminearum, suggesting their potential important roles in wheat resistance to F. graminearum infection. The outcomes of this study not only enhance our understanding of the TaXI gene family in wheat, but also help us to screen more candidate genes for further exploring resistance mechanism in wheat.

Abstract Background and aims 4‐phenylbutyric acid (4‐PBA) is a low molecular weight fatty acid that is used in clinical practice to treat inherited urea cycle disorders. In previous reports, it acted as a chemical chaperone inhibiting endoplasmic reticulum (ER) stress and unfolded protein response signaling. A few studies have suggested its function against hepatic fibrosis in mice models. However, its role in hepatocarcinogenesis remained unknown. Methods 4‐PBA was administered alone or in combination with diethylnitrosamine to investigate its long‐term effect on liver tumorigenesis. The role of 4‐PBA in oncogene‐induced hepatocellular carcinoma (HCC) mice model using sleeping beauty system co‐expressed with hMet and β‐catenin point mutation (S45Y) was also observed. RNA‐seq and PCR array were used to screen the pathways and genes involved. In vitro and in vivo studies were conducted to explore the effect of 4‐PBA on liver and validate the underlying mechanism. Results 4‐PBA alone didn't cause liver tumor in long term. However, it promoted liver tumorigenesis in HCC mice models via initiation of liver cancer stem cells (LCSCs) through Wnt5b‐Fzd5 mediating β‐catenin signaling. Peroxisome proliferator‐activated receptors (PPAR)‐α induced by 4‐PBA was responsible for the activation of β‐catenin signaling. Thus, intervention of PPAR‐α reversed 4‐PBA‐induced initiation of LCSCs and HCC development in vivo. Further study revealed that 4‐PBA could not only upregulate the expression of PPAR‐α transcriptionally but also enhance its stabilization via protecting it from proteolysis. Moreover, high PPAR‐α expression predicted poor prognosis in HCC patients. Conclusions 4‐PBA could upregulate PPAR‐α to initiate LCSCs by activating β‐catenin signaling pathway, promoting HCC at early stage. Therefore, more discretion should be taken to monitor the potential tumor‐promoting effect of 4‐PBA under HCC‐inducing environment.

Background: The viral shedding time (VST) of SARS-CoV-2 mainly determines its transmission and duration of infectiousness. However, it was heterogeneous in the existing studies. Here, we performed a meta-analysis to comprehensively summarize the VST of SARS-CoV-2.Methods: We searched PubMed, Web of Science, MedRxiv, BioRxiv, CNKI, CSTJ, and Wanfang up to October 25, 2020, for studies that reported VSTs of SARS-CoV-2. Pooled estimates and 95% CIs for the VSTs were calculated using log-transformed data. The VSTs in SARS-CoV-2 infections based on different demographic and clinical characteristics, treatments and specimens were stratified by subgroup analysis.Results: A total of 35 studies involving 3,385 participants met the inclusion criteria. The pooled mean VST was 16.8 days (95% CI: 14.8–19.4, I2 = 99.56%) in SARS-CoV-2 infections. The VST was significantly longer in symptomatic infections (19.7 days, 95% CI: 17.2–22.7, I2 = 99.34%) than in asymptomatic infections (10.9 days, 95% CI: 8.3–14.3, I2 = 98.89%) (P < 0.05). The VST was 23.2 days (95% CI: 19.0–28.4, I2 = 99.24%) in adults, which was significantly longer than that in children (9.9 days, 95% CI: 8.1–12.2, I2 = 85.74%) (P < 0.05). The VST was significantly longer in persons with chronic diseases (24.2 days, 95% CI: 19.2–30.2, I2 = 84.07%) than in those without chronic diseases (11.5 days, 95% CI: 5.3–25.0, I2 = 82.11%) (P < 0.05). Persons receiving corticosteroid treatment (28.3 days, 95% CI: 25.6–31.2, I2 = 0.00%) had a longer VST than those without corticosteroid treatment (16.2 days, 95% CI: 11.5–22.5, I2 = 92.27%) (P = 0.06). The VST was significantly longer in stool specimens (30.3 days, 95% CI: 23.1–39.2, I2 = 92.09%) than in respiratory tract specimens (17.5 days, 95% CI: 14.9–20.6, I2 = 99.67%) (P < 0.05).Conclusions: A longer VST was found in symptomatic infections, infected adults, persons with chronic diseases, and stool specimens.

The management of diabetic wounds is a therapeutic challenge in clinical settings. Current tissue engineering strategies for diabetic wound healing are insufficient, owing to the lack of an appropriate scaffold that can load a large number of stem cells and induce the interaction of stem cells to form granulation tissue. Herein we fabricated a book-shaped decellularized dermal matrix (BDDM), which shows a high resemblance to native dermal tissue in terms of its histology, microstructure, and ingredients, is non-cytotoxic and low-immunogenic, and allows adipose-derived stromal cell (ASC) attachment and proliferation. Then, a collagen-binding domain (CBD) capable of binding collagen was fused into basic fibroblast growth factor (bFGF) to synthetize a recombinant growth factor (termed as CBD–bFGF). After that, CBD–bFGF was tethered onto the collagen fibers of BDDM to improve its endothelial inducibility. Finally, a functional scaffold (CBD–bFGF/BDDM) was fabricated. In vitro and in vivo experiments demonstrated that CBD–bFGF/BDDM can release tethered bFGF with a sustained release profile, steadily inducing the interaction of stem cells down to endothelial differentiation. ASCs were cultured to form a cell sheet and then sandwiched by CBD–bFGF/BDDM, thus enlarging the number of stem cells loaded into the scaffold. Using a rat model, the ASC sheets sandwiched with CBD–bFGF/BDDM (ASCs/CBD–bFGF/BDDM) were capable of enhancing the formation of granulation tissue, promoting angiogenesis, and facilitating collagen deposition and remodeling. Therefore, the findings of this study demonstrate that ASCs/CBD–bFGF/BDDM could be applicable for diabetic wound healing.

The AP2/ERF is a large protein family of transcription factors, playing an important role in signal transduction, plant growth, development, and response to various stresses. AP2/ERF super-family is identified and functionalized in a different plant but no comprehensive and systematic analysis in wheat (Triticum aestivum L.) has been reported. However, a genome-wide and functional analysis was performed and identified 322 TaAP2/ERF putative genes from the wheat genome. According to the phylogenetic and structural analysis, TaAP2/ERF genes were divided into 12 subfamilies (Ia, Ib, Ic, IIa, IIb, IIc, IIIa, IIIb, IIIc, IVa, IVb, and IVc). Furthermore, conserved motifs and introns/exons analysis revealed may lead to functional divergence within clades. Cis-Acting analysis indicated that many elements were involved in stress-related and plant development. Chromosomal location showed that 320 AP2/ERF genes were distributed among 21 chromosomes and 2 genes were present in a scaffold. Interspecies microsynteny analysis revealed that maximum orthologous between Arabidopsis, rice followed by wheat. Segment duplication events have contributed to the expansion of the AP2/ERF family and made this family larger than rice and Arabidopsis. Additionally, AP2/ERF genes were differentially expressed in wheat seedlings under the stress treatments of heat, salt, and drought, and expression profiles were verified by qRT-PCR. Remarkably, the RNA-seq data exposed that AP2/ERF gene family might play a vital role in stress-related. Taken together, our findings provided useful and helpful information to understand the molecular mechanism and evolution of the AP2/ERF gene family in wheat.

