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Background Metabolic dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), in which the abnormalities in brown adipose tissue (BAT) play important roles. However, the cellular composition and function of BAT as well as its pathological significance in diabetes remain incompletely understood. Our objective is to delineate the single-cell landscape of BAT-derived stromal vascular fraction (SVF) and their characteristic alterations in T2DM rats. Methods T2DM was induced in rats by intraperitoneal injection of low-dose streptozotocin and high-fat diet feeding. Single-cell mRNA sequencing was then performed on BAT samples and compared to normal rats to characterize changes in T2DM rats. Subsequently, the importance of key cell subsets in T2DM was elucidated using various functional studies. Results Almost all cell types in the BAT-derived SVF of T2DM rats exhibited enhanced inflammatory responses, increased angiogenesis, and disordered glucose and lipid metabolism. The multidirectional differentiation potential of adipose tissue-derived stem cells was also reduced. Moreover, macrophages played a pivotal role in intercellular crosstalk of BAT-derived SVF. A novel Rarres2+macrophage subset promoted the differentiation and metabolic function of brown adipocytes via adipose-immune crosstalk. Conclusion BAT SVF exhibited strong heterogeneity in cellular composition and function and contributed to T2DM as a significant inflammation source, in which a novel macrophage subset was identified that can promote brown adipocyte function.

Abstract Objective The relationship between changes in Chinese visceral adiposity index (CVAI) and cardiometabolic diseases (CMD) in middle-aged and elderly individuals remains unclear. This study aimed to explore whether changes in the CVAI were associated with CMD incidence. Methods This study included 3,243 individuals aged over 45 years from the China Health and Retirement Longitudinal Study. The exposures were changes in the CVAI and cumulative CVAI from 2012 to 2015. Changes in the CVAI were classified using K-means clustering analysis, and the cumulative CVAI was calculated as follows: (CVAI2012 + CVAI2015)/2 × time (2015–2012). Multivariable logistic regression models were used to assess the relationship between different CVAI change classes and CMD incidence. Restricted cubic splines regression was used to assess the dose–response relationship between cumulative CVAI and CMD incidence. To investigate the relationship between combined exposure to each component of CAVI and CMD incidence, a weighted quantile sum regression analysis was employed. Results During the 5 years of follow-up, 776 (24%) incident CMD cases were identified. Changes in CVAI and cumulative CVAI were independently and positively associated with CMD. After adjusting for potential confounders, compared with Class 1, the adjusted ORs (95% CIs) for incident CMD were 1.18 (0.90–1.57) for Class 2, 1.40 (1.03–1.92) for Class 3, and 1.56 (1.04–2.34) for Class 4. When cumulative CVAI was categorized into quartiles, compared with Q1, the adjusted ORs (95% CIs) for incident CMD were 1.30 (1.00–1.70) for Q2, 1.34 (1.01–1.79) for Q3, and 1.63 (1.15–2.31) for Q4. In addition, cumulative CVAI in the overall population exhibited a linear association with CMD (P overall = 0.012, P non-linearity = 0.287), diabetes (P overall = 0.022, P non-linearity = 0.188), and stroke (P overall = 0.002, P non-linearity = 0.978), but showed no significant association with heart disease (P overall = 0.619, P non-linearity = 0.442). Conclusion Participants with higher baseline CVAI level and a change of elevating CVAI level may suffer an increased incidence of CMD. Furthermore, our findings elucidate the underlying mechanisms of the CVAI by highlighting TG as the primary contributor to the observed associations. Long-term CVAI monitoring is of significant importance for early identification and prevention of CMD, with significant implications for clinical practice.

Objective: To evaluate various treatment methods for benign rectal anastomotic stricture (AS) following surgery for colorectal cancer. Method: A systematic review of the literature was conducted, focusing on studies that reported outcomes of different treatment modalities for benign AS. The PubMed, Embase, Scopus, China National Knowledge Infrastructure, and Cochrane Library databases were searched from January 2000 to December 2023. The inclusion criteria were studies involving human subjects, published in English, and reporting on therapeutic outcomes for benign AS. Results: A total of 19 papers identified a range of therapeutic strategies, including nonoperative anastomotic dilation, endoscopic balloon dilation (EBD), transanal minimally invasive surgery (TAMIS), self-expandable metal stents (SEMS), endoscopic incision (EI) and newer techniques such as prostate resection instrumentation. Nonoperative anastomotic dilation can serve as an initial treatment for lower AS. EI demonstrated promise in cases where EBD was ineffective, providing an alternative method for managing AS. TAMIS and SEMS showed higher efficacy in refractory cases, with TAMIS being particularly effective for severe fibrotic or completely closed AS. The use of rigid instrumentation with an electric knife for transanal incisions demonstrated precision but lacked the flexibility needed for complex procedures. Conclusion: While traditional methods such as nonoperative anastomotic dilation and EBD remain first-line treatments for benign AS, advanced techniques such as EI, TAMIS, and SEMS offer promising alternatives, particularly in refractory cases. The choice of treatment should be tailored to individual patient conditions, with consideration for the technical expertise required and the potential for complications.

Abstract Enhancing the pooling level of medical insurance is an inevitable requirement to strengthen the mutual assistance capability of funds and achieving national health. In China, with the continuous expansion of the migrant population seeking medical treatment in other regions, the role of provincial-pooling of basic medical insurance is becoming increasingly prominent. While there is limited research on the impact and mechanism of provincial-pooling of basic medical insurance on the health of migrant population. Therefore, this study aims to explore the impact of provincial-pooling of basic medical insurance on the health performance of migrant population and analyze the mediating role of social integration. Using data of three waves (2014, 2016 and 2018) of the China Labor force Dynamics Survey, this study focuses on a sample of migrant population enrolled in Urban and Rural Resident Basic Medical Insurance and employs the estimation methods of time-varying difference-in-difference and mediating effect model. The results of time-varying difference-in-difference show that provincial-pooling of basic medical insurance improves the health performance of migrant population by 9.6% (p

Abstract Background Low anterior resection syndrome (LARS) is a distressing condition that affects approximately 25–80% of patients following surgery for rectal cancer. LARS is characterized by debilitating bowel dysfunction symptoms, including fecal incontinence, urgent bowel movements, and increased frequency of bowel movements. Although biofeedback therapy has demonstrated effectiveness in improving postoperative rectal control, the research results have not fulfilled expectations. Recent research has highlighted that stimulating the pudendal perineal nerves has a superior impact on enhancing pelvic floor muscle function than biofeedback alone. Hence, this study aims to evaluate the efficacy of a combined approach integrating biofeedback with percutaneous electrical pudendal nerve stimulation (B-PEPNS) in patients with LARS through a randomized controlled trial (RCT). Methods and analysis In this two-armed multicenter RCT, 242 participants with LARS after rectal surgery will be randomly assigned to undergo B-PEPNS (intervention group) or biofeedback (control group). Over 4 weeks, each participant will undergo 20 treatment sessions. The primary outcome will be the LARS score. The secondary outcomes will be anorectal manometry and pelvic floor muscle electromyography findings and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29) scores. Data will be collected at baseline, post-intervention (1 month), and follow-up (6 months). Discussion We anticipate that this study will contribute further evidence regarding the efficacy of B-PEPNS in alleviating LARS symptoms and enhancing the quality of life for patients following rectal cancer surgery. Trial registration Chinese Clincal Trials Register ChiCTR2300078101. Registered 28 November 2023.

ABSTRACT Abdominal aortic aneurysm (AAA) is a large-vessel disease with high mortality, characterized by complex pathogenic mechanisms. Current therapeutic approaches remain insufficient to halt its progression. Fungi are important members of the gut microbiota. However, their characteristic alterations and roles in AAA remain unclear. This study investigated the role of gut fungal communities in the development of AAA through metagenomic sequencing of fecal samples from 31 healthy individuals and 33 AAA patients. We observed significant dysbiosis in the gut mycobiomes of AAA patients compared to healthy individuals, characterized by an increase in pathogenic fungi like Candida species and a decrease in beneficial yeasts such as Saccharomyces cerevisiae. The changes in fungal populations correlated strongly with clinical indicators of AAA, highlighting their potential for diagnosing and predicting AAA progression. Furthermore, our animal experiments demonstrated that Saccharomyces cerevisiae significantly ameliorated pathological alterations in AAA mice, suggesting a protective role for specific yeast strains against AAA development. These findings underscore the significant impact of gut mycobiomes on AAA and suggest that modulating these fungal communities could offer a novel therapeutic approach. Our research advances the understanding of the influence of gut microbiome on vascular diseases and suggests potential non-surgical approaches for managing AAA. By elucidating the diagnostic and therapeutic potential of gut fungi in AAA, this study provided important clues for future clinical strategies and therapeutic developments in the field of vascular medicine.IMPORTANCEOur research highlights the crucial role of gut fungi in abdominal aortic aneurysm (AAA) development. By analyzing fecal samples from AAA patients and healthy controls, we discovered significant dysbiosis in gut fungal communities, characterized by an increase in harmful Candida species and a decrease in beneficial yeasts like Saccharomyces cerevisiae. This dysbiosis was correlated with the severity of AAA. Importantly, in animal experiments, supplementing with Saccharomyces cerevisiae significantly slowed AAA progression. These findings suggest that modulating gut fungi may offer a novel, non-surgical approach to the diagnosis and treatment of AAA, potentially reducing the need for invasive procedures.

