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Summary: Background: Existing studies have not provided robust evidence about the CVD risk of non-smoking patients with restrictive spirometric pattern (RSP) or airflow obstruction (AFO), and how the risk is modified by body shape. We aimed to bridge the gap. Methods: We used never-smokers' data from the China Kadoorie Biobank (CKB) and performed Cox models by sex (278,953 females and 50,845 males). Spirometry was used to assess the baseline spirometric pattern. CVD outcomes were captured through multiple sources. Findings: Females’ results were presented primarily, though males' results were similar. During a median 12-year (maximum 14.5 years) follow-up, both RSP and AFO patients had increased risks of acute myocardial infarction (AMI), other ischaemic heart disease (other IHD), heart failure, pulmonary heart disease, arrhythmia, and intracerebral haemorrhage (ICH). RSP was also associated with ischaemic stroke (IS). The HRs (95% CIs) for AFO in females ranged from 1.29 (1.15–1.45) for ICH to 8.84 (7.79–10.03) for pulmonary heart disease, while those for RSP ranged from 1.11 (1.08–1.15) for IS to 3.17 (2.80–3.59) for pulmonary heart disease. These risks increased with the severity of AFO and reduced FVC. RSP/AFO was more strongly associated with other IHD, heart failure, and pulmonary heart disease in underweight females than in normal and obese counterparts, respectively. Interpretation: With the confounding of smoking fully controlled, both RSP and AFO were associated with higher risks of various CVD outcomes, which further increased with the severity of AFO and reduced FVC. These associations were even stronger in underweight individuals. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Ministry of Science and Technology of the People's Republic of China, Kadoorie Charitable Foundation, UK Wellcome Trust, UK Medical Research Council, Cancer Research UK, and British Heart Foundation.

Abstract The Final Year Project (FYP) is one of the most important courses for every undergraduate student, and the effective operation of the FYPs in higher education still faces challenges, such as uneven resource distribution and limited efficiency. This study reports a mixed-methods approach to study the impact of a student-centered FYP allocation mechanism on student performance. This research aims to investigate how aligning students’ FYP choices with their interests can inspire motivation and enhance academic performance. More importantly, this mechanism improves students’ academic resilience, enabling them to navigate unexpected contextual factors. The study’s findings take into account various aspects, including student satisfaction with the allocation process, future improvement methods, and the relationship between interest and context. The outcomes observed in this study support our hypotheses, indicating the improvements in students’ academic performance as well as the pass and completion rates. Moreover, this research contributes to ‘resilience theory’ by exploring students’ adaptability to contextual changes and their enhancement of academic resilience. This study proposes recommendations for cultivating a dynamic student-centered classroom environment. Future work could pay attention to addressing the limitations of this study, exploring other factors influencing FYP allocation, and integrating more quantitative measures for a comprehensive assessment of its impact.

IntroductionNitrogen (N) and phosphorus (P) enrichment due to anthropogenic activities can significantly affect soil N transformations in forest ecosystems. However, the effects of N and P additions on nitrification and denitrification processes in Metasequoia glyptostroboides plantations, and economically important forest type in China, remain poorly understood.MethodsThis study investigated the responses of soil nitrification and denitrification rates, as well as the abundances of nitrifiers and denitrifiers, to different levels of N and P additions in a 6-year nutrient addition experiment in a M. glyptostroboides plantation.ResultsStepwise multiple regression analysis was used to identify the main predictors of nitrification and denitrification rates. The results showed that moderate N addition (N2 treatment, 2.4 mol·m-2) stimulated nitrification rates and abundances of ammonia-oxidizing archaea (AOA) and bacteria (AOB), while excessive N and P additions inhibited denitrification rates and reduced the abundance of nirS-type denitrifiers. AOB abundance was the main predictor of nitrification rates under N additions, whereas microbial biomass carbon and nirS gene abundance were the key factors controlling denitrification rates. Under P additions, tree growth parameters (diameter at breast height and crown base height) and AOB abundance were the primary predictors of nitrification and denitrification rates.DiscussionOur study reveals complex interactions among nutrient inputs, plant growth, soil properties, and microbial communities in regulating soil N transformations in plantation forests. This study also offers valuable insights for formulating effective nutrient management strategies to enhance the growth and health of M. glyptostroboides plantations under scenarios of increasing elevated nutrient deposition.