Background: This study aims to explore the role of low-dose rivaroxaban (≤10 mg daily) for the treatment of atherosclerotic cardiovascular disease (ASCVD).Methods: PubMed, Embase and the Cochrane Library were searched for randomized controlled trials (RCTs) of low-dose rivaroxaban in patients with ASCVD including coronary artery disease (CAD) and peripheral artery disease (PAD). Literature screening, data extraction, and risk of bias assessment were carried out independently by two researchers. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using random-effect models to determine risks of outcomes in ASCVD patients treated with rivaroxaban and comparators, and meta-analysis was conducted via Review Manager 5.3.5 software.Results: 3,768 records were obtained through literature search, and 9 articles representing 6 RCTs ultimately qualified for this study. The meta-analysis indicated that for patients with CAD, the addition of rivaroxaban (5 mg daily) to aspirin could significantly reduce the risk of major adverse cardiovascular events (MACEs) compared with aspirin alone (HR 0.81, 95% CI, 0.72 to 0.91, p = 0.0004, I2 = 60%, 4 studies). For PAD patients receiving rivaroxaban (5 mg daily) plus aspirin, there was no significant reduction in the risk of MACEs (HR 0.84, 95% CI, 0.63 to 1.13, p = 0.25, I2 = 74%, 2 studies); however, there was significant reduction in major adverse limb events (MALEs) (HR 0.54, 95% CI, 0.35 to 0.83, p = 0.005, one studies) and in the composite of MACEs or MALEs (HR 0.78, 95% CI, 0.64 to 0.95, p = 0.02, I2 = 66%, 2 studies) when compared with patients receiving aspirin alone. Meanwhile, rivaroxaban combined with aspirin significantly increased the risk of International Society on Thrombosis and Haemostasis (ISTH) major bleeding compared with aspirin alone in patients with CAD (HR 1.74, 95% CI, 1.43 to 2.13, p < 0.00001, I2 = 0%, 2 studies) and PAD (HR 1.47, 95% CI, 1.19 to 1.83, p = 0.0004, I2 = 0%, 2 studies).Conclusions: Compared with standard antiplatelet therapy, the addition of a 5 mg daily dose of rivaroxaban to standard antiplatelet therapy may improve cardiovascular or limb outcomes of patients with ASCVD, with an increase in major bleeding. Patients who would benefit from the addition of low-dose rivaroxaban to antiplatelet agents and appropriate dual-pathway antithrombotic strategies should be identified in clinical practice to individualize antithrombotic therapy.

IntroductionBasal cell carcinoma (BCC) located on the genitalia is rare; data on the clinicopathologic features and survival outcomes are only available through case reports and small case series studies.PurposeThis study aimed to explore the epidemiology and identify the prognostic factors of genital BCCs.MethodsWe queried the 18 registries of the Surveillance, Epidemiology, and End Results database for patients with primary BCCs of the genital skin from 2000 through 2017. The primary endpoint was overall survival (OS) and disease specific survival (DSS). Kaplan-Meier survival analysis was conducted to assess the impact of clinicopathological variables on OS and DSS. Multivariate Cox proportional hazards model was performed to evaluate risk factors for OS.ResultsA total of 1,607 cases of genital BCCs were identified. The cohort was composed of 1,352 women (84.1%) and 255 men (15.9%). The median (P25, P75) age of the entire cohort was 73(63–82)years. White patients accounted for 87.2% of the cases. For women and men, the most common site of involvement was the labia majora (89.6%) and scrotum (74.5%), respectively. The majority of patients with genital BCC had localized disease (75.5%). Kaplan-Meier survival analysis showed that female genital BCCs experienced better DSS than men (209.1 months vs 194.8 months); for men, BCCs located on the scrotum had better DSS and OS than those on the penis (P < 0.05 for both endpoints). All patients with distant disease died of disease-specific death, and the average survival time was 8.2 months. Multivariate analysis revealed that age, primary site, and stage were independent determinants of OS for men, while tumor size, histologic subtype, and race were not. For women, factors associated with worse OS included increasing age, tumor size more than 2 cm, and distant disease; factors associated with a decreased risk included “other” and “unknown” races.ConclusionThe prognosis of genital BCCs is excellent, while the survival of distant disease is very poor. Despite similar clinicopathologic features and overall survival outcomes, men and women should be treated as two different entities when making survival predictions.

Dynamic path flows, referring to the number of vehicles that choose each path in a network over time, are generally estimated with the partial observations as the input. The automatic vehicle identification (AVI) system and probe vehicle trajectories are now popular and can provide rich and complementary trip information, but the data fusion was rarely explored. Therefore, in this paper, the dynamic path flow estimation is based on these two data sources and transformed into a feature learning problem. To fuse the two data sources belonging to different detection ways at the data level, the virtual AVI points, analogous to the real AVI points (turning movements at nodes with AVI detectors), are defined and selected to statically observe the dynamic movement of the probe vehicles. The corresponding selection principles and a programming model considering the distribution of real AVI points are first established. The selected virtual AVI points are used to construct the input tensor, and the turning movement-based observations from both the data sources can be extracted and fused. Then, a three-dimensional (3D) convolutional neural network (CNN) model is designed to exploit the hidden patterns from the tensor and establish the high-dimensional correlations with path flows. As the path flow labels commonly with noises, the bootstrapping method is adopted for model training and the corresponding relabeling principle is defined to purify the noisy labels. The entire model is extensively tested based on a realistic road network, and the results show that the designed CNN model with the presented data fusion method can perform well in training time and estimation accuracy. The robustness of a model to noisy labels is also improved through the bootstrapping method. The dynamic path flows estimated by the trained model can be applied to travel information provision, proactive route guidance, and signal control with high real-time requirements.

Background: Measles transmissions due to case importations challenge public health systems globally and herd immunities in all countries. In 2019, an imported measles case and its subsequently outbreak was found in the Zhoushan Islands. Here, the process of epidemiological investigation and virus tracing were summarized to provide references for the prevention and control of measles in the future.Materials and methods: The data on the demographic, epidemiological, and clinical manifestation of measles cases in this outbreak were collected. The 450 bp fragments of the measles virus (MeV) N gene were amplified and sequenced. The genome of the first imported case was further isolated. Then, the maximum-likelihood and time-scaled phylogenetic analysis was conducted.Results: A total of 28 measles cases were confirmed. Their onsets were between March 13 and May 18, 2019. The first patient was from the Ukraine. He was confirmed at the Fever Clinic in Zhoushan hospital on March 15, 2019 and at the same time, another patient had visited the hospital due to another illness and 10 days later, this second case had onset (March 25, 2019). The epidemic curve shows sustained community transmission. The majority of the following cases (19/26) were clustered on the Donggang street which was close to where the second case worked. The 22 measles virus strains successfully isolated from this outbreak all belonged to the D8.2a sub-cluster and clustered with the KY120864/MVs/GirSomnath.IND/42.16/[D8] which was the predominant genotype in the Ukraine during 2018-2019. The analysis of the complete D8 genotype genome pointed to the fact that this prevailing strain originated from India in 2015 and its substitution rate was estimated as 6.91 × 10−4 (5.64–7.98 × 10−4) nucleotide substitutions/site/year.Conclusion: This outbreak was caused by an imported case from the Ukraine. There was a possible nosocomial infection between the first case and the second case. Then, the second case played an important role in the spread of virus due to her occupation. The molecular phylogenetic analysis could help to track the origin of the virus. Increasing and maintaining the high level of vaccination coverage (≥95%) and an efficient response to imported cases are essential to prevent and control the recurrence and outbreak of measles virus.