BackgroundAnastomotic stricture (AS) is a common complication following rectal cancer surgery with anastomosis, but its diagnosis and management pose significant challenges due to the lack of standardized diagnostic criteria. We present a case highlighting the complexities encountered in diagnosing and managing occult AS post-rectal cancer surgery.Case presentationA 51-year-old male patient presented with symptoms suggestive of AS following robot-assisted laparoscopic low anterior resection for rectal adenocarcinoma. Despite conventional evaluations, including colonoscopy, digital rectal examination, and radiography, AS was not identified. Following prolonged and ineffective treatment for suspected conditions such as low anterior resection syndrome (LARS), the patient underwent anal dilatation, resulting in significant symptom improvement.ConclusionsThis case underscores the challenges associated with diagnosing and managing occult AS following rectal cancer surgery. The absence of standardized diagnostic criteria and reliance on conventional modalities may lead to underdiagnosis and inadequate treatment. A comprehensive diagnostic approach considering intestinal diameter, elasticity, and symptoms related to difficult defecation may enhance diagnostic accuracy. Further research is needed to refine the diagnostic and therapeutic strategies for occult AS.

Abstract This study aimed to investigate the predictive factors of therapeutic efficacy for chronic subdural hematoma (CSDH) patients receiving atorvastatin combined with dexamethasone therapy by using clinical imaging characteristics in conjunction with computed tomography (CT) texture analysis (CTTA). Clinical imaging characteristics and CT texture parameters at admission were retrospectively investigated in 141 CSDH patients who received atorvastatin combined with dexamethasone therapy from June 2019 to December 2022. The patients were divided into a training set (n = 81) and a validation set (n = 60). Patients in the training data were divided into two groups based on the effectiveness of the treatment. Univariate and multivariate analyses were performed to assess the potential factors that could indicate the prognosis of CSDH patients in the training set. The receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of the significant factors in predicting the prognosis of CSDH patients and was validated using a validation set. The multivariate analysis showed that the hematoma density to brain parenchyma density ratio, singal min (minimum) and singal standard deviation of the pixel distribution histogram, and inhomogeneity were independent predictors for the prognosis of CSDH patients based on atorvastatin and dexamethasone therapy. The area under the ROC curve between the two groups was between 0.716 and 0.806. As determined by significant factors, the validation's accuracy range was 0.816 to 0.952. Clinical imaging characteristics in conjunction with CTTA could aid in distinguishing patients with CSDH who responded well to atorvastatin combined with dexamethasone.

Abstract Numerous studies have demonstrated the pivotal roles of intestinal microbiota in many physiopathological processes through complex interactions with the host. As a unique period in a woman's lifespan, pregnancy is characterized by changes in hormones, immunity, and metabolism. The gut microbiota also changes during this period and plays a crucial role in maintaining a healthy pregnancy. Consequently, anomalies in the composition and function of the gut microbiota, namely, gut microbiota dysbiosis, can predispose individuals to various pregnancy complications, posing substantial risks to both maternal and neonatal health. However, there are still many controversies in this field, such as “sterile womb” versus “in utero colonization.” Therefore, a thorough understanding of the roles and mechanisms of gut microbiota in pregnancy and its complications is essential to safeguard the health of both mother and child. This review provides a comprehensive overview of the changes in gut microbiota during pregnancy, its abnormalities in common pregnancy complications, and potential etiological implications. It also explores the potential of gut microbiota in diagnosing and treating pregnancy complications and examines the possibility of gut‐derived bacteria residing in the uterus/placenta. Our aim is to expand knowledge in maternal and infant health from the gut microbiota perspective, aiding in developing new preventive and therapeutic strategies for pregnancy complications based on intestinal microecology.

Objectives: Methylmalonic acidemia (MMA) is a rare inborn genetic disorder that is characterized by increased levels of methylmalonic acid in blood plasma and urine. Isolated methylmalonic acidemia is one of the most common types of MMA and is caused by mutations in the gene encoding methyl-malonyl coenzyme A mutase (MMUT). In this study, we investigated the possible mechanisms underlying the symptoms of isolated MMA in a patient by molecular analysis. Methods: PCR amplification and Sanger sequencing analysis was performed to identify variants in the MMUT gene in the proband and his family. Furthermore, minigene constructs were generated to validate the splicing defects in the MMUT gene variant identified in the proband. Results: The 3-year-old patient was admitted to the hospital with symptoms of MMA, including fever, convulsions, and vomiting. He showed metabolic acidosis, high levels of methylmalonic acid in blood and urine, and normal blood homocysteine levels. Genetic analysis demonstrated that the patient was a compound heterozygous carrier of two variants in the MMUT gene: a missense c.278G > A variant that has already been reported in a patient with the severe mut⁰ phenotype; and a novel splice site variant c.2125-2A > G. RT-PCR analysis showed that, while the novel variant clearly alters splicing, a minor amount of a full-length transcript is generated, suggesting that a wild-type protein may be produced although at a lower quantitative level. The patient's condition improved after treatment with vitamin B12. Serious complications were not reported during follow-up at age 5. Conclusions: We identified a novel splice site variant that partially disrupts normal splicing of the MMUT pre-mRNA. Production of a reduced amount of full-length transcript is responsible for the mild clinical phenotype observed in this patient. Functional studies have proven useful in exploring the genotype‐phenotype association and in providing guidance for the genetic diagnosis of MMA.

Purpose: Coronary microvascular dysfunction (CMD) is emerging as an important cause of myocardial ischemia, but there is a lack of a non-invasive method for reliable early detection of CMD. Aim: To develop an electrocardiogram (ECG)-based machine learning algorithm for CMD detection that will lay the groundwork for patient-specific non-invasive early detection of CMD. Methods: Vectorcardiography (VCG) was calculated from each 10-second ECG of CMD patients and healthy controls. Sample entropy (SampEn), approximate entropy (ApEn), and complexity index (CI) derived from multiscale entropy were extracted from ST-T segments of each lead in ECGs and VCGs. The most effective entropy subset was determined using the sequential backward selection algorithm under the intra-patient and inter-patient schemes, separately. Then, the corresponding optimal model was selected from eight machine learning models for each entropy feature based on five-fold cross-validations. Finally, the classification performance of SampEn-based, ApEn-based, and CI-based models was comprehensively evaluated and tested on a testing dataset to investigate the best one under each scheme. Results: ApEn-based SVM model was validated as the optimal one under the intra-patient scheme, with all testing evaluation metrics over 0.8. Similarly, ApEn-based SVM model was selected as the best one under the intra-patient scheme, with major evaluation metrics over 0.8. Conclusions: Entropies derived from ECGs and VCGs can effectively detect CMD under both intra-patient and inter-patient schemes. Our proposed models may provide the possibility of an ECG-based tool for non-invasive detection of CMD.

Background Neurosurgical patients are at an increased risk of deep venous thrombosis (DVT), which, if not properly managed, can lead to pulmonary embolism. This study aimed to investigate the accuracy of age-adjusted D-dimer thresholds combined with the modified Wells score as a predictor for lower extremity DVT diagnosis. Methods We conducted a study among patients aged >50 years with suspected lower extremity DVT in the neurosurgery intensive care unit between December 2019 and December 2020. Receiver operating characteristic curve analysis was performed to examine the diagnostic capacity of age-adjusted D-dimer combined with the modified Wells score. Results A total of 233 participants, with an average age of 71.81 ± 12.59 years, were enrolled in the study. The mean D-dimer levels were 0.73 ± 0.39 mg/L. Among the participants, 57 (57.9%, 33 males) were diagnosed with DVT. The age-adjusted D-dimer combined with the modified Wells score had the highest area under the curve for diagnosing lower extremity DVT compared to D-dimer and age-adjusted D-dimer alone, with an AUC of 0.858. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the age-adjusted D-dimer combined with the modified Wells score for DVT diagnosis were 78.95%, 80.68%, 57%, 92.2%, and 80.26%, respectively. When analyzing subgroups, the accuracy was 79.55% for participants with cerebral hemorrhage, 81.69% for those with craniocerebral injury, 74.99% for participants with intracranial infection, and 88.89% for those with craniocerebral tumor. Conclusion The combination of the age-adjusted D-dimer thresholds with the modified Wells score might effectively predict lower extremity DVT.

