Transcriptomic Establishment of Pig Macrophage Polarization Signatures.

Macrophages are the foremost controllers of innate and acquired immunity, playing important roles in tissue homeostasis, vasculogenesis, and congenital metabolism. In vitro macrophages are crucial models for understanding the regulatory mechanism of immune responses and the diagnosis or treatment of a variety of diseases. Pigs are the most important agricultural animals and valuable animal models for preclinical studies, but there is no unified method for porcine macrophage isolation and differentiation at present; no systematic study has compared porcine macrophages obtained by different methods. In the current study, we obtained two M1 macrophages (M1_IFNγ + LPS, and M1_GM-CSF) and two M2 macrophages (M2_IL4 + IL10, and M2_M-CSF), and compared the transcriptomic profiles between and within macrophage phenotypes. We observed the transcriptional differences either between or within phenotypes. Porcine M1 and M2 macrophages have consistent gene signatures with human and mouse macrophage phenotypes, respectively. Moreover, we performed GSEA analysis to attribute the prognostic value of our macrophage signatures in discriminating various pathogen infections. Our study provided a framework to guide the interrogation of macrophage phenotypes in the context of health and disease. The approach described here could be used to propose new biomarkers for diagnosis in diverse clinical settings including porcine reproductive and respiratory syndrome virus (PRRSV), African swine fever virus (ASFV), Toxoplasma gondii (T. gondii), porcine circovirus type 2 (PCV2), Haemophilus parasuis serovar 4 (HPS4), Mycoplasma hyopneumoniae (Mhp), Streptococcus suis serotype 2 (SS2), and LPS from Salmonella enterica serotype minnesota Re 595.

Cell-specific NFIA upregulation promotes epileptogenesis by TRPV4-mediated astrocyte reactivity.

BACKGROUND: The astrocytes in the central nervous system (CNS) exhibit morphological and functional diversity in brain region-specific pattern. Functional alterations of reactive astrocytes are commonly present in human temporal lobe epilepsy (TLE) cases, meanwhile the neuroinflammation mediated by reactive astrocytes may advance the development of hippocampal epilepsy in animal models. Nuclear factor I-A (NFIA) may regulate astrocyte diversity in the adult brain. However, whether NFIA endows the astrocytes with regional specificity to be involved in epileptogenesis remains elusive. METHODS: Here, we utilize an interference RNA targeting NFIA to explore the characteristics of NFIA expression and its role in astrocyte reactivity in a 4-aminopyridine (4-AP)-induced seizure model in vivo and in vitro. Combined with the employment of a HA-tagged plasmid overexpressing NFIA, we further investigate the precise mechanisms how NIFA facilitates epileptogenesis. RESULTS: 4-AP-induced NFIA upregulation in hippocampal region is astrocyte-specific, and primarily promotes detrimental actions of reactive astrocyte. In line with this phenomenon, both NFIA and vanilloid transient receptor potential 4 (TRPV4) are upregulated in hippocampal astrocytes in human samples from the TLE surgical patients and mouse samples with intraperitoneal 4-AP. NFIA directly regulates mouse astrocytic TRPV4 expression while the quantity and the functional activity of TRPV4 are required for 4-AP-induced astrocyte reactivity and release of proinflammatory cytokines in the charge of NFIA upregulation. NFIA deficiency efficiently inhibits 4-AP-induced TRPV4 upregulation, weakens astrocytic calcium activity and specific astrocyte reactivity, thereby mitigating aberrant neuronal discharges and neuronal damage, and suppressing epileptic seizure. CONCLUSIONS: Our results uncover the critical role of NFIA in astrocyte reactivity and illustrate how epileptogenic brain injury initiates cell-specific signaling pathway to dictate the astrocyte responses.

Fabrication of Poly(ε-caprolactone)-embedded Lignin-Chitosan Nanocomposite Porous Scaffolds from Pickering Emulsions.