Paper packaging materials are widely used as sustainable green materials in food packaging. The production or processing of paper materials is conducted in an environment that contains organic chlorides; therefore, potential food safety issues exist. In this study, the adsorption behavior of organic chlorides on paper materials was investigated. Chloropropanol, which has been extensively studied in the field of food safety, was employed as the research object. We studied the adsorption mechanism of chloropropanol on a crystalline nanocellulose (CNC) model. The results demonstrated that physical adsorption was the prevailing process, and the intermolecular hydrogen bonds acted as the driving force for adsorption. The adsorption effect assumed greatest significance under neutral and weakly alkaline conditions. A good linear relationship between the amount of chloropropanol adsorbed and the amount of CNC used was discovered. Thus, the findings of this study are crucial in monitoring the safety of products in systems containing chloropropanol and other chlorinated organic substances. This is particularly critical in the production of food-grade paper packaging materials.

Objective To compare the test-retest reliability and validity of three simple maximal isometric back extensor strength (BES) assessment protocols with different test postures, and to recommend an optimal clinical protocol to quantify BES. Methods Asymptomatic adults, aged over 45 years, were assessed for maximal isometric BES using external fixation of dynamometers, with the subject in standing, prone and sitting positions, respectively. Measurements were repeated at a one-week interval to examine test-retest reliability. Validation was performed by comparing with results obtained from isokinetic dynamometer assessments. Results Out of a total of 60 included participants, intra-class correlation coefficients (ICC) were 0.92, 0.93 and 0.90 in standing, prone and sitting positions, respectively. Correlation analyses revealed acceptable convergent validity in the standing and prone position (r = 0.50 and 0.54, respectively), whereas tests conducted in the sitting position showed a relatively low validity (r = 0.32). Among the three protocols, measurement error was lowest in the prone position. Conclusions Maximal isometric BES assessment in the prone position was shown to be the most reliable and valid protocol, and may be considered the preferred option for assessing BES in clinical practice.

Background Patients suffering from postoperative recurrent glioblastoma have an extremely unfavorable outcome because there are no proven therapeutic options. The median overall survival for those with relapsed glioblastoma after surgery is only 7.5 months. Case presentation: Between March 2015 and October 2019, a 44-year-old female patient with recurrent glioblastoma was treated by our medical team. After several failed rounds of therapy, the patient was subsequently treated with the anti-programmed death (PD)-1 antibody nivolumab, anti-vascular endothelial growth factor (VEGF) antibody bevacizumab, and cytotoxic agent temozolomide. Results The patient showed a sustainable complete response to the regimen. To date, there have been no serious toxic side effects. As of October 2019 (the last follow-up), the patient has been in complete remission for 17 months since recurrence. Conclusion The experience of this complicated case indicates the possible application of immune checkpoint inhibitors, anti-angiogenesis agents, and cytotoxic reagents for recurrent glioblastoma. The administration of this three-agent regimen appears safe and effective. However, further clinical trials are warranted.

Abstract Rice planthoppers and related viral diseases have become one of the most important factors affecting rice production in Asian countries, and the resulting abuse of pesticides is laying a hidden danger for future food security. As the most economically devastating species, the brown planthopper, Nilaparvata lugens (Stål), moves from the tropical Indochina Peninsula to temperate regions where it cannot overwinter annually with the feature of long‐range migration, and eventually appears in paddy fields of most East Asian countries. Compared with the overland migration that has been studied in more detail, there is relatively less understanding of N. lugens’ performance in transnational movement, especially in the representative overseas migration between China and Northeast Asia. Based on the light‐trap data from China and Korea and the matched meteorological data of East Asia in 2016, a typical overseas migration event was basically analyzed. The results are as follows. First, the source area of the N. lugens population in this migration was in southeastern Jiangsu and eastern Shanghai. They took off at dusk on 1 August, flying at the altitude of 1700–2200 m, and landed in southwestern Korea at 02:00–11:00 UTC on 3 August. Second, a southerly airflow belt was the main weather factor for population's overseas migration, and the confrontation between the western Pacific subtropical high and a northern high pressure in southern Korea was the main reason for population to land. Besides, we discussed the one‐off feature of overseas migration compared to overland migration. These results show the close relation between weather systems and the migration dynamics of N. lugens and may extend the perception for N. lugens’ behavioral chain in the long‐range migration between China and Northeast Asia, thus allowing a sufficient time for reasonable and effective control measures.

Current cell-based therapies on musculoskeletal tissue regeneration were mostly determined in rodent models. However, a direct translation of those promising cell-based therapies to humans exists a significant hurdle. For solving this problem, canine has been developed as a new large animal model to bridge the gap from rodents to humans. In this study, we reported the isolation and characterization of urine-derived stem cells (USCs) from mature healthy beagle dogs. The isolated cells showed fibroblast-like morphology and had good clonogenicity and proliferation. Meanwhile, these cells positively expressed multiple markers of MSCs (CD29, CD44, CD90, and CD73), but negatively expressed for hematopoietic antigens (CD11b, CD34, and CD45). Additionally, after induction culturing, the isolated cells can be differentiated into osteogenic, adipogenic, chondrogenic, and tenogenic lineages. The successful isolation and verification of USCs from canine were useful for studying cell-based therapies and developing new treatments for musculoskeletal injuries using the preclinical canine model.

Abstract The emergency treatment of thoracic injuries varies of general conditions and modern warfare. However, there are no unified battlefield treatment guidelines for thoracic injuries in the Chinese People’s Liberation Army (PLA). An expert consensus has been reached based on the epidemiology of thoracic injuries and the concept of battlefield treatment combined with the existing levels of military medical care in modern warfare. Since there are no differences in the specialized treatment for thoracic injuries between general conditions and modern warfare, first aid, emergency treatment, and early treatment of thoracic injuries are introduced separately in three levels in this consensus. At Level I facilities, tension pneumothorax and open pneumothorax are recommended for initial assessment during the first aid stage. Re-evaluation and further treatment for hemothorax, flail chest, and pericardial tamponade are recommended at Level II facilities. At Level III facilities, simple surgical operations such as emergency thoracotomy and debridement surgery for open pneumothorax are recommended. The grading standard for evidence evaluation and recommendation was used to reach this expert consensus.

Understanding about land cover and land use (LCLU) changes, as well as the associated impacts on ecosystem service values (ESV) is extremely important in the management of coastal ecosystems globally. Thus, this study assessed temporal LCLU changes, the underlying socioeconomic drivers and dynamics of ESV in the coastal zone of Tanzania. The LCLU data for 2000 and 2010 were from the Globe Land 30 mapping products at 30-meter spatial resolution developed by National Geomatics Center of China, while 2016 images were produced from Landsat 8. Classification of images was done from Landsat TM/ETM+ for 2000, 2010, and 2016 years complemented with MODIS and Normalized Difference Vegetation Index time series, and Chinese HJ imagery. LCLU categories and ecosystem service coefficients were used to compute ESV on each LCLU categories. Between 2000 and 2016, farmland, shrub land, waterbody, and artificial surface expanded while forest, grazing land, and wetlands declined. The ESV increased on farmland, shrub land, and waterbody, while the decline was found on forest, grazing land, and wetlands. The ESV and the total population ratios declined from $80.4, 63.8, and $46.0 million in 2000, 2010, and 2016, respectively. Perfect positive correlation was on LCLU change and ESV, population and households in crop farming, livestock keeping, and bioenergy use. Population pressure and socioeconomic activities have amplified the degradation of the coastal ecosystems. If not abetted, there is a danger of further impairments on these ecosystems. We advise to regulate population and socioeconomic activities to avoid more negative impacts of coastal LCLU change.