Abstract Background The axonemal microtubules of primary cilium undergo a conserved protein posttranslational modification (PTM) — polyglutamylation. This reversible procedure is processed by tubulin tyrosine ligase-like polyglutamylases to form secondary polyglutamate side chains, which are metabolized by the 6-member cytosolic carboxypeptidase (CCP) family. Although polyglutamylation modifying enzymes have been linked to ciliary architecture and motility, it was unknown whether they also play a role in ciliogenesis. Results In this study, we found that CCP5 expression is transiently downregulated upon the initiation of ciliogenesis, but recovered after cilia are formed. Overexpression of CCP5 inhibited ciliogenesis, suggesting that a transient downregulation of CCP5 expression is required for ciliation initiation. Interestingly, the inhibitory effect of CCP5 on ciliogenesis does not rely on its enzyme activity. Among other 3 CCP members tested, only CCP6 can similarly suppress ciliogenesis. Using CoIP-MS analysis, we identified a protein that potentially interacts with CCP — CP110, a known negative regulator of ciliogenesis, whose degradation at the distal end of mother centriole permits cilia assembly. We found that both CCP5 and CCP6 can modulate CP110 level. Particularly, CCP5 interacts with CP110 through its N-terminus. Loss of CCP5 or CCP6 led to the disappearance of CP110 at the mother centriole and abnormally increased ciliation in cycling RPE-1 cells. Co-depletion of CCP5 and CCP6 synergized this abnormal ciliation, suggesting their partially overlapped function in suppressing cilia formation in cycling cells. In contrast, co-depletion of the two enzymes did not further increase the length of cilia, although CCP5 and CCP6 differentially regulate polyglutamate side-chain length of ciliary axoneme and both contribute to limiting cilia length, suggesting that they may share a common pathway in cilia length control. Through inducing the overexpression of CCP5 or CCP6 at different stages of ciliogenesis, we further demonstrated that CCP5 or CCP6 inhibited cilia formation before ciliogenesis, while shortened the length of cilia after cilia formation. Conclusion These findings reveal the dual role of CCP5 and CCP6. In addition to regulating cilia length, they also retain CP110 level to suppress cilia formation in cycling cells, pointing to a novel regulatory mechanism for ciliogenesis mediated by demodifying enzymes of a conserved ciliary PTM, polyglutamylation.

In recent years, construction accidents have occurred frequently. The safety guarantee measures for construction personnel are thrown into sharp focus. Wearing helmets is one of the most important requirements to protect the safety of construction personnel, and the detection of wearing safety helmets has become necessary. For the problems of the existing helmet wearing detection algorithm such as too many parameters, substantial detection interferences, and low detection accuracy, in this paper a helmet wearing detection model YOLO-M is proposed. Firstly, MobileNetv3 is adopted as the backbone network of YOLOv5s for the feature extraction, which can reduce the number of model parameters and model size. Secondly, a residual edge is introduced in the feature fusion. The original feature map information is fused during feature fusion, and the detection ability of small targets is enhanced. At last, by changing the connection between CAM and SAM, a new attention module BiCAM is designed. The comparison experiments show that the detection accuracy of YOLO-M is 2.22% higher than YOLOv5s, and the model parameter quantity is reduced to 3/4 of YOLOv5s. Under the same detection conditions, the detection speed of YOLO-M is better than the other models, which meets the accuracy requirements of helmet detection in the construction scene.

Abstract Background Poverty is the greatest obstacle to the realization of human rights, among which illness is the leading cause in China. In 2015, China began to implement the health poverty alleviation project (HPAP). By 2020, all rural households living below the current poverty level (2300 yuan per person per year) have been lifted out of poverty. Methods This study introduces the concept of relative acquisition and constructs a scale based on the capability approach to measure the relative acquisition and compares its fairness of HPAP. Results The findings show that the values of the relative acquisition of HPAP in survey areas are all reached middle level (0.4–0.6), with 0 indicating the worst level and 1 indicating the best level. Specifically, the values of the functional activities of "health care", "health ability", "equal treatment opportunities" and "social support" are all above 0.4, while the values of "economic conditions" and "health education" are below 0.4. Conclusions The HPAP plays a significant role in reducing the economic burden of disease on patients. However, due to insufficient social support and health education, the HPAP objects lack endogenous motivation to fight against poverty, and the fairness also needs to be improved.

BackgroundWith the rising of fertility cost and the implementation of the “universal three-child” policy, the model of intergenerational support for grandchild is becoming an inevitable choice for more and more families in China. As the number of grandchildren increases and the interval between births extends, will the grandchild care intention and grandparents’ health be affected?MethodsBased on the data of China Family Panel Studies from 2018 and 2020, this study used multiple linear regression and multiple mediation tests to investigate the effect of grandchild care intention and intergenerational support on the health of older adults.ResultsFirstly, actively taking care of grandchild has increased the self-rated health and mental health of older adults by 11.8 and 10.7%, respectively. Secondly, there is heterogeneity in the effect of intergenerational support from adults on health in their parents, among them, economic support improves the physical health by 5.5%; life care increases the self-rated and physical health by 3.3 and 0.8% respectively; emotional comfort improves the physical and mental health by 2.5 and 2.9%, respectively. Thirdly, grandchild care intention has a mediating effect on the health of older adults through economic support, life care, and emotional comfort.ConclusionThe grandchild care intention has positive effect on the health of older adults. The intergenerational supports (economic support, emotional comfort, and life care) have heterogeneous effects on the health of older adults, such as economic support mainly affects the physical health. Older adults who actively take care of their grandchild are more likely to gain intergenerational support and feedback from their adult children, transforming intergenerational support into a “win-win” model of resource reciprocity between generations. Based on this, it is necessary to re-establish the value identity of “caring for older adults” and “raising grandchildren” at the cultural level, continuously improve the fertility support policies at the government level and establish “caring for older adults” support platform at the social level.

Objectives This study aimed to evaluate the cardioprotective effects and mechanism of scutellarin (Scu) on heart ischaemia/reperfusion (I/R) injury by using an isolated Langendorff rat heart model. Methods Myocardial function was evaluated via measurements of cardiac haemodynamic parameters. Myocardial infarct size was macroscopically estimated by using TTC staining. The release of creatine kinase (CK) and lactate dehydrogenase (LDH) was used to evaluate cardiac injury. GSH/GSSG, SOD, and MDA were determined as being indicators of oxidative stress. CRP, IL-6, and TNF-α were also analysed to assess inflammation in the heart tissues. Cardiomyocyte apoptosis was quantified by using a TUNEL kit. PPARγ, Nrf2, and NF-κB were assayed via Western blotting. Results The results indicated that I/R induced significant cardiac dysfunction, myocardial infarct, and apoptosis, as well as decreasing the GSH/GSSG ratio, SOD activity, Nrf2 protein expression, and PPARγ protein expression, but increased levels of TNF-α, MDA, CRP, IL-6, and NF-κB. Conclusion These data suggest that Scu attenuates cardiac I/R.

BackgroundThis study aimed to explore the association between health status (physical, mental, and self-rated health) and multidimensional poverty (subjective and objective poverty) in older adults.MethodA panel binary logit regression approach was applied to four waves of CLHLS data (2008, 2011, 2014, and 2018). In total,1,445 individuals were included after data cleaning.ResultsThe mean values and proportion of physical, mental, and self-rated health were 5.73 (87.42%), 0.93 (93.06%), and 3.46 (86.7%), respectively, and mean values and proportion of subjective and objective poverty were 0.19 (18.51%) and 0.21(21.4%). In addition, physical, mental, and self-rated health were all found to be associated with subjective poverty among older adults (r = −0.181, r = −0.630, r = −0.321, p

Since projection-based 3D bioprinting (PBP) could provide high resolution, it is well suited for printing delicate structures for tissue regeneration. However, the low crosslinking density and low photo-crosslinking rate of photocurable bioink make it difficult to print fine structures. Currently, an in-depth understanding of the is lacking. Here, a research framework is established for the analysis of printability during PBP. The gelatin methacryloyl (GelMA)-based bioink is used as an example, and the printability is systematically investigated. We analyze the photo-crosslinking reactions during the PBP process and summarize the specific requirements of bioinks for PBP. Two standard quantized models are established to evaluate 2D and 3D printing errors. Finally, the better strategies for bioprinting five typical structures, including solid organs, vascular structures, nerve conduits, thin-wall scaffolds, and micro needles, are presented.