BackgroundAccording to the Classification and Catalogue of Occupational Diseases, brucellosis is one of the notifiable occupational infectious diseases, which occurs from time to time in the occupational population. ObjectiveTo compare the work-related injury appraisal process and results of 13 cases of brucellosis at both provincial and municipal levels, analyze and summarize the bias in the practical work of labor capacity identification for occupational diseases such as brucellosis by appraisal management departments and experts, and propose suggestions for optimizing appraisal work. MethodsA comparative study was conducted on the objective examination results and labor capacity appraisal conclusions based on the occupational contact history, clinical diagnosis, occupational disease diagnosis staging, and labor capacity appraisal of 13 patients with brucellosis. The reasons for the inconsistency between the initial appraisal conclusion by institutions at the municipal level and the final appraisal conclusion by institutions at the provincial level were compared and analyzed. ResultsAll of the 13 patients with brucellosis applied for municipal-level labor capacity identification after being identified as work-related injuries, 11 of which did not receive a disability level, and 2 were rated as level 10 disability. Four of those who did not receive the disability rate applied for provincial-level labor capacity identification. As a result, 2 cases were maintained original appraisal conclusions, while the other 2 changed the conclusions to level 9 disability and level 10 disability respectively. It was the first time in Shijiangzhuang municipal-level primary labor capacity appraisal and Hebei provincial-level labor capacity re-appraisal that the work-related injury caused by occupational brucellosis was rated as level 9 disability or level 10 disability. Hence, the lessons learned from this comparative analysis are that the degree of target organ damage and (or) organ dysfunction are the direct basis for work-related injury appraisal; an objective and scientific labor capacity identification for occupational brucellosis should base on the each case of disability evaluation, identify the relevant target organ damage and the degree of dysfunction, and rate the disability level after a comprehensive appraisal.ConclusionThis analysis would be a guidance to the identification of labor capacity for occupational brucellosis in Hebei Province and the whole country. There is a hysteresis issue in the occupational disease provisions in the national standard GB/T 16180—2014 Standard for identify work ability—Gradation of disability caused by work-related injuries and occupatiaonal diseases. In current situation, appraisal experts should not only search for clauses that directly correspond to the occupational diseases and injuries, but also target conditions not covered in the clauses and conduct assessment based on the characteristics of occupational diseases, with scientific, accurate, and flexible application of the clauses in the standard and appendix, so as to make fair, just, and professional appraisal conclusions.

Abstract Key message The forest canopy gaps, formed by natural or anthropogenic factors, have been found to reduce soil carbon content and increase nutrient availability. The magnitudes of these effects have been observed to increase with gap age and size, and are largely influenced by changes in temperature, precipitation, and solar radiation. Context Local studies have illustrated the influence of canopy gaps on the spatial heterogeneity of soil carbon and nutrients, playing a pivotal role in driving forest regeneration and succession. Nevertheless, it remains largely unknown whether the response of soil carbon and nutrient content to gap formation is consistent across forest ecosystems at global scale. Aims The aim of this paper is to assess the homogeneity of the observed responses of soil carbon and nutrients following gap formation among a wide array of forest ecosystems and climatic regions. Methods We performed a meta-analysis synthesizing 2127 pairwise observations from 52 published articles to quantify the changes in in soil physical, chemical, and microbial variables resulting from gap creation in natural forests and plantations spanning tropical to boreal regions. Results Canopy gaps resulted in significant decrease of soil organic carbon (C org) and microbial carbon (C mic). The concentrations of ammonium (NH4 +), nitrate (NO3 −), and available phosphorus (available P) increased following gap creation. These changes mainly occurred in the growing season and in the mineral soil layer, becoming more pronounced with increasing gap age and size. The change in C org was negatively regulated by mean annual precipitation, and was associated with the changes in Nt and N mic . The change in NH4 + was positively regulated by mean annual temperature, and was associated with the changes in available P and oxidoreductases (Ox-EEAs). The model explaining the change in soil carbon content exhibited a higher explanatory power than the one accounting for changes in soil nutrient availability. Conclusion The results indicated that forest canopy gaps resulted in a reduction in soil carbon content and an increase in nutrient availability. These findings contribute to a better understanding of the role of small-scale disturbances as drivers of forest ecosystem succession.