Abstract Background To evaluate synchrotron radiation-based Fourier transform infrared microspectroscopy (SR-FTIR) as a tool for quantitative mapping of the content and distribution of the extracellular matrix in decellularized fibrocartilage bioscaffolds, and to provide a new platform for quantitatively characterizing bioscaffolds for tissue engineering. Methods Fibrocartilage was harvested and cut into book-shape bioscaffolds (N = 54), which were then decellularized. The structures and distribution of collagen fibrous and intrinsic ultrastructure in decellularized fibrocartilage bioscaffolds were evaluated by histological staining and scanning electron microscopy (SEM), respectively. The content of collagen and proteoglycan in the cellularized or decellularized bioscaffolds were also measured by SR-FTIR and biochemical assay. Results Book-shape fibrocartilage decellularized bioscaffolds were successfully obtained. Histological examination revealed that the structure of extracellular matrix endured during decellularization. Histology and DNA quantification analysis confirmed substantial removal of cells during decellularization. SEM demonstrated that intrinsic ultrastructure of the fibrocartilage bioscaffold was also well preserved. SR-FTIR quantitative analysis confirmed that decellularization had a significant effect on the content and distribution of collagen and proteoglycan in fibrocartilage bioscaffolds, these results are confirmed with the biochemical assay results. Conclusion SR-FTIR imaging can capture the histological morphology of decellularized bioscaffolds. Moreover, it can be used for quantitative mapping of the content and distribution of collagen in the bioscaffolds.

Background/Aims: Stem cell-derived exosomes (EXs) offer protective effects on various cells via their carried microRNAs (miRs). Meanwhile, miR-210 has been shown to reduce mitochondrial reactive oxygen species (ROS) overproduction. In this study, we determined the potential effects of endothelial progenitor cell-derived EXs (EPC-EXs) on hypoxia/ reoxygenation (H/R) injured endothelial cells (ECs) and investigated whether these effects could be boosted by miR-210 loading. Methods: Human EPCs were used to generate EPC-EXs, or transfected with scrambler control or miR-210 mimics to generate EPC-EXssc and EPC-EXsmiR-210. H/R-injured human ECs were used as a model for functional analysis of EXs on apoptosis, viability, ROS production and angiogenic ability (migration and tube formation) by flow cytometry, MTT, dihydroethidium and angiogenesis assay kits, respectively. For mechanism analysis, the mitochondrion morphology, membrane potential (MMP), ATP level and the expression of fission/fusion proteins (dynamin-related protein 1: drp1 and mitofusin-2: mfn2) were assessed by using JC-1 staining, ELISA and western blot, respectively. Results: 1) Transfection of miR-210 mimics into EPCs induced increase of miR-210 in EPC-EXsmiR-210 without change of average size; 2) EPC-EXsmiR-210, but not EPC-EXs or EPC-EXssc, significantly elevated miR-210 level in ECs; 3) EPC-EXsmiR-210 were more effective than EPC-EXs and EPC-EXssc in reducing H/R-induced EC apoptosis, ROS overproduction and angiogenic dysfunction; 4) EPC-EXs decreased mitochondrial fragmentation, elevated MMP and ATP level, as well as improved mitochondrial mfn2 and drp1 dysregulation, which were more effective in EPC-EXsmiR-210. Conclusion: Our results suggest that EPC-EXs protect ECs against H/R injury via improving mitochondrial function and miR-210 enrichment could boost their effects.

Linear power flow (LPF) is necessary for robust and fast centralized control of active distribution networks (ADNs). With penetration of distributed generators (DGs) into ADN, voltage-controlled nodes are becoming more common, to maintain a normal voltage profile in the distribution network. Existing three-phase LPF formulations under a rectangular coordinate system cannot cope with local voltage-controlled nodes, and does not consider multi-slack-node features of three-phase distribution network, detailed control characteristics and loss participation features of DGs. Here, a general three-phase LPF under a polar coordinate system is presented to address these issues. The proposed method can account for various connection ZIP loads, transformers, and single-phase or three-phase DGs. The detailed control model of the DGs and the distributed slack bus are taken into account. The effectiveness and advantages of the proposed method are validated with balanced 33, 70, 84, 119, and 874-node networks and modified IEEE 13, 34, 37, and 123 unbalanced networks.

In the past decades, as an emerging omic, metabolomics has been widely used in meat science research, showing promise in meat quality analysis and meat authentication. This review first provides a brief overview of the concept, analytical techniques, and analysis workflow of metabolomics. Additionally, the metabolomics research in quality analysis and authentication of meat is comprehensively described. Finally, the limitations, challenges, and future trends of metabolomics application in meat quality analysis and meat authentication are critically discussed. We hope to provide valuable insights for further research in meat quality.

Blockchain is a promising technology in the context of digital healthcare systems, but there are issues related to the control of accessing the electronic health records. In this paper, we propose a novel framework based on blockchain and multiple certificate authority that implement smart contracts and access health records securely. Our proposed solution provides the facilities of flexible policies to update a record or invoke the policy such that a patient has complete authority. A novel approach towards multiple certificate’s authority (CA) is introduced in the design through our proposed framework. Our proposed policies and methods overcome the shortcoming and security breaches faced by single certificate authority. Our proposed scheme provides a flexible access control mechanism for securing electronic health records as compared to the existing benchmark models. Moreover, our proposed method provides a re-enrolment facility in the case of a user lost enrolment.

The contact-dependent type VI secretion system (T6SS) in diverse microbes plays crucial roles in both inter-bacterial and bacteria-host interactions. As numerous microorganisms inhabit the intestinal ecosystem at a high density, it is necessary to consider the functions of T6SS in intestinal bacteria. In this mini-review, we discuss T6SS-dependent functions in intestinal microbes, including commensal microbes and enteric pathogens, and list experimentally verified species of intestinal bacteria containing T6SS clusters. Several seminal studies have shown that T6SS plays crucial antibacterial roles in colonization resistance, niche occupancy, activation of host innate immune responses, and modulation of host intestinal mechanics. Some potential roles of T6SS in the intestinal ecosystem, such as targeting of single cell eukaryotic competitors, competition for micronutrients, and stress resistance are also discussed. Considering the distinct activities of T6SS in diverse bacteria residing in the intestine, we suggest that T6SS research in intestinal microbes may be beneficial for the future development of new medicines and clinical treatments.

Abstract Reactive oxygen species (ROS) generated in aerobic metabolism and oxidative stress lead to macromolecules damage, such as to proteins, lipids, and DNA, which can be eliminated by the redox buffer mycothiol (AcCys‐GlcN‐Ins, MSH). Myo‐inositol‐phosphate synthase (Ino‐1) catalyzes the first committed step in the synthesis of MSH, thus playing a critical role in the growth of the organism. Although Ino‐1s have been systematically studied in eukaryotes, their physiological and biochemical functions remain largely unknown in bacteria. In this study, we report that Ino‐1 plays an important role in oxidative stress resistance in the gram‐positive Actinobacteria Corynebacterium glutamicum. Deletion of the ino‐1 gene resulted in a decrease in cell viability, an increase in ROS production, and the aggravation of protein carbonylation levels under various stress conditions. The physiological roles of Ino‐1 in the resistance to oxidative stresses were corroborated by the absence of MSH in the Δino‐1 mutant. In addition, we found that the homologous expression of Ino‐1 in C. glutamicum yielded a functionally active protein, while when expressed in Escherichia coliBL21(DE3), it lacked measurable activity. An examination of the molecular mass (Mr) suggested that Ino‐1 expressed in E. coliBL21(DE3) was not folded in a catalytically competent conformation. Together, the results unequivocally showed that Ino‐1 was important for the mediation of oxidative resistance by C. glutamicum.

