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[This corrects the article DOI: 10.1371/journal.pone.0280290.].

The inerter is a two-terminal component that can be added to the spring-and-damper configuration of a suspension system. It has the property that the force exerted is proportional to the relative acceleration at its terminals. Studies have demonstrated the inerter's benefit of providing superior vibration isolation when it is used in the vehicle suspension of passenger cars. However, similar benefit on another common vehicle class on the roads, namely heavy vehicles, remain to be shown, as these vehicles have vastly different parameter values than passenger cars. This study is an investigation on the performance improvement brought by an inerter in the suspension of common heavy vehicles. In the study, the parameter values of a truck and a bus were adopted in the quarter vehicle model with two different spring-damper-inerter configurations (parallel and serial inerter), and the improvements in vibration isolation and road holding capability were determined by optimization of inertance. Results show that the inerter is similarly effective in providing the said improvements when implemented on heavy vehicles instead of on passenger cars, judging from reductions in sprung mass acceleration and dynamic tire load. It is also observed that the performance benefit is associated with larger optimum inertance than that for passenger cars. Overall, the inerter has been shown to be beneficial in the parallel and serial configurations, both of which are common and can be practically implemented in the suspension of heavy vehicles.

OBJECTIVE:To evaluate the efficacy and safety of targeted therapy plus fulvestrant for postmenopausal patients with hormone receptor-positive advanced breast cancer. METHODS:Pubmed, Embase and Web of Science databases were systematically searched on February 26, 2018. Eligible studies were screened according to selection criteria, and two reviewers independently extracted outcome data which included progression-free survival, overall survival, objective response rate, clinical benefit rate and toxicities. RevMan 5.3 and STATA 11.0 software were used to conduct meta-analysis. RESULTS:Thirteen articles including twelve randomized-control trials fulfilled selection criteria. There was no evidence regarding the existence of publication bias and high-risk bias of quality in the selected studies. In previously endocrine therapy-treated postmenopausal patients with hormone-receptor positive advanced breast cancer, the PFS (HR = 0.77, 95%CI: 0.66-0.91) and ORR (RR = 1.78, 95%CI: 1.35-2.34) of combination therapy group were significantly higher than that from fulvestrant monotherapy group. Besides, a statistically significant difference in PFS was found across the two arms in postmenopausal women with PIK3CA-mutant ctDNA tumor (HR = 0.52, 95% CI: 0.39-0.69). Moreover, the risk of adverse events (RR = 1.09, 95%CI: 1.05-1.13), CTCAE≥3 (RR = 1.97, 95%CI: 1.49-2.60) and discontinuation due to adverse events (RR = 4.91, 95%CI: 3.37-7.15) were also significantly different between two treatment groups. Sensitivity analysis showed PLOMA-3 trial was an important factor of heterogeneity. DISCUSSION:Even though the combination of targeted therapy plus fulvestrant improved PFS and increased ORR in advanced breast cancer patients, the toxicities of combination therapy were also higher than fulvestrant monotherapy. Further studies related to inhibitors targeting the specific signaling pathway or receptors are urgently needed, and more efforts concerning precision medicine of targeted therapy plus endocrine therapy should be taken to improve the clinical benefits.

Previously rodent preclinical research in gliomas frequently involved implantation of cell lines such as C6 and 9L into the rat brain. More recently, mouse models have taken over, the genetic manipulability of the mouse allowing the creation of genetically accurate models outweighed the disadvantage of its smaller brain size that limited time allowed for tumor progression. Here we illustrate a method that allows glioma formation in the rat using the replication competent avian-like sarcoma (RCAS) virus / tumor virus receptor-A (tv-a) transgenic system of post-natal cell type-specific gene transfer. The RCAS/tv-a model has emerged as a particularly versatile and accurate modeling technology by enabling spatial, temporal, and cell type-specific control of individual gene transformations and providing de novo formed glial tumors with distinct molecular subtypes mirroring human GBM. Nestin promoter-driven tv-a (Ntv-a) transgenic Sprague-Dawley rat founder lines were created and RCAS PDGFA and p53 shRNA constructs were used to initiate intracranial brain tumor formation. Tumor formation and progression were confirmed and visualized by magnetic resonance imaging (MRI) and spectroscopy. The tumors were analyzed using histopathological and immunofluorescent techniques. All experimental animals developed large, heterogeneous brain tumors that closely resembled human GBM. Median survival was 92 days from tumor initiation and 62 days from the first point of tumor visualization on MRI. Each tumor-bearing animal showed time dependent evidence of malignant progression to high-grade glioma by MRI and neurological examination. Post-mortem tumor analysis demonstrated the presence of several key characteristics of human GBM, including high levels of tumor cell proliferation, pseudopalisading necrosis, microvascular proliferation, invasion of tumor cells into surrounding tissues, peri-tumoral reactive astrogliosis, lymphocyte infiltration, presence of numerous tumor-associated microglia- and bone marrow-derived macrophages, and the formation of stem-like cell niches within the tumor. This transgenic rat model may enable detailed interspecies comparisons of fundamental cancer pathways and clinically relevant experimental imaging procedures and interventions that are limited by the smaller size of the mouse brain.

Explosive blast-related injuries are one of the hallmark injuries of veterans returning from recent wars, but the effects of a blast overpressure on the brain are poorly understood. In this study, we used in vivo diffusion kurtosis imaging (DKI) and proton magnetic resonance spectroscopy (MRS) to investigate tissue microstructure and metabolic changes in a novel, direct cranial blast traumatic brain injury (dc-bTBI) rat model. Imaging was performed on rats before injury and 1, 7, 14 and 28 days after blast exposure (~517 kPa peak overpressure to the dorsum of the head). No brain parenchyma abnormalities were visible on conventional T2-weighted MRI, but microstructural and metabolic changes were observed with DKI and proton MRS, respectively. Increased mean kurtosis, which peaked at 21 days post injury, was observed in the hippocampus and the internal capsule. Concomitant increases in myo-Inositol (Ins) and Taurine (Tau) were also observed in the hippocampus, while early changes at 1 day in the Glutamine (Gln) were observed in the internal capsule, all indicating glial abnormality in these regions. Neurofunctional testing on a separate but similarly treated group of rats showed early disturbances in vestibulomotor functions (days 1-14), which were associated with imaging changes in the internal capsule. Delayed impairments in spatial memory and in rapid learning, as assessed by Morris Water Maze paradigms (days 14-19), were associated with delayed changes in the hippocampus. Significant microglial activation and neurodegeneration were observed at 28 days in the hippocampus. Overall, our findings indicate delayed neurofunctional and pathological abnormalities following dc-bTBI that are silent on conventional T2-weighted imaging, but are detectable using DKI and proton MRS.

Pompe disease is an inherited lysosomal storage disorder that results from a deficiency in acid α-glucosidase (GAA) activity due to mutations in the GAA gene. Pompe disease is characterized by accumulation of lysosomal glycogen primarily in heart and skeletal muscles, which leads to progressive muscle weakness. We have shown previously that the small molecule pharmacological chaperone AT2220 (1-deoxynojirimycin hydrochloride, duvoglustat hydrochloride) binds and stabilizes wild-type as well as multiple mutant forms of GAA, and can lead to higher cellular levels of GAA. In this study, we examined the effect of AT2220 on mutant GAA, in vitro and in vivo, with a primary focus on the endoplasmic reticulum (ER)-retained P545L mutant form of human GAA (P545L GAA). AT2220 increased the specific activity of P545L GAA toward both natural (glycogen) and artificial substrates in vitro. Incubation with AT2220 also increased the ER export, lysosomal delivery, proteolytic processing, and stability of P545L GAA. In a new transgenic mouse model of Pompe disease that expresses human P545L on a Gaa knockout background (Tg/KO) and is characterized by reduced GAA activity and elevated glycogen levels in disease-relevant tissues, daily oral administration of AT2220 for 4 weeks resulted in significant and dose-dependent increases in mature lysosomal GAA isoforms and GAA activity in heart and skeletal muscles. Importantly, oral administration of AT2220 also resulted in significant glycogen reduction in disease-relevant tissues. Compared to daily administration, less-frequent AT2220 administration, including repeated cycles of 4 or 5 days with AT2220 followed by 3 or 2 days without drug, respectively, resulted in even greater glycogen reductions. Collectively, these data indicate that AT2220 increases the specific activity, trafficking, and lysosomal stability of P545L GAA, leads to increased levels of mature GAA in lysosomes, and promotes glycogen reduction in situ. As such, AT2220 may warrant further evaluation as a treatment for Pompe disease.