Monitoring drought stress is crucial for estimating productivity and assessing the health status of forest ecosystems under global climate change. Solar-induced chlorophyll fluorescence (SIF) is mechanistically coupled to photosynthesis and has advantages over greenness-based vegetation indices in detecting drought. In recent years, SIF has commonly been used in monitoring drought stress in crop ecosystems. However, the response of tower-based SIF to drought stress in forest ecosystems remains unclear. In this study, we investigated the potential of tower-based SIF to monitor drought, which was quantified using the plant water stress index (PWSI) in a Chinese cork oak plantation. The results show the negative effect of drought on SIF, and afternoon depression of SIF emission under drought stress was observed. Canopy SIF (F) exhibited a nonlinear relationship with PWSI, while the quantum yield of SIF (ΦF) exhibited a significant linear relationship with PWSI at 687 nm and 760 nm (ΦF687: R2 = 0.90; ΦF760: R2 = 0.85). Incident radiation (PAR) and canopy structure affected the response of SIF to drought stress, with PAR as the main factor causing the nonlinear relationship between F and PWSI. Afternoon depression was described as the afternoon/morning ratio (AMR). AMRF and AMRΦF exhibited a negative linear response to PWSI. AMRF was less affected than F by PAR and canopy structures, and AMRΦF was more physiologically representative than ΦF. Moreover, AMRΦF was sensitive to VPD and REW, and it might be a good indicator of drought. Red SIF was more sensitive to drought than far-red SIF, as the R2 of PWSI with AMRΦF687 (R2 = 0.89) was higher than that with AMRΦF687 (R2 = 0.84). These results highlight the potential of tower-based SIF, especially red SIF, for drought monitoring in a plantation, and consideration of the physiological diurnal variation in SIF under drought stress is crucial for improving the accuracy of drought stress monitoring.

Microplastics (MPs) have been identified as emerging contaminants and have received global attention because they pose a severe threat to wildlife and the human food chain. In recent years, many studies related to the sources, distribution, and effects of MPs in marine, terrestrial, and wastewater environmental compartments have been reported, whereas a comprehensive overview of the presence and characteristics of MPs in unique coastal wetland ecosystems is still lacking. Therefore, this review summarizes the accumulation and sources of MPs in coastal wetlands, as well as their effects on these ecosystems, based on environmental monitoring and laboratory results published in the literature. First, the accumulation of MPs in coastal wetlands is briefly reviewed. Second, the sources of MPs in coastal wetlands are discussed. Third, the ecological effects of MPs on coastal wetlands are summarized. Finally, this review presents gaps in the MPs research and provides an outlook for future research in this field.

Halophytes play a crucial role in the ecological restoration of saline and alkaline land and hold promising benefits to food security in China. Although a variety of aspects of halophytes have been extensively addressed, there is still a lack of overall understanding of the leaf nitrogen (N) and phosphorus (P) stoichiometric characteristics, especially at a national scale. We compiled a national dataset of 311 observations from 113 sampling sites across China to explore the changing trends and influencing factors on leaf N and P concentrations, and N:P ratio of halophytes. The results showed that leaf N concentration decreased significantly with increasing latitude (LAT), which was mainly driven by the mean annual temperature (MAT) and mean annual precipitation (MAP). The leaf P concentration increased remarkably with increasing longitude (LON), which was induced by the variation in soil total P (TP) content. The leaf N:P ratio increased as LAT increased and LON decreased, which was potentially regulated by the MAT, MAP, and soil TP content. The scaling exponents of the N-P relationship differed significantly among halophyte types and were 0.40, 0.87, and 1.39 for euhalophyte, pseudohalophyte, and recretohalophyte, respectively. The leaf N concentration exhibited significant differences among ecosystem types and halophyte types, whereas the leaf P concentration and N:P ratio remained relatively stable. In summary, the leaf N concentration and N-P scaling exponent might be the classification criteria for halophyte types from the perspective of plant nutrient resource allocation. Moreover, this study characterized the spatial distribution and allocation strategy of leaf N and P stoichiometry in halophytes by data integration analysis, providing the basic information for nutrient management in the processes of the future domestication and introduction of halophytes.