Genetic engineering of probiotics, like bifidobacteria, may improve their microbial cell factory economy. This work designed a novel shuttle plasmid pBPES, which bears exogenous appA and is stable within Bifidobacterium longum JCM 1217. Cloning of three predicted promoters into pBPES proved that all of them drive appA expression in B. longum JCM 1217. Transformation of plasmids pBPES-tu and pBPES-groEL into B. longum JCM1217 resulted in much more phytase secretion suggests Ptu and PgroEL are strong promoters. Further in vitro and in vivo experiments suggested B. longum JCM 1217/pBPES-tu degrades phytate efficiently. In conclusion, the study screened two stronger promoters and constructed a recombinant live probiotic strain for effectively phytase secretion and phytate degradation in gut. The strategy used in the study provided a novel technique for improving the bioaccessibility of phytate and decreasing phosphorus excretion.

[This corrects the article DOI: 10.1371/journal.pone.0124724.].

Autonomous systems need to localize and track surrounding objects in 3D space for safe motion planning. As a result, 3D multi-object tracking (MOT) plays a vital role in autonomous navigation. Most MOT methods use a tracking-by-detection pipeline, which includes both the object detection and data association tasks. However, many approaches detect objects in 2D RGB sequences for tracking, which lacks reliability when localizing objects in 3D space. Furthermore, it is still challenging to learn discriminative features for temporally consistent detection in different frames, and the affinity matrix is typically learned from independent object features without considering the feature interaction between detected objects in the different frames. To settle these problems, we first employ a joint feature extractor to fuse the appearance feature and the motion feature captured from 2D RGB images and 3D point clouds, and then we propose a novel convolutional operation, named RelationConv, to better exploit the correlation between each pair of objects in the adjacent frames and learn a deep affinity matrix for further data association. We finally provide extensive evaluation to reveal that our proposed model achieves state-of-the-art performance on the KITTI tracking benchmark.

Stripe rust is a serious foliar disease posing a grave threat to wheat production worldwide. The most economical and environmentally friendly way to control this disease is to breed and deploy resistant cultivars. Zhongmai 175 is an elite winter wheat cultivar conferring resistance to a broad spectrum of Puccinia striiformis f. sp. tritici (Pst) races. To identify the resistance gene in the cultivar, genetic analysis was conducted using the parents, F1, F2 and F2:3 populations derived from the cross of Lunxuan 987/Zhongmai 175. Segregations in the F2 and F2:3 populations indicated a single dominant gene conferring resistance to stripe rust in Zhongmai 175, temporarily designated YrZM175. Bulked segregant analysis (BSA) with wheat iSelect 90K SNP array determined a preliminary location of YrZM175. Subsequently, YrZM175 was mapped on chromosome 2AS using simple sequence repeats (SSR), expressed sequence tags (EST) and newly-developed kompetitive allele specific PCR (KASP) markers, being flanked by Xgwm636 and Xwmc382 at genetic distances of 4.9 and 8.1 cM, respectively. Comparison of reaction patterns of YrZM175 on 23 Pst races or isolates and pedigree analysis with other genes on chromosome 2AS suggested that it is likely to be a new gene for resistance to stripe rust. The resistance gene and linked molecular markers will be useful in wheat breeding targeting for the improvement of stripe rust resistance.

Major cardiovascular risk factors in China, such as hyperlipidemia, hypertension, dietary factors, exposure to tobacco, diabetes, obesity and physical inactivity, have contributed to deteriorating trends in cardiovascular disease (CVD) deaths. In past years, a number of CVD prevention programs have been initiated in European and American countries and successfully brought down CVD related death rate by involving various parties such as physicians, patients, government agencies and payers. However, there is rare published literature that systemically reviewed such experience, which would be highly valuable for China and other countries with high CVD burden. In this article, we review the published literature on CVD prevention and control programs and report on interviews of local and foreign experts to provide recommendations for China-specific CVD prevention and control programs. In order to provide practical suggestions, we describe the type of programs as patient, physician, pharmacist, nurse, or payer-focused. Based on this evidence and identified challenges in China, programs focusing on disease management, treatment adherence, physician/health care provider education, financial incentives, and integrated healthcare are recommended for the prevention and control of CVD in China.

Change detection for high-resolution remote sensing images is more and more widespread in the application of monitoring the Earth’s surface. However, on the one hand, the ground truth could facilitate the distinction between changed and unchanged areas, but it is hard to acquire them. On the other hand, due to the complexity of remote sensing images, it is difficult to extract features of difference, let alone the construction of the classification model that performs change detection based on the features of difference in each pixel pair. Aiming at these challenges, this paper proposes a weakly supervised change detection method based on edge mapping and Stacked Denoising Auto-Encoders (SDAE) network called EM-SDAE. We analyze the difference in edge maps of bi-temporal remote sensing images to acquire part of the ground truth at a relatively low cost. Moreover, we design a neural network based on SDAE with a deep structure, which extracts the features of difference so as to efficiently classify changed and unchanged regions after being trained with the ground truth. In our experiments, three real sets of high-resolution remote sensing images are employed to validate the high efficiency of our proposed method. The results show that accuracy can even reach up to 91.18% with our method. In particular, compared with the state-of-the-art work (e.g., IR-MAD, PCA-k-means, CaffeNet, USFA, and DSFA), it improves the Kappa coefficient by 27.19% on average.

In recent years, the development of convolutional neural networks (CNNs) has promoted continuous progress in scene classification of remote sensing images. Compared with natural image datasets, however, the acquisition of remote sensing scene images is more difficult, and consequently the scale of remote sensing image datasets is generally small. In addition, many problems related to small objects and complex backgrounds arise in remote sensing image scenes, presenting great challenges for CNN-based recognition methods. In this article, to improve the feature extraction ability and generalization ability of such models and to enable better use of the information contained in the original remote sensing images, we introduce a multitask learning framework which combines the tasks of self-supervised learning and scene classification. Unlike previous multitask methods, we adopt a new mixup loss strategy to combine the two tasks with dynamic weight. The proposed multitask learning framework empowers a deep neural network to learn more discriminative features without increasing the amounts of parameters. Comprehensive experiments were conducted on four representative remote sensing scene classification datasets. We achieved state-of-the-art performance, with average accuracies of 94.21%, 96.89%, 99.11%, and 98.98% on the NWPU, AID, UC Merced, and WHU-RS19 datasets, respectively. The experimental results and visualizations show that our proposed method can learn more discriminative features and simultaneously encode orientation information while effectively improving the accuracy of remote sensing scene classification.

In order to achieve a better performance for point cloud analysis, many researchers apply deep neural networks using stacked Multi-Layer-Perceptron (MLP) convolutions over an irregular point cloud. However, applying these dense MLP convolutions over a large amount of points (e.g., autonomous driving application) leads to limitations due to the computation and memory capabilities. To achieve higher performances but decrease the computational complexity, we propose a deep-wide neural network, named ShufflePointNet, which can exploit fine-grained local features, but also reduce redundancies using group convolution and channel shuffle operation. Unlike conventional operations that directly apply MLPs on the high-dimensional features of a point cloud, our model goes “wider” by splitting features into groups with smaller depth in advance, having the respective MLP computations applied only to a single group, which can significantly reduce complexity and computation. At the same time, we allow communication between groups by shuffling the feature channel to capture fine-grained features. We further discuss the multi-branch method for wider neural networks being also beneficial to feature extraction for point clouds. We present extensive experiments for shape classification tasks on a ModelNet40 dataset and semantic segmentation task on large scale datasets ShapeNet part, S3DIS and KITTI. Finally, we carry out an ablation study and compare our model to other state-of-the-art algorithms to show its efficiency in terms of complexity and accuracy.