Nowadays, baculovirus-infected insect cells and tetracycline-inducible mammalian cell lines (T-REx-293) are intensively used for G protein-coupled receptor (GPCR) production for crystallography purposes. Here we constructed a suspension T-REx-293 cell line to stably express an engineered neurotensin receptor 1 (NTS1) mutant and we quantitatively compared this cell line with the transient baculovirus-insect cell system throughout a milligram-scale NTS1 expression and purification process. The two systems were comparable with respect to functional NTS1 expression levels and receptor binding affinity for the agonist [(3)H] neurotensin. However, NTS1 surface display on T-REx-293 cells determined by radio-ligand binding assays was 2.8 fold higher than that on insect cells. This work demonstrates two approaches for preparing milligram quantities of purified NTS1 suitable for structural studies and provides useful input to users in choosing and optimizing an appropriate expression host for other GPCRs.

This paper introduces an innovative segmentation model that extends the U-Net architecture with a Squeeze and Excitation (SE) mechanism, designed to enhance the detection of moving objects in video streams. By integrating this model into the ViBe motion detection algorithm, we have significantly improved detection accuracy and reduced false positive rates. Our approach leverages adaptive techniques to increase the robustness of the segmentation model in complex scenarios, without requiring extensive manual parameter tuning. Despite the notable improvements, we recognize that further training is necessary to optimize the model for specific applications. The results indicate that our method provides a promising direction for real-time motion detection systems that require high precision and adaptability to varying conditions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mpofu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: With the appearance and aggravation of the aging society, cancer has become one of the major problems that threaten the life and health of Chinese residents seriously., Objective: To explore the cancer epidemiological characteristics among the elderly in China from 2005 to 2016, and to provide strategies for cancer prevention and treatment., Methods: Stratified analysis was conducted on the cancer mortality data of the elderly aged ≥60 years in China, which were selected from the Chinese Cancer Registry Annual Report. Joinpoint regression model was used to calculted average annual percentage change (AAPC) to estimate the time trends. Age-period-cohort (APC) model was used to explore the age, period and birth cohort effect on the risk of cancer death. Bayesian age-period-cohort (BAPC) model was used to predict trends in cancer mortality among elderly by gender and region to 2035., Results: 2005-2016, cancer mortality in the elderly in China showed a decreasing trend (AAPC = -1.2%, P<0.001). Cancer mortality in rural areas was higher than that in urban areas, but the urban-rural difference gradually narrowed (t = 6.1, P<0.01). The APC model showed that cancer mortality increased with age. The relative risk (RR) for the period effect decreased. RR was lower for the later- born cohort than that for the earlier-born cohort in rural areas. Lung cancer mortality ranked first in both male and female, and showed an increasing trend among female in the 60-64, 80-84 and ≥85 age groups (AAPC60-64 = 1.0%, AAPC80-84 = 0.8%, AAPC≥85 = 2.0%, all P<0.05). By 2035, cancer mortality for the elderly was predicted to decline nationally, by sex and in rural areas, while rising in urban areas., Conclusion: Cancer mortality in the elderly in China showed a decreasing trend from 2005 to 2016, but it was still higher than the world average. Early cancer screening is important, especially in the elderly male and in rural areas., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To systematically assess the quality of clinical practice guidelines (CPGs) for Helicobacter pylori (HP) infection and identify gaps that limit their development., Study Design and Setting: CPGs for HP infection were systematically collected from PubMed, Embase, the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, and six online guideline repositories. Three researchers independently used the AGREE Ⅱ tool to evaluate the methodological quality of the eligible CPGs. In addition, the reporting and recommendation qualities were appraised by using the RIGHT and AGREE-REX tools, respectively. The distribution of the level of evidence and strength of recommendation among evidence-based CPGs was determined., Results: A total of 7,019 records were identified, and 24 CPGs met the eligibility criteria. Of the eligible CPGs, 19 were evidence-based and 5 were consensus-based. The mean overall rating score of AGREE II was 50.7% (SD = 17.2%). Among six domains, the highest mean score was for scope and purpose (74.4%, SD = 17.7%) and the lowest mean score was for applicability (24.3%, SD = 8.9). Only three of 24 CPGs were high-quality. The mean overall score of recommendation quality was 35.5% (SD = 12.2%), and the mean scores in each domain of AGREE-REX and RIGHT were all ≤ 60%, with values and preferences scoring the lowest (16.6%, SD = 11.9%). A total of 505 recommendations were identified. Strong recommendations accounted for 64.1%, and only 34.3% of strong recommendations were based on high-quality evidence., Conclusion: The overall quality of CPGs for HP infection is poor, and CPG developers tend to neglect some domains, resulting in a wide variability in the quality of the CPGs. Additionally, CPGs for HP infection lack sufficient high-quality evidence, and the grading of recommendation strength should be based on the quality of evidence. The CPGs for HP infection have much room for improvement and further researches are required to minimize the evidence gap., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Aims: The coronavirus disease 2019 (COVID-19) public health emergency has had a huge impact worldwide. We analyzed news headlines and keywords from the initial period of COVID-19, and explored the dissemination timeline of news related to the epidemic, and the impact of Internet-based media on the public using lifecycle theory and agenda-setting theory. We aimed to explore the impact of Baidu news headlines on public attention during the first wave of COVID-19, as well as the management mechanism of regulatory departments for social public opinion., Methods: We searched Baidu News using the keywords "Novel Coronavirus" and "COVID-19" from 8 January to 21 February 2020, a total of 45 days, and used Python V3.6 to extract news samples during the first wave of the epidemic. We used text analysis software to structurally process captured news topics and content summaries, applied VOSviewer V6.19 and Ucinet V6.0 to examine key aspects of the data., Results: We analyzed the impact of Baidu News headlines on social opinion during the first wave of COVID-19 in the budding, spread, and outbreak stage of the information lifecycle. From clustering visualization and social network analysis perspectives, we explored the characteristics of Baidu News during the initial stage of the COVID-19. The results indicated that agenda-setting coverage through online media helped to mitigate the negative impact of COVID-19. The findings revealed that news reporting generated a high level of public attention toward a specific emergency event., Conclusions: The public requires accurate and objective information on the progress of COVID-19 through Baidu News headlines to inform their planning for the epidemic. Meanwhile, government can enhance the management mechanism of news dissemination, correct false and inaccurate news, and guide public opinion in a positive direction. In addition, timely official announcements on the progress of the COVID-19 outbreak and responses to matters of public concern can help calm tensions and maintain social stability., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Su, Wang. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Previous studies have indicated a heightened susceptibility to cataract and glaucoma among rheumatoid arthritis (RA) patients, while it remains uncertain whether RA is causally associated with cataract and glaucoma. A two-sample mendelian randomization (MR) analysis was used to investigate the causal associations between RA, cataract and glaucoma in European and East Asian populations., Methods: In the European population, genome-wide association study (GWAS) summary statistics for cataract (372,386 individuals) and glaucoma (377,277 individuals) were obtained from the FinnGen consortium (R9), while RA summary data were derived from a meta-analysis of GWAS encompassing 97173 samples. In the East Asian population, summary data for cataract (212453 individuals), glaucoma (212453 individuals), and RA (22515 individuals) were sourced from the IEU Open GWAS project. Inverse-variance weighted (IVW, random-effects) method served as the primary analysis, complemented by MR‒Egger regression, weighted median, weighted mode and simple mode methods. Additionally, various sensitivity tests, including Cochran's Q test, MR‒Egger intercept, MR pleiotropy Residual Sum and Outlier test and leave-one-out test were performed to detect the heterogeneity, horizontal pleiotropy and stability of the analysis results., Results: Following stringent screening, the number of selected instrumental variables ranged from 8 to 56. The IVW results revealed that RA had an increased risk of cataract (OR = 1.041, 95% CI = 1.019-1.064; P = 2.08×10-4) and glaucoma (OR = 1.029, 95% CI = 1.003-1.057; P = 2.94×10-2) in European populations, and RA displayed a positive association with cataract (OR = 1.021, 95% CI = 1.004-1.039; P = 1.64×10-2) in East Asian populations. Other methods also supported those results by IVW, and sensitivity tests showed that our analysis results were credible and stable., Conclusions: This study revealed a positive causality between RA and the increased risk of cataract and glaucoma, which provides guidance for the early prevention of cataracts and glaucoma in patients with RA and furnishes evidence for the impact of RA-induced inflammation on ophthalmic diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Teng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The lack of accuracy in the current prostate specific antigen (PSA) test for prostate cancer (PCa) screening causes around 60-75% of unnecessary prostate biopsies. Therefore, alternative diagnostic methods that have better accuracy and can prevent over-diagnosis of PCa are needed. Researchers have examined various potential biomarkers for PCa, and of those fatty acids (FAs) markers have received special attention due to their role in cancer metabolomics. It has been noted that PCa metabolism prefers FAs over glucose substrates for continued rapid proliferation. Hence, we proposed using a urinary FAs based model as a non-invasive alternative for PCa detection. Urine samples collected from 334 biopsy-designated PCa positive and 232 biopsy-designated PCa negative subjects were analyzed for FAs and lipid related compounds by stir bar sorptive extraction coupled with gas chromatography/mass spectrometry (SBSE-GC/MS). The dataset was split into the training (70%) and testing (30%) sets to develop and validate logit models and repeated for 100 runs of random data partitioning. Over the 100 runs, we confirmed the stability of the models and obtained optimal tuning parameters for developing the final FA based model. A PSA model using the values of the patients' PSA test results was constructed with the same cohort for the purpose of comparing the performances of the FA model against PSA test. The FA final model selected 20 FAs and rendered an AUC of 0.71 (95% CI = 0.67-0.75, sensitivity = 0.48, and specificity = 0.83). In comparison, the PSA model performed with an AUC of 0.51 (95% CI = 0.46-0.66, sensitivity = 0.44, and specificity = 0.71). The study supports the potential use of urinary FAs as a stable and non-invasive alternative test for PCa diagnosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Noriega Landa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Conjugation of transferrin (Tf) to imaging or nanotherapeutic agents is a promising strategy to target breast cancer. Since the efficacy of these biomaterials often depends on the overexpression of the targeted receptor, we set out to survey expression of transferrin receptor (TfR) in primary and metastatic breast cancer samples, including metastases and relapse, and investigate its modulation in experimental models., Methods: Gene expression was investigated by datamining in twelve publicly-available datasets. Dedicated Tissue microarrays (TMAs) were generated to evaluate matched primary and bone metastases as well as and pre and post chemotherapy tumors from the same patient. TMA were stained with the FDA-approved MRQ-48 antibody against TfR and graded by staining intensity (H-score). Patient-derived xenografts (PDX) and isogenic metastatic mouse models were used to study in vivo TfR expression and uptake of transferrin., Results: TFRC gene and protein expression were high in breast cancer of all subtypes and stages, and in 60-85% of bone metastases. TfR was detectable after neoadjuvant chemotherapy, albeit with some variability. Fluorophore-conjugated transferrin iron chelator deferoxamine (DFO) enhanced TfR uptake in human breast cancer cells in vitro and proved transferrin localization at metastatic sites and correlation of tumor burden relative to untreated tumor mice., Conclusions: TfR is expressed in breast cancer, primary, metastatic, and after neoadjuvant chemotherapy. Variability in expression of TfR suggests that evaluation of the expression of TfR in individual patients could identify the best candidates for targeting. Further, systemic iron chelation with DFO may upregulate receptor expression and improve uptake of therapeutics or tracers that use transferrin as a homing ligand., Competing Interests: no authors have competing interests, (Copyright: © 2023 Fontana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Men who have sex with men (MSM) are at high risk of HIV acquisition. Long-acting injectable-pre-exposure prophylaxis (LAI-PrEP), requiring less frequent dosing, is being studied as an alternative method to daily oral HIV PrEP. With the addition of this potential new prevention method, it expands the scope for a wider user choice and is expected to increase the acceptability and uptake of HIV prevention measures. The aim of our study was to explore the willingness to use LAI-PrEP and associated influential factors., Methods: Participants were recruited from December 2020 to March 2021 through banner advertisements on web- and mobile app-based platforms on Blued, a large gay Chinese social media platform. MSM in our cross-sectional study was HIV-negative and currently lived in mainland China. Participants were asked about their willingness to use LAI-PrEP and reasons why they might be or not be willing to use LAI-PrEP. Multivariable logistic regression was used to analyze the factors associated with the willingness to use LAI-PrEP., Results: In total, 969 participants met the inclusion criteria and finished the survey. Nearly twenty percent (19.5%) of participants had never tested for HIV; 66.8% of MSM had multiple male partners; and 51.6% of MSM engaged in condomless sex with their partner. About three-fifths (66.3%) of MSM were aware of PrEP, and only 3.9% of MSM had used PrEP before. The willingness to use LAI-PrEP among MSM was 74.0% (95% CI: 71.4%-76.6%). MSM with higher education levels were less likely to show a willingness to use LAI-PrEP (AOR = 0.56, 95%CI: 0.38-0.84). Participants who had a history of HIV test (AOR = 1.68, 95%CI: 1.11-2.55), were willing to use daily oral PrEP (AOR = 10.64, 95%CI:7.43-15.21), had multiple male sexual partners (AOR = 1.33, 95%CI:0.93-1.90), who used rush popper(AOR = 1.49, 95%CI:1.05-2.13), and who were aware of PEP (AOR = 1.66, 95%CI: 1.02-2.70) were more likely to show willingness to use LAI-PrEP., Conclusions: In our study, MSM had quite high awareness but low uptake of PrEP. As LAI-PrEP is expected to be approved for use in China in the future, our study of MSM highlights the need for key population-focused education programs about PrEP and healthy sexual behavior. This study also provides some evidence for LAI-PrEP use among the Chinese MSM population in the future., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The neutrophil to lymphocyte*platelet ratio (NLPR) is a new index based on platelets, neutrophils, and lymphocytes associated with the prognosis of patients with infectious diseases and cancer. However, its use in acute ischemic stroke has rarely been reported. This study examined the relationship between levels of systemic immunoinflammatory indices at admission and patient outcomes at different times after onset to assess stroke prognosis by NLPR., Methods: This was a retrospective cohort study. The data from 1222 stroke patients were obtained from multi-parameter intelligent monitoring in the Intensive Care III database(MIMIC- III). Cox proportional risk model was conducted to evaluate the relation between NLPR, all-cause mortality, and ischemic. The results were further verified via a subgroup analysis., Results: After adjusting for multiple covariates, it was found that NLPR was related with all-cause mortality in stroke patients. High NLPR was accompanied by an increase in mortality with longer follow-up (30 days: HR = 1.52, 95% CI = 1.14-2.02,90 days: HR = 1.67, 95% CI = 1.29-2.16, 365 days: HR = 1.56, 95% CI = 1.24-1.96 and 2 years: HR = 1.52, 95% CI = 1.22-1.89)., Conclusion: The neutrophil to lymphocyte*platelet ratio (NLPR) are related to long-term adverse outcomes in patients with acute ischemic stroke. Therefore, NLPR is a promising inflammatory index for predicting the long-term prognosis of stroke., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Su et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The external institutional environment is the foundation for the survival and development of enterprises. Enterprises can only obtain legitimate and heterogeneous resources through continuous strategic reform and institutional innovation to match their internal strategies with the external environment. The paper selected the manufacturing enterprises that implemented service-oriented transformation strategies in China from 2016-2019 as a sample based on the realistic background of frequent institutional changes and overlapping market changes during China's economic transformation. The impact of different aspects of the institutional environment on service-oriented transformation and the moderating role of technological innovation capacity were examined empirically. The results showed that (1) improved government governance greatly facilitates the service-oriented transformation of manufacturing enterprises, which was more pronounced within the industry. The regulated development of the market facilitated service-oriented transformation within the industry in the short term, while the impact on cross-border transformation lagged. The improvement of the legalized business environment was conducive to the transformation of enterprises and promoted intra-industry transformation significantly more than cross-industry transformation. (2) Technological innovation capability strengthened the influence of institutional environment on intra-industry transformation, but had no significant impact on the relationship between institutional environment and cross-border transformation. (3) The moderating effect of technological innovation capability was markedly heterogeneous in terms of property rights and regional heterogeneity. The findings of this study provide an important reference for policy makers to break through the current institutional barriers to transformation and upgrading of the manufacturing industry, and to reshape and optimize the institutional environment for the integration and development of the secondary and tertiary industries., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Su et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Under the dual background of global industrial value chain and low-carbon emission reduction, the green transformation and upgrading of the manufacturing industry is an important way to promote production and promote sustainable economic development. Considering that the green transformation of the manufacturing industry is a typical complex adaptation system, based on the intrinsic relationship between the dynamic theory and the green transformation of the manufacturing industry, this paper takes the endogenous variable of the transformation of manufacturing enterprises as the entry point, simulates the transformation of new and old dynamic energy of green transformation, and explores the mechanism of green transformation and upgrading of manufacturing industry and the conversion process. According to the model, it is concluded that the green transformation of manufacturing enterprises is the result of the multi-stage transformation of enterprises. In this process, the change inertia overcomes old dynamic inertia and promotes the new dynamic to gradually replace the old dynamic. At the end of the article, specific suggestions are given to promote the green transformation of manufacturing enterprises from the aspects of ideology, policy support, digital empowerment, financial service guarantee system and communication and cooperation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: This study is intended to assess the prevalence of depression and anxiety in individuals who had recovered from COVID-19 and been discharged from hospital (RD hereafter) in Wuhan, China, and to explore the factors associated with these mental disorders., Methods: Participants of this study were the RD who were infected at the beginning of the outbreak from 13 communities in Jianghan District of Wuhan City, Hubei Province, China by convenience sampling in mid-2021. The Generalized Anxiety Disorder Questionnaire, the Patient Health Questionnaire, the Short Version of COVID-19 Stigma Scale, the Peace of Mind Scale, the Resilience Style Questionnaire, and the Perceived Social Support Questionnaire were used to collect relevant information of the participants. Descriptive analyses, Pearson correlation analysis, and logistic regression analysis were used to describe and analyze the data and to examine the factors associated with the mental health status of this population., Results: In total, we recruited 1601 participants from 3059 COVID-19 patients, and 1541 participants completed the questionnaire survey, with a response rate of 96.25%. Finally, 1297 participants met the inclusion and exclusion criteria in this study, of whom 28.8% and 37.9% reported mild to severe levels of anxiety and depression symptoms. Perceived better mental health status during hospitalization, higher frequency of alcohol use per week, peace of mind, higher education level, and resilience were negatively associated with anxiety, while stigma and history of psychological or emotional counseling before infection was positively associated with anxiety. More severe clinical classification of COVID-19 and stigma (AOR = 1.057, P<0.001) were both positively associated with depression, while perceived better mental health status during hospitalization (AOR = 0.564, P<0.001), higher frequency of alcohol use per week (AOR = 0.462, P = 0.004), peace of mind (AOR = 0.857, P<0.001), and social support (AOR = 0.972, P = 0.034) were negatively associated with depression., Conclusions: Tailored interventions on reducing stigma, enhancing mindfulness and social support should be taken into account to alleviate anxiety and depression among RD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Dai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In the context of global warming, although the coordinated development of tourism has led to regional economic growth, the high energy consumption-driven effects of such development have also led to environmental degradation. This research combines the undesired output of the Super-SBM model and social network analysis methods to determine the eco-efficiency of provincial tourism in China from 2010-2019 and analyzes its spatial correlation characteristics as well as its influencing factors. The aim of the project is to improve China's regional tourism eco-efficiency and promote cross-regional tourism correlation. The results show that (1) the mean value of provincial tourism eco-efficiency in China is maintained at 0.405~0.612, with an overall fluctuating upward trend. The tourism eco-efficiency of eastern China is higher than that of central, western and northeastern China, but the latter three regions have not formed a stable spatial distribution pattern. (2) The spatial network of provincial tourism eco-efficiency in China is multithreaded, dense and diversified. Throughout the network, affiliations are becoming closer, and network structure robustness is gradually improving, although the "hierarchical" spatial network structure remains. In individual networks, Jiangsu, Guangdong and Shandong provinces in eastern China have higher centrality degrees, closeness centrality and betweenness centrality than other provinces, which means they are dominant in the network. Hainan Province, also located in eastern China, has not yet built a "bridge" for tourism factor circulation. In the core-periphery model, the core-periphery areas of China's provincial tourism eco-efficiency are distributed in clusters, and the number of "core members" has increased. (3) The economic development level, information technology development level, and tourism technology level collectively drive the development and evolution of China's provincial tourism eco-efficiency spatial network., Competing Interests: We confirm that neither the manuscript nor any parts of its content are currently under consideration or published in another journal.