Poly(ε-caprolactone) (PCL)-incorporated lignin-chitosan biomass-based nanocomposite porous scaffolds have been effectively prepared by templating oil-in-water Pickering high internal phase emulsions (HIPEs). PCL is dissolved in oil and chitosan and lignin nanoparticles originate in water. The continuous phase of the emulsions is gelled by cross-linking of chitosan with genipin and then freeze-dried to obtain porous scaffolds. The resulting scaffolds display interconnected and tunable pore structures. An increase in PCL content increases the mechanical strength and greatly reduces the water absorption capacity of the scaffolds. Scaffolds loaded with the anti-bacterial drug enrofloxacin show a slow drug release profile, adjustable release rate, and favorable long-term anti-bacterial activity. Moreover, Pickering emulsion templates with suitable viscosity are used as 3D printing inks to construct porous scaffolds with personalized geometry. The results imply that the simplicity and versatility of the technique of combining freeze-drying with Pickering HIPE templates is a promising approach to fabricate hydrophobic biopolymer-incorporated biomass-based nanocomposite porous scaffolds for biomedical applications.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Asymmetric Hydrative Aldol Reaction (HAR) via Vinyl-Gold Promoted Intermolecular Ynamide Addition to Aldehydes.

Herein, we reported an intermolecular asymmetric hydrative aldol reaction through vinyl-gold intermediate under ambient conditions. This tandem alkyne hydration and sequential nucleophilic addition afforded a "base-free" approach to ß-hydroxy amides with high efficiency (up to 95 % yields, >50 examples). Vinyl gold intermediate was applied as reactive nucleophile and Fe(acac)3 was used as the critical co-catalyst to prevent undesired protodeauration, allowing this transformation to proceed under mild conditions with good functional group tolerance and excellent stereoselectivity (>20 : 1 d.r. and up to 99 % ee).

Clinical validation of an artificial intelligence-enabled wound imaging mobile application in diabetic foot ulcers.

There is a lifetime risk of 15% to 25% of development of diabetic foot ulcers (DFUs) in patients with diabetes mellitus. DFUs need to be followed up on and assessed for development of complications and/or resolution, which was traditionally performed using manual measurement. Our study aims to compare the intra- and inter-rater reliability of an artificial intelligence-enabled wound imaging mobile application (CARES4WOUNDS [C4W] system, Tetsuyu, Singapore) with traditional measurement. This is a prospective cross-sectional study on 28 patients with DFUs from June 2020 to January 2021. The main wound parameters assessed were length and width. For traditional manual measurement, area was calculated by overlaying traced wound on graphical paper. Intra- and inter-rater reliability was analysed using intra-class correlation statistics. A value of <0.5, 0.5-0.75, 0.75-0.9, and >0.9 indicates poor, moderate, good, and excellent reliability, respectively. Seventy-five wound episodes from 28 patients were collected and a total of 547 wound images were analysed in this study. The median wound area during the first clinic consultation and all wound episodes was 3.75 cm2 (interquartile range [IQR] 1.40-16.50) and 3.10 cm2 (IQR 0.60-14.84), respectively. There is excellent intra-rater reliability of C4W on three different image captures of the same wound (intra-rater reliability ranging 0.933-0.994). There is also excellent inter-rater reliability between three C4W devices for length (0.947), width (0.923), and area (0.965). Good inter-rater reliability for length, width, and area (range 0.825-0.934) was obtained between wound nurse measurement and each of the C4W devices. In conclusion, we obtained good inter-rater and intra-rater reliability of C4W measurements against traditional wound measurement. The C4W is a useful adjunct in monitoring DFU wound progress.

Clinical validation of a machine-learning-based handheld 3-dimensional infrared wound imaging device in venous leg ulcers.

Chronic venous insufficiency is a chronic disease of the venous system with a prevalence of 25% to 40% in females and 10% to 20% in males. Venous leg ulcers (VLUs) result from venous insufficiency. VLUs have a prevalence of 0.18% to 1% with a 1-year recurrence of 25% to 50%, bearing significant socioeconomic burden. It is therefore important for regular assessment and monitoring of VLUs to prevent worsening. Our study aims to assess the intra- and inter-rater reliability of a machine learning-based handheld 3-dimensional infrared wound imaging device (WoundAide [WA] imaging system, Konica Minolta Inc, Tokyo, Japan) compared with traditional measurements by trained wound nurse. This is a prospective cross-sectional study on 52 patients with VLUs from September 2019 to January 2021 using three WA imaging systems. Baseline patient profile and clinical demographics were collected. Basic wound parameters (length, width and area) were collected for both traditional measurements and measurements taken by the WA imaging systems. Intra- and inter-rater reliability was analysed using intra-class correlation statistics. A total of 222 wound images from 52 patients were assessed. There is excellent intra-rater reliability of the WA imaging system on three different image captures of the same wound (intra-rater reliability ranging 0.978-0.992). In addition, there is excellent inter-rater reliability between the three WA imaging systems for length (0.987), width (0.990) and area (0.995). Good inter-rater reliability for length and width (range 0.875-0.900) and excellent inter-rater reliability (range 0.932-0.950) were obtained between wound nurse measurement and each of the WA imaging system. In conclusion, high intra- and inter-rater reliability was obtained for the WA imaging systems. We also obtained high inter-rater reliability of WA measurements against traditional wound measurement. The WA imaging system is a useful clinical adjunct in the monitoring of VLU wound documentation.