The esterification of malic acid using traditional homogenous catalysts suffers from the difficulty in reuse of the catalyst and undesirable side reactions. In this work, Zr(SO4)2/SiO2 and Zr(SO4)2/activated carbon (AC) as solid acid catalysts were prepared for malic acid esterification with methanol. The conversion of malic acid over these two catalysts is comparable to that over H2SO4 and unsupported Zr(SO4)2∙4H2O catalysts; however; a 99% selectivity of dimethyl malate can be realized on these two supported catalysts, which is much higher than that of conventional H2SO4 (75%) and unsupported Zr(SO4)2∙4H2O (80%) catalysts, highlighting the critical role of AC and SiO2 supports in tuning the selectivity. We suggest that the surface hydroxyls of AC or lattice O2− ions from SiO2 donate electrons to Zr4+ in Zr(SO4)2/AC and Zr(SO4)2/SiO2 catalysts, which results in the increase in electron density on Zr4+. The enhanced electron density on Zr4+ reduces the degree of H delocalization from crystal water and then decreases the Brønsted acid strength. Consequently, the reduced Brønsted acid strength of Zr(SO4)2/AC and Zr(SO4)2/SiO2 catalysts suppresses the intermolecular dehydration side reaction. In addition, these two supported catalysts can be easily separated from the reaction system by simple filtration with almost no loss of activity.

Doubly Fed Induction Generator (DFIG) and Permanent Magnet Synchronous Generator (PMSG) are converter-interfaced wind turbines, which have much more complex short circuit behaviour after grid voltage drops. The research on short circuit current contributions provided by the wind turbines is very important for power system planning and relay protection's setting. Here, the Low Voltage Ride Through (LVRT) test data in north China are used to study the short circuit behaviour of DFIGs and PMSGs. The characteristics of two featured quantities, fundamental frequency component and peak current, are investigated. Unlike simulation or theoretical analysis, the field test data of real wind turbines from different manufacturers help utility operators to better understand the fault characteristics of converter-interfaced wind turbines.

Huge video data has posed great challenges on computing power and storage space, triggering the emergence of distributed compressive video sensing (DCVS). Hardware-friendly characteristics of this technique have consolidated its position as one of the most powerful architectures in source-limited scenarios, namely, wireless video sensor networks (WVSNs). Recently, deep convolutional neural networks (DCNNs) are successfully applied in DCVS because traditional optimization-based methods are computationally elaborate and hard to meet the requirements of real-time applications. In this paper, we propose a joint sampling−reconstruction framework for DCVS, named “JsrNet”. JsrNet utilizes the whole group of frames as the reference to reconstruct each frame, regardless of key frames and non-key frames, while the existing frameworks only utilize key frames as the reference to reconstruct non-key frames. Moreover, different from the existing frameworks which only focus on exploiting complementary information between frames in joint reconstruction, JsrNet also applies this conception in joint sampling by adopting learnable convolutions to sample multiple frames jointly and simultaneously in an encoder. JsrNet fully exploits spatial−temporal correlation in both sampling and reconstruction, and achieves a competitive performance in both the quality of reconstruction and computational complexity, making it a promising candidate in source-limited, real-time scenarios.

A new bacterial strain, designated 452T, was isolated from the rhizosphere soil of the mangrove Avicennia marina in China. As determined, its cell wall peptidoglycan contained LL-diaminopimelic acid; MK-9(H8) and MK-9(H6) were the major isoprenoid quinones; and iso-C16:0 (31.3%), anteiso-C15:0 (16.9%), and iso-C15:0 (12.5%) were the major cellular fatty acids (>10.0%). Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain 452T formed a distinct lineage in the clade of the genus Streptomyces, and was closely related to S. coerulescens DSM 40146T (99.6% sequence identity), S. bellus DSM 40185T (99.5%), and S. coeruleorubidus DSM 41172T (99.3%). The DNA-DNA relatedness between strain 452T and these type strains ranged between 29.3 and 42.3%. Based on the phenotypic, chemotaxonomic, and phylogenetic features, the strain 452T is considered to represent a novel species of the genus Streptomyces, for which the name Streptomyces nigra sp. nov. is proposed. The type strain is 452T (=KCTC 39960T = MCCC 1K03346T). Further, strain 452T extracts exhibited a pronounced antitumor activity against human cancer cell lines A549, HCT-116, and HepG2, but not against normal human colon cells CCD-18Co. Active substances in the fermentation broth of strain 452T were isolated by bioassay-guided analysis, and then purified using a macroporous resin, silica gel, sephadex LX-20 column, and semi-preparative high-performance liquid chromatography (HPLC). Eight proline-containing diketopiperazines, namely, cyclo(Pro-Ala), cyclo(Pro-Gly), cyclo(Pro-Phe), cyclo(Pro-Met), cyclo(Pro-Val), cyclo(Pro-Leu), cyclo(Pro-Tyr), and cyclo(L-Leu-trans-4-hydroxy-L-Pro), were identified by electrospray ionization mass spectrometry (MS) and nuclear magnetic resonance (NMR). The compounds displayed different levels of cytotoxicity. The highest cytotoxicity was exhibited by cyclo(Pro-Ala) and cyclo(Pro-Met) against A549 cells, and cyclo(Phe-Pro) and cyclo(Pro-Ala) against HCT-116 cells, with average IC50 values equal to 18.5, 27.3, 32.3, and 47.6 μg/mL, respectively. The diversity of diketopiperazines and other chemicals produced by 452T was further investigated using gas chromatography (GC)-MS and liquid chromatography (LC)-MS. The analysis revealed 16 types of metabolites with antitumor activity and 16 other types of diketopiperazines. Hence, extracts of the newly identified strain may be used a starting material for the development of antitumor agents.

Introduction: Anatomic repair of the anterior talofibular ligament (ATFL) is challenging when the local ligamentous tissue is severely attenuated. Anatomic reconstruction of the ATFL with tibial tuberosity–patellar tendon (TT-PT) autograft is a feasible choice that can avoid the complicated tendon–bone healing and restore ankle stability. Materials and methods: From 2009 to 2015, 31 chronic lateral ankle instability (CLAI) patients (31 ankles), who had a serious injury on the ATFL only, were treated with anatomic reconstruction of ATFL with TT-PT. American orthopedic foot and ankle society ankle–hindfoot score (AHS), visual analog scale for pain score (VAS), Karlsson–Peterson score, Tegner activity level, and objective examination comprehending range of motion were used to evaluate the clinical outcomes before and after operation. Radiographically, talar tilt angles and anterior drawer were assessed in pre- and postoperative ankle stress views. Results: Among the 31 ankles, 17 ankles with single-bundle ATFL and 14 ankles with double-bundle ATFL were found at operation. At a mean follow-up of 42 months (24–82 months), all patients were satisfied with the procedure. Mean AHS significantly increased from 60.5 ± 8.2 to 93.5 ± 4.8. Mean Karlsson–Peterson score significantly increased from 55.2 ± 11.0 preoperatively to 91.2 ± 6.9 at final follow-up. Average VAS significantly decreased from 5.9 ± 1.6 preoperatively to 1.4 ± 1.0 at the latest follow-up. Mean Tegner activity level was 3.7 ± 0.9 before operation, compared with 7.0 ± 0.8 after operation. On stress radiographs, mean talar tilt angle was 17.0 ± 3.4° before operation and 3.8 ± 2.1° at the latest follow-up. In addition, mean anterior tibiotalar translation was 7.5 ± 2.2 mm before operation and 1.8 ± 1.1 mm at the latest follow-up. Conclusion: Anatomic reconstruction of the ATFL using a TT-PT autograft allows bone–bone healing in talus and tendon–tendon/periosteum healing in fibula rather than requiring tendon–bone healing, which is an alternative choice for treating CLAI caused by single ATFL insufficiency.