To study the effects of different regeneration methods on the growth and bacterial community diversity of Populus × euramericana cv. '74/76' (poplar 107), we investigated the growth of poplar 107 trees under three regeneration methods in 2017 and 2020, and sequenced the 16S rDNA V5-V7 regions in stem endophytic, root endophytic, and rhizosphere soil bacteria present in samples from the three regeneration methods using the Illumina high-throughput sequencing platform. The growth analysis showed that stump grafting regeneration (ST) and stump sprouting regeneration (SP) presented similar tree height and diameter at breast height (DBH), which were significantly lower by planted seedling regeneration (CK). The high-throughput sequencing results showed that the rhizosphere soil bacteria appeared to be significantly more diverse and rich than the root and stem endophytic bacteria. Cluster analysis showed that the similarity of bacterial community structure among the rhizosphere soil, root, and stem was small. Thus, the three sample types showed significant differences in bacteria. While comparing the two years, 2020 was significantly more diverse and rich than 2017. With the increase in stand age, the abundance of Proteobacteria increased and the abundance of Acidobacteria decreased. Among the three regeneration methods, ST significantly increased the diversity of stem endophytic bacteria. Chthoniobacter was enriched in SP, which promoted the decomposition of organic matter, and more plant growth promoting rhizobacteria (PGPR) were accumulated in the rhizosphere of SP and ST. The composition of the bacterial community was similar in the three regeneration methods, but the community composition was different. Regeneration and transformation of poplar plantations can be better carried out by stump grafting and stump sprouting., Competing Interests: The authors have declared that no competing interests exist.

In this article, we investigate the chronological change of settlements of the Lower Xiajiadian (LXJD) culture in northeast China. On the basis of excavation data, two types of settlements can be identified based on the methods of site construction: earthen (rammed earth/mudbrick) settlements and stone-constructed settlements. After integrating and reanalyzing all published 14C radiocarbon data of different LXJD sites, we argue that there is a clear chronological difference between these two types of settlements. It is revealed by the OxCal model that settlements built with earthen structures are generally earlier than those constructed with stones, and the changes in settlement spatial distribution and constructive material largely happened after 1500 BC. By means of correlation analysis with other related archaeological evidence, we suggest that the underlying social dynamics that contributed to LXJD settlement changes can be explored through multiple prospects., Competing Interests: The authors have declared that no competing interests exist.

In this study, we analyzed GPC family genes in colorectal cancer (CRC) and the possible mechanism of action of GPC1 in CRC. CRC patient data were extracted from The Cancer Genome Atlas, and the prognostic significance of GPC1 expression and its association with clinicopathological features were identified by Kolmogorov-Smirnov test. CRC patients with high GPC1 expression had poor overall survival compared with patients with low GPC1 expression. In vitro experiments demonstrated that knockdown of GPC1 significantly inhibited the proliferation and migration and promoted cell apoptosis in CRC cell lines. Gene Ontology analysis of differential genes indicated that GPC1 may influence the TGF-β1 signaling pathway. Additional experiments revealed that silencing GPC1 suppressed the levels of TGF-β1 and p-SMAD2 but increased the expression of SMAD2. Taken together, these findings suggest that GPC1 may function as a tumor promoter in CRC cells through promoting TGF-β signaling pathway. Our results also indicate that GPC1 may serve as a critical effector in CRC progression and a new potential target for CRC therapy., Competing Interests: The authors declare no competing interests.

Background: On 1 February 2016, the World Health Organization declared Zika transmission a public health emergency of international concern. Monitoring and responding to community awareness, concern, and possible knowledge gaps are critical during public health emergencies. Here, we describe the review and analysis of micro-blogs posted on Sina-Weibo, China's largest social media platform, to develop and disseminate a Zika virus education campaign., Methods: We used CYYUN Voice Express' Weibo Spider tool and the search terms of "Zhaika" OR "Zika" OR "Zikv" to capture microblogs about Zika virus retrospectively from February 1 to December 31, 2016 and prospectively from June 1 to November 15, 2017. We described microblogs meeting our inclusion criteria by month and Zika virus outbreaks in Asia and by source (e.g., government agency, individual, or other). We identified common misleading or inaccurate content authored by individual micro-bloggers (i.e., not supported by available scientific evidence) through a qualitative review. We used this information to develop and disseminate health awareness material about the Zika virus through China CDC's 12320 Health Hotline Weibo account. An online survey was conducted to obtain feedback on the material., Results: We captured 15,888 microblogs meeting our inclusion criteria. Zika-related microblogs peaked in September 2016, corresponding to news reports about the Zika outbreak in Singapore (August to November 2016). Most microblogs (12,994 [82%]) were authored by individual users, followed by media agencies (842 [5%]), businesses (829 [5%]), international organizations (370 [2%]), and Chinese government agencies (235 [1%]). Relevant microblogs primarily focused on clinical symptoms and health risks, modes of transmission, and actions taken by individuals to prevent infection and seek health care. Incorrect and/or mis-leading information from individual users concentrated on modes of transmission and possible treatments. The microblog "#Zika is that far and this close" health campaign was posted on Sina-Weibo and Baidu (Internet search engine in China) on September 18, 2016. Younger respondents (p-value = 0.01), and those with at least a college education (p-value = 0.03), were more likely than other respondents to consider the online campaign reliable and trustworthy., Conclusion: Routine review of Sina-Weibo and other social media platforms could enhance the ability of public health staff to effectively respond to community concerns and awareness during public health emergencies. Advancements of social media monitoring tools and staff training could help to promote health awareness during emergencies by directly addressing public perceptions and concerns. Various approaches may be needed to reach different at-risk populations, particularly older and less educated populations who may prefer more traditional modes of communication., Competing Interests: The authors have declared that no competing interests exist.