Abstract Background With the rapid growth of the ageing population, the operating burden of China’s basic medical insurance fund is becoming increasingly heavy. To counter rapid population ageing and ameliorate a series of problems, China has adjusted its fertility policies several times. On January 1, 2016, the universal two-child policy was implemented. This study analysed the impacts of the adjustment to the fertility policy and potential improvements in fertility intention on the insured population and medical insurance fund sustainability. Methods We used an actuarial science method and took the urban and rural residents’ basic medical insurance (URRBMI) of China, which covers most urban and rural residents, as an example to build a dynamic forecast model of population growth and a dynamic actuarial model of medical insurance funds. Results Compared with the original policy, under the current fertility intention (40%) with the universal two-child policy, the ageing of the population structure of URRBMI participants will decline significantly after 2026, and individuals aged 65 and over will account for only 19.01% of the total participants in 2050. The occurrence of the current deficit and accumulated deficit of the URRBMI fund will be postponed for one year to 2022 and 2028, respectively. If fertility intentions continue to rise, the ageing degree of the population structure will decrease, and the deficit would be further delayed. Conclusions The universal two-child policy is conducive to improving the degree of overall population ageing, delaying the occurrence of a URRBMI fund deficit, and improving the sustainability of URRBMI funds. If fertility intention increases, the effects would be stronger. However, since the adjustment of the universal two-child policy has a certain time lag, it will take time to demonstrate this impact. Therefore, while actively promoting the universal two-child policy, other measures should be taken, such as improving the fertility desire among couples of childbearing age and reforming medical insurance payment methods.

Porcine parvovirus (PPV) is the primary cause of reproductive disorders in pigs. The porcine parvovirus 7 (PPV7) subtype was first identified in the United States in 2016. In this study, PPV7 was detected in different porcine samples, including serum, feces, saliva, and milk, from 69 pig farms in the Fujian and Guangdong regions of South China, and its coinfection with porcine circovirus 2 (PCV2), porcine circovirus 3 (PCV3), and porcine reproductive and respiratory syndrome virus (PRRSV) was determined. Whole-genome sequencing, phylogenetic analysis, and recombination analysis were performed on seven isolates, with each selected isolate originating from a different farm. There was a high rate of PPV7 positivity in blood, stool, and saliva but PPV7 DNA was absent from breast milk. The findings also showed that PPV7-positive samples had a high rate of coinfection with PCV2, PCV3, and PRRSV. Real-time PCR was used to determine the viral copy numbers of PCV2, PCV3, PRRSV, and PPV7 in serum samples and to assess whether PPV7 affected PCV2, PCV3, and PRRSV viral loads. Phylogenetic analysis showed that PPV7e and PPV7f were the most prevalent and widespread subtypes in the Fujian and Guangdong regions, respectively. While the PPV7a, PPV7b, PPV7c, and PPV7f subtypes were most prevalent in Fujian Province, PPV7a-e subtypes were prevalent in Guangdong, indicating that PPV7 has rich genetic diversity in these regions. A putative recombinant strain, 21FJ09, was identified using SimPlot and the Recombination Detection Program 4 software.

Subdural hematoma (SDH) is one of the most lethal types of traumatic brain injury. SDH caused by Intracranial Pressure Reduction (ICPR) is rare, and the mechanism remains unclear. Here, we report three cases of SDH that occurred after substandard cupping therapy and are conjected to be associated with ICPR. All of them had undergone cupping treatments. On the last cupping procedure, they experienced a severe headache after the cup placed on the occipital-neck junction (ONJ) was suddenly removed and were diagnosed with SDH the next day. In standard cupping therapy, the cups are not usually placed on the ONJ. We speculate that removing these cups on the soft tissue over the cisterna magna repeatedly created localized negative pressure, caused temporary but repeated ICPR, and eventually led to SDH development. The Monro-Kellie Doctrine can explain the mechanism behind this - it states that the intracranial pressure is regulated by a fixed system, with any change in one component causing a compensatory change in the other. The repeated ICPR promoted brain displacement, tearing of the bridging veins, and development of SDH. The literature was reviewed to illustrate the common etiologies and therapies of secondary ICPR-associated SDH. Despite the popularity of cupping therapy, its side effects are rarely mentioned. This case is reported to remind professional technicians to fully assess a patient's condition before cupping therapy and ensure that the cups are not placed at the ONJ.

BackgroundChronic subdural hematoma (CSDH) is common in elderly people with a clear or occult traumatic brain injury history. Surgery is a traditional method to remove the hematomas, but it carries a significant risk of recurrence and poor outcomes. Non-surgical treatment has been recently considered effective and safe for some patients with CSDH. However, it is a challenge to speculate which part of patients could obtain benefits from non-surgical treatment.ObjectiveTo establish and validate a new prediction model of self-absorption probability with chronic subdural hematoma.MethodThe prediction model was established based on the data from a randomized clinical trial, which enrolled 196 patients with CSDH from February 2014 to November 2015. The following subjects were extracted: demographic characteristics, medical history, hematoma characters in imaging at admission, and clinical assessments. The outcome was self-absorption at the 8th week after admission. A least absolute shrinkage and selection operator (LASSO) regression model was implemented for data dimensionality reduction and feature selection. Multivariable logistic regression was adopted to establish the model, while the experimental results were presented by nomogram. Discrimination, calibration, and clinical usefulness were used to evaluate the performance of the nomogram. A total of 60 consecutive patients were involved in the external validation, which enrolled in a proof-of-concept clinical trial from July 2014 to December 2018.ResultsDiabetes mellitus history, hematoma volume at admission, presence of basal ganglia suppression, presence of septate hematoma, and usage of atorvastatin were the strongest predictors of self-absorption. The model had good discrimination [area under the curve (AUC), 0.713 (95% CI, 0.637–0.788)] and good calibration (p = 0.986). The nomogram in the validation cohort still had good discrimination [AUC, 0.709 (95% CI, 0.574–0.844)] and good calibration (p = 0.441). A decision curve analysis proved that the nomogram was clinically effective.ConclusionsThis prediction model can be used to obtain self-absorption probability in patients with CSDH, assisting in guiding the choice of therapy, whether they undergo non-surgical treatment or surgery.

Soft Pneumatic-Network (Pneu-Net) Actuators (SPAs) have been used extensively in making soft grippers, due to their simple driving forms and large bending deformation. However, the capabilities of the regular SPAs in complex soft gripping application environments are alone insufficient. This work, thus, proposes a modular soft gripper that combines the functionalities of regular and herringbone actuators. The bending deformation characteristics of the two actuators under pneumatic pressures are verified by finite element (FE) simulations and experiments. The functional characteristics of the two actuators are investigated experimentally through a series of methods including the blocking force test, lifting test, grasping strength test, and suction force test. The experimental results show that the regular actuator has the advantages of greater longitudinal bending deformation and higher blocking force; while, the herringbone actuator has better lifting stability and grasping strength due to its conformal deformations both in longitudinal and transverse directions. In addition, the vacuum experiments demonstrate that the actuators can lift heavy plate-like objects through vacuum suction. Based on the functional behaviors of the two actuators, the proposed modular gripper is loaded onto automatic equipment, and the gripper is tested to hook, grasp, or lift various objects with different shapes, sizes, and weights. In essence, the modular and multi-functional characteristics of the design make it a promising candidate for relatively complex and advanced gripping applications.