[Sensitization Spectrum of 16 362 Patients with Allergic Diseases in Peking University Third Hospital].

Objective To retrospectively analyze the sensitization spectrum of 16 362 patients with allergic diseases treated in the Peking University Third Hospital and provide reference for the prevention and treatment of allergic diseases.Methods A total of 16 362 patients with allergic diseases treated in the Peking University Third Hospital from January 2009 to September 2021 were selected.The serum levels of total IgE and antigen-specific IgE(sIgE)were determined.Furthermore,the selected patients were classified into different groups according to gender,age,and disease occurrence month.Results The mean level of total IgE in 7919 patients was 92.4(34.8, 241.0)kU/L.The sIgE levels of 34 allergens in 5495 patients were determined via the ImmunoCAP system,with a positive sIgE rate of 54.23%.The top 5 allergens with high positive rates were mountain juniper pollen(43.78%),cat dander(38.76%),egg white(33.38%),Japanese hop(32.03%),and mugwort(31.82%).The sIgE levels of 20 allergens in 10 867 patients were determined via the EURO system,with a positive sIgE rate of 35.79%.The top 5 allergens with high positive rates were mugwort(15.86%),house dust mite mix(10.17%),cat dander(8.32%),house dust(4.71%),and tree pollen mix(4.04%).The analysis based on gender showed that the allergen positive rates in males were higher than those in females.The positive rates of egg white and cow's milk gradually decreased with the increase in age,while those of the inhaled allergens gradually increased during 10-19 years and then gradually decreased.The analysis based on disease occurrence month showed that the population with allergic diseases in Beijing surged in summer and autumn due to the inhaled allergens including mugwort,tree pollen mix,common ragweed,cocklebur,goosefoots,Japanese hop,timothy grass,and weed mix.Conclusions Among the 16 362 patients with allergic diseases treated in the Peking University Third Hospital,male patients showed higher sensitivity to allergens.The positive rates of egg white and cow's milk gradually decreased with the increase in age,while those of inhaled allergens were highest in patients of 10-19 years.The population of allergic diseases in Beijing surged in summer and autumn due to the inhaled allergens.

Alkyne Trifunctionalization via Divergent Gold Catalysis: Combining π-Acid Activation, Vinyl-Gold Addition, and Redox Catalysis.

Here we report the first example of alkyne trifunctionalization through simultaneous construction of C-C, C-O, and C-N bonds via gold catalysis. With the assistance of a γ-keto directing group, sequential gold-catalyzed alkyne hydration, vinyl-gold nucleophilic addition, and gold(III) reductive elimination were achieved in one pot. Diazonium salts were identified as both electrophiles (N source) and oxidants (C source). Vinyl-gold(III) intermediates were revealed as effective nucleophiles toward diazonium, facilitating nucleophilic addition and reductive elimination with high efficiency. The rather comprehensive reaction sequence was achieved with excellent yields (up to 95%) and broad scope (>50 examples) under mild conditions (room temperature or 40 °C).

Consultation Pricing of the Online Health Care Service in China: Hierarchical Linear Regression Approach.