The recent advances in gene chip technology have led to the identification of multiple metabolism-related genes that are closely associated with colorectal cancer (CRC). Nevertheless, none of these genes could accurately diagnose or predict CRC. The prognosis of CRC has been made by previous prognostic models constructed by using multiple genes, however, the predictive function of multi-gene prognostic models using metabolic genes for the CRC prognosis remains unexplored. In this study, we used the TCGA-CRC cohort as the test dataset and the GSE39582 cohort as the experimental dataset. Firstly, we constructed a prognostic model using metabolic genes from the TCGA-CRC cohort, which were also associated with CRC prognosis. We analyzed the advantages of the prognostic model in the prognosis of CRC and its regulatory mechanism of the genes associated with the model. Secondly, the outcome of the TCGA-CRC cohort analysis was validated using the GSE39582 cohort. We found that the prognostic model can be employed as an independent prognostic risk factor for estimating the CRC survival rate. Besides, compared with traditional clinical pathology, it can precisely predict CRC prognosis as well. The high-risk group of the prognostic model showed a substantially lower survival rate as compared to the low-risk group. In addition, gene enrichment analysis of metabolic genes showed that genes in the prognostic model are enriched in metabolism and cancer-related pathways, which may explain its underlying mechanism. Our study identified a novel metabolic profile containing 11 genes for prognostic prediction of CRC. The prognostic model may unravel the imbalanced metabolic microenvironment, and it might promote the development of biomarkers for predicting treatment response and streamlining metabolic therapy in CRC., Competing Interests: The authors have declared that no competing interests exist.

Background: This study aimed to develop and validate the Food and Nutrition Literacy Questionnaire for Chinese School-age Children (FNLQ-SC)., Methods: A comprehensive literature review and qualitative study were initially performed to identify the dimensions and core components of food and nutrition literacy. A cross-sectional survey of 4359 school-age children was conducted, and junior middle school students were used to analyze the reliability and validity of the questionnaire (n = 2452). The reliability of the questionnaire was determined by internal consistency, the construct validity was assessed by exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), and the content validity was assessed by the Pearson correlation coefficient., Results: From the literature review and qualitative methods, 19 core components of the FNLQ-SC were developed, including one dimension of food and nutrition knowledge and understanding, and four skill dimensions (ability of access, selection, preparing food and healthy eating). The overall FNLQ-SC questionnaire had acceptable internal consistency (Cronbach's α = 0.698). The EFA of skill components extracted 5 factors that were included in the conceptual framework in a slightly different model, and the cumulative contribution of variance accounted for 50.60% of the overall variance. The CFA of skill components showed an acceptable fit in general and the root mean square error of approximation (RMSEA) was 0.070 (between 0.50 to 0.80). The communality was greater than 0.20 for all components. The Pearson correlation coefficients between each dimension and the overall questionnaire ranged from 0.370 to 0.877. The average FNLQ-SC score of all 4395 participants was 61.91 ± 9.22, and the score for the knowledge and understanding dimension was higher than that for the skill dimensions. Multiple linear regression analysis indicated that not only social demographic characteristics (being a girl, being an only child, living someplace other than at school, having an urban registered permanent residence status, being from an affluent family, and being cared for by parents/grandparents with a higher education level) but also the home food environment were predictors of food and nutrition literacy in school-age children (R2 = 0.226, F = 81.401, P<0.05)., Conclusion: The Food and Nutrition Literacy Questionnaire (FNLQ-SC) developed here had good reliability, and it can potentially be a useful instrument for assessing food and nutrition literacy among Chinese school-age children., Competing Interests: The authors have declared that no competing interests exist.

With the outbreak of COVID-19, the importance of rural areas has been gradually highlighted, and the importance of rural ecological livability has been gradually recognized. A growing body of literature recognizes the importance of building a rural ecological livability (REL) system. It is urgent that we clarify the status quo and spatial-temporal differences in and distributional characteristics of rural ecological livability and that we carry out targeted and differentiated construction to promote rural ecological livability in post-epidemic China. This study proposes a conceptual model that incorporates various economic, social and environmental factors and develops a comprehensive multifactor (production-living-ecology) evaluation system. Using Fujian Province as an example, the entropy weight method is used to measure the REL level of 55 counties and cities, which are comprehensively evaluated from 2015 to 2019. Moran's I and Getis-Ord Gi* are used to analyze the spatial and distributional characteristics of the REL level in Fujian. The results show that the level of REL in Fujian Province has been relatively flat over the past five years, with a slight downward trend. The overall value of the rural ecological livability index in 2015 was 0.345, and its overall value in 2019 was 0.334, with an average value of 0.343. The REL of Fujian Province is spatially correlated, with high levels of livability in the southeast and low levels in the northeast. The autocorrelation in the level of ecological livability in Fujian's counties and cities continues to increase., Competing Interests: The authors have declared that no competing interests exist.

This paper examines the sentiment spillovers among oil, gold, and Bitcoin markets by employing spillovers index methods in a time-frequency framework. We find that the total sentiment spillover among crude oil, gold and Bitcoin markets is time-varying and is greatly affected by major market events. The directional sentiment spillovers are also time-varying. On average, the Bitcoin market is the major transmitter of directional sentiment spillovers, whereas the crude oil and gold markets are the major receivers. In particular, the sentiment spillover effects are major created at high-frequency components, implying that the markets rapidly process the sentiment spillover effects and the shock is transmitted over the short-term. Moreover, we also find that the sentiment spillover effects differ significantly in term of intensity and direction when compared with return and volatility spillover effects. The present study has certain applications for investors and policymakers., Competing Interests: The authors have declared that no competing interests exist.

Small cell lung cancer (SCLC) is a carcinoma of the lungs with strong invasion, poor prognosis and resistant to multiple chemotherapeutic drugs. It has posed severe challenges for the effective treatment of lung cancer. Therefore, searching for genes related to the development and prognosis of SCLC and uncovering their underlying molecular mechanisms are urgent problems to be resolved. This study is aimed at exploring the potential pathogenic and prognostic crucial genes and key pathways of SCLC via bioinformatic analysis of public datasets. Firstly, 117 SCLC samples and 51 normal lung samples were collected and analyzed from three gene expression datasets. Then, 102 up-regulated and 106 down-regulated differentially expressed genes (DEGs) were observed. And then, functional annotation and pathway enrichment analyzes of DEGs was performed utilizing the FunRich. The protein-protein interaction (PPI) network of the DEGs was constructed through the STRING website, visualized by Cytoscape. Finally, the expression levels of eight hub genes were confirmed in Oncomine database and human samples from SCLC patients. It showed that CDC20, BUB1, TOP2A, RRM2, CCNA2, UBE2C, MAD2L1, and BUB1B were upregulated in SCLC tissues compared to paired adjacent non-cancerous tissues. These suggested that eight hub genes might be viewed as new biomarkers for prognosis of SCLC or to guide individualized medication for the therapy of SCLC., Competing Interests: The authors have declared that no competing interests exist.

The standard GLM and GAM frequency-severity models assume independence between the claim frequency and severity. To overcome restrictions of linear or additive forms and to relax the independence assumption, we develop a data-driven dependent frequency-severity model, where we combine a stochastic gradient boosting algorithm and a profile likelihood approach to estimate parameters for both of the claim frequency and average claim severity distributions, and where we introduce the dependence between the claim frequency and severity by treating the claim frequency as a predictor in the regression model for the average claim severity. The model can flexibly capture the nonlinear relation between the claim frequency (severity) and predictors and complex interactions among predictors and can fully capture the nonlinear dependence between the claim frequency and severity. A simulation study shows excellent prediction performance of our model. Then, we demonstrate the application of our model with a French auto insurance claim data. The results show that our model is superior to other state-of-the-art models., Competing Interests: The authors have declared that no competing interests exist.

Background: Illness-related costs experienced by tuberculosis patients produce a severe economic impact on households, especially poor families. Few studies have investigated the full costs, including direct and indirect costs, at the patient and household levels in south-east China., Methods: A case follow-up study was conducted in the Bao'an district of Shenzhen City, China. Eligible new and previously treated individuals with pulmonary tuberculosis (TB) during January 1st 2013 to June 30th 2013 were enrolled. Medical and non-medical costs as well as income loss were calculated in diagnosis and treatment periods, respectively. Factors associated with costs due to TB diagnosis, treatment and TB care (diagnosis + treatment) were explored respectively with a linear regression model., Results: Of the total 514 TB patients enrolled, 95% were from the migrant population, and 65% were males, with a mean age of 32.25 (±10.11). The median costs due to TB diagnosis and TB treatment were 79 United States dollar (USD), 748USD (6.2897 China Yuan (CNY) = 1USD, 2013) per patient, respectively. The median costs due to TB care (diagnosis and treatment) per patient was 1218USD, corresponding to 26% of patients' annual income pre-illness. Those who visited more times to health facilities, hospitalized, received higher education, or occupied in national civil servant/services/retired staff might expense more before diagnosis. Costs due to TB treatment was significantly higher among migrant patients, sputum smear positive patients, and widowed/divorced population. Factors associated with less total costs were native patients, fewer times of visiting to health-care facilities and those with no hospitalization history due to TB., Conclusions: Although a free TB control policy is in force, patients with TB are still facing a heavy economic burden. More available interventions to reduce the financial burden on tuberculosis patients are urgently needed., Competing Interests: The authors have declared that no competing interests exist.