Based on the data of four periods of CLHLS (2008, 2011, 2014, 2018), the latent variable growth model (LGCM) was applied to 2344 older adults who completed four follow-up surveys, to study the trajectory of leisure activities and cognitive ability and explore the relationship between leisure activities and cognitive ability of older adults. The results showed that: (1) leisure activities and cognitive ability of older adults showed a non-linear downward trend; (2) leisure activities significantly and positively predicted the cognitive ability of older adults at every time point; (3) the initial level of leisure activity positively predicted the initial level of cognitive ability but negatively predicted the rate of cognitive decline; In addition, cognitive activities had a greater effect on cognitive ability than non-exercise physical activities; (4) the rate of decline of leisure activities also significantly and positively predicted the rate of decline of cognitive ability; (5) cross-lagged regression analysis further suggested the overall positive predictive effect of leisure activity on cognitive ability; (6) overall, education level had a significant contribution to cognitive ability, and the higher the education level, the slower the decline of cognitive ability; and (7) smoking could promote cognitive ability in older adults and no significant effect was found between alcohol drinking and cognitive ability. Accordingly, the government should encourage older adults to do more leisure activities, especially the cognitive activity, to effectively prevent cognitive decline.

Abstract Background Osteonecrosis of the femoral head (ONFH) is a complicated disease associated with trauma, hormone abuse and excessive alcohol consumption. Polymorphisms of long non-coding RNAs have been also linked with the development of ONFH. Our research aimed to explore the relationship between CARMEN (Cardiac Mesoderm Enhancer-Associated Non-Coding RNA) variants and ONFH risk. Methods Our study used Agena MassARRAY Assay to genotype 6 selected single nucleotide polymorphisms (SNPs) in 731 participants (308 alcohol-induced ONFH patients and 423 controls). We used odds ratios (ORs) and 95% confidence intervals (CIs) to calculate the effect of gene polymorphisms on the occurrence of alcohol-induced ONFH by logistic regression analysis and haplotype analysis. Results Our overall analysis illustrated that rs13177623 and rs12654195 had an association with a reduced risk of ONFH after adjustment for age and gender. We also found that rs13177623, rs12654195 and rs11168100 were associated with a decreased susceptibility to alcohol-induced ONFH in people ≤45 years. In addition, the necrotic sites stratification analysis showed that rs12654195 was only found to be related to alcohol-induced ONFH risk in the recessive model. In patients with different clinical stages, rs353300 was observed to be associated with a higher incidence of ONFH. Individuals with different genotypes of rs13177623, rs12654195 and rs11168100 had significantly different clinical parameters (cholinesterase, globulin, percentage of neutrophils and the absolute value of lymphocytes). Conclusions Our data provided new light on the association between CARMEN polymorphisms and alcohol-induced ONFH risk in the Chinese Han population.

Objective(s): Diabetes mellitus has been suggested to be the most common metabolic disorder associated with magnesium deficiency. This study aimed to investigate the effects and mechanisms of magnesium supplementation on insulin receptor activity in elderly type 2 diabetes using a rat model and to provide experimental evidence for insulin resistance improvement by magnesium supplementation. Materials and Methods: Rat model of type 2 diabetes was developed using a high-fat diet along with low dose streptozotocin (STZ) treatment. Magnesium supplement was given orally by mixing with the high-fat diet. Serum insulin level, insulin sensitivity, and insulin receptor affinity were assessed using radioimmunoassay (RIA). Insulin receptor, insulin receptor substrate (IRS-2), and β-Arrestin-2 gene and protein expression levels were measured using immunohistochemistry and RT-PCR. Xanthine oxidase assay, thiobarbituric acid reactive substance assay (TCA method), colorimetric assay, and ELISA were used to determine the serum SOD, MDA, T-AOC, and ox-LDL levels, respectively. Results: Magnesium supplementation enhanced insulin sensitivity and decreased insulin resistance in diabetic rats mainly through increasing insulin receptor expression, affinity, and augmenting insulin receptor signaling. Magnesium supplementation also inhibited lipid peroxidation in diabetic rats and protected against pancreatic cell injury in diabetic rats. In addition, we found that β-Arrestin-2 gene expression was suppressed in diabetes, which was possibly attributed to gene methylation modification, as β-arrestin 2 promotor was rich in methylation-regulating sites. Magnesium supplementation could affect β-Arrestin-2 gene expression and methylation.Conclusion: Magnesium supplementation has a positive effect on insulin receptor activity and insulin sensitivity in type 2 diabetes.

In this study, a Boundedly Rational Nested Logit (BRNL) model is proposed by introducing the concept of indifference threshold into Nested Logit (NL) model. In BRNL model, the traveler is assumed to choose randomly or in accordance with his preference if the expected cost difference between two alternatives is within the indifference band. Otherwise, the traveler will choose the alternative with the minimum expected cost. A nested method of successive average is developed to solve the proposed problem. Finally, the rationality of the model and effectiveness of the algorithm are proved by using a numerical example with three-mode transportation network. The results indicate that, different from NL model, the choices of the travelers in BRNL model do not depend on the costs always. The value of the indifference threshold will affect the choice probability. The larger the indifference threshold is, the less sensitive travelers are to the change of cost. In particular, if the indifference threshold is large enough, the travelers’ choices will always depend on the preference.

Hydrocephalus is a neurological condition due to the aberrant circulation and/or obstruction of cerebrospinal fluid (CSF) flow with consequent enlargement of cerebral ventricular cavities. However, it is noticed that a lot of patients may still go through symptomatic progression despite standard shunting procedures, suggesting that hydrocephalus is far more complicated than a simple CSF circulative/obstructive disorder. Growing evidence indicates that genetic factors play a fundamental role in the pathogenesis of some hydrocephalus. Although the genetic research of hydrocephalus in humans is limited, many genetic loci of hydrocephalus have been defined in animal models. In general, the molecular abnormalities involved in the pathogenesis of hydrocephalus include brain development and ependymal cell dysfunction, apoptosis, inflammation, free radical generation, blood flow, and cerebral metabolism. Moreover, recent studies have indicated that the molecular abnormalities relevant to aberrant cerebral glymphatic drainage turn into an attractive subject in the CSF circulation disorder. Furthermore, the prevalent risk factors could facilitate the development of hydrocephalus. In this review, we elicited some possible fundamental molecular mechanisms and facilitating risk factors involved in the pathogenesis of hydrocephalus, and aimed to widen the diagnosis and therapeutic strategies for hydrocephalus management. Such knowledge could be used to improve patient care in different ways, such as early precise diagnosis and effective therapeutic regimens.

Passerine nestlings frequently suffer from sub-optimal food conditions due to climate change-induced trophic mismatch between the nestlings and their optimal food resources. The ability of nestlings to buffer this challenge is less well understood. We hypothesized that poor food conditions might induce a higher immune response and lower growth rate of nestlings, and such physiological plasticity is conducive to nestling survival. To test this, we examined how food (grasshopper nymphs) abundance affects the expression of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β) genes, plasma IGF-1 levels, body mass, and fledging rates in wild Asian short-toed lark (Alaudala cheleensis) nestlings. Linear mixed models revealed that nymph biomass significantly influenced the expression of IFN-γ, TNF-α, and IL-1β genes, and the level of plasma IGF-1. The expressions of IFN-γ, TNF-α, and IL-1β genes were negatively correlated with nymph biomass and plasma IGF-1 level. Plasma IGF-1 level, nestling body mass growth rate, was positively correlated with nymph biomass. Despite a positive correlation between the nestling fledge rate and nymph biomass, more than 60% of nestlings fledged when nymph biomass was at the lowest level. These results suggest that immunity and growth plasticity of nestlings may be an adaptation for birds to buffer the negative effects of trophic mismatch.

Metal additive manufacturing (metal-AM) technology has made significant progress in the field of biomedicine in recent years. Originally, it was only used as an innovative resource for prototypes. With the development of technology, custom orthopedic implants could be produced for different patients. Titanium alloy is non-toxic and harmless in the human body. It has excellent biocompatibility and can promote the growth and regeneration of bones in its interior. Therefore, it is widely used in the medical industry. However, in the process of additive manufacturing and printing titanium alloys, there are often cases where the powder is not completely melted or the powder adheres to the product structure after printing, which introduces new biological risks. This paper summarizes the causes of powder adhesion from the perspective of the process involved in additive manufacturing, expounds the influence of different processes on the powder adhesion of titanium alloy forming parts, introduces the mainstream methods of powder sticking removal and summarizes the application of the additive manufacturing of titanium alloy in the medical field, which provides a theoretical basis for further development of the application of titanium alloy additive manufacturing technology in the medical industry.