BACKGROUND: Online health care services are a possible solution to alleviate the lack of medical resources in rural areas, and further understanding of the related medical service pricing system would contribute to improvement of the online health care community (OHC). Although many studies have investigated the OHC, the impact of physicians' reputations and wage levels on consulting prices in the OHC has rarely been discussed in the literature. OBJECTIVE: This study was designed to explore the determinants of consulting prices in the OHC. We addressed the following questions: (1) Are the prices of online health consultation services affected by wage levels at the doctor's location? (2) How does a physician's online and offline reputation affect their consulting prices? METHODS: Employing a large-scale sample of 16,008 doctors in China, we first used descriptive statistics to investigate the determinants of consulting prices in their entirety. Hierarchical linear modeling was then used to investigate the determinants of consulting prices in the OHC. RESULTS: The empirical results led to the conclusion that if doctors have more elevated clinic titles, work in higher-level hospitals, have better online reputations, and/or have made more past sales, their consulting prices will be higher. Additionally, the wage level in the city in which the doctor is working determines their opportunity cost and therefore also affects consulting prices. CONCLUSIONS: The findings indicate that the characteristics of the doctor, the doctor's online reputation, and past sales affect the consulting price. In particular, the wage level in the city affects the price of the consultation. These findings highlight that the OHC is important because it can indeed break through geographical restrictions and give rural residents the opportunity to obtain medical service from doctors in big cities. However, doctors from cities often charge higher fees because of their higher opportunity cost. The results reveal that one of the most important functions of the OHC is to reduce the medical disparity between urban and rural areas; however, planners appear to ignore the possibility that rural residents with lower incomes may not be able to afford such high medical consultation costs. Therefore, the government should consider providing incentives to encourage urban doctors to provide discounts to rural residents or directly offer appropriate subsidies.

An LC/MS/MS method for analyzing the steroid metabolome with high accuracy and from small serum samples.

Analyzing global steroid metabolism in humans can shed light on the etiologies of steroid-related diseases. However, existing methods require large amounts of serum and lack the evaluation of accuracy. Here, we developed an LC/MS/MS method for the simultaneous quantification of 12 steroid hormones: testosterone, pregnenolone, progesterone, androstenedione, corticosterone, 11-deoxycortisol, cortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, estriol, and estradiol. Steroids and spiked internal standards in 100 µl serum were extracted by protein precipitation and liquid-liquid extraction. The organic phase was dried by evaporation, and isonicotinoyl chloride was added for steroid derivatization, followed by evaporation under nitrogen and redissolution in 50% methanol. Chromatographic separation was performed on a reverse-phase PFP column, and analytes were detected on a triple quadrupole mass spectrometer with ESI. The lower limits of quantification ranged from 0.005 ng/ml for estradiol to 1 ng/ml for cortisol. Apparent recoveries of steroids at high, medium, and low concentrations in quality control samples were between 86.4% and 115.0%. There were limited biases (-10.7% to 10.5%) between the measured values and the authentic values, indicating that the method has excellent reliability. An analysis of the steroid metabolome in pregnant women highlighted the applicability of the method in clinical serum samples. We conclude that the LC/MS/MS method reported here enables steroid metabolome analysis with high accuracy and reduced serum consumption, indicating that it may be a useful tool in both clinical and scientific laboratory research.

A novel orally infected hamster model for Coxsackievirus A16 hand-foot-and-mouth disease and encephalomyelitis.

Coxsackievirus A16 (CV-A16) is one of the major causes of mild and self-limiting hand-foot-and-mouth disease (HFMD) in young children, which may occasionally leads to serious neurological complications. In this study, we had developed a novel, consistent, orally infected CV-A16 HFMD hamster model with encephalomyelitis. Four groups of 7-day-old hamsters in a kinetic study were orally infected with mouse-adapted CV-A16 strains and sacrificed at 1-4 days post infection (dpi), respectively. Tissues were studied by light microscopy, immunohistochemistry to detect viral antigens, in situ hybridization to detect viral RNA, and by viral titration. In a separate transmission experiment, orally infected index hamsters were housed together with contact hamsters to investigate oral and fecal viral shedding by virus culture and reverse transcription polymerase chain reaction (RT-PCR). At severe infection/death endpoints, index and contact hamster infection were also histopathologically analyzed. In the kinetic study, infected hamsters developed signs of infection at 4 dpi. Viral antigens/RNA were localized to brainstem (medulla/pons; reticular formation and motor trigeminal nucleus) and spinal cord anterior horn neurons, oral squamous epithelia and epidermis from 3 to 4 dpi. Salivary and lacrimal glands, myocardium, brown adipose tissue, intestinal smooth muscle, and skeletal muscle infection was also demonstrated. Viremia at 1 dpi and increasing viral titers in various tissues were observed from 2 dpi. In the transmission study, all contact hamsters developed disease 3-5 days later than index hamsters, but demonstrated similar histopathological findings at endpoint. Viral culture and RT-PCR positive oral washes and feces confirmed viral shedding. Our hamster model, orally infected by the natural route for human infection, confirmed CV-A16 neurotropism and demonstrated squamous epitheliotropism reminiscent of HFMD, attributes not found in other animal models. It should be useful to investigate neuropathogenesis, model person-to-person transmission, and for testing antiviral drugs and vaccines.