Objective The current research was designed to explore the relationship between the lipid accumulation index (LAP), coronary artery disease (CAD), and the triglyceride-glucose (TyG) index in patient with H-type hypertension. Methods From June 2021 to January 2022, our hospital’s information management system collected data on 186 patients with essential hypertension. The participants were categorized into two groups (H-type hypertension (n = 113) and non-H-type hypertension (n = 73)) based on their homocysteine levels. Both groups’ general condition, lipid accumulation index, triglyceride-glucose index, and Gensini score were compared to determine the factors influencing the severity of CAD in H-type hypertension patients. Results There were statistically significant differences (P < 0.05) in homocysteine (Hcy, GLP-1 and SAA) level, LAP, and TyG indexes, but not in body mass index (BMI), smoking, sex, age, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), diastolic blood pressure, and systolic blood pressure. Additionally, there were substantial variations between the two groups regarding the number of lesion branches, degree of stenosis, and Gensini score (P > 0.05). patient with grade III to IV lesions had substantially higher LAP and TyG indices than those with stage I to II (P < 0.05). TyG (OR = 2.687) and TyG-LAP (OR = 4.512) were the factors determining the incidence of coronary artery disease in H-type hypertension, according to multivariate logistic regression analysis. The lesion number, stenosis degree, and Gensini score (P < 0.05) varied among both groups. LAP and TyG indexes were substantially greater in patients with double and triple vessel lesions than in those without lesions or with single vessel lesions (P < 0.05); similarly, these two indexes were considerably higher in individuals with grade III to IV lesions than in patients with grade I to II lesions (P < 0.05). As per the Pearson correlation analysis, the LAP, TyG indices and SAAlevel were adversely connected to the Gensini score (r = 0.254, 0.262, 0.299, P < 0.05), the GLP-1 level was negatively correlated to the Gensini score (r = −0.291, P < 0.05). TyG (OR = 2.687) and TyG-LAP (OR = 4.512) were the factors determining the frequency of coronary artery disease in H-type hypertension, according to multivariate logistic regression analysis. Conclusion In conclusion, the LAP and TyG indexes were observed to be closely related to the degree of CAD in H-type individuals with hypertension, which can better understand the pathogenesis of coronary artery disease in patients with H-type hypertension and is of great significance for guiding clinical doctors to carry out personalized treatment and management.

Abstract Segmentation of intracranial aneurysm images acquired using magnetic resonance angiography (MRA) is essential for medical auxiliary treatments, which can effectively prevent subarachnoid hemorrhages. This paper proposes an image segmentation model based on a dense convolutional attention U-Net, which fuses deep and rich semantic information with shallow-detail information for adaptive and accurate segmentation of MRA-acquired aneurysm images with large size differences. The U-Net model serves as a backbone, combining dense block and convolution block attention module (CBAM). The dense block is composed of a batch normalization layer, an randomly rectified linear unit activation function, and a convolutional layer, for mitigation of vanishing gradients, for multiplexing of aneurysm features, and for improving the network training efficiency. The CBAM is composed of a channel attention module and a spatial attention module, improving the segmentation performance of feature discrimination and enhancing the acquisition of key feature information. Owing to the large variation of aneurysm sizes, multi-scale fusion is performed during up-sampling, for adaptive segmentation of MRA-acquired aneurysm images. The model was tested on the MICCAI 2020 ADAM dataset, and its generalizability was validated on the clinical aneurysm dataset (aneurysm sizes: 7 mm) supplied by the Affiliated Hospital of Qingdao University. A good clinical application segmentation performance was demonstrated.