Bile duct injury is a common complication of hepatobiliary surgeries in clinical practice with poorly satisfactory treatment outcomes. Implanting a tissue-engineered tubular scaffold for supporting and replacing defected native bile duct is an important treatment option for bile duct injury. Here a dual-layer tubular scaffold with poly (lactic-co-glycolic acid) (PLGA) inner layer and gelatin methacrylate (GelMA)/poly (ethylene glycol) diacrylate (PEGDA) outer layer was fabricated using a two-stage molding method for bile duct regeneration. Further, induced mesenchymal stem cells (MSC)-derived cholangiocyte-like cells were embedded in the outer layer during fabrication. The inner layer of PLGA offered adequate mechanical strength for the scaffold, and the outer layer of GelMA/PEGDA provided excellent biocompatibility and conditions for the MSCs and their induced differentiation. Moreover, cholic acid and its derivates are believed to induce MSC-cholangiocyte differentiation in two-dimensional culture and could affect the MSCs transforming to cholangiocyte-like cells in the hydrogel. Induced-MSC-laden GelMA/PEGDA-PLGA dual-layer tubular scaffold and PLGA single-layer scaffold were transplanted into animal models for assessing the repair effect on bile duct injury. After 12 wk, induced-MSC-laden dual-layer tubular scaffold promoted bile duct repairing and enhanced more intact biliary epithelium regenerating compared to PLGA single-layer scaffold. Therefore, the induced-MSC-laden dual-layer tubular scaffold with superior biocompatibility and distinct function of inducing differentiation exerted a satisfactory effect on bile duct regeneration and could provide an ideal option for the clinical treatment of bile duct injury in the future.

Chronic subdural hematoma (CSDH) is a common form of intracranial hemorrhage in the aging population. We aimed to investigate the predictive factors for atorvastatin efficacy as a monotherapy for moderate CSDH. We retrospectively reviewed the medical records of patients who were diagnosed with moderate CSDH and received atorvastatin monotherapy between February 5, 2014, and November 7, 2015, in multiple neurosurgical departments. Univariate, multivariate and receiver operating characteristic curve analyses were performed to identify the potential significant factors indicative of the good therapeutic efficacy or poor therapeutic efficacy of atorvastatin for mild CSDH, such as age, sex, history of injury, Markwalder grading scale–Glasgow Coma Scale (MGS-GCS), Activities of Daily Life-the Barthel Index scale (ADL-BI), American Society of Anesthesiologists Physical Status classification system (ASA-PS), blood cell counts, serum levels and computed tomography findings. A total of 89 patients (75 men and 14 women) aged 24–88 years (mean age 61.95 ± 15.30 years) were followed-up for 24 weeks. Computed tomography findings at admission showed mixed-density hematoma in 22 patients, isodense hematoma in 13 patients, high-density hematoma in 26 patients, and low-density hematoma in 28 patients. In total, 3, 80, and 6 patients had MGS-GCS grades of 0, 1, and 2, respectively. The efficacy rate at 6 months was 87.6% (78/89). Eleven patients were switched to surgery due to a worsened neurological condition, of whom 8, 1, 1, and 1 had high-density, low-density, isodense and mixed-density hematomas, respectively. These patients were switched to surgery over a range of 2–27 days, with a median interval of 12 days after the medication treatment. Univariate and multivariate analyses, confirmed by ROC curves, revealed that high-density hematoma, basal cistern compression, and hematoma volume to be independent risk factors for the efficacy of atorvastatin monotherapy in patients with moderate CSDH. Atorvastatin is an effective monotherapy for the treatment of mild CSDH. High-density hematoma, basal cistern compression, and hematoma volume are independent predictors of the efficacy of atorvastatin as a non-surgical treatment. The results suggested that ADL-BI was more sensitive than the MGS-GCS and ASA-PS for determining patient outcomes in our moderate CSDH cohort.

Titanium carbides attract attention from both academic and industry fields because of their intriguing mechanical properties and proven potential as appealing candidates in the variety of fields such as nanomechanics, nanoelectronics, energy storage and oil/water separation devices. A recent study revealed that the presence of Ti8C5 not only improves the impact strength of composites as coatings, but also possesses significant strengthening performance as an interlayer material in composites by forming strong bonding between different matrices, which sheds light on the design of impact protection composite materials. To further investigate the impact resistance and strengthening mechanism of Ti8C5, a pilot Molecular Dynamics (MD) study utilizing comb3 potential is carried out on a Ti8C5 nanosheet by subjecting it to hypervelocity impacts. The deformation behaviour of Ti8C5 and the related impact resist mechanisms are assessed in this research. At a low impact velocity ~0.5 km/s, the main resonance frequency of Ti8C5 is 11.9 GHz and its low Q factor (111.9) indicates a decent energy damping capability, which would eliminate the received energy in an interfacial reflection process and weaken the shock waves for Ti8C5 strengthened composites. As the impact velocity increases above the threshold of 1.8 km/s, Ti8C5 demonstrates brittle behaviour, which is signified by its insignificant out-of-plane deformation prior to crack initiation. When tracking atomic Von Mises stress distribution, the elastic wave propagation velocity of Ti8C5 is calculated to be 5.34 and 5.90 km/s for X and Y directions, respectively. These figures are inferior compared with graphene and copper, which indicate slower energy delocalization rates and thus less energy dissipation via deformation is expected prior to bond break. However, because of its relatively small mass density comparing with copper, Ti8C5 presents superior specific penetration. This study provides a fundamental understanding of the deformation and penetration mechanisms of titanium carbide nanosheets under impact, which is crucial in order to facilitate emerging impact protection applications for titanium carbide-related composites.

Digital aerial photogrammetry (DAP) has emerged as an alternative to airborne laser scanning (ALS) for forest inventory applications, as it offers a low-cost and flexible three-dimensional (3D) point cloud. Unlike the forest inventory attributes (e.g., tree height and diameter at breast height), the relative ability of DAP and ALS in predicting canopy structural variables (i.e., canopy cover and leaf area index (LAI)) has not been sufficiently investigated by previous studies. In this study, we comprehensively compared the canopy cover and LAI estimates using DAP- and ALS-based methods over 166 selected tropical forest sample plots with seven different tree species and forest types. We also explored the relationship between field-measured aboveground biomass (AGB) and the LAI estimates. The airborne LAI estimates were subsequently compared with the Sentinel-2-based LAI values that were retrieved using a one-dimensional radiative transfer model. The results demonstrated that the DAP-based method generally overestimated the two canopy variables compared to ALS-based methods but with relatively high correlations regardless of forest type and species (R2 of 0.80 for canopy cover and R2 of 0.76 for LAI). Under different forest types and species, the R2 of canopy cover and LAI range from 0.64 to 0.89 and from 0.54 to 0.87, respectively. Apparently, different correlations between AGB and LAI were found for different forest types and species where the mixed coniferous and broad-leaved forest shows the best correlation with R2 larger than 0.70 for both methods. The comparison with satellite retrievals verified that the ALS-based estimates are more consistent with Sentinel-2-based estimates than DAP-based estimates. We concluded that DAP data failed to provide analogous results to ALS data for canopy variable estimation in tropical forests.

Abstract Background Timing of breeding season of temperate passerines has been considered to be adjusted to their food availability. There is little work to reveal the cell stress responses of the nestlings hatched asynchronized with the food abundance peak, which is important for understanding the physiological link between the timing of breeding and the fitness of offspring. Methods Using gene expression level of blood HSP70 and HSP90 as indicators, we compared the cell stress response of Asian Short-toed Lark (Calandrella cheleensis) nestlings hatched under conditions of low, mid or high food (grasshopper nymph) availability in 2017. Results Nymph biomass, sample time and interaction of these two factors significantly influenced the blood gene expression level of HSP70 and HSP90 of Asian Short-toed Lark nestlings. HSP70 and HSP90 gene expression levels of the nestlings at 14:00 were significantly higher than those at 5:00. At either 5:00 or 14:00, the gene expression levels of HSP70 and HSP90 increase with the decrease of nymph biomass. Conclusions These results indicate that food availability is an important environment factor inducing cellular stress of Asian Short-toed Lark nestlings. The interactive effect of the nymph abundance and sample time on the HSPs response may be related with the daily temperature variation of the grassland. Over cell stress response may be one of physiological factor mediating the effect of food availability and the nestling’s fitness.

In order to improve the mode share of public transportation, an evolutionary game model based on the indifference threshold is established to analyze the travelers' mode choice behavior. The model supposes that the travelers' behavioral adjustment of decision-making of travelers follows the principle of random utility maximization only when the perceived difference in utility between modes is greater than the indifference threshold; otherwise, travelers choose randomly. A transportation network that includes private and public transportation is presented as an example to show how travelers adjust their mode choice when traffic management policy is changed. We divided the travelers into three categories based on the online survey data: high sensitivity, neutral sensitivity and low sensitivity to cost difference. The results show that, the proposed Δ-logit evolutionary game model has a unique stable equilibrium point and the point is the choice probability of the Δ-logit stochastic user equilibrium. Moreover, compared with the logit evolutionary game model, the Δ-logit evolutionary game model can predict the implementation effect of traffic policy and the time it takes for the traffic system to stabilize more accurately. In addition, the degree of sensitivity of travelers to cost difference affect the implementation effect of the policy.