Interferon (IFN)-sensitive and replication-incompetent influenza viruses are likely to be the alternatives to inactivated and attenuated virus vaccines. Some IFN-sensitive influenza vaccine candidates with modified non-structural protein 1 (NS1) are highly attenuated in IFN-competent hosts but induce robust antiviral immune responses. However, little research has been done on the manufacturability of these IFN-sensitive vaccine viruses. Here, RIG-I-knockout 293T cells were used to package the IFN-sensitive influenza A/WSN/33 (H1N1) virus expressing the mutant NS1 R38A/K41A. We found that the packaging efficiency of the NS1 R38A/K41A virus in RIG-I-knockout 293T cells was much higher than that in 293T cells. Moreover, the NS1 R38A/K41A virus almost lost its IFN antagonist activity and could no longer replicate in A549, MDCK, and Vero cells after 3–6 passages. This indicated that the replication of NS1 R38A/K41A virus is limited in conventional cells. Therefore, we further established a stable Vero cell line expressing the wild-type (WT) NS1 of the WSN virus, based on the Tet-On 3G system. The NS1 R38A/K41A virus was able to steadily propagate in this IFN-deficient cell line for at least 20 passages. In a mouse model, the NS1 R38A/K41A virus showed more than a 4-log reduction in lung virus titers compared to the WT virus at 3 and 5 days post infection. Furthermore, we observed that the NS1 R38A/K41A virus triggered high-level of IFN-α/β production in lung tissues and was eliminated from the host in a relatively short period of time. Additionally, this virus induced high-titer neutralizing antibodies against the WT WSN, A/Puerto Rico/8/1934 (PR8), or A/California/04/2009 (CA04) viruses and provided 100% protection against the WT WSN virus. Thus, we found that the replication of the NS1 R38A/K41A virus was limited in IFN-competent cells and mice. We also presented a promising IFN-deficient system, involving a RIG-I-knockout 293T cell line to package the IFN-sensitive vaccine virus and a stable Vero cell line expressing NS1 to propagate the IFN-sensitive vaccine virus. The IFN-deficient system is applicable for the manufacture of IFN-sensitive vaccine virus.

Reflective cracking is a common type of pavement distress, which manifests as cracks in an underlying layer propagating through to the surface of a pavement structure. To minimize reflective cracking of asphalt layers in composite pavements, four treatments are commonly used: standard/full rubblization, modified rubblization, crack and seat, and rock interlayer. The four types of treatment were evaluated to determine their effectiveness in mitigating reflective cracking via non-destructive Falling Weight Deflectometer tests and Surface Wave Method tests to measure layer modulus, along with field pavement performance surveys. It is found that moduli measurements from Surface Wave Method tests have reduced uncertainty comparing to those from Falling Weight Deflectometer tests, (2) the moduli of thin rock interlayers were captured by Surface Wave Method, but missed by Falling Weight Deflectometer. In addition, the Surface Wave Method results show that (1) crack and seat treatments provide the highest moduli, followed by modified rubblization, and (2) standard rubblization and rock interlayers provide moduli that are slightly lower than the other two treatments. Pavement performance survey was also conducted concurrently with the in-situ modulus tests. Based on the results of this study, modified rubblization and rock interlayer treatments are recommended for mitigation of reflective cracking.

Stem cell transplantation is one of most valuable methods in the treatment of myocardial infarction, and adipose-derived stem cells (ASCs) are becoming a hot topic in medical research. Previous studies have shown that ASCs can be differentiated into cardiomyocyte-like cells, but the efficiency and survival rates are low. We investigated the role and mechanism of microRNA-1 (miR-1) in the differentiation of ASCs into cardiomyocyte-like cells. ASCs and cardiomyocytes were isolated from neonatal rats. We constructed lentivirus for overexpressing miR-1 and used DAPT, an antagonist of the Notch1 pathway, for in vitro analyses. We performed cocultures with ASCs and cardiomyocytes. The differentiation efficiency of ASCs was detected by cell-specific surface antigens. Our results showed that miR-1 can promote the expression of Notch1 and reduce the expression of Hes1, a Notch pathway factor, and overexpression of miR-1 can promote the differentiation of ASCs into cardiomyocyte-like cells, which may occur by regulating Notch1 and Hes1.

Peroxiredoxin Q (PrxQ) that belonged to the cysteine-based peroxidases has long been identified in numerous bacteria, but the information on the physiological and biochemical functions of PrxQ remain largely lacking in Corynebacterium glutamicum. To better systematically understand PrxQ, we reported that PrxQ from model and important industrial organism C. glutamicum, encoded by the gene ncgl2403 annotated as a putative PrxQ, played important roles in adverse stress resistance. The lack of C. glutamicum prxQ gene resulted in enhanced cell sensitivity, increased ROS accumulation, and elevated protein carbonylation levels under adverse stress conditions. Accordingly, PrxQ-mediated resistance to adverse stresses mainly relied on the degradation of ROS. The physiological roles of PrxQ in resistance to adverse stresses were corroborated by its induced expression under adverse stresses, regulated directly by the stress-responsive ECF-sigma factor SigH. Through catalytical kinetic activity, heterodimer formation, and bacterial two-hybrid analysis, we proved that C. glutamicum PrxQ catalytically eliminated peroxides by exclusively receiving electrons from thioredoxin (Trx)/thioredoxin reductase (TrxR) system and had a broad range of oxidizing substrates, but a better efficiency for peroxynitrite and cumene hydroperoxide (CHP). Site-directed mutagenesis confirmed that the conserved Cys49 and Cys54 are the peroxide oxidation site and the resolving Cys residue, respectively. It was also discovered that C. glutamicum PrxQ mainly existed in monomer whether under its native state or functional state. Based on these results, a catalytic model of PrxQ is being proposed. Moreover, our result that C. glutamicum PrxQ can prevent the damaging effects of adverse stresses by acting as thioredoxin-dependent monomeric peroxidase could be further applied to improve the survival ability and robustness of the important bacterium during fermentation process.

A total of 1 590 fecal swabs and stool samples from sporadic acute gastroenteritis patients of all ages were collected from January 2013 to March 2018 in the Zhoushan Islands, China, with 99 (6.23%) samples subsequently identified as human norovirus (HuNoV) positive. Phylogenetic analysis of partial RdRp and VP1 gene regions identified 10 genotypes of the GII genogroup and 3 genotypes of the GI genogroup. The predominant genotype was GII.P17-GII.17 (42.86%, 33/77), followed by GII.Pe-GII.4_Sydney 2012 (24.68%, 19/77) and GII.P16-GII.2 (12.96%, 10/77). However, the prevailing genotype in the Zhoushan Islands has shifted on three separate occasions. The GII.Pe-GII.4_Sydney_2012 strain was dominant in 2013-2014, the GII.P17-17 strain was dominant in 2015-2016, and the GII.P16-GII.2 strain was dominant in 2017. Divergence analysis showed that the re-emerging GII.P16-GII.2 strains clustered with the Japanese 2010-2012 GII.P16-GII.2 strains, and the time of the most recent common ancestor was estimated to have occurred in 2012 to 2013. The evolutionary rates of the RdRp gene region of the GII.P16 genotype and the VP1 gene region of the GII.2 genotype were 2.64 × 10(-3) (95% HPD interval, 2.17-3.08 × 10(-3)) and 3.36 × 10(-3) (95% HPD interval, 2.66-4.04 × 10(-3)) substitutions/site/year, respectively. The migration pattern of the HuNoV GII.2 genotype in China demonstrated that the re-emerging GII.P16-GII.2 strains were first introduced into Hong Kong from Japan, and then spread from Hong Kong to other coastal areas. Our results also showed that the GII.P16-GII.2 strains in the Zhoushan Islands were likely introduced from Jiangsu Province, China, in 2016.