Soil and climatic conditions are known to have close associations with plant morphological and stoichiometric traits at a regional scale along latitudinal gradients; however, how latitude drives biotic and abiotic factors affecting plant nutrient acquisition to accommodate environmental nutrient deficiency remains unclear. We quantified soil, root, leaf, and leaf litter nitrogen (N) and phosphorus (P) concentrations to determine the potentially limiting nutrient and the simultaneous responses of root capture and leaf resorption to nutrient deficiency in seven Quercus acutissima forests across the North–South Transect of Eastern China. The results showed that the mean leaf and root N:P ratios in Q. acutissima were 21.58 and 20.23, respectively, which markedly exceeded the P limitation threshold of 16 for terrestrial plants. The mean leaf litter N and P were 10.63 mg/g and 0.51 mg/g, respectively, indicating that P resorption proficiency was relatively higher than N resorption proficiency. N displayed higher stoichiometric homeostasis than P in the leaf. The leaf and root N:P ratios showed a quadratic variation that first decreased and then increased as latitude increased, whereas the phosphorus resorption efficiency and root-soil accumulation factor of P displayed the opposite trend. Partial least square path modeling (PLS-PM) analysis demonstrated that root nutrient capture and leaf nutrient resorption were regulated by different influential factors. Overall, these findings provide new insights into plant strategies to adapt to environmental nutrient deficiency, as well as the scientific basis for predicting the spatial and temporal patterns of nutrient acquisition in the context of climate change.

Abstract Background Comitant strabismus (CS) is a heterogeneous disorder that is a major contributing factor to unilateral childhood-onset visual impairment. Studies have confirmed that genetic factors play an important role in the development of CS. The aim of this study was to identify the genetic cause of non-syndromic familial CS. Methods Fourteen unrelated CS families were recruited for the study. Twelve affected and 2 unaffected individuals from a large four-generation family (CS08) were selected to perform whole genome-wide linkage analysis. Parallel whole-exome sequencing (WES) was conducted in the same family (9 patients and 1 unaffected member) and 31 additional CS cases from 13 other unrelated families. Sanger sequencing was used to determine whether any of the remaining variants co-segregated with the disease phenotype in the corresponding family. Results Based on linkage analysis, CS in family CS08 mapped to a novel region of 34.17 centimorgan (cM) on chromosome 2q22.3-2q32.1 between markers D2S151 and D2S364, with a maximum log odds (LOD) score of 3.54 (theta = 0) at D2S142. Parallel WES identified a heterozygous variant, LRP2 c.335 A > G (p.Q112R), located in such a linkage interval that completely co-segregated with the disease in the family. Furthermore, another novel heterozygous variant (c.7274A > G, p.D2425G) in LRP2 that co-segregated was detected in 2 additional affected individuals from another unrelated family by WES. Both variants are predicted to be damaging by PolyPhen-2, SIFT and MutationTaster, and were absent in 100 ethnically matched normal controls. Conclusion LRP2 is a novel candidate genetic cause of non-syndromic familial CS.

Abstract Inner dynein arm (IDA), composed of a series of protein complex, is necessary to cilia and flagella bend formation and beating. Previous studies indicated that defects of IDA protein complex result in multiple morphological abnormalities of the sperm flagellum (MMAF) and male infertility. However, the genetic causes and molecular mechanisms in the IDAs need further exploration. Here we identified two loss-of-function variants of WDR63 in both MMAF and non-obstructive azoospermia (NOA) affected cohorts. WDR63 encodes an IDA-associated protein that is dominantly expressed in testis. We next generated Wdr63-knockout (Wdr63-KO) mice through the CRISPR-Cas9 technology. Remarkably, Wdr63-KO induced decreased sperm number, abnormal flagellar morphology and male infertility. In addition, transmission electron microscopy assay showed severely disorganized “9 + 2” axoneme and absent inner dynein arms in the spermatozoa from Wdr63-KO male mice. Mechanistically, we found that WDR63 interacted with WDR78 mainly via WD40-repeat domain and is necessary for IDA assembly. Furthermore, WDR63-associated male infertility in human and mice could be overcome by intracytoplasmic sperm injection (ICSI) treatment. In conclusion, the present study demonstrates that bi-allelic variants of WDR63 cause male infertility via abnormal inner dynein arms assembly and flagella formation and can be used as a genetic diagnostic indicator for infertility males.