Diet is believed to play a major role in maternal recovery, postpartum weight retention (PPWR) is one of the challenges for Chinese women. However, the association between puerperal women's diet and PPWR remained unclear and complicated in China. The study assessed the dietary quality of puerperal women using adjusted Chinese Dietary Balance Index-16 (DBI-16) and explored its associations with PPWR. Participants were enrolled in the Mother-Infant Cohort Study of China. Dietary intake and demographic characteristics were obtained by a semi-quantitative food frequency questionnaire and a self-designed questionnaire at 0-3 months postpartum. PPWR was calculated by the weight difference at 0-3months and 6-8months postpartum minus pre-pregnancy weight. Dietary quality was assessed using adjusted DBI-16. 316 puerperal women were enrolled. According to adjusted DBI-16, 84.8% of participants had an insufficient dietary intake (vegetables 84.8%, fruits 91.8%, dairy 87.3%, soybean 61.4% and aquatic foods 79.4%, respectively), 67.1% had an excessive intake (cereals 60%, meat 57.3% and eggs 64.9%, respectively), 98.4% had an imbalanced diet consumption. PPWR at 0-3, and 6-8 months were 6.0 (±5.1) kg and 5.2 (±7.7) kg, and the percentage of PPWR (≥5kg) were 63.0% and 52.8% respectively. Multivariable linear regression showed the intake of fish and shrimp at 0-3 months postpartum was negatively associated with PPWR at 6-8 months (β = -0.114, SE = 0.279, p < 0.05). The diet quality of Chinese puerperal women was unreasonable and imbalanced. Fish intake tended to be a favorable factor for postpartum weight loss., Competing Interests: The authors have declared that no competing interests exist.

Objective: To investigate the relationship between food patterns and mild cognitive impairment (MCI) among Chinese elderly to provide evidence for risk prevention and control of MCI among elderly population., Methods: Between February 2017 to October 2018, a stratified multistage cluster sampling method was used to select participants from 760 communities of six districts in Xi'an, China, for 49-item food frequency questionnaire survey. A total of 2311 participants aged 60 to 88 years were included in the study with 444 (19.2%) participants of MCI among Chinese community-dwelling elderly adults. Food patterns associated with risk of dementia were assessed by using a reduced rank regression (RRR) analysis, and the multivariate linear regression was used to test trends of risk factors across scores for the food pattern., Results: Four dietary patterns were extracted which explained 88.65% of the total variation in food intakes. Furthermore, the food pattern 1 (FP1) accounted for 60.25% of the total variation of all responsible variables and as a target dietary pattern in the study, which was related with high intake of legumes, vegetables, fruits, milk and dairy products, nuts and a low intake of noodles and cereals (p<0.05). Multivariate linear regression analysis showed that participants with a high score for FP1 had higher direction, memory and language function and FP1 can improve the ability of cognitive function (p<0.05)., Conclusion: The FP1 of Chinese dietary patterns was significantly correlated with higher cognitive function which can reduce the risk of MCI among Chinese elderly., Competing Interests: The authors have declared that no competing interests exist.

In imaging systems, image blurs are a major source of degradation. This paper proposes a parameter estimation technique for linear motion blur, defocus blur, and atmospheric turbulence blur, and a nonlinear deconvolution algorithm based on sparse representation. Most blur removal techniques use image priors to estimate the point spread function (PSF); however, many common forms of image priors are unable to exploit local image information fully. In this paper, the proposed method does not require models of image priors. Further, it is capable of estimating the PSF accurately from a single input image. First, a blur feature in the image gradient domain is introduced, which has a positive correlation with the degree of blur. Next, the parameters for each blur type are estimated by a learning-based method using a general regression neural network. Finally, image restoration is performed using a half-quadratic optimization algorithm. Evaluation tests confirmed that the proposed method outperforms other similar methods and is suitable for dealing with motion blur in real-life applications., Competing Interests: The authors have declared that no competing interests exist.

Background: As an essential component in reducing anthropogenic CO2 emissions to the atmosphere, tree planting is the key to keeping carbon dioxide emissions under control. In 1992, the United Nations agreed to take action at the Earth Summit to stabilize and reduce net zero global anthropogenic CO2 emissions. Tree planting was identified as an effective method to offset CO2 emissions. A high net photosynthetic rate (Pn) with fast-growing trees could efficiently fulfill the goal of CO2 emission reduction. Net photosynthetic rate model can provide refernece for plant's stability of photosynthesis productivity., Methods and Results: Using leaf phenotype data to predict the Pn can help effectively guide tree planting policies to offset CO2 release into the atmosphere. Tree planting has been proposed as one climate change solution. One of the most popular trees to plant are poplars. This study used a Populus simonii (P. simonii) dataset collected from 23 artificial forests in northern China. The samples represent almost the entire geographic distribution of P. simonii. The geographic locations of these P. simonii trees cover most of the major provinces of northern China. The northwestern point reaches (36°30'N, 98°09'E). The northeastern point reaches (40°91'N, 115°83'E). The southwestern point reaches (32°31'N, 108°90'E). The southeastern point reaches (34°39'N, 113°74'E). The collected data on leaf phenotypic traits are sparse, noisy, and highly correlated. The photosynthetic rate data are nonnormal and skewed. Many machine learning algorithms can produce reasonably accurate predictions despite these data issues. Influential outliers are removed to allow an accurate and precise prediction, and cluster analysis is implemented as part of a data exploratory analysis to investigate further details in the dataset. We select four regression methods, extreme gradient boosting (XGBoost), support vector machine (SVM), random forest (RF) and generalized additive model (GAM), which are suitable to use on the dataset given in this study. Cross-validation and regularization mechanisms are implemented in the XGBoost, SVM, RF, and GAM algorithms to ensure the validity of the outputs., Conclusions: The best-performing approach is XGBoost, which generates a net photosynthetic rate prediction that has a 0.77 correlation with the actual rates. Moreover, the root mean square error (RMSE) is 2.57, which is approximately 35 percent smaller than the standard deviation of 3.97. The other metrics, i.e., the MAE, R2, and the min-max accuracy are 1.12, 0.60, and 0.93, respectively. This study demonstrates the ability of machine learning models to use noisy leaf phenotype data to predict the net photosynthetic rate with significant accuracy. Most net photosynthetic rate prediction studies are conducted on herbaceous plants. The net photosynthetic rate prediction of P. simonii, a kind of woody plant, illustrates significant guidance for plant science or environmental science regarding the predictive relationship between leaf phenotypic characteristics and the Pn for woody plants in northern China., Competing Interests: Author Andrew Siu was employed by Amgen. This disclosure does not alter our adherence to the PLOS ONE polices on sharing data and materials. All authors declare no competing interests.

To accurately evaluate expression levels of target genes, stable internal reference genes is required for normalization of quantitative real-time PCR (qRT-PCR) data. However, there have been no systematical investigation on the stability of reference genes used in the bedstraw weed, Galium aparine L. (BGA). In this study, the expression profiles of seven traditionally used reference genes, namely 18S, 28S, ACT, GAPDH, EF1α, RPL7 and TBP in BGA were assessed under both biotic (developmental time and tissue), and abiotic (temperature, regions and herbicide) conditions. Four analytical algorithms (geNorm, Normfinder, BestKeeper and the ΔCt method) were used to analyze the suitability of these genes as internal reference genes. RefFinder, a comprehensive analytical software, was used to rank the overall stability of the candidate genes. The optimal normalization internal control genes were ranked as: 28S and RPL7 were best for all the different experimental conditions (developmental stages, tissues, temperature, regions and herbicide treatment); 28S and RPL7 for developmental stages; TBP and GAPDH for different tissues; 28S and GAPDH were relatively stable for different temperature; 28S and TBP were suitable for herbicide treatment. A specific set of reference genes were recommended for each experimental condition in BGA., Competing Interests: The authors have declared that no competing interests exist.

Talaromyces leycettanus JCM12802 is a great producer of thermophilic glycoside hydrolases (GHs). In this study, two cellulases (TlCel5A and TlCel6A) belonging to GH5 and GH6 respectively were expressed in Pichia pastoris and functionally characterized. The enzymes had acidic and thermophilic properties, showing optimal activities at pH 3.5-4.5 and 75-80°C, and retained stable at temperatures up to 60°C and over a broad pH range of 2.0-8.0. TlCel5A and TlCel6A acted against several cellulose substrates with varied activities (3,101.1 vs. 92.9 U/mg to barley β-glucan, 3,905.6 U/mg vs. 109.0 U/mg to lichenan, and 840.3 and 0.09 U/mg to CMC-Na). When using Avicel, phosphoric acid swollen cellulose (PASC) or steam-exploded corn straw (SECS) as the substrate, combination of TlCel5A and TlCel6A showed significant synergistic action, releasing more reduced sugars (1.08-2.87 mM) than the individual enzymes. These two cellulases may represent potential enzyme additives for the efficient biomass conversion and bioethanol production., Competing Interests: The authors have declared that no competing interests exist.