Benzene, toluene, and xylenes (BTX) commonly co-exist. Exposure to individual components and BTX-rich mixtures can induce hematological effects. However, the hematological effects of long-term exposure to BTX are still unclear, and respective reference levels based on empirical evidence should be developed. We conducted a follow-up study in BTX-exposed petrochemical workers. Long-term exposure levels were quantified by measuring cumulative exposure (CE). Generalized weighted quantile sum (WQS) regression models and Benchmark Dose (BMD) Software were used to evaluate their combined effects and calculate their BMDs, respectively. Many hematologic parameters were significantly decreased at the four-year follow-up (p < 0.05). We found positive associations of CE levels of benzene, toluene, and xylene with the decline in monocyte counts, lymphocyte counts, and hematocrit, respectively (β > 0.010, Ptrend < 0.05). These associations were stronger in subjects with higher baseline parameters, males, drinkers, or overweight subjects (Pinteraction < 0.05). BTX had positive combined effects on the decline in monocyte counts, red-blood-cell counts, and hemoglobin concentrations (Ptrend for WQS indices < 0.05). The estimated BMDs for CE levels of benzene, toluene, and xylene were 2.138, 1.449, and 2.937 mg/m3 × year, respectively. Our study demonstrated the hematological effects of long-term BTX co-exposure and developed 8h-RELs of about 0.01 ppm based on their hematological effects.

The ingot of S31254 super austenitic stainless steel (SASS) was annealed at 1220 °C for 70 h to eliminate the segregation of Mo element, and the grain size grows to the level of millimeter. The stress–strain response and microstructural evolution of coarse-grained S31254 SASS were investigated by hot compression tests in the temperature range of 950–1250 °C and strain rate range of 0.001–10 s−1. The results showed that the energy required for plastic deformation improved with the increase of strain rate and the decrease of deformation temperature. The hot deformation activation energy was calculated to be 542.91 kJ·mol−1 through the regression analysis of hyperbolic-sine function, and the constitutive equation was established. Processing maps were constructed, and two optimal hot working parameters ranges were clarified. Due to the low fraction of grain boundaries, the main deformation mechanism of coarse-grained S31254 SASS was dynamic recovery. However, when the deformation temperature improved to 1250 °C, recrystallized grains began to nucleate and grow along with the band-like structure within the austenitic grains. When the deformation temperature is 950–1150 °C, the microstructural stability of S31254 SASS under tension stress was excellent. However, when the temperature and the strain rate were 1250 °C and 0.5 s−1 respectively, the microstructural stability deteriorated resulting from the formation of δ-ferrite phase and local melting of austenitic grain boundaries.

2D Titanium carbide MXenes with a structural formula recognized as Tin+1Cn have attracted attention from both the academic and industry fields due to their intriguing mechanical properties and appealing potential in a variety of areas such as nano-electronic circuits/devices, bio sensors, energy storage and reinforcing material for composites. Based on mutli-body comb3 (third-generation Charge-Optimized Many-Body) potential, this work investigated the impact resistance of monolayer Tin+1Cn nanosheets (namely, Ti2C Ti3C2 and Ti4C3) under hypervelocity up to 7 km/s. The deformation behavior and the impact resist mechanisms of Tin+1Cn nanosheets were assessed. Penetration energy is found to positively correlate with the number of titanium atom layer (n). However, in tracking atomic Von Mises stress distribution, Ti2C exhibits the most significant elastic wave propagation velocity among the examined nanosheets, suggesting the highest energy delocalization rate and stronger energy dissipation via deformation prior to bond break. Consistently, Ti2C presents superior specific penetration energy due its Young’s-modulus-to-density ratio, followed by Ti3C2 and Ti4C3, suggesting an inverse correlation between the titanium atom layer number and specific penetration energy. This study provides a fundamental understanding of the deformation and penetration mechanisms of titanium carbide MXene nanosheets under impact, which could be beneficial to facilitating their emerging impact protection applications.

Abstract Background 21‐Hydroxylase deficiency (21‐OHD) caused by the CYP21A2 gene mutations is the most common form of congenital adrenal hyperplasia. It is an autosomal recessive disorder that results in defective synthesis of cortisol and aldosterone. The incidences of various CYP21A2 gene mutations and the genotype–phenotype correlations vary among different populations. Materials and Methods The clinical and molecular data of 22 patients were analyzed in this study. All patients were recruited from the neonatal intensive care unit. Locus‐specific polymerase chain reaction and Sanger sequencing were applied to identify gene micro‐conversions, and multiplex ligation‐dependent probe amplification was used to detect large fragment deletions/conversions. Then, the genotypes were categorized in to Null, A, B, C, and D groups to analyze the relationships between genotypes and phenotypes. Results All 22 patients were classified into classic salt wasting form of 21‐OHD. Molecular defects were detected in 44 alleles (100%). Micro‐conversion mutation IVS2‐13A/C>G (70.5%) is most common in our cohort, followed by large gene deletions and conversions (22.7%). The other mutations present were p.R357 W (4.5%) and E6 Cluster (2.3%). Genotypes of 22 patients (100%) were consistent with the predictive phenotypes. Conclusion In this study, we identified the mutation spectrum of CYP21A2 gene in Chinese patients, especially the younger age cohort in pediatrics. Micro‐conversions were the most popular mutations. Moreover, the genotypes and phenotypes were well correlated in this cohort of salt wasting 21‐OHD recruited from neonatal intensive care unit.

Berberine (BBR) has been reported that it has effects on inhibiting colorectal cancer (CRC). However, the mechanism of BBR on CRC also remains largely unknown. Herein, we investigated the therapeutic effects of BBR on CRC from the perspective of gut microbiota and metabolic alterations, which can provide a holistic view to understand the effects of BBR on CRC. First, azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse was used as CRC animal model, then the degree of colorectal carcinogenesis in AOM/DSS mice with or without BBR administration was measured. The composition and abundance of gut microbiota was investigated by using 16S rRNA. Meanwhile, feces samples were analyzed with 1H NMR spectroscopy to investigate the metabolic alterations. As a result, BBR significantly reduced intestinal tumor development with lower macroscopic polyps and ki-67 expression of intestinal tissue, and better colonic morphology in mice. Moreover, BBR altered the composition of gut microbiota in AOM/DSS mice obviously, which were characterized by a decrease of Actinobacteria and Verrucomicrobia significantly at the phylum level. At the genus level, it was able to suppress pathogenic species, such as f_Erysipelotrichaceae, Alistipes, and elevate some short-chain fatty acids (SCFA)-producing bacteria, including Alloprevotella, Flavonifractor, and Oscillibacter. Metabolic data further revealed that BBR induced metabolic changes in feces focus on regulating glycometabolism, SCFA metabolism and amino acid metabolism, which also provides evidence for alteration of the microbiota because these feces metabolites are the products of interactions between the host and the microbial community. This study showed that BBR induced alterations in microbiota and metabolic in AOM/DSS mice, which might providing new insight into the inhibition effects of BBR on CRC.

Abstract Background Cobalamin (cbl) C is a treatable rare hereditary disorder of cbl metabolism with autosomal recessive inheritance. It is the most common organic acidemia, manifested as methylmalonic academia combined with homocysteinemia. Early screening and diagnosis are important. The mutation spectrum of the MMACHC gene causing cblC varies among populations. The mutation spectrum in Chinese population is notably different from that in other populations. Methods A PCR followed by high‐resolution melting curve analysis (PCR‐HRM) method covering all coding exons of MMACHC gene was designed to verify 14 pathogenic MMACHC gene variants found in patients with cblC, including all common mutations in Chinese patients with cblC. Result By PCR‐HRM analysis, 14 pathogenic variants of MMACHC showed distinctly different melting curves, which were consistent with Sanger sequencing. The homozygous type of the most common mutation c.609G > A (p.Trp203Ter) can also be analyzed by specially designed PCR‐HRM. Conclusion The established PCR‐HRM method for screening common pathogenic MMACHC variants in Chinese patients with cblC has the advantages of high accuracy, high throughput, low cost, and high speed. It is suitable for the large‐sample screening of suspected children with methylmalonic acidemia and carriers in population.