Although an important greenhouse gas, methane flux in hilly forest ecosystems remains unclear. By using closed-path eddy covariance systems, methane flux was measured continuously from 2017 to 2019 in a mixed plantation in the Xiaolangdi area of the Yellow River in North China. The methane flux footprint and its diurnal and monthly variations were analysed, and its characteristics on rainy days are discussed. The results showed that: (a) the observation data were reliable with good spatial representation (b) The methane flux in the mixed plantation ecosystem had obvious diurnal and seasonal variations: the monthly average diurnal variation of the methane flux had a single-peak; the methane flux value was source in the daytime and sink at night. The daily mean maximum value of methane flux in growing season was lower than that in non-growing season with the maximum value appearing in March, and the minimum value in October. (c) The forest is an atmospheric CH4 source with the annual emission in 2017 of (3.31 g C·m-2·year -1) >2019 (2.94 g C·m-2·year-1) >2018 (2.81 g C·m-2·year -1), and the main influencing factor was precipitation. Rainfall affected CH4 flux with a lag period of approximately three days. Rainfall also changed the balance of CH4 flux between sink or source according to precipitation intensity and frequency.

Caenorhabditis elegans (C. elegans) has been a popular model organism for several decades since its first discovery of the huge research potential for modeling human diseases and genetics. Sorting is an important means of providing stage- or age-synchronized worm populations for many worm-based bioassays. However, conventional manual techniques for C. elegans sorting are tedious and inefficient, and commercial complex object parametric analyzer and sorter is too expensive and bulky for most laboratories. Recently, the development of lab-on-a-chip (microfluidics) technology has greatly facilitated C. elegans studies where large numbers of synchronized worm populations are required and advances of new designs, mechanisms, and automation algorithms. Most previous reviews have focused on the development of microfluidic devices but lacked the summaries and discussion of the biological research demands of C. elegans, and are hard to read for worm researchers. We aim to comprehensively review the up-to-date microfluidic-assisted C. elegans sorting developments from several angles to suit different background researchers, i.e., biologists and engineers. First, we highlighted the microfluidic C. elegans sorting devices' advantages and limitations compared to the conventional commercialized worm sorting tools. Second, to benefit the engineers, we reviewed the current devices from the perspectives of active or passive sorting, sorting strategies, target populations, and sorting criteria. Third, to benefit the biologists, we reviewed the contributions of sorting to biological research. We expect, by providing this comprehensive review, that each researcher from this multidisciplinary community can effectively find the needed information and, in turn, facilitate future research.

Objective: The newly defined cancer-testis (CT) gene, MEIOB, was previously found to play key roles in DNA double-strand break (DSB) repair. In this study, we aimed to investigate the effects and mechanisms of MEIOB in the carcinogenesis of triple-negative breast cancers (TNBCs). Methods: The Cancer Genome Atlas database was used to quantify the expression of MEIOB. Cox regression analysis was used to evaluate the association between MEIOB expression and the prognosis of human TNBC. The effects of MEIOB on cell proliferation and migration in TNBCs were also assessed in vitro. Patient-derived xenograft (PDX) models were used to assess the sensitivity of breast cancers with active MEIOB to PARP1 inhibitors. Results: We confirmed MEIOB as a CT gene whose expression was restricted to the testes and breast tumors, especially TNBCs. Its activation was significantly associated with poor survival in breast cancer patients [overall, hazard ratio (HR) = 1.90 (1.16–2.06); TNBCs: HR = 7.05 (1.16–41.80)]. In addition, we found that MEIOB was oncogenic and significantly promoted the proliferation of TNBC cells. Further analysis showed that MEIOB participated in DSB repair in TNBCs. However, in contrast to its function in meiosis, it mediated homologous recombination deficiency (HRD) through the activation of polyADP-ribose polymerase (PARP)1 by interacting with YBX1. Furthermore, activated MEIOB was shown to confer sensitivity to PARP inhibitors, which was confirmed in PDX models. Conclusions: MEIOB played an oncogenic role in TNBC through its involvement in HRD. In addition, dysregulation of MEIOB sensitized TNBC cells to PARP inhibitors, so MEIOB may be a therapeutic target of PARP1 inhibitors in TNBC.