This paper studies the heterogeneous effects of exchange rate and stock market on carbon emission allowance price in four emissions trading scheme pilots in China. We employ a panel quantile regression model, which can describe both individual and distributional heterogeneity. The empirical results illustrate that the effects of explanatory variables on carbon emission allowance price is heterogeneous along the whole quantiles. Specifically, exchange rate has a negative effect on carbon emission allowance price at lower quantiles, while becomes a positive effect at higher quantiles. In addition, a negative effect exists between domestic stock market and carbon emission allowance price, and the intensity decreasing along with the increase of quantile. By contrast, an increasing positive effect is discovered between European stock market and domestic carbon emission allowance prices. Finally, heterogeneous effects on carbon emission allowance price can also be proved in European Union Emission Trading Scheme (EU-ETS)., Competing Interests: No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed.

Certain plant genotypes can achieve optimal growth under appropriate environmental conditions. Under high planting density conditions, plants undergo competition for uptake and utilization of light and nutrients. However, the relationship between whole-genome expression patterns and the planting density in perennial woody plants remains unknown. In this study, whole-genome RNA sequencing of poplar (Populus × euramericana) was carried out at three different sampling heights to determine gene expression patterns under high (HD) and low (LD) planting densities. As a result, 4,004 differentially expressed genes (DEGs) were detected between HD and LD, of which 2,300, 701, and 1,003 were detected at the three positions, upper, middle and bottom, respectively. Function annotation results further revealed that a large number of the DEGs were involved in distinct biological functions. There were significant changes in the expression of metabolism-related and stimulus-related genes in response to planting density. There were 37 DEGs that were found at all three positions and were subsequently screened. Several DEGs related to plant light responses and photosynthesis were observed at different positions. Meanwhile, numbers of genes related to auxin/indole-3-acetic acid, and carbon and nitrogen metabolism were also revealed, displaying overall trends of upregulation under HD. These findings provide a basis for identifying candidate genes related to planting density and could increase our molecular understanding of the effect of planting density on gene expression., Competing Interests: The authors have declared that no competing interests exist.

Melaphidina aphids (Rhus-gall aphids; Eriosomatinae: Fordini) comprise five genera from eastern Asia and one monotypic genus from eastern North America. Melaphidina are unique in feeding on plant species of Rhus subgenus Rhus (Anacardiaceae), on which they form galls during the summer. The phylogenetic relationships among some species of Melaphidina aphids remain controversial. In this study, we sought to resolve the backbone phylogeny of Melaphidina aphids by sampling 15 accessions representing all six genera, all species, and all subspecies except Meitanaphis microgallis using 20 gene regions: five nuclear genes as well as 13 protein-coding genes and two rRNA genes of the mitochondrial genome. Phylogenetic analyses included Bayesian and maximum likelihood methods. Independent analyses of nuclear and mitochondrial genes returned congruent topologies, and analyses of all gene regions combined showed well-supported relationships among Melaphidina species. In particular, these were: (1) Nurudea (excluding N. ibofushi) is sister to a clade composed of the five remaining genera; (2) the monotypic North American genus Melaphis is sister to a clade comprising the four remaining genera; and (3) (Schlechtendalia + N. ibofushi) is sister to the clade (Floraphis (Meitanaphis + Kaburagia). Our results support the transfer of Meitanaphis flavogallis to Kaburagia as an additional subspecies or species, and the recognition of Floraphis as a distinct genus. This study provides important molecular resources for subsequent evolutionary studies using more nuclear genes on the Melaphidina aphids and their close allies., Competing Interests: The authors have declared that no competing interests exist.

Tea plant (Camellia sinensis) accumulates abundant flavonoid glycosides that are the major bioactive ingredients in tea. Biosynthesis of flavonoid glycosides are catalyzed by UDP-glucosyltransferases (UGTs) that are widely present in plants. Among one hundred and seventy-eight UGTs genes that we have previously identified in tea plant, few of them have been functionally characterized. In the present study, we further identified UGT73A17 gene that is responsible for the biosynthesis of a broad range of flavonoid glycosides. Sequence analysis revealed that the deduced UGT73A17 protein showed high identity with 7-O-glycosyltransferases at amino acid level and it was clustered into the clade containing several 7-O-glycosyltransferases from other plant species. Enzymatic assays revealed that the recombinant UGT73A17 protein (rUGT73A17) exhibited activity toward flavonols (kaempferol, quercetin, and myricetin), flavones (apigenin, luteolin, and tricetin), flavanone (naringenin), isoflavones (genistein) and epicatechin gallate, yielding 7-O-glucosides as the major in vitro products. In particular, rUGT73A17 displayed higher activity at high temperatures (eg. 50°C) than at low temperatures, which was consistent with its relatively high expression level at high temperatures. Two amino acid substitutions at I296L and V466A improved the enzymatic activity of rUGT73A17. Our study demonstrated that UGT73A17 is responsible for the biosynthesis of a broad range of flavonoid glucosides, which is also involved in heat response and quality of tea plant., Competing Interests: The authors have declared that no competing interests exist.

Background: Dietary protein restriction has long been thought to play an important role in the progression of chronic kidney disease (CKD); however, the effect of dietary protein on the rate of decline in kidney function remains controversial., Objective: We undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the influence of protein restriction on chronic kidney disease., Method: Ovid MEDLINE (from 1946 to March 5, 2016), EMBASE (from 1966 to March 5, 2016), and the Cochrane Library (Inception to March 5, 2016) were searched to identify RCTs comparing different levels of protein intake for at least 24 weeks in adult patients with CKD. The outcomes included kidney failure events, the rate of change in estimated glomerular filtration rate (eGFR) per year, all cause death events, and changes in proteinuria, serum phosphorus concentration, serum albumin, and body mass index (BMI)., Results: Nineteen trials with 2492 subjects were analyzed. A low protein diet reduced the risk of kidney failure (odds ratio (OR) = 0.59, 95% CI: 0.41 to 0.85) and end-stage renal disease (ESRD) (OR = 0.64, 95% CI: 0.43 to 0.96), but did not produce a clear beneficial effect for all cause death events (OR = 1.17, 95% CI: 0.67 to 2.06). The change in the mean difference (MD) for the rate of decline in the eGFR was significant (MD: -1.85, P = 0.001), and for proteinuria (MD: -0.44, P = 0.02). A low protein diet also reduced the serum phosphorus concentration (MD: -0.37, 95% CI: -0.5 to -0.24) and BMI (MD: -0.61, 95% CI: -1.05 to -0.17). However the change in albumin presented no significant difference between two groups (MD: 0.23, 95% CI: -0.51 to 0.97)., Conclusions: Based on the findings of our meta-analysis, protein-restricted diet may reduce the rate of decline in renal function and the risk of kidney failure for CKD populations, but did not produce a clear beneficial effect for all cause death events. Besides However, the optimal level of protein intake in different participants is left unanswered, and the nutritional status should be regarded with caution., Competing Interests: The authors have declared that no competing interests exist.

Background: Sexual transmission of HIV among men who have sex with men (MSM) increased markedly in China during the past decade. HIV incidence is a critical indicator in HIV surveillance and we use a HIV-1 BED-capture-enzyme immunoassay (BED-CEIA) to examine the incidence among MSM in Beijing from 2008 to 2016. Risk factors related to recent HIV infection were also assessed., Methods: Consecutive cross-sectional surveys on MSM were conducted yearly from 2008 through 2016. Demographic and behaviors data were collected. HIV status was determined and HIV positive specimens were tested for recent infection using BED-CEIA. Specimens with ODn values≤0.8 were considered recently infected, HIV incidence rates and prevalence were then calculated. Risk factors associated with recent HIV infection were assessed by univariate and multivariable logistic regression., Results: From 2008 to 2016, the numbers of eligible participants in the nine consecutive years ranged from 472 to 616. All the 261 eligible HIV-positive specimens were subjected to recent HIV infection testing. HIV prevalence ranged from 5.0% (3.3%-6.8%) to 10.2% (7.8%-12.7%), and incidence ranged from 1.57% (0.19%-2.95%) to 6.63% (3.65%-9.61%). MSM who never or sometimes used condoms during anal sex with men in the past 6 months (aOR = 1.515, 95%CI: 1.016-2.257, p = 0.041), or having syphilis infection (aOR = 1.561, 95%CI: 0.946-2.575, p = 0.081) were more likely to be recently infected with HIV. Being a Beijing resident (aOR = 0.409, 95%CI: 0.212-0.790, p = 0.008), or having only one male anal sex partner in the past 6 months (aOR = 0.467, 95%CI: 0.220-0.994, p = 0.048) were associated with a lower risk for recent HIV infection., Conclusions: The HIV incidence fluctuated among MSM in Beijing. Unprotected anal sex, having multiple sex partners, being a non-registered Beijing resident and having a syphilis infection play important roles in the recent HIV infection. Effective intervention measures for HIV and syphilis control and prevention should be continuously strengthened., Competing Interests: The authors have declared that no competing interests exist.