Phenyl doped graphitic carbon nitride nanosheets for sensing of copper ions in living cells.

Copper (Cu) is a vital metal element for humans and animals. Monitoring and evaluating the concentration level of Cu2+ in a biological body is an effective way to prevent a variety of diseases. In this work, phenyl doped graphitic carbon nitride (PDCN) nanosheets with strong green fluorescence exhibited a sensitive and selective detection for Cu2+ with a linear range from 0.1-2.0 µmol L-1. Furthermore, fluorescent imaging was applied to semiquantitatively detect Cu2+ in HeLa cells using PDCN nanosheets as the probe, which can avoid the interference of background autofluorescence. This work provided a low-cost and biologically friendly fluorescent probe to monitor the concentration level of Cu2+ in living cells.

Comparison and evaluation of Abbott chemiluminescent microparticle immunoassay and ChIVD light-initiated chemiluminescent assay in the detection of Treponema pallidum antibody.

BACKGROUND: Laboratory tests play an important role in the diagnosis of syphilis. This study aimed to compare and assess the performance of the Abbott chemiluminescent microparticle immunoassay (CMIA) and the ChIVD light-initiated chemiluminescent assay (LICA) in the detection of Treponema pallidum (TP) antibody. METHODS: A total of 10 498 serum samples were detected with two assays, and the Treponema pallidum particle agglutination assay (TPPA) and recombinant immunoblot assay (RIBA) methods were used for confirmation. The sensitivity, specificity, positive predictive value, and negative predictive value of the Abbott CMIA and ChIVD LICA were calculated. The coincidence rate between two assays was also evaluated. The causes of false positive and false negative of two assays were studied. RESULTS: For the Abbott CMIA and ChIVD LICA, the sensitivity was 94.44% and 98.15%, the specificity was 99.89% and 99.81%, the positive predictive value was 93.29% and 88.83%, and the negative predictive value was 99.91% and 99.97%, respectively. The coincidence rate between Abbott CMIA and ChIVD LICA was 99.26%, and κ value was .790. The disease of infertility, hypertensive disease, liver disease, and cancer were the common causes of false positive in both assays, while infertility was also the main reason lead to false negative. CONCLUSION: Our results demonstrated that the Abbott CMIA and ChIVD LICA generally had high sensitivity and specificity and therefore may be suitable for the detection of TP antibody and screening for syphilis.

Exploring Types of Information Sources Used When Choosing Doctors: Observational Study in an Online Health Care Community.

BACKGROUND: Patients attempt to make appropriate decisions based on their own knowledge when choosing a doctor. In this process, the first question usually faced is that of how to obtain useful and relevant information. This study investigated the types of information sources that are used widely by patients in choosing a doctor and identified ways in which the preferred sources differ in various situations. OBJECTIVE: This study aims to address the following questions: (1) What is the proportion in which each of the various information sources is used? (2) How does the information source preferred by patients in choosing a doctor change when there is a difference in the difficulty of medical decision making, in the level of the hospital, or in a rural versus urban situation? (3) How do information sources used by patients differ when they choose doctors with different specialties? METHODS: This study overcomes a major limitation in the use of the survey technique by employing data from the Good Doctor website, which is now China's leading online health care community, data which are objective and can be obtained relatively easily and frequently. Multinomial logistic regression models were applied to examine whether the proportion of use of these information sources changes in different situations. We then used visual analysis to explore the question of which type of information source patients prefer to use when they seek medical assistance from doctors with different specialties. RESULTS: The 3 main information sources were online reviews (OR), family and friend recommendations (FR), and doctor recommendations (DR), with proportions of use of 32.93% (559,345/1,698,666), 23.68% (402,322/1,698,666), and 17.48% (296,912/1,698,666), respectively. Difficulty in medical decision making, the hospital level, and rural-urban differences were significantly associated with patients' preferred information sources for choosing doctors. Further, the sources of information that patients prefer to use were found to vary when they looked for doctors with different medical specialties. CONCLUSIONS: Patients are less likely to use online reviews when medical decisions are more difficult or when the provider is not a tertiary hospital, the former situation leading to a greater use of online reviews and the latter to a greater use of family and friend recommendations. In addition, patients in large cities are more likely to use information from online reviews than family and friend recommendations. Among different medical specialties, for those in which personal privacy is a concern, online reviews are the most common source. For those related to children, patients are more likely to refer to family and friend recommendations, and for those related to surgery, they value doctor recommendations more highly. Our results can not only contribute to aiding government efforts to further promote the dissemination of health care information but may also help health care industry managers develop better marketing strategies.