Heterotrimeric G proteins are best known for their role in the transduction of extracellular signals to various downstream effectors. G proteins in higher eukaryotes are intensively studied; however, their roles in foliar pathogens are still elusive. In this study, we cloned the gene Stgg1 encoding G protein γ subunit in Setosphaeria turcica and investigated its function by RNA interference technology. Three independent Stgg1 targeted RNAi mutants R3, R5 and R6 with diverse silencing efficiency were generated. Knock-down of Stgg1 resulted in a significant reduction in mRNA levels of the genes encoding Gα (Stga1, Stga2, Stga3) but not for Gβ (Stgb1). Stgg1 RNAi mutants exhibited significantly elongated hyphal cells with blocked conidium production. In addition, Stgg1 RNAi mutants all appeared in lighter colony colour compatible with inhibited secondary metabolites. Further assays demonstrated that Stgg1 was required for biosynthesis of melanin and HT-toxin activity. Furthermore, down-regulation of Stgg1 largely inhibited the inflection capacity. Thus, we proposed that Stgg1 played crucial roles in conidiation, secondary metabolite production and pathogenicity of S. turcica and is, therefore, an ideal target for drug design against foliar pathogens.

Background The Wnt signaling pathway, an evolutionarily conserved molecular transduction cascade, has been identified as playing a pivotal role in various physiological and pathological processes of the liver, including homeostasis, regeneration, cirrhosis, and hepatocellular carcinoma (HCC). In this study, we aimed to use a bibliometric method to evaluate the emerging trends on Wnt signaling in liver diseases. Methods Articles were retrieved from the Web of Science Core Collection. We used a bibliometric software, CiteSpace V 5.3.R4, to analyze the active countries or institutions in the research field, the landmark manuscripts, important subtopics, and evolution of scientific ideas. Results In total, 1,768 manuscripts were published, and each was cited 33.12 times on average. The U.S. published most of the articles, and the most active center was the University of Pittsburgh. The top 5 landmark papers were identified by four bibliometric indexes including citation, burstness, centrality, and usage 2013. The clustering process divided the whole area into nine research subtopics, and the two major important subtopics were “liver zonation” and “HCC.” Using the “Part-of-Speech” technique, 1,743 terms representing scientific ideas were identified. After 2008, the bursting phrases were “liver development,” “progenitor cells,” “hepatic stellate cells,” “liver regeneration,” “liver fibrosis,” “epithelial-mesenchymal transition,” and etc. Conclusion Using bibliometric methods, we quantitatively summarized the advancements and emerging trends in Wnt signaling in liver diseases. These bibliometric findings may pioneer the future direction of this field in the next few years, and further studies are needed.

Finite element model updating precision depends heavily on sufficient vibration feature extraction. However, adequate amount of sample collection is generally time-consuming in frequency response (FR) model updating. Accurate vibration feature extraction with insufficient data has become a significant challenge in FR model updating. To update the finite element model with a small dataset, a novel approach based on transfer learning is firstly proposed in this paper. A readily available fault diagnosis dataset is selected as ancillary knowledge to train a high-precision mapping from FR data to updating parameters. The proposed transfer learning network is constructed with two branches: source and target domain feature extractor. Considering about the cross-domain feature discrepancy, a domain adaptation method is designed by embedding the extracted features into a shared feature space to train a reliable model updating framework. The proposed method is verified by a simulated satellite example. The comparison results manifest that sample amount dependency has prominently lessened this method and the updated model outperforms the method without transfer learning in accuracy with the small dataset. Furthermore, the updated model is validated through dynamic response out of the training set.

The excellent mechanical properties of Graphdiyne (GDY) family has enabled it as an appealing candidate in the field of impact protection. In this in silico study, Monolayer GDY nanosheets of different morphology including GDY, GY-3, GY-4, GY-5 and GY-6 are assessed under hypervelocity impacts (from 1 to 6 km s ^−1 ). Tracking the deformation mechanisms under impacts as well as the Probability density function based on atomic Von Mises stress distribution, the length of acetylenic chain clearly alters ductile behavior as well as the energy dissipation/delocalization rate of GDY family during the impact. Results also suggest the penetration energy is not only determined by the energy delocalization rate but also sensitive to impact velocity for nanosheet with various acetylenic chain length. GY-5 with a much lower energy delocalization rate presents a close penetration energy comparing with GDY at a low impact at ∼2.0 km s ^−1 , its superior ductility granted by long acetylenic chain not only dissipates kinetic energy of projectile via deformation, but also extends time for acceleration during the contact with projectile. Considering the impact resist performance of GDY family in terms of Specific penetration energy, GY-5 with the perfect balance between material density, ductility and Young’s modulus makes it the superior anti-ballistic material for impact velocity at 5 km s ^−1 , it induces severer local deformation, and leaves no time for a well-developed distributed pattern as observed in a lower impact velocity scenario. As such, extensive elastic deformation of the nanosheet is not captured under impact, nanosheets with shorter acetylenic chains and hence greater material strength demonstrates superior impact resist. This study provides a fundamental understanding of the deformation and penetration mechanisms of monolayer GDY nanosheets under impact, which is crucial in order to facilitate their emerging applications for impact protection.

In this study, a stochastic user equilibrium model on the modified random regret minimization is proposed by incorporating the asymmetric preference for gains and losses to describe its effects on the regret degree of travelers. Travelers are considered to be capable of perceiving the gains and losses of attributes separately when comparing between the alternatives. Compared to the stochastic user equilibrium model on the random regret minimization model, the potential difference of emotion experienced induced by the loss and gain in the equal size is jointly caused by the taste parameter and loss aversion of travelers in the proposed model. And travelers always tend to use the routes with the minimum perceived regret in the travel decision processes. In addition, the variational inequality problem of the stochastic user equilibrium model on the modified random regret minimization model is given, and the characteristics of its solution are discussed. A route-based solution algorithm is used to resolve the problem. Numerical results given by a three-route network show that the loss aversion produces a great impact on travelers’ choice decisions and the model can more flexibly capture the choice behavior than the existing models.

Proteus species are well-known opportunistic pathogens frequently associated with skin wound and urinary tract infections in humans and animals. O antigen diversity is important for bacteria to adapt to different hosts and environments, and has been used to identify serotypes of Proteus isolates. At present, 80 Proteus O-serotypes have been reported. Although the O antigen structures of most Proteus serotypes have been identified, the genetic features of these O antigens have not been well characterized. The O antigen gene clusters of Proteus species are located between the cpxA and secB genes. In this study, we identified 55 O antigen gene clusters of different Proteus serotypes. All clusters contain both the wzx and wzy genes and exhibit a high degree of heterogeneity. Potential functions of O antigen-related genes were proposed based on their similarity to genes in available databases. The O antigen gene clusters and structures were compared, and a number of glycosyltransferases were assigned to glycosidic linkages. In addition, an O serotype-specific suspension array was developed for detecting 31 Proteus serotypes frequently isolated from clinical specimens. To our knowledge, this is the first comprehensive report to describe the genetic features of Proteus O antigens and to develop a molecular technique to identify different Proteus serotypes.

The aim of this study is to investigate both the efficacy and mechanism of action of kaempferide (Kae) as a therapy for the treatment of cardiovascular disease. A rat model of myocardial ischemia/reperfusion (I/R) injury was established by ligation of the left anterior descending coronary artery for 30 min followed by a 2 h perfusion. In our study, we show that Kae remarkably improved cardiac function, alleviated myocardial injury via a decrease in myocardial enzyme levels, and attenuated myocardial infarct size in a dose-dependent manner. In addition, preconditioning treatment with Kae was found to significantly decrease serum TNF-α, IL-6, C-reactive protein (CRP), MDA, and ROS levels, while it was found to increase serum levels of SOD. Nuclear factor erythroid 2-related factor 2 (Nrf2) and cleaved caspase-3 expression levels were observed to be downregulated, while phospho-Akt (p-Akt) and phospho-glycogen synthase kinase-3β (p-GSK-3β) expression levels were upregulated. However, cotreatment with LY294002 (a PI3K inhibitor) or TDZD-8 (a GSK-3β inhibitor) was found to abolish the above cardioprotective effects observed with the Kae treatment. The data presented in this study provides evidence that Kae attenuates I/R-induced myocardial injury through inhibition of the Nrf2 and cleaved caspase-3 signaling pathways via a PI3K/Akt/GSK 3β-dependent mechanism.