[This corrects the article DOI: 10.1371/journal.pone.0187356.].

Extremophilic xylanases have attracted great scientific and industrial interest. In this study, a GH10 xylanase-encoding gene, Xyl10E, was cloned from Bispora sp. MEY-1 and expressed in Pichia pastoris GS115. Deduced Xyl10E shares the highest identities of 62% and 57% with characterized family GH10 xylanases from Talaromyces leycettanus and Penicillium canescens (structure 4F8X), respectively. Xyl10E was most active at 93 to 95°C and pH 4.0, retained more than 75% or 48% of the initial activity when heated at 80°C or 90°C for 30 min, respectively, and hardly lost activity at pH 1.0 to 7.0, but was completely inhibited by SDS. Two residues, A160 and A161, located on loop 4, were identified to play roles in catalysis. Mutants A160D/E demonstrated higher affinity to substrate with lower Km values, while mutants A161D/E mainly displayed elevated Vmax values. All of these mutants had significantly improved catalytic efficiency. According to the molecular dynamics simulation, the mutation of A160E was able to affect the important substrate binding site Y204 and then improve the substrate affinity, and the mutation of A161D was capable of forming a hydrogen bond with the substrate to promote the substrate binding or accelerate the product release. This study introduces a highly thermophilic fungal xylanase and reveals the importance of loop 4 for catalytic efficiency.

Background: It is unclear whether common genetic variants of the RET proto-oncogene contribute to disease susceptibility, clinical severity, and thyroid function in differentiated thyroid cancer (DTC)., Methods: A total of 300 DTC patients and 252 healthy controls were enrolled in this study. Seven RET tagging single nucleotide polymorphisms were genotyped using the KASPar platform., Results: Subgroup analysis showed that concomitant thyroid benign diseases were less likely to occur in DTC subjects with the rs1799939 AG or AG plus AA genotypes (odds ratio (OR) = 1.93 and 1.88, P = 0.009 and 0.011, respectively). A rare haplotype, CGGATAA, was associated statistically with a reduced risk of DTC (OR = 0.18, P = 0.001). Concerning the aggressive features of DTC, higher level of N stage was more likely to occur in subjects carrying the wild-type genotypes at rs1800860 site (for dominant model: OR = 0.48, P = 0.008). Another rare haplotype, CAAGCGT, conferred increased risk for the occurrence of distant metastasis (OR = 7.57, P = 0.009). Notably, higher thyroid stimulating hormone levels and lower parathyroid hormone levels were found in patients with rs2075912, rs2565200, and rs2742240 heterozygotes and rare homozygotes; similar results were observed between PTH levels and rs1800858., Conclusion: This study provided useful information on RET variants that should be subjected to further study.

Background and Objectives: The effects of uric acid-lowering therapy in patients with chronic kidney disease (CKD) remain uncertain. Therefore, we undertook a systematic review and meta-analysis to investigate the effects of uric acid-lowering agents on major clinical outcomes of CKD., Design, Setting, Participants, and Measurements: According to the pre-specified protocol that was registered with PROSPERO (No. CRD42016038030), we searched systematically in MEDLINE, EMBASE, and the Cochrane Library for trials up to February 2016. Prospective, randomized, controlled trials assessing the effects of uric acid-lowering agents on cardiovascular and kidney outcomes in patients with CKD were included. Random-effects analytical methods were used., Results: Sixteen eligible trials were identified, providing data for 1,211 patients with CKD, including 146 kidney failure events and 69 cardiovascular events. Uric acid-lowering therapy produced a 55% relative risk (RR) reduction (95% confidence interval [95% CI], 31-64) for kidney failure events (P < 0.001), and a 60% RR reduction (95% CI, 17-62) for cardiovascular events (P < 0.001), but had no significant effect on the risk of all-cause death (RR, 0.86; 95% CI, 0.50-1.46). The mean differences in rate of decline in the estimated glomerular filtration rate (4.10 mL/min/1.73 m2 per year slower in uric acid-lowering therapy recipients, 95% CI, 1.86-6.35) and the standardized mean differences in the change in proteinuria or albuminuria (-0.23 units of standard deviation greater in uric acid-lowering therapy recipients; 95% CI, -0.43 to -0.04) were also statistically significant., Conclusions: Uric acid-lowering therapy seemed to improve kidney outcomes and reduce the risk of cardiovascular events in adults with CKD.

Different subtypes of non-small cell lung cancer (NSCLC) have distinct sites of origin, histologies, genetic and epigenetic changes. In this study, we explored the mechanisms of ECT2 dysregulation and compared its prognostic value in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In addition, we also investigated the enrichment of ECT2 co-expressed genes in KEGG pathways in LUAD and LUSC. Bioinformatic analysis was performed based on data from the Cancer Genome Atlas (TCGA)-LUAD and TCGA-LUSC. Results showed that ECT2 expression was significantly upregulated in both LUAD and LUSC compared with normal lung tissues. ECT2 expression was considerably higher in LUSC than in LUAD. The level of ECT2 DNA methylation was significantly lower in LUSC than in LUAD. ECT2 mutation was observed in 5% of LUAD and in 51% of LUSC cases. Amplification was the predominant alteration. LUAD patients with ECT2 amplification had significantly worse disease-free survival (p = 0.022). High ECT2 expression was associated with unfavorable overall survival (OS) (p<0.0001) and recurrence-free survival (RFS) (p = 0.001) in LUAD patients. Nevertheless, these associations were not observed in patients with LUSC. The following univariate and multivariate analysis showed that the high ECT2 expression was an independent prognostic factor for poor OS (HR: 2.039, 95%CI: 1.457-2.852, p<0.001) and RFS (HR: 1.715, 95%CI: 1.210-2.432, p = 0.002) in LUAD patients, but not in LUSC patients. Among 518 genes co-expressed with ECT2 in LUAD and 386 genes co-expressed with ECT2 in LUSC, there were only 98 genes in the overlapping cluster. Some of the genes related KEGG pathways in LUAD were not observed in LUSC. These differences might help to explain the different prognostic value of ECT2 in LUAD and LUSC, which are also worthy of further studies.

Stone cell content is thought to be one of the key determinants for fruit quality in pears. However, the molecular mechanism of stone cell development remains poorly understood. In this study, we found that the stone cell clusters (SCCs) distribution and area in 'Dangshan Su' (with abundant stone cells) were higher as compared to 'Lianglizaosu' (low stone cell content bud sport of 'Dangshan Su') based on the histochemical staining, and the correlations of lignin content with stone cell content and SCC area was significant. The fruits of 'Dangshan Su' and 'Lianglizaosu' at three different developmental stages (23 and 55 days after flowering and mature) were sampled for comparative transcriptome analysis to explore the metabolic pathways associated with stone cell development. A total of 42444 unigenes were obtained from two varieties, among which 7203 differentially expressed genes (DEGs) were identified by comparison of the six transcriptomes. Specifically, many DEGs associated with lignin biosynthesis were identified, including coumaroylquinate 3-monooxygenase (C3H), shikimate O-hydroxycinnamoyltransferase (HCT), ferulate 5-hydroxylase (F5H), cinnamyl alcohol dehydrogenase (CAD) and peroxidase (POD), as well as genes related to carbon metabolism, such as sorbitol dehydrogenase-like (SDH-like) and ATP-dependent 6-phosphofructokinase (ATP-PFK). At the peak of the stone cell content (55 days after flowering), the expression level of these genes in 'Dangshan Su' was significantly increased compared with 'Lianglizaosu', indicating that these genes were closely related to stone cell development. We validated the transcriptional levels of 33 DEGs using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The results were consistent with the transcriptome analysis, indicating the reliability of transcriptome data. In addition, subcellular localization analysis of three DEGs in lignin synthesis (PbC3H, PbF5H and PbPOD) revealed that these proteins are mainly distributed in the cell membrane and cytoplasm. These results provide new insights into the molecular mechanism of stone cell formation.

Previous studies confirmed that dietary supplements of fish oil and krill oil can alleviate obesity in mice, but the underlying mechanism remains unclear. This study aims to discern whether oil treatment change the structure of the gut microbiota during the obesity alleviation. The ICR mice received high-fat diet (HFD) continuously for 12 weeks after two weeks of acclimatization with a standard chow diet, and the mice fed with a standard chow diet were used as the control. In the groups that received HFD with oil supplementation, the weight gains were attenuated and the liver index, total cholesterol, triglyceride and low-density lipoprotein cholesterol were reduced stepwise compared with the HFD group, and the overall structure of the gut microbiota, which was modulated in the HFD group, was shifted toward the structure found in the control group. Moreover, eighty-two altered operational taxonomic units responsive to oil treatment were identified and nineteen of them differing in one or more parameters associated with obesity. In conclusion, this study confirmed the effect of oil treatment on obesity alleviation, as well as on the microbiota structure alterations. We proposed that further researches are needed to elucidate the causal relationship between obesity alleviation and gut microbiota modulation.