Abstract Purpose The overexpression and knockdown of PLK4 were both reported to generate aneuploidy. Thus, we aimed to investigate whether genetic variants in PLK4 contribute to the development of hepatocellular carcinoma (HCC). Methods We evaluated associations of common variants in PLK4 and its promoter for the risk of HCC in our association study (1300 cases and 1344 controls). The genotype‐tissue expression (GTEx) and The cancer genome atlas (TCGA) databases were used to quantify the expression of PLK4. Cell proliferation and migration affected by PLK4 in HCC were assessed in vitro. Drug susceptibility testing (DST) model was used to assess the sensibility of PLK4‐activated HCC to CFI‐400945, a small molecule inhibitor of PLK4. Results Herein, we found a significant association between rs3811741, located in the PLK4 intron, and liver cancer risk (OR = 1.26, P = 9.81 × 10−5). Although PLK4 expressed at lower levels in somatic tissues compared to the testis, the risk allele A of rs3811741 was associated with increased PLK4 expression in liver cancer tissues. Additionally, PLK4 high expression was remarkably associated with shortened survival of HCC (HR = 1.97, P = .001). Furthermore, overexpression of PLK4 promoted, while knockdown of PLK4 suppressed cancer cell proliferation, migration, and invasion. DST model demonstrated that CFI‐400945 can effectively suppress rampant proliferation of HCC with highly expressed PLK4. Conclusion Taken together, our study demonstrated that PLK4 is a susceptibility gene and plays an oncogenic role in HCC. Furthermore, we identified that PLK4 sensitives HCC to CFI‐400945, which may be an ideal therapy target for HCC.

Online shopping for customized garments has become the fastest-growing field of the Chinese eBusiness market. Most consumers not only limit themselves to buying standardized garments but also want to buy garments customized to their preferences. This phenomenon has pushed the fashion textile and apparel industry to change its supply chain operations to meet the customization demand. Besides, the fashion textile and apparel industry also want to study how different channel factors will affect consumers' perceived value and further influence consumers' purchasing decisions. We initiated this study and empirically tested more than 200 experienced consumers. This study collaborated with a fashion textile and apparel company that aims to implement customized product lines soon. Based on the perceived value theory and risk management theory, we investigated whether product involvement and channel identification on supply chain design will affects potential customized product consumers' purchasing decisions. The findings reveal that channel recognition affects consumer decisions by having a positive impact on their perceived value. The perceived risk and shopping channel involvement of consumers have a negative impact on their perceived values and channel selections. In addition, product involvement has a moderating effect on the relationship between channel's perceived risk, perceived values, and channel selections as well.