LC-MS/MS determination of plasma catecholamines after selective extraction by borated zirconia.

For the first time, boronate affinity chromatography and metal oxide affinity chromatography mechanisms for cis-diol-compounds extraction are simultaneously realized on a single material, termed borated zirconia. This material was prepared by hydrolyzing zirconium butoxide with boric acid under non-aqueous environment. The diameter of formed particles is around 200 nm. By extracting catechol under different pH conditions or with phosphate ion competition, the dual affinity mechanisms of borated zirconia are confirmed. Benefiting from such unique feature, borated zirconia can function well under neutral condition. By using borated zirconia for dispersive solid phase extraction, specific capture of cis-diol-containing catecholamines, including epinephrine (E), norepinephrine (NE) and dopamine (DA), was achieved. A reliable LC-MS/MS method was established and validated for quantification of these target analytes in plasma samples after derivatisation with benzoyl chloride. The linear ranges are 0.010-0.200 ng·mL-1 for E and DA, and 0.050-1.000 ng·mL-1 for NE. The limits of quantification are 0.008, 0.020 and 0.004 ng·mL-1 for E, NE and DA respectively. By analyzing samples from healthy volunteers and schizophrenia patients, the plasma concentrations of E, NE and DA were found to be higher for the latter. Graphical AbstractSchematic representation of boronate combined metal oxide affinity chromatography (BMOAC) extraction of cis-diol catecholamines from human plasma by borated zirconia following with benzoyl chloride derivatization and LC-MS determination.

Defining the regulatory role of programmed cell death 4 in laryngeal squamous cell carcinoma.

Programmed cell death 4 (PDCD4) is decreased in many different kinds of malignant tumors. EMT endows tumor cells invasive and metastatic properties. However, few studies have determined the role of PDCD4 in the regulation of EMT in the context of laryngeal carcinoma. We examined the relationship between PDCD4 and EMT-associated proteins E-cadherin and N-cadherin using laryngeal carcinoma tissues. Gene manipulation was used to define the regulatory capacity of PDCD4. We report that PDCD4 and E-cadherin/N-cadherin expression were significantly changed in the carcinoma tissues, and their expression was associated with pathological grade, metastatic state, and clinical stage. The suppression of PDCD4 (and consequently, E-cadherin) was concomitant with increased proliferation and G2-phase arrest, decreased apoptosis, and increased cell invasion. PDCD4 upregulation reversed the above-mentioned results. In nude mice, PDCD4 knockdown increased tumor growth and pathological features, confirming the tumorigenic role of PDCD4. Finally, PDCD4 silencing was associated with dysregulation of the carcinogenic Wnt-ß-catenin and the STAT3-miR-21 signaling pathways. This study revealed a dynamic regulatory relationship between PDCD4 and critical factors for EMT, establishing a broad, functional role for PDCD4 in laryngeal carcinoma, which may be propagated by the STAT3-miR-21 pathway. These findings provide new information on an EMT-associated target that may lead to a novel therapy.

Understanding a Nonlinear Causal Relationship Between Rewards and Physicians' Contributions in Online Health Care Communities: Longitudinal Study.