Objective: To evaluate the influence of tranexamic acid on epidermal permeability barrier function in rosacea and its potential mechanisms. Methods: A randomized, vehicle controlled, split-face study was performed on 30 rosacea patients. This study involved 2 weeks of 3% tranexamic acid solution treatment and vehicle control treatment. Skin physiological parameters, including skin surface pH, stratum corneum hydration, and transepidermal water loss, were measured. The expression of protease-activated receptor 2 (PAR-2) in rosacea and normal skin samples was assessed with immunohistochemical staining. The expression of PAR-2 in HaCaT keratinocytes was determined using reverse transcription polymerase chain reaction after stimulation with tranexamic acid. Changes of intracellular calcium induced by PAR-2 activation were measured using Fluo-4 NW calcium assay. Results: Individuals with rosacea expressed a higher baseline level of PAR-2 compared with normal skin. Tranexamic acid improved the permeability barrier function in rosacea patients and inhibited calcium mobilization in keratinocytes induced by PAR-2 activation. The PAR-2 expression was not altered by tranexamic acid stimulation. Conclusion: Topical tranexamic acid could improve the epidermal permeability barrier function and clinical signs of rosacea, likely resulting from inhibition of PAR-2 activation and consequent calcium influx. Thus, tranexamic acid could serve as an adjuvant therapy for rosacea.

Acute myocardial infarction (AMI) is a serious cardiovascular disease. Investigating new susceptibility genes for effective methods of early diagnosis of AMI is important. In the current study, peripheral blood miR-19a levels were detected by real-time polymerase chain reaction. Significant differences and logistic correlation analyses were carried out by grouping of disease types and stratification of risk factors. Receiver-operator characteristic curve analysis was used to compare the current common clinical biochemical markers and evaluate the sensitivity and specificity of miR-19a for diagnosing AMI. Circulating miR-19a expression in the AMI group was higher than that in controls. The diagnostic effect of circulating miR-19a levels was superior to current clinical biochemical indices, such as CK, CK-MB, MYO, hs-TnI, and BNP. Our results show that there is a close association of circulating miR-19a levels with susceptibility to AMI. Circulating miR-19a levels could be a candidate diagnostic biomarker for AMI.

This paper introduces a new method for reconstructing virtual two-dimensional (2-D) microstructure of hot mix asphalt (HMA). Based on the method, the gradation of coarse aggregates and the film thickness of the asphalt binder can be defined by the user. The HMA microstructure then serves as the input to the computational fluid dynamic (CFD) software (ANSYS-FLUENT) to investigate the water flow pattern through it. It is found that the realistic flow fields can be simulated in the 2-D micro-structure and the flow patterns in some typical air void structures can be identified. These flow patterns can be used to explain the mechanism that could result in moisture damage in HMA pavement. The one-dimensional numerical permeability values are also derived from the flow fields of the 2-D HMA microstructure and compared with the measured values obtained by the Karol-Warner permeameter. Because the interconnected air voids channels in actual HMA samples cannot be fully represented in a 2-D model, some poor agreements need to be improved.

An indole−3−acetic acid producing Bacillus altitudinis WR10 was previously isolated from the root of wheat (Triticum aestivum L.). In this study, the strain WR10 was used for relieving abiotic stresses in wheat under low phosphorus and high saline in hydroponic co-culture models. Significantly, strain WR10 improved wheat seed relative germination rate under salinity stress (200/400 mM NaCl) and the root dry weight in wheat seedlings under phosphorus stress (10 μM KH2PO3) when insoluble phosphates are available. To provide insights into its abiotic stress-alleviating properties, the strain was characterized further. WR10 grows well under different culture conditions. Particularly, WR10 resists salt (12% NaCl) and hydrolyzes both inorganic and organic insoluble phosphates. WR10 uses many plant-derived substrates as sole carbon and energy sources. It produces catalase, amylase, phosphatase, phytase, reductase, and 1−aminocyclopropane−1−carboxylate (ACC) deaminase. In addition, WR10 possesses long peritrichous flagella, and its biofilm formation, as well as phytase production, is induced by abiotic stresses. Overall, the salinity-alleviating property of WR10 in wheat can be attributed to its inherent tolerance to NaCl, formation of biofilm, and production of enzymes, like catalase, amylase, and ACC deaminase. Meanwhile, B. altitudinis WR10 reduces low-phosphorus stress in wheat by production of phosphatases and phytases in the presence of insoluble phosphates.

Influenza A virus (IAV) has developed strategies to utilize host metabolites which, after identification and isolation, can be used to discover the value of immunometabolism. During this study, to mimic the metabolic processes of influenza virus infection in human cells, we infect A549 cells with H1N1 (WSN) influenza virus and explore the metabolites with altered levels during the first cycle of influenza virus infection using ultra-high-pressure liquid chromatography−quadrupole time-of-flight mass spectrometer (UHPLC−Q-TOF MS) technology. We annotate the metabolites using MetaboAnalyst and the Kyoto Encyclopedia of Genes and Genomes pathway analyses, which reveal that IAV regulates the abundance of the metabolic products of host cells during early infection to provide the energy and metabolites required to efficiently complete its own life cycle. These metabolites are correlated with the tricarboxylic acid (TCA) cycle and mainly are involved in purine, lipid, and glutathione metabolisms. Concurrently, the metabolites interact with signal receptors in A549 cells to participate in cellular energy metabolism signaling pathways. Metabonomic analyses have revealed that, in the first cycle, the virus not only hijacks cell metabolism for its own replication, but also affects innate immunity, indicating a need for further study of the complex relationship between IAV and host cells.

Major earthquakes can cause serious vegetation destruction in affected areas. However, little is known about the spatial patterns of damaged vegetation and its influencing factors. Elucidating the main influencing factors and finding out the key vegetation type to reflect spatial patterns of damaged vegetation are of great interest in order to improve the assessment of vegetation loss and the prediction of the spatial distribution of damaged vegetation caused by earthquakes. In this study, we used Moran’s I correlograms to study the spatial autocorrelation of damaged vegetation and its potential driving factors in the nine worst-hit Wenchuan earthquake-affected cities and counties. Both dependent and independent variables showed a positive spatial autocorrelation but with great differences at four aggregation levels (625 × 625 m, 1250 × 1250 m, 2500 × 2500 m, and 5000 × 5000 m). Shrubs can represent the characteristics of all damaged vegetation due to the significant linear relationship between their Moran’s I at the four aggregation levels. Clustering of similar high coverage of damaged vegetation occurred in the study area. The residuals of the standard linear regression model also show a significantly positive autocorrelation, indicating that the standard linear regression model cannot explain all the spatial patterns in damaged vegetation. Spatial autoregressive models without spatially autocorrelated residuals had the better goodness-of-fit to deal with damaged vegetation. The aggregation level 8 × 8 is a scale threshold for spatial autocorrelation. There are other environmental factors affecting vegetation destruction. Our study provides useful information for the countermeasures of vegetation protection and conservation, as well as the prediction of the spatial distribution of damaged vegetation, to improve vegetation restoration in earthquake-affected areas.