Abstract Background Propolis, a polyphenol-rich natural product, has been used as a functional food in anti-inflammation. However, its bioactive components and mechanisms have not been fully elucidated. To discover the bioactive components and anti-inflammatory mechanism, we prepared and separated 8 subfractions from ethyl acetate extract of Chinese propolis (EACP) and investigated the mechanism in oxidized low density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells (HUVECs) damage. Methods Eight subfractions were prepared and separated from ethyl acetate extract of Chinese propolis (EACP) with different concentrations of methanol-water solution, and analysed its chemical constituents by HPLC-DAD/Q-TOF-MS. Then 80% confluent HUVECs were stimulated with 40 μg/mL ox-LDL. Cell viability and apoptosis were evaluated by Sulforhodamine B (SRB) assay and Hoechst 33,258 staining, respectively. Levels of caspase 3, PARP, LC3B, p62, p-mTOR, p-p70S6K, p-PI3K, p-Akt, LOX-1 and p-p38 MAPK were assessed by western blotting and immunofluorescence assay, respectively. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were measured with fluorescent probes. Results Each subfraction exhibited similar protective effect although the contents of chemical constituents were different. EACP attenuated ox-LDL induced HUVECs apoptosis, depressed the ratio of LC3-II/LC3-I and enhanced the p62 level. In addition, treatment with EACP also activated the phosphorylation of PI3K/Akt/mTOR, and deactivated the level of LOX-1 and phosphorylation of p38 MAPK. The overproduction of ROS and the damage of MMP were also ameliorated after ECAP treatment. Conclusions These findings indicated that the bioactive component of propolis on anti-inflammatory activity was not determined by a single constituent, but a complex interaction including flavonoids, esters and phenolic acids. EACP attenuated ox-LDL induced HUVECs injury by inhibiting LOX-1 level and depressed ROS production against oxidative stress in ox-LDL induced HUVECs, further to activate PI3K/Akt/mTOR pathway and deactivate p38 MAPK to inhibit apoptosis and autophagy, which provide novel insights into the potential application of propolis on modulating chronic inflammation.

Increasing attention to sustainable development issues and recycling are forcing the recyclers to use different incentives to capture more market share. Recycling innovation input is one of the effective topics in reverse competitive chains. Because of the importance of this issue, firstly, a basic closed-loop supply chain (CLSC) system is discussed that includes an integrated manufacturer and a third-party collector. Then the impact of the integration with the innovation input into third-party product collectors is considered. Eventually, two models are constructed. The first model is a basic model that includes an integrated manufacturer and one third-party collector with innovation investment. The other model is the hybrid model that includes an integrated manufacturer and two third-party collectors with and without innovation input. Stackelberg game models are used to study the optimal pricing strategies for all three models and players’ attitudes toward different scenarios. Finally, numerical analysis is presented. Our findings are generated on the following three aspects. The collector’s recycling choice, recycling innovation input, and influence on recyclers and manufacturers. It is found that the manufacturer will always choose to recycle and prefers the hybrid recycling market, which depends on the rate of collection and the compensation from production-collecting. Moreover, the results reveal that the highest return rate of recyclers occurred under the hybrid model. However, the recyclers may not be able to invest the sustainable recycle innovation input under the exorbitant innovation barriers.

Programmed death 1 ligand 1 (PD-L1) is a negative co-stimulatory molecule in immune responses. Previous reports have indicated that inflammatory cytokines can upregulate the expression of PD-L1 in tumor cells, which in turn suppresses host immune responses. Periodontitis is characterized by persistent inflammation of the periodontium, which is initiated by infection with oral bacteria and results in damage to cells and the matrices of the periodontal connective tissues. In the present study, the expression and function of PD-L1 in periodontal tissue destruction were examined. Periodontal ligament cells (PDLCs) were stimulated by inflammatory cytokines and periodontal pathogens. The expression and function of PD-L1 on the surface of PDLCs was investigated using flow cytometry in vitro. Periodontal disease was induced by the injection of Porphyromonas gingivalis in mouse models. The expression levels of PD-L1 in the periodontal tissues of the mice were analyzed using flow cytometry and immunohistochemistry. PD-L1 was inducibly expressed on the PDLCs by the inflammatory cytokines and periodontal pathogens. The inflammation-induced expression of PD-L1 was shown to cause the apoptosis of activated T lymphocytes and improve the survival of PDLCs. Furthermore, in the mouse model of experimental periodontitis, the expression of PD-L1 in severe cases of periodontitis was significantly lower, compared with that in mild cases. By contrast, no significant differences were observed between the healthy control and severe periodontitis groups. The results of the present study showed that the expression of PD-L1 may inhibit the destruction of periodontal tissues, indicating the involvement of a possible protective feedback mechanism against periodontal infection. [ABSTRACT FROM AUTHOR]