BACKGROUND: The online health care community is not just a place for the public to share physician reviews or medical knowledge, but also a physician-patient communication platform. The medical resources of developing countries are relatively inadequate, and the online health care community is a potential solution to alleviate the phenomenon of long hospital queues and the lack of medical resources in rural areas. However, the success of the online health care community depends on online contributions by physicians. OBJECTIVE: The aim of this study is to examine the effect of incentive mechanisms on physician's online contribution behavior in the online health community. We addressed the following questions: (1) from which specialty area are physicians more likely to participate in online health care community activities, (2) what are the factors affecting physician online contributions, and (3) do incentive mechanisms, including psychological and material rewards, result in differences of physician online contributions? METHODS: We designed a longitudinal study involving a data sample in three waves. All data were collected from the Good Doctor website, which is the largest online health care community in China. We first used descriptive statistics to investigate the physician online contribution behavior in its entirety. Then multiple linear and quadratic regression models were applied to verify the causal relationship between rewards and physician online contribution. RESULTS: Our sample included 40,300 physicians from 3607 different hospitals, 10 different major specialty areas, and 31 different provinces or municipalities. Based on the multiple quadratic regression model, we found that the coefficients of the control variables, past physician online contributions, doctor review rating, clinic title, hospital level, and city level, were .415, .189, -.099, -.106, and -.143, respectively. For the psychological (or material) rewards, the standardized coefficient of the main effect was 0.261 (or 0.688) and the standardized coefficient of the quadratic effect was -0.015 (or -0.049). All estimates were statistically significant (P<.001). CONCLUSIONS: Physicians with more past physician online contribution, with higher review ratings, coming from lower level clinics, not coming from tertiary hospitals, and not coming from big cities were more willing to participate in online health care community activities. To promote physician online contribution, it is necessary to establish an appropriate incentive mechanism including psychological and material rewards. Finally, our findings suggest two guidelines for designing a useful incentive mechanism to facilitate physician online contribution. First, material reward is more useful than psychological reward. Second, as indicated by the concave-down-increasing causal relationship between rewards and physician online contribution, although an appropriate reward is effective in encouraging willingness on the part of physicians to contribute to the online health care community, the effect of additional rewards is limited.

[Investigation on the psychological quality of mine rescue staff].

OBJECTIVES: To evaluate the psychological quality and its influencing factors of mine rescue staff. METHODS: A total of 310 on front line rescue staff from the mines in Tangshan were sampled by random cluster sampling method.Our own designed measurement tools for psychological quality, including Eysenck personality questionnaire (EPQ), attention test scale, willpower test scale and reactive agility test were used to investigate the psychological quality of mine rescue staff. All tests were conducted in quiet state.Other information including age, length of service for rescue, sex, education, smoking and drinking, and so on were collected at the same time. The mood and influencing factors on psychological quality of the rescue staff were also analyzed. RESULTS: The personality traits of mine rescue staff are close to the national norm.0.6% (2/310) staff showed weak willpower.20.7% (64/310) staff had unstable mood. The E and N factor scores in 20-29 years old group (12.7 ± 4.3 and 12.1 ± 5.1) were higher than 30-39, 40-49, 50-59 years old groups (E factor scores:11.4 ± 3.9, 10.6 ± 3.7 and 10.7 ± 3.9; N factor scores:11.0 ± 5.1, 9.4 ± 4.9 and 6.3 ± 3.4, respectively) (FE = 4.28, FN = 11.35, all P < 0.01) . The L factor score in 40-49 and 50-58 years old groups (13.0 ± 4.2 and 14.8 ± 3.6) were higher than 20-29 and 30-39 years old groups (11.5 ± 3.8 and 12.2 ± 3.8) (F = 6.08, P < 0.01) . Multivariate analysis found that the psychological quality of mine rescue staff was mainly influenced by the length of service (ß'E factor = -0.12, ß'willpower = -0.12), the amount of participating rescue (ß'P factor = 0.12, ß'N factor = -0.14), alerting duty (ß'L factor = 0.16, ß 'error number of target tracking = -0.161) , daily training (ß'attention = 0.22,ß'total number of aimed at the test = -0.18) and life events (ß'N factor = -0.14,ß'L factor = 0.13,ß'correct number of target tracking = -0.18). CONCLUSION: The mine rescue staff had high level psychological quality, length of service. the amount of participating rescue, and life events in the year effect the psychological quality of mine rescue staff.

A Novel Polyfunctional Polyurethane Acrylate Derived from Castor Oil-Based Polyols for Waterborne UV-Curable Coating Application.

Because of its unique molecular structure and renewable properties, vegetable oil has gradually become the focus of researchers. In this work, castor oil was first transformed into a castor oil-based triacrylate structure (MACOG) using two steps of chemical modification, then it was prepared into castor oil-based waterborne polyurethane acrylate emulsion, and finally, a series of coating materials were prepared under UV curing. The results showed that with the increase in MACOG content, the glass transition temperature of the sample was increased from 20.3 °C to 46.6 °C, and the water contact angle of its surface was increased from 73.85 °C to 90.57 °C. In addition, the thermal decomposition temperature, mechanical strength, and water resistance of the samples were also greatly improved. This study not only provides a new idea for the preparation of waterborne polyurethane coatings with excellent comprehensive properties but also expands the application of biomass material castor oil in the field of coating.